AU2005207883A1

AU2005207883A1 - Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of colon cancer

Info

Publication number: AU2005207883A1
Application number: AU2005207883A
Authority: AU
Inventors: Michal Ayalon-Soffer; Yossi Cohen; Gad S. Cojocaru; Dvir Dahary; Alexander Diber; Guy Kol; Zurit Levine; Amit Novik; Sarah Pollock; Shirley Sameah-Greenwald; Osnat Sella-Tavor; Ronen Shemesh; Rotem Sorek; Amir Toporik; Shira Walach
Original assignee: Compugen Ltd
Current assignee: Compugen Ltd
Priority date: 2005-01-27
Filing date: 2005-01-27
Publication date: 2005-08-11

Description

WO 2005/072053 PCT/IB2005/000928 1 NOVEL NUCLEOTIDE AND AMINO ACID SEQUENCES, AND ASSAYS AND METHODS OF USE THEREOF FOR DIAGNOSIS OF COLON CANCER 5 FIELD OF THE INVENTION The present invention is related to novel nucleotide and protein sequences that are diagnostic markers for colon cancer, and assays and methods of use thereof. 10 BACKGROUND OF THE INVENTION Colon and rectal cancers are malignant conditions which occur in the corresponding segments of the large intestine. These cancers are sometimes referred to jointly as "colorectal cancer", and, in many respects, the diseases are considered identical. The major differences between them are the sites where the malignant growths occur and the fact that treatments may 15 differ based on the location of the tumors. More than 95 percent of cancers of the colon and rectum are adenocarcinomas, which develop in glandular cells lining the inside (lumen) of the colon and rectum. In addition to adenocarcinomas, there are other rarer types of cancers of the large intestine: these include carcinoid tumors usually found in the appendix and rectum; gastrointestinal stromal tumors 20 found in connective tissue in the wall -of the colon and rectum; and lymphomas, which are malignancies of immune cells in the colon, rectum and lymph nodes. As with other malignant conditions, a number of genetic abnormalities have been associated with colon tumors (Bos et al, (1987) Nature 327:293-297; Baker et al, (1989) 244:217-221; Nishisho et al, (1991) 253:665 669). 25 Colorectal cancer is the second most common cause of cancer death in the United States and the third most prevalent cancer in both men and women. Approximately 100,000 patients every year suffer from colon cancer and approximately half that number die of the disease. In large part this death rate is due to the inability to diagnose the disease at an early stage (Wanebo (1993) Colorectal Cancer, Mosby, St. Louis Mo.). In fact, the prognosis for a case of colon 30 cancer is vastly enhanced when malignant tissue is detected at the early stage known as polyps. Polyps are usually benign growths protruding from the mucous membrane. Nearly all cases of WO 2005/072053 PCT/IB2005/000928 2 colorectal cancer arise from adenomatous polyps, some of which mature into large polyps, undergo abnormal growth and development, and ultimately progress into cancer. This progression would appear to take at least 10 years in most patients, rendering it a readily treatable form of cancer if diagnosed early, when the cancer is localized. Simple removal of 5 malignant polyps (polypectomy) through colonoscopy is now routine, and curing the condition from this procedure is effectively guaranteed. However, early detection of polyps and tumors depends on diligent and ongoing examination of patients at risk. The most reliable detection procedures to date include fecal occult blood tests, sigmoidoscopy, barium enema X-ray, digital rectal exam, and colonoscopy. Normally a malignant colon cancer will not cause noticeable 10 symptoms (e.g., bowel obstruction, abdominal pain, anemia) until it has reached an advanced and far more serious stage of malignancy. At these stages, only risky, traumatic and/or invasive procedures are available, including chemotherapy, radiation therapy, and colonectomy. Although current understanding of the etiology of colon cancer is undergoing continual refinement, extensive research in this area points to a combination of factors, including age, 15 hereditary and non-hereditary conditions, and environmental/dietary factors. Age is a key risk factor in the development of colorectal cancer, since men and women over 40 years of age become increasingly susceptible to that cancer. Incidence rates increase considerably in each subsequent decade of life. A number of hereditary and nonhereditary conditions have also been linked to a heightened risk of developing colorectal cancer, including familial adenomatous 20 polyposis (FAP), hereditary nonpolyposis colorectal cancer (Lynch syndrome or HNPCC), a personal and/or family history of colorectal cancer or adenomatous polyps, inflammatory bowel disease, diabetes mellitus, and obesity. In the case of FAP, the tumor suppressor gene APC (adenomatous polyposis coli), located at 5q21, has been either mutationally inactivated or deleted (Alberts et al., Molecular 25 Biology of the Cell 1288 (3d ed. 1994)). The APC protein plays a role in a number of functions, including cell adhesion, apoptosis, and repression of the c-myc oncogene. Of those patients with colorectal cancer who have normal APC genes, over 65% have such mutations in the cancer cells but not in other tissues. In the case of H-PNCC, patients manifest abnormalities in the tumor suppressor gene HNPCC, but only about 15% of tumors contain the mutated gene. A host of 30 other genes have also been implicated in colorectal cancer, including the K-ras, c-Ki-ras, N-ras, WO 2005/072053 PCT/IB2005/000928 3 H-ras and c-myc oncogenes, and the tumor suppressor genes DCC (deleted in colon carcinoma), Wg/Wnt signal transduction pathway components and p53. Some tyrosine kinases have been shown up-regulated in colorectal tumor tissues or cell lines like IT29. Focal adhesion kinase (FAK) and its up-stream kinase c-src and c-yes in 5 colonic epithelial cells may play an important role in the promotion of colorectal cancers through the extracellular 1 5 matrix (ECM) and integrin-mediated signaling pathways. The formation of c-src/FAK complexes may coordinately deregulate VEGF expression and apoptosis inhibition. Recent evidences suggest that a specific signal-transduction pathway for cell survival 10 that implicates integrin engagement leads to FAK activation and thus activates PI-3 kinase and akt. In turn, akt phosphorylates BAD and blocks apoptosis in epithelial cells. The activation of c-sre in colon cancer may induce VEGF expression through the hypoxia pathway. Other genes that may be implicated in colorectal cancer include Cox enzymes (Ota, S. et al. Aliment Pharmacol. Ther. 16 (Suppl 2): 102-106 (2002)), estrogen (alAzzawi, F. and Wahab, M. 15 Climacteric 5: 3-14 (2002)), peroxisome proliferator-activated receptor-y (PPAR-y) (Gelman, L. et al. Cell Mol. Life Sci. 5 5: 932-943 (1999)), IGF-I (Giovannucci (2001)), thymine DNA glycosylase (TDG) (Hardeland, U. et al. Prog. Nucleic Acid Res. Mol. Biol. 68: 235-253 (2001)) and EGF (Mendelsohn, J. EndocrineRelated Cancer 8: 3-9 (2001)). 20 Procedures used for detecting, diagnosing, monitoring, staging, and prognosticating colon cancer are of critical importance to the outcome of the patient. For example, patients diagnosed with early colon cancer generally have a much greater five-year survival rate as compared to the survival rate for patients diagnosed with distant metastasized colon cancer. 25 Because colon cancer is highly treatable when detected at an early, localized stage, screening should be a part of routine care for all adults starting at age 50, especially those with first-degree relatives with colorectal cancer. One major advantage of colorectal cancer screening over its counterparts in other types of cancer is its ability to not only detect precancerous lesions, but to remove them as well. The key colorectal cancer screening tests in use today are fecal occult 30 blood test, sigmoidoscopy, colonoscopy, double-contrast barium enema, and the WO 2005/072053 PCT/IB2005/000928 4 carcinoembryonic antigen (CEA) test. New diagnostic methods which are more sensitive and specific for detecting early colon cancer are clearly needed. Visual examination of the colon for abnormalities can be performed through endoscopic 5 or radiographic techniques such as rigid proctosigmoidoscopy, flexible sigmoidoscopy, colonoscopy, and barium-contrast enema. These methods enable one to detect, biopsy, and remove adenomatous polyps. Despite the advantages of these procedures, there are accompanying downsides: they are expensive, and uncomfortable, and also carry with them a risk of complications. Sigmoidoscopy, by definition, is limited to the sigmoid colon and below, 10 colonoscopy is a relatively expensive procedure, and both share the risk of possible bowel perforation and hemorrhaging. Double-contrast barium enema (DCBE) enables detection of lesions better than FOBT, and almost as well a colonoscopy, but it may be limited in evaluating the winding rectosigmoid region. Another method of colon cancer diagnosis is the detection of carcinoembryonic antigen 15 (CEA) in a blood sample from a subject, which when present at high levels, may indicate the presence of advanced colon cancer. But CEA levels may also be abnonnally high when no cancer is present. Thus, this test is not selective for colon cancer, which limits the test's value as an accurate and reliable diagnostic tool. In addition, elevated CEA levels are not detectable until late-stage colon cancer, when the cure rate is low, treatment options limited, and patient 20 prognosis poor. Several classification systems have been devised to stage the extent of colorectal cancer, including the Dukes' system and the more detailed International Union against Cancer-American Joint Committee on Cancer TNM staging system, which is considered by many in the field to be 25 a more useful staging system. These most widely used staging systems generally use at least one of the following characteristics for staging: the extent of tumor penetration into the colon wall, with greater penetration generally correlating with a more dangerous tumor; the extent of invasion of the tumor through the colon wall and into other neighboring tissues, with greater invasion generally correlating with a more dangerous tumor; the extent of invasion of the tumor 30 into the regional lymph nodes, with greater invasion generally correlating with a more WO 2005/072053 PCT/IB2005/000928 5 dangerous tumor; and the extent of metastatic invasion into more distant tissues, such as the liver, with greater metastatic invasion generally correlating with a more dangerous disease state. "Dukes A" and "Dukes B" colon cancers are neoplasia that have invaded into the wall of the colon but have not spread into other tissues. Dukes A colon cancers are cancers that have not 5 invaded beyond the submucosa. Dukes B colon cancers are subdivided into two groups: Dukes B1 and Dukes B2. "Dukes Bl" colon cancers are neoplasias that have invaded up to but not through the muscularis propria. Dukes B2 colon cancers are cancers that have breached completely through the muscularis propria. Over a five year period, patients with Dukes A cancer who receive surgical treatment (i.e. removal of the affected tissue) have a greater than 10 90% survival rate. Over the same period, patients with Dukes BI and Dukes B2 cancer receiving surgical treatment have a survival rate of about 85% and 75% respectively. Dukes A, BI and B2 cancers are also referred to as TI, T2 and T3-T4 cancers, respectively. "Dukes C" colon cancers are cancers that have spread to the regional lymph nodes, such as the lymph nodes of the gut. Patients with Dukes C cancer who receive surgical treatment alone have a 35% 15 survival rate over a five year period, but this survival rate is increased to 60% in patients that receive chemotherapy. "Dukes D" colon cancers are cancers that have metastasized to other organs. The liver is the most common organ in which metastatic colon cancer is found. Patients with Dukes D colon cancer have a survival rate of less than 5% over a five year period, regardless of the treatment regimen. 20 The TNM system, which is used for either clinical or pathological staging, is divided into four stages, each of which evaluates the extent of cancer growth with respect to primary tumor (T), regional lymph nodes (N), and distant metastasis (M). The system focuses on the extent of tumor invasion into the intestinal wall, invasion of adjacent structures, the number of regional lymph nodes that have been affected, and whether distant metastasis has occurred. 25 Stage 0 is characterized by in situ carcinoma (Tis), in which the cancer cells are located inside the glandular basement membrane (intraepithelial) or lamina propria, (intramucosal). In this stage, the cancer has not spread to the regional lymph nodes (NO), and there is no distant metastasis (N40). In stage 1, there is still no spread of the cancer to the regional lymph nodes and no distant metastasis, but the tumor has invaded the submucosa (T I) or has progressed 30 further to invade the muscularis propria (T2). Stage R also involves no spread of the cancer to the regional lymph nodes and no distant metastasis, but the tumor has invaded the subserosa, or WO 2005/072053 PCT/IB2005/000928 6 the nonperitonealized pericolic or perirectal tissues (T3), or has progressed to invade other organs or structures, and/or has perforated the visceral peritoneum (T4). Stage 3 is characterized by any of the T substages, no distant metastasis, and either metastasis in 1 to 3 regional lymph nodes (Nl) or metastasis in four or more regional lymph nodes (N2). Lastly, stage 4 involves any 5 of the T or N substages, as well as distant metastasis. Currently, pathological staging of colon cancer is preferable over clinical staging as pathological staging provides a more accurate prognosis. Pathological staging typically involves examination of the resected colon section, along with surgical examination of the abdominal cavity. 10 SUMMARY OF THE INVENTION The background art does not teach or suggest markers for colon cancer that are sufficiently sensitive and/or accurate, alone or in combination. From the foregoing, it is clear that procedures used for detecting, diagnosing, monitoring, staging, prognosticating, and 15 preventing the recurrence of colorectal cancer are of critical importance to the outcome of the patient. Moreover, current procedures, while helpful in each of these analyses, are limited by their specificity, sensitivity, invasiveness, and/or their cost. It would therefore be desirable to provide more sensitive and accurate methods and reagents for the early diagnosis, staging, prognosis, monitoring, and treatment of diseases associated with colon cancer, or to indicate a 20 predisposition to such for preventative measures, as well as to determine whether or not such cancer has metastasized and for monitoring the progress of colon cancer in a human which has not metastasized for the onset of metastasis. The present invention overcomes the deficiencies of the background art by providing novel markers for colon cancer that are both sensitive and accurate. Furthermore, these markers 25 are able to distinguish between different stages of colon cancer, such as adenocarcinoma (mucinous or signet ring cell originating); leiomyocarcomas; carcinoid. Furthermore, at least some of these markers are able to distinguish, alone or in combination, between colon cancer between non-cancerous polyps. These markers are overexpressed in colon cancer specifically, as opposed to normal colon tissue. The measurement of these markers, alone or in combination, in 30 patient samples provides information that the diagnostician can correlate with a probable WO 2005/072053 PCT/IB2005/000928 7 diagnosis of colon cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between colon cancer and non-cancerous states. According to preferred embodiments of the present invention, examples of suitable biological samples include but are not limited to blood, serum, plasma, blood cells, urine, 5 sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, milk, neuronal tissue, colon tissue or mucous and any human organ or tissue. In a preferred embodiment, the biological sample comprises colon tissue and/or a serum sample and/or a urine sample and/or a stool sample and/or any other tissue or liquid sample. The sample can optionally be diluted with a suitable 10 eluant before contacting the sample to an antibody and/or performing any other diagnostic assay. Information given in the text with regard to cellular localization was determined according to four different software programs: (i) tmhmm (from Center for Biological Sequence Analysis, Technical University of Denmark DTU, 15 http://www.cbs.dtu.dk/services/TMHMM/TMHMM2.0b.guide.php) or (ii) tmpred (from EMBnet, maintained by the ISREC Bionformatics group and the LICR Information Technology Office, Ludwig Institute for Cancer Research, Swiss Institute of Bioinformatics, http://www.ch.embnet.org/software/TMPREDfon.htnil) for transmembrane region prediction; (iii) signalphmm or (iv) signalpnn (both from Center for Biological Sequence 20 Analysis, Technical University of Denmark DTU, http://www.cbs.dtu.dkc/services/SignalP/background/prediction.php) for signal peptide prediction. The terms "signalphmm" and "signalp_nn" refer to two modes of operation for the program SignaiP: himm refers to Hidden Markov Model, while nn refers to neural networks. Localization was also determined through manual inspection of known protein localization 25 and/or gene structure, and the use of heuristics by the individual inventor. In some cases for the manual inspection of cellular localization prediction inventors used the ProLoc computational platform [Einat Hazkani-Covo, Erez Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) "Evolution of multicellularity in metazoa: comparative analysis of the subcellular localization of proteins in Saccharomyces, Drosophila and Caenorhabditis." Cell Biology 30 International 2004;28(3):171-8.], which predicts protein localization based on various parameters including, protein domains (e.g., prediction of trans-membranous regions and WO 2005/072053 PCT/IB2005/000928 8 localization thereof within the protein), p1, protein length, amino acid composition, homology to pre-annotated proteins, recognition of sequence patterns which direct the protein to a certain organelle (such as, nuclear localization signal, NLS, mitochondria localization signal), signal peptide and anchor modeling and using unique domains from Pfam that are specific to a single 5 compartment. Information is given in the text with regard to SNPs (single nucleotide polymorphisms). A description of the abbreviations is as follows. "T - > C", for example, means that the SNP results in a change at the position given in the table from T to C. Similarly, "M - > Q", for example, means that the SNP has caused a change in the corresponding amino acid sequence, 10 from methionine (M) to glutamine (Q). If, in place of a letter at the right hand side for the nucleotide sequence SNP, there is a space, it indicates that a frameshift has occurred. A frameshift may also be indicated with a hyphen (-). A stop codon is indicated with an asterisk at the right hand side (*). As part of the description of an SNP, a comment may be found in parentheses after the above description of the SNP itself. This comment may include an FTId, 15 which is an identifier to a SwissProt entry that was created with the indicated SNP. An FTId is a unique and stable feature identifier, which allows construction of links directly from position specific annotation in the feature table to specialized protein-related databases. The FTId is always the last component of a feature in the description field, as follows: FTId=XXX_number, in which XXX is the 3-letter code for the specific feature key, separated by an underscore from 20 a 6-digit number. In the table of the amino acid mutations of the wild type proteins of the selected splice variants of the invention, the header of the first column is "SNP position(s) on amino acid sequence", representing a position of a known mutation on amino acid sequence. SNPs may optionally be used as diagnostic markers according to the present invention, alone or in combination with one or more other SNPs and/or any other diagnostic marker. Preferred 25 embodiments of the present invention comprise such SNPs, including but not limited to novel SNPs on the known (WT or wild type) protein sequences given below, as well as novel nucleic acid and/or amino acid sequences formed through such SNPs, and/or any SNP on a variant amino acid and/or nucleic acid sequence described herein. Information given in the text with regard to the Homology to the known proteins was 30 determined by Smith-Waterman version 5.1.2 using special (non default) parameters as follows: -model=sw.model WO 2005/072053 PCT/IB2005/000928 9 -GAPEXT=0 -GAPOP=1 00.0 -MATRIX=blosum100 5 Information is given with regard to overexpression of a cluster in cancer based on ESTs. A key to the p values with regard to the analysis of such overexpression is as follows: - library-based statistics: P-value without including the level of expression in cell lines (P1) - library based statistics: P-value including the level of expression in cell-lines (P2) 10 - EST clone statistics: P-value without including the level of expression in cell-lines (SP1) - EST clone statistics: predicted overexpression ratio without including the level of expression in cell-lines (R3) - EST clone statistics: P-value including the level of expression in cell-lines (SP2) 15 - EST clone statistics: predicted overexpression ratio including the level of expression in cell-lines (R4) Library-based statistics refer to statistics over an entire library, while EST clone statistics refer to expression only for ESTs from a particular tissue or cancer. Information is given with regard to overexpression of a cluster in cancer based on 20 microarrays. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. There are two types of microarray results: those from microarrays prepared according to a design by the present inventors, for which the microarray fabrication procedure is described in detail in Materials and Experimental Procedures section herein; and those results from 25 microarrays using Affyinetrix technology. As a microarray reference, in the specific segment paragraphs, the unabbreviated tissue name was used as the reference to the type of chip for which expression was measured. For microarrays prepared according to a design by the present inventors, the probe name begins with the name of the cluster (gene), followed by an identifying number. Oligonucleotide microarray results taken from Affymetrix data were from chips 30 available from Affymetrix Inc, Santa Clara, CA, USA (see for example data regarding the Human Genome U133 (HG-U133) Set at WO 2005/072053 PCT/IB2005/000928 10 www.affymetrix.comi/products/arrays/specific/hgul33.affx; GeneChip Human Genome U133A 2.0 Array at www.affymetrix.comi/products/arrays/specific/hgul33av2.affx; and Human Genome U133 Plus 2.0 Array at www.affymetrix.com/products/arrays/specific/hgul33plus.affx). The probe names follow the 5 Affymetrix naming convention. The data is available from NCBI Gene Expression Omnibus (see www.nebi.nlm.nih.gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002, Vol. 30, No. 1 207-210). The dataset (including results) is available from www.ncbi.nlm.nih.gov/geo/query/ace.cgi?acc=GSEl133 for the Series GSE1133 database (published on March 2004); a reference to these results is as follows: Su et al (Proc Natl Acad 10 Sci U S A. 2004 Apr 20;101(16):6062-7. Epub 2004 Apr 09). A list of probes is given below. >M85491_0_0_25999 GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC >M85491_0_14_0 GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG 15 >H53626_0_16_0 ATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTTC >H53626_0_0_8391 GGGTCTGGGGTGCTCTCCTGGTCTTTGTGTCGGCGTTCCCCTCCCTACCT >HSENA78_0_1_0 20 TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC >HUMGROG5_0_0_16626 GCAGAAACTTTGCAGTAACACCTTCAGTGAGTTCAAGGCTAGGATCCCTG >R00299_0_8_0 CCAAGGCTCGTCTGCGCACCTTGTGTCTTGTAGGGTATGGTATGTGGGAC 25 >S67314_0_0_741 CACAGAGCCAGGATGTTCTTCTGACCTCAGTATCTACTCCAGCTCCAGCT >S67314_0_0_744 TGGCATGCTGGAACATGGACTCTAGCTAGCAAGAAGGGCTCAAGGAGGTG >Z44808_0_8_0 30 AAAAGCATGAGTTTCTGACCAGCGTTCTGGACGCGCTGTCCACGGACATG >Z44808_0_0_72347 WO 2005/072053 PCT/IB2005/000928 11 ATGTTCTTAGGAGGCAAGCCAGGAGAAGCCGGGTCTGACTTTTCAGCTCA >Z44808_0_0_72349 TCCTCCAGACCCAAAGCCACAACCCATCGCAAGTCAAGAACACTTTCCAG >Z25299_0_3_0 5 AACTCTGGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTG >HUMCA1XIA_0_0_14909 GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG >I-UMCAlXIA_0_18_0 TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG 10 >HSS100PCB00_12280 CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA >HUMPHOSLIP 0 0 18458 AAGGAAGCAGGACCAGTGGATGTGAGGCGTGGTCGAAGAACAACAGAAAG >HUMPHOSLIP_0_0_18487 15 ACAGGGGCCAGATGGTGACCCATGACCCAGCCTAAAAGGCAGCCAGAGGG >D11853_0_0_0 GAGGCCCCTGGGTGGGAATGGGGACAGGAATTGACAGTGGAAGGGGTTCT >D11853_0_0_3085 TGACTCCCTACATACTCCAGGACTAGCTTAGGTCCCAACCCAATAGTTCC 20 >D11853_0_0_3082 TGGTCCCCATGTGATTCTCCGAGGATCCTGAGGGTCGTGGTTTATGGAGA >M779030021402 ACGTGATGGTTGGAACGCGTACCTTAGAGCTTCCAGTTCCGTCTTAGGAC >AA583399012_0 25 ATCCCCACTGAACCCAGTGCTTTCACCAGCCATATTAGCTCCCACTCACC >AA583399_0_0_1681 CACCGCATGCTGCCAATCTGATGGTGGAGACAGAACAGCAGTCCCGGATG >AA583399_0_1_1687 TTTCCACACTCAGTGCCACGAAGTGCAGCTCTAAGCTGGGGATTTCTGTG 30 >HUMCACHIA_0_12_0

ACCCAGCTCCATGTGCGTTCTCAGGGAATGGACGCCAGTGTACTGCCAAT

WO 2005/072053 PCT/IB2005/000928 12 >HUMCACH1A 0 3 14917 AGAGAATATCACTCCGATGGTCGGTTTCTGACTGTCACGCTAAGGGCAAC >HUMCACH1A_0_0_14922 GAACACAGAGAACGTCAGCGGTGAAGGCGAGAACCGAGGCTGCTGTGGAA 5 >HUMCACH1A 0 0 14913 GACTCAGGAGATGAACAGCTCCCAACTATTTGCCGGGAAGACCCAGAGAT >HUMCACH1A_0_0_14924 GGCCCAGCATTGGGAACCTTGAGCATGTGTCTGAAAATGGGCATCATTCT >HUMCEA 0 0 96 10 CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC >HUMCEA_0_0_15183 CCTGGTGGGAGCCCATGAGAAGCGAGTTCTCTGTGCAACGGACTTAGTAA >HUMCEA 0 0 15182 GCTCCCTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCT 15 >HUMCEA_0_0_15168 TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC >HUMCEA_0_0_15180 TTTAACACAGGATTGGGACAGGATTCAGAGGGACACTGTGGCCCTTCTAC >M780350021693 20 CCATCCACATTTATGGAAACACTTGCTGTATATCTGGTGATTTACGTGTci >M780350021691 CCTTTCACCACTGTGTGCAAGCGAATACACGCGGAACAATCCTAGTGAAT >M7803501_21707 TTTGCTAGAAATCTGGTGTGGTGCAGGAGCGACTCCAGGATTCACTCTGT 25 >T23657_0_18_0 TCCGTGACCCTCAGAGATCCTTTGCCCTGGGAATCCAGTGGATTGTAGTT >T51958_0_0_50903 CCCATGGTGGCCAGAGTGTCAGGTCTCATCGTGACGCTCTTGTCCTCCTC >T51958 0 0 50916 30 GGGGCTGTGCCCAGTCCCCCTGTCAGACCCTCAATGACTGAGGCCTGGGG >Z17877_0_4_0 WO 2005/072053 PCT/IB2005/000928 13 ACTTTGCACTGGAACTTACAACACCCGAGCAAGGACGCGACTCTCCCGAC >HSHCGI_0_0_10611 GCCTACTGATTCATCCACATACAATTCTCAGCGTATATCCAAATGCAGTC >HSHCGI_0_0_10620 5 GGACCTCTAAGTCTACAGGTGGTCAAAATGCTGTATCCACCCAATTCCAC The following list of abbreviations for tissues was used in the TAA histograms. The term "TAA" stands for "Tumor Associated Antigen", and the TAA histograms, given in the text, represent the cancerous tissue expression pattern as predicted by the biomarkers selection 10 engine, as described in detail in examples 1-5 below: "BONE" for "bone"; "COL" for "colon"; "EPI" for "epithelial"; "GEN" for "general"; 15 "LIVER" for "liver"; "LUN" for "lung"; "LYMPH" for "lymph nodes"; "MARROW" for "bone marrow"; "OVA" for "ovary"; 20 "PANCREAS" for "pancreas"; "PRO" for "prostate"; "STOMACH" for "stomach"; "TCELL" for "T cells"; "THYROID" for "Thyroid"; 25 "MAM" for "breast"; "BRAIN" for "brain"; "UTERUS" for "uterus"; "SKIN" for "skin"; "KIDNEY" for "kidney"; 30 "MUSCLE" for "muscle"; "ADREN" for "adrenal"; WO 2005/072053 PCT/IB2005/000928 14 "HEAD" for "head and neck"; "BLADDER" for "bladder"; It should be noted that the terms "segment", "seg" and "node" are used interchangeably 5 in reference to nucleic acid sequences of the present invention; they refer to portions of nucleic acid sequences that were shown to have one or more properties as described below. They are also the building blocks that were used to construct complete nucleic acid sequences as described in greater detail below. Optionally and preferably, they are examples of oligonucleotides which are embodiments of the present invention, for example as amplicons, 10 hybridization units and/or from which primers and/or complementary oligonucleotides may optionally be derived, and/or for any other use. As used herein the phrase "colon cancer" refers to cancers of the colon or colorectal cancers. The term "marker" in the context of the present invention refers to a nucleic acid 15 fragment, a peptide, or a polypeptide, which is differentially present in a sample taken from subjects (patients) having colon cancer as compared to a comparable sample taken from subjects who do not have colon cancer. The phrase "differentially present" refers to differences in the quantity of a marker present in a sample taken from patients having colon cancer as compared to a comparable 20 sample taken from patients who do not have colon cancer. For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and/or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the 25 polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker can be considered to be differentially present. As used herein the phrase "diagnostic" means identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The 30 "sensitivity" of a diagnostic assay is the percentage of diseased individuals who test positive (percent of "true positives"). Diseased individuals not detected by the assay are "false WO 2005/072053 PCT/IB2005/000928 15 negatives." Subjects who are not diseased and who test negative in the assay are termed "true negatives." The "specificity" of a diagnostic assay is 1 minus the false positive rate, where the "false positive" rate is defined as the proportion of those without the disease who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it 5 suffices if the method provides a positive indication that aids in diagnosis. As used herein the phrase "diagnosing" refers to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and/or prospects of recovery. The term "detecting" may also optionally encompass any of the above. 10 Diagnosis of a disease according to the present invention can be effected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a "biological sample obtained from the subject" may also optionally comprise a sample that has not been physically removed from 15 the subject, as described in greater detail below. As used herein, the term "level" refers to expression levels of RNA and/or protein or to DNA copy number of a marker of the present invention. Typically the level of the marker in a biological sample obtained from the subject is different (i.e., increased or decreased) from the level of the same variant in a similar sample 20 obtained from a healthy individual (examples of biological samples are described herein). Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and/or polypeptide of the variant of interest in the subject. Examples include, but are not limited to, fine needle biopsy, needle biopsy, core needle 25 biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy/sample is obtained the level of the variant can be determined and a diagnosis can thus be made. Determining the level of the same variant in normal tissues of the same origin is preferably effected along-side to detect an elevated expression and/or amplification and/or a 30 decreased expression, of the variant as opposed to the normal tissues.

WO 2005/072053 PCT/IB2005/000928 16 A "test amount" of a marker refers to an amount of a marker in a subject's sample that is consistent with a diagnosis of colon cancer. A test amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). A "control amount" of a marker can be any amount or a range of amounts to be 5 compared against a test amount of a marker. For example, a control amount of a marker can be the amount of a marker in a patient with colon cancer or a person without colon cancer. A control amount can be either in absolute amount (e.g., microgram/ml) or a relative amount (e.g., relative intensity of signals). "Detect" refers to identifying the presence, absence or amount of the object to be 10 detected. A "label" includes any moiety or item detectable by spectroscopic, photo chemical, biochemical, immunochemical, or chemical means. For example, useful labels include 32P, 35s fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin-streptavadin, dioxigenin, haptens and proteins for which antisera or monoclonal 15 antibodies are available, or nucleic acid molecules with a sequence complementary to a target. The label often generates a measurable signal, such as a radioactive, chromogenic, or fluorescent signal, that can be used to quantify the amount of bound label in a sample. The label can be incorporated in or attached to a primer or probe either covalently, or through ionic, van der Waals or hydrogen bonds, e.g., incorporation of radioactive nucleotides, or biotinylated 20 nucleotides that are recognized by streptavadin. The label may be directly or indirectly detectable. Indirect detection can involve the binding of a second label to the first label, directly or indirectly. For example, the label can be the ligand of a binding partner, such as biotin, which is a binding partner for streptavadin, or a nucleotide sequence, which is the binding partner for a complementary sequence, to which it can specifically hybridize. The binding partner may itself 25 be directly detectable, for example, an antibody may be itself labeled with a fluorescent molecule. The binding partner also may be indirectly detectable, for example, a nucleic acid having a complementary nucleotide sequence can be a part of a branched DNA molecule that is in turn detectable through hybridization with other labeled nucleic acid molecules (see, e.g., P. D. Fahrlander and A. Klausner, Bio/Technology 6:1165 (1988)). Quantitation of the signal is 30 achieved by, e.g., scintillation counting, densitometry, or flow cytometry.

WO 2005/072053 PCT/IB2005/000928 17 Exemplary detectable labels, optionally and preferably for use with immunoassays, include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the 5 sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture. "Immunoassay" is an assay that uses an antibody to specifically bind an antigen. The 10 immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen. The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," when referring to a protein or peptide (or other epitope), refers to a binding reaction that is determinative of the presence of the protein in a 15 heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, 20 polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of 25 irnmunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be 30 at least twice background signal or noise and more typically more than 10 to 100 times background.

WO 2005/072053 PCT/IB2005/000928 18 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NOs: 1 and 2. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 89, 90, 91, 92, 93, 94, 95, 96, 97, 5 98 and 99.According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 534 and 535. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NOs: 3, 4, 5 and 6. According to preferred embodiments of the present invention, there is provided an 10 isolated polynucleotide comprising a segment SEQ ID NOs: 100, 101, 102, 103, 104, 105, 106 and 107. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 536, 537, 538 and 539. According to preferred embodiments of the present invention, there is provided an 15 isolated polynucleotide comprising a transcript SEQ ID NO. 7. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120,121 and 122. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide comprising SEQ ID NOs 540. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript selected from the group consisting of SEQ ID NO. 8 and 9. According to preferred embodiments of the present invention, there is provided an 25 isolated polynucleotide comprising a segment selected from the group consisting of SEQ ID NOs: 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 and 142. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 541, 542. 30 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 10.

WO 2005/072053 PCT/IB2005/000928 19 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 143, 144, 145, 146, 147, 148 and 149. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide comprising SEQ ID NOs 543. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 11, 12, 13 and 14. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 150, 151, 152, 153, 154, 155, 156, 10 157,158,159,160, 161, 162, 163, 164, 165, 166and 167. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 544, 545, 546 and 547. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 15. 15 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183 and 184. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 548. 20 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 16. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195 and 196. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 549. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 17 and 18. According to preferred embodiments of the present invention, there is provided an 30 isolated polynucleotide comprising a segment SEQ ID NOs: 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210 and 211.

WO 2005/072053 PCT/IB2005/000928 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 550 and 551. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 19, 20, 21 and 22. 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 212, 213, 214, 215, 216, 217, 218 and 219. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 552, 553, 554 and 555. 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 23, 24, 25, 26 and 27. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239 and 240. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 556, 557, 558 and 559. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 28, 29, 30, 31 and 32. According to preferred embodiments of the present invention, there is provided an 20 isolated polynucleotide comprising a segment SEQ ID NOs: 241, 242, 243, 244, 245, 246, 247, 248, 249, 250 and 251. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 560, 561, 562 and 563. According to preferred embodiments of the present invention, there is provided an 25 isolated polynucleotide comprising a transcript SEQ ID NO. 33, 34, and 35. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 267, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278,279,280,281,282,283,284. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 564, 565, and 566.

WO 2005/072053 PCT/IB2005/000928 21 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 36, 37, 38, 39, 40, 41, 42 and 43. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 285, 286, 287, 288, 289, 290, 291, 5 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305 and 306. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 567, 568, 569, 570, 571, 572, 573 and 574. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 44. 10 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 307, 308, 309, 310, 311, 312, 313, 314, 315 and 316. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 575. 15 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 45, 46, 47 and 48. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 20 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361 and 362. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 576, 577, 578 and 579. According to preferred embodiments of the present invention, there is provided an 25 isolated polynucleotide comprising a transcript SEQ ID NO. 49. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 363, 364 and 365. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NO. 580. 30 . According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 50, 51, 52, 53, 54, 55 and 56.

WO 2005/072053 PCT/IB2005/000928 22 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 5 4 1 1 , 41 2 , 413, 414, 415, 416, 417 and 418. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 581, 582, 583, 584, 585, 586 and 587. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 57, 58, 59, 60, 61, 62, 63, 64, 65, 10 66, 67, 68, 69, 70, 71, 72 , 73 and 74. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 43, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448 and 449. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601 and 602. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 75, 76, 77, 78, 79 and 80. 20 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474 and 475. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide comprising SEQ ID NOs 603, 604, 605, 606 and 607. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 81, 82, 83 and 84. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 476, 477, 478, 479, 480, 481, 482, 30 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503 and 504.

WO 2005/072053 PCT/IB2005/000928 23 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs 608, 609, 610 and 611. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a transcript SEQ ID NO. 85, 86, 87 and 88. 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a segment SEQ ID NOs: 505-532 and 533. According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising SEQ ID NOs: 612, 613, 614 and 615. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encodings from clusters M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCAIXIA, HSSIOOPCB, HUMPHOSLIP, D11853, R1 1723, M77903 and HSKITCR. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 608, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 207 of SSRA _HUMAN, which also corresponds to amino acids 1 - 207 of SEQ ID NO. 608, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino 20 acids 208 - 214 of SEQ ID NO. 608, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 608, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 25 about 90% and most preferably at least about 95% homologous to acids 208 - 214 in SEQ ID NO. 608. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 609, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 207 of SSRAHUMAN, which 30 also corresponds to amino acids I - 207 of SEQ ID NO. 609.

WO 2005/072053 PCT/IB2005/000928 24 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 610, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 181 of SSRAHUMAN, which also corresponds to amino acids I - 181 of SEQ ID NO. 610, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 182 - 192 of SEQ ID NO. 610, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 610, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to acids 182 - 192 in SEQ ID NO. 610. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 611, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 93 of SSRAHUMAN, which also corresponds to amino acids 1 - 93 of SEQ ID NO. 611, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 94 20 104 of SEQ ID NO. 611, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 611, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 25 about 90% and most preferably at least about 95% homologous to amino acids 94 - 104 in SEQ ID NO. 611. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 30 least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 1 - 110 of SEQ ID NO. 604, and a second amino acid sequence being at least 90 % WO 2005/072053 PCT/IB2005/000928 25 homologous to amino acids 1 - 112 of Q8IXMO, which also corresponds to amino acids 111 222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a head of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids I - 1 10 of SEQ ID NO. 604. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 83 of Q96AC2, which also corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84 15 222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 20 about 90% and most preferably at least about 95% homologous to amino acids 84 - 222 in SEQ ID NO. 604. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid 25 sequence being at least 90 % homologous to amino acids I - 83 of Q8N2G4, which also corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84 222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and 30 in a sequential order.

WO 2005/072053 PCT/IB2005/000928 26 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 84 - 222 in SEQ 5 ID NO. 604. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 604, comprising a first amino acid sequence being at least 90 % homologous to amino acids 24 - 106 of BAC85518, which also corresponds to amino acids 1 - 83 of SEQ ID NO. 604, and a second amuino acid sequence being 10 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 84 222 of SEQ ID NO. 604, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of SEQ ID NO. 604, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 84 - 222 in SEQ ID NO. 604. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 64 of Q96AC2, which also corresponds to amino acids 1 - 64 of SEQ ID NO. 605, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 65 - 93 25 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 30 about 90% and most preferably at least about 95% homologous to amino acids 65 - 93 in SEQ ID NO. 605.

WO 2005/072053 PCT/IB2005/000928 27 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 64 of Q8N2G4, which also corresponds to amino acids 1 - 64 of SEQ ID NO. 605, and a second amino acid sequence being 5 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide corresponding to amino acids 65 - 93 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 65 - 93 in SEQ ID NO. 605. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of SEQ ID NO. 605, second amino acid sequence being at least 90 % homologous to amino acids 22 - 80 of BAC85273, which also corresponds 20 to amino acids 6 - 64 of SEQ ID NO. 605, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 65 - 93 of SEQ ID NO. 605, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 5 of SEQ ID NO. 605. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 28 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 65 - 93 in SEQ ID NO, 605. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90 % homologous to amino acids 24 - 87 of BAC85518, which also corresponds to amino acids I - 64 of SEQ ID NO. 605, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 10 acids 65 - 93 of SEQ ID NO. 605, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 605, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to amino acids 65 - 93 in SEQ ID NO. 605. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 605, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 63 of Q96AC2, which also 20 corresponds to amino acids I - 63 of SEQ ID NO. 606, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64 - 84 of SEQ ID NO. 606, wherein said first and second amino acid sequences are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 606, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64 - 84 in SEQ ID NO. 606. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 29 sequence being at least 90 % homologous to amino acids I - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 5 acids 64 - 90 of SEQ ID NO. 607, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 10 about 90% and most preferably at least about 95% homologous to amino acids 64 - 90 in SEQ ID NO. 607. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 63 of Q8N2G4, which also 15 corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64 - 90 of SEQ ID NO. 607 wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64 - 90 in SEQ ID NO. 607. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 5 of SEQ ID NO. 607, second amino acid sequence being at 30 least 90 % homologous to amino acids 22 - 79 of BAC85273, which also corresponds to amino acids 6 - 63 of SEQ ID NO. 607, and a third amino acid sequence being at least 70%, optionally WO 2005/072053 PCT/IB2005/000928 30 at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64 - 90 of SEQ ID NO. 607, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 5 of SEQ ID NO. 607. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64 - 90 in SEQ ID NO. 607. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 607, comprising a first amino acid sequence being at least 90 % homologous to amino acids 24 - 86 of BAC85518, which also corresponds to amino acids 1 - 63 of SEQ ID NO. 607, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and 20 most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 64 - 90 of SEQ ID NO. 607, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 607, comprising a polypeptide being at 25 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 64 - 90 in SEQ ID NO. 607. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid 30 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence WO 2005/072053 PCT/IB2005/000928 31 corresponding to amino acids I - 26 of SEQ ID NO. 588, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also corresponds to amino acids 27 - 201 of SEQ ID NO. 588, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 588, and a third amino acid sequence being at least 90 % homologous to 5 amino acids 189 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 356 of SEQ ID NO. 588, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 588, comprising a polypeptide being 10 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino acids I - 26 of SEQ ID NO. 588. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid 15 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and nost preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids I - 109 of SEQ ID NO. 588, a second amino acid sequence being at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 268 of SEQ ID NO. 588, and a third amino acid sequence being at least 70%, 20 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 356 of SEQ ID NO. 588, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a head of SEQ ID NO. 588, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 588. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of SEQ ID NO. 588, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 32 about 90% and most preferably at least about 95% homologous to amino acids 269 - 356 in SEQ ID NO. 588. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 588, comprising a first amino acid 5 sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 588, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 588, and a second amino acid sequence being at least 90 % homologous to amino acids 130 - 356 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 356 of SEQ ID NO. 588, wherein said first amino acid sequence, bridging 10 amino acid and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to amino acids 1 - 26 of SEQ ID NO. 15 589, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also corresponds to amino acids 27 - 201 of SEQ ID NO. 589, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 589, a third amino acid sequence being at least 90 % homologous to amino acids 189 - 297 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 311 of SEQ ID NO. 589, and a fourth amino acid 20 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 589. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 33 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 312 - 315 in SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence to amino acids 1 - 109 of SEQ ID NO. 589, a second amino acid sequence being at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 10 110 - 268 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 589. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 315 in SEQ ID NO. 589. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids I - 128 of SEQ ID NO. 589, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid sequence being at 30 least 90 % homologous to amino acids 130 - 311 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 311 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, WO 2005/072053 PCT/IB2005/000928 34 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 5 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 312 - 315 in 10 SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 311 of Q9UJZI, which also corresponds to amino acids 1 - 311 of SEQ ID NO. 589, and a second amino acid sequence 15 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 312 - 315 in SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids I - 109 of SEQ ID NO. 589, a second amino acid sequence being at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to 30 amino acids 110 - 268 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most WO 2005/072053 PCT/IB2005/000928 35 preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a head of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 315 in SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 589, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 589, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 311 of SEQ ID NO. 638, which also corresponds to 20 amino acids 130 - 311 of SEQ ID NO. 589, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 25 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 312 - 315 in SEQ 30 ID NO. 589.

WO 2005/072053 PCT/IB2005/000928 36 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 589, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 311 of Q9UJZl, which also corresponds to amino acids 1 - 311 of SEQ ID NO. 589, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 312 - 315 of SEQ ID NO. 589, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 589, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 312 - 315 in SEQ ID NO. 589. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 590, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of Q9PO42, which also corresponds to amino 20 acids 27 - 201 of SEQ ID NO. 590, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 590, a third amino acid sequence being at least 90 % homologous to amino acids 189 - 254 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 268 of SEQ ID NO. 590, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 25 polypeptide sequence corresponding to amino acids 269 - 290 of SEQ ID NO. 590, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 590, comprising a polypeptide being 30 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072053 PCT/IB2005/000928 37 least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 590. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a polypeptide being at 5 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 290 in SEQ ID NO. 590. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid 10 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 109 of SEQ ID NO. 590, and a second amino acid sequence being at least 90 % homologous to corresponding to amino acids 1 - 181 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 290 of SEQ ID NO. 590, wherein said first amino 15 acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 590, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of 20 SEQ ID NO. 590. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 590, a bridging amino acid L 25 corresponding to amino acid 129 of SEQ ID NO. 590, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 268 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 268 of SEQ ID NO. 590, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 30 269 - 290 of SEQ ID NO. 590, wherein said first amino acid sequence, bridging amino acid, WO 2005/072053 PCT/IB2005/000928 38 second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a polypeptide being at 5 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 290 in SEQ ID NO. 590. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 590, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZ1, which also corresponds to amino acids 1 - 268 of SEQ ID NO. 590, and a second amino acid sequence 15 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 290 of SEQ ID NO. 590, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of SEQ ID NO. 590, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 290 in SEQ ID NO. 590. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 591, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also corresponds to 30 amino acids 27 - 201 of SEQ ID NO. 591, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 591, a third amino acid sequence being at least 90 % homologous to amino WO 2005/072053 PCT/IB2005/000928 39 acids 189 - 226 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 240 of SEQ ID NO. 591, a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID NO. 5 591, and a fifth amino acid sequence being at least 90 % homologous to amino acids 227 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 282 - 397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 591, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1-26 of SEQ ID NO. 591. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 591, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding amino acids 241 - 281 corresponding to SEQ ID NO. 591. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 109 of SEQ ID NO. 591, a second amino acid sequence being 25 at least 90 % homologous to amino acids I - 131 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 240 of SEQ ID NO. 591, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID NO. 591, a fourth amino acid sequence being at least 90 % homologous to 30 amino acids 132 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 282 - 309 of SEQ ID NO. 591, and a fifth amino acid sequence being at least 70%, optionally at least 80%, WO 2005/072053 PCT/IB2005/000928 40 preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310 - 397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a 5 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 591, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of 10 SEQ ID NO. 591. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 591, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 591. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 591, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 310 - 397 in 20 SEQ ID NO. 591. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 591, a bridging amino acid L corresponding 25 to amino acid 129 of SEQ ID NO. 591, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 240 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 240 of SEQ ID NO. 591, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID 30 NO. 591, and a fourth amino acid sequence being at least 90 % homologous to amino acids 241 - 356 of SEQ ID NO. 638, which also corresponds to amino acids 282 - 397 of SEQ ID NO.

WO 2005/072053 PCT/IB2005/000928 41 591, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for an edge portion of SEQ ID NO. 591, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 591. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 591, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 240 of Q9UJZ1, which also corresponds to amino acids 1 - 240 of SEQ ID NO. 591, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 15 acids 241 - 281 of SEQ ID NO. 591, and a third amino acid sequence being at least 90 % homologous to amino acids 241 - 356 of Q9UJZ1, which also corresponds to amino acids 282 397 of SEQ ID NO. 591, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for an edge portion of SEQ ID NO. 591, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 591. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 592, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also corresponds to 30 amino acids 27 - 201 of SEQ ID NO. 592, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 592, a third amino acid sequence being at least 90 % homologous to to WO 2005/072053 PCT/IB2005/000928 42 amino acids 189 - 254 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 268 of SEQ ID NO. 592, and a fourth amino acid sequence being at least 90 % homologous to amino acids 298 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence, bridging 5 amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 10 least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 592. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 15 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1 - 109 of SEQ ID NO. 592, a second amino acid sequence being at least 90 % homologous to 25 amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 268 of SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence and third amino acid 30 sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 43 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of 5 SEQ ID NO. 592. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 313 in SEQ 10 ID NO. 592. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 592, a bridging amino acid L 15 corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 268 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 268 of SEQ ID NO. 592, and a third amino acid sequence being at least 90 % homologous to amino acids 312 - 356 of SEQ ID NO. 638, which also corresponds to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence, bridging amino 20 acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 25 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 44 sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZl, which also corresponds to amino acids I - 268 of SEQ ID NO. 592, and a second amino acid sequence being at least 90 % homologous to amino acids 312 - 356 of Q9UJZ1, which also corresponds to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence and second 5 amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more 10 preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1 - 109 of SEQ ID NO. 592, a second amino acid sequence being at least 90 % homologous to amino acids 1 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 268 of 20 SEQ ID NO. 592, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 592, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 592. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 592, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 45 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 269 - 313 in SEQ IDNO. 592. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 592, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 592, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 268 of SEQ ID NO. 638, which also corresponds to 10 amino acids 130 - 268 of SEQ ID NO. 592, and a third amino acid sequence being at least 90 % homologous to amino acids 312 - 356 of SEQ ID NO. 638, which also corresponds to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino 20 acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) -x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 592, comprising a first amino acid 25 sequence being at least 90 % homologous to amino acids 1 - 268 of Q9UJZ1, which also corresponds to amino acids 1 - 268 of SEQ ID NO. 592, and a second amino acid sequence being at least 90 % homologous to amino acids 312 - 356 of Q9UJZ1, which also corresponds to amino acids 269 - 313 of SEQ ID NO. 592, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 592, comprising a WO 2005/072053 PCT/IB2005/000928 46 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a 5 sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) -x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 10 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 593, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 187 of SEQ ID NO. 639, which also corresponds to amino acids 27 - 201 of SEQ ID NO. 593, a bridging amino acid A corresponding to amino acid 202 of SEQ ID NO. 593, a third amino acid sequence being at least 90 % homologous to amino 15 acids 189 - 226 of SEQ ID NO. 639, which also corresponds to amino acids 203 - 240 of SEQ ID NO. 593, a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID NO. 593, a fifth amino acid sequence being at least 90 % homologous to amino acids 227 - 254 of 20 SEQ ID NO. 639, which also corresponds to amino acids 282 - 309 of SEQ ID NO. 593, and a sixth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310 - 331 of SEQ ID NO. 593, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, 25 fourth amino acid sequence, fifth amino acid sequence and sixth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 30 least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 593.

WO 2005/072053 PCT/IB2005/000928 47 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 593, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 5 sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 310 - 331in SEQ 10 ID NO. 593. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence 15 corresponding to amino acids I - 109 of SEQ ID NO. 593, a second amino acid sequence being at least 90 % homologous to amino acids 1 - 131 of SEQ ID NO. 640, which also corresponds to amino acids 110 - 240 of SEQ ID NO. 593, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 20 241 - 281 of SEQ ID NO. 593, and a fourth amino acid sequence being at least 90 % homologous to amino acids 132 - 181 of SEQ ID NO. 640, which also corresponds to amino acids 282 - 331 of SEQ ID NO. 593, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 593. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 593, comprising an amino WO 2005/072053 PCT/IB2005/000928 4B acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 593, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 593, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 240 of SEQ ID NO. 638, which also corresponds to 10 amino acids 130 - 240 of SEQ ID NO. 593, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID NO. 593, a fourth amino acid sequence being at least 90 % homologous to amino acids 241 - 268 of SEQ ID NO. 638, which also corresponds to amino acids 282 - 309 of 15 SEQ ID NO. 593, and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310 - 331 of SEQ ID NO. 593, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are 20 contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 593, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 310 - 331 in SEQ 30 ID NO. 593.

WO 2005/072053 PCT/IB2005/000928 49 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 593, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 240 of Q9UJZl, which also corresponds to amino acids I - 240 of SEQ ID NO. 593, a second amino acid sequence being at 5 least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 241 - 281 of SEQ ID NO. 593, a third amino acid sequence being at least 90 % homologous to amino acids 241 - 268 of Q9UJZ1, which also corresponds to amino acids 282 309 of SEQ ID NO. 593, and a fourth amino acid sequence being at least 70%, optionally at 10 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 310 - 331 of SEQ ID NO. 593, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for an edge portion of SEQ ID NO. 593, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 241 - 281 corresponding to SEQ ID NO. 593. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of SEQ ID NO. 593, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 310 - 331 in SEQ ID NO. 593. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 594, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 134 of SEQ ID NO. 639, which also corresponds to 30 amino acids 27 - 148 of SEQ ID NO. 594, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most WO 2005/072053 PCT/IB2005/000928 50 preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149 - 183 of SEQ ID NO. 594, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a head of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 594. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 149 - 183 in SEQ ID NO. 594. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 594, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 594, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 148 of SEQ ID NO. 638, which also corresponds to 20 amino acids 130 - 148 of SEQ ID NO. 594, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149 - 183 of SEQ ID NO. 594, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 25 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 149 - 183 in 30 SEQ ID NO. 594.

WO 2005/072053 PCT/IB2005/000928 51 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 594, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 148 of Q9UJZI, which also corresponds to amino acids 1 - 148 of SEQ ID NO. 594, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 149 - 183 of SEQ ID NO. 594, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 594, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 149 - 183 in SEQ ID NO. 594. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 595, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 180 of SEQ ID NO. 639, which also corresponds to 20 amino acids 27 - 194 of SEQ ID NO. 595, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195 - 220 of SEQ ID NO. 595, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 595, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 595. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 52 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 195 - 220 in SEQ ID NO. 595. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 595, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 595, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 194 of SEQ ID NO. 638, which also corresponds to 10 amino acids 130 - 194 of SEQ ID NO. 595, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195 - 220 of SEQ ID NO. 595, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 15 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 195 - 220 in 20 SEQ ID NO. 595. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 595, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 194 of Q9UJZ1, which also corresponds to amino acids I - 194 of SEQ ID NO. 595, and a second amino acid sequence 25 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 195 - 220 of SEQ ID NO. 595, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of SEQ ID NO. 595, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 53 about 90% and most preferably at least about 95% homologous to amino acids 195 - 220 in SEQ ID NO. 595. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid 5 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids I - 26 of SEQ ID NO. 596, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 134 of SEQ ID NO. 639, which also corresponds to amino acids 27 - 148 of SEQ ID NO. 596, a third amino acid sequence being at least 90 % 10 homologous to amino acids 180 - 187 of SEQ ID NO. 639, which also corresponds to amino acids 149 - 156 of SEQ ID NO. 596, a bridging amino acid A corresponding to amino acid 157 of SEQ ID NO. 596, and a fourth amino acid sequence being at least 90 % homologous to amino acids 189 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 158 - 311 of SEQ ID NO. 596, wherein said first amino acid sequence, second amino acid sequence, third 15 amino acid sequence, bridging amino acid and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 596, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 20 least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 596. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 25 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 54 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 109 of SEQ ID NO. 596, a second amino acid sequence being at least 90 % homologous to amino acids I - 39 of SEQ ID NO. 640, which also corresponds to 5 amino acids 110 - 148 of SEQ ID NO. 596, a third amino acid sequence being at least 90 % homologous to amino acids 85 - 159 of SEQ ID NO. 640, which also corresponds to amino acids 149 - 223 of SEQ ID NO. 596, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 10 224 - 311 of SEQ ID NO. 596, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 596, comprising a polypeptide being 15 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 109 of SEQ ID NO. 596. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596, comprising a 20 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino 25 acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 596, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 224 - 311 in 30 SEQIDNO.596.

WO 2005/072053 PCT/IB2005/000928 55 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids I - 128 of SEQ ID NO. 596, a bridging amino acid L corresponding 5 to amino acid 129 of SEQ ID NO. 596, a second amino acid sequence being at least 90 % homologous to amino acids 130 - 148 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 148 of SEQ ID NO. 596, and a third amino acid sequence being at least 90 % homologous to corresponding to amino acids 194 - 356 of SEQ ID NO. 638, which also corresponds to amino acids 149 - 311 of SEQ ID NO. 596, wherein said first amino acid 10 sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 15 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 596, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 148 of Q9UJZ1, which also corresponds to amino acids 1 - 148 of SEQ ID NO. 596, and a second amino acid sequence being at least 90 % homologous to amino acids 194 - 356 of Q9UJZ 1, which also corresponds to 25 amino acids 149 - 311 of SEQ ID NO. 596, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 596, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 30 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino WO 2005/072053 PCT/IB2005/000928 56 acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 597, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 143 of SEQ ID NO. 639, which also corresponds to 10 amino acids 27 - 157 of SEQ ID NO. 597, and a third amino acid sequence being at least 90 % homologous to amino acids 295 - 342 of SEQ ID NO. 639, which also corresponds to amino acids 158 - 205 of SEQ ID NO. 597, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a head of SEQ ID NO. 597, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 597. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a 25 sequence starting from any of amino acid numbers 157-x to 157; and ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of Q96FY2, which also 30 corresponds to amino acids 1 - 128 of SEQ ID NO. 597, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 597, a second amino acid sequence being at least 90 % WO 2005/072053 PCT/IB2005/000928 57 homologous to amino acids 130 - 157 of SEQ ID NO. 639,, which also corresponds to amino acids 130 - 157 of SEQ ID NO. 597, and a third amino acid sequence being at least 90 % homologous to amino acids 309 - 356 of ID NO. 639, which also corresponds to amino acids 158 - 205 of SEQ ID NO. 597, wherein said first amino acid sequence, bridging amino acid, 5 second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 10 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157-x to 157; and ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 597, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 157 of Q9UJZ1, which also corresponds to amino acids 1 - 157 of SEQ ID NO. 597, and a second amino acid sequence being at least 90 % homologous to amino acids 309 - 356 of Q9UJZ1, which also corresponds to 20 amino acids 158 - 205 of SEQ ID NO. 597, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 597, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 25 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157-x to 157; and ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 58 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 598, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 128 of SEQ ID NO. 639, which also corresponds to 5 amino acids 27 - 142 of SEQ ID NO. 598, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143 - 161 of SEQ ID NO. 598, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 598. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 143 - 161 in SEQ ID NO. 598. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 128 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 128 of SEQ ID NO. 598, a bridging amino acid L corresponding to amino acid 129 of SEQ ID NO. 598, a second amino acid sequence being at 25 least 90 % homologous to amino acids 130 - 142 of SEQ ID NO. 638, which also corresponds to amino acids 130 - 142 of SEQ ID NO. 598, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143 - 161 of SEQ ID NO. 598, wherein said first amino acid sequence, bridging amino acid, 30 second amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 59 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 143 - 161 in 5 SEQ ID NO. 598. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 598, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 142 of Q9UJZ1, which also corresponds to amino acids 1 - 142 of SEQ ID NO. 598, and a second amino acid sequence 10 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 143 - 161 of SEQ ID NO. 598, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of SEQ ID NO. 598, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 143 - 161 in SEQ ID NO. 598. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 61 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 61 of SEQ ID NO. 600, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 25 acids 62 - 102 of SEQ ID NO. 600, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 600, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 30 about 90% and most preferably at least about 95% homologous to the sequence amino acids 62 102 in SEQ ID NO. 600.

WO 2005/072053 PCT/IB2005/000928 60 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 600, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 61 of Q9UJZl, which also corresponds to amino acids 1 - 61 of SEQ ID NO. 600, and a second amino acid sequence being 5 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62 - 102 of SEQ ID NO. 600, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 600, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 62 - 102 in SEQ ID NO. 600. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 601, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 47 of SEQ ID NO. 639, which also corresponds to 20 amino acids 27 - 61 of SEQ ID NO. 601, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62 - 72 of SEQ ID NO. 601, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 601, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 601. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 61 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 62 - 72 in SEQ ID NO. 601. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 61 of Q96FY2, which also corresponds to amino acids 1 - 61 of SEQ ID NO. 601, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 10 acids 62 - 72 of SEQ ID NO. 601, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to amino acids 62 - 72 in SEQ ID NO. 601. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 601, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 61 of Q9UJZ1, which also 20 corresponds to amino acids 1 - 61 of SEQ ID NO. 601, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 62 - 72 of SEQ ID NO. 601, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 601, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 62 - 72 in SEQ ID NO. 601. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 62 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 26 of SEQ ID NO. 602, a second amino acid sequence being at least 90 % homologous to amino acids 13 - 80 of SEQ ID NO. 639, which also corresponds to 5 amino acids 27 - 94 of SEQ ID NO. 602, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95 - 111 of SEQ ID NO. 602, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 602, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 26 of SEQ ID NO. 602. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 95 - 111 in SEQ ID NO. 602. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 94 of SEQ ID NO. 638, which also corresponds to amino acids 1 - 94 of SEQ ID NO. 602, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and 25 most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95 - 111 of SEQ ID NO. 602, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a polypeptide being at 30 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 63 about 90% and most preferably at least about 95% homologous to amino acids 95 - Ill in SEQ ID NO. 602. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 602, comprising a first amino acid 5 sequence being at least 90 % homologous to amino acids 1 - 94 of Q9UJZl, which also corresponds to amino acids 1 - 94 of SEQ ID NO. 602, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 95 - 111 of SEQ ID NO. 602, wherein said first amino acid sequence and second amino 10 acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 602, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 95 - 111 in SEQ 15 ID NO. 602. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 581, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 67 of PLTPHUMAN, which also corresponds to amino acids 1 - 67 of SEQ ID NO. 581, and a second amino acid sequence being 20 at least 90 % homologous to amino acids 163 - 493 of PLTPHUMAN, which also corresponds to amino acids 68 - 398 of SEQ ID NO. 581, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 581, comprising a 25 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EK, having a structure as follows: a sequence starting from any of amino acid numbers 67-x to 67; and ending at any of amino acid 30 numbers 68+ ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072053 PCT/IB2005/000928 64 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 582, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 427 of PLTPHUMAN, which also corresponds to amino acids I - 427 of SEQ ID NO. 582, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 428 - 432 of SEQ ID NO. 582, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 582, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 428 - 432 in SEQ ID NO. 582. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 584, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 67 of PLTPHUMAN, which also corresponds to amino acids 1 - 67 of SEQ ID NO. 584, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 20 acids 68 - 98 of SEQ ID NO. 584, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 584, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 25 about 90% and most preferably at least about 95% homologous to amino acids 68 - 98 in SEQ ID NO. 584. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 585, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 183 of PLTPHUMAN, which also 30 corresponds to amino acids I - 183 of SEQ ID NO. 585, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 65 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 184 - 200 of SEQ ID NO. 585, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of SEQ ID NO. 585, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 184 - 200in SEQ ID NO. 585. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 586, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 205 of PLTP HUMAN, which also corresponds to amino acids 1 - 205 of SEQ ID NO. 586, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 15 amino acids 206 - 217 of SEQ ID NO. 586, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 586, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 20 about 90% and most preferably at least about 95% homologous to amino acids 206 - 217 in SEQ ID NO. 586. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 587, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 109 of PLTP HUMAN, which also 25 corresponds to amino acids 1 - 109 of SEQ ID NO. 587, a second amino acid sequence bridging amino acid sequence comprising of L, a third amino acid sequence being at least 90 % homologous to amino acids 163 - 183 of PLTP_HUMAN, which also corresponds to amino acids 111 - 131 of SEQ ID NO. 587, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 30 preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132 - 148 of SEQ ID NO. 587, wherein said first amino acid sequence, second amino acid WO 2005/072053 PCT/IB2005/000928 66 sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 587, comprising a 5 polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least three amino acids comprise FLK having a structure as follows (numbering according to SEQ ID NO. 587): a sequence starting from any of amino acid 10 numbers 109-x to 109; and ending at any of amino acid numbers 111 -P ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 587, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to amino acids 132 - 148 in SEQ ID NO. 587. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 576, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 1056 of SEQ ID NO. 634, which 20 also corresponds to amino acids 1 - 1056 of SEQ ID NO. 576, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1057 - 1081 of SEQ ID NO. 576, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 576, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1057 - 1081 in SEQ ID NO. 576. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 577, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 67 sequence being at least 90 % homologous to amino acids 1 - 714 of SEQ ID NO. 634, which also corresponds to amino acids 1 - 714 of SEQ ID NO. 577, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 5 amino acids 715 - 729 of SEQ ID NO. 577, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 577, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 10 about 90% and most preferably at least about 95% homologous to amino acids 715 - 729 in SEQ ID NO. 577. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 578, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 648 of SEQ ID NO. 634, which 15 also corresponds to amino acids 1 - 648 of SEQ ID NO. 578, a second amino acid sequence being at least 90 % homologous to amino acids 667 - 714 of SEQ ID NO. 634, which also corresponds to amino acids 649 - 696 of SEQ ID NO. 578, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 20 amino acids 697 - 738 of SEQ ID NO. 578, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 578, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 25 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+ ((n-2) -x), in which x varies from 0 to n-2. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 578, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 68 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 697 - 738 in SEQ ID NO. 578. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 579, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 260 of SEQ ID NO. 634, which also corresponds to amino acids 1 - 260 of SEQ ID NO. 579, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 10 amino acids 261 - 273 of SEQ ID NO. 579, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 579, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to amino acids 261 - 273 in SEQ ID NO. 579. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 575, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 13 of GFR2_HUMAN, which also 20 corresponds to amino acids 1 - 13 of SEQ ID NO. 575, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 14 - 30 of SEQ ID NO. 575, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 575, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 14 - 30 in SEQ ID NO. 575. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 69 sequence being at least 90 % homologous to amino acids I - 123 of SEQ ID NO. 631, which also corresponds to amino acids 1 - 123 of SEQ ID NO. 567, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 5 amino acids 124 - 156 of SEQ ID NO. 567, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 567, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 10 about 90% and most preferably at least about 95% homologous to amino acids 124 - 156 in SEQ ID NO. 567. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 15 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 73 of SEQ ID NO. 567, and a second amino acid sequence being at least 90 % homologous to amino acids 1799 - 1881 of SEQ ID NO. 629, which also corresponds to amino acids 74 - 156 of SEQ ID NO. 567, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 567, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino acids 1 - 73 of SEQ ID NO. 567. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 567, comprising a first amino acid sequence being at least 90 % homologous to to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 567, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 567, a second amino acid sequence being at 30 least 90 % homologous to amino acids 54 - 124 of SEQ ID NO. 630, which also corresponds to amino acids 54 - 124 of SEQ ID NO. 567, and a third amino acid sequence being at least 70%, WO 2005/072053 PCT/IB2005/000928 70 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 125 - 156 of SEQ ID NO. 567, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 5 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 567, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 125 - 156 in 10 SEQ ID NO. 567. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 568, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO. 631, which also corresponds to amino acids 1 - 123 of SEQ ID NO. 568, and a second amino acid sequence 15 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124 - 169 of SEQ ID NO. 568, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a tail of SEQ ID NO. 568, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 124 - 169 in SEQ ID NO. 568. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 568, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 568, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 568, a second amino acid sequence being at least 90 % homologous to amino acids 54 - 122 of SEQ ID NO. 630, which also corresponds to amino 30 acids 54 - 122 of SEQ ID NO. 568, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least WO 2005/072053 PCT/IB2005/000928 '71 95% homologous to a polypeptide sequence corresponding to amino acids 123 - 136 of SEQ ID NO. 568, and a fourth amino acid sequence being at least 90 % homologous to amino acids 123 - 155 of SEQ ID NO. 630, which also corresponds to amino acids 137 - 169 of SEQ ID NO. 568, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, 5 third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 568, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 123 - 136, corresponding to SEQ ID NO. 568. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 569, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO. 631, which 15 also corresponds to amino acids I - 123 of SEQ ID NO. 569, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124 - 180 of SEQ ID NO. 569, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 569, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence amino acids 124 - 180 in SEQ ID NO. 569. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 569, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 569, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 569, a second amino acid sequence being at least 90 % 30 homologous to amino acids 54 - 123 of SEQ ID NO. 630, which also corresponds to amino acids 54 - 123 of SEQ ID NO. 569, a third amino acid sequence being at least 70%, optionally at WO 2005/072053 PCT/IB2005/000928 72 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124 - 148 of SEQ ID NO. 569, and a fourth amino acid sequence being at least 90 % homologous to amino acids 124 - 155 of SEQ ID NO. 630, which also corresponds to amino acids 149 - 180 of SEQ ID NO. 5 569, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 569, comprising an amino 10 acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 124 - 148, corresponding to SEQ ID NO. 569. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a first amino acid 15 sequence being at least 90 % homologous to amino acids 1 - 123 of SEQ ID NO. 631, which also corresponds to amino acids I - 123 of SEQ ID NO. 570, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 124 - 145 of SEQ ID NO. 570, wherein said first amino acid sequence and second 20 amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 570, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 124 - 148 in SEQ 25 ID NO. 570. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 570, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 570, a bridging amino acid G corresponding 30 to amino acid 53 of SEQ ID NO. 570, a second amino acid sequence being at least 90 % homologous to amino acids 54 - 124 of SEQ ID NO. 630, which also corresponds to amino WO 2005/072053 PCT/IB2005/000928 73 acids 54 - 124 of SEQ ID NO. 570, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 125 - 145 of SEQ ID NO. 570, wherein said first amino acid sequence, bridging amino acid, 5 second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 570, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 10 about 90% and most preferably at least about 95% homologous to amino acids 125 - 145 in SEQ ID NO. 570. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 101 of SEQ ID NO. 631, which 15 also corresponds to amino acids 1 - 101 of SEQ ID NO. 571, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102 - 122 of SEQ ID NO. 571, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 571, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 102 - 122 in SEQ ID NO. 571. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 571, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 571, a bridging amino acid G corresponding to amino acid 53 of SEQ ID NO. 571, a second amino acid sequence being at least 90 % 30 homologous to amino acids 54 - 101 of SEQ ID NO. 630, which also corresponds to amino acids 54 - 101 of SEQ ID NO. 571, and a third amino acid sequence being at least 70%, WO 2005/072053 PCT/IB2005/000928 74 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102 - 122 of SEQ ID NO. 571, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 5 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 571, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 102 - 122 in SEQ 10 ID NO. 571. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 572, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 62 of SEQ ID NO. 631, which also corresponds to amino acids 1 - 62 of SEQ ID NO. 572, a bridging amino acid P corresponding 15 to amino acid 63 of SEQ ID NO. 572, a second amino acid sequence being at least 90 % homologous to amino acids 64 - 123 of SEQ ID NO. 631, which also corresponds to amino acids 64 - 123 of SEQ ID NO. 572, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 20 124 - 155 of SEQ ID NO. 572, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 572, comprising a polypeptide being at 25 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 124 - 155 in SEQ ID NO. 572. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 572, comprising a first amino acid 30 sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 572, a bridging amino acid G corresponding WO 2005/072053 PCT/IB2005/000928 75 to amino acid 53 of SEQ ID NO. 572, a second amino acid sequence being at least 90 % homologous to LSDDEETIS corresponding to amino acids 54 - 62 of SEQ ID NO. 630, which also corresponds to amino acids 54 - 62 of SEQ ID NO. 572, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 572, and a third amino acid sequence being at 5 least 90 % homologous to amino acids 64 - 155 of SEQ ID NO. 630, which also corresponds to amino acids 64 - 155 of SEQ ID NO. 572, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 573 comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 62 of SEQ ID NO. 631 which also corresponds to amino acids 1 - 62 of SEQ ID NO. 573, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 573, a second amino acid sequence being at least 90 % homologous to amino acids 64 - 101 of SEQ ID NO. 631, which also corresponds to amino 15 acids 64 - 101 of SEQ ID NO. 573, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102 - 109 of SEQ ID NO. 573, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 20 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 573, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 102 - 109 in SEQ 25 ID NO. 573. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 573, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 52 of SEQ ID NO. 630 which also corresponds to amino acids 1 - 52 of SEQ ID NO. 573, a bridging amino acid G corresponding 30 to amino acid 53 of SEQ ID NO. 573, a second amino acid sequence being at least 90 % homologous to amino acids 54 - 62 of SEQ ID NO. 630, which also corresponds to amino acids WO 2005/072053 PCT/IB2005/000928 76 54 - 62 of SEQ ID NO. 573, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 573, a third amino acid sequence being at least 90 % homologous to amino acids 64 101 of SEQ ID NO. 630, which also corresponds to amino acids 64 - 101 of SEQ ID NO. 573, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 5 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102 - 109 of SEQ ID NO. 573, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 573, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 102 - 109 in SEQ ID NO. 573. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 62 of SEQ ID NO. 631, which also corresponds to amino acids I - 62 of SEQ ID NO. 574, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 574, a second amino acid sequence being at least 90 % 20 homologous to amino acids 64 - 101 of SEQ ID NO. 631, which also corresponds to amino acids 64 - 101 of SEQ ID NO. 574, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 102 - 133 of SEQ ID NO. 574, wherein said first amino acid sequence, bridging amino acid, 25 second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 574, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 30 about 90% and most preferably at least about 95% homologous to amino acids 102 - 133 in SEQ ID NO. 574.

WO 2005/072053 PCT/IB2005/000928 77 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 574, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 52 of SEQ ID NO. 630, which also corresponds to amino acids 1 - 52 of SEQ ID NO. 574, a bridging amino acid G corresponding 5 to amino acid 53 of SEQ ID NO. 574, a second amino acid sequence being at least 90 % homologous to amino acids 54 - 62 of SEQ ID NO. 630, which also corresponds to amino acids 54 - 62 of SEQ ID NO. 574, a bridging amino acid P corresponding to amino acid 63 of SEQ ID NO. 574, a third amino acid sequence being at least 90 % homologous to amino acids 64 101 of SEQ ID NO. 630, which also corresponds to amino acids 64 - 101 of SEQ ID NO. 574, 10 and a fourth amino acid sequence being at least 90 % homologous to amino acids 124 - 155 of SEQ ID NO. 630, which also corresponds to amino acids 102 - 133 of SEQ ID NO. 574, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 574, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino 20 acids in length, wherein at least two amino acids comprise KV, having a structure as follows: a sequence starting from any of amino acid numbers 101-x to 101; and ending at any of amino acid numbers 102+ ((n-2) -x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptid e encoding for SEQ ID NO. 564, comprising a first amino acid 25 sequence being at least 90 % homologous to amino acids 1 - 1617 of SEQ ID NO. 627, which also corresponds to amino acids 1 - 1617 of SEQ ID NO. 564, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1618 - 1645 of SEQ ID NO. 564, wherein said first amino acid 30 sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 78 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 564, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1618 - 1645 in 5 SEQ ID NO. 564. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 565, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 2062 of SEQ ID NO. 627, which also corresponds to amino acids 1 - 2062 of SEQ ID NO. 565, and a second amino acid 10 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 2063 - 2074 of SEQ ID NO. 565, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of SEQ ID NO. 565, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 2063 - 2074 in SEQ ID NO. 565. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 566, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 587 of SEQ ID NO. 627, which also corresponds to amino acids 1 - 587 of SEQ ID NO. 566, and a second amino acid sequence 25 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 588 - 603 of SEQ ID NO. 566, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of SEQ ID NO. 566, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 79 about 90% and most preferably at least about 95% homologous to amino acids 588 - 603 in SEQ ID NO. 566. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 560, comprising a first amino acid 5 sequence being at least 90 % homologous to amino acids 1 - 131 of SEQ ID NO. 625, which also corresponds to amino acids 1 - 131 of SEQ ID NO. 560, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132 - 139 of SEQ ID NO. 560, wherein said first and second amino acid sequences 10 are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 560, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 132 - 139 in SEQ 15 ID NO. 560. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 561, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 131 of SEQ ID NO. 625, which also corresponds to amino acids 1 - 131 of SEQ ID NO. 561, and a second amino acid sequence 20 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 132 - 156 of SEQ ID NO. 561, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a tail of SEQ ID NO. 561, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 132 - 156 in SEQ ID NO. 561. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for SEQ ID NO. 562, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 81 of SEQ ID NO. 625, which also WO 2005/072053 PCT/IB2005/000928 80 corresponds to amino acids I - 81 of SEQ ID NO. 562, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 82 - 89 of SEQ ID NO. 562, wherein said first and second amino acid sequences are 5 contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 562, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 82 - 89 in SEQ 10 ID NO. 562. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 563, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 82 of SEQ ID NO. 625 which also corresponds to amino acids 1 - 82 of SEQ ID NO. 563. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 552, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 116 of FABH HUMAN, which also corresponds to amino 20 acids 1 - 116 of SEQ ID NO. 552, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 215 of SEQ ID NO. 552, wherein said firstand second amino acid sequences are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 552, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 117 - 215 in SEQ ID NO. 552. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 552, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 81 sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 552, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 5 amino acids 117 - 215 of SEQ ID NO. 552, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 552, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 10 about 90% and most preferably at least about 95% homologous to amino acids 117 - 215 in SEQ ID NO. 552. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 15 least 90% and most preferably at least 95% homologous to a polypeptide sequence amino acids 1 - 116 of FABHHUMAN, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 178 of SEQ ID NO. 553, wherein said 20 first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 117 - 178 in SEQ 25 ID NO. 553. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 553, and a second amino acid sequence 30 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to WO 2005/072053 PCT/IB2005/000928 82 amino acids 117 - 178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a polypeptide being at 5 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to acids 117 - 178 in SEQ ID NO. 553. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid 10 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 116 of FABHHUMAN, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 15 preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 178 of SEQ ID NO. 553, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a polypeptide being at 20 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 117 - 178 in SEQ ID NO. 553. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 553, comprising a first amino acid 25 sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 553, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 178 of SEQ ID NO. 553, wherein said first and second amino acid sequences 30 are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 83 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 553, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 117 - 178 in SEQ 5 ID NO. 553. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 554, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence 10 corresponding to amino acids 1 - 116 of FABH _HUMAN, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 554, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 126 of SEQ ID NO. 554, wherein said first and second amino acid sequences are 15 contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 554, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 117 - 126 in SEQ 20 ID NO. 554. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 554, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids 1 - 116 of SEQ ID NO. 554, and a second amino acid sequence 25 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 117 - 126 of SEQ ID NO. 554, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of SEQ ID NO. 554, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 84 about 90% and most preferably at least about 95% homologous to amino acids 117 - 126 in SEQ ID NO. 554. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 555, comprising a first amino acid 5 sequence being at least 90 % homologous to amino acids 1 - 24 of FABHHUMAN, which also corresponds to amino acids 1 - 24 of SEQ ID NO. 555, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 25 - 35 of SEQ ID NO. 555, and a third amino acid sequence being at least 90 % 10 homologous to amino acids 25 - 133 of FABH HUMAN, which also corresponds to amino acids 36 - 144 of SEQ ID NO. 555, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 555, comprising an amino 15 acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for amino acids 25 - 35 corresponding to SEQ ID NO. 555. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 555, comprising a first amino acid 20 sequence being at least 90 % homologous to amino acids 1 - 24 of AAP35373, which also corresponds to amino acids 1 - 24 of SEQ ID NO. 555, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 25 - 35 of SEQ ID NO. 555, and a third amino acid sequence being at least 90 % 25 homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25 - 133 of AAP35373, which also corresponds to amino acids 36 - 144 of SEQ ID NO. 555, wherein said first, second and third amino acid sequences are contiguous and in a 30 sequential order.

WO 2005/072053 PCT/IB2005/000928 85 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 555, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 5 sequence encoding for amino acids 25 - 35 corresponding to SEQ ID NO. 555. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 534, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 476 of EPB2_HUMAN, which also corresponds to amino acids I - 476 of SEQ ID NO. 534, and a second amino acid sequence 10 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 477 - 496 of SEQ ID NO. 534, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of SEQ ID NO. 534, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 477 - 496 in SEQ ID NO. 534. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for SEQ ID NO. 535, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 270 of EPB2_HUMAN, which also corresponds to amino acids 1 - 270 of SEQ ID NO. 535, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 25 amino acids 271 - 301 of SEQ ID NO. 535, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 535, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 30 about 90% and most preferably at least about 95% homologous to amino acids 271 - 301 in SEQ ID NO. 535.

WO 2005/072053 PCT/IB2005/000928 86 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 536, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 319 of CEA6 HUMAN, which also corresponds to amino acids 1 - 319 of SEQ ID NO. 536, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 320 - 324 of SEQ ID NO. 536, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 536, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 320 - 324in SEQ ID NO. 536. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 234 of CEA6_HUMAN, which also corresponds to amino acids 1 - 234 of SEQ ID NO. 537, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 20 amino acids 235 - 256 of SEQ ID NO. 537, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 537, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 25 about 90% and most preferably at least about 95% homologous to amino acids 235 - 256 in SEQ ID NO. 537. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 537, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 234 of Q13774, which also 30 corresponds to amino acids 1 - 234 of SEQ ID NO. 537, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 87 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 235 - 256 of SEQ ID NO. 537, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of SEQ ID NO. 537, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to acids 235 - 256 in SEQ ID NO. 537. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 538, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 320 of CEA6_HUMAN, which also corresponds to amino acids 1 - 320 of SEQ ID NO. 538, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 15 amino acids 321 - 390 of SEQ ID NO. 538, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 538, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 20 about 90% and most preferably at least about 95% homologous to amino acids 321 - 390 in SEQ ID NO. 538. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 539, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 141 of CEA6_HUMAN, which 25 also corresponds to amino acids 1 - 141 of SEQ ID NO. 539, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 142 - 183 of SEQ ID NO. 539, wherein said first and second amino acid sequences are contiguous and in a sequential order. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 539, comprising a polypeptide being at WO 2005/072053 PCT/IB2005/000928 88 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 142 - 183 in SEQ ID NO. 539. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 540, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 167 of Q9HAP5, which also corresponds to amino acids 1 - 167 of SEQ ID NO. 540, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 10 amino acids 168 - 180 of SEQ ID NO. 540, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 540, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to amino acids 168 - 180 in SEQ ID NO. 540. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 541, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 357 of Q8N441, which also 20 corresponds to amino acids 1 - 357 of SEQ ID NO. 541, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 358 - 437 of SEQ ID NO. 541, and a third amino acid sequence being at least 90 % homologous to amino acids 358 - 504 of Q8N441, which also corresponds to amino acids 438 25 584 of SEQ ID NO. 541, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of SEQ ID NO. 541, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for acids 358 - 437 corresponding to SEQ ID NO. 541.

WO 2005/072053 PCT/IB2005/000928 89 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 269 of Q9H4D7, which also corresponds to amino acids 1 - 269 of SEQ ID NO. 542, and a second amino acid sequence 5 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 270 - 490 of SEQ ID NO. 542, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a tail of SEQ ID NO. 542, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 270 - 490 in SEQ ID NO. 542. According to preferred embodiments of the present invention, there is provided an 15 isolated chimeric polypeptide encoding for SEQ ID NO. 542, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 269 of Q8N441, which also corresponds to amino acids 1 - 269 of SEQ ID NO. 542, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 20 amino acids 270 - 490 of SEQ ID NO. 542, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 542, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 25 about 90% and most preferably at least about 95% homologous to amino acids 270 - 490 in SEQ ID NO. 542. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 543, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 81 of SZ05_HUMAN, which also 30 corresponds to amino acids 1 - 81 of SEQ ID NO. 543.

WO 2005/072053 PCT/IB2005/000928 90 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 544, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 74 of MI2B._HUMAN, which also corresponds to amino acids 1 - 74 of SEQ ID NO. 544. 5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 545, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 103 of MI2BHUMAN, which also corresponds to amino acids 1 - 103 of SEQ ID NO. 545. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for SEQ ID NO. 546, comprising a first amino acid sequence being at least 90 % homologous to amino acids I - 61 of M12B HUMAN, which also corresponds to amino acids 1 - 61 of SEQ ID NO. 546, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino 15 acids 62 - 98 of SEQ ID NO. 546, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 546, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 20 about 90% and most preferably at least about 95% homologous to amino acids 62 - 98 in SEQ ID NO. 546. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 547, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 25 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 103 of SEQ ID NO. 547, and a second amino acid sequence being at least 90 % homologous to amino acids 34 - 107 of MI2B HUMAN, which also corresponds to amino acids 104 - 177 of SEQ ID NO. 547, wherein said first and second amino acid sequences are contiguous and in a sequential order. 30 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 547, comprising a polypeptide being WO 2005/072053 PCT/IB2005/000928 91 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 103 of SEQ ID NO. 547. According to preferred embodiments of the present invention, there is provided an 5 isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90 % homologous to amino acids 151 - 461 of DCORHUMAN, which also 10 corresponds to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 15 least about 90% and most preferably at least about 95% homologous to amino acids I - 29 of SEQ ID NO. 548. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 20 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90 % homologous to amino acids 40 - 350 of AAA59968, which also corresponds to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 29 of SEQ ID NO. 548. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 548, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 92 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids I - 29 of SEQ ID NO. 548, and a second amino acid sequence being at least 90 % homologous to amino acids 86 - 396 of AAH14562, which also corresponds 5 to amino acids 30 - 340 of SEQ ID NO. 548, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 10 least about 90% and most preferably at least about 95% homologous to amino acids 1 - 29 of SEQ ID NO. 548. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 15 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 44 of SEQ ID NO. 549, second amino acid sequence being at least 90 % homologous to amino acids 74 - 191 of Q9NWT9, which also corresponds to amino acids 45 - 162 of SEQ ID NO. 549, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 163 - 238 of SEQ ID NO. 549, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 549, comprising a polypeptide being 25 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids I - 44 of SEQ ID NO. 549. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 549, comprising a polypeptide being at 30 least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 93 about 90% and most preferably at least about 95% homologous to amino acids 163 - 238 in SEQ ID NO. 549. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 549, comprising a first amino acid 5 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 44 of SEQ ID NO. 549, and a second amino acid sequence being at least 90 % homologous to amino acids 21 - 214 of TESC_1-HUMAN, which also corresponds to amino acids 45 - 238 of SEQ ID NO. 549, wherein said first and second amino 10 acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a bead of SEQ ID NO. 549, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 44 of 15 SEQ ID NO. 549. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence 20 corresponding to amino acids 1 - 130 of SEQ ID NO. 550, and a second amino acid sequence being at least 90 % homologous to amino acids 1 - 172 of Q96C98, which also corresponds to amino acids 131 - 302 of SEQ ID NO. 550, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a head of SEQ ID NO. 550, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 130 of SEQ ID NO. 550. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for SEQ ID NO. 550, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at WO 2005/072053 PCT/IB2005/000928 94 least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 74 of SEQ ID NO. 550, and a second amino acid sequence being at least 90 % homologous to amino acids 53 - 280 of Q9BVA2, which also corresponds to amino acids 75 - 302 of SEQ ID NO. 550, wherein said first and second amino acid sequences 5 are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 550, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids I - 74 of 10 SEQ ID NO. 550. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence 15 corresponding to amino acids 1 - 34 of SEQ ID NO. 551, and a second amino acid sequence being at least 90 % homologous to corresponding to amino acids 60 - 172 of Q96C98, which also corresponds to amino acids 35 - 147 of SEQ ID NO. 551, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a head of SEQ ID NO. 551 comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 34 of SEQ ID NO. 551. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 551, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 1 - 34 of SEQ ID NO. 551, and a second amino acid sequence being at least 90 % homologous to corresponding to amino acids 168 - 280 of Q9BVA2, which 30 also corresponds to amino acids 35 - 147 of SEQ ID NO. 551, wherein said first and second amino acid sequences are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 95 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 551, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 34 of 5 SEQ ID NO. 551. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of SEQ ID NO. 548, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 1 - 29 of SEQ ID 10 NO. 548. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 556, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 441 of SMO2_HUMAN, which also corresponds to amino acids 1 - 441 of SEQ ID NO. 556, and a second amino acid sequence 15 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 442 - 464 of SEQ ID NO. 556, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an An 20 isolated polypeptide encoding for a tail of SEQ ID NO. 556, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 442 - 464 in SEQ ID NO. 556. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for SEQ ID NO. 557, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 428 of SM02_HUMAN, which also corresponds to amino acids 1 - 428 of SEQ ID NO. 557, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to 30 amino acids 429 - 434 of SEQ ID NO. 557, wherein said first and second amino acid sequences are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 96 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of SEQ ID NO. 557, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to amino acids 429 - 434 in SEQ 5 ID NO. 557. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for SEQ ID NO. 558, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 441 of SMO2_HUMAN, which also corresponds to amino acids 1 - 441 of SEQ ID NO. 558, and a second amino acid sequence 10 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide sequence corresponding to amino acids 442 - 454 of SEQ ID NO. 558, wherein said first and second amino acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of SEQ ID NO. 558, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous amino acids 442 - 454 in SEQ ID NO. 558. According to preferred embodiments of the present invention, there is provided an 20 isolated chimeric polypeptide encoding for SEQ ID NO. 559, comprising a first amino acid sequence being at least 90 % homologous to amino acids 1 - 170 of SM02_HUMAN, which also corresponds to amino acids 1 - 170 of SEQ ID NO. 559, and a second amino acid sequence being at least 90 % homologous to amino acids 188 - 446 of SM02_HUMAN, which also corresponds to amino acids 171 - 429 of SEQ ID NO. 559, wherein said first and second amino 25 acid sequences are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of SEQ ID NO. 559, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally 30 at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino WO 2005/072053 PCT/IB2005/000928 97 acids in length, wherein at least two amino acids comprise TD, having a structure as follows: a sequence starting from any of amino acid numbers 170-x to 170; and ending at any of amino acid numbers 171+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 5 antibody capable of specifically binding to an epitope of an amino acid sequence from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR. Optionally said amino acid sequence corresponds to a bridge, edge portion, tail, head or insertion. 10 Optionally the antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein. According to preferred embodiments of the present invention, there is provided a kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUMODCA, 15 R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCAlXIA, HSSIOOPCB, HUMPHOSLIP, D11853, RI1723, M77903 and HSKITCR. Optionally the kit comprises a NAT-based technology. Optionally the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence. 20 Optionally the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence. Optionally the kit comprises an antibody. Optionally the kit further comprises at least one reagent for performing an ELISA or a Western blot. 25 According to preferred embodiments of the present invention, there is provided an method for detecting colon cancer, comprising detecting overexpression of a splice variant from clusters of M85491, T10888, H14624, H53626, HSENA78, HUMGROG5, HUIVIODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCAlXIA, HSS100PCB, HUMPHOSLIP, D11853, RI1723, M77903 and HSKITCR. 30 Optionally detecting overexpression is performed with a NAT-based technology. Optionally said detecting overexpression is performed with an immunoassay.

WO 2005/072053 PCT/IB2005/000928 98 Optionally the immunoassay comprises an antibody. According to preferred embodiments of the present invention, there is provided a biomarker capable of detecting colon cancer, comprising nucleic acid sequences or a fragment thereof, or amino acid sequences or a fragment thereof from clusters of M85491, T10888, 5 H14624, H53626, HSENA78, HUMGROG5, HUMODCA, R00299, Z19178, S67314, Z44808, Z25299, HUMF5A, HUMANK, Z39818, HUMCA1XIA, HSS100PCB, HUMPHOSLIP, D11853, R11723, M77903 and HSKITCR. According to preferred embodiments of the present invention, there is provided a method for screening for colon cancer, comprising detecting colon cancer cells with a biomarker or an 10 antibody or a method or assay. According to preferred embodiments of the present invention, there is provided a method for diagnosing colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay. According to preferred embodiments of the present invention, there is provided a method 15 for monitoring disease progression of colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay. According to preferred embodiments of the present invention, there is provided a method of selecting a therapy for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay and selecting a therapy according to said 20 detection. According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name AA583399_PEA_1 TO AA583399_PEA 1_TI AA583399_PEA_1_T2 AA583399 PEA_1_T3 AA583399_PEA_1_T4 AA583399_PEA_1_T5 WO 2005/072053 PCT/IB2005/000928 99 AA583399 PEA_1_T6 AA583399 PEA_1_T7 AA583399_PEA_1_T8 AA583399 PEA_1_T9 AA583399 PEA_1_T1O AA583399 PEA 1_Tl AA583399 PEAIT12 AA583399 PEA 1_T15 AA583399_PEA 1_T16 AA583399 PEA 1_T17 a nucleic acid sequence comprising a sequence selected from the table below: Segment Naie AA583399 PEA 1_node_0 AA583399 PEA_1_node_3 AA583399_PEA 1_node_9 AA583399 PEA1_node 10 AA583399_PEA1node12 AA583399_PEA 1 node_14 AA583399 PEAInode_21 AA583399_PEAInode_24 AA583399 PEA1_node_25 AA583399_PEAInode_29 AA583399_PEA 1_node_1 AA583399 PEA_1_node_2 AA583399 PEA1_node_4 AA583399 PEA_1_node_5 AA583399_PEA 1_node_6 AA583399_PEA 1_node_7 WO 2005/072053 PCT/IB2005/000928 100 AA583399_PEA_1_node 8 AA583399_PEA_1_node_11 AA583399 PEA_1_node_19 AA583399_PEA 1 node 27 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name AA583399 PEA_1 P3 AA583399_PEA_1_P2 AA583399_PEA_1_P4 AA583399_PEA_1 P5 AA583399_PEA_1 P6 AA583399_PEA_1_P8 AA583399 PEA_1_PlO AA583399_PEA 1 P11 AA583399 PEA_1 P12 AA583399 PEA_1_P14 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name A1684092_PEA_1_T2 A1684092 PEA_1_T3 10 a nucleic acid sequence comprising a sequence in the table below: Segment Name WO 2005/072053 PCT/IB2005/000928 201 A1684092_PEA_1_node_0 A1684092 PEA_1_node_2 A1684092 PEA_1_node_4 A1684092_PEA_1_node 5 A1684092_PEA_1_node_6 A1684092 PEA 1_node_7 A1684092_PEA 1_node 8 A1684092_PEA_1_node 9 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: Protein Name A1684092_PEA_1_P1 A1684092_PEA_1_P3 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HUMCACH1APEA1TO HUMCACH1APEA 1_TI HUMCACH1APEA_1_T2 HUMCACH1A PEA 1 T3 HUMCACH1A PEA 1_T4 HUJMCACH1APEA_1 T6 HUMCACH1APEA_1 T7 HUMCACH1APEA_1_T8 HUMCACH1APEA_1 T12 HUMCACH1APEA_1_T13 WO 2005/072053 PCT/IB2005/000928 102 HUMCACH1A PEA 1_T14 HUMCACH1APEA_1 T15 HUMCACHIAPEA_1 T16 HUMCACHIAPEA_1 T17 HUMCACH1APEA_1 T18 HUMCACHIA PEA 1 T19 HUMCACH1APEA_1_T20 HUMCACH1APEA_1 T22 a nucleic acid sequence comprising a sequence in the table below: Segment INanae HUMCACHIAPEA1_node_2 HUMCACHIA PEA 1 node_5 HUMCACHIAPEA 1_node 9 HUMCACHIAPEA1_node 11 HUMCACH1APEAInode_14 HUMCACHIAPEA 1_node_16 HUMCACHIA PEA 1 node_27 HUMCACHIA PEA 1 node 30 HUMCACH1APEA_1_node 33 HUMCACHlAPEAInode41 HUMCACHIA PEA 1 node_43 HUMCACH1A PEA_1_node_45 HUMCACHI1APEA_1_node_47 HUMCACHIAPEA 1 node_55 HUMCACH1A PEA 1 node 57 HUMCACH1A PEAInode 70 HUMCACH1APEA_1 node_72 HUMCACH1APEA 1_node_74 WO 2005/072053 PCT/IB2005/000928 103 HUMCACH1APEA 1 node_86 HUMCACH1APEA_1 node_92 HUMCACHIAPEA 1_node_94 HUMCACH1APEA_1_node_103 HUMCACH1APEA 1_node_104 HUMCACHIAPEA_1_node_106 HUMCACH1A PEA 1_node 109 HUMCACH1A PEA_1 node 113 HUMCACHIAPEA 1_node 114 HUMCACH1APEA_1_node_116 HUMCACHIAPEA_1_node_119 HUMCACH1APEA 1_node_121 HUMCACH1APEA_1 node_123 HUMCACHIAPEAInode125 HUMCACH1APEA 1_node_128 HUMCACH1A PEA 1 node 0 HUMCACHIAPEA_1node_3 HUMCACH1APEA_1_node_7 HUMCACH1APEA 1_node_23 HUMCACH1A PEA 1 node_26 HUMCACH1APEA_1_node 32 HUMCACH1A PEA 1 node 35 HUMCACHlAPEA 1 node_37 HUMCACHIAPEA 1 node 39 HUMCACH1APEA 1_node_49 HUMCACHIA PEA 1 node_51 HUMCACHIA PEA 1 node_53 HUMCACHIAPEAInode_58 HUMCACHIAPEA 1 node_60 HUMCACHIAPEA 1 node_62 WO 2005/072053 PCT/IB2005/000928 -104 HUMCACH1APEA_1Inode_64 HUMCACH IAPEA_1_node_66 HUMCACHIAPEA_1_node_68 HUMCACH 1 APEA_1_node_76 HUMCACH1 APEA_1_node_77 HUMCACH1APEA_1_node_79 HUMCACH1APEA_1_node81 HUMCACHIA PEA_1 node_84 HUMCACH1APEA_1_node_88 HUMCACH1APEA_1_node_90 HUMCACHIAPEA 1_node_96 HUMCACH1APEA_1_node_98 HUMCACH1A PEA 1 node_100 HUMCACH1APEA_1_node101 HUMCACH1APEA_1 node_107 HUMCACH 1 APEA_1 node 111 HUMCACH1APEA_1_node 117 HUMCACH1APEA_1_node_124 HUMCACH1APEA_1 node_126 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: 5 Protein Name HUMCACH1APEA_1_P2 HUMCACH1APEA_1_P3 HUMCACH1A PEA 1 P4 HUMCACI1APEA_1_P5 HUMCACH1APEA_1 P7 WO 2005/072053 PCT/IB2005/000928 105 HUMCACHIAPEA_1 P8 HUMCACH1APEA_1_P9 HUMCACH1APEA_1_PlO HUMCACH1APEA_1 P11 HUMCACH1APEA_1 P12 HUMCACHIAPEA_1_P13 HUMCACH1APEA_1_P14 HUMCACH1APEA1 P15 HUMCACHIAPEA_1 P17 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Naae HUMCEAPEA_1_T8 HUMCEA PEA_1_T9 HUMCEAPEA_1_T12 - HUMCEA PEA 1 T14 HUMCEAPEA_1_T16 HUMCEA PEA 1_T20 HUMCEAPEA_1_T25 HUMCEA PEA_1_T26 HUMCEAPEA_1_T29 HUMCEAPEA_1_T30 5 a nucleic acid sequence comprising a sequence in the table below: Segment Name HUMCEAPEA_1_node 0 HUMCEAPEA_1 node 2 HUMCEAPEA_1_node 6 WO 2005/072053 PCT/IB2005/000928 106 HUMCEAPEAInode 11 HUMCEAPEA_1_node_12 HUMCEA PEA_1_node 31 HUMCEAPEA_1_node 36 HUMCEAPEA_1 node_42 HUMCEA PEA_1_node_43 HUMCEAPEA_1 node_44 HUMCEA PEA 1 node 46 HUMCEAPEA 1 node 48 HUMCEAPEA_1_node63 HUMCEAPEA_1_node 65 HUMCEAPEA_1 node 67 HUMCEAPEA 1 node 3 HUMCEA PEAI 1node_7 HUMCEA PEA_1 node 8 HUMCEAPEA_1_node 9 HUMCEAPEA 1_node_10 HUMCEA PEA_1 node 15 HUMCEA PEA_1 node 16 HUMCEA PEA_I node 17 HUMCEAPEA_1_node 18 HUMCEAPEA_1_node 19 HUMCEA PEA_1 node_20 HUMCEAPEA_1_node 21 HUMCEAPEA_1_node_22 HUMCEAPEAI node 23 HUMCEAPEA 1 node 24 HUMCEAPEA_1_node 27 HUMCEAPEA_1 node 29 HUMCEA PEA_1 node 30 WO 2005/072053 PCT/IB2005/000928 107 HUMCEAPEA_1_node 33 HUMCEAPEA_1_node 34 HUMCEAPEA_1_node_35 HUMCEAPEA_1_node_45 HUMCEAPEA_1 node_49 HUMCEAPEA_1_node 50 HUMCEA PEA_1_node_51 HUMCEAPEA_1_node 56 HUMCEAPEA_1_node 57 HUMCEAPEA_1_node 58 HUMCEA PEA_1_node_60 HUMCEA PEA_1_node_61 HUMCEAPEA_1_node_62 HUMCEA PEA_1_node_64 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name HUMCEA PEA_1_P4 HUMCEAPEA_1_P5 HUMCEAPEA_1_P7 HUMCEA PEA 1_PlO HUMCEAPEA_1_P14 HUMCEA PEA_1_P19 HUMCEAPEA_1_P20 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: WO 2005/072053 PCT/IB2005/000928 10 8 Transcript Name M78035 TO M78035_T3 M78035_T4 M78035_T7 M78035_T9 M78035_TI1 M78035_T17 M78035_T18 M78035_T19 M78035_T20 M78035_T27 M78035 T28 a nucleic acid sequence comprising a sequence in the table below: Segment N e M78035node_4 M78035_node_6 M78035 node_10 M78035node_17 M78035 node 18 M78035_node 21 M78035 node_25 M78035 node_33 M78035node_55 M78035 node_58 M78035_node 60 M78035_node 62 M78035_node 63 WO 2005/072053 PCT/IB2005/000928 109 M78035node_64 M78035node_65 M78035 node 69 M78035node71 M78035node_14 M78035 node_15 M78035node_20 M78035node_24 M78035 node_26 M78035node_28 M78035node_29 M78035node_30 M78035node_31 M78035node_34 M78035 node_35 M78035node_37 M78035node_40 M78035 node_48 M78035 node_49 M78035 node_50 M78035node_52 M78035node_53 M78035node_54 M78035_node 56 M78035 node_57 M78035 node_59 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: WO 2005/072053 PCT/IB2005/000928 110 Protein Name M78035P2 M78035 P4 M78035_P6 M78035_P8 M78035 P18 M78035_P19 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: 5 Transcript Name R30650 PEA_2_T2 R30650_PEA 2_T3 R30650_PEA_2_T6 R30650_PEA_2_T14 R30650 PEA_2_T15 R30650PEA_2_T18 R30650PEA 2_T21 R30650PEA_2_T23 a nucleic acid sequence comprising a sequence in the table below: Segment Name R30650_PEA2node 0 R30650_PEA_2_node 1 R30650 PEA 2_node 3 R30650PEA 2_node 5 R30650 PEA 2_node_9 WO 2005/072053 PCT/IB2005/000928 R30650 PEA_2 node_11 R30650_PEA_2_node 14 R30650_PEA_2 node_20 R30650 PEA_2_node_22 R30650_PEA_2_node 24 R30650_PEA_2_node_26 R30650_PEA_2_node 32 R30650 PEA_2_node_34 R30650_PEA_2_node_36 R30650_PEA_2_node_37 R30650_PEA_2_node_39 R30650_PEA_2_node 41 R30650_PEA_2_node_42 R30650_PEA_2_node 44 R30650_PEA 2 node 46 R30650_PEA 2_node 50 R30650_PEA_2_node 56 R30650 PEA 2 node 60 R30650_PEA_2_node 63 R30650_PEA 2_node 67 R30650 PEA_2_node_70 R30650_PEA_2_node_72 R30650 PEA_2_node 73 R30650 PEA_2_node_75 R30650 PEA_2 node_79 R30650_PEA_2_node 86 R30650_PEA_2_node 87 R30650_PEA_2_node 89 R30650_PEA_2_node_93 R30650 PEA_2_node 8 WO 2005/072053 PCT/IB2005/000928 112 R30650_PEA_2_node 17 R30650 PEA_2_node_28 R30650 PEA_2_node_31 R30650_PEA_2_node_48 R30650_PEA_2_node 53 R30650 PEA 2_node_58 R30650_PEA_2_node_68 R30650_PEA_2_node_77 R30650_PEA_2_node 82 R30650_PEA_2_node_85 R30650_PEA_2_node_88 R30650 PEA_2_node 90 R30650 PEA_2_node 91 R30650_PEA_2_node_92 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name R30650 PEA 2_P4 R30650_PEA_2_P5 R30650_PEA_2_P8 R30650 PEA_2_P12 R30650 PEA 2_P13 R30650_PEA_2_P15 R30650_PEA_2_P17 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: WO 2005/072053 PCT/IB2005/000928 113 Transcript Name T23657 TO T23657 TI T23657 T2 T23657 T3 T23657_T4 T23657_T5 T23657_T6 T23657_T7 T23657_TS T23657 T9 T23657 T1O T23657 T11 T23657_T12 T23657T13 T23657T14 T23657_T15 T23657_T16 T23657_T17 T23657_T19 T23657 T20 T23657_T21 T23657 T22 T23657 T23 T23657 T24 T23657_T28 T23657_T30 T23657_T31 T23657_T32 T23657_T35 WO 2005/072053 PCT/IB2005/000928 114 T23657_T37 T23657_T38 a nucleic acid sequence comprising a sequence in the table below: Segment Name T23657_node_2 T23657 node_3 T23657 node_8 T23657_node_16 T23657 node 18 T23657_node_23 T23657_node 24 T23657_node_27 T23657_node_29 T23657_node 34 T23657_node 37 T23657 node 38 T23657 node_39 T23657 node_40 T23657_node_45 T23657_node_46 T23657_node_49 T23657_node_0 T23657 node_4 T23657_node_6 T23657 node_11 T23657_node 20 T23657_node_22 T23657_node_25 WO 2005/072053 PCT/IB2005/000928 115 T23657_node_26 T23657_node_28 T23657_node_30 T23657_node_31 T23657_node 32 T23657_node_41 T23657_node 42 T23657_node_43 T23657 node 44 According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide comprising an amino acid sequence in the table below: Protein-Name T23657_P1 T23657 P2 T23657_P3 T23657 P4 T23657 P5 T23657_P6 T23657 P7 T23657 P8 T23657 P9 T23657_P1O T23657 P11 T23657_P12 T23657 P16 T23657 P17 WO 2005/072053 PCT/IB2005/000928 116 T23657_P19 T23657 P21 T23657_P22 T23657_P23 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name T51958 PEA_1_T4 T51958_PEA_1_T5 T51958 PEA_1_T6 T51958 PEA 1_T8 T51958 PEA_1_T12 T51958_PEA_1_T16 T51958 PEA1_T33 T51958PEA 1_T35 T51958_PEA_1_T37 T51958_PEA_1_T39 T51958_PEA 1_T40 T51958_PEA_1_T41 5 a nucleic acid sequence comprising a sequence in the table below: Segment Name T51958_PEA_1_node 0 T51958 PEA 1_node_7 T51958_PEA_1_node_8 T51958 PEA_1_node 9 T51958PEA 1_node 14 WO 2005/072053 PCT/IB2005/000928 117 T51958_PEA1_node_16 T51958 PEA 1_node_18 T51958 PEA 1_node_21 T51958_PEA1_node_22 T51958 PEA1_node_24 T51958_PEA1_node_27 T51958_PEA1_node_29 T51958_PEA 1 node_33 T51958_PEA1_node 40 T51958_PEA 1_node_41 T51958 PEA1_node 46 T51958_PEAInode 51 T51958_PEA_1 node 55 T51958_PEA1_node 67 T51958 PEA 1_node 70 T51958 PEA 1_node 74 T51958 PEA 1 node 78 T51958_PEA1node11 T51958_PEA 1_node 15 T51958 PEA 1_node 20 T51958 PEA 1_node_26 T51958 PEA 1_node 35 T51958_PEA1_node 36 T51958 PEA1_node_38 T51958PEA 1_node 39 T51958_PEA1_node 42 T51958 PEA 1_node_43 T51958 PEA1_node 44 T51958 PEA 1_node_45 T51958_PEA1_node 47 WO 2005/072053 PCT/IB2005/000928 118 T51958 PEA 1 node 48 T51958_PEA1_node 49 T51958 PEA1_node_50 T51958_PEA1_node_54 T51958_PEA 1_node 61 T51958_PEAInode71 T51958 PEA1_node 72 T51958_PEA 1_node 75 T51958_PEA 1_node 76 T51958 PEA 1_node_77 T51958 PEA1_node 80 T51958 PEA1node 82 T51958 PEA 1_node 84 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: 5 Protein Name T51958_PEA 1_P5 T51958 PEA_1_P6 T51958 PEA_1_P28 T51958_PEA 1_P30 T51958 PEA_1_P34 T51958PEA 1_P35 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Nam e WO 2005/072053 PCT/IB2005/000928 119 Z17877_PEA_1_TO Z17877_PEA_1_T2 Z17877 PEA 1_T3 Z17877 PEA 1_T4 Z17877_PEAIT6 Z17877_PEA 1_T7 Z17877_PEA 1_T8 Z17877_PEA1 T11 Z17877_PEA 1_T12 a nucleic acid sequence comprising a sequence in the table below: Segment Name 217877 PEA 1_node 0 Z17877 PEA 1_node 3 Z17877 PEA_1_node_8 Z17877 PEA_1_node 9 Z17877_PEA 1_node_10 Z17877_PEA 1_node 11 Z17877_PEA_1_node 13 Z17877 PEA 1_node_15 Z17877 PEA_1_node 16 Z17877 PEA 1_node_18 Z17877 PEA_1_node 1 Z17877_PEA_1_node_2 Z17877_PEAInode 4 Z17877_PEA_1_node 5 Z17877 PEA_1_node 6 Z17877_PEA 1 node_14 Z17877_PEA 1_node 17 WO 2005/072053 PCT/IB2005/000928 120 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below Protein Name Z17877_PEA_1_P1 Z17877_PEA_1_P2 Z17877_PEA_1_P3 Z17877 PEA_1 P6 5 According to preferred embodiments of the present invention, there is provided an isolated polynucleotide comprising a nucleic acid sequence in the table below and/or: Transcript Name HSHCGI PEA_3_TO HSHCGIPEA_3_T1 HSHCGIPEA_3_T2 HSHCGIPEA_3_T3 HSHCGI PEA_3_T4 HSHCGIPEA_3_T5 HSHCGIPEA_3_T6 HSHCGIPEA_3_T7 HSHCGIPEA_3_T8 HSHCGIPEA_3_T9 HSHCGIPEA3T1O HSHCGI PEA_3_Ti I HSHCGIPEA_3_T12 HSHCGIPEA_3_T13 HSHCGIPEA_3_T14 HSHCGI PEA 3_T15 WO 2005/072053 PCT/IB2005/000928 121 HSHCGIPEA_3_T17 HSHCGIPEA_3_T18 HSHCGI PEA_3_T19 HSHCGIPEA_3_T20 HSHCGI PEA_3_T21 HSHCGIPEA_3_T22 HSHCGI PEA_3_T23 HSHCGIPEA 3_T24 a nucleic acid sequence comprising a sequence in the table below: Segment Name HSHCGIPEA_3_node 0 HSHCGI PEA_3_node_2 HSHCGI PEA3_node_7 HSHCGIPEA_3_node_8 HSHCGI PEA_3_node_14 HSHCGIPEA_3_node 16 HSHCGIPEA_3_node_18 HSHCGI PEA_3_node_20 HSHCGI PEA_3_node_26 HSHCGIPEA_3_node_28 HSIHCGIPEA_3_node 30 HSHCGIPEA_3_node_32 HSHCGI PEA_3_node 33 HSHCGIPEA_3_node 34 HSHCGIPEA_3_node_36 HSHCGI PEA_3_node I HSHCGI PEA_3_node_4 HSHCGIPEA_3_node_6 WO 2005/072053 PCT/IB2005/000928 122 HSHCGIPEA_3_node 9 HSHCGI PEA_3_node 11 HSHCGIPEA 3_node_13 HSHCGIPEA_3_node 19 HSHCGIPEA_3_node 21 HSHCGIPEA_3_node 22 HSHCGI PEA_3_node_23 HSHCGI PEA_3_node_24 HSHCGIPEA_3_node_27 HSHCGIPEA_3_node_31 HSHCGI PEA_3_node 35 According to preferred embodiments of the present invention, there is provided an isolated polypeptide comprising an amino acid sequence in the table below: ProteiD Name HSHCGI PEA_3_P17 HSHCGIPEA_3_P18 HSHCGI PEA_3_P19 HSHCGI PEA_3_P1 HSHCGIPEA_3_P4 HSHCGIPEA 3_P6 HSHCGIPEA_3_P7 HSHCGI PEA_3_P8 HSHCGIPEA_3_P9 HSHCGIPEA_3_P12 HSHCGIPEA_3_P13 HSHCGIPEA_3_P14 HSHCGIPEA_3_P15 HSHCGIPEA_3_P16 WO 2005/072053 PCT/IB2005/000928 123 HSHCGIPEA_3 P20 HI-ISHCGIPEA_3_P21 HSHCGIPEA_3_P22 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P17, comprising a first amino acid sequence being at least 90 % homologous to 5 MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCPQCITQIGETSCGFFKCPLCKTSVR RDAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKI-IYV corresponding to amino acids 1 - 218 of TM31 _HUMAN, which also corresponds to amino acids 1 - 218 of 10 HSHCGIPEA_3 P17, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EIPLMPTVERSQEARCYP corresponding to amino acids 219 - 236 of HSHCGIPEA_3_P17, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EIPLMPTVERSQEARCYP in HSHCGIPEA_3_P17. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P19, comprising a first amino acid sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR RDAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES 25 KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK TKQNMPPRQLLE corresponding to amino acids I - 248 of TM31_HUMANV2, which also corresponds to amino acids 1 - 248 of HSHCGIPEA_3_P19, and a second amino acid WO 2005/072053 PCT/IB2005/000928 124 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWRKNSVKQNQDTTPSQGA corresponding to amino acids 249 - 267 of HSHCGIPEA_3_P19, wherein said first amino acid sequence and second amino acid sequence 5 are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P19, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 NWRKNSVKQNQDTTPSQGA in HSHCGIPEA_3_P19. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA-3_P4, comprising a first amino acid sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR 15 KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK TKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1 - 256 of TM31_HUMANV1, which also corresponds to amino acids 1 - 256 of HSHCGIPEA_3_P4, and a second amino 20 acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence YDGPPQMYFAY corresponding to amino acids 257 - 267 of HSHCGIPEA_3_P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence YDGPPQMYFAY in HSHCGIPEA_3_P4. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA 3_P6, comprising a first amino acid WO 2005/072053 PCT/IB2005/000928 125 sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKJQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE 5 KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK TKQNMPPRQLLEDIKVVLCR corresponding to amino acids I - 256 of TM31HUMAN_VI, which also corresponds to amino acids I - 256 of HSHCGI PEA_3 P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 10 the sequence PTPG corresponding to amino acids 257 - 260 of HSHCGIPEA_3_P6, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P6, comprising a polypeptide 15 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PTPG in HSHCGIPEA_3_P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P7, comprising a first amino acid 20 sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK 25 TKQNMPPRQLLEDIKVVLCRS corresponding to amino acids 1 - 257 of TM3 1_HUMAN_Vi, which also corresponds to amino acids 1 - 257 of HSHCGIPEA_3_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA WO 2005/072053 PCT/IB2005/000928 126 corresponding to amino acids 258 - 310 of HSHCGI.PEA_3_P7, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3-P7, comprising a polypeptide 5 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SFSHTSSPDLTNQLNHIFLEVKSFSFSTQPLFLWNWRKNSVKQNQDTTPSQGA in HSHCGIPEA_3_P7. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for HSHCGIPEA_3-P8, comprising a first amino acid sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE 15 KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK TKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQ LQADRKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAG corresponding to amino acids 1 - 342 of TM31_HUMANVi, which also corresponds to amino acids 1 - 342 of HSHCGIPEA_3_P8, and a second amino acid sequence being at least 70%, optionally at least 20 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KSPVSEY corresponding to amino acids 343 - 349 of HSHCGIPEA_3_P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a tail of HSHCGIPEA_3_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KSPVSEY in HSHCGIPEA_3_P8. According to preferred embodiments of the present invention, there is provided an 30 isolated chimeric polypeptide encoding for HSHCGIPEA_3_P9, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 127 MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK 5 TKQNMPPRQLLEDIKVVLCR corresponding to amino acids 1 - 256 of TM31 HUMANV1, which also corresponds to amino acids I - 256 of HSHCGI PEA_3 P9, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TGEKTQ corresponding to amino acids 257 -262 of HSHCGI PEA 3 P9, 10 wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 15 at least about 90% and most preferably at least about 95% homologous to the sequence TGEKTQ in HSHCGIPEA_3_P9. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGI PEA_3_P12, comprising a first amino acid sequence being at least 90 % homologous to 20 MNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAPSHSLFRASSAG KVTFPVCLLASYDEISGQGASSQDTKTFDVALSEELHAALSEWLTAIRAWFCEVPSS corresponding to amino acids 312 - 425 of TM3 1_HUMAN, which also corresponds to amino acids 1 - 114 of HSHCGIPEA_3_P12. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for USHCGIPEA_3_P14, comprising a first amino acid sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFTDQVEHE 30 KQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDLKKLVDSLK

TKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQ

WO 2005/072053 PCT/IB2005/000928 128 LQADRKKDENRFFKSMNKNDMKS corresponding to amino acids 1 - 319 of TM31_HUMAN_Vi, which also corresponds to amino acids 1 - 319 of HSHCGIPEA_3_P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 5 polypeptide having the sequence CK corresponding to amino acids 320 - 321 of HSHCGIPEA_3_P14, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P16, comprising a first amino 10 acid sequence being at least 90 % homologous to MASGQFVNKLQEEVICPICLDILQKPVTIDCGHNFCLKCITQIGETSCGFFKCPLCKTSVR KNAIRFNSLLRNLVEKIQALQASEVQSKRKEATCPRHQEMFHYFCEDDGKFLCFVCRES KDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDVFT corresponding to amino acids 1 - 171 of TM3 1_HUMAN V1, which also corresponds to amino 15 acids 1 - 171 of HSH CGIPEA_3_P16, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRKTPSHDLWKQKHLCQSSWNPLLH corresponding to amino acids 172 - 196 of HSHCGIPEA_3_P16, wherein said first amino acid sequence and second amino acid sequence 20 are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HSHCGIPEA_3_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 VRKTPSHDLWKQKHLCQSSWNPLLH in HSHCGIPEA_3_P16. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P21, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 30 the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ corresponding to amino acids 1 28 of HSHCGIPEA_3_P21, and a second amino acid sequence being at least 90 % WO 2005/072053 PCT/IB2005/000928 129 homologous to FLCFVCRESKDHKSHNVSLIEEAAQNYQGQIQEQIQVLQQKEKETVQVKAQGVHRVDV FTDQVEHEKQRILTEFELLHQVLEEEKNFLLSRIYWLGHEGTEAGKHYVASTEPQLNDL KKLVDSLKTKQNMPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITG 5 SLKKFKDQLQADRKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGR TTSGPPNHHSSAPSHSLFRASSAGKVTFPVCLLASYDEISGQGASSQDTKTFDVALSEEL HAALSEWLTAIRAWFCEVPSS corresponding to amino acids 112 - 425 of TM31 _HUMAN, which also corresponds to amino acids 29 - 342 of HSHCGIPEA_3_P21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of HSHCGIPEA 3 P21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MHHSDWGNIMWIFQMSPLQNFRKEERNQ of HSHCGIPEA_3_P21. 15 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HSHCGIPEA_3_P22, comprising a first amino acid sequence being at least 90 % homologous to MPPRQLLEDIKVVLCRSEEFQFLNPTPVPLELEKKLSEAKSRHDSITGSLKKFKDQLQAD RKKDENRFFKSMNKNDMKSWGLLQKNNHKMNKTSEPGSSSAGGRTTSGPPNHHSSAP 20 SHSLFRASSAGKVTFPVCLLASYDEISGQGASSQDTKTFDVALSEELHAALSEWLTAIRA WFCEVPSS corresponding to amino acids 241 - 425 of TM31_HUMAN, which also corresponds to amino acids 1 - 185 of HSHCGIPEA_3_P22. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P5, comprising a first amino acid 25 sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV 30 VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR

NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW

WO 2005/072053 PCT/IB2005/000928 13 0 WEHIAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVP SWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINS VEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTPPPQPQQCMEFDKEATVPCSATG REKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIASNGPQGQIRAHVQL 5 TVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRMHIFQ NGSLVIHDVAPEDSGRYTCIAGNSCNIKHTEAPLYVV corresponding to amino acids I 682 of PTK7_HUMANV4, which also corresponds to amino acids 1 - 682 of T51958_PEA_1 P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 10 homologous to a polypeptide having the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS corresponding to amino acids 683 - 733 of T51958_PEA_1 P5, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 15 isolated polypeptide encoding for a tail of T51958_PEAIPS, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GMGWGGLCCTGSGGPRRLSPCTQPLCTEHGTEAIFVAAVGIRPSHHAAAQS in T51958_PEA_1_PS. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA 25 SFNIKWIEAGPVVLK-IPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVATVP 30 SWLKKPQDSQLEEGKPGYLDCLTQATPKPTVVWYRNQMLISEDSRFEVFKNGTLRINS

VEVYDGTWYRCMSSTPAGSIEAQARVQVLEKLKFTPPPQPQQCMEFDKEATVPCSATG

WO 2005/072053 PCT/IB2005/000928 131 REKPTIKWERADGSSLPEWVTDNAGTLHFARVTRDDAGNYTCIASNGPQGQIRAHVQL TVAVFITFKVEPERTTVYQGHTALLQCEAQGDPKPLIQWKGKDRILDPTKLGPRM corresponding to amino acids I - 641 of PTK7_HUMANV4, which also corresponds to amino acids 1 - 641 of T51958_PEA_1_P6, and a second amino acid sequence being at least 70%, 5 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence APW corresponding to amino acids 642 - 644 of T51958_PEA_1_P6, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for T51958_PEA_1_P28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH 15 TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of PTK7_HUMANV11, which also corresponds to 20 amino acids 1 - 409 of T51958_PEA_1_P28, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410 - 459 of T51958PEA1_P28, wherein said first amino acid 25 sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P28, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_1_P28.

