EP1263949A2

EP1263949A2 - Secretory polypeptides and corresponding polynucleotides

Info

Publication number: EP1263949A2
Application number: EP01908799A
Authority: EP
Inventors: Scott Panzer; Peter A. Spiro; Steven C. Banville; Purvi Shah; Michael S. Chalup; Simon C. Chang; Alice Chen; Steven A. D'sa; Stefan R. Amshey; Christopher R. Dahl; Tam C. Dam; Susan E. Daniels; Gerard E. Dufour; Vincent Flores; Willy T. Fong; Lila B. Greenawalt; Jennifer L. Hillman; Anissa L. Jones; Tommy F. Liu; Ann M. Roseberry
Original assignee: Incyte Genomics Inc
Current assignee: Incyte Corp
Priority date: 2000-02-24
Filing date: 2001-02-01
Publication date: 2002-12-11
Also published as: AU2001236631A1; WO2001062918A2; CA2418496A1; WO2001062918A3

Abstract

The present invention provides purified secretory polynucleotides (sptm). Also encompassed are the polypeptides (SPTM) encoded by sptm. The invention also provides for the use of sptm, or complements, oligonucleotides, or fragments thereof in diagnostic assays. The invention further provides for vectors and host cells containing sptm for the expression of SPTM. The invention additionally provides for the use of isolated and purified SPTM to induce antibodies and to screen libraries of compounds and the use of anti-SPTM antibodies in diagnostic assays. Also provided are microarrays containing sptm and methods of use.

Description

SECRETORY MOLECULES

TECHNICAL FIELD

The present invention relates to secretory molecules and to the use of these sequences in the 5 diagnosis, study, prevention, and treatment of diseases associated with, as well as effects of exogenous compounds on, cell signaling and the expression of secretory molecules.

BACKGROUND OF THE INVENTION

Protein transport and secretion are essential for cellular function. Protein transport is mediated0 by a signal peptide located at the amino terminus of the protein to he transported or secreted. The signal peptide is comprised of about ten to twenty hydrophobic amino acids which target the nascent protein from the ribosome to a particular membrane bound compartment such as the endoplasmic reticulum (ER). Proteins targeted to the ER may either proceed through the secretory pathway or remain in any of the secretory organelles such as the ER, Golgi apparatus, or lysosomes. Proteins that 5 transit through the secretory pathway are either secreted into the extracellular space or retained in the plasma membrane. Proteins that are retained in the plasma membrane contain one or more transmembrane domains, each comprised of about 20 hydrophobic amino acid residues. Proteins that are secreted from the cell are generally synthesized as inactive precursors that are activated by post- translational processing events during transit through the secretory pathway. Such events include o glycosylation, proteolysis, and removal of the signal peptide by a signal peptidase. Other events that may occur during protein transport include chaperone-dependent unfolding and folding of the nascent protein and interaction of the protein with a receptor or pore complex. Examples of secretory proteins with amino terminal signal peptides are discussed below and include proteins with important roles in cell-to-cell signaling. Such proteins include transmembrane receptors and cell surface markers, 5 extracellular matrix molecules, cytokines, hormones, growth and differentiation factors, neuropeptides, vasomediators, ion channels, transporters/pumps, and proteases. (Reviewed in Alberts, B. et al. (1994) Molecular Biology of The Cell, Garland Publishing, New York NY, pp. 557-560, 582-592.)

G-protein coupled receptors (GPCRs) comprise a superfamily of integral membrane proteins which transduce extracellular signals. Not all GPCRs contain N-terminal signal peptides. GPCRs o include receptors for biogenic amines such as dopamine, epinephrine, histamine, gl tamate

(metabotropic-type), acetylcholine (muscarinic-type), and serotonin; for lipid mediators of inflammation such as prostaglandins, platelet activating factor, and leukotrienes; for peptide hormones such as calcitonin, C5a anaphylatoxin, follicle stimulating hormone, gonadotropin releasing hormone, neurokinin, oxytocin, and thrombin; and for sensory signal mediators such as retinal photopigments and 5 olfactory stimulatory molecules. The stracture of these highly conserved receptors consists of seven hydrophobic transmembrane regions, cysteine disulfide bridges between the second and third extracellular loops, an extracellular N-terminus, and a cytoplasmic C-terminus. The N-terminus interacts with ligands, the disulfide bridges interact with agonists and antagonists, and the large third intracellular loop interacts with G proteins to activate second messengers such as cyclic AMP, phospholipase C, inositol triphosphate, or ion channels. (Reviewed in Watson, S. and Arkinstall, S. (1994) The G-protein Linked Receptor Facts Book. Academic Press, San Diego CA, pp. 2-6; and Bolander, F.F. (1994) Molecular Endocrinology. Academic Press, San Diego CA, pp. 162-176.) Other types of receptors include cell surface antigens identified on leukocytic cells of the immune system. These antigens have been identified using systematic, monoclonal antibody ( Ab)- based "shot gun" techniques. These techniques have resulted in the production of hundreds of mAbs directed against unknown cell surface leukocytic antigens. These antigens have been grouped into "clusters of differentiation" based on common immunocytochemical localization patterns in various differentiated and undifferentiated leukocytic cell types. Antigens in a given cluster are presumed to* identify a single cell surface protem and are assigned a "cluster of differentiation" or "CD" designation. Some of the genes encoding proteins identified by CD antigens have been cloned and verified by standard molecular biology techniques. CD antigens have been characterized as both transmembrane proteins and cell surface protems anchored to the plasma membrane via covalent attachment to fatty acid-containing glycolipids such as glycosylphosphatidylinositol (GPI). (Reviewed in Barclay, A.N. et al. (1995) The Leucocyte Antigen Facts Book. Academic Press, San Diego CA, pp; 17-20.)

Matrix proteins (MPs) are transmembrane and extracellular proteins which function in formation, growth, remodeling, and maintenance of tissues and as important mediators and regulators of the inflammatory response. The expression and balance of MPs may be perturbed by biochemical changes that result from congenital, epigenetic, or infectious diseases. In addition, MPs affect leukocyte migration, proliferation, differentiation, and activation in the immune response. MPs are frequently characterized by the presence of one or more domains which may include collagen-like domains, EGF-like domains, immunoglobulin-like domains, and fibronectin-like domains. In addition, MPs may be heavily glycosylated and may contain an Arginine-Glycine- Aspartate (RGD) tripeptide motif which may play a role in adhesive interactions. MPs include extracellular proteins such as fibronectin, collagen, galectin, vitronectin and its proteolytic derivative somatome in B; and cell adhesion receptors such as cell adhesion molecules (CAMs), cadherins, and integrins. (Reviewed in Ayad, S. et al. (1994) The Extracellular Matrix Facts Book. Academic Press, San Diego CA, pp. 2-16; Ruoslahti, E. (1997) Kidney Int. 51:1413-1417; Sjaastad, M.D. and Nelson, W.J. (1997) BioEssays 19:47-55.) Cytokines are secreted by hematopoietic cells in response to injury or infection. Interleukins, neurotropbins, growth factors, interferons, and chemokines all define cytokine families that work in conjunction with cellular receptors to regulate cell proliferation and differentiation. In addition, cytokines effect activities such as leukocyte migration and function, hematopoietic cell proliferation, temperature regulation, acute response to infection, tissue remodeling, and apoptosis. 5 Chemokines, in particular, are small chemoattractant cytokines involved in inflammation, leukocyte proliferation and migration, angiogenesis and angiostasis, regulation of hematopoiesis, HIV infectivity, and stimulation of cytokine secretion. Chemokines generally contain 70-100 amino acids and are subdivided into four subfamilies based on the presence of conserved cysteine-based motifs. (Callard, R. and Gearing, A. (1994) The Cytokine Facts Book. Academic Press, New York NY, pp.0 181-190, 210-213, 223-227.)

Growth and differentiation factors are secreted proteins which function in intercellular communication. Some factors require oligomerization or association with MPs for activity. Complex interactions among these factors and their receptors trigger intracellular signal transduction pathways that stimulate or inhibit cell division, cell differentiation, cell signaling, and cell motility. Most growth 5 and differentiation factors act on cells in their local environment (paracrine signaling). There are three broad classes of growth and differentiation factors. The first class includes the large polypeptide growth factors such as epidermal growth factor, fibroblast growth factor, transforming growth factor, insulin-like growth factor, and platelet-derived growth factor. The second class includes the hematopoietic growth factors such as the colony stimulating factors (CSFs). Hematopoietic growth o factors stimulate the proliferation and differentiation of blood cells such as B-lymphocytes, T- lymphocytes, erythrocytes, platelets, eosinophils, basophils, neutrophils, macrophages, and their stem cell precursors. The third class includes small peptide factors such as bombesin, vasopressin, oxytocin, endothelin, transferrin, angiotensin II, vasoactive intestinal peptide, and bradykinin which function as hormones to regulate cellular functions other than proliferation. 5 Growth and differentiation factors play critical roles in neoplastic transformation of cells in vitro and in tumor progression in vivo. Inappropriate expression of growth factors by tumor cells may contribute to vascularization and metastasis of tumors. During hematopoiesis, growth factor misregulation can result in anemias, leukemias, and lymphomas. Certain growth factors such as interferon are cytotoxic to tumor cells both in vivo and in vitro. Moreover, some growth factors and o growth factor receptors are related both structurally and functionally to oncoproteins. In addition, growth factors affect transcriptional regulation of both proto-oncogenes and oncosuppressor genes. (Reviewed in Pimentel, E. (1994) Handbook of Growth Factors. CRC Press, Ann Arbor MI, pp. 1-9.) Proteolytic enzymes or proteases either activate or deactivate proteins by hydrolyzing peptide bonds. Proteases are found in the cytosol, in membrane-bound compartments, and in the extracellular 5 space. The major families are the zinc, serine, cysteine, thiol, and carboxyl proteases. Ion channels, ion pumps, and transport proteins mediate the transport of molecules across cellular membranes. Transport can occur by a passive, concentration-dependent mechanism or can be linked to an energy source such as ATP hydrolysis. Symporters and antiporters transport ions and small molecules such as amino acids, glucose, and drugs. Symporters transport molecules and ions 5 unidirectionally, and antiporters transport molecules and ions bidirectionally. Transporter superfamilies include facultative transporters and active ATP-binding cassette transporters which are involved in multiple-drug resistance and the targeting of antigenic peptides to MHC Class I molecules. These transporters bind to a specific ion or other molecule and undergo a conformational change in order to transfer the ion or molecule across the membrane. (Reviewed in Alberts, B. et al. (1994) o Molecular Biology of The Cell. Garland Publishing, New York NY, pp. 523-546.)

Ion channels are formed by transmembrane proteins which create a lined passageway across the membrane through which water and ions, such as Na\ K⁺, Ca²⁺, and CI^", enter and exit the cell. For example, chloride channels are involved in the regulation of the membrane electric potential as well as absorption and secretion of ions across the membrane. Chloride channels also regulate the internal pH5 of membrane-bound organelles.

Ion pumps are ATPases which actively maintain membrane gradients. Ion pumps are classified as P, V, or F according to their structure and function. All have one or more binding sites for ATP in their cytosolic domains. The P-class ion pumps include Ca²⁺ ATPase and Na⁺/K⁺ ATPase and function in transporting H⁺, Na⁺, K⁺, and Ca²⁺ ions. P-class pumps consist of two α and two β transmembrane o subunits. The V- and F-class ion pumps have similar structures but transport only H⁺. F class H⁺ pumps mediate transport across the membranes of mitochondria and chloroplasts, while V-class H⁺ pumps regulate acidity inside lysosomes, endosomes, and plant vacuoles.

A family of structurally related intrinsic membrane proteins known as facilitative glucose transporters catalyze the movement of glucose and other selected sugars across the plasma membrane. 5 The proteins in this family contain a highly conserved, large transmembrane domain comprised of 12 α-helices, and several weakly conserved, cytoplasmic and exoplasmic domains. (Pessin, J.E. and Bell, G.I. (1992) Annu. Rev. Physiol. 54:911-930.)

Amino acid transport is mediated by Na⁺ dependent amino acid transporters. These transporters are involved in gastrointestinal and renal uptake of dietary and cellular amino acids and in o neuronal reuptake of neurotransmitters. Transport of cationic amino acids is mediated by the system y-t- family and the cationic amino acid transporter (CAT) family. Members of the CAT family share a high degree of sequence homology, and each contains 12-14 putative transmembrane domains. (Ito, K. and Groudine, M. (1997) J. Biol. Chem. 272:26780-26786.)

Hormones are secreted molecules that travel through the circulation and bind to specific 5 receptors on the surface of, or within, target cells. Although they have diverse biochemical compositions and mechanisms of action, hormones can be grouped into two categories. One category includes small lipophilic hormones that diffuse through the plasma membrane of target cells, bind to cytosolic or nuclear receptors, and form a complex that alters gene expression. Examples of these molecules include retinoic acid, thyroxine, and the cholesterol-derived steroid hormones such as progesterone, estrogen, testosterone, cortisol, and aldosterone. The second category includes hydrophilic hormones that function by binding to cell surface receptors that transduce signals across the plasma membrane. Examples of such hormones include amino acid derivatives such as catecholamines and peptide hormones such as glucagon, insulin, gastrin, secretin, cholecystokinin, adrenocorticotropic hormone, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, and vasopressin. (See, for example, Lodish et al. (1995) Molecular Cell Biology, Scientific American Books Inc., New York NY, pp. 856-864.)

Neuropeptides and vasomediators (NP/VM) comprise a large family of endogenous signaling molecules. Included in this family are neuropeptides and neuropeptide hormones such as bombesin, neuropeptide Y, neurotensin, neuromedinN, melanocortins, opioids, galanin, somatostatin, tachykinins, urotensin II and related peptides involved in smooth muscle stimulation, vasopressin, vasoactive intestinal peptide, and circulatory system-borne signaling molecules such as angiotensin, complement, calcitonin, endothelins, formyl-methionyl peptides, glucagon, cholecystokinin and gastrin. NP/VMs can transduce signals directly, modulate the activity or release of other neurotransmitters and hormones, and act as catalytic enzymes in cascades. The effects of NP/VMs range from extremely brief to long- lasting. (Reviewed in Martin, CR. et al. (1985) Endocrine Physiology, Oxford University Press, New York, NY, pp. 57-62.)

The discovery of new secretory molecules satisfies a need in the art by providing new compositions which are useful in the diagnosis, study, prevention, and treatment of diseases associated with, as well as effects of exogenous compounds on, cell signaling and the expression of secretory molecules.

SUMMARY OF THE INVENTION

The present invention relates to nucleic acid sequences comprising human polynucleotides encoding secretory polypeptides that contain signal peptides and/or transmembrane domains. These human polynucleotides (sptm) as presented in the Sequence Listing uniquely identify partial or full length genes encoding structural, functional, and regulatory polypeptides involved in cell signaling.

The invention provides an isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 -79 ; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). In one alternative, the polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79. In another alternative, the polynucleotide comprises at least 60 contiguous nucleotides of a polynucleotide sequence selected 5 from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO:l-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The invention further provides a composition for the detection of o expression of secretory polynucleotides comprising at least one isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ . ID NO:l-79; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence 5 complementary to b); and e) an RNA equivalent of a) through d); and a detectable label.

The invention also provides a method for detecting a target polynucleotide in a sample, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence o selected from the group consisting of SEQ ID NO:l-79; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The method comprises a) amplifying said target polynucleotide or a fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof. 5 The invention also provides a method for detecting a target polynucleotide in a sample, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:l-79; c) a polynucleotide sequence complementary to 0 a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide, and b) detecting the presence or absence of 5 said hybridization complex, and, optionally, if present, the amount thereof. In one alternative, the probe comprises at least 30 contiguous nucleotides. In another alternative, the probe comprises at least 60 contiguous nucleotides.

The invention further provides a recombinant polynucleotide comprising a promoter sequence operably linked to an isolated polynucleotide comprising a polynucleotide sequence selected from the 5 group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 - 79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 -79 ; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). In one alternative, the invention provides a cell transformed with the0 recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide. In a further alternative, the invention provides a method for producing a secretory polypeptide, the method comprising a) culturing a cell under conditions suitable for expression of the secretory polypeptide, wherein said cell is transformed with the recombinant polynucleotide, and b) recovering the secretory polypeptide so expressed. 5 The invention also provides a purified secretory polypeptide (SPTM) encoded by at least one polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79. Additionally, the invention provides an isolated antibody which specifically binds to the secretory polypeptide. The invention further provides a method of identifying a test compound which specifically binds to the secretory polypeptide, the method comprising the steps of a) providing a test o compound; b) combining the secretory polypeptide with the test compound for a sufficient time and under suitable conditions for binding; and c) detecting binding of the secretory polypeptide to the test compound, thereby identifying the test compound which specifically binds the secretory polypeptide. The invention further provides a microarray wherein at least one element of the microarray is an isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide comprising5 a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence complementary to b); and e) an RNA equivalent of a) through d). The invention also provides a method o for generating a transcript image of a sample which contains polynucleotides. The method comprises a) labeling the polynucleotides of the sample, b) contacting the elements of the microarray with the labeled polynucleotides of the sample under conditions suitable for the formation of a hybridization complex, and c) quantifying the expression of the polynucleotides in the sample.

Additionally, the invention provides a method for screening a compound for effectiveness in 5 altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO:l-79; c) a polynucleotide sequence complementary to a); d) a polynucleotide sequence 5 complementary to b); and e) an RNA equivalent of a) through d). The method comprises a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound.

The invention further provides a method for assessing toxicity of a test compound, said method0 comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide comprising a polynucleotide sequence selected from the group consisting of i) a polynucleotide sequence selected from the group consisting of SEQ ID NO:l- 79; ii) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a 5 polynucleotide sequence selected from the group consisting of SEQ ID NO : 1 -79 ; iii) a polynucleotide sequence complementary to i), iv) a polynucleotide sequence complementary to ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence selected from the group consisting of i) a o polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; ii) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79; iii) a polynucleotide sequence complementary to i), iv) a polynucleotide sequence complementary to ii), and v) an RNA equivalent of i)-iv), and alternatively, the target polynucleotide comprises a fragment of a polynucleotide sequence5 selected from the group consisting of i-v above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.

DESCRIPTION OF THE TABLES o Table 1 shows the sequence identification numbers (SEQ ID NO:s) and template identification numbers (template IDs) corresponding to the polynucleotides of the present invention, along with polynucleotide segments of each template sequence as defined by the indicated "start" and "stop" nucleotide positions. The reading frames of the polynucleotide segments are shown, and the polypeptides encoded by the polynucleotide segments constitute either signal peptide (SP) or 5 transmembrane (TM) domains, as indicated. The membrane topology of the encoded polypeptide sequence is indicated, the N-terminus (N) fisted as being oriented to either the cytosolic (in) or non- cytosolic (out) side of the cell membrane or organelle.

Table 2 shows the sequence identification numbers (SEQ ID NO:s) corresponding to the polynucleotides of the present invention, along with component sequence identification numbers 5 (component IDs) corresponding to each template. The component sequences, which were used to assemble the template sequences, are defined by the indicated "start" and "stop" nucleotide positions along each template.

Table 3 shows the tissue distribution profiles for the templates of the invention.

Table 4 summarizes the bioinformatics tools which are useful for analysis of the o polynucleotides of the present invention. The first column of Table 4 lists analytical tools, programs, and algorithms, the second column provides brief descriptions thereof, the third column presents appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score, the greater the homology between5 two sequences).

DETAILED DESCRIPTION OF THE INVENTION

Before the nucleic acid sequences and methods are presented, it is to be understood that this invention is not limited to the particular machines, methods, and materials described. Although o particular embodiments are described, machines, methods, and materials similar or equivalent to these embodiments may be used to practice the invention. The preferred machines, methods, and materials set forth are not intended to limit the scope of the invention which is limited only by the appended claims.

The singular forms "a", "an", and "the" include plural reference unless the context clearly 5 dictates otherwise. All technical and scientific terms have the meanings commonly understood by one of ordinary skill in the art. All publications are incorporated by reference for the purpose of describing and disclosing the cell lines, vectors, and methodologies which are presented and which might be used in connection with the invention. Nothing in the specification is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. 0

Definitions

As used herein, the lower case "sptm" refers to a nucleic acid sequence, while the upper case "SPTM" refers to an amino acid sequence encoded by sptm. A "full-length" sptm refers to a nucleic acid sequence containing the entire coding region of a gene endogenously expressed in human tissue.5 "Adjuvants" are materials such as Freund's adjuvant, mineral gels (aluminum hydroxide), and surface active substances (lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanin, and dinitrophenol) which may be administered to increase a host's immunological response.

"Allele" refers to an alternative form of a nucleic acid sequence. Alleles result from a 5 "mutation," a change or an alternative reading of the genetic code. Any given gene may have none, one, or many allelic forms. Mutations which give rise to alleles include deletions, additions, or substitutions of nucleotides. Each of these changes may occur alone, or in combination with the others, one or more times in a given nucleic acid sequence. The present invention encompasses allelic sptm.

"Amino acid sequence" refers to a peptide, a polypeptide, or a protein of either natural or0 synthetic origin. The amino acid sequence is not limited to the complete, endogenous amino acid sequence and may be a fragment, epitope, variant, or derivative of a protein expressed by a nucleic acid sequence.

"Amplification" refers to the production of additional copies of a sequence and is carried out using polymerase chain reaction (PCR) technologies well known in the art. 5 "Antibody" refers to intact molecules as well as to fragments thereof, such as Fab, F(ab')₂» and

Fv fragments, which are capable of binding the epitopic determinant. Antibodies that bind SPTM polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or peptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and o can be conjugated to a carrier protein if desired. Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal.

"Antisense sequence" refers to a sequence capable of specifically hybridizing to a target sequence. The antisense sequence may include DNA, RNA, or any nucleic acid mimic or analog such5 as peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2'-methoxyethyl sugars or 2'-methoxyethoxy sugars; or oligonucleotides having modified bases such as 5-methyl cytosine, 2'-deoxyuracil, or 7-deaza-2'-deoxyguanosine.

"Antisense sequence" refers to a sequence capable of specifically hybridizing to a target o sequence. The antisense sequence can be DNA, RNA, or any nucleic acid mimic or analog.

"Antisense technology" refers to any technology which relies on the specific hybridization of an antisense sequence to a target sequence.

A "bin" is a portion of computer memory space used by a computer program for storage of data, and bounded in such a manner that data stored in a bin may be retrieved by the program. 5 "Biologically active" refers to an amino acid sequence having a structural, regulatory, or biochemical function of a naturally occurring amino acid sequence.

"Clone joining" is a process for combining gene bins based upon the bins' containing sequence information from the same clone. The sequences may assemble into a primary gene transcript as well as one or more splice variants. "Complementary" describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing (5'-A-G-T-3^T pairs with its complement 3'-T-C-A-5').

A "component sequence" is a nucleic acid sequence selected by a computer program such as PHRED and used to assemble a consensus or template sequence from one or more component sequences. A "consensus sequence" or "template sequence" is a nucleic acid sequence which has been assembled from overlapping sequences, using a computer program for fragment assembly such as the GEL VIEW fragment assembly system (Genetics Computer Group (GCG), Madison WI) or using a relational database management system (RDMS).

"Conservative amino acid substitutions" are those substitutions that, when made, least interfere with the properties of the original protein, i.e., the structure and especially the function of the protein is conserved and not significantly changed by such substitutions. The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative substitutions.

Original Residue Conservative Substitution

Ala Gly, Ser

Arg His, Lys

Asn Asp, Gin, His

Asp Asn, Glu Cys Ala, Ser

Gin Asn, Glu, His

Glu Asp, Gin, His

Gly Ala

His Asn, Arg, Gin, Glu He Leu, Val

Leu He, Val

Lys Arg, Gin, Glu

Met Leu, He

Phe His, Met, Leu, Trp, Tyr Ser Cys, Thr Thr Ser, Val Trp Phe, Tyr Tyr His, Phe, Trp Val fie, Leu, Thr Conservative substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain.

"Deletion" refers to a change in either a nucleic or amino acid sequence in which at least one 5 nucleotide or amino acid residue, respectively, is absent.

"Derivative" refers to the chemical modification of a nucleic acid sequence, such as by replacement of hydrogen by an alkyl, acyl, amino, hydroxyl, or other group.

The terms "element" and "array element" refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray. o "E-value" refers to the statistical probability that a match between two sequences occurred by chance.

A "fragment" is a unique portion of sptm or SPTM which is identical in sequence to but shorter in length than the parent sequence. A fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 10 to5 1000 contiguous amino acid residues or nucleotides. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 5, 100, 150, 250 or at least 500 contiguous amino acid residues or nucleotides in length. Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or o first 25 % or 50%) of a polypeptide as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing and the figures, may be encompassed by the present embodiments.

A fragment of sptm comprises a region of unique polynucleotide sequence that specifically identifies sptm, for example, as distinct from any other sequence in the same genome. A fragment of 5 sptm is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish sptm from related polynucleotide sequences. The precise length of a fragment of sptm and the region of sptm to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.

A fragment of SPTM is encoded by a fragment of sptm. A fragment of SPTM comprises a o region of unique amino acid sequence that specifically identifies SPTM. For example, a fragment of

SPTM is useful as an immunogenic peptide for the development of antibodies that specifically recognize SPTM. The precise length of a fragment of SPTM and the region of SPTM to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment. A "full length" nucleotide sequence is one containing at least a start site for translation to a protein sequence, followed by an open reading frame and a stop site, and encoding a "full length" polypeptide.

"Hit" refers to a sequence whose annotation will be used to describe a given template. Criteria 5 for selecting the top hit are as follows: if the template has one or more exact nucleic acid matches, the top hit is the exact match with highest percent identity. If the template has no exact matches but has significant protein hits, the top hit is the protein hit with the lowest E-value. If the template has no significant protein hits, but does have significant non-exact nucleotide hits, the top hit is the nucleotide hit with the lowest E-value. 0 "Homology" refers to sequence similarity either between a reference nucleic acid sequence and at least a fragment of an sptm or between a reference amino acid sequence and a fragment of an SPTM.

"Hybridization" refers to the process by which a strand of nucleotides anneals with a complementary strand through base pairing. Specific hybridization is an indication that two nucleic acid sequences share a high degree of identity. Specific hybridization complexes form under defined5 annealing conditions, and remain hybridized after the "washing" step. The defined hybridization conditions include the annealing conditions and the washing step(s), the latter of which is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid probes that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely o determinable and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency.

Generally, stringency of hybridization is expressed with reference to the temperature under which the wash step is carried out. Generally, such wash temperatures are selected to be about 5°C to 20°C lower than the thermal melting point (T for the specific sequence at a defined ionic strength and 5 pH. The T_m is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating T_m and conditions for nucleic acid hybridization is well known and can be found in Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual. 2^nd ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; specifically see volume 2, chapter 9. o High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68 °C in the presence of about 0.2 x SSC and about 0.1 % SDS, for 1 hour. Alternatively, temperatures of about 65°C, 60°C, or 55°C may be used. SSC concentration may be varied from about 0.2 to 2 x SSC, with SDS being present at about 0.1 %. Typically, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, denatured 5 salmon sperm DNA at about 100-200 μg/ml. Useful variations on these conditions will be readily apparent to those skilled in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their resultant proteins.

Other parameters, such as temperature, salt concentration, and detergent concentration may be 5 varied to achieve the desired stringency. Denaturants, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as RNA:DNA hybridizations. Appropriate hybridization conditions are routinely determinable by one of ordinary skill in the art.

"Immunogenic" describes the potential for a natural, recombinant, or synthetic peptide, epitope, polypeptide, or protein to induce antibody production in appropriate animals, cells, or cell lines. i o "Insertion" or "addition" refers to a change in either a nucleic or amino acid sequence in which at least one nucleotide or residue, respectively, is added to the sequence.

"Labeling" refers to the covalent or noncovalent joining of a polynucleotide, polypeptide, or antibody with a reporter molecule capable of producing a detectable or measurable signal.

"Microarray" is any arrangement of nucleic acids, amino acids, antibodies, etc., on a substrate. 15 The substrate may be a solid support such as beads, glass, paper, nitrocellulose, nylon, or an appropriate membrane.

"Linkers" are short stretches of nucleotide sequence which may be added to a vector or an sptm to create restriction endonuclease sites to facilitate cloning. "Polylinkers" are engineered to incorporate multiple restriction enzyme sites and to provide for the use of enzymes which leave 5' or 3' overhangs 20 (e.g., BamHI, EcoRI, and Hindlll) and those which provide blunt ends (e.g., EcoRV, SnaBI, and Stul).

"Naturally occurring" refers to an endogenous polynucleotide or polypeptide that may be isolated from viruses or prokaryotic or eukaryotic cells.

"Nucleic acid sequence" refers to the specific order of nucleotides joined by phosphodiester bonds in a linear, polymeric arrangement. Depending on the number of nucleotides, the nucleic acid

25 sequence can be considered an oligomer, oUgonucleotide, or polynucleotide. The nucleic acid can be

DNA, RNA, or any nucleic acid analog, such as PNA, may be of genomic or synthetic origin, may be either double-stranded or single-stranded, and can represent either the sense or antisense (complementary) strand.

"Oligomer" refers to a nucleic acid sequence of at least about 6 nucleotides and as many as

3 o about 60 nucleotides, preferably about 15 to 40 nucleotides, and most preferably between about 20 and

30 nucleotides, that may be used in hybridization or amplification technologies. Oligomers may be used as, e.g., primers for PCR, and are usually chemically synthesized.

"Operably linked" refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably 35 linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame.

"Peptide nucleic acid" (PNA) refers to a DNA mimic in which nucleotide bases are attached to a pseudopeptide backbone to increase stability. PNAs, also designated antigene agents, can prevent 5 gene expression by targeting complementary messenger RNA.

The phrases "percent identity" and "% identity", as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore o achieve a more meaningful comparison of the two sequences .

Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison WI). CLUSTAL V is described in Higgins, D.G.5 and Sharp, P.M. (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. (1992) CABIOS 8:189-191. For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4. The "weighted" residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the "percent similarity" between aligned polynucleotide sequence pairs. o Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, MD, and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis 5 programs including "blastn," that is used to determine alignment between a known polynucleotide sequence and other sequences on a variety of databases. Also available is a tool called "BLAST 2 Sequences" that is used for direct pairwise comparison of two nucleotide sequences. "BLAST 2 Sequences" can be accessed and used interactively at http://www.ncbi.nlm.nih.gov/gorf/bl2/. The "BLAST 2 Sequences" tool can be used for both blastn and blastp (discussed below). BLAST o programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the "BLAST 2 Sequences" tool Version 2.0.9 (May-07-1999) set at default parameters. Such default parameters may be, for example:

Matrix: BLOSUM62

Reward for match: 1 5 Penalty for mismatch: -2 Open Gap: 5 and Extension Gap: 2 penalties

Gap x drop-off: 50

Expect: 10

Word Size: 11 5 Filter: on

Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such o lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in figures or Sequence Listings, may be used to describe a length over which percentage identity may be measured.

Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in 5 nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.

The phrases "percent identity" and "% identity", as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment o methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the hydrophobicity and acidity of the substituted residue, thus preserving the structure (and therefore function) of the folded polypeptide.

Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment 5 program (described and referenced above). For pairwise alignments of polypeptide sequences using

CLUSTAL V, the default parameters are set as follows: Ktuple=l, gap penalty=3, window=5, and "diagonals saved"=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the "percent similarity" between aligned polypeptide sequence pairs. o Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences" tool Version 2.0.9 (May-07-1999) with blastp set at default parameters. Such default parameters may be, for example: Matrix: BLOSUM62

Open Gap: 11 and Extension Gap: 1 penalty 5 Gap x drop-off: 50 Expect: 10

Word Size: 3

Filter: on

Percent identity may be measured over the length of an entire defined polypeptide sequence, for 5 example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in figures or Sequence Listings, may be used to describe a i o length over which percentage identity may be measured.

"Post-translational modification" of an SPTM may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu and the SPTM. 15 "Probe" refers to sptm or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. "Primers" are short nucleic acids, usually DNA oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended 2 o along the target DNA strand by a DNA polymerase enzyme. Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR).

Probes and primers as used in the present invention typically comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 30, 40, 50, 60, 70, 80, 90, 100, or 25 at least 150 consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the figures and Sequence Listing, may be used.