WO 2005/072053 PCT/IB2005/000928 132 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP 5 VHVYWLLDGAPVQDTERR-FAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW 10 WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of Q8NFA5, which also corresponds to amino acids 1 409 of T51958_PEA_1 P28, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410 - 459 of T51958_PEA_1_P28, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA__P28, comprising a polypeptide being 20 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_1_P28. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for T51958_PEA_1_P28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH 30 TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV

VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR

WO 2005/072053 PCT/IB2005/000928 133 NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of Q8NFA6, which also corresponds to amino acids I 409 of T51958_PEA_1 P28, and a second amino acid sequence being at least 70%, optionally 5 at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410 - 459 of T51958_PEA_1_P28, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P28, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in 15 T51958_PEA_1_P28. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP 20 VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW 25 WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of Q8NFA7, which also corresponds to amino acids 1 409 of T51958_PEA_1 P28, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV WO 2005/072053 PCT/IB2005/000928 134 corresponding to amino acids 410 - 459 of T51958_PEA_1_P28, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P28, comprising a polypeptide being 5 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_1_P28. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for T51958_PEA_1_P28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH 15 TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of Q8NFA8, which also corresponds to amino acids 1 20 409 of T51958_PEA_1_P28, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410 - 459 of T51958_PEA_1_P28, wherein said first amino acid 25 sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P28, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_1_P28.

WO 2005/072053 PCT/IB2005/000928 135 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEAIP28, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP 5 .VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIADESFARVVLAPQDVV VARYEEAMFHCQFSAQPPPSLQWLFEDETPITNRSRPPHLRRATVFANGSLLLTQVRPR NAGIYRCIGQGQRGPPIILEATLHLAEIEDMPLFEPRVFTAGSEERVTCLPPKGLPEPSVW 10 WEHAGVRLPTHGRVYQKGHELVLANIAESDAGVYTCHAANLAGQRRQDVNITVA corresponding to amino acids 1 - 409 of AAN04862, which also corresponds to amino acids I 409 of T51958_PEA_1 P28, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV corresponding to amino acids 410 - 459 of T51958_PEA_1_P28, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P28, comprising a polypeptide being 20 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SEHLCPEGQGEVEGNTGLGVMDRGFPGTHLRSSQFWALQAWESVHYWESV in T51958_PEA_1_P28. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for T51958_PEA_1_P30, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIK corresponding to amino acids 1 - 122 of PTK7_HUMAN_V13, which also corresponds 30 to amino acids 1 - 122 of T51958_PEA_1_P30, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most WO 2005/072053 PCT/IB2005/000928 13 6 preferably at least 95% homologous to a polypeptide having the sequence CESQGGCAQSPCQTLND corresponding to amino acids 123 - 139 of T51958_PEA_1_P30, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P30, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CESQGGCAQSPCQTLND in T51958_PEA_1_P30. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P34, comprising a first amino acid sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA 15 SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPR corresponding to amino acids 1 - 157 of PTK7_HUMANV3, which also corresponds to amino acids 1 - 157 of T51958_PEA_1_P34. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T51958_PEA_1_P35, comprising a first amino acid 20 sequence being at least 90 % homologous to MGAARGSPARPRRLPLLSVLLLPLLGGTQTAIVFIKQPSSQDALQGRRALLRCEVEAPGP VHVYWLLDGAPVQDTERRFAQGSSLSFAAVDRLQDSGTFQCVARDDVTGEEARSANA SFNIKWIEAGPVVLKHPASEAEIQPQTQVTLRCHIDGHPRPTYQWFRDGTPLSDGQSNH TVSSKERNLTLRPAGPEHSGLYSCCAHSAFGQACSSQNFTLSIA corresponding to amino 25 acids 1 - 220 of PTK7_HUMANVi1, which also corresponds to amino acids I - 220 of T51958_PEA_1_P35, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEPGVGAEGMR corresponding to amino acids 221 - 231 of T51958 PEA_1 P35, wherein said first amino acid sequence and second 30 amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 137 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T51958_PEA_1_P35, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 GEPGVGAEGMR in T51958_PEA_1_P35. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P2, comprising a first amino acid sequence being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC 10 QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH 15 QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG 20 QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of S21CHUMAN, which also corresponds to amino acids 1 - 675 of T23657 P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence FQLPEVHHSLNVLNRKFQKQTVHNL corresponding to amino acids 676 - 700 25 of T23657 P2, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 30 90% and most preferably at least about 95% homologous to the sequence FQLPEVHHSLNVLNRKFQKQTVHNL in T23657_P2.

WO 2005/072053 PCT/IB2005/000928 138 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P3, comprising a first amino acid sequence being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC 5 QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH 10 QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG 15 QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of S21CHUMAN, which also corresponds to amino acids I - 675 of T23657 P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF corresponding to amino acids 676 - 682 of T23657 P3, wherein said 20 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 25 90% and most preferably at least about 95% homologous to the sequence TIKHKAF in T23657_P3. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P4, comprising a first amino acid sequence being at least 90 % homologous to 30 MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC

QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG

WO 2005/072053 PCT/IB2005/000928 139 MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH 5 QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1 - 625 of 10 S21C_HUMAN, which also corresponds to amino acids 1 - 625 of T23657 P4, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626 - 646 of T23657 P4, a third amino acid sequence being at least 90 % homologous to 15 GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 626 - 675 of S2 1 C_HUMAN, which also corresponds to amino acids 647 - 696 of T23657_P4, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TIKHKAF corresponding to amino 20 acids 697 - 703 of T23657_P4, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of T23657_P4, comprising an amino acid 25 sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T23657 P4. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P4, comprising a polypeptide being at least 30 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about WO 2005/072053 PCT/IB2005/000928 140 90% and most preferably at least about 95% homologous to the sequence TIKHKAF in T23657_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P5, comprising a first amino acid sequence 5 being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG 10 QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC 15 HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLR corresponding to amino acids 1 - 604 of S2 1 C_HUMAN, which also corresponds to amino acids 1 - 604 of T23657_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P6, comprising a first amino acid sequence 20 being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG 25 QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC 30 HAGCPAATETNVDGQKV corresponding to amino acids I - 547 of S21CHUMAN, which also corresponds to amino acids 1 - 547 of T23657_P6, and a second amino acid sequence being WO 2005/072053 PCT/IB2005/000928 141 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQL VRESPSFWFSYSL corresponding to amino acids 548 - 620 of T23657 P6, wherein said first 5 amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMPLQGNALQL VRESPSFWFSYSL in T23657 P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P7, comprising a first amino acid sequence being at least 90 % homologous to 15 MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM 20 GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQK corresponding to amino acids I - 546 of S21CHUMAN, which 25 also corresponds to amino acids I - 546 of T23657_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MCP corresponding to amino acids 547 - 549 of T23657_P7, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P8, comprising a first amino acid sequence WO 2005/072053 PCT/IB2005/000928 142 being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG 5 VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF 10 SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQK corresponding to amino acids 1 - 546 of S21C-HUMAN, which also corresponds to amino acids I - 546 of T23657_P8, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 QHSCTNGNSTMCP corresponding to amino acids 547 - 559 of T23657P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 20 90% and most preferably at least about 95% homologous to the sequence QHSCTNGNSTMCP in T23657_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P10, comprising a first amino acid sequence being at least 90 % homologous to 25 MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM 30 GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH

QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES

WO 2005/072053 PCT/IB2005/000928 143 QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRIL corresponding to amino acids 1 - 625 of 5 S2IC-HUMAN, which also corresponds to amino acids 1 - 625 of T23657 P10, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTVQCEEAMVSCTVCSLHKGM corresponding to amino acids 626 - 646 of T23657 P10, and a third amino acid sequence being at least 90 % homologous to 10 GGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAI ACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 626 722 of S21CHUMAN, which also corresponds to amino acids 647 - 743 of T23657 P10, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of T23657_PlO, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GTVQCEEAMVSCTVCSLHKGM, corresponding to T23657_PlO. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P11, comprising a first amino acid sequence being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG 25 MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES 30 QFSLSASEAATLF corresponding to amino acids 1 - 425 of S21CHUMAN, which also corresponds to amino acids I - 425 of T23657_P11, and a second amino acid sequence being at WO 2005/072053 PCT/IB2005/000928 144 least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ASCPKAT corresponding to amino acids 426 - 432 of T23657 P11, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657 P11, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ASCPKAT in T23657_Pll. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P12, comprising a first amino acid sequence being at least 90 % homologous to MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG 15 MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES 20 QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFF TFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCG QQGSCLVYQNSAMSRYILIMGLLYK corresponding to amino acids 1 - 675 of 25 S21C_HUMAN, which also corresponds to amino acids 1 - 675 of T23657 P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EEENEFRRL corresponding to amino acids 676 - 684 of T23657P12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 30 sequential order.

WO 2005/072053 PCT/IB2005/000928 145 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657 P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence EEENEFRRL in 5 T23657_P12. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P16, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 MGTSPMADPVPAGRQHGSGLDPTTRLSPLC corresponding to amino acids 1 - 30 of T23657_P16, and a second amino acid sequence being at least 90 % homologous to SLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLCHAGCPAATETNVDGQKVY RDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLVFIFVVIFFTFLSSIPALTATLRCVRDPQ RSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSAMSRYILI 15 MGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 491 - 722 of S21C_HUMAN, which also corresponds to amino acids 31 - 262 of T23657_P16, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a head of T23657_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGTSPMADPVPAGRQHGSGLDPTTRLSPLC of T23657_P16. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for T23657_P17, comprising a first amino acid sequence being at least 90 % homologous to MYFSLCHAGCPAATETNVDGQKVYRDCSCIPQNLSSGFGHATAGKCTSTCQRKPLLLV FIFVVIFFTFLSSIPALTATLRCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLL WQDQCGQQGSCLVYQNSAMSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCL 30 PSQSSAPDSATDSQLQSSV corresponding to amino acids 525 - 722 of S21CHUMAN, which also corresponds to amino acids 1 - 198 of T23657_P17.

WO 2005/072053 PCT/IB2005/000928 146 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P21, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 MWTAR corresponding to amino acids 1 - 5 of T23657 P21, and a second amino acid sequence being at least 90 % homologous to RCVRDPQRSFALGIQWIVVRILGGIPGPIAFGWVIDKACLLWQDQCGQQGSCLVYQNSA MSRYILIMGLLYKVLGVLFFAIACFLYKPLSESSDGLETCLPSQSSAPDSATDSQLQSSV corresponding to amino acids 604 - 722 of S21 C_HUMAN, which also corresponds to amino 10 acids 6 - 124 of T23657 P21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of T23657_P21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least 15 about 90% and most preferably at least about 95% homologous to the sequence MWTAR of T23657_P21. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for T23657_P23, comprising a first amino acid sequence being at least 90 % homologous to 20 MPLHQLGDKPLTFPSPNSAMENGLDHTPPSRRASPGTPLSPGSLRSAAHSPLDTSKQPLC QLWAEKHGARGTHEVRYVSAGQSVACGWWAFAPPCLQVLNTPKGILFFLCAAAFLQG MTVNGFINTVITSLERRYDLHSYQSGLIASSYDIAACLCLTFVSYFGGSGHKPRWLGWG VLLMGTGSLVFALPHFTAGRYEVELDAGVRTCPANPGAVCADSTSGLSRYQLVFMLG QFLHGVGATPLYTLGVTYLDENVKSSCSPVYIAIFYTAAILGPAAGYLIGGALLNIYTEM 25 GRRTELTTESPLWVGAWWVGFLGSGAAAFFTAVPILGYPRQLPGSQRYAVMRAAEMH QLKDSSRGEASNPDFGKTIRDLPLSIWLLLKNPTFILLCLAGATEATLITGMSTFSPKFLES QFSLSASEAATLFGYLVVPAGGGGTFLGGFFVNKLRLRGSAVIKFCLFCTVVSLLGILVF SLHCPSVPMAGVTASYGGSLLPEGHLNLTAPCNAACSCQPEHYSPVCGSDGLMYFSLC HAGCPAATETNVDGQKV corresponding to amino acids 1 - 547 of S21CHUMAN, which 30 also corresponds to amino acids 1 - 547 of T23657_P23, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least WO 2005/072053 PCT/IB2005/000928 147 90% and most preferably at least 95% homologous to a polypeptide having the sequence SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNL SEKAPPSGFHIRCNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS corresponding to amino acids 548 - 661 of T23657_P23, wherein said first amino acid sequence 5 and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of T23657_P23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 SGAAAYRPCPPLDPGKGPPCLPLVIGAIVGLPRCTETVAVSLRIFPLVLAMHCREMHFNL SEKAPPSGFHIRCNFLYIPQQHSCTNGNSTVSWGRVCACPELSLQHPEAELCRS in T23657_P23. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P4, comprising a first amino acid 15 sequence being at least 90 % homologous to MYLHIGEEIDGVDMRAEVGLLSRNHVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV 20 GMYSPGYSEHIPLGKFYNNRAIISNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPIN IQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWF NQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYA 25 QMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQT APAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKV EQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCT ATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVD GKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKG 30 RYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPI WO 2005/072053 PCT/IB2005/000928 148 PVVKKKKL corresponding to amino acids 126 - 1013 of Q9ULM1, which also corresponds to amino acids 1 - 888 of R30650_PEA_2_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P4, comprising a first amino acid 5 sequence being at least 90 % homologous to MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV 10 GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPIN IQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWF NQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 474 - 977 15 of Q8WUJ3, which also corresponds to amino acids I - 504 of R30650 PEA_2 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT 20 RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF 25 KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 505 - 888 of R30650_PEA_2 P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_2 P4, comprising a polypeptide being 30 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WO 2005/072053 PCT/IB2005/000928 149 NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLTNFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF 5 LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL in R30650_PEA_2_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P4, comprising a first amino acid 10 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMPAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1 - 91 of R30650_PEA_2 P4, and a second amino acid sequence being at least 90 % homologous to 15 VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL INCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG 20 LDHSGRTLPIGQNFPIRGIQLYDGPlNIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF 25 AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 8 - 804 of Q9NPN9, which also corresponds to amino acids 92 - 888 of R30650_PEA_2_P4, wherein said 30 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 150 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD ofR30650_PEA 2 P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P4, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 10 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV 15 GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1 389 of R30650_PEA_2_P4, and a second amino acid sequence being at least 90 % homologous to 20 SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH YQQYQPVVTLQKGYTII-IWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFC 25 SMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEV KMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGI PWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKG SFRPIWVTLDTEDHKAKIFQVVPTPVVKKKKL corresponding to amino acids 2 - 500 of Q9H1K5, which also corresponds to amino acids 390 - 888 of R30650_PEA_2_P4, wherein 30 said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 151 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 MYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFAL GFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVT VHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCK MITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSV GMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQ 10 DADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYD DGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_2_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P5, comprising a first amino acid sequence being at least 90 % homologous to 15 MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG 20 YIPKPRQDCNAVSTFWMANPNNNLlNCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN SLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKF VALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGD 25 KTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWRGAICSGCYAQMYIQAYK TSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWL 1NFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSH YYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTE RAVVDVPMPKKLFGSQLKTKDHFLEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSED 30 GIQVVVIDGNQGRVVSHTSFRNSILQGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPW

TRVLEKLGADRGLKLKEQMAFVGFKGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL

WO 2005/072053 PCT/IB2005/000928 152 corresponding to amino acids 18 - 1013 of Q9ULMI, which also corresponds to amino acids 1 996 of R30650_PEA_2_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2 P5, comprising a first amino acid 5 sequence being at least 90 % homologous to MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL 10 IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG YIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN SLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPlNIQNCTFRKF 15 VALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGD KTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 366 - 977 of Q8WUJ3, which also corresponds to amino acids 1 - 612 of R30650_PEA_2_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL 25 QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 613 - 996 of R30650_PEA_2_P5, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 30 isolated polypeptide encoding for a tail of R30650_PEA_2 P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at WO 2005/072053 PCT/IB2005/000928 153 least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF 5 AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL in R30650_PEA_2_P5. According to preferred embodiments of the present invention, there is provided an 10 isolated chimeric polypeptide encoding for R30650_PEA_2_P5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE 15 IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1 - 199 of R30650_PEA_2_P5, and a second amino acid sequence being at least 90 % homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL 20 INCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND 25 NWLVRHPDCTNVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKF AFCSMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHF LEVKMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSIL 30 QGIPWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGF KGSFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 8 - 804 of WO 2005/072053 PCT/IB2005/000928 154 Q9NPN9, which also corresponds to amino acids 200 - 996 of R30650_PEA_2 P5, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a head of R30650_PEA_2_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE 10 IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGD of R30650_PEA_2_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 15 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL 20 IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG YIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN SLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1 - 497 of 25 R30650_PEA_2_P5, and a second amino acid sequence being at least 90 % homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH YQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH 30 NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFC

SMKGCERIKIKALIPKNAGVSDCTATAYPKFTERAVVDVPMPKKLFGSQLKTKDHFLEV

WO 2005/072053 PCT/IB2005/000928 155 KMESSKQHFFHLWNDFAYIEVDGKKYPSSEDGIQVVVIDGNQGRVVSHTSFRNSILQGI PWQLFNYVATIPDNSIVLMASKGRYVSRGPWTRVLEKLGADRGLKLKEQMAFVGFKG SFRPIWVTLDTEDHKAKIFQVVPIPVVKKKKL corresponding to amino acids 2 - 500 of Q9H1K5, which also corresponds to amino acids 498 - 996 of R30650_PEA_2_P5, wherein 5 said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 10 at least about 90% and most preferably at least about 95% homologous to the sequence MDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVRPKLTVTIDTNVNSTI LNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQVKVAGKPMYLHIGEE IDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFGGHIKFALGFKAAHLE GTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLL 15 IKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPG YIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYS EHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPR EPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKN SLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_2_P5. 20 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA2__P8, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI 25 GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK 30 corresponding to amino acids 1 - 348 of R30650_PEA_2_P8, a second amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 156 AHPGKICNRPIDIQATTMDG\NLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKP VRPKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPN QVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDT FGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSI 5 HHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIF HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLS IISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTL ASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIR 10 GIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWR GAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKG YTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFV RTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 1 - 788 of Q9ULM1, 15 which also corresponds to amino acids 349 - 1136 of R30650_PEA_2 P8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence KQRTISWR corresponding to amino acids 1137 - 1144 of R30650_PEA_2_P8, wherein said first amino acid sequence, second amino acid sequence and third amino acid 20 sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2 P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRIHPWSFLTVKGNPSSSVEDHIEYHGHRG 30 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK of R30650_PEA_2_P8.

WO 2005/072053 PCT/IB2005/000928 157 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650 PEA 2 P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 5 KQRTISWR in R30650_PEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P8, comprising a first amino acid sequence being at least 90 % homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI 10 GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH 15 PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR 20 DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGI QLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF 25 GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 1 - 977 of Q8WUJ3, which also corresponds to amino acids 1 - 977 of R30650_PEA_2_P8, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT

RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS

WO 2005/072053 PCT/IB2005/000928 158 DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGKQRTISWR corresponding to amino acids 978 - 1144 of R30650_PEA_2_P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 5 isolated polypeptide encoding for a tail of R30650_PEA_2 P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS 10 DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSGKQRTISWR in R30650_PEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650-PEA_2_P8, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 15 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV 20 NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG 25 GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 1 - 564 of R30650_PEA_2_P8, a second amino acid sequence being at least 90 % homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT FDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL 30 INCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN

GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV

WO 2005/072053 PCT/IB2005/000928 159 WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT 5 RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 8 - 579 of Q9NPN9, which also corresponds to amino acids 565 - 1136 of R30650_PEA_2 P8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% 10 homologous to a polypeptide having the sequence KQRTISWR corresponding to amino acids 1137 - 1144 of R30650_PEA_2 P8, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2_P8, comprising a polypeptide 15 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG 20 YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV 25 KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of R30650_PEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_2_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 30 least about 90% and most preferably at least about 95% homologous to the sequence KQRTISWR in R30650_PEA_2_P8.

WO 2005/072053 PCT/IB2005/000928 160 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P8, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG 10 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH 15 TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino 20 acids 1 - 862 of R30650_PEA_2_P8, a second amino acid sequence being at least 90 % homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL VRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH 25 YQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2 - 275 of Q9H1K5, which also corresponds to amino acids 863 - 1136 of R30650_PEA_2_P8, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 30 polypeptide having the sequence KQRTISWR corresponding to amino acids 1137 - 1144 of WO 2005/072053 PCT/IB2005/000928 161 R30650_PEA_2_PS, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650 PEA 2 P8, comprising a polypeptide 5 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG 10 YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTTLNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV 15 KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS 20 ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_2 P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at 25 least about 90% and most preferably at least about 95% homologous to the sequence KQRTISWR in R30650_PEA_2_P8. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P15, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 30 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI

WO 2005/072053 PCT/IB2005/000928 162 GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG 5 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK corresponding to amino acids 1 - 348 of R30650_PEA_2 P15, and a second amino acid sequence being at least 90 % homologous to AHPGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKP VRPKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPN 10 QVKVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDT FGGHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSI HHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPS DRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIF HHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLS 15 IISARYSPHQDADPLKPREPAIIR-IFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTL ASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRJWGPGGLDHSGRTLPIGQNFPIR GIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRV FFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWLVRHPDCINVPDWR GAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVVTLQKG 20 YTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGVFV RTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 1 - 788 of Q9ULM1, which also corresponds to amino acids 349 - 1136 of R30650._PEA_2_P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 25 isolated polypeptide encoding for a head of R30650_PEA_2_P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN 30 FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG

YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV

WO 2005/072053 PCT/IB2005/000928 163 NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWK of R30650_PEA_2_P15. 5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P15, comprising a first amino acid sequence being at least 90 % homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN 10 FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR 15 PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH 20 VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGI QLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNVTGIAFEDVPITSRVFF GEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND corresponding to amino acids 25 1 - 977 of Q8WUJ3, which also corresponds to amino acids 1 - 977 of R30650_PEA_2_P15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT 30 RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino WO 2005/072053 PCT/IB2005/000928 164 acids 978 - 1136 of R30650_PEA_2-P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_2_P15, comprising a polypeptide being 5 at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG in 10 R30650_PEA2P15. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P15, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGI-DQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG 20 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD corresponding to amino acids 25 1 - 564 of R30650_PEA_2_P15, and a second amino acid sequence being at least 90 % homologous to VDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNT FDFCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNL INCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDN 30 GVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDV

WLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGG

WO 2005/072053 PCT/IB2005/000928 165 LDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPH NNVTGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKND NWLVRHPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALT RSTHYQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILS 5 DVHNRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 8 - 579 of Q9NPN9, which also corresponds to amino acids 565 - 1136 of R30650_PEA_2_P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 10 isolated polypeptide encoding for a head of R30650_PEA_2_P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN 15 FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR 20 PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNUVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGD of R30650_PEA_2_P15. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P15, comprising a first amino acid 25 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG 30 YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV

NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG

WO 2005/072053 PCT/IB2005/000928 166 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG 5 GHIKFALGFKAAHLEGTELK-IMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS ARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS 10 GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH corresponding to amino acids 1 - 862 of R30650_PEA_2_P15, and a second amino acid sequence being at least 90 % homologous to SGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSALAFRLNNAWQSCPHNNV TGIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYPGSYLTKNDNWL 15 VRIPDCINVPDWRGAICSGCYAQMYIQAYKTSNLRMKIIKNDFPSHPLYLEGALTRSTH YQQYQPVVTLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVH NRLLKQTSKTGVFVRTLQMDKVEQSYPGRSHYYWDEDSG corresponding to amino acids 2 - 275 of Q9H1K5, which also corresponds to amino acids 863 - 1136 of R30650_PEA_2_P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 20 sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of R30650_PEA_2_P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRIIILIDNGGELHAGSALCPFQGN FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRHPWSFLTVKGNPSSSVEDHIEYHGHRG 30 SAAARVFKLFQTEHGEYFNVSLSSEWVQDVEWTEWFDHDKVSQTKGGEKISDLWKAH

PGKICNRPIDIQATTMDGVNLSTEVVYKKGQDYRFACYDRGRACRSYRVRFLCGKPVR

WO 2005/072053 PCT/IB2005/000928 167 PKLTVTIDTNVNSTILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQVLPCRSCAPNQV KVAGKPMYLHIGEEIDGVDMRAEVGLLSRNIIVMGEMEDKCYPYRNHICNFFDFDTFG GHIKFALGFKAAHLEGTELKHMGQQLVGQYPIHFHLAGDVDERGGYDPPTYIRDLSIHH TFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDR 5 DSKMCKMITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHH VPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIIS ARYSPHQDADPLIPREPAIRHFIAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLAS GGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDH of R30650_PEA_2_P15. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for R30650_PEA_2_P17, comprising a first amino acid sequence being at least 90 % homologous to MGAAGRQDFLFKAMLTISWLTLTCFPGATSTVAAGCPDQSPELQPWNPGHDQDHHVHI GQGKTLLLTSSATVYSIHISEGGKLVIKDHDEPIVLRTRHILIDNGGELHAGSALCPFQGN 15 FTIILYGRADEGIQPDPYYGLKYIGVGKGGALELHGQKKLSWTFLNKTLHPGGMAEGG YFFERSWGHRGVIVHVIDPKSGTVIHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAV NDEGSRNLDDMARKAMTKLGSKHFLHLGFRIHPWSFLTVKGNPSSSVEDHIEYHGHRG SAAARVFKLFQTEHGEYFNVSLSSEWVQ corresponding to amino acids 1 - 321 of Q8WUJ3, which also corresponds to amino acids 1 - 321 of R30650_PEA_2_P17, and a second 20 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEEFQTIW corresponding to amino acids 322 - 329 of R30650_PEA_2_P17, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of R30650_PEA_2_P17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEEFQTIW in R30650PEA_2_P17. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035P4, comprising a first amino acid sequence WO 2005/072053 PCT/IB2005/000928 168 being at least 90 % homologous to MPGLMRMRERYSASK-PLKGARIAGCLHMTVETAVLIETLVTLGAEVQWSSCNIFSTQD HAAAAIAKAGIPVYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYP QLLPGIRGISEETTTGVHNLYKMMANGILKVPAINVNDSVTKSKFDNLYGCRESLIDGIK 5 RATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTT MDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVN IKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDK YPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 29 - 432 of SAHHHUMAN, which also corresponds to amino 10 acids 1 - 404 of M78035_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035P6, comprising a first amino acid sequence being at least 90 % homologous to MILDDGGDLTNLIHTKYPQLLPGIRGISEETTTGVHNLYKMMANGILKVPAINVNDSVT 15 KSKFDNLYGCRESLIDGIKRATDVMIAGKVAVVAGYGDVGKGCAQALRGFGARVIITEI DPINALQAAMEGYEVTTMDEACQEGNIFVTTTGCIDIILGRHFEQMKDDAIVCNIGHFD VEIDVKWLNENAVEKVNIKPQVDRYRLKNGRRIILLAEGRLVNLGCAMGHPSFVMSNS FTNQVMAQIELWTHPDKYPVGVHFLPKKLDEAVAEAHLGKLNVKLTKLTEKQAQYLG MSCDGPFKPDHYRY corresponding to amino acids 127 - 432 of SAHH._HUMAN, which 20 also corresponds to amino acids 1 - 306 of M78035_P6. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for M78035P8, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 MSDKLPYKV corresponding to amino acids 1 - 9 of M78035_P8, and a second amino acid sequence being at least 90 % homologous to VYAWKGETDEEYLWCIEQTLYFKDGPLNMILDDGGDLTNLIHTKYPQLLPGIRGISEET TTGVHNLYKMMANGILKVPAINVNDSVTKSKFDNLYGCRESLIDGIKRATDVMIAGKV AVVAGYGDVGKGCAQALRGFGARVIITEIDPINALQAAMEGYEVTTMDEACQEGNIFV 30 TTTGCIDIILGRHFEQMKDDAIVCNIGHFDVEIDVKWLNENAVEKVNIKPQVDRYRLKN

GRRIILLAEGRLVNLGCAMGHPSFVMSNSFTNQVMAQIELWTHPDKYPVGVHFLPKKL

WO 2005/072053 PCT/IB2005/000928 169 DEAVAEAHLGKLNVKLTKLTEKQAQYLGMSCDGPFKPDHYRY corresponding to amino acids 99 - 432 of SAHHHUMAN, which also corresponds to amino acids 10 - 343 of M78035_P8, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 5 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of M78035_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDKLPYKV of M78035_P8. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEAPEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT 15 LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVL corresponding to amino acids 1 - 234 of CEA5_HUMAN, which also corresponds to amino acids 1 - 234 of HUMCEAPEA_1 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKN RRGGAASVLGGSGSTPYDGRNR corresponding to amino acids 235 - 315 of HUMCEAPEA_1_P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 25 According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCEAPEA_1_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKN 30 RRGGAASVLGGSGSTPYDGRNR in HUMCEA PEA_1_P4.

WO 2005/072053 PCT/IB2005/000928 170 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEAPEA 1_P5, comprising a first amino acid sequence being at least 90 % homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ 5 HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDA PTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTC QAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWV 10 NNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDD PTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQ ANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVN GQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTP IISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFV 15 SNLATGRNNSIVKSITVS corresponding to amino acids I - 675 of CEA5_HUMAN, which also corresponds to amino acids 1 - 675 of HUMCEAPEA_1_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS corresponding to amino 20 acids 676 - 719 of HUMCEAPEAlP5, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCEAPEA_1_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 25 at least about 90% and most preferably at least about 95% homologous to the sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS in HUMCEAPEA_1_P5. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEAPEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to 30 MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ

HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT

WO 2005/072053 PCT/IB2005/000928 171 LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDA PTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTC QAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWV 5 NNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDD PTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQ ANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVN GQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTP IISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFV 10 SNLATGRNNSIVKSITV corresponding to amino acids 1 - 674 of CEAS-HUMAN, which also corresponds to amino acids 1 - 674 of HUMCEAPEA_1_P7, and a second amino acid sequence being at least 90 % homologous to SAGATVGIMIGVLVGVALI corresponding to amino acids 684 - 702 of CEA5_HUMAN, which also corresponds to amino acids 675 - 693 of HUMCEAPEA1 1P7, wherein said first amino acid sequence and second amino acid sequence 15 are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEAPEA_1_P7, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 20 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise VS, having a structure as follows: a sequence starting from any of amino acid numbers 674-x to 674; and ending at any of amino acid numbers 675+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an 25 isolated chimeric polypeptide encoding for HUMCEAPEA_1_P10, comprising a first amino acid sequence being at least 90 % homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV 30 NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDS corresponding to amino acids 1 - 228 of CEA5_HUMAN, which also corresponds to amino acids 1 - 228 of WO 2005/072053 PCT/IB2005/000928 172 HUMCEAPEA_1_P10, and a second amino acid sequence being at least 90 % homologous to VILNVLYGPDDPTISPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNI TEKNSGLYTCQANNSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEA QNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPV 5 TLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITP NNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 407 - 702 of CEA5_HUMAN, which also corresponds to amino acids 229 - 524 of HUMCEAPEA_ _P1O, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 10 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEAPEA_1_PlO, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 15 least about 50 amino acids in length, wherein at least two amino acids comprise SV, having a structure as follows: a sequence starting from any of amino acid numbers 228-x to 228; and ending at any of amino acid numbers 229+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEAPEA_1_P19, comprising a first amino 20 acid sequence being at least 90 % homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT LHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILN 25 corresponding to amino acids 1 - 232 of CEA5_HUMAN, which also corresponds to amino acids 1 - 232 of HUMCEAPEA_1_P19, and a second amino acid sequence being at least 90 % homologous to VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNN GTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI 30 corresponding to amino acids 589 - 702 of CEA5_HUMAN, which also corresponds to amino WO 2005/072053 PCT/IB2005/000928 173 acids 233 - 346 of HUMCEAPEA_1_P19, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEAPEA_1_P19, 5 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise NV, having a structure as follows: a sequence starting from any of amino acid numbers 232-x to 232; and 10 ending at any of amino acid numbers 233+ ((n-2) - x), in which x varies from 0 to n-2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCEAPEA_1_P20, comprising a first amino acid sequence being at least 90 % homologous to MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ 15 HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYT LHVIKSDLVNEEATGQFRVYP corresponding to amino acids I - 142 of CEA5_HUMAN, which also corresponds to amino acids 1 - 142 of HUMCEAPEA_1 P20, and a second amino acid sequence being at least 90 % homologous to ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLT 20 LFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHS ASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASG TSPGLSAGATVGIMIGVLVGVALI corresponding to amino acids 499 - 702 of CEA5_HUMAN, which also corresponds to amino acids 143 - 346 of HUMCEAPEA_1_P20, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 25 sequential order. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for an edge portion of HUMCEAPEA_1_P20, 30 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino WO 2005/072053 PCT/IB2005/000928 174 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise PE, having a structure as follows: a sequence starting from any of amino acid numbers 142-x to 142; and ending at any of amino acid numbers 143+ ((n-2) - x), in which x varies from 0 to n-2. 5 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1APEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MPTSETESVNTENVSGEGENRGCCGSL corresponding to amino acids 466 - 492 of CCADHUMANV3, which also corresponds to amino acids 1 - 27 of 10 HUMCACH1A_PEA_1 P7, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WCWWRRRGAAKAGPSGCRRWG corresponding to amino acids 28 - 48 of HUMCACH IAPEA1 _P7, and a third amino acid sequence being at least 90 % homologous to 15 QAISKSKLSRRWRRWNRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTISSEHYNQPDWL TQIQDIANKVLLALFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGITETILVELEIMS PLGISVFRCVRLLRIFKVTRHWTSLSNLVASLLNSMKSIASLLLLLFLFIIIFSLLGMQLFG GKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWNAVMYDGIMAYGGPSSSGMIVCIYF IILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARKESLENKKNNKPE 20 VNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVPAGPRPRRISELN MKEKIAPIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSSAALAAEDPIRSHSFR NTILGYFDYAFTAIFTVEILLKMTTFGAFLHKGAFCRNYFNLLDMLVVGVSLVSFGIQSS AISVVKILRVLRVLRPLRAINRAKGLKHVVQCVFVAIRTIGNIMIVTTLLQFMFACIGVQ LFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSPVVRERIWQNSDFNFDNVLSAMMA 25 LFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVAFFMMNIFVGFVIVTFQE QGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWYVVNSSPFEYMMFVL IMLNTLCLAMQHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFKPKGYFSDAWNT FDSLIVIGSIIDVALSEADPTESENVPVPTATPGNSEESNRISITFFRLFRVMRLVKLLSRGE GIRTLLWTFIKSFQALPYVALLIAMLFFIYAVIGMQMFGKVAMRDNNQlNRNNNFQTFP 30 QAVLLLFRCATGEAWQEIMLACLPGKLCDPESDYNPGEEYTCGSNFAIVYFISFYMLCA

FLINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKGRIKHLDVVTLLRRI

WO 2005/072053 PCT/IB2005/000928 175 QPPLGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKIKTEGNLEQA NEELRAVIKKIWKKTSMKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFKKRKEQGL VGKYPAKNTTIALQAGLRTLHDIGPEIRRAISCDLQDDEPEETKREEEDDVFKRNGALLG NHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCHNHHNHNSI 5 GKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRT RYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQN YGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFN FECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATP PATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVP 10 SSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAA STLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 494 - 2161 of CCADHUMANV3, which also corresponds to amino acids 49 - 1716 of HUMCACH1A_PEA_1_P7, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential 15 order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for an edge portion of HUMCACH1 APEA_1 P7, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to 20 the sequence encoding for WCWWRRRGAAKAGPSGCRRWG, corresponding to HUMCACH1APEA_1_P7. According to preferred embodiments of the present invention, there is provided a bridge portion of HUMCACH1A_PEA_1_P7, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, 25 preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise L, having a structure as follows (numbering according to HUMCACH1A_PEA_1_P7): a sequence starting from any of amino acid numbers 492-x to 492; and ending at any of amino acid numbers 28 + ((n-2) - x), in which x varies from 0 to n-2. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACHIAPEA1_P13, comprising a first WO 2005/072053 PCT/IB2005/000928 l76 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL corresponding to amino acids 1 - 47 of HUMCACH1A_PEA_1_P13, and a second amino acid 5 sequence being at least 90 % homologous to DDEVTVGKFYATFLIQDYFRKFKKRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRR AISCDLQDDEPEETKREEEDDVFKRNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQ RPSIPPASDTEKPLFPPAGNSVCHNHHNHNSIGKQVPTSTNANLNNANMSKAAHGKRPS IGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLPTICREDPEIHGY 10 FRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERPRGYHHPQGFLE DDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPIFPHRTALPLHL MQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLIQVEQSEALDQ VNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSLVEAVLISEGL GRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVGPLSHRQDYE 15 LQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1598 - 2161 of CCADHUMAN, which also corresponds to amino acids 48 - 611 of HUMCACH1APEA1 P13, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an 20 isolated polypeptide encoding for a head of HUMCACH1APEA_1 P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLRPRCLLRRTAHPPHSAPAPAPARSKCLGSWSNVLIRESSVWSLRL of HUMCACH1APEA_1_P13. 25 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH1APEA_1_P14, comprising a first amino acid sequence being at least 90 % homologous to MSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSSVKRTRYYETYIRSDSGDEQLP TICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTWSRQNYGYYSRYPGRNIDSERP 30 RGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRRSSFNFECLRRQSSQEEVPSSPI

FPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRSWATPPATPPYRDWTPCYTPLI

WO 2005/072053 PCT/IB2005/000928 177 QVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPASLTVPSSFRNKNSDKQRSADSL VEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEMESAASTLLNGNVRPRANGDVG PLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITTL corresponding to amino acids 1763 - 2161 of CCADHUMAN, which also corresponds to amino acids 1 - 399 of 5 HUMCACH1APEA_1_P14. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for HUMCACH 1 A_PEA_1p 17, comprising a first amino acid sequence being at least 90 % homologous to MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQ 10 AAIDAARQAKAAQTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLN NPIRRACISIVEWKPFDIFILLAIFANCVALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVET FLKIIAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVILEQLTKETEGGNHSSGKSGGFDV KALRAFRVLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFIGKMH KTCFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLT 15 VFQCITMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSG corresponding to amino acids 1 - 407 of CCADHUMAN, which also corresponds to amino acids 1 - 407 of HUJMCACH1APEA_1_P17, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence HGGSRL 20 corresponding to amino acids 408 -413 of HUMCACH1A_PEAl P17, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a tail of HUMCACH1A_PEA_1_P17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence HGGSRL in HUMCACH1A_PEA_1_P17. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to 30 MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKG

AQTGAGLSQEAEDVDVSRARRVTDAPQGTLCGTGNRNSGSQSARVVGVAHLGEAFRV

WO 2005/072053 PCT/IB2005/000928 178 GVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPD YERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGGWRMGVRRTGQVGP TMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59 - 313 of MYEOHUMANVI, which also corresponds to amino acids 1 - 255 of 5 AA583399_PEA_1_P2. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_1_P4, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 10 the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG corresponding to amino acids 1 - 27 of AA583399_PEA1 1P4, and a second amino acid sequence being at least 90 % homologous to RNSGSQSARVVGVAHLGEAFRVGVEQAISSCPEEVHGRHGLSMEIMWARMDVALRSP GRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTV VTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLLLLIIILTC corresponding 15 to amino acids 150 - 313 of MYEOHUMANVI, which also corresponds to amino acids 28 191 of AA583399_PEA_1_P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. According to preferred embodiments of the present invention, there is provided an isolated polypeptide encoding for a head of AA583399_PEA_1_P4, comprising a polypeptide 20 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MSDLFIGFLVCSLSPLGTGTRCSCSPG of AA583399_PEA_1_P4. According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_1_P5, comprising a first amino 25 acid sequence being at least 90 % homologous to MEIMWARMDVALRSPGRGLLAGAGALCMTLAESSCPDYERGRRACLTLHRHPTPHCS TWGLPLRVAGSWLTVVTVEALGGWRMGVRRTGQVGPTMHPPPVSGASPLLLHHLLLL LLIILTC corresponding to amino acids 192 - 313 of MYEOHUMAN_V2, which also corresponds to amino acids 1 - 122 of AA583399_PEA_1_P5. 30 According to preferred embodiments of the present invention, there is provided an isolated chimeric polypeptide encoding for AA583399_PEA_1_P10, comprising a first amino WO 2005/072053 PCT/IB2005/000928 179 acid sequence being at least 90 % homologous to MFTRQAGHFVEGSKAGRSRGRLCLSQALRVAVRGAFVSLWFAAGAGDRERNKGDKG AQTGAGLSQEAEDVDVSRARRVTDAPQGTLCGTGNRNSGSQSARAVGVAHLGEAFRV GVEQAISSCPEEVHGRHGLSMEIMWAQMDVALRSPGRGLLAGAGALCMTLAESSCPD 5 YERGRRACLTLHRHPTPHCSTWGLPLRVAGSWLTVVTVEALGRWRMGVRRTGQVGPT MHPPPVSGASPLLLHHLLLLLLIIILTC corresponding to amino acids 59 - 313 of MYEOHUMANV3, which also corresponds to amino acids 1 - 255 of AA583399_PEA_1_PlO. According to preferred embodiments of the present invention, there is provided an 10 antibody capable of specifically binding to an epitope of an amino acid sequence as described herein. Optionally the amino acid sequence corresponds to a bridge, edge portion, tail, head or insertion as described herein. Optionally the antibody is capable of differentiating between a splice variant having said 15 epitope and a corresponding known protein. According to preferred embodiments of the present invention, there is provided a kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant as described herein. Optionally the kit comprises a NAT-based technology. 20 Optionally said the kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence as described herein. Optionally the kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence as described herein.The kit optionally comprises an antibody as described herein.The kit optionally further comprises at least one reagent for performing an ELISA or a Western blot. 25 There is optionally provided a method for detecting colon cancer, comprising detecting overexpression of a splice variant as described herein. Detecting overexpression is optionally performed with a NAT-based technology. Optionally s detecting overexpression is performed with an immunoassay, optionally wherein said immunoassay comprises an antibody as described herein. A biomarker capable of 30 detecting colon cancer, comprising any of the above nucleic acid sequences or a fragment thereof, or any of the above amino acid sequences or a fragment thereof. A method for screening WO 2005/072053 PCT/IB2005/000928 180 for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method for diagnosing colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method for monitoring disease progression and/or treatment efficacy and/or relapse of 5 colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein. A method of selecting a therapy for colon cancer, comprising detecting colon cancer cells with a biomarker or an antibody or a method or assay as described herein and selecting a therapy according to said detection. According to preferred embodiments of the present invention, preferably any of the 10 above nucleic acid and/or amino acid sequences further comprises any sequence having at least about 70%, preferably at least about 80%, more preferably at least about 90%, most preferably at least about 95% homology thereto. Unless otherwise noted, all experimental data relates to variants of the present invention, named according to the segment being tested (as expression was tested through RT-PCR as 15 described). All nucleic acid sequences and/or amino acid sequences shown herein as embodiments of the present invention relate to their isolated form, as isolated polynucleotides (including for all transcripts), oligonucleotides (including for all segments, amplicons and primers), peptides (including for all tails, bridges, insertions or heads, optionally including other antibody epitopes 20 as described herein) and/or polypeptides (including for all proteins). It should be noted that oligonucleotide and polynucleotide, or peptide and polypeptide, may optionally be used interchangeably. Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The 25 following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). All of these are hereby incorporated by reference 30 as if fully set forth herein. As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

WO 2005/072053 PCT/IB2005/000928 181 BRIEF DESCRIPTION OF DRAWINGS Figure 1. is schematic summary of cancer biomarkers selection engine and the wet 5 validation stages. Figure 2. Schematic illustration, depicting grouping of transcripts of a given cluster based on presence or absence of unique sequence regions. Figure 3 is schematic summary of quantitative real-time PCR analysis. 10 Figure 4 is schematic presentation of the oligonucleotide based microarray fabrication. Figure 5 is schematic summary of the oligonucleotide based microarray experimental flow. 15 Figure 6 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster M85491. 20 Figure 7 is a histogram showing expression of the Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in normal and cancerous colon tissues. 25 Figure 8 is a histogram showing the expression of M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in different normal tissues. Figure 9 is histogram, showing Cancer and cell-line vs. normal tissue expression for 30 Cluster T10888, demonstrating overexpression in colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma..

WO 2005/072053 PCT/IB2005/000928 182 Figure 10 is a histogram showing expression of the CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 (TI0888) transcripts which are detectable by amplicon as depicted in sequence name T10888 juncl 1-17, in nonnal and cancerous colon tissues. 5 Figure 11 is a the histogram showing the expression of T10888 transcripts, which are detectable by amplicon as depicted in sequence name T10888juncll-17, in different normal tissues. 10 Figure 12 is a histogram showing Cancer and cell-line vs. normal tissue expression for Cluster H14624. Figure 13 is a histogram, showing Cancer and cell-line vs. normal tissue expression for Cluster H53626, demonstrating overexpression in the epithelial malignant tumors, a mixture of 15 malignant tumors from different tissues and myosarcoma. Figure 14 is a histogram showing expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626 junc24-27F1R3, in normal and cancerous colon 20 tissues. Figure 15 is the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626seg25, in normal and cancerous colon tissues. 25 Figure 16 is a a histogram, showing Cancer and cell-line vs. normal tissue expression for Cluster HSENA78, demonstrating overexpression in the epithelial malignant tumors and lung malignant tumors. Figure 17 is a histogram, showing Cancer and cell-line vs. normal tissue expression for 30 the Cluster HUMODCA, demonstrating overexpression in the brain malignant tumors, WO 2005/072053 PCT/IB2005/000928 183 colorectal cancer, epithelial malignant tumors and a mixture of malignant tumors from different tissues. Figure 18 is a histogram, showing Cancer and cell-line vs. normal tissue expression for 5 the cluster R00299, demonstratin overexpression in the lung malignant tumors. Figure 19 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster Z44808, demonstrating overexpression in the colorectal cancer, lung cancer and pancreas carcinoma. 10 Figure 20 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster Z25299, demonstrating overexpression in the brain malignant tumors, a mixture of malignant tumors from different tissues and ovarian carcinoma. 15 Figure 21 is a histogram showing expression of Z25299 transcripts, which are detectable by amplicon as depicted in sequence name Z25299seg20, in normal and cancerous colon tissues. Figure 22 is a histogram showing the expression of Secretory leukocyte protease inhibitor 20 Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues Z25299 transcripts which are detectable by amplicon as depicted in sequence name Z25299seg20 in different normal tissues. 25 Figure 23 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster HUMANK, demonstrating overexpression in epithelial malignant tumors. Figure 24 is the histograms showing Cancer and cell-line vs. normal tissue 30 expression for the cluster HUMCA1XIA, demonstrating overexpression in the bone malignant WO 2005/072053 PCT/IB2005/000928 184 tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors. Figure 25 is the histograms showing Cancer and cell-line vs. normal tissue expression for 5 the cluster HSS 1 OOPCB, demonstrating overexpression in the mixture of malignant tumors from different tissues. Figure 26 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster D1 1853, demonstrating overexpression in the brain malignant tumors, colorectal 10 cancer and a mixture of malignant tumors from different tissues. Figure 27 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster RI 1723, demonstrating overexpression in the epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors 15 Figure 28 is the histogram showing expression of the RI 1723 transcripts, which are detectable by amplicon as depicted in sequence name RI 1723 seg1 3 in normal and cancerous colon tissues. 20 Figure 29 is the histogram showing expression of the R1 1723 transcripts, which are detectable by amplicon as depicted in sequence name R11723 junc11-18 in normal and cancerous colon tissues. Figure 30 is the histogram showing the expression of R1 1723 transcripts, detectable by 25 amplicon depicted in sequence name RI 1723seg13 in different normal tissues. Figure 31 is the histogram showing the expression of RI 1723 transcripts, detectable by amplicon in sequence name RI 1723 junc1 1-18 in different normal tissues. 30 Figure 32 is a histogram showing over expression of the SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein WO 2005/072053 PCT/IB2005/000928 185 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808junc8-11 in cancerous colon samples relative to the normal samples 5 Figure 33 is the histograms showing Cancer and cell-line vs. normal tissue expression for the cluster M77903, demonstrating overexpression in ovarian carcinoma and uterine malignancies. 10 Figure 34 is the histogram showing expression of the SSR-alpha M77903 transcripts, which are detectable by amplicon, as depicted in sequence name M77903segl8 in normal and cancerous colon tissues. Figure 35 is the histogram showing low over expression for amplicon M77903 junc20 15 34-35 in the experiment carried out with colon. Figure 36 is the histogram showing low over expression for amplicon M77903 junc20 28 in the experiment carried out with colon 20 Figures 37-38 are histograms showing differential expression of 6 sequences: (M85491seg24, M77903 seg18, M77903junc20-28, Z44808 junc8-11, Z25299 seg 20 and HSKITCR seg3 in nonnal and cancerous colon tissues, in different combinations. Figure 39 is a histogram showing the expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) 25 (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808 junc8-11 in different normal tissues. Figure 40 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster AA583399, demonstrating overexpression in brain malignant tumors, epithelial 30 malignant tumors, a mixture of malignant tumors from different tissues and gastric carcinoma.

WO 2005/072053 PCT/IB2005/000928 186 Figure 41 is the histogram showing expression of the AA583399 transcripts, which are detectable by amplicon as depicted in sequence name AA583399seg30-32, in normal and cancerous colon tissues. Figure 42 is the histogram showing expression of the AA583399 transcripts which are 5 detectable by amplicon as depicted in sequence name AA583399seg17 in normal and cancerous colon tissues. Figure 43 is the histogram showing expression of the AA583399 transcripts which are detectable by amplicon as depicted in sequence name AA583399seg1 in normal and cancerous colon tissues. 10 Figure 44 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster A1684092, demonstrating overexpression in brain malignant tumors, epithelial malignant tumors and a mixture of malignant tumors from different tissues. Figure 45 is the histogram showing expression of the AA5315457 transcripts which are detectable by amplicon as depicted in sequence name AA5315457seg8 in normal and cancerous 15 colon tissues. Figure 46 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HUMCACH1 A, demonstrating overexpression in a mixture of malignant tumors from different tissues. Figure 47 is the histogram showing expression of the Voltage-dependent L-type calcium 20 channel alpha-ID subunit Calcium channel, L type, alpha-i polypeptide, isoform 2 Transcripts, which are detectable by seg 113, 35, 109, 125,_in normal and cancerous colon tissues. Figure 48 is the histogram showing expression of the HUMCACHIA Transcripts, which are detectable by amplicon as depicted in sequence name HUMCACHIAseglO1in nonnal and cancerous colon tissues. 25 Figure 49 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HUMCEA, demonstrating overexpression in epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. Figure 50 is the histogram showing expression of the HUMCEA transcripts which are detectable by seg12 and seg9jn normal and cancerous colon tissues.

WO 2005/072053 PCT/IB2005/000928 187 Figure 51 is the histogram showing expression of the Carcinoembryonic antigen-related cell adhesion molecule 5 CEACAM5 HUMCEA transcripts which are detectable by armplicon as depicted in sequence name HUMCEA seg31 in nonnal and cancerous colon tissues. Figure 52 is the histogram showing expression of the Carcinoembryonic antigen-related 5 cell adhesion molecule 5 CEACAM5 HUMCEA transcripts which are detectable by amplicon as depicted in sequence name HUMCEA seg33 in normal and cancerous colon tissues. Figure 53 is the histogram showing expression of the Carcinoembryonic antigen-related cell adhesion molecule 5 CEACAIV5 HUMCEA transcripts which are detectable by amplicon as depicted in sequence name HUMCEA seg35 in normal and cancerous colon tissues. 10 Figure 54 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster M78035, demonstrating overexpression in brain malignant tumors, colorectal cancer, epithelial malignant tumors, a mixture of malignant tumors from different tissues, malignant tumors involving the lymph nodes and pancreas carcinoma. Figure 55 is the histogram showing expression of the S-adenosylhomocysteine hydrolase 15 (AHCY) M78035 transcripts, which are detectable by amplicon as depicted in sequence name M78035seg42, in normal and cancerous colon tissues Figure 56 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster R30650, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues. 20 Figure 57 is the histogram showing expression of the R30650 transcripts which are detectable by amplicon as depicted in sequence name R30650 seg76 in normal and cancerous colon tissues. Figure 58 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster T23657, demonstrating overexpression in epithelial malignant tumors. 25 Figure 59 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLC04A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 segl7-18, in normal and cancerous colon tissues. Figure 60 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as 30 depicted in sequence name T23657 seg22, in normal and cancerous colon tissues.

WO 2005/072053 PCT/IB2005/000928 188 Figure 61 is the histogram showing expression of solute carrier organic anion transporter family, member 4A1 (SLCO4A1) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg29-32, in normal and cancerous colon tissues. Figure 62 is the histogram showing expression of solute carrier organic anion transporter 5 family, member 4A1 (SLCO4AI) T23657 transcripts, which are detectable by amplicon as depicted in sequence name T23657 seg41, in normal and cancerous colon tissues. Figure 63 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster T51958, demonstrating overexpression in epithelial malignant tumors and a mixture of malignant tumors from different tissues. 10 Figure 64 is the histogram showing expression of PTK7 protein tyrosine kinase 7 (PTK7) T51958 transcripts which are detectable by amplicon as depicted in sequence name T 51958seg38 in normal and cancerous colon tissues. 15 Figure 65 is the histogram showing expression of PTK7 protein tyrosine kinase 7 (PTK7) T51958 transcripts which are detectable by amplicon as depicted in sequence name T 51958seg7 in nonnal and cancerous colon tissues. Figure 66 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster Z 17877, demonstrating overexpression in brain malignant tumors and malignant 20 tumors involving the bone marrow. Figure 67 is the histogram showing expression of c-myc-P64 mRNA, initiating from promoter PO Z 17877 transcripts, which are detectable by amplicon as depicted in sequence name Z17877seg8, in normal and cancerous colon tissues. Figure 68 is the histogram showing combined expression of 19 sequences (T23657seg 25 29, T23657seg 22, T23657seg 41, T23657segl7-18, AA315457seg8, R30650seg76, HUM CEASeg 33, CEA-Seg35, CEA-Seg3l, AA583399segl, AA583399seg17, AA58339-seg30-32, HUMCACH1Aseg101, HSHCGI seg20, HSHCGI seg35, M78035seg 42, T51958seg7, T51958 seg3 and, Z17877 seg8 ) in normal and cancerous colon tissues. Figure 69 is the histogram showing expression of TRIM31 tripartite motif 30 HSHCGI transcripts which are detectable by amplicon as depicted in sequence name HSHCGI seg20in normal and cancerous colon tissues.

WO 2005/072053 PCT/IB2005/000928 189 Figure 70 is the histogram showing expression of TRIM31 tripartite motif HSHCGI transcripts which are detectable by amplicon as depicted in sequence name HSHCGI seg35 in normal and cancerous colon tissues. Figure 71 is a histogram showing the expression of fibroblast growth factor receptor-like 5 1 (FGFRL1) transcripts detectable by or according to 1153626 seg25 amplicon(s) and H53626 seg25F and H53626 seg25R in different normal tissues. Figure 72 is a histogram showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon(s) and H53626 seg25F and H53626 junc24-27F I R3 in different normal tissues. 10 Figure 73 is a histogram showing over expression of the Matrix metalloproteinase 11 (stromelysin 3) (MMP 11) transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 junc21-27, in cancerous colon samples relative to the normal samples. Figure 74 is a histogram showing over expression of the Matrix metalloproteinase 11 (stromelysin 3) (MMP 11) transcripts, which are detectable by amplicon as depicted in sequence 15 name HSSTROL3 seg25, in cancerous colon samples relative to the normal samples. Figure 75 is the histogram showing Cancer and cell-line vs. normal tissue expression for the cluster HSSTROL3, demonstrating overexpression in transitional cell carcinoma, epithelial malignant tumors, a mixture of malignant tumors from different tissues and pancreas carcinoma. 20 Figure 76 is a histogram showing the expression of of Stromelysin-3 HSSTROL3 transcripts, which are detectable by amplicon as depicted in sequence name HSSTROL3 seg24, in different normal tissues. 25 DESCRIPTION OF PREFERRED EMBODIMENTS The present invention is of novel markers for colon cancer that are both sensitive and accurate. Biomolecular sequences (amino acid and/or nucleic acid sequences) uncovered using the methodology of the present invention and described herein can be efficiently utilized as tissue or pathological markers and/or as drugs or drug targets for treating or preventing a 30 disease.

WO 2005/072053 PCT/IB2005/000928 190 These markers are specifically released to the bloodstream under conditions of colon cancer and/or other colon pathology, and/or are otherwise expressed at a much higher level and/or specifically expressed in colon cancer tissue or cells. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can 5 correlate with a probable diagnosis of colon cancer and/or pathology. The present invention therefore also relates to diagnostic assays for colon cancer and/or colon pathology, and methods of use of such markers for detection of colon cancer and/or colon pathology, optionally and preferably in a sample taken from a subject (patient), which is more preferably some type of blood sample. 10 In another embodiment, the present invention relates to bridges, tails, heads and/or insertions, and/or analogs, homologs and derivatives of such peptides. Such bridges, tails, heads and/or insertions are described in greater detail below with regard to the Examples. As used herein a "tail" refers to a peptide sequence at the end of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice variant 15 having such a tail may optionally be considered as a chimera, in that at least a first portion of the splice variant is typically highly homologous (often 100% identical) to a portion of the corresponding known protein, while at least a second portion of the variant comprises the tail. As used herein a "head" refers to a peptide sequence at the beginning of an amino acid sequence that is unique to a splice variant according to the present invention. Therefore, a splice 20 variant having such a head may optionally be considered as a chimera, in that at least a first portion of the splice variant comprises the head, while at least a second portion is typically highly homologous (often 100% identical) to a portion of the corresponding known protein. As used herein "an edge portion" refers to a connection between two portions of a splice variant according to the present invention that were not joined in the wild type or known 25 protein. An edge may optionally arise due to a join between the above "known protein" portion of a variant and the tail, for example, and/or may occur if an internal portion of the wild type sequence is no longer present, such that two portions of the sequence are now contiguous in the splice variant that were not contiguous in the known protein. A "bridge" may optionally be an edge portion as described above, but may also include a join between a head and a "known 30 protein" portion of a variant, or a join between a tail and a "known protein" portion of a variant, or a join between an insertion and a "known protein" portion of a variant.

WO 2005/072053 PCT/IB2005/000928 191 Optionally and preferably, a bridge between a tail or a head or a unique insertion, and a "known protein" portion of a variant, comprises at least about 10 amino acids, more preferably at least about 20 amino acids, most preferably at least about 30 amino acids, and even more preferably at least about 40 amino acids, in which at least one amino acid is from the 5 tail/head/insertion and at least one amino acid is from the "known protein" portion of a variant. Also optionally, the bridge may comprise any number of amino acids from about 10 to about 40 amino acids (for example, 10, 11, 12, 13.. .37, 38, 39, 40 amino acids in length, or any number in between). It should be noted that a bridge cannot be extended beyond the length of the sequence in 10 either direction, and it should be assumed that every bridge description is to be read in such manner that the bridge length does not extend beyond the sequence itself. Furthermore, bridges are described with regard to a sliding window in certain contexts below. For example, certain descriptions of the bridges feature the following format: a bridge between two edges (in which a portion of the known protein is not present in the variant) may 15 optionally be described as follows: a bridge portion of CONTIG-NAME P1 (representing the name of the protein), comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise 20 XX (2 amino acids in the center of the bridge, one from each end of the edge), having a structure as follows (numbering according to the sequence of CONTIG-NAME Pl): a sequence starting from any of amino acid numbers 49-x to 49 (for example); and ending at any of amino acid numbers 50 + ((n-2) - x) (for example), in which x varies from 0 to n-2. In this example, it should also be read as including bridges in which n is any number of amino acids between 10-50 25 amino acids in length. Furthermore, the bridge polypeptide cannot extend beyond the sequence, so it should be read such that 49-x (for example) is not less than 1, nor 50 + ((n-2) - x) (for example) greater than the total sequence length. In another embodiment, this invention provides antibodies specifically recognizing the splice variants and polypeptide fragments thereof of this invention. Preferably such antibodies 30 differentially recognize splice variants of the present invention but do not recognize a WO 2005/072053 PCT/IB2005/000928 192 corresponding known protein (such known proteins are discussed with regard to their splice variants in the Examples below). In another embodiment, this invention provides an isolated nucleic acid molecule encoding for a splice variant according to the present invention, having a nucleotide sequence as 5 set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an isolated nucleic acid molecule, having a nucleotide sequence as set forth in any one of the sequences listed herein, or a sequence complementary thereto. In another embodiment, this invention provides an oligonucleotide of at least about 12 nucleotides, specifically hybridizable with the nucleic acid molecules of this 10 invention. In another embodiment, this invention provides vectors, cells, liposomes and compositions comprising the isolated nucleic acids of this invention. In another embodiment, this invention provides a method for detecting a splice variant according to the present invention in a biological sample, comprising: contacting a biological sample with an antibody specifically recognizing a splice variant according to the present 15 invention under conditions whereby the antibody specifically interacts with the splice variant in the biological sample but do not recognize known corresponding proteins (wherein the known protein is discussed with regard to its splice variant(s) in the Examples below), and detecting said interaction; wherein the presence of an interaction correlates with the presence of a splice variant in the biological sample. 20 In another embodiment, this invention provides a method for detecting a splice variant nucleic acid sequences in a biological sample, comprising: hybridizing the isolated nucleic acid molecules or oligonucleotide fragments of at least about a minimum length to a nucleic acid material of a biological sample and detecting a hybridization complex; wherein the presence of a hybridization complex correlates with the presence of a splice variant nucleic acid sequence in 25 the biological sample. According to the present invention, the splice variants described herein are non-limiting examples of markers for diagnosing colon cancer and/or colon pathology. Each splice variant marker of the present invention can be used alone or in combination, for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of 30 progression, therapy selection and treatment monitoring of colon cancer and/or colon pathology.

WO 2005/072053 PCT/IB2005/000928 193 According to optional but preferred embodiments of the present invention, any marker according to the present invention may optionally be used alone or combination. Such a combination may optionally comprise a plurality of markers described herein, optionally including any subcombination of markers, and/or a combination featuring at least one other 5 marker, for example a known marker. Furthermore, such a combination may optionally and preferably be used as described above with regard to determining a ratio between a quantitative or semi-quantitative measurement of any marker described herein to any other marker described herein, and/or any other known marker, and/or any other marker. With regard to such a ratio between any marker described herein (or a combination thereof) and a known marker, more 10 preferably the known marker comprises the "known protein" as described in greater detail below with regard to each cluster or gene. According to other preferred embodiments of the present invention, a splice variant protein or a fragment thereof, or a splice variant nucleic acid sequence or a fragment thereof, may be featured as a biomarker for detecting colon cancer and/or colon pathology, such that a 15 biomarker may optionally comprise any of the above. According to still other preferred embodiments, the present invention optionally and preferably encompasses any amino acid sequence or fragment thereof encoded by a nucleic acid sequence corresponding to a splice variant protein as described herein. Any oligopeptide or peptide relating to such an amino acid sequence or fragment thereof may optionally also 20 (additionally or alternatively) be used as a biomarker, including but not limited to the unique amino acid sequences of these proteins that are depicted as tails, heads, insertions, edges or bridges. The present invention also optionally encompasses antibodies capable of recognizing, and/or being elicited by, such oligopeptides or peptides. The present invention also optionally and preferably encompasses any nucleic acid 25 sequence or fragment thereof, or amino acid sequence or fragment thereof, corresponding to a splice variant of the present invention as described above, optionally for any application. Non-limiting examples of methods or assays are described below. The present invention also relates to kits based upon such diagnostic methods or assays. 30 Nucleic acid sequences and Oligonucleotides WO 2005/072053 PCT/IB2005/000928 194 Various embodiments of the present invention encompass nucleic acid sequences described hereinabove; fragments thereof, sequences hybridizable therewith, sequences homologous thereto, sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or 5 more nucleotides, either naturally occurring or artificially induced, either randomly or in a targeted fashion. The present invention encompasses nucleic acid sequences described herein; fragments thereof, sequences hybridizable therewith, sequences homologous thereto [e.g., at least 50 %, at least 55 %, at least 60%, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at 10 least 95 % or more say 100 % identical to the nucleic acid sequences set forth below], sequences encoding similar polypeptides with different codon usage, altered sequences characterized by mutations, such as deletion, insertion or substitution of one or more nucleotides, either naturally occurring or man induced, either randomly or in a targeted fashion. The present invention also encompasses homologous nucleic acid sequences (i.e., which form a part of a polynucleotide 15 sequence of the present invention) which include sequence regions unique to the polynucleotides of the present invention. In cases where the polynucleotide sequences of the present invention encode previously unidentified polypeptides, the present invention also encompasses novel polypeptides or portions thereof, which are encoded by the isolated polynucleotide and respective nucleic acid fragments 20 thereof described hereinabove. A "nucleic acid fragment" or an "oligonucleotide" or a "polynucleotide" are used herein interchangeably to refer to a polymer of nucleic acids. A polynucleotide sequence of the present invention refers to a single or double stranded nucleic acid sequences which is isolated and provided in the form of an RNA sequence, a complementary polynucleotide sequence (cDNA), a 25 genomic polynucleotide sequence and/or a composite polynucleotide sequences (e.g., a combination of the above). As used herein the phrase "complementary polynucleotide sequence" refers to a sequence, which results from reverse transcription of messenger RNA using a reverse transcriptase or any other RNA dependent DNA polymerase. Such a sequence can be 30 subsequently amplified in vivo or in vitro using a DNA dependent DNA polymerase.

WO 2005/072053 PCT/IB2005/000928 195 As used herein the phrase genomicc polynucleotide sequence" refers to a sequence derived (isolated) from a chromosome and thus it represents a contiguous portion of a chromosome. As used herein the phrase "composite polynucleotide sequence" refers to a sequence, 5 which is composed of genomic and cDNA sequences. A composite sequence can include some exonal sequences required to encode the polypeptide of the present invention, as well as some intronic sequences interposing therebetween. The intronic sequences can be of any source, including of other genes, and typically will include conserved splicing signal sequences. Such intronic sequences may further include cis acting expression regulatory elements. 10 Preferred embodiments of the present invention encompass oligonucleotide probes. An example of an oligonucleotide probe which can be utilized by the present invention is a single stranded polynucleotide which includes a sequence complementary to the unique sequence region of any variant according to the present invention, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion 15 according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein). Alternatively, an oligonucleotide probe of the present invention can be designed to hybridize with a nucleic acid sequence encompassed by any of the above nucleic acid sequences, 20 particularly the portions specified above, including but not limited to a nucleotide sequence coding for an amino sequence of a bridge, tail, head and/or insertion according to the present invention, and/or the equivalent portions of any nucleotide sequence given herein (including but not limited to a nucleotide sequence of a node, segment or amplicon described herein). Oligonucleotides designed according to the teachings of the present invention can be 25 generated according to any oligonucleotide synthesis method known in the art such as enzymatic synthesis or solid phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as 30 detailed in, for example, "Molecular Cloning: A laboratory Manual" Sambrook et al., (1989); "Current Protocols in Molecular Biology" Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et WO 2005/072053 PCT/IB2005/000928 196 al., "Current Protocols in Molecular Biology", John Wiley and Sons, Baltimore, Maryland (1989); Perbal, "A Practical Guide to Molecular Cloning", John Wiley & Sons, New York (1988) and "Oligonucleotide Synthesis" Gait, M. J., ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting and purification by for 5 example, an automated trityl-on method or HPLC. Oligonucleotides used according to this aspect of the present invention are those having a length selected from a range of about 10 to about 200 bases preferably about 15 to about 150 bases, more preferably about 20 to about 100 bases, most preferably about 20 to about 50 bases. Preferably, the oligonucleotide of the present invention features at least 17, at least 18, at least 10 19, at least 20, at least 22, at least 25, at least 30 or at least 40, bases specifically hybridizable with the biomarkers of the present invention. The oligonucleotides of the present invention may comprise heterocylic nucleosides consisting of purines and the pyrimidines bases, bonded in a 3' to 5' phosphodiester linkage. Preferably used oligonucleotides are those modified at one or more of the backbone, 15 internucleoside linkages or bases, as is broadly described hereinunder. Specific examples of preferred oligonucleotides useful according to this aspect of the present invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone, as disclosed in U.S. Pat. NOs: 4,469,863; 4,476,301; 20 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466, 677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050. Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters, 25 methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside 30 units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms can also be used.

WO 2005/072053 PCT/IB2005/000928 197 Alternatively, modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are fonned by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic intermucleoside linkages. These include those having 5 morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, 0, S and CH 2 component parts, as 10 disclosed in U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623, 070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439. Other oligonucleotides which can be used according to the present invention, are those 15 modified in both sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for complementation with the appropriate polynucleotide target. An example for such an oligonucleotide mimetic, includes peptide nucleic acid (PNA). United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of 20 which is herein incorporated by reference. Other backbone modifications, which can be used in the present invention are disclosed in U.S. Pat. No: 6,303,374. Oligonucleotides of the present invention may also include base modifications or substitutions. As used herein, "unmodified" or "natural" bases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). 25 Modified bases include but are not limited to other synthetic and natural bases such as 5 methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil 30 (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8 substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5- WO 2005/072053 PCT/IB2005/000928 198 substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8 azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further bases particularly useful for increasing the binding affinity of the oligomeric compounds of the invention include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 5 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methyleytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6 1.2 'C and are presently preferred base substitutions, even more particularly when combined with 2'-O-methoxyethyl sugar modifications. Another modification of the oligonucleotides of the invention involves chemically 10 linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not liniited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., hexyl-S tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues, a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-0-hexadecyl-rac 15 glycero-3-H-phosphonate, a polyamine or a polyethylene glycol chain, or adamantane acetic acid, a palmityl moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety, as disclosed in U.S. Pat. No: 6,303,374. It is not necessary for all positions in a given oligonucleotide molecule to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in 20 a single compound or even at a single nucleoside within an oligonucleotide. It will be appreciated that oligonucleotides of the present invention may include further modifications for more efficient use as diagnostic agents and/or to increase bioavailability, therapeutic efficacy and reduce cytotoxicity. To enable cellular expression of the polynucleotides of the present invention, a nucleic 25 acid construct according to the present invention may be used, which includes at least a coding region of one of the above nucleic acid sequences, and further includes at least one cis acting regulatory element. As used herein, the phrase "cis acting regulatory element" refers to a polynucleotide sequence, preferably a promoter, which binds a trans acting regulator and regulates the transcription of a coding sequence located downstream thereto. 30 Any suitable promoter sequence can be used by the nucleic acid construct of the present invention.

WO 2005/072053 PCT/IB2005/000928 199 Preferably, the promoter utilized by the nucleic acid construct of the present invention is active in the specific cell population transformed. Examples of cell type-specific and/or tissue specific promoters include promoters such as albumin that is liver specific, lymphoid specific promoters [Calame et al., (1988) Adv. Immunol. 43:235-275]; in particular promoters of T-cell 5 receptors [Winoto et al., (1989) EMBO J. 8:729-733] and immunoglobulins; [Banerji et al. (1983) Cell 33729-740], neuron-specific promoters such as the neurofilament promoter [Byrne et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477], pancreas-specific promoters [Edlunch et al. (1985) Science 230:912-916] or mammary gland-specific promoters such as the milk whey promoter (U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). 10 The nucleic acid construct of the present invention can further include an enhancer, which can be adjacent or distant to the promoter sequence and can function in up regulating the transcription therefrom. The nucleic acid construct of the present invention preferably further includes an appropriate selectable marker and/or an origin of replication. Preferably, the nucleic acid 15 construct utilized is a shuttle vector, which can propagate both in E coli (wherein the construct comprises an appropriate selectable marker and origin of replication) and be compatible for propagation in cells, or integration in a gene and a tissue of choice. The construct according to the present invention can be, for example, a plasnid, a bacmid, a phagemid, a cosmid, a phage, a virus or an artificial chromosome. 20 Examples of suitable constructs include, but are not limited to, pcDNA3, pcDNA3.1 (+/-), pGL3, PzeoSV2 (+/-), pDisplay, pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available from Invitrogen Co. (www.invitrogen.com). Examples of retroviral vector and packaging systems are those sold by Clontech, San Diego, Calif., includingRetro-X vectors pLNCX and pLXSN, which permit cloning into multiple cloning sites and the trasgene 25 is transcribed from CMV promoter. Vectors derived from Mo-MuLV are also included such as pBabe, where the transgene will be transcribed from the 5'LTR promoter. Currently preferred in vivo nucleic acid transfer techniques include transfection with viral or non-viral constructs, such as adenovirus, lentivirus, Herpes simplex I virus, or adeno associated virus (AAV) and lipid-based systems. Useful lipids for lipid-mediated transfer of the 30 gene are, for example, DOTMA, DOPE, and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65 (1996)]. The most preferred constructs for use in gene therapy are viruses, most WO 2005/072053 PCT/IB2005/000928 200 preferably adenoviruses, AAV, lentiviruses, or retroviruses. A viral construct such as a retroviral construct includes at least one transcriptional promoter/enhancer or locus-defining element(s), or other elements that control gene expression by other means such as alternate splicing, nuclear RNA export, or post-translational modification of messenger. Such vector 5 constructs also include a packaging signal, long terminal repeats (LTRs) or portions thereof, and positive and negative strand primer binding sites appropriate to the virus used, unless it is already present in the viral construct. In addition, such a construct typically includes a signal sequence for secretion of the peptide from a host cell in which it is placed. Preferably the signal sequence for this purpose is a mammalian signal sequence or the signal sequence of the 10 polypeptide variants of the present invention. Optionally, the construct may also include a signal that directs polyadenylation, as well as one or more restriction sites and a translation termination sequence. By way of example, such constructs will typically include a 5' LTR, a tRNA binding site, a packaging signal, an origin of second-strand DNA synthesis, and a 3' LTR or a portion thereof. Other vectors can be used that are non-viral, such as cationic lipids, 15 polylysine, and dendrimers. Hybridization assays Detection of a nucleic acid of interest in a biological sample may optionally be effected by hybridization-based assays using an oligonucleotide probe (non-limiting examples of probes 20 according to the present invention were previously described). Traditional hybridization assays include PCR, RT-PCR, Real-time PCR, RNase protection, in-situ hybridization, primer extension, Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection) (NAT type assays are described in greater detail below). More recently, PNAs have been described (Nielsen et al. 1999, Current 25 Opin. Biotechnol. 10:71-75). Other detection methods include kits containing probes on a dipstick setup and the like. Hybridization based assays which allow the detection of a variant of interest (i.e., DNA or RNA) in a biological sample rely on the use of oligonucleotides which can be 10, 15, 20, or 30 to 100 nucleotides long preferably from 10 to 50, more preferably from 40 to 50 nucleotides 30 long.

WO 2005/072053 PCT/IB2005/000928 201 Thus, the isolated polynucleotides (oligonucleotides) of the present invention are preferably hybridizable with any of the herein described nucleic acid sequences under moderate to stringent hybridization conditions. Moderate to stringent hybridization conditions are characterized by a hybridization 5 solution such as containing 10 % dextrane sulfate, I M NaCl, I % SDS and 5 x 106 cpm IP labeled probe, at 65 'C, with a final wash solution of 0.2 x SSC and 0.1 % SDS and final wash at 65'C and whereas moderate hybridization is effected using a hybridization solution containing 10 % dextrane sulfate, 1 M NaCl, 1 % SDS and 5 x 106 cpm 32 P labeled probe, at 65 'C, with a final wash solution of 1 x SSC and 0.1 % SDS and final wash at 50 *C. 10 More generally, hybridization of short nucleic acids (below 200 bp in length, e.g. 17-40 bp in length) can be effected using the following exemplary hybridization protocols which can be modified according to the desired stringency; (i) hybridization solution of 6 x SSC and 1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 pig/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature 15 of 1 - 1.5 'C below the Tm, final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS at 1 - 1.5 'C below the Tm; (ii) hybridization solution of 6 x SSC and 0.1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 pg/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature of 2 - 2.5 "C below the Tm, final wash solution of 3 M TMACI, 0.01 20 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS at 1 - 1.5 'C below the Tm, final wash solution of 6 x SSC, and final wash at 22 "C; (iii) hybridization solution of 6 x SSC and 1 % SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5 % SDS, 100 pg/ml denatured salmon sperm DNA and 0.1 % nonfat dried milk, hybridization temperature. 25 The detection of hybrid duplexes can be carried out by a number of methods. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Such labels refer to radioactive, fluorescent, biological or enzymatic tags or labels of standard use in the art. A label can be conjugated to either the oligonucleotide probes or the nucleic acids derived from the biological sample.

WO 2005/072053 PCT/IB2005/000928 202 Probes can be labeled according to numerous well known methods. Non-limiting examples of radioactive labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in 5 sensitivity of the method of the invention, include biotin and radio-nucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe. For example, oligonucleotides of the present invention can be labeled subsequent to synthesis, by incorporating biotinylated dNTPs or rNTP, or some similar means (e.g., photo 10 cross-linking a psoralen derivative of biotin to RNAs), followed by addition of labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin) or the equivalent. Alternatively, when fluorescently-labeled oligonucleotide probes are used, fluorescein, lissamine, phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5, Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al. (1992), Academic Press San Diego, Calif] can be attached to the 15 oligonucleotides. Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes. 20 It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. For instance, samples may be hybridized to an irrelevant probe and treated with RNAse A prior to hybridization, to assess false hybridization. Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing 25 the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods. As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples of radioactive labels include 3 H, 14C, 32 P, and 3S. 30 Those skilled in the art will appreciate that wash steps may be employed to wash away excess target DNA or probe as well as unbound conjugate. Further, standard heterogeneous assay WO 2005/072053 PCT/IB2005/000928 203 formats are suitable for detecting the hybrids using the labels present on the oligonucleotide primers and probes. It will be appreciated that a variety of controls may be usefully employed to improve accuracy of hybridization assays. 5 Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and a-nucleotides and the like. Probes of the invention can be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA. 10 NAT Assays Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example). As used herein, a "primer" defines an oligonucleotide which is capable of annealing to 15 (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions. Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit 20 particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and 25 Sambrook et al., 1989, supra). The terminology "amplification pair" (or "primer pair") refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes 30 include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based WO 2005/072053 PCT/IB2005/000928 204 amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions. In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially 5 expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of 10 differentially expressed nucleic acid sequences. The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods. Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes 15 employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning -A Laboratory Manual, 20 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.). It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected 25 based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity. The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in greater detail 30 below). The pair of oligonucleotides according to this aspect of the present invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures WO 2005/072053 PCT/IB2005/000928 205 which differ by less than that 7 'C, preferably less than 5 "C, more preferably less than 4 'C, most preferably less than 3 'C, ideally between 3 'C and 0 *C. Polynerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing 5 the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands 10 of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to fonn complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired 15 target sequence. The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be "PCR-amplified." 20 Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as "Ligase Amplification Reaction" (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is 25 added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base 30 changes: see for example Segev, PCT Publication No. W09001069 Al (1990). However, because the four oligonucleotides used in this assay can pair to form two short ligatable WO 2005/072053 PCT/IB2005/000928 206 fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions. Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially 5 amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5' end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo-and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of 10 transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs). Q-Beta (Q3) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for QP replicase. A previously identified 15 major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to 20 detect a mutation at the junction site, but not elsewhere. A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and QP systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., > 25 55 degrees C). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies. 30 The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the WO 2005/072053 PCT/IB2005/000928 207 population with each cycle. The final yield of any such doubling system can be expressed as: (I+X)n =y, where "X" is the rmean efficiency (percent copied in each cycle), "n" is the number of cycles, and "y" is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 5 100 %. If 20 cycles of PCR are performed, then the yield will be 220, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85 %, then the yield in those 20 cycles will be only 1.8520, or 220,513 copies of the starting material. In other words, a PCR running at 85 % efficiency will yield only 21 % as much final product, compared to a reaction running at 100 % efficiency. A reaction that is reduced to 50 % mean efficiency will 10 yield less than 1 % of the possible product. In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50 % mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes 15 prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products. Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA 20 (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to 25 penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling. Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also 30 the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq WO 2005/072053 PCT/IB2005/000928 208 polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3' end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. 5 This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect. A similar 3-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the 10 drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory. The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis. 15 When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal 20 intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the "Cycling Probe Reaction" (CPR), and "Branched DNA" (bDNA). 25 Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe 30 molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates WO 2005/072053 PCT/IB2005/000928 209 at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation. Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline 5 phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased. The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, 10 Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF). The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, 15 and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing. A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning 20 the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor-intense and expensive to be practical and effective in the clinical setting. In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule 25 can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or 30 by primer extension in the presence of chain-terminating nucleotide analogs.

WO 2005/072053 PCT/IB2005/000928 210 Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct 5 sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis). Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated 10 by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the "Mismatch Chemical Cleavage" (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory. 15 RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes have 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. 20 Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites. A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly 25 clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number. Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a 30 match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based WO 2005/072053 PCT/IB2005/000928 211 on the differences in the melting temperature of short DNA fragments differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip 5 oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations. With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are 10 inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest. Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor sequence changes. One of these methods, termed "Denaturing Gradient Gel Electrophoresis" (DGGE) is 15 based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes in their electrophoretic mobilities. The fragments to be 20 analyzed, usually PCR products, are "clamped" at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC "clamp" to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the 25 technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes. Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during 30 electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long WO 2005/072053 PCT/IB2005/000928 212 running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGE). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations. 5 A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to 10 running the gel. Single-Strand Conformation Polymorphism (SSCP): Another common method, called "Single-Strand Conformation Polymorphism" (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence 15 electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations. The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is 20 labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions. 25 Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments 30 as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the WO 2005/072053 PCT/IB2005/000928 213 analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations). In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of 5 greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90 % of single-base substitutions within a 200 base-pair fragment, the detection drops 10 to less than 50 % for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened. According to a presently preferred embodiment of the present invention the step of 15 searching for any of the nucleic acid sequences described here, in tumor cells or in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, QP-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific 20 oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting. Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes the candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as 25 phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station. describe the fabrication of fluidics devices and particularly microcapillary devices, in silicon and glass substrates. Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the 30 reporter groups already incorporated into the nucleic acid, which is now bound to the probes WO 2005/072053 PCT/IB2005/000928 214 attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be detennined. It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or 5 pathological condition both rapidly and easily. Amino acid sequences and peptides The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one 10 or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms "polypeptide," "peptide" and "protein" include glycoproteins, as well as non-glycoproteins. Polypeptide products can be biochemically synthesized such as by employing standard 15 solid phase techniques. Such methods include but are not limited to exclusive solid phase synthesis, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry. 20 Solid phase polypeptide synthesis procedures are well known in the art and further described by John Morrow Stewart and Janis Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce Chemical Company, 1984). Synthetic polypeptides can optionally be purified by preparative high performance liquid chromatography [Creighton T. (1983) Proteins, structures and molecular principles. WH 25 Freeman and Co. N.Y.], after which their composition can be confined via amino acid sequencing. In cases where large amounts of a polypeptide are desired, it can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516 544, Studier et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511 30 514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 WO 2005/072053 PCT/IB2005/000928 215 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463. The present invention also encompasses polypeptides encoded by the polynucleotide sequences of the present invention, as well as polypeptides according to the amino acid 5 sequences described herein. The present invention also encompasses homologues of these polypeptides, such homologues can be at least 50 %, at least 55 %, at least 60%, at least 65 %, at least 70 %, at least 75 %, at least 80 %, at least 85 %, at least 95 % or more say 100 % homologous to the amino acid sequences set forth below, as can be determined using BlastP software of the National Center of Biotechnology Information (NCBI) using default parameters, 10 optionally and preferably including the following: filtering on (this option filters repetitive or low-complexity sequences from the query using the Seg (protein) program), scoring matrix is BLOSUM62 for proteins, word size is 3, E value is 10, gap costs are 11, 1 (initialization and extension), and number of alignments shown is 50. Optionally and preferably, nucleic acid sequence homology/identity may be determined by using BlastN software of the National Center 15 of Biotechnology Information (NCBI) using default parameters, which preferably include using the DUST filter program, and also preferably include having an E value of 10, filtering low complexity sequences and a word size of 11. Finally, the present invention also encompasses fragments of the above described polypeptides and polypeptides having mutations, such as deletions, insertions or substitutions of one or more amino acids, either naturally occurring or 20 artificially induced, either randomly or in a targeted fashion. It will be appreciated that peptides identified according the present invention may be degradation products, synthetic peptides or recombinant peptides as well as peptidomimetics, typically, synthetic peptides and peptoids and semipeptoids which are peptide analogs, which may have, for example, modifications rendering the peptides more stable while in a body or 25 more capable of penetrating into cells. Such modifications include, but are not limited to N terminus modification, C terminus modification, peptide bond modification, including, but not limited to, CH2-NH, CH2-S, CH2-S=O, O=C-NH, CH2-0, CH2-CH2, S=C-NH, CH=CH or CF=CH, backbone modifications, and residue modification. Methods for preparing peptidomimetic compounds are well known in the art and are specified. Further details in this 30 respect are provided hereinunder.

WO 2005/072053 PCT/IB2005/000928 216 Peptide bonds (-CO-NH-) within the peptide may be substituted, for example, by N methylated bonds (-N(CH3)-CO-), ester bonds (-C(R)H-C-0-0-C(R)-N-), ketomethylen bonds (-CO-CH2-), a-aza bonds (-NH-N(R)-CO-), wherein R is any alkyl, e.g., methyl, carba bonds ( CH2-NH-), hydroxyethylene bonds (-CH(OH)-CH2-), thioamide bonds (-CS-NH-), olefinic 5 double bonds (-CH=CH-), retro amide bonds (-NH-CO-), peptide derivatives (-N(R)-CH2-CO-), wherein R is the "normal" side chain, naturally presented on the carbon atom. These modifications can occur at any of the bonds along the peptide chain and even at several (2-3) at the same time. Natural aromatic amino acids, Trp, Tyr and Phe, may be substituted for synthetic non 10 natural acid such as Phenylglycine, TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe, halogenated derivatives of Phe or o-methyl-Tyr. In addition to the above, the peptides of the present invention may also include one or more modified amino acids or one or more non-amino acid monomers (e.g. fatty acids, complex carbohydrates etc). 15 As used herein in the specification and in the claims section below the term "amino acid" or "amino acids" is understood to include the 20 naturally occurring amino acids; those amino acids often modified post-translationally in vivo, including, for example, hydroxyproline, phosphoserine and phosphothreonine; and other unusual amino acids including, but not limited to, 2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine, nor-leucine and ornithine. 20 Furthermore, the term "amino acid" includes both D- and L-amino acids. Table I non-conventional or modified amino acids which can be used with the present invention. Table 1 25 Non-conventional amino Code Non-conventional amino acid Code acid a-aminobutyric acid Abu L-N-methylalanine Nmala a-amino-a-methylbutyrate Mgabu L-N-methylarginine Nmarg aminocyclopropane- Cpro L-N-methylasparagine Nmasn WO 2005/072053 PCTIIB2005/000928 217 Carboxylate L-N-methylaspartic acid Nrnasp aminoisobutyric acid ibL-N-methylcysteine Nmcys arninonorbornyl- N orb L-N-rnethylglutamnine Nmgin Carboxylate L-N-methylglutamic acid Nmglu Cyclohexylalanine Ch-exa L-N-methylhistidine Nmhis Cyclopentylalanine Cpen L-N-methylisolleucine -Nmile D-alanine Dal L-N-methylleucine -Ninleu D-arginine D5arg L-N-methyllysie Nmlys D-aspartic acid Dasp L-N-methylmethionine Nmmuet D-cystoine Dcys L-N-methylnorleucine -Nnle D-glutamine D6g9n L-N-methylnorvaline Nrnnva D-glutamic acid Dglu L-N-methylornithine N T4mom D-histidine Dh-is L-N-methylphenylalanine Nm-phe D-isoleucine Dile L-N-methylproline -Nmpro D-leucine D-eu L-N methylserine Nrnser D-.Iysine Dlys L-N-methylthreonine Nmth D-methionine Dmet L-N-methyltryptophan Nmtrp D-omithine 150n L-N-methyltyrosine Nmtyr D-phenylalanine Dphe L-N-rnethylvaline Nrnval D-proline Dpro L-N-methylethylglycine Nmetg D-serine Dser L-N-inethyl-t--butylglycine Nmt-bug D-threonine Dthr L-norleucine NMe D-tryptophan Dtrp L-norvaline Nva D-tyrosine Dtyr - U-methyl-aminoisobutyrate EMaib D-vlin Dvl amehyl-y-aminobutyrate Mgab-u D-ax-methylalanine Dmala ax-nethylcyclohexylalanine Mohexa D-ax-methylarginine Dmarg a-methylcyclopentylalanine- MTcpen D-u-methylasparagine Dmasn c-niethyl-cx-napthylalanine -Manap D-ct-methylaspartate Dmasp (X- methylpenicillamine Mpen WO 2005/072053 PCT/1B2005/000928 21B D-cc-rethylcystei-ne Dmcys N-(4-aminobutyl)glycilne Nglu D-a-mnethylglutamine Dmgln N-(2-aminoethyl)glycine Naeg D-a-methylhistidine Dmhis N-(3-aminopropyl)glycine Norn D-at-methylisoleucine Dmile N- amino-ct-methylbutyrate Ninaabu D-ct-methylle-ucine Drnleu u--napthylalanine Anap D-cL-methyllysine Drnlys N-benizylglycine Nphe D-u.-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln D-u.-methylomithine Dinorn N-(carbamylmethyl)glycine Nasn D-a-metliylphenylalanilie Dmphe N-(2-carboxyethyl)glycine Nglu D-oa-methylproline Dmnpro N-(carboxymethyl)glycine Nasp D-a-methylserine Dmser N-cyclobutylglycine Ncbut D-c-methylthreonine Dmthr N-cycloheptylglycine Nchep D-a-methyltryptophan Dmtrp N-cyclohexylglycine Nchex D-c-methyltyrosine Dmty N-cyclodecylglycine Ncdec D-ca-methylvaline Dinval N-cyclododeclglycine Ncdod D-a-rnethylalnine Dnmala N-cyclooctylglycine Neoct D-a-niethylarginine Dnarg N-cyclopropylglycine Ncpro D-a-methylasparagine Dnmasn N-cycloundecylglycine Ncund D-c-methylasparatate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm D-a-methylcysteine Drncys N-(3,3- Nbhe diphenylpropyl)glycine D-N-methylleucine Dnrnleu N-(3-indolylyethyl) glycine Nhtrp D-N-methyllysine Dnrnlys N-methyl-y-aminobutyrate Nmgabu N- Nnichexa D-N-methylmethionine Dnmnet inethylcyclohexylalanine D-.N-methylornithine Dnom N-methyleyclopenitylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnphe N-methylaminoisobutyrate Ninaib D-N-methylproline D-nmpro N-(l -methylpropyl)glycine Nile D-N-methylserine Dnmser WO 2005/072053 PCTIIB2005/000928 219 N-(2-rnethylprplgyieNe D-N-1-nethylserine Dnr-nser N-(2-methylpropyl)glycine Nleu D-N-i-nethylthreonine Dnmthr D-N-n-ethyltryptophan D1nm~trp N-( 1 -methylethyl)glycine INva D-N-inethyltyrosine Dnmyr N-methyla-napthylalanine 1'4manap D-N-methylvaline Dun--val N-rnethylpenicillamine Nmpen 'y-aminobutyric acid G-a-bu N-(p-.hydroxyphenyl)glycine Nhtyr L-t-butylglycine Thug N-(thiomethyl)glycine NKcys L-ethylglycine Etg penicillamine Pen L-hornophenylalanine Hphe L-cc-methylalanine Mala L-a-methylarginine Marg L-c-Inthylasparagine Masn L-a-metliylaspartate Masp L-c-methyl-l-butylglycine Mtb-ug L-cc-methylcysteine Mcys L-methylethylglycine Metg L-c-rethylglutanmine Mgln L-ct-methylglutamate Mglu L-cc-methylhistidine Mhis L-a-methylhomo Mhphe phenylalanine L-a-methylisoleucine Mile N-(2-rnethylthioety~lcn Nmet D-N-rnethylglutamine Dnmgln N-(3- Narg guanidinopropyl)glycine D-N-methylglutamnate Dnglu N-(1-hydroxyethyl)glycine Nthr D-N-methylhistidine Dnmhis N-(hydroxyethyl)glycine Nser D-N-methylisoleucine Dnle N-(imidazolylethyl)glycine Nhis D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtrp D-N-methyllysine Dnmlys N-methyl-y-aminobutyrate Nmgabu N- Nmchexa D-N-inethylmethionine Dnnuet methylcyclohexylalanine D-N-methylornitrmne, Dnmorn N-methylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylaminoisobutyrate N maib D-N-methylproline Dnmpro N-(1 -methylpropyl)glycine Niq~le D-N-methylserine Dnser WO 2005/072053 PCTIIB2005/000928 220 N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-rnethyltryptophan D-n-mtrp N-(1 -methylethyl)glycine Nval D-N-rnethyltyrosine Dnmtyr N-methyla-napthylalanine N- m-anap D-N-rnethylvaline Dnmval N-methylpenicillamine Nmpen y-aminobutyric acid Gabu N-(p-hiydroxyphenyl)glycine Nhtyr L-1-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-hornophenylalanine Hphe L-a-methylalanine Mal-a L-c-methylarginine M~arg L-Qx-rethylasparagiie Masn L-ca-rethylaspartate MasP L-a-rnetliyl-t-butylglycine Mtbug L-cx-methyleysteine Mcs L-methylethylglycine Metg L-cx-methylglutamine Mgln L-cc-nethylglutamate Mglu L-ot-methylhistidine Mhis Lu-Mhphe methyihomophenylalanine L-ax-methylisoleucine Mile N-(2-methylthioethyl)glycine Nrnet L-a-methylleucine Mleu L-u-methyllysine Mlys L-cc-methylrnethionine Mmet L-a-methylnorleucine Mnle L-a-meothylnorvaline Mnva L-oi-methylornithine Mom L-a-methylphenylalanine Mphe L-a-methylproline Mpro L-c-methylserine mser L-cx-methylthreonie Mthr L-c-methylvaline Mtrp L-c-methyltyrosine Mtyr L-c-methylleucine ~v-al -L-N- Nmhplie Nnbhm methyihomophenylalanine N-(N-(2,2-diphenylethyl) N-(N-(3,3--diphenylpropyl) carbamylmethyl-glycine Nnbhm carbamylmethyl(1 )glycine Nbe 1 -carboxy--l-(2,2-diphenyl N4mbc ethylaniino)cyclopropane Table]I Cont!.

WO 2005/072053 PCT/IB2005/000928 221 Since the peptides of the present invention are preferably utilized in diagnostics which require the peptides to be in soluble fonn, the peptides of the present invention preferably include one or more non-natural or natural polar amino acids, including but not limited to serine and threonine which are capable of increasing peptide solubility due to their hydroxyl-containing 5 side chain. The peptides of the present invention are preferably utilized in a linear form, although it will be appreciated that in cases where cyclicization does not severely interfere with peptide characteristics, cyclic forms of the peptide can also be utilized. The peptides of present invention can be biochemically synthesized such as by using 10 standard solid phase techniques. These methods include exclusive solid phase synthesis well known in the art, partial solid phase synthesis methods, fragment condensation, classical solution synthesis. These methods are preferably used when the peptide is relatively short (i.e., 10 kDa) and/or when it cannot be produced by recombinant techniques (i.e., not encoded by a nucleic acid sequence) and therefore involves different chemistry. 15 Synthetic peptides can be purified by preparative high performance liquid chromatography and the composition of which can be confirmed via amino acid sequencing. In cases where large amounts of the peptides of the present invention are desired, the peptides of the present invention can be generated using recombinant techniques such as described by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier et al. (1990) 20 Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science 224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant Molecular Biology, Academic Press, NY, Section VIII, pp 421-463 and also as described above. 25 Antibodies "Antibody" refers to a polypeptide ligand that is preferably substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds 30 and recognizes an epitope (e.g., an antigen). The recognized immunoglobulin genes include the kappa and lambda light chain constant region genes, the alpha, gamma, delta, epsilon and mu WO 2005/072053 PCT/IB2005/000928 222 heavy chain constant region genes, and the myriad-immunoglobulin variable region genes. Antibodies exist, e.g., as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. This includes, e.g., Fab' and F(ab)' 2 fragments. The term "antibody," as used herein, also includes antibody fragments either produced by the 5 modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies. It also includes polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, or single chain antibodies. "Fc" portion of an antibody refers to that portion of an immunoglobulin heavy chain that comprises one or more heavy chain constant region domains, CHI, CH2 and CH3, but does not include the heavy chain variable 10 region. The functional fragments of antibodies, such as Fab, F(ab')2, and Fv that are capable of binding to macrophages, are described as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy 15 chain; (2) Fab', the fragment of an antibody molecule that can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together by two disulfide 20 bonds; (4) Fv, defined as a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody ("SCA"), a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. 25 Methods of producing polyclonal and monoclonal antibodies as well as fragments thereof are well known in the art (See for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988, incorporated herein by reference). Antibody fragments according to the present invention can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli or mammalian cells (e.g. Chinese hamster 30 ovary cell culture or other protein expression systems) of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by WO 2005/072053 PCT/IB2005/000928 223 conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab')2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' 5 monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly. These methods are described, for example, by Goldenberg, U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained therein, which patents are hereby incorporated by reference in their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126 (1959)]. Other methods of cleaving antibodies, such as separation 10 of heavy chains to form monovalent light-heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody. Fv fragments comprise an association of VH and VL chains. This association may be noncovalent, as described in Inbar et al. [Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. 15 Alternatively, the variable chains can be linked by an intermolecular disulfide bond or cross linked by chemicals such as glutaraldehyde. Preferably, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (sFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VH and VL domains connected by an oligonucleotide. The structural gene is inserted into an expression 20 vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing sFvs are described, for example, by [Whitlow and Filpula, Methods 2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778, which is hereby incorporated by reference in its entirety. 25 Another form of an antibody fragment is a peptide coding for a single complementarity determining region (CDR). CDR peptides ("minimal recognition units") can be obtained by constructing genes encoding the CDR of an antibody of interest. Such genes are prepared, for example, by using the polymerase chain reaction to synthesize the variable region from RNA of antibody-producing cells. See, for example, Larrick and Fry [Methods, 2: 106-10 (1991)]. 30 Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') or WO 2005/072053 PCT/IB2005/000928 224 other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human inununoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as 5 mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in 10 which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323 15 329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)]. Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially 20 performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science, 239:1534 1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been 25 substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); 30 Marks et al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal WO 2005/072053 PCT/IB2005/000928 225 Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(l):86-95 (1991)]. Similarly, human antibodies can be made by introduction of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human 5 antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al., Bio/Technology 10,: 779 783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368 812-13 (1994); 10 Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995). Preferably, the antibody of this aspect of the present invention specifically binds at least one epitope of the polypeptide variants of the present invention. As used herein, the term "epitope" refers to any antigenic determinant on an antigen to which the paratope of an antibody 15 binds. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or carbohydrate side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. Optionally, a unique epitope may be created in a variant due to a change in one or more 20 post-translational modifications, including but not limited to glycosylation and/or phosphorylation, as described below. Such a change may also cause a new epitope to be created, for example through removal of glycosylation at a particular site. An epitope according to the present invention may also optionally comprise part or all of a unique sequence portion of a variant according to the present invention in combination with at 25 least one other portion of the variant which is not contiguous to the unique sequence portion in the linear polypeptide itself, yet which are able to form an epitope in combination. One or more unique sequence portions may optionally combine with one or more other non-contiguous portions of the variant (including a portion which may have high homology to a portion of the known protein) to form an epitope. 30 Immunoassays WO 2005/072053 PCT/IB2005/000928 226 In another embodiment of the present invention, an immunoassay can be used to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises: providing an antibody that specifically binds to a marker; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample. 5 To prepare an antibody that specifically binds to a marker, purified protein markers can be used. Antibodies that specifically bind to a protein marker can be prepared using any suitable methods known in the art. After the antibody is provided, a marker can be detected and/or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, 10 an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). Generally, a sample obtained from a subject can be contacted with the antibody that specifically binds the marker. Optionally, the antibody can be fixed to a solid support to facilitate washing and 15 subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are not limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies can also be attached to a solid support. After incubating the sample with antibodies, the mixture is washed and the antibody marker complex formed can be detected. This can be accomplished by incubating the washed 20 mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture. 25 Throughout the assays, incubation and/or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations and the like. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range 30 of temperatures, such as 10 'C to 40 "C.

WO 2005/072053 PCT/IB2005/000928 227 The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample can be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibody-marker complex with an antibody that specifically binds the marker under suitable incubation 5 conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and/or signal. Preferably used are antibodies which specifically interact with the polypeptides of the 10 present invention and not with wild type proteins or other isoforms thereof, for example. Such antibodies are directed, for example, to the unique sequence portions of the polypeptide variants of the present invention, including but not limited to bridges, heads, tails and insertions described in greater detail below. Preferred embodiments of antibodies according to the present invention are described in greater detail with regard to the section entitled "Antibodies". 15 Radio-immunoassay (RIA): In one version, this method involves precipitation of the desired substrate and in the methods detailed hereinbelow, with a specific antibody and radiolabelled antibody binding protein (e.g., protein A labeled with I 125) immobilized on a precipitable carrier such as agarose beads. The number of counts in the precipitated pellet is proportional to the amount of substrate. 20 In an alternate version of the RIA, a labeled substrate and an unlabelled antibody binding protein are employed. A sample containing an unknown amount of substrate is added in varying amounts. The decrease in precipitated counts from the labeled substrate is proportional to the amount of substrate in the added sample. Enzyme linked immunosorbent assay (ELISA): This method involves fixation of a sample 25 (e.g., fixed cells or a proteinaceous solution) containing a protein substrate to a surface such as a well of a microtiter plate. A substrate specific antibody coupled to an enzyme is applied and allowed to bind to the substrate. Presence of the antibody is then detected and quantitated by a colorimetric reaction employing the enzyme coupled to the antibody. Enzymes commonly employed in this method include horseradish peroxidase and alkaline phosphatase. If well 30 calibrated and within the linear range of response, the amount of substrate present in the sample WO 2005/072053 PCT/IB2005/000928 228 is proportional to the amount of color produced. A substrate standard is generally employed to improve quantitative accuracy. Western blot: This method involves separation of a substrate from other protein by means of an acrylamide gel followed by transfer of the substrate to a membrane (e.g., nylon or PVDF). 5 Presence of the substrate is then detected by antibodies specific to the substrate, which are in turn detected by antibody binding reagents. Antibody binding reagents may be, for example, protein A, or other antibodies. Antibody binding reagents may be radiolabelled or enzyme linked as described hereinabove. Detection may be by autoradiography, colorimetric reaction or chemiluminescence. This method allows both quantitation of an amount of substrate and 10 determination of its identity by a relative position on the membrane which is indicative of a migration distance in the acrylamide gel during electrophoresis. Inmmunohistochemical analysis: This method involves detection of a substrate in situ in fixed cells by substrate specific antibodies. The substrate specific antibodies may be enzyme linked or linked to fluorophores. Detection is by microscopy and subjective evaluation. If 15 enzyme linked antibodies are employed, a colorimetric reaction may be required. Fluorescence activated cell sorting (FACS): This method involves detection of a substrate in situ in cells by substrate specific antibodies. The substrate specific antibodies are linked to fluorophores. Detection is by means of a cell sorting machine which reads the wavelength of light emitted from each cell as it passes through a light beam. This method may 20 employ two or more antibodies simultaneously. Radio-imaging Methods 25 These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non invasive, and can be used to detect and/or measure a wide variety of tissue events and/or functions, such as detecting cancerous cells for example. Unlike PET, SPECT can optionally be used with two labels simultaneously. SPECT has some other advantages as well, for example 30 with regard to cost and the types of labels that can be used. For example, US Patent No.

WO 2005/072053 PCT/IB2005/000928 229 6,696,686 describes the use of SPECT for detection of breast cancer, and is hereby incorporated by reference as if fully set forth herein. Display Libraries 5 According to still another aspect of the present invention there is provided a display library comprising a plurality of display vehicles (such as phages, viruses or bacteria) each displaying at least 6, at least 7, at least 8, at least 9, at least 10, 10-15, 12-17, 15-20, 15-30 or 20 50 consecutive amino acids derived from the polypeptide sequences of the present invention. Methods of constructing such display libraries are well known in the art. Such methods 10 are described in, for example, Young AC, et al., "The three-dimensional structures of a polysaccharide binding antibody to Cryptococcus neoformans and its complex with a peptide from a phage display library: implications for the identification of peptide mimotopes" J Mol Biol 1997 Dec 12;274(4):622-34; Giebel LB et al. "Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities" Biochemistry 1995 Nov 15 28;34(47):15430-5; Davies EL et al., "Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes" J Immunol Methods 1995 Oct 12;186(1):125-35; Jones C RT al. "Current trends in molecular recognition and bioseparation" J Chromatogr A 1995 Jul 14;707(1):3-22; Deng SJ et al. "Basis for selection of improved carbohydrate-binding single-chain antibodies from synthetic gene libraries" Proc Natl Acad Sci 20 U S A 1995 May 23;92(11):4992-6; and Deng SJ et al. "Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display" J Biol Chem 1994 Apr 1;269(13):9533-8, which are incorporated herein by reference. The following sections relate to Candidate Marker Examples (first section) and to 25 Experimental Data for these Marker Examples (second section). It should be noted that Table numbering is restarted within each section. CANDIDATE MARKER EXAMPLES SECTION 30 This Section relates to Examples of sequences according to the present invention, including illustrative methods of selection thereof WO 2005/072053 PCT/IB2005/000928 230 Description of the methodology undertaken to uncover the biomolecular sequences of the present invention Human ESTs and cDNAs were obtained from GenBank versions 136 (June 15, 2003 ftp.ncbi.nih.gov/genbank/release.notes/gb1 36 .release.notes); NCBI genome assembly of April 5 2003; RefSeq sequences from June 2003; Genbank version 139 (December 2003); Human Genome from NCBI (Build 34) (from Oct 2003); and RefSeq sequences from December 2003; and from the LifeSeq library of Incyte Corporation (Wilmington, DE, USA; ESTs only). With regard to GenBank sequences, the human EST sequences from the EST (GBEST) section and the human mRNA sequences from the primate (GBPRI) section were used; also the human 10 nucleotide RefSeq mRNA sequences were used (see for example www.nebi.nlm.nih.gov/Genbank/GenbankOverview.html and for a reference to the EST section, see www.nebi.nlm.nih.gov/dbEST/; a general reference to dbEST, the EST database in GenBank, may be found in Boguski et al, Nat Genet. 1993 Aug;4(4):332-3; all of which are hereby incorporated by reference as if fully set forth herein). 15 Novel splice variants were predicted using the LEADS clustering and assembly system as described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); US patent No: 6,625,545; and U.S. Pat. Apple. No. 10/426,002, published as US20040101876 on May 27 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from 20 repeats, vectors and inmunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into "clusters" that represent genes or partial genes. These were annotated using the GeneCarta (Compugen, Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich pool of annotations, sequence information (particularly of 25 spliced sequences), chromosomal information, alignments, and additional information such as SNPs, gene ontology terms, expression profiles, functional analyses, detailed domain structures, known and predicted proteins and detailed homology reports. A brief explanation is provided with regard to the method of selecting the candidates. However, it should noted that this explanation is provided for descriptive purposes only, and is 30 not intended to be limiting in any way. The potential markers were identified by a computational process that was designed to find genes and/or their splice variants that are over-expressed in WO 2005/072053 PCT/IB2005/000928 231 tumor tissues, by using databases of expressed sequences. Various parameters related to the information in the EST libraries, determined according to a manual classification process, were used to assist in locating genes and/or splice variants thereof that are over-expressed in cancerous tissues. The detailed description of the selection method is presented in Example 1 5 below. The cancer biomarkers selection engine and the following wet validation stages are schematically summarized in Figure 1. EXAMPLE I Identification of differentially expressed gene products - Algorithm In order to distinguish between differentially expressed gene products and constitutively 10 expressed genes (i.e., house keeping genes ) an algorithm based on an analysis of frequencies was configured. A specific algorithm for identification of transcripts over expressed in cancer is described hereinbelow. Dry analysis Library annotation - EST libraries are manually classified according to: 15 (i) Tissue origin (ii) Biological source - Examples of frequently used biological sources for construction of EST libraries include cancer cell-lines; normal tissues; cancer tissues; fetal tissues; and others such as nonnal cell lines and pools of normal cell-lines, cancer cell-lines and combinations thereof. A specific description of 20 abbreviations used below with regard to these tissues/cell lines etc is given above. (iii) Protocol of library construction - various methods are known in the art for library construction including normalized library construction; non-normalized library construction; subtracted libraries; ORESTES and others. It will be 25 appreciated that at times the protocol of library construction is not indicated. The following rules are followed: EST libraries originating from identical biological samples are considered as a single library. EST libraries which included above-average levels of contamination, such as DNA 30 contamination for example, were eliminated. The presence of such contamination was determined as follows. For each library, the number of unspliced ESTs that are not fully contained within WO 2005/072053 PCT/IB2005/000928 232 other spliced sequences was counted. If the percentage of such sequences (as compared to all other sequences) was at least 4 standard deviations above the average for all libraries being analyzed, this library was tagged as being contaminated and was eliminated from further consideration in the below analysis (see also Sorek, R. & Safer, H.M. A novel algorithm for 5 computational identification of contaminated EST libraries. Nucleic Acids Res 31, 1067-74 (2003)for further details). Clusters (genes) having at least five sequences including at least two sequences from the tissue of interest were analyzed. Splice variants were identified by using the LEADS software package as described above. 10 EXAMPLE 2 Identification of genes over expressed in cancer. Two different scoring algorithms were developed. Libraries score -candidate sequences which are supported by a number of cancer libraries, 15 are more likely to serve as specific and effective diagnostic markers. The basic algorithm - for each cluster the number of cancer and normal libraries contributing sequences to the cluster was counted. Fisher exact test was used to check if cancer libraries are significantly over-represented in the cluster as compared to the total number of cancer and normal libraries. 20 Library counting: Small libraries (e.g., less than 1000 sequences) were excluded from consideration unless they participate in the cluster. For this reason, the total number of libraries is actually adjusted for each cluster. Clones no. score - Generally, when the number of ESTs is much higher in the cancer libraries relative to the nonnal libraries it might indicate actual over-expression. 25 The algorithm Clone counting: For counting EST clones each library protocol class was given a weight based on our belief of how much the protocol reflects actual expression levels: (i) non-normalized: 1 (ii) normalized: 0.2 30 (iii) all other classes : 0.1 WO 2005/072053 PCT/IB2005/000928 233 Clones number score - The total weighted number of EST clones from cancer libraries was compared to the EST clones from normal libraries. To avoid cases where one library contributes to the majority of the score, the contribution of the library that gives most clones for a given cluster was limited to 2 clones. 5 The score was computed as c+1 C 1 +1 N where: 10 c - weighted number of "cancer" clones in the cluster. C- weighted number of clones in all "cancer" libraries. n - weighted number of "normal" clones in the cluster. N- weighted number of clones in all "normal" libraries. Clones number score significance - Fisher exact test was used to check if EST clones from 15 cancer libraries are significantly over-represented in the cluster as compared to the total number of EST clones from cancer and normal libraries. Two search approaches were used to find either general cancer-specific candidates or tumor specific candidates. " Libraries/sequences originating from tumor tissues are counted as well as 20 libraries originating from cancer cell-lines ("normal" cell-lines were ignored). " Only libraries/sequences originating from tumor tissues are counted EXAMPLE 3 25 Identification of tissue specific genes For detection of tissue specific clusters, tissue libraries/sequences were compared to the total number of libraries/sequences in cluster. Similar statistical tools to those described in above were employed to identify tissue specific genes. Tissue abbreviations are the same as for cancerous tissues, but are indicated with the header "normal tissue".

WO 2005/072053 PCT/IB2005/000928 234 The algorithm - for each tested tissue T and for each tested cluster the following were examined: 1. Each cluster includes at least 2 libraries from the tissue T. At least 3 clones (weighed - as described above) from tissue T in the cluster; and 5 2. Clones from the tissue T are at least 40 % from all the clones participating in the tested cluster Fisher exact test P-values were computed both for library and weighted clone counts to check that the counts are statistically significant. 10 EXAMPLE 4 Identification of splice variants over expressed in cancer of clusters which are not over expressed in cancer Cancer-specific splice variants containing a unique region were identified. Identification of unique sequence regions in splice variants 15 A Region is defined as a group of adjacent exons that always appear or do not appear together in each splice variant. A "segment" (sometimes referred also as "seg" or "node") is defined as the shortest contiguous transcribed region without known splicing inside. Only reliable ESTs were considered for region and segment analysis. An EST was 20 defined as unreliable if: (i) Unspliced; (ii) Not covered by RNA; (iii) Not covered by spliced ESTs; and (iv) Alignment to the genome ends in proximity of long poly-A stretch or starts in 25 proximity of long poly-T stretch. Only reliable regions were selected for further scoring. Unique sequence regions were considered reliable if: (i) Aligned to the genome; and (ii) Regions supported by more than 2 ESTs. 30 The algorithm Each unique sequence region divides the set of transcripts into 2 groups: WO 2005/072053 PCT/IB2005/000928 235 (i) Transcripts containing this region (group TA). (ii) Transcripts not containing this region (group TB). The set of EST clones of every cluster is divided into 3 groups: (i) Supporting (originating from) transcripts of group TA (Si). 5 (ii) Supporting transcripts of group TB (S2). (iii) Supporting transcripts from both groups (S3). Library and clones number scores described above were given to SI group. Fisher Exact Test P-values were used to check if: Si is significantly enriched by cancer EST clones compared to S2; and 10 S1 is significantly enriched by cancer EST clones compared to cluster background (S1+S2+S3). Identification of unique sequence regions and division of the group of transcripts accordingly is illustrated in Figure 2. Each of these unique sequence regions corresponds to a segment, also termed herein a "node". 15 Region 1: common to all transcripts, thus it is not considered; Region 2: specific to Transcript 1: T_1 unique regions (2+6) against T_2+3 unique regions (3+4); Region 3: specific to Transcripts 20 2+3: T_2+3 unique regions (3+4) against TI unique regions (2+6); Region 4: specific to Transcript 3: T_3 unique regions (4) against T1+2 unique regions (2+5+6); Region 5: specific to Transcript 1+2: Tl1+2 unique regions (2+5+6) against T3 unique regions (4); Region 6: specific to Transcript 1: same as region 2. 25 EXAMPLE 5 Identification of cancer specific splice variants of genes over expressed in cancer A search for EST supported (no mRNA) regions for genes of: (i) known cancer markers 30 (ii) Genes shown to be over-expressed in cancer in published micro-array experiments.

WO 2005/072053 PCT/IB2005/000928 236 Reliable EST supported-regions were defined as supported by minimum of one of the following: (i) 3 spliced ESTs; or (ii) 2 spliced ESTs from 2 libraries; 5 (iii) 10 unspliced ESTs from 2 libraries, or (iv) 3 libraries. Actual Marker Examples The following examples relate to specific actual marker examples. 10 EXPERIMENTAL EXAMPLES SECTION This Section relates to Examples describing experiments involving these sequences, and illustrative, non-limiting examples of methods, assays and uses thereof The materials and experimental procedures are explained first, as all experiments used them as a basis for the work 15 that was performed. The markers of the present invention were tested with regard to their expression in various cancerous and non-cancerous tissue samples. A description of the samples used in the panel is provided in Table 1 below. A description of the samples used in the normal tissue panel 20 is provided in Table 2 below. Tests were then performed as described in the "Materials and Experimental Procedures" section below. Table 1: Tissue samples in testing panel WO 2005/072053 PCT/IB2005/000928 237 COLON PANEL. | sample name Lot No. tissue Isource pathology Grade gendeag 58-B-Adeno G1 A609152 Colon biochain Adenocarcinoma 1 M/73 59-B-Adeno G1 A609059 Colon biochain Adenocarcinoma, Ulcer 1 M/158 14-CGtolypold Adeno G1 D-C CG-222 2) Rectum chilov Well polypold adeocarcinoma Duke's C F/49 17-CG-Adeno G1-2 CG-163 Rectum lIchilov Adenocarcinoma 2 M/73 10-CG-Adeno Gi-2 D-B2 CG-311 Sigmod ccl)chilov Adenocarcinoma Astier-Coll r B2. 1-2 M/88 12-CG-Adeno G1-2 D-C2 CG-337 Colon ilchilov Adenocarcinoma Astler-Coller C2. 1-2 NA 6-CG-Adeno G1-2 D-C2 CG-303 (3) Colon lchilov Adenocarcinoma Astler-Coller C2. 1-2 F177 5-CG-Adeno G2 CG-308 2 Colon SignIchilov Adenocarcinoma. 2 F/89 16-CG-Adeno G2 CG-278C colon lichilov Adenocarcinoma 2 F160 53--Adeno G2 A609148 Colon biochain Adenocarcinoma 2 F48 61-B-Adeno G2 A606258 Colon bochain Adenocarcinoma, U cer 2 M/41 60-B-Adeno G2 A609058 Colon biochain Adenocarcinoma, Ulce 2 M/67 22-CG-Adeno G2 D-3 CG-229C Colon ihilov Adenocarcinoma Duke's 2 Ff55 -CG-Adeno G2 D-B2 CG-335 Cecun ichi Adenocarcinoma Dukes B2. 2 1/66 12-CG-Adeno G2 D-32 CG-340 Colon Sign ichilv Adenocarcinoma Astler-Coller B2. 2 M/66 28-CG-Adeno G2 D-B2 CG-284 sigma ichilov Adenocarcinoma Duke's B2 2 F/72 2-CG-Adeno G2 D-C2 CG-307 X2 Cecum Ichilov Adenocarcinoma Astler-Coller C2. 2 F/89 9-CG-Adeno G2 D-D CG-297 X2 Rectum lchilov Adenocarcinoma Dukes D. 2 M/62 13-CG-Adeno G2 D -D CG-290 X2 Rectosigm ichilov Adenocarcinoma Dukes D. 2 M/47 26-CG-Adeno G2 D-D CG-283 sigma Ichiov Colonic adenocarcinoma Duke's D 2 F/63 4-CG-Adeno G3 CG-276 Colon lchilov Carcinoma. 3 M/64 53-B-Adeno G3 A609161 Colon biochain Adenocarcinoma 3 F/53 54-B-Adeno G3 A609142 Colon biochain Adenocarcinoma 3 M/53 55---Adeno G3 A609144 Colon biochain Adenocarcinoma 3 M/68 57-B-Adeno G3 A609150 Colon bochain Adenocarcinoma 3 F/45 72-CG-Adeno G3 CG-309 colon Ichilov Adenocarcinoma 3 F/88 20-CG-Adeno G3 D-B2 CG-249 Colon lchilov Ulcerated adenocarcoma Duke's B2 3 M/36 7-CG-Adeno D-A CG-235 Rectum Ichilov Adenocarcinoma intramucosal Duke's A. F66 23-CG-Adeno D-C CG-282 sigma Ichilov Mucinus adenocarcinom a Astler CFller C M/51 3-CG-Muc adeno D-D CG-224 Colon Ichilov Mucinois adenocarcinom Duke's D M/48 18-CG-Adeno CG-22C Colon Ichilov Adenocarcinoma NA 19-CG-Adeno CG-19C (1) Colon Ichilov Adenocarc noma NA 21-CG-Adeno CG-8C Colon chilov Adenocarcinoma NA 24-CG-Adeno CG-12 (2) Colon Ichilov Adenocarcinoma NA 25-CG-Adeno CG-2 Colon Ichilov Adenocarcinoma NA 27-CG-Adeno CG-4 Colon Ichilov Adenocarcinoma NA 8-CG-diverticolosis, diverticulitis CG-291 Wall of sig Ichilov Diverticolosis and diverticulitis of the Colon F/65 46-CG-Crohn's disease CG-338C Cecum Ichilov Crohn's disease M/22 47-CG-Crohn's disease CG-338AC Colon Ichilov Crohn's disease. M/22 42-CG-N M20 CG-249N Colon Ichilov Normal M/36 43-CG-N M8 CG-291N W of sig chilov Normal F/65 44-CG-N M21 CG-18N Colon Ichilov Normal NA 45-CG-N M 11 CG-337N Colon Ichilov Normal M/75 49-CG-N M14 CG-222N Rectum Ichilov Normal F/49 50-CG-N M5 CG-308N Sigma Ichilov Within normal limits F/80 51-CG-N M26 CG-283N Sigma pchilov Normal F/63 41 -B-N A501156 lColon biochain Normal PM M/78 52-CG-N CG-309TR [Colon Ichilov Within normal limits F/88 62-B3-N A608273 Colon biochain Normal PM IM/66 63-B-N A609260 Colon biochain Normal PM IM/61 64-B-N A609261 Colon biochain Normal PM F/68 65-B-N A607115 Colon biochain Normal PM M/24 66-B-N A609262 Colon biochain Normal PM M/58 67-B-N A406029 Colon biochain NraME (Poo of 10) & 69-B-N A411078 Colon biochain Nor.,ma: P M (Po of. 10)F& 70-Cl-N 1110101IColon Iclontech Normal PM (Pool of 3) ,71 -Am-N 1071P10B IColon jAmbion lNormal (IC BLEED) F/34 115-CG-Adeno D-A 10G-45 lRectum Ilonilov |Adenocarcinoma intramucosal ukes A, IF/66 Table 2: Tissue samples in nonnal panel: Lot no. Source ITissue Pathology Sex/Age WO 2005/072053 PCT/IB2005/000928 238 1-Am-Colon (C71) 071P1OB Ambion Colon PM F/43 2-B-Colon (C69) A411078 Biochain Colon PM-Pool of 1 OM&F 3-Cl-Colon (C70) 1110101 Clontech Colon PM-Pool of 3 M&F 4-Am-Small Intestine 091PO201AAmbion Small Intestine PM M/75 5-B-Small Intestine A501158 Biochain Small Intestine PM M/63 6-B-Rectum A605138 Biochain Rectum PM M/25 7-B-Rectum A610297 Biochain Rectum PM M/24 8-B-Rectum A610298 Biochain Rectum PM M/27 9-Am-Stomach 11OP04A Ambion Stomach PM M/16 10-B-Stomach A501159 Biochain Stomach PM M/24 11-B-Esophagus A603814 Biochain Esophagus PM M/26 12-B-Esophagus A603813 Biochain Esophagus PM M/41 13-Am-Pancreas 071P25C Ambion Pancreas PM M/25 14-CG-Pancreas CG-255-2 Ichilov Pancreas PM M/75 15-B-Lung A409363 Biochain Lung PM F/26 16-Am-Lung (L93) 111P003AAmbion Lung PM F/61 17-B-Lung (L92) A503204 Biochain Lung PM M/28 18-Am-Ovaiy (047) 061P43A Ambion Ovary PM F/16 19-B-Ovary (048) A504087 Biochain Ovary PM F/51 20-B-Ovary (046) A504086 Biochain Ovary PM F/41 21-Am-Cervix 101P0101AAmbion Cervix PM F/40 22-B-Cervix A408211 Biochain Cervix PM F/36 23-B-Cervix A504089 Biochain Cervix PM-Pool of 5 M&F 24-B-Uterus A411074 Biochain Uterus PM-Pool of 10 M&F 25-B-Uterus A409248 Biochain Uterus PM F/43 26-B-Uterus A504090 Biochain Uterus PM-Pool of 5 M&F 27-B-Bladder A501 157 Biochain Bladder PM M/29 28-Am-Bladder 071P02C Ambion Bladder PM M/20 29-B-Bladder A504088 Biochain Bladder PM-Pool of 5 M&F 30-Am-Placenta 021P33A Ambion Placenta PB F/33 WO 2005/072053 PCT/IB2005/000928 239 31-B-Placenta A410165 Biochain Placenta PB F/26 32-B-Placenta A411073 Biochain Placenta PB-Pool of 5 M&F 33-B-Breast (B59) A607155 Biochain Breast PM F/36 34-Am-Breast (B63) 26486 Ambion Breast PM F/43 35-Am-Breast (B64) 23036 Ambion Breast PM F/57 36-Cl-Prostate (P53) 1070317 Clontech Prostate PB-Pool of 47 M&F 37-Am-Prostate (P42) 061P04A Ambion Prostate PM M/47 38-Am-Prostate (P59) 25955 Ambion Prostate PM M/62 39-Am-Testis 11 1P0104AAmbion Testis PM M/25 40-B-Testis A411147 Biochain Testis PM M/74 41-Cl-Testis 1110320 Clontech Testis PB-Pool of 45 M&F 42-CG-Adrenal CG-184-10 Ichilov Adrenal PM F/81 43-B-Adrenal A610374 Biochain Adrenal PM F/83 44-B-Heart A411077 Biochain Heart PB-Pool of 5 M&F 45-CG-Heart CG-255-9 Ichilov Heart PM M/75 46-CG-Heart CG-227-1 Ichilov Heart PM F/36 47-Am-Liver 081PO101AAmbion Liver PM M/64 48-CG-Liver CG-93-3 Ichilov Liver PM F/19 49-CG-Liver CG- 124-4 Ichilov Liver PM F/34 50-Cl-BM 1110932 Clontech Bone Marrow PM-Pool of 8 M&F 51 -CGEN-Blood WBC#5 CGEN Blood M 52-CGEN-Blood WBC#4 CGEN Blood M 53-CGEN-Blood WBC#3 CGEN Blood M 54-CG-Spleen CG-267 Ichilov Spleen PM F/25 55-CG-Spleen 111P0106B Ambion Spleen PM M/25 56-CG-Spleen A409246 Biochain Spleen PM F/12 56-CG-Thymus CG-98-7 Ichilov Thymus PM F/28 58-Am-Thymus 1OPOlO1AAmbion Thymus PM M/14 59-B-Thymus A409278 Biochain Thymus PM M/28 60-B-Thyroid A610287 Biochain Thyroid PM M/27 WO 2005/072053 PCT/IB2005/000928 240 61-B-Thyroid A610286 Biochain Thyroid PM M/24 62-CG-Thyroid CG-1 19-2 Ichilov Thyroid PM F/66 63-Cl-Salivary Gland 1070319 Clontech Salivary Gland PM-Pool of 24M&F 64-Am-Kidney 11 1PI01B Ambion Kidney PM-Pool of 14M&F 65-Cl-Kidney 1110970 Clontech Kidney PM-Pool of 14M&F 66-B-Kidney A41 1080 Biochain Kidney PM-Pool of 5 M&F 67-CG-Cerebellum CG-183-5 Ichilov Cerebellum PM M/74 68-CG-Cerebellum CG-212-5 Ichilov Cerebellum PM M/54 69-B-Brain A411322 Biochain Brain PM M/28 70-Cl-Brain 1120022 Clontech Brain PM-Pool of 2 M&F 71-B-Brain A411079 Biochain Brain PM-Pool of 2 M&F 72-CG-Brain CG-151-1 Ichilov Brain PM F/86 73-Am-Skeletal Muscle 101PO13A Ambion Skeletal Muscle PM F/28 74-Cl-Skeletal Muscle 1061038 Clontech Skeletal Muscle PM-Pool of 2 M&F Materials and Experimental Procedures 5 RNA preparation - RNA was obtained from Clontech (Franklin Lakes, NJ USA 07417, www.clontech.com), BioChain Inst. Inc. (Hayward, CA 94545 USA www.biochain.com), ABS (Wilmington, DE 19801, USA, http://www.absbioreagents.com) or Ambion (Austin, TX 78744 USA, http://www.ambion.com). Alternatively, RNA was generated from tissue samples using TRI-Reagent (Molecular Research Center), according to Manufacturer's instructions. Tissue and 10 RNA samples were obtained from patients or from postmortem. Total RNA samples were treated with DNaseI (Ambion) and purified using RNeasy columns (Qiagen). RT PCR - Purified RNA (1 pg) was mixed with 150 ng Random Hexamer primers (Invitrogen) and 500 ptM dNTP in a total volume of 15.6 ll. The mixture was incubated for 5 min at 65 'C and then quickly chilled on ice. Thereafter, 5 pl of 5X SuperscriptIl first strand 15 buffer (Invitrogen), 2.4pl 0.1M DTT and 40 units RNasin (Promega) were added, and the mixture was incubated for 10 min at 25 'C, followed by further incubation at 42 'C for 2 min.

WO 2005/072053 PCT/IB2005/000928 241 Then, I pl (200units) of SuperscriptIl (Invitrogen) was added and the reaction (final volume of 25pl) was incubated for 50 min at 42 0 C and then inactivated at 70 'C for 15min. The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8). Real-Time RT-PCR analysis- cDNA (5pl), prepared as described above, was used as a 5 template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers and UNG Enzyme (Eurogentech or ABI or Roche). The amplification was effected as follows: 50 "C for 2 min, 95 "C for 10 min, and then 40 cycles of 95 "C for 15sec, followed by 60 "C for 1 min. Detection was performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence was 10 registered and was used to calculate the relative transcript quantity in the RT reactions. The relative quantity was calculated using the equation Q=efficiency^-ct. The efficiency of the PCR reaction was calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities were normalized to the geometric mean of the relative quantities of 15 several housekeeping (HSKP) genes. Schematic summary of quantitative real-time PCR analysis is presented in Figure 3. As shown, the x-axis shows the cycle number.The CT = Threshold Cycle point, which is the cycle that the amplification curve crosses the fluorescence threshold that was set in the experiment. This point is a calculated cycle number in which PCR products signal is above the background level (passive dye ROX) and still in the 20 Geometric/Exponential phase (as shown, once the level of fluorescence crosses the measurement threshold, it has a geometrically increasing phase, during which measurements are most accurate, followed by a linear phase and a plateau phase; for quantitative measurements, the latter two phases do not provide accurate measurements). The y-axis shows the normalized reporter fluorescence. It should be noted that this type of analysis provides relative 25 quantification. The sequences of the housekeeping genes measured in all the examples on tissue testing 30 panel were as follows: PBGD (GenBank Accession No. BCO 19323), WO 2005/072053 PCT/IB2005/000928 242 PBGD Forward primer (SEQ ID NO:529): TGAGAGTGATTCGCGTGGG PBGD Reverse primer (SEQ ID NO:530): CCAGGGTACGAGGCTTTCAAT PBGD-amplicon (SEQ ID NO:53 1): TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAGACGGAC 5 AGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG HPRTl (GenBank Accession No. NM_000194), HPRT1 Forward primer (SEQ ID NO:532): TGACACTGGCAAAACAATGCA HPRT1 Reverse primer (SEQ ID NO:533): GGTCCTTTTCACCAGCAAGCT 10 HPRT1-amplicon (SEQ ID NO:612): TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATAATCCAA AGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC G6PD (GenBank Accession No. NM_000402) 15 G6PD Forward primer (SEQ ID NO:613): gaggccgteaccaagaacat G6PD Reverse primer (SEQ ID NO:614): ggacagccggtcagagetc G6PD-amplicon (SEQ ID NO:615): gaggccgtcaccaagaacattcacgagtcctgcatgagccagataggctggaaccgcatcatcgtggagaagcccttegggagggacct gcagagetctgaccggctgtcc 20 RPS27A (GenBank Accession No. NM_002954) RPS27A Forward primer (SEQ ID NO:642): CTGGCAAGCAGCTGGAAGAT R-PS27A Reverse primer (SEQ ID NO:1260): TTTCTTAGCACCACCACGAAGTC RPS27A-amplicon (SEQ ID NO:1261): 25 CTGGCAAGCAGCTGGAAGATGGACGTACTTTGTCTGACTACAATATTCAAAAGGAG TCTACTCTTCATCTTGTGTTGAGACTTCGTGGTGGTGCTAAGAAA The sequences of the housekeeping genes measured in all the examples on normal tissue panel were as follows: 30 RPL19 (GenBank Accession No. NM_000981), WO 2005/072053 PCT/IB2005/000928 243 RPLI9 Forward primer (SEQ ID NO:1262): TGGCAAGAAGAAGGTCTGGTTAG RPL19 Reverse primer (SEQ ID NO:1263): TGATCAGCCCATCTTTGATGAG RPL19 -amplicon (SEQ ID NO:1264): TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCAATGCCA 5 ACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATCA TATA box (GenBank Accession No. NM_003194), TATA box Forward primer (SEQ ID NO:1265): CGGTTTGCTGCGGTAATCAT TATA box Reverse primer(SEQ ID NO:1266): TTTCTTGCTGCCAGTCTGGAC TATA box -amplicon (SEQ ID NO: 1267): 10 CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACTGATTTT CAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAACAGTCCAGACTG GCAGCAAGAAA Ubiquitin(GenBank Accession No. BC000449) Ubiquitin Forward primer (SEQ ID NO:1268): ATTTGGGTCGCGGTTCTTG 15 Ubiquitin Reverse primer (SEQ ID NO:1269): TGCCTTGACATTCTCGATGGT Ubiquitin -amplicon (SEQ ID NO:1270): ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAATGCAGAT CTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA 20 SDHA (GenBank Accession No. NM_004168) SDHA Forward primer (SEQ ID NO:1271): TGGGAACAAGAGGGCATCTG SDHA Reverse primer (SEQ ID NO:1272): CCACCACTGCATCAAATTCATG SDHA-amplicon (SEQ ID NO:1273): TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGT 25 AGTGGATCATGAATTTGATGCAGTGGTGG Oligonucleotide-based micro-array experiment protocol Microarray fabrication 30 Microarrays (chips) were printed by pin deposition using the MicroGrid II MGII 600 robot from BioRobtics Limited (Cambridge, UK). 50-mer oligonucleotides target sequences WO 2005/072053 PCT/IB2005/000928 244 were designed by Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et at, "Optical technologies and infornatics", Proceedings of SPIE. Vol 4266, pp. 86-95 (2001). The designed oligonucleotides were synthesized and purified by desalting with the Sigma-Genosys system (The Woodlands, TX, US) and all of the oligonucleotides were joined to a C6 amino-modified 5 linker at the 5' end, or being attached directly to CodeLink slides (Cat #25-6700-01. Amersham Bioscience, Piscataway, NJ, US). The 50-mer oligonucleotides, forming the target sequences, were first suspended in Ultra-pure DDW (Cat # 01-866-lA Kibbutz Beit-Haemek, Israel) to a concentration of 50pM. Before printing the slides, the oligonucleotides were resuspended in 300mM sodium phosphate (pH 8.5) to final concentration of 150mM and printed at 35-40% 10 relative humidity at 21'C. Each slide contained a total of 9792 features in 32 subarrays. Of these features, 4224 features were sequences of interest according to the present invention and negative controls that were printed in duplicate. An additional 288 features (96 target sequences printed in triplicate) contained housekeeping genes from Human Evaluation Library2, Compugen Ltd, Israel. 15 Another 384 features are E.coli spikes 1-6, which are oligos to E-Coli genes which are commercially available in the Array Control product (Array control- sense oligo spots, Ambion Inc. Austin, TX. Cat #1781, Lot #1 12K06). Post-coupling processing of printed slides 20 After the spotting of the oligonucleotides to the glass (CodeLink) slides, the slides were incubated for 24 hours in a sealed saturated NaC1 humidification chamber (relative humidity 70 75%). Slides were treated for blocking of the residual reactive groups by incubating them in blocking solution at 50'C for 15 minutes (10ml/slide of buffer containing 0.lM Tris, 50mM 25 ethanolamine, 0.1% SDS). The slides were then rinsed twice with Ultra-pure DDW (double distilled water). The slides were then washed with wash solution (10ml/slide. 4X SSC, 0.1% SDS)) at 50'C for 30 minutes on the shaker. The slides were then rinsed twice with Ultra-pure DDW, followed by drying by centrifugation for 3 minutes at 800 rpm. Next, in order to assist in automatic operation of the hybridization protocol, the slides 30 were treated with Ventana Discovery hybridization station barcode adhesives. The printed slides were loaded on a Bio-Optica (Milan, Italy) hematology staining device and were WO 2005/072053 PCT/IB2005/000928 245 incubated for 10 minutes in 50ml of 3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess fluid was dried and slides were then incubated for three hours in 20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc. Redding CA). 5 The following protocol was then followed with the Genisphere 900-RP (random primer), with mini elute columns on the Ventana Discovery HybStationTM, to perform the microarray experiments. Briefly, the protocol was performed as described with regard to the instructions and information provided with the device itself. The protocol included cDNA synthesis and labeling. cDNA concentration was measured with the TBS-380 (Turner Biosystems. 10 Sunnyvale, CA.) PicoFlour, which is used with the OliGreen ssDNA Quantitation reagent and kit. Hybridization was performed with the Ventana Hybridization device, according to the provided protocols (Discovery Hybridization Station Tuscon AZ). 15 The slides were then scanned with GenePix 4000B dual laser scanner from Axon Instruments Inc, and analyzed by GenePix Pro 5.0 software. Schematic summary of the oligonucleotide based microarray fabrication and the experimental flow is presented in Figures 4 and 5. Briefly, as shown in Figure 4, DNA oligonucleotides at 25uM were deposited (printed) 20 onto Amersham 'CodeLink' glass slides generating a well defined 'spot'. These slides are covered with a long-chain, hydrophilic polymer chemistry that creates an active 3-D surface that covalently binds the DNA oligonucleotides 5'-end via the C6-amine modification. This binding ensures that the full length of the DNA oligonucleotides is available for hybridization to the cDNA and also allows lower background, high sensitivity and 25 reproducibility. Figure 5 shows a schematic method for performing the microarray experiments. It should be noted that stages on the left-bhand or right-hand side may optionally be performed in any order, including in parallel, until stage 4 (hybridization). Briefly, on the left-hand side, the target oligonucleotides are being spotted on a glass microscope slide (although optionally other 30 materials could be used) to form a spotted slide (stage 1). On the right hand side, control sample RNA and cancer sample RNA are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled WO 2005/072053 PCT/IB2005/000928 246 probes. It should be noted that the control and cancer samples come from corresponding tissues (for example, nonnal prostate tissue and cancerous prostate tissue). Furthermore, the tissue from which the RNA was taken is indicated below in the specific examples of data for particular clusters, with regard to overexpression of an oligonucleotide from a "chip" (microarray), as for 5 example "prostate" for chips in which prostate cancerous tissue and normal tissue were tested as described above. In stage 3, the probes are mixed. In stage 4, hybridization is performed to form a processed slide. In stage 5, the slide is washed and scanned to form an image file, followed by data analysis in stage 6.

WO 2005/072053 PCT/IB2005/000928 247 DESCRIPTION FOR CLUSTER M85491 Cluster M85491 features 2 transcript(s) and 11 segment(s) of interest, the names for 5 which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SEQ ID NO: M85491_PEA_1_T16 I M85491_PEA_1_T20 2 Table 2 - Segments of interest Sgmen ame SEQ ID NO, M85491_PEA 1_node_0 89 M85491_PEA 1 node_13 90 M85491 PEAInode_21 91 M85491_PEA_1_node 23 92 M85491_PEA_1_node_24 93 M85491_PEA 1_node_8 94 M85491_PEAInode_9 95 M85491_PEA_1_node_10 96 M85491_PEA_1_node_18 97 M85491_PEA 1 node_19 98 M85491_PEA_1_node_6 99 10 Table 3 - Proteins of interest Protein Name SEQ ID NO: M85491_PEA_1_P13 534 WO 2005/072053 PCT/IB2005/000928 248 M85491 PEA_1_P14 535 These sequences are variants of the known protein Ephrin type-B receptor 2 [precursor] (SwissProt accession identifier EPB2_HUMAN; known also according to the synonyms EC 2.7.1.112; Tyrosine-protein kinase receptor EPH-3; DRT; Receptor protein-tyrosine kinase 5 HEK5; ERK), SEQ ID NO: 616, referred to herein as the previously known protein. Protein Ephrin type-B receptor 2 [precursor] is known or believed to have the following function(s): Receptor for members of the ephrin-B family. The sequence for protein Ephrin type-B receptor 2 [precursor] is given at the end of the application, as "Ephrin type-B receptor 2 [precursor] amino acid sequence" (SEQ ID NO:616). Known polymorphisms for this sequence 10 are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein S1.NPgpoitioR(s) on Conment Amino acid sequence 671 A -> R. /FTId=VAR004162. 1-20 MALRRLGAALLLLPLLAAVE MWVPVLALPVCTYA 923 E ->K 956 L ->V 958 V ->L 154 G ->D 476 K ->KQ 495 - 496 Missing 532 E->D 568 R ->RR 589 M ->1 788 I->F 853 S ->A WO 2005/072053 PCT/IB2005/000928 249 Protein Ephrin type-B receptor 2 [precursor] localization is believed to be Type I membrane protein. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: protein amino acid phosphorylation; transmembrane receptor protein 5 tyrosine kinase signaling pathway; neurogenesis, which are annotation(s) related to Biological Process; protein tyrosine kinase; receptor; transmembrane-ephrin receptor; ATP binding; transferase, which are annotation(s) related to Molecular Function; and integral membrane protein, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBI 10 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster M85491 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 15 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 6 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and a mixture of malignant tumors from different tissues. Table 5 - Normal tissue distribution Name of Tissue Number bladder 0 Bone 0 Brain 10 Colon 31 epithelial 10 WO 2005/072053 PCT/IB2005/000928 250 general 12 Kidney 0 Liver 0 Lung 5 Breast 8 Muscle 5 Ovary 36 pancreas 10 Skin 0 stomach 0 Table 6 - P values and ratios for expression in cancerous tissue ,Name of Tissue P1 P2 SPI R3 SP2 R4 bladder 5.4e-01 6.0e-01 3.2e-01 2.5 4.6e-01 1.9 Bone I 2.8e-01 1 1.0 7.0e-01 1.8 Brain 3.4e-01 3.6e-01 1.2e-01 2.9 1.8e-02 2.7 Colon 3.4e-02 5.7e-02 8.2e-02 2.8 2.0e-01 2.1 epithelial 1.7e-03 3.5e-03 2.0e-03 2.8 1.1e-02 2.2 general 4.8e-04 5.2e-04 6.7e-04 2.3 1.3e-03 1.9 Kidney 4.3e-01 3.7e-01 1 1.1 7.0e-01 1.5 Liver 1 4.5e-01 1 1.0 6.9e-01 1.5 Lung 2.2e-01 2.7e-01 6.9e-02 3.6 3.4e-02 3.6 Breast 8.2e-01 7.3e-01 6.9e-01 1.2 6.8e-01 1.2 Muscle 9.2e-01 4.8e-01 1 0.8 1.5e-01 3.2 Ovary 8.5e-01 7.3e-01 9.0e-01 0.7 6.7e-01 1.0 pancreas 5.5e-01 2.0e-01 6.7e-01 1.2 3.5e-01 1.8 Skin 2.9e-01 4.7e-01 1.4e-01 7.0 6.4e-01 1.6 stomach 1.5e-01 3.2e-01 1 1.0 8.0e-01 1.3 WO 2005/072053 PCT/IB2005/000928 251 As noted above, cluster M85491 features 2 transcript(s), which were listed in Table I above. These transcript(s) encode for protein(s) which are variant(s) of protein Ephrin type-B 5 receptor 2 [precursor]. A description of each variant protein according to the present invention is now provided. Variant protein M85491_PEA_1_P13 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 M85491_PEA_1_Ti6. An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 15 Comparison report between M85491_PEA_1_P13 and EPB2_HUMAN: 1.An isolated chimeric polypeptide encoding for M8549 1_PEA_1 P13, comprising a first amino acid sequence being at least 90 % homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR 20 TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN SRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSG 25 GREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAV NGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYEL QYYEK corresponding to amino acids 1 - 476 of EPB2 HUMAN, which also corresponds to amino acids 1 - 476 of M85491_PEA_1_P13, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 30 preferably at least 95% homologous to a polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG corresponding to amino acids 477 - 496 of WO 2005/072053 PCT/IB2005/000928 252 M85491_PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of M85491_PEA1_P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VPIGWVLSPSPTSLRAPLPG in M85491_PEA_1_P13. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 15 Variant protein M85491_PEA_ P3 is encoded by the following transcript(s): M85491 PEA_1Tl 6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_ PEA 1 T16 is shown in bold; this coding portion starts at position 143 and ends at position 1630. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 20 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491_PEA_1P13 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 799 G->A Yes 1066 C -> T Yes 1519 A -> G Yes 1872 C -> T Yes 2044 T -> C Yes WO 2005/072053 PCT/IB2005/000928 253 2156 G ->A Yes 2606 C ->A Yes 2637 G -> C Yes Variant protein M85491_PEA_1P14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 M85491_PEA_1_T20. An alignment is given to the known protein (Ephrin type-B receptor 2 [precursor]) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between M85491_PEA_1-P14 and EPB2_HUMAN: 1.An isolated chimeric polypeptide encoding for M85491_PEA 1 P14, comprising a first amino acid sequence being at least 90 % homologous to MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIR 15 TYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYY EADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGF YLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSLVAARGSCIANAEEVD VPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding to amino acids 1 270 of EPB2 HUMAN, which also corresponds to amino acids 1 - 270 of 20 M85491_PEA_1_P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL corresponding to amino acids 271 - 301 of M85491_PEA_1_P14, wherein said first and second amino acid sequences are contiguous and 25 in a sequential order. 2.An isolated polypeptide encoding for a tail of M85491_PEA_1_P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 254 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL in M85491_PEA_1_P14. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. 10 Variant protein M85491_PEA_1_P14 is encoded by the following transcript(s): M85491_PEA_1_T20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript M85491_PEA 1 T20 is shown in bold; this coding portion starts at position 143 and ends at position 1045. The transcript also has the following SNPs as listed in 15 Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M85491 PEA1_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic'acid Previously known SNP? sequence, 799 G ->A Yes 1135 T->C Yes 1160 T -> C Yes 1172 A -> C Yes 1176 T -> A Yes 20 WO 2005/072053 PCT/IB2005/000928 255 As noted above, cluster M85491 features II segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster M85491_PEA_1_node_0 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491 PEA IT16 and M85491 PEA 1_T20. 10 Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segnent location on transcripts jrauscript ri~ure Segment starting position, Segnient 'ending position M85491_PEAIT16 1 203 M85491_PEA 1_T20 1 203 Segment cluster M85491_PEAInode_13 according to the present invention is 15 supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491 PEAIT20. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position JSegnent ending position M85491_PEA_1_T20 954 1182 20 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment, shown in Table 11. Table 11 - Oligonucleotides related to this segment WO 2005/072053 PCT/IB2005/000928 256 Oligonucleotide name overexpressed in cancers Chip reference M85491_0_0_25999 colorectal cancer Colon Segment cluster M85491_PEA-1_node_21 according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): M85491 PEA 1 T16. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcriptname Segmnt starting position Segment ending position M85491_PEAIT16 1110 1445 10 Segment cluster M85491_PEA_1_node_23 according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491 PEAIT16. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA1_T16 1446 1570 15 Segment cluster M85491_PEA_1_node_24 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491 PEA 1 T16. Table 14 below 20 describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 257 M85491_PEA 1 T16 1571 2875 Segment cluster M85491 PEA 1 node 8 according to the present invention is supported by 25 libraries. The number of libraries was detennined as previously described. This segment 5 can be found in the following transcript(s): M85491 PEA IT16 and M85491 PEAIT20. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA1T16 269 672 M85491_PEA_1 T20 269 672 Microarray (chip) data is also available for this segment as follows. As described above 10 with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment with regard to colon cancer, shown in Table 16. Table 16 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference M85491 0_14_0 colorectal cancer Colon 15 Segment cluster M85491_PEA_1_node_9 according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 17 below describes the starting and ending position of this segment on each transcript. 20 Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491 PEA 1 T16 673 856 M85491_PEA_1 T20 673 856 WO 2005/072053 PCT/IB2005/000928 258 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster M85491_PEA_1_node_10 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This 10 segment can be found in the following transcript(s): M85491_PEA_1_T16 and M85491_PEA_1_T20. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segnent ending position M85491_PEA_1 T16 857 953 M85491_PEA1_T20 857 953 15 Segment cluster M85491_PEA_1_node_18 according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491_PEA_1_T16. Table 19 below describes the starting and ending position of this segment on each transcript. 20 Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491 PEA_1_T16 954 1044 Segment cluster M85491 _PEA _Inode_19 according to the present invention is supported by 15 libraries. The number of libraries was determined as previously described. This WO 2005/072053 PCT/IB2005/000928 259 segment can be found in the following transcript(s): M85491_PEA 1_T16. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position M85491_PEA_1_T16 1045 1109 5 Segment cluster M85491 PEA_1_node_6 according to the present invention is supported by II libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): M85491 PEAIT16 and M85491_PEA_1_T20. Table 21 below describes the starting and ending position of this segment on each transcript. 10 Table 21 - Segment location on transcripts Transcript name Segment starting position Segden't eng position M85491_PEA 1 T16 204 268 M85491_PEA_1_T20 204 268 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/qfmsU9VtxS/DylcLC9j8v:EPB2HUMAN Sequence documentation: 20 Alignment of: M85491 PEA 1 P13 x EPB2_HUMAN Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 260 Quality: 4726.00 Escore: 0 Matching length: 476 Total length: 476 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 15 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 20 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 l ill IIllliii I lli ll li II Il llll ll l ll l l l 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 25 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 | 1 111111111111 || |11111111111l l IIIl i l I l l I Il l Il 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 201 TQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 WO 2005/072053 PCT/IB2005/000928 261 251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300 iii I 111111111 I lii|i jil|l I iii I I I I | IIl 251 IGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPINSRTTSEGA 300 5 301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350 301 TNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDS 350 10 351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400 351 GGREDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLA 400 401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450 401 HTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD 450 451 SITLSWSQPDQPNGVILDYELQYYEK 476 20 451 SITLSWSQPDQPNGVILDYELQYYEK 476 25 Sequence name: /tmp/rmnzuDbot6/GiHbjeU8iR:EPB2 HUMAN Sequence documentation: 30 Alignment of: M85491 PEA 1 P14 x EPB2 HUMAN WO 2005/072053 PCT/IB2005/000928 262 Alignment segment 1/1: Quality: 2673.00 5 Escore: 0 Matching length: 270 Total length: 270 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 1i 1l 1l illilllillllilll Ilill lilill lI l i lll11 l1 lil 1 MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYD 50 20 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 lil li I l li l l l liill l l lil l ll l l l l l 11l l i i l l l Ili l ll i 51 ENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQV 150 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 30 151 DLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRI 200 WO 2005/072053 PCT/IB2005/000928 263 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 I 1 I I I Ii l I I l I I i i i i i i iii II I | 1 i i i i Ii I II i i 201 IQNGAIFQETLSGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVP 250 5 251 IGRCMCKAGFEAVENGTVCR 270 11l1 II111111II 1 liii 251 IGRCMCKAGFEAVENGTVCR 270 10 15 Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in normal and cancerous colon tissues Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by or according to seg24 , M85491seg24 amplicon 20 and M8549 1 seg24F and M8549 1 seg24R primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BCO 19323; amplicon - PBGD-amplicon, SEQ ID NO:53 1), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; G6PD amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_002954; RPS27A 25 amplicon, SEQ ID NO:1261) was measured similarly. For each RT (RT-PCR) sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, "Tissue samples in testing panel", above), to obtain a value of fold up-regulation 30 for each sample relative to median of the normal PM samples.

WO 2005/072053 PCT/IB2005/000928 264 Figure 7 is a histogram showing over expression of the above-indicated Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts in cancerous colon samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.. 5 As is evident from Figure 7, the expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41,52, 62-67, 69-71 Table 1, "Tissue samples in testing panel"). Notably over-expression of at least 3 fold was found in 13 out of 37 adenocarcinoma samples. 10 Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts detectable by the above amplicon(s) in colon cancer samples versus the normal tissue samples was determined by 15 T test as 6.83E-04 Threshold of 3 fold over expression was found to differentiate between cancer and normal samples with P value of 2.66E-02 in as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non 20 limiting illustrative example only of a suitable primer pair: M85491seg24F forward primer; and M85491seg24R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: M85491seg24. 25 M85491seg24F (SEQ ID NO: 1274)- GGCGTCTTTCTCCCTCTGAAC M85491seg24R (SEQ ID NO: 1275)- GTCCCATTCTGGGTGCTGTG WO 2005/072053 PCT/IB2005/000928 265 M85491seg24 (SEQ ID NO: 1276) GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGTGAGACCC CTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGCACCCAGAATGGG AC 5 Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase 10 receptor EPH-3) M85491 transcripts which are detectable by ainplicon as depicted in sequence name M8549]seg24 in different normal tissues. Expression of Ephrin type-B receptor 2 precursor transcripts detectable by or according to M85491 seg24 amplicon(s) and M85491 seg24F and M85491 seg24R was measured by real 15 time PCR. In parallel the expression of four housekeeping genes -RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the 20 geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 Tissue samples in normal panel), to obtain a value of relative expression of each sample relative to median of the lung samples. The results are described in Figure 8, presenting the histogram showing the expression of 25 M85491 transcripts which are detectable by amplicon as depicted in sequence name M85491seg24 in different normal tissues. Forward primer (SEQ ID NO: 1274): GGCGTCTTTCTCCCTCTGAAC 30 Reverse primer (SEQ ID NO: 1275): GTCCCATTCTGGGTGCTGTG WO 2005/072053 PCT/IB2005/000928 266 Amplicon (SEQ ID NO: 1276): GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGTGAGACCC CTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGCACCCAGAATGGG AC 5 DESCRIPTION FOR CLUSTER T10888 Cluster T10888 features 4 transcript(s) and 8 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 10 application. The selected protein variants are given in table 3. Table ] - Transcripts of interest Transcript Name, SEQ ID NO: T10888_PEA_1_Ti 3 T10888_PEA 1_T4 4 T10888_PEA_1_T5 5 T10888_PEA 1 T6 6 Table 2 - Segments of interest T10888 NaE 1SE QeI NO: T10888 PEA 1 node_11 100 T10888_PEA1 node_12 101 T10888_PEA1_node17 102 T10888_PEA 1 node_4 103 T10888_PEA 1_node_6 104 T10888PEA 1 node_7 105 T10888_PEAI 1node_9 106 T10888_PEA_1_node_15 107 15 Table 3 - Proteins ofinterest WO 2005/072053 PCT/IB2005/000928 Protein Name SEQ ID NO: T10888_PEA 1 P2 536 T10888_PEA 1 P4 537 T10888_PEA_1 P5 538 T10888_PEA 1_P6 539 These sequences are variants of the known protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor (SwissProt accession identifier CEA6 HUMAN; known also according to the synonyms Normal cross-reacting antigen; Nonspecific crossreacting antigen; 5 CD66c antigen), SEQ ID NO: 617, referred to herein as the previously known protein. The sequence for protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor is given at the end of the application, as "Carcinoembryonic antigen-related cell adhesion molecule 6 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. 10 Table 4 - Amino acid mutations for Known Protein SNP positions) on Comment amnino acid sequence 138 F->L 239 V ->G Protein Carcinoembryonic antigen-related cell adhesion molecule 6 precursor localization is believed to be Attached to the membrane by a GPI-anchor. The previously known protein also has the following indication(s) and/or potential 15 therapeutic use(s): Cancer. It has been investigated for clinical/therapeutic use in humans, for example as a target for an antibody or small molecule, and/or as a direct therapeutic; available information related to these investigations is as follows. Potential pharmaceutically related or therapeutically related activity or activities of the previously known protein are as follows: Immunostimulant. A therapeutic role for a protein represented by the cluster has been predicted. 20 The cluster was assigned this field because there was information in the drug database or the public databases (e.g., described herein above) that this protein, or part thereof, is used or can be WO 2005/072053 PCT/IB2005/000928 268 used for a potential therapeutic indication: Imaging agent; Anticancer; Immunostimulant; Immunoconjugate; Monoclonal antibody, murine; Antisense therapy; antibody. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: signal transduction; cell-cell signaling, which are annotation(s) 5 related to Biological Process; and integral plasma membrane protein, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 10 Cluster T10888 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in nonnal tissues is also given according to the previously described methods. The tern "number" in the right hand colurnn of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs 15 in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 9 and Table 5. This cluster is overexpressed (at least at a minimum level) in the 20 following pathological conditions: colorectal cancer, a mixture of malignant tumors from different tissues, pancreas carcinoma and gastric carcinoma. Table 5 - Normal tissue distribution Name of Tissue Number bladder 0 Colon 107 epithelial 52 general 22 head and neck 40 lung 237 WO 2005/072053 PCT/IB2005/000928 269 breast 0 pancreas 32 prostate 12 stomach 0 Table 6 - P values and ratios for expression in cancerous tissue Ndmne of Tissue P1 P2 SPI R3 SP2 R4 bladder 5.4e-01 3.4e-01 5.6e-01 1.8 4.6e-01 1.9 colon 1.2e-01 1.7e-01 2.8e-05 3.7 7.9e-04 2.8 epithelial 3.3e-02 2.le-01 2.8e-20 2.8 4.8e-10 1.9 general 3.3e-05 2.2e-03 1.9e-44 4.9 4.6e-27 3.3 head and neck 4.6e-01 4.3e-01 1 0.8 7.5e-01 1.0 lung 7.6e-0I 8.2e-01 8.9e-01 0.6 1 0.3 breast 3.7e-02 4.le-02 1.5e-01 3.3 3.le-01 2.4 pancreas 2.6e-01 2.4e-01 8.6e-23 2.8 1.5e-19 4.5 prostate 9.le-01 9.3e-01 .4.le-02 1.2 1.0e-01 1.0 stomach 4.5e-02 5.6e-02 5.le-04 4.1 4.7e-04 6.3 As noted above, cluster T10888 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein 5 Carcinoembryonic antigen-related cell adhesion molecule 6 precursor. A description of each variant protein according to the present invention is now provided. Variant protein T10888_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 T10888_PEA_1_Ti. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 15 WO 2005/072053 PCT/IB2005/000928 270 Comparison report between T10888 PEA 1 P2 and CEA6 HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP 5 QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVS corresponding to amino acids 1 - 319 of 10 CEA6_HUMAN, which also corresponds to amino acids 1 - 319 of T10888_PEA_1_P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DWTRP corresponding to amino acids 320 - 324 of T10888 PEA _1 P2, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of T10888 PEA_1 P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DWTRP in T10888PEA_1_P2. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 25 region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA _1 P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P2 30 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072053 PCT/IB2005/000928 271 Table 7 - Amino acid mutations SNP position(s) on antino acid Alternative amino acid(s) Previously known SNP'? sequence 13 No 232 N ->D No 324 P-> No 63 I-> No 92 G No Variant protein T10888 PEA 1 P2 is encoded by the following transcript(s): T10888_PEA_1_T1, for which the sequence(s) is/are given at the end of the application. The 5 coding portion of transcript T10888_PEA_1_TI is shown in bold; this coding portion starts at position 151 and ends at position 1122. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888 PEA_1 P2 sequence provides support for the deduced 10 sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nricleotide Alternative nucleic acid Previously knon SNP sequ~ec 119 C -> T No 120 A ->T No 1062 A ->G Yes 1120 C-> No 1297 G ->T Yes 1501 A ->G Yes 1824 G ->A No 2036 A ->C No 2036 A ->G No WO 2005/072053 PCT/IB2005/000928 272 2095 A> C No 2242 A-> C No 2245 A-> C No 189 C ->No 2250 A-> T Yes 2339 C ->A Yes 276 G ->A Yes 338 T-> No 424 G-> No 546 A ->G No 702 C -> T No 844 A ->G No 930 C ->T Yes Variant protein T10888_PEA_1_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T10888_PEA_1-T4. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between T10888 PEA_1_P4 and CEA6_HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEA_1 _P4, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWPTTAKLTIESTPFNVAEGKEVLLLAHNLP 15 QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL

WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL

WO 2005/072053 PCT/IB2005/000928 273 corresponding to amino acids 1 - 234 of CEA6 HUMAN, which also corresponds to amino acids I - 234 of T10888_PEA_1 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of T10888_PEA_1_P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1 P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL in T10888_PEA_1_P4. Comparison report between T10888_PEA_1 P4 and Q13774 (SEQ ID NO:1382): 1.An isolated chimeric polypeptide encoding for T10888_PEA_1 P4, comprising a first 15 amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 20 corresponding to amino acids 1 - 234 of Q13774, which also corresponds to amino acids 1 - 234 of TI 0888_PEA_1 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLLSSQLWPPSASRLECWPGWL corresponding to amino acids 235 - 256 of T10888 PEA_1 P4, wherein said first and second 25 amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1 P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LLLSSQLWPPSASRLECWPGWL in T10888_PEA_1 P4. 30 WO 2005/072053 PCT/IB2005/000928 274 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA 1 P4 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations SNP positions) on amino acid Alternative aminoacid(s) Previously known SNP? sequence 13 V -> No 232 N->D No 63 I-> No 92 G -> No 15 Variant protein T10888_PEA_1_P4 is encoded by the following transcript(s): T10888_PEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_1_T4 is shown in bold; this coding portion starts at position 151 and ends at position 918. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative 20 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 275 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C -> T No 120 A ->T No 978 C-> No 1155 G ->T Yes 1359 A ->G Yes 1682 G ->A No 1894 A ->C No 1894 A ->G No 1953 A ->C No 2100 A ->C No 2103 A ->C No 2108 A ->T Yes 189 C-> No 2197 C ->A Yes 276 G ->A Yes 338 T-> No 424 G-> No 546 A ->G No 702 C->T No 844 A ->G No 958 G-> No Variant protein T10888_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T10888_PEA_1_T5. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the WO 2005/072053 PCT/IB2005/000928 276 application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between T10888_PEA_1_P5 and CEA6_HUMAN: 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_P5, comprising a first 5 amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPEVQNTTYL WWVNGQSLPVSPRLQLSNGNMTLTLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLY 10 GPDVPTISPSKANYRPGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGS YMCQAHNSATGLNRTTVTMITVSG corresponding to amino acids 1 - 320 of CEA6_HUMAN, which also corresponds to amino acids 1 - 320 of T10888_PEA1 1P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 15 having the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV corresponding to amino acids 321 - 390 of T10888_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P5, comprising a 20 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence KWIHEALASHFQVESGSQRRARKKFSFPTCVQGAHANPKFSPEPSQFTSADSFPLVFLFF VVFCFLISHV in T10888_PEA_1_P5. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal 30 peptide prediction programs agree that this protein has a signal peptide, both trans-membrane WO 2005/072053 PCT/IB2005/000928 277 region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.. Variant protein T10888_PEA_1_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) onamino acid Alternative amino acids) Previously known SNP? sequence 13 V-> No 232 N ->D No 63 1 -> No 92 G-> No 10 Variant protein T10888_PEA_1_P5 is encoded by the following transcript(s): T10888_PEA 1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript T10888_PEA_1_T5 is shown in bold; this coding portion starts at position 151 and ends at position 1320. The transcript also has the following SNPs as listed in 15 Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C -> T No 120 A -> T No WO 2005/072053 PCT/IB2005/000928 278 1062 A ->G Yes 1943 C ->A Yes 2609 C ->T Yes 2647 C ->G No 2701 C ->T Yes 2841 T ->C Yes 189 C-> No 276 G -> A Yes 338 T -> No 424 G No 546 A ->G No 702 C ->T No 844 A ->G No 930 C ->T Yes Variant protein T10888_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 T10888_PEA_1_T6. An alignment is given to the known protein (Carcinoembryonic antigen related cell adhesion molecule 6 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. Comparison report between T10888_PEA_1_P6 and CEA6_HUMAN: 10 1.An isolated chimeric polypeptide encoding for T10888_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLAHNLP QNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRETIYPNASLLIQNVTQNDTG FYTLQVIKSDLVNEEATGQFHVY corresponding to amino acids 1 - 141 of CEA6_HUMAN, 15 which also corresponds to amino acids 1 - 141 of T10888_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072053 PCT/IB2005/000928 279 REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI corresponding to amino acids 142 - 183 of T10888PEA_1 P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of T10888_PEA_1_P6, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence REYFHMTSGCWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI in T10888_PEA_1_P6. 10 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 15 region prediction program predicts that this protein has a trans-membrane region.. Variant protein T10888_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein T10888_PEA_1_P6 20 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SN? sequence 13 V-> No 63 I-> No 92 G No Variant protein T10888_PEA_1_P6 is encoded by the following transcript(s): 25 T10888_PEA_1_T6, for which the sequence(s) is/are given at the end of the application. The WO 2005/072053 PCT/IB2005/000928 280 coding portion of transcript T10888_PEA_1 T6 is shown in bold; this coding portion starts at position 151 and ends at position 699. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein T10888_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 119 C ->T No 120 A ->T No 189 C-> No 276 G ->A Yes 338 T-> No 424 G-> No 546 A ->G No As noted above, cluster T10888 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are 10 portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. Segment cluster T10888_PEA_1_node_11 according to the present invention is supported 15 by 57 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_Tl and T10888_PEA_1_T5. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_Ti 854 1108 WO 2005/072053 PCT/IB2005/000928 281 T10888_PEA_1_T5 854 1108 Segment cluster T10888-PEAInode_12 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): T10888_PEA_1_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position, T10888_PEA_1_T5 1109 3004 10 Segment cluster T10888_PEA_1_node_17 according to the present invention is supported by 160 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_Ti and T10888_PEA_1_T4. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript nanie Segment starting position Segment ending position T10888_PEA 1 Ti 1109 2518 T10888_PEA1 1T4 967 2376 15 Segment cluster T10888_PEA_1_node_4 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_1, T10888_PEA_1_T4, 20 T10888_PEA_1_T5 and T10888_PEA_1_T6. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 282 T10888_PEA 1_TI 1 214 T10888_PEA_1_T4 1 214 T10888_PEA_1_T5 1 214 T10888 PEA_1 T6 1 214 Segment cluster T10888_PEA 1_node 6 according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): T10888_PEAITi, T10888_PEA_1_T4, T10888_PEA_1_T5 and T10888 PEA_1_T6. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending Iosiion T10888 PEA_ IT1 215 574 T10888_PEA_1_T4 215 574 T10888 PEA 1 T5 215 574 T18PEA 1 T6 215 574 10 Segment cluster T10888_PEA_1_node_7 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_T6. Table 20 below describes the starting and ending position of this segment on each transcript. 15 Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_T6 575 1410 WO 2005/072053 PCT/IB2005/000928 283 Segment cluster T10888_PEA-1_node_9 according to the present invention is supported by 72 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_ITi, T10888_PEA_1T4 and T10888_PEA_1_T5. Table 21 below describes the starting and ending position of this segment 5 on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA_1_TI 575 853 T10888_PEA_1_T4 575 853 T10888_PEA 1 T5 575 853 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 10 Segment cluster T10888_PEA_1_node_15 according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): T10888_PEA_1_T4. Table 22 below describes the starting and ending position of this segment on each transcript. 15 Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position T10888_PEA1 1T4 854 966 20 Variant protein alignment to the previously known protein: Sequence name: /tmp/tM4EgaoKvm/vuztUrlRc7:CEA6_HUMAN WO 2005/072053 PCT/IB2005/000928 284 Sequence documentation: Alignment of: T10888_PEA_1_P2 x CEA6_HUMAN 5 Alignment segment 1/1: Quality: 3163.00 Escore: 0 Matching length: 319 Total length: 319 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 2 0 i I l l l l l i l l l 1l l l I Illl il l l l l l l l l l l l l l l l l l l l l l l 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 25 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 30 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 WO 2005/072053 PCT/IB2005/000928 285 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 5 I l l l l l | | | | | l l l l l l l1 1 l1 l l l l l l l l l l l l l i l l i l l l l l l i 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 301 AHNSATGLNRTTVTMITVS 319 10 301 AHNSATGLNRTTVTMITVS 319 15 Sequence name: /tmp/Yjllgj7TCe/PgdufzLOlW:CEA6_HUMAN Sequence documentation: 20 Alignment of: T10888_PEA_1_P4 x CEA6_HUMAN Alignment segment 1/1: 25 Quality: 2310.00 Escore: 0 Matching length: 234 Total length: 234 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072053 PCTIIB2005/000928 286 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 5 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLTVGYVIGTQQATPGPAYSGRET 100 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLTVGYVIGTQQATPGPAYSGRET 100 10 101 IYPNASLLIQNVTQNDTGFYTLQVTKSDLVNEEATGQFHVYPELPKPSIS 150 101 IYPNASLLTQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSTS 150 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 201 TLL SVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 20 201 TLLSVKRNDAGSYBCEIQNPASAN.SDPVTLNVL 234 25 Sequence name: /tmp/Yjll gj7TCe/PgdufzLOlW:Q 13774 Sequence documentation: 30 Aligninent of: Tl0888_PEA 1-P4 x Q3774 WO 2005/072053 PCT/IB2005/000928 287 Alignment segment 1/1: Quality: 2310.00 Escore: 0 5 Matching length: 234 Total length: 234 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 15 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 20 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 li l l l l l l l l l l l l l l l l l l i l l l i l l11 l ll1 l l1 1 l l1 l l l l l I 101 TYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 2 5 I l l l l l l l l l l l l l l l l Ill l l l l l l l l l l l l Ill l l l l l l l l l I 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 30 | 1| 11| l I I201I i LI I 1111 1 I23 30 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVL 234 WO 2005/072053 PCT/IB2005/000928 288 5 Sequence name: /tinp/x5xDBacdpj/rTXRGepv3y:CEA6_HUMAN Sequence documentation: 10 Alignment of: T10888_PEA_1_P5 x CEA6_HUMAN Alignment segment 1/1: Quality: 3172.00 Escore: 0 15 Matching length: 320 Total length: 320 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 25 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 l i l l l l I 1ll l l l 1l1ll l l ll l l l l l l l l l l 1l i l l l l l 11l l l l l l 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 30 101 IYPNASLLIQNVTQNDTGFYTLQVTKSDLVNEEATGQFHVYPELPKPSIS 150 l i l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i WO 2005/072053 PCT/IB2005/000928 289 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSIS 150 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 1l1l1lllll111llillllIll1llll1l111l1lllllllllllll 5 151 SNNSNPVEDKDAVAFTCEPEVQNTTYLWWVNGQSLPVSPRLQLSNGNMTL 200 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 201 TLLSVKRNDAGSYECEIQNPASANRSDPVTLNVLYGPDVPTISPSKANYR 250 10 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 l i l l l l l l l l l l l l l l l l l l l i i l l l l l l l l1 1 1 l l l l l l l i l l l 251 PGENLNLSCHAASNPPAQYSWFINGTFQQSTQELFIPNITVNNSGSYMCQ 300 15 301 AHNSATGLNRTTVTMITVSG 320 301 AHNSATGLNRTTVTMITVSG 320 20 Sequence name: /tmp/VAhvYFeatq/QNEM573uCo :CEA6_HUMAN 25 Sequence documentation: Alignment of: T10888_PEA_1_P6 x CEA6 HUMAN . 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 290 Quality: 1393.00 Escore: 0 Matching length: 143 Total length: 143 5 Matching Percent Similarity: 99.30 Matching Percent Identity: 99.30 Total Percent Similarity: 99.30 Total Percent Identity: 99.30 Gaps: 0 10 Alignment: 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 l il i l l l l l l ll i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i l 15 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 20 101 IYPNASLLTQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYRE 143 l i l l l l l l l l l l l l l l l l l ll l l l l l l l l l l l l l l I 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPE 143 25 Alignment of: T10888_PEA_1 P6 x CEA6_HUMAN Alignment segment 1/1: Quality: 101.00 30 Escore: 0 WO 2005/072053 PCT/IB2005/000928 291 Matching length: 141 Total length: 183 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 77.05 Total Percent Identity: 77.05 Gaps: 1 Alignment: 10 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 11i 1l 1ll1 111llll 1llllll 1llllllll1llll11llll1l11ll1 l 1 MGPPSAPPCRLHVPWKEVLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 50 15 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 lillllll1ll1lll1lillill11lll1l1ll11l1llllIlllIl 51 VLLLAHNLPQNRIGYSWYKGERVDGNSLIVGYVIGTQQATPGPAYSGRET 100 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYREYFHMTSG 150 2 0 l i l l 1 l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i 101 IYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVY ......... .141 151 CWGSVLLPTYGIVRPGLCLWPSLHYILYQGLDI 183 25 141 ................................. 141 Expression of CEA6_HUMvAN Carcinoembryonic antigen-related cell adhesion molecule 6 (T10888)] transcripts which are detectable by amplicon as depicted in sequence name [T10888 junc11-17] in normal and cancerous colon tissues. 30 Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to juncl1-17 [node(s)/edge], T10888 junci1-17 WO 2005/072053 PCT/IB2005/000928 292 amplicon (SEQ ID NO: 1279) and juncl 1-17 primers (SEQ ID NO: 1277-1278) was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon, SEQ ID NO:531), HPRTl (GenBank Accession No. NM_000194; amplicon - HPRTI-amplicon, SEQ ID NO:612), G6PD (GenBank 5 Accession No. NM_000402; G6PD amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_002954; RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples 10 (Sample Nos. 41, 52, 62-67, 69-71, Table 1, "Tissue samples in testing panel", above), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 10 is a histogram showing over expression of the above-indicated CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts in cancerous colon samples relative to the normal samples. As is evident from Figure 10, the 15 expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, "Tissue samples in testing panel", above). Notably an over-expression of at least 3 fold was found in 15 out of 36 adenocarcinoma samples 20 Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by the above amplicon(s) in colon cancer samples versus the normal tissue samples was determined by T test 25 as 5.36E-03. Threshold of 3 fold overexpression was found to differentiate between cancer and normal samples with P value of 7.41E-03 as checked by exact fisher test. The above values demonstrate statistical significance of the results. Primer pairs are also optionally and preferably encompassed within the present 30 invention; for example, for the above experiment, the following primer pair was used as a non- WO 2005/072053 PCT/IB2005/000928 293 limiting illustrative example only of a suitable primer pair: T10888junc11-17F forward primer; and T10888juncl1-1 7R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon 5 was obtained as a non-limiting illustrative example only of a suitable amplicon: T10888juncll 17. Forward: (SEQ ID NO: 1277)- CCAGCAATCCACACAAGAGCT Reverse (SEQ ID NO: 1278)- CAGGGTCTGGTCCAATCAGAG Amplicon (SEQ ID NO: 1279) 10 CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATAGCGGAT CCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGGACCACAGTCACG ATGATCACAGTCTCTGATTGGACCAGACCCTG 15 Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 T10888 transcripts, which are detectable by amplicon as depicted in sequence name T 10888junc11-17 in different normal tissues. 20 Expression of CEA6_HUMAN Carcinoembryonic antigen-related cell adhesion molecule 6 transcripts detectable by or according to T10888 junc1 1-17 amplicon (SEQ ID NO: 1282) and T10888 juncll-17F (SEQ ID NO: 1280) and T10888 juncll-17R (SEQ ID NO: 1281) was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL19 25 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the 30 geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos.

WO 2005/072053 PCT/IB2005/000928 294 18-20 Table 2 Tissue samples in normal panel), to obtain a value of relative expression of each sample relative to median of the ovary samples. The results are described in Figure 11, presenting the histogram showing the expression of T10888 transcripts, which are detectable by amplicon as depicted in sequence name 5 T10888juncl 1-17 in different normal tissues. Forward primer (SEQ ID NO: 1280): CCAGCAATCCACACAAGAGCT Reverse primer (SEQ ID NO: 1281): CAGGGTCTGGTCCAATCAGAG Amplicon (SEQ ID NO: 1282): 10 CCAGCAATCCACACAAGAGCTCTTTATCCCCAACATCACTGTGAATAATAGCGGAT CCTATATGTGCCAAGCCCATAACTCAGCCACTGGCCTCAATAGGACCACAGTCACG ATGATCACAGTCTCTGATTGGACCAGACCCTG 15 DESCRIPTION FOR CLUSTER H14624 20 Cluster H14624 features 1 transcript(s) and 15 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 25 Table I - Transcripts of interest Transcript Name SEQ ID NO: H14624_T20 7 Table 2 - Segments of interest WO 2005/072053 PCT/IB2005/000928 295 Segment Name SEQ ID NO: H14624 node 0 108 H14624_node_16 109 H14624_node_3 110 H14624 node 10 111 H14624_node_11 112 H14624_node_12 113 H14624_node_13 114 H14624_node 14 115 H14624 node 15 116 H14624_node 4 117 H14624_node 5 118 H14624 node 6 119 H14624_node 7 120 H14624_node 8 121 H14624_node_9 122 Table 3 - Proteins of interest Protein Name SEQ ID NO: H14624_P15 540 Cluster H14624 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 5 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 10 Overall, the following results were obtained as shown with regard to the histograms in Figure 12 and Table 4. This cluster is overexpressed (at least at a minimum level) in the WO 2005/072053 PCT/IB2005/000928 296 following pathological conditions: colorectal cancer, epithelial malignant tumors, a mixture of malignant tumors from different tissues, lung malignant tumors and pancreas carcinoma. Table 4 - Normal tissue distribution Name of Tissue Numrber adrenal 0 bladder 410 bone 71 brain 42 colon 6 epithelial 91 general 74 head and neck 0 kidney 0 lung 30 breast 949 ovary 7 pancreas 2 prostate 94 stomach 3 Thyroid 128 uterus 54 5 Table 5 - P values and ratiosfor expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 adrenal 4.2e-01 4.6*-01 4.6e-01 2.2 5.3e-01 1.9 bladder 5.4e-0l 6.0e-01 1.2e-02 1.6 2.2e-01 1.0 bone 4.9e-01 8.5*-01 1.8e-01 1.3 7.5e-01 0.6 brain 4.7e-01 7.0*-01 6.3e-05 2.3 9.4e-03 1.4 colon 4.4e-02 9.9*-02 4.5e-03 5.4 2.0e-02 3.9 WO 2005/072053 PCT/IB2005/000928 297 epithelial 7.7e-03 3.6e-01 1.5e-11 2.0 2.9e-02 1.1 general 5.le-03 5.9e01 8.3e-21 2.2 1.5e-04 1.2 head and neck 1.4e-01 2.8e-01 4.6e-01 2.2 7.5e-01 1.3 kidney 6.5e-01 7.2--01 5.8e-01 1.7 7.0e-01 1.4 lung 6.le-02 1.4e-01 3.3e-05 5.8 8.le-03 2.9 breast 2.4e-01 4.le-01 1 0.3 1 0.2 ovary 8.5e-01 7.-01 6.8e-01 1.2 1.6e-01 1.6 pancreas 7.5e-03 4.9*-02 1.2e-21 22.4 2.4e-16 15.1 prostate 8.3e-01 8.9e-01 7.2e-01 0.8 8.8c-01 0.6 stomach 4.6e-01 8.5*-01 1.0e-03 2.7 1.le-01 1.4 Thyroid 7.0e-01 7.0*-01 5.9e-01 1.0 5.9e-01 1.0 uterus 4.le-01 7.3*-01 2.3e-01 1.2 6.2e-01 0.7 As noted above, cluster H14624 features 1 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. Variant protein H14624_P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) H14624_T20. One 5 or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between H14624_P15 and Q9HAP5 (SEQ ID NO: 1384): 1.An isolated chimeric polypeptide encoding for H14624_P15, comprising a first amino 10 acid sequence being at least 90 % homologous to MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLCHGIEYQNMR LPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLC VQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLPATEE corresponding to amino acids 1 - 167 of Q9HAP5, which also corresponds to amino acids 1 - 167 of 15 H14624_P15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKPSLLLPHSLLG corresponding to amino acids 168 - 180 of H14624_P15, wherein said first and second amino acid sequences are continuous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 298 2.An isolated polypeptide encoding for a tail of H14624 P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKPSLLLPHSLLG in H14624_P15. 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein H14624_P15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is 15 known or not; the presence of known SNPs in variant protein H14624_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Priously known SNP? sequence 11 L-> No 170 P -> S Yes 28 F-> No 29 G-> No 38 S-> No 45 A -> V Yes 60 L -> No Variant protein H14624_P15 is encoded by the following transcript(s): H14624_T20, for 20 which the sequence(s) is/are given at the end of the application. The coding portion of transcript H14624_T20 is shown in bold; this coding portion starts at position 857 and ends at position WO 2005/072053 PCT/IB2005/000928 299 1396. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H14624P15 sequence provides support for the deduced sequence of this variant protein 5 according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously Inown SNP? sequence 389 A -> G No 476 C->T No 969 G -> No 988 G -> T Yes 990 C->T Yes 1034 C -> No 1168 C->T Yes 1364 C->T Yes 488 T -> C No 819 C -> G Yes 851 C -> No 887 C -> No 922 G -> A Yes 934 C -> T Yes 938 T -> No 943 C -> No As noted above, cluster H14624 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular 10 interest. A description of each segment according to the present invention is now provided. Segment cluster H14624_node_0 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072053 PCT/IB2005/000928 300 found in the following transcript(s): H14624_T20. Table 8 below describes the starting and ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 1 573 5 Segment cluster H14624_node_16 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20. Table 9 below describes the starting and ending position of this segment on each transcript. 10 Table 9 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 1359 1745 Segment cluster H14624_node_3 according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be 15 found in the following transcript(s): H14624_T20. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 574 822 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are 20 included in a separate description.

WO 2005/072053 PCT/IB2005/000928 301 Segment cluster H14624_node_10 according to the present invention can be found in the following transcript(s): H 14624_T20. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segrnent starting position Segment ending position H14624_T20 1070 1079 5 Segment cluster H14624_node_11 according to the present invention is supported by 99 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20. Table 12 below describes the starting and 10 ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position. Segment ending position H14624_T20 1080 1114 Segment cluster H14624_node_12 according to the present invention can be found in the 15 following transcript(s): H14624_T20. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 1115 1135 20 Segment cluster H14624_node_13 according to the present invention is supported by 124 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624 T20. Table 14 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 302 Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 1136 1227 Segment cluster H 14624_node_14 according to the present invention is supported by 114 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 1228 1287 10 Segment cluster H14624_node_15 according to the present invention is supported by 124 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): H14624_T20. Table 16 below describes the starting and ending position of this segment on each transcript. 15 Table 16 - Segment location on transcripts Transcript name Segment starting position Segent ending position H14624 T20 1288 1358 Segment cluster H14624_node_4 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be 20 found in the following transcript(s): H14624_T20. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 303 Transcript name Segment starting position Segment ending position H14624_T20 823 892 Segment cluster H14624_node_5 according to the present invention can be found in the following transcript(s): H14624_T20. Table 18 below describes the starting and ending position 5 of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position segment ending position H14624_T20 893 903 Segment cluster H14624_node_6 according to the present invention can be found in the 10 following transcript(s): H14624_T20. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Traiscript name Se gment starting position Segment ending position H14624_T20 904 927 15 Segment cluster H14624_node_7 according to the present invention can be found in the following transcript(s): H14624_T20. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 928 934 20 WO 2005/072053 PCT/IB2005/000928 304 Segment cluster H14624_node_8 according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H14624_T20. Table 21 below describes the starting and ending position of this segment on each transcript. 5 Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position H14624_T20 935 1014 Segment cluster H14624_node_9 according to the present invention is supported by 87 libraries. The number of libraries was detennined as previously described. This segment can be 10 found in the following transcript(s): H14624_T20. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment startingosition Segment ending position H14624_T20 1015 1069 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/UpblSbFkrj/N4PrGQAB2V:Q9HAP5 20 Sequence documentation: Alignment of: H14624 P15 x Q9HAP5 Alignment segment 1/1: 25 WO 2005/072053 PCT/IB2005/000928 305 Quality: 1702.00 Escore: 0 Matching length: 167 Total length: 167 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLC 50 15 1 MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLC 50 51 HGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFA 100 51 HGIEYQNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFA 100 20 101 PVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDND 150 101 PVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDND 150 25 151 LCIPLASSDHLLPATEE 167 151 LCIPLASSDHLLPATEE 167 30 0~ ~ ~ P I ""; /; r "'o " " '812 8 WO 2005/072053..000092 306 306 WO 2005/072053 PCT/IB2005/000928 307 DESCRIPTION FOR CLUSTER H53626 Cluster H53626 features 2 transcript(s) and 20 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 5 Table I - Transcripts of interest Transcript Name SEQ ID NO: H53626_PEA 1_T15 8 H53626_PEA 1_T16 9 Table 2 - Segments of interest Segment Namne SEQ ID NO: H53626_PEA_1 node_15 123 H53626_PEA_1_node_22 124 H53626_PEA 1_node 25 125 H53626_PEA1node_26 126 H53626PEA_1_node 27 127 H53626PEA_1 node_34 128 H53626_PEA 1_node_35 129 H53626PEA 1 node_36 130 H53626PEA 1 node_11 131 H53626_PEA1node_12 132 H53626_PEA 1 node 16 133 H53626PEA 1_node_19 134 H53626PEA_1 node 20 135 H53626PEA_1 node 24 136 H53626PEA 1_node_28 137 H53626PEA 1_node_29 138 H53626PEA_1 node_30 139 H53626PEA_1 node 31 140 WO 2005/072053 PCT/IB2005/000928 308 H53626_PEA_1_node_32 141 H53626 PEA 1 node 33 142 Table 3 - Proteins of interest Protein Name: SEQ ID NO: H53626_PEA 1 P4 541 H53626_PEA_1_P5 542 5 Cluster 1-153626 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in nonnal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to 10 the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 13 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors 15 from different tissues and myosarcoma. 20 Table 4 - Normal tissue distribution Name of Tissue Number WO 2005/072053 PCT/IB2005/000928 309 Adrenal 4 Bone 239 Brain 39 Colon 0 Epithelial 12 General 18 head and neck 0 Kidney 8 Lung 26 Breast 8 Muscle 0 Ovary 7 Pancreas 10 Prostate 8 Skin 0 Stomach 73 Thyroid 0 Uterus 0 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 SPI R3 SP2 R4 adrenal 6.4*-01 4.2e-01 2.le-01 3.1 1.3e-02 4.1 bone 5.8*-01 8.1e-01 9.8e-01 0.3 1 0.3 Brain 2.8*-01 3.3e-01 8.7e-01 0.7 9.4e-01 0.5 Colon 2.3*-01 1.4e-01 1 1.2 4.6e-01 1.9 epithelial 7.2*-02 3.7e-03 5.8e-02 1.6 1.4e-08 4.3 general 2.7e-03 1.8e-05 7.8e-04 1.6 8.2e-13 3.0 Head and neck 2.le-01 3.3e-01 O.Oe+00 0.0 0.Oe+00 0.0 Kidney 7.3e-01 5.8e-01 5.8e-01 1.3 4.0e-02 2.0 WO 2005/072053 PCT/IB2005/000928 310 lung 8.4e-01 S.8e-01 7.9e-01 0.8 3.7e-02 2.0 Breast 6.5'-01 2.7e-01 6.9e-01 1.2 7.8e-02 1.9 Muscle 1 2.9e-01 1 1.0 3.5e-03 4.1 Ovary 6.7e-01 5.6e-ol 1.5e-0l 1.7 7.0e-02 2.7 pancreas 2.3e-01 2.0e-01 3.9e-01 1.9 8.2e-02 2.3 prostate 9.0e-01 9.0e-01 6.7e-01 1.1 1.3e-01 1.9 skin 1 4.4e-01 1 1.0 4.1e-01 2.1 stomach 9.0*-01 3.4e-01 1 0.3 6.le-01 0.9 Thyroid 2.4e-01 2.4e-01 1 1.1 1 1.1 Uterus 2.1e-01 2.4e-01 2.9e-01 2.5 2.6e-01 2.2 As noted above, cluster H53626 features 2 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. Variant protein H53626_PEA 1_P4 according to the present invention has an amino acid 5 sequence as given at the end of the application; it is encoded by transcript(s) H53626_PEA_1_T15. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between H53626_PEA_1_P4 and Q8N441(SEQ ID NO:1385): 10 1.An isolated chimeric polypeptide encoding for H53626 PEA 1 P4, comprising a first amino acid sequence being at least 90 % homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPP LTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVV LDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVAS 15 GHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINAT YKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCKVRSDVKPVIQWLKRVEYGAEGR HNSTIDVGGQKFVVLPTGDVWSRPDGSYLNKLLITRARQDDAGMYICLGANTMGYSFR SAFLTVLP corresponding to amino acids 1 - 357 of Q8N441, which also corresponds to amino acids 1 - 357 of H53626_PEA_1 P4, second amino acid sequence being at least 70%, optionally 20 at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence WO 2005/072053 PCT/IB2005/000928 311 GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMG LGCSPGLCVGVPLPTSFPLALA corresponding to amino acids 358 - 437 of H53626_PEA_1_P4, and a third amino acid sequence being at least 90 % homologous to DPKPPGPPVASSSSATSLPWPVVIGIPAGAVFILGTLLLWLCQAQKKPCTPAPAPPLPGH 5 RPPGTARDRSGDKDLPSLAALSAGPGVGLCEEHGSPAAPQHLLGPGPVAGPKLYPKLY TDIHTHTHTHSHTHSHVEGKVHQHIHYQC corresponding to amino acids 358 - 504 of Q8N441, which also corresponds to amino acids 438 - 584 of H53626_PEA1 1P4, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of H53626_PEA_1_P4, 10 comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMG LGCSPGLCVGVPLPTSFPLALA, corresponding to H53626_PEA_1_P4. 15 The location of the variant protein was detennined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: membrane. The protein localization is believed to be membrane because although both signal 20 peptide prediction programs agree that this protein has a signal peptide, both trans-membrane region prediction programs predict that this protein has a trans-membrane region downstream of this signal peptide.. Variant protein H53626_PEA_1_P4 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the 25 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 312 SNP positions) on amino acid .Alternative amino acid(s) Previously known SNP? sequence 193 R ->L Yes 300 G-> No 319 Y ->H No 442 P->Q Yes 504 R -> L Yes 521 G -> No 544 P -> L Yes 573 E -> G No Variant protein H53626_PEA__P4 is encoded by the following transcript(s): H53626_PEA_1_T15, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H53626_PEA_1_T15 is shown in bold; this coding portion starts at 5 position 17 and ends at position 1768. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 7 - Nucleic acid SNPs SN? position on nucleotide Alternative nucleic acid Previously known SNP? sequence 76 G->A Yes 340 G -> T No 1647 C -> T Yes 1734 A -> G No 1797 G -> No 1948 A -> G Yes 2193 C -> T Yes WO 2005/072053 PCT/IB2005/000928 313 2308 C ->T Yes 2333 C ->G Yes 2648 C ->T Yes 2649 G ->A Yes 2765 C -> T Yes 594 G -> T Yes 2972 G -> A Yes 3027 C ->G Yes 907 T ->C Yes 916 C-> No 971 T ->C No 1135 G ->A Yes 1341 C ->A Yes 1527 G ->T Yes 1579 C-> No Variant protein H53626_PEA_1_PS according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 H53626_PEA_1_Ti6. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between H53626_PEA_1_P5 and Q9H4D7(SEQ ID NO:1386): 1.An isolated chimeric polypeptide encoding for H53626_PEA_1_P5, comprising a first 10 amino acid sequence being at least 90 % homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPP LTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVV LDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVAS GHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINAT 15 YKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids I - 269 of 09H4D7. which also corresponds to amino acids 1 - 269 of H53626_PEA_1_P5, and a WO 2005/072053 PCT/IB2005/000928 314 second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLG 5 TARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNS TQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKA GDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP corresponding to amino acids 270 - 490 of H53626_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 2.An isolated polypeptide encoding for a tail of H53626_PEA_1_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLG 15 TARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNS TQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKA GDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP in H53626_PEA_1_P5. Comparison report between H53626_PEA__P5 and Q8N441 (SEQ ID NO: 1385): 20 1.An isolated chimeric polypeptide encoding for H53626PEA_1 P5, comprising a first amino acid sequence being at least 90 % homologous to MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPP LTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVV LDDISPGKESLGPDSSSGGQEDPASQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVAS 25 GHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLKNLRPEDSGKYTCRVSNRAGAINAT YKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK corresponding to amino acids 1 - 269 of Q8N441, which also corresponds to amino acids 1 - 269 of H53626_PEA_1_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 30 having the sequence

TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLG

WO 2005/072053 PCT/IB2005/000928 315 TARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNS TQTSTHTHTHTLTHTHTWRARSTSTSTISARRH-IRICSGHGGAGQTGRLGGWRTELQTKA GDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP corresponding to amino acids 270 - 490 of H53626_PEA_1_P5, wherein said first and second amino acid 5 sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of H53626_PEA__P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLG TARRGRPATAAETRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNS TQTSTHTHTHTLTHTHTWRARSTSTSTISARRHRICSGHGGAGQTGRLGGWRTELQTKA GDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDACMHTHARTRAP in H53626_PEA_1_P5. 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 20 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein H53626_PEA_1_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 25 the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence WO 2005/072053 PCT/IB2005/000928 316 193 R ->L Yes 274 Q ->K Yes 336 A ->S Yes 353 A-> No 376 Q->* Yes 405 R -> G No 426 G -> No 476 Y -> C Yes Variant protein H53626_PEA_1_P5 is encoded by the following transcript(s): H53626_PEA_1_TI6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript H53626_PEA_1_T16 is shown in bold; this coding portion starts at 5 position 17 and ends at position 1486. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein H53626_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 9 -Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 76 G ->A Yes 340 G ->T No 1688 C ->T Yes 1803 C ->T Yes 1828 C ->G Yes 2143 C ->T Yes 2144 G ->A Yes 2260 C ->T Yes 2467 G -> A Yes 2522 C -> G Yes WO 2005/072053 PCT/IB2005/000928 317 594 G ->T Yes 836 C ->A Yes 1022 G ->T Yes 1074 C-> No 1142 C ->T Yes 1229 A ->G No 1292 G-> No 1443 A ->G Yes As noted above, cluster H53626 features 20 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster H53626_PEA_1_node_15 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_TI5 and H53626_PEAIT16. 10 Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626 PEA 1_T15 96 343 H53626_PEA 1 T16 96 343 Segment cluster H53626_PEA_1_node_22 according to the present invention is supported 15 by 42 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 318 Transcript name Segment starting position Segment ending position H53626_PEA_1_TI5 450 734 H53626_PEA_1_T16 450 734 Segment cluster H53626_PEA_1_node_25 according to the present invention is supported by 41 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): H53626_PEA1T15. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Trascript name Segment starting position H53626_PEA_1TI5 824 1088 Segment cluster H53626_PEA_1_node_26 according to the present invention is supported 10 by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_T15. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626 PEA_1_TI5 1089 1328 15 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides (related to colon cancer) were found to hit this segment, shown in Table 15. Table 15 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference H53626_0_0_8391 colorectal cancer Colon WO 2005/072053 PCT/IB2005/000928 319 Segment cluster H53626_PEA _node_27 according to the present invention is supported by 106 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_TI5 and H53626_PEA_1_T16. Table 16 below describes the starting and ending position of this segment on each transcript. 5 Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA 1 TI5 1329 2228 H53626_PEA_1 T16 824 1723 Segment cluster H53626_PEA_1_node_34 according to the present invention is supported by 121 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name 'Segmnenitstarting position H53626_PEA 1_T15 2507 2977 H53626_PEA 1 T16 2002 2472 Segment cluster H53626_PEA_1_node_35 according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA_1_TI5 2978 3148 H53626_PEA_1 T16 2473 2643 Segment cluster H53626_PEA_1_node_36 according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 320 can be found in the following transcript(s): H53626 PEA_1_T15 and H53626 PEA 1 Tl6. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position H53626 PEA 1_T15 3149 3322 H53626_PEA_1 T16 2644 2817 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster H53626_PEAInode11 according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626 PEA 1 T15 and H53626 PEA_1_T16. 10 Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts TransEriname Segment starting position Segment ending position H53626_PEA 1 T15 1 55 H53626_PEA 1_T16 1 55 Segment cluster H53626 PEA 1 node_12 according to the present invention is supported 15 by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626 PEAIT15 and H53626_PEA_1_T16. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA_1_T15 56 95 H53626_PEA_1_T16 56 95 WO 2005/072053 PCT/IB2005/000928 321 Segment cluster H53626-PEA_1_node_16 according to the present invention can be found in the following transcript(s): H53626_PEAI_T15 and H53626_PEA_1_T16. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA_1 T15 344 368 H53626_PEA_1_T16 344 368 5 Segment cluster H53626_PEA_1_node_19 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA 1_TI5 369 419 H53626_PEA 1 T16 369 419 10 Segment cluster H53626_PEA_1_node_20 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1T15 and H53626_PEA_1_T16. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position H53626_PEA_1_TI5 420 449 H53626_PEA 1 T16 420 449 15 Segment cluster H53626_PEA_1_node_24 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_TI5 and H53626_PEA_1_T16. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 322 Transcript name Segment starting position Segment ending position H53626_PEA 1_TI5 735 823 H53626 PEA_1 T16 735 823 Segment cluster H53626 PEA 1 node_28 according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 26 below describes the starting and ending position of this segment on each transcript. 5 Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA1_TI5 2229 2306 H53626PEA 1 T16 1724 1801 Segment cluster H53626PEA_1_node_29 according to the present invention is supported by 73 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): 1153626_PEA_T15 and H53626_PEA_1_T16. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA 1_Ti5 2307 2396 H53626_PEA 1 T16 1802 1891 Segment cluster H53626_PEA_1_node_30 according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA 1_T15 2397 2442 WO 2005/072053 PCT/IB2005/000928 323 H53626_PEA1 16 1892 1937 Segment cluster H53626_PEA_1_node_31 according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA115 and H53626_PEA_1_T16. Table 29 below describes the starting and ending position of this segment on each transcript. 5 Table 29 - Segment location on transcripts Transcript name Segment starting position H53626_PEA 1_T15 2443 2469 H53626_PEA 1 T16 1938 1964 Segment cluster H53626_PEA_1_node_32 according to the present invention is supported by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_T16. Table 30 below describes the starting and ending position of this segment on each transcript. 10 Table 30 - Segment location on transcripts Transcript name Segment starting position Se gment ending position H53626 PEA 1_15 2470 2498 H53626_PEA 1 16 1965 1993 Segment cluster H53626_PEA_1_node_33 according to the present invention can be found in the following transcript(s): H53626_PEA_1_T15 and H53626_PEA_1_16. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position H53626_PEA_115 2499 2506 H53626_PEA_1_T16 1994 2001 15 Expression of Homo sapiens fibroblast growth factor receptor-like I (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626 junc24 27F1R3 in normal and cancerous colon tissues.

WO 2005/072053 PCT/IB2005/000928 324 Expression of Homo sapiens fibroblast growth factor receptor-like I (FGFRL1) transcripts detectable by or according to junc24-27, H53626 junc24-27F1R3 amplicon (SEQ ID NO: 1285) and H53626 junc24-27F1 (SEQ ID NO: 1283) and H53626 junc24-27R3 (SEQ ID NO: 1284) primers was measured by real time PCR. In parallel the expression of four 5 housekeeping genes -PBGD (GenBank Accession No. BCO19323; anplicon - PBGD-amplicon, SEQ ID NO:531), HPRTl (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), and G6PD (GenBank Accession No. NM_000402; G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_002954; RPS27A ainplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon 10 was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3 above, "Tissue sample in colon cancer testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. 15 Figure 14 is a histogram showing over expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRLI) transcripts in cancerous colon samples relative to the normal samples. As is evident from Figure 14, the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon in cancer samples was significantly higher than in the non-cancerous samples (Sample Nos. 41, 20 52, 62-67, 69-71 Table 3, "Tissue sample in colon cancer testing panel"). Notably an over expression of at least 5 fold was found in 13 out of 36 adenocarcinoma samples. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non 25 limiting illustrative example only of a suitable primer pair: H53626 junc24-27F1 forward primer; and H53626 junc24-27R3reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: H53626 junc24 30 27F1R3. Forward primer (SEQ ID NO: 1283): GTCCTTCCAGTGCAAGACCCA WO 2005/072053 PCT/IB2005/000928 325 Reverse primer (SEQ ID NO: 1284): TGGGCCTGGCAAAGCC Amplicon (SEQ ID NO: 1285): GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTCGTCCTC GGCCACTAGCCTGCCGTGGCCCGTGGTCATCGGCATCCCAGCCGGCGCTGTCTTCAT 5 CCTGGGCACCCTGCTCCTGTGGCTTTGCCAGGCCCA Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable by amplicon as depicted in sequence name H53626 seg25 in 10 normal and cancerous colon tissues. Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to seg25, H53626 seg25 amplicon(SEQ ID NO: 1288) and H53626 seg25F (SEQ ID NO: 1286)and H53626 seg25R (SEQ ID NO: 1287) primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD 15 (GenBank Accession No. BC019323; amplicon - PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; G6PD amplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_002954; RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric 20 mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3 above, "Tissue samples in colon cancer testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. 25 Figure 15 is a histogram showing over expression of the above-indicated Homo sapiens fibroblast growth factor receptor-like 1 (FGFRLI) transcripts in cancerous colon samples relative to the normal samples. As is evident from Figure 15, the expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by the above amplicon was higher in a few cancer samples than in the non-cancerous samples (Sample Nos. 41, 52, 62 30 67, 69-71 Table 3, "Tissue samples in colon cancer testing panel"). Notably an over-expression of at least 5 fold was found in 6 out of 36 adenocarcinoma samples.

WO 2005/072053 PCT/IB2005/000928 326 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: H53626 seg25F forward primer; and H53626 seg25R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: H53626 seg25. Forward primer (SEQ ID NO: 1286): CCGACGGCTCCTACCTCAA Reverse primer (SEQ ID NO: 1287): GGAAGCTGTAGCCCATGGTGT 10 Amplicon (SEQ ID NO: 1288): CCGACGGCTCCTACCTCAATAAGCTGCTCATCACCCGTGCCCGCCAGGACGATGCG GGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTTCC It should be noted that the variant expression pattern was found to be similar to the expression 15 pattern of the wild-type (previously known) transcript. However, in some cases (as for colon cancer) overexpression of the variant (for example H53626_FGF-RL_Ti6 transcript) seems to be higher than that the of previously known transcript. Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626 20 transcripts, which are detectable by amplicon as depicted in sequence name H53626 seg25 in different normal tissues. Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL 1) transcripts detectable by or according to H53626 seg25 amplicon (SEQ ID NO: 1288) and H53626 seg25F 25 (SEQ ID NO: 1286) and H53626 seg25R (SEQ ID NO: 1287) was measured by real time PCR. In parallel the expression of four housekeeping genes: RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon 30 SDHA-amplicon, SEQ ID NO: 1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the WO 2005/072053 PCT/IB2005/000928 327 housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 above, "Tissue samples in normal panel"), to obtain a value of relative expression of each sample relative to median of the lung samples. 5 Forward primer (SEQ ID NO: 1286): CCGACGGCTCCTACCTCAA Reverse primer (SEQ ID NO: 1287): GGAAGCTGTAGCCCATGGTGT Amplicon (SEQ ID NO: 1288): CCGACGGCTCCTACCTCAATAAGCTGCTCATCACCCGTGCCCGCCAGGACGATGCG 10 GGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTTCC The results are presented in Figure 71, showing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon(s) 15 and H53626 seg25F and H53626 seg25R in different normal tissues. Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRLl) H53626 transcripts which are detectable by amplicon as depicted in sequence name H53626 junc24 27F 1 R3 in different normal tissues 20 Expression of Homo sapiens fibroblast growth factor receptor-like 1 (FGFRL1) transcripts detectable by or according to H53626junc24-27F1R3 amplicon (SEQ ID NO:1285) and H53626 junc24-27F1 (SEQ ID NO:1283) and H53626 junc24-27R3 (SEQ ID NO:1284) was measured by real time PCR. In parallel the expression of four housekeeping genes - RPL19 25 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon, SEQ ID NO: 1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of 30 the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the lung samples (Sample Nos. 15-17 Table 2 above, WO 2005/072053 PCT/IB2005/000928 328 "Tissue samples in normal panel"), to obtain a value of relative expression of each sample relative to median of the lung samples. Forward primer (SEQ ID NO: 1283): GTCCTTCCAGTGCAAGACCCA 5 Reverse primer (SEQ ID NO: 1284): TGGGCCTGGCAAAGCC Amplicon (SEQ ID NO: 1285): GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTCGTCCTC GGCCACTAGCCTGCCGTGGCCCGTGGTCATCGGCATCCCAGCCGGCGCTGTCTTCAT CCTGGGCACCCTGCTCCTGTGGCTTTGCCAGGCCCA 10 The results are presented in Figure 72, showing the expression of fibroblast growth factor receptor-like I (FGFRL1) transcripts detectable by or according to H53626 seg25 amplicon(s) and H53626 seg25F and H53626 junc24-27FIR3 in different normal tissues. 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/KlMec2ReKO/eg1EUS2AXY:Q8N441 20 Sequence documentation: Alignment of: H53626 PEA 1 P4 x Q8N441 25 Alignment segment 1/1: Quality: 4882.00 Escore: 0 Matching length: 504 Total 30 length: 584 WO 2005/072053 PCT/IB2005/000928 329 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 86.30 Total Percent Identity: 86.30 5 Gaps: 1 Alignment: 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 10111111111111111 11 1111111 1111111llllllll1 llllllll 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 1 1 1l 1 1l l ll l l l l l l l l l l l l l l l l l l l l l l l l i l l l l l l l l l I l Il 15 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 20 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 25 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 251 THPVNTTVDFGGTTSFQCKVRSDVKPVTQWLKRVEYGAEGRHNSTIDVGG 300 251 THPVNTTVDFGGTTSFQCKVRSDVKPVIQWLKRVEYGAEGRHNSTIDVGG 300 WO 2005/072053 PCTIIB2005/000928 330 301 QKFVVLPTGDVWSRPDGSYLNKLLITRARQDDAGMYICLGANTMGYSFRS 350 301 QKFVVLPTGDVWSRPDGSYLNKLLITRARQDDAGMYICLGANTMGYSFRS 350 5 351 AFLTVLPGARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAE 400 351 AFLTVLB................................................. 357 10 401 GGQPRGTVSTAPGMGLGCSPGLCVGVPLPTSFPLALADPKPPGPPVASSS 450 358.......................................... DPKPPGPPVASSS 370 451 SATSLPWPVVTGIPAGAVFILGTLLLWLCQAQKKPCTPAPAPPLPGHRPP 500 15I1 111 11111 iI 111I111 371 SATSLPWPVVIGIPAGAVFILGTLLLWLCQAQKKPCTPAPAPPLPGURPP 420 501 GTARDRSGDKDLPSLAALSAGPGVGLCEEHGSPAAPQHLLGPGPVAGPKL 550 20 421 GTARDRSGDKDLPSLAALSAGPGVGLCEEHGSPAAPQHLLGPGPVAGPKL 470 551 YPKLYTDIHTHTHTESHTHSHVEGKVHQHIHYQC 584 471 YPKLYTDIHTHTTH-SH-THSHVEGKVHQHIHYQC 504 25 30 sequence name: /tmp/oSUZaRW3WK/oSh3fN5Zt0 :Q9H4D7 WO 2005/072053 PCT/IB2005/000928 331 Sequence documentation: Alignment of: H53626_PEA_1_P5 x Q9H4D7 5 Alignment segment 1/1: Quality: 2644.00 Escore: 0 10 Matching length: 269 Total length: 269 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 15 Identity: 100.00 Gaps: 0 Alignment: 20 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 25 II |1 ||1 i iII iI 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 30 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 WO 2005/072053 PCT/IB2005/000928 332 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 111111111 11111 1i111111 ii ii II II|IIlIII1IIII 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 5 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 iI |11 l i ll 1111 I Ii 1ii l 11 1 I I 1111i ii 11 I I II I I I I 111II1 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 251 THPVNTTVDFGGTTSFQCK 269 10 ii iii 1 1 I 251 THPVNTTVDFGGTTSFQCK 269 15 Sequence name: /tmp/oSUZaRW3WK/oSh3fN5ZtO:Q8N441 20 Sequence documentation: Alignment of: H53626PEA_1_P5 x Q8N441 Alignment segment 1/1: 25 Quality: 2644.00 Escore: 0 Matching length: 269 Total length: 269 30 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 WO 2005/072053 PCT/IB2005/000928 333 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 l1illl llllll11 l11 l llllll llllll llllll Illlllll[1 11 1 1 li 1 MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQ 50 10 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 51 CPVEGDPPPLTMWTKDGRTIHSGWSRFRVLPQGLKVKQVEREDAGVYVCK 100 15 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 101 ATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPASQQWARPRFT 150 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 20 l 1ll 11lFllllllll 1lllllilllll111 l1FF lllll1 lllllllil 151 QPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPR 200 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 25 201 KKKWTLSLKNLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTG 250 251 THPVNTTVDFGGTTSFQCK 269 251 THPVNTTVDFGGTTSFQCK 269 30 WO 2005/072053 PCT/IB2005/000928 334 DESCRIPTION FOR CLUSTER HSENA78 Cluster HSENA78 features 1 transcript(s) and 7 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end 5 of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name, SEQ ID NO: HSENA78_T5 10 Table 2 - Segments of interest SegmentNarne S IEQ 1f NO: HSENA78 node_0 143 HSENA78_node 2 144 HSENA78_node 6 145 HSENA78_node 9 146 HSENA78 node_3 147 HSENA78_node 4 148 HSENA78 node 8 149 10 Table 3 - Proteins of interest Protein Name SEQ ID NO: HSENA78 P2 543 These sequences are variants of the known protein Small inducible cytokine B5 precursor (SwissProt accession identifier SZ05 HUMAN; known also according to the synonyms CXCL5; Epithelial-derived neutrophil activating protein 78; Neutrophil-activating peptide 15 ENA- 78), SEQ ID NO: 618, referred to herein as the previously known protein. Protein Small inducible cytokine B5 precursor is known or believed to have the following function(s): Involved in neutrophil activation. The sequence for protein Small inducible WO 2005/072053 PCT/IB2005/000928 335 cytokine B5 precursor is given at the end of the application, as "Small inducible cytokine B5 precursor amino acid sequence". Protein Small inducible cytokine B5 precursor localization is believed to be Secreted. The following GO Annotation(s) apply to the previously known protein. The following 5 annotation(s) were found: chemotaxis; signal transduction; cell-cell signaling; positive control of cell proliferation, which are annotation(s) related to Biological Process; and chemokine, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available 10 from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HSENA78 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The tern "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs 15 in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 16 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors and lung malignant tumors. 20 Table 4 -Normal tissue distribution Name of Tissue Number colon 0 epithelial 2 general 38 kidney 0 lung 3 breast 8 skin 0 stomach 36 WO 2005/072053 PCT/IB2005/000928 336 uterus 4 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 colon 2.6e-01 3.3e-01 1.7e-01 2.7 2.7e-01 2.2 epithelial 2.5e-01 9.0e-02 3.2e-03 4.1 8.5e-07 5.5 general 8.4e-01 7.2e-01 1 0.3 1 0.4 kidney 1 7.2e-01 1 1.0 1.7e-01 1.9 lung 8.5e-01 4.8e-01 4.le-01 1.9 4.0e-05 3.8 breast 9.5e-01 8.7e-01 1 0.8 6.8e-01 1.2 skin 2.9e-01 4.7e-01 1.4e-01 7.0 6.4e-01 1.6 stomach 5.0e-01 4.3e-01 7.5e-01 1.0 4.3e-01 1.3 uterus 7.le-01 8.5e-01 6.6e-01 1.3 8.0e-01 1.0 As noted above, cluster HSENA78 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Small inducible 5 cytokine B5 precursor. A description of each variant protein according to the present invention is now provided. Variant protein HSENA78_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSENA78_T5. An alignment is given to the known protein (Small inducible cytokine B5 precursor) at the end of 10 the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HSENA78_P2 and SZ05_HUMAN: 1.An isolated chimeric polypeptide encoding for HSENA78_P2, comprising a first amino 15 acid sequence being at least 90 % homologous to MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHP KMISNLQVFAIGPQCSKVEVV corresponding to amino acids 1 - 81 of SZ05_HUMAN, which also corresponds to amino acids 1 - 81 of HSENA78_P2.