Methods for preparing and using probes and primers are described in the references, for example Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2^nd ed., vol. 1-3, Cold 3 o Spring Harbor Press, Plainview NY; Ausubel et al., 1987, Current Protocols in Molecular Biology,

Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis et al., 1990, PCR Protocols, A Guide to Methods and Applications, Academic Press, San Diego CA. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge MA). Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection 5 programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas TX) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome- wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for Genome Research, o Cambridge MA) allows the user to input a "mispriming library," in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user's specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge5 UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing o primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.

"Purified" refers to molecules, either polynucleotides or polypeptides that are isolated or separated from their natural environment and are at least 60% free, preferably at least 75% free, and 5 most preferably at least 90% free from other compounds with which they are naturally associated.

A "recombinant nucleic acid" is a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence. This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques o such as those described in Sambrook, supra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a recombinant nucleic acid may include a nucleic acid sequence operably linked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell. Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal.

"Regulatory element" refers to a nucleic acid sequence from nontranslated regions of a gene, 5 and includes enhancers, promoters, introns, and 3' untranslated regions, which interact with host proteins to carry out or regulate transcription or translation.

"Reporter" molecules are chemical or biochemical moieties used for labeling a nucleic acid, an amino acid, or an antibody. They include radionuclides; enzymes; fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors; magnetic particles; and other moieties known in0 the art.

An "RNA equivalent," in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose. 5 "Sample" is used in its broadest sense. Samples may contain nucleic or amino acids, antibodies, or other materials, and may be derived from any source (e.g., bodily fluids including, but not limited to, saliva, blood, and urine; cbromosome(s), organelles, or membranes isolated from a cell; genomic DNA, RNA, or cDNA in solution or bound to a substrate; and cleared cells or tissues or blots or imprints from such cells or tissues). o "Specific binding" or "specifically binding" refers to the interaction between a protein or peptide and its agonist, antibody, antagonist, or other binding partner. The interaction is dependent upon the presence of a particular structure of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope "A," the presence of a polypeptide containing epitope A, or the presence of free unlabeled A, in a reaction 5 containing free labeled A and the antibody will reduce the amount of labeled A that binds to the antibody.

"Substitution" refers to the replacement of at least one nucleotide or amino acid by a different nucleotide or amino acid.

"Substrate" refers to any suitable rigid or semi-rigid support including, e.g., membranes, filters, o chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles or capillaries. The substrate can have a variety of surface forms, such as wells, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.

A "transcript image" refers to the collective pattern of gene expression by a particular tissue or cell type under given conditions at a given time. "Transformation" refers to a process by which exogenous DNA enters a recipient cell. Transformation may occur under natural or artificial conditions using various methods well known in the art. Transformation may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. The method is selected based on the host cell being 5 transformed.

"Transformants" include stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as cells which transiently express inserted DNA or RNA.

A "transgenic organism," as used herein, is any organism, including but not limited to animals l o and plants, in which one or more of the cells of the organism contains heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art. The nucleic acid is introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization,

15 but rather is directed to the introduction of a recombinant DNA molecule. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, and plants and animals. The isolated DNA of the present invention can be introduced into the host by methods known in the art, for example infection, transfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in

20 references such as Sambrook et al. (1989), supra.

A "variant" of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 25 % sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version 2.0.9 (May-07-1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 30%, at least

25 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or even at least 98% or greater sequence identity over a certain defined length. The variant may result in "conservative" amino acid changes which do not affect structural and/or chemical properties. A variant may be described as, for example, an "allelic" (as defined above), "splice," "species," or "polymorphic" variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser

3 o number of polynucleotides due to alternate splicing of ex ns during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotide sequences that vary from one species to another. The resulting polypeptides generally will have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between

35 individuals of a given species. Polymorphic variants also may encompass "single nucleotide polymorphisms" (SNPs) in which the polynucleotide sequence varies by one base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state.

In an alternative, variants of the polynucleotides of the present invention may be generated through recombinant methods. One possible method is a DNA shuffling technique such as MOLECULARBREEDING (Maxygen Inc., Santa Clara CA; described in U.S. Patent Number 5,837,458; Chang, C-C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians, F.C et al. (1999) Nat. Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-319) to alter or improve the biological properties of SPTM, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then subjected to selection or screening procedures that identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through "artificial" breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurring genes in a directed and controllable manner. A "variant" of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool Version 2.0.9 (May-07- 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98% or greater sequence identity over a certain defined length of one of the polypeptides.

THE INVENTION

In a particular embodiment, cDNA sequences derived from human tissues and cell fines were aligned based on nucleotide sequence identity and assembled into "consensus" or "template" sequences which are designated by the template identification numbers (template IDs) in column 2 of Table 1.

The sequence identification numbers (SEQ ID NO:s) corresponding to the template IDs are shown in column 1. Segments of the template sequences are defined by the "start" and "stop" nucleotide positions fisted in columns 3 and 4. These segments, when translated in the reading frames indicated in column 5, have similarity to signal peptide (SP) or transmembrane (TM) domain consensus sequences, as indicated in column . The invention incorporates the nucleic acid sequences of these templates as disclosed in the Sequence Listing and the use of these sequences in the diagnosis and treatment of disease states characterized by defects in cell signaling. The invention further utilizes these sequences in hybridization and amplification technologies, and in particular, in technologies which assess gene expression patterns 5 correlated with specific cells or tissues and their responses in vivo or in vitro to pharmaceutical agents, toxins, and other treatments. In this manner, the sequences of the present invention are used to develop a transcript image for a particular cell or tissue.

Derivation of Nucleic Acid Sequences l o cDNA was isolated from libraries constructed using RNA derived from normal and diseased human tissues and cell lines. The human tissues and cell lines used for cDNA library construction were selected from a broad range of sources to provide a diverse population of cDNAs representative of gene transcription throughout the human body. Descriptions of the human tissues and cell lines used for cDNA library construction are provided in the LIFESEQ database (Incyte Genomics, Inc. (Incyte), Palo is Alto CA). Human tissues were broadly selected from, for example, cardiovascular, dermatologic, endocrine, gastrointestinal, hematopoietic/immune system, musculoskeletal, neural, reproductive, and urologic sources.

Cell lines used for cDNA library construction were derived from, for example, leukemic cells, teratocarcinomas, neuroepitheliomas, cervical carcinoma, lung fibroblasts, and endothelial cells. Such

20 cell lines include, for example, THP-1, lurkat, HUVEC, hNT2, WI38, HeLa, and other cell fines commonly used and available from public depositories (American Type Culture Collection, Manassas VA). Prior to mRNA isolation, cell lines were untreated, treated with a pharmaceutical agent such as 5'-aza-2 -deoxycytidine, treated with an activating agent such as lipopolysaccharide in the case of leukocytic cell lines, or, in the case of endothelial cell lines, subjected to shear stress.

25

Sequencing of the cDNAs

Methods for DNA sequencing are well known in the art. Conventional enzymatic methods employ the Klenow fragment of DNA polymerase I, SEQUENASE DNA polymerase (U.S. Biochemical Corporation, Cleveland OH), Taq polymerase (Applied Biosystems, Foster City CA),

3 o thermostable T7 polymerase (Amersham Pharmacia Biotech, Inc. (Amersham Pharmacia Biotech),

Piscataway NJ), or combinations of polymer ases and proofreading exonucleases such as those found in fheELONGASE amplification system (Life Technologies Inc. (Life Technologies), Gaithersburg MD), to extend the nucleic acid sequence from an oligonucleotide primer annealed to the DNA template of interest. Methods have been developed for the use of both single-stranded and double-stranded

35 templates. Chain termination reaction products may be electrophoresed on urea-polyacrylamide gels and detected either by autoradiography (for radioisotope-labeled nucleotides) or by fluorescence (for fluorophore-labeled nucleotides). Automated methods for mechanized reaction preparation, sequencing, and analysis using fluorescence detection methods have been developed. Machines used to prepare cDNAs for sequencing can include the MICROLAB 2200 liquid transfer system (Hamilton Company 5 (Hamilton), Reno NV), Peltier thermal cycler (PTC200; MJ Research, Inc. (MJ Research), Watertown MA), and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing can be carried out using, for example, the ABI 373 or 377 (Applied Biosystems) or MEGABACE 1000 (Molecular Dynamics, Inc. (Molecular Dynamics), Sunnyvale CA) DNA sequencing systems, or other automated and manual sequencing systems well known in the art. i o The nucleotide sequences of the Sequence Listing have been prepared by current, state-of-the- art, automated methods and, as such, may contain occasional sequencing errors or unidentified nucleotides. Such unidentified nucleotides are designated by an N. These infrequent unidentified bases do not represent a hindrance to practicing the invention for those skilled in the art. Several methods employing standard recombinant techniques may be used to correct errors and complete the missing

15 sequence information. (See, e.g., those described in Ausubel, F.M. et al. (1997) Short Protocols in Molecular Biology, John Wiley & Sons, New York NY; and Sambrook, J. et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Plainview NY.)

Assembly of cDNA Sequences

2 o Human polynucleotide sequences may be assembled using programs or algorithms well known in the art. Sequences to be assembled are related, wholly or in part, and may be derived from a single or many different transcripts. Assembly of the sequences can be performed using such programs as PHRAP (Phils Revised Assembly Program) and the GELVIEW fragment assembly system (GCG), or other methods known in the art. 25 Alternatively, cDNA sequences are used as "component" sequences that are assembled into

"template" or "consensus" sequences as follows. Sequence chromatograms are processed, verified, and quality scores are obtained using PHRED. Raw sequences are edited using an editing pathway known as Block 1 (See, e.g., iheLIFESEQ Assembled User Guide, Incyte Genomics, Palo Alto, CA). A series of BLAST comparisons is performed and low-information segments and repetitive elements (e.g.,

3 o dinucleotide repeats, Alu repeats, etc.) are replaced by "n's", or masked, to prevent spurious matches.

Mitochondrial and ribosomal RNA sequences are also removed. The processed sequences are then loaded into a relational database management system (RDMS) which assigns edited sequences to existing templates, if available. When additional sequences are added into the RDMS, a process is initiated which modifies existing templates or creates new templates from works in progress (i.e., 35 nonfinal assembled sequences) containing queued sequences or the sequences themselves. After the new sequences have been assigned to templates, the templates can be merged into bins. If multiple templates exist in one bin, the bin can be split and the templates reannotated.

Once gene bins have been generated based upon sequence alignments, bins are "clone joined" based upon clone information. Clone joining occurs when the 5 ' sequence of one clone is present in one 5 bin and the 3' sequence from the same clone is present in a different bin, indicating that the two bins should be merged into a single bin. Only bins which share at least two different clones are merged.

A resultant template sequence may contain either a partial or a full length open reading frame, or all or part of a genetic regulatory element. This variation is due in part to the fact that the full length cDNAs of many genes are several hundred, and sometimes several thousand, bases in length. With o current technology, cDNAs comprising the coding regions of large genes cannot be cloned because of vector limitations, incomplete reverse transcription of the mRNA, or incomplete "second strand" synthesis. Template sequences may be extended to include additional contiguous sequences derived from the parent RNA transcript using a variety of methods known to those of skill in the art. Extension may thus be used to achieve the full length coding sequence of a gene. 5

Analysis of the cDNA Sequences

The cDNA sequences are analyzed using a variety of programs and algorithms which are well known in the art. (See, e.g., Ausubel, 1997, supra, Chapter 7.7; Meyers, R.A. (Ed.) (1995) Molecular Biology and Biotechnology. Wiley VCH, New York NY, pp. 856-853; and Table 4.) These analyses o comprise both reading frame determinations, e.g., based on triplet codon periodicity for particular organisms (Fickett, J.W. (1982) Nucleic Acids Res. 10:5303-5318); analyses of potential start and stop codons; and homology searches.

Computer programs known to those of skill in the art for performing computer-assisted searches for amino acid and nucleic acid sequence similarity, include, for example, Basic Local5 Alignment Search Tool (BLAST; Altschul, S.F. (1993) J. Mol. Evol. 36:290-300; Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410). BLAST is especially useful in determining exact matches and comparing two sequence fragments of arbitrary but equal lengths, whose alignment is locally maximal and for which the alignment score meets or exceeds a threshold or cutoff score set by the user (Karlin, S. et al. (1988) Proc. Natl. Acad. Sci. USA 85:841-845). Using an appropriate search tool (e.g., o BLAST or HMM), GenBank, SwissProt, BLOCKS, PFAM and other databases may be searched for sequences containing regions of homology to a query sptm or SPTM of the present invention.

Other approaches to the identification, assembly, storage, and display of nucleotide and polypeptide sequences are provided in "Relational Database for Storing Biomolecule Information," U.S.S.N. 08/947,845, filed October 9, 1997; "Project-Based Full-Length Biomolecular Sequence 5 Database," U.S.S.N. 08/811,758, filed March 6, 1997; and "Relational Database and System for Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807, filed March 4, 1998, all of which are incorporated by reference herein in their entirety.

Protein hierarchies can be assigned to the putative encoded polypeptide based on, e.g., motif, BLAST, or biological analysis. Methods for assigning these hierarchies are described, for example, in "Database System Employing Protein Function Hierarchies for Viewing Biomolecular Sequence Data," U.S.S.N. 08/812,290, filed March 6, 1997, incorporated herein by reference. Human Secretory Sequences

The sptm of the present invention may be used for a variety of diagnostic and therapeutic purposes. For example, an sptm may be used to diagnose a particular condition, disease, or disorder associated with cell signaling. Such conditions, diseases, and disorders include, but are not limited to, a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; an immune system disorder such as such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma; and a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases 5 of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorder of the central nervous system, cerebral palsy, a neuroskeletal disorder, an autonomic nervous system disorder, a cranial nerve disorder, a spinal cord disease, muscular dystrophy and other neuromuscular disorder, a peripheral nervous system disorder, dermatomyositis and polymyositis, inherited, metabolic, endocrine,0 and toxic myopathy, myasthenia gravis, periodic paralysis, a mental disorder including mood, anxiety, and schizophrenic disorder, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postherpetic neuralgia, and Tourette's disorder. The sptm can be used to detect the presence of, or to quantify the amount of, an sptm-related polynucleotide in a sample. This information is then compared to information obtained from appropriate5 reference samples, and a diagnosis is established. Alternatively, a polynucleotide complementary to a given sptm can inhibit or inactivate a therapeutically relevant gene related to the sptm.

Analysis of sptm Expression Patterns

The expression of sptm may be routinely assessed by hybridization-based methods to o determine, for example, the tissue-specificity, disease-specificity, or developmental stage-specificity of sptm expression. For example, the level of expression of sptm may be compared among different cell types or tissues, among diseased and normal cell types or tissues, among cell types or tissues at different developmental stages, or among cell types or tissues undergoing various treatments. This type of analysis is useful, for example, to assess the relative levels of sptm expression in fully or partially 5 differentiated cells or tissues, to determine if changes in sptm expression levels are correlated with the development or progression of specific disease states, and to assess the response of a cell or tissue to a specific therapy, for example, in pharmacological or toxicological studies. Methods for the analysis of sptm expression are based on hybridization and amplification technologies and include membrane-based procedures such as northern blot analysis, high-throughput procedures that utilize, for example, o microarrays, and PCR-based procedures.

Hybridization and Genetic Analysis

The sptm, their fragments, or complementary sequences, may be used to identify the presence of and/or to determine the degree of similarity between two (or more) nucleic acid sequences. The sptm 5 may be hybridized to naturally occurring or recombinant nucleic acid sequences under appropriately selected temperatures and salt concentrations. Hybridization with a probe based on the nucleic acid sequence of at least one of the sptm allows for the detection of nucleic acid sequences, including genomic sequences, which are identical or related to the sptm of the Sequence Listing. Probes may be selected from non-conserved or unique regions of at least one of the polynucleotides of SEQ ID NO:l- 5 79 and tested for their ability to identify or amplify the target nucleic acid sequence using standard protocols.

Polynucleotide sequences that are capable of hybridizing, in particular, to those shown in SEQ ID NO:l-79 and fragments thereof, can be identified using various conditions of stringency. (See, e.g., WaM, G.M. and S.L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A.R. (1987) Methods0 Enzymol. 152:507-511.) Hybridization conditions are discussed in "Definitions."

A probe for use in Southern or northern hybridization may be derived from a fragment of an sptm sequence, or its complement, that is up to several hundred nucleotides in length and is either single-stranded or double-stranded. Such probes may be hybridized in solution to biological materials such as plasmids, bacterial, yeast, or human artificial chromosomes, cleared or sectioned tissues, or to5 artificial substrates containing sptm. Microarrays are particularly suitable for identifying the presence of and detecting the level of expression for multiple genes of interest by examining gene expression correlated with, e.g., various stages of development, treatment with a drug or compound, or disease progression. An array analogous to a dot or slot blot may be used to arrange and link polynucleotides to the surface of a substrate using one or more of the following: mechanical (vacuum), chemical, o thermal, or UV bonding procedures. Such an array may contain any number of sptm and may be produced by hand or by using available devices, materials, and machines.

Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T.M. et al. (1995) U.S. Patent No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application W095/251116; Shalon, D. et al.5 (1995) PCT application WO95/35505; Heller, R.A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150- 2155; and Heller, MJ. et al. (1997) U.S. Patent No. 5,605,662.)

Probes may be labeled by either PCR or enzymatic techniques using a variety of commercially available reporter molecules. For example, commercial kits are available for radioactive and chemiluminescent labeling (Amersham Pharmacia Biotech) and for alkaline phosphatase labeling (Life o Technologies). Alternatively, sptm may be cloned into commercially available vectors for the production of RNA probes. Such probes may be transcribed in the presence of at least one labeled nucleotide (e.g., ³ P-ATP, Amersham Pharmacia Biotech).

Additionally the polynucleotides of SEQ ID NO: 1-79 or suitable fragments thereof can be used to isolate full length cDNA sequences utilizing hybridization and/or amplification procedures well 5 known in the art, e.g., cDNA fibrary screening, PCR amplification, etc. The molecular cloning of such full length cDNA sequences may employ the method of cDNA library screening with probes using the hybridization, stringency, washing, and probing strategies described above and in Ausubel, supra. Chapters 3, 5, and 6. These procedures may also be employed with genomic libraries to isolate genomic sequences of sptm in order to analyze, e.g., regulatory elements,

Genetic Mapping

Gene identification and mapping are important in the investigation and treatment of almost all conditions, diseases, and disorders. Cancer, cardiovascular disease, Alzheimer's disease, arthritis, diabetes, and mental illnesses are of particular interest. Each of these conditions is more complex than the single gene defects of sickle cell anemia or cystic fϊbrosis, with select groups of genes being predictive of predisposition for a particular condition, disease, or disorder. For example, cardiovascular disease may result from malfunctioning receptor molecules that fail to clear cholesterol from the bloodstream, and diabetes may result when a particular individual' s immune system is activated by an infection and attacks the insulin-producing cells of the pancreas. In some studies, Alzheimer's disease has been linked to a gene on chromosome 21 ; other studies predict a different gene and location. Mapping of disease genes is a complex and reiterative process and generally proceeds from genetic linkage analysis to physical mapping. As a condition is noted among members of a family, a genetic linkage map traces parts of chromosomes that are inherited in the same pattern as the condition. Statistics link the inheritance of particular conditions to particular regions of chromosomes, as defined by RFLP or other markers. (See, for example, Lander, E. S. and Botstein, D. (1986) Proc. Natl. Acad. Sci. USA 83:7353-7357.) Occasionally, genetic markers and their locations are known from previous studies. More often, however, the markers are simply stretches of DNA that differ among individuals. Examples of genetic linkage maps can be found in various scientific journals or at the Online Mendelian Inheritance in Man (OMIM) World Wide Web site.

In another embodiment of the invention, sptm sequences may be used to generate hybridization probes useful in chromosomal mapping of naturally occurring genomic sequences. Either coding or noncoding sequences of sptm may be used, and in some instances, noncoding sequences may be preferable over coding sequences. For example, conservation of an sptm coding sequence among members of a multi-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial PI constructions, or single chromosome cDN A libraries. (See, e.g., Harrington, J.J. et al. (1997) Nat. Genet. 15:345-355; Price, CM. (1993) Blood Rev. 7:127-134; andTrask, BJ. (1991) Trends Genet. 7:149-154.)

Fluorescent in situ hybridization (FISH) may be correlated with other physical chromosome 5 mapping techniques and genetic map data. (See, e.g., Meyers, supra, pp. 965-968.) Correlation between the location of sptm on a physical chromosomal map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA associated with that disorder. The sptm sequences may also be used to detect polymorphisms that are genetically linked to the inheritance of a particular condition, disease, or disorder. i o In situ hybridization of chromosomal preparations and genetic mapping techniques, such as linkage analysis using established chromosomal markers, may be used for extending existing genetic maps. Often the placement of a gene on the chromosome of another mammalian species, such as mouse, may reveal associated markers even if the number or arm of the corresponding human chromosome is not known. These new marker sequences can be mapped to human chromosomes and

15 may provide valuable information to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once a disease or syndrome has been crudely correlated by genetic linkage with a particular genomic region, e.g., ataxia-telangiectasia to 1 lq22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation. (See, e.g., Gatti, R.A. et al. (1988) Nature 336:577-580.) The nucleotide sequences of the subject invention may

2 o also be used to detect differences in chromosomal architecture due to translocation, inversion, etc. , among normal, carrier, or affected individuals.

Once a disease-associated gene is mapped to a chromosomal region, the gene must be cloned in order to identify mutations or other alterations (e.g., translocations or inversions) that may be correlated with disease. This process requires a physical map of the chromosomal region containing the disease-

25 gene of interest along with associated markers. A physical map is necessary for determining the nucleotide sequence of and order of marker genes on a particular chromosomal region. Physical mapping techniques are well known in the art and require the generation of overlapping sets of cloned DNA fragments from a particular organelle, chromosome, or genome. These clones are analyzed to reconstruct and catalog their order. Once the position of a marker is determined, the DNA from that

3 o region is obtained by consulting the catalog and selecting clones from that region. The gene of interest is located through positional cloning techniques using hybridization or similar methods.

Diagnostic Uses

The sptm of the present invention may be used to design probes useful in diagnostic assays. 35 Such assays, well known to those skilled in the art, may be used to detect or confirm conditions, disorders, or diseases associated with abnormal levels of sptm expression. Labeled probes developed from sptm sequences are added to a sample under hybridizing conditions of desired stringency. In some instances, sptm, or fragments or oligonucleotides derived from sptm, may be used as primers in amplification steps prior to hybridization. The amount of hybridization complex formed is quantified 5 and compared with standards for that cell or tissue. If sptm expression varies significantly from the standard, the assay indicates the presence of the condition, disorder, or disease. Qualitative or quantitative diagnostic methods may include northern, dot blot, or other membrane or dip-stick based technologies or multiple-sample format technologies such as PCR, enzyme-linked immunosorbent assay (ELISA)-like, pin, or chip-based assays. i o The probes described above may also be used to monitor the progress of conditions, disorders, or diseases associated with abnormal levels of sptm expression, or to evaluate the efficacy of a particular therapeutic treatment. The candidate probe may be identified from the sptm that are specific to a given human tissue and have not been observed in GenBank or other genome databases. Such a probe may be used in animal studies, preclinical tests, clinical trials, or in monitoring the treatment of

15 an individual patient. In a typical process, standard expression is established by methods well known in the art for use as a basis of comparison, samples from patients affected by the disorder or disease are combined with the probe to evaluate any deviation from the standard profile, and a therapeutic agent is administered and effects are monitored to generate a treatment profile. Efficacy is evaluated by determining whether the expression progresses toward or returns to the standard normal pattern.

2 o Treatment profiles may be generated over a period of several days or several months. Statistical methods well known to those skilled in the art may be use to determine the significance of such therapeutic agents.

The polynucleotides are also useful for identifying individuals from minute biological samples, for example, by matching the RFLP pattern of a sample's DNA to that of an individual's DNA. The

25 polynucleotides of the present invention can also be used to determine the actual base-by-base DNA sequence of selected portions of an individual's genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, an individual can be identified through a unique set of DNA sequences. Once a unique ID database is established for an individual, positive identification of that individual can be made from

3 o extremely small tissue samples.

In a particular aspect, oligonucleotide primers derived from the sptm of the invention may be used to detect single nucleotide polymorphisms (SNPs). SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not limited to, single-stranded conformation polymorphism (SSCP) and 35 fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from sptm are used to amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In fSCCP, the oligonucleotide primers are fluorescently labeled, which allows detection of the amplimers in high- throughput equipment such as DNA sequencing machines. Additionally, sequence database analysis methods, termed in silico SNP (isSNP), are capable of identifying polymorphisms by comparing the sequences of individual overlapping DNA fragments which assemble into a common consensus sequence. These computer-based methods filter out sequence variations due to laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San Diego CA).

DNA-based identification techniques are critical in forensic technology. DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc., can be amplified using, e.g., PCR, to identify individuals. (See, e.g., Erlich, H. (1992) PCR Technology, Freeman and Co. , New York, NY). Similarly, polynucleotides of the present invention can be used as polymorphic markers.

There is also a need for reagents capable of identifying the source of a particular tissue. Appropriate reagents can comprise, for example, DNA probes or primers prepared from the sequences of the present invention that are specific for particular tissues. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination.

The polynucleotides of the present invention can also be used as molecular weight markers on nucleic acid gels or Southern blots, as diagnostic probes for the presence of a specific mRNA in a particular cell type, in the creation of subtracted cDNA libraries which aid in the discovery of novel polynucleotides, in selection and synthesis of oligomers for attachment to an array or other support, and as an antigen to elicit an immune response. Disease Model Systems Using sptm

The polynucleotides encoding SPTM or their mammalian homologs may be "knocked out" in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Patent Number 5,175,383 and U.S. Patent Number 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphofransferase gene (neo; Capecchi, M.R. (1989) Science 244: 1288- 1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J.D. (1996) Clin. Invest. 97:1999-2002; Wagner, K.U. et al. (1997) Nucleic Acids Res. 25:4323-4330). 5 Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.

The polynucleotides encoding SPTM may also be manipulated in vitro in ES cells derived from o human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J.A. et al. (1998) Science 282:1145-1147).

The polynucleotides encoding SPTM of the invention can also be used to create "knockin"5 humanized animals (pigs) or transgenic animals (mice or rats) to model human disease. With knockin technology, a region of sptm is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal o inbred to overexpress sptm, resulting, e.g., in the secretion of SPTM in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).

Screening Assays

SPTM encoded by polynucleotides of the present invention may be used to screen for molecules 5 that bind to or are bound by the encoded polypeptides. The binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the bound molecule. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.

Preferably, the molecule is closely related to the natural ligand of the polypeptide, e.g. , a ligand0 or fragment thereof, a natural substrate, or a structural or functional mimetic. (See, Coligan et al., (1991) Current Protocols in Immunology 1(2): Chapter 5.) Similarly, the molecule can be closely related to the natural receptor to which the polypeptide binds, or to at least a fragment of the receptor, e.g., the active site. In either case, the molecule can be rationally designed using known techniques. Preferably, the screening for these molecules involves producing appropriate cells which express the 5 polypeptide, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide or cell membrane fractions which contain the expressed polypeptide are then contacted with a test compound and binding, stimulation, or inhibition of activity of either the polypeptide or the molecule is analyzed.

An assay may simply test binding of a candidate compound to the polypeptide, wherein binding 5 is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. Alternatively, the assay may assess binding in the presence of a labeled competitor.

Additionally, the assay can be carried out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libraries, or natural product mixtures. The assay may also simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide, measuring o polypeptide/molecule activity or binding, and comparing the polypeptide/molecule activity or binding to a standard.

Preferably, an ELISA assay using, e.g., a monoclonal or polyclonal antibody, can measure polypeptide level in a sample. The antibody can measure polypeptide level by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate. 5 All of the above assays can be used in a diagnostic or prognostic context. The molecules discovered using these assays can be used to treat disease or to bring about a particular result in a patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule. Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptide from suitably manipulated cells or tissues. 0

Transcript Imaging and Toxicological Testing

Another embodiment relates to the use of sptm to develop a transcript image of a tissue or cell type. A transcript image represents the global pattern of gene expression by a particular tissue or cell type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and 5 their relative abundance under given conditions and at a given time. (See Seilhamer et al.,

"Comparative Gene Transcript Analysis," U.S. Patent Number 5,840,484, expressly incorporated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, o wherein the polynucleotides of the present invention or their complements comprise a subset of a plurality of elements on a microarray. The resultant transcript image would provide a profile of gene activity pertaining to cell signaling.

Transcript images which profile sptm expression may be generated using transcripts isolated from tissues, cell lines, biopsies, or other biological samples. The transcript image may thus reflect sptm expression in vivo, as in the case of a tissue or biopsy sample, or in vitro, as in the case of a cell line.

Transcript images which profile sptm expression may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals, as well as toxicological testing of 5 industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints or toxicant signatures, which are indicative of mechanisms of action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog. 24:153- 159; Steiner, S. and Anderson, N. L. (2000) Toxicol. Lett. 112-113:467-71, expressly incorporated by reference herein). If a test compound has a signature similar to that of a compound with known i o toxicity, it is likely to share those toxic properties. These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome- wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization

15 procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National ^■ Institute of Environmental Health Sciences, released February 29, 2000, available at

20 http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.

In one embodiment, the toxicity of a test compound is assessed by treating a biological sample containing nucleic acids with the test compound. Nucleic acids that are expressed in the treated biological sample are hybridized with one or more probes specific to the polynucleotides of the

25 present invention, so that transcript levels corresponding to the polynucleotides of the present invention may be quantified. The transcript levels in the treated biological sample are compared with levels in an untreated biological sample. Differences in the transcript levels between the two samples are indicative of a toxic response caused by the test compound in the treated sample.

Another particular embodiment relates to the use of SPTM encoded by polynucleotides of the

3 o present invention to analyze the proteome of a tissue or cell type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individually to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a cell's proteome may thus be generated by separating and 35 analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an 5 agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally proportional to the level of the protein in the sample. The optical densities of equivalentiy positioned protein spots from different samples, for example, from biological samples either treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for0 example, standard methods employing chemical or enzymatic cleavage followed by mass spectrometry. The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification.

A proteomic profile may also be generated using antibodies specific for SPTM to quantify the5 levels of SPTM expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal. Biochem. 270:103-11; Mendoze, L. G. et al. (1999) Biotechniques 27:778-88). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino- o reactive fluorescent compound and detecting the amount of fluorescence bound at each array element.

Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the transcript level. There is a poor correlation between transcript and protein abundances for some proteins in some tissues (Anderson, N. L. and Seilhamer, J. (1997) Electrophoresis 18:533-537), so proteome toxicant signatures may be useful in the 5 analysis of compounds which do not significantly affect the transcript image, but which alter the proteomic profile. In addition, the analysis of transcripts in body fluids is difficult, due to rapid degradation of mRNA, so proteomic profiling may be more reliable and informative in such cases. In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins that are expressed in the treated biological o sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the corresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the SPTM encoded by polynucleotides of 5 the present invention. In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the SPTM encoded by polynucleotides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological 5 sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample.

Transcript images may be used to profile sptm expression in distinct tissue types. This process can be used to determine cell signaling activity in a particular tissue type relative to this activity in a i o different tissue type. Transcript images may be used to generate a profile of sptm expression characteristic of diseased tissue. Transcript images of tissues before and after treatment may be used for diagnostic purposes, to monitor the progression of disease, and to monitor the efficacy of drug treatments for diseases which affect cell signaling activity.

Transcript images of cell lines can be used to assess cell signaling activity and/or to identify

15 cell lines that lack or misregulate this activity. Such cell lines may then be treated with pharmaceutical agents, and a transcript image following treatment may indicate the efficacy of these agents in restoring desired levels of this activity. A similar approach may be used to assess the toxicity of pharmaceutical agents as reflected by undesirable changes in cell signaling activity. Candidate pharmaceutical agents may be evaluated by comparing their associated transcript images with those of pharmaceutical agents

20 of known effectiveness.