WO 2005/072053 PCT/IB2005/000928 337 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein HSENA78_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is 10 known or not; the presence of known SNPs in variant protein HSENA78 P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positi (s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 80 V-> No 81 V-> No Variant protein HSENA78_P2 is encoded by the following transcript(s): HSENA78_T5, 15 for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HSENA78_T5 is shown in bold; this coding portion starts at position 149 and ends at position 391. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 20 HSENA78_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 92 C -> T Yes WO 2005/072053 PCT/IB2005/000928 338 144 C ->T No 1151 A ->T Yes 1389 T ->C No 1867 C ->G Yes 145 C ->T No 181 C ->T Yes 316 G ->A Yes 388 G No 390 T-> No 605 T No 972 C ->T Yes 1105 A ->G Yes As noted above, cluster HSENA78 features 7 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster HSENA78_node_0 according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 8 below describes the starting and ending position of this segment on each transcript. 10 Table 8 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 1 257 Segment cluster HSENA78_node_2 according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 9 below describes the starting and ending position of this segment on each transcript. 15 Table 9 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 339 Transcript name Segment starting position Segment ending position HSENA78_T5 258 390 Segment cluster HSENA78_node_6 according to the present invention is supported by 68 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 10 below describes the starting and ending position of this segment on each transcript. 5 Table 10 - Segment location on transcripts Transcriptname Sgnment starting position Segment ending position HSENA78_T5 585 2370 Segment cluster HSENA78_node_9 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 11 below describes the starting and ending position of this segment on each transcript. 10 Table 11 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 2394 2546 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 15 Segment cluster HSENA78_node_3 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 391 500 20 WO 2005/072053 PCT/IB2005/000928 340 Segment cluster HSENA78_node 4 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSENA78_T5. Table 13 below describes the starting and ending position of this segment on each transcript. 5 Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78_T5 501 584 Segment cluster HSENA78 node_8 according to the present invention can be found in the following transcript(s): HSENA78_T5. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position HSENA78T5 2371 2393 10 Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment with regard to colon cancer, shown in Table 15. Table 15 - Oligonucleotides related to this gene Oligotiucleotide name Overexpressed in cancers Chip reference HSENA78_0_1_0 Colon cancer Colon 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/5kiQY6MxWx/pLnTrxsCqk:SZO5_HUMAN 20 Sequence documentation: Alignment of: HSENA78_P2 x SZO 5HUMAN WO 2005/072053 PCT/IB2005/000928 341 Alignment segment 1/1: Quality: 767.00 Escore: 0 5 Matching length: 81 Total length: 81 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 1 MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50 1 MSLLSSPAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCV 50 51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81 20 i IlIiIiiiiiiI| 1|1|11 1111111i I I 51 CLQTTQGVHPKMISNLQVFAIGPQCSKVEVV 81 25 WO 2005/072053 PCT/IB2005/000928 342 DESCRIPTION FOR CLUSTER HUMGROG5 Cluster HUMGROG5 features 4 transcript(s) and 18 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 5 Table 1 - Transcripts of interest Transcript Name SEQ ID NO HUMGROG5_PEA lT3 11 HUMGROG5 PEA 1_T4 12 HUMGROG5 PEA_1_T6 13 HUMGROG5 PEA_1_T9 14 Table 2 - Segments of interest Segment Name SEQ ID NO: HUMGROG5 PEA_1_node_18 150 HUMGROG5 PEA 1_node_19 151 HUMGROG5 PEA_1_node 21 152 HUMGROG5 PEA_1_node 23 153 HUMGROG5_PEA_1_node 6 154 HUMGROG5 PEA 1_node_10 155 HUMGROG5_PEA 1_node 11 156 HUMGROG5 PEA_1_node_12 157 HUMGROG5 PEA_1_node_13 158 HUMGROG5 PEA_1_node 14 159 HUMGROG5 PEA_1_node 15 160 HUMGROG5 PEA_1_node_16 161 HUMGROG5_PEA_1_node 17 162 HUMGROG5 PEAI 1node_20 163 HUMGROG5_PEAInode_22 164 HUMGROG5_PEA_1_node 7 165 WO 2005/072053 PCT/IB2005/000928 343 HUMGROG5_PEA_1_node_8 166 HUMGROG5_PEA_1_node_9 167 Table 3 - Proteins of interest Protein Name SEQ ID NO: HUMGROG5 PEA_1_P2 544 HUMGROG5_PEA 1_P3 545 HUMGROG5 PEA_1_P7 546 HUMGROG5PEA 1_P12 547 These sequences are variants of the known protein Macrophage inflammatory protein-2 5 beta precursor (SwissProt accession identifier MI2BHUMAN; known also according to the synonyms MIP2-beta; CXCL3; Growth regulated protein gamma; GRO-gamma), SEQ ID NO: 619, referred to herein as the previously known protein. Protein Macrophage inflammatory protein-2-beta precursor is known or believed to have the following function(s): May play a role in inflammation and exert its effects on endothelial 10 cells in an autocrine fashion. The sequence for protein Macrophage inflammatory protein-2-beta precursor is given at the end of the application, as "Macrophage inflannatory protein-2-beta precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 27-28 AA->G 15 Protein Macrophage inflammatory protein-2-beta precursor localization is believed to be Secreted. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: chemokine, which are annotation(s) related to Molecular Function; 20 and extracellular snace. which are annotation(s) related to Cellular Comnonent.

WO 2005/072053 PCT/IB2005/000928 344 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nhn.nih.gov/projects/LocusLink/>. As noted above, cluster HUMGROG5 features 4 transcript(s), which were listed in Table 5 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Macrophage inflammatory protein-2-beta precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMGROG5_PEA_1_P2 according to the present invention has an 10 amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_1_T3. An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to 15 each such aligned protein is as follows: Comparison report between HUMGROG5_PEA_1_P2 and MI2BHUMAN: 1.An isolated chimeric polypeptide encoding for HUMGROG5_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQS 20 VNVRSPGPHCAQTEV corresponding to amino acids 1 - 74 of MI2BHUMAN, which also corresponds to amino acids 1 - 74 of HUMGROG5_PEA_1_P2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 25 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein HUMGROG5_PEA_l_P2 also has the following non-silent SNPs (Single 30 Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether WO 2005/072053 PCT/IB2005/000928 345 the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_1_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Amino acid mutations SNP position(s) on arnino acid Alternative amino acid(s) Previously known SNP? sequence 3 H -> R Yes 33 A-> No 5 Variant protein HUMGROG5_PEA_1_P2 is encoded by the following transcript(s): HUMGROG5_PEA_1_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5PEA_1_T3 is shown in bold; this coding portion starts at position 196 and ends at position 420. The transcript also has the following SNPs as 10 listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5PEA__P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 203 A -> G Yes 292 G -> No 1062 A ->G Yes 1294 A ->G Yes 1764 A ->G Yes 1901 A->T Yes 15 Variant protein HUMGROG5_PEA_1_P3 according to the present invention has an amino acid seauence as given at the end of the annlication: it is encoded by transcrint(s) WO 2005/072053 PCT/IB2005/000928 346 HUMGROG5_PEA_1_T4. An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to 5 each such aligned protein is as follows: Comparison report between HUMGROG5_PEA_1_P3 and MI2BHUMAN: 1.An isolated chimeric polypeptide encoding for HUMGROG5_PEA_1_P3, comprising a first amino acid sequence being at least 90 % homologous to MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQS 10 VNVRSPGPHCAQTEVIATLKNGKKACLNPASPMVQKIIEKILNK corresponding to amino acids 1 - 103 of MI2BHUMAN, which also corresponds to amino acids I - 103 of HUMGROG5_PEA_1_P3. The location of the variant protein was determined according to results from a number of 15 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. 20 Variant protein HUMGROG5_PEA_1_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_1_P3 sequence provides support for the deduced sequence of this variant 25 protein according to the present invention). Table 7 -Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 3 H ->R Yes 33 A-> No WO 2005/072053 PCT/IB2005/000928 347 Variant protein HUMGROG5_PEA_1_P3 is encoded by the following transcript(s): HUMGROG5_PEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_1_T4 is shown in bold; this coding portion 5 starts at position 196 and ends at position 504. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_1_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 203 A -> G Yes 292 G-> No 949 A ->G Yes 1181 A ->G Yes 1651 A ->G Yes 1788 A ->T Yes Variant protein HUMGROG5_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 15 HUMGROG5_PEA_1_T9. An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 20 Comparison report between HUMGROG5_PEA_1_P7 and MI2BHUMAN: 1.An isolated chimeric polypeptide encoding for HUMGROG5_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 348 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQGIHLKNIQS VN corresponding to amino acids 1 - 61 of MI2BHUMAN, which also corresponds to amino acids 1 - 61 of HUMGROG5_PEA_1_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 5 preferably at least 95% homologous to a polypeptide having the sequence SHTQEWEESLSQPRIPHGSENHRKDTEQGEHQLTGEK corresponding to amino acids 62 98 of HUMGROG5_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMGROG5_PEA_1_P7, comprising a 10 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHTQEWEESLSQPRIPHGSENHRKDTEQGEHQLTGEK in HUMGROG5_PEA_1_P7. 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 20 region prediction program predicts that this protein has a trans-membrane region.. Variant protein HUMGROG5_PEA_1_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 25 HJMGROG5_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 3 H -> R Yes WO 2005/072053 PCT/IB2005/000928 349 33 A-> No Variant protein HUMGROG5_PEA_1_P7 is encoded by the following transcript(s): HUMGROG5_PEA__T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_1_T9 is shown in bold; this coding portion 5 starts at position 196 and ends at position 489. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 10 - Nucleic acid SNPs SNP position on nucleotide Aternative iucleic acid Previously known SNP? 203 A ->G Yes 292 G-> No 793 A-> G Yes 930 A -> T Yes Variant protein HUMGROG5_PEA_1_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMGROG5_PEA_1_T6. An alignment is given to the known protein (Macrophage inflammatory protein-2-beta precursor) at the end of the application. One or more alignments to 15 one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMGROG5_PEA_1_P12 and MI2BHUMAN: 1.An isolated chimeric polypeptide encoding for HUMGROG5_PEA_1 P12, comprising 20 a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence

MHKKGSPILGSHTARVAGTSPPALPLLAQLPDASAEPHGPRHALRRPQQSPAPAGGAAA

WO 2005/072053 PCT/IB2005/000928 350 PAPGGRQPARSRWVPAPWGPRAGRGWGGRPAPTAPLNQRVYSSL corresponding to amino acids 1 - 103 of HUMGROG5_PEA_1_P12, and a second amino acid sequence being at least 90 % homologous to GASVVTELRCQCLQTLQGIHLKNIQSVNVRSPGPHCAQTEVIATLKNGKKACLNPASPM 5 VQKIIEKILNKGSTN corresponding to amino acids 34 - 107 of MI2BHUMAN, which also corresponds to amino acids 104 - 177 of HUMGROG5_PEA_1_P12, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of HUMGROG5_PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MHKKGSPILGSHTARVAGTSPPALPLLAQLPDASAEPHGPRHALRRPQQSPAPAGGAAA PAPGGRQPARSRWVPAPWGPRAGRGWGGRPAPTAPLNQRVYSSL of HUMGROG5_PEA_1_P12. 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal 20 peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide.. Variant protein HUMGROG5_PEA_1_P12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates 25 whether the SNP is known or not; the presence of known SNPs in variant protein HiUMGROG5_PEA_1_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence WO 2005/072053 PCT/IB2005/000928 351 70 S No Variant protein HUMGROG5_PEA_1_P12 is encoded by the following transcript(s): HUMGROG5_PEA_ 1_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMGROG5_PEA_1_T6 is shown in bold; this coding portion 5 starts at position 84 and ends at position 614. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMGROG5_PEA_1_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 12 - Nucleic acid SNPs SNP. position on nucleotide Alternative nocleic acid Previously known SNP? sequence 203 A ->G Yes 292 G No 932 A ->G Yes 1069 A->T Yes As noted above, cluster HUJMGROG5 features 18 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 15 provided. Segment cluster HUMGROG5_PEA_1_node_18 according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA1_T3 and 20 HUMGROG5_PEA_1_T4. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 352 Transcript name Segment starting position Segment ending position HUMGROG5 PEA 1 T3 617 1433 HUMGROG5 PEA 1 T4 504 1320 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides 5 were found to hit this segment with regard to colon cancer, shown in Table 14. Table 14 - Oligonucleotides related to this segment alig6oucleotide nae Qverexpr ssed incancers Chip reference HUMGROG5_0 0_16626 colorectal cancer Colon Segment cluster HUMGROG5_PEA_1_node_19 according to the present invention is 10 supported by 40 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5 PEA_1_T3 1434 1593 HUMGROG5 PEA_1_T4 1321 1480 HUMGROG5 PEA_1_T6 602 761 HUMGROG5 PEA 1 T9 463 622 15 Segment cluster HUMGROG5_PEA_1_node_21 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, WO 2005/072053 PCT/IB2005/000928 353 HUMGROG5_PEA IT4, HUMGROG5 PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcriptriame Segment starting position Segment ending position HUMGROG5_PEA_1_T3 1607- 1782 HUMGROG5 PEA_1_T4 1494 1669 HUMGROG5 PEA 1_T6 775 950 HUMGROG5 PEA 1_T9 636 811 Segment cluster HUMGROG5_PEA_node_23 according to the present invention is 5 supported by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcripiname Segment starting position Segmlient ending position HUMGROG5PEA_1 T3 1796 2131 HUMGROG5 PEA_1_T4 1683 2018 HUMGROG5 PEA1 1T6 964 1299 UGROG5_PEA_1_T9 825 1160 10 Segment cluster HUMGROG5_PEA_1_node_6 according to the present invention is supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, 15 HUMGROG5_PEA_1_T4, HU{JMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5 PEA_1_T3 1 222 WO 2005/072053 PCT/IB2005/000928 354 HUMGROG5_PEAI1 T4 1 222 HUMGROG5 PEA_1_T6 1 222 HUMGROG5_PEAIT9 1 222 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster HUMGROG5_PEA_1_node_10 according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Trankript name Segmnt starting position Sent ending position HUMGROG5 PEA 1 T3 296 315 HUMGROG5 PEA 1T4 296 315 HUMGROG5 PEA 1T6 394 413 HUMGROG5_PEA 1 T9 296 315 10 Segment cluster HUMGROG5_PEA_1_node_11 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, 15 HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5_PEA_1_T3 316 378 HUMGROG5 PEA 1 T4 316 378 HUMGROG5_PEA 1T6 414 476 WO 2005/072053 PCT/IB2005/000928 355 HUMGROG5_PEA_1 T9 316 378 Segment cluster HUMGROG5-PEA-1_node_12 according to the present invention can be found in the following transcript(s): HUMGROG5_PEA__T3, HUMGROG5_PEA_1_T4 and HUMGROG5_PEA_1_T6. Table 21 below describes the starting and ending position of this segment on each transcript. 5 Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5 PEA 1 T3 379 399 HUMGROG5_PEA 1_T4 379 399 HUMGROG5 PEA_1_T6 477 497 Segment cluster HUMGROG5_PEA_1_node_13 according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4 and HiUMGROG5_PEA_1_T6. Table 22 below describes the starting and ending position of this segment on each transcript. 10 Table 22 - Segment location on transcripts Transcriptname Segment starting position Segment ending position HUMGROG5 PEA 1_T3 400 419 HUMGROG5 PEA_1_T4 400 419 HUMGROG5 PEA_1_T6 498 517 Segment cluster HUMGROG5_PEA_1_node_14 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This 15 segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5_PEA_1_T3 420 451 WO 2005/072053 PCT/IB2005/000928 356 Segment cluster HUMGROG5_PEAI node_15 according to the present invention is supported by 7 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA__T3. Table 24 below describes the starting and ending position of this segment on each transcript. 5 Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROGSPEA_1_T3 452 499 Segment cluster HUMGROG5_PEA_1_node_16 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3. Table 25 below describes the starting and ending position of this segment on each transcript. 10 Table 25 - Segment location on transcripts Transcript nanie Segment starting position Segnment ending position HUMGROG5_PEA_1_T3 500 532 Segment cluster HUMGROG5_PEA_1_node_17 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 26 15 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5PEA 1_T3 533 616 HUMGROG5_PEA 1 T4 420 503 HUMGROG5 PEA_1_T6 518 601 HUMGROG5_PEA 1 T9 379 462 Segment cluster HUMGROG5_PEA_1_node_20 according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 27 below describes the starting 20 and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 357 Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5_PEA_1T3 1594 1606 HUMGROG5_PEA_1_T4 1481 1493 HUMGROG5_PEA_1 T6 762 774 HUMGROG5_PEA_1 T9 623 635 Segment cluster HUMGROG5_PEA_1_node_22 according to the present invention can 5 be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name -.Segment tarting position Segment ending position HUMGROG5_PEA1 1T3 1783 1795 HUMGROG5 PEA_1 T4 1670 1682 HUMGROG5 PEA_1_T6 951 963 HUMGROG5_PEA 1T9 812 824 10 Segment cluster HUMGROG5_PEA_1_node_7 according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T3, HUMGROG5_PEA_1_T4, HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 29 15 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5_PEA 1 T3 223 270 HUMGROG5 PEA1 1T4 223 270 WO 2005/072053 PCT/IB2005/000928 358 HUMGROG5 PEA 1 T6 223 270 HUMGROG5_PEA 1_T9 223 270 Segment cluster HUMGROG5_PEA_1_node_8 according to the present invention can be found in the following transcript(s): HUMGROG5_PEA_1T3, HUMGROG5_PEA_1_T4, 5 HUMGROG5_PEA_1_T6 and HUMGROG5_PEA_1_T9. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name segment startig positi> Segment ending position HUMGROG5 PEA_1 T3 271 295 HUMGROG5_PEA 1 T4 271 295 HUMGROG5_PEA 1T6 271 295 HUMGROG5 PEA1 1T9 271 295 10 Segment cluster HUMGROG5_PEA_1 node_9 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMGROG5_PEA_1_T6. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMGROG5_PEA_1_T6 296 393 15 Variant protein alignment to the previously known protein: 20 Sequence name: /tmp/2xnO9xcDbu/OFuYQZgnpt:MI2BHUMAN WO 2005/072053 PCT/IB2005/000928 359 Sequence documentation: Alignment of: HUMGROG5_PEA1 1P2 x MI2B HUMAN 5 Alignment segment 1/1: Quality: 701.00 Escore: 0 10 Matching length: 75 Total length: 75 Matching Percent Similarity: 100.00 Matching Percent Identity: 98.67 Total Percent Similarity: 100.00 Total Percent 15 Identity: 98.67 Gaps: 0 Alignment: 20 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 I i l l l l l l l l l l l l l l l l l l l l1 1 ll l l l l l l l l l l l l l l l l llii 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 51 GIHLKNIQSVNVRSPGPHCAQTEVM 75 25 iii I i I I I 1 11 l : 51 GIHLKNIQSVNVRSPGPHCAQTEVI 75 30 WO 2005/072053 PCT/IB2005/000928 360 Sequence name: /tmp/PMlNwtDTrf/oTkbZ2ktxi:MI2B HUMAN Sequence documentation: 5 Alignment of: HUMGROG5 PEA 1 P3 x MI2B HUMAN Alignment segment 1/1: 10 Quality: 979.00 Escore: 0 Matching length: 103 Total length: 103 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 25 51 GIHLKNIQSVNVRSPGPHCAQTEVIATLKNGKKACLNPASPMVQKIIEKI 100 I|I l11111I111 I11 I I1I 1111|1 1 1 I II 11 1 1 1 51 GIHLKNIQSVNVRSPGPHCAQTEVIATLKNGKKACLNPASPMVQKIIEKI 100 30 101 LNK 103 I II WO 2005/072053 PCT/IB2005/000928 361 101 LNK 103 5 Sequence name: /tmp/HOryq4XO77/kw3t8ORy6X:MI2B HUMAN 10 Sequence documentation: Alignment of: HUMGROGSPEA 1 P7 x MI2BHUMAN Alignment segment 1/1: 15 Quality: 567.00 Escore: 0 Matching length: 61 Total length: 61 20 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 30 l l l iii L LLl LLLLLL lllllllllll lil l QTL 50 30 1 MAHATLSAAPSNPRLLRVALLLLLLVAASRRAAGASVVTELRCQCLQTLQ 50 WO 2005/072053 PCT/IB2005/000928 362 51 GIHLKNIQSVN 61 lii 111111 51 GIHLKNIQSVN 61 5 10 Sequence name: /tmp/eJBNVFGEc7/N3fotcYJO7:MI 2 B HUMAN Sequence documentation: Alignment of: HUMGROG5_PEA_1_P12 x MI2BHUMAN 15 Alignment segment 1/1: Quality: 721.00 Escore: 0 20 Matching length: 74 Total length: 74 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 25 Identity: 100.00 Gaps: 0 Alignment: 30 104 GASVVTELRCQCLQTLQGIHLKNIQSVNVRSPGPHCAQTEVIATLKNGKK 153 l i l l l l l l l l l l l l l l l l l l l l l l l l l l l l l 1 1 l l l l ll l l l l l l l l l WO 2005/072053 PCTIIB2005/000928 363 34~ GASVVTELRCQCLQTLQGIHLKNTQSVNVRSPGPHCAQTEVIATLKNGKK 83 154 ACLNPASPMVQKITEKTLNKGSTN 177 5 84 ACLNPASPMVQKIIEKILNKGSTN 107 10 WO 2005/072053 PCT/IB2005/000928 364 DESCRIPTION FOR CLUSTER HUMODCA Cluster HUMODCA features I transcript(s) and 17 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 5 Table 1 - Transcripts of interest Transcript Name SEQ ID NO: HUMODCA T17 15 Table 2 - Segments of interest Segment Name SEQ ID NO: HUMODCA node 1 168 HUMODCA node 25 169 HUMODCA node 32 170 HUMODCA node_36 171 HUMODCA node 39 172 HUMODCA node_41 173 HUMODCA node 0 174 HUMODCA node_10 175 HUMODCA node_12 176 HUMODCA node_13 177 HUMODCA node_2 178 HUMODCA node_27 179 HUMODCA node_3 180 HUMODCA node 30 181 HUMODCA node 34 182 HUMODCA node_38 183 HUMODCA node_40 184 Table 3 - Proteins of interest WO 2005/072053 PCT/IB2005/000928 365 Protein Name SEQ ID NO: HUMODCA P9 548 These sequences are variants of the known protein Ornithine decarboxylase (SwissProt accession identifier DCORHUMAN; known also according to the synonyms EC 4.1.1.17; ODC), SEQ ID NO: 620, referred to herein as the previously known protein. 5 Protein Ornithine decarboxylase is known or believed to have the following function(s): Polyamine biosynthesis; first (rate-limiting) step. The sequence for protein Ornithine decarboxylase is given at the end of the application, as "Ornithine decarboxylase amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP. position(s) aon Comment amino acid secluence, 415 Q ->E 10 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: polyamine biosynthesis, which are annotation(s) related to Biological Process; and ornithine decarboxylase; lyase, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBl 15 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HUMODCA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 20 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million).

WO 2005/072053 PCT/IB2005/000928 366 Overall, the following results were obtained as shown with regard to the histograms in Figure 17 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: brain malignant tumors, colorectal cancer, epithelial malignant tumors and a mixture of malignant tumors from different tissues. 5 Table 5 - Normal tissue distribution Name of Tissue Number Adrenal 120 Bladder 82 Bone 161 Brain 53 colon 0 epithelial 107 general 94 head and neck 10 kidney 114 liver 107 lung 120 lymph nodes 165 breast 61 bone marrow 156 muscle 55 ovary 36 pancreas 102 prostate 140 skin 188 stomach 109 T cells 278 Thyroid 128 uterus 118 WO 2005/072053 PCT/IB2005/000928 367 Table 6 - P values and ratiosfor expression in cancerous tissue Name of Tissue P1 P2 SPI SP2 R4 adrenal 8.3e-01 7.8e-01 1 0.2 8.5e-0l 0.7 bladder 5.4e-01 5.le-01 6.2e-01 1.1 5.0e-01 1.1 bone 8.3e-01 3.2e-01 1 0.2 8.4e-01 0.7 brain 2.6e-01 3.8e-02 6.5e-04 2.8 8.7e-10 3.6 colon 2.2e-02 5.8e-03 1.5e-03 6.9 6.7e-05 9.9 epithelial 6.4e-02 2.7e-03 1.4e-03 1.5 1.6e-12 2.1 general 1.3e-03 5.4e-08 1.9e-08 1.7 1.4e-39 2.6 head and neck 1.7e-01 1.7e-01 1 1.2 7.5e-01 1.3 kidney 7.7e-01 7.6e-01 7.le-01 0.8 6.6e-01 0.9 liver 7.3e-01 5.7e-01 1 0.3 2.4e-01 1.2 lung 7.8e-01 5.8e-01 7.6e-01 0.6 7.3e-04 1.7 lymph nodes 3.9e-01 2.5e-01 1.8e-01 1.1 1.4e-04 2.1 breast 7.8e-01 4.7e-01 7.7e-01 0.8 6.4e-01 1.0 bone marrow 3.4e-01 2.6e-01 2.8e-01 2.1 1.6e-01 1.2 muscle 8.5e-01 6.le-01 1 0.2 7.1 e-05 1.0 ovary 1.7e-01 9.3e-02 3.8e-01 1.7 2.2e-02 2.6 pancreas 2.2e-01 3.2e-01 5.7e-02 1.6 6.6e-03 1.5 prostate 5.0e-01 4.9e-01 3.8e-02 1.9 4.5e-02 1.7 skin 6.2e-01 5.8e-01 5.4e-02 0.9 1.5e-02 0.5 stomach 4.2e-01 2.6e-01 3.7e-01 0.7 7.3e-03 2.3 T cells 1 1 5.5e-01 1.5 8.le-01 0.9 Thyroid 8.3e-02 8.3e-02 5.9e-01 1.3 5.9e-01 1.3 uterus 4.2e-01 2.4e-01 1.6e-01 1.2 4.9e-02 1.7 As noted above, cluster HUMODCA features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ornithine decarboxylase. A description of each variant protein according to the present invention is now 5 provided.

WO 2005/072053 PCT/IB2005/000928 368 Variant protein HUMODCAP9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMODCAT17. An alignment is given to the known protein (Ornithine decarboxylase) at the end of the application. One or more alignments to one or more previously published protein sequences are 5 given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMODCAP9 and DCORHUMAN: I.An isolated chimeric polypeptide encoding for HUMODCAP9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 10 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1 29 of HUMODCA P9, and a second amino acid sequence being at least 90 % homologous to LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFV QAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSG 15 VRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFN CILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFEN MGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCA WESGMKRHRAACASASINV corresponding to amino acids 151 - 461 of DCOR HUMAN, which also corresponds to amino acids 30 - 340 of HUMODCAP9, wherein said first and 20 second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of HUMODCA P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL of HUMODCA P9. 25 Comparison report between HUMODCAP9 and AAA59968(SEQ ID NO:1387): I.An isolated chimeric polypeptide encoding for HUMODCA_P9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1 30 29 of HUMODCA P9, and a second amino acid sequence being at least 90 % homologous to

LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFV

WO 2005/072053 PCT/IB2005/000928 369 QAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSG VRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFN CILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFEN MGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCA 5 WESGMKRHRAACASASINV corresponding to amino acids 40 - 350 of AAA59968, which also corresponds to amino acids 30 - 340 of HUMODCAP9, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of HUMODCA P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL of HUMODCAP9. Comparison report between HUMODCAP9 and AAH14562(SEQ ID NO:1388): I.An isolated chimeric polypeptide encoding for HUMODCAP9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 15 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL corresponding to amino acids 1 29 of HUMODCAP9, and a second amino acid sequence being at least 90 % homologous to LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFV QAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSG 20 VRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFN CILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFEN MGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCA WESGMKRHRAACASASINV corresponding to amino acids 86 - 396 of AAH14562, which also corresponds to amino acids 30 - 340 of HJMODCAP9, wherein said first and second 25 amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of HUMODCA P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL of HUTMODCAP9. 30 WO 2005/072053 PCT/IB2005/000928 370 The location of the variant protein was detennined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein HUMODCAP9 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein HUMODCAP9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP positi6n(s) on amiino acid Alternative amino acid(s) Previously known SNP? s equence 150 I -> S No 150 I -> V No 262 F -> L No 263 E-> No 263 E -> G No 30 L-> No 301 N -> No 301 N -> K No 309 E -> K No 312 D ->N No 323 E ->K No 329 H ->P No 174 I-> No 34 I-> No 59 L-> No WO 2005/072053 PCT/IB2005/000928 371 70 V-> No 86 T-> No 86 T ->N No 90 A-> No 94 A-> No 97 V-> No 97 V ->G No 198 N ->D No 200 G-> No 3 S-> No 207 C ->G No 207 C ->R No 223 P-> No 262 F-> No Variant protein HUMODCAP9 is encoded by the following transcript(s): HUMODCA_T17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMODCA_T 17 is shown in bold; this coding portion starts at 5 position 528 and ends at position 1547. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMODCAP9 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 8 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid sequence 28 C ->G Yes 210 C-> No 536 T-> No 615 T-> No WO 2005/072053 PCT/IB2005/000928 37 2 628 T-> No 703 T-> No 736 T-> No 784 C-> No 784 C -> A No 797 A-> No 797 A ->T No 808 C-> No 217 C-> No 817 T-> No 817 T -> G No 869 C ->T Yes 975 A ->G No 976 T ->G No 1048 T-> No 1119 A ->G No 1127 C-> No 1127 C ->G No 1146 T ->C No 366 G ->C No 1146 T ->G No 1194 C-> No 1283 T ->C Yes 1311 T-> No 1311 T ->C No 1315 A-> No 1315 A ->G No 1430 C-> No 1430 C ->A No 1433 C ->G No WO 2005/072053 PCT/IB2005/000928 373 366 G ->T No 1433 C ->T Yes 1452 G ->A No 1461 G ->A No 1494 G ->A No 1513 A -> C No 1632 T-> No 1673 C-> No 1739 T-> No 1739 T ->G No 1742 T ->C No 447 G ->A Yes 1786 C-> No 1786 C ->G No 1832 T ->C Yes 1877 C ->T No 464 T -> G Yes 473 A->G Yes 506 G->A Yes 521 T -> No As noted above, cluster HUMODCA features 17 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster I-IUMODCAnodeI according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCAT17. Table 9 below describes the starting 10 and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 374 Table 9 - Segment location on transcripts Transcript name Segment starting, position Segment ending position HUMODCAT17 118 256 Segment cluster HUMODCAnode 25 according to the present invention is supported by 5 190 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position, Segment ending position HUMODCA T17 614 748 10 Segment cluster HUMODCAnode 32 according to the present invention is supported by 249 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 11 below describes the starting and ending position of this segment on each transcript. 15 Table 11 - Segment location on transcripts Transcript name Segment starting position Segimentending position HUMODCA T17 915 1077 Segment cluster HUMODCAnode_36 according to the present invention is supported by 348 libraries. The number of libraries was determined as previously described. This segment can 20 be found in the following transcript(s): HUMODCA_T 17. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 375 Transcript name Segment starting position Segment ending position HUMODCAT17 1191 1405 Segment cluster HUMODCA node_39 according to the present invention is supported by 297 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMODCA_T17. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segmeni starting position Segment enldingposition HUMODCAT17 1461 1633 10 Segment cluster HUMODCA node_41 according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment endig position HUMODCAT17 1728 1893 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster HUMODCAnode_0 according to the present invention is supported by 20 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 376 Transcript name Segment starting position Segment ending position HUMODCAT17 1 117 Segment cluster HUMODCA node_10 according to the present invention is supported by 107 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMODCA17. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position HUMODCAT17 385 494 10 Segment cluster HUMODCA node_12 according to the present invention is supported by 132 libraries. The number oflibraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA T17. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segmenending position HUMODCAT17 495 586 15 Segment cluster HIUMODCAnode_13 according to the present invention is supported by 126 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCAT17. Table 18 below describes the starting 20 and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 377 HUMODCAT17 587 613 Segment cluster HUMODCA node_2 according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMODCAT17. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment eding position HUMODCAT17 257 328 10 Segment cluster HUMODCA node 27 according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUZMODCA_T17. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMODCAT17 749 830 15 Segment cluster HUMODCA node 3 according to the present invention is supported by 85 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 21 below describes the starting 20 and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUTMODCAT17 329 384 WO 2005/072053 PCT/IB2005/000928 378 Segment cluster HUMODCA node_30 according to the present invention is supported by 196 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCAT17. Table 22 below describes the starting 5 and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position HUMODCAT17 831 914 Segment cluster HUMODCA node_34 according to the present invention is supported by 10 259 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCAT17. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name . Segment starting position HUMODCAT17 1078 1190 15 Segment cluster HUMODCA_ node_38 according to the present invention is supported by 272 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 24 below describes the starting and ending position of this segment on each transcript. 20 Table 24 - Segment location on transcripts Transcript name Segment starting position HUMODCAT17 1406 1460 WO 2005/072053 PCT/IB2005/000928 379 Segment cluster HUMODCA node_40 according to the present invention is supported by 239 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMODCA_T17. Table 25 below describes the starting and ending position of this segment on each transcript. 5 Table 25 - Segment location on transcripts Transcript name 'Segment starting position Segnment ending position HUMODCAT17 1634 1727 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/y03EwE6iO1/dRQ5l2K6e2:DCOR HUMAN Sequence documentation: 15 Alignment of: HUMODCA P9 x DCOR HUMAN Alignment segment 1/1: 20 Quality: 3056.00 Escore: 0 Matching length: 311 Total length: 311 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 WO 2005/072053 PCT/IB2005/000928 380 Alignment: 30 LVLRTATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 79 151 LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 200 80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129 l i l l ll l lIll lIIf l[l lfl l I l i i l If f [ I l l1 l l l1 [ 10 201 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 250 130 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 179 251 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 300 15 180 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229 301 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 350 20 230 YSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGF 279 351 YSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGF 400 280 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 329 401 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 450 330 RAACASASINV 340 30 45 1 || l I 461 30 451 RAACASASINV 461.

WO 2005/072053 PCT/IB2005/000928 381 5 Sequence name: /tmp/y03EwE6i0l/dRQ512K6e2:AAA59968 Sequence documentation: 10 Alignment of: HUMODCAP9 x AAA59968 Alignment segment 1/1: Quality: 3056.00 15 Escore: a Matching length: 311 Total length: 311 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 20 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 25 30 LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 79 li l l l l ll l l l l l l l l ll l l l l l l l l l l l l il1 111 1 1ii 1111111 1 1 40 LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 89 30 80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129 l IlllI llllillll111 11 llllllill111111 11111||I |1111 WO 2005/072053 PCT/IB2005/000928 382 90 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 139 130 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 179 |liii II iiI 1 1 11 11 i III IIIIl lIIiIIlI IIIii 5 140 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 189 180 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229 | l i 1 1111111 iiI iii I1 11 I I 1 i1111 i i i 1111111ii ii 190 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 239 10 230 YSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGF 279 llllllllillllllil1111 llili l l i lli 11111 1 1 I I 1111111 240 YSSSIWGPTCDGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGF 289 15 280 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 329 11 1 i I I Ii | 1|| l |1i i Ii I1111111 |1 I | 11 1 1 ilIIIII1 290 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 339 330 RAACASASINV 340 20i I I I I 1 I 340 RAACASASINV 350 25 Sequence name: /tmp/y03EwE6i0l/dRQ512K6e2:AAH14562 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 383 Alignment of: HUMODCA P9 x AAH14562 Alignment segment 1/1: 5 Quality: 3056.00 Escore: 0 Matching length: 311 Total length: 311 Matching Percent Similarity: 100.00 Matching Percent 10 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 30 LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 79 86 LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGS 135 20 80 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 129 136 GCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPGSEDVKLKFEE 185 25 130 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 179 186 ITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ 235 180 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 229 236 TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKY 285 WO 2005/072053 PCTIIB2005/000928 384 230 YSSSIWGPTCDGLDRTVERCDLPEMHVGDWM'LFENMGAYTVAAASTFNGF 279 286 YSSSTWGPTCDGLDRTVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGF 335 5 280 QRPTIYYVMVSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 329 336 QRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQDASTLPVSCAWESGMKRH 385 10 330 RAACASASINV 340 386 PAACASASTNV 396 15 20 WO 2005/072053 PCT/IB2005/000928 385 DESCRIPTION FOR CLUSTER R00299 Cluster R00299 features 1 transcript(s) and 12 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 5 Table 1 - Transcripts of interest Transcript-Name SEQ ID NO: R00299_T2 16 Table 2 - Segments of interest Segment Name SE5Q 1ID NO: R00299_node_2 185 R00299_node 30 186 R00299_node 10 187 R00299_node 14 188 R00299_node 15 189 R00299_node 20 190 R00299_node_23 191 R00299_node_25 192 R00299_node_28 193 R00299_node 31 194 R00299_node_5 195 R00299_node_9 196 Table 3 - Proteins of interest Protein Name SEQ ID NO R00299_P3 549 10 WO 2005/072053 PCT/IB2005/000928 386 These sequences are variants of the known protein Tescalcin (SwissProt accession identifier TESCHUMAN; known also according to the synonyms TSC), SEQ ID NO: 621, referred to herein as the previously known protein. Protein Tescalcin is known or believed to have the following function: Binds calcium. 5 The sequence for protein Tescalcin is given at the end of the application, as "Tescalcin amino acid sequence". The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: calcium binding, which are annotation(s) related to Molecular Function. 10 The GO assignment relies on information from one or more of the SwissProt/TremBI Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nhn.nih.gov/projects/LocusLink/>. Cluster R00299 can be used as a diagnostic marker according to overexpression of 15 transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 18 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: lung malignant tumors. Table 4 -Normal tissue distribution Name of Tissue Number bone 0 Colon 0 epithelial 11 general 11 Liver 0 WO 2005/072053 PCT/IB2005/000928 387 lung 1 lymph nodes 22 bone marrow 31 ovary 0 pancreas 14 prostate 16 stomach 76 T cells 0 Thyroid 0 Table 5 -P values and ratiosfor expression in Cancerous tissue Name of Tissne P1 P2 SPI R3 SP2 R4 bone 1 6.7e-O1 1 1.0 7.Oe-01 1.4 colon 5.0e-02 5.3e-02 2.4e-01 2.8 2.le-01 2.8 epithelial 7.7e-02 9.5e-02 4.0e-01 1.3 6.1e-03 1.9 general 2.3e-01 2.6e-01 5.3e-01 1.0 2.6e-04 1.9 liver 1 4.5e-01 1 1.0 6.9e-01 1.5 lung 4.9e-01 2.7e-01 6.5e-01 1.7 5.6e-04 3.8 lymph nodes 8.5e-01 8.7e-01 1 0.5 2.oe-01 1.1 bone marrow 8.6e-01 8.5e-01 1 0.5 2.3e-01 1.4 ovary 4.0e-01 4.4e-01 1 1.1 1 1.1 pancreas - 7.2e-01 6.9e-01 6.7e-01 1.0 3.5e-01 1.5 prostate 8.7e-01 9.le-01 6.7e-01 1.0 7.5e-01 0.9 stomach 6.6e-01 7.5e-01 1 0.4 6.7e-01 0.7 T cells 1 6.7e-01 1 1.0 5.2e-01 1.8 Thyroid 1.8e-01 1.8e-01 6.7e-01 1.6 6.7e-01 1.6 As noted above, cluster R00299 features 1 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Tescalcin. A 5 description of each variant protein according to the present invention is now provided.

WO 2005/072053 PCT/IB2005/000928 388 Variant protein R00299_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R00299_T2. An alignment is given to the known protein (Tescalcin) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the 5 application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between R00299_P3 and Q9NWT9(SEQ ID NO:1389): 1.An isolated chimeric polypeptide encoding for R00299 P3, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 10 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1 - 44 of R00299_P3, second amino acid sequence being at least 90 % homologous to SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLA 15 DEINFEDFLTIMSYFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNV corresponding to amino acids 74 - 191 of Q9NWT9, which also corresponds to amino acids 45 162 of R00299_P3, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIE TKMHVRFLNMETMALCH corresponding to amino acids 163 - 238 of R00299_P3, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of R00299 P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 25 at least about 90% and most preferably at least about 95% homologous to the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV of R00299 P3. 3.An isolated polypeptide encoding for a tail of R00299 P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 VEELLSGNPHIEIESARSIADGALvMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIE TKMHVRFLNMETMALCH in R00299_P3.

WO 2005/072053 PCT/IB2005/000928 389 Comparison report between R00299 P3 and TESCHUMAN: I.An isolated chimeric polypeptide encoding for R00299 P3, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 5 the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV corresponding to amino acids 1 - 44 of R00299 P3, and a second amino acid sequence being at least 90 % homologous to SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLA DEINFEDFLTIMSYFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNVVE 10 ELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETK MHVRFLNMETMALCH corresponding to amino acids 21 - 214 of TESC HUMAN, which also corresponds to amino acids 45 - 238 of R00299_P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of R00299 P3, comprising a polypeptide 15 being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV of R00299_P3. The location of the variant protein was determined according to results from a number of 20 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide.. 25 Variant protein R00299 P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R00299 P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). 30 Table 6 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 390 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 120 R ->G No 120 R ->W No Variant protein R00299 P3 is encoded by the following transcript(s): R00299 T2 for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R00299_T2 is shown in bold; this coding portion starts at position 142 and ends at position 855. 5 The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R00299_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 7 - Nucleic acid SNPs SNP position on nucleoide Alfternative nucleic acid Previously known'SNP? 'Sequence 177 C ->A Yes 499 C ->G No 499 C ->T No 900 G ->T Yes 916 G-> No 969 G-> No 969 G -> A No 987 A -> C No As noted above, cluster R00299 features 12 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are 15 of particular interest. A description of each segment according to the present invention is now provided.

WO 2005/072053 PCT/IB2005/000928 391 Segment cluster R00299_node_2 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 8 below describes the starting and 5 ending position of this segment on each transcript. Table 8 - Segment location on transcripts Transcript name Segment starting position Sgmeht ending position R00299_T2 1 271 Segment cluster R00299 node 30 according to the present invention is supported by 75 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts [Transcpt anie Segment starting position Segment ending pos ition R00299_T2 790 961 According to an optional embodiment of the present invention, short segments related to 15 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster R00299_node 10 according to the present invention is supported by 46 libraries. The number of libraries was determined as previously described. This segment can be 20 found in the following transcript(s): R00299 T2. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment starting position Segment ending position R00299_T2 346 422 WO 2005/072053 PCT/IB2005/000928 392 Segment cluster R00299_node_14 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 11 below describes the starting and 5 ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment starting position Segment ending position R00299_T2 423 537 Segment cluster R00299_node_15 according to the present invention can be found in the 10 following transcript(s): R00299_T2. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting position Segnentending position R00299_T2 538 562 15 Segment cluster R00299_node_20 according to the present invention is supported by 66 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position Segment ending position R00299_T2 563 624 20 Segment cluster R00299 node_23 according to the present invention is supported by 71 libraries. The number of libraries was determined as previously described. This segment can be WO 2005/072053 PCT/IB2005/000928 393 found in the following transcript(s): R00299_T2. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position R00299_T2 625 732 5 Segment cluster R00299_node_25 according to the present invention is supported by 62 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 15 below describes the starting and ending position of this segment on each transcript. 10 Table 15 - Segment location on transcripts ransrip name Segmei startIn position Segment ending position R00299_T2 733 780 Segment cluster R00299_node_28 according to the present invention can be found in the following transcript(s): R00299_T2. Table 16 below describes the starting and ending position 15 of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position R00299_T2 781 789 Segment cluster R00299 node_31 according to the present invention is supported by 48 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R00299_T2. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 394 Transcript name Segment starting position Segment ending position R00299_T2 962 1069 Segment cluster R00299 node 5 according to the present invention is supported by 45 libraries. The number of libraries was detennined as previously described. This segment can be 5 found in the following transcript(s): R00299_T2. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts T rnsciipt name Segment starting position R00299 T2 272 341 10 Segment cluster R00299_node_9 according to the present invention can be found in the following transcript(s): R00299-T2. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Tra riptame 'Segment mtgtir position Segment ending position R00299_T2 342 345 15 Microarray (chip) data is also available for this gene as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotide was found to hit this segment with regard to colon cancer, shown in Table 20. 20 Table 20 - Oligonucleotide related to this gene Oligonucleotide name Overexpressed in cancers Chip reference R00299_0_8_0 Colon cancer Colon WO 2005/072053 PCT/IB2005/000928 395 Variant protein alignment to the previously known protein: Sequence name: /tmp/OleVDhrKQ0/EjblgLomjM:Q9NWT9 5 Sequence documentation: Alignment of: R00299_P3 x Q9NWT9 10 Alignment segment 1/1: Quality: 1162.00 Escore: 0 Matching length: 118 Total 15 length: 118 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 20 Gaps: 0 Alignment: 45 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 94 74 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVAFFDNR 123 95 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTMDEEQVELSRKEKLRFLFH 144 30 124 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTMDEEQVELSRKEKLRFLFH 173 WO 2005/072053 PCT/IB2005/000928 396 145 MYDSDSDGRITLEEYRNV 162 174 MYDSDSDGRITLEEYRNV 191 5 10 Sequence name: /tmp/OleVDhrKQ0/EjblgLomjM:TESC HUMAN Sequence documentation: Alignment of: R00299_P3 x TESC HUMAN 15 Alignment segment 1/1: Quality: 1920.00 Escore: 0 20 Matching length: 194 Total length: 194 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 25 Identity: 100.00 Gaps: 0 Alignment: 30 45 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNR 94 1lill 1lll1ll1l11ll l l11l11ll1 l1 I lilllll11I ii l ji WO 2005/072053 PCT/IB2005/000928 397 21 SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVAFFDNR 70 95 NLRKGPSGLADEINFEDFLTIMSYFRPIDTTMDEEQVELSRKEKLRFLFH 144 5 71 NLRKGPSGLADEINFEDFLTIMSYFRPTDTTMDEEQVELSRKEKLRFLFH 120 145 MYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMMEAASVCM 194 lI llllII l 1 1i l lllll Il i lI lI i 1 lill l 1i lliill i 121 MYDSDSDGRTTLEEYRNVVEELLSGNPHIEKESARSIADGAMMEAASVCM 170 10 195 GQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH 238 Ill11Illl 1l 111l1il111 1il1l1 liili lilill I ii 171 GQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH 214 15 DESCRIPTION FOR CLUSTER Z19178 Cluster Z19178 features 2 transcript(s) and 15 segment(s) of interest, the names for which 20 are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SEQ ID NO : Z19178_PEA_1_T5 17 Z19178_PEA_1_T9 18 Table 2 - Segments of interest Segment Name SEQ ID NO: Z19178_PEA 1 node_15 197 Z19178_PEA1node_17 198 WO 2005/072053 PCT/IB2005/000928 398 Z19178_PEAInode_2 199 Z19178_PEA1node_22 200 Z19178_PEA1node23 201 Z19178_PEA1_node_24 202 Z19178_PEA1_node_10 203 Z19178_PEA 1 node 11 204 Z19178_PEA_1_node_14 205 719178_PEA 1 node_18 206 Z19178_PEA1 node 19 207 Z19178_PEA1_node_3 208 Z19178_PEA1_node_4 209 Z19178_PEA 1_node 5 210 Z19178_PEAI node 9 211 Table 3 - Proteins of interest Proebin Name SEQ ID NO: Z19178_PEA_1_P5 550 Z19178_PEA1 _P6 551 These sequences are variants of the known protein Skeletal muscle LIM-protein 2 5 (SwissProt accession identifier SLI2_HUMAN; known also according to the synonyms SLIM 2; Four and a half LIM domains protein 3; FHL-3), SEQ ID NO: 622, referred to herein as the previously known protein. The sequence for protein Skeletal muscle LIM-protein 2 is given at the end of the application, as "Skeletal muscle LIM-protein 2 amino acid sequence". 10 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: muscle development, which are annotation(s) related to Biological Process.

WO 2005/072053 PCT/IB2005/000928 399 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from Chttp://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 5 As noted above, cluster Z19178 features 2 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Skeletal muscle LIM-protein 2. A description of each variant protein according to the present invention is now provided. 10 Variant protein ZI 9178_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z19178_PEA_1_T5. An alignment is given to the known protein (Skeletal muscle LIM-protein 2) at the end of the application. One or more alignments to one or more previously published 15 protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z19178 PEA 1 P5 and Q96C98(SEQ ID NO:1390): 1.An isolated chimeric polypeptide encoding for Z 19178_PEA_1_P5, comprising a first 20 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVR LQSAASPAARSAPAWPGPQELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDC 25 YCSAFSSQCSACGETV corresponding to amino acids 1 - 130 of Z19178 PEA_1 P5, and a second amino acid sequence being at least 90 % homologous to MPGSRKLCEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKFAPRCARCS KTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSC KRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP 30 corresponding to amino acids 1 - 172 of Q96C98, which also corresponds to amino acids 131 - WO 2005/072053 PCT/IB2005/000928 400 302 of Z19178_PEAIPS, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of Z19178 PEA-_ P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVR LQSAASPAARSAPAWPGPQELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDC YCSAFSSQCSACGETV of Z 19178 PEA 1 P5. 10 Comparison report between Z19178PEAIP5 and Q9BVA2(SEQ ID NO:1391): 1.An isolated chimeric polypeptide encoding for Z19178_PEA-lP5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 15 GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVR LQSAASPAARSAPAWPGPQ corresponding to amino acids 1 - 74 of Z19178_PEA_lP5, and a second amino acid sequence being at least 90 % homologous to ELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCSACGETVMPG SRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKAPRCARCSKTL 20 TQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCKRP IVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 53 - 280 of Q9BVA2, which also corresponds to amino acids 75 302 of Z19178_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a head of ZJ9178_PEA_1_P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GGGGRADWRPKGRWGRGLAPAAGWGAGVRGPGGAGPRSLPRGGVGAALPLAHTVR 30 LQSAASPAARSAPAWPGPQ of Z19178_PEA_1_P5.

WO 2005/072053 PCT/IB2005/000928 401 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal 5 peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide.. Variant protein Z19178 PEA_1 P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 4, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein Z19178 PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 4 - Amino acid mutations SNP positions) on amino acid Aiternative amino> acid(s) Previously known SNP? Sequence 247 No 278 T ->N No 15 Variant protein Z19178 PEAl_P5 is encoded by the following transcript(s): Z19178_PEA_1_T5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z19178 PEA_I_T5 is shown in bold; this coding portion starts at position 1 and ends at position 907. The transcript also has the following SNPs as listed in Table 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid 20 listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_IP5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Nucleic acid SNPs S NP. position on nucleotide Alteinative nucleic acid Previously known SNP? sequence WO 2005/072053 PCT/IB2005/000928 402 607 G ->A Yes 742 G No 834 C A No 1082 C ->G Yes 1089 T ->A Yes 1110 C ->T Yes 1236 C ->T Yes 1326 C ->T No 1450 C ->T No 1523 C ->T No Variant protein Z 19178_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Z19178_PEA 1 T9. An alignment is given to the known protein (Skeletal muscle LIM-protein 2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Z19178 PEA_1_P6 and Q96C98(SEQ ID NO:1390): 1.An isolated chimeric polypeptide encoding for Z19178_PEA_1_P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL corresponding to amino 15 acids 1 - 34 of Z19178_PEA_1_P6, and a second amino acid sequence being at least 90 % homologous to TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCK RPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 60 - 172 of Q96C98, which also corresponds to amino acids 35 20 147 of Z19178_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 403 2.An isolated polypeptide encoding for a head of Z19178_PEA1 P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL of Z19178 PEA 1 P6. 5 Comparison report between Z19178_PEA_1_P6 and Q9BVA2(SEQ ID NO:1391): 1.An isolated chimeric polypeptide encoding for Z19178_PEA_1_P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL corresponding to amino 10 acids 1 - 34 of Z19178_PEA_1 P6, and a second amino acid sequence being at least 90 % homologous to TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELFAPKCSSCK RPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDGDQVLCQGCSQAGP corresponding to amino acids 168 - 280 of Q9BVA2, which also corresponds to amino acids 35 15 - 147 of Z19178_PEA_1-P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of Z19178_PEA_1 P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 20 sequence MNPSPARTVSCSAMTATAVRFPRSAPLVGRLSCL ofZl9178PEA1P6. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide.. Variant protein Z19178_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the 30 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_1_P6 WO 2005/072053 PCT/IB2005/000928 404 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positions) on abnino acid Alternative amino acid(s) Previously known SNP? sequence' 123 T ->N No 92 K-> No 5 Variant protein Z19178 PEA_1 P6 is encoded by the following transcript(s): Z19178_PEA_1_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z19178 PEAIT9 is shown in bold; this coding portion starts at position 379 and ends at position 819. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z19178_PEA_1 P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP positi n nucletide Alternative nucleic acid Previously known SNP? 'sequence 519 G -> A Yes 654 G -> No 746 C ->A No 994 C -> G Yes 1001 T -> A Yes 1022 C -> T Yes 1148 C ->T Yes 1238 C ->T No 1362 C ->T No 1435 C ->T No WO 2005/072053 PCT/IB2005/000928 405 As noted above, cluster Z19178 features 15 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster Z19178_PEA 1_node 15 according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178 PEA_1_T5. Table 8 below describes the starting and ending position of this segment on each transcript. 10 Table 8 - Segment location on transcripts TrAnscxipt naine ~ Segmert starting position Segjmekt ending position Z19178_PEA_1_T5 449 568 Segment cluster Z19178_PEA_1_node_17 according to the present invention is supported by 50 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Z19178 PEA 1 T5 and Z19178_PEA_1T9. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name. Segment starting position. "Segment ending position Z19178_PEA_1_T5 569 699 Z19178_PEA_1_T9 481 611 20 Segment cluster Z 19178 PEA_1 node_2 according to the present invention is supported by 43 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEAIT5 and Z19178_PEA_1_T9. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 406 Transcript name Segment starting position Segment ending position Z19178_PEA 1 T5 1 217

~

719178_PEA_1_T9 1 217 Segment cluster Z19178 PEA_node_22 according to the present invention is supported by 61 libraries. The number of libraries was determined as previously described, This segment 5 can be found in the following transcript(s): Z19178 PEA_1_T5 and Z19178_PEA_1_T9. Table 11 below describes the starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment starting position Segen ending on Z19178_PEA 1 TS 756 1000 :6: 1000 Z19178 PEA IT9 668 912 10 Segment cluster Z19178_PEA_1_node 23 according to the present invention is supported by 81 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_1_T5 and Z19178_PEA_1-T9. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment starting.psition Segment ending position Z19178_PEA_1_T5 1001 1404 1Z9178_PEA_1_T9 913 1316 15 Segment cluster Z19178 PEA 1 node_24 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178 PEA_1_T5 and Z19178 PEAIT9. Table 20 13 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 407 Table 13 - Segment location on transcripts Transcript name Segment starting position Segmnen ding position Z19178_PEA_1_T5 1405 1554 Z19178_PEA IT9 1317 1466 5 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster Z19178_PEA 1 node_10 according to the present invention is supported 10 by 60 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178 PEA 1 T5 and Z19178 PEAIT9. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcrit naeSegment starting p position Segment ending position Z19178_PEA 1 T5 277 325 Z19178_PEA_1_T9 359 407 15 Segment cluster Z19178 PEAInode 11 according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA_ IT5 and Z19178_PEA_1_T9. Table 15 below describes the starting and ending position of this segment on each transcript. 20 Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178_PEA_1_TS 326 398 Z19178_PEA_1_T9 408 480 WO 2005/072053 PCT/IB2005/000928 408 Segment cluster Z19178_PEA_1_node_14 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z19178_PEA_1_T5. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178_PEA1_T5 399 448 10 Segment cluster Z19178_PEA _node_18 according to the present invention is supported by 47 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEA 1 T5 and Z19178-PEA_1_T9. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Traniscript narue., Segment starting position Sement ending position, Z19178_PEA_1_T5 700 751 Z19178 PEA 1 T9 612 663 15 Segment cluster Z19178_PEA 1_node_19 according to the present invention can be found in the following transcript(s): Z19178_PEA_1_T5 and Z19178_PEA_1_T9. Table 18 below describes the starting and ending position of this segment on each transcript. 20 Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178_PEA1_T5 752 755 Z19178_PEA_1_T9 664 667 WO 2005/072053 PCT/IB2005/000928 409 Segment cluster Z19178_ PEA _node_3 according to the present invention can be found in the following transcript(s): Z19178 PEA_1_T5 and Z19178_PEAIT9. Table 19 below describes the starting and ending position of this segment on each transcript. 5 Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178 PEA 1 TS 218 223 Z19178_PEA_1_T9 218 223 Segment cluster Z19178 PEA 1_node_4 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): Z19178 PEA_1_T9. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178 PEA__T9 224 266 15 Segment cluster Z19178_PEA_1_node_5 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178_PEAIT9. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178_PEA_1_T9 267 305 20 WO 2005/072053 PCT/IB2005/000928 410 Segment cluster Z19178 PEA 1 node_9 according to the present invention is supported by 58 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z19178 PEAIT5 and Z19178_PEA__T9. Table 22 below describes the starting and ending position of this segment on each transcript. 5 Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z19178_PEA1 T5 224 276 Z19178_PEA_1_T9 306 358 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/HCEUPaHOOb/Molk3qa5mK:Q96C98 15 Sequence documentation: Alignment of: Z19178_PEA 1 P5 x Q96C98 Alignment segment 1/1: 20 Quality: 1799.00 Escore: 0 Matching length: 172 Total length: 172 25 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 WO 2005/072053 PCT/IB2005/000928 411 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 131 MPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKF 180 lilll ll illllllllllililil li11l 11l 1 iiliii) l iiii 1 MPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVPCYENKF 50 10 181 APRCARCSKTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPY 230 i||l 11111111 11 1 |11111 i i I i i i I i iiiiii I I I I 51 APRCARCSKTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPY 100 15 231 CVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHENCFSCARCSTSL 280 II i 111111111i i l li ll i i l I I ll I i llll 111 i ll 1 1 i 101 CVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSL 150 281 VGQGFVPDGDQVLCQGCSQAGP 302 151 VGQGFVPDGDQVLCQGCSQAGP 172 25 Sequence name: /tmp/HCEUPaHOOb/Molk3qa5mK:SLI2 HUMAN 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 412 Alignment of: Z19178_PEA_1_P5 x SLI2 HUMAN Alignment segment 1/1: 5 Quality: 2249.00 Escore: 0 Matching length: 22B Total length: 228 Matching Percent Similarity: 96.49 Matching Percent 10 Identity: 94.74 Total Percent Similarity: 96.49 Total Percent Identity: 94.74 Gaps: 0 15 Alignment: 75 ELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCS 124 53 ELFYEDRHFHEGCFRCCRCQRSLADEPFTRQDSELLCNDCYCSAFSSQCS 102 20 125 ACGETVMPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVP 174 103 ACGETVMPGSRKLEYGGQTWHEHCFLCIGCEQPLGSRPFVPDKGAHYCVP 152 25 175 CYENKFAPRCARCSKTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTS 224 153 CYENNFAPRCARCTKTLTQGGLTYRDLPWHPKCLVCTGCQTPLAGQQFTS 202 225 RDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCA 274 203 RDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFTCD 252 WO 2005/072053 PCT/IB2005/000928 413 275 RCSTSLVGQGFVPDGDQVLCQGCSQAGP 302 III IlII I I IIIII I I I I 1 k 253 RCSNSLVGQGFVPDGDQVLCQGCSQAGP 280 5 10 Sequence name: /tmp/HCEUPaHOOb/Molk3qa5mK:Q9BVA2 Sequence documentation: 15 Alignment of: Z19178_PEA_1_P5 x Q9BVA2 Alignment segment 1/1: Quality: 2394.00 20 Escore: 0 Matching length: 228 Total length: 228 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 30 75 ELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCS 124 WO 2005/072053 PCT/IB2005/000928 414 I i|||1 I||| || IIi II I 11 I11111111111111 53 ELFYEDRHFHEGCFRCCRCQRSLADEPFTCQDSELLCNDCYCSAFSSQCS 102 125 ACGETVMPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVP 174 5 il li il l i i llill illi 1li 1i Iii 11ill 1l iii 103 ACGETVMPGSRKLEYGGQTWHEHCFLCSGCEQPLGSRSFVPDKGAHYCVP 152 175 CYENKFAPRCARCSKTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTS 224 ||1|1 Ii||||IIi!II 11li||||||Ii1|[11 111l11 10 153 CYENKFAPRCARCSKTLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTS 202 225 RDEDPYCVACFGELFAPKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCA 274 IIill illi li ll i ll lll lll! I l llllll1 lll11 Il li il 203 RDEDPYCVACFGELFAPKCSSCKPIVGLGGGKYVSFEDRHWHHNCFSCA 252 15 275 RCSTSLVGQGFVPDGDQVLCQGCSQAGP 302 253 RCSTSLVGQGFVPDGDQVLCQGCSQAGP 280 20 25 Sequence name: /tmp/n1VRxocMJO/rZHvyWGjFT:Q96C98 Sequence documentation: Alignment of: Z19178_PEA 1 P6 x Q96C98 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 415 Quality: 1169.00 Escore: 0 Matching length: 113 Total 5 length: 113 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 10 Gaps: 0 Alignment: 35 TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 84 60 TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 109 85 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDG 134 II l il I I Il l l ll l l ill I I i l l I ll I I lll I ) I l I II 20 110 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDG 159 135 DQVLCQGCSQAGP 147 160 DQVLCQGCSQAGP 172 25 30 Sequence name: /tmp/nlVRxocMJO/rZHvyWGjFT:SLI2

HUMAN

WO 2005/072053 PCT/IB2005/000928 416 Sequence documentation: Alignment of: Z19178_PEA_1_P6 x SLI2 HUMAN 5 Alignment segment 1/1: Quality: 1090.00 Escore: 0 10 Matching length: 113 Total length: 113 Matching Percent Similarity: 96.46 Matching Percent Identity: 93.81 Total Percent Similarity: 96.46 Total Percent 15 Identity: 93.81 Gaps: 0 Alignment: 20 35 TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 84 168 TLTQGGLTYRDLPWHPKCLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 217 85 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDG 134 2 5 I I I I I I I I I I I I I I I I I I I I I I I : j I I 1 11 1I I 218 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFTCDRCSNSLVGQGFVPDG 267 135 DQVLCQGCSQAGP 147 30 268 DQVLCQGCSQAGP 280 WO 2005/072053 PCT/IB2005/000928 417 5 Sequence name: /tmp/nlVRxocMJO/rZHvyWGjFT:Q9BVA2 Sequence documentation: 10 Alignment of: Z19178_PEA_1_P6 x Q9BVA2 . Alignment segment 1/1: Quality: 1169.00 15 Escore: 0 Matching length: 113 Total length: 113 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 20 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 25 35 TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 84 168 TLTQGGVTYRDQPWHRECLVCTGCQTPLAGQQFTSRDEDPYCVACFGELF 217 30 85 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDG 134 I||111|111 111111 IJII I I II I I1111 WO 2005/072053 PCT/IB2005/000928 418 218 APKCSSCKRPIVGLGGGKYVSFEDRHWHHNCFSCARCSTSLVGQGFVPDG 267 135 DQVLCQGCSQAGP 147 IlI 'I l 111 Ill 5 268 DQVLCQGCSQAGP 280 WO 2005/072053 PCT/IB2005/000928 419 DESCRIPTION FOR CLUSTER S67314 Cluster S67314 features 4 transcript(s) and 8 segment(s) of interest, the names for which 5 are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SEQ ID NO: S67314_PEA 1_T4 19 S67314 PEA 1_T5 20 S67314 PEA1 T6 21 S67314_PEA1 T7 22 Table 2 - Segrnents of interest e ent Name SEQ ID NO S67314_PEA_1 node_0 212 S67314_PEA1 node_11 213 S67314_PEAInode13 214 S67314_PEA1_node15 215 S67314_PEA1_node_17 216 S67314_PEA1 node_4 217 S67314_PEAInode_10 218 S67314_PEA1node_3 219 10 Table 3 - Proteins of interest Protein Name SEQ ID NO: S67314_PEA 1 P4 552 S67314_PEA_1_P5 553 WO 2005/072053 PCT/IB2005/000928 420 S67314_PEAIP6 554 S67314_PEA 1_P7 555 These sequences are variants of the known protein Fatty acid-binding protein, heart (SwissProt accession identifier FABHHUMAN; known also according to the synonyms H FABP; Muscle fatty acid-binding protein; M-FABP; Mammary-derived growth inhibitor; 5 MDGI), SEQ ID NO: 623, referred to herein as the previously known protein. Protein Fatty acid-binding protein, heart is known or believed to have the following function(s): FABP are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. The sequence for protein Fatty acid-binding protein, heart is given at the end of the application, as "Fatty acid-binding protein, heart amino acid sequence". 10 Known polymorphisms for this sequence are as shown in Table 4. Table 4- Amino acid mutations for Known Protein N position(s) on Comment ,amino acid sequence V-> A 104 L ->K 124 C->S 129 E ->Q Protein Fatty acid-binding protein, heart localization is believed to be Cytoplasmic. The following GO Annotation(s) apply to the previously known protein. The following 15 annotation(s) were found: negative control of cell proliferation, which are annotation(s) related to Biological Process; and lipid binding, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBI Protein knowledgebase, available from <http://www.expasy.chl/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 20 As noted above, cluster S67314 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Fatty acid- WO 2005/072053 PCT/IB2005/000928 421 binding protein, heart. A description of each variant protein according to the present invention is now provided. Variant protein S67314 PEA_1 P4 according to the present invention has an amino acid 5 sequence as given at the end of the application; it is encoded by transcript(s) S67314-PEA__T4. An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as 10 follows: Comparison report between S67314 PEA _1_P4 and FABHHUMAN: I.An isolated chimeric polypeptide encoding for S67314 PEA _P4, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 15 the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of FABHHUMAN, which also corresponds to amino acids 1 - 116 of S67314_PEA_1 P4, and a second amino acid sequence being at least 70%, 20 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL corresponding to amino acids 117 - 215 of S67314 PEA 1_P4, wherein said firstand second amino acid sequences are 25 contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA-1_P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHCGQITFSKCNCKTGINNTNLVGLLGSL in S67314 PEA 1 P4.

WO 2005/072053 PCT/IB2005/000928 422 Comparison report between S67314_PEA_1_P4 and AAP35373(SEQ ID NO:1392): I.An isolated chimeric polypeptide encoding for S67314 PEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF 5 KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids I 116 of S67314-PEA_1_P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL corresponding to amino acids 117 - 215 of S67314 PEA 1 P4, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA1 1P4, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRWATLELYLIGYYYCSFSQACSKKPSPPLRAVEAGTREWLWVRVVSGGNFLCSGFGL TQAGTQILPYRLHDCGQITFSKCNCKTGINNTNLVGLLGSL in S67314_PEA_1_P4. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the 25 trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.. Variant protein S67314 PEA_1_P4 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 5, (given according to their position(s) on the 30 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_1_P4 WO 2005/072053 PCT/IB2005/000928 423 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 5 - Amino acid mutations SNP positions) on amin acid Alternative amino acid(s) Previou ly.known SNP? sequence 53 K ->R Yes 5 Variant protein S67314_ PEAl_P4 is encoded by the following transcript(s): S67314_PEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA 1 T4 is shown in bold; this coding portion starts at position 925 and ends at position 1569. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Nucleic acid SNPs SNP position on ucleotide Alternative nucleic acid Previously known SN? sequence 580 T ->C Yes 1082 A->G Yes 1670 A ->C Yes 15 Variant protein S67314_PEA_1_P5 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_TS. An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end of the application. One or more alignments to one or more previously published 20 protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072053 PCT/IB2005/000928 424 Comparison report between S67314 PEA 1 P5 and FABHHUMAN: 1.An isolated chimeric polypeptide encoding for S67314_PEA I_P5, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 5 the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids I - 116 of FABH-HUMAN, which also corresponds to amino acids 1 - 116 of S67314_PEA_1 P5, and a second amino acid sequence being at least 70%, 10 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV corresponding to amino acids 117 - 178 of S67314 PEA_1 P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of S67314 PEA_IP5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG 20 KSIV in S67314PEA1_P5. Comparison report between S67314_PEA_1_P5 and AAP35373(SEQ ID NO:1392): 1.An isolated chimeric polypeptide encoding for S67314_PEAI P5, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF 25 KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of AAP35373, which also corresponds to amino acids 1 116 of S67314_PEA_1_P5, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG WO 2005/072053 PCT/IB2005/000928 425 KSIV corresponding to amino acids 117 - 178 of S67314_PEA_1 P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314 PEA_1 P5, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVLTAWPSIYRRQVKVLREDEITILPWHLQWSREKATKLLRPTLPSYNNHGWEELRVG KSIV in S67314PEA1_P5. 10 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. 15 In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.. Variant protein S67314_PEA_1 P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 20 the SNP is known or not; the presence of known SNPs in variant protein S67314_PEAIP5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 -Amino acid mutations SNPposition(s) on amino acid Alternative amino acids) Previously known SNP? sequence 53 K->R Yes 25 Variant protein S67314 PEA _1 P5 is encoded by the following transcript(s): S67314_PEA_1_TS, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA_1_T5 is shown in bold; this coding portion starts at WO 2005/072053 PCT/IB2005/000928 426 position 925 and ends at position 1458. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314 PEA _P5 sequence provides support for the deduced 5 sequence of this variant protein according to the present invention). Table 8 - Nucleic acid SNPs SNP position on nucIeotide Alternative nucleic acid Previously known SNP? sequence 580 T->C Yes 1082 A ->G Yes 1326 A->G Yes Variant protein S67314 PEA_1_P6 according to the present invention has an amino acid 10 sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEAl-T6. An alignment is given to the known protein (Fatty acid-binding protein, heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as 15 follows: Comparison report between S67314_PEA _P6 and FABHHUMAN: 1.An isolated chimeric polypeptide encoding for S67314_PEA_1_P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 20 the sequence MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids 1 - 116 of FABHHUMAN, which also corresponds to amino acids 1 - 116 of S67314_PEA_1 P6, and a second amino acid sequence being at least 70%, 25 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most WO 2005/072053 PCT/IB2005/000928 427 preferably at least 95% homologous to a polypeptide having the sequence MEKLQLRNVK corresponding to amino acids 117 - 126 of S67314 PEA 1 P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA1 _P6, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MEKLQLRNVK in S67314_PEA 1 P6. Comparison report between S67314-PEA_1_P6 and AAP35373 (SEQ ID NO:1392): 1.An isolated chimeric polypeptide encoding for S67314 PEA _1_P6, comprising a first 10 amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILTLKTHSTF KNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQETTLVRELIDGKLIL corresponding to amino acids I - 116 of AAP35373, which also corresponds to amino acids I 116 of S67314_ PEA 1 P6, and a second amino acid sequence being at least 70%, optionally at 15 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MEKLQLRNVK corresponding to amino acids 117 - 126 of S67314_PEA1 1P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of S67314_PEA_1 P6, comprising a 20 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MEKLQLRNVK in 867314_PEA_1_P6. The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted 30 protein..

WO 2005/072053 PCT/IB2005/000928 428 Variant protein S67314 PEA 1 P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_1_P6 5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Amino acid mutations SNP position(s) on amino acid Alternaiv amino acids) Previously known SNP? sequence 53 K ->R Yes Variant protein S67314__PEA 1 P6 is encoded by the following transcript(s): 10 S67314_PEA_1_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA 1 T6 is shown in bold; this coding portion starts at position 925 and ends at position 1302. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein S67314_PEA_1 P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs SNP position on nucleotide Alternativenucleic acid Previously known SNP? sequence 580 T ->C Yes 1082 A ->G Yes 1444 T ->C Yes 20 Variant protein S67314_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) S67314_PEA_1_T7. An alignment is given to the known protein (Fatty acid-binding protein, WO 2005/072053 PCT/IB2005/000928 429 heart) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between S67314 PEA_1_P7 and FABHHUMAN: l.An isolated chimeric polypeptide encoding for S67314 PEA_1 P7, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSL corresponding to amino acids 1 - 24 of FABHHUMAN, which also corresponds to amino acids 1 - 24 of S67314 PEA 1 P7, second 10 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AHILITFPLPS corresponding to amino acids 25 - 35 of S67314_PEA-1_P7, and a third amino acid sequence being at least 90 % homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI 15 VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25 - 133 of FABHHUMAN, which also corresponds to amino acids 36 - 144 of S67314_PEA_1_P7, wherein said first, second, third and fourth amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of S67314_PEA_1_P7, 20 comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AHILITFPLPS, corresponding to S67314_PEA_1_P7. Comparison report between S67314_PEA 1 P7 and AAP35373(SEQ ID NO:1392): 25 1.An isolated chimeric polypeptide encoding for S67314_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MVDAFLGTWKLVDSKNFDDYMKSL corresponding to amino acids 1 - 24 of AAP35373, which also corresponds to amino acids 1 - 24 of S67314_PEA _1 P7, second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at 30 least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AHILITFPLPS corresponding to amino acids 25 - 35 of S67314_PEA_1_P7, and a third amino WO 2005/072053 PCT/IB2005/000928 430 acid sequence being at least 90 % homologous to GVGFATRQVASMTKPTTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSI VTLDGGKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA corresponding to amino acids 25 - 133 of AAP35373, which also corresponds to amino acids 36 - 144 of 5 S67314_PEA_1_P7, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of S67314 PEA_1_P7, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% 10 homologous to the sequence encoding for AHILITFPLPS, corresponding to S67314_PEA_1_P7. The location of the variant protein was detennined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: intracellularly. The protein localization is believed to be intracellular because neither of the trans-membrane region prediction programs predicted a trans-membrane region for this protein. In addition both signal-peptide prediction programs predict that this protein is a non-secreted protein.. 20 Variant protein S67314_PEA_1_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the 25 present invention). Table 11 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 64 K->R Yes WO 2005/072053 PCT/IB2005/000928 431 Variant protein S67314._PEA 1 P7 is encoded by the following transcript(s): S67314_PEA_1_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript S67314_PEA__T7 is shown in bold; this coding portion starts at position 925 and ends at position 1356. The transcript also has the following SNPs as listed in 5 Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein S67314 PEA 1 _P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nuleotide Ailenative nuclpic acid Previously known SNP? sequence. 580 T -> C Yes 1115 A ->G Yes 2772 G -> A Yes 2896 C -> A Yes 2918 G ->C Yes 3003 A ->G Yes 3074 T ->G Yes 1344 T ->C Yes 1522 ->T No 1540 ->A No 1540 ->T No 1578 G -> A Yes 1652 G -> A Yes 2263 G ->A Yes 2605 T -> C Yes 10 WO 2005/072053 PCT/IB2005/000928 432 As noted above, cluster S67314 features 8 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster S67314_PEA_1_node_0 according to the present invention is supported by 90 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEA_1_T4, S67314_PEA_1_T5, 10 S67314_PEA__T6 and S67314_PEA_1_T7. Table 13 below describes the starting and ending position of this segment on each transcript. Table 13 - Segment location on transcripts Transcript name Segment starting position n S67314_PEA_1_T4 1 997 S67314_PEA_1 T5 1 997 S67314 PEA 1_T6 1 997 S67314 PEA_1_T7 1 997 15 Segment cluster S67314 PEA 1 node 11 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314_PEAIT4. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position Segment ending position S67314_PEA_1_T4 1273 2110 20 Segment cluster S67314 PEA 1 node 13 according to the present invention is supported by 76 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 433 can be found in the following transcript(s): S67314 PEA_1_T7. Table 15 below describes the starting and ending position of this segment on each transcript. Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position S67314_PEA_1_T7 1306 3531 5 Segment cluster S67314 PEA _Inode_15 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314 PEA 1 T5. Table 16 below describes the starting and ending position of this segment on each transcript. 10 Table 16 - Segment location on transcripts LGransefipt name f Segment starting position Segment ending position S67314_PEA_1 T5 1273 1733 Segment cluster S67314 PEA 1 node_17 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): S67314_PEA 1 T6. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position S67314_PEA_1_T6 1273 1822 Microarray (chip) data is also available for this segment as follows. As described above 20 with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment with regard to colon cancer, shown in Table 18. Table 18 - Oligonucleotides related to this segment WO 2005/072053 PCT/IB2005/000928 434 Oligonucleotide name Overexpressed in cancers Chip reference S67314_0_0_744 colorectal cancer Colon As a general note, oligonucleotide S67314 0 0 741 was overexpressed in colon cancer; this oligonucleotide maps to at least one part of this cluster. Segment cluster S67314 PEA 1_node_4 according to the present invention is supported 5 by 101 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314 PEA 1_T4, S67314_PEA_1_T5, S67314_PEA__T6 and S67314_PEA-1_T7. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting Position Segment endi position S67314_PEA_1_T4 998 1170 S67314_PEA_1_T5 998 1170 S67314_PEA_1_T6 998 1170 S67314_PEA 1 T7 1031 1203 10 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster S67314_PEA 1 node_10 according to the present invention is supported 15 by 64 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): S67314 PEA 1T4, S67314 PEA 1 T5, S67314_PEA_1_T6 and S67314_PEA_1_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position S67314_PEA_1 T4 1171 1272 S67314_PEA_1_T5 1171 1272 WO 2005/072053 PCT/IB2005/000928 435 S67314_PEAI 1T6 1171 1272 S67314-PEA_1_T7 1204 1305 Segment cluster S67314 PEA_1_node_3 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): S67314 PEAIT7. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segient ending position S67314_PEAI T7 998 1030 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/EQ0nMn6tqU/R73CUVKUk5:FABHHUMAN 15 Sequence documentation: Alignment of: S67314 PEA 1 P4 x FABH HUMAN . 20 Alignment segment 1/1: Quality: 1095.00 Escore: 0 Matching length: 115 Total 25 length: 115 WO 2005/072053 PCT/IB2005/000928 436 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 2 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDTLT 51 1 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 50 52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSTVTLDGGKLVHLQKWDGQ 101 15 51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 100 102 ETTLVRELIDGKLIL 116 101 ETTLVRELIDGKLIL 115 20 25 Sequence name: /tmp/EQOnMn6tqU/R73CUVKUk5:AAP35373 Sequence documentation: 30 Alignment of: S67314 PEA 1 P4 x AAP35373 WO 2005/072053 PCT/IB2005/000928 437 Alignment segment 1/1: Quality: 1107.00 Escore: 0 5 Matching length: 116 Total length: 116 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00 Gaps: 0 Alignment: 15 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 illillililil1!i i li I i I I li I llI lilil li li li, i ii 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 101 QETTLVRELIDGKLIL 116 25 101 QETTLVRELIDGKLIL 116 30 WO 2005/072053 PCT/IB2005/000928 438 Sequence name: /tmp/ql4YPTBbdQ/SeofJfCmJW:FABH HUMAN Sequence documentation: 5 Alignment of: S67314 PEA_1_P5 x FABH HUMAN Alignment segment 1/1: Quality: 1095.00 10 Escore: 0 Matching length: 115 Total length: 115 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 2 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 51 1 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTTIEKNGDILT 50 25 52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 101 51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 100 102 ETTLVRELIDGKLIL 116 30T| LV|||| G| LI||11 101 ETTLVRELIDGKLIL 115 WO 2005/072053 PCT/IB2005/000928 439 5 Sequence name: /tmp/q14YPIBbdQ/SeofjfCmJW:AAP35373 Sequence documentation: 10 Alignment of: S67314PEA_1_P5 x AAP35373 Alignment segment 1/1: 15 Quality: 1107.00 Escore: 0 Matching length: 116 Total length: 116 Matching Percent Similarity: 100.00 Matching Percent 20 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 30 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVLQKWDG 100 WO 2005/072053 PCT/IB2005/000928 440 111|| 1 iiI | 1II I I 1 1111 i l i i I | 1 1 i iiiiiiiiII i i1 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 101 QETTLVRELIDGKLIL 116 5 111111 I11111[ 101 QETTLVRELIDGKLIL 116 10 Sequence name: /tmp/PXra2DxL1v/Q8GTrzNMVX:FABH HUMAN 15 Sequence documentation: Alignment of: S67314_PEA_1_P6 x FABH HUMAN Alignment segment 1/1: 20 Quality: 1095.00 Escore: 0 Matching length: 115 Total length: 115 25 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072053 PCT/IB2005/000928 441 2 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 51 1 VDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDILT 50 5 52 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 101 51 LKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDGQ 100 10 102 ETTLVRELIDGKLIL 116 101 ETTLVRELIDGKLIL 115 15 Sequence name: /tmp/PXra2DxL1v/Q8GTrzNMVX:AAP35373 20 Sequence documentation: Alignment of: S67314_PEA_1_P6 x AAP35373 25 Alignment segment 1/1: Quality: 1107.00 Escore: 0 Matching length: 116 Total 30 length: 116 WO 2005/072053 PCT/IB2005/000928 442 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDTL 50 1 MVDAFLGTWKLVDSKNFDDYMKSLGVGFATRQVASMTKPTTIIEKNGDIL 50 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSTVTLDGGKLVHLQKWDG 100 15 51 TLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGGKLVHLQKWDG 100 101 QETTLVRELIDGKLIL 116 101 QETTLVRELIDGKLIL 116 20 25 Sequence name: /tmp/xYzWyViDom/twDu3T69pd:FABH HUMAN Sequence documentation: 30 Alignment of: S67314_PEA 1_P7 x FABH HUMAN WO 2005/072053 PCT/IB2005/000928 443 Alignment segment 1/1: Quality: 1160.00 Escore: 0 5 Matching length: 132 Total length: 143 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 92.31 Total Percent 10 Identity: 92.31 Gaps: 1 Alignment: 15 2 VDAFLGTWKLVDSKNFDDYMKSLAHILITFPLPSGVGFATRQVASMTKPT 51 1 VDAFLGTWKLVDSKNFDDYMKSL ........... .GVGFATRQVASMTKPT 39 52 TIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGG 101 20 40 TIIEKNGDTLTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDGG 89 102 KLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 144 25 90 KLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 132 30 WO 2005/072053 PCT/IB2005/000928 444 Sequence name: /tmp/xYzWyViDom/twDu3T69pd:AAP35373 Sequence documentation: 5 Alignment of: S67314_PEA_1_P7 x AAP35373 Alignment segment 1/1: Quality: 1172.00 10 Escore: 0 Matching length: 133 Total length: 144 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 92.36 Total Percent Identity: 92.36 Gaps: 1 Alignment: 20 1 MVDAFLGTWKLVDSKNFDDYMKSLAHTLTTFPLPSGVGFATRQVASMTKP 50 1 MVDAFLGTWKLVDSKNFDDYMKSL ........... .GVGFATRQVASMTKP 39 25 51 TTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDG 100 40 TTIIEKNGDILTLKTHSTFKNTEISFKLGVEFDETTADDRKVKSIVTLDG 89 101 GKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 144 90 GKLVHLQKWDGQETTLVRELIDGKLILTLTHGTAVCTRTYEKEA 133 WO 2005/072053 PCT/IB2005/000928 445 5 WO 2005/072053 PCT/IB2005/000928 446 DESCRIPTION FOR CLUSTER Z44808 Cluster Z44808 features 5 transcript(s) and 21 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 5 application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SEQ ID NO: Z44808_PEA1_TI11 23 Z44808_PEA_1_T4 24 Z44808_PEA 1_T5 25 Z44808_PEA_1_T8 26 Z44808_PEA_1 T9 27 Table 2 - Segments of interest Segrnnt Nane SEQ ID NO: Z44808_PEA_1 node_0 220 Z44808 PEA_1_node_16 221 Z44808 PEA 1 node_2 222 Z44808_PEA_1_node 24 223 Z44808_PEAInode 32 224 Z44808_PEA 1_node_33 225 Z44808_PEA 1 node_36 226 Z44808_PEAInode_37 227 Z44808_PEA_1_node_41 228 Z44808_PEA_1_node 11 229 Z44808_PEA 1 node_13 230 Z44808_PEA1_node_18 231 Z44808-PEA1_node_22 232 Z44808_PEA1_node_26 233 WO 2005/072053 PCT/IB2005/000928 447 Z44808 PEA_1_node_30 234 Z44808_PEA_1_node34 235 Z44808_PEA_1_node 35 236 Z44808 PEA 1 node 39 237 Z44808 PEA 1 node 4 238 Z44808 PEA 1 node_6 239 Z44808 PEA 1 node 824 Table 3 - Proteins of interest Protein Name SEQIDO Z44808_PEA_1_P5 556 Z44808_PEA_1_P6 557 Z44808_PEA_1_P7 558 Z44808_PEA_1_P11 559 These sequences are variants of the known protein SPARC related modular calcium 5 binding protein 2 precursor (SwissProt accession identifier SMO2_HUMAN; known also according to the synonyms Secreted modular calcium-binding protein 2; SMOC-2; Smooth muscle-associated protein 2; SMAP-2; MSTP 117), SEQ ID NO: 624, referred to herein as the previously known protein. Protein SPARC related modular calcium-binding protein 2 precursor is known or believed 10 to have the following function(s): calcium binding . The sequence for protein SPARC related modular calcium-binding protein 2 precursor is given at the end of the application, as "SPARC related modular calcium-binding protein 2 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 -Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 169-170 KT -> TR WO 2005/072053 PCT/IB2005/000928 448 212 S -> P 429 - 446 TPRGHAESTSNRQPRKQG -> RSKRNL 434 A ->V 439 N ->Y Protein SPARC related modular calcium-binding protein 2 precursor localization is believed to be Secreted (Probable). Cluster Z44808 can be used as a diagnostic marker according to overexpression of 5 transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the right hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 10 Overall, the following results were obtained as shown with regard to the histograms in Figure 19 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: colorectal cancer, lung cancer and pancreas carcinoma. 15 Table 5 - Normal tissue distribution Name of Tissue Number' bladder 123 bone 304 brain 18 colon 0 epithelial 40 general 37 kidney 2 lung 0 breast 61 WO 2005/072053 PCT/IB2005/000928 449 ovary 116 pancreas 0 prostate 128 stomach 36 uterus 195 Table 6 - P values and ratios fbr expression in cancerous tissue Nname of Tissue P1 P2 SPi 3 SP2 bladder 6.8e-01 7.6e-01 7.7e-01 0.8 9.le-01 0.6 bone 7.0e-01 8.8e-01 9.9e-01 0.3 1 0.2 brain 6.8e-01 7.2e-01 3.0e-02 2.6 1.7e-01 1.6 colon 9.2e-03 1.3e-02 1.2e-01 3.6 1.6e-01 3.1 epithelial 2.le-02 4.0e-01 1.0e-04 1.9 2.7e-01 1.0 general 2.6e-02 7.2e-01 4.9e-07 1.9 3.0e-01 1.0 kidney 7.3e-01 8.le-01 1 1.0 1 1.0 lung 4.0e-03 1.8e-02 8.0e-04 12.2 2.1e-02 6.0 breast 4.8e-01 6.le-01 9.8e-02 2.0 3.9e-01 1.2 ovary 8.le-01 8.3e-Ol 9.le-01 0.6 9.7e-01 0.5 pancreas 1.2e-01 2.le-01 1.Oe-03 6.5 5.9e-03 4.6 prostate 8.4e-01 8.9e-01 9.0e-01 0.6 9.8e-01 0.4 stomach 5.0e-01 8.7e-01 9.6e-04 1.5 1.9e-01 0.8 uterus 6.7e-01 7.9e-01 9.2e-01 0.5 1 0.3 As noted above, cluster Z44808 features 5 transcript(s), which were listed in Table 1 5 above. These transcript(s) encode for protein(s) which are variant(s) of protein SPARC related modular calcium-binding protein 2 precursor. A description of each variant protein according to the present invention is now provided. Variant protein Z44808_PEA_1 P5 according to the present invention has an amino acid 10 sequence as given at the end of the application; it is encoded by transcript(s) WO 2005/072053 PCT/IB2005/000928 450 Z44808 PEA 1 T4. An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to 5 each such aligned protein is as follows: Comparison report between Z44808_ PEA_1_P5 and SMO2_HUMAN: I.An isolated chimeric polypeptide encoding for Z44808 PEA 1_P5, comprising a first amino acid sequence being at least 90 % homologous to 10 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGR TFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDD GTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEELPQREGTGKTDDAA APALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKN DNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPA 15 KARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQ ELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1 - 441 of SMO2_HUMAN, which also corresponds to amino acids I - 441 of Z44808_PEA_1_PS, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 20 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DAMVVSSRPKATTHRKSRTLSRR corresponding to amino acids 442 - 464 of Z44808_PEA_1_P5, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z44808_PEA_1_P5, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DAMVVSSRPKATTHRKSRTLSRR in Z44808_PEA_1_P5. The location of the variant protein was determined according to results from a number of 30 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: WO 2005/072053 PCT/IB2005/000928 451 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. 5 Variant protein Z44808_PEA_1 P5 is encoded by the following transcript(s): Z44808_PEA_1_T4, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808_PEA_1_T4 is shown in bold; this coding portion starts at position 586 and ends at position 1977. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_1_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 549 A ->G No 648 T ->G No 4403 G ->T No 4456 G ->A Yes 4964 G ->C Yes 1025 C-> No 1677 T -> C No 2691 C -> T Yes 3900 T -> C No 3929 G -> A Yes 4099 G -> T Yes 4281 T ->C No 4319 G->C Yes 15 WO 2005/072053 PCT/IB2005/000928 452 Variant protein Z44808_PEA__P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_IT5. An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor) at the end of the application. One or more alignments to 5 one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z44808 PEA 1 P6 and SMO2 HUMAN: 10 1.An isolated chimeric polypeptide encoding for Z44808-PEA 1 P6, comprising a first amino acid sequence being at least 90 % homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGR TFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDD GTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAA 15 APALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKN DNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTAR-AHPA KARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQ ELMGCLGVAKEDGKADTKKRHJ corresponding to amino acids I - 428 of SMO2 _HUMAN, 20 which also corresponds to amino acids 1 - 428 of Z44808_PEA_lP6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RSKRNL corresponding to amino acids 429 - 434 of Z44808_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a tail of Z44808_PEAl P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RSKRNL in Z44808_PEA_1_P6. 30 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized WO 2005/072053 PCT/IB2005/000928 453 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. 5 Variant protein Z44808_PEA 1 P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808 PEA 1 P6 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 8 - Amino acid mutations SNP positions) on amino acid Alteniative amino acid(s) Previovsiy known SNP? sequence 147 A-> No Variant protein Z44808_PEA 1 P6 is encoded by the following transcript(s): Z44808_PEA_1T5, for which the sequence(s) is/are given at the end of the application. The 15 coding portion of transcript Z44808_PEA_1_T5 is shown in bold; this coding portion starts at position 586 and ends at position 1887. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA-1_P6 sequence provides support for the deduced 20 sequence of this variant protein according to the present invention). Table 9 -Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid sequence 549 A ->G No 648 T ->G No 2866 G -> A Yes WO 2005/072053 PCT/IB2005/000928 454 3374 G-> C Yes 1025 C ->No 1677 T-> C No 2310 T-> C No 2339 G-> A Yes 2509 G -> T Yes 2691 T -> C No 2729 G -> C Yes 2813 G->T No Variant protein Z44808_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Z44808_PEAIT9. An alignment is given to the known protein (SPARC related modular calcium-binding protein 2 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Z44808_PEA 1 P7 and SMO2 HUMAN: 1.An isolated chimeric polypeptide encoding for Z44808_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGR 15 TFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDD GTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAA APALETQPQGDEEDIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKN DNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPA KARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE 20 RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQ ELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1 - 441 WO 2005/072053 PCT/IB2005/000928 455 of SMO2_HUMAN, which also corresponds to amino acids 1 - 441 of Z44808 PEA 1 P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LLWLRGKVSFYCF corresponding to amino acids 442 - 454 5 of Z44808_PEA_1 P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z44808_PEA_1 P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 10 sequence LLWLRGKVSFYCF in Z44808_PEA_1_P7. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 15 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z44808_PEA_1 _P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the 20 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 147 A No 25 Variant protein Z44808 PEA _P7 is encoded by the following transcript(s): Z44808_PEA_1_T9, for which the sequence(s) is/are given at the end of the application. The WO 2005/072053 PCT/IB2005/000928 456 coding portion of transcript Z44808_PEA 1 T9 is shown in bold; this coding portion starts at position 586 and ends at position 1947. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein Z44808_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 549 A ->G No 648 T ->G No 1025 C-> No 1677 T ->C No 2169 C ->A Yes 10 Variant protein Z44808_PEA_1_P11 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z44808_PEA_1_Ti1. The identification of this transcript was performed using a non-EST based method for identification of alternative splicing, described in the following reference: "Sorek R et al., Genome Res. (2004) 14:1617-23." An alignment is given to the known protein 15 (SPARC related modular calcium-binding protein 2 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 20 Comparison report between Z44808 PEA 1_P11 and SMO2_HUMAN: 1.An isolated chimeric polypeptide encoding for Z44808_PEA_1_P11, comprising a first amino acid sequence being at least 90 % homologous to

MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGR

WO 2005/072053 PCT/IB2005/000928 457 TFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDD GTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKTPRCPGSVNEKLPQREGTGKT corresponding to amino acids I - 170 of SMO2 HUMAN, which also corresponds to amino acids 1 - 170 of Z44808_PEA_1_P11, and a second amino acid sequence being at least 90 % 5 homologous to DIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGL YKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQ GCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLD KNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE 10 DGKADTKKRHTPRGHAESTSNRQPRKQG corresponding to amino acids 188 - 446 of SMO2_HUMAN, which also corresponds to amino acids 171 - 429 of Z44808_PEA_1_P11, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of Z44808_PEA-1_P11, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in 15 length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise TD, having a structure as follows: a sequence starting from any of amino acid numbers 170-x to 170; and ending at any of amino acid numbers 171+ ((n-2) -x), in which x varies from 0 to n-2. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 25 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z44808_PEA-1._P11 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 30 the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_1_P11 WO 2005/072053 PCT/IB2005/000928 458 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations SNI position(s) on amino acid Alteinative'amino acid(s) Previously known SNP? 147 A No 5 Variant protein Z44808 PEA_1_P11 is encoded by the following transcript(s): Z44808_PEA_1_Tl 1, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z44808._PEA_1_TI 1 is shown in bold; this coding portion starts at position 586 and ends at position 1872. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z44808_PEA_1_P11 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Nucleic acid SNPs SNP position on nuceotide Alternative nucleic acid Previously known, SNP? sequence 549 A ->G 648 T-> G No 2720 G-> A Yes 3228 G-> C Yes 1025 C ->NO 1626 T-> C No 2164 T-> C No 2193 G ->A Yes 2363 G -> T Yes 2545 T->C No 2583 G -> C Yes WO 2005/072053 PCT/IB2005/000928 459 2667 G->T No As noted above, cluster Z44808 features 21 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster Z44808_PEA_1_node_0 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808 PEA_1_Ti 1, Z44808_PEA_1_T4, 10 Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808_PEA_1_T9. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment starting position gment ending position Z44808_PEA_1_TI1 1 669 Z44808_PEA_1_T4 1 669 Z44808_PEA _1T5 1 669 Z44808_PEA_1 T8 1 669 Z44808_PEA_1 T9 1 669 15 Segment cluster Z44808_PEA_1_node_16 according to the present invention is supported by 39 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA 1 T11, Z44808_PEA_1_T4 Z44808_PEAIT5, Z44808_PEAIT8 and Z44808_PEA_1_T9. Table 15 below describes the starting and ending position of this segment on each transcript. 20 Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA_1_Tl1 1172 1358 WO 2005/072053 PCT/IB2005/000928 460 Z44808_PEA_1_T4 1223 1409 Z44808_PEAI 1T5 1223 1409 Z44808_PEA I T8 1223 1409 Z44808_PEAIT9 1223 1409 Segment cluster Z44808 PEA-1_node_2 according to the present invention is supported by 34 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z44808_PEA I_T11, Z44808_PEA 1 T4, Z44808_PEA__T5, Z44808_PEA_1_T8 and Z44808_PEAIT9. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts ,Transcript' name Segment starting position Z44808_PEA1_TI1 670 841 Z44808 PEA 1_T4 670 841 Z44808_PEA_1_T5 670 841 Z44808_PEA_1_T8 670 841 Z44808_PEA_1_T9 670 841 10 Segment cluster Z44808_PEA_1_node_24 according to the present invention is supported by 52 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808 PEA 1_ TI, Z44808_PEAIT4, Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808 PEA 1 T9. Table 17 below describes 15 the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA_1_T1 1545 1819 Z44808_PEA_1_T4 1596 1870 WO 2005/072053 PCT/IB2005/000928 461 Z44808_PEAl_T5 1596 1870 Z44808_PEA_1_T8 1596 1870 Z44808_PEA__T9 1596 1870 Segment cluster Z44808_PEA_1 node 32 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z44808_PEA_1 T4 and Z44808_PEA_1_T8. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name Segment starting 'position,, Segmefit ending position Z44808_PEA 1_T4 1909 3593 Z44808_PEA 1_T8 1909 2397 10 Segment cluster Z44808 PEA_ Inode 33 according to the present invention is supported by 133 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA_1_Ti 1, Z44808_PEA_1_T4 and Z44808_PEAIT5. Table 20 below describes the starting and ending position of this segment on each transcript. 15 Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA_1_Tl1 1858 2734 Z44808_PEA_1_T4 3594 4470 744808_PEA_1_T5 2004 2880 Segment cluster Z44808 PEA 1_node_36 according to the present invention is supported by 117 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): Z44808_PEA_1-Tll, Z44808_PEA_1_T4 and WO 2005/072053 PCT/IB2005/000928 462 Z44808_PEAIT5. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segmeit starting position Segment ending position Z44808 PEA_1 T11 2829 3080 Z44808_PEA 1_T4 4565 4816 Z44808 PEA_1_T5 2975 3226 5 Segment cluster Z44808_PEA_1_node 37 according to the present invention is supported by 120 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA1_Tl 1, Z44808_PEA_1_T4 and Z44808_PEA_1_T5. Table 22 below describes the starting and ending position of this segment 10 on each transcript. Table 22 - Segment location on transcripts Transipt tam Segint starting position Segment ending poston Z44808_PEA1_TI1 3081 3429 Z44808_PEA_1_T4 4817 5165 Z44808_PEA,_1_T5 3227 3575 Segment cluster Z44808 PEA 1_node 41 according to the present invention is supported 15 by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA1_T9. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA_1_T9 1974 2206 WO 2005/072053 PCT/IB2005/000928 463 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster Z44808_PEA_1_node_11 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808 PEA _IT4, Z44808 PEA _IT5, Z44808_PEA 1_T8 and Z44808_PEAIT9. Table 24 below describes the starting and ending position of this segment on each transcript. 10 Table 24 - Segment location on transcripts Z44808Segment staPtEngAposition Segment er~qi position Z44808_PEA_1 T4 1097 1147 Z44808_PEA_1_T5 1097 1147 Z44808_PEA_1_T8 10907 1147 Z44808_PEA_1_T9 1097 1147 Segment cluster Z44808 PEA _Inode 13 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Z44808_PEA_1_ T1, Z44808 PEA_1_T4, Z44808_PEAIT5, Z44808_PEA_1_T8 and Z44808_PEA_1_T9. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA 1_TI1 1097 1171 Z44808_PEA_1_T4 1148 1222 Z44808_PEA_1_TS 1148 1222 Z44808_PEA_1_T8 1148 1222 Z44808_PEA_1_T9 1148 1222 WO 2005/072053 PCT/IB2005/000928 464 Segment cluster Z44808 PEA_ I node 18 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808 PEA __T1 1, Z44808_PEA_1_T4, 5 Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808 PEA_1_T9. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA_1_11 1359 1441 Z44808_PEA_1_T4 1410 1492 Z44808_PEA 1 T5 1410 1492 Z44808_PEA 1_T8 1410 1492 Z44808_PEA_T9 1410 1492 10 Segment cluster Z44808 PEA_1 node 22 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEAI_TI 1, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEAIT8 and Z44808_PEA_1_T9. Table 27 below describes the starting and ending position of this segment on each transcript. 15 Table 27 - Segment location on transcripts Transcript name Segment starting position Z44808_PEA1_T1 1442 1544 Z44808_PEA_1_T4 1493 1595 Z44808 PEA1_T5 1493 1595 Z44808_PEA __T8 1493 1595 Z44808_PEA_1_T9 1493 1595 WO 2005/072053 PCT/IB2005/000928 465 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment, shown in Table 28. 5 Table 28 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Z44808_0_8_0 Lung squamous cell LUN carcinoma Segment cluster Z44808 PEA_1_node 26 according to the present invention is supported by 2 libraries. The number of libraries was detennined as previously described. This segment 10 can be found in the following transcript(s): Z44808 PEA_1_T5. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Trncitname Segment Starting, position, Segment ending positi&n Z44808_PEA_1_T5 1871 1965 Segment cluster Z44808 PEA 1_node 30 according to the present invention is supported 15 by 44 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA 1_T 11, Z44808_PEA_1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808_PEA_1 T9. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA1TI1 1820 1857 Z44808_PEA 1_T4 1871 1908 Z44808_PEA_1_T5 1966 2003 Z44808_PEA_1_T8 1871 1908 WO 2005/072053 PCT/IB2005/000928 466 Z44808_PEA_1_T9 1871 1908 Segment cluster Z44808_PEA 1 node_34 according to the present invention is supported by 70 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z44808_PEA T11, Z44808_PEA_1_T4 and Z44808_PEA _1T5. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Trnscriptaine Segnien starting position Segment ending position Z44808_PEA 1 TI1 2735 2809 Z44808_PEA 1_T4 4471 4545 Z44808_PEA1 T5 2881 2955 10 Segment cluster Z44808_PEA_1_node_35 according to the present invention can be found in the following transcript(s): Z44808 PEA_1_T1 1, Z44808_PEA_1_T4 and Z44808_PEA_1_T5. Table 33 below describes the starting and ending position of this segment on each transcript. 15 Table 33 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA1_TI1 2810 2828 Z44808_PEA 1_T4 4546 4564 Z44808_PEA_1_T5 2956 2974 Segment cluster Z44808 PEA_1_node_39 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): Z44808_PEA1._T9. Table 34 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 4 6'7 Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA 1T9 1909 1973 Segment cluster Z44808_PEA_1_node_4 according to the present invention is supported 5 by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808-PEA lT 1, Z44808-PEA1_T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808_PEA_1_T9. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transriptame Seginent starting position Segment endinposition Z44808_PEA_111 842 948 Z44808_PEA 1T4 842 948 Z44808_PEA 1 T5 842 948 Z44808_PEA_1_T8 842 948 Z44808_PEA 1T9 842 948 10 Segment cluster Z44808_PEA-1_node_6 according to the present invention is supported by 30 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z44808_PEA l_T 1, Z44808_PEAIT4, 15 Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808_PEA _1T9. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z44808_PEA 1 TI1 949 1048 Z44808_PEA_1_T4 949 1048 Z44808_PEA_1_TS 949 1048 WO 2005/072053 PCT/IB2005/000928 468 Z44808_PEA_1-T8 949 1048 Z44808_PEAIT9 949 1048 Segment cluster Z44808_PEA_1_node_8 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): Z44808 PEA 1 T 1, Z44808_PEA 1 T4, Z44808_PEA_1_T5, Z44808_PEA_1_T8 and Z44808_PEAIT9. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript nanme Segment starting position Segment ending position Z44808_PEA1_TI1 1049 1096 Z44808_PEA _1T4 1049 1096 Z44808_PEA_1 T5 1049 1096 Z44808_PEA_1_T8 1049 1096 Z44808_PEAIT9 1049 1096 10 Variant protein alignment to the previously known protein: Sequence name: /tmp/vUqLu6eAVZ/K3JDuPvaLo:SMO2_HUMAN 15 Sequence documentation: Alignment of: Z44808 PEA 1 P5 x SMO2 HUMAN 20 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 469 Quality: 4440.00 Escore: 0 Matching length: 441 Total length: 441 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 15 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 20 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 25 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 WO 2005/072053 PCT/IB2005/000928 470 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTAR2AHPAKARDLYKGRQ 300 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 5 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 ||I |IIII I| lII il I i I ||| ||| 1|| || J||||l I I 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 10 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441 401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441 20 Sequence name: /tmp/QSUNfTsJ5y/kLOw5Vb6SD:SMO2 HUMAN 25 Sequence documentation: Alignment of: Z44808 PEA 1 P6 x SMO2 HUMAN Alignment segment 1/1: 30 WO 2005/072053 PCT/IB2005/000928 471 Quality: 4310.00 Escore: 0 Matching length: 428 Total length: 428 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 II i l l ll l l l l l l l l l l 1ll l l lll l l l l l ill l i i li l I l l 15 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 li l l l l l l l l l1 1 1 l l l l l1 i l l l l l l l l l l l l l l 1 ll l l l l l 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 20 101 ARKEFQQVFTPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 25 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 l i l l l l 1 ll l l l l l l l l l l l l l ll l l l l l l l l l l l l l l l l l l l l 1 1 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 30 111111111111 111 11 111111111 | 1lllllll lllllllI 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 WO 2005/072053 PCT/IB2005/000928 472 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 1111111l11l 11111l1l~iiI liiiII1111 ii ii|IIII| 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 5 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 10 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 iIi 11111111111I1II1 II|i||||II II II ill 111III1II 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 401 DKSISVQELMGCLGVAKEDGKADTKKRH 428 15 | 1 1 11|1i1| 1 11111111 401 DKSISVQELMGCLGVAKEDGKADTKKRH 428 20 Sequence name: /tmp/MZVdR4PVdM/5uN8RwViJ1:SMO2_HUMAN 25 Sequence documentation: Alignment of: Z44808 PEA_1 P7 x SMO2_HUMAN Alignment segment 1/1: 30 WO 2005/072053 PCT/IB2005/000928 473 Quality: 4440.00 Escore: 0 Matching length: 441 Total length: 441 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 15 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 51 PLCASDGRTFLSRCEFQRAKCKDPQLETAYRGNCKDVSRCVAERKYTQEQ 100 1111 !1 11111|i 11111 111| 111 |1 |l lll I l 1l1lll li ll 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 20 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 25 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 3 0 I l l l l 1l l l l l l l l l l l l l l l l l l l I l l l l l l l l l l l l l 1l l l l !l l l 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 WO 2005/072053 PCT/IB2005/000928 474 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 IlIIlIIiIIlIiiiiiIIII|IllIIiIIII II 11I11 I 1 1I l1 I11 I I II 111111 I 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 5 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 l ii Ii 11i1i 11 lII III 11111111I I I Ii I I |lI I I II l 1 II I1 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 10 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 l i l l l l l l l l li l l l l l l l l l l l l l l l l l1 1 ll l l l li l l1 i l l l l llI 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441 15 I I 1 II iI I I I Ii I I I I I 401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQ 441 20 Sequence name: /tmp/3fGVxqLloe/J5mQduAdOF:SMO2_HUMAN 25 Sequence documentation: Alignment of: Z44808_PEA 1 P11 x SMO2_HUMAN Alignment segment 1/1: 30 WO 2005/072053 PCT/IB2005/000928 4'75 Quality: 4228.00 Escore: 0 Matching length: 429 Total length: 446 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 96.19 Total Percent Identity: 96.19 Gaps: 1 10 Alignment: 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 15 1 MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQK 50 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 I iiI I 1 1 1 1 1 1111i 1111lI I IIiIIIiiiIIIIIliiIII 11 1 1 1 1 1 11i11 I 51 PLCASDGRTFLSRCEFQRAKCKDPQLEIAYRGNCKDVSRCVAERKYTQEQ 100 20 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 101 ARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGRPISGTAVAHKT 150 25 151 PRCPGSVNEKLPQREGTGKT.................DIASRYPTLWTEQ 183 151 PRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQ 200 184 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 233 201 VKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQ 250 WO 2005/072053 PCT/IB2005/000928 476 234 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTAAHPAKARDLYKGRQ 283 SI I iI I IlIil l i I i I ll I i I I li1Ii i I 1 i l1l I 111i 11 Il 251 CHPSTGYCWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQ 300 5 284 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 333 l Ii l l l l l l l l l l l l l li l l l l l i l l i ll1 1 1 1 1 1 1 1 1 1 1 1 1 I| 301 LQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEER 350 10 334 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 383 ||1111 I | I II I I I i I I I I Ii lil |1 | I I i I I il I 11 I ii 351 VVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNN 400 384 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG 429 15 I l I l |1| I ii i l l l11l l 1i I 401 DKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG 446 Expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) 20 Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808junc8-11 in normal and cancerous colon tissues Expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by or according to junc8- 11, Z44808juncs- 11 amplicon (SEQ ID 25 NO: 1291) and primers Z44808junc8-11F (SEQ ID NO: 1289) and Z44808junc8-11R (SEQ ID NO: 1290) was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon, SEQ ID NO:53 1), HPRT1 (GenBank Accession No. NM 000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; G6PD amplicon, SEQ ID NO:615), 30 RPS27A (GenBank Accession No. NM _002954; RPS27A amplicon, SEQ ID NO:1261) was measured similarly. For each RT sample, the expression of the above amplicon was normalized WO 2005/072053 PCT/IB2005/000928 477 to the geometric mean of the quantities of the housekeeping genes. The nonnalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, "Tissue samples in testing panel"), to obtain a value of fold up-regulation for each sample relative to median of the normal 5 PM samples. Figure 32 is a histogram showing over expression of the above-indicated SM02_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts in cancerous colon samples relative to the normal samples. 10 As is evident from Figure 32, the expression of SM02_HUIVIAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by the above amplicon in cancer samples was higher in a few samples than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above, "Tissue samples in testing panel"). Notably an over 15 expression of at least 5 fold was found in 4 out of 36 adenocarcinoma samples.

WO 2005/072053 PCT/IB2005/000928 4'78 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: Z44808junc8-11 F forward primer; and Z44808junc8-1 IR reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z44808junc8 11. 10 Primers: Forward primer Z44808junc8-1 F (SEQ ID NO: 1289): GAAGGCACAGGAAAAACAGATATTG Reverse primer Z44808junc8-11R (SEQ ID NO: 1290): TGGTGCTCTTGGTCACAGGAT 15 Amplicon Z44808junc8-11(SEQ ID NO: 1291): GAAGGCACAGGAAAAACAGATATTGCATCACGTTACCCTACCCTTTGGACTGAACA GGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTCATCCTGTGACCAAG AGCACCA 20 Expression of SM02_HUMAN SPARC related modular calcium-binding protein 2 precursor 25 (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808 junc8-1 1 in different normal tissues Expression of SM02_HUMAN SPARC related modular calcium-binding protein 2 precursor 30 (Secreted modular calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated protein 2) transcripts detectable by or according to Z44808junc8-11 amplicon (SEQ ID NO: 1291) and WO 2005/072053 PCT/IB2005/000928 primers: Z44808junc8-11F (SEQ ID NO: 1289) and Z44808junc8-11R (SEQ ID NO: 1290) was measured by real time PCR. In parallel the expression of four housekeeping genes -RPL 19 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO: 1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), Ubiquitin 5 (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was nonnalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 10 18-20, Table 2, "Tissue samples in normal panel"), to obtain a value of relative expression of each sample relative to median of the ovary samples. Primers: Forward primer Z44808junc8-1 IF (SEQ ID NO: 1289): 15 GAAGGCACAGGAAAAACAGATATTG Reverse primer Z44808junc8-1 IR (SEQ ID NO: 1290): TGGTGCTCTTGGTCACAGGAT Amplicon Z44808junc8-11(SEQ ID NO: 1291): GAAGGCACAGGAAAAACAGATATTGCATCACGTTACCCTACCCTTTGGACTGAACA 20 GGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTCATCCTGTGACCAAG AGCACCA The results are shown in Figure 39, demonstrating the expression of SMO2_HUMAN SPARC related modular calcium-binding protein 2 precursor (Secreted modular calcium-binding protein 25 2) (SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts which are detectable by amplicon as depicted in sequence name Z44808 junc8- 11 in different normal tissues.

WO 2005/072053 PCT/IB2005/000928 480 stomach 219 uterus 113 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPI R3 SP2 R4 bladder 8.2e-01 8.5e-01 9.2e-01 0.6 9.7e-01 0.5 bone 5.5e-01 7.3e-01 4.0e-0l 2.1 4.9e-01 1.5 brain 8.8e-02 1.5e-01 2.3e-03 7.7 1.2e-02 4.8 colon 3.3e-01 2.8e-01 4.2e-01 1.6 4.2e-01 1.5 epithelial 2.5e-01 7.6e-01 3.8e-01 1.0 1 0.6 general 6.4e-03 2.5e-01 1.7e-06 1.6 5.2e-01 0.9 head and neck 3.6e-01 5.9e-01 7.6e-01 0.6 1 0.3 kidney 7.4e-01 8.4e-01 2.le-01 2.1 4.2e-01 1.4 liver 4.le-01 9.le-01 4.2e-02 3.2 6.4e-01 0.8 lung 7.6e-01 8.3e-01 9.8e-01 0.5 1 0.3 breast 5.0e-01 5.5e-01 9.8e-02 1.6 3.4e-01 1.1 ovary 3.7e-02 3.0e-02 6.9e-03 6.1 4.9e-03 5.6 pancreas 3.8e-01 3.6e-01 3.6e-01 1.7 3.9e-01 1.5 prostate 9.le-01 9.2e-01 8.9e-0l 0.5 9.4e-01 0.5 skin 6.0e-01 8.le-01 9.3e-01 0.4 1 0.1 stomach 3.0e-01 8.le-01 9.le-01 0.6 1 0.3 uterus 1.6e-01 1.3e-01 3.2e-02 1.6 3.0e-01 1.1 As noted above, cluster Z25299 features 5 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein 5 Antileukoproteinase 1 precursor. A description of each variant protein according to the present invention is now provided. Variant protein Z25299_PEA_2_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 Z25299_PEA_2_Ti. An alignment is given to the known protein (Antileukoproteinase 1 WO 2005/072053 PCT/IB2005/000928 481 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between Z25299_PEA_2_P2 and ALKIHUMAN: I.An isolated chimeric polypeptide encoding for Z25299-PEA_2_P2, comprising a first amino acid sequence being at least 90 % homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCP GKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLK 10 CCMGMCGKSCVSPVK corresponding to amino acids I - 131 of ALKIHUMAN, which also corresponds to amino acids 1 - 131 of Z25299_PEA 2 P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKQGMRAH corresponding to amino acids 132 - 139 of Z25299_PEA_2 P2, wherein said 15 first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z25299_PEA_2 P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKQGMRAH in Z25299_PEA_2_P2. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 25 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z25299_PEA_2_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 30 the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P2 WO 2005/072053 PCT/IB2005/000928 482 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP position(s) on amino acid Alternative amnino acid(s) Previously know, SNP? sequence 136 M ->T Yes 20 P-> No 43 C ->R No 48 K ->N No 83 R ->K No 84 R-> W No 5 Variant protein Z25299_PEA_2_P2 is encoded by the following transcript(s): Z25299_PEA_2_Ti, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_2_TI is shown in bold; this coding portion starts at position 124 and ends at position 540. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternativernucleic acid Previously known SNP? sqence 122 C ->T No 123 C->T No 530 T ->C Yes 989 C ->T Yes 1127 C ->T Yes 1162 A -> C Yes WO 2005/072053 PCT/IB2005/000928 483 1180 A ->A C Yes 1183 A-> C Yes 1216 A-> C Yes 1262 G -> A Yes 183 T -> No 250 T ->C No 267 A ->C No 267 A ->G No 339 C ->T Yes 371 G ->A No 373 A ->T No 435 C ->T No Variant protein Z25299_PEA 2 P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Z25299_PEA_2_T2. An alignment is given to the known protein (Antileukoproteinase 1 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Z25299_PEA_2_P3 and ALK1_HUMAN: 1.An isolated chimeric polypeptide encoding for Z25299_PEA_2_P3, comprising a first amino acid sequence being at least 90 % homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCP GKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLK 15 CCMGMCGKSCVSPVK corresponding to amino acids 1 - 131 of ALK HUMAN, which also corresponds to amino acids 1 - 131 of Z25299_PEA_2_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GEKRHHKQLRDQEVDPLEMRRHSAG corresponding to amino acids 132 - 156 of WO 2005/072053 PCT/IB2005/000928 484 Z25299_PEA_2_P3, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z25299_PEA_2 P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GEKRHHKQLRDQEVDPLEMRRHSAG in Z25299_PEA_2_P3. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 10 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z25299_PEA_2_P3 also has the following non-silent SNPs (Single 15 Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 8 - Amino acid mutations SNP positin(s) on amino acid Alternative amino acld(s) Previously known SNP? sequence 20 P-> No 43 C -> R No 48 K ->N No 83 R ->K No 84 R ->W No Variant protein Z25299_PEA_2_P3 is encoded by the following transcript(s): Z25299_PEA_2_T2, for which the sequence(s) is/are given at the end of the application. The WO 2005/072053 PCT/IB2005/000928 485 coding portion of transcript Z25299_PEA 2 T2 is shown in bold; this coding portion starts at position 124 and ends at position 591. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein Z25299_PEA_2_P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternativenucleic acid Previously known SNP? sequence 122 C -> T No 123 C -> T No 183 T-> No 250 T ->C No 267 A ->C No 267 A ->G No 339 C ->T Yes 371 G ->A No 373 A ->T No 435 C ->T No 10 Variant protein Z25299_PEA_2_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) Z25299_PEA_2_T6. An alignment is given to the known protein (Antileukoproteinase 1 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the 15 relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Z25299_PEA_2_P7 and ALKI_HUMAN: WO 2005/072053 PCT/IB2005/000928 486 I.An isolated chimeric polypeptide encoding for Z25299_PEA2 P7, comprising a first amino acid sequence being at least 90 % homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCP GKKRCCPDTCGIKCLDPVDTPNP corresponding to amino acids 1 - 81 of ALKI _HUMAN, 5 which also corresponds to amino acids 1 - 81 of Z25299_PEA_2_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence RGSLGSAQ corresponding to amino acids 82 - 89 of Z25299 PEA_2 P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 10 2.An isolated polypeptide encoding for a tail of Z25299_PEA_2_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence RGSLGSAQ in Z25299_PEA_2_P7. 15 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 20 region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z25299_PEA_2_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P7 25 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 20 P -> No WO 2005/072053 PCT/IB2005/000928 487 43 C ->R No 48 K ->N No 82 R ->S No Variant protein Z25299_PEA_2_P7 is encoded by the following transcript(s): Z25299_PEA_2_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_2_T6 is shown in bold; this coding portion starts at 5 position 124 and ends at position 390. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previuslykniown SNP? sequence 122 C -> T No 123 C -> T No 576 A -> C Yes 594 A ->C Yes 597 A ->C Yes 630 A ->C Yes 676 G ->A Yes 183 T-> No 250 T->C No 267 A ->C No 267 A ->G No 339 C ->T Yes 369 A ->T No 431 C ->T No 541 C ->T Yes WO 2005/072053 PCT/IB2005/000928 488 Variant protein Z25299_PEA_2_PlO according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Z25299_PEA_2_T9. An alignment is given to the known protein (Antileukoproteinase I precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Z25299_PEA_2_PlO and ALKIHUMAN: 1.An isolated chimeric polypeptide encoding for Z25299_PEA_2_P10, comprising a first amino acid sequence being at least 90 % homologous to MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCP GKKRCCPDTCGIKCLDPVDTPNPT corresponding to amino acids 1 - 82 of ALKIHUMAN, 15 which also corresponds to amino acids 1 - 82 of Z25299_PEA2_P10. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 20 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Z25299_PEA_2_PO also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the 25 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_PO sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 489 SNP positions) on aiino acid Alternative amino acid(s) Previously known SNP? sequence 20 P No 43 C ->R No 48 K->N No Variant protein Z25299_PEA_2._PO is encoded by the following transcript(s): Z25299_PEA_2_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z25299_PEA_2_T9 is shown in bold; this coding portion starts at 5 position 124 and ends at position 369. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last colunm indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z25299_PEA_2_P 10 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 13 - Nucleic acid SNPs SNP position on nuoleotide Alternative nucleic acid Previously known SNP? sequence 122 C -> T No 123 C -> T No 451 A -> C Yes 484 A ->C Yes 530 G ->A Yes 183 T-> No 250 T ->C No 267 A ->C No 267 A ->G No 339 C ->T Yes 395 C ->T Yes 430 A ->C Yes WO 2005/072053 PCT/IB2005/000928 490 448 A->C Yes As noted above, cluster Z25299 features 11 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are 5 of particular interest. A description of each segment according to the present invention is now provided. Segment cluster Z25299_PEA_2_node_20 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): Z25299_PEA_2_Ti. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transript namSe Segment starting po esitio Z25299_PEA 2_Ti 518 1099 15 Segment cluster Z25299_PEA_2_node_21 according to the present invention is supported by 162 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_Ti, Z25299_PEA_2_T6 and Z25299_PEA_2_T9. Table 15 below describes the starting and ending position of this segment on each transcript. 20 Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z25299_PEA_2 TI 1100 1292 Z25299_PEA_2 T6 514 706 Z25299_PEA 2_T9 368 560 WO 2005/072053 PCT/IB2005/000928 491 Segment cluster Z25299_PEA_2_node_23 according to the present invention is supported by 2 libraries. The number of libraries was detenrined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_T2. Table 16 below describes the starting and ending position of this segment on each transcript. 5 Table 16 - Segment location on transcripts Transcript iame Segment starting position Segment ending position Z25299 PEA_2_T2 518 707 Segment cluster Z25299_PEA_2_node_24 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): Z25299 PEA 2_T2 and Z25299 PEA_2_T3. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Tiiscrpt name Segment starting position Segment ending psitioh Z25299_PEA_2_T2 708 886 Z25299_PEA 2 T3 518 696 15 Segment cluster Z25299_PEA2node8 according to the present invention is supported by 218 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_T1, Z25299_PEA 2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6 and Z25299_PEA_2_T9. Table 18 below describes the starting and ending position of this segment on each transcript. 20 Table 18 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z25299_PEA 2_Tl 1 208 Z25299_PEA_2 T2 1 208 Z25299_PEA 2_T3 1 208 WO 2005/072053 PCT/IB2005/000928 492 Z25299_PEA 2_T6 1 208 Z25299_PEA_2_T9 1 208 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster Z25299_PEA_2_node_12 according to the present invention is supported by 228 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6 and Z25299_PEA_2_T9. Table 20 below describes 10 the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript naie Segment starting position Segant ending position Z25299_PEA_2_TI 209 245 Z25299_PEA_2 T2 209 245 Z25299_PEA_2_T3 209 245 Z25299_PEA_2_T6 209 245 Z25299_PEA 2_T9 209 245 Segment cluster Z25299_PEA_2_node_13 according to the present invention is supported by 246 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3, Z25299_PEA_2_T6 and Z25299_PEA_2_T9. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z25299_PEA 2 TI 246 357 Z25299_PEA_2 T2 246 357 WO 2005/072053 PCT/IB2005/000928 493 Z25299_PEA 2 T3 246 357 Z25299_PEA 2_T6 246 357 Z25299_PEA_2_T9 246 357 Segment cluster Z25299_PEA_2_node_14 according to the present invention can be found in the following transcript(s): Z25299_PEA_2_Ti, Z25299_PEA_2_T2, 5 Z25299_PEA_2_T3, Z25299_PEA_2_T6 and Z25299_PEA_2_T9. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript naihe Segment starting position Segment ending position Z25299_PEA_2_Ti 358 367 Z25299_PEA 2_T2 358 367 Z25299_PEA_2 T3 358 367 Z25299_PEA 2 T6 358 367 Z25299_PEA_2 T9 358 367 10 Segment cluster Z25299_PEA_2_node_17 according to the present invention can be found in the following transcript(s): Z25299_PEA_2_Tl, Z25299_PEA_2_T2 and Z25299_PEA_2_T3. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position Z25299_PEA_2_TI 368 371 Z25299_PEA 2_T2 368 371 Z25299_PEA_2_T3 368 371 15 WO 2005/072053 PCT/IB2005/000928 494 Segment cluster Z25299-PEA_2_node_18 according to the present invention is supported by 221 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_T1, Z25299_PEA_2_T2, Z25299_PEA_2_T3 and Z25299_PEA_2_T6. Table 25 below describes the starting and ending 5 position of this segment on each transcript. Table 25 - Segment location on transcripts Transript nane Segment starting position Segment ending position Z25299_PEA_2 Ti 372 427 Z25299_PEA_2_T2 372 427 Z25299_PEA_2 T3 372 427 Z25299_PEA_2_T6 368 423 Segment cluster Z25299-PEA_2_node_19 according to the present invention is supported 10 by 197 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z25299_PEA_2_TI, Z25299_PEA_2_T2, Z25299_PEA_2_T3 and Z25299_PEA_2_T6. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting posiion Segment ending position Z25299_PEA_2_TI 428 517 Z25299PEA 2_T2 428 517 Z25299PEA 2_T3 428 517 Z25299_PEA_2 T6 424 513 15 WO 2005/072053 PCT/IB2005/000928 495 Variant protein alignment to the previously known protein: Sequence name: /tmp/oXgeQ4MeyL/K6VqblMQu2:ALK1HUMAN Sequence documentation: 5 Alignment of: Z25299 PEA 2 P2 x ALKI HUMAN Alignment segment 1/1: 10 Quality: 1371.00 Escore: 0 Matching length: 131 Total length: 131 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 25 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLN 100 l I 1 1 l I i l I I I IlIII I I 11111 I 11111111111111 I | | 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLN 100 30 101 PPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK 131 l i 111I | 1 11111 iI I iiiiIIII i i1 I l I WO 2005/072053 PCT/IB2005/000928 496 101 PPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK 131 5 Sequence name: /tmp/rbf3l4VLIm/yR43i4SbP4:ALK1_HUMAN 10 Sequence documentation: Alignment of: Z25299_PEA_2_P3 x ALK1_HUMAN Alignment segment 1/1: 15 Quality: 1371.00 Escore: 0 Matching length: 131 Total length: 131 20 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 30 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 WO 2005/072053 PCT/IB2005/000928 497 51 CQSDWQCPGKKRCCPDTCGTKCLDPVDTPNPTRRKPGKCPVTYGQCLMLN 100 I I1|11| lI 111I ii 1 ii 11lI |11 I 1 i 11 I l 1i I1 I 11 i lIi 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLN 100 5 101 PPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK 131 llii!|11111111Iill111I1lIi1l1 101 PPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK 131 10 Sequence name: /tmp/KCtSXACZXe/rK4T6LKeRX:ALK1 HUMAN 15 Sequence documentation: Alignment of: Z25299_PEA_2_P7 x ALK1_HUMAN 20 Alignment segment 1/1: Quality: 835.00 Escore: 0 Matching length: 81 Total 25 length: 81 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 30 Gaps: 0 WO 2005/072053 PCT/IB2005/000928 498 Alignment: 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 5 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNP 81 I lI IIl 1 I1111 ii I 11 I 11111111 I 11111[ 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNP 81 10 15 Sequence name: /tmp/LcBlcAxB6c/NSI9pqfxoU:ALKIHUMAN Sequence documentation: 20 Alignment of: Z25299_PEA_2_PlO x ALK1 HUMAN Alignment segment 1/1: Quality: 844.00 25 Escore: 0 Matching length: 82 Total length: 82 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 30 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 WO 2005/072053 PCT/IB2005/000928 499 Gaps: 0 Alignment: 5 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 111l1I1111111iii iii iil III 1 1 11111 I 1II 11I Il 11l I l111111111 l 1 MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPE 50 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPT 82 10 1111 I i I i I I I I i I I i I I I i I 51 CQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPT 82 15 Expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G Z25299 transcripts, which are detectable by amplicon as depicted in sequence name 20 Z25299 seg20, were examined for expression in normal and cancerous colon tissues. Transcripts detectable by or according to seg20, Z25299 seg20 amplicon (SEQ ID NO: 1294) and Z25299 seg20F (SEQ ID NO: 1292) and Z25299 seg20R (SEQ ID NO: 1293) primers were measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD 25 (GenBank Accession No. BC019323; amplicon - PBGD-amplicon, SEQ ID NO:531), HPRT1 (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; HPRTI-arnplicon, SEQ ID NO:615), RPS27A (GenBank Accession No. NM_002954; RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the 30 geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) WO 2005/072053 PCT/IB2005/000928 500 samples (Sample Nos. 41, 52, 62-67, 69-71, Table 1, above Tissue samples in testing panel), to obtain a value of fold up-regulation for each sample relative to median of the normal PM samples. Figure 21 is a histogram showing over expression of the above-indicated variant. 5 Transcript expression in cancerous colon samples relative to the normal samples are shown. As is evident from Figure 21, transcripts detectable by the above amplicon(s) in cancer samples were significantly higher than in the non-cancerous samples (Sample Nos. 41,52, 62 67, 69-71 Table 1 Tissue samples in testing panel). Notably an over-expression of at least 5 fold 10 was found in 7 out of 36 adenocarcinoma samples. Statistical analysis was applied to verify the significance of these results, as described below. The P value for the difference in the expression levels of this variant was determined. Transcripts detectable by the above amplicon in colon cancer samples versus the normal 15 tissue samples were determined by T test as 6.98E-02. Threshold of 5 fold overexpression was found to differentiate between cancer and normal samples with P value of 1.33E-02 as checked by exact fisher test. The above values demonstrate statistical significance of the results.

WO 2005/072053 PCT/IB2005/000928 501 Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: Z25299 seg20F forward primer; and Z25299 seg20R reverse primer. 5 The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: Z25299 seg20. Forward primer (SEQ ID NO: 1292): CTCCTGAACCCTACTCCAAGCA Reverse primer (SEQ ID NO: 1293): CAGGCGATCCTATGGAAATCC 10 Amplicon (SEQ ID NO: 1294): CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTCAAGAGAA CTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCCTG 15 Expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues Z25299 transcripts which are detectable by amplicon as depicted in sequence name Z25299seg20 in different normal tissues 20 Expression of Secretory leukocyte protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues transcripts detectable by or according to Z25299seg20 amplicon (SEQ ID NO: 1294) and primers: Z25299seg20F (SEQ ID NO: 1294) and Z25299seg20R (SEQ ID NO: 1294) was measured by real time PCR. In parallel the 25 expression of four housekeeping genes -RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon), TATA box (GenBank Accession No. NM_003194; TATA amplicon), Ubiquitin (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon) and SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the 30 quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples (Sample Nos. 18-20, Table 2, WO 2005/072053 PCT/IB2005/000928 502 "Tissue samples on normal panel"), to obtain a value of relative expression of each sample relative to median of the ovary samples. Forward primer (SEQ ID NO: 1292): CTCCTGAACCCTACTCCAAGCA 5 Reverse primer (SEQ ID NO: 1293): CAGGCGATCCTATGGAAATCC Amplicon (SEQ ID NO: 1294): CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTCAAGAGAA CTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCCTG The results are demonstrated in Figure 22, showing the expression of Secretory leukocyte 10 protease inhibitor Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues Z25299 transcripts which are detectable by amplicon as depicted in sequence name Z25299seg20 in different normal tissues. 15 20 DESCRIPTION FOR CLUSTER HUMF5A Cluster HUMF5A features 3 transcript(s) and 33 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table I - Transcripts of interest Transcript Name SEQ ID NO: HUMF5APEA_1 T1 33 HUMF5APEA_1 T3 34 HUMF5APEA 1 T7 35 25 Table 2 - Segments of interest WO 2005/072053 PCT/IB2005/000928 503 SegmeintNaine SEQ ID NO: HUMF5APEA_1 node_0 252 HUMF5APEA 1 node_4 253 HUMFSAPEA 1 node 6 254 HUMF5A PEA_1 node_8 255 HUMF5APEA_1 node_10 256 HUMFSA PEA 1 node 12 257 HUMF5APEA 1_node 14 258 HUMF5APEA 1 node_18 259 HUMF5A PEA 1_node 21 260 HUMF5APEA 1 node_22 261 HUMF5APEA 1_node 24 262 HUMF5A PEA 1 node_26 263 HUMF5APEAI 1node_27 264 HUJMFSA PEA_1_node 29 265 HUMF5APEA 1 node_35 266 HUMF5APEA_1 node_37 267 HUMFSAPEA_1_node_39 268 HUMFSAPEA_1_node_47 269 HUMF5APEA 1_node_50 270 HUMF5APEA_1 node_53 271 HUMF5APEA_1_node_56 272 HUMF5APEA_1 node_60 273 HUMF5APEA_1_node_2 274 HUMF5APEAI 1node_16 275 HUMF5APEA_1_node_31 276 HUMF5APEA_1_node_32 277 HUMF5APEA 1 node_33 278 HUMF5APEA_1 node_41 279 HTUMF5APEA_1_node_43 280 WO 2005/072053 PCT/IB2005/000928 504 HUMF5APEA 1_node 45 281 HUMF5APEA_1_node_51 282 HUMF5APEA 1_node_57 283 HUMF5APEAInode_59 284 Table 3 - Proteins of interest Protein Name SEQ I NO Coresponding Transcript(s) HUMF5A_PEA 1_P3 564 HUMF5APEA_1_TI HUMFSA_PEA 1_P4 565 HUMF5APEA_1_T3 HUMF5APEA_1_P8 566 HUMF5APEA_1_T7 These sequences are variants of the known protein Coagulation factor V precursor 5 (SwissProt accession identifier FA5_HUMAN; known also according to the synonyms Activated protein C cofactor), SEQ ID NO: 626, , referred to herein as the previously known protein. Protein Coagulation factor V precursor is known or believed to have the following function(s): Coagulation factor V is a cofactor that participates with factor Xa to activate 10 prothrombin to thrombin. The sequence for protein Coagulation factor V precursor is given at the end of the application, as "Coagulation factor V precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 107 D -> H (in dbSNP:6019). /FTId=VAR_013886. 334 R -> G (in APCR; Hong Kong). /FTId=VAR013620. 334 R -> T (in APCR; Cambridge). /FTId=VAR_013621. 413 M -> T (in dbSNP:6033). /FTId=VAR_013887. 513 R ->K (in dbSNP:6020). /FTId=VAR_013622. 534 R -> Q (in APCR; Leiden; dbSNP:6025).

WO 2005/072053 PCT/IB2005/000928 505 /FTId=VAR 001213. 809 P -> S (in dbSNP:6031). /FTId=VAR 013888. 817 N -> T (in dbSNP:6018). /FTId=VAR_013889. 858 K -> R (in dbSNP:4524). /FTld=VAR 001214. 865 H -> R (in dbSNP:4525). /FTId=VAR 001215. 925 K-> E (in dbSNP:6032). /FTId=VAR 013890. 1146 H-> Q (in dbSNP:6005). /FTId=VAR_013891. 1285 L -> I (in dbSNP:1046712). /FTId=VAR_013892. 1327 H-> R (in dbSNP:1800595). /FTId=VAR_013893. 1530 E ->A (in dbSNP:6007). /FTId=VAR 013894. 1685 T -> S (in dbSNP:601 1). /FTId=VAR-013895. 1749 L -> V (in dbSNP:6034). /FTId=VAR_013896. 1764 V -> M (in dbSNP:6030). /FTId=VAR_013897. 1820 M ->I (in dbSNP:6026). /FTId=VAR 013898. 2102 R -> H (in APCR). /FTId=VAR_017329. 2222 D -> G (in dbSNP:6027). /FTId=VAR_013899. 2213 T ->A The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cell adhesion; blood coagulation, which are annotation(s) related to Biological Process; and blood coagulation factor; copper binding, which are annotation(s) related to Molecular Function. 5 The GO assignment relies on information from one or more of the SwissProt/TrenIB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. As noted above, cluster HUMF5A features 3 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Coagulation 10 factor V precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMF5A_ PEA_1 P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) WO 2005/072053 PCT/IB2005/000928 506 HUMF5APEA_1_Ti. An alignment is given to the known protein (Coagulation factor V precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein 5 is as follows: Comparison report between HUMF5APEA__P3 and FA5_HUMAN VI (SEQ ID NO 627): 1.An isolated chimeric polypeptide encoding for HUMF5APEA_1 P3, comprising a first amino acid sequence being at least 90 % homologous to 10 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLS VTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKPLSIHPQGIR YSKLSEGASYLDHTFPAEKMDDAVAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHEN LIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGY VNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTA 15 NMTVGPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFI AAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNP NMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTM IRAVQPGETYTYKWNILEFDEPTENDAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSL DRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTIN 20 GYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPESTVMATRK MHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEEFNLTALALENGTEFVSS NTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSHQQATTAGSPLRHLIGKNSVLNSSTAEHS SPYSEDPIEDPLQPDVTGIRLLSLGAGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLA 25 HKVGRHLSQDTGSPSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVG RWHLASEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPKFPR VRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHPLRSEAYNTFSER RLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCPPGLYQTV PPEEHYQTFPIQDPDQMHSTSDPSHRSSSPELSEMLEYDRSHKSFPTDISQMSPSSEHEV 30 WQTVISPDLSQVTLSPELSQTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPD

LSHTTLSLDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSHMTLS

WO 2005/072053 PCT/IB2005/000928 507 PELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSPALGQMPLSPDPSHTT LSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQ MSLSPDLSQVTLSPDISDTTLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQ MPSPSSPTLNDTFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY 5 KTDVRTNINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRETDIEDSDDIP EDTTYKK corresponding to amino acids 1 - 1617 of FA5_HUMAN_Vi, which also corresponds to amino acids I - 1617 of HUMF5APEA_1_P3, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 GSMKSISEFLVLLSELKWMMLSKFVLKJ corresponding to amino acids 1618 - 1645 of HUMF5APEA_1 P3, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMF5APEA_1_P3, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GSMKSISEFLVLLSELKWMMLSKFVLKI in HUMF5APEA_1_P3. It should be noted that the known protein sequence (FA5 _HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino 20 acid sequence for FA5_HUMAN_Vi. These changes were previously known to occur and are listed in the table below. Table 5 - Changes to FA5_HUMAN_V1 SNP position(s) on Type of change amino acid sequence 859 variant 866 variant 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized WO 2005/072053 PCT/IB2005/000928 508 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 5 Variant protein HUMF5APEA_1_P3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5APEA_1_P3 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 6 - Amino acid imutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 15 G ->S Yes 107 D ->H Yes 413 M ->T Yes 513 R ->K Yes 534 R ->Q Yes 781 S -> R Yes 809 P ->S Yes 817 N ->T Yes 858 R ->K Yes 865 R ->H Yes 915 T ->S Yes 925 K ->E Yes 969 N ->S Yes 980 R ->L Yes 1146 H ->Q Yes 1169 D-> No 1285 L ->I Yes WO 2005/072053 PCT/IB2005/000928 509 1327 H ->R Yes 1397 L ->F Yes 1404 P ->S Yes 1530 E ->A Yes Variant protein HUMF5APEA_1_P3 is encoded by the following transcript(s): HUMF5APEA_1_TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMF5APEA _1 T1 is shown in bold; this coding portion starts at 5 position 183 and ends at position 5117. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein -IUMFSA_PEA 1 P3 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 7 - Nucleic acid SNPs SNP position on nucleotide. Alternative nucleic acid Previously known SNP? sequence 16 C->T Yes 225 G -> A Yes 419 A -> G Yes 501 G -> C Yes 587 G -> A Yes 734 G -> T Yes 746 G -> C Yes 951 C -> T Yes 998 C -> T Yes 1420 T -> C Yes 1424 A -> G Yes 1562 C -> T Yes 1720 G -> A Yes 1783 G -> A Yes WO 2005/072053 PCT/IB2005/000928 510 1898 G ->A Yes 2102 C ->T Yes 2108 C ->A Yes 2390 T ->C Yes 2417 C -T Yes 2471 A ->G Yes 2483 G -> A Yes 2525 T ->G Yes 2607 C -> T Yes 2632 A ->C Yes 2755 G -> A Yes 2776 G -> A Yes 2925 A -> T Yes 2955 A ->G Yes 3088 A ->G Yes 3121 G ->T Yes 3437 A ->G Yes 3620 C ->G Yes 3686 A ->C Yes 3688 A-> No 3689 T-> No 3764 C -> T Yes 3986 T -> C Yes 4035 C ->A Yes 4130 C ->T Yes 4162 A ->G Yes 4277 C -> T Yes 4371 C ->T Yes 4392 C -> T Yes 4771 A ->C Yes WO 2005/072053 PCT/IB2005/000928 511 5152 A ->G Yes 5184 C ->G Yes 5375 C ->G Yes 5420 G -> A Yes 5590 G ->A Yes 6573 T -> C Yes 6684 A ->G Yes 6795 A -> G Yes Variant protein HUMF5APEA_1_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMF5APEA_1_T3. An alignment is given to the known protein (Coagulation factor V precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HUMF5APEA_1_P4 and FA5_HUMANVi: 1.An isolated chimeric polypeptide encoding for HUMF5A_PEA_1_P4, comprising a first amino acid sequence being at least 90 % homologous to MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLS VTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKIVHFKNKADKPLSIHPQGIR 15 YSKLSEGASYLDHTFPAEKMDDAVAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHEN LIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGY VNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTA NMTVGPEGKWIISSLTPKIHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFI AAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNP 20 NMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTM IRAVQPGETYTYKWNILEFDEPTENDAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSL DRRGIQRAADIEQQAVFAVFDENKSWYLEDN1NKFCENPDEVKRDDPKFYESNISTIN

GYVPESITTLGFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES

WO 2005/072053 PCT/IB2005/000928 512 VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPESTVMATRK MHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEEFNLTALALENGTEFVSS NTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSHQQATTAGSPLRHLIGKNSVLNSSTAEHS SPYSEDPIEDPLQPDVTGIRLLSLGAGEFRSQEHAKRKGPKVERDQAAKI-IRFSWMKLLA 5 HKVGRHLSQDTGSPSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVG RWHLASEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPKFPR VRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKIHTHHAPLSPRTFIIPLRSEAYNTFSER RLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCPPGLYQTV PPEEHYQTFPIQDPDQMHSTSDPSHRSSSPELSEMLEYDRSHKSFPTDISQMSPSSEHEV 10 WQTVISPDLSQVTLSPELSQTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPD LSHTTLSLDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSHMTLS PELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSPALGQMPLSPDPSHTT LSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQ MSLSPDLSQVTLSPDISDTTLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQ 15 MPSPSSPTLNDTFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY KTDVRTNINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRETDIEDSDDIP EDTTYKKVVFRKYLDSTFTKRDPRGEYEEHLGILGPIIRAEVDDVIQVRFKNLASRPYSL HAHGLSYEKSSEGKTYEDDSPEWFKEDNAVQPNSSYTYVWHATERSGPESPGSACRA WAYYSAVNPEKDIHSGLIGPLLICQKGILHKDSNMPVDMREFVLLFMTFDEKKSWYYE 20 KKSRSSWRLTSSEMKKSHEFHATNGMIYSLPGLKMYEQEWVRLHLLNIGGSQDIHVVH FHGQTLLENGNKQHQLGVWPLLPGSFKTLEMKASKPGWWLLNTEVGENQRAGMQTP FLIMDRDCRMPMGLSTGIISDSQIKASEFLGYWEPRLARLNNGGSYNAWSVEKLAAEFA SKPWIQVDMQKEVIITGIQTQGAKHYLKSCYTTEFYVAYSSNQINWQIFKGNSTRNVMY FNGNSDASTIKENQFDPPIVARYIRISPTRAYNRPTLRLELQGCE corresponding to amino 25 acids 1 - 2062 of FA5_HUMANVi, which also corresponds to amino acids 1 - 2062 of HUJMF5APEA_1 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DVPHPWVWKMER corresponding to amino acids 2063 - 2074 of HUMF5APEA_1_P4, wherein said first amino acid sequence and 30 second amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 513 2.An isolated polypeptide encoding for a tail of HUMF5APEA_1 P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DVPHPWVWKMER in HUMF5APEA_1_P4. 5 It should be noted that the known protein sequence (FA5_HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for FA5_HUMAN_Vi. These changes were previously known to occur and are listed in the table below. 10 Table 8 - Changes to FA5HUMAN V1 SNP position(s) o.n Type of change, aminoa 0-acid sequence 859 variant 866 variant The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMF5A_PEAlP4 also has the following non-silent SNPs (Single 20 Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMF5A_PEA_1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). 25 Table 9 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 514 SNP position(s) on aiinoacid Alternative amino acid(s) Previously known SNP? sequence 15 G ->S Yes 107 D H Yes 413 M ->T Yes 513 R ->K Yes 534 R ->Q Yes 781 S->R Yes 809 P ->S Yes 817 N ->T Yes 858 R ->K Yes 865 R ->H Yes 915 T ->S Yes 925 K->E Yes 969 N ->S Yes 980 R->L Yes 1146 H -> Q Yes 1169 D -> No 1285 L -> I Yes 1327 H -> R Yes 1397 L -> F Yes 1404 P -> S Yes 1530 E -> A Yes 1685 T -> S Yes 1749 L->V Yes 1764 V->M Yes 1820 M ->I Yes Variant protein HUMFSAPEA_1_P4 is encoded by the following transcript(s): HUMF5APEA_1_T3, for which the sequence(s) is/are given at the end of the application. The WO 2005/072053 PCT/IB2005/000928 515 coding portion of transcript HUMF5APEA_1_T3 is shown in bold; this coding portion starts at position 183 and ends at position 6404. The transcript also has the following SNPs as listed in Table 10 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 5 known SNPs in variant protein HUMF5APEA 1_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Nucleic acid SNPs 'SNP position on, nucleotide Alternative nucleic acid Previously known SNP? sequence 16 C ->T Yes 225 G ->A Yes 419 A ->G Yes 501 G ->C Yes 587 G ->A Yes 734 G ->T Yes 746 G ->C Yes 951 C ->T Yes 998 C ->T Yes 1420 T ->C Yes 1424 A -G Yes 1562 C ->T Yes 1720 G ->A Yes 1783 G ->A Yes 1898 G->A Yes 2102 C ->T Yes 2108 C ->A Yes 2390 T ->C Yes 2417 C ->T Yes 2471 A ->G Yes 2483 G -> A Yes WO 2005/072053 PCT/IB2005/000928 516 2525 T ->G Yes 2607 C ->T Yes 2632 A ->C Yes 2755 G -> A Yes 2776 G A Yes 2925 A-> T Yes 2955 A-> G Yes 3088 A-> G Yes 3121 G-> T Yes 3437 A ->G Yes 3620 C ->G Yes 3686 A ->C Yes 3688 A-> No 3689 T-> No 3764 C -> T Yes 3986 T ->C Yes 4035 C ->A Yes 4130 C ->T Yes 4162 A ->G Yes 4277 C ->T Yes 4371 C ->T Yes 4392 C ->T Yes 4771 A ->C Yes 5204 A ->G Yes 5236 C ->G Yes 5427 C -> G Yes 5472 G -> A Yes 5642 G ->A Yes 6618 T ->C Yes 6729 A -> G Yes WO 2005/072053 PCT/IB2005/000928 517 6840 A -> G Yes Variant protein HUMF5APEA_1PS according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMF5APEA_1-T7. An alignment is given to the known protein (Coagulation factor V precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HUMF5APEA_1_P8 and FA5_HUMAN: 1.An isolated chimeric polypeptide encoding for HUMF5A_PEA_1_P8, comprising a first amino acid sequence being at least 90 % homologous to MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLS VTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKIPLSIHPQGIR 15 YSKLSEGASYLDHTFPAEKMDDAVAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHEN LIEDFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGY VNGTMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTA NMTVGPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFI AAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNP 20 NMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTM IRAVQPGETYTYKWNILEFDEPTENDAQCLfRPYYSDVDIMRDIASGLIGLLLICKSRSL DRRGIQRAADIEQQAVFAVFDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMS corresponding to amino acids 1 - 587 of FA5_HUMAN, which also corresponds to amino acids 1 - 587 of HUMF5A PEA 1 P8, and a second amino acid sequence being at least 70%, 25 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SKSEYYFCSSVFHSCG corresponding to amino acids 588 - 603 of HUMF5APEA_1_PS, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 518 2.An isolated polypeptide encoding for a tail of HUMFSA_PEA_1_P8, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SKSEYYFCSSVFHSCG in HUMF5A_PEA_1_P8. 5 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 10 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMF5A_PEA_1_P8 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 11, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 15 the SNP is known or not; the presence of known SNPs in variant protein HUMF5APEAl_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Amino acid mutations SNP position(s) ona aino acid Alternative ano acid(s) Previously known SNP? sequence 15 G->S Yes 107 D ->H Yes 413 M ->T Yes 513 R ->K Yes 534 R ->Q Yes 20 The glycosylation sites of variant protein HUMF5APEA_1_P8, as compared to the known protein Coagulation factor V precursor, are described in Table 12 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates WO 2005/072053 PCT/IB2005/000928 519 whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 12 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Pos ition in variant protein? acid sequence 821 no 554 yes 554 1703 no 741 no 55 yes 55 297 yes 297 752 no 468 yes 468 460 yes 460 1559 no 782 no 1479 no 938 no 776 no 760 no 1103 no 1499 no 1106 no 977 no 2010 no 239 yes 239 1074 no 2209 no 1083 no WO 2005/072053 PCT/IB2005/000928 520 51 yes 51 382 yes 382 The phosphorylation sites of variant protein HUMF5APEA_1_PS, as compared to the known protein Coagulation factor V precursor, are described in Table 13 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates 5 whether the phosphorylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 13 - Phosphorylation sites) Positions) on known amino Present inyariant protein? acidsequence 724 no 726 no 1543 no 1538 no 693 no 1593 no 1522 no Variant protein HUMF5APEA_1_P8 is encoded by the following transcript(s): 10 HUMF5APEA_1_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMF5APEA _1T7 is shown in bold; this coding portion starts at position 183 and ends at position 1991. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein HUMF5A_PEA 1_P8 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 521 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 16 C ->T Yes 225 G ->A Yes 419 A ->G Yes 501 G->C Yes 587 G ->A Yes 734 G ->T Yes 746 G ->C Yes 951 C ->T Yes 998 C ->T Yes 1420 T ->C Yes 1424 A ->G Yes 1562 C ->T Yes 1720 G ->A Yes 1783 G ->A Yes 1898 G ->A Yes 2088 G ->A Yes 2095 G -> A Yes As noted above, cluster HUMF5A features 33 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster HUMF5APEA_1_node_0 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Tl, 10 HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 15 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 522 Table 15 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1 TI 1 340 HUMF5A PEA_1_T3 1 340 HUMF5A PEA_1 T7 1 340 Segment cluster HUMF5APEA_1_node_4 according to the present invention is 5 supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1_T1 433 555 HUMF5APEA_1 T3 433 555 HUMF5APEA 1_T7 433 555 10 Segment cluster HUMF5APEA_1_node_6 according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI, 15 HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 523 HUMF5A PEA 1_Ti 556 768 HUMFSAPEA_1_T3 556 768 HUMF5APEA 1_T7 556 768 Segment cluster HUMF5A_PEA_1_node_8 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMF5APEA_1_Ti, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name iSegmn Segment startingcr po'silion ending position, HUMF5APEA 1_Ti 769 912 HUMF5A PEA 1_T3 769 912 HUMF5APEA_1 T7 769 912 10 Segment cluster HUMF5APEA_1_node_10 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti, HUMF5A PEA 1 T3 and HUMF5A PEA 1 T7. Table 19 below describes the starting and 15 ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1 TI 913 1134 HUMF5APEAI 1T3 913 1134 HUMF5APEA_1_T7 913 1134 WO 2005/072053 PCT/IB2005/000928 524 Segment cluster HUMF5APEAInode_12 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMF5APEA_1_Ti, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5A PEA_1_T1 1135 1300 HUMF5APEA 1_T3 1135 1300 HUMF5APEA 1 T7 1135 1300 10 Segment cluster HUMF5APEA_1_node_14 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 21 below describes the starting and 15 ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1_T1 1301 1478 HUMF5A PEA 1 T3 1301 1478 HUMF5APEA_1_T7 1301 1478 Segment cluster HUMF5APEA_1_node_18 according to the present invention is 20 supported by 10 libraries. The number of libraries was determined as previously described. This WO 2005/072053 PCT/IB2005/000928 525 segment can be found in the following transcript(s): HUMF5APEA_1_Ti, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript name Segment segment starting position ending position 1JUMF5A PEA_1 TI 1579 1793 HUMF5APEA 1 T3 1579 1793 HUMF5APEA 1 T7 1579 1793 5 Segment cluster HUMF5APEA_1_node_21 according to the present invention is supported by 12 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI, 10 HUMF5APEA_1_T3 and HUMF5APEA_1T7. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript nature Segment Segment starting position ending position HUMF5A PEA_1_Ti 1794 1944 HUMF5APEAI 1T3 1794 1944 HUIVIF5APEA_1 T7 1794 1944 15 Segment cluster HUMF5APEA_1_node_22 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T7. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 526 Transcript name Segment Segment starting position ending position HUMF5APEA_1 T7 1945 2097 Segment cluster HUMF5APEA_1_node_24 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts -transcript name6 SegmentSgmn starting position ending position HUMF5APEA_1 TI 1945 2157 HUMF5APEA 1_T3 1945 2157 10 Segment cluster HUMF5A_PEA_1_node_26 according to the present invention is supported by 33 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEA_1_TI and HUMF5APEA_1_T3. Table 26 below describes the starting and ending position of this 15 segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1 Ti 2158 3766 HUMF5APEA_1_T3 2158 3766 WO 2005/072053 PCT/IB2005/000928 527 Segment cluster HUMF5APEA_1 node_27 according to the present invention is supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T1 and HUMF5APEA_1T3. Table 27 below describes the starting and ending position of this 5 segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1 Ti 3767 3936 HUMF5APEA 1 T3 3767 3936 Segment cluster HUMF5APEA_1_node_29 according to the present invention is 10 supported by 22 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI and HUMF5A_PEA_1_T3. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript nane- Segm ent, Segmient, starting position ending position HUMF5APEA_1_TI 3937 4978 I-UMF5APEA_1_T3 3937 4978 15 Segment cluster HUMF5APEA_node_35 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti and 20 HUMF5APEA_1_T3. Table 29 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 528 Table 29 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1_Ti 5102 5338 HUMF5APEA_1_T3 5154 5390 Segment cluster HUMF5APEA_1_node_37 according to the present invention is 5 supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T1 and HUMFSA_PEA_1_T3. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcrip Inae Segment $&grnent starting, p3osiin ending position HUMF5APEA_1 T1 5339 5549 HUMF5APEA 1_T3 5391 5601 10 Segment cluster HUMF5APEA_1_node_39 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T1 and 15 HUMF5APEA_1_T3. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMFSAPEA_1_TI 5550 5729 I-IUMF5APEA 1 T3 5602 5781 WO 2005/072053 PCT/IB2005/000928 529 Segment cluster HUMF5A_PEA_1 node_47 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMF5APEA_1_TI and HUMF5APEAlT3. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name Segment Segment string position enIng position HUMF5APEA 1_Ti 6023 6178 HUMF5APEA_1 T3 6075 6230 10 Segment cluster HUJMF5APEA_1_node_50 according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 33 below describes the starting and ending position of this 15 segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1 Ti 6179 6316 HUMF5APEA 1 T3 6231 6368 Segment cluster HUMF5APEA_1_node_53 according to the present invention is 20 supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T1 and WO 2005/072053 PCT/IB2005/000928 530 HUMF5APEAIT3. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1_TI 6324 6475 HUMF5APEAI 1T3 6369 6520 5 Segment cluster HUMF5APEA_1_node_56 according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 35 below describes the starting and ending position of this 10 segment on each transcript. Table 35 - Segment location on transcripts Tnscript name Segmnent Segment; starting position ending position HUMF5APEA 1_Ti 6476 6611 HUMF5APEA_1_T3 6521 6656 Segment cluster HUMF5APEA_1_node_60 according to the present invention is 15 supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_T1 and HUMF5APEA_1_T3. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 531 HUMF5APEA_1_TI 6666 6951 HUMF5APEA_1_T3 6711 6996 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster HUMF5APEA _1node_2 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This 10 segment can be found in the following transcript(s): HUMF5APEA_1_T1, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1 T1 341 432 HUMF5APEA 1 T3 341 432 HUMF5APEA_1 T7 341 432 15 Segment cluster IUMF5APEA_1_node_16 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti, HUMF5APEA_1_T3 and HUMF5APEA_1_T7. Table 38 below describes the starting and 20 ending position of this segment on each transcript. Table 38 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 532 Transcript name Segment Segment starting position ending position HUMF5APEA1Ti 1479 1578 HUMF5APEA_1_T3 1479 1578 HUMF5APEA_1 T7 1479 1578 Segment cluster HUMF5APEA_1_node_31 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Trncipt Danm e~nn Segment strtngpoiton ening, position HUMF5APEA_1_T1 4979 5033 HUMF5APEA_1_T3 4979 5033 10 Segment cluster HUMF5APEA_1_node_32 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A_PEAIT3. Table 40 below describes the starting and ending position of this segment on each transcript. 15 Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUME5APEA_1_T3 5034 5085 WO 2005/072053 PCT/IB2005/000928 533 Segment cluster HUMF5APEA_1_node_33 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 41 below describes the starting and ending position of this 5 segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1 Ti 5034 5101 HUMF5APEA 1 T3 5086 5153 Segment cluster HUMF5A_PEA_1_node41 according to the present invention is 10 supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5A PEA 1 TI and HUMF5A_PEA_1_T3. Table 42 below describes the starting and ending position of this segment on each transcript. Table 42 - Segment location on transcripts Transcript name Segment Seginent starting position ending position HUMF5APEA_1 TI 5730 5846 HUMF5APEA_1_T3 5782 5898 15 Segment cluster HUMF5APEA_1_node_43 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_TI and 20 HUMF5APEA_1_T3. Table 43 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 534 Table 43 - Segment location on transcripts Transcript name Segment Segnient starting position ending position HUMF5APEA_1 Ti 5847 5918 HUMF5APEA_1_T3 5899 5970 Segment cluster HUMF5APEAlnode_45 according to the present invention is 5 supported by 12 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1_T1 5919 6022 HUMF5APEA_1_T3 5971 6074 10 Segment cluster HUMF5A_PEA_1_node_51 according to the present invention can be found in the following transcript(s): HUMF5APEA_1_TI. Table 45 below describes the starting and ending position of this segment on each transcript. 15 Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA_1_T1 6317 6323 WO 2005/072053 PCT/IB2005/000928 535 Segment cluster HUMF5APEA_1_node_57 according to the present invention is supported by 18 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMF5APEA_1ITi and HUMF5APEA_1_T3. Table 46 below describes the starting and ending position of this 5 segment on each transcript. Table 46 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMF5APEA 1_Ti 6612 6658 HUMF5APEA 1_T3 6657 6703 Segment cluster HUMF5A_PEAInode_59 according to the present invention can be 10 found in the following transcript(s): HUMF5APEA_1_Ti and HUMF5APEA_1_T3. Table 47 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts Transcript name Segment Segment staxting position, enin psii1 HUMF5A PEA_1 T1 6659 6665 HUMF5APEA 1_T3 6704 6710 15 Variant protein alignment to the previously known protein: 20 Sequence name: FA5 HUMAN_V1 WO 2005/072053 PCT/IB2005/000928 536 Sequence documentation: Alignment of: HUMF5APEA_1_P3 x FAS HUMAN VI 5 Alignment segment 1/1: Quality: 16060.00 Escore: 0 Matching length: 1617 Total 10 length: 1617 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 20I lllI111ll l l l1ll l l l1l 1l I llIlI 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKV 100 25 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKV 100 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 i i I i i| | i I | | I I I I I | |11 1 I II I Ii I|| | | | | | | | i l l Il 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 30 . . 151 EWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTE 200 WO 2005/072053 PCT/IB2005/000928 537 11||11111111111|11111||11111111||1111|11111 Iii 151 EWSISEDSGPTHDDPPCLTHTYYSHENLTEDFNSGLIGPLLICKKGTLTE 200 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 5 lilli llI l i lllil li iilliillil 11i1i 1l iii 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 10 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 il llillill111 1 il il l l liilli lli llillll11 li l 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 15 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 l i l l i i l l l l l l l i l l l l l l l i l l l 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 20 401 DESFTKHTVNPNMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGV 450 401 DESFTKHTVNPNMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGV 450 451 TFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTENDAQC 500 2 5 l i l l i i l l i l i l l i l l i l l i l l i i i i l i l l i i l i i l l i l i l l l l i i l i1 451 TFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTENDAQC 500 501 LTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAV 550 30 501 LTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQPAADIEQQAVFAV 550 WO 2005/072053 PCT/IB2005/000928 538 551 FDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTINGYVPESITTL 600 li lll I ll il1l1l 11llllll 111lll ILl il ii| II111 111|111 551 FDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTINGYVPESITTL 600 5 601 GFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES 650 11||1 |11111 II I11 1111111111I iI Il l i I 1111 ll I i il 601 GFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES 650 651 VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPE 700 10 I I l1 l l i l l i l l i l l i l l i l 1l I I i 1 i i1 iiI I i 651 VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPE 700 701 STVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEE 750 l Il l l l l l l l l l l ll l l l l l l 1ll iiIlIlIl ll l Il I I l I 1 1 Il 15 701 STVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEE 750 751 FNLTALALENGTEFVSSNTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSH 800 II~l 11ll II | | |I ll 1 11ll1 I Il 1111l il 111|| 1l1|||| 751 FNLTALALENGTEFVSSNTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSH 800 20 801 QQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLL 850 l i l l l l l l l l l l l l l l l l l l i l l i i l l i l i l l I i l l i 801 QQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLL 850 25 851 SLGAGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGS 900 851 SLGAGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGS 900 901 PSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVGRWHLA 950 901 PSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVGRWHLA 950 WO 2005/072053 PCT/IB2005/000928 539 951 SEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPK 1000 951 SEKGSYEIIQDTDEDTAVNNWLTSPQNASRAWGESTPLANKPGKQSGHPK 1000 5 1001 FPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHP 1050 1001 FPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHP 1050 10 1051 LRSEAYNTFSERRLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDH 1100 1051 LRSEAYNTFSERRLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDH 1100 1101 NQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQMHSTSDPSHRSSS 1150 15I11 II11 1111111 |||11111111 111 |11 llllillilllll11 l 1101 NQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQMHSTSDPSHRSSS 1150 1151 PELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELS 1200 20 1151 PELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELS 1200 1201 QTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLS 1250 lI l l l l lI l 1 l l l l! ll i l l l l l l l l i l1 ! l l l l l l l l i i l i li l iI 1201 QTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLS 1250 25 1251 LDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSH 1300 1251 LDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSH 1300 30 1301 MTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSP 1350 l i l l l l l l 1l 1l l l l l l l l l l l l l l l l l l l l l 1 | 1 1 | |1 1 1 1 1 1 | | 1 1 1 WO 2005/072053 PCT/IB2005/000928 540 1301 MTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSP 1350 1351 ALGQMPLSPDPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQI 1400 F ll I | } l F F I FI F Ii I | 1 111 I ll F F F FII 5 1351 ALGQMPLSPDPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQI 1400 1401 PLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSPDISDTTLLPD 1450 1401 PLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSPDISDTTLLPD 1450 10 1451 LSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLND 1500 1451 LSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLND 1500 15 1501 TFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY 1550 1501 TFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY 1550 1551 KTDVRTNINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRE 1600 20 1111111FF 1111111FF 1111111FF 11111111111111FF F 111111 1551 KTDVRTNINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRE 1600 1601 TDIEDSDDIPEDTTYKK 1617 25 1601 TDIEDSDDIPEDTTYKK 1617 30 WO 2005/072053 PCT/IB2005/000928 541 Sequence name: FA5 HUMANV1 Sequence documentation: 5 Alignment of: HUMF5APEA_1_P4 x FA5_HUMAN Vi Alignment segment 1/1: Quality: 20532.00 10 Escore: 0 Matching length: 2062 Total length: 2062 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 l i l l l l l l l l l l l l l l l lI l l l ll1 1 l l l l l l1 1 l l l l l l l l l l l l i l l 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 25 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTTSGLLGPTLYAEVGDIIKV 100 l i l l l l l l l l l l l l l l l l l l l l l l l l l L l l l l l l l l l l l l l l l l 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKV 100 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 30 1 l11i l1l Il l l l l l l l l l l l l l l l l l l l lI 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 WO 2005/072053 PCT/IB2005/000928 542 151 EWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTE 200 l ii il i l l l l l li ll iil ill lll li li l lI lI I 151 EWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTE 200 5 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 ||1||11111111II11 1|111111 1 1111111 1111 lil i l llIllII 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 10 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 l i l l l l ll i l l l l l l l l l l l l 1 1 1 l1 1 l l l il l l l l l l l l l i 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 15 I I 111 I I 11111i i I I I I I 111111i I I I I 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 20 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 401 DESFTKHTVNPNMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGV 450 401 DESFTKHTVNPNMKEDGILGPTIRAQVRDTLKIVFKNMASRPYSIYPAGV 450 25 451 TFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTENDAQC 500 llllllllllIlIllll1IIlII11lIlIIIlIlIilllillllilli1i1 451 TFSPYEDEVNSSFTSGRNNTMIRAVQPGETYTYKWNILEFDEPTENDAQC 500 30 501 LTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAV 550 WO 2005/072053 PCT/IB2005/000928 543 501 LTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAV 550 551 FDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTINGYVPESITTL 600 5 551 FDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTINGYVPESITTL 600 601 GFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES 650 1ill1llII Ilill l1lllll|1lllllllllilllllllllllii1 601 GFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGES 650 10 651 VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPE 700 651 VTVTMDNVGTWMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPE 700 15 701 STVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEE 750 701 STVMATRKMHDRLEPEDEESDADYDYQNRLAAALGIRSFRNSSLNQEEEE 750 751 FNLTALALENGTEFVSSNTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSH 800 20 111111 I111111 I|1I 111111 I11 11 111 l 1 1 111111 I l I 751 FNLTALALENGTEFVSSNTDIIVGSNYSSPSNISKFTVNNLAEPQKAPSH 800 801 QQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLL 850 i il l i l l il l l l l lI l l l l I I ll l l l l l l l l l l l l l l l l l l l l l 25 801 QQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPLQPDVTGIRLL 850 851 SLGAGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGS 900 111|||1 IIII111111111I11111111111llllllllllllllliI 851 SLGAGEFRSQEHAKRKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGS 900 30 901 PSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVGRWHLA 950 WO 2005/072053 PCT/IB2005/000928 544 li lllI lllillll1 ilil11 l11 llll1 ll1 lll1 lli lllllI lli11 901 PSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVGRWHLA 950 951 SEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPK 1000 5 i lll1 l1 lilllllllllll 1ll 1llll ll ll llll 1ll l 1l 1ll 951 SEKGSYEIIQDTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPK 1000 1001 FPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHP 1050 10 1001 FPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEKHTHHAPLSPRTFHP 1050 1051 LRSEAYNTFSERRLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDH 1100 l l l l l l I 111 l l l l l l Il l l ll l l l l l l l li l l l i li l l i i l 1051 LRSEAYNTFSERRLKHSLVLHKSNETSLPTDLNQTLPSMDFGWIASLPDH 1100 15 1101 NQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQMHSTSDPSHRSSS 1150 lilll111illll1ll11l l1l11llIllllIlIllllllIIIlIllili 1101 NQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQMHSTSDPSHRSSS 1150 20 1151 PELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELS 1200 lIllllll111l11Illllllll l1l11l11 llllllll1llllllili 1151 PELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELS 1200 1201 QTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLS 1250 1201 QTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLS 1250 1251 LDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSH 1300 30 1251 LDLSQTNLSPELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSH 1300 WO 2005/072053 PCT/IB2005/000928 545 1301 MTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSP 1350 1301 MTLSPELSQTNLSPALGQMPISPDLSHTTLSLDFSQTNLSPELSQTNLSP 1350 5 1351 ALGQMPLSPDPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQI 1400 1351 ALGQMPLSPDPSHTTLSLDLSQTNLSPELSQTNLSPDLSEMPLFADLSQI 1400 1401 PLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSPDISDTTLLPD 1450 1011111111I1111 Iil I II I 11l1I1 1401 PLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSPDISDTTLLPD 1450 1451 LSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLND 1500 15 1451 LSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLND 1500 1501 TFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY 1550 1501 TFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPY 1550 20 1551 KTDVRTNINSSRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRE 1600 1551 KTDVRTNINSSRDPDNTAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRE 1600 25 1601 TDIEDSDDIPEDTTYKKVVFRKYLDSTFTKRDPRGEYEEHLGILGPIIRA 1650 1601 TDIEDSDDIPEDTTYKKVVFRKYLDSTFTKRDPRGEYEEHLGILGPIIRA 1650 1651 EVDDVIQVRFKNLASRPYSLHAHGLSYEKSSEGKTYEDDSPEWFKEDNAV 1700 1651 EVDDVIQVRFKNLASRPYSLHAHGLSYEKSSEGKTYEDDSPEWFKEDNAV 1700 WO 2005/072053 PCT/IB2005/000928 546 1701 QPNSSYTYVWHATERSGPESPGSACRAWAYYSAVNPEKDIHSGLIGPLLI 1750 1701 QPNSSYTYVWHATERSGPESPGSACRAWAYYSAVNPEKDTHSGLIGPLLI 1750 5 1751 CQKGILHKDSNMPVDMREFVLLFMTFDEKKSWYYEKKSRSSWRLTSSEMK 1800 l11 l11 l1 llI111 |1 I IIIII Ilii 11i1i11 l11 1il I IIi 1751 CQKGILHKDSNMPVDMREFVLLFMTFDEKKSWYYEKKSRSSWRLTSSEMK 1800 10 1801 KSHEFHAINGMIYSLPGLKMYEQEWVRLHLLNIGGSQDIHVVHFHGQTLL 1850 |lii LI li l i II 1 1 1 I I 11 IIIII I|1 1 IilIIIlIIII1 ||1 1801 KSHEFHAINGMIYSLPGLKMYEQEWVRLHLLNIGGSQDIHVVHFHGQTLL 1850 1851 ENGNKQHQLGVWPLLPGSFKTLEMKASKPGWWLLNTEVGENQRAGMQTPF 1900 15 111111i11 1111I l 1 111111i i 1111111 1I ii 1 1 1851 ENGNKQHQLGVWPLLPGSFKTLEMKASKPGWWLLNTEVGENQRAGMQTPF 1900 1901 LIMDRDCRMPMGLSTGIISDSQIKASEFLGYWEPRLARLNNGGSYNAWSV 1950 20 1901 LIMDRDCRMPMGLSTGIISDSQIKASEFLGYWEPRLARLNNGGSYNAWSV 1950 1951 EKLAAEFASKPWIQVDMQKEVIITGIQTQGAKHYLKSCYTTEFYVAYSSN 2000 1951 EKLAAEFASKPWIQVDMQKEVIITGIQTQGAKHYLKSCYTTEFYVAYSSN 2000 25 2001 QINWQIFKGNSTRNVMYFNGNSDASTIKENQFDPPIVARYIRISPTPAYN 2050 2001 QINWQIFKGNSTRNVMYFNGNSDASTIKENQFDPPIVARYIRISPTRAYN 2050 30 2051 RPTLRLELQGCE 2062 lI I I I I I I WO 2005/072053 PCT/IB2005/000928 547 2051 RPTLRLELQGCE 2062 5 Sequence name: FA5_HUMAN 10 Sequence documentation: Alignment of: HUMF5APEA_1_P8 x FA5 HUMAN Alignment segment 1/1: 15 Quality: 5863.00 Escore: 0 Matching length: 588 Total length: 588 20 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.83 Total Percent Similarity: 100.00 Total Percent Identity: 99.83 Gaps: 0 25 Alignment: 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 30 1 MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPT 50 WO 2005/072053 PCT/IB2005/000928 548 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDITKV 100 11| |11111111 111 111 11111111111111 1lllllil1 lllll ll ll 51 NSSLNLSVTSFKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKV 100 5 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 101 HFKNKADKPLSIHPQGIRYSKLSEGASYLDHTFPAEKMDDAVAPGREYTY 150 151 EWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTE 200 10 111111111111111111111 I111 I1111111 1111111111111111 151 EWSISEDSGPTHDDPPCLTHIYYSHENLIEDFNSGLIGPLLICKKGTLTE 200 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 15 201 GGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNGTMPDITVCAH 250 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 251 DHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV 300 20 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 l i l l l l l l l l l l l l l l1 l i l l l l l1 l l l l l l l l l l l l l l l l l l1 l l l lli 301 GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRW 350 25 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 I I 11 111I iiIII I I Il1 Il I||1 11 11I11i I 1111 1I1 I i 351 EYFIAAEEVIWDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYE 400 401 DESFTKHTVNPNMKEDGILGPITRAQVRDTLKIVFKNMASRPYSIYPEGV 450 30 I I 1 1i I I I I I 1 I 11i1i 11i i 1 I I 401 DESFTKHTVNPNMKEDGILGPIIRAQVRDTLKIVFKNMASRPYSIYPHGV 450 WO 2005/072053 PCTIIB2005/000928 549 451 TFSPYEDEVNSSFTSGRIINTMIRAVQPGETYTYKWNTLEFDEPTENDAQC 500 451 TFSPYEDEVNSSFTSGRNNTIRAVQPGETYTYKWNILEFDEPTENDAQC 500 5 501 LTRPYYSDVDTMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAV 550 501 LTRPYYSDVDTMRDIASGLIGLLLICKSRSLDRRGIQRAADIEQQAVFAV 550 10 551 FDENKSWYLEDNINKFCENPDEVKRDDPKFYESNTMSS 588 551 FDENKSWYLEDNTNKFCENPDEVKRDDPKFYESNIMST 588 15 PBGD-amplicon, SEQ ID NO:531HPRT1-amplicon, SEQ ID NO:612HPRT1-amplicon, SEQ ID NO: 615RPS27A amplicon, SEQ ID NO: 1261 20 25 30 WO 2005/072053 PCT/IB2005/000928 550 DESCRIPTION FOR CLUSTER HUMANK Cluster HUMANK features 8 transcript(s) and 22 segment(s) of interest, the names for which are given in Tables I and 2, respectively, the sequences themselves are given at the end 5 of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Na e SEQ ID NO: HUMANKT3 36 HUMANKT13 37 HUMANKT23 38 HUMANKT24 39 HUMANKT26 40 HUMANK T27 41 HUMANKT28 42 HUMANKT35 43 Table 2 - Segments of interest Segnt Name SEQ ID NO: HUMANK node_91 285 HUMANK node_92 286 HUMANK node_93 287 HUMANK node_100 288 HUMANK node 108 289 HUMANK node 113 290 HUMANK node 115 291 HUMANK node 117 292 HUMANK node 119 293 HUMANK node120 294 HUMANK node 94 295 WO 2005/072053 PCT/IB2005/000928 551 HUMANK node_95 296 HUMANK node 98 297 HUMANK node_99 298 HUMANK node_102 299 HUMANK node 103 300 HUMANK node_104 301 HUMANK node_105 302 HUMANIK node_106 303 HUMANK node_112 304 HUMANK node_114 305 HUMANK node_116 306 Table 3 - Proteins of interest Protein Name SEQ 1D NO: Correspon ingTranscript(s) HUMANKP12 567 HUMANKT13 HUMANK P21 568 HUMANKT26 HUMANK P22 569 HUMANKT27 HUMANKP23 570 HUMAN T28 HUMANKP27 571 HUMANKT35 HUMAN P29 572 HUMAN T3 HUMANKP33 573 HUMAN T23 HUMANKP34 574 HUMAN T24 These sequences are variants of the known protein Ankyrin 1 (SwissProt accession 5 identifier ANK1_HUMAN; known also according to the synonyms Erythrocyte ankyrin; Ankyrin R), SEQ ID NO: 628, referred to herein as the previously known protein. Protein Ankyrin 1 is known or believed to have the following function(s): Attach integral membrane proteins to cytoskeletal elements; bind to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins 10 fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the WO 2005/072053 PCT/IB2005/000928 552 cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. The sequence for protein Ankyrin 1 is given at the end of the application, as "Ankyrin 1 amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. 5 Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid scqiuience 20 R -> T. /FTId=VAR_000595. 462 V -> I (in HS). /FTId=VAR_000596. 618 R -> H (in Brueggen). /FTId=VAR 000597. 749 V ->A. /FTId=VAR000598. 844 D -> E. /FTId=VAR_000599. 1285 E ->D. /FTId=VAR000601. 1391 S ->T. /FTId=VAR 000600. 1591 D ->N (in Duesseldorf). /FTId=VAR_000602. 1698 R ->D. /FTId=VAR 000603. 229 A ->S 1545 V -> I Protein Ankyrin I localization is believed to be Cytoplasmic surface of erythrocytic plasma membrane. The following GO Annotation(s) apply to the previously known protein. The following 10 annotation(s) were found: exocytosis; cytoskeleton organization and biogenesis; signal transduction, which are annotation(s) related to Biological Process; structural protein; structural protein of cytoskeleton; cytoskeletal adaptor, which are annotation(s) related to Molecular Function; and cytoskeleton; plasma membrane; actin cytoskeleton; basolateral plasma membrane, which are annotation(s) related to Cellular Component. 15 The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nib.gov/projects/LocusLink/>.

WO 2005/072053 PCT/IB2005/000928 553 Cluster HUMANK can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of 5 the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in 10 Figure 23 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors. Table 5 - Normal tissue distribution Name of Tissue Number Bladder 0 Brain 41 Epithelial 2 General 20 head and neck 0 Kidney 0 bone marrow 62 Muscle 225 Ovary 0 Pancreas 4 prostate 8 uterus 0 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SP[ R3 SP2 R4 bladder 5.4e-01 6.Oe-01 5.6e-01 1.8 6.8e-01 1.5 WO 2005/072053 PCT/IB2005/000928 554 brain 8.9e-01 8.9e-01 1 0.1 1 0.2 epithelial 1.0e-01 1.7e-01 L.8e-03 3.8 1.8e-02 2.6 general 9.le-01 9.5e-01 9.3e-01 0.5 1 0.4 head and neck 4.3e-01 2.8e-0l 1 1.1 7.5e-01 1.4 kidney 6.5e-01 7.2e-01 5.8e-01 1.7 7.0e-01 1.4 bone marrow 7.le-01 8.4e-01 1 0.3 9.0e-01 0.6 muscle 5.4e-01 6.2e-01 1 0.1 1 0.2 ovary 3.8e-01 4.2e-01 6.9e-02 2.4 1.6e-01 1.9 pancreas 5.5e-01 2.0e-01 4.2e-01 1.7 1.5e-01 2.6 prostate 9.le-01 9.3e-01 6.7e-01 1.1 7.5e-01 1.0 uterus 4.7e-01 6.4e-01 6.6e-01 1.5 8.0e-01 1.2 5 As noted above, cluster HUMANK features 8 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Ankyrin 1. A description of each variant protein according to the present invention is now provided. Variant protein HUMANKP12 according to the present invention has an amino acid 10 sequence as given at the end of the application; it is encoded by transcript(s) HUMANK_T13. An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 15 Comparison report between HUMANKP12 and AAH07930 (SEQ ID NO 631): 1.An isolated chimeric polypeptide encoding for HUMANKP12, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQ 20 EHEE corresponding to amino acids 1 - 123 of AAH07930, which also corresponds to amino WO 2005/072053 PCT/IB2005/000928 555 acids 1 - 123 of HUMANKP12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP corresponding to amino acids 124 - 156 of 5 HUMANKP12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 10 sequence VTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP in HUMANK_P12. Comparison report between HUMANKP12 and ANKIHUMAN Vi (SEQ ID NO 629): 1.An isolated chimeric polypeptide encoding for HUMANKP12, comprising a first 15 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLK corresponding to amino acids 1 - 73 of HUMANKP12, and a second 20 amino acid sequence being at least 90 % homologous to GNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEEVTVEGPLEDP SELEVDIDYFMKHSKDHTSTPNP corresponding to amino acids 1799 - 1881 of ANKIHUMAN VI, which also corresponds to amino acids 74 - 156 of HUMANKP12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 25 sequential order. 2.An isolated polypeptide encoding for a head of HUMANK_ P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 30 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHII-IQELDKELGESEGLSDDEE TISTRVVRRRVFLK of HUMANKP12.

WO 2005/072053 PCT/IB2005/000928 556 It should be noted that the known protein sequence (ANKIHUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for ANK1-HUMANV1. These changes were previously known to occur and are 5 listed in the table below. Table 7 - Changes to ANK1_HUMAN_VI SNP p osition(s) oh Type of change amino acid sequence 1 init met Comparison report between HUMANKP12 and Q8N604 (SEQ ID NO: 630): 10 1.An isolated chimeric polypeptide encoding for HUMANK_P12, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANKP12, a bridging amino acid G corresponding to amino acid 53 of 15 HUMANKP12, a second amino acid sequence being at least 90 % homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIRKVVRQIDLSS ADAAQEHEEV corresponding to amino acids 54 - 124 of Q8N604, which also corresponds to amino acids 54 - 124 of HUMANK-P12, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP corresponding to amino acids 125 - 156 of HUMANKP12, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P12, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP in HUMANKP12.

WO 2005/072053 PCT/IB2005/000928 557 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP position(s) on aimno acid Alternative amino acid(s) Previ ously known $NP? sequence 12 L -> P No 63 T ->P No 82 G-> No 82 G ->V No 89 Q->P No 15 Variant protein HUMANKP12 is encoded by the following transcript(s): HUMANK_T 13, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANK_T13 is shown in bold; this coding portion starts at position 2053 and ends at position 2520. The transcript also has the following SNPs as listed in Table 9 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK P 12 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072053 PCT/IB2005/000928 558 Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C ->T No 1969 A ->G No 2005 -> G No 2014 C ->A No 2087 T ->C No 2238 C ->A No 2239 A ->C No 2297 G-> No 2297 G ->T No 2318 A ->C No 2533 ->C No 2533 T No 2733 A-> No 2733 A ->C No 2742 A ->C No 2772 A ->C No 2796 A-> No 2796 A ->C No 2890 C ->T No 3305 G No 3306 ->C No 4118 T->A Yes 4175 -> T No 4228 G -> No 4603 G -> T Yes 5012 T -> No WO 2005/072053 PCT/IB2005/000928 559 Variant protein HUMANKP21 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT26. An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or 5 more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP21 and AAH07930 (SEQ ID NO: 631): 1.An isolated chimeric polypeptide encoding for HUMANKP21, comprising a first 10 amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQ EHEE corresponding to amino acids 1 - 123 of AAH07930, which also corresponds to amino acids 1 - 123 of HUMANKP21, and a second amino acid sequence being at least 70%, 15 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 124 - 169 of HUMANKP21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of HUMANKP21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ in HUMANKP21. 25 Comparison report between HUMANKP21 and Q8N604: 1.An isolated chimeric polypeptide encoding for HUMANK_P21, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE 30 corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANK_P21, a bridging amino acid G corresponding to amino acid 53 of WO 2005/072053 PCT/IB2005/000928 560 HUMANK_P21, a second amino acid sequence being at least 90 % homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSS ADAAQEHE corresponding to amino acids 54 - 122 of Q8N604, which also corresponds to amino acids 54 - 122 of HUMANKP21, a third amino acid sequence being at least 70%, 5 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence EVTVEGPLEDPSEL corresponding to amino acids 123 - 136 of HUMANKP21, and a fourth amino acid sequence being at least 90 % homologous to EVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 123 - 155 of Q8N604, which also corresponds to amino acids 137 10 - 169 of HUMANKP21, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of HUMANKP21, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 15 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for EVTVEGPLEDPSEL, corresponding to HUMANKP21. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP21 also has the following non-silent SNPs (Single 25 Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP21 sequence provides support for the deduced sequence of this variant protein according to the present invention). 30 Table 10 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 561 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 12 L ->P No 63 T ->P No 82 G No 82 G ->V No 89 Q ->P No Variant protein HUMANK P21 is encoded by the following transcript(s): HUMANKT26, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT26 is shown in bold; this coding portion starts at position 5 2053 and ends at position 2559. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP21 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 1 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C T No 1969 A ->G No 2005 -> G No 2014 C -> A No 2087 T -> C No 2238 C ->A No 2239 A ->C No 2297 G -No 2297 G ->T No 2318 A ->C No WO 2005/072053 PCT/IB2005/000928 562 2635 No 2635 -> T No 2835 A -> No 2835 A -> C No 2844 A ->C No 2874 A ->C No 2898 A-> No 2898 A ->C No 2992 C ->T No 3407 -> G No 3408 -> C No 4220 T -> A Yes 4277 -> T No 4330 G-> No 4705 G ->T Yes 5114 T-> No Variant protein HUMANKP22 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT27. 5 An aligrunent is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP22 and AAH07930: 10 1.An isolated chimeric polypeptide encoding for HUMANKP22, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQ EHEE corresponding to amino acids 1 - 123 of AAH07930, which also corresponds to amino 15 acids 1 - 123 of HUMANK P22, and a second amino acid sequence being at least 70%, WO 2005/072053 PCT/IB2005/000928 563 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEVDIDYFMKHSKVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 124 - 180 of HUMANKP22, wherein said first amino acid 5 sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding' for a tail of HUMANK P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 10 VTVEGPLEDPSELEVDIDYFMKHSKVELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ in HUMANKP22. Comparison report between HUMANKP22 and Q8N604: 1.An isolated chimeric polypeptide encoding for HUMANK_P22, comprising a first 15 amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANKP22, a bridging amino acid G corresponding to amino acid 53 of HUMANKP22, a second amino acid sequence being at least 90 % homologous to 20 LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSS ADAAQEHEE corresponding to amino acids 54 - 123 of Q8N604, which also corresponds to amino acids 54 - 123 of HUMANKP22, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 VTVEGPLEDPSELEVDIDYFMKHSK corresponding to amino acids 124 - 148 of HUMANK_P22, and a fourth amino acid sequence being at least 90 % homologous to VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 124 - 155 of Q8N604, which also corresponds to amino acids 149 - 180 of HUMANKP22, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid 30 sequence and fourth amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 564 2.An isolated polypeptide encoding for an edge portion of HUMANK _P22, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for VTVEGPLEDPSELEVDIDYFMKHSK, corresponding to 5 HUMANKP22. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 10 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP22 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the 15 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK P22 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 12 L ->P No 63 T ->P No 82 G-> No 82 G->V No 89 Q->P No 20 Variant protein HUMANKP22 is encoded by the following transcript(s): HUMANKT27, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT27 is shown in bold; this coding portion starts at position WO 2005/072053 PCT/IB2005/000928 565 2053 and ends at position 2592. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP22 sequence provides support for the deduced sequence of this 5 variant protein according to the present invention). Table 13 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C ->T No 1969 A ->G No 2005 ->G No 2014 C ->A No 2087 T ->C No 2238 C ->A No 2239 A ->C No 2297 G-> No 2297 G ->T No 2318 A ->C No 2668 -> C No 2668 -> T No 2868 A -> No 2868 A -> C No 2877 A ->C No 2907 A ->C No 2931 A-> No 2931 A ->C No 3025 C ->T No 3440 ->G No 3441 ->C No WO 2005/072053 PCT/IB2005/000928 56G6 4253 T -> A Yes 4310 T No 4363 G-> No 4738 G -> T Yes 5147 T -> No Variant protein HUMANKP23 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT28. 5 An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP23 and AAH07930: 10 1.An isolated chimeric polypeptide encoding for HUMANKP23, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQ EHEE corresponding to amino acids 1 - 123 of AAH07930, which also corresponds to amino 15 acids 1 - 123 of HUJMANK P23, and a second amino acid sequence being at least' 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VTVEGPLEDPSELEDHTSTPNP corresponding to amino acids 124 - 145 of HUMANKP23, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a 20 sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK .P23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VTVEGPLEDPSELEDHTSTPNP in HUMANKP23. 25 Comparison report between HUMANKP23 and Q8N604: WO 2005/072053 PCT/IB2005/000928 567 1.An isolated chimeric polypeptide encoding for HUMANKP23, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 5 of HUMANKP23, a bridging amino acid G corresponding to amino acid 53 of HUMANKP23, a second amino acid sequence being at least 90 % homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSS ADAAQEHEEV corresponding to amino acids 54 - 124 of Q8N604, which also corresponds to amino acids 54 - 124 of HUMANKP23, and a third amino acid sequence being at least 70%, 10 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence TVEGPLEDPSELEDHTSTPNP corresponding to amino acids 125 - 145 of HUMANKP23, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of HUMANK P23, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence TVEGPLEDPSELEDHTSTPNP in HUMANKP23. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 25 region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP23 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANK _P23 30 sequence provides support for the deduced sequence of this variant protein according to the present invention).

WO 2005/072053 PCT/IB2005/000928 568 Table 14 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 12 L ->P No 63 T->P No 82 G-> No 82 G ->V No 89 Q ->P No Variant protein HUMANKP23 is encoded by the following transcript(s): HUMANK T28, for which the sequence(s) is/are given at the end of the application. The coding 5 portion of transcript HUMANKT28 is shown in bold; this coding portion starts at position 2053 and ends at position 2487. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs' in variant protein HUMANK P23 sequence provides support for the deduced sequence of this 10 variant protein according to the present invention). Table 15 - Nucleic acid SNPs SNP position ~on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C ->T No 1969 A ->G No 2005 -> G No 2014 C ->A No 2087 T->C No 2238 C ->A No 2239 A ->C No 2297 G-> No 2297 G ->T No WO 2005/072053 PCT/IB2005/000928 569 2318 A -> C No 2500 ->C No 2500 ->T No 2700 A-> No 2700 A ->C No 2709 A ->C No 2739 A ->C No 2763 A-> No 2763 A ->C No 2857 C -> T No 3272 ->G No 3273 ->C No 4085 T -> A Yes 4142 -> T No 4195 G -> No 4570 G -> T Yes 4979 T-> No Variant protein HUMANK P27 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT35. 5 An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP27 and AAH07930: 10 1.An isolated chimeric polypeptide encoding for HUMANKP27, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 1 - 101 of AAH07930, which also corresponds to amino acids 1 - 101 of HUIJMANKP27, WO 2005/072053 PCT/IB2005/000928 570 and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAECSPLCWGEAGGLEAKRW corresponding to amino acids 102 - 122 of HUMANKP27, wherein said first amino acid sequence and second amino 5 acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P27, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VGAECSPLCWGEAGGLEAKRW in HUMANK P27. 10 Comparison report between HUMANK P27 and Q8N604: 1.An isolated chimeric polypeptide encoding for HUMANKP27, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE 15 corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANKP27, a bridging amino acid G corresponding to amino acid 53 of HUMANKP27, a second amino acid sequence being at least 90 % homologous to LSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 54 - 101 of Q8N604, which also corresponds to amino acids 54 - 101 of 20 HUMANK P27, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VGAECSPLCWGEAGGLEAKRW corresponding to amino acids 102 - 122 of HUMANKP27, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are 25 contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P27, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VGAECSPLCWGEAGGLEAKRW in HUMANKP27. 30 WO 2005/072053 PCT/IB2005/000928 571 The location of the variant protein was detern-ined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP27 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 10 the SNP is known or not; the presence of known SNPs in variant protein HUMANKP27 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Amino acid imutations SNP position(s) on amino acid Alternative amino acid(s) Previously know SNP? sequence 12 L->P No 63 T -> P No 82 G-> No 82 G ->V No 89 Q ->P No 15 Variant protein HUMANKP27 is encoded by the following transcript(s): HUMANKT35, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT35 is shown in bold; this coding portion starts at position 2053 and ends at position 2418. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid 20 listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP27 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 572 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C >T No 1969 A->G No 2005 -> G No 2014 C ->A No 2087 T -> C No 2238 C ->A No 2239 A ->C No 2297 G No 2297 G ->T No 2318 A ->C No Variant protein HUMANK P29 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT3. An 5 alignment is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP29 and AAH07930: 10 1.An isolated chimeric polypeptide encoding for HUMANKP29, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TIS corresponding to amino acids 1 - 62 of AAH07930, which also corresponds to amino acids 1 - 62 of HUMANK P29, a bridging amino acid P corresponding to amino acid 63 of 15 HUMANKP29, a second amino acid sequence being at least 90 % homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE corresponding to amino acids 64 - 123 of AAH07930, which also corresponds to amino acids 64 - 123 of HUMANK P29, and a third amino acid sequence being at least 70%, optionally at least WO 2005/072053 PCT/IB2005/000928 573 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 124 - 155 of HUMANK_P29, wherein said first amino acid sequence, bridging amino acid, second amino 5 acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANKP29, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ in HUMANKP29. 10 Comparison report between HUMANK P29 and Q8N604: 1.An isolated chimeric polypeptide encoding for HUMANKP29, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE 15 corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANKP29, a bridging amino acid G corresponding to amino acid 53 of HUMANK_P29, a second amino acid sequence being at least 90 % homologous to LSDDEETIS corresponding to amino acids 54 - 62 of Q8N604, which also corresponds to amino acids 54 - 62 of HUMANKP29, a bridging amino acid P corresponding to amino acid 20 63 of HUMANKP29, and a third amino acid sequence being at least 90 % homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHEE VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 64 - 155 of Q8N604, which also corresponds to amino acids 64 - 155 of HUMANK P29, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid 25 and third amino acid sequence are contiguous and in a sequential order. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 30 secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072053 PCT/IB2005/000928 574 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMANKP29 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 18, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP29 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 18 -Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 12 L ->P No 63 P->T No 82 G-> No 82 G ->V No 89 Q->P No 10 Variant protein HUMANKP29 is encoded by the following transcript(s): HUMANKT3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT3 is shown in bold; this coding portion starts at position 2053 and ends at position 2517. The transcript also has the following SNPs as listed in Table 19 (given 15 according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP29 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 19 - Nucleic acid SNPs SN]P position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C -> T No WO 2005/072053 PCT/IB2005/000928 575 1969 A->G No 2005 -> G No 2014 C -> A No 2087 T -> C No 2238 C-> A No 2239 A-> C No 2297 G ->No 2297 G-> T No 2318 A-> C No 2593 -> C No 2593 -> T No 2793 A -> No 2793 A ->C No 2802 A ->C No 2832 A ->C No 2856 A-> No 2856 A ->C No 2950 C ->T No 3242 G ->T Yes 3244 C ->A Yes 3245 T ->A Yes 3246 C ->T Yes 3379 ->G No 3380 ->C No 4192 T -> A Yes 4249 -> T No 4302 G -> No 4677 G -> T Yes 5086 T -> No WO 2005/072053 PCT/IB2005/000928 576 Variant protein HUMANKP33 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT23. An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or 5 more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANKP33 and AAH07930: 1.An isolated chimeric polypeptide encoding for HUMANKP33, comprising a first 10 amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TIS corresponding to amino acids 1 - 62 of AAH07930, which also corresponds to amino acids I - 62 of HUMANKP33, a bridging amino acid P corresponding to amino acid 63 of HUMANKP33, a second amino acid sequence being at least 90 % homologous to 15 RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64 101 of AAH07930, which also corresponds to amino acids 64 - 101 of HUMANKP33, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DHTSTPNP corresponding to amino acids 102 - 109 of HUMANKP33, 20 wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P33, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence DHTSTPNP in HUMANKP33. Comparison report between HUMANKP33 and Q8N604: 1.An isolated chimeric polypeptide encoding for HUMANKP33, comprising a first amino acid sequence being at least 90 % homologous to 30 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLIHIHQELDKELGESE corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 WO 2005/072053 PCT/IB2005/000928 577 of BUMANKP33, a bridging amino acid G corresponding to amino acid 53 of HUMANK_P33, a second amino acid sequence being at least 90 % homologous to LSDDEETIS corresponding to amino acids 54 - 62 of Q8N604, which also corresponds to amino acids 54 - 62 of HUMANKP33, a bridging amino acid P corresponding to amino acid 5 63 of HUMANK-P33, a third amino acid sequence being at least 90 % homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64 101 of Q8N604, which also corresponds to amino acids 64 - 101 of HUMANK P33, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 10 having the sequence DHTSTPNP corresponding to amino acids 102 - 109 of HUMANKP33, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK _P33, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DHTSTPNP in HUMANKP33. The location of the variant protein was determined according to results from a number of 20 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 25 Variant protein HUMANK_P33 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP33 sequence provides support for the deduced sequence of this variant protein according to the 30 present invention). Table 20 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 578 SNP positions) on amino amino acids) Previously known SNP? sequence 12 L ->P No 63 P->T No 82 G No 82 G->V No 89 Q->P No Variant protein HUMANKP33 is encoded by the following transcript(s): HUMANKT23, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT23 is shown in bold; this coding portion starts at position 5 2053 and ends at position 2379. The transcript also has the following SNPs as listed in Table 21 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HIUMANKP33 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 21 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C -> T No 1969 A -> G No 2005 -> G No 2014 C -> A No 2087 T -> C No 2238 C -> A No 2239 A -> C No 2297 G -> No 2297 G ->T No 2318 A ->C No WO 2005/072053 PCT/IB2005/000928 579 2392 ->C No 2392 ->T No 2592 A -> No 2592 A ->C No 2601 A ->C No 2631 A ->C No 2655 A-> No 2655 A ->C No 2749 C ->T No 3164 -> G No 3165 ->C No 3977 T -> A Yes 4034 -> T No 4087 G -> No 4462 G -> T Yes 4871 T-> No Variant protein HUMANKP34 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMANKT24. 5 An alignment is given to the known protein (Ankyrin 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMANK P34 and AAH07930: 10 1.An isolated chimeric polypeptide encoding for HUMANKP34, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESEGLSDDEE TIS corresponding to amino acids 1 - 62 of AAH07930, which also corresponds to amino acids 1 - 62 of HUMANK P34, a bridging amino acid P corresponding to amino acid 63 of 15 HUIANKP34, a second amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 580 RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64 101 of AAH07930, which also corresponds to amino acids 64 - 101 of HUMANK P34, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide 5 having the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 102 - 133 of HUMANK P34, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMANK P34, comprising a 10 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ in HUMANKP34. Comparison report between HUMANKP34 and Q8N604: 15 1 .An isolated chimeric polypeptide encoding for HUMANKP34, comprising a first amino acid sequence being at least 90 % homologous to MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGESE corresponding to amino acids 1 - 52 of Q8N604, which also corresponds to amino acids 1 - 52 of HUMANKP34, a bridging amino acid G corresponding to amino acid 53 of 20 HUMANKP34, a second amino acid sequence being at least 90 % homologous to LSDDEETIS corresponding to amino acids 54 - 62 of Q8N604, which also corresponds to amino acids 54 - 62 of HUMANK_P34, a bridging amino acid P corresponding to amino acid 63 of HUMANKP34, a third amino acid sequence being at least 90 % homologous to RVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTKK corresponding to amino acids 64 25 101 of Q8N604, which also corresponds to amino acids 64 - 101 of HUMANK P34, and a fourth amino acid sequence being at least 90 % homologous to VELRGSGLQPDLIEGRKGAQIVKRASLKRGKQ corresponding to amino acids 124 - 155 of Q8N604, which also corresponds to amino acids 102 - 133 of HUMANK P34, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, bridging amino 30 acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 581 2.An isolated chimeric polypeptide encoding for an edge portion of HUMANKP34, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 5 least about 50 amino acids in length, wherein at least two amino acids comprise KV, having a structure as follows: a sequence starting from any of amino acid numbers 101-x to 101; and ending at any of amino acid numbers 102+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of 10 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 15 Variant protein HUMANKP34 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 22, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP34 sequence provides support for the deduced sequence of this variant protein according to the 20 present invention). Table 22 - Amino acid mutations SNP'position(s) on amino acid Alternative amino acid(s) Previouslyknown SNP? sequence 12 L -> P No 63 P ->T No 82 G-> No 82 G ->V No 89 Q ->P No WO 2005/072053 PCT/IB2005/000928 582 Variant protein HUMANKP34 is encoded by the following transcript(s): HUMANKT24, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMANKT24 is shown in bold; this coding portion starts at position 2053 and ends at position 2451. The transcript also has the following SNPs as listed in Table 23 5 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMANKP34 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 23 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1603 C->T No 1969 A ->G No 2005 -> G No 2014 C ->A No 2087 T->C No 2238 C ->A No 2239 A ->C No 2297 G -> No 2297 G ->T No 2318 A ->C No 2527 -> C No 2527 -> T No 2727 A -> No 2727 A ->C No 2736 A ->C No 2766 A->C No 2790 A-> No 2790 A ->C No 2884 C ->T No WO 2005/072053 PCT/IB2005/000928 583 3299 G No 3300 C No 4112 T -> A Yes 4169 -> T No 4222 G -> No 4597 G -> T Yes 5006 T-> No As noted above, cluster HUMANK features 22 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 5 provided. Segment cluster HUMANKnode_91 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANK_T13, HUMANKT23, 10 HUMANKT24, HUMANKT26, HUMANK_T27, HUMANKT28 and HUMANKT35. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript n~ame Segmient' Segment starting position ending position HUMANKT3 1 1543 HUMANK T13 1 1543 HUMANKT23 1 1543 HUMANK T24 1 1543 HUMANKT26 1 1543 HUMANKT27 1 1543 HUMANKT28 1 1543 HUMANK T35 1 1543 WO 2005/072053 PCT/IB2005/000928 584 Segment cluster HUMANK node_92 according to the present invention is supported by 19 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, 5 HUMANKT24, HUMANKT26, HUMANKT27, HUMANKT28 and HUMANKT35. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transriet tnaie Segment Segment starting position ending position HUMANK T3 1544 1928 HUMANK T13 1544 1928 HUMANK T23 1544 1928 HUMANK T24 1544 1928 HUMANKT26 1544 1928 HUMANKT27 1544 1928 HUMANKT28 1544 1928 HUMANK T35 1544 1928 10 Segment cluster HUMANK_node_93 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27, HUMANKT28 and HUMANKT35. Table 26 below describes the starting and ending position of this segment on each transcript. 15 Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANK T3 1929 2178 HUMANKT13 1929 2178 WO 2005/072053 PCT/IB2005/000928 585 HUMANKT23 1929 2178 HUMANK T24 1929 2178 HUMANK T26 1929 2178 HUMANK T27 1929 2178 HUIMANKT28 1929 2178 HUMANKT35 1929 2178 Segment cluster HUMANK node_100 according to the present invention is supported by 1 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMANKT35. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segmet starting position ending position HUMANKT35 2356 2490 10 Segment cluster HUMANKnode_108 according to the present invention is supported by 33 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HUMANK T3, HUMANKT24, HUMANKT26 and HUMANKT27. Table 28 below describes the starting and ending position of this segment on each transcript. 15 Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2422 2556 HUMANKT24 2356 2490 HUMANK T26 2464 2598 WO 2005/072053 PCT/IB2005/000928 586 HUMANKT27 2497 2631 Segment cluster HUMANK_node_113 according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMANK T3, HUMANK_T13, HUMANK T23, HUMANKT24, HUMANKT26, HUMANKT27 and HUMANKT28. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name. Segment Segme t starting position) sending Position HUMANKT3 2596 2735 HUMANK T13 2536 2675 HUMANK T23 2395 2534 HUMANKT24 2530 2669 HUMANKT26 2638 2777 HUMANKT27 2671 2810 HUMANK T28 2503 2642 10 Segment cluster HUMANKnode 115 according to the present invention is supported by 63 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, HUMANK T24, HUMANK T26, HUMANKT27 and HUMANKT28. Table 30 below 15 describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2821 3234 WO 2005/072053 PCT/IB2005/000928 587 HUMANKT13 2761 3174 HUMANK T23 2620 3033 HUMANKT24 2755 3168 HUMANKT26 2863 3276 HUMANKT27 2896 3309 HUMANKT28 2728 3141 Segment cluster HUMANKnode_117 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27 and HUMANKT28. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 3249 4438 HUMANK T13 3175 4364 HUMANK T23 3034 4223 HUMANK T24 3169 4358 HUMANK T26 3277 4466 HUMANK T27 3310 4499 HUMANKT28 3142 4331 10 Segment cluster HUMANK node 119 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27 and HUMANKT28. Table 32 below 15 describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 588 Table 32 - Segment location on transcripts Transcript name Segment Segment starting position, ending position HUMANKT3 4439 4797 HUMANKT13 4365 4723 HUMANKT23 4224 4582 HUMANKT24 4359 4717 HUMANKT26 4467 4825 HUMANKT27 4500 4858 HUMANKT28 4332 4690 Segment cluster HUMANKnode 120 according to the present invention is supported by 5 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANK T3, HUMANKT13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27 and HUMANKT28. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment "Segment starting position ending position HUMANK T3 4798 5100 HUMANKT13 4724 5026 HUMANK T23 4583 4885 HUMANKT24 4718 5020 HUMANKT26 4826 5128 HUMANKT27 4859 5161 HUMANK T28 4691 4993 10 WO 2005/072053 PCT/IB2005/000928 589 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster HUMANK node_94 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT3, HUMANK_T13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27, HUMANKT28 and HUMANKT35. Table 34 below describes the starting and ending position of this segment on each transcript. 10 Table 34 - Segment location on transcripts Transcript name Segment Segment starting posito endingpsto HUMANK T3 2179 2240 HUMANK T13 2179 2240 HUMANK T23 2179 2240 HUMANK T24 2179 2240 HUMANK T26 2179 2240 HUMANK T27 2179 2240 HUMANKT28 2179 2240 HUMANKT35 2179 2240 Segment cluster HUMANKnode_95 according to the present invention is supported by 28 libraries. The number of libraries was determined as previously described. This segment can 15 be found in the following transcript(s): HUMANKT3, HUMANK_T13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27, HUMANKT28 and HUMANKT35. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 590 Transcript nane Segment Segment starting position ending position HUMANK T3 2241 2271 HUMANK T13 2241 2271 HUMANKT23 2241 2271 HUMANKT24 2241 2271 HUMANKT26 2241 2271 HUMANKT27 2241 2271 HUMANK T28 2241 2271 HUMANKT35 2241 2271 Segment cluster HUMANKnode 98 according to the present invention is supported by 53 libraries. The number of libraries was determined as previously described. This segment can 5 be found in the following transcript(s): HUMANK T3, HUMANKT13, HUMANKT23, HUMANKT24, HUMANKT26, HUMANKT27, HUJMANKT28 and HUMANKT35. Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Txanscript name Segment Segment starting position ending position HUMANKT3 2272 2348 HUMANK T13 2272 2348 HUMANK T23 2272 2348 HUMANK T24 2272 2348 -IUMANKT26 2272 2348 HUMANKT27 2272 2348 HUMANKT28 2272 2348 HUMANKT35 2272 2348 10 WO 2005/072053 PCT/IB2005/000928 591 Segment cluster HUMANKnode_99 according to the present invention can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANK T23, HUMANKT24, HUMANKT26, HUMANKT27, HUMANK T28 and HUMANKT35. Table 37 below describes the starting and ending position of this segment on each transcript. 5 Table 37 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2349 2355 HUMANK 13 2349 2355 HUMANKT23 2349 2355 HUMANK T24 2349 2355 HUMANKT26 2349 2355 HUMANK T27 2349 2355 HUMANKT28 2349 2355 HUMANKT35 2349 2355 Segment cluster HUMANKnode_102 according to the present invention is supported by 57 libraries. The number of libraries was determined as previously described. This segment can 10 be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT26, HUMANKT27 and HUMANKT28. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2356 2387 HUMANKT13 2356 2387 HUMANKT26 2356 2387 HUMANKT27 2356 2387 WO 2005/072053 PCT/IB2005/000928 592 HUMANKT28 2356 2387 Segment cluster HUMANK node_103 according to the present invention can be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT26, HUMANKT27 5 and HUMANKT28. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2388 2409 HUMANK T13 2388 2409 HUMANK T26 2388 2409 HUMANKT27 2388 2409 HUMANKT28 2388 2409 10 Segment cluster HUMANK node_104 according to the present invention can be found in the following transcript(s): HUMANKT3, HUMANK T13, HUMANKT26, HUMANKT27 and HUMANKT28. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 2410 2421 HUMANK T13 2410 2421 HUMANKT26 2410 2421 HUMANK_ 27 2410 2421 HUMANKT28 2410 2421 WO 2005/072053 PCT/IB2005/000928 593 Segment cluster HUMANKnode 105 according to the present invention is supported by 33 libraries. The number of libraries was detennined as previously described. This segment can 5 be found in the following transcript(s): HUMANKT13, HUMANK T26, HUMANKT27 and HUMANKT28. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript naie Segment 'Segment starting position ending position HUMANKT13 2422 2463 HUMANK T26 2422 2463 HUMANK T27 2422 2463 HUMANKT28 2422 2463 10 Segment cluster HUMANK node_106 according to the present invention is supported by 31 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMANKT13 and HUMANKT27. Table 42 below describes the starting and ending position of this segment on each transcript. 15 Table 42 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT13 2464 2496 HIJMANK T27 2464 2496 Segment cluster HUMANK node 112 according to the present invention is supported by 56 libraries. The number of libraries was determined as previously described. This segment can 20 be found in the following transcript(s): HUMANKT3, HUMANKT13, HUMANKT23, WO 2005/072053 PCT/IB2005/000928 594 HUMANKT24, HUMANKT26, HUMANK T27 and HUMANKT28. Table 43 below describes the starting and ending position of this segment on each transcript. Table 43 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANK T3 2557 2595 HUMANKT13 2497 2535 HUMANK T23 2356 2394 HUMANK T24 2491 2529 HUMANKT26 2599 2637 HUMANKT27 2632 2670 HUMANK T28 2464 2502 5 Segment cluster HUMANK-node 114 according to the present invention is supported by 55 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HUMANK T3, HUMANKT13, HUMANKT23, HUMANKT24, HUMAN T26, HUMANKT27 and HUMANKT28. Table 44 below 10 describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANK T3 2736 2820 HUMANK T13 2676 2760 HUMANKT23 2535 2619 HUMANKT24 2670 2754 HUMANK T26 2778 2862 HUMANKT27 2811 2895 HUMANKT28 2643 2727 WO 2005/072053 PCT/IB2005/000928 595 Segment cluster HUMANKnode_116 according to the present invention can be found in the following transcript(s): HUMANKT3. Table 45 below describes the starting and ending 5 position of this segment on each transcript. Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMANKT3 3235 3248 10 Variant protein alignment to the previously known protein: Sequence name: AAH07930 Sequence documentation: 15 Alignment of: HUMANKP12 x AAH07930 Alignment segment 1/1: 20 Quality: 1185.00 Escore: 0 Matching length: 123 Total length: 123 Matching Percent Similarity: 100.00 Matching Percent 25 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 WO 2005/072053 PCT/IB2005/000928 596 Gaps: 0 Alignment: 5 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEE 123 111 i i i I I II I 1111111 il 15 101 KIIRKVVRQIDLSSADAAQEHEE 123 20 Sequence name: ANK1 HUMANV1 Sequence documentation: 25 Alignment of: HUMANKP12 x ANKIHUMANV1 Alignment segment 1/1: 30 Quality: 815.00 Escore: 0 WO 2005/072053 PCT/IB2005/000928 597 Matching length: 84 Total length: 84 Matching Percent Similarity: 100.00 Matching Percent Identity: 98.81 5 Total Percent Similarity: 100.00 Total Percent Identity: 98.81 Gaps: 0 Alignment: 10 73 KGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHE 122 :lllllllllllllill 111 l li1 11 11 1 ||11111 I liii 1 1798 QGNEFQNIPGEQVTEEQFTDEQGNIVTKKIIRKVVRQIDLSSADAAQEHE 1847 15 123 EVTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP 156 1848 EVTVEGPLEDPSELEVDIDYFMKHSKDHTSTPNP 1881 20 Sequence name: Q8N604 25 Sequence documentation: Alignment of: HUMANKP12 x Q8N604 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 598 Quality: 1184.00 Escore: 0 Matching length: 128 Total length: 128 5 Matching Percent Similarity: 97.66 Matching Percent Identity: 96.88 Total Percent Similarity: 97.66 Total Percent Identity: 96.88 Gaps: 0 10 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHTHQELDKELGE 50 15 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETTSTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 II 1 1 i l l l l l l l l l l l ll l l l l l l l l l l l l l l l l l l l l lI lI 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 20 101 KIIRKVVRQIDLSSADAAQEHEEVTVEG 128 101 KIIRKVVRQIDLSSADAAQEHEEVELRG 128 25 30 Sequence name: AAH07930 WO 2005/072053 PCT/IB2005/000928 599 Sequence documentation: AlignmenL of: HUMANKP21 x AAH07930 5 Alignment segment 1/1: Quality: 1185.00 Escore: 0 Matching length: 123 Total 10 length: 123 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 2 0 I l l l 1l l l l1ll l l l l l i l lill l l l l l l l l l i 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 25 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEE 123 |l Ii i i I I I I 11 I1111 Ii 101 KIIRKVVRQIDLSSADAAQEHEE 123 30 WO 2005/072053 PCT/IB2005/000928 600 5 Sequence name: Q8N604 Sequence documentation: Alignment of: HUMANKP21 x Q8N604 10 Alignment segment 1/1: Quality: 1370.00 Escore: 0 15 Matching length: 155 Total length: 169 Matching Percent Similarity: 99.35 Matching Percent Identity: 99.35 Total Percent Similarity: 91.12 Total Percent 20 Identity: 91.12 Gaps: 1 Alignment: 25 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 1111111| ||1 1 1|| 11 |111 |I| 111 11 lll l llll lll lll lII 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 3 0 lI i lI l l l l l llI l l l l l l l llIl1l l l l l l l l l1 l l l l l l lI l l l l 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 WO 2005/072053 PCT/IB2005/000928 601 101 KIIRKVVRQIDLSSADAAQEHEEVTVEGPLEDPSELEVELRGSGLQPDLI 150 1 1 11 1 11 111 111 11 1 1111h 1 1111 111 111 11 1 101 KIIRKVVRQIDLSSADAAQEHE ............... EVELRGSGLQPDLI 136 5 151 EGRKGAQIVKRASLKRGKQ 169 137 EGRKGAQIVKRASLKRGKQ 155 10 15 Sequence name: AAH07930 Sequence documentation: Alignment of: HUMANKP22 x AAH07930 20 Alignment segment 1/1: Quality: 1185.00 Escore: 0 25 Matching length: 123 Total length: 123 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 30 Identity: 100.00 Gaps: 0 WO 2005/072053 PCT/IB2005/000928 602 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 5 l i l l 1l l 1 1l l i l l l l l i l i l l ll1 i l l i l l l l l l l l l1 i l i 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 li llll ill lll ill illlllllllllllll1 l111 l1 ll1 ll1 lllii 10 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEE 123 101 KIIRKVVRQIDLSSADAAQEHEE 123 15 20 Sequence name: Q8N604 Sequence documentation: 25 Alignment of: HUMANK P22 x Q8N604 .. Alignment segment 1/1: Quality: 1370.00 30 Escore: 0 WO 2005/072053 PCT/IB2005/000928 603 Matching length: 155 Total length: 180 Matching Percent Similarity: 99.35 Matching Percent Identity: 99.35 5 Total Percent Similarity: 85.56 Total Percent Identity: 85.56 Gaps: 1 Alignment: 10 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 11111111 1111||||1 1111111 111111111 l l l l l ll ll ll 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 15 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 II I 1111111 111111111 I1 | 1111|111|I111111111 I 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEEVTVEGPLEDPSELEVDIDYFMKHSKVE 150 20 i I Ii I I 1 I I I I I 101 KIIRKVVRQIDLSSADAAQEHEE ......................... VE 125 151 LRGSGLQPDLIEGRKGAQIVKRASLKRGKQ 180 ||1 I I I I I| | l III If II I I I i I 25 126 LRGSGLQPDLIEGRKGAQIVKRASLKRGKQ 155 30 WO 2005/072053 PCT/IB2005/000928 604 Sequence name: AAH07930 Sequence documentation: 5 Alignment of: HUMANKP23 x AAH07930 Alignment segment 1/1: Quality: 1185.00 10 Escore: 0 Matching length: 123 Total length: 123 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHTHQELDKELGE 50 25 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEE 123 30RKVVl lillSlllll El12 101 KIIRKVVRQIDLSSADAAQEHEE 123 WO 2005/072053 PCT/IB2005/000928 605 5 Sequence name: Q8N604 Sequence documentation: 10 Alignment of: EUMANKP23 x Q8N604 Alignment segment 1/1: 15 Quality: 1184.00 Escore: 0 Matching length: 128 Total length: 128 Matching Percent Similarity: 97.66 Matching Percent 20 Identity: 96.88 Total Percent Similarity: 97.66 Total Percent Identity: 96.88 Gaps: 0 25 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 ll l l l lll I I ll11 l11 ll lI lI ll ll ll Il lI ll ll I llI lll li 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 30 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 WO 2005/072053 PCT/IB2005/000928 606 Il lii lll lll ij l Il lil ililllll lll 1ll liii Ill I 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEEVTVEG 128 5 : I 101 KITRKVVRQIDLSSADAAQEHEEVELRG 128 10 Sequence name: AAH07930 15 Sequence documentation: Alignment of: HUMANKP27 x AAH07930 Alignment segment 1/1: 20 Quality: 984.00 Escore: 0 Matching length: 102 Total length: 102 25 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.02 Total Percent Similarity: 100.00 Total Percent Identity: 99.02 Gaps: 0 30 Alignment: WO 2005/072053 PCT/IB2005/000928 607 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 li|i1111111111111 111111 1|| 11 l11i|lllllllllllllllll 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 5 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 II Il Il 11Illlll l l i l ill I l l ii Ill~ll Ill ill ill 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 10 101 KV 102 101 KI 102 15 Sequence name: Q8N604 20 Sequence documentation: Alignment of: HUMANKP27 x Q8N604 25 Alignment segment 1/1: Quality: 971.00 Escore: 0 Matching length: 102 Total 30 length: 102 WO 2005/072053 PCT/IB2005/000928 608 Matching Percent Similarity: 99.02 Matching Percent Identity: 98.04 Total Percent Similarity: 99.02 Total Percent Identity: 98.04 5 Gaps: 0 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 10 I I I I I I I I I 1i iii 1 1 I I I 111111111 11i i i1 1 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 | | l i l l i l l l l l l l l l l l l l l l l l l Il l I il IIl I l l Il l i l 15 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KV 102 101 KI 102 20 25 Sequence name: AAH07930 Sequence documentation: 30 Alignment of: HUMANKP29 x AAH07930 WO 2005/072053 PCT/IB2005/000928 609 Alignment segment 1/1: Quality: 1172.00 Escore: 0 5 Matching length: 123 Total length: 123 Matching Percent Similarity: 99.19 Matching Percent Identity: 99.19 Total Percent Similarity: 99.19 Total Percent 10 Identity: 99.19 Gaps: 0 Alignment: 15 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 li li lllli ll ill11 l 1 l lll llllllIlI 1111 111 |||11111111 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 2 0 1 i I 11 1 1 1 i 1 I I 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 I | | | | 1 1 1 1 1 |1 I l lI 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEE 123 I I I ||i I 1 I1 1 I I I111 i11 i I 25 101 KIIRKVVRQIDLSSADAAQEHEE 123 30 WO 2005/072053 PCT/IB2005/000928 610 Sequence name: Q8N604 Sequence documentation: 5 Alignment of: HUMANK P29 x Q8N604 Alignment segment 1/1: Quality: 1457.00 10 Escore: 0 Matching length: 155 Total length: 155 Matching Percent Similarity: 98.71 Matching Percent Identity: 98.71 15 Total Percent Similarity: 98.71 Total Percent Identity: 98.71 Gaps: 0 Alignment: 20 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 lillllllllllll Iliii 1ll1ll1l1l1l1llll1lllll1lilll 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 25 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 l l I l li II l l l l l l l l l l l l 1 1 l l l l l l l l l l l l I l l i i I 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 KIIRKVVRQIDLSSADAAQEHEEVELRGSGLQPDLIEGRKGAQIVKRASL 150 30 I l I l lI l iI l1 i 1iii i i 101 KIIRKVVRQIDLSSADAAQEHEEVELRGSGLQPDLIEGRKGAQIVKRASL 150 WO 2005/072053 PCT/IB2005/000928 611 151 KRGKQ 155 I I I I 151 KRGKQ 155 5 10 Sequence name: AAH07930 Sequence documentation: 15 Alignment of: HUMANK P33 x AAH07930 Alignment segment 1/1: Quality: 967.00 20 Escore: 0 Matching length: 101 Total length: 101 Matching Percent Similarity: 99.01 Matching Percent Identity: 99.01 25 Total Percent Similarity: 99.01 Total Percent Identity: 99.01 Gaps: 0 Alignment: 30 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 WO 2005/072053 PCT/IB2005/000928 612 Iil l l l ill lJ l illl I I I I I llll lil lIlli ll 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 5 11111111 l I111 11 I I 1 111 II II 111 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 K 101 10 101 K 101 15 Sequence name: Q8N604 Sequence documentation: 20 Alignment of: HUMANKP33 x Q8N604 Alignment segment 1/1: 25 Quality: 954.00 Escore: 0 Matching length: 101 Total length: 101 Matching Percent Similarity: 98.02 Matching Percent 30 Identity: 98.02 WO 2005/072053 PCT/IB2005/000928 613 Total Percent Similarity: 98.02 Total Percent Identity: 98.02 Gaps: 0 5 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 llllllllllll lllllllll liiill |1111111111111I11 I 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 10 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 I 11 11lllill1llllll111 liilll1lllllllIi 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 15 101 K 101 101 K 101 20 Sequence name: AAH07930 25 Sequence documentation: Alignment of: HUMANKP34 x AAH07930 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 614 Quality: 971.00 Escore: 0 Matching length: 102 Total length: 102 5 Matching Percent Similarity: 99.02 Matching Percent Identity: 98.04 Total Percent Similarity: 99.02 Total Percent Identity: 98.04 Gaps: 0 10 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 15 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 51 SEGLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 20 101 KV 102 101 KI 102 25 30 Sequence name: Q8N604 WO 2005/072053 PCT/IB2005/000928 615 Sequence documentation: Alignment of: HUMANKP34 x Q8N604 5 Alignment segment 1/1: Quality: 1152.00 Escore: 0 Matching length: 133 Total 10 length: 155 Matching Percent Similarity: 98.50 Matching Percent Identity: 98.50 Total Percent Similarity: 84.52 Total Percent Identity: 84.52 15 Gaps: 1 Alignment: 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 2 0 l i 1l l i I I lI I lI I l i ii 1 l I I i I I I I i I 1 MWTFVTQLLVTLVLLSFFLVSCQNVMHIVRGSLCFVLKHIHQELDKELGE 50 51 SEGLSDDEETISPRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 25 51 SEDLSDDEETISTRVVRRRVFLKGNEFQNIPGEQVTEEQFTDEQGNIVTK 100 101 K ...................... .VELRGSGLQPDLIEGRKGAQIVKRASL 128 101 KIIRKVVRQIDLSSADAAQEHEEVELRGSGLQPDLIEGRKGAQIVKRASL 150 30 129 KRGKQ 133 WO 2005/072053 PCT/IB2005/000928 616 151 KRGKQ 155 5 DESCRIPTION FOR CLUSTER Z39819 10 Cluster Z39819 features 1 transcript(s) and 10 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SEQ ID NO: Z39819_PEA1 T2 44 15 Table 2 - Segments of interest Segment Name SEQ ID NO: Z39819_PEA1 node_2 307 Z39819_PEA 1 node_6 308 Z39819_PEA1_node_10 309 Z39819_PEA1_node_14 310 Z39819_PEA1_node_16 311 Z39819_PEA1 node_21 312 Z39819_PEA1 node_3 313 Z39819_PEA1_node_8 314 Z39819_PEA1_node_12 315 Z39819_PEA1_node 19 316 WO 2005/072053 PCT/IB2005/000928 617 Table 3 - Proteins of interest Protein Name SEQ ID NO: Corresponding Transcript(s) Z39819_PEA_1 P6 575 Z39819_PEA_1_T2 These sequences are variants of the known protein GDNF family receptor alpha 2 precursor (SwissProt accession identifier GFR2_HUMAN; known also according to the 5 synonyms GFR-alpha 2; Neurturin receptor alpha; NTNR-alpha; NRTNR-alpha; TGF-beta related neurotrophic factor receptor 2; GDNF receptor beta; GDNFR-beta; RET ligand 2), SEQ ID NO:632, referred to herein as the previously known protein. Protein GDNF family receptor alpha 2 precursor is known or believed to have the following function(s): Receptor for neurturin. Mediates the NRTN-induced autophosphorylation 10 and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. The sequence for protein GDNF family receptor alpha 2 precursor is given at the end of the application, as "GDNF family receptor alpha 2 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP positions) on Comment 'amnino acid sequence 6 V ->A 462 Q ->L 15 Protein GDNF family receptor alpha 2 precursor localization is believed to be attached to the membrane by a GPI-anchor (By similarity). The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: transmembrane receptor protein tyrosine kinase signaling pathway, 20 which are annotation(s) related to Biological Process; and receptor; glial cell line-derived neurotrophic factor receptor, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBI Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

WO 2005/072053 PCT/IB2005/000928 618 As noted above, cluster Z39819 features 1 transcript(s), which were listed in Table I above. These transcript(s) encode for protein(s) which are variant(s) of protein GDNF family 5 receptor alpha 2 precursor. A description of each variant protein according to the present invention is now provided. Variant protein Z39819_PEA_1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 Z39819_PEA_1_T2. An alignment is given to the known protein (GDNF family receptor alpha 2 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 15 Comparison report between Z39819_PEA_1_P6 and GFR2_HUMAN: 1.An isolated chimeric polypeptide encoding for Z39819_PEA__P6, comprising a first amino acid sequence being at least 90 % homologous to MILANVFCLFFFL corresponding to amino acids 1 - 13 of GFR2_HUMAN, which also corresponds to amino acids 1 - 13 of Z39819_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 20 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GPRAPRLAPPSGLCPGQ corresponding to amino acids 14 - 30 of Z39819_PEA1 _P6, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Z39819_PEA_1_P6, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GPRAPRLAPPSGLCPGQ in Z39819_PEA_1_P6. The location of the variant protein was determined according to results from a number of 30 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: WO 2005/072053 PCT/IB2005/000928 619 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 5 The glycosylation sites of variant protein Z39819_PEA1 1P6, as compared to the known protein GDNF family receptor alpha 2 precursor, are described in Table 5 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). 10 Table 5 - Glycosylation site(s) Position(s) on known amino Present in variant protein? acid sequence 413 No 357 No 52 No Variant protein Z39819_PEA_1_P6 is encoded by the following transcript(s): Z39819_PEA_1_T2, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Z39819_PEA_1 T2 is shown in bold; this coding portion starts at 15 position 715 and ends at position 804. The transcript also has the following SNPs as listed in Table 6 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Z39819_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 6 - Nucleic acid SNPs SNP position on nucleotide 'Alternative nucleic acid Previously known SNP? sequence 633 C ->G No 1088 T ->G No WO 2005/072053 PCT/IB2005/000928 620 1114 G->C No 1120 G->C No 1372 C-> No 1380 C-> No 1872 C -> T No 2058 A -> T Yes 2090 G ->T Yes 2161 T ->C No 2165 A-> No 2165 A ->C No 2256 C ->A No As noted above, cluster Z39819 features 10 segment(s), which were listed in Table 2 5 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 10 Segment cluster Z39819_PEA_1_node_2 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_1_T2. Table 7 below describes the starting and ending position of this segment on each transcript. Table 7 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA__T2 1 679 15 WO 2005/072053 PCT/IB2005/000928 621 Segment cluster Z39819_PEAInode_6 according to the present invention is supported by 17 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA_1_T2. Table 8 below describes the starting and ending position of this segment on each transcript. 5 Table 8 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA_1_T2 755 1028 Segment cluster Z39819_PEA_1 node_10 according to the present invention is supported by 23 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): Z39819_PEA_1_T2. Table 9 below describes the starting and ending position of this segment on each transcript. Table 9 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA 1_T2 1113 1467 15 Segment cluster Z39819_PEA_1_node_14 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEAIT2. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA_1_T2 1578 1718 20 WO 2005/072053 PCT/IB2005/000928 622 Segment cluster Z39819_PEA_1_node 16 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819 PEA_1_T2. Table 11 below describes the 5 starting and ending position of this segment on each transcript. Table 11 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA IT2 1719 1891 Segment cluster Z39819 PEA 1 node_21 according to the present invention is supported 10 by 61 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEA _IT2. Table 12 below describes the starting and ending position of this segment on each transcript. Table 12 - Segment location on transcripts Transcript name Segment segment starting position ending position Z39819_PEA1 1T2 1946 3332 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 20 Segment cluster Z39819_PEA_1_node_3 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819_PEAIT2. Table 13 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 623 Table 13 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA 1 T2 680 754 Segment cluster Z39819 PEA 1_node_8 according to the present invention is supported 5 by 14 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z3981 9_PEAIT2. Table 14 below describes the starting and ending position of this segment on each transcript. Table 14 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA 1_T2 1029 1112 10 Segment cluster Z39819_ PEA 1 node_12 according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): Z39819 PEAIT2. Table 15 below describes the starting and ending position of this segment on each transcript. 15 Table 15 - Segment location on transcripts Transcript name Segment Segment starting position ending position Z39819_PEA_1_T2 1468 1577 Segment cluster Z39819 PEA 1_node_19 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 624 can be found in the following transcript(s): Z39819 PEA_1_T2. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transeript name Segment Segment starting position ending position Z39819_PEA 1_T2 1892 1945 5 Variant protein alignment to the previously known protein: Sequence name: GFR2_HUMAN 10 Sequence documentation: Alignment of: Z39819_PEAlP6 x GFR2 HUMAN 15 Alignment segment 1/1: Quality: 146.00 Escore: 0 Matching length: 26 Total 20 length: 26 Matching Percent Similarity: 69.23 Matching Percent Identity: 69.23 Total Percent Similarity: 69.23 Total Percent Identity: 69.23 25 Gaps: 0 Alignment: WO 2005/072053 PCT/IB2005/000928 625 1 MILANVFCLFFFLGPRAPRLAPPSGL 26 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i i i 1 MILANVFCLFFFLDETLRSLASPSSL 26 5 DESCRIPTION FOR CLUSTER HUMCA1XIA Cluster HUMCAIXIA features 4 transcript(s) and 46 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. 10 Table 1 - Transcripts of interest anscript Name SEQ ID NO. HUMCAlXIA T16 45 HUTMCA1XIA T17 46 HUMCAlXIAT19 47 HUMCA1XIAT20 48 Table 2 - Segments of interest Segment Name SE Q ID NO: HUMCA1XIA node_0 317 HUMCA1XIA node_2 318 HUMCA1XIA node_4 319 HUMCA1XIA node 6 320 HUJMCA1XIA node_8 321 HUMCAlXIA node 9 322 HUMCA1XIA node_18 323 HUMCA1XIA node_54 324 HUMCA1XIA node_55 325 HUMCA1XIAnode_92 326 HUMCAIXIA node 11 327 WO 2005/072053 PCT/IB2005/000928 626 HUMCAIXIA node_15 328 HUMCAlXIA node_19 329 HUMCAIXIA node_21 330 HUMCAIXIA node_23 331 HUMCAIXIA node_25 332 HUMCAIXIA node_27 333 HUMCA1XIA node_29 334 HUMCA1XIA node31 335 HUMCAIXIA node 33 336 HUMCA1XIA node_35 337 HUMCA1XIA node537 338 HUMCA1XIAnode 39 339 HUMCA1XIA_node_41 340 HUMCA1XIA node43 341 HUMCA1XIA node45 342 HUMCAIXIA node47 350 HUMCA1XIAnode_49 344 HUMCA1XIA node 51 345 HUMCAlXIA node_57 346 HUMCA1XIAnode_59 347 HUTMCAlXIA node 62 348 HUMCAlXIA node 64 349 HUMCA1XIA node_66 350 HUMCA1XIAnode_68 351 HUMCA1XIAnode_70 352 HUMI\CA1XIA-node_72 353 HUTMCA1XIA node_74 354 H-UMCA1XIA node 76 355 HUMCA1XIA-node_78 356 HUMCA1XIA node_81 357 WO 2005/072053 PCT/IB2005/000928 627 HUMCAIXIA node_83 358 HUMCAIXIA node_85 359 HUMCAlXIA node_87 360 HUMCAlXIA node_89 361 HUMCAlXIA node_9136 Table 3 - Proteins of interest Protein Name SEQ ID NO: Corresponding Tr nscri pt(s) HUMCAlXIAP14 576 HUMCAlXIAT16 HUMCAIXIA_P15 577 HUMCAlXIA T17 HUMCA1XIAP16 578 HUMCA1XIA T19 HUMCA1XIAP17 579 HUMCA1XIA T20 These sequences are variants of the known protein Collagen alpha 1 (SwissProt accession 5 identifier CAIBHUMAN; known also according to the synonyms XI), SEQ ID NO: 633, referred to herein as the previously known protein. Protein Collagen alpha I is known or believed to have the following function(s): May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils. The sequence for protein Collagen alpha 1 is given at the end of the application, as "Collagen alpha 10 1 amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amiAno acid sequence 625 G ->V (in STL2). /FTId VAR 013583. 676 G -> R (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR 013584. 921 - 926 Missing (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR_013585. 1313 - 1315 Missing (in STL2; overlapping phenotype with Marshall WO 2005/072053 PCT/IB2005/000928 628 syndrome). /FTId=VAR 013586. 1516 G -> V (in STL2; overlapping phenotype with Marshall syndrome). /FTId=VAR 013587. 941 - 944 KDGL -> RMGC 986 Y ->H 1074 R ->P 1142 G ->D 1218 M ->W 1758 T -> A 1786 S ->N The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: cartilage condensation; vision; hearing; cell-cell adhesion; extracellular matrix organization and biogenesis, which are annotation(s) related to Biological Process; extracellular matrix structural protein; extracellular matrix protein, adhesive, which are 5 annotation(s) related to Molecular Function; and extracellular matrix; collagen; collagen type XI, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 10 Cluster HUMCA1XIA can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs 15 in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 24 and Table 5. This cluster is overexpressed (at least at a minimum level) in the 20 following pathological conditions: bone malignant tumors, epithelial malignant tumors, a mixture of malignant tumors from different tissues and lung malignant tumors.