Antisense Molecules

The polynucleotides of the present invention are useful in antisense technology. Antisense technology or therapy relies on the modulation of expression of a target protein through the specific

25 binding of an antisense sequence to a target sequence encoding the target protein or directing its expression. (See, e.g., Agrawal, S., ed. (1996) Antisense Therapeutics, Humana Press Inc., Totawa NJ; Alama, A. et al. (1997) Pharmacol. Res. 36(3):171-178; Crooke, S.T. (1997) Adv. Pharmacol. 40:1-49; Sharma, H.W. and R. Narayanan (1995) Bioessays 17(12):1055-1063; andLavrosky, Y. et al. (1997) Biochem. Mol. Med. 62(l):ll-22.) An antisense sequence is a polynucleotide sequence

3 o capable of specifically hybridizing to at least a portion of the target sequence. Antisense sequences bind to cellular mRNA and/or genomic DNA, affecting translation and/or transcription. Antisense sequences can be DNA, RNA, or nucleic acid mimics and analogs. (See, e.g., Rossi, J.J. et al. (1991) Antisense Res. Dev. l(3):285-288; Lee, R. et al. (1998) Biochemistry 37(3):900-1010; Pardridge, W.M. et al. (1995) Proc. Natl. Acad. Sci. USA 92(12):5592-5596; and Nielsen, P. E. an Haaima, G. 35 (1997) Chem. Soc. Rev. 96:73-78.) Typically, the binding which results in modulation of expression occurs through hybridization or binding of complementary base pairs. Antisense sequences can also bind to DNA duplexes through specific interactions in the major groove of the double helix.

The polynucleotides of the present invention and fragments thereof can be used as antisense sequences to modify the expression of the polypeptide encoded by sptm. The antisense sequences can 5 be produced ex vivo, such as by using any of the ABI nucleic acid synthesizer series (Applied

Biosystems) or other automated systems known in the art. Antisense sequences can also be produced biologically, such as by transforming an appropriate host cell with an expression vector containing the sequence of interest. (See, e.g., Agrawal, supra.)

In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences l o into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J.E., et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K.J., et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as

15 refrovirus and adeno-associated virus vectors. (See, e.g., Miller, A.D. (1990) Blood 76:271; Ausubel, F.M. et al. (1995) Current Protocols in Molecular Biology, John Wiley & Sons, New York NY; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other systems known in the art. (See, e.g., Rossi, J.J. (1995) Br. Med. Bull. 51(l):217-225; Boado, R.J. et al. (1998) J. Pharm. Sci. 87(11):1308-

20 1315; and Morris, M.C et al. (1997) Nucleic Acids Res. 25(14):2730-2736.)

Expression

In order to express a biologically active SPTM, the nucleotide sequences encoding SPTM or fragments thereof may be inserted into an appropriate expression vector, i.e., a vector which contains

25 the necessary elements for transcriptional and translational. control of the inserted coding sequence in a suitable host. Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding SPTM and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, supra, Chapters 4, 8, 16, and 17;

30 and Ausubel, supra, Chapters 9, 10, 13, and 16.)

A variety of expression vector/host systems may be utilized to contain and express sequences encoding SPTM. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus);

35 plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal (mammalian) cell systems. (See, e.g., Sambrook, supra; Ausubel, 1995, supra, Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Bitter, G.A. et al. (1987) Methods Enzymol. 153:516-544; Scorer, CA. et al. (1994) Bio/Technology 12:181-184; Engelhard, E.K. et al. (1994) 5 Proc. Natl. Acad. Sci. USA 91 :3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945 ; Takamatsu, N. (1987) EMBO J. 6:307-311; Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105; The McGraw Hill Yearbook of Science and Technology (1992) McGraw Hill, New York NY, pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; and Harrington,0 J.J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al., (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R.M. et al. (1985) Nature 317(6040):813-815; McGregor, D.P. et al. (1994) Mol. Immunol.5 31(3):219-226; and Verma, I.M. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.

For long term production of recombinant proteins in mammalian systems, stable expression of SPTM in cell lines is preferred. For example, sequences encoding SPTM can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous o expression elements and a selectable marker gene on the same or on a separate vector. Any number of selection systems may be used to recover transformed cell fines. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.; Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14; Hartman, S.C. and R.CMulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051; Rhodes, CA. (1995) Methods Mol.5 Biol. 55:121-131.)

Therapeutic Uses of sptm

The polynucleotides encoding SPTM of the invention may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe o combined immunodeficiency (SCID)-Xl disease characterized by X-linked inheritance (Cavazzana-

Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R.M. et al. (1995) Science 270:475- 480; Bordignon, C et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R.G. et al. (1995) 5 Hum. Gene Therapy 6:667-703), thalassemias, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX deficiencies (Crystal, R.G. (1995) Science 270:404-410; Verma, I.M. and Somia, N. (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human 5 immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C virus (HBV, HCV); fungal parasites, such as Candida albicans and Paracoccidioides brasiliensis; and protozoan parasites such as Plasmodium falciparum and Trypanosoma cruzi). In the case where a genetic deficiency in sptm expression or regulation causes disease, the expression of sptm from an appropriate population of o transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.

In a further embodiment of the invention, diseases or disorders caused by deficiencies in sptm are treated by constructing mammalian expression vectors comprising sptm and introducing these vectors by mechanical means into sptm-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold5 particle delivery, (iii) fiposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R.A. and Anderson, W.F. (1993) Annu. Rev. Biochem. 62:191-217; Ivies, Z. (1997) Cell 91:501-510; Boulay, J-L. and Recipon, H. (1998) Curr. Opin. Biotechnol. 9:445- 450).

Expression vectors that may be effective for the expression of sptm include, but are not limited o to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX vectors (Invitrogen, Carlsbad CA),

PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Sfratagene, La Jolla CA), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto CA). The sptm of the invention may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an inducible promoter5 (e.g., the tetracycline-regulated promoter (Gossen, M. and Bujard, H. (1992) Proc. Natl. Acad. Sci. U.S.A. 89:5547-5551; Gossen, M. et al., (1995) Science 268:1766-1769; Rossi, F.M.V. and Blau, H.M. (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX plasmid (Invitrogen); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter o (Rossi, F.M.V. and Blau, H.M. supra), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding SPTM from a normal individual.

Commercially available liposome transformation kits (e.g., the PERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells in culture and require minimal effort to optimize experimental 5 parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F.L. andEb, AJ. (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J. 1 :841-845). The introduction of DNA to primary cells requires modification of these standardized mammalian transfection protocols.

In another embodiment of the invention, diseases or disorders caused by genetic defects with 5 respect to sptm expression are treated by constructing a refrovirus vector consisting of (i) sptm under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cώ-acting RNA sequences and coding sequences required for efficient vector propagation. Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on0 published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650; Bender, M.A. et al. (1987) J. Virol. 61:1639-1646; Adam, M.A. and Miller, A.D. (1988) J. Virol. 62:3802-3806; Dull, T. et al.5 (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol. 72:9873-9880). U.S. Patent Number 5,910,434 to Rigg ("Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant") discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4⁺ T-cells), and the return of transduced cells to a patient are procedures well known to o persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M.L. (1997) J. Virol. 71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).

In the alternative, an adenovirus-based gene therapy delivery system is used to deliver sptm to 5 cells which have one or more genetic abnormalities with respect to the expression of sptm. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus vectors have proven to be versatile for importing genes encoding immunoregulatory proteins into intact islets in the pancreas (Csete, M.E. et al. (1995) Transplantation 27:263-268). Potentially useful adenoviral vectors are described in U.S. Patent o Number 5,707,618 to Armentano ("Adenovirus vectors for gene therapy"), hereby incorporated by reference. For adenoviral vectors, see also Antinozzi, P.A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I.M. and Somia, N. (1997) Nature 18:389:239-242, both incorporated by reference herein. In another alternative, a herpes-based, gene therapy delivery system is used to deliver sptm to target cells which have one or more genetic abnormalities with respect to the expression of sptm. The 5 use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing sptm to cells of the central nervous system, for which HSV has a tropism. The construction and packaging of herpes-based vectors are well known to those with ordinary skill in the art. A replication-competent herpes simplex virus (HSV) type 1 -based vector has been used to deliver a reporter gene to the eyes of primates (Liu, X. et al. (1999) Exp. Eye Res.169:385-395). The construction of a HSV-1 virus vector has also been disclosed in detail in U.S. Patent Number 5,804,413 to DeLuca ("Herpes simplex virus strains for gene transfer"), which is hereby incorporated by reference. U.S. Patent Number 5,804,413 teaches the use of recombinant HSV d92 which consists of a genome containing at least one exogenous gene to be transferred to a cell under the control of the appropriate promoter for purposes including human gene therapy. Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22. For HSV vectors, see also Goins, W. F. et al. 1999 J.

Virol. 73:519-532 andXu, H. et al., (1994) Dev. Biol. 163:152-161, hereby incorporated by reference. The manipulation of cloned herpesvirus sequences, the generation of recombinant virus following the transfection of multiple plasmids containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.

In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver sptm to target cells. The biology of the prototypic alphavirus, Semliki Forest Virus (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and Li, K-J. (1998) Curr. Opin. Biotech. 9:464-469). During alphavirus RNA replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins. This subgenomic RNA replicates to higher levels than the full-length genomic RNA, resulting in the overproduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting sptm into the alphavirus genome in place of the capsid-coding region results in the production of a large number of sptm RNAs and the synthesis of high levels of SPTM in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S.A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of sptm into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA and RNA transfections, and performing alphavirus infections, are well known to those with ordinary skill in the art.

Antibodies Anti-SPTM antibodies may be used to analyze protein expression levels. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, and Fab fragments. For descriptions of and protocols of antibody technologies, see, e.g., Pound J.D. (1998) Immunochemical Protocols, Humana Press, Totowa, NJ. The amino acid sequence encoded by the sptm of the Sequence Listing may be analyzed by appropriate software (e.g., LASERGENE NAVIGATOR software, DNASTAR) to determine regions of high immunogenicity. The optimal sequences for immunization are selected from the C-terminus, the N-terminus, and those intervening, hydrophilic regions of the polypeptide which are likely to be exposed to the external environment when the polypeptide is in its natural conformation. Analysis used to select appropriate epitopes is also described by Ausubel (1997, supra, Chapter 11.7). Peptides used for antibody induction do not need to have biological activity; however, they must be antigenic. Peptides used to induce specific antibodies may have an amino acid sequence consisting of at least five amino acids, preferably at least 10 amino acids, and most preferably at least 15 amino acids. A peptide which mimics an antigenic fragment of the natural polypeptide may be fused with another protein such as keyhole limpet hemocyanin (KLH; Sigma, St. Louis MO) for antibody production. A peptide encompassing an antigenic region may be expressed from an sptm, synthesized as described above, or purified from human cells.

Procedures well known in the art may be used for the production of antibodies. Various hosts including mice, goats, and rabbits, may be immunized by injection with a peptide. Depending on the host species, various adjuvants may be used to increase immunological response.

In one procedure, peptides about 15 residues in length may be synthesized using an ABI 431 A peptide synthesizer (Applied Biosystems) using fmoc-chemistry and coupled to KLH (Sigma) by reaction with M-maleimidobenzoyl-N-hydroxysuccinimide ester (Ausubel, 1995, supra). Rabbits are immunized with the peptide-KLH complex in complete Freund's adjuvant. The resulting antisera are tested for antipeptide activity by binding the peptide to plastic, blocking with 1 % bovine serum albumin

(BSA), reacting with rabbit antisera, washing, and reacting with radioiodinated goat anti-rabbit IgG. Antisera with antipeptide activity are tested for anti-SPTM activity using protocols well known in the art, including ELISA, radioimmunoassay (RIA), and immunoblotting.

In another procedure, isolated and purified peptide may be used to immunize mice (about 100 μg of peptide) or rabbits (about 1 mg of peptide). Subsequently, the peptide is radioiodinated and used to screen the immunized animals' B-lymphocytes for production of antipeptide antibodies. Positive cells are then used to produce hybridomas using standard techniques. About 20 mg of peptide is sufficient for labeling and screening several thousand clones. Hybridomas of interest are detected by screening with radioiodinated peptide to identify those fusions producing peptide-specific monoclonal antibody. In a typical protocol, wells of a multi-well plate (FAST, Becton-Dickinson, Palo Alto, CA) are coated with affinity-purified, specific rabbit-anti-mouse (or suitable anti-species IgG) antibodies at 10 mg/ml. The coated wells are blocked with 1 % BSA and washed and exposed to supernatants from hybridomas. After incubation, the wells are exposed to radiolabeled peptide at 1 mg/ml.

Clones producing antibodies bind a quantity of labeled peptide that is detectable above 5 background. Such clones are expanded and subjected to 2 cycles of cloning. Cloned hybridomas are injected into pristane-treated mice to produce ascites, and monoclonal antibody is purified from the ascitic fluid by affinity chromatography on protein A (Amersham Pharmacia Biotech). Several procedures for the production of monoclonal antibodies, including in vitro production, are described in Pound (supra). Monoclonal antibodies with antipeptide activity are tested for anti-SPTM activity usingo protocols well known in the art, including ELISA, RIA, and immunoblotting.

Antibody fragments containing specific binding sites for an epitope may also be generated. For example, such fragments include, but are not limited to, the F(ab 2 fragments produced by pepsin digestion of the antibody molecule, and the Fab fragments generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, construction of Fab expression libraries in filamentous 5 bacteriophage allows rapid and easy identification of monoclonal fragments with desired specificity (Pound, supra, Chaps. 45-47). Antibodies generated against polypeptide encoded by sptm can be used to purify and characterize full-length SPTM protein and its activity, binding partners, etc.

Assays Using Antibodies o Anti-SPTM antibodies may be used in assays to quantify the amount of SPTM found in a particular human cell. Such assays include methods utilizing the antibody and a label to detect expression level under normal or disease conditions. The peptides and antibodies of the invention may be used with or without modification or labeled by joining them, either covalently or noncovalently, with a reporter molecule. 5 Protocols for detecting and measuring protein expression using either polyclonal or monoclonal antibodies are well known in the art. Examples include ELISA, RIA, and fluorescent activated cell sorting (FACS). Such immunoassays typically involve the formation of complexes between the SPTM and its specific antibody and the measurement of such complexes. These and other assays are described in Pound (supra). o Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

The disclosures of all patents, applications, and publications mentioned above and below,5 including U.S. Ser. No. 60/205,287, U.S. Ser. No. 60/205,324, U.S. Ser. No. 60/205,286, U.S. Ser. No. 60/205,323, U.S. Ser. No. 60/185,215, U.S. Ser. No. 60/185,216, and U.S. Ser. No. 60/205,232, are hereby expressly incorporated by reference.

EXAMPLES 5 I. Construction of cDNA Libraries

RNA was purchased from CLONTECH Laboratories, Inc. (Palo Alto CA) or isolated from various tissues. Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates o were centrifuged over CsCl cushions or exfracted with chloroform. RNA was precipitated with either isopropanol or sodium acetate and ethanol, or by other routine methods.

Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA purity. In most cases, RNA was treated with DNase. For most libraries, poly(A+) RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega Corporation (Promega), Madison WI), 5 OLIGOTEX latex particles (QIAGEN, Inc. (QIAGEN), Valencia CA), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Inc., Austin TX).

In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP o vector system (Stratagene Cloning Systems, Inc. (Stratagene), La Jolla CA) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, Chapters 5.1 through 6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For 5 most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S 1000, SEPHAROSE

CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel elecfrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, Carlsbad CA), PBK-CMV plasmid (Stratagene), 0 or pINCY (Incyte Genomics, Palo Alto CA), or derivatives thereof. Recombinant plasmids were transformed into competent E. coli cells including XL 1 -Blue, XLl-BlueMRF, or SOLR from Stratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.

II. Isolation of cDNA Clones Plasmids were recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: the Magic or WIZARD Minipreps DNA purification system (Promega); the AGTC Miniprep purification kit (Edge BioSystems, Gaithersburg MD); and the QIAWELL 8, QIAWELL 8 Plus, and QIAWELL 8 Ultra 5 plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification Mt (QIAGEN). Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4°C

Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format. (Rao, V.B. (1994) Anal. Biochem. 216:1-14.) Host cell lysis and thermal o cycfing steps were carried out in a single reaction mixture. Samples were processed and stored in 384- well plates, and the concentration of amplified plasmid DNA was quantified fluorometricaHy using PICOGREEN dye (Molecular Probes, Inc. (Molecular Probes), Eugene OR) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland). 5 III. Sequencing and Analysis cDNA sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 thermal cycler (Applied Biosystems) or the PTC- 200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific Corp., Sunnyvale CA) or the MICROLAB 2200 liquid transfer system (Hamilton). cDNA sequencing o reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems). Electrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (Applied Biosystems) in 5 conjunction with standard ABI protocols and base calling software; or other sequence analysis systems known in the art. Reading frames within the cDNA sequences were identified using standard methods (reviewed in Ausubel, 1997, supra. Chapter 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VIII.

o IV. Assembly and Analysis of Sequences

Component sequences from chromatograms were subject to PHRED analysis and assigned a quality score. The sequences having at least a required quality score were subject to various preprocessing editing pathways to eliminate, e.g., low quality 3' ends, vector and linker sequences, polyA tails, Alu repeats, mitochondrial and ribosomal sequences, bacterial contamination sequences, and 5 sequences smaller than 50 base pairs. In particular, low-information sequences and repetitive elements (e.g., dinucleotide repeats, Alu repeats, etc.) were replaced by "n's", or masked, to prevent spurious matches.

Processed sequences were then subject to assembly procedures in which the sequences were assigned to gene bins (bins). Each sequence could only belong to one bin. Sequences in each gene bin 5 were assembled to produce consensus sequences (templates). Subsequent new sequences were added to existing bins using BLASTn (v.1.4 WashU) and CROSSMATCH. Candidate pairs were identified as all BLAST hits having a quality score greater than or equal to 150. Alignments of at least 82% local identity were accepted into the bin. The component sequences from each bin were assembled using a version of PHRAP. Bins with several overlapping component sequences were assembled using DEEP o PHRAP. The orientation (sense or antisense) of each assembled template was determined based on the number and orientation of its component sequences. Template sequences as disclosed in the sequence listing correspond to sense strand sequences (the "forward" reading frames), to the best determination. The complementary (antisense) strands are inherently disclosed herein. The component sequences which were used to assemble each template consensus sequence are fisted in Table 2 along with their5 positions along the template nucleotide sequences.

Bins were compared against each other and those having local similarity of at least 82% were combined and reassembled. Reassembled bins having templates of insufficient overlap (less than 95% local identity) were re-split. Assembled templates were also subject to analysis by STITCHER/EXON MAPPER algorithms which analyze the probabilities of the presence of splice variants, alternatively o spliced exons, splice junctions, differential expression of alternative spliced genes across tissue types or disease states, etc. These resulting bins were subject to several rounds of the above assembly procedures.

Once gene bins were generated based upon sequence alignments, bins were clone joined based upon clone information. If the 5' sequence of one clone was present in one bin and the 3' sequence from5 the same clone was present in a different bin, it was likely that the two bins actually belonged together in a single bin. The resulting combined bins underwent assembly procedures to regenerate the consensus sequences.

The final assembled templates were subsequently annotated using the following procedure. Template sequences were analyzed using BLASTn (v2.0, NCBI) versus gbpri (GenBank version 120). o "Hits" were defined as an exact match having from 95 % local identity over 200 base pairs through

100% local identity over 100 base pairs, or a homolog match having an E-value, i.e. a probability score, of < 1 x 10^"8. The hits were subject to frameshift FASTx versus GENPEPT (GenBank version 120). (See Table 4). In this analysis, a homolog match was defined as having an E-value of ≤ 1 x 10^"8. The assembly method used above was described in "System and Methods for Analyzing Biomolecular Sequences," U.S.S.N. 09/276,534, filed March 25, 1999, and the LIFESEQ Gold user manual (Incyte) both incorporated by reference herein.

Following assembly, template sequences were subjected to motif, BLAST, and functional analyses, and categorized in protein hierarchies using methods described in, e.g., "Database System 5 Employing Protein Function Hierarchies for Viewing Biomolecular Sequence Data," U.S.S.N. 08/812,290, filed March 6, 1997; "Relational Database for Storing Biomolecule Information," U.S.S.N. 08/947,845, filed October 9, 1997; "Project-Based Full-Length Biomolecular Sequence Database," U.S.S.N. 08/811,758, filed March 6, 1997; and "Relational Database and System for Storing Information Relating to Biomolecular Sequences," U.S.S.N. 09/034,807, filed March 4, 1998, o all of which are incorporated by reference herein.

The template sequences were further analyzed by translating each template in all three forward reading frames and searching each translation against the Pfam database of hidden Markov model- based protein families and domains using the HMMER software package (available to the public from Washington University School of Medicine, St. Louis MO). (See also World Wide Web site 5 http://pfam.wustl.edu/ for detailed descriptions of Pfam protein domains and families.)

Additionally, the template sequences were translated in all three forward reading frames, and each translation was searched against hidden Markov models for signal peptides using the HMMER software package. Construction of hidden Markov models and their usage in sequence analysis has been described. (See, for example, Eddy, S.R. (1996) Curr. Opin. Str. Biol. 6:361-365.) Only those o signal peptide hits with a cutoff score of 11 bits or greater are reported. A cutoff score of 11 bits or greater corresponds to at least about 91-94% true-positives in signal peptide prediction. Template sequences were also translated in all three forward reading frames, and each translation was searched against TMAP, a program that uses weight matrices to delineate transmembrane segments on protein sequences and determine orientation, with respect to the cell cytosol (Persson, B. and Argos, P. (1994)5 J. Mol. Biol. 237:182-192, and Persson, B. and Argos, P. (1996) Protein Sci. 5:363-371.) Regions of templates which, when translated, contain similarity to signal peptide or transmembrane consensus sequences are reported in Table 1.

Template sequences are further analyzed using the bioinformatics tools listed in Table 4, or using sequence analysis software known in the art such as MACDNASIS PRO software (Hitachi o Software Engineering, South San Francisco CA) and LASERGENE software (DNASTAR). Template sequences may be further queried against public databases such as the GenBank rodent, mammalian, vertebrate, prokaryote, and eukaryote databases.

V. Analysis of Polynucleotide Expression Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound. (See, e.g., Sambrook, supra, ch. 7; Ausubel, 1995, supra, ch. 4 and 16.)

Analogous computer techniques applying BLAST were used to search for identical or related molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This analysis is much faster than multiple membrane-based hybridizations. In addition, the sensitivity, of the computer search can be modified to determine whether any particular match is categorized as exact or similar. The basis of the search is the product score, which is defined as:

BLAST Score x Percent Identity

5 x minimum {length(Seq. 1), length(Seq. 2)}

The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score o +5 for every base that matches in a high-scoring segment pair (HSP), and -4 for every mismatch. Two sequences may share more than one HSP (separated by gaps). If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment. For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 70% overlap at one end, or by 88% identity and 100% overlap at the other. A product score of 50 is produced either by 100% identity and 50% overlap at one end, or 79% identity and 100% overlap.

Alternatively, polynucleotide sequences encoding SPTM are analyzed with respect to the tissue sources from which they were derived. Polynucleotide sequences encoding SPTM were assembled, at least in part, with overlapping Incyte cDNA sequences. Each cDNA sequence is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following organ/tissue categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; hemic and immune system; liver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The number of libraries in each category for each polynucleotide sequence encoding SPTM is counted and divided by the total number of libraries across all categories for each polynucleotide sequence encoding SPTM. Similarly, each human tissue is classified into one of the following disease/condition categories: cancer, cell line, developmental, inflammation, neurological, trauma, cardiovascular, pooled, and other, and the number of libraries in each category for each polynucleotide sequence encoding SPTM is counted and divided by the total number of libraries across all categories for each polynucleotide sequence encoding SPTM. 5 The resulting percentages reflect the tissue-specific and disease-specific expression of cDNA encoding SPTM. Percentage values of tissue-specific expression are reported in Table 3. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto CA). VI. Tissue Distribution Profiling 0 A tissue distribution profile is determined for each template by compiling the cDNA library tissue classifications of its component cDNA sequences. Each component sequence, is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; hemic and immune5 system; liver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. Template sequences, component sequences, and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto CA).

Table 3 shows the tissue distribution profile for the templates of the invention. For each o template, the three most frequently observed tissue categories are shown in column 2, along with the percentage of component sequences belonging to each category. Only tissue categories with percentage values of > 10% are shown. A tissue distribution of "widely distributed" in column 2 indicates percentage values of <10% in all tissue categories. 5 VII. Transcript Image Analysis

Transcript images are generated as described in Seilhamer et al., "Comparative Gene Transcript Analysis," U.S. Patent Number 5,840,484, incorporated herein by reference.

VIII. Extension of Polynucleotide Sequences and Isolation of a Full-length cDNA o Oligonucleotide primers designed using an sptm of the Sequence Listing are used to extend the nucleic acid sequence. One primer is synthesized to initiate 5' extension of the template, and the other primer, to initiate 3' extension of the template. The initial primers may be designed using OLIGO 4.06 software (National Biosciences, Inc. (National Biosciences), Plymouth MN), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to 5 anneal to the target sequence at temperatures of about 68 °C to about 72°C Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations are avoided. Selected human cDNA libraries are used to extend the sequence. If more than one extension is necessary or desired, additional or nested sets of primers are designed.

High fidelity amplification is obtained by PCR using methods well known in the art. PCR is performed in 96-well plates using the PTC-200 thermal cycler (MJ Research). The reaction mix contains DNA template, 200 nmol of each primer, reaction buffer containing Mg²⁺, (NH₄)₂S0₄, and β- mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Stratagene), with the following parameters for primer pair PCI A and PCI B: Step 1: 94°C, 3 min; Step 2: 94°C, 15 sec; Step 3: 60°C, 1 min; Step 4: 68 °C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68 °C, 5 min; Step 7: storage at 4°C In the alternative, the parameters for primer pair T7 and SK+ are as follows: Step 1 : 94 °C, 3 min; Step 2: 94°C, 15 sec; Step 3: 57°C, 1 min; Step 4: 68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68 °C, 5 min; Step 7: storage at 4°C

The concentration of DNA in each well is determined by dispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v); Molecular Probes) dissolved in IX Tris-EDTA (TE) and 0.5 μl of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Incorporated (Corning), Corning NY), allowing the DNA to bind to the reagent. The plate is scanned in a FLUOROSKAN II (Labsystems Oy) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixture is analyzed by electrophoresis on a 1 % agarose mini-gel to determine which reactions are successful in extending the sequence.

The extended nucleotides are desalted and concentrated, transferred to 384- well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison WI), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides are separated on low concentration (0.6 to 0.8%) agarose gels, fragments are excised, and agar digested with AGAR ACE (Promega). Extended clones are religated using T4 ligase (New England Biolabs, Inc., Beverly MA) into pUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent E. coli cells. Transformed cells are selected on antibiotic-containing media, individual colonies are picked and cultured overnight at 37 ° C in 384- well plates in LB/2x carbenicillin liquid media.

The cells are lysed, and DNA is amplified by PCR using Taq DNA polymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following parameters: Step 1 : 94°C, 3 min; Step 2: 94°C, 15 sec; Step 3: 60°C, 1 min; Step 4: 72°C, 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72°C, 5 min; Step 7: storage at 4°C DNA is quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA recoveries are reamplified using the same conditions as described above. Samples are diluted with 20% dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems). 5 In like manner, the sptm is used to obtain regulatory sequences (promoters, introns, and enhancers) using the procedure above, oligonucleotides designed for such extension, and an appropriate genomic library.

IX. Labeling of Probes and Southern Hybridization Analyses o Hybridization probes derived from the sptm of the Sequence Listing are employed for screening cDNAs, mRNAs, or genomic DNA. The labeling of probe nucleotides between 100 and 1000 nucleotides in length is specifically described, but essentially the same procedure may be used with larger cDNA fragments. Probe sequences are labeled at room temperature for 30 minutes using a T4 polynucleotide kinase, γ³²P-ATP, and 0.5X One-Phor-AU Plus (Amersham Pharmacia Biotech) 5 buffer and purified using a ProbeQuant G-50 Microcolumn (Amersham Pharmacia Biotech). The probe mixture is diluted to 10⁷ dpm/μg/ml hybridization buffer and used in a typical membrane-based hybridization analysis.

The DNA is digested with a restriction endonuclease such as Eco RV and is electrophoresed through a 0.7% agarose gel. The DNA fragments are transferred from the agarose to nylon membrane o (NYTRAN Plus, Schleicher & Schuell, Inc., Keene NH) using procedures specified by the manufacturer of the membrane. Prehybridization is carried out for three or more hours at 68 °C, and hybridization is carried out overnight at 68 °C To remove non-specific signals, blots are sequentially washed at room temperature under increasingly stringent conditions, up to 0. lx saline sodium citrate (SSC) and 0.5% sodium dodecyl sulfate. After the blots are placed in a PHOSPHORIMAGER cassette 5 (Molecular Dynamics) or are exposed to autoradiography film, hybridization patterns of standard and experimental lanes are compared. Essentially the same procedure is employed when screening RNA.

X. Chromosome Mapping of sptm

The cDNA sequences which were used to assemble SEQ ID NO: 1-79 are compared with o sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith- Waterman algorithm. Sequences from these databases that match SEQ ID NO: 1-79 are assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as PHRAP (Table 4). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome 5 Research (WIGR), and Genethon are used to determine if any of the clustered sequences have been previously mapped. Inclusion of a mapped sequence in a cluster will result in the assignment of all sequences of that cluster, including its particular SEQ ID NO:, to that map location. The genetic map locations of SEQ ID NO:l-79 are described as ranges, or intervals, of human chromosomes. The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome's p- arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of recombination.) The cM distances are based on genetic markers mapped by Genethon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters. 0

XI. Microarray Analysis

Probe Preparation from Tissue or Cell Samples

Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and polyA⁺ RNA is purified using the oligo (dT) cellulose method. Each polyA⁺ RNA sample is reverse5 transcribed using MMLV reverse-transcriptase, 0.05 pg/μl oligo-dT primer (21mer), IX first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500 μM dGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng polyA⁺ RNA with GEMB RIGHT kits (Incyte). Specific control polyA⁺ RNAs are synthesized by in vitro transcription from non-coding yeast o genomic DNA (W. Lei, unpublished). As quantitative confrols, the control mRNAs at 0.002 ng, 0.02 ng, 0.2 ng, and 2 ng are diluted into reverse transcription reaction at ratios of 1:100,000, 1:10,000, 1 : 1000, 1 : 100 (w/w) to sample mRNA respectively. The control mRNAs are diluted into reverse transcription reaction at ratios of 1:3, 3:1, 1:10, 10:1, 1:25, 25:1 (w/w) to sample mRNA differential expression patterns. After incubation at 37° C for 2 hr, each reaction sample (one with Cy3 and another 5 with Cy5 labefing) is freated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at

85° C to the stop the reaction and degrade the RNA. Probes are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc. (CLONTECH), Palo Alto CA) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100% ethanol. The probe is then dried to completion o using a SpeedVAC (Savant Instruments Inc., Holbrook NY) and resuspended in 14 μl 5X SSC/0.2%

SDS.

Microarray Preparation

Sequences of the present invention are used to generate array elements. Each array element is 5 amplified from bacterial cells containing vectors with cloned cDNA inserts. PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 μg. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech). Purified array elements are immobilized on polymer-coated glass slides. Glass microscope 5 slides (Corning) are cleaned by ultrasound in 0.1 % SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4% hydrofluoric acid (VWR Scientific Products Corporation (VWR), West Chester, PA), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated slides are cured in a 110°C oven. Array elements are applied to the coated glass substrate using a procedure described in US0 Patent No. 5,807,522, incorporated herein by reference. 1 μl of the array element DNA, at an average concentration of 100 ng/μl, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 nl of array element sample per slide.

Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water.5 Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate - buffered saline (PBS) (Tropix, Inc., Bedford, MA) for 30 minutes at 60° C followed by washes in 0.2% SDS and distilled water as before.

Hybridization o Hybridization reactions contain 9 μl of probe mixture consisting of 0.2 μg each of Cy3 and

Cy5 labeled cDNA synthesis products in 5X SSC, 0.2% SDS hybridization buffer. The probe mixture is heated to 65° C for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm² coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 μl of5 5x SSC in a corner of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C in a first wash buffer (IX SSC, 0.1 % SDS), three times for 10 minutes each at 45° C in a second wash buffer (0. IX SSC), and dried.