WO 2005/072053 PCT/IB2005/000928 629 Table 5 - Normal tissue distribution Name of Tisue Number adrenal 0 Bone 207 brain 13 colon 0 epithelial 11 general 11 Head and neck 0 kidney 0 Lung 0 breast 8 pancreas 0 stomach 73 uterus 9 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue 1 PSP R3 SP2 R4 adrenal 4.2e-01 1.9e-01 9.6e-02 3.4 8.2e-02 3.6 bone 2.4e-01 6.3e-01 7.7e-10 4.3 5.3e-03 1.6 brain 5.0e-01 6.9e-01 1.8e-01 2.1 4.2e-01 1.3 colon 1.3e-02 2.9e-02 2.4e-01 3.0 3.5e-01 2.4 epithelial 3.9e-04 3.2e-03 1.3e-03 2.3 1.8e-02 1.7 general 5.6e-05 1.6e-03 9.5e-17 4.5 1.le-09 2.8 head and neck 1.2e-01 2.le-01 1 1.3 1 1.1 kidney 6.5e-01 7.2e-01 3.4e-01 2.4 4.9e-01 1.9 lung 5.3e-02 9.le-02 5.5e-05 7.3 5.0e-03 4.0 breast 4.3e-01 5.6e-01 6.9e-01 1.4 8.2e-01 1.1 WO 2005/072053 PCT/IB2005/000928 630 pancreas 3.3e-01 1.8e-01 4.2e-01 2.4 1.5e-01 3.7 stomach 5.Oe-01 6.le-01 6.9e-01 1.0 6.7e-01 0.8 uterus 7.le-01 7.0e-01 6.6e-01 1.1 6.4e-01 1.1 As noted above, cluster HUMCA1XIA features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Collagen alpha 1. A description of each variant protein according to the present invention is now provided. 5 Variant protein HUMCA I XIAP14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMCAlXIAT16. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 10 variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCA1XIA_P14 and CAIB_HUMANV5 (SEQ ID NO 634): 1.An isolated chimeric polypeptide encoding for HUMCA1XIAP14, comprising a first amino acid sequence being at least 90 % homologous to 15 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT 20 EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP 25 GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVK

GADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPT

WO 2005/072053 PCT/IB2005/000928 631 GDPGPSGQAGEKGKLGVPGLPGYPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPR GQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGP PGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQG LPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP 5 V corresponding to amino acids 1 - 1056 of CAlB HUMAN-V5, which also corresponds to amino acids 1 - 1056 of HUMCAIXIAP14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSMMIINSQTIMVVNYSSSFITLML corresponding to amino acids 1057 - 1081 of 10 HUMCA1XIAP14, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMCAlXIA P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence VSMMIINSQTIMVVNYSSSFITLML in HUMCAIXIAP14. It should be noted that the known protein sequence (CAlB HUMAN) has one or more changes than the sequence given at the end of the application and named as being the amino acid sequence for CAlB HUMAN_V5. These changes were previously known to occur and are 20 listed in the table below. Table 7 - Changes to CA1B_HUMAN V5 SNP position(s) on Type of change amino acid sequence 987 conflict The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072053 PCT/IB2005/000928 632 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMCAlXIAP14 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP position(s) on amino a Alternativamino acid(s) P eviously known SNP? sequence 8 W ->G Yes 46 D ->E Yes 559 G ->S Yes 832 G Yes 986 H ->Y Yes 1061 I -> M Yes 1070 V -> A Yes 10 Variant protein HUMCAIXIA_P14 is encoded by the following transcript(s): HUMCA1XIA_T16, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA _T 16 is shown in bold; this coding portion starts at position 319 and ends at position 3561. The transcript also has the following SNPs as listed in 15 Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIAP14 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 63 3 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A -> G No 241 T ->A Yes 340 T ->G Yes 456 T ->G Yes 1993 G ->A Yes 2812 G ->T Yes 3274 C -> T Yes 3282 C ->T Yes 3501 A -> G Yes 3527 T -> C Yes Variant protein HUMCA1XIAP15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMCA1XIA_T17. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCA1XIAP15 and CAIB_HUMAN: 10 1.An isolated chimeric polypeptide encoding for HUMCA1XIA_P15, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM 15 IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED

TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN

WO 2005/072053 PCT/IB2005/000928 634 GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAG 5 PRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQG PIGPPGEK corresponding to amino acids 1 - 714 of CAlBHUMAN, which also corresponds to amino acids 1 - 714 of HUMCAIXIAP15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 MCCNLSFGILIPLQK corresponding to amino acids 715 - 729 of HUMCAlXIA P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMCA1XIA P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MCCNLSFGILIPLQK in HUMCA1XIAP15. The location of the variant protein was detennined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMCAlXIA P15 also has the following non-silent SNPs (Single 25 Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCAIXIAP15 sequence provides support for the deduced sequence of this variant protein according to the present invention). 30 Table 10 -Amino acid mutations WO 2005/072053 PCT/IB2005/000928 635 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence, 8 W ->G Yes 46 D-> E Yes 559 G -> S Yes The glycosylation sites of variant protein HUMCAIXIA_P15, as compared to the known protein Collagen alpha 1, are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation 5 site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 11 - Glycosylation site(s) Positions on known amino Present in variant protein? acid squenc ,e 1640 no Variant protein HUMCA1XIA_P15 is encoded by the following transcript(s): 10 HUMCA1XIA_T17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIAT17 is shown in bold; this coding portion starts at position 319 and ends at position 2505. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein HUMCA1XIA_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A -> G No 241 T -> A Yes WO 2005/072053 PCT/IB2005/000928 636 340 T ->G Yes 456 T ->G Yes 1993 G ->A Yes 2473 C -> T Yes Variant protein HUMCA 1 XIAP16 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMCA1XIA_T19. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCA1XIA P16 and CAIBHUMAN: 10 1.An isolated chimeric polypeptide encoding for HUMCA1XIA_P16, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM 15 IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQT EANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSED TLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSIN GHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPG 20 RPGLPGADGLPGPPGTMLMLPFRYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPM GLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMP GEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA corresponding to amino acids 1 - 648 of CA1B_HUMAN, which also corresponds to amino acids 1 - 648 of HUMCAlXIA P16, a second amino acid sequence being at least 90 % 25 homologous to GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to amino acids 667 - 714 of CA1B_1-HUMAN, which also corresponds to amino acids 649 - 696 of HUMCA1XIAP16, and a third amino acid sequence being at least 70%, WO 2005/072053 PCT/IB2005/000928 637 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE corresponding to amino acids 697 - 738 of HUMCAIXIA_P16, wherein said first amino acid sequence, second amino 5 acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of HUMCA1XIA P16, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 10 least about 50 amino acids in length, wherein at least two amino acids comprise AG, having a structure as follows: a sequence starting from any of amino acid numbers 648-x to 648; and ending at any of amino acid numbers 649+ ((n-2) - x), in which x varies from 0 to n-2. 3.An isolated polypeptide encoding for a tail of HUMCAIXIA P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE in HUMCAlXIAP16. The location of the variant protein was determined according to results from a number of 20 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 25 Variant protein HUMCAlXIAP16 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIAP16 sequence provides support for the deduced sequence of this variant protein according to the 30 present invention). Table 13 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 638 SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 8 W->G Yes 46 D->E Yes 559 G -> S Yes The glycosylation sites of variant protein HUMCA1XIA P16, as compared to the known protein Collagen alpha 1, are described in Table 14 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation 5 site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 14 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? ,acid sequence 1640 no Variant protein HUMCA1XIA P16 is encoded by the following transcript(s): 10 HUMCA1XIA_T19, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIA_TI 9 is shown in bold; this coding portion starts at position 319 and ends at position 2532. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein HUMCA1XIAP16 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A ->G No 241 T ->A Yes WO 2005/072053 PCT/IB2005/000928 6 39 340 T ->GYes 456 T -> G Yes 1993 G-> A Yes 2606 C ->A Yes 2677 T-> G Yes 2849 C ->T Yes Variant protein HUMCA1XIAP17 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMCAIXIAT20. An alignment is given to the known protein (Collagen alpha 1) at the end of the application. One or more alignments to. one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMCAIXIA_P17 and CAIB_HUMAN: 10 1.An isolated chimeric polypeptide encoding for HUMCA1XIA_P17, comprising a first amino acid sequence being at least 90 % homologous to MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTT GFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIY NEHGIQQIGVEVGRSPVFLFEDHTGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTM 15 IVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEH YSPDCDSSAPKAAQAQEPQIDE corresponding to amino acids 1 - 260 of CA1B_HUMAN, which also corresponds to amino acids 1 - 260 of HUMCA1XIA P17, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 VRSTRPEKVFVFQ corresponding to amino acids 261 - 273 of HUMCA1XIAP17, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMCAIXIA P17, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 640 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRSTRPEKVFVFQ in HUMCAIXIAP17. The location of the variant protein was detennined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HUMCA1XIAP17 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCAlXIAP17 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 16 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 8 W G Yes 46 D->Ees The glycosylation sites of variant protein HUMCA1XIA P17, as compared to the known protein Collagen alpha 1, are described in Table 17 (given according to their position(s) on the 20 amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 17 - Glycosylation site(s) Position(s) on known amino Present in variant protein? acid sequence WO 2005/072053 PCT/IB2005/000928 641 1640 no Variant protein HUMCAIXIAP17 is encoded by the following transcript(s): HUMCA IXIA_T20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMCA1XIAT20 is shown in bold; this coding portion starts at 5 position 319 and ends at position 1137. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMCA1XIA P17 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 18 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 157 A->G No 241 T->A Yes 340 T -> G Yes 456 T -> G Yes 1150 A -> C Yes As noted above, cluster HUMCA1XIA features 46 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now 15 provided. Segment cluster HUMCA1XIAnode_0 according to the present invention is supported by 13 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA T16, HUMCA1XIA_T17, 20 HUMCA1XIA_T19 and HUMCA1XIA_T20. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 642 Transcript name Segment Segment starting position ending position HUMCA1XIAT16 1 424 HUMCAIXIA17 1 424 HUMCAIXIA T19 1 424 HUMCA1XIAT20 1 424 Segment cluster HUMCAIXIAnode 2 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAlXIA T16, HUMCAIXIAT17, HUMCA1XIA19 and HUMCAIXIAT20. Table 20 below describes the starting and ending position of this segment on each transcript. Table 20 - Segment location on transcripts Transcript name Segn Segment startit position ending position HUMCA1XIAT16 425 592 HUMCA1XIA_17 425 592 HUMCA1XIA_19 425 592 HUMCA1XIAT20 425 592 10 Segment cluster HUMCA1XIA node 4 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT16, HUMCAIXIAT17, HUMCA1XIA_T19 and HUMCA1XIAT20. Table 21 below describes the starting and ending 15 position of this segment on each transcript. Table 21 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 643 Transcript name Segment Segment starting position ending position HUMCA1XIA 16 593 806 HUMCA1XIAT17 593 806 HUMCA1XIA T19 593 806 HUMCA1XIAT20 593 806 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides 5 were found to hit this segment (in relation to colon cancer), shown in Table 22. Table 22 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers- Chip rference HUMCAIXIA_0_18_0 colorectal cancer Colon Segment cluster HUMCA1XIA_node_6 according to the present invention is supported 10 by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA T16, HUMCA1XIA_T17, HUMCA1XIA19 and HUMCA1XIAT20. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA16 807 969 HUMCAIXIAT17 807 969 HUMCA1XIA_19 807 969 HUMCAlXIAT20 807 969 15 WO 2005/072053 PCT/IB2005/000928 644 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment, shown in Table 24. 5 Table 24 - Oligonucleotides related to this segment Oligonucleotide name Overexpressed in cancers Chip reference HUMCA1XIA_0_18_0 breast malignant tumors BRS HUMCA1XIA 0 18_0 colorectal cancer Colon HUMCA1XIA_0_18 0 lung malignant tumors LIN Segment cluster HUMCA1XIA node_8 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): HUMCAlXIA T16, HUMCA1XIA-T17, HUMCAIXIAT19 and HUMCA1XIAT20. Table 25 below describes the starting and ending position of this segment on each transcript. Table 25 - Segment location on transcripts Transcript name Segnt Segment starting position ending position HUMCA1XIA T16 970 1098 HUMCAIXIA_T17 970 1098 HUMCAIXIAT19 970 1098 HUMCA1XIAT20 970 1098 15 Segment cluster HUMCA1XIAnode_9 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIAT20. Table 26 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 Table 26 - Segment location on transcripts Transcript name Segment SegMent starting position ending position HUMCA1XIA_T20 1099 1271 Segment cluster HUMCAlXIA node 18 according to the present invention is supported 5 by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA T16, HUMCA1XIATI7 and HUMCA1XIAT19. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position 7 ending position HUMCA1XIAT16 1309 1522 HUMCAlXIA T17 1309 1522 HUMCAIXIA_T19 1309 1522 10 Segment cluster HUMCA1XIA node_54 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T19. Table 28 below describes the 15 starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T19 2407 2836 WO 2005/072053 PCT/IB2005/000928 646 Segment cluster HUMCAIXIA node_55 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT17 and HUMCAIXIA-T19. Table 29 below describes the starting and ending position of this segment on each transcript. 5 Table 29 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT17 2461 2648 HUMCAIXIAT19 2837 3475 Segment cluster HUMCAIXIA node 92 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): HUMCAlXIA T16. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts ~Trinseript name Segment, Segment starting positine6ngpsto HUMCAIXIAT16 3487 3615 15 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 20 Segment cluster HUMCAlXIA node_1 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, HUMCA1XIAT17 and WO 2005/072053 PCT/IB2005/000928 647 HUMCAIXIA_Tl9. Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript name segment Segment starting position ending position HUMCAIXIA _T16 1099 1215 HUMCA1XIAT17 1099 1215 HUMCA1XIAT19 1099 1215 5 Segment cluster HUMCA 1XIA node _15 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT16, HUMCAlXIAT17 and HUMCA1XIA_TI9. Table 33 below describes the starting and ending position of this segment 10 on each transcript. Table 33 - Segment location on transcripts Transcript name Segmen Segment startingposition ending position HUMCAlXIAT16 1216 1308 HUMCAXIAT17 1216 1308 HUMCAXIAT19 1216 1308 Segment cluster HUMCA1XIA_node 19 according to the present invention is supported 15 by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA T16, HUMCA1XIA_TI7 and HUMCAlXIAT19. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 648 Transcript name Segment Segment starting position ending position HUMCA1XIAT16 1523 1563 HUMCAXIA _T17 1523 1563 HUMCA1XIA T19 1523 1563 Segment cluster HUMCAXIA node_21 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA_T16, HUMCAXIAT17 and HUMCA1XIA_T19. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name Segment Segment starting position ending1positio HUMCA1XIAT16 1564 1626 HUMCAlXIA T17 1564 1626 HUMCAXIAT19 1564 1626 10 Segment cluster HUMCA1XIA node_23 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16, HUMCAlXIAT17 and HUMCA1XIA_T19. Table 36 below describes the starting and ending position of this segment 15 on each transcript. Table 36 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_T16 1627 1668 WO 2005/072053 PCT/IB2005/000928 649 HUMCAIXIA T17 1627 1668 HUMCA1XIAT19 1627 1668 Segment cluster HUMCAlXIA node_25 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): IUMCA1XIA T16, HUMCA1XIA17 and HUMCAIXIAT19. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segmrrent 'Segmen starting position ending position HUMCAIXIA 16 1669 1731 HUMCA1XIA 17 1669 1731 HUMCAXIAT19 1669 1731 10 Segment cluster HUMCA1XIA node_27 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA T16, HUMCAIXIA _T17 and HUMCA1XIAT19. Table 38 below describes the starting and ending position of this segment 15 on each transcript. Table 38 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIA 16 1732 1806 HUMCA1XIA 17 1732 1806 HUMCA1XIA19 1732 1806 WO 2005/072053 PCT/IB2005/000928 650 Segment cluster HUMCA1XIA node_29 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA T16, HUMCA1XIAT17 and HUMCAIXIA_Ti9. Table 39 below describes the starting and ending position of this segment 5 on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIA 16 1807 1890 HUMCA1XIAT17 1807 1890 HUMCA1XIA T19 1807 1890 Segment cluster HUMCAIXIA node_31 according to the present invention is supported 10 by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA T16, HUMCAlXIA17 and HUMCA1XIA_Ti 9. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIA_T16 1891 1947 HUMCA1XIAT17 1891 1947 HUMCAXIA_T19 1891 1947 15 Segment cluster HUMCA1XIA node 33 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16, HUMCA1XIA-T17 and WO 2005/072053 PCT/IB2005/000928 651 HUMCAIXIA_T19. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIA16 1948 2001 HUMCA1XIA T17 1948 2001 HUMCAXIAT19 1948 2001 5 Segment cluster HUMCA1XIA node_35 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIA_T16, HUJMCA1XIA17 and HUMCAIXIA_T19. Table 42 below describes the starting and ending position of this segment 10 on each transcript. Table 42 - Segment location on transcripts TInscript name Segment Segment starting position ending position HUMCA1XIA 16 2002 2055 HUMCA1XIA17 2002 2055 HUMCAlXIA19 2002 2055 Segment cluster HUMCA1XIAnode_37 according to the present invention is supported 15 by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA T16, HUMCAIXIA17 and HUMCA1XIA19. Table 43 below describes the starting and ending position of this segment on each transcript. Table 43 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 652 Transcript name Segment Segment starting position ending position HUMCAXIAT16 2056 2109 HUMCAXIA_T17 2056 2109 HUMCAXIA119 2056 2109 Segment cluster HUMCAXIA node_39 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA T6, HUMCA1XIAT17 and HUMCA1XIA_T19. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2110 2163 HUMCAIXIA_17 2110 2163 HUMCA1XIA-T19 2110 2163 10 Segment cluster HUMCA1XIA node _41 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16, HUMCA1XIA17 and HUMCA1XIAT19. Table 45 below describes the starting and ending position of this segment 15 on each transcript. Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA_16 2164 2217 WO 2005/072053 PCT/IB2005/000928 653 HUMCAIXIAT17 2164 2217 HUMCAXIAT19 2164 2217 Segment cluster HUMCAIXIA node 43 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAlXIA T16, HUMCAIXIATi7 and HUMCAIXIATI9. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIAT16 2218 2262 HUMCA1XIAT17 2218 2262 HUMCA1XIAT19 2218 2262 10 Segment cluster HUMCA1XIAnode_45 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16 and HUMCAIXIA_T17. Table 47 below describes the starting and ending position of this segment on each transcript. 15 Table 47 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA T16 2263 2316 HUMCA1XIAT17 2263 2316 Segment cluster HUMCAIXIA node_47 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 654 can be found in the following transcript(s): HUMCAIXIA_TI6, HUMCA IXIATI7 and HUMCAIXIA_T19. Table 48 below describes the starting and ending position of this segment on each transcript. Table 48 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAXIAT16 2317 2361 HUMCA1XIAT17 2317 2361 HUMCA1XIA T19 2263 2307 5 Segment cluster HUMCA1XIA_node 49 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16, HUMCA1XIATI7 and 10 HUMCA1XIA_T 19. Table 49 below describes the starting and ending position of this segment on each transcript. Table 49 - Segment location on transcripts Transcript name SegIment Segment starting position ending position HUMCA1XIA T16 2362 2415 HUMCA1XIAT17 2362 2415 HUMCA1XIA T19 2308 2361 15 Segment cluster HUMCAIXIA node_51 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAIXIAT16, HUMCA1XIAT17 and HUMCA1XIA_T19. Table 50 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 655 Table 50 - Segment location on transcripts Tfanscript name Segment Segment starting position ending position HUMCA1XIAT16 2416 2460 HUMCAIXIAT17 2416 2460 HUMCA1XIAT19 2362 2406 Segment cluster HUMCA XIA Anode_57 according to the present invention is supported 5 by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA_ T16. Table 51 below describes the starting and ending position of this segment on each transcript. Table 51 - Segment location on transcripts Transcript nai e i Segment starting position enlding p 1sio1 HUMCA1XIAT16 2461 2514 10 Segment cluster HUMCA1XIA node_59 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA IXIAT16. Table 52 below describes the starting and ending position of this segment on each transcript. 15 Table 52 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAlXIA T16 2515 2559 WO 2005/072053 PCT/IB2005/000928 656 Segment cluster HUMCA IXIA node 62 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 53 below describes the starting and ending position of this segment on each transcript. 5 Table 53 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2560 2613 Segment cluster HUMCAlXIA node 64 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): HUMCAIXIA_T 16. Table 54 below describes the starting and ending position of this segment on each transcript. Table 54 - Segment location on transcripts Transcript name Segment Segnent starting position ending position HUMCA1XIAT16 2614 2658 15 Segment cluster HUMCA1XIA node 66 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16. Table 55 below describes the starting and ending position of this segment on each transcript. Table 55 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2659 2712 20 WO 2005/072053 PCT/IB2005/000928 657 Segment cluster HUMCAIXIAnode_68 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 56 below describes the 5 starting and ending position of this segment on each transcript. Table 56 - Segment location on transcripts Transcript ge Segmentment starting position ending position HUMCAIXIAT16 2713 2820 Segment cluster HUMCA1XIA node_70 according to the present invention is supported 10 by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 57 below describes the starting and ending position of this segment on each transcript. Table 57 - Segment location on transcripts Transcript name Segment Segment ;tarting position ending position HUMCA1XIA T16 2821 2874 15 Segment cluster HUMCA1XIA node_72 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 58 below describes the starting and ending position of this segment on each transcript. 20 Table 58 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIA T16 2875 2928 WO 2005/072053 PCT/IB2005/000928 658 Segment cluster HUMCAlXIA-node_74 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCA1XIA_T16. Table 59 below describes the starting and ending position of this segment on each transcript. Table 59 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIAT16 2929 2973 10 Segment cluster HUMCAIXIA node_76 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIAT16. Table 60 below describes the starting and ending position of this segment on each transcript. Table 60 - Segment location on transcripts Transcrit name Segmnent Segment starting position ending position HUMCA1XIA_T16 2974 3027 15 Segment cluster HUMCA1XIA node 78 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 61 below describes the 20 starting and ending position of this segment on each transcript. Table 61 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 659 HUMCAIXIA TI6 3028 3072 Segment cluster HUMCAIXIA-node_81 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAIXIA T16. Table 62 below describes the starting and ending position of this segment on each transcript. Table 62 - Segment location on transcripts Transcript name Segment Segment starting posit[loll endl~ing position HUMCA1XIAT16 3073 3126 10 Segment cluster HUMCAIXIA node 83 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA_T16. Table 63 below describes the starting and ending position of this segment on each transcript. Table 63 - Segment location on transcripts Transcript naniie Segment Segmenrt starting position ending position HUMCA1XIAT16 3127 3180 15 Segment cluster HUMCAlXIA node 85 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIAT16. Table 64 below describes the 20 starting and ending position of this segment on each transcript. Table 64 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 660 Transcript name Segment Segment starting position ending position HUMCAIXIA_16 3181 3234 Segment cluster HUMCAlXIAnode_87 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): HUMCAlXIAT16. Table 65 below describes the starting and ending position of this segment on each transcript. Table 65 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCA1XIA T16 3235 3342 10 Segment cluster HUMCA 1 XIA node 89 according to the present invention is supported by 9 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCA1XIA16. Table 66 below describes the starting and ending position of this segment on each transcript. Table 66 - Segment location on transcripts TrAnscript name Segment Segment starting position ending position HUMCAlXIAT16 3343 3432 15 Segment cluster HUMCAlXIA node 91 according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMCAlXIA_16. Table 67 below describes the 20 starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 661 Table 67 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMCAIXIA T16 3433 3486 5 Variant protein alignment to the previously known protein: Sequence name: CA1BHUMANV5 Sequence documentation: 10 Alignment of: HUMCA1XIAP14 x CAIB HUMAN V5 Alignment segment 1/1: 15 Quality: 10456.00 Escore: 0 Matching length: 1058 Total length: 1058 Matching Percent Similarity: 99.91 Matching Percent 20 Identity: 99.91 Total Percent Similarity: 99.91 Total Percent Identity: 99.91 Gaps: 0 25 Alignment: 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 lI l l l l l l l l l l l l l l l l i l l i l l i I l l1 1 I l l l l l l l l 1i l l i l l i WO 2005/072053 PCT/IB2005/000928 662 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 5 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 11i1ll 1ll1ll 11l 11l 11ll 1ll iil1l 111l ll lll li i Jill) 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 10 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 l i l l l l l l li ll l li l l l l l l i l l 1 l l1 l i l i l l l l i l l i l i l l l i l l 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 15 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 lillllllllll11lll1ll111lllillil1llil1lil1llill1lli1 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 25 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 lllIll lllll 1 11 1 1 1 II I 1ll 1l1illlll 1ll 1lllllll ll ill 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 30 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 WO 2005/072053 PCT/IB2005/000928 66 3 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 5 lilli 1llilil 1li l ii i liii iiii l 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 10 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 IIlllll llli llilll ill 1llillil1 l11111111111111 11|| 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 15 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 IF lllll Illlll lilll ili l i i i ill 1 1 1 1 1li ili 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 20 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750 701 LPGPQGPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPP 750 751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800 30 751 GPQGPIGYPGPRGVKGADGVRGLKGSKGEKGEDGFPGFKGDMGLKGDRGE 800 WO 2005/072053 PCT/IB2005/000928 664 801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850 llil lil l1 lllilill1 il llilil1 l lil111 11ii 1111111111111 801 VGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPGYPGRQG 850 5 851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900 lilillllll1lll1li1llIllililll1lillill1llllillill 851 PKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKP 900 901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950 101 1 ||1 111111111111111111111111111 I i ll i ilI l 901 GPKGTSGGDGPPGPPGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQ 950 951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000 l i l i l i l l il li I I I I Il I l l f ill i l i l illl11 i 15 951 RGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERGHPGPPGPPGEQGLPG 1000 1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050 1001 AAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQ 1050 20 1051 GPPGPVVS 1058 lIMli 1 1051 GPPGPVGS 1058 25 30 Sequence name: CAIB HUMAN WO 2005/072053 PCT/IB2005/000928 665 Sequence documentation: Alignment of: HUMCAIXIAP15 x CAIB HUMAN 5 Alignment segment 1/1: Quality: 7073.00 Escore: 0 Matching length: 714 Total 10 length: 714 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 2011| |1il l i l 11i li li |||||| ii 111 il i1 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 liiil!ll IIlllllllllllll ll illi ll lI11 11 1 il lili li 25 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 30 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 WO 2005/072053 PCT/IB2005/000928 666 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 5 l i i l l i l l i l l l i l i l l i l l i l l i l li1l i l i l li1 i l i li1 i iI I 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 10 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 l i l l l l l l l l l l l l l l l l l l l l l l i l l l i l l i l i l l l i l l i l1 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 15 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 20 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 25 IlI llI II 1 1Ill l I I ij IllIlI 1 11 1illilIlIJIIIII I I I II 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 30 501 GDGSKGPTTSAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 WO 2005/072053 PCT/IB2005/000928 667 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 11I1I111111 I liII I 1 i11 I| 1 i i1 | IIliii 11111 ||11 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 5 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 ||11 1 1 1 1 1 11 1 11 1 1 1 111111 li 1 11 1 11 1 11 1 1 111 1 1 11 1 I 1 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 1 0 l i I I I l I l l I I l1li l l i i i l l l i i i l l i i 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 701 LPGPQGPIGPPGEK 714 15 701 LPGPQGPIGPPGEK 714 20 Sequence name: CA1B HUMAN Sequence documentation: 25 Alignment of: HUMCA1XIAP16 x CA1B HUMAN . Alignment segment 1/1: 30 Quality: 6795.00 Escore: 0 WO 2005/072053 PCT/IB2005/000928 668 Matching length: 696 Total length: 714 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 97.48 Total Percent Identity: 97.48 Gaps: 1 Alignment: 10 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 I II II I|11 i|ii I II I lilil I II I i i i 11|| 1 I I 1111111ii ii 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 15 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 11 1 1i1 I I I iiiIiiiiil i illii |II II i ii i l 11|1 i i 111l 1 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 2 0 i I i li i i I i 101 ILFTVKPKKGIQSFLLSIYNEHGTQQIGVEVGRSPVFLFEDHTGKPAPED 150 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 25 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 30 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 WO 2005/072053 PCT/IB2005/000928 669 251 AQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVTEGPTVTEETIAQTEA 300 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 5 li i i ll i il i i li llI ll 1I i 1i]| 1iiii i 301 NIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDS 350 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 l i l l l l l l l l l l i l l l l l i l i l l i il i l liii li li 10 351 QRKNSEDTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEE 400 401 FGPGVPAETDITETSINGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 lill i il illl ll lillll llll l ii i lllllllillillli i I li li lii I 401 FGPGVPAETDITETSTNGHGAYGEKGQKGEPAVVEPGMLVEGPPGPAGPA 450 15 451 GTMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 1||111 Ei11111111111||||1 |||111111111111li1111111 liii 451 GIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPFRYG 500 20 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 501 GDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSG 550 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 551 AKGESGDPGPQGPRGVQGPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDR 600 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEA.. 648 li liL l il l l lll lll lll ll l lll i l l l l l I lli Ll 65i i 30 601 GFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGEDGEIGPRGLPGEAGP 650 WO 2005/072053 PCT/IB2005/000928 670 649 .................. GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 682 111 I 11I 1I 1111 i II1lI 111 11111 ii i I I I 651 RGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQG 700 5 683 LPGPQGPIGPPGEK 696 701 LPGPQGPIGPPGEK 714 10 Sequence name: CAlB HUMAN 15 Sequence documentation: Alignment of: HUMCAlXIA P17 x CAIB HUMAN 20 Alignment segment 1/1: Quality: 2561.00 Escore: 0 Matching length: 260 Total 25 length: 260 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 30 Gaps: C WO 2005/072053 PCT/IB2005/000928 671 Alignment: 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 5 1 MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNS 50 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 51 PEGISKTTGFCTNRKNSKGSDTAYRVSKQAQLSAPTKQLFPGGTFPEDFS 100 10 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 101 ILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDHTGKPAPED 150 15 151 YPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 |1 1 1 1 1F 11| 1 1 1 11 F Il Il 1 F1111| 1 1 1 111111 F l 1 1 |1FF | 151 YPLFRTVNIADGKWHRVATSVEKKTVTMIVDCKKKTTKPLDRSERAIVDT 200 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 20 |l111 Filillillllll ll 1 FFl ll FFll 1lit FilillFll1 i1 i 201 NGITVFGTRILDEEVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKA 250 251 AQAQEPQIDE 260 Il 1 11l Il F 25 251 AQAQEPQIDE 260 30 DESCRIPTION FOR CLUSTER HSS100PCB WO 2005/072053 PCT/IB2005/000928 672 Cluster HSS I OOPCB features 1 transcript(s) and 3 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table I - Transcripts of interest Transcript Name SEQ ID NO: HSSI00PCBTi 49 5 Table 2 - Segments of interest Segment Name SEQ ID NO HSS100PCB node_3 363 HSS100PCB node_4 364 HSS100PCB node_5 365 Table 3 - Proteins of interest Protein Name SEQ ID NO: CorrespondingiTranscript(s) HSSIOOPCBP3 580 HSS100PCBTi 10 These sequences are variants of the known protein S-100P protein (SwissProt accession identifier SlOP_HUMAN), SEQ ID NO: 635, referred to herein as the previously known protein. The sequence for protein S-100P protein is given at the end of the application, as "S-100P protein amino acid sequence". Known polymorphisms for this sequence are as shown in Table 15 4. Table 4 - Amino acid mutations for Known Protein SNP position(s) on Comment amino acid sequence 32 E->T 44 F ->E WO 2005/072053 PCT/IB2005/000928 673 5 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: calcium binding; protein binding, which are annotation(s) related to Molecular Function. The GO assignment relies on information from one or more of the SwissProt/TremBl 10 Protein knowledgebase, available from <http://www.expasy.cb/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. Cluster HSS100PCB can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given 15 according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 20 Overall, the following results were obtained as shown with regard to the histograms in Figure 25 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: a mixture of malignant tumors from different tissues. Table 5 - Normal tissue distribution Name of Tissue Number bladder 41 colon 37 epithelial 38 general 22 kidney 0 WO 2005/072053 PCT/IB2005/000928 674 liver O Lung 18 breast 0 bone marrow 0 ovary 0 pancreas 0 prostate 46 stomach 553 uterus 13 Table 6 - P values and ratios for expression in cancerous tissue Name of Tissue P P2 SPI R3 SP2 R4 bladder 3.3e-01 2.9e-01 2.9e-02 2.8 3.5e-02 2.8 colon 3.0e-01 1.9e-01 5.2e-01 1.2 2.4e-01 1.7 epithelial 4.7e-02 1.6e-02 2.0e-01 1.2 6.le-02 1.3 general 1.le-03 6.8e-05 1.4e-02 1.5 4.9e-04 1.7 kidney 6.5e-01 7.2e-01 5.8e-01 1.7 7.Oe-01 1.4 liver 9.le-01 4.9e-01 1 1.0 7.7e-02 2.1 lung 6.8e-01 7.3e-01 2.2e-02 2.9 1.3e-O1 1.7 breast 2.8e-01 3.2e-01 4.7e-01 2.0 6.8e-01 1.5 bone marrow 1 6.7e-01 1 1.0 2.8e-01 2.8 ovary 2.6e-01 3.Oe-01 4.7e-01 2.0 5.9e-01 1.7 pancreas 3.3e-01 4.4e-O1 7.6e-02 3.7 1.Se-01 2.8 prostate 9.le-01 9.3e-01 5.8e-01 0.6 7.6e-01 0.5 stomach 3.7e-01 3.2e-01 1 0.1 1 0.3 uterus 9.4e-01 7.0e-01 1 0.6 4.le-01 1.1 As noted above, cluster HSS 1 OOPCB features 1 transcript(s), which were listed in Table 1 5 above. These transcript(s) encode for protein(s) which are variant(s) of protein S-1OOP protein. A description of each variant protein according to the present invention is now provided.

WO 2005/072053 PCT/IB2005/000928 675 Variant protein HSS1OOPCB_P3 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HSS100PCB_TI. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HSS100PCBP3 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCBP3 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 7- Amino acid mutations Ni osition(s) on amino acid Aternative amino acid(s) Previously known SNP? sequence SM ->R Yes 11 M ->L Yes 20 L->F Yes Variant protein HSS100PCB_P3 is encoded by the following transcript(s): HSS100PCBTi, for which the sequence(s) is/are given at the end of the application. The 20 coding portion of transcript HSS100PCB_Ti is shown in bold; this coding portion starts at position 1057 and ends at position 1533. The transcript also has the following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HSS100PCBP3 sequence provides support for the deduced 25 sequence of this variant protein according to the present invention).

WO 2005/072053 PCT/IB2005/000928 676 Table 8 - Nucleic acid SNPs SNP position on nucleotide Altenative nucleic acid Proiously kiown SNP? sequence 52 C -> T Yes 107 A ->C Yes 458 C ->T Yes 468 A ->G Yes 648 C ->T Yes 846 C ->G Yes 882 G ->A Yes 960 C -> T No 965 C ->T Yes 1058 T ->G Yes 1087 A ->C Yes 1114 C T Yes 1968 G ->A Yes 1971 C ->T Yes 2010 C ->A Yes 2099 G -> No As noted above, cluster HSS100PCB features 3 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) 5 are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. Segment cluster HSS1OOPCBnode_3 according to the present invention is supported by 10 16 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_TI. Table 9 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 677 Table 9 - Segment location on transcripts Transcript name Segment Segment starting position eding position HSS100PCBTI 1 1133 Segment cluster HSS 1 OOPCB node-4 according to the present invention is supported by 5 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HSS100PCB_TI. Table 10 below describes the starting and ending position of this segment on each transcript. Table 10 - Segment location on transcripts Transcript name Segment Segment starting position ending position HSS100PCBTi 1134 1923 10 Microarray (chip) data is also available for this segment as follows. As described above with regard to the cluster itself, various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer. The following oligonucleotides were found to hit this segment (related to colon cancer), shown in Table 11. Table 11 - Oligonucleotides related to this segment Oligonucleotide name Overepressed in cancers Chip reference HSS10OPCB0_0_12280 colorectal cancer Colon 15 Segment cluster HSS100PCBnode_5 according to the present invention is supported by 141 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HSS100PCB_TI. Table 12 below describes the starting 20 and ending position of this segment on each transcript. Table 12 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 678 Transcript name Segment Segment starting position ending position HSS100PCBTI 1924 2201 5 10 15 DESCRIPTION FOR CLUSTER HUMPHOSLIP Cluster HUMPHOSLIP features 7 transcript(s) and 53 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the 20 end of the application. The selected protein variants are given in table 3. Table I - Transcripts of interest Transcript Name SEQ ID NO: HUMPHOSLIPPEA_2 T6 50 HUMPHOSLIPPEA_2_T7 51 HUMPHOSLIPPEA_2_T14 52 HUMPHOSLIPPEA_2_T16 53 HUMPHOSLIPPEA_2_T17 54 WO 2005/072053 PCT/IB2005/000928 679 HUMPHOSLIPPEA_2_TI8 55 HUMPHOSLIP PEA_2_T19 56 Table 2 - Segments of interest Segment Name SEQ ID NO: HUMPHOSLIPPEA 2 node_0 366 HUMPHOSLIP PEA 2_node_19 367 HUMPHOSLIP PEA 2 node 34 368 HUMPHOSLIP PEA 2 node 68 369 HUMPHOSLIPPEA_2_node_70 370 HUMPHOSLIP PEA 2 node 75 371 HUMPHOSLIPPEA_2_node_2 372 HUMPHOSLIPPEA_2_node_3 373 HUMPHOSLIP PEA 2_node_4 374 HUMPHOSLIP PEA 2 node 6 375 HUMPHOSLIPPEA_2_node_7 376 HUMPHOSLIPPEA 2 node_8 377 HUMPHOSLIPPEA_2_node_9 378 HUMPHOSLIPPEA 2_node_14 379 HUMPHOSLIP PEA 2 node_15 380 HUMPHOSLIP PEA 2 node_16 381 HUMPHOSLIPPEA_2_node_17 382 HUMPHOSLIPPEA_2_node_23 383 HUMPHOSLIPPEA_2_node_24 384 HUMPHOSLIP PEA 2_node_25 385 HUMPHOSLIPPEA_2_node_26 386 HUMPHOSLIP PEA_2_node_29 387 HUMPHOSLIPPEA_2_node_30 388 HUMPHOSLIPPEA_2_node_33 389 WO 2005/072053 PCT/IB2005/000928 680 HUMPHOSLIPPEA_2 node 36 390 HUMPHOSLIP PEA_2_node_37 391 HUMPHOSLIP PEA_2_node 39 392 HUMPHOSLIP PEA 2 node 40 393 HUMPHOSLIPPEA_2_node 41 394 HUMPHOSLIPPEA_2_node 42 395 HUMPHOSLIP PEA_2_node_44 396 HUMPHOSLIP PEA_2_node_45 397 HUMPHOSLIP PEA_2_node_47 398 HUMPHOSLIP PEA 2_node_51 399 HUMPHOSLIPPEA_2_node 52 400 HUMPHOSLIP PEA_2_node 53 401 HUMPHOSLIP PEA_2 node_54 402 HUMPHOSLIPPEA_2_node55 403 HUMPHOSLIPPEA_2_node_58 404 HLJMPHOSLIPPEA_2_node 59 405 HUMPHOSLIPPEA_2_node_60 406 HUMPHOSLIP PEA_2_node 61 407 HUMPHOSLIP PEA_2_node_62 408 HUMPHOSLIP PEA_2_node 63 409 HUMPHOSLIPPEA_2_node 64 410 HUMPHOSLIP PEA_2 node_65 411 HUMPHOSLIPPEA_2_node_66 412 HUMPHOSLIP PEA_2 node_67 413 HUMPHOSLIP PEA_2_node_69 414 HUMPHOSLIP PEA_2_node 71 415 HUMPHOSLIPPEA_2_node_72 416 HUMPHOSLIPPEA_2_node_73 417 HUMPHOSLIPPEA_2 node_74 418 WO 2005/072053 PCT/IB2005/000928 6 81 Table 3 - Proteins of interest Protein Name SEQ ID NO: Corresponding Transcript(s) HUMPHOSLIP PEA_2_PlO 581 HUMPHOSLIPPEA_2 T17 HUMPHOSLIP PEA_2_P12 582 HUMPHOSLIPPEA_2_T19 HUMPHOSLIPPEA_2 P30 583 HUMPHOSLIPPEA_2_T6 HUMPHOSLIPPEA_2_P31 584 HUMPHOSLIPPEA_2_T7 HUMPHOSLIP PEA_2_P33 585 HUMPHOSLIPPEA_2_T14 HUMPHOSLIPPEA 2_P34 586 HUMPHOSLIP PEA 2 T16 HUMPHOSLIPPEA 2_P35 587 HUMPHOSLIP PEA 2 T18 These sequences are variants of the known protein Phospholipid transfer protein precursor (SwissProt accession identifier PLTPHUMAN; known also according to the synonyms Lipid 5 transfer protein II), SEQ ID NO: 636, referred to herein as the previously known protein. Protein Phospholipid transfer protein precursor is known or believed to have the following function(s): Converts HDL into larger and smaller particles. May play a key role in extracellular phospholipid transport and modulation of hdl particles. The sequence for protein Phospholipid transfer protein precursor is given at the end of the application, as "Phospholipid transfer protein 10 precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SNP positions) on Comment amino acid sequence 282 R ->Q. /FTId=VAR 017020. 372 R ->H. /FTId=VAR017021. 380 R -> W (in dbSNP:6065903). /FTId=VAR 017022. 444 F -> L (in dbSNP:1804161). /FTId=VAR 012073. 487 T ->K (in dbSNP:1056929). /FTId=VAR_012074. 18E V Protein Phospholipid transfer protein precursor localization is believed to be Secreted.

WO 2005/072053 PCT/IB2005/000928 682 The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: lipid metabolism; lipid transport, which are annotation(s) related to Biological Process; lipid binding, which are annotation(s) related to Molecular Function; and extracellular, which are annotation(s) related to Cellular Component. 5 The GO assignment relies on information from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. For this cluster, at least one oligonucleotide was found to demonstrate overexpression of 10 the cluster, although not of at least one transcript/segment as listed below. Microarray (chip) data is also available for this cluster as follows. Various oligonucleotides were tested for being differentially expressed in various disease conditions, particularly cancer, as previously described. The following oligonucleotides were found to hit this cluster (in relation to colon cancer) but not other segments/transcripts below, shown in Table 5. 15 Table 5 - Oligonucleotides related to this cluster Oligonucleotide name Overexpressed in cancers Chip reference HUMPHOSLIP 0_0_18458 colorectal cancer Colon As noted above, cluster HUMPHOSLIP features 7 transcript(s), which were listed in 20 Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Phospholipid transfer protein precursor. A description of each variant protein according to the present invention is now provided. Variant protein HUMPHOSLIPPEA_2_PlO according to the present invention has an 25 amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIPPEA_2_T17. An alignment is given to the known protein (Phospholipid transfer protein precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief WO 2005/072053 PCT/IB2005/000928 683 description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMPHOSLIPPEA2_Pl10 and PLTPHUMAN: I.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA_2_P10, 5 comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH FYYNISE corresponding to amino acids 1 - 67 of PLTPHUMAN, which also corresponds to amino acids 1 - 67 of HUMPHOSLIPPEA_2_P10, and a second amino acid sequence being at least 90 % homologous to 10 KVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMK DPVASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMES YFRAGALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKP SGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSN HSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVTNHAGFLTI 15 GADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV corresponding to amino acids 163 493 of PLTP HUMAN, which also corresponds to amino acids 68 - 398 of HUMPHOSLIPPEA_2_P10, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of 20 HUMPHOSLIP PEA_2_P1O, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise EK, having a structure as follows: a sequence starting from any of amino acid 25 numbers 67-x to 67; and ending at any of amino acid numbers 68+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 30 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide WO 2005/072053 PCT/IB2005/000928 684 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMPHOSLIPPEA__2_PIO also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on 5 the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_PlO sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positions) on amino acid Alternative amino acids) Previously known SNIP? 16 H->R Yes 18 E -> V Yes 113 S -> F Yes 118 V -> No 140 R -> No 140 R -> P No 150 N -> No 160 P -> No 201 P -> No 274 M-> No 285 R ->W Yes 292 Q-> No 315 L ->* No 330 M ->I Yes 349 F -> L Yes 392 T ->K Yes 10 The glycosylation sites of variant protein -UMPHOSLIPPEA_2_P10, as compared to the known protein Phospholipid transfer protein precursor, are described in Table 7 (given WO 2005/072053 PCT/IB2005/000928 685 according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 7 - Glycosylation sites) Position(s) on know n amino Present in variant protein? Position in variant protein? acid sequence' 94 No 143 No 64 Yes 64 245 Yes 150 398 Yes 303 117 No 5 Variant protein HUMPHOSLIPPEA_2_PlO is encoded by the following transcript(s): HUMPHOSLIPPEA_2_T17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA_2_T17 is shown in bold; this coding portion starts at position 276 and ends at position 1469. The transcript also has the 10 following SNPs as listed in Table 8 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P10 sequence provides support for the deduced sequence of this variant protein according to the present invention). 15 Table 8 -Nucleic acid SNPs -SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 174 G -> T No 175 A -> T No 322 A ->G Yes 328 A ->.T Yes WO 2005/072053 PCT/IB2005/000928 686 431 G-> A Yes 551 C-> T Yes 613 C->T Yes 628 T No 694 G No 694 G ->C No 723 A-> No 753 C-> No 876 C-> No 1037 C ->T Yes 1097 G-> No 1128 C ->T Yes 1149 C-> No 1219 T ->A No 1230 C ->T Yes 1265 G ->C Yes 1322 T -> A Yes 1450 C -> A Yes 1469 C -> T No 1549 C ->T Yes 1565 A ->G No 1565 A ->T No 1630 A ->G Yes 1654 T->A No 1731 G -> T Yes 1864 G->A Yes 1893 G-> T Yes 2073 G -> A Yes 2269 C -> T Yes 2325 G -> T Yes WO 2005/072053 PCT/IB2005/000928 687 2465 C -> T Yes 2566 C -> TYes 2881 A ->G No Variant protein HUMPHOSLIP PEA_2_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMPHOSLIPPEA_2_TI9. An alignment is given to the known protein (Phospholipid transfer protein precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HUMPHOSLIP PEA 2_P12 and PLTP_HUMAN: 1.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA 2 P12, comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH FYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINAS 15 AEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRF LLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRG AFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDK VPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVP PDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLK 20 TMLQIGVMPMLN corresponding to amino acids 1 - 427 of PLTPHUMAN, which also corresponds to amino acids 1 - 427 of HUMPHOSLIP_PEA_2_P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GKAGV corresponding to amino acids 428 - 432 of HUMPHOSLIP PEA 2 P12, wherein said 25 first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMIPHOSLIPPEA_2_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 688 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GKAGV in HUMPHOSLIPPEA_2_P12. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HUMPHOSLIPPEA_2_P12 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 9, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P12 sequence provides support for the deduced sequence of this 15 variant protein according to the present invention). Table 9 - Amino acid mutations SNP position(s) on amino acid Alternative ami no acid(s) Previously known SNP? sequence 16 H -> R Yes 18 E ->V Yes 81 D ->H Yes 124 S ->Y Yes 160 T-> No 160 T ->N No 208 S->F Yes 213 V-> No 235 R ->P No 235 R-> No 245 N-> No 255 P-> No WO 2005/072053 PCT/IB2005/000928 689 296 P-> No 369 M-> No 380 R -> W Yes 387 Q -> No 410 L -> * No 425 M -> I Yes The glycosylation sites of variant protein HUMPHOSLIP-PEA-2 P12, as compared to the known protein Phospholipid transfer protein precursor, are described in Table 10 (given according to their position(s) on the amino acid sequence in the first column; the second column 5 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 10 - Glycosylation site(s) Position(s) on knw amino Present in variant protein? Position in variant protein? -acid sequence 94 Yes 94 143 Yes 143 64 Yes 64 245 Yes 245 398 Yes 398 117 Yes 117 Variant protein HUMPHOSLIPPEA_2 P12 is encoded by the following transcript(s): 10 HUMPHOSLIPPEA_2_Ti9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA_2_T19 is shown in bold; this coding portion starts at position 276 and ends at position 1571. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is 15 known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P12 WO 2005/072053 PCT/IB2005/000928 690 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs SNP position on nucleotide, Alternative nucleic acid PrIeviously 1kown SNP? sequen ce 174 G ->T No 175 A ->T No 322 A ->G Yes 328 A ->T Yes 431 G ->A Yes 516 G ->C Yes 644 G ->A Yes 646 C ->A Yes 754 C-> No 754 C ->A No 836 C ->T Yes 898 C ->T Yes 913 T-> No 979 G -> No 979 G ->C No 1008 A-> No 1038 C-> No 1161 C-> No 1322 C ->T Yes 1382 G No 1413 C ->T Yes 1434 C-> No 1504 T ->A No 1515 C ->T Yes WO 2005/072053 PCT/IB2005/000928 691 1550 G ->C Yes 1690 T ->A Yes 1818 C ->A Yes 1837 C ->T No 1917 C ->T Yes 1933 A ->G No 1933 A ->T No 1998 A ->G Yes 2022 T ->A No 2099 G -> T Yes 2232 G -> A Yes 2261 G ->T Yes 2441 G ->A Yes 2637 C ->T Yes 2693 G ->T Yes 2833 C ->T Yes 2934 C ->T Yes 3249 A ->G No Variant protein HUMPHOSLIPPEA_2_P30 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMPHOSLIPPEA_2_T6. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither 10 trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMPHOSLIPPEA_2_P30 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) WO 2005/072053 PCT/IB2005/000928 692 on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P30 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 12 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 16 H ->R Yes 18 E ->V Yes 37 R-> Q Yes Variant protein HUMPHOSLIPPEA_2_P30 is encoded by the following transcript(s): HUMPHOSLIPPEA_2_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA_2_T6 is shown in bold; this coding 10 portion starts at position 276 and ends at position 431. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P30 sequence provides support for the deduced sequence of this variant protein according to the present invention). 15 Table 13 - Nucleic acid SNPs SNP position on nucleotide Alternative nicleic acid Previouslyknown SNP? sequence 174 G ->T No 175 A ->T No 322 A -> G Yes 328 A ->T Yes 385 G ->A Yes 470 G->C Yes 598 G ->A Yes WO 2005/072053 PCT/IB2005/000928 693 600 C ->A Yes 708 C-> No 708 C ->A No 790 C ->T Yes 852 C ->T Yes 867 T-> No 933 G-> No 933 G ->C No 962 A -> No 992 C-> No 1115 C-> No 1276 C ->T Yes 1336 G-> No 1367 C ->T Yes 1388 C-> No 1458 T ->A No 1469 C -> T Yes 1504 G->C Yes 1561 T -> A Yes 1689 C ->A Yes 1708 C ->T No 1788 C ->T Yes 1804 A->G No 1804 A->T No 1869 A->G Yes 1893 T->A No 1970 G -> T Yes 2103 G -> A Yes 2132 G -> T Yes 2312 G -> A Yes WO 2005/072053 PCT/IB2005/000928 694 2508 C ->T Yes 2564 G ->T Yes 2704 C -> T Yes 2805 C ->T Yes 3120 A G No Variant protein HUMPHOSLIPPEA_2_P31 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMPHOSLIPPEA_2_T7. An alignment is given to the known protein (Phospholipid transfer protein precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between HUMPHOSLIP PEA_2 P31 and PLTPHUMAN: 1.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA_2_P31, comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH FYYNISE corresponding to amino acids 1 - 67 of PLTPHUMAN, which also corresponds to 15 amino acids I - 67 of HUMPHOSLIP PEA_2 P31, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence PGLERGADKFPVVGGSSLFLALDLTLRPPVG corresponding to amino acids 68 - 98 of HUMPHOSLIP PEA_2_P31, wherein said first amino acid sequence and second amino acid 20 sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMPHOSLIPPEA_2_P31, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence PGLERGADKFPVVGGSSLFLALDLTLRPPVG in HUMPHOSLIPPEA_2_P31. 25 WO 2005/072053 PCT/IB2005/000928 695 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignaIP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 5 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein HUMPHOSLIPPEA_2_P31 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates 10 whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P31 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s Previously known SNP? sequence 16 H-> R Yes 18 E ->V Yes 15 The glycosylation sites of variant protein HUMPHOSLIPPEA_2_P31, as compared to the known protein Phospholipid transfer protein precursor, are described in Table 15 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). 20 Table 15 - Glycosylation site(s) Positions) on known amino Present in variant protein? Position in variant protein? acid sequence 94 No 143 No 64 Yes 64 WO 2005/072053 PCT/IB2005/000928 696 245 No 398 No 117 No Variant protein HUMPHOSLIPPEA_2_P31 is encoded by the following transcript(s): HUMPHOSLIPPEA_2_T7, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA_2_T7 is shown in bold; this coding 5 portion starts at position 276 and ends at position 569. The transcript also has the following SNPs as listed in Table 16 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIP PEA _2_P31 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 16 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 174 G->T No 175 A -> T No 322 A ->G Yes 328 A ->T Yes 431 G ->A Yes 608 G ->C Yes 736 G ->A Yes 738 C -> A Yes 846 C -> No 846 C ->A No 928 C->T Yes 990 C ->T Yes 1005 T-> No 1071 G-> No 1071 G ->C No WO 2005/072053 PCT/IB2005/000928 697 1100 A-> No 1130 C-> No 1253 C-> No 1414 C ->T Yes 1474 G-> No 1505 C ->T Yes 1526 C-> No 1596 T ->A No 1607 C ->T Yes 1642 G ->C Yes 1699 T ->A Yes 1827 C ->A Yes 1846 C ->T No 1926 C ->T Yes 1942 A ->G No 1942 A ->T No 2007 A -> G Yes 2031 T-> A No 2108 G-> T Yes 2241 G-> A Yes 2270 G-> T Yes 2450 G->A Yes 2646 C -> T Yes 2702 G -> T Yes 2842 C -> T Yes 2943 C -> T Yes 3258 A ->G No WO 2005/072053 PCT/IB2005/000928 698 Variant protein HUMPHOSLIPPEA_2_P33 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) HUMPHOSLIPPEA_2_T14. An alignment is given to the known protein (Phospholipid transfer protein precursor) at the end of the application. One or more alignments to one or more 5 previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between HUMPHOSLIPPEA_2_P33 and PLTPHUMAN: 1.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA_2_P33, 10 comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH FYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINAS AEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRF LLNQQ corresponding to amino acids 1 - 183 of PLTPHUMAN, which also corresponds to 15 amino acids 1 - 183 of HUMPHOSLIPPEA_2_P33, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL corresponding to amino acids 184 - 200 of HUMPHOSLIPPEA_2_P33, wherein said first amino acid sequence and second amino acid 20 sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMPHOSLIPPEA_2_P33, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL in HUMPHOSLIPPEA_2_P33. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 30 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.

WO 2005/072053 PCT/IB2005/000928 699 Variant protein HUMPHOSLIPPEA_2_P33 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 17, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 5 HUMPHOSLIPPEA_2_P33 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 17 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 16 H ->R Yes 18 E ->V Yes 81 D -> H Yes 124 S ->Y Yes 160 T -> No 160 T -> N No The glycosylation sites of variant protein HUMPHOSLIPPEA_2 P33, as compared to 10 the known protein Phospholipid transfer protein precursor, are described in Table 18 (given according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 18 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 94 Yes 94 143 Yes 143 64 Yes 64 245 No 398 No WO 2005/072053 PCT/IB2005/000928 700 117 Yes 117 Variant protein HUMPHOSLIPPEA_2_P33 is encoded by the following transcript(s): HUMPHOSLIPPEA_2_T14, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA_2_T14 is shown in bold; this 5 coding portion starts at position 276 and ends at position 875. The transcript also has the following SNPs as listed in Table 19 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P33 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 19 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 174 G ->T No 175 A ->T No 322 A ->G Yes 328 A ->T Yes 431 G ->A Yes 516 G ->C Yes 644 G ->A Yes 646 C ->A Yes 754 C-> No 754 C ->A No 921 C -> T Yes 983 C ->T Yes 998 T-> No 1064 G-> No 1064 G ->C No 1093 A-> No WO 2005/072053 PCT/IB2005/000928 701 1123 C-> No 1246 C-> No 1407 C -> T Yes 1467 G-> No 1498 C ->T Yes 1519 C-> No 1589 T ->A No 1600 C ->T Yes 1635 G ->C Yes 1692 T ->A Yes 1820 C->A Yes 1839 C ->T No 1919 C ->T Yes 1935 A ->G No 1935 A ->T No 2000 A -> G Yes 2024 T -> A No 2101 G -> T Yes 2234 G -> A Yes 2263 G -> T Yes 2443 G -> A Yes 2639 C -> T Yes 2695 G ->T Yes 2835 C ->T Yes 2936 C ->T Yes 3251 A ->G No Variant protein HUMPHOSLIP_PEA_2_P34 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) WO 2005/072053 PCT/IB2005/000928 702 HUMPHOSLIPPEA_2_Ti6. An alignment is given to the known protein (Phospholipid transfer protein precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each 5 such aligned protein is as follows: Comparison report between HUMPHOSLIPPEA_2_P34 and PLTPHUMAN: 1.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA_2_P34, comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH 10 FYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYNAS AEGVSIRTGLELSRDPAGRMKVSNVSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRF LLNQQICPVLYHAGTVLLNSLLDTVPV corresponding to amino acids 1 - 205 of PLTPHUMAN, which also corresponds to amino acids 1 - 205 of HUMPHOSLIPPEA_2_P34, and a second amino acid sequence being at least 70%, optionally 15 at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence LWTSLLALTIPS corresponding to amino acids 206 - 217 of HUMPHOSLIPPEA_2_P34, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of HUMPHOSLIP PEA_2 P34, comprising 20 a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence LWTSLLALTIPS in HUMPHOSLIPPEA_2_P34. The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 30 Variant protein HUMPHOSLIP PEA_2_P34 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 20, (given according to their position(s) WO 2005/072053 PCT/IB2005/000928 703 on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P34 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 20 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 16 H ->R Yes 18 E ->V Yes 81 D ->H Yes 124 S ->Y Yes 160 T-> No 160 T ->N No 211 L -No The glycosylation sites of variant protein HUJMPHOSLIPPEA_2_P34, as compared to the known protein Phospholipid transfer protein precursor, are described in Table 21 (given according to their position(s) on the amino acid sequence in the first column; the second column 10 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 21 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 94 Yes 94 143 Yes 143 64 Yes 64 245 No 398 No 117 Yes 117 WO 2005/072053 PCT/IB2005/000928 704 Variant protein HUMPHOSLIPPEA_2_P34 is encoded by the following transcript(s): HUMPHOSLIPPEA_2_Ti6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA 2_T16 is shown in bold; this 5 coding portion starts at position 276 and ends at position 926. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P34 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 22 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously kiown SNP? sequence 174 G ->T No 175 A ->T No 322 A ->G Yes 328 A ->T Yes 431 G ->A Yes 516 G ->C Yes 644 G ->A Yes 646 C ->A Yes 754 C-> No 754 C ->A No 836 C ->T Yes 891 C ->T Yes 906 T-> No 972 G-> No 972 G -> C No 1001 A-> No 1031 C-> No WO 2005/072053 PCT/IB2005/000928 705 1154 C-> No 1315 C ->T Yes 1375 G-> No 1406 C ->T Yes 1427 C-> No 1497 T ->A No 1508 C ->T Yes 1543 G ->C Yes 1600 T ->A Yes 1728 C ->A Yes 1747 C ->T No 1827 C ->T Yes 1843 A ->G No 1843 A ->T No 1908 A ->G Yes 1932 T ->A No 2009 G ->T Yes 2142 G -A Yes 2171 G -T Yes 2351 G -A Yes 2547 C -T Yes 2603 G -T Yes 2743 C -> T Yes 2844 C ->T Yes 3159 A ->G No Variant protein HUMPHOSLIPPEA_2_P35 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 HUMPHOSLIPPEA_2_T18. An alignment is given to the known protein (Phospholipid WO 2005/072053 PCT/IB2005/000928 706 transfer protein precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between HUMPHOSLIPPEA_2_P35 and PLTP HUMAN: 1.An isolated chimeric polypeptide encoding for HUMPHOSLIPPEA_2_P35, comprising a first amino acid sequence being at least 90 % homologous to MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGH FYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWF corresponding to 10 amino acids 1 - 109 of PLTPHUMAN, which also corresponds to amino acids 1 - 109 of HUMPHOSLIPPEA_2_P35, a second amino acid sequence bridging amino acid sequence comprising of L, a third amino acid sequence being at least 90 % homologous to KVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 163 - 183 of PLTPHUMAN, which also corresponds to amino acids 111 - 131 of HUMPHOSLIPPEA_2 P35, and a fourth 15 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VWAATGRRVARVGMLSL corresponding to amino acids 132 - 148 of HUMPHOSLIPPEA_2_P35, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a 20 sequential order. 2.An isolated polypeptide encoding for an edge portion of HUMPHOSLIPPEA_2_P35, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 25 least about 50 amino acids in length, wherein at least two amino acids comprise FLK having a structure as follows (numbering according to HUMPHOSLIPPEA 2_P35): a sequence starting from any of amino acid numbers 109-x to 109; and ending at any of amino acid numbers 111 + ((n-2) - x), in which x varies from 0 to n-2. 3.An isolated polypeptide encoding for a tail of HUMPHOSLIPPEA_2_P35, comprising 30 a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 707 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VWAATGRRVARVGMLSL in HUMPHOSLIPPEA_2_P35. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 10 Variant protein HUMPHOSLIPPEA_2_P35 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P35 sequence provides support for the deduced sequence of this 15 variant protein according to the present invention). Table 23 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SN? 16 H ->R Yes 18 E ->V Yes 81 D ->H Yes The glycosylation sites of variant protein HUMPHOSLIP PEA_2 P35, as compared to the known protein Phospholipid transfer protein precursor, are described in Table 24 (given 20 according to their position(s) on the amino acid sequence in the first column; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 24 - Glycosylation site(s) WO 2005/072053 PCT/IB2005/000928 70 B Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 94 Yes 94 143 No 64 Yes 64 245 No 398 No 117 No Variant protein HUMPHOSLIPPEA_2_P35 is encoded by the following transcript(s): HUMPHOSLIPPEA_2_Ti 8, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript HUMPHOSLIPPEA 2 _T 8 is shown in bold; this 5 coding portion starts at position 276 and ends at position 719. The transcript also has the following SNPs as listed in Table 25 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein HUMPHOSLIPPEA_2_P35 sequence provides support for the deduced sequence of this variant protein according to the 10 present invention). Table 25 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic adid Previously known SNP? sequence G 174 G -> T No 175 A->T No 322 A ->G Yes 328 A ->T Yes 431 G ->A Yes 516 G ->C Yes 765 C ->T Yes 827 C ->T Yes WO 2005/072053 PCT/IB2005/000928 709 842 T-> No 908 G-> No 908 G ->C No 937 A-> No 967 C-> No 1090 C-> No 1251 C ->T Yes 1311 G-> No 1342 C ->T Yes 1363 C-> No 1433 T ->A No 1444 C ->T Yes 1479 G ->C Yes 1536 T ->A Yes 1664 C ->A Yes 1683 C ->T No 1763 C ->T Yes 1779 A ->G No 1779 A ->T No 1844 A ->G Yes 1868 T -> A No 1945 G ->T Yes 2078 G ->A Yes 2107 G ->T Yes 2287 G -> A Yes 2483 C -> T Yes 2539 G ->T Yes 2679 C ->T Yes 2780 C ->T Yes 3095 A->G No WO 2005/072053 PCT/IB2005/000928 710 As noted above, cluster HUMPHOSLIP features 53 segment(s), which were listed in 5 Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 10 Segment cluster HUMPHOSLIPPEA_2_node_0 according to the present invention is supported by 150 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): I-IUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2-T14, HUMPHOSLIPPEA_2-T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA_2_T19. 15 Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 1 264 HUMPHOSLIP PEA_2 T7 1 264 HUMPHOSLIP PEA_2_T14 1 264 HUMPHOSLIPPEA_2_T16 1 264 HUMPHOSLIPPEA_2 T17 1 264 HUMPHOSLIPPEA_2_T18 1 264 HIUMPHOSLIP PEA 2_T19 1 264 Segment cluster HUMPHOSLIPPEA_2 node_19 according to the present invention is 20 supported by 186 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, WO 2005/072053 PCT/IB2005/000928 711 HUMPHOSLIP PEA_2 T7, HUMPHOSLIP PEA 2 T14, HUMPHOSLIPPEA_2_T16 and HUMPHOSLIPPEA_2_T19. Table 27 below describes the starting and ending position of this segment on each transcript. Table 27 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 559 714 HUMPHOSLIP PEA_2 T7 697 852 HUMPHOSLIPPEA_2_T14 605 760 HUMPHOSLIPPEA_2 T16 605 760 HUMPHOSLIP PEA_2_T19 605 760 5 Segment cluster HUMPHOSLIP-PEA 2 node_34 according to the present invention is supported by 191 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 10 HUMPHOSLIPPEA_2_T7, HUMPHOSLIP PEA-2_T14, HUMPHOSLIP PEA_2_T16, HUMPHOSLIPPEA 2_T17, HUMPHOSLIPPEA 2 T18 and HUMPHOSLIP PEA_2_T19. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 971 1111 HUMPHOSLIPPEA_2_T7 1109 1249 HUMPHOSLIPPEA_2_T14 1102 1242 HUMPHOSLIPPEA_2 T16 1010 1150 HUMPHOSLIPPEA_2_T17 732 872 HUMPHOSLIP.PEA_2_T18 946 1086 HUMPHOSLIP PEA 2_T19 1017 1157 WO 2005/072053 PCT/IB2005/000928 712 Segment cluster HUMPHOSLIPPEA_2_node_68 according to the present invention is supported by 131 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 29 below describes the starting and ending position of this segment on each transcript. Table 29 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1867 2285 HUMPHOSLIPPEA_2_T7 2005 2423 HUMPHOSLIPPEA_2_T14 1998 2416 HUMPHOSLIPPEA_2_T16 1906 2324 HUMPHOSLIPPEA_2_T17 1628 2046 HUMPHOSLIPPEA_2_T18 1842 2260 HUMPHOSLIPPEA_2_T19 1996 2414 10 Segment cluster HUMPHOSLIPPEA_2_node_70 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 15 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 713 HUMPHOSLIPPEA_2 T6 2298 2529 HUMPHOSLIPPEA_2_T7 2436 2667 HUMPHOSLIP PEA_2 T14 2429 2660 HUMPHOSLIPPEA_2_T16 2337 2568 HUMPHOSLIPPEA_2_Ti? 2059 2290 HUMPHOSLIP PEA_2_TI8 2273 2504 HUIMPHOSLIPPEA_2_T19 2427 2658 Segment cluster HUMPHOSLIPPEA_2_node_75 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMPHOSLIP PEA_2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2 T16, HUMPHOSLIPPEA_2_17, HUMPHOSLIPPEA_218 and HUMPHOSLIP PEA 2_19. Table 31 below describes the starting and ending position of this segment on each transcript. Table 31 - Segment location on transcripts Transcript name Segment Sedgent starig position ndin osto HUMPHOSLIPPEA_2_T6 2846 3125 HUMPHOSLIPPEA_2 T7 2984 3263 HUMPHOSLIPPEA_2 14 2977 3256 HUMPHOSLIPPEA_2_16 2885 3164 HUMPHOSLIPPEA_2 T17 2607 2886 HUMPHOSLIPPEA_2 18 2821 3100 HUMPHOSLIPPEA_219 2975 3254 10 WO 2005/072053 PCT/IB2005/000928 714 According to an optional embodiment of the present invention, short segments related to the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. 5 Segment cluster HUMPHOSLIPPEA_2_node_2 according to the present invention is supported by 159 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA 2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIP PEA_2_T16, HUMPHOSLIPPEA_2_TI7, HUMPHOSLIPPEA_2_TI8 and HUMPHOSLIP PEA 2 TI 9. 10 Table 32 below describes the starting and ending position of this segment on each transcript. Table 32 - Segment location on transcripts Transcript nane Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 265 337 HUMPHOSLIPPEA_2 T7 265 337 HUMPHOSLIPPEA_2_T14 265 337 HUJMPHOSLIPPEA 2_T16 265 337 HUMPHOSLIPPEA 2_T17 265 337 HUMPHOSLIP PEA_2_T18 265 337 HUMPHOSLIPPEA 2_T19 265 337 Segment cluster HUMPHOSLIP PEA_2_node_3 according to the present invention can 15 be found in the following transcript(s): HUMPHOSLIP PEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 715 Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T7 338 355 HUMPHOSLIPPEA_2_T14 338 355 HUMPHOSLIP PEA_2_T16 338 355 HUMPHOSLIP PEA_2 T17 338 355 HUMPHOSLIPPEA_2_TI8 338 355 HUMPHOSLIPPEA_2_T19 338 355 Segment cluster HUMPHOSLIPPEA_2_node_4 according to the present invention can be found in the following transcript(s): HUMPHOSLIP PEA_2 T7, 5 HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA 2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 34 below describes the starting and ending position of this segment on each transcript. Table 34 - Segment location on transcripts Transcript name Segment Segment starting posto, ending position HUMPHOSLIP PEA_2_T7 356 375 HUMPHOSLIP PEA_2_T14 356 375 HUMPHOSLIPPEA_2_T16 356 375 HUMPHOSLIP PEA_2_T17 356 375 HUMPHOSLIP PEA 2_T18 356 375 HUMPHOSLIP PEA 2_T19 356 375 10 Segment cluster HUMPHOSLIPPEA_2_node_6 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA2._T16, HUMPHOSLIPPEA_2_T17, WO 2005/072053 PCT/IB2005/000928 716 HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA 2 T19. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 - Segment location on transcripts Transcript name, Segment " segment starting position ending position HUMPHOSLIP PEA_2 T7 376 383 HUMPHOSLIPPEA_2_T14 376 383 HUMPHOSLIPPEA_2 16 376 383 HUMPHOSLIP PEA_2 T17 376 383 HUMPHOSLIPPEA_2_T18 376 383 HUMPHOSLIP PEA 2_19 376 383 5 Segment cluster HUMPHOSLIP PEA_2_node_7 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2 T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_17, HUMPHOSLIP PEA_2 T18 and HUMPHOSLIP PEA 2 19. 10 Table 36 below describes the starting and ending position of this segment on each transcript. Table 36 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA 2_T6 338 343 HUMPHOSLIPPEA_2_T7 384 389 HUMPHOSLIPPEA_214 384 389 HUMPHOSLIPPEA_2_T16 384 389 HUMPHOSLIPPEA_2_T17 384 389 HUMPHOSLIP PEA_2_18 384 389 HUMPHOSLIPPEA_2_19 384 389 WO 2005/072053 PCT/IB2005/000928 717 Segment cluster HUMPHOSLIP PEA 2 node_8 according to the present invention is supported by 171 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA 2 T6, 5 HUMPHOSLIP_PEA_2_T7, HUMPHOSLIPPEA 2 T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA 2 T19. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript nam, Semn -Segment starting position ending position HUMPHOSLIP PEA 2 T6 344 378 HUMPHOSLIPPEA_2_T7 390 424 HUMPHOSLIP PEA_2_T14 390 424 HUMPHOSLIPPEA_2 T16 390 424 HUMPHOSLIP PEA_2_T17 390 424 HUMPHOSLIP PEA 2 T18 390 424 HUMPHOSLIPPEA_2_T19 390 424 10 Segment cluster HUMPHOSLIPPEA_2_node_9 according to the present invention is supported by 168 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, 15 HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 379 429 WO 2005/072053 PCT/IB2005/000928 718 HUMPHOSLIP_PEA_2 T7 425 475 HUMPHOSLIPPEA_2_T14 425 475 HUMPHOSLIP_PEA_2_T16 425 475 HUMPHOSLIP PEA_2_T17 425 475 HUMPHOSLIP PEA 2 T18 425 475 HUMPHOSLIP PEA_2_T19 425 475 Segment cluster HUMPHOSLIP PEA 2 node_14 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMPHOSLIP _PEA_2_T7. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T7 476 567 10 Segment cluster HUMPHOSLIP_PEA_2 node_15 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIP PEA_2 T14, HUMPHOSLIP_PEA_2_T16, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA 2 T19. Table 40 below describes the starting and ending position of this segment on each transcript. 15 Table 40 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA 2 T6 430 445 HUMPHOSLIP PEA 2 T7 568 583 HUMPHOSLIPPEA 2_T14 476 491 WO 2005/072053 PCT/IB2005/000928 719 HUMPHOSLIP PEA 2_T16 476 491 HUMPHOSLIPPEA_2_T18 476 491 HUMPHOSLIPPEA_2_T19 476 491 Segment cluster HUMPHOSLIPPEA_2_node_16 according to the present invention is supported by 179 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIP PEA_ -T6, HUMPHOSLIP_PEA 2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_TIS and HUMPHOSLIPPEA_2_T19. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segmeit starting position. ending position HUMPHOSLIPPEA_2_T6 446 534 HUMPHOSLIPPEA_2_T7 584 672 HUMPHOSLIP PEA_2_T14 492 580 HUMPHOSLIP PEA_2_T16 492 580 HUMPHOSLIPPEA_2 T18 492 580 HUMPHOSLIP PEA 2_T19 492 580 10 Segment cluster HUMPHOSLIPPEA_2_node_17 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2-T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, 15 HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 42 below describes the starting and ending position of this segment on each transcript. Table 42 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 720 Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 535 558 HUMPHOSLIP PEA_2_T7 673 696 HUMPHOSLIP PEA_2_T14 581 604 HUMPHOSLIP PEA 2_T16 581 604 HUMPHOSLIPPEA_2_T18 581 604 HUMPHOSLIPPEA 2_T19 581 604 Segment cluster HUMPHOSLIPPEA_2_node_23 according to the present invention is supported by 168 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, -IUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIP PEA_2 T17, HUMPHOSLIPPEA 2 T18 and HUMPHOSLIPPEA 2_T19. Table 43 below describes the starting and ending position of this segment on each transcript. Table 43 - Segment location on transcripts Transcript name Seement Segment starting position enigposition HUMPHOSLIPPEA_2_T6 715 766 HUMPHOSLIPPEA_2_T7 853 904 HUMPHOSLIP PEA_2_T14 761 812 HUMPHOSLIP PEA_2_T16 761 812 HUMPHOSLIP PEA_2_T17 476 527 HUMPHOSLIP PEA 2_T18 605 656 HUMPHOSLIP PEA_2 T19 761 812 10 Segment cluster HUMPHOSLIPPEA 2 node_24 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, WO 2005/072053 PCT/IB2005/000928 721 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIP-PEA_217, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name segment, segment, starting position ending position HUMPHOSLIPPEA_2_T6 767 778 HUMPHOSLIP PEA_2_T7 905 916 HUMPHOSLIPPEA_2_T14 813 824 HUMPHOSLIP PEA_2_16 813 824 HUMPHOSLIPPEA_217 528 539 HUMPHOSLIPPEA_2 T18 657 668 HUMPHOSLIP PEA 2_T19 813 824 5 Segment cluster HUMPHOSLIP PEA_2_node_25 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_14 and 10 HUMPHOSLIPPEA_2_T18. Table 45 below describes the starting and ending position of this segment on each transcript. Table 45 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T14 825 909 HUMPHOSLIP PEA_2_T18 669 753 15 Segment cluster HUMPHOSLIPPEA_2_node_26 according to the present invention is supported by 163 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, WO 2005/072053 PCT/IB2005/000928 722 HUMPHOSLIP PEA 2 T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIP PEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA 2_T6 779 842 HUMPHOSLIPPEA_2_T7 917 980 HUMPHOSLIPPEA_2_T14 910 973 HUMPHOSLIP PEA_2_T16 825 888 HUMPHOSLIPPEA_2 T17 540 603 HUMPHOSLIP PEA_2_T18 754 817 HUMPHOSLIPPEA_2_T19 825 888 5 Segment cluster HUMPHOSLIPPEA_2_node_29 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIP PEA_2_T17, 10 HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA 2 T19. Table 47 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 843 849 HUMPHOSLIP PEA_2_T7 981 987 HUMPHOSLIP PEA_2_T14 974 980 HUMPHOSLIP PEA_2_T17 604 610 HUMPHOSLIPPEA_2_T18 818 824 HUMPHOSLIP PEA 2_T19 889 895 WO 2005/072053 PCT/IB2005/000928 723 Segment cluster HUMPHOSLIPPEA_2_node_30 according to the present invention is supported by 181 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_218 and HUMPHOSLIPPEA_2_T19. Table 48 below describes the starting and ending position of this segment on each transcript. Table 48 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 850 934 HUMPHOSLIP PEA_2_T7 988 1072 HUMPHOSLIPPEA_214 981 1065 HUMPHOSLIP PEA_2_16 889 973 HUMPHOSLIPPEA_2_17 611 695 HUMPHOSLIP PEA 2_T18 825 909 HUMPHOSLIPPEA 2_T19 896 980 10 Segment cluster HUMPHOSLIPPEA_2_node_33 according to the present invention is supported by 173 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 15 HUMPHOSLIP_PEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_19. Table 49 below describes the starting and ending position of this segment on each transcript. Table 49 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 724 HUMPHOSLIPPEA_2_T6 935 970 HUMPHOSLIPPEA_2_T7 1073 1108 HUMPHOSLIP PEA_2 T14 1066 1101 HUMPHOSLIPPEA_2T116 974 1009 HUMPHOSLIP PEA_2_T17 696 731 HUMPHOSLIP PEA_2 T18 910 945 HUMPHOSLIPPEA_2_T19 981 1016 Segment cluster HUMPHOSLIPPEA_2_node_36 according to the present invention is supported by 163 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIP PEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2T117, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA_2_T19. Table 50 below describes the starting and ending position of this segment on each transcript. Table 50 - Segment location on transcripts Transcript name SOgment Segment starting position. ending position HUMPHOSLIP PEA_2 T6 1112 1156 HUMPHOSLIPPEA_2_T7 1250 1294 HUMPHOSLIP PEA_2_T14 1243 1287 HUMPHOSLIPPEA_2_T16 1151 1195 HUMPHOSLIPPEA_2_T17 873 917 HUMPHOSLIP PEA 2_T18 1087 1131 HUMPHOSLIPPEA_2 T19 1158 1202 10 Segment cluster HUMPHOSLIP_PEA 2 node 37 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2_14, HUMPHOSLIPPEA_2_T16, WO 2005/072053 PCT/IB2005/000928 725 HUMPHOSLIPPEA_2_T17, HUMPHOSLIP PEA_2_TIS and HUMPHOSLIP PEA 2 T19. Table 51 below describes the starting and ending position of this segment on each transcript. Table 51 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2 T6 1157 1171 HUMPHOSLIPPEA_2 T7 1295 1309 HUMPHOSLIPPEA_2_T14 1288 1302 HUMPHOSLIP PEA_2_T16 1196 1210 HUMPHOSLIPPEA_2_T17 918 932 HUMPHOSLIPPEA_2 Ti8 1132 1146 HUMPHOSLIPPEA_2_T19 1203 1217 5 Segment cluster HUMPHOSLIP PEA 2 node 39 according to the present invention is supported by 166 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIP PEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, 10 HUMPHOSLIPPEA_2_T17, HUMPHOSLIP PEA_2_T18 and HUMPHOSLIP_PEA_2_T19. Table 52 below describes the starting and ending position of this segment on each transcript. Table 52 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1172 1201 HUMPHOSLIPPEA_2_T7 1310 1339 HUMPHOSLIPPEA-2_T14 1303 1332 HUMPHOSLIPPEA_2_T16 1211 1240 HUMPHOSLIPPEA 2_T17 933 962 HUMPHOSLIPPEA_2_T18 1147 1176 WO 2005/072053 PCT/IB2005/000928 726 HUMPHOSLIP PEA_2_T19 1218 1247 Segment cluster HUMPHOSLIP PEA 2 node 40 according to the present invention is supported by 199 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIP-PEA 2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2 T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIP PEA 2 T18 and HUMPHOSLIP PEA 2 T19. Table 53 below describes the starting and ending position of this segment on each transcript. Table 53 - Segment location on transcripts Transcript name segment Segment starting poSito ending position HUMPHOSLIPPEA_2_T6 1202 1288 HUMPHOSLIPPEA_2_T7 1340 1426 HUMPHOSLIPPEA_2_T14 1333 1419 HUMPHOSLIPPEA_2 T16 1241 1327 HUMPHOSLIP PEA_2_T17 963 1049 HUMPHOSLIPPEA 2 T18 1177 1263 HUMPHOSLIP PEA_2_T19 1248 1334 10 Segment cluster HUMPHOSLIPPEA 2 node_41 according to the present invention is supported by 186 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 15 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 54 below describes the starting and ending position of this segment on each transcript. Table 54 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 727 Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 1289 1318 HUMPHOSLIP PEA_2_T7 1427 1456 HUMPHOSLIP PEA_2_T14 1420 1449 HUMPHOSLIPPEA_2_T16 1328 1357 HUMPHOSLIP PEA_2_T17 1050 1079 HUMPHOSLIPPEA_2_T18 1264 1293 HUMPHOSLIP PEA_2_T19 1335 1364 Segment cluster HUMPHOSLIPPEA_2_node_42 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2 T6, 5 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIP-PEA_2_T17, HUMPHOSLIP PEA_2_T18 and HUMPHOSLIP PEA_2_T19. Table 55 below describes the starting and ending position of this segment on each transcript. Table 55 - Segment location on transcripts ran, riptnam Segment Segment starting position ending position HUMPHOSLIPPEA_2 T6 1319 1336 HUMPHOSLIPPEA_2_T7 1457 1474 HUMPHOSLIPPEA_2 T14 1450 1467 HUMPHOSLIP PEA_2_T16 1358 1375 HUMPHOSLIPPEA_2_T17 1080 1097 HUMPHOSLIPPEA 2_Ti8 1294 1311 HUMPHOSLIPPEA_2_T19 1365 1382 10 Segment cluster HUMPHOSLIPPEA_2 node_44 according to the present invention is supported by 185 libraries. The number of libraries was determined as previously described.

WO 2005/072053 PCT/IB2005/000928 728 This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIP PEA__2 T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_Ti8 and HUMPHOSLIPPEA_2_Ti9. Table 56 below describes the starting and ending position of this segment on each transcript. 5 Table 56 - Segment location on transcripts Transcript name, Seg ent Segment starting position ending position HUMPHOSLIPPEA_2_T6 1337 1363 HUMPHOSLIPPEA_2 T7 1475 1501 HUMPHOSLIP PEA_2_T14 1468 1494 HUMPHOSLIPPEA_2 T16 1376 1402 HUMPHOSLIPPEA_2_T17 1098 1124 HUMPHOSLIP PEA_2 T18 1312 1338 HUMPHOSLIP PEA_2_T19 1383 1409 Segment cluster HUMPHOSLIPPEA_2_node_45 according to the present invention is supported by 197 libraries. The number of libraries was determined as previously described. 10 This segment can be found in the following transcript(s): HUMPHOSLIP PEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 57 below describes the starting and ending position of this segment on each transcript. Table 57 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 1364 1404 HUMPHOSLIPPEA_2_T7 1502 1542 HUMPHOSLIPPEA_2_T14 1495 1535 HUMPHOSLIPPEA_2_T16 1403 1443 WO 2005/072053 PCT/IB2005/000928 729 HUMPHOSLIP PEA_2 T17 1125 1165 HUMPHOSLIP PEA_2_T18 1339 1379 HUMPHOSLIPPEA_2_T19 1410 1450 Segment cluster HUMPHOSLIPPEA 2 node_47 according to the present invention is supported by 223 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2-T16, HUMPHOSLIP PEA_2_T17, HUMPHOSLIPPEA_2_TIS and HUMPHOSLIPPEA_2_T19. Table 58 below describes the starting and ending position of this segment on each transcript. Table 58 - Segment location on transcripts Transcript name Segient Segment -starting position, ending position HUMPHOSLIP PEA_2 T6 1405 1447 HUMPHOSLIPPEA_2 T7 1543 1585 HUMPHOSLIPPEA_2_T14 1536 1578 HUMPHOSLIPPEA_2 T16 1444 1486 HUMPHOSLIP PEA_2_T17 1166 1208 HUMPHOSLIP PEA_2_T18 1380 1422 HUMPHOSLIP PEA 2_T19 1451 1493 10 Segment cluster HUMPHOSLIPPEA_2_node_51 according to the present invention can be found in the following transcript(s): HUMPHOSLIP PEA 2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, 15 HUMPHOSLIP_PEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP_PEA_2_TI9. Table 59 below describes the starting and ending position of this segment on each transcript. Table 59 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 730 Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1448 1462 HUMPHOSLIPPEA_2 T7 1586 1600 HUMPHOSLIP PEA_2_T14 1579 1593 HUMPHOSLIP PEA 2 T16 1487 1501 HUMPHOSLIP PEA 2 T17 1209 1223 HUMPHOSLIP PEA_2_T18 1423 1437 HUMPHOSLIPPEA_2_T19 1494 1508 Segment cluster HUMPHOSLIP PEA 2 node_52 according to the present invention is supported by 235 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIPPEA 2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2 T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_TiS and HUMPHOSLIP PEA_2_T19. Table 60 below describes the starting and ending position of this segment on each transcript. Table 60 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2 T6 1463 1511 HUMPHOSLIPPEA_2_T7 1601 1649 HUMPHOSLIP PEA 2_T14 1594 1642 HUMPHOSLIPPEA_2_T16 1502 1550 HUMPHOSLIPPEA_2_T17 1224 1272 HUMPHOSLIPPEA_2_T18 1438 1486 HUMPHOSLIP PEA_2_T19 1509 1557 10 WO 2005/072053 PCT/IB2005/000928 731 Segment cluster HUMPHOSLIPPEA_2_node_53 according to the present invention is supported by 5 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T19. Table 61 below describes the starting and ending position of this segment on each transcript. 5 Table 61 - Segment location on transcripts Transcript name Segment Segment starting position, ending position HUMPHOSLIP PEA_2 T19 1558 1640 Segment cluster HUMPHOSLIP PEA 2 node_54 according to the present invention is supported by 236 libraries. The number of libraries was determined as previously described. 10 This segment can be found in the following transcript(s): HUMPHOSLIP PEA_2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA 2_T18 and HUMPHOSLIPPEA 2 T19. Table 62 below describes the starting and ending position of this segment on each transcript. Table 62 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA 2_T6 1512 1552 HUMPHOSLIPPEA_2_T7 1650 1690 HUMPHOSLIPPEA_2_T14 1643 1683 HUMPHOSLIPPEA_2_T16 1551 1591 HUJMPHOSLIPPEA_2 T17 1273 1313 HUMPHOSLIPPEA_2 TI8 1487 1527 HUMPHOSLIPPEA_2 T19 1641 1681 15 Segment cluster HUMPHOSLIP PEA_2 node_55 according to the present invention is supported by 232 libraries. The number of libraries was determined as previously described.

WO 2005/072053 PCT/IB2005/000928 732 This segment can be found in the following transcript(s): HUMPHOSLIPPEA 2 T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2 T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIP PEA 2 T18 and HUMPHOSLIP PEA_2_T19. Table 63 below describes the starting and ending position of this segment on each transcript. 5 Table 63 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1553 1588 HUMPHOSLIPPEA_2_T7 1691 1726 HUMPHOSLIPPEA_2 T14 1684 1719 HUMPHOSLIP PEA 2_16 1592 1627 HUMPHOSLIPPEA_2_T17 1314 1349 HUMPHOSLIPPEA_2_T18 1528 1563 HUMPHOSLIPPEA_2 T19 1682 1717 Segment cluster HUMPHOSLIP PEA _2 node 58 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 10 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA 2_T14, HUMPHOSLIP_PEA 2 T16, HUMPHOSLIP_PEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 64 below describes the starting and ending position of this segment on each transcript. Table 64 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1589 1612 HUMPHOSLIPPEA_2_T7 1727 1750 HUMPHOSLIPPEA_2_14 1720 1743 HUMPHOSLIPPEA_216 1628 1651 HUMPHOSLIPPEA_2 T17 1350 1373 WO 2005/072053 PCT/IB2005/000928 733 HUMPHOSLIPPEA_2_T18 1564 1587 HUMPHOSLIP PEA_2_T19 1718 1741 Segment cluster HUMPHOSLIPPEA 2_node_59 according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSL1P_PEA 2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIP PEA 2 T19. Table 65 below describes the starting and ending position of this segment on each transcript. Table 65 - Segment location on transcripts Transcript name Segment Segment startingiposition ending position HUMPHOSLIP PEA_2_T6 1613 1648 HUMPHOSLIP PEA_2_T7 1751 1786 HUMPHOSLIPPEA_2_T14 1744 1779 HUMPHOSLIPPEA_2_T16 1652 1687 HUMPHOSLIPPEA_2_T17 1374 1409 HUMPHOSLIPPEA_2_TIS 1588 1623 HUMPHOSLIPPEA 2_T19 1742 1777 10 Segment cluster HUMPHOSLIPPEA_2_node_60 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, 15 HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 66 below describes the starting and ending position of this segment on each transcript. Table 66 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 734 Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1649 1671 HUMPHOSLIP PEA_2_T7 1787 1809 HUMPHOSLIPPEA_2_T14 1780 1802 HUMPHOSLIP PEA_2_T16 1688 1710 HUMPHOSLIPPEA_2_T17 1410 1432 HUMPHOSLIP PEA_2_T18 1624 1646 HUMPHOSLIPPEA_2 T19 1778 1800 Segment cluster HUMPHOSLIPPEA_2_node_61 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 5 HUMPHOSLIPPEA_2_T7, HUMPHOSLIP PEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 67 below describes the starting and ending position of this segment on each transcript. Table 67 - Segment location on transcripts Transcript name Segment Segrent starting position ending position HUMPHOSLIP PEA_2_T6 1672 1680 HUMPHOSLIPPEA_2_T7 1810 1818 HUMPHOSLIPPEA_2_T14 1803 1811 HUMPHOSLIPPEA_2_T16 1711 1719 HUMPHOSLIP PEA_2_T17 1433 1441 HUMPHOSLIPPEA 2_T18 1647 1655 HUMPHOSLIPPEA 2_T19 1801 1809 10 Segment cluster HUMPHOSLIPPEA_2_node_62 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, WO 2005/072053 PCT/IB2005/000928 735 HUMPHOSLIPPEA_2_T7, HUMPHOSLIP PEA 2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_17, HUMPHOSLIPPEA_2_TI8 and HUMPHOSLIP PEA_2_T19. Table 68 below describes the starting and ending position of this segment on each transcript. Table 68 - Segment location on transcripts Transcipt name Segment Segment starting position ending' position HUMPHOSLIP PEA_2_T6 1681 1703 HUMPHOSLIPPEA_2_T7 1819 1841 HUMPHOSLIP PEA_2_14 1812 1834 HUMPHOSLIP PEA_2_16 1720 1742 HUMPHOSLIPPEA_217 1442 1464 HUMPHOSLIPPEA 2_T18 1656 1678 HUMPHOSLIPPEA_2_T19 1810 1832 5 Segment cluster HUMPHOSLIPPEA_2_node_63 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA 2_T6, HUMPHOSLIPPEA_2T7, HUMPHOSLIP PEA_2_T14, HUMPHOSLIPPEA_2_T16, 10 HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA 2 T18 and HUMPHOSLIP PEA_219. Table 69 below describes the starting and ending position of this segment on each transcript. Table 69 - Segment location on transcripts Transcript name Segment Segment starting position ending position. HUMPHOSLIP PEA_2_T6 1704 1727 HUMPHOSLIPPEA_2_T7 1842 1865 HUMPHOSLIPPEA_2_T14 1835 1858 HUMPHOSLIP PEA_2_16 1743 1766 HUMPHOSLIP PEA_2 17 1465 1488 HUMPHOSLIP PEA_2_T18 1679 1702 WO 2005/072053 PCT/IB2005/000928 '736 HUMPHOSLIP PEA_2_T19 1833 1856 Segment cluster HUMPHOSLIPPEA 2_node_64 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA 2_T6, 5 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 70 below describes the starting and ending position of this segment on each transcript. Table 70 - Segment location on transcripts Transcript name Segment Segment starting position endn I) itiPC HUMPHOSLIPPEA_2 T6 1728 1734 HUMPHOSLIPPEA_2_T7 1866 1872 HUMPHOSLIP PEA_2 T14 1859 1865 HUMPHOSLIPPEA_2_T16 1767 1773 HUMPHOSLIPPEA_2_T17 1489 1495 HUMPHOSLIPPEA_2_T18 1703 1709 HUMPHOSLIP PEA_2_T19 1857 1863 10 Segment cluster HUMPHOSLIPPEA 2 node_65 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. 15 Table 71 below describes the starting and ending position of this segment on each transcript. Table 71 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA 2_T6 1735 1754 WO 2005/072053 PCT/IB2005/000928 737 HUMPIOSLIPPEA_2_T7 1873 1892 HUMPHOSLIP PEA_2_T14 1866 1885 HUMPHOSLIPPEA 2_T16 1774 1793 HUMPHOSLIPPEA_2_T17 1496 1515 HUMPHOSLIP PEA_2_T18 1710 1729 HUMPHOSLIPPEA_2_T19 1864 1883 Segment cluster HUMPHOSLIPPEA_2_node_66 according to the present invention is supported by 180 libraries. The number of libraries was determined as previously described. 5 This segment can be found in the following transcript(s): HUMPHOSLIP PEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 72 below describes the starting and ending position of this segment on each transcript. Table 72 - Segment location on transcripts Transcript name Segment segmnt starting position ending position HUMPHOSLIPPEA_2_T6 1755 1844 HUMPHOSLIP PEA_2_T7 1893 1982 HUMPI-IOSLIPPEA_2_T14 1886 1975 HUMPHOSLIPPEA_2_T16 1794 1883 HUMPHOSLIP PEA_2_T17 1516 1605 HUMPHOSLIP PEA_2_T18 1730 1819 HUMPHOSLIPPEA_2_T19 1884 1973 10 Segment cluster HUMPHOSLIPPEA_2_node_67 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA 2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, WO 2005/072053 PCT/IB2005/000928 738 HUMPHOSLIPPEA 2 TI7, HUMPHOSLIPPEA 2 TI8 and HUMPHOSLIP PEA 2 T19. Table 73 below describes the starting and ending position of this segment on each transcript. Table 73 - Segment location on transcripts Transcript iame Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 1845 1866 HUMPHOSLIP PEA_2_T7 1983 2004 HUMPHOSLIP PEA_2_T14 1976 1997 HUMPHOSLIP PEA_2_T16 1884 1905 HUMPHOSLIPPEA_2_T17 1606 1627 HUMPHOSLIP PEA 2_T18 1820 1841 HUMPHOSLIP PEA 2_T19 1974 1995 5 Segment cluster HUMPHOSLIPPEA_2_node_69 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA 2_T6, HUIPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA 2 T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. 10 Table 74 below describes the starting and ending position of this segment on each transcript. Table 74 - Segment location on transcripts Transcript name Segmn Segment starting position ending position HUMPHOSLIPPEA 2_T6 2286 2297 HTMPHOSLIPPEA_2_T7 2424 2435 HUMPHOSLIPPEA_2_T14 2417 2428 HUMPHOSLIPPEA_216 2325 2336 HUMPHOSLIPPEA_2_T17 2047 2058 HUMPHOSLIP PEA_2_T18 2261 2272 HUMPHOSLIP PEA_2_19 2415 2426 WO 2005/072053 PCT/IB2005/000928 739 Segment cluster HUMPIOSLIPPEA_2_node_71 according to the present invention can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 5 HUMPHOSLIP PEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 75 below describes the starting and ending position of this segment on each transcript. Table 75 - Segment location on transcripts Transcript name Segmeit Segment starting position' ending position HUMPHOSLIPPEA_2_T6 2530 2542 HUMPHOSLIPPEA_2_T7 2668 2680 HUMPHOSLIPPEA_2_T14 2661 2673 HUMPHOSLIP PEA_2_T16 2569 2581 HUMPHOSLIPPEA_2_T17 2291 2303 HUMPHOSLIP PEA_2_T18 2505 2517 HUMPHOSLIPPEA 2_T19 2659 2671 10 Segment cluster HUMPHOSLIPPEA_2_node_72 according to the present invention is supported by 7 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIP PEA 2 T14, HUMPHOSLIPPEA_2_T16, 15 HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_T18 and HUMPHOSLIPPEA_2_T19. Table 76 below describes the starting and ending position of this segment on each transcript. Table 76 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIP PEA_2_T6 2543 2647 WO 2005/072053 PCT/IB2005/000928 740 HUMPHOSLIP PEA_2_T7 2681 2785 HUMPHOSLIP PEA_2_T14 2674 2778 HUMPHOSLIP PEA_2_T16 2582 2686 HUMPHOSLIP PEA_2_T17 2304 2408 HUMPHOSLIPPEA_2 T18 2518 2622 HUMPHOSLIPPEA_2_T19 2672 2776 Segment cluster HUMPHOSLIPPEA-2_node_73 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This 5 segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, HUMPHOSLIPPEA_2_T17, HUMPHOSLIPPEA_2_TI8 and HUMPHOSLIPPEA_2_T19. Table 77 below describes the starting and ending position of this segment on each transcript. Table 77 - Segment location on transcripts Transcript name Segment segInieut starting position' endling. position, HUMPHOSLIP PEA_2_T6 2648 2755 HUMPHOSLIP PEA_2_T7 2786 2893 HUMPHOSLIPPEA_2_T14 2779 2886 HUMPHOSLIP PEA_2_T16 2687 2794 HUMPHOSLIPPEA_2_T17 2409 2516 HUMPHOSLIP PEA_2_TiS 2623 2730 HUMPHOSLIPPEA_2_T19 2777 2884 10 Segment cluster HUMPHOSLIPPEA_2_node_74 according to the present invention is supported by 10 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): HUMPHOSLIPPEA_2_T6, 15 HUMPHOSLIPPEA_2_T7, HUMPHOSLIPPEA_2_T14, HUMPHOSLIPPEA_2_T16, WO 2005/072053 PCT/IB2005/000928 741 HUMPHOSLIP-PEA 2_T17, HUMPHOSLIP PEA 2 T18 and HUMPHOSLIPPEA 2 T19. Table 78 below describes the starting and ending position of this segment on each transcript. Table 78 - Segment location on transcripts Transcript name Segment Segment starting position ending position HUMPHOSLIPPEA_2_T6 2756 2845 HUMIPHOSLIPPEA_2_T7 2894 2983 HUMPHOSLIP PEA_2_T14 2887 2976 HUMPHOSLIP PEA_2_T16 2795 2884 HUMPHOSLIPPEA_2_T17 2517 2606 HUMPHOSLIP PEA 2_T18 2731 2820 HUMPHOSLIPPEA_2_T19 2885 2974 5 Variant protein alignment to the previously known protein: Sequence name: PLTP HUMAN 10 Sequence documentation: Alignment of: HUMPHOSLIPPEA_2_PlO x PLTPHUMAN 15 Alignment segment 1/1: Quality: 3716.00 Escore: 0 Matching length: 398 Total 20 length: 493 WO 2005/072053 PCT/IB2005/000928 742 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 80.73 Total Percent Identity: 80.73 5 Gaps: 1 Alignment: 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 1 0I l I l l I l I lI l l l l I Il l l lI IIlI Il I l I l l 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISE................................. 67 15 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 67 .................................................. 67 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 20 68 ............ .KVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 105 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 200 25 106 DTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPN 155 l i l l l l l l l l l l l l l l i l l l l l l l l I1 1 1 1 1 1 1|1 1 1 1 I | | 201 DTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPN 250 156 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 205 3 0I i l i l l l i l l l i l l i l l l i l l l i l l l [ I i l i l l l1 l l i l l 251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300 WO 2005/072053 PCT/IB2005/000928 743 206 MLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASV 255 1111l11I1i1111lI 11 Il I I I I I |1111 I IIlIlII 11 I II l i i i 301 MLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASV 350 5 256 TIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHS 305 Ii i~ III 1111111i I i~ i Il iiiii 111 IIII IIIii 351 TIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHS 400 10 306 ALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVT 355 401 ALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHEVVT 450 356 NHAGFLTTGADLHFAKGLREVTEKNRPADVRASTAPTPSTAAV 398 15 I I I I i I I I I i i i ~I 1 1 1 1 1 1 1 Ii1i ii1 451 NHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV 493 20 Sequence name: PLTP HUMAN 25 Sequence documentation: Alignment of: HUMPHOSLIPPEA_2 P12 x PLTP HUMAN Alignment segment 1/1: 30 WO 2005/072053 PCT/IB2005/000928 744 Quality: 4101.00 Escore: 0 Matching length: 427 Total length: 427 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 lII lll 1111l11111llllliii llllll1ll1llllllllllll 15 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 20 101 FRRQLLYWFFYDGGYTNASAEGVSTRTGLELSRDPAGRMKVSNVSCQASV 150 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 25 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 200 SIIIIl IIIilII I I II 11 11I I I II I I 1 1 I IIIII I 111 i i i I I I iiI IiI 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 200 201 DTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPN 250 3 0 I I I I I I lI l lilI l Il l l l i Il Ii l 201 DTVPVRSSVDELVGIDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPN 250 WO 2005/072053 PCT/IB2005/000928 745 251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300 SI l ii i 11 11 I I li I I I iI l i ii l i i liii I I I I I I II I i 251 RAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLD 300 5 301 MLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASV 350 i i ii i I ii il I liii 111111111 1 l1i1i11lI 11 301 MLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASV 350 10 351 TIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHS 400 351 TIALVPPDQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHS 400 401 ALESLALIPLQAPLKTMLQIGVMPMLN 427 15 1111 1 i I I I 1 I I I I I II II I I 401 ALESLALIPLQAPLKTMLQIGVMPMLN 427 20 Sequence name: PLTPHUMAN 25 Sequence documentation: Alignment of: HUMPHOSLIPPEA 2 P31 x PLTPHUMAN Alignment segment 1/1: 30 WO 2005/072053 PCT/IB2005/000928 746 Quality: 639.00 Escore: 0 Matching length: 67 Total length: 67 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 11l I I l~ ~ i i i IIIII 1 1 1 1 I I I I 1111 llIIi i I III11 1 III 15 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISE 67 || || I li i l || |i |ii 51 IPDLRGKEGHFYYNISE 67 20 25 Sequence name: PLTP HUMAN Sequence documentation: 30 Alignment of: HUMPHOSLIP PEA 2 P33 x PLTPHUMAN WO 2005/072053 PCT/IB2005/000928 747 Alignment segment 1/1: Quality: 1767.00 Escore: 0 5 Matching length: 184 Total length: 184 Matching Percent Similarity: 100.00 Matching Percent Identity: 99.46 Total Percent Similarity: 100.00 Total Percent 10 Identity: 99.46 Gaps: 0 Alignment: 15 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 2 0I I l Il1 1 1 I I i I I ii Ii I I I l Il I l i l i lI I 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 l I lI I l l 1 i 111i I I I I | I li l I I I I I I 111|| 1111111| ||| 25 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQV 184 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQI 184 30 WO 2005/072053 PCT/IB2005/000928 748 5 Sequence name: PLTPHUMAN Sequence documentation: Alignment of: HUMPHOSLIPPEA 2 P34 x PLTPHUMAN 10 Alignment segment 1/1: Quality: 1971.00 Escore: 0 15 Matching length: 205 Total length: 205 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 20 Identity: 100.00 Gaps: 0 Alignment: 25 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 WO 2005/072053 PCT/IB2005/000928 749 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 lIi ll i ii j j i i ii!i iii, Ill J i ii I JII | ill i 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 5 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 200 ilI~ II 1 1 li i 111 II l I II II li 11111 I||1I1 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLL 200 10 201 DTVPV 205 201 DTVPV 205 15 Sequence name: PLTP HUMAN 20 Sequence documentation: Alignment of: HUMPHOSLIP PEA 2 P35 x PLTPHUMAI . 25 Alignment segment 1/1: Quality: 1158.00 Escore: 0 Matching length: 132 Total 30 length: 184 WO 2005/072053 PCT/IB2005/000928 '750 Matching Percent Similarity: 100.00 Matching PercenL Identity: 98.48 Total Percent Similarity: 71.74 Total Percent Identity: 70.65 5 Gaps: 1 Alignment: 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 1 MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETIT 50 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 15 51 IPDLRGKEGHFYYNISEVKVTELQLTSSELDFQPQQELMLQITNASLGLR 100 101 FRRQLLYWFL........................................ 110 101 FRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSNVSCQASV 150 20 111.............KVYDFLSTFITSGMRFLLNQQV 132 1 I I I 111111 1 1 1 1 I 151 SRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQI 184 25 DESCRIPTION FOR CLUSTER DI11853 Cluster D11853 features 18 transcript(s) and 31 segment(s) of interest, the names for 30 which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3.

WO 2005/072053 PCT/IB2005/000928 751 Table 1 - Transcripts of interest Transcript Name SEQ ID NO: D11853_PEA_1_T1 57 D11853_PEA_1_T3 58 D11853 PEA_1 T7 59 D11853_PEA_1_T8 60 D11853PEA1_T9 61 D11853_PEA 1 TIO 62 D11853_PEA_1_T13 63 D11853_PEA_1_T14 64 D11853_PEA_1 TI5 65 D11853 PEA 1_T16 66 D11853_PEA1 T17 67 D11853_PEA1 T19 68 D11853_PEA 1 T21 69 D11853_PEA1_T23 70 D11853_PEA 1_T24 71 D11853_PEA 1_T25 72 D11853_PEA_1_T26 73 D11853_PEA 1 T27 74 Table 2 - Segments of interest Segment Name SEQ ID NO D11853_PEAI node_3 419 D11853_PEA_1_node_6 420 D11853_PEA1_node_9 421 D11853_PEA_1 node 17 422 D11853_PEA 1_node_21 423 D11853_PEAInode_22 424 WO 2005/072053 PCT/IB2005/000928 752 D11853_PEA1node23 425 D11853_PEA 1_node_25 426 D11853 PEA 1_node_26 427 D11853_PEA1_node_27 428 D11853_PEA 1_node_30 429 D11853_PEA1 node_32 430 D11853_PEA 1_node 0 431 DM1853PEA1 node_1 432 D11853_PEA 1_node_2 433 D11853_PEA1 node_4 434 D11853_PEA 1_node_5 435 D11853_PEA1node_7 436 D11853_PEA1_node_8 437 D11853_PEA 1 node_10 438 D11853 PEA 1_node_12 439 D11853_PEA1 node_13 440 D1853 PEA 1node_14 441 D11853_PEA 1 node_15 442 D11853 PEA1_node_16 443 D11853_PEA1 node_18 444 D11853_PEA1 node_19 445 DM1853PEA1node20 446 D11853_PEA 1 node_24 447 D11853_PEA1 node_28 448 D11853_PEA1node_29 449 Table 3 - Proteins of interest Protein Name SEQ ID NO: Corresponding Transcript(s) D11853_PEA_1_P1 588 D11853_PEA_1_Ti WO 2005/072053 PCT/IB2005/000928 753 D11853_PEA1 P2 589 D11853_PEA_1_T3 D11853_PEA1_P7 590 D11853_PEA_1_T10 D 11853PEAIP9 591 DI 1853_PEA_1_T13 D11853_PEA_1_P1O 592 D11853_PEA1_T14 D11853_PEA1_P11 593 D11853_PEA1_TI5 D11853_PEA_1_P12 594 D11853 PEA 1 T16; D11853_PEA 1_T23 D 11853PEA_1_P14 595 D11853 PEA_1_T19 D11853_PEA1 P16 596 D11853_PEA_1_T24 D11853_PEA1 P18 597 D11853_PEA1_T26 D11853_PEA 1_P19 598 D11853_PEA_1_T27 D11853_PEA_1_P20 599 D11853 PEA_1 T7; D11853_PEA117; D11853_PEA1_T25 D11853_PEA1 P21 600 D11853_PEA1_T8 D11853_PEA1_P22 601 D11853_PEA1_T9 D11853_PEA1 P24 602 D11853_PEA1_T21 These sequences are variants of the known protein Membrane associated protein SLP-2 (SwissProt accession identifier Q9UJZ1; known also according to the synonyms Stomatin-like protein 2; Stomatin- like 2; Hypothetical protein FLJ14499), SEQ ID NO: 637, referred to 5 herein as the previously known protein. The sequence for protein Membrane associated protein SLP-2 is given at the end of the application, as "Membrane associated protein SLP-2 amino acid sequence". The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: ligand, which are annotation(s) related to Molecular Function; and 10 cytoskeleton; membrane, which are annotation(s) related to Cellular Component. The GO assignment relies on information from one or more of the SwissProt/TremB1 Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>.

WO 2005/072053 PCT/IB2005/000928 754 Cluster D11853 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs 5 in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 26 and Table 4. This cluster is overexpressed (at least at a minimum level) in the 10 following pathological conditions: brain malignant tumors, colorectal cancer and a mixture of malignant tumors from different tissues. Table 4 - Normal tissue distribution Name of Tissue Nme adrenal 160 bladder 82 Bone 71 brain 70 colon 31 epithelial 106 general 88 head and neck 0 kidney 71 liver 53 lung 108 lymph nodes 107 breast 158 bone marrow 0 muscle 94 WO 2005/072053 PCT/IB2005/000928 755 ovary 131 pancreas 113 prostate 106 skin 193 stomach 73 Thyroid 0 uterus 140 Table 5 - P values and ratios for expression in cancerous tissue N,,ame of' Tissu P1 P2, ~ R3 SP2 R adrenal 7.4e-01 6.9e-01 9.5e-01 0.4 7.le-01 0.7 bladder 7.0e-01 6.6e-01 6.2e-01 1.1 7.1e-01 1.0 bone 4.9e-01 6.3e-01 7.9e-01 0.9 2.le-01 1.1 brain 7.4e-02 2.0e-02 I.Oe-01 1.5 5.2e-12 3.2 colon 2.6e-03 5.7e-04 9.9e-03 4.3 1.3e-02 4.0 epithelial 3.2e-01 2.5e-02 3.3e-01 1.0 9.1e-08 1.8 general 4.9e-02 2.3e-04 3.6e-03 1.3 1.4e-23 2.2 head and neck 2.le-01 1.le-01 1 1.1 4.2e-01 2.0 kidney 8.6e-01 8.8e-01 9.7e-01 0.4 8.le-01 0.6 liver 5.2e-01 9.le-02 1 0.5 1.0e-01 2.4 lung 7.le-01 7.3e-01 8.9e-01 0.6 1.3e-01 0.9 lymph nodes 5.9e-01 6.6e-01 4.le-01 1.3 6.0e-01 0.9 breast 1.9e-01 1.5e-01 2.6e-01 1.0 1.4e-01 1.3 bone marrow 4.3e-01 2.5e-01 1 3.3 1.5e-01 4.0 muscle 6.7e-01 5.le-01 1 0.2 1.6e-02 0.7 ovary 6.3e-01 4.9e-01 6.9e-01 0.9 2.8e-01 1.0 pancreas 2.2e-01 1.7e-01 3.8e-02 0.9 5.5e-05 1.6 prostate 8.7e-01 8.3e-01 8.3e-01 0.7 1.Se-01 1.0 skin 5.0e-01 4.9e-01 6.9e-01 0.8 3.3e-02 0.9 WO 2005/072053 PCT/IB2005/000928 756 stomach 5.2e-01 3.9e-01 1 0.4 2.0e-01 1.5 Thyroid 4.6e-01 4.6e-O1 1 1.2 1 1.2 uterus 6.le-01 3.6e-01 1.7e-01 1.0 1.2e-01 1.3 As noted above, cluster DI11853 features 18 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Membrane associated protein SLP-2. A description of each variant protein according to the present invention is now provided. 5 Variant protein DI11853_PEA_1_P1 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) D11853_PEA_1_Ti. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more aligmnents to one or more previously 10 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between D1 1853_PEA_1_P1 and Q9P042 (SEQ ID NO 639): I.An isolated chimeric polypeptide encoding for D11853_PEA_1_P1, comprising a first 15 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of D11853_PEA_1_P1, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP 20 EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13 - 187 of Q9P042, which also corresponds to amino acids 27 201 of D11853_PEA_1 P1, a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_1_P1, and a third amino acid sequence being at least 90 % homologous to 25 TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRIL AAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGA LTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 189 - 342 of Q9PO42, which also corresponds to amino acids 203 - 356 of D11853_PEA_1_P1, WO 2005/072053 PCT/IB2005/000928 757 wherein said first amino acid sequence, second amino acid sequence, bridging amino acid and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of DI11853_PEA_1_P1, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D 1853_PEA_1_P1. Comparison report between DI 853_PEA_1_P1 and BAC85377 (SEQ ID NO 640): 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P1, comprising a first 10 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to 15 amino acids 1 - 109 of D1l853_PEA_1_Pl, a second amino acid sequence being at least 90 % homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino 20 acids I - 159 of BAC85377, which also corresponds to amino acids 110 - 268 of Dl 1853_PEA_1_P1, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP 25 GTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 269 - 356 of DI 1853_PEA_1_P1, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1 P1, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence WO 2005/072053 PCT/IB2005/000928 758 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA1Pl. 3.An isolated polypeptide encoding for a tail of D11853_PEA_1_P1, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP GTPDSLSSGSSRDVQGTDASLDEELDRVKMS in D1 1853_PEA_1_Pl. 10 Comparison report between Dl 1853 PEA-1iPi and Q96FY2 (SEQ ID NO: 638): 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P1, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVERMGRFHRI 15 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids I - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of DI11853_PEA_1_P1, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1_P1, and a second amino acid sequence being at least 90 % homologous to 20 AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAV LAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVT SMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 130 - 356 of Q96FY2, which also corresponds to amino acids 130 25 - 356 of DI11853_PEA_1_P1, wherein said first amino acid sequence, bridging amino acid and second amino acid sequence are contiguous and in a sequential order. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 30 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal- WO 2005/072053 PCT/IB2005/000928 759 peptide prediction programs (I-IMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. Variant protein D11853_PEA_1_P1 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the 5 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P1 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP positions) on amino acid Alternative aniino acid(s) Previously known SNP? 25 P-> No 32 L-> No 178 K ->No 178 K -> R No 178 K -> T NO 185 R-> G No 187 K-> T No 206 E ->K No 230 E ->K No 230 E ->Q No 235 E-> No 235 E ->D No 239 Q->P No 244 A -> G No 244 A -> No 267 Q -> H No 278 V -> G No 284 S ->N No 284 S -> T No WO 2005/072053 PCT/IB2005/000928 760 299P-> No 299 P->A No 326 G -> No 329 D ->N No 340 Q -> No Variant protein D1 1853 PEA_1-P1 is encoded by the following transcript(s): DI11853_PEA_1TI, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D1 1853_PEA_1_TI is shown in bold; this coding portion starts at 5 position 108 and ends at position 1175. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI11853_PEA_1_P1 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 7 - Nucleic acid SNPs SNP position on nucleotide Alteinatiye nucleic, acid Previously known SNP2 sequence 180 C-> No 182 G-> No 185 -> C No 201 T -> No 640 A ->C No 640 A ->G No 641 G-> No 641 G ->A No 660 C ->G No 667 A ->C No 723 G ->A No 795 G ->A No 795 G ->C No WO 2005/072053 PCT/IB2005/000928 761 812 A-> No 812 A -> C No 823 A ->C No 838 C -> No 838 C ->G No 908 A ->C No 932 A ->C No 940 T ->G No 958 G ->A No 958 G -> C No 966 ->C No 966 ->T No 973 ->G No 1002 C -> No 1002 C -> G No 1033 -> G No 1083 G-> No 1092 G ->A No 1112 C ->T No 1127 G-> No 1208 G ->A No 1211 A-> No 1211 A ->C No 1257 T-> No 1260 T ->C No 1260 T ->G No 1297 T ->C Yes WO 2005/072053 PCT/IB2005/000928 762 Variant protein DI11853_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) DI11853_PEA_1_T3. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously 5 published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between D11853-PEA_1_P2 and Q9P042 (SEQ ID NO: 639): 1 An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P2, comprising a first 10 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of D11853_PEA_1_P2, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP 15 EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13 - 187 of Q9P042, which also corresponds to amino acids 27 201 of D11853_PEA_1 P2, a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_1_P2, a third amino acid sequence being at least 90 % homologous to 20 TVLESEGTRESAINVABGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRIL AAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQ corresponding to amino acids 189 - 297 of Q9P042, which also corresponds to amino acids 203 - 311 ofDl 1853_PEA_1 P2, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 25 95% homologous to a polypeptide having the sequence VRAL corresponding to amino acids 312 - 315 of D1 1853_PEA_1_P2, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P2, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 763 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of Dl 1853 PEA 1 P2. 3.An isolated polypeptide encoding for a tail of D11853_PEA 1 P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRAL in D11853_PEA_1lP2. Comparison report between D1 1853 PEA_1_P2 and BAC85377 (SEQ ID NO: 640): I .An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P2, comprising a first 10 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to 15 amino acids 1 - 109 of D1 1853_PEA_1 P2, a second amino acid sequence being at least 90 % homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino 20 acids 1 - 159 of BAC85377, which also corresponds to amino acids 110 - 268 of Dl 1853_PEA_1_P2, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQVRAL corresponding to 25 amino acids 269 - 315 of D11853_PEA_1_P2, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1 P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 30 sequence

MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI

WO 2005/072053 PCT/IB2005/000928 '764 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of DI1853_PEA_1_P2. 3.An isolated polypeptide encoding for a tail of D11853_PEA_1 P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQVRAL in D11853_PEA_1_P2. Comparison report between D1 1853_PEA_ 1 P2 and Q96FY2: 10 1.An isolated chimeric polypeptide encoding for DI 1853 PEA_1 P2, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to 15 amino acids 1 - 128 of D1 1853_PEA1 _P2, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA1 _P2, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAV 20 LAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVT SMVAQ corresponding to amino acids 130 - 311 of Q96FY2, which also corresponds to amino acids 130 - 311 of D11853_PEA_1_P2, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRAL corresponding 25 to amino acids 312 - 315 of D11853_PEA 1_P2, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRAL in D11853PEA1_P2.

WO 2005/072053 PCT/IB2005/000928 765 Comparison report between D I 1853_PEA__P2 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P2, comprising a first amino acid sequence being at least 90 % homologous to 5 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK DIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQI NQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSN 10 TILLPSNPGDVTSMVAQ corresponding to amino acids 1 - 311 of Q9UJZl, which also corresponds to amino acids 1 - 311 of D11853 PEA 1 P2, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRAL corresponding to amino acids 312 - 315 of DI11853_PEA 1 P2, wherein said first amino acid 15 sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P2, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRAL in D11853PEA_1_P2. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignaiP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal 25 peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. Variant protein Dl1853_PEA_1_P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 30 the SNP is known or not; the presence of known SNPs in variant protein Dl 1853_PEA_1_P2 WO 2005/072053 PCT/IB2005/000928 766 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SN?? sequence 25 P-> No 32 L-> No 178 K ->No 178 K-> R No 178 K-> T No 185 R-> G No 187 K-> T No 206 E ->K No 230 E ->Q No 230 E ->K No 235 E ->D No 235 E-> No 239 Q->P No 244 A -> No 244 A -> G No 267 Q -> H No 278 V -> G No 284 S -> T No 284 S ->N No 299 P -> A No 299 P -> No 5 Variant protein D11853_PEA__ P2 is encoded by the following transcript(s): D11853_PEA_1_T3, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_1_T3 is shown in bold; this coding portion starts at WO 2005/072053 PCT/IB2005/000928 position 108 and ends at position 1052. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI 1853_PEA_1_P2 sequence provides support for the deduced 5 sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequenice, 180 C-> No 182 G-> No 185 -> C No 201 T-> No 640 A ->C No 640 A ->G No 641 G-> No 641 G ->A No 660 C ->G No 667 A->C No 723 G ->A No 795 G ->A No 795 G -> C No 812 A-> No 812 A ->C No 823 A ->C No 838 C-> No 838 C ->G No 908 A ->C No 932 A ->C No 940 T ->G No WO 2005/072053 PCT/IB2005/000928 768 958 G->A No 958 G -> C No 966 ->C No 966 T No 973 G No 1002 C -> No 1002 C -> G No 1033 -> G No 1066 C ->T No 1508 G-> No 1517 G ->A No 1537 C ->T No 1552 G-> No 1633 G -A No 1636 A -No 1636 A -C No 1682 T -No 1685 T -C No 1685 T ->G No 1722 T ->C Yes Variant protein D1 1853_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_T10. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1_P7 and Q9P042: WO 2005/072053 PCT/IB2005/000928 769 I.An isolated chimeric polypeptide encoding for DI11853_PEA_1_P7, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 5 Dl 1853_PEA_1_P7, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13 - 187 of Q9P042, which also corresponds to amino acids 27 10 201 of DI11853_PEA_1 P7, a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_1_P7, a third amino acid sequence being at least 90 % homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRIL AAALTQH corresponding to amino acids 189 - 254 of Q9P042, which also corresponds to amino acids 203 - 268 of D11853_PEA_1_P7, and a fourth amino acid sequence being at least 15 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 269 - 290 of D11853_PEA_1_P7, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous 20 and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of Dl 1853_PEA 1_P7. 25 3.An isolated polypeptide encoding for a tail of D1 1853_PEA_1 P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in DI11853_PEA_1_P7. 30 Comparison report between Dl 1853_PEA_1_P7 and BAC85377: WO 2005/072053 PCT/IB2005/000928 770 1.An isolated chimeric polypeptide encoding for DI11853_PEA-1_P7, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 5 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids I - 109 of DI11853_PEA_1_P7, and a second amino acid sequence being at least 90 % homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC 10 WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHVRGPWVGMGTGIDSGR GSLIYA corresponding to amino acids 1 - 181 of BAC85377, which also corresponds to amino acids 110 - 290 of D11853-PEA_1 P7, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 20 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_1_P7. Comparison report between D1 1853_PEA_1_P7 and Q96FY2 (SEQ ID NO 638): 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P7, comprising a first 25 amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of D11853_PEA 1 P7, a bridging amino acid L corresponding to amino 30 acid 129 of D11853_PEA_1 P7, a second amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 771 AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAV LAKAKAKAEAIRILAAALTQH corresponding to amino acids 130 - 268 of Q96FY2, which also corresponds to amino acids 130 - 268 of D1l853_PEA_1 P7, and a third amino acid 5 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 269 - 290 of D11853_PEA_1_P7, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 10 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in DI11853_PEA_1_P7. 15 Comparison report between D1 1853_PEA_1_P7 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D 11853_PEA _P7, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV 20 EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK DIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQI NQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 1 - 268 of Q9UJZl, which also corresponds to amino acids 1 - 268 of D11853_PEA 1 P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 25 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 269 - 290 of Dll853_PEA_1_P7, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA1 _P7, comprising a 30 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 772 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in D1 1853_PEA_1_P7. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. 10 Variant protein Dli853_PEA_1_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA 1 P7 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amirio acid(s) Previously known SNP? sequence, 25 P-> No 32 L-> No 178 K-> No 178 K ->R No 178 K ->T No 185 R ->G No 187 K ->T No 206 E ->K No 230 E ->K No 230 E ->Q No 235 E-> No 235 E ->D No WO 2005/072053 PCT/IB2005/000928 773 239 Q->P No 244 A -> No 244 A -- >G No 267 Q -> H No Variant protein D11853_PEA_1_P7 is encoded by the following transcript(s): D1 853_PEA1T10, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D1 1853_PEA_1_T1O is shown in bold; this coding portion starts at 5 position 108 and ends at position 977. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 11 - Nucleic acid SNPs SNP position on nucleotide Alternative nucIeic acid Previously known SNP? sequence 180 C-> No 182 G-> No 185 ->C No 201 T-> No 640 A ->C No 640 A ->G No 641 G-> No 641 G ->A No 660 C ->G No 667 A ->C No 723 G ->A No 795 G ->A No 795 G ->C No 812 A-> No WO 2005/072053 PCT/IB2005/000928 774 812 A->C No 823 A ->C No 838 C-> No 838 C->G No 908 A ->C No 1137 A ->C No 1145 T -> G No 1163 G->A No 1163 G -> C No 1171 ->C No 1171 ->T No 1178 ->G No 1207 C -> No 1207 C -> G No 1238 -> G No 1288 G -> No 1297 G -> A No 1317 C -> T No 1332 G -> No 1413 G -> A No 1416 A -> No 1416 A ->C No 1462 T-> No 1465 T ->C No 1465 T ->G No 1502 T ->C Yes Variant protein D11853_PEA_1_P9 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) WO 2005/072053 PCT/IB2005/000928 775 Dl1853_PEA_1_T13. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein 5 is as follows: Comparison report between DI11853_PEA_1_P9 and Q9P042: I.An isolated chimeric polypeptide encoding for DI11853_PEA_1_P9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 10 the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of D11853_PEA_1_P9, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR 15 corresponding to amino acids 13 - 187 of Q9P042, which also corresponds to amino acids 27 201 of D1 1853_PEA1 _P9, a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_1_P9, a third amino acid sequence being at least 90 % homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQLNQA corresponding to amino acids 189 - 226 of Q9P042, which also corresponds to amino acids 203 - 240 of D11853 PEA 1 P9, a 20 fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of D11853 PEA_1 P9, and a fifth amino acid sequence being at least 90 % homologous to 25 AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILL PSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKM S corresponding to amino acids 227 - 342 of Q9P042, which also corresponds to amino acids 282 - 397 of D1 1853_PEA_1_P9, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence and fifth 30 amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 776 2.An isolated polypeptide encoding for a head of Dl1853_PEA_1 P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D 1853_PEA__P9. 5 3.An isolated polypeptide encoding for an edge portion of D11853_PEA_1_P9, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to 10 D11853_PEA1_P9. Comparison report between Dl 1853_PEA_1_P9 and BAC85377: 1.An isolated chimeric polypeptide encoding for DI11853_PEA1_P9, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 15 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1 - 109 of Dl 1853_PEA_1 P9, a second amino acid sequence being at least 90 % 20 homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI LASEAEKAEQINQA corresponding to amino acids 1 - 131 of BAC85377, which also corresponds to amino acids 110 - 240 of D1 1853_PEA_1_P9, a third amino acid sequence being 25 at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of D11853_PEA_1_P9, a fourth amino acid sequence being at least 90 % homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 132 30 - 159 of BAC85377, which also corresponds to amino acids 282 - 309 of D11853_PEA_1_P9, and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least WO 2005/072053 PCT/IB2005/000928 777 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP GTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 310 - 397 of 5 Dl 1853_PEAlP9, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of Dll853_PEA1 -P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_1_P9. 15 3.An isolated polypeptide encoding for an edge portion of Dl1853_PEA__P9, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to 20 D11853_PEA_1_P9. 4.An isolated polypeptide encoding for a tail of Dl1853_PEA1 _P9, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP GTPDSLSSGSSRDVQGTDASLDEELDRVKMS in DI 1853_PEA__P9. Comparison report between D 11853 PEA_1_P9 and Q96FY2: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P9, comprising a first 30 amino acid sequence being at least 90 % homologous to

MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI

WO 2005/072053 PCT/IB2005/000928 778 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids I - 128 of DI 1853 PEA_1 P9, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1 P9, a second amino acid sequence being at least 90 % 5 homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 130 - 240 of Q96FY2, which also corresponds to amino acids 130 - 240 of D 1853_PEA_1_P9, a third amino acid sequence being at least 70%, optionally at least 10 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of D11853_PEA_1_P9, and a fourth amino acid sequence being at least 90 % homologous to 15 AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILL PSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKM S corresponding to amino acids 241 - 356 of Q96FY2, which also corresponds to amino acids 282 - 397 of D1 1853_PEA1 _P9, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are 20 contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of D11853_PEA__P9, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for 25 AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to D11853_PEA_1_P9. Comparison report between D 11853 PEA_1_P9 and Q9UJZ1: 1 .An isolated chimeric polypeptide encoding for D11853_PEA_1_P9, comprising a first 30 amino acid sequence being at least 90 % homologous to

MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI

WO 2005/072053 PCT/IB2005/000928 779 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK DIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQI NQA corresponding to amino acids I - 240 of Q9UJZ1, which also corresponds to amino acids 5 1 - 240 of Dl 853_PEA_1_P9, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of Dl 1853_PEA_1_P9, and a third amino acid sequence being at least 90 % 10 homologous to AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILL PSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKM S corresponding to amino acids 241 - 356 of Q9UJZl, which also corresponds to amino acids 282 - 397 of D1 1853_PEA_1 P9, wherein said first amino acid sequence, second amino acid 15 sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of Dl1853_PEA__P9, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for 20 AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to D11853_PEA_1_P9. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 25 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. Variant protein D11853_PEA_1_P9 also has the following non-silent SNPs (Single 30 Nucleotide Polymorphisms) as listed in Table 12, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether WO 2005/072053 PCT/IB2005/000928 780 the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Amino acid mutations SNP positions) oi amino acid Alternative aniino acid(s) Previously Ilnowa SNP? sequence 25 P-> No 32 L-> No 178 K-> No 178 K ->R No 178 K ->T No 185 R ->G No 187 K ->T No 206 E ->K No 230 E ->K No 230 E ->Q No 235 E-> No 235 E ->D No 239 Q ->P No 285 A G No 285 A-> No 308 Q ->H No 319 V ->G No 325 S ->N No 325 S -> T No 340 P -> No 340 P ->A No 367 G-> No 370 D ->N No WO 2005/072053 PCT/IB2005/000928 781 381 Q-> No Variant protein DlI 853_PEA_1_P9 is encoded by the following transcript(s): DI 1853_PEA_1_T13, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D1 1853_PEA_1_T13 is shown in bold; this coding portion starts at 5 position 108 and ends at position 1298. The transcript also has the following SNPs as listed in Table 13 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P9 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 13 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 180 C -> No 182 G -> No 185 -> C No 201 T-> No 640 A ->C No 640 A ->G No 641 G-> No 641 G ->A No 660 C -> G No 667 A -> C No 723 G -> A No 795 G ->A No 795 G ->C No 812 A-> No 812 A ->C No 823 A ->C No 961 C-> No WO 2005/072053 PCT/IB2005/000928 782 961 C ->G No 1031 A ->C No 1055 A ->C No 1063 T ->G No 1081 G ->A No 1081 G ->C No 1089 ->C No 1089 ~>T No 1096 ->G No 1125 C -> No 1125 C -> G No 1156 -> G No 1206 G-> No 1215 G ->A No 1235 C ->T No 1250 G-> No 1331 G ->A No 1334 A-> No 1334 A ->C No 1380 T-> No 1383 T->C No 1383 T ->G No 1420 T ->C Yes Variant protein D11853_PEA_1_PlO according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_T14. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the WO 2005/072053 PCT/IB2005/000928 783 relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Dl 1853_PEAIPl10 and Q9P042: 1.An isolated chimeric polypeptide encoding for DI11853_PEA_1_PO, comprising a first 5 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of D11853_PEA_1_PO, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP 10 EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13 - 187 of Q9PO42, which also corresponds to amino acids 27 201 of D11853_PEA_1_PlO, a bridging amino acid A corresponding to amino acid 202 of D11853-PEA1_PlO, a third amino acid sequence being at least 90 % homologous to 15 TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRIL AAALTQH corresponding to amino acids 189 - 254 of Q9P042, which also corresponds to amino acids 203 - 268 of D11853 PEA 1_P10, and a fourth amino acid sequence being at least 90 % homologous to AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 298 - 342 of Q9P042, which also corresponds to amino acids 269 20 - 313 of D11853_PEA_1_PO, wherein said first amino acid sequence, second amino acid sequence, bridging amino acid, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D 11853_PEA_1_PO. 3.An isolated chimeric polypeptide encoding for an edge portion of D11853 PEA_1_P10, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino 30 acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a WO 2005/072053 PCT/IB2005/000928 784 structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between D 11853 PEA 1 PlO and BAC85377: 5 1.An isolated chimeric polypeptide encoding for Dl 1853_PEA_1_PlO, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 10 LEPGLNILIPVLDRIRYVQSLKEIV[NVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids 1 - 109 of D1 1853_PEA_1PlO, a second amino acid sequence being at least 90 % homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 15 LASEAEKAEQFNQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 1 - 159 of BAC85377, which also corresponds to amino acids 110 - 268 of D11853_PEA_1_P1O, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 269 - 313 of D11853_PEA_1_Pl0, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853 PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853_PEA_1_PlO. 30 3.An isolated polypeptide encoding for a tail of D11853_PEAI_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 785 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS in D11853_PEA1_P1O. 5 Comparison report between D 11853_PEA I PO and Q96FY2: 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_PlO, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV 10 EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of D1 1853_PEAIP10, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1_P10, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES 15 MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAV LAKAKAKAEAIRILAAALTQH corresponding to amino acids 130 - 268 of Q96FY2, which also corresponds to amino acids 130 - 268 of D11853 PEA 1_PO, and a third amino acid sequence being at least 90 % homologous to AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to 20 amino acids 312 - 356 of Q96FY2, which also corresponds to amino acids 269 - 313 of D11853_PEA_1_PlO, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of D11853_PEA_1_P10, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in 25 length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. 30 Comparison report between D11853_PEA_1_Pl0 and Q9UJZI: WO 2005/072053 PCT/IB2005/000928 786 1.An isolated chimeric polypeptide encoding for DI 1853_PEA_1_P10, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV 5 EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK DIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQI NQAAGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 1 - 268 of Q9UJZ1, which also corresponds to amino acids 1 - 268 of D1 1853_PEA _ P10, and a second amino acid sequence being at least 90 % homologous to 10 AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 312 - 356 of Q9UJZl, which also corresponds to amino acids 269 - 313 of Dl 1853_PEA_1_PlO, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2-An isolated chimeric polypeptide encoding for an edge portion of DI 1853 PEA_1_P10, 15 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise HA, having a structure as follows: a sequence starting from any of amino acid numbers 268-x to 268; and 20 ending at any of amino acid numbers 269+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. Variant protein D11853_PEA_1_PlO also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 14, (given according to their position(s) on the 30 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P10 WO 2005/072053 PCT/IB2005/000928 787 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 14 - Amino acid mutations SNP positioi(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 25 P-> No 32 L-> No 178 K-> No 178 K ->R No 178 K ->T No 185 R ->G No 187 K ->T No 206 E ->K No 230 E ->K No 230 E ->Q No 235 E-> No 235 E ->D No 239 Q->P No 244 A -> No 244 A->G No 267 Q -> H No 283 G -> No 286 D->N No 297 Q -> No 5 Variant protein D11853_PEA_1_PlO is encoded by the following transcript(s): D11 853_PEA_1_T14, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA _1_T14 is shown in bold; this coding portion starts at position 108 and ends at position 1046. The transcript also has the following SNPs as listed in Table 15 (given according to their position on the nucleotide sequence, with the alternative WO 2005/072053 PCT/IB2005/000928 78 8 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI1853_PEA_1_PIO sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 15 -Nucleic acid SNPs SNP position on niucleotide Alternative nucleic acid Previously known SNP? seqne 180 C-> No 182 G-> No 185 C No 201 T No 640 A-> C No 640 A-> G No 641 G No 641 G ->A No 660 C -> G No 667 A -> C No 723 G -> A No 795 G -> A No 795 G ->C No 812 A-> No 812 A ->C No 823 A ->C No 838 C-> No 838 C ->G No 908 A ->C No 954 G-> No 963 G ->A No 983 C ->T No 998 G-> No WO 2005/072053 PCT/IB2005/000928 789 1079 G ->A No 1082 A-> No 1082 A ->C No 1128 T-> No 1131 T ->C No 1131 T ->G No 1168 T ->C Yes Variant protein D11853_PEA_1_Pt1 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_Ti5. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1_P11 and Q9P042: 1.An isolated chimeric polypeptide encoding for D 11853_PEA_1_P11, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P11, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKR corresponding to amino acids 13 - 187 of Q9P042, which also corresponds to amino acids 27 20 201 of D11853_PEA_1_P11, a bridging amino acid A corresponding to amino acid 202 of D11853_PEA_1_P11, a third amino acid sequence being at least 90 % homologous to TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA corresponding to amino acids 189 - 226 of Q9P042, which also corresponds to amino acids 203 - 240 of D1 1853_PEA_1_P11, a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, WO 2005/072053 PCT/IB2005/000928 790 more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of Dl 1853_PEA_1_P11, a fifth amino acid sequence being at least 90 % homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding 5 to amino acids 227 - 254 of Q9P042, which also corresponds to amino acids 282 - 309 of D11853_PEA_1_P11, and a sixth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 310 - 331 of D1 1853 PEA_1_P11, wherein said first amino acid 10 sequence, second amino acid sequence, bridging amino acid, third amino acid sequence, fourth amino acid sequence, fifth amino acid sequence and sixth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA1 1P11, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR ofD1 1853 PEA 1 P11. 3.An isolated polypeptide encoding for an edge portion of Dl1853_PEA_1_P11, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% 20 homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to D11853_PEA_1_P11. 4.An isolated polypeptide encoding for a tail of D11853_PEA_1_P11, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in D1 1853_PEA_1_P11. Comparison report between D1 1853_PEA_1 P11 and BAC85377: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P11, comprising a first 30 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having WO 2005/072053 PCT/IB2005/000928 791 the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to amino acids I - 109 of D 1853_PEA_1_P11, a second amino acid sequence being at least 90 % 5 homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADC WGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI LASEAEKAEQINQA corresponding to amino acids I - 131 of BAC85377, which also corresponds to amino acids 110 - 240 of D11853-PEA_1_P11, a third amino acid sequence 10 being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of D 1853_PEA_1_P11, and a fourth amino acid sequence being at least 90 % homologous to 15 AGEASAVLAKAKAKAEAIRILAAALTQHVRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 132 - 181 of BAC85377, which also corresponds to amino acids 282 - 331 of D11853 PEA 1_P11, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P11, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 25 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLJ of D11853_PEA1P11. 3.An isolated polypeptide encoding for an edge portion of D11853 PEA1_P11, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% 30 homologous to the sequence encoding for WO 2005/072053 PCT/IB2005/000928 792 AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to D11853_PEA_1_P11. Comparison report between D1 1853 PEA IPI 1 and Q96FY2: 5 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P11, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to 10 amino acids 1 - 128 of D 11853_PEA_1_Pl1, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1_P11, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA 15 corresponding to amino acids 130 - 240 of Q96FY2, which also corresponds to amino acids 130 - 240 of Dl 1853-PEA_1_P11, a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino 20 acids 241 - 281 of D11853_PEA_1_P11, a fourth amino acid sequence being at least 90 % homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 241 - 268 of Q96FY2, which also corresponds to amino acids 282 - 309 of D11853_PEA_1_P11, and a fifth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a 25 polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 310 - 331 of D11853 PEA_1_P11, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence, third amino acid sequence, fourth amino acid sequence and fifth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for an edge portion of D11853_PEA_1_P11, 30 comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% WO 2005/072053 PCT/IB2005/000928 793 homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to D11853_PEA_1P11. 3.An isolated polypeptide encoding for a tail of D11853_PEA_1_P11, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in DI11853_PEA_1_P11. Comparison report between DI11853 PEAI PI 1 and Q9UJZ I: 10 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P11, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK 15 DIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQI NQA corresponding to amino acids 1 - 240 of Q9UJZ1, which also corresponds to amino acids 1 - 240 of D1 1853-PEA 1 P11, a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL corresponding to amino acids 241 - 281 of D11853 PEAl_P11, a third amino acid sequence being at least 90 % homologous to AGEASAVLAKAKAKAEAIRILAAALTQH corresponding to amino acids 241 - 268 of Q9UJZ1, which also corresponds to amino acids 282 - 309 of Dl1853_PEA_1_P11, and a fourth amino acid sequence being at least 70%, optionally at least 80%, preferably at least 25 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRGPWVGMGTGIDSGRGSLIYA corresponding to amino acids 310 - 331 of D1 1853_PEA_1_P11, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 30 2.An isolated polypeptide encoding for an edge portion of D 11853_PEA_1_Pll, comprising an amino acid sequence being at least 70%, optionally at least about 80%, preferably WO 2005/072053 PCT/IB2005/000928 794 at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence encoding for AGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQASSVPSL, corresponding to Dl1853_PEA_1_P11. 5 3.An isolated polypeptide encoding for a tail of D11853_PEA_1_P11, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRGPWVGMGTGIDSGRGSLIYA in DI11853_PEA_1_P11. 10 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a 15 signal peptide. Variant protein D11853_PEA_1_P11 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 16, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Dl 1853_PEA_1_P1 20 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 16 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence. 25 P-> No 32 L-> No 178 K-> No 178 K ->R No 178 K ->T No 185 R ->G No WO 2005/072053 PCT/IB2005/000928 795 187 K ->T No 206 E ->K No 230 E ->K No 230 E -> Q No 235 E-> No 235 E -> D No 239 Q->P No 285 A -> No 285 A -> G No 308 Q -> H No Variant protein D11853_PEA_1_P11 is encoded by the following transcript(s): DI11853_PEA_1_Ti5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D1 1853_PEA_1_TI5 is shown in bold; this coding portion starts at 5 position 108 and ends at position 1100. The transcript also has the following SNPs as listed in Table 17 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Di11853_PEA_1_P11 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 17 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SN P? sequence 180 C -> No 182 G -> No 185 -> C No 201 T-> No 640 A ->C No 640 A ->G No 641 G-> No 641 G ->A No WO 2005/072053 PCT/IB2005/000928 796 660 C ->G No 667 A ->C No 723 G ->A No 795 G->A No 795 G->C No 812 A -> No 812 A -> C No 823 A -> C No 961 C -> No 961 C -> G No 1031 A -> C No 1260 A -> C No 1268 T -> G No 1286 G -> A No 1286 G -> C No 1294 -> C No 1294 -> T No 1301 -> No 1330 C-> No 1330 C -> G No 1361 -> G No 1411 G -> No 1420 G -> A No 1440 C -> T No 1455 G -> No 1536 G -> A No 1539 A -> No 1539 A -> C No 1585 T -> No 1588 T -> C No WO 2005/072053 PCT/IB2005/000928 797 1588 T ->G No 1625 T ->C Yes Variant protein D1 1853_PEA_1_P12 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEAl_T16. An aligmnent is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853._PEA 1 P12 and Q9P042: 1.An isolated chimeric polypeptide encoding for D 11853_PEA_1_P12, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P12, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDJRYVQSLKEIV1NVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFR corresponding to amino acids 13 - 134 of Q9P042, which also corresponds to amino acids 27 - 148 of D11853 PEA 1 P12, and a third amino acid sequence being at least 70%, 20 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP corresponding to amino acids 149 - 183 of D1 1853_PEA_1 P12, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a head of D11853._PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D1 1853_PEA_1_P12.

WO 2005/072053 PCT/IB2005/000928 798 3.An isolated polypeptide encoding for a tail of D11853_PEA_1 P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP in DI 1853_PEA_1_P12. 5 Comparison report between DI 1853_PEA_1_P12 and Q96FY2: 1.An isolated chimeric polypeptide encoding for Dl 1853_PEAl_P12, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 10 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of D11853 PEA1 P12, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1 P12, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFR corresponding to amino acids 130 - 148 of 15 Q96FY2, which also corresponds to amino acids 130 - 148 of Dl 1853_PEA __P12, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP corresponding to amino acids 149 - 183 of D11853_PEA_1_P12, wherein said first amino acid sequence, bridging 20 amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA1 1P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP in D1 1853_PEA_1_P12. Comparison report between D 11853_PEA 1_P12 and Q9UJZ 1: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P12, comprising a first amino acid sequence being at least 90 % homologous to 30 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI

LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV

WO 2005/072053 PCT/IB2005/000928 799 EDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 1 - 148 of Q9UJZ1, which also corresponds to amino acids 1 - 148 of D11853_PEA 1 P12, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 5 the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP corresponding to amino acids 149 - 183 of D11853_PEA_1_P12, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P12, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VSRSEPELGFEDTNLTLLIFSEGQDQSQALLSVGP in D1 1853 PEA 1_P12. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. 20 Variant protein D11853_PEA_1 P12 is encoded by the following transcript(s): D1 1853_PEA_1_Ti 6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D1 1853_PEA_1_T16 is shown in bold; this coding portion starts at position 108 and ends at position 656. The transcript also has the following SNPs as listed in Table 18 (given according to their position on the nucleotide sequence, with the alternative 25 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI 1853_PEA_1_P12 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 18 -Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence WO 2005/072053 PCT/IB2005/000928 800 180 C-> No 182 G-> No 185 -> C No 201 T-> No 789 A ->C No 789 A ->G No 790 G-> No 790 G ->A No 809 C ->G No 816 A ->C No 872 G ->A No 944 G ->A No 944 G ->C No 961 A-> No 961 A ->C No 972 A ->C No 987 C-> No 987 C -> G No 1057 A ->C No 1081 A ->C No 1089 T ->G No 1107 G->A No 1107 G -> C No 1115 -> C No 1115 ->T No 1122 -> G No 1151 C -> No 1151 C -> G No 1182 -> G No 1232 G -> No WO 2005/072053 PCT/IB2005/000928 801 1241 G-> A No 1261 C-> T No 1276 G No 1357 G-> A No 1360 A ->No 1360 A ->C No 1406 T-> No 1409 T -> C No 1409 T ->G No 1446 T -> C Yes Variant protein D11853_PEA 1_P14 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_T19. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1_P14 and Q9P042: L.An isolated chimeric polypeptide encoding for D11853_PEA_1_P14, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P14, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQV corresponding to amino acids 13 - 180 of Q9P042, which also corresponds to amino acids 27 - 194 of 20 D1 1853_PEA_1_P14, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% WO 2005/072053 PCT/IB2005/000928 802 homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG corresponding to amino acids 195 - 220 of Dl 1853 PEA-1_P14, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 5 2.An isolated polypeptide encoding for a head of D11853_PEA 1 P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D1 1853 PEA 1 P14. 3.An isolated polypeptide encoding for a tail of Dl 1853_PEA_1 P14, comprising a 10 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG in D1 1853_PEA_1_P14. Comparison report between Dl 1853PEA1 P14 and Q96FY2: 15 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P14, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to 20 amino acids I - 128 of D1 1853 PEA_1 P14, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1_P14, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKES MQMQV corresponding to amino acids 130 - 194 of Q96FY2, which also corresponds to amino 25 acids 130 - 194 of D11853_PEA_1_P14, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG corresponding to amino acids 195 - 220 of D11853_PEA_1_P14, wherein said first amino acid sequence, bridging amino acid, second 30 amino acid sequence and third amino acid sequence are contiguous and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 803 2.An isolated polypeptide encoding for a tail of D 11853 PEA_1 P14, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG in D1 1853_PEA_1_P14. 5 Comparison report between D1 1853_PEA_1_P14 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P14, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 10 LEPGLNILIPVLDRIRYVQSLKEIVlNVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYEIK DIHVPPRVKESMQMQV corresponding to amino acids I - 194 of Q9UJZI, which also corresponds to amino acids 1 - 194 of D1 1853_PEA_1_P14, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 15 90% and most preferably at least 95% homologous to a polypeptide having the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG corresponding to amino acids 195 - 220 of D11853_PEA_1_P14, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P14, comprising a 20 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GAKEGWEKGLRAPVPGGSRLPSCYDG in D11853_PEA_1_P14. The location of the variant protein was determined according to results from a number of 25 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. 30 Variant protein D11853_PEA_1_P14 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 19, (given according to their position(s) on the WO 2005/072053 PCT/IB2005/000928 804 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D 11853 PEA_1_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 19 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 25 P-> No 32 L-> No 178 K-> No 178 K ->R No 178 K ->T No 185 R ->G No 187 K ->T No Variant protein D11853_PEA-1_P14 is encoded by the following transcript(s): D11853_PEA_1_Ti 9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA_1_T 19 is shown in bold; this coding portion starts at 10 position 108 and ends at position 767. The transcript also has the following SNPs as listed in Table 20 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_1_P14 sequence provides support for the deduced sequence of this variant protein according to the present invention). 15 Table 20 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 180 C-> No 182 G-> No 185 -> C No WO 2005/072053 PCT/IB2005/000928 805 201 T No 640 A-> C No 640 A-> G No 641 G No 641 G-> A No 660 C ->G No 667 A ->C No 867 G ->A No 939 G ->A No 939 G ->C No 956 A-> No 956 A ->C No 967 A ->C No 982 C-> No 982 C ->G No 1052 A ->C No 1076 A ->C No 1084 T -> G No 1102 G->A No 1102 G->C No 1110 -> C No 1110 -> T No 1117 -> G No 1146 C -> No 1146 C -> G No 1177 -> G No 1227 G-> No 1236 G->A No 1256 C -> T No 1271 G -> No WO 2005/072053 PCT/IB2005/000928 806 1352 G A No 1355 A ->No 1355 A-> C No 1401 T No 1404 T -> C No 1404 T -> G No 1441 T -> C Yes Variant protein Dll853_PEA_1_P16 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 DI11853_PEA_1_T24. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1 P16 and Q9P042: 1.An isolated chimeric polypeptide encoding for DI11853_PEA_1_P16, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P16, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDK VFR corresponding to amino acids 13 - 134 of Q9PO42, which also corresponds to amino acids 27 - 148 of D 11853_PEA_1_P16, a third amino acid sequence being at least 90 % homologous 20 to VEAERRKR corresponding to amino acids 180 - 187 of Q9P042, which also corresponds to amino acids 149 - 156 of D11853_PEA_1_P16, a bridging amino acid A corresponding to amino acid 157 of DI11853_PEA_1_P16, and a fourth amino acid sequence being at least 90 % homologous to

TVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIRIL

WO 2005/072053 PCT/IB2005/000928 807 AAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGA LTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 189 - 342 of Q9PO42, which also corresponds to amino acids 158 - 311 of D11853 PEA_1 P16, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence, 5 bridging amino acid and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D1 1853 PEA_1_P16. 10 3.An isolated chimeric polypeptide encoding for an edge portion of Dl 1853_PEA_1_P16, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a 15 structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between D1 1853_PEA 1_P16 and BAC85377: 1.An isolated chimeric polypeptide encoding for DI11853_PEA_1_P16, comprising a first 20 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI corresponding to 25 amino acids 1 - 109 of DI11853 PEA_1_P16, a second amino acid sequence being at least 90 % homologous to MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 1 - 39 of BAC85377, which also corresponds to amino acids 110 - 148 of D11853_PEA_1_P16, a third amino acid sequence being at least 90 % homologous to VEAERRKRATVLESEGTRESAINVAEGKIKQAQILASEAEKAEQINQAAGEASAVLAKA 30 KAKAEAIRILAAALTQH corresponding to amino acids 85 - 159 of BAC85377, which also corresponds to amino acids 149 - 223 of D11853_PEA_1 P16, and a fourth amino acid WO 2005/072053 PCT/IB2005/000928 808 sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP GTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 224 - 311 of 5 D11853_PEA_1_P16, wherein said first amino acid sequence, second amino acid sequence, third amino acid sequence and fourth amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of Dl1853 PEA_1_P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRI of D11853 PEA 1 P16. 15 3.An isolated chimeric polypeptide encoding for an edge portion of D 11853 PEA_1_P16, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a 20 structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) -x), in which x varies from 0 to n-2. 4.An isolated polypeptide encoding for a tail of D11853_PEA_1 P16, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 25 sequence NGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVP GTPDSLSSGSSRDVQGTDASLDEELDRVKMS in Dl 1853_PEA_1_P16. Comparison report between D1 1853_PEA_1_P16 and Q96FY2: 30 1.An isolated chimeric polypeptide encoding for Dl 1853_PEA_1_P16, comprising a first amino acid sequence being at least 90 % homologous to WO 2005/072053 PCT/IB2005/000928 809 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids I - 128 of Dl 1853_PEA__ P16, a bridging amino acid L corresponding to amino 5 acid 129 of D11853_PEA_1 P16, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFR corresponding to amino acids 130 - 148 of Q96FY2, which also corresponds to amino acids 130 - 148 of D1 1853_PEA1 1P16, and a third amino acid sequence being at least 90 % homologous to VEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKA 10 KAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVA QAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 194 - 356 of Q96FY2, which also corresponds to amino acids 149 - 311 of D11853_PEA_1_P16, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 2.An isolated chimeric polypeptide encoding for an edge portion of D 11853 PEA_1_P16, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a 20 structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between D 11853 PEA1_P16 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D11853 PEA 1 P16, comprising a first 25 amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFR corresponding to amino acids 1 - 148 of Q9UJZ1, which also corresponds to amino acids 1 - 148 of D11853_PEA_1 P16, and a second 30 amino acid sequence being at least 90 % homologous to

VEAERRKRATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKA

WO 2005/072053 PCT/IB2005/000928 810 KAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVA QAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 194 - 356 of Q9UJZ1, which also corresponds to amino acids 149 - 311 of DI11853_PEA_1_P16, wherein said first amino acid sequence and second amino acid sequence 5 are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of D11853 PEA-1_P16, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 10 least about 50 amino acids in length, wherein at least two amino acids comprise RV, having a structure as follows: a sequence starting from any of amino acid numbers 148-x to 148; and ending at any of amino acid numbers 149+ ((n-2) - x), in which x varies from 0 to n-2. The location of the variant protein was determined according to results from a number of 15 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. 20 Variant protein D11853_PEA_1_P16 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 21, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P16 sequence provides support for the deduced sequence of this variant protein according to the 25 present invention). Table 21 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 25 P -> No 32 L No WO 2005/072053 PCT/IB2005/000928 811 161 E ->K No 185 E ->K No 185 E ->Q No 190 E-> No 190 E-> D No 194 Q-> P No 199 A ->No 199 A-> G No 222 Q-> H No 233 V ->G No 239 S ->N No 239 S ->T No 254 P-> No 254 P ->A No 281 G-> No 284 D ->N No 295 Q-> No Variant protein D11853_PEA 1 P16 is encoded by the following transcript(s): DI11853_PEAIT24, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D 11853 PEA 1 T24 is shown in bold; this coding portion starts at 5 position 108 and ends at position 1040. The transcript also has the following SNPs as listed in Table 22 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI11853 PEA__1._P16 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 22 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 180 C-> No WO 2005/072053 PCT/IB2005/000928 812 182 G ->No 185 -> C No 201 T -> No 588 G-> A No 660 G-> A No 660 G ->C No 677 A-> No 677 A ->C No 688 A ->C No 703 C-> No 703 C ->G No 773 A ->C No 797 A ->C No 805 T -> G No 823 G ->A No 823 G ->C No 831 ->C No 831-> T No 838 -G No 867 C -> No 867 C -> G No 898 -> G No 948 G -> No 957 G->A No 977 C ->T No 992 G -> No 1073 G->A No 1076 A -> No 1076 A -> C No 1122 T -> No WO 2005/072053 PCT/IB2005/000928 813 1125 T ->C No 1125 T ->G No 1162 T ->C Yes Variant protein D11853_PEA_1_P18 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 DI11853_PEA_1_T26. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1 P18 and Q9PO42: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P18, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P18, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGILSLDK VFRERESLNASI corresponding to amino acids 13 - 143 of Q9P042, which also corresponds to amino acids 27 - 157 of D11853_PEA_1_P18, and a third amino acid sequence being at least 90 20 % homologous to VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 295 - 342 of Q9P042, which also corresponds to amino acids 158 - 205 of D11853_PEA_1_P18, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P18, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D11853_PEA_1_P18.

WO 2005/072053 PCT/IB2005/000928 814 3.An isolated chineric polypeptide encoding for an edge portion of D1 1853_PEA_1_P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at 5 least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157-x to 157; and ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2. Comparison report between D11853 PEAliP18 and Q96FY2: 10 1.An isolated chimeric polypeptide encoding for D11853_PEA_1-P18, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRJMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to 15 amino acids 1 - 128 of Dl 1853_PEA_1_P18, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1 P18, a second amino acid sequence being at least 90 % homologous to AQTTMRSELGKLSLDKVFRERESLNASI corresponding to amino acids 130 157 of Q96FY2, which also corresponds to amino acids 130 - 157 of D11853_PEA1 1P18, and a third amino acid sequence being at least 90 % homologous to 20 VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding to amino acids 309 - 356 of Q96FY2, which also corresponds to amino acids 158 - 205 of D11853_PEA_1_P18, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of D11853 PEAlP18, 25 comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157-x to 157; and 30 ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2.

WO 2005/072053 PCT/IB2005/000928 815 Comparison report between DI11853_PEA I P18 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1_P18, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 5 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASI corresponding to amino acids 1 157 of Q9UJZ1, which also corresponds to amino acids 1 - 157 of DI 1853_PEA_1_P18, and a second amino acid sequence being at least 90 % homologous to VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS corresponding 10 to amino acids 309 - 356 of Q9UJZ1, which also corresponds to amino acids 158 - 205 of Dl 1853_PEA_1_P18, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated chimeric polypeptide encoding for an edge portion of Dl 1853 PEA_1_P18, comprising a polypeptide having a length "n", wherein n is at least about 10 amino acids in 15 length, optionally at least about 20 amino acids in length, preferably at least about 30 amino acids in length, more preferably at least about 40 amino acids in length and most preferably at least about 50 amino acids in length, wherein at least two amino acids comprise IV, having a structure as follows: a sequence starting from any of amino acid numbers 157-x to 157; and ending at any of amino acid numbers 158+ ((n-2) - x), in which x varies from 0 to n-2. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal 25 peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. Variant protein D11853_PEA_1_P18 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 23, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 30 the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_1_P18 WO 2005/072053 PCT/IB2005/000928 816 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 23 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 25 P No 32 L-> No 175 G-> No 178 D -> N No 189 Q -> No 5 Variant protein D11853_PEA_1 P18 is encoded by the following transcript(s): DI11853_PEA_1_T26, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Dl 1853_PEA_1_T26 is shown in bold; this coding portion starts at position 108 and ends at position 722. The transcript also has the following SNPs as listed in Table 24 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11 853_PEA_1_P18 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 24 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 180 C-> No 182 G-> No 185 -> C No 201 T-> No 630 G-> No 639 G ->A No 659 C ->T No WO 2005/072053 PCT/IB2005/000928 817 674 G No 755 G -> A No 758 A-> No 758 A ->C No 804 T ->No 807 T-> C No 807 T-> G No 844 T-> C Yes Variant protein D11853 PEA _ P19 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_T27. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1_P19 and Q9PO42: I.An isolated chimeric polypeptide encoding for D 11853_PEA_1_P19, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P19, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIV1NVP EQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS corresponding to amino acids 13 - 128 of Q9P042, which also corresponds to amino acids 27 142 of D1 1853 PEA_1_P19, and a third amino acid sequence being at least 70%, optionally at 20 least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SRLTLQWEQQRCPGYRCKS corresponding to amino acids 143 - 161 of D11853_PEA_1_P19, wherein said first amino acid WO 2005/072053 PCT/IB2005/000928 818 sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P19, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 5 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR ofD1 1853 PEA 1 P19. 3.An isolated polypeptide encoding for a tail of D11853_PEA_1_P19, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 10 sequence SRLTLQWEQQRCPGYRCKS in D1 1853_PEA_1_P19. Comparison report between Di11853 PEA_1 P19 and Q96FY2: I.An isolated chimeric polypeptide encoding for Dl 1853_PEA_1 P19, comprising a first amino acid sequence being at least 90 % homologous to 15 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLPJMDPYKASYGV EDPEYAVTQ corresponding to amino acids 1 - 128 of Q96FY2, which also corresponds to amino acids 1 - 128 of Dl 1853_PEA_1_P19, a bridging amino acid L corresponding to amino acid 129 of D11853_PEA_1 P19, a second amino acid sequence being at least 90 % 20 homologous to AQTTMRSELGKLS corresponding to amino acids 130 - 142 of Q96FY2, which also corresponds to amino acids 130 - 142 of D1 1853_PEA 1_P19, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SRLTLQWEQQRCPGYRCKS corresponding to amino acids 143 - 161 of 25 D11853_PEA_1_P19, wherein said first amino acid sequence, bridging amino acid, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853 PEA_1 P19, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 30 sequence SRLTLQWEQQRCPGYRCKS in D11853_PEA_1_P19.

WO 2005/072053 PCT/IB2005/000928 819 Comparison report between Dl 1853 PEA 1 P19 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for D 11853 PEA 1 P19, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI 5 LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGV EDPEYAVTQLAQTTMRSELGKLS corresponding to amino acids 1 - 142 of Q9UJZ1, which also corresponds to amino acids I - 142 of DI11853 PEA_1 P19, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 10 SRLTLQWEQQRCPGYRCKS corresponding to amino acids 143 - 161 of Dl 1853_PEA_1_P19, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1 P19, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 15 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SRLTLQWEQQRCPGYRCKS in D1 1853_PEA-1_P19. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 20 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. Variant protein D 1853 PEA__1_P19 also has the following non-silent SNPs (Single 25 Nucleotide Polymorphisms) as listed in Table 25, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Dl 1853_PEA_1_P19 sequence provides support for the deduced sequence of this variant protein according to the present invention). 30 Table 25 - Amino acid mutations WO 2005/072053 PCT/IB2005/000928 820 SNP positions) on amnino acid Alternative amino acid(s) Previously known SNP? sequence 25 P-> No 32 L -> No 144 R -> K No 151 Q->* No 156 G -> No Variant protein D11853_PEA_1_P19 is encoded by the following transcript(s): DI11853_PEA_1_T27, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D 11853 PEA 1_T27 is shown in bold; this coding portion starts at 5 position 108 and ends at position 590. The transcript also has the following SNPs as listed in Table 26 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853_PEA_1_P19 sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 26 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previ usly kiown SNP? sequence 180 C -> No 182 G -> No 185 -> C No 201 T-> No 538 G -> A No 558 C -> T No 573 G-> No 654 G -> A No 657 A -> No 657 A -> C No WO 2005/072053 PCT/IB2005/000928 821 703 T-> No 706 T -> C No 706 T ->G No 743 T C Yes Variant protein D11853 PEA 1_P20 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA__T7, D11853_PEA_1_T17 and D11853 PEA 1 T25. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal-peptide prediction programs 10 (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. Variant protein D11853_PEA_1_P20 is encoded by the following transcript(s): D11853_PEA_1_T7, D11853_PEA_1_T17 and D11853_PEA_1_T25, for which the sequence(s) is/are given at the end of the application. 15 The coding portion of transcript Di11853 PEA_1 T7 is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following SNPs as listed in Table 27 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D 11853 PEA 1 P20 sequence provides support for 20 the deduced sequence of this variant protein according to the present invention). Table 27 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 406 C -> No 408 G-> No 411 -> C No WO 2005/072053 PCT/IB2005/000928 822 427 T-> No 1357 A ->C No 1357 A ->G No 1358 G No 1358 G-> A No 1377 C -> G No 1384 A ->C No 1440 G ->A No 1512 G-> A No 1512 G ->C No 1529 A-> No 1529 A ->C No 1540 A ->C No 1555 C-> No 1555 C ->G No 1625 A ->C No 1649 A ->C No 1657 T -> G No 1675 G -> A No 1675 G -> C No 1683 -> C No 1683 -> T No 1690 -> G No 1719 C -> No 1719 C -> G No 1750 -> G No 1800 G -> No 1809 G->A No 1829 C -> T No 1844 G -> No WO 2005/072053 PCT/IB2005/000928 823 1925 G ->A No 1928 A-> No 1928 A ->C No 1974 T-> No 1977 T ->C No 1977 T ->G No 2014 T ->C Yes The coding portion of transcript D11853_PEA_1 T17 is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following SNPs as listed in Table 28 (given according to their position on the nucleotide sequence, with 5 the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D11853_PEA_1_P20 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 28 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 406 C-> No 408 G-> No 411 -> C No 427 T -> No 1357 A->C No 1357 A ->G No 1358 G-> No 1358 G ->A No 1377 C ->G No 1384 A ->C No 1440 G ->A No 1512 G ->A No 1512 G ->C No WO 2005/072053 PCT/IB2005/000928 824 1529 A-> No 1529 A -> C No 1540 A -> C No 1555 C-> No 1555 C ->GNo 1625 A -> C No 1649 A -> C No 1657 T-> G No 1675 G-> A No 1675 G ->C No 1683 ->C No 1683 ->T No 1690 ->G No 1719 C -> No 1719 C ->G No 1750 ->G No 1800 G-> No 1809 G ->A No 1829 C -> T No 1844 G -> No 1925 G->A No 1928 A -> No 1928 A -> C No 1974 T -> No 1977 T -> C No 1977 T->G No 2014 T -> C Yes The coding portion of transcript D11853_PEA_1 _T25 is shown in bold; this coding portion starts at position 108 and ends at position 287. The transcript also has the following WO 2005/072053 PCT/IB2005/000928 825 SNPs as listed in Table 29 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D1 1853 PEA_1 P20 sequence provides support for the deduced sequence of this variant protein according to the present invention). 5 Table 29 - Nucleic acid SNPs SNP position oni ncleotide Alternative nucleic acid Previously known SNP? sequence 406 C-> No 408 G-> No 411 ->C No 427 T-> No 1489 A ->C No 1489 A ->G No 1490 G-> No 1490 G ->A No 1509 C ->G No 1516 A ->C No 1572 G ->A No 1644 G ->A No 1644 G ->C No 1661 A-> No 1661 A ->C No 1672 A ->C No 1687 C-> No 1687 C ->G No 1757 A ->C No 1986 A ->C No 1994 T ->G No 2012 G ->A No WO 2005/072053 PCT/IB2005/000928 826 2012 G -> C No 2020 ->C No 2020 ->T No 2027 ->G No 2056 C -> No 2056 C -> G No 2087 -> G No 2120 C ->T No 2562 G No 2571 G ->A No 2591 C ->T No 2606 G-> No 2687 G ->A No 2690 A-> No 2690 A ->C No 2736 T-> No 2739 T->C No 2739 T ->G No 2776 T ->C Yes Variant protein D11853_PEA_1_P21 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 Di11853_PEA_1_T8. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between D1 1853_PEA_1_P21 and Q96FY2: WO 2005/072053 PCT/IB2005/000928 827 1.An isolated chimeric polypeptide encoding for D 11853_PEA 1 P21, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGPAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEP corresponding to amino acids 1 - 61 of Q96FY2, which also corresponds to amino acids 1 5 61 of D 1853_PEA_1_P21, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT corresponding to amino acids 62 - 102 of D11853_PEA_1_P21, wherein said first amino acid sequence and second 10 amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1_P21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT in 15 D11853_PEA_1_P21. Comparison report between D1 1853 PEA_1_P21 and Q9UJZ1: 1.An isolated chimeric polypeptide encoding for DI11853_PEA__P21, comprising a first amino acid sequence being at least 90 % homologous to 20 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEP corresponding to amino acids I - 61 of Q9UJZ I, which also corresponds to amino acids 1 61 of D11853_PEA_1_P21, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 25 VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT corresponding to amino acids 62 - 102 of D 11853_PEA_1_P21, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA 1 P21, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 30 more preferably at least about 90% and most preferably at least about 95% homologous to the WO 2005/072053 PCT/IB2005/000928 828 sequence VRNLFCPPWASQMTNPSRHAMSGGLPLGLPALLAPDSVGQT in D11853_PEA_1_P21. The location of the variant protein was determined according to results from a number of 5 different software programs and analyses, including analyses from SignaIP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptideNN:NO) predicts that this protein has a signal peptide. 10 Variant protein D11853_PEA_1_P21 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 30, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Dl 1853 PEA_1_P21 sequence provides support for the deduced sequence of this variant protein according to the 15 present invention). Table 30 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequences, 25 P-> No 32 L-> No Variant protein D11853_PEA_1_P21 is encoded by the following transcript(s): D11853_PEA_1_T8, for which the sequence(s) is/are given at the end of the application. The 20 coding portion of transcript D11853_PEAI_T8 is shown in bold; this coding portion starts at position 108 and ends at position 413. The transcript also has the following SNPs as listed in Table 31 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D 11853_PEA_1_P21 sequence provides support for the deduced 25 sequence of this variant protein according to the present invention). Table 31 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 829 SNP position on nucleotide Alternative nucleic acid Previously inown SNP? sequence 180 C ->No 182 G No 185 -> C No 201 T -> No 1131 A -> C No 1131 A ->G No 1132 G-> No 1132 G ->A No 1151 C ->G No 1158 A ->C No 1214 G -> A No 1286 G -> A No 1286 G ->C No 1303 A-> No 1303 A ->C No 1314 A ->C No 1329 C-> No 1329 C ->G No 1399 A ->C No 1423 A ->C No 1431 T ->G No 1449 G ->A No 1449 G ->C No 1457 ->C No 1457 ->T No 1464 ->G No 1493 C -> No 1493 C -> G No WO 2005/072053 PCT/IB2005/000928 830 1524 G No 1574 G ->No 1583 G-> A No 1603 C-> T No 1618 G ->No 1699 G ->A No 1702 A-> No 1702 A ->C No 1748 T-> No 1751 T ->C No 1751 T ->G No 1788 T ->C Yes Variant protein D11853 PEA_1__P22 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEA_1_T9. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 10 Comparison report between Di 1853_PEA_1_P22 and Q9P042: 1.An isolated chimeric polypeptide encoding for D1 1853_PEA_1 P22, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of 15 D11853_PEA_1_P22, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEP corresponding to amino acids 13 - 47 of Q9P042, which also corresponds to amino acids 27 - 61 of D1 1853__PEA_1_P22, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having WO 2005/072053 PCT/IB2005/000928 831 the sequence ELLLFWACSMC corresponding to amino acids 62 - 72 of DI11853 PEA _IP22, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of D11853_PEA_1_P22, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR of D1 1853 PEA 1 P22. 3.An isolated polypeptide encoding for a tail of DI 1853_PEA_1_P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELLLFWACSMC in Dl 1853_PEA_1_P22. Comparison report between D 11853 PEA_1_P22 and Q96FY2: 1.An isolated chimeric polypeptide encoding for DI11853_PEA_1_P22, comprising a first 15 amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEP corresponding to amino acids 1 - 61 of Q96FY2, which also corresponds to amino acids I 61 of D11853_PEA_1_P22, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 20 95% homologous to a polypeptide having the sequence ELLLFWACSMC corresponding to amino acids 62 - 72 of Di11853 PEA_1_P22, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1 P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 25 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence ELLLFWACSMC in Dl 1853_PEA_1_P22. Comparison report between D1 1853_PEA__P22 and Q9UJZI: 1.An isolated chimeric polypeptide encoding for D11853_PEA_1_P22, comprising a first 30 amino acid sequence being at least 90 % homologous to

MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI

WO 2005/072053 PCT/IB2005/000928 832 LEP corresponding to amino acids 1 - 61 of Q9UJZ1, which also corresponds to amino acids 1 61 of DI 1853_PEA_ _P22, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence ELLLFWACSMC corresponding to 5 amino acids 62 - 72 of D 1853_PEA 1 P22, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of D11853_PEA_1 P22, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 10 sequence ELLLFWACSMC in D1 1853_PEA_1_P22. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 15 secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a signal peptide. Variant protein D11853._PEA 1 P22 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 32, (given according to their position(s) on the 20 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein DI 1853_PEA_1_P22 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 32 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? Sequence 25 P-> No 32 L -> No 25 WO 2005/072053 PCT/IB2005/000928 833 Variant protein D11853_PEA_1 P22 is encoded by the following transcript(s): DI 1853_PEA-1_T9, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript D11853_PEA 1 T9 is shown in bold; this coding portion starts at position 108 and ends at position 323. The transcript also has the following SNPs as listed in 5 Table 33 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein D 11853 PEA 1 P22 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 33 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SN]? sequence 180 C-> No 182 G-> No 185 ->C No 201 T-> No 757 A -> C No 757 A ->G No 758 G-> No 758 G ->A No 777 C ->G No 784 A ->C No 840 G ->A No 912 G ->A No 912 G ->C No 929 A-> No 929 A ->C No 940 A ->C No 955 C-> No 955 C ->G No 1025 A ->C No WO 2005/072053 PCT/IB2005/000928 834 1049 A C No 1057 T-> G No 1075 G-> A No 1075 G-> C No 1083 -> C No 1083 -> T No 1090 -> G No 1119 C -> No 1119 C -> G No 1150 -> G No 1200 G -> No 1209 G ->A No 1229 C ->T No 1244 G-> No 1325 G ->A No 1328 A-> No 1328 A ->C No 1374 T-> No 1377 T -> C No 1377 T ->G No 1414 T ->C Yes Variant protein DI11853._PEA_1_P24 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 D11853_PEAIT21. An alignment is given to the known protein (Membrane associated protein SLP-2) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: WO 2005/072053 PCT/IB2005/000928 835 Comparison report between DI11853-PEA 1 P24 and Q9P042: 1.An isolated chimeric polypeptide encoding for DI 1853_PEA_1_P24, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 5 the sequence MLARAARGTGALLLRGSLLASGRAPR corresponding to amino acids 1 - 26 of D11853_PEA_1_P24, a second amino acid sequence being at least 90 % homologous to RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVP EQSAVTL corresponding to amino acids 13 - 80 of Q9PO42, which also corresponds to amino acids 27 - 94 of Dl 1853 PEA__P24, and a third amino acid sequence being at least 70%, 10 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTGVPECQHCGCHQPSC corresponding to amino acids 95 - 111 of D11853_PEA _1 P24, wherein said first amino acid sequence, second amino acid sequence and third amino acid sequence are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a head of Dl1853 PEA_1_P24, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MLARAARGTGALLLRGSLLASGRAPR ofD1 1853 PEA 1 P24. 3.An isolated polypeptide encoding for a tail of D11853_PEA_1 P24, comprising a 20 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GTGVPECQHCGCHQPSC in D11853_PEA_1_P24. Comparison report between D 11853_PEA_1_P24 and Q96FY2: 25 1.An isolated chimeric polypeptide encoding for DI11853_PEA_1 P24, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL corresponding to amino acids 1 - 94 of Q96FY2, which also corresponds to amino acids 1 - 94 of D11853_PEA_1 P24, and a second 30 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having WO 2005/072053 PCT/IB2005/000928 836 the sequence GTGVPECQHCGCHQPSC corresponding to amino acids 95 - 111 of D11853_PEA_1 P24, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Dl 1853 PEA_1 P24, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GTGVPECQHCGCHQPSC in D11853_PEA_1_P24. Comparison report between D11853_PEA_1 P24 and Q9UJZ1: 10 1.An isolated chimeric polypeptide encoding for DI 1853 PEA_ 1 P24, comprising a first amino acid sequence being at least 90 % homologous to MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVERMGRFHRI LEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL corresponding to amino acids 1 - 94 of Q9UJZ1, which also corresponds to amino acids 1 - 94 of D1 1853 PEA 1_P24, and a second 15 amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence GTGVPECQHCGCHQPSC corresponding to amino acids 95 - 111 of DI11853_PEA_1_P24, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of D11853_PEA_1 P24, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence GTGVPECQHCGCHQPSC in D11853_PEA_1_P24. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because one of the two signal peptide prediction programs (HMM:Signal peptide,NN:NO) predicts that this protein has a 30 signal peptide.

WO 2005/072053 PCT/IB2005/000928 837 Variant protein Dl 1853_PEAIP24 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 34, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Dl 1853_PEA_1_P24 5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 34 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) Previously known SNP? sequence 25 P -> No 32 L-> No Variant protein Dll853_PEA_1_P24 is encoded by the following transcript(s): 10 D11853_PEA _1T21, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript Dl 1853_PEA__T21 is shown in bold; this coding portion starts at position 108 and ends at position 440. The transcript also has the following SNPs as listed in Table 35 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein D 11853 PEA__1_P24 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 35 -Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 180 C-> No 182 G-> No 185 -> C No 201 T-> No 479 A ->C No 479 A ->G No WO 2005/072053 PCT/IB2005/000928 838 480 G ->No 480 G-> A No 499 C-> G No 506 A ->CNo 562 G A No 634 G ->A No 634 G-> C No 651 A ->No 651 A -> C No 662 A ->C No 677 C-> No 677 C ->G No 747 A ->C No 771 A->C No 779 T ->G No 797 G ->A No 797 G ->C No 805 -> C No 805 -> T No 812 -> G No 841 C -> No 841 C -> G No 872 -> G No 922 G -> No 931 G -> A No 951 C->T No 966 G -> No 1047 G->A No 1050 A -> No 1050 A->C No WO 2005/072053 PCT/IB2005/000928 839 1096 T-> No 1099 T -> C No 1099 T ->G No 1136 T ->C Yes As noted above, cluster D11853 features 31 segment(s), which were listed in Table 2 5 above and for which the sequence(s) are given at the end of the application. These segment(s) are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 10 Segment cluster D11853 PEA _Inode 3 according to the present invention is supported by 24 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_1_T7, D11853 PEA 1_T17 and D1 1853_PEA_1_T25. Table 36 below describes the starting and ending position of this segment on each transcript. 15 Table 36 - Segment location on transcripts 'Transcript name Segment,- Segmnent starting position ending position D11853_PEA1_T7 153 378 D11853_PEAI _T17 153 378 D11853_PEA_1_T25 153 378 Segment cluster D11853 PEA__1node_6 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment 20 can be found in the following transcript(s): D11853_PEA_1_T7, D11853_PEAIT8, WO 2005/072053 PCT/IB2005/000928 840 D11853_PEA_1_117 and D11853_PEA_1_T25. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA_1_T7 517 890 D1853_PEA 1_T8 291 664 D11853_PEAI T17 517 890 D11853_PEA 1 T25 517 890 5 Segment cluster D11853-PEA_1_node 9 according to the present invention is supported by I libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D 11853 PEA 1 T25. Table 38 below describes the starting and ending position of this segment on each transcript. 10 Table 38 - Segment location on transcripts Transcript name Segment Segment,, staringposiion ending position D11853_PEA 1T25 1108 1239 Segment cluster D 11853 PEA Inode 17 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): D11853 PEA 1 T16 and D11853_PEA_1_T23. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA_1_T16 552 700 WO 2005/072053 PCT/IB2005/000928 841 D11853_PEA_1T23 552 700 Segment cluster D 11853 PEA 1_node 21 according to the present invention is supported by 6 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853 PEA 1 T19 and D11853_PEA_1_T23. Table 40 below describes the starting and ending position of this segment on each transcript. Table 40 - Segment location on transcripts Transcript namne Segment,- Segment starting position ending position D11853_PEA_1 19 687 830 D11853_PEA_1 T23 836 979 10 Segment cluster DI11853 PEA Inode_22 according to the present invention is supported by 287 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): DI11853_PEA I TI, D11853_PEA 1_T3, D11853_PEA_1T7, D11853_PEA_1_T8, D11853_PEA1_T9, D11853 PEA 1 T10, D11853_PEA_1 13, D11853_PEA 1 T14, D11853 PEA 1 115, D11853_PEA_1T16, 15 D11853_PEA_1_T17, D11853_PEA_1_T19, D11853_PEA_1_T21, D11853_PEA_1_T23, D11853_PEA_1_T24 and D11853_PEA_1_T25. Table 41 below describes the starting and ending position of this segment on each transcript. Table 41 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA_11 687 831 D11853_PEA 1T3 687 831 D11853_PEA 1 T7 1404 1548 D11853_PEA_1_T8 1178 1322 WO 2005/072053 PCT/IB2005/000928 842 D11853_PEA _lT9 804 948 D11853 PEA I TIO 687 831 D11853 PEA_1_T13 687 831 D11853_PEA 1_T14 687 831 D11853_PEA 1_TI5 687 831 D11853_PEAI1T16 836 980 D11853_PEA1_T17 1404 1548 D11853_PEA 1_T19 831 975 D11853_PEA1_T21 526 670 D11853_PEA1_T23 980 1124 D11853_PEA 1_T24 552 696 D11853_PEAI _T25 1536 1680 Segment cluster D 11853_PEA_1_node_23 according to the present invention is supported by 4 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853 PEA_1_T13 and D11853 PEA_1_T15. Table 42 below describes the starting and ending position of this segment on each transcript. Table 42 - Segment location on transcripts Transcript name Segment Se sment starting position ending position D11853_PEA 1_T13 832 954 D11853_PEA_1_T15 832 954 10 Segment cluster D11853 PEA 1 node 25 according to the present invention is supported by 11 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D1 1853 PEA-1_T10, D11853_PEA_1_T15 and D11 853_PEAIT25. Table 43 below describes the starting and ending position of this segment on each transcript.

WO 2005/072053 PCT/IB2005/000928 843 Table 43 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA_1T10 912 1116 D11853_PEA_1_T15 1035 1239 D11853_PEA_1T25 1761 1965 Segment cluster DI11853 PEA _ node_26 according to the present invention is supported 5 by 290 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D1 1853 PEAI_TI, D11853 PEAI_T3, D11853_PEA_1_T7, D11853_PEAIT8, D11853_PEA_1_T9, D11853_PEA_1T1O, D11853_PEA1_T13, D11853_PEA_1 T15, D11853_PEA_1_T16, D11853_PEA_1_T17, D11853_PEA1_T19, D11853_PEA1_T21, D11853_PEA 1T23, D11853_PEA_1T24 and 10 D11 853_PEA1_T25. Table 44 below describes the starting and ending position of this segment on each transcript. Table 44 - Segment location on transcripts Transcript name Segment Segment startingposition1 eding position D11853 PEA 1 T3 912 1040 D11853_PEA_1_T7 1629 1757 D11853_PEA_1_T8 1403 1531 D11853_PEA_1 T9 1029 1157 D11853_PEA 1_T10 1117 1245 D11853_PEA113 1035 1163 D11853_PEA_115 1240 1368 D11853_PEA _1T16 1061 1189 D11853_PEA117 1629 1757 WO 2005/072053 PCT/IB2005/000928 844 D11853_PEA_1_T19 1056 1184 D11853_PEA 1 T21 751 879 D11853_PEA_1_T23 1205 1333 D11853_PEA1 1T24 777 905 D11853_PEA1 1T25 1966 2094 Segment cluster DI11853_PEA_1_node_27 according to the present invention is supported by 8 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D1 1853 PEA IT3 and D11853_PEA_1_T25. Table 45 below describes the starting and ending position of this segment on each transcript. Table 45 - Segment location on transcripts Transcript namie Segient Segment starting position ending position D11853_PEA 1_T3 1041 1460 D11853_PEA 1 T25 2095 2514 10 Segment cluster D 11853 PEA 1 node_30 according to the present invention is supported by 249 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D 11853_PEA 1 TI, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853 PEA_1 T1, D11853_PEA_1_T13, D11853_PEA_1_T14, D11853_PEA_1_TI5, D11853_PEA_1_T16, 15 D11853_PEA_1_T17, D11853_PEA_1_T19, D11853 PEA_1_T21, D11853_PEA_1_T23, D11853_PEA_1_T24, D11853_PEA_1_T25, D11853_PEA_1_T26 and D11853_PEA_1_T27. Table 46 below describes the starting and ending position of this segment on each transcript. Table 46 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 845 D11853 PEA_1_1 1088 1207 D11853 PEA 1_T3 1513 1632 D11853_PEA_1_T7 1805 1924 D11853_PEA_1T8 1579 1698 D11853_PEA 1 T9 1205 1324 D11853_PEA_1 TI 1293 1412 D11853_PEA_1T13 1211 1330 D11853_PEA_114 959 1078 D11853_PEA 1_15 1416 1535 D11853_PEA1 T16 1237 1356 D11853_PEA_1 T17 1805 1924 D11853_PEA_119 1232 1351 D11853_PEA1_T21 927 1046 D11853_PEA_1 T23 1381 1500 D11853_PEA_1 T24 953 1072 D11853_PEA_1T25 2567 2686 D11853_PEA1_T26 635 754 D11853_PEA_1 T27 534 653 Segment cluster D1 1853_PEA1_node_32 according to the present invention is supported by 215 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D1 1853 PEA 1 Ti, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA__1T8, D11853_PEA1_T9, D11853_PEA_1_TIO, D11853_PEA_113, D11853_PEA_1_T14, D11853 PEA 1 T15, D11853_PEA_1_T16, D11853_PEA_117, D11853_PEA_1_T19, D11853_PEA_1_T21, D11853_PEA_1_T23, D11853_PEA1 T24, D11853 PEA1_T25, D11853_PEA_1_T26 and D11853_PEA1_T27. 10 Table 47 below describes the starting and ending position of this segment on each transcript. Table 47 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 846 Transcript name Segment Segment starting position ending position D11853_PEA 1_TI 1208 1437 D11853_PEA 1_T3 1633 1745 D11853_PEAI 1T7 1925 2037 D11853_PEA1 1T8 1699 1811 D11853_PEA IT9 1325 1437 D11853_PEA1T1O 1413 1525 D11853 PEA1 13 1331 1443 D11853_PEA1_T14 1079 1191 D11853 PEA 1 15 1536 1648 D11853_PEA 1 16 1357 1469 D11853_PEA_1 17 1925 2154 D11853_PEA 1 T19 1352 1464 D11853 PEA1_T21 1047 1159 D11853_PEA1 1T23 1501 1613 D11853_PEA_1T24 1073 1185 D11853_PEA 1T25 2687 2799 D11853 PEA1_T26 755 984 D11853_PEA1_T27 654 766 According to an optional embodiment of the present invention, short segments related to 5 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster D 11853_PEA_1_node 0 according to the present invention is supported by 14 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): D11853_PEA-I_Ti, D11853_PEA_1_T3, WO 2005/072053 PCT/IB2005/000928 847 D11853_PEA_1_T7, D11853 PEA 1 T8, D11853_PEA_1_T9, D11853_PEAITIO, D11853_PEA-1_T13, D11853 PEA 1 T14, D11853 PEA 1 T15, D11853_PEA1T16, D11853_PEA-1_T17, D11853 PEA 1 T19, D11853_PEA 1 T21, D11853_PEA_ IT23, D11853_PEAI_T24, D11853_PEA_1_T25, D11853_PEAIT26 and D11853_PEA1_T27. 5 Table 48 below describes the starting and ending position of this segment on each transcript. Table 48 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA_1_TI 1 41 D11853 PEA_1_T3 1 41 D11853_PEA_1 T7 1 41 D11853_PEA 1_T8 1 41 D11853_PEA_1 T9 1 41 D11853_PEA 1 T1O 1 41 D11853_PEA_1_13 1 41 D11853_PEA 1_T14 1 41 D11853_PEA 1_T15 1 41 D11853_PEA1 1T16 1 41 D11853_PEA 1 17 1 41 D11853_PEAI 1T19 1 41 D11853_PEA_1T21 1 41 D11853_PEA_1_T23 1 41 D11853_PEA 1T24 1 41 D11853_PEA_1_T25 1 41 D11853_PEA 1T26 1 41 D11853_PEA 1_T27 1 41 Segment cluster D 11853_PEA-1_node_1 according to the present invention is supported 10 by 158 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 848 can be found in the following transcript(s): D11853_PEA 1 TI, D11853 PEA_1_T3, D11853_PEA1 _T7, D11853PEA_1T8, D11853_PEAIT9, D11853 PEA_ 1 T10, D11853_PEA 1T13, D11853_PEA1T14, D11853 PEA1 1T15, D11853 PEA 1 T16, D11853_PEA_1_T17, D11853 PEA 1_T19, D11853 PEA 1 T21, D11853_PEA1_T23, 5 D11853_PEA 1T24, D11853_PEA-1_T25, D11853_PEA_1_T26 and D11853 PEA 1 T27. Table 49 below describes the starting and ending position of this segment on each transcript. Table 49 - Segment location on transcripts Transcript name gnent Segment starting position end'n posito D11853 PEA 1_TI 42 110 D11853_PEA 1 T3 42 110 D11853_PEA 1_T7 42 110 D11853_PEA 1_T8 42 110 D11853_PEA_1_T9 42 110 D11853_PEA1 1T10 42 110 D11853_PEA 113 42 110 D11853_PEA_114 42 110 D11853_PEA1_115 42 110 D11853_PEA 1_16 42 110 D11853_PEA1 117 42 110 D11853_PEA1 119 42 110 D11853_PEA_1T21 42 110 D11853_PEA_1T23 42 110 D11853_PEA_1T24 42 110 D11853_PEA_1T25 42 110 D11853_PEA1 1T26 42 110 D11853_PEA_1_T27 42 110 WO 2005/072053 PCT/IB2005/000928 849 Segment cluster DI11853_PEA_1_node_2 according to the present invention is supported by 247 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D1 1853_PEA_ I_TI, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1T8, D11853_PEA_1_T9, D11853 PEA-I_T0I, 5 D11853_PEA_1_T13, D11853_PEA_1 T14, D11853_PEA_1_T15, D11853 PEA_1 _T16, D11853_PEA1_T17, D11853PEA1T19, D11853 PEA_1 T21, D11853 PEA IT23, D11853_PEA1_T24, D11853_PEA1_T25, D11853 PEA_1_T26 and D11853_PEA1_T27. Table 50 below describes the starting and ending position of this segment on each transcript. Table 50 - Segment location on transcripts Transcript name Segiment Segment starting position ending position D11853_PEA_1_T 111 152 D11853 PEA_1 T3 111 152 D11853_PEA_1_T7 111 152 D11853_PEA1'TS ill 152 D11853_PEA 1_T9 111 152 D11853_PEA1 T9O 111 152 D11853_PEA_1 T13 111 152 D11853_PEAI 1T13 111 152 D11853_PEA1_TI 111 152 D11853_PEA__T15 1l1 152 D11853_PEA_1_T16 111 152 D11853_PEA1 1T17 111 152 D11853_PEA 1_T21 111 152 D11853_PEA 1_T21 111 152 D11853_PEA_1 T24 111 152 D11853_PEA_1_T25 111 152 D11853_PEA1 T26 111 152 D11853 PEA_1 T27 111 152 10 WO 2005/072053 PCT/IB2005/000928 850 Segment cluster DI11853 PEA 1 node_4 according to the present invention is supported by 258 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D1 1853_PEA 1 TI, D11853_PEA_1_T3, 5 D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA 1 _T1, D11853_PEA_1_T13, D11853_PEAIT14, D11853 PEA 1 T15, D11853_PEAl1 TI6, D11853_PEA_1_T17, D11853_PEA1_T19, D11853_PEA1_T21, D11853_PEA1_T23, D11853_PEA_1_T24, D11853_PEA_1 T25, D11853_PEA IT26 and D11853_PEAIT27. Table 51 below describes the starting and ending position of this segment on each transcript. 10 Table 51 - Segment location on transcripts Transcript name Segmen Segment starting position ending position D11853_PEA_1_Ti 153 185 D11853_PEA_1 T3 153 185 D11853_PEA_1_T7 379 411 D11853_PEA1 T8 153 185 D11853_PEA_1_T9 153 185 D11853_PEA1 T10 153 185 D11853_PEAI _T13 153 185 D11853 PEA1_T14 153 185 D11853_PEA_1_TI5 153 185 D11853_PEA 1_T16 153 185 D11853_PEA_1_T17 379 411 D11853 PEA 1 T19 153 185 D11853_PEA_1 T21 153 185 D11853_PEA1_T23 153 185 D11853_PEA_T24 153 185 D11853_PEA_1 T25 379 411 D11853_PEA_1_T26 153 185 D11853_PEA_T27 153 185 WO 2005/072053 PCT/IB2005/000928 851 Segment cluster DI11853 PEA 1 node 5 according to the present invention is supported by 291 libraries. The number of libraries was detennined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_TI, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEAIT8, D11853_PEA_1_T9, D11853_PEA1T10, D11853 PEA 1 T13, D11853_PEA_1_T14, D11853_PEA_1_T15, D11853_PEA_1Tt6, D11853_PEA1T17, D11853_PEA1T19, D11853_PEA1_T21, D11853_PEA_1_T23, D11853_PEA1_T24, D11853_PEA1_T25, D11853_PEA_1_T26 and D11853_PEA1_T27. 10 Table 52 below describes the starting and ending position of this segment on each transcript. Table 52 - Segment location on transcripts Transcript name Segment gme starting position ending position D11853 PEA_1_Ti 186 290 D11853 PEAIT3 186 290 Df1853_PEA 1 T7 412 516 D11853 PEA 1 T8 186 290 DI1853_PEA_1_T9 186 290 D11853_PEA 1 TIO 186 290 D11853_PEA_1_T13 186 290 DI1853_PEA_1_T14 186 290 D11853_PEA_1_T15 186 290 D11853_PEA 1 T16 186 290 D11853_PEA1_T17 412 516 D11853_PEAIT19 186 290 D11853 PEA_1_T21 186 290 D11853_PEAIT23 186 290 D11853_PEA_1_T24 186 290 D11853_PEA1_T25 516 D11853 PEA_1_T26 186 290 WO 2005/072053 PCT/IB2005/000928 852 D11853_PEA_1_T27 186 290 Segment cluster DI11853_PEA_1_node_7 according to the present invention is supported by 20 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_T7, D11853_PEA_1_TS, D11853_PEA_1_T9, D11853_PEA_1_T17 and D11853_PEA_1_T25. Table 53 below describes the starting and ending position of this segment on each transcript. Table 53 - Segment location on transcripts Transcript name Segm1ent Segmenit starting position ending position D11853 PEA 1_T7 891 1007 D11853_PEA 1 T8 665 781 D11853_PEA 1 T9 291 407 D11853_PEA_1 T17 891 1007 D11853_PEA_1_T25 891 1007 10 Segment cluster DI11853_PEA_1_node_8 according to the present invention is supported by 304 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): D11853_PEA_1Ti, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA_1_TlO, 15 D11853_PEA_1_T13, D11853_PEA_1_T14, D11853_PEA_1_T15, D11853_PEA_1_T16, D11853_PEA_1_T17, D11853_PEA_1_T19, D11853_PEA_1_T21, D11853_PEA_1_T23, D11853_PEA_1_T24, D11853_PEA_1_T25, D11853_PEA_1_T26 and D11853_PEA_1_T27. Table 54 below describes the starting and ending position of this segment on each transcript. Table 54 - Segment location on transcripts Transcript name Segment Segment starting position ending position WO 2005/072053 PCT/IB2005/000928 853 D11853_PEA 1_1 291 390 D11853_PEA 1_T3 291 390 D11853_PEA_1_T7 1008 1107 D11853_PEA1 1T8 782 881 D11853_PEA 1 T9 408 507 D11853_PEA_1_T10 291 390 D11853_PEAI T13 291 390 D11853PEA1 14 291 390 D11853_PEA 1 T15 291 390 D11853_PEA_1_T16 291 390 D11853_PEA 1_T17 1008 1107 D11853_PEA_119 291 390 D11853 PEA 1_T21 291 390 D11853_PEA_1_T23 291 390 D11853_PEAIT24 291 390 D11853_PEA1_T25 1008 1107 D11853_PEA1 1T26 291 390 D11853_PEA1_T27 291 390 Segment cluster D11853_PEA_1_node_10 according to the present invention is supported by 237 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_TI, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA 1 T9, D11853_PEA_1_T10, D11853_PEA_1_T13, D11853_PEA_1T14, D11853_PEA_1T15, D11853_PEA_1_T16, D11853_PEA_1_17, D11853_PEA 1T19, D11853_PEA 1 T23, D11853 PEA_1_T24, D11853 PEA 1 T25, D11853 PEA 1 T26 and D11853 PEA 1 T27. Table 55 below 10 describes the starting and ending position of this segment on each transcript. Table 55 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 854 Transcript name Segment Segment starting position ending position D11853_PEA 1 Ti 391 449 D11853_PEA_1_T3 391 449 D11853_PEA_1_T7 1108 1166 D11853_PEA1 1T8 882 940 D11853_PEA_1_T9 508 566 D11853_PEA_1T10 391 449 D11853 PEA 1_13 391 449 D11853_PEA_1_T14 391 449 D11853_PEA1 TI5 391 449 D11853_PEA 1_16 391 449 D11853 PEA 1_17 1108 1166 D11853_PEA1T119 391 449 D11853_PEA1_T23 391 449 D11853_PEA1_T24 391 449 D11853_PEA1 1T25 1240 1298 D11853_PEA1 1T26 391 449 D11853_PEA 1 T27 391 449 Segment cluster D11853_PEAInode_12 according to the present invention is supported by 239 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1 T1, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA_1T10, D11853 PEA_1_13, D11853_PEA_1_14, D11853_PEA1 1T15, D11853_PEA_116, D11853_PEA_1_T17, D11853_PEA_1_T19, D11853_PEA1_T23, D11853_PEA_1_T24, D11853_PEA1_T25, D11853_PEA_1_T26 and D11853_PEA1_T27. Table 56 below 10 describes the starting and ending position of this segment on each transcript. Table 56 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 8 55 Transcript name Segment Segment starting position ending position D11853_PEAITI 450 482 D11853_PEA 1 T3 450 482 D11853_PEA1_T7 1167 1199 D11853 PEA1 1T8 941 973 D11853_PEA 1 T9 567 599 D11853_PEA_1T10 450 482 D11853_PEA11-T13 450 482 D11853_PEA_1_T14 450 482 DI11853PEA 1 15 450 482 D11853_PEA1 16 450 482 D11853_PEA 1 17 1167 1199 D11853_PEA1 19 450 482 D11853_PEA_1_T23 450 482 D _1853 PEA_1_T24 450 482 D11853 PEA 1 T25 1299 1331 D11853_PEA1 1T26 450 482 D11853_PEA_1_T27 450 482 Segment cluster D11853_PEA_1_node_13 according to the present invention can be found in the following transcript(s): D1 1853_PEA1_1, D1 1853_PEA_1_T3, 5 D11853_PEA1_T7, D11853_PEA_1_T8, D11853_PEA1_T9, D11853_PEA1T10, D11853_PEA113, D11853_PEA_1_T14, D11853_PEA_1_T15, D11853_PEA116, D11853 PEA 1 17, D11853_PEA_1_T19, D11853_PEA1_T23, D11853_PEA_1_T24, D11853_PEA1_T25, D11853_PEA_1_T26 and D11853_PEA1_T27. Table 57 below describes the starting and ending position of this segment on each transcript. 10 Table 57 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 856 Transcript name Segment Segment starting position ending position D11853_PEA_1_Ti 483 495 D11853_PEA 1 T3 483 495 D11853_PEA_1_T7 1200 1212 D11853_PEA_1_T8 974 986 D11853_PEA_1_T9 600 612 D11853_PEA10TO 483 495 D11853_PEA 1 T13 483 495 D11853_PEAIT14 483 495 D11853_PEA 1 T15 483 495 D11853_PEA_1_T16 483 495 D11853_PEA 1 17 1200 1212 D11853_PEA 1_19 483 495 D11853_PEA1_T23 483 495 D11853_PEA_1_T24 483 495 D11853_PEA_1_T25 1332 1344 D11853_PEA 1 T26 483 495 D11853_PEA1_T27 483 495 Segment cluster D11853_PEA_1_node_14 according to the present invention can be found in the following transcript(s): D11853_PEA_1_Ti, D1 1853_PEA_1_T3, 5 D11853_PEA1_T7, D11853 PEA_1_T8, D11853_PEA__T9, D11853_PEA_1_T1O, D11853_PEA_1_T13, D11853_PEA_1_T14, D11853_PEA_1T15, D11853_PEA_1_T16, D11853_PEA_1_T17, D11853_PEA_1_T19, D11853_PEA_1_T23, D11853_PEA_1_T24, D11853_PEA_1_T25, D11853_PEA_1_T26 and D11853_PEA1_T27. Table 58 below describes the starting and ending position of this segment on each transcript. 10 Table 58 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 857 Transcript name Segment Segment starting position ending position D11853 PEA 1_TI 496 511 D11853_PEA1 T3 496 511 D11853_PEA1 1T7 1213 1228 D11853 PEA 1 T8 987 1002 D11853_PEA_1_T9 613 628 D11853_PEA_1_T10 496 511 D11853_PEA_1-T13 496 511 D11853 PEA 1 T14 496 511 D11853_PEAI1T15 496 511 D11853_PEA_1 T16 496 511 D11853_PEA1 T17 1213 1228 D11853_PEA1 T19 496 511 D11853_PEA 1T23 496 511 D11853_PEA 1T24 496 511 D11853_PEA_1_T25 1345 1360 D11853_PEA 1 T26 496 511 D11853_PEA 1_T27 496 511 Segment cluster D11853_PEA_1_node_15 according to the present invention can be found in the following transcript(s): D11853_PEA 1 TI, D1 1853_PEA_1_T3, 5 D11853_PEA_11T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA_1T10, D11853_PEA_11T13, D11853_PEA_1_T14, D11853_PEA_1_T15, D11853 PEA 1 T16, D11853_PEA_117, D11853_PEA_1_T19, D11853_PEA_1_T23, D11853_PEA_1T24, D11853_PEA_1_T25, D11853_PEA_1_T26 and D11853_PEA_11T27. Table 59 below describes the starting and ending position of this segment on each transcript. 10 Table 59 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 858 Transcript name Segment Segment starting position ending position D11853_PEA1TI 512 533 D11853_PEA_1_T3 512 533 D11853_PEAI 1T7 1229 1250 D11853_PEAIT8 1003 1024 D11853_PEA 1 T9 629 650 D11853_PEA1 T1O 512 533 D11853_PEA_1 T13 512 533 D11853_PEA_1_T14 512 533 D11853 PEA 1 TI5 512 533 D11853_PEA 1 T16 512 533 D11853_PEA1_T17 1229 1250 D11853_PEA1_T19 512 533 D11853_PEA 1_T23 512 533 D11853_PEA 1 T24 512 533. D11853_PEA 1 T25 1361 1382 D11853_PEA 1 T26 512 533 D11853_PEA1_T27 512 533 Segment cluster D11853_PEA1node_16 according to the present invention can be found in the following transcript(s): D11853_PEA_1_Ti, D11853_PEA_1_T3, 5 D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853PEA_1_T1O, D11853_PEA_1_T13, D11853_PEA_1_T14, D11853_PEA_1_TI5, D11853_PEA_1_T16, D11853_PEA_1_T17, D11853_PEA_1 T19, D11853_PEA_1_T23, D11853_PEA_1_T24, D11853_PEA_1_T25 and D11853_PEA_1_T26. Table 60 below describes the starting and ending position of this segment on each transcript. 10 Table 60 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 Transcript name Segment Segment starting position ending position D11853_PEA 1_TI 534 551 D11853_PEA 1_T3 534 551 D11853_PEA_1_T7 1251 1268 D11853_PEA_1_T8 1025 1042 D11853_PEA 1 T9 651 668 D11853_PEA 1_TIO 534 551 D11853_PEA 1_T13 534 551 D11853PEA_1T14 534 551 D11853_PEA 1 TI5 534 551 D11853_PEA I T16 534 551 D11853_PEA 1_T17 1251 1268 D11853_PEA1_T19 534 551 D11853_PEA 1_T23 534 551 D11853_PEA_1_T24 534 551 D11853_PEA1_T25 1383 1400 D11853_PEA1_T26 534 551 Segment cluster DI11853_PEAInode_18 according to the present invention is supported by 230 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_TI, D11853_PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA_1_TIO, D11853_PEA1_T13, D11853_PEA_1_T14, D11853-PEA1_TI5, D11853_PEAIT16, D11853 PEA 1_T17, D11853_PEAJ1 TI9, D11853_PEA 1 T21, D11853 PEA 1 T23, D11853_PEA_1_T25 and D11853_PEA_1_T26. Table 61 below describes the starting and 10 ending position of this segment on each transcript. Table 61 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 860 Transcript name Segment Segment starting position ending position D11853_PEA1_Ti 552 582 D11853_PEA_1_T3 552 582 D11853_PEAIT7 1269 1299 D11853 PEA_1 T8 1043 1073 D11853 PEA 1_T9 669 699 D11853_PEA_1_TIO 552 582 D11853 PEAI T13 552 582 D11853_PEA_1_T14 552 582 D11853 PEA_1_15 552 582 D11853_PEA_1_T16 701 731 D11853 PEA_1_17 1269 1299 D11853 PEA I T19 552 582 D11853 PEA1 _T21 391 421 D11853 PEA 1_T23 701 731 D11853_PEA_1_T25 1401 1431 D11853_PEA _1T26 552 582 Segment cluster D11853_PEA_1_node_19 according to the present invention can be found in the following transcript(s): D11853_PEA._1_T1, D11853_PEA 1 T3, 5 D11853_PEA_1_T7, D11853_PEA 1_T8, D11853_PEA1_T9, D11853_PEA__1T10, D11853_PEA_1_T13, D11853_PEA_1_T14, D11853 PEAlT15, D11853_PEA_1_T16, D11853_PEA_1._17, D11853_PEA_1 T19, D11853 PEA_ 1T21, D11853_PEA_1_T23 and DI 853_PEA_1_T25. Table 62 below describes the starting and ending position of this segment on each transcript. 10 Table 62 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 8 61 Transcript name Segment Segment starting position ending position D11853_PEA 1_Ti 583 587 D11853_PEA_1_T3 583 587 P11853 PEA_1_T7 1300 1304 D11853_PEA 1_TS 1074 1078 D11853_PEA_1_T9 700 704 D11853_PEA_1_TIO 583 587 D11853_PEA 1 T13 583 587 D11853_PEA_1T14 583 587 D11853_PEA_115 583 587 D11853_PEA_116 732 736 D11853_PEA_1 17 1300 1304 D11853_PEA_1_T19 583 587 D11853_PEA_1_T21 422 426 D11853_PEA_1 T23 732 736 D11853_PEA_1_T25 1432 1436 Segment cluster D 11853 PEA_1 node_20 according to the present invention is supported by 257 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_TI, D11853 PEA_1_T3, D11853_PEA_1_T7, D11853_PEA_1_T8, D11853_PEA_1_T9, D11853_PEA_1_T10, D11853_PEA1_T13, D11853_PEA_1_T14, D11853_PEA1TI5, D11853_PEA_1_T16, D11853_PEA1_17, D11853_PEA_119, D11853_PEA_11T21, D11853_PEA_1_T23 and D11853 PEA1_T25. Table 63 below describes the starting and ending position of this segment 10 on each transcript. Table 63 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 862 Transcript name Segment Segment starting position ending position D11853_PEA_1TI 588 686 D11853_PEA_1_T3 588 686 D11853_PEA 1 T7 1305 1403 D11853_PEA_1_T8 1079 1177 D11853_PEA 1_T9 705 803 D11853_PEA_1 T1O 588 686 D11853_PEA_1_T13 588 686 D11853_PEA_1_T14 588 686 D11853_PEA 1_Ti5 588 686 D11853_PEA_116 737 835 D11853_PEA_1_T17 1305 1403 D11853PEA 1_19 588 686 D11853_PEA_1_T21 427 525 D11853_PEA_1_T23 737 835 D11853_PEA_1_T25 1437 1535 Segment cluster D 11853 PEA 1 node 24 according to the present invention is supported by 254, libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D11853_PEA_1_TI, D11853_PEA_1_T3, D11853_PEA_1T7, D11853_PEA1_T8, D11853_PEA_1_T9, D11853_PEA_1T10, D11853_PEA_113, D11853_PEA_1_T14, D11853_PEA_1_T15, D11853_PEA_1_16, D11853_PEA_1_17, D11853_PEA_1_19, D11853_PEA1__T21, D11853_PEA_1_T23, D11853 PEA 1 T24 and D11853_PEA_1_T25. Table 64 below describes the starting and 10 ending position of this segment on each transcript. Table 64 - Segment location on transcripts WO 2005/072053 PCT/IB2005/000928 863 Transcript naine Segment Segment starting position ending position D11853_PEA 1_TI 832 911 D11853 PEA_1_T3 832 911 D11853_PEA_1_T7 1549 1628 D11853_PEA1 _T8 1323 1402 D11853_PEA_1_T9 949 1028 D11853_PEA 1_T10 832 911 D11853_PEA_1T13 955 1034 D11853 PEA 1_T14 832 911 D11853_PEA 1_TI5 955 1034 D11853_PEA 1_T16 981 1060 D11853 PEA 1_17 1549 1628 D11853_PEA 1_T19 976 1055 D11853_PEA1_T21 671 750 D11853_PEA 1_T23 1125 1204 D11853_PEA 1T24 697 776 D11853_PEA_1_T25 1681 1760 Segment cluster D11853_PEA1node_28 according to the present invention can be found in the following transcript(s): D11853_PEA_1_T3, D11853_PEA_1_T25 and 5 D1 1853_PEA_1_T26. Table 65 below describes the starting and ending position of this segment on each transcript. Table 65 - Segment location on transcripts Transcript name Segment Segment starting position ending position D11853_PEA 1_T3 1461 1465 D11853_PEA_1_T25 2515 2519 WO 2005/072053 PCT/IB2005/000928 864 D11853_PEA_1_T26 583. 587 Segment cluster D 11853 PEA 1 node 29 according to the present invention is supported by 248 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): D1 1853 PEA 1 TI, D11853_PEA_1_T3, D11853_PEA1_T7, D11853_PEA_1_T8, D11853 PEA 1 T9, D11853_PEA_1_T1O, D11853_PEAIT13, D11853_PEA_1_T14, D11853_PEA 1_T15, D11853_PEA_1_T16, D11853-PEA_1_T17, D11853_PEA_1_T19, D11853_PEA_1_T21, D11853_PEA 1 T23, D11853_PEA1_T24, D11853 PEA 1 T25 and D11853_PEA1_T26. Table 66 below 10 describes the starting and ending position of this segment on each transcript. Table 66 - Segment location on transcripts Transcript name segment Segment starting position, ending position D11853_PEA 1_1 1041 1087 D11853_PEA 1 T3 1466 1512 D11853_PEA_1_T7 1758 1804 D11853 PEA_T8 1532 1578 D11853_PEA_1 T9 1158 1204 D11853_PEA1 T1O 1246 1292 D11853_PEA 1_T13 1164 1210 D11853_PEA114 912 958 D11853_PEA 1_15 1369 1415 D11853_PEA1 16 1190 1236 D11853 PEA 1_T17 1758 1804 D11853 PEA 1_19 1185 1231 D11853_PEA1_T21 880 926 D11853_PEA1 1T23 1334 1380 D11853_PEA1_T24 906 952 D11853_PEA1_T25 2520 2566 WO 2005/072053 PCT/IB2005/000928 865 D11853_PEAI_T26 588 634 Variant protein alignment to the previously known protein: 5 Sequence name: Q9PO42 Sequence documentation: Alignment of: D11853_PEA_1_P1 x Q9PO42 10 Alignment segment 1/1: Quality: 3115.00 Escore: 0 15 Matching length: 330 Total length: 330 Matching Percent Similarity: 99.70 Matching Percent Identity: 99.70 Total Percent Similarity: 99.70 Total Percent 20 Identity: 99.70 Gaps: 0 Alignment: 25 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 301 1 III III II III 1 1 WO 2005/072053 PCT/IB2005/000928 866 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 5 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 226 lI l l l l l1 I l i l l l l l l l l l l i li I l l l l l l l l l i l l l l l l l l i 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 10 227 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 276 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 262 15 277 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 326 263 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 312 327 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 356 2 0 I I I| I I I I I I I I I I I 313 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 342 25 Sequence name: BAC85377 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 867 Alignment of: Dll853 PEA 1_P1 x BAC85377 Alignment segment 1/1: 5 Quality: 1512.00 Escore: 0 Matching length: 159 Total length: 159 Matching Percent Similarity: 100.00 Matching Percent 10 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 20 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 25 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 259 101 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 150 260 ILAAALTQH 268 301 I[A lQ15 151 ILAAALTQH 159 WO 2005/072053 PCT/IB2005/000928 868 5 Sequence name: Q96FY2 Sequence documentation: 10 Alignment of: D11853 PEA 1 P1 x Q96FY2 Alignment segment 1/1: 15 Quality: 3343.00 Escore: 0 Matching length: 356 Total length: 356 Matching Percent Similarity: 99.72 Matching Percent 20 Identity: 99.72 Total Percent Similarity: 99.72 Total Percent Identity: 99.72 Gaps: 0 25 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 30 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 WO 2005/072053 PCT/IB2005/000928 869 F l l lI llllllFF llF IF ll lll F llllllll llll 1 FlFGF 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 5 lI I lFi1111 F Ill il li lll ll 11111FF l|F111F 11111 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 10 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 201 PATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 15 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 20 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 351 DRVKMS 356 25 H1IM1F 351 DRVKMS 356 30 WO 2005/072053 PCT/IB2005/000928 870 Sequence name: Q9P042 Sequence documentation: 5 Alignment of: D11853_PEA 1 P2 x Q9P042 Alignment segment 1/1: 10 Quality: 2691.00 Escore: 0 Matching length: 285 Total length: 285 Matching Percent Similarity: 99.65 Matching Percent 15 Identity: 99.65 Total Percent Similarity: 99.65 Total Percent Identity: 99.65 Gaps: 0 20 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILTPVLDRIRYV 62 25 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 30 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 lilllllllllllllllilllllllll11 lll11111111 |1 |11 ||11 WO 2005/072053 PCT/IB2005/000928 871 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 226 5 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 227 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 276 I| 11 1 11111111111111111||i)|i!i i 1 111ill IIlliil lili 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 262 10 277 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQ 311 II~ li 1I|1i I i II 1 i1i1 i1111 i1|1 263 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQ 297 15 20 Sequence name: BAC85377 Sequence documentation: Alignment of: D11853 PEA 1 P2 x BAC85377 . 25 Alignment segment 1/1: Quality: 1512.00 Escore: 0 30 Matching length: 159 Total length: 159 WO 2005/072053 PCT/IB2005/000928 872 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 5 Gaps: 0 Alignment: 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 10 i I I 1 1111 I I I I I I I 1111111 I I I I i I I I | I I | I I I I I 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 II I 1 ili iI 11 I 1 11 1 1 1111 111i 111ll I 111i 1 15 51 AINQAADCWGIRCLRYEIKDIEVPPRVKESMQMQVEAERRKRATVLESEG 100 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 259 1i iii lI I11 I I| | || I 11 111111111ii ii I iiI I I I 1i ii111 101 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 150 20 260 ILAAALTQH 268 151 ILAAALTQH 159 25 30 Sequence name: Q96FY2 WO 2005/072053 PCT/IB2005/000928 873 Sequence documentation: Alignment of: D11853_PEA_1_P2 x Q96FY2 5 Alignment segment 1/1: Quality: 2919.00 Escore: 0 Matching length: 311 Total 10 length: 311 Matching Percent Similarity: 99.68 Matching Percent Identity: 99.68 Total Percent Similarity: 99.68 Total Percent Identity: 99.68 15 Gaps: 0 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 25 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 I i l l l l l l l l l l l l l l1 l l ll l l l lI lI I I1 1 I| | | II 1111111111I 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 30 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 WO 2005/072053 PCTIIB2005/000928 874 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 201 RATVLESEGTRESAINVAEGKKQAQTLASEAEKAEQINQAAGEASAVLAK 250 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLADSNTILJPS 300 10 251 AKAKAEAIRTLAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTTLLPS 300 301 NPGDVTSMVAQ 311 301 NPGDVTSMVAQ 311 15 20 Sequence name: Q9UJZ1 Sequence documentation: 25 Alignment of: D11853_PEA_1_P2 x Q9UJZ1 Alignment segment 1/1: Quality: 2934.00 30 Escore: 0 WO 2005/072053 PCT/IB2005/000928 875 Matching length: 311 Total length: 311 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 10 I MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 l llll 1ill i i ll IIl i i iii 1i lJi l 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 15 51 RMGRFHPRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 li lI lI lhill I lll l llil li I I 11111111 111111111I 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 20 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 I llllilll l l ll I Il I 1 1 1 I I i l i l I 25 151 ESLNASIVDAINQAADCWGIRCLRYETKDTHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 |l llllll11111l IllIll lli llI l I l lil Ili l j Ii IIj 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 30 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 WO 2005/072053 PCT/IB2005/000928 876 l111illililllllllllllillllll111!11111 111111111|| 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 301 NPGDVTSMVAQ 311 5 I i I 1111 301 NPGDVTSMVAQ 311 10 Sequence name: Q9PO42 15 Sequence documentation: Alignment of: D11853 PEA 1 P7 x Q9P042 Alignment segment 1/1: 20 Quality: 2290.00 Escore: 0 Matching length: 242 Total length: 242 25 Matching Percent Similarity: 99.59 Matching Percent Identity: 99.59 Total Percent Similarity: 99.59 Total Percent Identity: 99.59 Gaps: 0 30 Alignment: WO 2005/072053 PCT/IB2005/000928 877 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 5 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 10 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 226 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 227 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH 268 20 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH 254 25 Sequence name: BAC85377 Sequence documentation: 30 Alignment of: D11853 PEA 1 P7 x BAC85377 WO 2005/072053 PCT/IB2005/000928 878 Alignment segment 1/1: Quality: 1724.00 5 Escore: 0 Matching length: 181 Total length: 181 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 15 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 20 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 l i l l l l I l l li l l i l l i l l i l i l i l i l l i l l i1 l i l l i i i i l l il i i 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 259 101 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 150 260 ILAAALTQHVRGPWVGMGTGIDSGRGSLIYA 290 30 151 ILAAALTQHVRGPWVGMGTGIDSGRGSLIYA 181 WO 2005/072053 PCT/IB2005/000928 879 5 Sequence name: Q96FY2 Sequence documentation: 10 Alignment of: D11853 PEA 1 P7 x Q96FY2 .. Alignment segment 1/1: Quality: 2518.00 15 Escore: 0 Matching length: 268 Total length: 268 Matching Percent Similarity: 99.63 Matching Percent Identity: 99.63 20 Total Percent Similarity: 99.63 Total Percent Identity: 99.63 Gaps: 0 Alignment: 25 1 MLARAARGTGALLLRGSLLASGRAPRPASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 30 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 l i l l l l l l l l ll l l ll l l llII I l l 11 li l li i l i l l i I I i WO 2005/072053 PCT/IB2005/000928 880 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 5 101 IDGVLYLRTMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 IIll II II 1 ||11 |l III I Fl |1 ilII II1 II II l 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 10 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 Iiii 11111 11i111111111111111l1l111i11l11 l1111111I 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 15 251 AKAKAEAIRILAAALTQH 268 FIlil II FII FI I iiiii iI| 251 AKAKAEAIRILAAALTQH 268 20 Sequence name: Q9UJZ1 25 Sequence documentation: Alignment of: D11853_PEA 1 P7 x Q9UJZ1 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 881 Quality: 2533.00 Escore: 0 Matching length: 268 Total length: 268 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 IIi I I lI l lII l L l l l l l l li iill l l l ll l l l 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 20 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 25 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 3 0I I Il I I I I I I I IIlII l lI l I 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 WO 2005/072053 PCT/IB2005/000928 882 251 AKAKAEAIRILAAALTQH 268 I11 I1111 111111111 251 AKAKAEAIRILAAALTQH 268 5 10 Sequence name: Q9PO42 Sequence documentation: 15 Alignment of: D11853_PEA_1_P9 x Q9PO42 Alignment segment 1/1: Quality: 3015.00 20 Escore: 0 Matching length: 330 Total length: 371 Matching Percent Similarity: 99.70 Matching Percent Identity: 99.70 25 Total Percent Similarity: 88.68 Total Percent Identity: 88.68 Gaps: 1 Alignment: 30 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 WO 2005/072053 PCT/IB2005/000928 883 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 5 li i i lll il 111l1l 1ll Illil ii i l1 1 lii l 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 li Ii lil I li l l i l l I ilI lI li lli i li I I[l il l 10 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 226 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 15 227 LASEAEKAEQINQAAGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQAS 276 213 LASEAEKAEQINQA-- - ..................................... 226 20 277 SVPSLAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSA 326 227 ..... .AGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSA 271 327 FSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGS 376 272 FSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGS 321 377 SRDVQGTDASLDEELDRVKMS 397 30 322 SRDVQGTDASLDEELDRVKMS 342 WO 2005/072053 PCT/IB2005/000928 884 5 Sequence name: BAC85377 Sequence documentation: 10 Alignment of: D11853 PEA 1 P9 x BAC85377 Alignment segment 1/1: Quality: 1412.00 15 Escore: 0 Matching length: 159 Total length: 200 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 20 Total Percent Similarity: 79.50 Total Percent Identity: 79.50 Gaps: 1 Alignment: 25 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 30 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 WO 2005/072053 PCT/IB2005/000928 885 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEGGARHGPLKI 259 5 101 TRESAINVAEGKKQAQTLASEAEKAEQINQA ................... .131 260 GAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIRILAAALTQH 309 132 - -...................... AGEASAVLAKAKAKAEAIRILAAALTQH 159 10 15 Sequence name: Q96FY2 Sequence documentation: 20 Alignment of: D11853 PEA 1 P9 x Q96FY2 Alignment segment 1/1: Quality: 3243.00 25 Escore: 0 Matching length: 356 Total length: 397 Matching Percent Similarity: 99.72 Matching Percent Identity: 99.72 30 Total Percent Similarity: 89.42 Total Percent Identity: 89.42 WO 2005/072053 PCT/IB2005/000928 886 Gaps: 1 Alignment: 5 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 10 i i l l iIli i l i l i i iIii i i i1ii i111i 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 li l l lI l I l l i l l i l l i l l i l l l i l I l l i l l l i l l l1 1 1 i I li l II 15 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 151 ESLNASIVDAINQAADCWGIRCLRYEIKDTHVPPRVKESMQMQVEAERRK 200 20 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEG 250 lilll lil li l, lljj jjj lililill1 I Ill1lli 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA .......... 240 25 251 GARHGPLKIGAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIR 300 241 ..--...............................