Detection o Reporter-labeled hybridization complexes are detected with a microscope equipped with an

Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara CA) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of Cy5. The excitation laser light is focused on the array using a 20X microscope objective (Nikon, Inc., Melville NY). The slide containing the array is placed on a computer-controlled X-Y stage on the microscope and raster- scanned past the objective. The 1.8 cm x 1.8 cm array used in the present example is scanned with a resolution of 20 micrometers.

In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially. Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT R1477, 5 Hamamatsu Photonics Systems, Bridgewater NJ) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultiplier tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5. Each array is typically scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores simultaneously. o The sensitivity of the scans is typically calibrated using the signal intensity generated by a cDNA control species added to the probe mix at a known concentration. A specific location on the array contains a complementary DNA sequence, allowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1 : 100,000. When two probes from different sources (e.g., representing test and control cells), each labeled with a different fluorophore, are 5 hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture.

The output of the photomultiplier tube is digitized using a 12-bit RTI-835H analog-to-digital (A/D) conversion board (Analog Devices, Inc., Norwood, MA) installed in an IBM-compatible PC o computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore's emission spectrum. 5 A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).

o XII. Complementary Nucleic Acids

Sequences complementary to the sptm are used to detect, decrease, or inhibit expression of the naturally occurring nucleotide. The use of oligonucleotides comprising from about 15 to 30 base pairs is typical in the art. However, smaller or larger sequence fragments can also be used. Appropriate oligonucleotides are designed from the sptm using OLIGO 4.06 software (National Biosciences) or 5 other appropriate programs and are synthesized using methods standard in the art or ordered from a commercial supplier. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5 ' sequence and used to prevent transcription factor binding to the promoter sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding and processing of the transcript.

5

XIII. Expression of SPTM

Expression and purification of SPTM is accomplished using bacterial or virus-based expression systems. For expression of SPTM in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of o cDNA transcription. Examples of such promoters include, but are not limited to, the trp-lac (tac) hybrid promoter and the T5 or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21 (DE3). Antibiotic resistant bacteria express SPTM upon induction with isopropyl beta-D- thiogalactopyranoside (IPTG). Expression of SPTM in eukaryotic cells is achieved by infecting insect5 or mammalian cell lines with recombinant Autographica californica nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding SPTM by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to o infect Spodoptera frugiperda (Sf9) insect cells in most cases, or human hepatocytes, in some cases.

Infection of the latter requires additional genetic modifications to baculovirus. (See e.g. , Engelhard, supra; and Sandig, supra.)

In most expression systems, SPTM is synthesized as a fusion protein with, e.g., glutathione S- transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, 5 affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from Schistosoma iaponicum, enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from SPTM at specifically engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffmity purification o using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak

Company, Rochester NY). 6-His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, supra, Chapters 10 and 16). Purified SPTM obtained by these methods can be used directly in the following activity assay. 5 XIV. Demonstration of SPTM Activity

An assay for SPTM activity measures the expression of SPTM on the cell surface. cDNA encoding SPTM is subcloned into an appropriate mammalian expression vector suitable for high levels of cDNA expression. The resulting construct is transfected into a nonhuman cell line such as NIH3T3. 5 Cell surface proteins are labeled with biotin using methods known in the art. Immunoprecipitations are performed using SPTM-specific antibodies, and immunoprecipitated samples are analyzed using SDS- PAGE and immunoblotting techniques. The ratio of labeled immunoprecipitant to unlabeled immunoprecipitant is proportional to the amount of SPTM expressed on the cell surface.

Alternatively, an assay for SPTM activity measures the amount of SPTM in secretory,0 membrane-bound organelles. Transfected cells as described above are harvested and lysed. The lysate is fractionated using methods known to those of skill in the art, for example, sucrose gradient ultracentrifugation. Such methods allow the isolation of subcellular components such as the Golgi apparatus, ER, small membrane-bound vesicles, and other secretory organelles. Immunoprecipitations from fractionated and total cell lysates are performed using SPTM-specific antibodies, and5 immunoprecipitated samples are analyzed using SDS-PAGE and immunoblotting techniques. The concentration of SPTM in secretory organelles relative to SPTM in total cell lysate is proportional to the amount of SPTM in transit through the secretory pathway.

XV. Functional Assays o SPTM function is assessed by expressing sptm at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include pCMV SPORT (Life Technologies) and pCR3.1 (Invifrogen Corporation, Carlsbad CA), both of which contain the cytomegalovirus promoter. 5-10 μg of recombinant vector are transiently transfected into a human cell 5 line, preferably of endothelial or hematopoietic origin, using either liposome formulations or electroporation. 1-2 μg of an additional plasmid containing sequences encoding a marker protein are co-transfected.

Expression of a marker protein provides a means to distinguish transfected cells from nontransfected cells and is a reliable predictor of cDNA expression from the recombinant vector. o Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP; CLONTECH), CD64, or a

CD64-GFP fusion protein. Flow cytometry (FCM), an automated laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties.

FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding 5 or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree sidelight scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane 5 composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. (1994) Flow Cytometry, Oxford, New York NY.

The influence of SPTM on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding SPTM and either CD64 or CD64-GFP. CD64 and CD64- o GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Inc., Lake Success NY). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding SPTM and other genes of interest can be analyzed by northern analysis5 or microarray techniques.

XVI. Production of Antibodies

SPTM substantially purified using polyacrylamide gel electrophoresis (PAGE; see, e.g., Harrington, M.G. (1990) Methods Enzymol. 182:488-495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols. o Alternatively, the SPTM amino acid sequence is analyzed using LASERGENE software

(DNASTAR) to determine regions of high immunogenicity, and a corresponding peptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for selection of appropriate epitopes, such as those near the C-terminus or in hydrophilic regions are well described in the art. (See, e.g., Ausubel, 1995, supra, Chapter 11.) 5 Typically, peptides 15 residues in length are synthesized using an ABI 431Apeptide synthesizer (Applied Biosystems) using fmoc-chemistry and coupled to KLH (Sigma) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity. (See, e.g., Ausubel, supra.) Rabbits are immunized with the peptide-KLH complex in complete Freund's adjuvant. Resulting antisera are tested for antipeptide activity by, for example, binding the peptide to o plastic, blocking with 1 % BSA, reacting with rabbit antisera, washing, and reacting with radioiodinated goat anti-rabbit IgG. Antisera with antipeptide activity are tested for anti-SPTM activity using protocols well known in the art, including ELISA, RIA, and immunoblotting.

XVII. Purification of Naturally Occurring SPTM Using Specific Antibodies Naturally occurring or recombinant SPTM is substantially purified by immunoaffinity chromatography using antibodies specific for SPTM. An immunoaffinity column is constructed by covalently coupling anti-SPTM antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is 5 blocked and washed according to the manufacturer's instructions.

Media containing SPTM are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of SPTM (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/SPTM binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), l o and SPTM is collected.

XVIII. Identification of Molecules Which Interact with SPTM

SPTM, or biologically active fragments thereof, are labeled with ¹²⁵I Bolton-Hunter reagent. (See, e.g., Bolton, A.E. and W.M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules 15 previously arrayed in the wells of a multi-well plate are incubated with the labeled SPTM, washed, and any wells with labeled SPTM complex are assayed. Data obtained using different concentrations of SPTM are used to calculate values for the number, affinity, and association of SPTM with the candidate molecules.

Alternatively, molecules interacting with SPTM are analyzed using the yeast two-hybrid system 20 as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (CLONTECH).

SPTM may also be used in the PATHCALLING process (CuraGen Corp., New Haven CT) which employs the yeast two-hybrid system in a high-throughput manner to determine all interactions between the proteins encoded by two large libraries of genes (Nandabalan, K. et al. (2000) U.S. Patent 25 No. 6,057,101).

All publications and patents mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described method and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. 3 o Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the above-described modes for carrying out the invention which are obvious to those skilled in the field of molecular biology or related fields are intended to be within the scope of the following claims.

35 Table 1

SEQ

ID Template Domain

NO: ID Start Stop Frame Type Topology

1 LG: 223939. .1: :2000FEB18 202 288 forward 1 TM N in

2 LG: 397140. .1: :2000FEB18 508 588 forward 1 TM

2 LG: 397140. .1: :2000FEB18 236 319 forward 2 TM N out

2 LG: 397140. .1: :2000FEB18 377 463 forward 2 TM N out

2 LG: 397140. ,1: :2000FEB18 288 374 forward 3 TM

2 LG: 397140. .1: :2000FEB18 480 566 forward 3 TM

3 LG: 1094205.1-.2000FEB18 826 912 forward 1 TM N in

3 LG: 1094205.1-.2000FEB18 867 953 forward 3 TM N out

4 LG: 481361. .5: :2000FEB18 115 201 forward 1 TM N out

4 LG: :481361. .5: :2000FEB18 295 354 forward 1 TM N out

4 LG: ,481361. .5: :2000FEB18 373 459 forward 1 TM N out

4 LG: ;481361. .5: :2000FEB18 101 187 forward 2 TM N out

4 LG: :481361. .5: :2000FEB18 369 443 forward 3 TM N out

5 LG: :981170. .1: :2000FEB18 10 78 forward 1 TM N out

5 LG: :981170. .1: :2000FEB18 598 648 forward 1 TM N out

5' LG: :981170. .1: :2000FEB18 790 876 forward 1 TM N out

5 LG: :981170. .1: :2000FEB18 1057 1143 forward 1 TM N out

5 LG: :981170. .1: :2000FEB18 1372 1458 forward 1 TM N out

5 LG: :981170. .1: :2000FΞB18 1678 1764 forward 1 TM N out

5 LG: :981170. .1: :2000FEB18 1885 1959 forward 1 TM N out

5 LG: :981170. .1: :2000FEB18 11 82 forward 2 TM N out

5 LG: :981170, .1; :2000FEB18 731 817 forward 2 TM N out

5 LG: :981170, .1: :2000FEB18 1025 1105 forward 2 TM N out

5 LG: :981170. .1: :2000FEB18 1364 1450 forward 2 TM N out

5 LG: :981170. .1: :2000FEB18 1643 1696 forward 2 TM N out

5 LG: :981170. .1: :2000FEB18 1895 1954 forward 2 TM N out

5 LG: :981170. .1: :2000FEB18 24 110 forward 3 TM N out

5 LG: :981170. .1: :2000FEB18 843 899 forward 3 TM N out

5 LG: :981170. .1: :2000FΞB18 1068 1136 forward 3 TM N out

5 LG: :981170. .1: :2000FEB18 1599 1655 forward 3 TM N out

5 LG: :981170. .1: :2000FEB18 1707 1793 forward 3 TM N out

5 LG: :981170. .1: :2000FEB18 1875 1961 forward 3 TM N out

6 LI: :197613. .1: :2000FEB01 140 226 forward 2 TM N out

6 LI: :19761s, .1: :2000FΞB01 269 355 forward 2 TM N out

7 LI: :902682, .1: :2000FEB01 225 311 forward 3 TM N out

8 LI: :212029. .1: :2000FEB01 2087 2149 forward 2 TM N out

8 LI: :212029, .1: :2000FΞB01 2162 2224 forward 2 TM N out

9 LI: :249170. .1: :2000FEB01 208 282 forward 1 TM N in

10 LI: : 813218. .1: :2000FEB01 466 552 forward 1 TM N out

10 LI: :813218. .1: :2000FEB01 137 202 forward 2 TM N out

10 LI: :813218. .1: :2000FEB01 356 436 forward 2 TM N out

10 LI: :813218 .1: :2000FEB01 452 520 forward 2 TM N out

11 LI: :902522, .3: :2000FEB01 99 158 forward 3 TM N out

12 LI: :474304. .1: :2000FEB01 64 147 forward 1 TM N in

12 LI: :474304. .1: :2000FEB01 217 285 forward 1 TM N in

12 LI: :474304 .1: :2000FEB01 298 372 forward 1 TM N in

12 LI: :474304. .1: :2000FEB01 26 88 forward 2 TM N out

12 LI: :474304 .1 :2000FEB01 110 172 forward 2 TM N out

12 LI: :474304 .1 :2000FEB01 200 271 forward 2 TM N out

12 LI: :474304 .1 :2000FEB01 332 418 forward 2 TM N out

12 LI: :474304 .1 :2000FEB01 890 952 forward 2 TM N out

12 LI: :474304 .1 :2000FEB01 72 158 forward 3 TM N out

12 LI: :474304 .1 :2000FEB01 273 332 forward 3 TM N out

12 LI :474304 .1 :2000FEB01 330 383 forward 3 TM N out

12 LI :474304 .1 :2000FEB01 606 674 forward 3 TM N out

13 LI :027320 .1 :2000FEB01 544 603 forward 1 TM N out

13 LI :027320 .1 :2000FEB01 694 768 forward 1 TM N out Table 1 (cont.)

LI: 027320. 1: 2000FEB01 1102 1182 forward 1 TM N out

LI: 027320. 1: 2000FEB01 1180 1236 forward 1 TM N out

LI: 027320. .1: 2000FEB01 545 604 forward 2 TM

LI: 027320. .1: :2000FEB01 851 913 forward 2 TM

LI: 027320. .1: :2000FEB01 932 994 forward 2 TM

LI: 027320. .1: :2000FEB01 1013 1075 forward 2 TM

LI: 027320. .1: :2000FEB01 1172 1228 forward 2 TM

LI: 027320. .1: :2000FEB01 579 665 forward 3 TM N in

LI: 027320. .1: :2000FEB01 720 806 forward 3 TM N in

LI: 027320. .1: :2000FEB01 828 908 forward 3 TM N in

LI: 027320. .1: 2000FEB01 1020 1103 forward 3 TM N in

LI: 027320. ,1: :2000FEB01 1116 1202 forward 3 TM N in

LI: 228319. .1: :2000FEB01 76 162 forward 1 TM N out

LI: :228319. .1: :2000FEB01 119 187 forward 2 TM N in

LI: 228319. .1: :2000FEB01 506 592 forward 2 TM N in

LI: :228319. .1: :2000FEB01 63 149 forward 3 TM N in

LI: 228319. .1: :2000FEB01 369 455 forward 3 TM N in

LI: :228319. .1: :2000FEB01 708 770 forward 3 TM N in

LI: 228319. .1: :2000FEB01 786 848 forward 3 TM N in

LG: 197267. .2: :2000MAY19 11 88 forward 2 TM N in

LG: 197267. .2: :2000MAY19 200 271 forward 2 TM N in

LG: :403332. .1: :2000MAY19 352 417 forward 1 TM N in

LG: 403332. .1: :2000MAY19 490 552 forward 1 TM N in

LG: :403332. .1: :2000MAY19 562 624 forward 1 TM N in

LG: :403332, .1: :2000MAY19 721 783 forward 1 TM N in

LG: :403332. .1: :2000MAY19 796 858 forward 1 TM N in

LG: :403332 .1: :2000MAY19 871 948 forward 1 TM N in

LG: :403332 .1: :2000MAY19 1012 1098 forward 1 TM N in

LG: :403332. .1: :2000MAY19 1138 1188 forward 1 TM N in

LG: :403332, .1: :2000MAY19 1192 1278 forward 1 TM N in

LG: :403332 .1: :2000MAY19 1453 1530 forward 1 TM N in

LG: :403332 .1: :2000MAY19 365 427 forward 2 TM N in

LG: :403332^*. .1: :2000MAY19 521 607 forward 2 TM N in

LG: :403332 .1: :2000MAY19 644 727 forward 2 TM N in

LG: :403332 .1: :2000MAY19 800 886 forward 2 TM N in

LG: :403332 .1: :2000MAY19 911 973 forward 2 TM N in

LG: :403332 .1: :2000MAY19 986 1048 forward 2 TM N in

LG: :403332 .1: :2000MAY19 1211 1297 forward 2 TM N in

LG: :403332 .1: :2000MAY19 1445 1504 forward 2 TM N in

LG: :403332. .1: :2000MAY19 375 461 forward 3 TM

LG: :403332 .1 :2000MAY19 495 557 forward 3 TM

LG: :403332 .1: :2000MAY19 594 656 forward 3 TM

LG: : 403332 .1: :2000MAY19 681 767 forward 3 TM

LG: :403332 .1 :2000MAY19 990 1052 forward 3 TM

LG: :403332 .1 :2000MAY19 1077 1139 forward 3 TM

LG :403332 .1 :2000MAY19 1203 1274 forward 3 TM

LG :403332 .1 :2000MAY19 1332 1385 forward 3 TM

LG: :983076 .3 :2000MAY19 479 565 forward 2 TM N in

LG :983076 .3 .-2000MAY19 704 790 forward 2 TM N in

LG :983076 .3 :2000MAY19 114 200 forward 3 TM N out

LG :983076 .3 :2000MAY19 261 317 forward 3 TM N out

LG: :983076 .3 :2000MAY19 501 587 forward 3 TM N out

LG: :983076 .3 :2000MAY19 738 794 forward 3 TM N out

LG: :216612 .3 .^•2000MAY19 120 206 forward 3 TM N in

LG :216612 .3 :2000MAY19 234 284 forward 3 TM N in

LG :216612 .3 :2000MAY19 327 413 forward 3 TM N in

LG :216612 .3 :2000MAY19 444 530 forward 3 TM N in

LG :216612 .3 :2000MAY19 810 887 forward 3 TM N in

LG :322465 .1 :2000MAY19 239 319 forward 2 TM N out

LG :322465 .1 ^•.2000MAY19 276 329 forward 3 TM N out Tat>le 1 (cont.)

LG: 093477. 1:2000MAY19 25 Ill forward 1 TM N out

LG: 093477. 1:2000MAY19 11 85 forward 2 TM N out

LG: 093477. 1:2000MAY19 242 295 forward 2 TM N out

LG: 093477. 1:2000MAY19 24 110 forward 3 TM N in

LG: 093477. , 1:2000MAY19 657 719 forward 3 TM N in

LG: 222880. ,1:2000MAY19 211 297 forward 1 TM

LG: 222880. 1-.2000MAY19 1663 1749 forward 1 TM

LG: 222880. , 1:2000MAY19 1801 1863 forward 1 TM

LG: 222880. ,1:2000MAY19 1906 1968 forward 1 TM

LG: 222880. , 1-.2000MAY19 2269 2316 forward 1 TM

LG: 222880. ,1:2000MAY19 425 487 forward 2 TM N in

LG: 222880. 1:2000MAY19 506 568 forward 2 TM N in

LG: 222880. .1:2000MAY19 611 691 forward 2 TM N in

LG: 222880. .1:2000MAY19 698 784 forward 2 TM N in

LG: 222880. .1:2000MAY19 875 961 forward 2 TM N in

LG: 222880. , 1:2000MAY19 1016 1078 forward 2 TM N in

LG: 222880. .1-.2000MAY19 1106 1168 forward 2 TM N in

LG: 222880. .1:2000MAY19 1544 1630 forward 2 TM N in

LG: 222880. .1:2000MAY19 1691 1774 forward 2 TM N in

LG: 222880. ,1:2000MAY19 1940 2026 forward 2 TM N in

LG: 222880. .1-.2000MAY19 2315 2395 forward 2 TM N in

LG: 222880. .1:2000MAY19 1710 1784 forward 3 TM M out

LG: 222880. .1:2000MAY19 1809 1895 forward 3 TM N out

LG: 222880. .1:2000MAY19 1926 2009 forward 3 TM N out

LG: :222880. .1:2000MAY19 2064 2129 forward 3 TM N out

LG: :898320. .3:2000MAY19 151 237 forward 1 TM N out

LG: ;898320. .3:2000MAY19 478 534 forward 1 TM N out

LG: :898320. .3:2000MAY19 736 822 forward 1 TM N out

LG: : 898320, .3:2000MAY19 1528 1599 forward 1 TM N out

LG: :898320. .3:2000MAY19 1663 1710 forward 1 TM N out

LG: :898320. .3:2000MAY19 2017 2088 forward 1 TM N out

LG: :898320, .3:2000MAY19 2131 2184 forward 1 TM N out

LG: :898320 .3:2000MAY19 719 796 forward 2 TM N in

LG: :898320 .3:2000MAY19 1334 1420 forward 2 TM N in

LG: :898320, .3:2000MAY19 1598 1681 forward 2 TM N in

LG: :898320 .3:2000MAY19 1733 1819 forward 2 TM N in

LG: :898320 .3:2000MAY19 1919 1984 forward 2 TM N in

LG: :898320 .3.-2000MAY19 2078 2140 forward 2 TM N in

LG: :898320 .3:2000MAY19 2159 2245 forward 2 TM N in

LG: :898320 .3:2000MAY19 90 176 forward 3 TM N out

LG: :898320 .3:2000MAY19 411 485 forward 3 TM N out

LG: :898320 .3:2000MAY19 501 578 forward 3 TM N out

LG: :898320 .3:2000MAY19 600 686 forward 3 TM N out

LG: :898320 .3:2000MAY19 783 854 forward 3 TM N out

LG: :898320 -3:2000MAY19 912 989 forward 3 TM N out

LG: :898320 .3:2000MAY19 1023 1097 forward 3 TM N out

LG: :898320 .3-.2000MAY19 1164 1226 forward 3 TM N out

LG :898320 .3:2000MAY19 1236 1298 forward 3 TM N out

LG :898320 .3:2000MAY19 1335 1421 forward 3 TM N out

LG: :898320 -3-.2000MAY19 2016 2093 forward 3 TM N out

LG :898320 .3:2000MAY19 2151 2237 forward 3 TM N out

LG : 1327047.1:2000MAY19 466 552 forward 1 TM N out

LG : 1327047.1.-2000MAY19 137 202 forward 2 TM N out

LG: : 1327047.1 :2000MAY19 356 436 forward 2 TM N out

LG : 1327047.1:2000MAY19 452 520 forward 2 TM N out

LG : 1327047.1:2000MAY19 1131 1217 forward 3 TM

LG :235157 -21:2000MAY19 11 91 forward 2 TM N out

LG :235157 .21:2000MAY19 161 247 forward 2 TM N out

LG :235157 .21:2000MAY19 467 529 forward 2 TM N out

LG :235157 .21:2000MAY19 551 613 forward 2 TM N out Table 1 (cont.)

LG: 235157. 21 . :2000MAY19 686 760 forward 2 TM N out

LG: 235157. 2. . :2000MAY19 785 862 forward 2 TM N out

LG: 085713. 1: 2000MAY19 97 183 forward 1 TM N out

LG: 085713. 1: 2000MAY19 1489 1575 forward 1 TM N out

LG: 085713. 1: :2000MAY19 1786 1854 forward 1 TM W out

LG: 085713. 1: :2000MAY19 2275 2361 forward 1 TM N out

LG: 085713. 1: 2000MAY19 2407 2493 forward 1 TM N out

LG: 085713. 1: 2000MAY19 134 211 forward 2 TM N in

LG: 085713. 1: :2000MAY19 1481 1528 forward 2 TM N in

LG: 085713. 1: :2000MAY19 2099 2164 forward 2 TM N in

LG: 085713. 1: 2000MAY19 2387 2449 forward 2 TM N in

LG: 085713. 1: 2000MAY19 2474 2536 forward 2 TM N in

LG: 085713. 1: 2000MAY19 72 158 forward 3 TM W out

LG: 085713. ,1: ;2000MAY19 1488 1574 forward 3 TM N out

LG: 085713. 1: :2000MAY19 2037 2108 forward 3 TM N out

LG: 085713. 1: 2000MAY19 2184 2270 forward 3 TM N out

LG: 085713. 1: :2000MAY19 2346 2432 forward 3 TM N out

LG: 482421. .1: :2000MAY19 385 456 forward 1 TM N out

LG: 482421. .1: :2000MAY19 715 777 forward 1 TM N out

LG: 482421. .1: :2000MAY19 841 909 forward 1 TM N out

LG: 482421. .1: :2000MAY19 970 1056 forward 1 TM N out

LG: ;482421. .1: :2000MAY19 1222 1284 forward 1 TM N out

LG: :482421. .1: :2000MAY19 1423 1491 forward 1 TM N out

LG: :482421. .1: :2000MAY19 2185 2271 forward 1 TM N out

LG: : 482421. .1: :2000MAY19 2518 2604 forward 1 TM N out

LG: :482421. .1: :2000MAY19 2674 2760 forward 1 TM N out

LG: :482421. .1: :2000MAY19 11 64 forward 2 TM N out

LG: :482421. .1: :2000MAY19 260 346 forward 2 TM N out

LG: : 482421. .1: :2000MAY19 416 502 forward 2 TM N out

LG: : 482421. .1: :2000MAY19 506 586 forward 2 TM N out

LG: : 482421. .1: :2000MAY19 857 943 forward 2 TM N out

LG: :482421. .1: :2000MAY19 965 1021 forward 2 TM N out

LG: :482421. .1: :2000MAY19 1934 1987 forward 2 TM N out

LG: : 482421. .1: :2000MAY19 2120 2206 forward 2 TM N out

LG: : 482421, .1: :2000MAY19 2549 2635 forward 2 TM N out

LG: :482421, .1: :2000MAY19 2693 2773 forward 2 TM N out

LG: :482421. .1: :2000MAY19 12 65 forward 3 TM N out

LG: :482421, .1: :2000MAY19 258 332 forward 3 TM N out

LG: :482421 .1: :2000MAY19 603 689 forward 3 TM N out

LG: :482421. .1: :2000MAY19 690 773 forward 3 TM N out

LG: :482421, .1: :2000MAY19 822 905 forward 3 TM N out

LG: :482421 .1 :2000MAY19 972 1028 forward 3 TM N out

LG: :482421 .1 :2000MAY19 1074 1130 forward 3 TM N out

LG: :482421 .1 :2000MAY19 2403 2489 forward 3 TM N out

LG: :482421 .1 :2000MAY19 2550 2636 forward 3 TM N out

LG: .^•482421 .1 :2000MAY19 2673 2753 forward 3 TM N out

LG :330944 .4 :2000MAY19 389 475 forward 2 TM N out

LI :223060 .1 :2000MAY01 433 519 forward 1 TM N in

LI :223060 .1 :2000MAY01 1267 1353 forward 1 TM N in

LI :223060 .1 :2000MAY01 1639 1704 forward 1 TM N in

LI :223060 .1 :2000MAY01 1759 1842 forward 1 TM N in

LI :223060 .1 :2000MAY01 260 334 forward 2 TM N out

LI :223060 .1 :2000MAY01 938 1003 forward 2 TM N out

LI :223060 .1 :2000MAY01 1553 1639 forward 2 TM N out

LI :223060 .1 .-2000MAY01 1428 1514 forward 3 TM N out

LI :213087 .1 -.2000MAY01 732 818 forward 3 TM N in

LI :405330 .1 :2000MAY01 103 165 forward 1 TM

LI :405330 .1 :2000MAY01 406 492 forward 1 TM

LI :405330 .1 :2000MAY01 1276 1362 forward 1 TM

LI :405330 .1 :2000MAY01 1396 1449 forward 1 TM Table 1 (cont.)

LI: 405330. 1: 2000MAY01 1615 1674 forward 1 TM

LI: 405330. 1: 2000MAY01 1864 1917 forward 1 TM

LI: 405330. 1: :2000MAY01 1966 2016 forward 1 TM

LI: 405330. 1: :2000MAY01 2017 2097 forward 1 TM

LI: 405330. 1: :2000MAY01 2257 2319 forward 1 TM

LI: 405330. 1: :2000MAY01 2329 2397 forward 1 TM

LI: 405330. 1: ;2000MAY01 2416 2478 forward 1 TM

LI: 405330. 1: :2000MAY01 485 550 forward 2 TM N out

LI: :405330. 1: :2000MAY01 671 757 forward 2 TM N out

LI: ;405330. 1: :2000MAY01 1283 1357 forward 2 TM N out

LI: :405330. 1: :2000MAY01 1511 1579 forward 2 TM N out

LI: :405330. ,1: :2000MAY01 1877 1933 forward 2 TM N out

LI: :405330. ,1: :2000MAY01 2339 2395 forward 2 TM N out

LI: :405330. ,1: :2000MAY01 2411 2473 forward 2 TM N out

LI: :405330. .1: :2000MAY01 249 320 forward 3 TM N in

LI: :405330. .1: :2000MAY01 678 764 forward 3 TM N in

LI: :405330. .1: :2000MAY01 990 1070 forward 3 TM N in

LI: :405330. .1: :2000MAY01 1650 1721 forward 3 TM N in

LI: :405330. .1: :2000MAY01 2265 2351 forward 3 TM N in

LI: :405330. .1: :2000MAY01 2433 2513 forward 3 TM N in

LI: :350243. .2: :2000MAY01 3799 3852 forward 1 TM

LI: :350243. .2: :2000MAY01 4453 4533 forward 1 TM

LI: :350243, .2: :2000MAY01 5392 5460 forward 1 TM

LI: :350243, .2: :2000MAY01 5944 6030 forward 1 TM

LI: :350243, .2: :2000MAY01 6256 6333 forward 1 TM

LI: :350243, .2: :2000MAY01 7003 7071 forward 1 TM

LI: :350243, .2 :2000MAY01 7333 7398 forward 1 TM

LI: :350243, .2: :2000MAY01 7552 7626 forward 1 TM

LI: :350243, .2: :2000MAY01 7780 7845 forward 1 TM

LI: :350243, .2: :2000MAY01 7867 7923 forward 1 TM

LI: :350243 .2 :2000MAY01 7954 8025 forward 1 TM

LI: :350243 .2 :2000MAY01 8407 8490 forward 1 TM

LI: :350243 .2 :2000MAY01 4361 4447 forward 2 TM N out

LI; :350243, .2: :2000MAY01 4724 4807 forward 2 TM N out

LI :350243 .2 :2000MAY01 5402 5488 forward 2 TM N out

LI :350243 .2: :2000MAY01 5618 5668 forward 2 TM N out

LI: :350243 .2 :2000MAY01 5687 5767 forward 2 TM N out

LI :350243 .2 :2000MAY01 6263 6334 forward 2 TM N out

LI :350243 .2 :2000MAY01 6488 6574 forward 2 TM N out

LI :350243 .2 :2000MAY01 7610 7696 forward 2 TM N out

LI :350243 .2 :2000MAY01 7814 7900 forward 2 TM N out

LI :350243 .2 :2000MAY01 7991 8047 forward 2 TM N out

LI :350243 .2 :2000MAY01 8501 8587 forward 2 TM N out

LI :350243 .2 :2000MAY01 8699 8785 forward 2 TM N out

LI :350243 .2 .-2000MAY01 3975 4052 forward 3 TM N in

LI :350243 .2 :2000MAY01 5037 5108 forward 3 TM N in

LI :350243 .2 :2000MAY01 6090 6155 forward 3 TM N in

LI :350243 .2 :2000MAY01 6276 6338 forward 3 TM N in

LI :350243 .2 .-2000MAY01 6357 6419 forward 3 TM N in

LI :350243 .2 :2000MAY01 6492 6557 forward 3 TM N in

LI :350243 .2 :2000MAY01 7005 7055 forward 3 TM N in

LI :350243 .2 :2000MAY01 7185 7271 forward 3 TM N in

LI :350243 .2 :2000MAY01 7365 7439 forward 3 TM N in

LI :350243 .2 -.2000MAY01 7650 7727 forward 3 TM N in

LI :350243 .2 :2000MAY01 7818 7868 forward 3 TM N in

LI :350243 .2 :2000MAY01 7881 7949 forward 3 TM N in

LI :350243 .2 :2000MAY01 8445 8507 forward 3 TM N in

LI :350243 .2 :2000MAY01 8526 8585 forward 3 TM N in

LI : 445188 .1 :2000MAY01 10 63 forward 1 TM N in

LI .-445188 .1 :2000MAY01 169 240 forward 1 TM N in Table 1 (cont.)

32 LI 445188.-1:2000MAY01 337 408 forward 1 TM N in 32 LI 445188 .1:2000MAY01 406 471 forward 1 TM N in 32 LI 445188 .1:2000^'MAY01 796 861 forward 1 TM N in 32 LI 445188 .1:2000MAY01 967 1041 forward 1 TM N in 32 LI 445188 .1:2000MAY01 1135 1209 forward 1 TM N in 32 LI 445188..1:2000MAY01 1228 1314 forward 1 TM N in 32 LI 445188 .1:2000MAY01 1396 1473 forward 1 TM N in 32 LI 445188 .1:2000MAY01 131 217 forward 2 TM N in 32 LI 445188 .1.-2000MAY01 335 421 forward 2 TM N in 32 LI 445188 .1:2000MAY01 980 1042 forward 2 TM N in 32 LI 445188 .1:2000MAY01 1136 1189 forward 2 TM N in 32 LI 445188 .1:2000MAY01 1445 1522 forward 2 TM N in 32 LI 445188 .1:2000MAY01 12 59 forward 3 TM N out 32 LI 445188 .1:2000MAY01 135 221 forward 3 TM N out 32 LI 445188 .1:2000MAY01 258 344 forward 3 TM N out 32 LI 445188 .1:2000MAY01 351 431 forward 3 TM N out 32 LI 445188 .1:2000MAY01 573 650 forward 3 TM N out 32 LI 445188 .1-.2000MAY01 819 893 forward 3 TM N out 32 LI 445188 .1:2000MAY01 1008 1094 forward 3 TM N out 32 LI 445188 .1:2000MAY01 1149 1235 forward 3 TM N out 32 LI 445188 .1:2000MAY01 1695 1763 forward 3 TM N out ^•33 LI 244378 .1:2000MAY01 28 114 forward 1 TM N out 33 LI 244378 .1:2000MAY01 403 462 forward 1 TM N out 33 LI 244378 .1:2000MAY01 466 549 forward 1 TM N out 33 LI 244378 .1.-2000MAY01 1972 2058 forward 1 TM W out 33 LI 244378 .1:2000MAY01 11 76 forward 2 TM N in 33 LI 244378 .1:2000MAY01 401 487 forward 2 TM N in 33 LI 244378 -1:2000MAY01 533 619 forward 2 TM N in 33 LI 244378 .1:2000MAY01 1313 1369 forward 2 TM N in 33 LI 244378 .1:2000MAY01 1985 2035 forward 2 TM N in 33 LI 244378 .1:2000MAY01 24 86 forward 3 TM N out 33 LI 244378 .1:2000MAY01 108 170 forward 3 TM N out 33 LI 244378 .1:2000MAY01 1980 2045 forward 3 TM N out 34 LI 236574 .15-.2000MAY01 1 81 forward 1 TM N out 34 LI 236574 .15:2000MAY01 97 183 forward 1 TM N out 34 LI 236574 .15.-2000MAY01 95 166 forward 2 TM N out 34 LI 236574 .15:2000MAY01 239 325 forward 2 TM N out 34 LI 236574 .15:2000MAY01 93 155 forward 3 TM N in 35 LI 010100 .20:2000MAY01 43 96 forward 1 TM N in 35 LI 010100 .20:2000MAY01 169 255 forward 1 TM N in 35 LI 010100 .20:2000MAY01 328 399 forward 1 TM N in 35 LI 010100 .20:2000MAY01 658 720 forward 1 TM N in 35 LI 010100 .20:2000MAY01 742 804 forward 1 TM N in 35 LI 010100 .20:2000MAY01 910 996 forward 1 TM N in 35 LI 010100 .20:2000MAY01 1117 1203 forward 1 TM N in 35 LI 010100 .20:2000MAY01 1240 1317 forward 1 TM N in 35 LI 010100 .20:2000MAY01 1528 1611 forward 1 TM N in 35 LI 010100 .20-.2000MAY01 1822 1908 forward 1 TM N in 35 LI 010100 .20:2000MAY01 2206 2280 forward 1 TM N in 35 LI 010100 .20:2000MAY01 2671 2754 forward 1 TM N in 35 LI 010100 .20:2000MAY01 2899 2973 forward 1 TM N in 35 LI 010100 .20:2000MAY01 3037 3123 forward 1 TM N in 35 LI 010100 -20:2000MAY01 3349 3435 forward 1 TM N in 35 LI 010100 .20:2000MAY01 26 109 forward 2 TM N in 35 LI 010100 .20:2000MAY01 146 232 forward 2 TM N in 35 LI 010100 -20:2000MAY01 530 592 forward 2 TM N in 35 LI 010100 .20.-2000MAY01 743 796 forward 2 TM N in 35 LI 010100 .20:2000MAY01 953 1039 forward 2 TM N in 35 LI 010100 -20:2000MAY01 1154 1207 forward 2 TM N in 35 LI 010100 .20:2000MAY01 1274 1360 forward 2 TM N in Table 1 (cont.)

35 LI 010100. 20:2000MAY01 1364 1435 forward 2 TM N in 35 LI 010100.20:2000MAY01 1544 1630 forward 2 TM N in 35 LI 010100.20:2000MAY01 1748 1822 forward 2 TM N in 35 LI 010100.20:2000MAY01 1922 2008 forward 2 TM N in 35 LI 010100.20:2000MAY01 2354 2440 forward 2 TM N in 35 LI 010100.20:2000MAY01 2663 2731 forward 2 TM N in 35 LI 010100.20:2000MAY01 2732 2818 forward 2 TM N in 35 LI 010100.20:2000MAY01 3287 3373 forward 2 TM N in 35 LI 010100.20:2000MAY01 3386 3472 forward 2 TM N in 35 LI 010100.20:2000MAY01 141 227 forward 3 TM 35 LI 010100.20:2000MAY01 375 452 forward 3 TM 35 LI 010100.20:2000MAY01 768 824 forward 3 TM 35 LI 010100.20.-2000MAY01 969 1049 forward 3 TM 35 LI 010100..20:2000MAY01 1146 1214 forward 3 TM 35 LI 010100..20:2000MAY01 1281 1367 forward 3 TM 35 LI 010100..20:2000MAY01 1590 1652 forward 3 TM 35 LI 010100..20:2000MAY01 1704 1766 forward 3 TM 35 LI 010100..20:2000MAY01 1908 1976 forward 3 TM 35 LI 010100..20-.2000MAY01 2208 2294 forward 3 TM 35 LI 010100..20.-2000MAY01 2700 2762 forward 3 TM 35 LI 010100..20.-2000MAY01 2781 2843 forward 3 TM 35 LI 010100.-20:2000MAY01 2862 2924 forward 3 TM 35 LI 010100..20:2000MAY01 2946 3020 forward 3 TM 35 LI 010100..20:2000MAY01 3051 3131 forward 3 TM 35 LI 010100..20:2000MAY01 3135 3206 forward 3 TM 35 LI 010100..20:2000MAY01 3324 3389 forward 3 TM 36 LI 037940..6:2000MAY01 163 249 forward 1 TM N in 36 LI 037940..6:2000MAY01 14 100 forward 2 TM 36 LI 037940..6:2000MAY01 161 247 forward 2 TM 36 LI 037940..6:2000MAY01 365 451 forward 2 TM 36 LI 037940..6:2000MAY01 12 92 forward 3 TM N out 36 LI 037940..6:2000MAY01 387 473 forward 3 TM N out 37 LI 228550..3.-2000MAY01 1537 1602 forward 1 TM N in 37 LI 228550..3:2000MAY01 1603 1680 forward 1 TM N in 37 LI 228550..3.-2000MAY01 1846 1899 forward 1 TM N in 37 LI 228550..3:2000MAY01 4165 4239 forward 1 TM N in 37 LI 228550..3:2000MAY01 4549 4629 forward 1 TM N in 37 LI 228550..3:2000MAY01 4651 4737 forward 1 TM N in 37 LI 228550..3:2000MAY01 5371 5430 forward 1 TM N in 37 LI 228550..3:2000MAY01 7300 7362 forward 1 TM N in 37 LI 228550..3:2000MAY01 7408 7470 forward 1 TM N in 37 LI 228550.3:2000MAY01 7582 7659 forward 1 TM N in 37 LI 228550.3:2000MAY01 1622 1678 forward 2 TM N in 37 LI 228550.3:2000MAY01 1718 1804 forward 2 TM N in 37 LI 228550.3:2000MAY01 1841 1927 forward 2 TM N in 37 LI 228550.3:2000MAY01 1976 2038 forward 2 TM N in 37 LI 228550.3:2000MAY01 2066 2128 forward 2 TM N in 37 LI 228550.3.-2000MAY01 2150 2236 forward 2 TM N in 37 LI 228550.3:2000MAY01 2546 2608 forward 2 TM N in 37 LI 228550.3:2000MAY01 3746 3829 forward 2 TM N in 37 LI 228550.3:2000MAY01 4457 4543 forward 2 TM N in 37 LI 228550.3:2000MAY01 4724 4810 forward 2 TM N in 37 LI 228550.3:2000MAY01 7229 7303 forward 2 TM N in 37 LI 228550.3:2000MAY01 7637 7723 forward 2 TM N in 37 LI 228550.3:2000MAY01 3978 4031 forward 3 TM N in 37 LI 228550.3:2000MAY01 4362 4424 forward 3 TM N in 37 LI 228550.3:2000MAY01 4440 4502 forward 3 TM N in 37 LI 228550.3:2000MAY01 4575 4637 forward 3 TM N in 37 LI 228550.3:2000MAY01 4671 4733 forward 3 TM N in 37 LI 228550.3:2000MAY01 5070 5135 forward 3 TM N in Table 1 (cont.)

LI: 228550.3 -.2000MAY01 6963 7049 forward 3 TM N in

LI: 228550.3 :2000MAY01 7308 7361 forward 3 TM N in

LI: :228550.3:2000MAY01 7482 7535 forward 3 TM N in

LI: : 228550.3 :2000MAY01 7617 7703 forward 3 TM N in

LI: : 027320.1:2000MAY01 637 723 forward 1 TM N in

LI: :027320.1:2000MAY01 796 882 forward 1 TM N in

LI: : 027320.1:2000MAY01 970 1050 forward 1 TM N in

LI: :027320.1:2000MAY01 1081 1167 forward 1 TM N in

LI: :027320.1:2000MAY01 692 778 forward 2 TM N in

LI: : 027320.1:2000MAY01 857 928 forward 2 TM N in

LI: : 027320.1:2000MAY01 932 1012 forward 2 TM N in

LI: :027320.1:2000MAY01 1079 1165 forward 2 TM N in

LI: :027320.1:2000MAY01 1220 1306 forward 2 TM N in

LI: : 027320.1:2000MAY01 1032 1118 forward 3 TM N out

LI: :027320.1:2000MAY01 1128 1190 forward 3 TM N out

LI: :027320.1:2000MAY01 1242 1292 forward 3 TM N out

LI: :321475.1:2000MAY01 610 681 forward 1 TM N out

LI: :321475.1:2000MAY01 1081 1167 forward 1 TM N out

LI: : 321475.1:2000MAY01 1207 1284 forward 1 TM N out

LI: ;321475.1:2000MΑY01 125 187 forward 2 TM N out

LI: :321475.1:2000MAY01 200 262 forward 2 TM N out

LI: : 321475.1:2000MAY01 356 442 forward 2 TM N out

LI: :321475.1:2000MAY01 641 727 forward 2 TM N out

LI: : 321475.1:2000MAY01 791 877 . forward 2 TM N out

LI: :321475.1:2000MAY01 920 982 forward 2 TM N out

LI: : 321475.1:2000MAY01 1013 1075 forward 2 TM N out

LI: : 321475.1:2000MAY01 1124 1186 forward 2 TM N out

LI: :321475.1:2000MAY01 1202 1264 forward 2 TM N out

LI: :321475.1:2000MAY01 1409 1495 forward 2 TM N out

LI: :321475.1:2000MAY01 822 908 forward 3 TM N in

LI: :321475.1:2000MAY01 1125 1208 forward 3 TM N in

LI: : 899552.5 :2000MAY01 286 351 forward 1 TM N in

LI: : 899552.5 :2000MAY01 970 1056 forward 1 TM N in

LI: : 899552.5 :2000MAY01 1114 1176 forward 1 TM N in

LI: :899552.5:2000MAY01 1900 1947 forward 1 TM N in

LI: :899552.5:2000MAY01 1079 1165 forward 2 TM N in

LI: : 899552.5 :2000MAY01 1691 1765 forward 2 TM N in

LI: :899552.5:2000MAY01 834 896 forward 3 TM N in

LI: :899552.5:2000MAY01 915 977 forward 3 TM N in

LI: : 899552.5 :2000MAY01 996 1058 forward 3 TM N in

LI: :1071848.1:2000MAY01 961 1020 forward 1 TM N out

LI: : 1071848.1: 2000MAY01 1117 1194 forward 1 TM N out

LI: : 1071848.1:2000MAY01 1058 1144 forward 2 TM N out

LI: : 1071848.1:2000MAY01 996 1067 forward 3 TM N in

LI: : 1071848.1:2000MAY01 1080 1142 forward 3 TM N in

LI : 1071848.1-.2000MAY01 1155 1217 forward 3 TM N in

LI: :1072337.2:2000MAY01 49 135 forward 1 TM N out

LI :1072337.2:2000MAY01 463 525 forward 1 TM N out

LI :1072337.2:2000MAY01 652 726 forward 1 TM N out

LI :1072337.2:2000MAY01 2344 2397 forward 1 TM N out

LI :1072337.2:2000MAY01 2518 2589 forward 1 TM N out

LI :1072337.2:2000MAY01 2614 2667 forward 1 TM N out

LI :1072337.2:2000MAY01 2923 3000 forward 1 TM N out

LI : 1072337.2: 2000MAY01 3181 3252 forward 1 TM N out

LI :1072337.2:2000MAY01 3577 3657 forward 1 TM N out

LI : 1072337.2 :2000MAY01 4264 4344 forward 1 TM N out

LI : 1072337.2 :2000MAY01 77 136 forward 2 TM N out

LI :1072337.2:2000MAY01 230 316 forward 2 TM N out

LI : 1072337.2 :2000MAY01 1997 2047 forward 2 TM N out

LI : 1072337.2 :2000MAY01 2057 2125 forward 2 TM N out Table 1 (coπt.)

LI: 1072337 .2 2000MAY01 2609 2686 forward 2 TM N out

LI: 1072337 .2 2000MAY01 2861 2914 forward 2 TM N out

LI. 1072337 .2 2000MAY01 3242 3328 forward 2 TM N out

LI: 1072337 .2 2000MAY01 3440 3496 forward 2 TM N out

LI- 1072337 .2 2000MAY01 3587 3673 forward 2 TM N out

LI 1072337 .2 2000MAY01 4391 4468 forward 2 TM N out

LI- 1072337 .2 2000MAY01 2382 2435 forward 3 TM N in

LI 1072337 .2 2000MAY01 2529 2594 forward 3 TM N in

LI 1072337 .2 2000MAY01 2877 2948 forward 3 TM N in

LI- 1072337 .2 2000MAY01 2994 3065 forward 3 TM N in

LI 1072337 .2 2000MAY01 3618 3695 forward 3 TM N in

LI 107233^ .2 ^•2000MAY01 4386 4460 forward 3 TM N in

LI- 251489. 5:2000MAY01 31 117 forward 1 TM N out

LI 251489. 5:2000MAY01 44 130 forward 2 TM N out

LI 902018. 107:2000MAY01 595 681 forward 1 TM N out

LI 902018. 107:2000MAY01 1429 1515 forward 1 TM N out

LI 902018. 107:2000MAY01 2098 2184 forward 1 TM N out

LI 902018. 107:2000MAY01 2341 2409 forward 1 TM N out

LI 902018. 107:2000MAY01 2833 2895 forward 1 TM N out

LI 902018. 107:2000MAY01 2926 2988 forward 1 TM N out

LI 902018. 107:2000MAY01 3616 3666 forward 1 TM N out

LI 902018. 107:2000MAY01 3766 3837 forward 1 TM N out

LI 902018. 107:2000MAY01 3937 3990 forward 1 TM N out

LI 902018. 107:2000MAY01 2675 2761 forward 2 TM N in

LI 902018 107:2000MAY01 3611 3697 forward 2 TM N in

LI 902018 107:2000MAY01 4043 4117 forward 2 TM N in

LI 902018 107:2000MAY01 4151 4237 forward 2 TM N in

LI 902018. 107:2000MΛY01 3057 3143 forward 3 TM N in

LI 902018 107:2000MAY01 3555 3638 forward 3 TM N in

LI 902018 107:2000MAY01 3681 3734 forward 3 TM N in

LI 902018. 107:2000MAY01 3915 3977 forward 3 TM N in

LI 902018 107-.2000MAY01 4002 4064 forward 3 TM N in

LI 902018 107:2000MAY01 4080 4160 forward 3 TM N in

LI 902018. 107:2000MAY01 4170 4226 forward 3 TM N in

LI 220495 1:2000MAY01 91 150 forward 1 TM N out

LI 220495. 1.-2000MAY01 205 291 forward 1 TM N out

LI 220495 1:2000MAY01 499 579 forward 1 TM N out

LI 220495 1:2000MAY01 637 699 forward 1 TM N out

LI 220495 1:2000MAY01 718 780 forward 1 TM N out

LI 220495 1:2000MAY01 853 936 forward 1 TM N out

LI 220495 1:2000MAY01 994 1080 forward 1 TM N out

LI 220495 1:2000MAY01 1513 1590 forward 1 TM N out

LI 220495 1:2000MAY01 1591 1671 forward 1 TM N out

LI 220495 1-.2000MAY01 1702 1788 forward 1 TM N out

LI ^■220495 1:2000MAY01 1939 2022 forward 1 TM N out

LI .220495 1:2000MAY01 2344 2430 forward 1 TM N out

LI :220495 1:2000MAY01 2542 2592 forward 1 TM N out

LI :220495 1:2000MAY01 779 832 forward 2 TM N in

LI :220495 1:2000MAY01 851 916 forward 2 TM N in

LI :220495 1-.2000MAY01 1418 1504 forward 2 TM N in

LI :220495 1:2000MAY01 1589 1642 forward 2 TM N in

LI :220495 1:2000MAY01 1682 1768 forward 2 TM N in

LI :220495 1-.2000MAY01 1823 1885 forward 2 TM N in

LI :220495 1:2000MAY01 1898 1960 forward 2 TM N in

LI :220495 1:2000MAY01 2894 2974 forward 2 TM N in

LI .-220495 1:2000MAY01 486 536 forward 3 TM N in

LI :220495 1.-2000MAY01 618 677 forward 3 TM N in

LI :220495 1:2000MAY01 960 1034 forward 3 TM N in

LI :220495 1:2000MAY01 1692 1751 forward 3 TM N in

LI :220495 1: 2000MAY01 1812 1895 forward 3 TM N in Table 1 (cont*•)

LI:220495 .1:2000MAY01 1932 1991 forward TM N in LI:220495.1-.2000MAY01 2307 2366 forward TM N in LI: 220495.1:2000MAY01 2391 2462 forward TM N in LI:220495.1:2000MAY01 2835 2921 forward TM N in LI:220495.1:2000MAY01 2970 3056 forward TM N in LI:399478.1:2000MAY01 823 885 forward TM N in LI:399478.1:2000MAY01 982 1059 forward TM N in LI:399478.1:2000MAY01 1087 1173 forward TM N in LI:399478.1:2000MAY01 1330 1416 forward TM N in LI:399478.1:2000MAY01 1639 1716 forward TM N in LI:399478.1:2000MΛY01 1756 1836 forward TM N in LI-.399478.1-.2000MAY01 1849 1899 forward TM N in LI:399478.1:2000MAY01 2497 2574 forward TM N in LI .-399478.1.-2000MAY01 2716 2772 forward TM N in LI:399478.1:2000MAY01 107 178 forward TM N out LI:399478.1:2000MAY01 1025 1087 forward TM N out LI:399478.1:2000MAY01 1103 1165 forward TM N out LI:399478.1:2000MAY01 1640 1702 forward TM N out LI:399478.1:2000MAY01 1718 1780 forward TM N out LI:399478.1:2000MAY01 2063 2149 forward TM N out LI:399478.1:2000MΛY01 519 605 forward TM N in LI-.399478.1:2000MAY01 834 914 forward TM N in LI:399478.1:2000MΛY01 1014 1076 forward TM N in LI:399478.1:2000MΛY01 1101 1163 forward TM N in LI:399478.1:2000MAY01 1386 1439 forward TM N in LI:399478.1:2000MAY01 1509 1595 forward TM N in LI:399478.1:2000MAY01 1659 1745 forward TM N in LI:399478.1:2000MAY01 1803 1886 forward TM N in LI:399478.1:2000MAY01 2583 2669 forward TM N in LI --229648.2.-2000MAY01 556 606 forward TM LI:229648.2:2000MAY01 1009 1095 forward TM LI:229648.2:2000MAY01 1324 1410 forward TM LI:229648.2:2000MAY01 1633 1719 forward TM LI:229648.2:2000MAY01 1840 1914 forward 1 TM LI:229648.2:2000MAY01 776 832 forward 2 TM N in LI:229648.2:2000MAY01 983 1069 forward TM N in LI:229648.2:2000MAY01 1610 1663 forward TM KT in LI:229648.2:2000MAY01 1862 1921 forward TM N in LI:229648.2:2000MAY01 726 812 forward TM N in LI:229648.2:2000MAY01 1002 1088 forward TM N in LI:229648.2:2000MAY01 1533 1589 forward TM N in LI-.229648 -2:2000MAY01 1641 1727 forward TM N in LI:229648.2:2000MAY01 1809 1895 forward TM N in LI:025643.2:2000MAY01 1526 1591 forward TM LI:025643.2:2000MAY01 1542 1598 forward TM N out LI:233942.1:2000MAY01 184 270 forward TM N out LI:233942.1:2000MAY01 541 627 forward TM N out LI:233942.1:2000MAY01 671 745 forward TM N out LI:233942.1:2000MAY01 1352 1438 forward TM N out LI:233942.1:2000MAY01 1715 1768 forward TM N out LI:233942.1:2000MAY01 2021 2104 forward TM N out LI:233942.1:2000MAY01 138 221 forward TM N in LI:233942.1:2000MAY01 558 614 forward TM N in LI:233942.1:2000MAY01 684 758 forward TM N in LI-.233942.1:2000MAY01 1179 1256 forward TM N in LI:233942.1:2000MAY01 1986 2057 forward TM N in LI .-089158.1:2000MAY01 2443 2526 forward TM N out LI:089158.1:2000MAY01 2602 2652 forward TM N out LI -.089158.1:2000MAY01 3772 3858 forward TM N out LI:089158.1:2000MAY01 1052 1120 forward TM N in Table 1 (cont.)

LI: 089158.1:2000MAY01 1523 1597 forward 2 TM N in

LI: 089158.1:2000MAY01 1643 1729 forward 2 TM N in

LI: 089158.1-.2000MAY01 2396 2476 forward 2 TM N in

LI: 089158.1:2000MAY01 3335 3421 forward 2 TM N in

LI: :089158.1:2000MAY01 1020 1100 forward 3 TM N in

LI: 089158.1:2000MAY01 1497 1583 forward 3 TM N in

LI: 089158.1:2000MAY01 1722 1790 forward 3 TM N in

LI: :089158.1:2000MAY01 3069 3146 forward 3 TM N in

LI: :101046.1:2000MAY01 292 378 forward 1 TM N out

LI: :101046.1:2000MAY01 811 897 forward 1 TM N out

LI: :101046.1:2000MAY01 1261 1308 forward 1 TM N out

LI: ; 101046.1:2000MAY01 368 451 forward 2 TM N in

LI: :101046.1:2000MAY01 827 913 forward 2 TM N in

LI: :101046.1:2000MAY01 2102 2188 forward 2 TM N in

LI: : 101046.1:2000MAY01 711 785 forward 3 TM N out

LI: :101046.1:2000MAY01 873 932 forward 3 TM N out

LI: :101046.1:2000MAY01 1002 1079 forward 3 TM N out

LI: :368676.2:2000MAY01 2077 2163 forward 1 TM

LI: :368676.2:2000MAY01 3079 3165 forward 1 TM

LI: :368676.2:2000MAY01 2984 3058 forward 2 TM N in

LI: :368676.2:2000MAY01 2937 3023 forward 3 TM

LI: :238713.1:2000MAY01 844 930 forward 1 TM

LI: :238713.1:2000MAY01 110 184 forward 2 TM N out

LI: :238713.1:2000MAY01 194 256 forward 2 TM N out

LI: :238713.1:2000MAY01 728 814 forward 2 TM N out

LI: :238713.1:2000MAY01 297 383 forward 3 TM N out

LI: :238713.1:2000MAY01 423 485 forward 3 TM N out

LI: : 238713.1:2000MAY01 570 656 forward 3 TM N out

LI: :238713.1:2000MAY01 696 782 forward 3 TM N out

LI: :238713.1:2000MAY01 1101 1154 forward 3 TM N out

LI: :238713.1:2000MAY01 1635 1721 forward 3 TM N out

LI: :720928.1:2000MAY01 208 264 forward 1 TM N out

LI: :720928.1:2000MAY01 637 693 forward 1 TM N out

LI: :221874.1:2000MAY01 877 954 forward 1 TM N out

LI: :221874.1:2000MAY01 2086 2172 forward 1 TM N out

LI: : 221874.1:2000MAY01 1187 1258 forward 2 TM N out

LI: :221874.1:2000MAY01 2171 2230 forward 2 TM W out

LI: :221874.1:2000MAY01 348 434 forward 3 TM N in

LI: :221874.1:2000MAY01 1116 1190 forward 3 TM N in

LI : 1143545.3 :2000MAY01 458 523 forward 2 TM

LI : 1143545.3 -.2000MAY01 2144 2230 forward 2 TM

LI: : 1143605.1:2000MAY01 349 435 forward 1 TM N in

LI: :1143605.1:2000MAY01 445 528 forward 1 TM N in

LI : 1143605.1:2000MAY01 544 624 forward 1 TM N in

LI : 1143605.1 : 2000MAY01 775 861 forward 1 TM W in

LI : 1143605.1 : 2000MAY01 1102 1188 forward 1 TM N in

LI : 1143605.1:2000MAY01 1240 1302 forward 1 TM N in

LI : 1143605.1:2000MAY01 1378 1464 forward 1 TM N in

LI : 1143605.1:2000MAY01 1726 1800 forward 1 TM N in

LI : 1143605.1:2000MAY01 1828 1890 forward 1 TM N in

LI :1143605.1:2000MAY01 1918 1980 forward 1 TM N in

LI : 1143605.1:2000MAY01 17 82 forward 2 TM N out

LI : 1143605.1 : 2000MAY01 368 445 forward 2 TM N out

LI :1143605.1:2000MAY01 632 718 forward 2 TM N out

LI : 1143605.1-.2000MAY01 899 958 forward 2 TM N out

LI : 1143605.1 : 2000MAY01 1043 1102 forward 2 TM N out

LI : 1143605.1:2000MAY01 1157 1243 forward 2 TM N out

LI : 1143605.1:2000MAY01 1607 1681 forward 2 TM N out

LI : 1143605.1 : 2000MAY01 1766 1849 forward 2 TM N out

LI : 1143605.1.-2000MAY01 1859 1927 forward 2 TM N out Table 1 (cont.) I: 1143605.1:2000MAY01 1940 1999 forward 2 TM N out I: 1143605.1 : 2000MAY01 351 437 forward 3 TM N out I: 1143605.1 -.2000MAY01 513 584 forward 3 TM M out I: 1143605.1:2000MAY01 735 821 forward 3 TM N out I: 1143605.1:2000MAY01 1326 1412 forward 3 TM N out I: 1143605.1:2000MAY01 1446 1526 forward 3 TM N out I: 1143605.1:2000MAY01 1605 1688 forward 3 TM N out

LI: 1143605.1:2000MAY01 1806 1868 forward 3 TM N out I: 1143605.1:2000MAY01 1893 1955 forward 3 TM KT out

LI: 474069.7 :2000MAY01 706 783 forward 1 TM I: 474069.7:2000MAY01 1366 1428 forward 1 TM I: 474069.7 :2000MAY01 1738 1824 forward 1 TM I: 474069.7 -.2000MAY01 698 748 forward 2 TM N in I: 474069.7 :2000MAY01 965 1051 forward 2 TM N in

LI: 474069.7 :2000MAY01 1241 1300 forward 2 TM N in

LI: 474069.7 :2000MAY01 1487 1537 forward 2 TM N in

LI: 474069.7 :2000MAY01 2030 2107 forward 2 TM N in

LI: 474069.7 :2000MAY01 27 92 forward 3 TM N in

LI: 474069.7.-2000MAY01 699 785 forward 3 TM N in

LI: 474069.7 :2000MAY01 936 1001 forward 3 TM N in

LI: 474069.7 :2000MAY01 1929 2003 forward 3 TM N in

LI: 245193.3 :2000MAY01 1195 1275 forward 1 TM N in

LI: 245193.3 :2000MAY01 1579 1656 forward 1 TM N in

LI: 245193.3 :2000MAY01 1789 1860 forward 1 TM N in

LI: 245193.3 :2000MAY01 2029 2091 forward 1 TM N in

LI: 245193.3 :2000MAY01 1562 1621 forward 2 TM N in

LI: 245193.3 :2000MAY01 1880 1957 forward 2 TM N in

LI: 245193.3 :2000MAY01 2156 2206 forward 2 TM N in

LI: 245193.3 :2000MAY01 2513 2575 forward 2 TM N in

LI: 245193.3 :2000MAY01 2591 2653 forward 2 TM N in

LI: 245193.3 :2000MAY01 2669 2731 forward 2 TM N in

LI: 245193.3 :2000MAY01 1548 1634 forward 3 TM N in

LI: 245193.3.-2000MAY01 1659 1745 forward 3 TM N in

LI: 245193.3 :2000MAY01 2154 2231 forward 3 TM N in

LI: 245193.3 :2000MAY01 2364 2450 forward 3 TM N in

LI: 245193.3 :2000MAY01 2571 2618 forward 3 TM N in

LI: 245193.3 :2000MAY01 2649 2735 forward 3 TM N in

LI: 403872.1:2000MAY01 562 624 forward 1 TM

LI: 403872.1:2000MAY01 730 780 forward 1 TM

LI: 403872.1:2000MAY01 1498 1575 forward 1 TM

LI: 403872.1:2000MAY01 1648 1722 forward 1 TM

LI: 403872.1-.2000MAY01 2359 2433 forward 1 TM

LI::403872.1:2000MAY01 371 454 forward 2 TM N in

LI: 403872.1:2000MAY01 731 781 forward 2 TM N in

LI: 403872.1:2000MAY01 956 1012 forward 2 TM N in

LI: 403872.1:2000MAY01 1106 1192 forward 2 TM N in

LI: 403872.1:2000MAY01 1541 1600 forward 2 TM N in

LI: 403872.1:2000MAY01 1661 1747 forward 2 TM N in

LI: 403872.1:2000MAY01 1994 2050 forward 2 TM N in

LI::403872.1:2000MAY01 2261 2332 forward 2 TM N in

LI: 403872.1:2000MAY01 2357 2443 forward 2 TM N in

LI: 403872.1:2000MAY01 543 629 forward 3 TM N out

LI::403872.1:2000MAY01 708 782 forward 3 TM N out

LI: 403872.1:2000MAY01 1530 1601 forward 3 TM N out

LI::403872.1:2000MAY01 1656 1715 forward 3 TM N out

LI: 403872.1:2000MAY01 1983 2069 forward 3 TM N out

LI:: 403872.1: 2000MAY01 2145 2225 forward 3 TM N out

LI: 403872.1:2000MAY01 2226 2309 forward 3 TM N out

LI: : 403872.1:2000MAY01 2349 2426 forward 3 TM N out

LI:: 1086294.1:2000MAY01 748 834 forward 1 TM N out Table 1 (cont.) LI : 1086294 . 1 : 2000MAY01 2278 2352 forward 1 TM N out LI:1086294.1:2000MAY01 2306 2356 forward 2 TM N out LI:337514.3:2000MAY01 1906 1992 forward 1 TM N in LI:337514.3:2000MAY01 1512 1598 forward 3 TM N out LI:230711.1:2000MAY01 898 978 forward 1 TM N out LI:230711.1:2000MAY01 1327 1389 forward 1 TM N out LI:230711.1:2000MAY01 2059 2145 forward 1 TM N out LI:230711.1:2000MAY01 134 220 forward 2 TM N out LI:230711.1:2000MAY01 1517 1591 forward 2 TM N out LI:230711.1:2000MAY01 1631 1708 forward 2 TM N out LI:230711.1:2000MAY01 2033 2119 forward 2 TM N out LI:230711.1:2000MAY01 114 188 forward 3 TM N in LI:230711.1:2000MAY01 570 620 forward 3 TM N in LI: 230711.1:2000MAY01 648 716 forward 3 TM N in LI: 230711.1:2000MAY01 1101 1160 forward 3 TM N in LI:040338.2:2000MAY01 794 880 forward 2 TM N in LI:040338.2:2000MAY01 162 233 forward 3 TM N out LI:040338.2:2000MAY01 708 791 forward 3 TM N out LI:399174.2:2000MAY01 622 693 forward 1 TM LI.-399174.2.-2000MAY01 958 1008 forward 1 TM LI:399174.2:2000MAY01 1027 1080 forward 1 TM LI:399174.2:2000MAY01 1303 1377 forward 1 TM LI:399174.2:2000MAY01 965 1018 forward 2 TM N in LI:399174.2:2000MAY01 126 200 forward 3 TM N out LI:197275.5:2000MAY01 211 285 forward 1 TM N out LI:197275.5:2000MAY01 761 811 forward 2 TM N out LI.-197275.5.-2000MAY01 210 281 forward 3 TM N out LI:197275.5:2000MΑY01 537 623 forward 3 TM N out LI:336872.1:2000MAY01 175 231 forward 1 TM N out LI:336872.1:2000MAY01 1099 1185 forward 1 TM N out LI:336872.1:2000MAY01 1450 1536 forward 1 TM N out LI:336872.1:2000MAY01 182 247 forward 2 TM N in LI: 336872.1.-2000MAY01 1001 1072 forward 2 TM N in LI:336872.1:2000MAY01 1169 1246 forward 2 TM N in LI: 336872.1:2000MAY01 1373 1447 forward 2 TM N in LI:336872.1:2000MAY01 171 224 forward 3 TM N out LI:336872.1:2000MAY01 1089 1175 forward 3 TM N out LI: 336872.1:2000MAY01 1302 1364 forward 3 TM N out LI: 1092901.1:2000MAY01 172 258 forward 1 TM N out LI: 1092901.1:2000MAY01 299 379 forward 2 TM N out LI:1092901.1:2000MAY01 425 511 forward 2 TM N out LI:022387.5:2000MAY01 1195 1281 forward 1 TM N out LI:022387.5:2000MAY01 710 796 forward 2 TM N out LI:022387.5:2000MAY01 1214 1276 forward 2 TM N out LI:022387.5:2000MAY01 675 743 forward 3 TM N out LI:022387.5:2000MAY01 1092 1175 forward 3 TM M out LI:022387.5:2000MAY01 1215 1301 forward 3 TM N out LI.-1188334.1.-2000MΛY01 208 294 forward 1 TM M out LI:1188334.1:2000MAY01 370 456 forward 1 TM N out LI: 1188334.1:2000MAY01 11 82 forward 2 TM N out LI:1188334.1:2000MAY01 131 190 forward 2 TM N out LI:1188334.1:2000MAY01 12 80 forward 3 TM N in LI:1188334.1:2000MAY01 123 194 forward 3 TM N in LI:1188664.1:2000MAY01 274 348 forward 1 TM N in LI:1188664.1:2000MAY01 607 657 forward 1 TM N in LI:1188664.1:2000MAY01 254 304 forward 2 TM N in LI:1188664.1:2000MAY01 494 580 forward 2 TM N in LI:247388.1:2000MAY01 1126 1212 forward 1 TM N out LI:247388.1:2000MAY01 134 220 forward 2 TM N in LI:247388.1:2000MAY01 389 448 forward 2 TM N in Table 1 (cont.)