AGEASAVLAKAKAKAEAIR 259 301 ILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMV 350 260 ILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMV 309 WO 2005/072053 PCT/IB2005/000928 887 351 AQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS 397 lillillillill111ill 1111111l 11lli iI i iii!Ii i 310 AQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS 356 5 10 Sequence name: Q9UJZ1 Sequence documentation: 15 Alignment of: D11853 PEA 1_P9 x Q9UJZ1 Alignment segment 1/1: Quality: 3258.00 20 Escore: 0 Matching length: 356 Total length: 397 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 89.67 Total Percent Identity: 89.67 Gaps: 1 Alignment: 30 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 WO 2005/072053 PCT/IB2005/000928 888 lli llll1 l llillilll1 11 11 1ilijil i il l 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKETVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 Ililli lli lli ll iillll i lII I lili i II lill1 iil1 i 10 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 15 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEG 250 Ililllill Il!!lli ii l lli I I I I 1 1JIll IIi 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA .......... .. 240 20 251 GARHGPLKIGAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIR 300 liiilll llill lii il! 241 - - --...............................

AGEASAVLAKAKAKAEAIR 259 301 ILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMV 350 25 260 ILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMV 309 351 AQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS 397 30 310 AQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEELDRVKMS 356 WO 2005/072053 PCT/IB2005/000928 889 5 Sequence name: Q9PO42 Sequence documentation: 10 Alignment of: D11853_PEA 1 P1O x Q9P042 Alignment segment 1/1: Quality: 2614.00 15 Escore: 0 Matching length: 287 Total length: 330 Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65 20 Total Percent Similarity: 86.67 Total Percent Identity: 86.67 Gaps: 1 Alignment: 25 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 iil l l ll i l ll l l l l l l l ll l l l l l l l ll111 I lI l l l ll l1 l li 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 30 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 11111111 I 1111|i|I 111111111 I I111ll1 lllllll11 llllII WO 2005/072053 PCT/IB2005/000928 890 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 5 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKRATVLESEGTRESAINVAEGKKQAQI 226 li l ll Iilli llil1 liill 11lilli11llil J ill 11 1 i1 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 10 227 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQH ........ .268 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 262 15 269 ---------...................................

AMGVYGALTKAPVPG 283 263 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 312 284 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 313 313 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 342 25 Sequence name: BAC85377 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 891 Alignment of: D11853 PEA 1 P1O x BAC85377 . . Alignment segment 1/1: 5 Quality: 1515.00 Escore: 0 Matching length: 162 Total length: 162 Matching Percent Similarity: 98.77 Matching Percent 10 Identity: 98.77 Total Percent Similarity: 98.77 Total Percent Identity: 98.77 Gaps: 0 15 Alignment: 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 20 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 l l l l ll l l ll , 1 1 l i i I I lllllll 1||||| | I||||III|||I 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 25 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 259 lIillllllll1111111 1 IlllIllIlIIII li ii I III I h lli 101 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 150 260 ILAAALTQHAMG 271 30 [ 111111 I i 151 ILAAALTQHVRG 162 WO 2005/072053 PCT/IB2005/000928 892 5 Sequence name: Q96FY2 Sequence documentation: 10 Alignment of: D11853 PEA 1 PlO x Q96FY2 Alignment segment 1/1: 15 Quality: 2842.00 Escore: 0 Matching length: 313 Total length: 356 Matching Percent Similarity: 99.68 Matching Percent 20 Identity: 99.68 Total Percent Similarity: 87.64 Total Percent Identity: 87.64 Gaps: 1 25 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 30 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 WO 2005/072053 PCT/IB2005/000928 893 51 RMGRFHRILEPGLNTLTPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRTMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 10 151 ESLNASIVDAINQAADCWGIRCLRYEIKDTHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 15 251 AKAKAEAIRILAAALTQH -- -................................ 268 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 20 269 ........... .AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 307 || I 1I|| I 1111 l I iii I 1 1 1 i il I I I ii | 1 i i 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 308 DRVKMS 313 25 111111 351 DRVKMS 356 30 WO 2005/072053 PCT/IB2005/000928 894 Sequence name: Q9UJZ1 Sequence documentation: 5 Alignment of: D11853 PEA 1 P10 x Q9UJZl Alignment segment 1/1: 10 Quality: 2857.00 Escore: 0 Matching length: 313 Total length: 356 Matching Percent Similarity: 100.00 Matching Percent 15 Identity: 100.00 Total Percent Similarity: 87.92 Total Percent Identity: 87.92 Gaps: 1 20 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 25 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 30 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 li l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l i WO 2005/072053 PCT/IB2005/000928 895 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 5 151 ESLNASIVDAINQAADCWGIRCLRYEIKDTHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 10 251 AKAKAEAIRILAAALTQH ------................................ 268 I I i I ! I l IIi ii ii I I 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 15 269 -............ AMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 307 I I I I I iiiiiI I i ii I [11 [11 I I I i I iiiiI II I 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 308 DRVKMS 313 20 111111 351 DRVKMS 356 25 Sequence name: Q9P042 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 896 Alignment of: D11853 PEA 1 P11 x Q9P042 Alignment segment 1/1: 5 Quality: 2190.00 Escore: 0 Matching length: 242 Total length: 283 Matching Percent Similarity: 99.59 Matching Percent 10 Identity: 99.59 Total Percent Similarity: 85.16 Total Percent Identity: 85.16 Gaps: 1 15 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 20 77 QSLKEIVINVPEQSAVTLDNVTLQTDGVLYLRIMDPYKASYGVEDPEYAV 126 lilllllllllll111111lllill i i Jll 11111I II ll I li 11 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 25 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 177 IKDIHVPPRVKESMQMQVEAERRKATVLESEGTRESAINVAEGKKQAQI 226 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 WO 2005/072053 PCT/IB2005/000928 897 227 LASEAEKAEQINQAAGQERVEAEGGARHGPLKIGAGAGSLGYFDFMGQAS 276 213 LASEAEKAEQINQA.............

...................

226 5 277 SVPSLAGEASAVLAKAKAKAEAIRILAAALTQH 309 227 ..... .AGEASAVLAKAKAKAEAIRILAAALTQH 254 10 15 Sequence name: BAC85377 Sequence documentation: Alignment of: D11853_PEA_1_Pll x BAC85377 20 Alignment segment 1/1: Quality: 1624.00 Escore: 0 25 Matching length: 181 Total length: 222 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 81.53 Total Percent 30 Identity: 81.53 Gaps: 1 WO 2005/072053 PCT/IB2005/000928 898 Alignment: 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 159 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 160 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 209 10 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 210 TRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEGGARHGPLKI 259 IIli i i l1l11 ll1lll llll li 101 TRESAINVAEGKKQAQILASEAEKAEQINQA ---................... 131 15 260 GAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIRILAAALTQH 309 i| 1I |1i iI I i 111||1|||111111 132 ---...................... AGEASAVLAKAKAKAEAIRILAAALTQH 159 20 310 VRGPWVGMGTGIDSGRGSLIYA 331 160 VRGPWVGMGTGIDSGRGSLIYA 181 25 Sequence name: Q96FY2 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 899 Alignment of: D11853 PEA_1 P11 x Q96FY2 Alignment segment 1/1: 5 Quality: 2418.00 Escore: 0 Matching length: 268 Total length: 309 10 Matching Percent Similarity: 99.63 Matching Percent Identity: 99.63 Total Percent Similarity: 86.41 Total Percent Identity: 86.41 Gaps: 1 15 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 li l ll ll ll lll l l l l l li ll1 1 l! l l lllli li l li111 li l l11 Ii l 20 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 li i i illlll l il i il liii i ll lili lli i l il l I li ii 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 25 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 l i l l iill liii lli l ll l l li l I|||| |||il||l |||i ||||||||| 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 30 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 ll l lli ! l! li i !lilil!lil iilliillill! JIJIJI liiii WO 2005/072053 PCT/IB2005/000928 900 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEG 250 5 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA .......... .240 251 GARHGPLKIGAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIR 300 | |1 1 I I i I I I I l I 1 i 241 --.-..-...--..........................

AGEASAVLAKAKAKAEAIR 259 10 301 ILAAALTQH 309 I I I 260 ILAAALTQH 268 15 20 Sequence name: Q9UJzl Sequence documentation: Alignment of: D11853_PEA_1_P11 x Q9UJZ1 25 Alignment segment 1/1: Quality: 2433.00 Escore: 0 30 Matching length: 268 Total length: 309 WO 2005/072053 PCT/IB2005/000928 901 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 86.73 Total Percent Identity: 86.73 5 Gaps: 1 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 10 11lli1 l ll 1lilli 1illill 1 i 1ii I 11111 I1 1II Ii 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 15 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 20 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 ill11i 1lili 1lill 1i1l 111l 1 II ll ill illillli I li 151 ESLNASIVDAINQAADCWGTRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 25 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGQERVEAEG 250 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQA .......... .240 251 GARHGPLKIGAGAGSLGYFDFMGQASSVPSLAGEASAVLAKAKAKAEAIR 300 30 241 -.--..--.. --. --.. -.. -.. .. .. .. .. .. ... .AGEASAVLAKAKAKAEAIR 259 WO 2005/072053 PCT/IB2005/000928 902 301 ILAAALTQH 309 II 11111 260 ILAAALTQH 268 5 10 Sequence name: Q9P042 Sequence documentation: 15 Alignment of: Dll853_PEA 1 P12 x Q9PO42 Alignment segment 1/1: Quality: 1167.00 20 Escore: 0 Matching length: 122 Total length: 122 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 30 27 PASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 WO 2005/072053 PCT/IB2005/000928 903 li l Ili i lillll 1 1 1 lili 11 11i 1 111ii I 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILTPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFR 148 I I III I i I 111 1,111i I I 10 113 TQLAQTTMRSELGKLSLDKVFR 134 15 Sequence name: Q96FY2 Sequence documentation: 20 Alignment of: D11853 PEA 1 Pl2 x Q96FY2 Alignment segment 1/1: 25 Quality: 1385.00 Escore: 0 Matching length: 148 Total length: 148 Matching Percent Similarity: 99.32 Matching Percent 30 Identity: 99.32 WO 2005/072053 PCT/IB2005/000928 904 Total Percent Similarity: 99.32 Total Percent Identity: 99.32 Gaps: 0 5 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 10 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 lIilllI llll lll li ll lll llll11 l l11 ll1 i lll11 lllillli 51 RMGRFHRLEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 15 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR 148 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFR 148 20 Sequence name: Q9UJZ1 25 Sequence documentation: Alignment of: D11853_PEA 1 P12 x Q9UJZ1 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 905 Quality: 1400.00 Escore: 0 Matching length: 148 Total length: 148 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 111|||1 || 1111111 I I 11111111|1llllll llllllllli 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 20 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR 148 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR 148 25 30 Sequence name: Q9P042 WO 2005/072053 PCT/IB2005/000928 906 Sequence documentation: Alignment of: D11853_PEA_1_P14 x Q9P042 5 Alignment segment 1/1: Quality: 1628.00 Escore: 0 Matching length: 170 Total 10 length: 170 Matching Percent Similarity: 99.41 Matching Percent Identity: 99.41 Total Percent Similarity: 99.41 Total Percent Identity: 99.41 15 Gaps: 0 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNTLTPVLDRIRYV 76 2 0 i I l i lii i i i i i i i i i i ii | | | iil l1 1i i 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRTLEPGLNILIPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 liili llllll11 l1 lll111 ll1 ll 1l 11ll 1111ll IlI llll1 ll 25 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 176 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 30 177 IKDIHVPPRVKESMQMQVGA 196 WO 2005/072053 PCT/IB2005/000928 907 163 IKDIHVPPRVKESMQMQVEA 182 5 Sequence name: Q96FY2 10 Sequence documentation: Alignment of: D11853_PEA_1_P14 x Q96FY2 15 Alignment segment 1/1: Quality: 1846.00 Escore: 0 Matching length: 196 Total 20 length: 196 Matching Percent Similarity: 98.98 Matching Percent Identity: 98.98 Total Percent Similarity: 98.98 Total Percent Identity: 98.98 25 Gaps: 0 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 3 0 l iI l l l l l l l l l llIl lI l l l l l l l l l l l i l l l l l l l l l l lI l 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 WO 2005/072053 PCT/IB2005/000928 908 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 lillllllllllll1ll1l1111lllll1 lllll 1l11l 1lllllIl 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 5 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 l i l l l l l lI l l l l l l l l l l l l l l l l i l l i l l l l l l l l l l l lI l I l l 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 10 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVGA 196 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEA 196 15 Sequence name: Q9UJZ1 20 Sequence documentation: Alignment of: D11853_PEA_1_P14 x Q9UJZ1 25 Alignment segment 1/1: Quality: 1861.00 Escore: 0 Matching length: 196 Total 30 length: 196 WO 2005/072053 PCT/IB2005/000928 909 Matching Percent Similarity: 99.49 Matching Percent Identity: 99.49 Total Percent Similarity: 99.49 Total Percent Identity: 99.49 5 Gaps: 0 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 0 i l l 1i l I I l l l i l l i l l i l l l l l l l l i l l 1l l I i l i I il l 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 lilllllllllllllllllllllllllllll|1||111|11111111111 15 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 I il l l i l l l1 1 1i l li l[ l i l l l l l l l l l l l l l l l ll l l l l l l II 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 20 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVGA 196 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEA 196 25 30 Sequence name: Q9P042 WO 2005/072053 PCT/IB2005/000928 910 Sequence documentation: Alignment of: D11853_PEA_1_P16 x Q9P042 5 Alignment segmenL 1/1: Quality: 2564.00 Escore: 0 Matching length: 285 Total 10 length: 330 Matching Percent Similarity: 99.65 Matching Percent Identity: 99.65 Total Percent Similarity: 86.06 Total Percent Identity: 86.06 15 Gaps: 1 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGNILIPVLDRIRYV 76 2 0 l i1 l l l i l l i l 1l l l l l i l l l l i l i 1l l i l l il I l l il1 l l i l l i l i 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 l i l l l l l l l l l l 1 1ll l ill l l l l l l l l l l ll l l l l l l l l lI l lI lII I 25 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFR............................ 148 lii llllllllllll ill Il | 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 30 149 .................. VEAERRKRATVLESEGTRESAINVAEGKKQAQI 181 WO 2005/072053 PCT/IB2005/000928 911 li lll 1111111 i 11111 11111 1111111 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 182 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 231 5 11111 11111111111||1111111111|1111 l 11ll 1 ll11 I 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 262 232 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 281 I|1l1111111111lIIii III | II I 1111 I III 111 11II 1I11I11II1 10 263 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 312 282 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 311 I IIIIIIIIIIIIIIIIIIIII 111 1I I11 II 1 1 I I 1 313 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 342 15 20 Sequence name: BAC85377 Sequence documentation: 25 Alignment of: D11853_PEA_1_P16 x BAC85377 Alignment segment 1/1: Quality: 961.00 30 Escore: 0 WO 2005/072053 PCT/IB2005/000928 912 Matching length: 114 Total length: 159 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 71.70 Total Percent Identity: 71.70 Gaps: 1 Alignment: 10 110 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR ........... .148 1 MDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRERESLNASIVD 50 15 149 ..................................VEAERRKRATVLESEG 164 51 AINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRKRATVLESEG 100 165 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 214 20 I1IIiii I I I I I |111l11 I I 11 1 1 1 1 I1 I 1111 11 I I I ii I I i 101 TRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAKAKAKAEAIR 150 215 ILAAALTQH 223 I 111111 25 151 ILAAALTQH 159 30 WO 2005/072053 PCT/IB2005/000928 913 Sequence name: Q96FY2 Sequence documentation: 5 Alignment of: D11853 PEA 1 P16 x Q96FY2 Alignment segment 1/1: Quality: 2792.00 10 Escore: 0 Matching length: 311 Total length: 356 Matching Percent Similarity: 99.68 Matching Percent Identity: 99.68 15 Total Percent Similarity: 87.08 Total Percent Identity: 87.08 Gaps: 1 Alignment: 20 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 25 51 RMGRFHRILEPGLNTLIPVLDRTRYVQSLKETVINVPEQSAVTLDNVTLQ 100 l il l i l l l l l l li l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l ll1 1 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR .. 148 30 I I l I I i I 1 i l1 I11 l1 lI 11 I I I I I II I I| I I I II 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 WO 2005/072053 PCT/IB2005/000928 914 149 ... ....... ....... .......................... VEAERRK 155 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 5 156 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 205 11I111 liii 1111111I II 111111 ii Ii I II 1III 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 10 206 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 255 iI I I i iI ||IIIIII|1II I I 1 1 1 1 1 1 11 1 1 1 1 1 I I I I1I1I1I I I 251 AKAKAEATRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 256 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 305 15 IIIiII I iI 1 1I I IIi II 111I1i1iii 11i iii 1! 11I 1l 1l 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 306 DRVKMS 311 III 11 20 351 DRVKMS 356 25 Sequence name: Q9UJZl Sequence documentation: 30 Alignment of: D11853_PEA_1_P16 x Q9UJZl WO 2005/072053 PCT/IB2005/000928 915 Alignment segment 1/1: Quality: 2807.00 5 Escore: 0 Matching length: 311 Total length: 356 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 10 Total Percent Similarity: 87.36 Total Percent Identity: 87.36 Gaps: 1 Alignment: 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 lii lll ll liii 1 llll l l l l l 11111 ll 1 l ll li l 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 20 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 l i l l i l l l l l l l l i l l i l l l l l l l l lI l l l l l l l l l l i l l l l ll1 51 PMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFR.. 148 25 I I I I 1I I l1 I I I I I I I I 1 I 111 |1 I 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 149 ........ ....................................... .VEAERRK 155 lil l I 30 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 WO 2005/072053 PCT/IB2005/000928 916 156 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 205 1I 11I1 1III 11II 11II iii I II 1 III11 1 IIII111ii|I 1II I| 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 5 206 AKAKAEAIRTLAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 255 1111 II II iII1 l II1111IIII1111I |11111 IIII 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 256 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 305 10 iiII1i1111 l11 I1l1 I|1 liiiII|I|II I 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 306 DRVKMS 311 15 351 DRVKMS 356 20 Sequence name: Q9P042 Sequence documentation: 25 Alignment of: D11853_PEA_1_P18 x Q9PO42 Alignment segment 1/1: 30 Quality: 1601.00 Escore: 0 WO 2005/072053 PCT/IB2005/000928 917 Matching length: 179 Total length: 330 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 5 Total Percent Similarity: 54.24 Total Percent Identity: 54.24 Gaps: 1 Alignment: 10 . 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 15 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 127 TQLAQTTMRSELGKLSLDKVFRERESLNASI................... 157 20 11l11111 111I11i11i 11ii il 1l 11| 1 I I I I 113 TQLAQTTMRSELGKLSLDKVFRERESLNASIVDAINQAADCWGIRCLRYE 162 157 .................... .- ......................... 157 25 163 IKDIHVPPRVKESMQMQVEAERRKRPTVLESEGTRESAINVAEGKKQAQI 212 157 ................................................ 157 213 LASEAEKAEQINQAAGEASAVLAKAKAKAEAIRILAAALTQHNGDAAASL 262 30 158 ................................

VAQAMGVYGALTKAPVPG 175 WO 2005/072053 PCT/IB2005/000928 918 |II|1111111111Ii 263 TVAEQYVSAFSKLAKDSNTILLPSNPGDVTSMVAQAMGVYGALTKAPVPG 312 176 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 205 5 II11ii1I lII iI I |1 1 iii 313 TPDSLSSGSSRDVQGTDASLDEELDRVKMS 342 10 Sequence name: Q96FY2 15 Sequence documentation: Alignment of: D11853_PEA_1_P18 x Q96FY2 Alignment segment 1/1: 20 Quality: 1819.00 Escore: 0 Matching length: 205 Total length: 356 25 Matching Percent Similarity: 99.51 Matching Percent Identity: 99.51 Total Percent Similarity: 57.30 Total Percent Identity: 57.30 Gaps: 1 30 Alignment: WO 2005/072053 PCTIIB2005/000928 919 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWJVE 50 1 MLARAkARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 5 51 'RNGRFHRTLEPGLNILTPVLDRTRYVQSLKEIVTNVPEQSAVTLDNVTLQ 100 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEJVINVPEQSAVTLDNVTLQ 100 10 101 TDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 101 TDGVLYLRTMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLSLDKVFRER 150 151 ESLNAST................................................. 157 15 1 1 1 151 ESLNASTVDAINQAADCWGTRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 157......................................................... 157 20 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQINQAAGEASAVLAK 250 157......................................................... 157 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 25 158.......... VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 199 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 30 200 DRVKMS 205 111111 WO 2005/072053 PCT/IB2005/000928 920 351 DRVKMS 356 5 Sequence name: Q9UJZl 10 Sequence documentation: Alignment of: D11853_PEA_1 P18 x Q9UJZ1 Alignment segment 1/1: 15 Quality: 1834.00 Escore: 0 Matching length: 205 Total length: 356 20 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 57.58 Total Percent Identity: 57.58 Gaps: 1 25 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 lilllllGT LLL l LL llllllllll L lll Vlil i lllllllli111 5 30 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 WO 2005/072053 PCT/IB2005/000928 921 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 }|1 11 I 111111111111111i 11 1111 1111111 1111 111|||| 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 5 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLSLDKVFRER 150 151 ESLNASI........................................... 157 10 1111111 151 ESLNASIVDAINQAADCWGIRCLRYEIKDIHVPPRVKESMQMQVEAERRK 200 157 .................................................. 157 15 201 RATVLESEGTRESAINVAEGKKQAQILASEAEKAEQTNQAAGEASAVLAK 250 157 .................................................. 157 251 AKAKAEAIRILAAALTQHNGDAAASLTVAEQYVSAFSKLAKDSNTILLPS 300 20 158 .......... VAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 199 301 NPGDVTSMVAQAMGVYGALTKAPVPGTPDSLSSGSSRDVQGTDASLDEEL 350 25 200 DRVKMS 205 111111 351 DRVKMS 356 30 WO 2005/072053 PCT/IB2005/000928 922 Sequence name: Q9P042 5 Sequence documentation: Alignment of: D11853_PEA_1_P19 x Q9P042 Alignment segment 1/1: 10 Quality: 1110.00 Escore: 0 Matching length: 116 Total length: 116 15 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 l il l l l l l l l l l l l l l l l l l l l l l l l l l l 1l l il l l l l l l l l il l 25 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 77 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 126 l l l l l l l l l il l l l l l l l l l l l l l l l l l 1l l l 1l l l l l i 63 QSLKEIVINVPEQSAVTLDNVTLQIDGVLYLRIMDPYKASYGVEDPEYAV 112 30 127 TQLAQTTMRSELGKLS 142 WO 2005/072053 PCT/IB2005/000928 923 113 TQLAQTTMRSELGKLS 128 5 Sequence name: Q96FY2 10 Sequence documentation: Alignment of: D11853_PEA_1 P19 x Q96FY2 . 15 Alignment segment 1/1: Quality: 1328.00 Escore: 0 Matching length: 142 Total 20 length: 142 Matching Percent Similarity: 99.30 Matching Percent Identity: 99.30 Total Percent Similarity: 99.30 Total Percent Identity: 99.30 25 Gaps: 0 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 3 0 l i l I li l l l1l1llil l l l ll l l i 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 WO 2005/072053 PCT/IB2005/000928 924 51 RMGRFHRILEPGLNILIPVLDRTRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 111111111I I IIIiIIlIIiiiiIIIIIIIIII I I i1l111l i11 i 1 I I |1 l I I I 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 5 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS 142 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQPAQTTMRSELGKLS 142 10 15 Sequence name: Q9UJZ1 Sequence documentation: Alignment of: D11853_PEA_1_P19 x Q9UJZ1 20 Alignment segment 1/1: Quality: 1343.00 Escore: 0 25 Matching length: 142 Total length: 142 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 30 Identity: 100.00 Gaps: 0 WO 2005/072053 PCT/IB2005/000928 925 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 5 i i il iii i| I| 1 1 I I I I I I li||||||1J 1 Ii 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 II | I11 11111 i iIIII iIII I i 1 1 1 Ii I|1III| II ||liii 10 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTLDNVTLQ 100 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS 142 I | I i i i i i I I I I I I I | | | | I l I li i Iiii 1 1 II 101 IDGVLYLRIMDPYKASYGVEDPEYAVTQLAQTTMRSELGKLS 142 15 20 Sequence name: Q96FY2 Sequence documentation: 25 Alignment of: D11853_PEA_1_P21 x Q96FY2 Alignment segment 1/1: Quality: 587.00 30 Escore: 0 WO 2005/072053 PCT/IB2005/000928 926 Matching length: 68 Total length: 68 Matching Percent Similarity: 95.59 Matching Percent Identity: 92.65 5 Total Percent Similarity: 95.59 Total Percent Identity: 92.65 Gaps: 0 Alignment: 10 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 1Il I1l| lii i Il I I i1 II IlI I I l I 11 11 1 1 11 i i iI I 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 15 51 RMGRFHRILEPVRNLFCP 68 51 RMGRFHRILEPGLNILIP 68 20 Sequence name: Q9UJZ1 25 Sequence documentation: Alignment of: D11853_PEA lP21 x Q9UJZl 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 927 Quality: 587.00 Escore: 0 Matching length: 68 Total length: 68 5 Matching Percent Similarity: 95.59 Matching Percent Identity: 92.65 Total Percent Similarity: 95.59 Total Percent Identity: 92.65 Gaps: 0 10 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 Si iiiI lIllilllilii 11I|Il1 11 11 I I l I l l i1 I I 1 lil11 i11 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPVRNLFCP 68 51 RMGRFHRILEPGLNILIP 68 20 25 Sequence name: Q9PO42 Sequence documentation: 30 Alignment of: D11853 PEA 1 P22 x Q9PO42 WO 2005/072053 PCT/IB2005/000928 928 Alignment segment 1/1: Quality: 348.00 Escore: 0 5 Matching length: 37 Total length: 37 Matching Percent Similarity: 97.30 Matching Percent Identity: 97.30 Total Percent Similarity: 97.30 Total Percent 10 Identity: 97.30 Gaps: 0 Alignment: 15 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPEL 63 II 1 1 I l l i i l l l l l l l l l l l l l l l I| I 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGL 49 20 Sequence name: Q96FY2 25 Sequence documentation: Alignment of: D11853 PEA 1 P22 x Q96FY2 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 929 Quality: 581.00 Escore: 0 Matching length: 63 Total length: 63 5 Matching Percent Similarity: 98.41 Matching Percent Identity: 98.41 Total Percent Similarity: 98.41 Total Percent Identity: 98.41 Gaps: 0 10 Alignment: 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 l i l l l l l l l l l l ll l i l l l l l l l l l l l l l l l l l l l lII l l l I 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPEL 63 51 RMGRFHRILEPGL 63 20 25 Sequence name: Q9UJZl Sequence documentation: 30 Alignment of: D11853 PEA 1 P22 x Q9UJZ1 WO 2005/072053 PCT/IB2005/000928 930 Alignment segment 1/1: Quality: 581.00 Escore: 0 5 Matching length: 63 Total length: 63 Matching Percent Similarity: 98.41 Matching Percent Identity: 98.41 Total Percent Similarity: 98.41 Total Percent 10 Identity: 98.41 Gaps: 0 Alignment: 15 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 IiI ii II 11 1 1 I 1iii1 i IIiiiII I II III I II || I 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPEL 63 2 0 1 1 1 I l l 1 1 1 1 1 1 51 RMGRFHRILEPGL 63 25 Sequence name: Q9PO42 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 931 Alignment of: D11853 PEA lP24 x Q9P042 Alignment segment 1/1: 5 Quality: 650.00 Escore: 0 Matching length: 68 Total length: 68 Matching Percent Similarity: 100.00 Matching Percent 10 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 27 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 76 l i l l l l 11 Fl l l l l l l l l l l l l ll l l l l I|| | 1 1 1 1111111 | | 13 RASSGLPRNTVVLFVPQQEAWVVERMGRFHRILEPGLNILIPVLDRIRYV 62 20 77 QSLKEIVINVPEQSAVTL 94 li l l l l l l l l l l l l ll | 63 QSLKEIVINVPEQSAVTL 80 25 30 Sequence name: Q96FY2 WO 2005/072053 PCT/IB2005/000928 932 Sequence documentation: Alignment of: D11853_PEA_1_P24 x Q96FY2 5 Alignment segment 1/1: Quality: 883.00 Escore: 0 Matching length: 94 Total 10 length: 94 Matching Percent. Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MLARAARGTGALLLRGSLLASGAPRASSGLPRNTVVLFVPQQEAWVVE 50 20 1 MLARAARGTGALLLRGSLLASGRAPRPASSGLPRNTVVLFVPQQEAWVVE 50 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL 94 25 51 RMGRFBRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL 94 30 WO 2005/072053 PCT/IB2005/000928 933 Sequence name: Q9UJZ1 Sequence documentation: 5 Alignment of: D11853 PEA_1_P24 x Q9UJZl Alignment segment 1/1: Quality: 883.00 10 Escore: 0 Matching length: 94 Total length: 94 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 lill lill 1 1 llllll lilli llllll i I i i 11 11 ii ii 1 MLARAARGTGALLLRGSLLASGRAPRRASSGLPRNTVVLFVPQQEAWVVE 50 25 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL 94 51 RMGRFHRILEPGLNILIPVLDRIRYVQSLKEIVINVPEQSAVTL 94 30 WO 2005/072053 PCT/IB2005/000928 934 5 DESCRIPTION FOR CLUSTER R1 1723 Cluster R 11723 features 6 transcript(s) and 26 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the 10 application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest Transcript Name SQI O R11723_PEA 1_Ti5 75 R11723_PEA 1_T17 76 R11723 PEA 1 T19 77 R11723_PEA 1_T20 78 R11723_PEA 1_T5 79 R11723_PEA 1 T6 80 Table 2 - Segments of interest Segment Name SEQI D NO: R11723_PEA1node13 450 R11723_PEA1 node_16 451 R11723PEA 1 node_19 452 R11723_PEA1node_2 453 R11723_PEA 1 node_22 454 R11723_PEA 1 node_31 455 R11723_PEA 1_node 10 456 R11723_PEA1node11 457 WO 2005/072053 PCT/IB2005/000928 935 R11723_PEAI -node 15 458 R11723 PEA 1 node_18 459 RI 1723 PEA1_node_20 460 R11723_PEA Inode_21 461 R11723_PEA 1 node 23 462 R11723_PEA 1 node_24 463 R11723_PEA 1 node_25 464 RI 1723_PEA_1_node_26 465 R11723_PEA 1 node 27 466 R11723_PEA1_node_28 467 R11723_PEA 1_node 29 468 R11723_PEA 1 node 3 469 R11723_PEA 1_node_30 470 R11723PEA 1 node_4 471 R11723_PEA 1 node_5 472 R11723_PEA1 node 6 473 R11723_PEA 1 node_7 474 R11723_PEA 1_node 8 475 Table 3 - Proteins of interest Protein Name SEQ TD NO: R11723_PEA 1_P2 603 R11723_PEA_1 P6 604 R11723_PEA_1_P7 605 R11723_PEA_1 P13 606 R11723_PEA 1_PlO 607 5 Cluster Ri 1723 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given WO 2005/072053 PCT/IB2005/000928 936 according to the previously described methods. The tenn "number" in the right hand column of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to the expression of all ESTs in that category, according to parts per million). 5 Overall, the following results were obtained as shown with regard to the histograms in Figure 27 and Table 4. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: epithelial malignant tumors, a mixture of malignant tumors from different tissues and kidney malignant tumors. 10 Table 4 - Normal tissue distribution Name of tissue Number adrenal 0 brain 30 epithelial 3 general 17 Head and neck 0 kidney 0 Lung 0 breast 0 ovary 0 pancreas 10 skin 0 uterus 0 Table 5 - P values and ratios for expression in cancerous tissue Name of Tissue P1 P2 SPi R3 SP2 R4 adrenal 4.2e-01 4.6e-01 4.6e-01 2.2 5.3e-01 1.9 brain 2.2e-01 2.0e-01 1.2e-02 2.8 5.0e-02 2.0 WO 2005/072053 PCT/IB2005/000928 937 epithelial 3.Oe-05 6.3e-05 1.8e-05 6.3 3.4e-06 6.4 general 7.2e-03 4.0e-02 1.3e-04 2.1 1.le-03 1.7 head and neck 1 5.0e-01 1 1.0 7.5e-01 1.3 kidney 1.5e-01 2.4e-01 4.4e-03 5.4 2.8e-02 3.6 lung 1.2e-01 1.6e-01 1 1.6 1 1.3 breast 5.9e-01 4.4e-01 1 1.1 6.8e-01 1.5 ovary 1.6e-02 1.3e-02 l.Oe-0l 3.8 7.0e-02 3.5 pancreas 5.5e-01 2.Oe-01 3.9e-01 1.9 1.4e-01 2.7 skin 1 4.4e-01 1 1.0 1.9e-02 2.1 uterus 1.5e-02 5.4e-02 1.9e-01 3.1 1.4e-01 2.5 5 As noted above, cluster R11723 features 6 transcript(s), which were listed in Table 1 above. A description of each variant protein according to the present invention is now provided. Variant protein R1 1723_PEA_1_P2 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 10 RI 1723_PEA_1_T6. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither 15 trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein Ri 1723_ PEA_1 P2 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 6, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether 20 the SNP is known or not; the presence of known SNPs in variant protein RI 1723-PEA_1_P2 WO 2005/072053 PCT/IB2005/000928 938 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 6 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 107 H->P Yes 70 G -> No 70 G->C No 5 Variant protein R11723_PEA_1_P2 is encoded by the following transcript(s): R11723_PEA_1_T6, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript RI 1723_PEA_1_T6 is shown in bold; this coding portion starts at position 1716 and ends at position 2051. The transcript also has the following SNPs as listed in Table 7 (given according to their position on the nucleotide sequence, with the alternative 10 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA_1_P2 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 1231 C ->T Yes 1278 G -> C Yes 1923 G -> No 1923 G -> T No 2035 A -> C Yes 2048 A -> C No 2057 A -> G Yes 15 WO 2005/072053 PCT/IB2005/000928 939 Variant protein RI 1723 PEA 1_P6 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) RI 1723_PEA_1_Ti5. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the 5 variant protein according to the present invention to each such aligned protein is as follows: Comparison report between RI 1723 PEA_ P6 and Q8IXMO (SEQ ID NO: 1393): 1.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P6, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 10 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR corresponding to amino acids 1 - 110 of RI 1723_PEA_1_P6, and a second amino acid sequence 15 being at least 90 % homologous to MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHV RPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids I - 112 of Q8IXMO, which also corresponds to amino acids 111 222 of RI 1723_PEA._1 P6, wherein said first and second amino acid sequences are contiguous 20 and in a sequential order. 2.An isolated polypeptide encoding for a head of RI 1723_PEA_1_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 25 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR of R11723_PEA_1_P6.

WO 2005/072053 PCT/IB2005/000928 940 Comparison report between RI 1723_PEA _P6 and Q96AC2 (SEQ ID NO:1394): I.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 5 MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids I - 83 of Q96AC2, which also corresponds to amino acids 1 - 83 of RI 1723_PEA-1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL 10 RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of Ri 1723_PEA_1 P6, comprising a 15 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ 20 CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723_PEA_1_P6. Comparison report between R11723_PEA__P6 and Q8N2G4 (SEQ ID NO:1395): 1.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P6, comprising a first amino acid sequence being at least 90 % homologous to 25 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids I - 83 of Q8N2G4, which also corresponds to amino acids 1 - 83 of R1 1723_PEA_1_P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 30 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL

RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ

WO 2005/072053 PCT/IB2005/000928 941 CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEAl-P6, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ 10 CHNNQPWADTSRRERQRKEKHSMRTQ in RI 1723-PEA_1_P6. Comparison report between RI 1723_PEA_1_P6 and BAC85518 (SEQ ID NO:1396): I.An isolated chimeric polypeptide encoding for RI 1723-PEA _P6, comprising a first amino acid sequence being at least 90 % homologous to 15 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAGIMYRKSCASSAACLIASAG corresponding to amino acids 24 - 106 of BAC85518, which also corresponds to amino acids 1 - 83 of RI 1723 PEA 1 P6, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence 20 SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino acids 84 - 222 of RI 1723_PEA_1_P6, wherein said first and second amino acid sequences are contiguous and in a sequential order. 25 2.An isolated polypeptide encoding for a tail of R11723_PEA_1_P6, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLL 30 RGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQ CHNNQPWADTSRRERQRKEKHSMRTQ in R1 1723 PEA 1 P6.

WO 2005/072053 PCT/IB2005/000928 942 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 5 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein RI 1723_PEA_1_P6 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 8, (given according to their position(s) on the 10 amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein Rl 1723_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 8 - Amino acid mutations SNPpoitons)on niii aidAltemtv amn aids) -Prevkisly, known SNIP?, sequence 180 G-> No 180 G -> C No 217 H -> P Yes 15 Variant protein RI 1723_PEA 1 P6 is encoded by the following transcript(s): Ri 1723_PEA_1_TI 5, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript RI 1723_PEA _ T15 is shown in bold; this coding portion starts at position 434 and ends at position 1099. The transcript also has the following SNPs as listed in 20 Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R1 1723_PEA_1_P6 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 943 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 971 No 971 G -> T No 1083 A ->C Yes 1096 A ->C No 1105 A ->G Yes Variant protein Ri 1723_PEA_1_P7 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) 5 R11723_PEA_1_Ti7. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between RI 1723_PEA_1_P7 and Q96AC2: 10 1.An isolated chimeric polypeptide encoding for R1 1723_PEA-_P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 1 - 64 of Q96AC2, which also corresponds to amino acids 1 - 64 of R11723_PEA 1_P7, and a second amino acid sequence being at least 70%, 15 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of Ri 1723_PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 20 2.An isolated polypeptide encoding for a tail of RI 1723_PEA-1 P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7.

WO 2005/072053 PCT/IB2005/000928 944 Comparison report between RI 1723_PEA lP7 and Q8N2G4: 1 .An isolated chimeric polypeptide encoding for Ri 1723_PEA_1_P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV 5 MEQSAG corresponding to amino acids I - 64 of Q8N2G4, which also corresponds to amino acids 1 - 64 of Ri 1723 PEA__P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of 10 RI 1723-PEA_1_P7, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of R11723_PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the 15 sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7. Comparison report between RI 1723_PEA_1_P7 and BAC85273: 1.An isolated chimeric polypeptide encoding for RI 1723_PEA-_1 P7, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more 20 preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of Ri 1723_PEA_1_P7, second amino acid sequence being at least 90 % homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG corresponding to amino acids 22 - 80 of BAC85273, which also corresponds to amino acids 6 25 64 of R1 1723_PEA_1 P7, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of RI 1723_PEA_1 _P7, wherein said first, second and third amino acid sequences are contiguous 30 and in a sequential order.

WO 2005/072053 PCT/IB2005/000928 945 2.An isolated polypeptide encoding for a head of RI 1723_PEA1 _P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG of RI 1723 PEA 1 P7. 5 3.An isolated polypeptide encoding for a tail of RI 1723-PEA_1_P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEAIP7. 10 Comparison report between RI 1723_PEA_1_P7 and BAC85518: 1.An isolated chimeric polypeptide encoding for R 11723_PEA 1 P7, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSAG corresponding to amino acids 24 - 87 of BAC85518, which also corresponds to 15 amino acids 1 - 64 of R11723_PEAl_P7, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT corresponding to amino acids 65 - 93 of Ri 1723_PEA 1 P7, wherein said first and second amino acid sequences are contiguous and in 20 a sequential order. 2.An isolated polypeptide encoding for a tail of RI 1723_PEA_1 P7, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT in RI 1723_PEA_1_P7. 25 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide 30 prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region..

WO 2005/072053 PCT/IB2005/000928 946 Variant protein R11723_PEA_1_P7 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA_1_P7 5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino acids) Previously known SNP? sequence 67 C ->S Yes Variant protein RI 1723 PEA_1_P7 is encoded by the following transcript(s): 10 RI 1723_PEA_1_T17, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEA_1_T17 is shown in bold; this coding portion starts at position 434 and ends at position 712. The transcript also has the following SNPs as listed in Table 11 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of 15 known SNPs in variant protein RI 1723 -PEA_1_P7 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 11 - Nucleic acid SNPs 'SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence, 625 G ->T Yes 633 G ->C Yes 1303 C ->T Yes 20 Variant protein Ri1723_PEA_1_P13 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) R11723_PEA_1_T19 and R11723_PEA__T5. One or more alignments to one or more WO 2005/072053 PCT/IB2005/000928 947 previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between RI 1723-PEA_1_P13 and Q96AC2: 5 l.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P13, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of RI 1723_PEA_1 P13, and a second amino acid sequence being at least 70%, 10 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT corresponding to amino acids 64 - 84 of Ri 1723_PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of R11723_PEA_1 P13, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT in RI 1723_PEA_1_P13. 20 The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane 25 region prediction program predicts that this protein has a trans-membrane region.. Variant protein R1 1723_PEA._1_P13 is encoded by the following transcript(s): R 1723_PEA_1_T19, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript R11723_PEAlT19 is shown in bold; this coding portion starts at 30 position 434 and ends at position 685. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative WO 2005/072053 PCT/IB2005/000928 948 nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723 PEA_1_P13 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 778 G ->T Yes 786 G ->C Yes 1456 C ->T Yes 5 Variant protein R11723_PEA_1_PlO according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) RI 1723_PEA_1_T20. One or more alignments to one or more previously published protein 10 sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between Ri 1723_PEA_1_Pl10 and Q96AC2: 1.An isolated chimeric polypeptide encoding for RI 1723 PEA _1 PlO, comprising a first 15 amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids I - 63 of Q96AC2, which also corresponds to amino acids I - 63 of R11723_PEA-1_P10, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of R1 1723_PEA_1_Pl0, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of R1 1723__PEA_1_P10, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, WO 2005/072053 PCT/IB2005/000928 949 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PlO. Comparison report between R 11723_PEAiPO and Q8N2G4: 5 l.An isolated chimeric polypeptide encoding for RI 1723_PEA__PO, comprising a first amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q8N2G4, which also corresponds to amino acids 1 - 63 of RI 1723 PEA_ _Pl0, and a second amino acid sequence being at least 70%, 10 optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723_PEA_1Pl10, wherein said first and second amino acid sequences are contiguous and in a sequential order. 15 2.An isolated polypeptide encoding for a tail of Ri1723_PEA_1__P, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA1_P10. 20 Comparison report between RI 1723 PEA_1_PlO and BAC85273 (SEQ ID NO:1397): 1.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_P10, comprising a first amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence MWVLG corresponding to amino acids 1 - 5 of Ri 1723_PEA _1._PlO, second 25 amino acid sequence being at least 90 % homologous to IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA corresponding to amino acids 22 - 79 of BAC85273, which also corresponds to amino acids 6 63 of RI 1723_PEA_1_Pl0, and a third amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 30 95% homologous to a polypeptide having the sequence WO 2005/072053 PCT/IB2005/000928 950 DRVSLCHEAGVQWNNFSTLQPLPPRLK corresponding to amino acids 64 - 90 of RI 1723-PEAIPl0, wherein said first, second and third amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a head of R11723_PEA_1_Pl0, comprising a 5 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence MWVLG of R 11723 PEA I PlO. 3.An isolated polypeptide encoding for a tail of R11723_PEA_1_P10, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, 10 more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PO. Comparison report between RI 1723_PEA_1_PlO and BAC85518: I.An isolated chimeric polypeptide encoding for RI 1723_PEA_1_PlO, comprising a first 15 amino acid sequence being at least 90 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 24 - 86 of BAC85518, which also corresponds to amino acids 1 - 63 of R11723_PEA_1_Pl0, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most 20 preferably at least 95% homologous to a polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLIK corresponding to amino acids 64 - 90 of Ri 1723_PEA_1_P10, wherein said first and second amino acid sequences are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of R11723_PEA _1P1O, comprising a 25 polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK in RI 1723_PEA_1_PlO. The location of the variant protein was determined according to results from a number of 30 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: WO 2005/072053 PCT/IB2005/000928 951 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region.. Variant protein R11723_PEA_1P 10 also has the following non-silent SNPs (Single 5 Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein R11723_PEA_1_PlO sequence provides support for the deduced sequence of this variant protein according to the present invention). 10 Table 13 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 66 V->F Yes Variant protein R11723_PEA_1_PlO is encoded by the following transcript(s): RI 1723_PEA_1_T20, for which the sequence(s) is/are given at the end of the application. The coding portion of transcript RI 1723_PEA_1_T20 is shown in bold; this coding portion starts at 15 position 434 and ends at position 703. The transcript also has the following SNPs as listed in Table 14 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein RI 1723_PEA_1_P10 sequence provides support for the deduced sequence of this variant protein according to the present invention). 20 Table 14 - Nucleic acid SNPs SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 629 G -> T Yes 637 G-> C Yes 1307 C->T Yes As noted above, cluster R1 1723 features 26 segment(s), which were listed in Table 2 above and for which the sequence(s) are given at the end of the application. These segment(s) WO 2005/072053 PCT/IB2005/000928 952 are portions of nucleic acid sequence(s) which are described herein separately because they are of particular interest. A description of each segment according to the present invention is now provided. 5 Segment cluster Ri 1723_PEA_1_node_13 according to the present invention is supported by 5 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723-PEA_1_T19, R11723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 15 below describes the starting and ending position of this segment on each transcript. 10 Table 15 - Segment location on transcripts Transcript name Segment starting position Segment ding position R11723_PEA_1 T19 624 776 R11723_PEA 1_T5 624 776 R11723_PEA 1 T6 658 810 Segment cluster RI 1723_PEA_1_node_16 according to the present invention is supported by 3 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): R11723_PEA_1_T17, R11723_PEA_1_19 and R1 1723_PEA_1_T20. Table 16 below describes the starting and ending position of this segment on each transcript. Table 16 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1 T17 624 1367 R11723_PEA 1T19 777 1520 R11723_PEA_1_T20 628 1371 20 Segment cluster RI 1723_PEA_1_node_19 according to the present invention is supported by 45 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 953 can be found in the following transcript(s): RI 1723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 17 below describes the starting and ending position of this segment on each transcript. Table 17 - Segment location on transcripts Transit name Segment starting position Seginnt ending position R11723_PEA 1 T5 835 1008 R11723_PEA_1_T6 869 1042 5 Segment cluster RI 1723_PEA_1_node_2 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_119, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. 10 Table 18 below describes the starting and ending position of this segment on each transcript. Table 18 - Segment location on transcripts Transcript name ,Segment starting positi)oti Segment ending position R11723_PEA1 15 1 309 R11723_PEA 1_T17 1 309 R11723_PEA 1_119 1 309 R11723_PEA 1 T20 1 309 R11723_PEA 1T5 1 309 R11723_PEA 1 T6 1 309 Segment cluster R1 1723_PEA_1_node_22 according to the present invention is supported 15 by 65 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R1 1723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 19 below describes the starting and ending position of this segment on each transcript. Table 19 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 954 R11723_PEA_1_T5 1083 1569 R11723_PEAIT6 1117 1603 Segment cluster RI 1723_PEA_1_node_31 according to the present invention is supported by 70 libraries. The number of libraries was detennined as previously described. This segment 5 can be found in the following transcript(s): R11723_PEA_1_Ti5, R11723_PEA_1_T5 and R1 1723_PEA_1_T6. Table 20 below describes the starting and ending position of this segment on each transcript (it should be noted that these transcripts show alternative polyadenylation). Table 20 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1 T15 1060 1295 R11723_PEA 1 T5 1978 2213 R11723_PEA_1_T6 2012 2247 According to an optional embodiment of the present invention, short segments related to 10 the above cluster are also provided. These segments are up to about 120 bp in length, and so are included in a separate description. Segment cluster R1 1723_PEA_1_node_10 according to the present invention is supported by 38 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): R11723_PEAITI5, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEAIT6. Table 21 below describes the starting and ending position of this segment on each transcript. Table 21 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1_T15 486 529 R11723_PEA_1 T17 486 529 R11723_PEA_1 T19 486 529 R11723_PEA 1_T20 486 529 WO 2005/072053 PCT/IB2005/000928 955 R11723_PEA 1T5 486 529 R1 1723_PEA_1_T6 520 563 Segment cluster RI 1723_PEA_1_node_11 according to the present invention is supported by 42 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R11723_PEA_1_15, R11723_PEA_1_17, R11723_PEA_119, R11723_PEA_1-T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 22 below describes the starting and ending position of this segment on each transcript. Table 22 - Segment location on transcripts Transcript na megment starting position Segment ending position R11723 PEA 1 15 530 623 R11723 PEA 1T17 530 623 R11723_PEA 1_19 530 623 R11723_PEA_1_T20 530 623 R11723 PEA 1 T5 530 623 R11723 PEA 1 T6 564 657 10 Segment cluster R11723_PEA_1_node_15 according to the present invention can be found in the following transcript(s): R1 1723_PEA_1_T20. Table 23 below describes the starting and ending position of this segment on each transcript. Table 23 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T20 624 627 15 Segment cluster RI 1723_PEA_1_node_18 according to the present invention is supported by 40 libraries. The number of libraries was determined as previously described. This segment WO 2005/072053 PCT/IB2005/000928 956 can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T5 and Ri 1723_PEAIT6. Table 24 below describes the starting and ending position of this segment on each transcript. Table 24 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723 PEA 1_T15 624 681 R11723_PEA_1_T5 777 834 R11723_PEA_1_T6 811 868 5 Segment cluster R1 1723_PEA_1_node_20 according to the present invention can be found in the following transcript(s): RI 1723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 25 below describes the starting and ending position of this segment on each transcript. 10 Table 25 - Segment location on transcripts Transcript name Segment starting position Segmen t end ing position n R11723_PEA 1 TS 1009 1019 R11723PEA 1_T6 1043 1053 Segment cluster RI 1723_PEA_1_node_21 according to the present invention is supported by 36 libraries. The number of libraries was determined as previously described. This segment 15 can be found in the following transcript(s): Rl 1723_PEA_1_T5 and R1 1723_PEA_1_T6. Table 26 below describes the starting and ending position of this segment on each transcript. Table 26 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T5 1020 1082 R11723_PEA_1_T6 1054 1116 WO 2005/072053 PCT/IB2005/000928 957 Segment cluster RI 1723_PEA_1_node_23 according to the present invention is supported by 39 libraries. The number of libraries was detennined as previously described. This segment can be found in the following transcript(s): RI 1723_PEAIT5 and RI 1723_PEA_1_T6. Table 27 below describes the starting and ending position of this segment on each transcript. 5 Table 27 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723PEA 1 T5 1570 1599 R11723_PEA_1_T6 1604 1633 Segment cluster RI 1723_PEA1node_24 according to the present invention is supported by 51 libraries. The number of libraries was detennined as previously described. This segment 10 can be found in the following transcript(s): R11723_PEA_1_Ti5, R11723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 28 below describes the starting and ending position of this segment on each transcript. Table 28 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1_Ti5 682 765 R11723_PEA_1_T5 1600 1683 R11723_PEA 1 T6 1634 1717 15 Segment cluster R1 1723_PEA_1_node_25 according to the present invention is supported by 54 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T5 and RI 1723_PEA_1_T6. Table 29 below describes the starting and ending position of this segment 20 on each transcript. Table 29 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 958 R11723_PEA1 T15 766 791 R11723_PEA_1_T5 1684 1709 R11723_PEAI 1T6 1718 1743 Segment cluster RI 1723_PEA_1_node_26 according to the present invention is supported by 62 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T5 and R1 1723_PEA_1_T6. Table 30 below describes the starting and ending position of this segment on each transcript. Table 30 - Segment location on transcripts Transcript name Segmeit starting position Segmenn ending position R11723_PEA_1 T15 792 904 R11723_PEA_1 T5 1710 1822 R11723_PEA 1 T6 1744 1856 10 Segment cluster R1 1723_PEA_1_node_27 according to the present invention is supported by 67 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA-1_T5 and RI 1723_PEA_1_T6. Table 31 below describes the starting and ending position of this segment 15 on each transcript. Table 31 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1 T15 905 986 R11723_PEA 1_T5 1823 1904 R11723_PEA 1_T6 1857 1938 WO 2005/072053 PCT/IB2005/000928 959 Segment cluster RI 1723_PEA_1_node_28 according to the present invention can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 32 below describes the starting and ending position of this segment on each transcript. 5 Table 32 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1_Ti5 987 1010 R11723_PEA 1_T5 1905 1928 R11723_PEA 1 T6 1939 1962 Segment cluster R1 1723_PEA-1_node_29 according to the present invention is supported by 69 libraries. The number of libraries was determined as previously described. This segment 10 can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T5 and R1 1723_PEA_1_T6. Table 33 below describes the starting and ending position of this segment on each transcript. Table 33 - Segment location on transcripts Transcript name Segment'starting position Segmelt ending position R11723_PEA 1_T15 1011 1038 R11723_PEA1 T5 1929 1956 R11723_PEA 1_T6 1963 1990 15 Segment cluster R1 1723_PEA_1_node_3 according to the present invention can be found in the following transcript(s): R11723_PEA_1_TI5, R11723_PEA_1-T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 34 below describes the starting and ending position of this segment on each transcript. 20 Table 34 - Segment location on transcripts Transcript name Segment starting position Segment ending position WO 2005/072053 PCT/IB2005/000928 960 R11723_PEA1 TI5 310 319 R11723 PEA 1 T17 310 319 R11723_PEA_1_T19 310 319 R11723_PEA_1_T20 310 319 R11723_PEA 1 T5 310 319 R11723_PEA1 1T6 310 319 Segment cluster RI 1723_PEA_1_node_30 according to the present invention can be found in the following transcript(s): R11723_PEA_1_Ti5, R11723_PEA_1_T5 and 5 RI 1723_PEA_1_T6. Table 35 below describes the starting and ending position of this segment on each transcript. Table 35 -Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA 1_Ti5 1039 1059 R11723PEA 1 T5 1957 1977 R11723_PEA_1 T6 1991 2011 10 Segment cluster RI 1723_PEA_1_node_4 according to the present invention is supported by 25 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEAIT6. Table 36 below describes the starting and ending position of this segment on each transcript. 15 Table 36 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1 T15 320 371 R11723_PEA_1 T17 320 371 R11723_PEA 1_T19 320 371 WO 2005/072053 PCT/IB2005/000928 961 R11723 PEA_1 T20 320 371 R11723_PEAI 1T5 320 371 R11723_PEA_1_T6 320 371 Segment cluster RI 1723_PEA_1_node_5 according to the present invention is supported by 26 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R11723_PEA_1_15, R11723_PEA_1_T17, R11723_PEA_1_19, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 37 below describes the starting and ending position of this segment on each transcript. Table 37 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1 TI5 372 414 R11723_PEA_1_T17 372 414 R11723_PEA_1 19 372 414 R11723 PEA 1T20 372 414 R11723_PEA1 1T5 372 414 R11723_PEA 1_T6 372 414 10 Segment cluster RI 1723_PEA_1_node_6 according to the present invention is supported by 27 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R11723_PEA_1_T15, R11723_PEA_1_T17, R11723_PEA_1_T19, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. 15 Table 38 below describes the starting and ending position of this segment on each transcript. Table 38 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1 T15 415 446 R11723_PEA 1_117 415 446 WO 2005/072053 PCT/IB2005/000928 962 R11723_PEA 1 19 415 446 R11723_PEA_1 T20 415 446 R11723_PEA_1_T5 415 446 R11723_PEA 1 T6 415 446 Segment cluster Ri 1723_PEA_1_node_7 according to the present invention is supported by 29 libraries. The number of libraries was determined as previously described. This segment 5 can be found in the following transcript(s): R11723_PEA_1-T15, R11723_PEA_117, R11723_PEA_119, R11723_PEA_1_T20, R11723_PEA_1_T5 and R11723_PEA_1_T6. Table 39 below describes the starting and ending position of this segment on each transcript. Table 39 - Segment location on transcripts Transcript name ~ Segment starting position Segment ending position R11723_PEA_1 15 447 485 R11723_PEA 1 17 447 485 R11723_PEA 1 19 447 485 RI1723 PEA1 T20 447 485 R11723_PEA1 1T5 447 485 R11723_PEA 1 T6 447 485 10 Segment cluster RI 1723_PEA_1_node_8 according to the present invention is supported by 2 libraries. The number of libraries was determined as previously described. This segment can be found in the following transcript(s): R1 1723_PEA_1_T6. Table 40 below describes the starting and ending position of this segment on each transcript. 15 Table 40 - Segment location on transcripts Transcript name Segment starting position Segment ending position R11723_PEA_1_T6 486 519 WO 2005/072053 PCT/IB2005/000928 963 It should be noted that the variants of this cluster are variants of the hypothetical protein PSECO181 (referred to herein as "PSEC"). Furthermore, use of the known protein (WT protein) for detection of ovarian cancer, alone or in combination with one or more variants of this cluster and/or of any other cluster and/or of any known marker, also comprises an embodiment of the 5 present invention. It should be noted that the nucleotide transcript sequence of known protein (PSEC, also referred to herein as the "wild type" or WT protein) feature at least one SNP that appears to affect the coding region, in addition to certain silent SNPs. This SNP does not have an effect on the R11723PEA lT5 splice variant sequence): "G-> " resulting in a missing nucleotide 10 (affects amino acids from position 91 onwards). The missing nucleotide creates a frame shift, resulting in a new protein. This SNP was not previously identified and is supported by 5 ESTs out of~70 ESTs in this exon. Expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence 15 name RI 1723 segl3 in normal and cancerous colon tissues. Expression of transcripts detectable by or according to segi 3, RI 1723 seg1 3 amplicon (SEQ ID NO: 1297) and R11723 seg13F (SEQ ID NO: 1295) and R11723 seg13R (SEQ ID NO: 1296) primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD-amplicon, 20 SEQ ID NO:53 1), HPRTI (GenBank Accession No. NM_000194; amplicon - HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; HPRT1-amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_002954; RPS27A amplicon, SEQ ID NO:1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The 25 normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3, above: "Tissue samples in colon cancer testing panel"), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples. Figure 28 is a histogram showing differential expression of the above-indicated 30 transcripts in cancerous colon samples relative to the normal samples. Values represent the average of duplicate experiments. Error bars indicate the minimal and maximal values obtained.

WO 2005/072053 PCT/IB2005/000928 964 As is evident from Figure 28, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher by more than 5 fold than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3: "Tissue samples in colon cancer testing panel"). However, the expression of transcripts detectable by the above amplicon in a several 5 other cancer samples was lower than in the non-cancerous samples. Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non 10 limiting illustrative example only of a suitable primer pair: RI 1723 seg13F forward primer; and R1 1723 segl3R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RI 1723 segl3. 15 R1 1723segl3F (SEQ ID NO: 1295) - ACACTAAAAGAACAAACACCTTGCTC RI 1723seg13R (SEQ ID NO: 1296) - TCCTCAGAAGGCACATGAAAGA RI 1723seg13 - amplicon (SEQ ID NO: 1297): ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAGCAGTTG ACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA 20 25 30 Expression of R11723 transcripts, which are detectable by amplicon as depicted in sequence name R11723junc11-18 in normal and cancerous colon tissues.

WO 2005/072053 PCT/IB2005/000928 965 Expression of transcripts detectable by or according to juncl -18, RI 1723 juncl 1-18 amplicon (SEQ ID NO: 1300) and RI 1723 junc 11-18F (SEQ ID NO: 1298) and Ri 1723 junc1 1 18R (SEQ ID NO: 1299) primers was measured by real time PCR. In parallel the expression of four housekeeping genes -PBGD (GenBank Accession No. BC019323; amplicon - PBGD 5 amplicon, SEQ ID NO:531), HPRTI (GenBank Accession No. NM_000194; amplicon HPRT1-amplicon, SEQ ID NO:612), G6PD (GenBank Accession No. NM_000402; H-PRT1 amplicon, SEQ ID NO:615), and RPS27A (GenBank Accession No. NM_002954; RPS27A amplicon, SEQ ID NO: 1261), was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping 10 genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the normal post-mortem (PM) samples (Sample Nos. 41, 52, 62-67, 69-71, Table 3, above: "Tissue samples in colon cancer testing panel"), to obtain a value of fold differential expression for each sample relative to median of the normal PM samples. Figure 29 is a histogram showing differential expression of the above-indicated 15 transcripts in a few cancerous colon samples relative to the normal samples (Sample Nos. 41, 52, 62-67, 69-71 Table 3: "Tissue samples in colon cancer testing panel"). As is evident from Figure 29, the expression of transcripts detectable by the above amplicon in a few cancer samples was higher by more than 5 fold than in the non-cancerous samples (Sample Nos. 41, 52, 62-67, 69-71 Table 1: "Tissue samples in colon cancer testing 20 panel"). However, the expression of transcripts detectable by the above amplicon in a several other cancer samples was lower than in the non-cancerous samples Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non limiting illustrative example only of a suitable primer pair: R1 1723 junc11-18F forward primer; 25 and Ri 1723 junc 1 1-1 8R reverse primer. The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: R1 1723 junc11 18. 30 WO 2005/072053 PCT/IB2005/000928 9 6 6 RI 1723junc11-18F (SEQ ID NO: 1298)- AGTGATGGAGCAAAGTGCCG R1 1723 junc11 -1I8R (SEQ ID NO: 1299)- CAGCAGCTGA TGCAAACTGAG RI 1723 junc1 1-18 amplicon (SEQ ID NO: 1300) AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCATCAGCGG 5 CCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCAGGGAAACTGAACT CAGTTTGCATCAGCTGCTG 10 Expression of RI 1723 transcripts, which are detectable by amplicon as depicted in sequence name RI 1723seg13 in different normal tissues. Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon 15 (SEQ ID NO: 1297) and R11723seg13F (SEQ ID NO: 1295) , R11723seg13R (SEQ ID NO: 1296) was measured by real time PCR. In parallel the expression of four housekeeping genes RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon, SEQ ID NO:1270) and 20 SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples to obtain a value of relative expression of each sample relative to median of the ovary 25 samples. The results are described in Figure 30, presenting the histogram showing the expression of R11723 transcripts, detectable by amplicon depicted in sequence name R11723seg13 in different normal tissues. 30 WO 2005/072053 PCT/IB2005/000928 967 R 11723seg13F (SEQ ID NO: 1295) - ACACTAAAAGAACAAACACCTTGCTC RI 1723seg13R (SEQ ID NO: 1296) - TCCTCAGAAGGCACATGAAAGA RI 1723seg13 - amplicon (SEQ ID NO: 1297): ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAGCAGTTG 5 ACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTCTGAGGA 10 Expression of R1 1723 transcripts, which are detectable by amplicon as depicted in sequence name Ri 1723 junc1 1-18 in different normal tissues. Expression of R11723 transcripts detectable by or according to R11723seg13 amplicon 15 (SEQ ID NO: 1300) and R11723junc11-18F (SEQ ID NO:1298), R11723junc11-18R (SEQ ID NO:1299) was measured by real time PCR. In parallel the expression of four housekeeping genes- RPL19 (GenBank Accession No. NM_000981; RPL19 amplicon, SEQ ID NO:1264), TATA box (GenBank Accession No. NM_003194; TATA amplicon, SEQ ID NO:1267), UBC (GenBank Accession No. BC000449; amplicon - Ubiquitin-amplicon, SEQ ID NO:1270) and 20 SDHA (GenBank Accession No. NM_004168; amplicon - SDHA-amplicon, SEQ ID NO:1273) was measured similarly. For each RT sample, the expression of the above amplicon was normalized to the geometric mean of the quantities of the housekeeping genes. The normalized quantity of each RT sample was then divided by the median of the quantities of the ovary samples to obtain a value of relative expression of each sample relative to median of the ovary 25 samples. The results are described in Figure 31, presenting the histogram showing the expression of R1 1723 transcripts, detectable by amplicon depicted in sequence name R1 1723 junc11-1 8 in different normal tissues.

WO 2005/072053 PCT/IB2005/000928 968 R11723juncl 1-18F (SEQ ID NO: 1298)- AGTGATGGAGCAAAGTGCCG RI 1723 junc1 1-18R (SEQ ID NO: 1299)- CAGCAGCTGATGCAAACTGAG RI 1723 juncll-18 amplicon (SEQ ID NO: 1300) AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCATCAGCGG 5 CCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCAGGGAAACTGAACT CAGTTTGCATCAGCTGCTG 10 It was found that the known protein (wild type) transcript expression pattern for the above cluster (PSEC) is similar to the variant expression pattern, except that in some cases (such as ovarian cancer) the variant overexpression in cancer was found to be higher. 15 Variant protein alignment to the previously known protein: Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8IXMO Sequence documentation: 20 Alignment of: R11723_PEA_1_P6 x Q8IXM . Alignment segment 1/1: 25 Quality: 1128.00 Escore: 0 Matching length: 112 Total length: 112 Matching Percent Similarity: 100.00 Matching Percent 30 Identity: 100.00 WO 2005/072053 PCT/IB2005/000928 969 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 5 Alignment: 111 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 160 1 MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLRE 50 10 161 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 210 51 GEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRE 100 15 211 RQRKEKHSMRTQ 222 11i1 111111111 101 RQRKEKHSMRTQ 112 20 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q96AC 2 25 Sequence documentation: Alignment of: R11723_PEA_1_P6 x Q96AC2 . . 30 Alignment segment 1/1: WO 2005/072053 PCT/IB2005/000928 970 Quality: 835.00 Escore: 0 Matching length: 83 Total length: 83 5 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 10 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 111II111 iii 111111111111111111I I~iiIIIIIIIIIIII|I 15 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 ii~ ii I| II I i 111 111ii 1I | 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 20 25 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:Q8N2G4 Sequence documentation: 30 Alignment of: R11723 PEA 1_P6 x Q8N2G4 WO 2005/072053 PCT/IB2005/000928 971 Alignment segment 1/1: Quality: 835.00 Escore: 0 5 Matching length: 83 Total length: 83 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 10 Identity: 100.00. Gaps: 0 Alignment: 15 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 20 li l l l l l l lI I l l l l l l l 111 1! I l l llI iI I 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 25 Sequence name: /tmp/gp6eQTLWqk/mFtjUpUzhb:BAC85518 30 Sequence documentation: WO 2005/072053 PCT/IB2005/000928 972 Alignment of: R11723 PEA 1 P6 x BAC85518 Alignment segment 1/1: 5 Quality: 835.00 Escore: 0 Matching length: 83 Total length: 83 Matching Percent Similarity: 100.00 Matching Percent 10 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 15 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1lil l lll lll 11l l Il 11l 1 l l ll l lll 11ill l l li l l lll l l i 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFTVNCTVNV 73 20 51 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 83 74 QDMCQKEVMEQSAGIMYRKSCASSAACLIASAG 106 25 30 Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:Q96AC2 WO 2005/072053 PCT/IB2005/000928 973 Sequence documentation: Alignment of: R11723_PEA 1 P7 x Q96AC2 5 Alignment segment 1/1: Quality: 654.00 Escore: 0 Matching length: 64 Total 10 length: 64 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 15 Gaps: 0 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 2 0 l i l l l 1 1 1l l l l l l l l l l l l l i l Il l l l l l l l l l l l l l i l l i l l i l 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSAG 64 25 51 QDMCQKEVMEQSAG 64 30 WO 2005/072053 PCT/IB2005/000928 974 Sequence name: /tmp/VXjdFlzdBX/bexTxThOTh:Q8N2G4 Sequence documentation: 5 Alignment of: R11723 PEA 1 P7 x Q8N2G4 Alignment segment 1/1: Quality: 654.00 10 Escore: 0 Matching length: 64 Total length: 64 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 15 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 20 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 I I 1l l1 1 1Ill l l l l l l l l l l I l lI l l l l l l l l l l l ll l l l i 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 25 51 QDMCQKEVMEQSAG 64 51 QDMCQKEVMEQSAG 64 30 WO 2005/072053 PCT/IB2005/000928 975 Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85273 5 Sequence documentation: Alignment of: R11723 PEA 1 P7 x BAC85273 Alignment segment 1/1: 10 Quality: 600.00 Escore: 0 Matching length: 59 Total length: 59 15 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 20 Alignment: 6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55 11||11|1lii1111|111|1|1 II I11lllllilill1ll11 25 22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71 56 KEVMEQSAG 64 i 11I 1 I I 1 72 KEVMEQSAG 80 30 WO 2005/072053 PCT/IB2005/000928 976 5 Sequence name: /tmp/VXjdFlzdBX/bexTxTh0Th:BAC85518 Sequence documentation: Alignment of: R11723_PEA_1_P7 x BAC85518 10 Alignment segment 1/1: Quality: 654.00 Escore: 0 15 Matching length: 64 Total length: 64 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent 20 Identity: 100.00 Gaps: 0 Alignment: 25 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 lllll1 11 Il l il lll ll l l i ll ll l lllll 1 1 IIli li 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73 51 QDMCQKEVMEQSAG 64 30 | I 1 1 I i I 74 QDMCQKEVMEQSAG 87 WO 2005/072053 PCT/IB2005/000928 977 5 Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:Q96AC2 Sequence documentation: 10 Alignment of: R11723_PEA_1_PlO x Q96AC2 Alignment segment 1/1: 15 Quality: 645.00 Escore: 0 Matching length: 63 Total length: 63 Matching Percent Similarity: 100.00 Matching Percent 20 Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 25 Alignment: 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 30 51 QDMCQKEVMEQSA 63 WO 2005/072053 PCT/IB2005/000928 978 51 QDMCQKEVMEQSA 63 5 Sequence name: /tmp/OLMSexEmIh/pc7Z7XmlYR:Q8N2G4 10 Sequence documentation: Alignment of: R11723_PEA_1_P1O x Q8N2G4 15 Alignment segment 1/1: Quality: 645.00 Escore: 0 Matching length: 63 Total 20 length: 63 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 25 Gaps: 0 Alignment: 1 MWVLGTAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 3 0 liI l l lI l l l l l l l l l l l l l l l l l l l l i l 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 WO 2005/072053 PCT/IB2005/000928 979 51 QDMCQKEVMEQSA 63 51 QDMCQKEVMEQSA 63 5 10 Sequence name: /tmp/OLMSexEmIh/pc7Z7Xm1YR:BAC85273 Sequence documentation: 15 Alignment of: R11723 PEA 1 PlO x BAC85273 Alignment segment 1/1: Quality: 591.00 20 Escore: 0 Matching length: 58 Total length: 58 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 30 . 6 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 55 WO 2005/072053 PCT/IB2005/000928 980 22 IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQ 71 56 KEVMEQSA 63 5 1 1 1 1 1l i i 1l 72 KEVMEQSA 79 10 Sequence name: /tmp/OLMSexEmIh/pc7Z7XmlYR:BAC85518 15 Sequence documentation: Alignment of: R11723_PEA_1_PlO x BAC85518 Alignment segment 1/1: 20 Quality: 645.00 Escore: 0 Matching length: 63 Total length: 63 25 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 30 Alignment: WO 2005/072053 PCT/IB2005/000928 981 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 lillllllllllllllllllllllllllllll11llllllllllllilll 24 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 73 5 51 QDMCQKEVMEQSA 63 74 QDMCQKEVMEQSA 86 10 15 Alignment of: R11723 PEA 1 P13 x Q96AC2 Alignment segment 1/1: Quality: 645.00 20 Escore: 0 Matching length: 63 Total length: 63 Matching Percent Similarity: 100.00 Matching Percent Identity: 100.00 25 Total Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: 30 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 WO 2005/072053 PCT/IB2005/000928 982 1 MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNV 50 51 QDMCQKEVMEQSA 63 5 51 QDMCQKEVMEQSA 63 10 DESCRIPTION FOR CLUSTER M77903 15 Cluster M77903 features 4 transcript(s) and 29 segment(s) of interest, the names for which are given in Tables 1 and 2, respectively, the sequences themselves are given at the end of the application. The selected protein variants are given in table 3. Table 1 - Transcripts of interest ranscript Name SEQ ID NO M77903_TI1 81 M77903 T12 82 M77903_T34 83 M77903_T36 84 20 Table 2 - Segments of interest Segment Name SEQ ID NO: M77903_node 2 476 M77903node_13 477 M77903_node 16 478 WO 2005/072053 PCT/IB2005/000928 983 M77903_node 18 479 M77903_node_35 480 M77903node_36 481 M77903_node_37 482 M77903 node_38 483 M77903_node 40 484 M77903_node_44 485 M77903_node 46 486 M77903 node 47 487 M77903_node 48 488 M77903_node 49 489 M77903_node 51 490 M77903 node 52 491 M77903node_1 492 M77903 node 5 493 M77903_node 9 494 M77903 node 10 495 M77903node_11 496 M77903_node_12 497 M77903_node_15 498 M77903_node 17 499 M77903node_20 500 M77903_node 28 501 M77903_node_34 502 M77903node_41 503 M77903_node 42 504 Table 3 - Proteins of interest Protein Name SEQ ID NO: Corresponding Transcript(s) WO 2005/072053 PCT/IB2005/000928 984 M77903_P4 608 M77903T11 M77903_P5 609 M77903_T12 M77903_P15 610 M77903_T34 M77903_P16 611 M77903_T36 These sequences are variants of the known protein Translocon-associated protein, alpha subunit precursor (SwissProt accession identifier SSRAHUMAN; known also according to the synonyms TRAP-alpha; Signal sequence receptor alpha subunit; SSR-alpha), SEQ ID NO: 641, 5 referred to herein as the previously known protein. Protein Translocon-associated protein, alpha subunit precursor is known or believed to have the following function(s): TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocation apparatus after completion of the translocation 10 process or may function as a membrane-bound chaperone facilitating folding of translocated proteins. The sequence for protein Translocon-associated protein, alpha subunit precursor is given at the end of the application, as "Translocon-associated protein, alpha subunit precursor amino acid sequence". Known polymorphisms for this sequence are as shown in Table 4. Table 4 - Amino acid mutations for Known Protein SN,,P positioii(s) on Comment amino. acid sequence 28 L->S 130 Y ->H 15 Protein Translocon-associated protein, alpha subunit precursor localization is believed to be Type I membrane protein. Endoplasmic reticulum. The following GO Annotation(s) apply to the previously known protein. The following annotation(s) were found: co-translational membrane targeting; positive control of cell 20 proliferation, which are annotation(s) related to Biological Process; signal sequence receptor; calcium binding, which are annotation(s) related to Molecular Function; and endoplasmic reticulum; integral membrane protein, which are annotation(s) related to Cellular Component.

WO 2005/072053 PCT/IB2005/000928 985 The GO assignment relies on infonnation from one or more of the SwissProt/TremBl Protein knowledgebase, available from <http://www.expasy.ch/sprot/>; or Locuslink, available from <http://www.ncbi.nlm.nih.gov/projects/LocusLink/>. 5 Cluster M77903 can be used as a diagnostic marker according to overexpression of transcripts of this cluster in cancer. Expression of such transcripts in normal tissues is also given according to the previously described methods. The term "number" in the left hand colunm of the table and the numbers on the y-axis of the figure below refer to weighted expression of ESTs in each category, as "parts per million" (ratio of the expression of ESTs for a particular cluster to 10 the expression of all ESTs in that category, according to parts per million). Overall, the following results were obtained as shown with regard to the histograms in Figure 33 and Table 5. This cluster is overexpressed (at least at a minimum level) in the following pathological conditions: ovarian carcinoma and uterine malignancies. 15 Table 5 - Normal tissue distribution Name of Tissue Number Adrenal 120 Bladder 123 Bone 129 Brain 79 Colon 31 Epithelial 124 General 129 head and neck 263 Kidney 118 Liver 107 Lung 147 WO 2005/072053 PCT/IB2005/000928 986 Lymph nodes 126 Breast 211 bone marrow 251 Muscle 109 Ovary 3 Pancreas 144 Prostate 142 Skin 163 Stomach 183 T cells 278 Thyroid 128 Uterus 81 Table 6 - P values and ratios for expression in cancerous tissue Name offisue P1 P2 SPi R3 SP2 R4 adrenal 3.8e-01 2.8e-01 4.le-01 1.4 2.4e-01 1.6 bladder 3.7e-01 4.le-01 1.6e-01 1.8 3.0e-01 1.4 Bone 2.0e-01 2.4e-01 7.7e-01 1.0 6.6e-01 0.9 Brain 5.9e-01 5.5e-01 8.4e-01 0.7 7.9e-01 0.8 Colon 7.0e-02 1.1e-02 6.le-02 2.9 2.5e-02 3.2 epithelial 4.2e-02 5.8e-02 1.3e-01 1.2 4.7e-01 1.0 general 4.0e-02 2.0e-02 6.le-01 1.0 8.9e-01 0.9 head and neck 4.5e-01 4.6e-01 1 0.4 9.0e-01 0.5 kidney 6.5e-01 7.6e-01 2.8e-01 1.2 5.3e-01 0.9 Liver 5.3e-01 5.8e-01 1 0.4 9.1e-01 0.6 Lung 6.le-01 7.3e-01 3.7e-01 1.2 7.0e-01 0.9 Lymph nodes 2.4e-01 5.8e-01 7.1e-01 0.9 8.7e-01 0.6 breast 8.0e-01 8.3e-01 9.9e-01 0.4 9.le-01 0.5 bone marrow 7.5e-01 6.8e-01 1 0.1 9.5e-01 0.5 WO 2005/072053 PCT/IB2005/000928 987 muscle 4.0e-01 2.6e-01 6.2e-01 1.5 8.3e-01 0.7 Ovary 7.8e-03 8.7e-03 1.0e-02 5.8 3.le-02 4.4 pancreas 5.6e-01 6.6e-0l 7.8e-01 0.6 8.6e-01 0.6 prostate 4.5e-01 4.3e-01 6.2e-01 0.9 4.3e-01 0.8 Skin 4.9e-01 5.3e-01 3.6e-01 1.4 9.3e-01 0.4 stomach 2.9e-01 5.5e-01 7.5e-01 0.6 9.4e-01 0.5 T cells 6.7e-01 5.0e-01 5.5e-01 1.5 5.7e-01 1.1 Thyroid 5.7e-01 5.7e-01 7.4e-01 1.1 7.4e-01 1.1 uterus 7.4e-03 2.5e-02 4.6e-01 1.1 6.Oe-01 0.9 5 As noted above, cluster M77903 features 4 transcript(s), which were listed in Table 1 above. These transcript(s) encode for protein(s) which are variant(s) of protein Translocon associated protein, alpha subunit precursor. A description of each variant protein according to the present invention is now provided. 10 Variant protein M77903_P4 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903Ti 1. An alignment is given to the known protein (Translocon-associated protein, alpha subunit precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the 15 relationship of the variant protein according to the present invention to each such aligned protein is as follows: Comparison report between M77903_P4 and SSRAHUMAN: 1.An isolated chimeric polypeptide encoding for M77903_P4, comprising a first amino acid sequence being at least 90 % homologous to 20 MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDE PTDLVEDKEEEDVSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLD

ASFRYPQDYQFYIQNFTALPLNTVVPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLN

WO 2005/072053 PCT/IB2005/000928 988 GNVFQDAVFNQTVTVIEREDGLDGET corresponding to amino acids I - 207 of SSRAHUMAN, which also corresponds to amino acids 1 - 207 of M77903 P4, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having 5 the sequence VRDPYRK corresponding to amino acids 208 - 214 of M77903_P4, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of M77903 P4, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably 10 at least about 90% and most preferably at least about 95% homologous to the sequence VRDPYRK in M77903_P4. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized 15 programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein M77903_P4 also has the following non-silent SNPs (Single Nucleotide 20 Polymorphisms) as listed in Table 7, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 7 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 6 R G No 24 G-> No 28 L ->S Yes 48 E ->G No WO 2005/072053 PCT/IB2005/000928 989 54 A ->T Yes 58 E->K No 63 D-> No 89 F-> No 116 I->M No 130 Y ->H No 130 Y ->N No 178 K-> No The glycosylation sites of variant protein M77903 P4, as compared to the known protein Translocon-associated protein, alpha subunit precursor, are described in Table 8 (given according to their position(s) on the amino acid sequence in the first column; the second column 5 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 8 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 191 Yes 191 136 Yes 136 Variant protein M77903_P4 is encoded by the following transcript(s): M77903_TI 1, for 10 which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_TI 1 is shown in bold; this coding portion starts at position 200 and ends at position 841. The transcript also has the following SNPs as listed in Table 9 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 15 M77903P4 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 9 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 990 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 72 G ->T Yes 120 C ->G No 147 G ->C Yes 215 C ->G No 271 C-> No 282 T ->C Yes 342 A ->G No 359 G ->A Yes 371 G ->A No 388 T-> No 464 T-> No 547 T ->C No 547 T ->G No 587 T ->A No 587 T ->C No 731 A-> No 927 A-> No 1117 T-> No 1118 G-> No 1296 T ->A Yes 1324 T-> No 1326 T-> No 1408 T ->G No 1450 T ->G No 1660 C-> No 1664 C ->T Yes 1665 T-> No 1797 T-> No WO 2005/072053 PCT/IB2005/000928 991 1802 T-> No 1913 G -> A Yes 1985 T -> No 2168 A ->G Yes 2205 T -> C Yes 2466 A ->C No 2466 A -> G Yes 2535 T ->G Yes 2597 T No 2648 T ->C No 2720 A -> T No 2738 G -> A Yes 2782 C ->T Yes 2790 C-> No 2861 C ->T No 2931 T ->G No 3043 T ->G No 3103 T ->G No 3120 T ->G No 3125 T ->G No 3500 A ->C Yes 3566 A ->G Yes 5060 G ->A Yes 5156 -> T No 5533 G ->C No 5789 G ->A Yes 5866 T ->C Yes 6591 C->T Yes 6619 G ->A Yes 6905 A -> T Yes WO 2005/072053 PCT/IB2005/000928 992 6922 G ->C Yes 7046 C->G Yes 7319 A ->G Yes 7706 C ->T Yes 7894 G ->A Yes 8099 C ->G Yes 8324 T ->C No 8555 T->C Yes 8627 G -> T Yes 8644 T-> C Yes 8704 T -> C No 8781 C ->T Yes 8787 C ->T Yes 8827 C ->T No 8847 T-C No 8847 T ->G No 8909 G ->A No 8947 G ->A Yes 8960 T -> C Yes 9096 T ->C No 9096 T ->G No 9207 A -> G No 9424 T -> C Yes 9516 A -> No 9596 C -> T Yes Variant protein M77903_PS according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T12. An 5 alignment is given to the known protein (Translocon-associated protein, alpha subunit WO 2005/072053 PCT/IB2005/000928 993 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between M77903_P5 and SSRAHUMAN: 1.An isolated chimeric polypeptide encoding for M77903_P5, comprising a first amino acid sequence being at least 90 % homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDE PTDLVEDKEEEDVSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLD 10 ASFRYPQDYQFYIQNFTALPLNTVVPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLN GNVFQDAVFNQTVTVIEREDGLDGET corresponding to amino acids 1 - 207 of SSRA-HUMAN, which also corresponds to amino acids 1 - 207 of M77903_PS. The location of the variant protein was determined according to results from a number of 15 different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. 20 Variant protein M77903_P5 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 10, (given according to their position(s) on the amino acid sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein M77903_P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). 25 Table 10 - Amino acid mutations SNP position(s) on amino acid Alternative amino acid(s) Previously known SNP? sequence 6 R -> G No 24 G -> No 28 L -> S Yes WO 2005/072053 PCT/IB2005/000928 994 48 E ->G No 54 A ->T Yes 58 E ->K No 63 D-> No 89 F-> No 116 I->M No 130 Y ->H No 130 Y ->N No 178 K-> No The glycosylation sites of variant protein M77903_P5, as compared to the known protein Translocon-associated protein, alpha subunit precursor, are described in Table 11 (given according to their position(s) on the amino acid sequence in the first column; the second column 5 indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). Table 11 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Posi tion in variant protein? acid sequence 191 Yes 191 136 Yes 136 Variant protein M77903_P5 is encoded by the following transcript(s): M77903_T12, for 10 which the sequence(s) is/are given at the end of the application. The coding portion of transcript M77903_T12 is shown in bold; this coding portion starts at position 200 and ends at position 820. The transcript also has the following SNPs as listed in Table 12 (given according to their position on the nucleotide sequence, with the alternative nucleic acid listed; the last column indicates whether the SNP is known or not; the presence of known SNPs in variant protein 15 M77903P5 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 12 - Nucleic acid SNPs WO 2005/072053 PCT/IB2005/000928 995 SNP position on nucleotide Alternative nucleic acid Previously known SNP? sequence 72 G ->T Yes 120 C ->G No 147 G ->C Yes 215 C ->G No 271 C-> No 282 T ->C Yes 342 A ->G No 359 G ->A Yes 371 G ->A No 388 T -No 464 T-> No 547 T->C No 547 T ->G No 587 T ->A No 587 T ->C No 731 A-> No 833 A-> No 1023 T-> No 1024 G-> No 1202 T ->A Yes 1230 T-> No 1232 T -> No 1314 T ->G No 1356 T ->G No 1566 C-> No 1570 C ->T Yes 1571 T-> No 1703 T-> No WO 2005/072053 PCT/IB2005/000928 996 1708 T No 1819 G ->A Yes 1891 T No 2074 A -> G Yes 2111 T ->C Yes 2372 A ->C No 2372 A ->G Yes 2441 T ->G Yes 2503 T -> No 2554 T ->C No 2626 A ->T No 2644 G -> A Yes 2688 C ->T Yes 2696 C-> No 2767 C ->T No 2837 T ->G No 2949 T ->G No 3009 T ->G No 3026 T ->G No 3031 T ->G No 3406 A -> C Yes 3472 A ->G Yes 4966 G ->A Yes 5062 -> T No 5439 G -> C No 5695 G ->A Yes 5772 T -> C Yes 6497 C -> T Yes 6525 G -> A Yes 6811 A ->T Yes WO 2005/072053 PCT/IB2005/000928 997 6828 G ->C Yes 6952 C ->G Yes 7225 A -> G Yes 7612 C ->T Yes 7800 G ->A Yes 8005 C -> G Yes 8230 T -C No 8461 T ->C Yes 8533 G ->T Yes 8550 T ->C Yes 8610 T ->C No 8687 C ->T Yes 8693 C -> T Yes 8733 C ->T No 8753 T ->C No 8753 T ->G No 8815 G ->A No 8853 G ->A Yes 8866 T ->C Yes 9002 T ->C No 9002 T ->G No 9113 A ->G No 9330 T ->C Yes 9422 A-> No 9502 C -> T Yes Variant protein M77903_P15 according to the present invention has an amino acid sequence as given at the end of the application; it is encoded by transcript(s) M77903_T34. An 5 alignment is given to the known protein (Translocon-associated protein, alpha subunit WO 2005/072053 PCT/IB2005/000928 998 precursor) at the end of the application. One or more alignments to one or more previously published protein sequences are given at the end of the application. A brief description of the relationship of the variant protein according to the present invention to each such aligned protein is as follows: 5 Comparison report between M77903_P15 and SSRAHUMAN: 1.An isolated chimeric polypeptide encoding for M77903_P15, comprising a first amino acid sequence being at least 90 % homologous to MRLLPRLLLLLLLVFPATVLFRGGPRGLLAVAQDLTEDEETVEDSIIEDEDDEAEVEEDE PTDLVEDKEEEDVSGEPEASPSADTTILFVKGEDFPANNIVKFLVGFTNKGTEDFIVESLD 10 ASFRYPQDYQFYIQNFTALPLNTVVPPQRQATFEYSFIPAEPMGGRPFGLVINLNYKDLN corresponding to amino acids 1 - 181 of SSRAHUMAN, which also corresponds to amino acids 1 - 181 of M77903_P15, and a second amino acid sequence being at least 70%, optionally at least 80%, preferably at least 85%, more preferably at least 90% and most preferably at least 95% homologous to a polypeptide having the sequence VRSSKPSFCLS corresponding to 15 amino acids 182 - 192 of M77903_P15, wherein said first amino acid sequence and second amino acid sequence are contiguous and in a sequential order. 2.An isolated polypeptide encoding for a tail of M77903P15, comprising a polypeptide being at least 70%, optionally at least about 80%, preferably at least about 85%, more preferably at least about 90% and most preferably at least about 95% homologous to the sequence 20 VRSSKPSFCLS in M77903_P15. The location of the variant protein was determined according to results from a number of different software programs and analyses, including analyses from SignalP and other specialized programs. The variant protein is believed to be located as follows with regard to the cell: 25 secreted. The protein localization is believed to be secreted because both signal-peptide prediction programs predict that this protein has a signal peptide, and neither trans-membrane region prediction program predicts that this protein has a trans-membrane region. Variant protein M77903_P15 also has the following non-silent SNPs (Single Nucleotide Polymorphisms) as listed in Table 13, (given according to their position(s) on the amino acid 30 sequence, with the alternative amino acid(s) listed; the last column indicates whether the SNP is WO 2005/072053 PCT/IB2005/000928 999 known or not; the presence of known SNPs in variant protein M77903_P15 sequence provides support for the deduced sequence of this variant protein according to the present invention). Table 13 - Amino acid mutations SNP positions) on amino acid Alternative amino acid(s) ePrviously known SNP? sequence 6 R ->G No 24 G No 28 L ->S Yes 48 E ->G No 54 A ->T Yes 58 E ->K No 63 D-> No 89 F-> No 116 I ->M No 130 Y ->H No 130 Y ->N No 178 K-> No 5 The glycosylation sites of variant protein M77903_P15, as compared to the known protein Translocon-associated protein, alpha subunit precursor, are described in Table 14 (given according to their position(s) on the amino acid sequence in the first colunm; the second column indicates whether the glycosylation site is present in the variant protein; and the last column indicates whether the position is different on the variant protein). 10 Table 14 - Glycosylation site(s) Position(s) on known amino Present in variant protein? Position in variant protein? acid sequence 191 No 136 Yes 136

Claims

1. An isolated polynucleotide comprising a polynucleotide having a sequence of R11723_PEA_1_T5.

2. The isolated polynucleotide of claim 1, comprising a node having a sequence of: R11723_PEA_1_node_13.

3. An isolated polypeptide comprising a polypeptide having a sequence of: R11723_PEA_1_P13.

4. The isolated of claim 3, comprising a chimeric polypeptide encoding for RI 1723_PEA_1_P13, comprising a first amino acid sequence being at least 95 % homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1 - 63 of Q96AC2, which also corresponds to amino acids 1 - 63 of RI 1723_PEA_1_P13, and a second amino acid sequence being at least about 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT corresponding to amino acids 64 - 84 of R1 1723_PEA_1_P13, wherein said first and second amino acid sequences are contiguous and in a sequential order. 4. The isolated polypeptide of claim 4, comprising a tail of RI 1723_PEA_1_P13, comprising a polypeptide being at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT in RI 1723_PEA_1_P13.

5. The isolated oligonucleotide of claim 1, comprising an amplicon according to SEQ ID NO: 1297.

6. A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of claim 5. WO 2005/072053 PCT/IB2005/000928 1842

7. The primer pair of claim 6, comprising a pair of isolated oligonucleotides: SEQ NOs 1295 and 1296.

8. An antibody capable of specifically binding to an epitope of an amino acid sequence of claim 3.

9. The antibody of claim 8, wherein said amino acid sequence comprises said tail of claim 4.

10. The antibody of claim 8, wherein said antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein PSEC.

11. A kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant according to claim 1.

12. The kit of claim 11, wherein said kit comprises a NAT-based technology.

13. The kit of claim 11, wherein said kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence according to claim 1.

14. The kit of claim 11, wherein said kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence according to claim 1. 12. A kit for detecting colon cancer, comprising a kit detecting overexpression of a splice variant according to claim 3, said kit comprising an antibody according to claim 8. 13. The kit of claim 12, wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot. WO 2005/072053 PCT/IB2005/000928 1843 14. A method for detecting colon cancer, comprising detecting overexpression of a splice variant according to claim 1.

15. The method of claim 14, wherein said detecting overexpression is performed with a NAT-based technology.

16. A method for detecting colon cancer, comprising detecting overexpression of a splice variant according to claim 3, wherein said detecting overexpression is performed with an immunoassay.

17. The method of claim 16, wherein said immunoassay comprises an antibody according to claim 8.

18. A biomarker capable of detecting colon cancer, comprising a nucleic acid sequence according to claim 1 or a fragment thereof, or an amino acid sequence according to claim 3 or a fragment thereof.

19. A method for screening for colon cancer, comprising detecting colon cancer cells with a biomarker according to claim 18.

20. A method for diagnosing colon cancer, comprising detecting colon cancer cells with a biomarker according to claim 18.

21. A method for monitoring disease progression and/or treatment efficacy and/or relapse of colon cancer, comprising detecting colon cancer cells with a biomarker according to claim 18.

22. A method of selecting a therapy for colon cancer, comprising detecting colon cancer cells with a biomarker according to claim 18 and selecting a therapy according to said detection.