72 LI: 247388.1 :2000MAY01 968 1033 forward 2 TM N in

72 LI: 247388.1 :2000M&Y01 741 812 forward 3 TM Kf in

72 LI: 247388.1 :2000MAY01 1200 1277 forward 3 TM N in

73 LI: 816339.4 :2000MAY01 466 534 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 562 648 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 937 1017 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 1162 1248 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 1306 1368 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 1390 1452 forward 1 TM N in

73 LI: 816339.4 :2000MAY01 407 487 forward 2 TM N out

73 LI: 816339.4 :2000MAY01 575 652 forward 2 TM N out

73 LI: 816339.4 :2000MAY01 698 784 forward 2 TM N out

73 LI: :816339.4 :2000MAY01 950 1012 forward 2 TM N out

73 LI: 816339.4 :2000MAY01 1043 1105 forward 2 TM N out

73 LI: ;816339.4 :2000MAY01 1136 1198 forward 2 TM N out

73 LI: 816339.4 :2000MAY01 1244 1306 forward 2 TM N out

73 LI: 816339.4 :2000MAY01 1334 1396 forward 2 TM N out

73 LI: :816339.4 :2000MAY01 1424 1486 forward 2 TM N out

73 LI: :816339.4 :2000MAY01 468 554 forward 3 TM N out

73 LI: :816339.4 :2000MAY01 591 644 forward 3 TM N out

73 LI: :816339.4 -.2000MAY01 933 1010 forward 3 TM N out

73 LI: : 816339.4 :2000MAY01 1182 1244 forward 3 TM N out

73 LI: :816339.4 :2000MAY01 1257 1319 forward 3 TM N out

74 LI: : 1188967.: 1:2000MAY01 14 67 forward 2 TM N out

74 LI: :1188967.: 1:2000MAY01 272 325 forward 2 TM N out

75 LI: :236230.3 :2000MAY01 1081 1149 forward 1 TM N in

75 LI: :236230.3 :2000MAY01 1195 1281 forward 1 TM N in

75 LI: :236230.3 .-2000MAY01 1330 1416 forward 1 TM N in

75 LI: :236230.3 :2000MAY01 182 253 forward 2 TM N out

75 LI: :236230.3 :2000MAY01 1016 1102 forward 2 TM N out

75 LI: :236230.3 :2000MAY01 1154 1240 forward 2 TM N out

75 LI :236230.3 :2000MAY01 1346 1432 forward 2 TM N out

75 LI: :236230.3 :2000MAY01 63 149 forward 3 TM N out

75 LI :236230.3 :2000MAY01 396 449 forward 3 TM N out

75 LI :236230.3 :2000MAY01 567 644 forward 3 TM N out

75 LI :236230.3 :2000MAY01 1107 1181 forward 3 TM N out

75 LI :236230.3 :2000MAY01 1320 1382 forward 3 TM N out

75 LI :236230.3 :2000MAY01 1410 1472 forward 3 TM N out

76 LI :246728.3 :2000MAY01 1633 1695 forward 1 TM N out

76 LI :246728.3 :2000MAY01 1783 1854 forward 1 TM N out

76 LI :246728.3 :2000MAY01 2492 2566 forward 2 TM N out

76 LI :246728.3 :2000MAY01 792 854 forward 3 TM N in

76 LI :246728.3 :2000MAY01 2325 2375 forward 3 TM N in

77 LI : 1190057. 1:2000MAY01 646 696 forward 1 TM N in

77 LI : 1190057. 1-.2000MAY01 1195 1263 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 1591 1668 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 2104 2169 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 2233 2295 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 2320 2382 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 2623 2703 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 3124 3207 forward 1 TM N in

77 LI : 1190057. 1:2000MAY01 1217 1270 forward 2 TM N out

77 LI : 1190057. 1:2000MAY01 1595 1681 forward 2 TM N out

77 LI : 1190057. 1:2000MAY01 2267 2353 forward 2 TM N out

77 LI : 1190057. 1:2000MAY01 2420 2491 forward 2 TM N out

77 LI -.1190057. 1:2000MAY01 2624 2698 forward 2 TM N out

77 LI : 1190057. 1:2000MAY01 2720 2785 forward 2 TM N out

77 LI -.1190057. 1:2000MAY01 3014 3067 forward 2 TM N out

77 LI : 1190057. 1:2000MAY01 3116 3202 forward 2 TM N out

77 LI :1190057. 1:2000MAY01 1905 1991 forward 3 TM N in Table 1 (cont.)

77 LI: : 1190057.1.-2000MAY01 2217 2297 forward 3 TM N in

77 LI: : 1190057.1: 2000MAY01 2601 2657 forward 3 TM N in

77 LI: : 1190057.1:2000MAY01 3072 3143 forward 3 TM N in

78 LI: :221836.3 :2000MAY01 775 846 forward 1 TM N out

78 LI: :221836.3: :2000MAY01 2050 2106 forward 1 TM N out

78 LI: :221836.3 :2000MAY01 2197 2265 forward 1 TM N out

78 LI: :221836.3 :2000MAY01 2539 2613 forward 1 TM N out

78 LI: :221836.3: :2000MAY01 2216 2302 forward 2 TM

78 LI: :221836.3 :2000MΔY01 2582 2668 forward 2 TM

78 LI: :221836.3 :2000MAY01 1899 1976 forward 3 TM N out

78 LI: :221836.3 :2000MAY01 2034 2120 forward 3 TM N out

78 LI: :221836.3 :2000MAY01 2199 2261 forward 3 TM N out

78 LI: :221836.3 :2000MAY01 2283 2345 forward 3 TM N out

78 LI: :221836.3 :2000MAY01 2490 2564 forward 3 TM N out

79 LI: :334047.3 :2000MAY01 115 201 forward 1 TM N out

79 LI: :334047.3 :2000MAY01 56 142 forward 2 TM N in

79 LI: :334047.3 :2000MAY01 497 577 forward 2 TM N in

Table 2

SEQ Component SEQ Component SEQ Component

ID ID ID ID ID ID

NO: Start Stop NO: Start Stop NO: Start Stop

1 2079155F6 1 474 5 4774836H1 1896 2149 5 4340882T6 1846 2111

1 2079155H1 1 287 5 4229676H1 1940 2149 5 5016835H1 1893 2144

1 6485024H1 30 531 5 4254348H1 2050 2148 6 6206710H1 1 518

1 269086H1 55 416 5 1993010H1 483 763 6 1632421H1 231 457

1 g4194935 215 662 5 3471007H1 681 951 6 3255825H1 242 491

1 g3174230 294 608 5 3915086H1 718 875 6 1951956T6 1 423

2 g3405927 511 865 5 2708491F6 775 1111 6 gl099892 61 470

2 4061048T8 213 755 5 2708491H1 776 1069 6 1356903H1 545 744

2 5961372H1 1 539 5 6307323H1 845 1181 6 4987735H1 279 444

3 4318348F6 361 482 5 551890H1 939 1121 6 4987835H1 279 444

3 g4739876 483 760 5 4492287H1 940 1315 7 3170506F6 176 241

3 g5637692 483 760 5 3783242H1 1095 1382 7 6387831H1 334 463

3 g5392945 603 1049 5 1479372H1 1229 1476 7 5607909H1 1 243

3 5338818H1 827 1078 5 2761062H1 1232 1497 7 3558469F6 14 444

3 6484158H1 1 544 5 2761062R6 1232 1489 7 3558469H1 14 293

3 5792010H1 36 340 5 6001120H1 1289 1774 7 g2006934 14 114

3 5785018H1 36 336 5 6977932H1 1468 1665 7 6109819H1 33 325

3 5793390H1 36 306 5 7033269H1 1506 2033 7 g2464233 46 103

3 6555681H1 125 694 5 3466972H1 1516 1770 7 3170506H1 176 452

3 3903879H1 156 435 5 2788543H1 1517 1748 8 g2069455 1 404

3 g4850881 306 759 5 5858122H1 1588 1848 8 1597036H1 1 218

4 g2411092 1 241 5 2705868F6 1617 1980 8 6429759H1 68 471

4 7104605H1 1 533 5 5022301H1 1617 1884 8 4013148H1 178 462

4 4699688T6 146 533 5 2705868H1 1618 1886 8 g2064597 256 604

5 6440110H1 1 71 5 5373405T6 1620 2144 8 3296932F6 312 950

5 5406681H1 1 122 5 1479486T6 1623 2109 8 3296932H1 312 563

5 6953084H1 63 615 5 2761062T6 1622 2108 8 5839392H1 315 545

5 5373405H1 63 285 5 2705868T6 1635 2107 8 1254055H1 421 639

5 5373405F8 83 602 5 3468165H1 1631 1895 8 3527901H1 434 704

5 3942701H1 190 481 5 1993688T6 1696 2108 8 3402996H1 549 697

5 4340882H1 392 586 5 1993688F6 1703 2147 8 3503954F6 615 1002

5 4340882F6 392 865 5 1993688H1 1703 1950 8 3503954H1 616 915

5 3323337H1 449 716 5 666099H1 1721 1946 8 3985708H1 623 812

5 1479486F6 453 867 5 g3423957 1776 2148 8 6117978H1 729 1018

5 1479486H1 453 688 5 g3241592 1821 2154 8 3620240H1 767 976

Table 2 (cont.)

5912238H1 872 1066 9 6146280H1 39 573 12 1356974H1 109 353

1961296H1 965 1237 9 gl556832 14 174 12 3694703H1 215 496

3406891F6 1026 1582 9 6334269H1 187 736 12 1241180H1 253 311

3406891H1 1026 1266 9 6147106H1 189 743 12 5432511H1 253 362

6196163H1 1193 1793 9 g2180097 1 381 12 5864554H1 391 666

6196263H1 1193 1660 9 6145722H1 314 826 12 4959207H1 409 524

6059105H1 1200 1336 9 gl969671 44 388 12 5641442H1 415 654

3296932T6 1249 1867 9 6147235H1 444 987 12 g2163443 423 741

4367370H2 1253 1496 9 gll09940 188 316 12 2923379H1 430 686

1908946F6 1257 1607 9 6146408H1 530 954 12 4699556H1 430 683

1908946H1 1257 1499 9 6149660H1 543 1006 12 040379H1 431 592 gl958480 1311 1530 9 6144394H1 586 1189 12 3032206H1 430 716

2270984R6 1377 1831 9 gl970587 1 235 12 2509521H1 434 662

2270975H1 1377 1613 10 g993188 793 1107 12 2509521F6 434 665

2270984H1 1377 1605 10 g3752938 851 1199 12 1703965H1 437 682 g850966 1497 1759 10 3070204H1 595 886 12 5605693H1 437 697

5028068H1 1499 1786 10 4420032H1 906 1146 12 5546287H1 474 665

1808792T6 1564 2151 10 3448504T6 187 819 12 3801120H1 653 948

987831H1 1575 1772 10 4401644H1 1029 1282 12 4878230H1 661 910

3406891T6 1593 2149 10. 5092611H1 1 214 12 60135211B1 810 1213

3410491H1 1602 1683 10 5092611F6 1 621 12 60135113V1 834 1227

3503954T6 1606 2156 10 1667402H1 159 214 12 60135211V1 834 1227

1808792F6 1606 2061 10 3410836H1 533 781 13 70319065D1 190 589

1808792H1 1606 1852 10 3448604H1 535 785 13 70320239D1 212 793

2270984T6 1688 2209 10 3448504R6 535 884 13 70320883D1 212 645 g3231619 1764 2196 10 5955967H1 566 794 13 70318969D1 213 774

1908946T6 1856 2139 10 g2367695 570 959 13 70317969D1 398 791 g851209 1874 2177 10 5499560R6 579 1009 13 70318139D1 398 931 g3765675 1877 2174 10 g2629724 594 1046 13 70317613D1 398 857 g3755028 1885 2189 10 g4089777 675 993 13 70318020D1 398 856 gll53884 1912 2174 10 gl440904 708 1042 13 70317863D1 398 791

5511650H1 2088 2271 10 gl941334 715 940 13 70319554D1 398 791 g2016674 1 372 10 g2078942 715 957 13 70318409D1 398 695

6147645H1 830 1263 10 g2901697 748 1048 13 70319562D1 398 741

6338012H1 1 401 11 2967428H1 1 284 13 70317555D1 398 635

6336313H1 22 565 12 3002696H1 1 285 13 70318235D1 399 928

6577916H1 22 400 12 3002696F6 1 394 13 70320237D1 399 852 g907436 1 324 12 1356974F6 109 495 13 70318920D1 399 812

Table 2 (cont.)

13 70320035D1 411 741 14 5962837H1 290 797 15 5313986H1 245 479

13 70318273D1 417 856 14 gl040085 419 732 15 817768H1 254 505

13 4120208H1 332 571 14 g982880 468 732 15 3984239H1 265 539

13 70320719D1 447 856 14 70060347V1 660 1048 15 g810072 267 601

13 3882715H1 1 312 15 gl855688 706 918 15 g2064405 265 723

13 2797803F6 1 452 15 g2464352 752 910 15 3374148H1 269 527

13 2797803H1 1 245 15 gl471158 757 906 15 gl025985 271 535

13 2788120H1 4 256 15 2127070H1 769 901 15 6548704H1 274 571

13 70317458D1 481 876 15 g2836064 779 901 15 g896704 276 572

13 70318194D1 481 856 15 g3665793 787 901 15 2501178H1 276 513

13 70320117D1 521 856 15 g2969091 800 901 15 g842912 278 529

13 70319709D1 559 988 15 1473808H1 1 110 15 g920007 323 566

13 70319736D1 639 1133 15 gl548716 7 330 15 4772879H1 286 566

13 70319869D1 715 856 15 gl940204 1 464 15 - 4240190H1 296 541

13 2797803T6 97 633 15 6298845H1 40 208 15 2751946H1 326 585

13 70320906D1 743 1133 15 2204071H1 40 222 15 2500349T6 331 858

13 70320282D1 743 856 15 gl859154 40 370 15 gll66133 332 498

13 3873636H1 291 586 15 6736659H1 65 581 15 gl471157 339 531 σ^*- 13 70319282D1 877 1310 15 1494078H1 66 277 15 -319110T6 345 865

13 70319385D1 904 1133 15 1803588H1 72 335 15 5213230H1 356 581

13 g2329469 121 408 15 2277953H1 119 392 15 977791H1 357 574

13 3873636T6 1 336 15 2500164H1 126 380 15 977791R1 357 785

13 70321152D1 466 931 15 2500349F6 126 614 15 2771133H1 361 606

13 70317918D1 466 930 15 2500349H1 126 376 15 2132792R6 373 512

13 70320713D1 466 856 15 3886423H1 209 462 15 1699741H1 374 602

13 70320635D1 466 856 15 2604501H1 221 478 15 1927601H1 386 626

13 70320227D1 466 855 15 3899701H1 225 501 15 1803588T6 396 863

13 70317509D1 466 856 15 2717183H1 231 467 15 2413149H1 403 565

13 70320434D1 466 876 15 7058162H1 192 582 15 612807H1 427 521

13 70320694D1 468 856 15 3614668H1 134 417 15 5122537T6 413 870

13 70320790D1 466 838 15 3986769H1 264 521 15 5028542H1 423 679

13 70318744D1 466 880 15 3246169H1 221 454 15 4365757H1 421 681

13 70318259D1 467 930 15 6916455H1 221 496 15 6736648H1 428 901

13 70318517D1 481 931 15 4856582H1 213 492 15 g2537655 437 871

14 g982879 1 359 15 319110R6 228 742 15 1348978H1 438 680

14 gl039681 62 330 15 319110H1 228 610 15 955324R1 438 901

14 1850733F6 165 655 15 4651030H1 279 521 15 2132792H1 436 685

14 1850733H1 165 450 15 gl856065 227 715 15 1348899H1 438 697

Table 2 (cont.)

15 955324H1 438 680 15 2132792T6 636 862 16 3441272H1 802 1039

15 1616045H1 441 659 15 2687592H1 650 886 16 2645796T6 875 1050

15 1637850H1 450 654 15 5083760H1 677 931 16 g834367 200 342

15 1635340H1 450 654 15 2204071T6 678 858 16 2645796H1 884 1050

15 4835330H1 453 722 15 g809963 684 901 16 2645796F6 884 1175

15 3267673H1 453 707 15 2103287H1 690 912 16 4730205H1 244 413

15 1621983H1 453 665 15 g896705 691 905 16 418633T6 1004 1574

15 g5110236 456 914 15 g3601113 695 908 16 3873188H1 361 619

15 g3254447 461 913 15 glll4641 695 877 16 1301651T6 1104 1576

15 g3961279 466 901 15 5551489H1 706 900 17 6816661H1 1 424

15 2872292H1 466 733 16 2738293F6 1 355 17 6816661J1 303 880

15 4958730H1 469 733 16 2738293H1 1 169 18 6765038H1 1 356

15 g5878660 470 907 16 1301651F6 1104 1404 18 6823189H1 1 515

15 g5544770 475 901 16 1301651H1 1104 1232 18 6823189J1 268 821

15 4567732H1 489 759 16 2130054R6 1113 1391 18 6927865H1 598 1049

15 374248H1 498 720 16 2130054H1 1113 1285 18 gl012738 705 947

15 g4005355 504 901 16 1232594H1 1113 1253 19 6485634R9 1 494 . ¹⁵ g5365013 508 913 16 2738293T6 1129 1578 19 6488342R9 1 385

^ 15 5992634H1 507 803 16 412176F1 1153 1615 19 4347981T9 299 607

15 g3988037 521 919 16 g4312034 1174 1553 19 4347981F8 359 958

15 906113H1 541 796 16 g776598 1269 1557 19 4347981H1 855 958

15 906113R1 541 901 16 g787388 1308 1554 20 4187505H1 1 114

15 537271H1 542 794 16 g5541568 1355 1615 20 4187505F8 1 618

15 905790T1 541 858 16 2562775H1 471 729 20 4187505F9 1 583

15 2751121H1 551 642 16 5290883H1 544 798 20 6064542T8 300 655

15 611349H1 563 824 16 4014888H1 1 215 20 4187505T8 386 774

15 2491963H1 563 818 16 3632619T6 662 1050 20 4187505T9 409 774

15 g3232145 568 912 16 g5177519 10 495 20 2721392Η1 600 830

15 g3802367 572 924 16 g776684 711 998 21 1930289T6 1293 1817

15 gl548831 584 877 16 g786907 711 959 21 5784355T6 1318 1728

15 5164893H1 599 862 16 6950344H1 146 736 21 3659618T6 1332 1820

15 g3770372 602 901 16 1232594F1 727 1253 21 2762471H1 1353 1596

15 1473995H1 616 805 16 g4223240 748 1170 21 3400826H1 1373 1600

15 1473995T1 616 861 16 418633R6 158 575 21 g3647867 1385 1792

15 5986850H1 620 901 16 1220942H1 772 1035 21 g4302533 1430 1884

15 g4511097 621 901 16 412176R1 158 612 21 954028H1 1436 1704

15 6212219H1 625 901 16 416149H1 158 363 21 7081513H1 1 524

15 g4332172 627 914 16 412176H1 158 344 21 2509720H1 252 479

Table 2 (cont.)

3242083H1 367 616 21 g6471216 1557 1864 22 g4073477 2082 2485

3644604F6 369 626 21 g5110284 1565 2014 22 g4900706 2083 2480

3644604H1 370 665 21 g4373194 1572 1928 22 g6198867 2084 2488

5741818H1 406 601 21 g5664143 1577 1926 22 2466234H1 2106 2334

7082116H1 437 980 21 2293651H1 1576 1806 22 4824519F6 939 1471

2060770H1 625 869 21 g3869595 1585 1927 22 g2444680 949 1228

5113293H1 708 973 21 725947H1 1585 1828 22 3960643H2 962 1234 gl891059 713 1017 21 g2401363 1589 1886 22 g2816130 1111 1586

6479360H1 821 1302 21 6773275J1 1592 2142 22 g5395011 1122 1577

5784455H1 850 1085 21 gll56118 1606 1886 22 gl812285 1238 1577

5784355H1 850 1112 21 gl892265 1659 1925 22 gll94260 1297 1389

5794459H1 850 1145 21 g4242906 1677 1860 22 g2818085 1298 1586

5784355F6 855 1390 21 5399680H1 1684 1881 22 3248605H1 1302 1611

6832370H1 873 1476 21 g764351 1720 1939 22 g6472165 1303 1565

3734122H1 873 1159 21 g2716497 1721 2098 22 1781932R6 1312 1806

6836219H1 945 1256 21 g2804847 1743 2084 22 1781932H1 - 1312 1579

5104159H1 959 1198 21 957645T1 1747 1843 22 g2819140 1345 1570

4512707H1 1004 1259 21 957645R6 1747 1886 22 4365019H1 1372 1640

1836548H1 1054 1110 21 957645T6 1747 1843 22 6521348H1 1423 1950

1006724H1 1060 1307 21 957645H1 1747 1852 22 1454503F6 1596 2079

523339H1 1124 1369 21 g2930525 1756 2091 22 1454503H1 1596 1797

630148H1 1154 1436 21 825718H1 1892 2187 22 1454503F1 1596 2144

5897974H1 1196 1465 21 3169276F6 1905 2315 22 031646H1 1628 1864

459407H1 1219 1502 21 3169276H1 1906 2174 22 1698275H1 1730 1954

1930289F6 1289 1794 21 4880539H1 2029 2262 22 2477996H1 1833 2038

1930289H1 1289 1559 21 551186H1 2088 2334 22 gl088089 1838 2109 g6398856 1470 1886 21 5223525H1 2143 2294 22 6051243H1 1859 2290 g5368595 1474 1928 21 gl959837 2258 2561 22 6051243J1 1859 2290 g5662921 1484 1926 21 3314476F6 2280 2591 22 719445H1 1906 2117 g2279246 1491 1886 21 3314476H1 2280 2530 22 1454503T6 1941 2444 g3432804 1495 1928 21 6773275H1 2281 2746 22 1753732H1 1969 2210 g3927268 1499 1890 21 2134443H1 2500 2591 22 1753732F6 1969 2336 g3751389 1532 1885 21 3169276T6 2500 2591 22 g6040701 2013 2480

3028225H1 1536 1817 22 478871H1 2084 2377 22 g2779360 2014 2292 g3244749 1546 1891 22 g3931712 2092 2342 22 g5879420 2024 2486

1696241T6 1547 1867 22 g4533567 2097 2481 22 g5848637 2028 2490

1696241F6 1554 1907 22 g5856043 2081 2480 22 g4989391 2035 2488

1696241H1 1554 1797 22 g3932376 2082 2484 22 g4136876 2036 2488

Table; 2 (cont.) g4734230 2036 2481 23 gl099119 641 962 24 7059154H1 135 293

3011670T6 2038 2442 23 2752130H1 776 960 24 1671750H1 174 387

1306758T6 2045 2444 23 gl099240 776 1080 24 1511456H1 174 374

3698556H1 2046 2293 23 gl018781 866 1119 24 1746566H1 177 451 g6132228 2080 2481 23 219949R6 875 1273 24 1746566F6 177 633 g5813048 2080 2480 23 219949H1 875 1016 24 5163064H1 194 458 g5595187 2080 2481 23 215836H1 875 1112 24 4401870H1 194 456

919527H1 2154 2367 23 219949T6 875 1237 24 2850494H1 194 474

2288878H1 2216 2464 23 2752130T6 913 1077 24 620602H1 195 454

043873H1 2227 2474 23 2017342H1 1100 1334 24 6317553H1 202 488 g4332802 2257 2480 24 g6038562 1 431 24 6317552H1 202 488

2929901H1 2277 2381 24 g6398073 1 423 24 4543261F6 217 615

2929910H1 2277 2496 24 2114662H1 226 409 24 4543261H1 217 479

2130537H1 2284 2487 24 4802387F8 403 845 24 2886956H1 219 490 g659717 2325 2492 24 3814249H1 637 864 24 g3116861 220 535

4594675H1 2398 2486 24 g3764669 22 458 24 2298804H1 223 477 g856894 1 320 24 g5595942 31 436 24 3530239H1 224 499

2493973H1 1 312 24 g4526293 31 392 24 6043133H1 223 484

1306758H1 1 206 24 g2359335 39 217 24 4986150H1 239 517

1306758F6 1 245 24 3426470H1 38 296 24 3506149H1 238 548

2892162H1 3 128 24 3751121H1 64 360 24 gll65727 258 501

6460769H2 27 92 24 5102466H1 67 320 24 1747695H1 261 510

6464146H2 27 600 24 g5543678 70 341 24 1747316H1 261 523

6784388H1 281 734 24 g5857639 70 492 24 1231741H1 276 527

3297069H1 291 401 24 gl483656 70 494 24 3221695H1 279 600

3011670F6 367 436 24 gl687609 70 310 24 g2184331 285 732

3011670H1 367 674 24 g2240940 70 414 24 1692992H1 306 516

4571406H1 659 940 24 gl728565 70 496 24 1692983H1 306 516

4571406F9 660 1290 24 g2191816 70 412 24 551035H1 318 578

7161658H1 663 1132 24 g2914811 70 480 24 1398934H1 318 577

2731281H1 894 1128 24 g2910290 70 370 24 033465H1 318 595

4824519H1 939 1194 24 g3051051 70 382 24 2483413H1 329 583

5092611H1 1 214 24 g2206444 70 408 24 4567659H1 334 601

5092611F6 1 621 24 g2912492 70 325 24 g919123 349 531

1667402H1 159 214 24 gl516143 71 240 24 g892506 347 650

3410836H1 533 781 24 3250685H1 79 373 24 1696018H1 364 566

3448604H1 535 785 24 720142H1 79 209 24 4996050H1 377 649

3448504R6 535 884 24 4567816H1 121 383 24 4249442H1 380 586

Table 2 (cont.)

524140H1 374 618 25 2902677H1 1204 1500 25 6518401H1 806 1348

5290888H1 385 616 25 5821366H1 1235 1554 25 3919118F8 847 1404

1876529H1 389 658 25 5819630H1 1235 1546 25 2869957T6 850 1394

749418H1 402 648 25 5816778H1 1235 1549 25 g2037747 890 1199

4802787H1 403 660 25 3640567H1 1374 1579 25 6321277H1 969 1213

070211H1 404 562 25 5814634H1 1235 1560 25 2463542F6 969 1516

3488984H1 404 625 25 5817645H1 1235 1562 25 2463542H1 969 1188 g856452 405 698 25 5822469H1 1234 1486 25 552697H1 979 1207 g777504 405 703 25 5813545H1 1235 1493 25 6815232H1 996 1477

2410459H1 407 651 25 5812917H1 1235 1509 25 3484912H1 1007 1342 g759872 415 726 25 5818829H1 1235 1458 25 7040095H1 1020 1549

179723H1 419 544 25 5817650H1 1235 1402 25 6743438H1 1 343

2701594H1 423 676 25 g4295078 1242 1433 25 5959701H1 1 541

5432663H1 427 693 25 g5934094 1284 1720 25 7199644H1 39 460

1319180H1 432 542 25 g5741261 1288 1723 25 3801333H1 46 327

3324294H1 509 779 25 2463542T6 1288 1769 25 6146685H1 131 608

2303707H1 510 635 25 gl982163 1341 1571 25 3021452H1 203 499

5020923H1 514 790 25 2655535F7 226 649 25 2655535H1 226 520

2298247H1 518 638 25 2655535F6 226 655 25 g867230 2483 2782

3614560H1 547 781 25 6887246J1 370 475 25 gl477035 2519 2783

6741535H1 680 937 25 6887246H1 379 482 25 6158466H1 2530 2692 g6397955 22 223 25 1902994H1 381 630 25 646057H1 2530 2784

6754236J1 1 584 25 4096762H1 416 721 25 3535428H1 2550 2782

6754123J1 1 509 25 4510286H1 455 705 25 gl479354 2562 2781

6757969J1 1 550 25 007733H1 530 799 25 g3095823 2573 2706

6203321H1 1 292 25 5910362H1 646 948 25 2878073H1 2577 2784

6758815J1 1 591 25 2857263H1 653 766 25 g944173 2582 2679

6757686J1 1 479 25 2857263F6 653 1118 25 3702759H1 2594 2782 g3594017 10 463 25 6212439H1 655 938 25 g5325988 2594 2782 g6399041 22 486 25 2869957H1 667 946 25 g969343 2630 2782 g3077101 1343 1721 25 2869957F6 667 1228 25 2043940H1 2651 2782

2552885T6 1025 1390 25 g942739 676 955 25 661586H1 2658 2813 g2594419 1042 1432 25 gl477126 687 1120 25 5056769H1 2702 2789 gl647965 1086 1408 25 gl527541 687 1069 25 6332343H1 1960 2520 g4451382 1116 1433 25 g969342 687 806 25 5327933H1 1964 2225

3919118T8 1167 1620 25 g2184408 725 1175 25 g3658839 1983 2394 g316154 1190 1474 25 5307452H1 767 1019 25 g3927414 1988 2423 g2958693 1358 1720 25 2655535T6 768 1384 25 5275308H1 2005 2238

Table 2 (cont.)

2673389H1 2047 2295 25 3769037H1 1634 1888 26 g727700 2038 2283 g274328 2457 2782 25 3509114H1 1638 1908 26 2228104H1 2043 2111

7237473H1 2048 2569 25 3927329H1 1656 1922 26 3597053F7 1997 2600

5333974H1 2054 2302 25 2593752H1 1679 1869 26 2839674H2 2043 2159

1982603H1 2091 2315 25 gl981200 1681 1968 26 2932162H1 2043 2135

2044369H1 2192 2427 25 1683135H1 1757 1897 26 6096855H1 2043 2204 g4196655 2192 2327 25 5832853H1 1792 2069 26 3717718H1 2043 2155

4726834H1 2192 2469 25 806178H1 1796 2022 26 gl294859 2046 2640

1772731H1 2244 2461 25 3558496H1 1804 2073 26 3448635H1 2048 2289

4266001H1 2279 2468 25 2795155H1 1843 2089 26 3900947R8 2055 2678

4730142H1 2304 2558 25 1982603R6 1867 2315 26 2814661H1 1998 2286 g2555947 2309 2616 25 2876519H1 1883 2138 26 3901994H1 2055 2321

840781H1 2310 2582 25 g3804453 1895 2327 26 2604117H1 2069 2314

4492313H1 2310 2757 25 g5812417 1896 2308 26 4538547H1 2069 2325

4593969H1 2310 2579 25 5563230H1 1959 2187 26 g789232 2070 2294

4492214H1 2315 2782 26 3719577H1 1538 1698 26 gl677967 2093 2316 g5109339 2326 2784 26 g2166727 1572 1672 26 gl783925 2101 2388

613645H1 2337 2571 26 gl259102 2007 2205 26 g4690089 2125 2583

2132842H1 2376 2617 26 693434H1 2012 2270 26 g4685239 2125 2332 g4073710 2384 2785 26 6021316H1 2013 2538 26 g858499 2138 2459 gl527498 2413 2783 26 2605880H1 2014 2246 26 5725860H2 2176 2244 g2184179 2453 2785 26 2605880F6 2014 2595 26 123421H1 2177 2318

2721848H1 2456 2707 26 4132607F6 1614 2100 26 g777923 2177 2289

2637714H1 2456 2709 26 g2166556 1633 1729 26 g789198 2203 2454 g2569732 1382 1794 26 g2013024 1983 2258 26 g781495 2204 2455

3042074H1 1471 1786 26 gl321421 2014 2246 26 2667384H1 2205 2433

4714518H1 1907 1991 26 1258355F6 2015 2225 26 gl697403 2230 2531

4261452H1 1474 1733 26 1258355F1 2015 2511 26 g3933029 2237 2737

2773951H1 1488 1742 26 1258355H1 2015 2216 26 2939915H1 2235 2393 g3050704 1508 1703 26 4584658H1 2019 2164 26 4643005H1 2235 2484

6023537H1 1527 1763 26 2211736H1 2025 2282 26 4704174F9 1 569

2653867H1 1534 1820 26 2956194H1 2026 2103 26 3122989H1 273 555 g4522739 1927 2326 26 5853223H1 2026 2227 26 4704174H1 322 569 g3960542 1580 1841 26 3597053H1 1993 2297 26 4777379H1 348 606 glll9058 1591 1716 26 6718635H1 2026 2279 26 2834749F6 405 694

6411539H1 1616 2116 26 4728680H1 2026 2159 26 2834749H1 420 694 g5369593 1952 2423 26 3210462H1 2026 2225 26 5911946H1 436 722

2097957H1 1626 1902 26 g707728 2026 2234 26 4721035H1 446 695

Table 2 (cont.)

1601324H1 453 599 26 1262991R1 2417 2917 26 6494640H1 2583 2945 g4876168 456 887 26 1262991H1 2417 2655 26 g4622298 2586 2949

5372175H1 456 681 26 4978404H1 2446 2697 26 g6439089 2592 2960

1992918H1 466 560 26 4508011H1 2457 2720 26 1258355T6 2592 2910

2782119H1 516 746 26 3735710H1 2461 2698 26 g5540648 2607 2960 gl628776 669 1024 26 6217351H1 2472 2933 26 2273680H1 2614 2887

6256994H1 670 928 26 g2524340 2476 2948 26 g4620011 2619 2949 gl312588 674 886 26 2117643T6 2489 2846 26 1711022H1 2630 2844

2101267H1 697 941 26 g3645213 2494 2955 26 6587024H1 2633 2749 gl948843 762 1091 26 g4372648 2495 2775 26 1472231H1 2634 2836

7076736H1 791 1279 26 g3596913 2496 2958 26 1472231T1 2634 2906

2135134F6 816 1213 26 g4372672 2500 2951 26 5177089H1 2643 2915

2135134H1 816 1077 26 g3674408 2514 2955 26 1711022F7 2646 2964

2792758H1 907 1221 26 g4310744 2515 2963 26 gl860279 2645 2949

5151110H1 1175 1353 26 723560H1 2516 2722 26 g3837895 2646 2958

6529106H1 1196 1624 26 g3595253 2521 2964 26 gl644779 2650 2945

3136230H1 1206 1482 26 g2525244 2522 2770 26 5645429H1 2650 2902

3136230F6 1206 1635 26 4160050T6 2527 2934 26 g858397 2651 2926

7041019H1 1218 1660 26 g4665502 2536 2964 26 g4107761 2656 2949

178010H1 1249 1493 26 2743458H1 2544 2802 26 g839957 2659 2950

4109878H1 1348 1617 26 2738862H1 2544 2790 26 g657066 2662 2963

2135134T6 1388 1727 26 2743458F7 2544 2949 26 g5325849 2682 2956 g434268 1404 1671 26 g5637396 2548 2955 26 g727611 2687 2950

2809378T6 1477 1727 26 g3432798 2549 2950 26 1413430H1 2685 2938 g707734 1513 1698 26 g5369924 2550 2979 26 2887585H1 2686 2946

2900195H1 1510 1714 26 g4310271 2552 2949 26 gl242496 2689 2949

7088770H1 2241 2784 26 g3841661 2554 2953 26 1796886H1 2696 2945

2688875H1 2289 2543 26 g4888429 2557 2949 26 gl688397 2697 2945 gl688483 2301 2695 26 4620145H1 2558 2805 26 1711022T7 2706 2842

3126776H1 2302 2574 26 2605880T6 2563 2848 26 g2941734 2711 2965

4132607T6 2348 2933 26 3207727H1 2565 2825 26 3022288H1 2725 2949

3900947T8 2378 2822 26 gl783745 2570 2949 26 g777818 2734 2959 g3924091 2375 2772 26 gl677968 2571 2950 26 g434265 2732 2949

764214H1 2380 2661 26 3980476H1 2573 2751 26 g789233 2736 2941 gl697306 2396 2775 26 3966076H1 2572 2704 26 g789199 2741 2954 g5589502 2398 2775 26 3966076F7 2572 2963 26 g3144224 2745 2949 g2210147 2404 2787 26 3966076T7 2572 2859 26 2737665H1 2751 2945

2900195T6 2417 2907 26 g5445604 2583 2959 26 g4195279 2774 2953

Table 2 (cont.)

26 4718419H1 2784 2980 28 999643H1 1449 1694 30 3817033H1 949 1206

26 gl948844 2803 2958 28 6805084J1 1475 1968 30 5007439H1 954 1182

26 g2524323 2860 2949 28 1631088F6 1521 1966 30 5187677H1 997 1255

26 g2106662 2878 2948 28 2092882H1 1521 1721 30 5003069H1 1121 1381

27 6506033H1 273 426 28 gl242302 1550 1775 30 6838881H1 1261 1723

27 6506133H1 273 434 28 g2955269 1564 1775 30 g772660 1266 1605

27 5742229H1 319 613 28 139470H1 1620 1736 30 g769304 1267 1535

27 6334334H1 237 643 28 2072462H1 1639 1906 30 g564397 1267 1459

27 3388613F6 1 485 28 4286166H1 1641 1911 30 g900136 1342 1684

27 3388613H1 1 291 28 gl242305 1660 1775 30 5077690H1 1399 1642

27 gl815060 33 488 28 085524H1 1714 1911 30 6742827H1 1434 1983

27 6941841H1 79 525 28 gl210407 1752 1950 30 1398653H1 1574 1839

28 5372512H1 1 156 28 gll96175 1753 1950 30 1398653F6 1574 1819

28 3481951H1 1 300 28 4287958H1 1768 1911 30 5085840H1 1578 1764

28 086514H1 116 324 28 1631088H1 1789 1966 30 5188226H1 1630 1896

28 6773036J1 136 255 29 g5446946 632 897 30 1429039H1 1640 1909

28 3228141H1 256 535 29 g3075841 221 576 30 5390274H1 1752 2017

28 469821H1 427 664 29 g2767512 248 577 30 5719068H1 1774 2172

CX) 28 4323062H1 454 579 29 g2818989 248 593 30 1926364H1 1778 2016

28 g6131888 498 919 29 3394790H1 353 636 30 4987108F8 2070 2609

28 2997736H1 585 872 29 g2901002 453 708 30 4986308H1 2070 2366

28 648674H1 723 978 29 804254H1 569 849 30 4643979H1 2083 2337

28 g6474252 755 1175 29 2906845H1 1 78 30 4987108T8 2105 2606

28 2720552F6 824 1376 29 2741409T6 1 548 30 4987108T9 2118 2684

28 2720552H1 824 1055 29 2741409F6 7 488 30 7351533H1 2126 2615

28 3731554H1 848 1141 29 2741409H1 7 269 30 2073148T6 2288 2745

28 gl294839 880 1372 29 658133H1 12 268 30 607997H1 2302 2551

28 gl294842 880 1336 29 3836585H1 31 316 30 1625327T6 2305 2743

28 5837915H1 1008 1273 29 4796210H1 129 412 30 1398653T6 2312 2756

28 5598427H1 1063 1333 29 6205209H1 154 370 30 1625327F6 2312 2753

28 7060462H1 1093 1625 29 1447527H1 218 457 30 1625327H1 2312 2521

28 2925401H1 1115 1340 30 7189828H2 1 573 30 2073148F6 2312 2787

28 3147672H1 1212 1519 30 7031283H1 176 699 30 g5235046 2312 2790

28 7353404H1 1216 1753 30 g4406653 255 2784 30 2073148H1 2312 2565

28 g2018589 1262 1572 30 5594735H1 403 643 30 g4988528 2313 2787

28 5290315H1 1344 1593 30 4858522H1 468 592 30 g3238921 2317 2785

28 2720552T6 1402 1736 30 5151418H1 659 780 30 g5850283 2319 2784

28 g570734 1437 1695 30 6440827H1 673 1152 30 g5233757 2323 2787

Table 2 (cont.)

30 g4688102 2337 2784 31 70339709D1 9243 9540 31 g3150717 8508 8904

30 2606717H1 2337 2597 31 70322912D1 9243 9521 31 1978921H1 8533 8804

30 g5451665 2363 2784 31 70346838D1 9243 9361 31 g3427618 8559 8904

30 g6473523 2372 2789 31 70346734D1 9243 9361 31 gl885652 8614 8904

30 1689007H1 2390 2605 31 70338406D1 9258 9657 31 2917437F6 8632 9171

30 g2883211 2398 2787 31 70346872D1 9262 9521 31 2917437H1 8633 8895

30 g6471739 2401 2788 31 g4325928 8675 8909 31 1242917H1 7364 7579

30 g3765856 2401 2784 31 2874640H1 8718 8904 31 1887279F6 7369 7953

30 2840911H1 2418 2684 31 6019242H1 8727 8917 31 1887279H1 7369 7448

30 g5445474 2428 2784 31 70404974D1 8821 9213 31 6873590H1 7384 7978

30 g6199495 2432 2784 31 3387504H1 8840 8897 31 1904771H1 7463 7736

30 g2817078 2436 2793 31 6299464H1 8898 9207 31 1594587T6 7476 7994

30 g5367496 2437 2784 31 6300602H1 8898 9216 31 2158441H1 7477 7745

30 g900137 2445 2791 31 6343373H1 8905 9205 31 1434154H1 7497 7745

30 g3254684 2451 2790 31 4570393H1 8939 9203 31 388880H1 7499 7757

30 g821905 2459 2792 31 70340823D1 8943 9202 31 347519H1 7502 7737

30 g816772 2543 2792 31 6602501H1 8954 9535 31 1922153T6 7506 7994 oc 30 g560418 2544 2784 31 6080143H1 8956 9450 31 038495H1 7515 7757

-ti 30 g3051927 2582 2790 31 70406005D1 8957 9207 31 038806H1 7515 7797

30 g2358712 2597 2784 31 3903264H1 8957 9192 31 1922153R6 7530 7991

30 g796532 2689 2791 31 70405554D1 8957 9122 31 039364H1 7529 7762

31 6111576H1 9012 9325 31 3171665H1 8957 9054 31 1922153H1 7530 7801

31 5158913H1 9018 9313 31 6576424H1 8962 9187 31 1645260H1 7572 7680

31 5159112H1 9018 9178 31 6731345H1 8964 9514 31 g3052905 7573 8094

31 6100031H1 9056 9341 31 5177674H2 8964 9233 31 3714030H1 7598 7910

31 70405514D1 9077 9213 31 5605333H1 8964 9106 31 g3146667 7603 8097

31 70333057D1 9083 9540 31 6823919H1 8969 9510 31 2880781T6 7616 7992

31 70321671D1 9083 9258 31 6823919J1 8969 9505 31 g4187707 7634 8100

31 70404961D1 9124 9213 31 6859476H1 8985 9421 31 1887279T6 7636 7992

31 6112811H1 9200 9519 31 6855538H1 8985 9515 31 g3897482 7653 8095

31 70337581D1 9209 9540 31 5752336H1 8989 9520 31 g4969820 7654 8097

31 70337708D1 9209 9540 31 5756348H1 8990 9549 31 g4689698 7657 8097

31. 70347673D1 9209 9540 31 6604143H1 8989 9547 31 g2718258 7659 8095

31 70337784D1 9215 9521 31 5296001H1 8992 9145 31 g4260707 7661 8100

31 6107901H1 9218 9540 31 7220264H1 9007 9505 31 g6450348 7669 8101

31 6116727H1 9225 9517 31 7313036H1 9006 9503 31 1384216F6 7675 8102

31 5442124H1 9226 9473 31 g3399851 8504 8903 31 1384216H1 7675 7953

31 70337937D1 9235 9540 31 gl939318 8504 8895 31 1383157H1 7675 7890

Table 2 (cont.)

1384216T6 7677 7992 31 3188576H1 8270 8606 31 71064013V1 5073 5658 g5742420 7680 8097 31 6160420H1 8289 8582 31 71250536V1 5100 5657 g4435778 7689 8098 31 4358203H1 8289 8572 31 71065578V1 5254 5657 g5590793 7708 8098 31 273134H1 8307 8488 31 71112003V1 5355 5678

2312710H1 7709 7944 31 4461544H1 8325 8508 31 6093082H1 5376 5664

3465757H1 7722 8000 31 2950731T6 8348 8863 31 71114663V1 5379 5655 g6138571 7718 8097 31 2026064T6 8348 8866 31 5506319H1 5391 5647 g853538 7740 7992 31 3731083H1 8401 8571 31 g5675608 5471 5935

3861860H1 7754 7939 31 4627722H1 8422 8688 31 1233336H1 5529 5670 gl277259 7774 8101 31 g3897842 8446 8904 31 1233340H1 5529 5669 g6503686 7774 8091 31 3527823H1 8448 8639 31 1233275F1 5529 6093 g6044658 7779 8097 31 g5878132 8463 8908 31 1233275H1 5529 5771 g2023638 7782 8105 31 g6476346 8474 8905 31 5350013H1 5593 5663

408644H1 7784 7992 31 g3841840 8481 8904 31 1350122F1 5617 6131 g843313 7788 8091 31 g3432813 8495 8904 31 1350122H1 5617 5864 g2952680 7805 8104 31 g848912 2041 2367 31 6582104H1 5749 6350 g2229584 7806 8097 31 6155860H1 2079 2380 31 1272111F1 5749 6328

3122773H1 7863 8172 31 5160887H2 2077 2339 31 1272111H1 5749 5966 gl963933 7882 8014 31 1730365H1 2137 2253 31 1268160F1 5837 6376 g3058765 7903 8097 31 7289495H1 2498 2716 31 1268160H1 5837 5970

4295759H1 7935 8174 31 g5839114 2563 3016 31 7001273H1 5888 6459

3296620H1 7949 8097 31 g6139732 2641 3042 31 2880781F6 5919 6392

1252602T6 7949 8061 31 360481H1 2850 3061 31 2880781H1 5919 6235

4179145H1 8046 8317 31 7086425H1 3497 3853 31 087051H1 5952 6255 gl859398 8055 8246 31 3825611H1 3604 3881 31 6983691H1 5984 6152

2950731F6 8069 8580 31 7280555H1 3778 4288 31 6201190H1 6031 6471

2950731H1 8069 8345 31 638057H1 4220 4486 31 6201790H1 6042 6471

6028146H1 8097 8380 31 6972901H1 4316 4865 31 gl959108 6053 6610

5486417H1 8097 8370 31 1912997H1 4535 4745 31 7080464H1 6067 6583

5486517H1 8097 8304 31 5519751H1 4653 4868 31 g2191498 6075 6507

3214839H1 8129 8371 31 4285086F6 4774 5061 31 2534081H1 6250 6492

961014H1 8139 8419 31 71059434V1 4774 5377 31 5926420H1 6346 6644 gl939317 8141 8602 31 71250506V1 4774 5349 31 4846224H2 6368 6676

2026064R6 8157 8553 31 71249863V1 4774 5433 31 6782312H1 6413 7032

2026064H1 8157 8432 31 4285086H1 4776 5097 31 7162675H1 6428 6832

6833043H1 8221 8813 31 71249286V1 4781 5353 31 2483472H1 6560 6820

6582104T1 8245 8801 31 71063350V1 4930 5441 31 6774735J1 6564 7115

2957010H1 8248 8528 31 4248781H1 4989 5249 31 3350377H1 6564 6849

Table 2 (cont.)

3374950H1 6564 6842 31 103247H1 7254 7488 31 70683497V1 740 1394

6432475H1 6598 7078 31 gl312411 7271 7738 31 70680391V1 747 1268

6782312J1 6592 7292 31 5509393H1 7289 7520 31 5808779H2 755 992

6436285H1 6598 7058 31 4402891H1 7309 7388 31 6433283H1 841 1387

705724H1 6672 6920 31 3256579H1 7314 7559 31 7359432H1 845 1364 g573365 6676 7044 31 3254592H1 7314 7550 31 7196090H1 851 1329

1594587F6 6687 7069 31 1661957H1 7330 7555 31 70046830V1 863 1263

1594587H1 6687 6915 31 5285340H1 7345 7413 31 70569476V1 878 1120

6774735H1 6732 7173 31 7281173H1 1 510 31 70569482V1 877 1456

2541992H1 6721 6923 31 6622925J1 63 589 31 2171346F6 883 1372

4541545H1 6758 7002 31 6911740H1 63 480 31 2171346H1 883 1121

755175R1 6768 7321 31 6850369H1 187 771 31 2170895H1 883 1117

755175H1 6768 6985 31 6852822H1 187 514 31 70679948V1 928 1514

756456H1 6768 7031 31 6538053H1 253 621 31 70683916V1 930 1509

1252602H1 6783 6920 31 70682475V1 297 917 31 7237350H1 933 1413

1252602F6 6783 6978 31 70683802V1 297 796 31 7237380H1 933 1397

2150018H1 6786 7056 31 1518525F6 297 749 31 1813175H1 936 1204

2490476H1 6812 7065 31 1518525H1 297 485 31 70569167V1 940 1120

1655265H1 6866 7129 31 6476129H1 308 901 31 5547274H1 949 1151

6997276H1 6919 7496 31 2450348H1 346 615 31 5547274F8 949 1018 g843312 6925 7278 31 4661820H2 361 420 31 6717279H1 952 1536 g853537 6925 7255 31 70683210V1 385 1052 31 70682430V1 971 1509 g2115300 6929 7315 31 6331467H1 425 996 31 7203232H1 981 1352

6307352H1 6936 7393 31 6911740J1 483 1063 31 70684182V1 1013 1517

1889141H1 6950 7270 31 70682237V1 528 1146 31 70681054V1 1034 1633

3388377H1 7017 7341 31 5546278H1 537 759 31 70681099V1 1034 1633

7360267H1 7024 7239 31 5546278F8 537 1007 31 2207642H1 1046 1286 gl986541 7052 7349 31 7104540H1 555 1088 31 70570849V1 1056 1126

3414787H1 7098 7329 31 6084311H1 575 1119 31 70684761V1 1095 1515

4750579H2 7106 7385 31 7040029H1 606 1128 31 70679678V1 1100 1650

4576939H1 7113 7253 31 7039822H1 606 1246 31 70679671V1 1135 1520

2573123H1 7128 7366 31 7103540H1 607 993 31 70684064V1 1135 1732

6501709H1 7132 7450 31 4559288H1 695 888 31 70682692V1 1170 1671

837427H1 7133 7372 31 4559288F8 699 1263 31 70687134V1 1215 1435

6837032H1 7133 7387 31 70708922V1 703 964 31 70680881V1 1229 1685

2742578H1 7170 7414 31 2137232F6 709 1120 31 70680492V1 1277 1923 g923876 7189 7484 31 2137232H1 709 997 31 6345849H1 1279 1540

3230227H1 7210 7362 31 7343723H1 721 1319 31 70680243V1 1282 1652

Table 2 (cont.)

70684419V1 1321 1825 31 1407176T6 1887 2312 32 6570162H1 907 1178

70684171V1 1321 1825 31 g6397504 1899 2369 32 6265054H1 907 1175

70685150V1 1325 1818 31 g2675405 1913 2390 32 6264218H1 907 1175

2013142R6 1336 1776 31 1904789T6 1914 2329 32 g4532299 979 1419

2013142H1 1336 1518 31 70686880V1 1918 2138 32 6586921H1 1010 1531

4257159F7 1340 1952 31 6879724J1 1922 2510 32 5331958H1 1030 1159

4257159H1 1340 1514 31 1904789H1 1921 2184 32 g5112058 1065 1520

6879724H1 1358 1902 31 1904789F6 1921 2366 32 g2100884 1065 1539

6779454J1 1374 1931 31 g4312534 1952 2364 32 5565058H1 1065 1297

70047152V1 1374 1888 31 6955654H1 1972 2379 32 6563309H1 1225 1789

7284681H1 1382 1855 31 6880650J1 1978 2213 32 6563209H1 1225 1773

70680875V1 1399 1941 31 5498289H1 1990 2241 32 g3174367 1230 1354 g2224530 1461 8904 31 g4534624 1991 2369 32 6563509H1 1264 1773

5546278T8 1485 2054 32 3427795F6 1 425 32 2798241T6 1278 1780

2013142T6 1492 2039 32 3427795H1 1 125 32 4073773T6 1314 1782

70047143V1 1501 1932 32 6413185H1 1 199 32 1003401H1 1326 1569

70704799V1 1537 1725 32 2798241F6 4 507 32 3894976T6 1329 1780

6842915H1 1547 2041 32 2798241H1 4 190 32 g2101001 1364 1680

5680223H1 1582 1832 32 gl063751 13 303 32 6342025H1 1412 1818 g4533055 1617 2079 32 890219H1 20 279 32 g5593969 1422 1818 g5512485 1621 2079 32 4755289H1 60 323 32 g2357643 1509 1825

7282247H1 1629 2142 32 6908205J1 358 968 32 g822002 1552 1825 g4568745 1637 2079 32 gl064447 401 679 32 6322537H1 1570 1816 g317862 1662 2037 32 6744456H1 421 990 33 1634654H1 1610 1839 g3039050 1670 2078 32 7100413H1 477 1038 33 60117794D3 1 562

4257159T7 1676 2261 32 3074435H1 562 828 33 60117794D1 1 460

3520727R6 1685 2079. 32 3894976H1 626 934 33 70158065V1 1 384

3520727T6 1685 2020 32 3894976F6 633 1124 33 g4309459 2 310

3520727H1 1685 1970 32 182014H1 678 871 33 60211518U1 18 510

70689194V1 1689 1909 32 5374989H1 761 997 33 60211520U1 18 304

4527468H1 1728 1976 32 3990437H1 826 1119 33 777324R6 60 552

1518525T6 1744 2324 32 4073773H1 832 1124 33 777324H1 60 303 g848911 1748 2062 32 4073881F6 832 1310 33 70159276V1 75 428 g897000 1748 2092 32 4073773F6 832 1251 33 60211517U1 85 162 g846844 1748 1979 32 4073249H1 832 1045 33 961319H1 87 308

5948631H1 1767 2077 32 g3803176 860 1322 33 961184T1 87 271

4947717H1 1816 2060 32 g3016772 860 1149 33 2275142H1 96 359 g4328051 1836 2079 32 g3677768 860 1186 33 70160733V1 113 620

Table 2 (cont.)

5085664H1 131 306 33 70457420V1 915 1479 33 70454189V1 1351 1752

70157316V1 ^' 168 682 33 1600238H1 928 1161 33 70455783V1 1376 1882

70159504V1 185 551 33 70454132V1 949 1490 33 777324T6 1381 2019

70159696V1 185 655 33 70454972V1 949 1611 33 70456596V1 1407 2011

564074H1 223 436 33 70455589V1 954 1447 33 3987203H1 1406 1705

70159471V1 309 826 33 1563424H1 958 1224 33 70157664V1 1410 1852 gll47353 351 769 33 4106652H1 984 1142 33 2132279T6 1411 2028

60211524U1 377 847 33 70158516V1 988 1257 33 g761771 1447 1605

70159585V1 380 935 33 4959017H1 990 1264 33 2148914H1 1468 1724 gll48991 452 799 33 71188204V1 994 1446 33 60117794B1 1486 2036

1561109F6 518 999 33 60211523U1 1037 1544 33 g2882479 1488 1831

1561109H1 518 734 33 70454512V1 1039 1519 33 5434158H1 1500 1741

70158015V1 522 1007 33 70454364V1 1051 1604 33 1354153H1 1503 1772

70161128V1 578 1105 33 70454390V1 1051 1603 33 714828H1 1536 1699

60211519U1 586 1130 33 70456889V1 1070 1701 33 70277464V1 1544 1934

3807313H1 607 849 33 70452566V1 1097 1581 33 910569H1 1543 1843

70455557V1 618 1130 33 71190479V1 1107 1395 33 2276506R6 1548 2003

70157813V1 629 1216 33 70272589V1 1127 1424 33 2276506H1 1548 1658

70159960V1 636 1144 33 70456244V1 1127 1681 33 70160695V1 1558 2009

3495050H1 646 942 33 g2183587 1145 1416 33 70273430V1 1578 2068

70277446V1 656 941 33 3088034H1 1157 1443 33 60117794B2 1581 2055

60211521U1 658 1131 33 70456004V1 1169 1806 33 6321907H1 1597 1884

689505H1 669 909 33 3245093H1 1179 1437 33 2276506T6 1599 2026

70159857V1 700 1193 33 70159879V1 1196 1700 33 70158895V1 1606 2066

70272966V1 727 1249 33 6034154H1 1199 1788 33 70454932V1 1651 2061

2132279R6 753 1363 33 70159176V1 1226 1777 33 1561109T6 1647 2029

2132279H1 753 1001 33 gl886430 1247 1678 33 g3173670 1668 2072

70157717V1 762 1216 33 71128906V1 1247 1507 33 g2718341 1670 2067

70157909V1 773 1216 33 71188432V1 1254 1589 33 506569H1 1707 1938

70456567V1 795 1370 33 71191660V1 1255 1810 33 g6029335 1710 2067

4741196H1 828 1088 33 1662925F6 1290 1775 33 g5366970 1765 2074

4588447H1 828 994 33 1663527F6 1290 1621 33 70457179V1 1781 1980

71191743V1 832 1483 33 1663527H1 1290 1524 33 g5444610 1790 2067

71189175V1 837 1294 33 1662925H1 1290 1411 33 g2554086 1793 2052

70457596V1 863 1238 33 5658206H1 1301 1535 33 1638111F6 1809 2198

70456909V1 882 1428 33 70457670V1 1313 1838 33 71156557V1 1820 1960

71191729V1 881 1404 33 g2902092 1320 1660 33 g765481 1866 2070

1580127H1 886 1072 33 70455019V1 1343 1884 33 g2742608 1869 2074

Table 2 (cont.) g3679767 1900 2198 35 70408459D1 1908 2338 35 gl766452 2086 2417 g6197210 1917 2072 35 70409112D1 1911 2427 35 70401307D1 2099 2441 g3805642 1940 2070 35 70401329D1 1910 2427 35 6507755H1 2109 2637 g2368950 1945 2069 35 70402712D1 1917 2338 35 70831953V1 2115 2668 g2183586 1957 2020 35 70408374D1 1919 2338 35 3987571H1 2119 2384 g2541498 1994 2067 35 70403748D1 1923 2338 35 70401747D1 2124 2360

1638111H1 1999 2198 35 70400493D1 1925 2338 35 3426754H1 2130 2401

2756125H1 2094 2198 35 3021378H1 1931 2239 35 485095H1 2143 2396

1635764H1 2099 2198 35 70400784D1 1935 2338 35 3492396H1 2150 2434

1632232H1 1610 1822 35 70410219D1 1938 2338 35 3931556H1 2156 2448 g6200220 1636 2068 35 70403042D1 1941 2338 35 3930720H1 2156 2466

5804093H1 1 177 35 70401079D1 1942 2338 35 3934202H1 2158 2442

2684902H1 8 257 35 70409409D1 1942 2337 35 4889738H1 2172 2465

5833363H1 27 136 35 70403961D1 1943 2338 35 4906569H2 2195 2471 g3280141 29 431 35 70409163D1 1947 2427 35 7272031H1 2200 2720

4203938H1 100 374 35 70402796D1 1950 2338 35 ^• 71219448V1 2202 2828

2563955H1 179 402 35 3700809H1 1951 2251 35 5468686H1 2207 2384

70408909D1 1832 2372 35 70402339D1 1963 2338 35 4914352H1 2208 2502

70403746D1 1839 2338 35 3475377H1 1965 2116 35 gl636142 2209 2466

70403011D1 1835 2338 35 5640458H1 1965 2103 35 6160218H1 2219 2480

70401407D1 1845 2338 35 70400757D1 1967 2338 35 3873766H1 2234 2528

70401227D1 1839 2339 35 70403528D1 1969 2338 35 70403069D1 2234 2337

70402036D1 1840 2338 35 70403542D1 1974 2426 35 5425426H1 2245 2514

70409006D1 1848 2338 35 70408826D1 1978 2337 35 3643322H1 2257 2528

70408788D1 1854 2338 35 70400431D1 1993 2654 35 2123362F6 2257 2701

70403814D1 1854 2338 35 70403190D1 1999 2427 35 2123362H1 2257 2585

70408844D1 1865 2338 35 70408542D1 2001 2337 35 033931H1 2257 2335

70409308D1 1865 2337 35 70410141D1 2005 2338 35 4615229H1 2260 2522

70403074D1 1869 2338 35 70401284D1 2002 2338 35 3212960H1 2260 2557

70400541D1 1870 2338 35 71220096V1 2021 2742 35 6729709H1 2268 2832

70409808D1 1872 2337 35 7262840H1 2031 2527 35 2821789H1 2283 2592

70401172D1 1879 2338 35 3277490H1 2025 2282 35 6815772J1 2289 2737

70401503D1 1883 2338 35 4806444H1 2027 2305 35 6815772H1 2289 2738

70408973D1 1899 2338 35 5464475H1 2039 2303 35 4199572H1 2313 2480

70401272D1 1906 2338 35 70410172D1 2029 2427 35 2795091H1 2323 2571

70409425D1 1903 2338 35 4725604H1 2044 2327 35 1389192H1 2325 2575

70401367D1 1909 2338 35 gl010563 2062 2431 35 gl628772 2328 2690

70402747D1 1908 2338 35 2744790H1 2075 2336 35 70403666D1 2340 2804

Table 2 (cont.)

35 2501716H1 2341 2567 35 70409421D1 1804 2338 35 70408367D1 . 1803 2338

35 3562675H1 2344 2655 35 70402038D1 1803 2304 35 70402838D1 1803 2338

35 3229405H1 2346 2449 35 70403722D1 1803 2277 35 70403713D1 1803 2359

35 4807968H1 2346 2604 35 70410122D1 1803 2338 35 70402007D1 1804 2336

35 2207651H1 2350 2546 35 70408553D1 1803 2296 35 70409325D1 1804 2337

35 5921344H1 2352 2625 35 70401060D1 1803 2304 35 70409816D1 1803 2338

35 6553789H1 2361 2831 35 70409920D1 1805 2338 35 70408486D1 1803 2337

35 3370548H1 2359 2635 35 70409860D1 1803 2266 35 70401965D1 1804 2320

35 6553802H1 2361 2837 35 70409739D1 1803 2336 35 70403142D1 1804 2339

35 5203637H1 2361 2624 35 70402741D1 1803 2324 35 70400962D1 1803 2338

35 2360538H1 2370 2620 35 70403761D1 1803 2338 35 70408422D1 1803 2320

35 5512063H1 2374 2618 35 70401941D1 1803 2337 35 70408820D1 1804 2337

35 466927H1 2384 2614 35 70402900D1 1803 2251 35 70400582D1 1803 2336

35 2867737H1 2404 2706 35 70403535D1 1803 2252 35 70410053D1 1803 2336

35 5022887H1 2406 2691 35 70401221D1 1803 2241 35 70401113D1 1803 2319

35 6361886H1 2430 2806 35 70402260D1 1803 2238 35 70409463D1 1804 2334

35 1750069H1 2444 2698 35 70402886D1 1803 2251 35 70402134D1 1803 2398

35 70409940D1 2447 2654 35 70403149D1 1803 2277 35 70401254D1 1803 2313

^*•© O 35 1459993H1 2451 2698 35 70409015D1 1803 2254 35 70401763D1 1803 2349

35 1591570H1 2457 2667 35 70403254D1 1803 2226 35 70402564D1 1803 2338

35 70400763D1 2458 2659 35 70401797D1 1803 2338 35 70401261D1 1803 2318

35 70402011D1 1804 2338 35 70401877D1 1803 2194 35 70400898D1 1803 2284

35 70402022D1 1804 2338 35 70402928D1 1803 2194 35 70403285D1 1803 2340

35 70401984D1 1804 2338 35 70402401D1 1803 2251 35 70403790D1 1803 2278

35 70403362D1 1804 2344 35 70401108D1 1803 2157 35 70402785D1 1803 2315

35 70409507D1 1803 2338 35 70403940D1 1803 2339 35 70409925D1 1803 2330

35 70400560D1 1803 2337 35 70409514D1 1803 2338 35 70410196D1 1804 2299

35 70408612D1 1803 2338 35 70400487D1 1803 2162 35 70409675D1 1803 2302

35 70408741D1 1803 2338 35 70409135D1 1804 2341 35 70409070D1 1804 2367

35 70403513D1 1803 2321 35 70401488D1 1804 2338 35 70401207D1 1804 2240

35 70409234D1 1803 2338 35 70410083D1 1803 2338 35 70409958D1 1803 2252

35 70409561D1 1803 2336 35 70401410D1 1803 2338 35 70401936D1 1804 2252

35 70402084D1 1803 2304 35 70401822D1 1804 2427 35 70404095D1 1804 2233

35 70402132D1 1803 2338 35 70409405D1 1804 2338 35 70402994D1 1803 2249

35 70404004D1 1803 2338 35 70402730D1 1803 2362 35 70400636D1 1804 2338

35 70402821D1 1803 2337 35 70400849D1 1804 2338 35 70403096D1 1804 2210

35 70403962D1 1803 2295 35 70404129D1 1804 2338 35 70409831D1 1804 2252

35 70402206D1 1803 2338 35 70408998D1 1804 2338 35 70403804D1 1803 2302

Table 2 (cont.)

70409643D1 1804 2313 35 5844479H1 2750 2990 35 4741922H1 749 1030

70402932D1 1803 2254 35 3739173H1 2768 2968 35 7189954H1 752 1208

70402629D1 1804 2317 35 793322H1 2782 2978 35 6926389H1 1008 1571

70408768D1 1803 2208 35 gll86329 2822 3147 35 4776088H1 1134 1387

70403063D1 1803 2109 35 627833H1 2950 3186 35 2214468F6 1174 1631

70404055D1 1803 2108 35 1365903H1 2960 3198 35 2214468H1 1174 1420

70402323D1 1803 2110 35 1880754H1 2998 3282 35 2212841H1 1174 1399

70408812D1 1805 2338 35 4318269H1 2998 3264 35 6989363H1 1174 1639

70409104D1 1805 2337 35 856560R1 3000 3571 35 7007113H1 1298 1772

70408438D1 1805 2337 35 856560H1 3000 3186 35 7007165H1 1298 1834

70401075D1 1803 2319 35 4370060H1 3034 3306 35 7266085H1 1330 1885

70403544D1 1804 2198 35 5714869H1 3036 3301 35 6450746H1 1384 1895

70408402D1 1806 2338 35 5522327H1 3060 3290 35 2944529H1 1458 1560

70400531D1 1805 2337 35 2918451H1 3179 3459 35 7286863H1 1603 2193

70402219D1 1804 2291 35 g2567520 3239 3726 35 6757054H1 1619 2276

70402089D1 1807 2338 35 g2344517 3268 3725 35 7264414H1 1685 2348

70401825D1 1807 2338 35 6373991H1 3274 3536 35 6825784H1 1686 1922

1954602F6 1809 2353 35 g5545977 3324 3722 35 6825784J1 1686 1922

70403675D1 1807 2337 35 g6046858 3332 3730 35 7361696H1 1704 2248

70403886D1 1806 2338 35 gll62523 3346 3716 35 4797422H1 1724 2008

70402238D1 1809 2338 35 g694395 3474 ^' ^' 3700 35 70400437D1 1754 2337

1954602H1 1809 2131 35 5574617H1 3485 3724 35 70401090D1 1761 2338

70404096D1 1816 2338 35 6594032J1 1 551 35 70409807D1 1774 2338

70409147D1 1818 2338 35 6445080H1 23 407 35 70409354D1 1775 2338

5858068H1 2465 2736 35 2719866H1 66 321 35 70409253D1 1791 2337

3713316H1 2484 2679 35 glll8206 183 545 35 70409150D1 1796 2337

721887H1 2502 2694 35 4588942H1 237 476 35 70401695D1 1803 2338 g959590 2512 2820 35 5621363H1 268 564 35 70400797D1 1815 2337

2596901H1 2588 2671 35 4456238R6 282 551 35 70409128D1 1797 2338

3989566H1 2601 2867 35 4456238F6 282 551 35 70402543D1 1800 2337

6944124H1 2626 2802 35 4456238H1 282 553 35 70402249D1 1798 2338

3400559H1 2673 2919 35 6471492H1 387 942 35 70402246D1 1800 2338

097934H1 2682 2866 35 5713424H1 440 752 35 70408860D1 1807 2336

6804789J1 2681 3271 35 7213908H1 512 984 35 3398388H1 1798 2050

5274591H1 2704 2955 35 6757054J1 584 1183 35 70404125D1 1801 2338

5760373H1 2710 2981 35 5742313H1 626 906 35 70402651D1 1803 2195

2897406H1 2720 3008 35 6611978H1 665 788 35 70403707D1 1803 2338

3395763H1 2725 3003 35 3070545H1 686 962 35 70402959D1 1802 2338

Table 2 (cont.)

70408464D1 1803 2301 37 70618269V1 5139 5670 37 70618812V1 5372 5746

70408915D1 1803 2338 37 70621136V1 5131 5648 37 70503581V1 5358 5593

70410162D1 1803 2292 37 6894475J1 5133 5663 37 70617418V1 5376 6105

70410097D1 1802 2338 37 70619097V1 5143 5540 37 5318827H1 5423 5719

70401266D1 1803 2224 37 70616216V1 5159 5538 37 4696141H1 5364 5605

70402758D1 1803 2338 37 2485114H1 5160 5405 37 3559054H1 5362 5656

70408969D1 1803 2270 37 70620234V1 5178 5658 37 862836H1 5364 5626

70402907D1 1803 2140 37 70879023V1 5182 5658 37 70621195V1 5405 5842

70400530D1 1803 2338 37 70618332V1 5184 5669 37 70620447V1 5403 6074

70410094D1 1803 2338 37 70620057V1 5141 5754 37 70616133V1 5404 5955

70409720D1 1803 2338 37 70619914V1 5206 5686 37 70880367V1 5417 5985

70402087D1 1803 2338 37 4261932H1 5214 5489 37 70615666V1 5408 5883

70401876D1 1803 2338 37 70650034V1 5223 5581 37 70615899V1 5411 6074

70401160D1 1803 2338 37 g273566 5225 5652 37 70615906V1 5420 5883

70401129D1 1803 2338 37 70880890V1 5181 5772 37 70620788V1 5422 6011

70401829D1 1803 2423 37 70624446V1 5194 5760 37 70619384V1 5423 6095

70402085D1 1803 2418 37 5483092H1 5248 5549 37 7352079H1 5485 5748

70400655D1 1803 2426 37 5477863H1 5246 5515 37 70618060V1 5452 5977

70403265D1 1803 2347 37 70617479V1 5207 5803 37 6247388H1 5422 6026

70400589D1 1803 2328 37 5726773H1 5253 5918 37 2528121H1 5422 5746

70404011D1 1803 2320 37 70879133V1 5262 5658 37 70620749V1 5443 6099

70401668D1 1803 2338 37 70620636V1 5213 5857 37 70498315V1 5453 5700

70400417D1 1803 2337 37 70616839V1 5223 5881 37 70620969V1 5454 5992

70403763D1 1803 2342 37 70619815V1 5225 5879 37 70618329V1 5465 6017 gl713124 1 225 37 70879948V1 5274 5520 37 70620484V1 5472 6145

542565R6 1 574 37 70621903V1 5359 5757 37 70616943V1 5480 5964

542565H1 1 270 37 70618382V1 5315 5905 37 70616995V1 5486 5993

544741H1 1 223 37 1890857F6 5303 5840 37 3865123H1 5486 5687

6785188H1 58 523 37 1890857H1 5303 5541 37 70618253V1 5507 5998

4623103H1 157 318 37 70504360V1 5308 5498 37 70619738V1 5509 6115 g2704045 274 790 37 3040285H1 5393 5663 37 70619181V1 5504 6230

3033590H1 376 650 37 70619930V1 5350 5885 37 70620918V1 5521 6074 gl276226 5072 5610 37 70619070V1 5415 5743 37 6262661H1 5507 5608

70882057V1 5076 5658 37 70620328V1 5360 5985 37 70888391V1 5563 6008

70617362V1 5079 5552 37 70496941V1 5416 5680 37 70617133V1 5533 6012

1981909H1 5086 5337 37 70498283V1 5416 5694 37 70879158V1 5595 5759

7170527H1 5086 5710 37 70618563V1 5290 5529 37 70619674V1 5548 6011

70616182V1 5094 5578 37 3785328H1 5356 5662 37 70620880V1 5570 6190

Table 2 (cont.)

70619138V1 5593 6082 37 71225106V1 380 591 37 6792454H1 4247 4809

70620826V1 5579 5690 37 71225845V1 648 1232 37 512449R6 4249 4619

70618435V1 5616 6301 37 71224962V1 708 1268 37 512449H1 4249 4438

70619862V1 5613 6059 37 70857749V1 759 1308 37 70619775V1 4264 4860

70620613V1 5615 6328 37 70858791V1 781 1316 37 7181830H1 4337 4861

1516536H1 5596 5840 37 70854894V1 817 1388 37 70879670V1 4427 5087

70619476V1 5631 6020 37 70857824V1 834 1385 37 6894475H1 4442 4838

6935004H1 5623 6174 37 70855972V1 920 1308 37 5981116H1 4464 4755

2640363H1 5629 5912 37 70857266V1 994 1308 37 70617408V1 4473 5161

3604521H1 5635 5746 37 6772619H1 1598 1776 37 70616799V1 4495 5126

70619382V1 5713 6146 37 7185296H1 1642 2055 37 70617065V1 4500 4850

70818695V1 5659 6204 37 7073243H1 3204 3547 37 3490263H1 4506 4813

70620844V1 5664 6228 37 6766490H1 3385 3817 37 gl859643 4567 4932

3760875H1 5641 5966 37 7017748H1 3445 3942 37 g4087359 4571 4982

3943020H1 5645 5969 37 6114505F6 3540 3996 37 g3000977 4574 4983

70620559V1 5673 6335 37 6434044H1 3665 4132 37 g4989741 4574 4940

70616094V1 5672 6266 37 4710907H1 3710 3990 37 g2000399 4580 4815

4201144H1 5656 5973 37 7234428H1 3753 4245 37 3256884H1 4642 4905

4201180H1 5656 5972 37 2858673H1 3903 4178 37 70613861V1 4650 5146

70881782V1 5733 6187 37 4029137H1 4031 4292 37 70615630V1 4675 5042

4902889H1 5668 5767 37 5015760F6 4037 4340 37 3409903H1 4666 4940

7218613H1 5666 6233 37 5015760H1 4037 4275 37 70620029V1 4686 5307

70620784V1 5742 6067 37 g846225 4127 4487 37 70616134V1 4698 5317

1478381H1 5702 5967 37 70615817V1 4144 4521 37 70615913V1 4709 5342

3472002H1 5757 6011 37 70619303V1 4186 4682 37 3472617H1 4738 4994

70882025V1 5814 6382 37 70616967V1 4186 4621 37 70616331V1 4758 5407

70620923V1 5854 6402 37 70620336V1 4186 4723 37 70879269V1 4760 5260

70616260V1 5818 6436 37 70623727V1 4186 4438 37 70616143V1 4803 5484

70880143V1 5867 6322 37 70879730V1 4186 4809 37 70619735V1 4837 5303

70616268V1 5819 6421 37 70616808V1 4186 4780 37 7359868H1 4826 5403

6307739H1 5814 6207 37 70621137V1 4186 4698 37 70618473V1 4836 5424

7215905H1 5846 6309 37 2583232F6 4186 4675 37 70617594V1 4839 5512

70615731V1 5872 6442 37 70621004V1 4186 4714 37 70615967V1 4854 5424

70618948V1 5844 6363 37 70627216V1 4186 4535 37 70616258V1 4872 5558

1483044F6 5842 6402 37 2583232H1 4186 4499 37 70618513V1 4872 5502

1483044H1 5842 6067 37 g273352 4223 4554 37 5636144H1 4877 5171 g5689372 1 6921 37 g273351 4223 4511 37 70616075V1 4881 5586

6764731J1 177 746 37 6772536H1 4229 4365 37 70619645V1 4886 5554

Table 2 (cont.)

70621119V1 4890 5408 37 5186625H1 7798 8038 37 1634329F6 7026 7583 gl484780 4893 5372 37 6399472H1 7835 8038 37 g4113770 7028 7329

2208615F6 4892 5326 37 gl484726 7836 8047 37 1634329H1 7026 7260

2208615H1 4892 5180 37 4464454H1 7937 8038 37 6023847H1 7040 7258 gl938974 4900 5441 37 1954133H1 6925 7182 37 gl955189 7044 7363

6534152H1 4900 5213 37 g4685458 6927 7426 37 1880801H1 7070 7228

6416152H1 4900 5191 37 g4072884 6932 7428 37 70961362V1 7079 7662

512449T6 4910 5294 37 g4072585 6932 7387 37 glll4689 7080 7235 gl859530 4917 5335 37 g4301838 6932 7349 37 2558518H2 7092 7383

7069813H1 4932 5511 37 g4971726 6932 7328 37 3417896H2 7107 7366 gl999705 4935 5233 37 g5706977 6932 7258 37 4314435H1 7117 7402

70619554V1 4938 5557 37 g4982867 6932 7325 37 2611381H1 7141 7403

70880135V1 4954 5576 37 g5444767 6936 7432 37 2345823H1 7156 7396

70616830V1 5008 5634 37 4435811H1 6939 7223 37 g848451 7179 7508

70620540V1 5004 5493 37 g4531759 6943 7428 37 g848137 7179 7509

70625529V1 5006 5596 37 g6040411 6943 7372 37 70960910V1 7180 7787

7240188H1 5007 5436 37 g5545712 6943 7311 37 5857373H1 7187 7467

70881149V1 5025 5658 37 71287859V1 6955 7613 37 2578818H1 7245 7494

70620009V1 5038 5484 37 g4991288 6954 7324 37 6410914H1 7255 7606

70615572V1 5040 5582 37 g5111387 6957 7452 37 877308H1 7260 7510

70818665V1 5051 5653 37 6207366H1 6957 7366 37 1677670H1 7272 7531

70615553V1 5064 5522 37 g851259 6964 7272 37 856524H1 7274 7491

70617505V1 5064 5424 37 g5913695 6967 7431 37 5756606H1 7270 7640

70618274V1 5064 5658 37 2428623H1 6973 7220 37 856524R1 7275 7708

70616969V1 5067 5474 37 2768162H1 6972 7242 37 4597131H1 7283 7569 gl269975 5068 5435 37 5609278H1 6974 7263 37 4597139H1 7284 7566 g5437930 7703 8018 37 g848048 6975 7259 37 3047862H1 7298 7628 g2010328 7739 8038 37 g844877 6975 7232 37 2721155H1 7319 7585 g851258 7740 8059 37 5608655H1 6974 7165 37 2367879H1 7326 7575 gl999704 7753 8038 37 g848452 6980 7281 37 2367940H1 7326 7565 gl968457 7754 8032 37 g2912608 6988 7412 37 2561929H1 7348 7640

3695683H1 7756 8032 37 g2789254 6992 7462 37 g789819 7372 7676

3992490H1 7764 8042 37 g2010327 6997 7317 37 gl893853 7379 7868 gl237712 7776 8043 37 452519H1 6996 7196 37 1386867H1 7411 7694

2568186H1 7779 8040 37 gl696891 7007 7370 37 2102141H1 7411 7664

3090238H1 7786 8018 37 gl927797 7013 7427 37 70961741V1 7419 7998

2755544H1 7791 8028 37 2952058H1 7018 7316 37 4062984H1 7418 7717

5304805H1 7791 7852 37 1632083H1 7026 7252 37 6609732T1 7423 7993

Table 2 (cont.)

71288471V1 7438 8037 37 2922847H1 7627 7906 37 70880732V1 6119 6798

542802H1 7435 7687 37 467740H1 7635 7761 37 70621039V1 6120 6715

3183469H1 7439 7753 37 1299807T6 7661 8006 37 70617737V1 6127 6361

2889919H1 7448 7745 37 3116753H1 7661 7964 37 70618993V1 6128 6687

71287912V1 7454 8031 37 1634329T6 7664 7988 37 4414769F7 6128 6645

542420T6 7463 8001 37 1299807F6 7666 8046 37 70881349V1 6128 6536 gl696890 7457 7674 37 1302535H1 7666 7925 37 7353816H1 6128 6524

1992524H1 7468 7735 37 4381913H1 7669 7885 37 70616076V1 6128 6508

7315008H1 7477 8036 37 gl955188 7671 8028 37 70621068V1 6128 6454

6498781H1 7485 8037 37 gl023550 7676 7877 37 1893190H1 6128 6313

2363076H1 7491 7743 37 3506258H1 7699 7987 37 4414737H1 6128 6311

70962526V1 7505 8038 37 3190265H1 7703 8019 37 70880409V1 6128 6245

2541325T6 7508 8030 37 3640143H1 5850 6067 37 5552794H1 6135 6392

5439901H1 7508 7781 37 gl058796 5863 6279 37 6721737H1 6159 6670

70960239V1 7521 8139 37 70879938V1 5903 6331 37 1620586F6 6172 6775

70959969V1 7516 8138 37 6619878H1 5884 6248 37 1620586H1 6172 6418

70962026V1 7521 7999 37 70879734V1 5954 6378 37 6554848H1 6178 6323 gl058797 7531 7842 37 70618709V1 5900 6607 37 2670967H1 6197 6488 g844876 7532 7854 37 5896140F8 5944 6198 37 gl812162 6262 6573

70961850V1 7536 8042 37 5902302H1 5925 6216 37 6754444J1 6298 6912 g6199311 7544 7773 37 g836224 5932 6315 37 gll65739 6307 6641

2262402H1 7545 7800 37 70618193V1 5971 6538 37 6323675H1 6344 6619

70960408V1 7558 8043 37 70620855V1 5963 6415 37 70615665V1 6361 6466

1677670T6 7558 7995 37 g863194 5933 6079 37 70619085V1 6398 6854

2870359H1 7574 7879 37 6191238H1 5937 6216 37 g6402120 6414 6886

70962112V1 7573 8038 37 70618603V1 5998 6489 37 70882125V1 6416 6912

3476271H1 7578 7871 37 4344847H1 5946 6174 37 gl938861 6416 6874

5287659H1 7583 7851 37 5710016H1 5946 6086 37 g3918125 6419 6903

2622502H1 7584 7868 37 5958086H1 5957 6352 37 g2963681 6423 6874

943201R1 7592 7941 37 1456815H1 5983 6240 37 g5858735 6427 6921

943201H1 7592 7915 37 70615575V1 6005 6067 37 6377385H1 6428 6703

943201T1 7592 7898 37 5075968H1 6005 6316 37 g3742521 6436 6921

1376382T6 7598 7997 37 3049230H1 6046 6358 37 g3744266 6445 6921

2317068H1 7600 7870 37 5904031H1 6023 6268 37 g3740229 6449 6921

1242031H1 7601 7832 37 5896849H1 6021 6258 37 g5425723 6450 6921

3992490R6 7603 8032 37 5271038H1 6026 6217 37 g5451756 6452 6878

877515H1 7623 7717 37 7236094H1 6128 6380 37 g2840870 6463 6874

877515T1 7623 8002 37 3605141H1 6109 6376 37 g5658296 6466 6912

Table 2 (cont.) g6140517 6481 6920 37 g2902901 6914 7411 38 70318920D1 518 927

6303334H1 6482 6791 37 g4269453 6914 7429 38 70320035D1 530 857 g5658227 6488 6921 37 g4875491 6914 7431 38 70318273D1 536 970

70505089V1 6504 6667 37 g4267673 6914 7427 38 4120208H1 545 788

542420R6 6508 6863 37 g6504581 6915 7330 38 70320719D1 565 970

542420H1 6508 6762 37 g6504381 6915 7326 38 70317918D1 584 1042 g3872787 6520 6875 37 g3173140 6914 7283 38 70321152D1 584 1043

1837912H1 6545 6824 37 g3058614 6914 7255 38 70320434D1 584 989 g3872172 6548 6903 37 gll93529 6913 7182 38 70320713D1 584 970 gl813182 6551 6874 37 gl893755 6914 7160 38 70320635D1 584 970

7334638H1 6569 6912 37 g3433586 6915 7468 38 70320227D1 584 969 g5849171 6575 6874 37 g6138320 6915 7313 38 70317509D1 584 970 g3179214 6588 6875 37 1362613F6 6917 7542 38 70320694D1 586 970 g5658864 6592 6921 37 71288170V1 6917 7498 38 70320790D1 584 953

6428653H1 6610 6912 37 70962658V1 6917 7465 38 70318744D1 584 993 gl226529 6615 6892 37 71286924V1 6917 7465 38 70318259D1 585 1042 g5857904 6636 6891 37 70961637V1 6917 7486 38 70318517D1 599 1043 g836225 6686 6913 37 70956912V1 6917 7299 38 70317458D1 599 989 gl231446 6700 6920 37 1362613H1 6917 7140 38 70318194D1 599 970

70613460V1 6761 6913 37 g3658929 6918 7421 38 70320117D1 639 970

70624483V1 6809 6913 37 7109112H1 6923 7198 38 70319709D1 676 1100

4582057H1 6814 7103 38 2788120H1 217 469 38 70319736D1 755 1245

2541325F6 6837 7357 38 6469701H1 244 630 38 70319869D1 833 970

2541325H1 6837 7098 38 70319065D1 309 706 38 2797803T6 850 1390 gl273237 6847 7420 38 70320239D1 331 908 38 70320906D1 859 1245

70962108V1 6907 7533 38 70320883D1 331 761 38 70320282D1 859 970

70961943V1 6917 7464 38 70318969D1 332 889 38 3873636H1 897 1195 g4268343 6914 7451 38 70318139D1 517 1043 38 6932926H1 965 1317 g4243879 6914 7427 38 70317613D1 517 971 38 70319282D1 990 1423 g5435797 6914 7436 38 70318020D1 517 970 38 7076550H1 998 1422 g3765880 6914 7419 38 70317863D1 517 906 38 70319385D1 1017 1245 g3920399 6914 7422 38 70319554D1 517 906 38 g2329469 1076 1366 g5837342 6914 7400 38 70317969D1 517 906 38 3882715H1 117 429 g4438024 6914 7349 38 70319562D1 517 857 38 2797803F6 214 667 g4110613 6914 7355 38 70318409D1 517 811 38 2797803H1 214 458 g3149204 6914 7324 38 70317555D1 517 751 38 6990517H1 1 513 g5367473 6914 7311 38 70318235D1 518 1040 38 3873636T6 1149 1488 g4891812 6914 7310 38 70320237D1 518 966 39 71282176V1 208 705

Table 2 (cont.)

70947005V1 228 721 39 70944537V1 688 1129 40 5152317H1 11 258

70948844V1 229 721 39 70941941V1 694 1129 40 6731218H1 30 603

70942023V1 240 925 39 70941413V1 628 1129 40 6948820H1 280 873

70947964V1 287 743 39 70942815V1 642 899 40 2421526H1 530 761

5509756F6 208 693 39 6770687J1 726 1309 40 6073677H1 552 616

6881073H1 294 841 39 4491504H1 941 1521 40 3738019F6 561 931

70944164V1 208 694 39 70944142V1 644 1129 40 3738019H1 561 848

5511496R6 301 739 39 2286793R6 979 1416 40 4818484H1 684 950

3786301H1 329 524 39 2286793H1 979 1221 40 2844496F6 690 1186

71281455V1 353 832 39 70944214V1 644 1129 40 g5365267 722 1017

70944870V1 208 677 39 4319902H1 663 959 40 5913982H1 781 1038

5513185F6 430 674 39 3786595H1 1024 1317 40 626987R6 856 1174

5509756H1 208 469 39 4319902T6 1063 1547 40 626987T6 856 1137

71031868V1 208 427 39 4319902F6 663 1057 40 626987H1 856 1127

70949830V1 223 721 39 5509756R6 675 1128 40 gl229837 888 991

5513185H1 430 650 39 70944571V1 678 1129 40 gl757731 912 1213

5514146R6 461 721 39 71282102V1 677 1129 40 2844496H1 956 1186

71031732V1 528 1128 39 70400930D1 1073 1582 40 1787217H1 976 1219

70941524V1 571 1129 39 70400517D1 1073 1521 40 3024706H1 992 1272

71281828V1 578 1150 39 70403161D1 1073 1352 40 6833501H1 1019 1579

71281414V1 587 1150 39 5513185R6 1077 1462 40 6495087H1 1099 1672

70944681V1 626 1129 39 70403184D1 1092 1590 40 3759406F6 1207 1605

70947006V1 174 721 39 70943645V1 683 1129 40 6129674H1 1218 1777

70947327V1 182 721 39 70402851D1 1092 1582 40 3759406H1 1296 1605

70950064V1 1 551 39 70408976D1 1092 1586 40 gl329304 1415 1897

5514146F6 1 450 39 70409982D1 1092 1586 40 3529782H1 1548 1834

5514146H1 1 253 39 70400662D1 1092 1582 40 g5589620 1561 1983

70941486V1 208 801 39 70403896D1 1093 1593 40 g4391274 1604 1981

70948652V1 1 500 39 2286793T6 1106 1546 40 gl327148 1607 1980

70941948V1 208 791 39 3789471H1 1130 1318 40 gl202759 1697 2000

70941325V1 208 779 39 6517607H1 1193 1586 40 5664383H1 1797 2028

70944422V1 208 733 39 7111257H1 1234 1565 40 3738019T6 1943 2138

70948684V1 64 639 39 70402275D1 1353 1582 41 g6143336 1 144

71281664V1 208 710 39 70401863D1 1377 1761 41 g2879555 1 209

70948520V1 118 721 39 532083R6 1378 1587 41 963305H1 1 293

70949432V1 143 721 39 532083H1 1378 1594 41 4663761H1 10 156

70950259V1 167 721 39 70410195D1 1483 1542 41 3081565H1 12 110

71281141V1 208 711 40 5640011H1 1 251 41 3581329H1 32 334

Table 2 (cont.)

41 3581329F6 32 521 42 5017862H1 3568 3888 42 987342R1 3909 4502

41 gl958399 51 636 42 6436182H1 3575 4177 42 987342H1 3909 4235

41 g2537611 149 655 42 2991108H1 3568 3895 42 3414596H1 3918 4171

41 g2537515 149 624 42 70593249V1 3604 4184 42 1968627H1 3944 4210

41 5909807H1 278 437 42 4949408H1 3573 3885 42 2079587H1 3963 4238

41 4741915H1 587 870 42 1582264H1 3573 3758 42 1942952R6 3975 4493

41 4741915F6 587 999 42 g2011219 3574 3973 42 1942952H1 3975 4279

41 g711286 905 1109 42 1694330F6 3575 4133 42 4266394H1 3977 4042

41 g762724 905 1183 42 1694330H1 3575 3805 42 4547820H1 3985 4270

41 g704731 905 1156 42 70596251V1 3605 4113 42 5566036H1 3987 4274

41 7210740H1 985 1345 42 70592924V1 3600 4113 42 1495578H1 3993 4245

42 g4186965 4402 4699 42 6040536H1 3651 4116 42 2290489H1 4000 4265

42 g749963 4403 4665 42 4729196H1 3661 3924 42 70636253V1 4001 4113

42 3735811H1 4400 4570 42 008776H1 3679 3953 42 4837424H1 4018 4326

42 g817541 4407 4703 42 3712443H1 3682 3965 42 1942952T6 4024 4650

42 5470839H1 4408 4627 42 70595569V1 3693 4227 42 2415411H1 4047 4237

42 g5857465 4409 4690 42 3893442H1 3703 3987 42 4597196H1 4052 4319

42 g4089465 4416 4698 42 70594859V1 3705 4113 42 038747H1 4055 4308O O 42 g5673112 4434 4698 42 2674702H1 3707 3953 42 416329H1 4080 4326

42 g832504 4432 4707 42 g843423 3723 3961 42 411642H1 4080 4297

42 239758H1 4434 4672 42 4166512H1 3729 4032 42 413609H1 4080 4303

42 239683H1 4434 4675 42 4490386H1 3768 4346 42 g858610 4095 4388

42 g5630172 4436 4696 42 439941R6 3800 4179 42 6168330H1 4105 4470

42 g5847690 4442 4696 42 447820H1 3801 4033 42 gl577324 4113 4324

42 g3144984 4443 4665 42 70592549V1 3809 4113 42 4862551H1 4128 4322

42 1343411H1 4452 4676 42 6045881H1 3811 4361 42 g844960 4134 4537

42 g2569470 4474 4695 42 2331457H1 3811 4063 42 g848470 4135 4445

42 g4989544 4479 4696 42 gl745095 3819 4246 42 1216752H1 4142 4377

42 g560358 4490 4690 42 g894451 3824 4209 42 2603819H1 4157 4401

42 g894410 4511 4656 42 g750070 3824 4064 42 2544424H1 4158 4402

42 g2732080 4516 4696 42 g2565679 3834 4200 42 2754442H1 4171 4452

42 571723H1 4519 4690 42 3359221H1 3855 4137 42 917070T1 4185 4683

42 g858663 4524 4661 42 g2565784 3861 4200 42 917070H1 4185 4357

42 3328937H1 4533 4695 42 5283035H1 3883 4166 42 5897064H1 4192 4506

42 g3418413 4586 4690 42 6879635H1 3902 4480 42 5902845H1 4192 4491

42 g5662220 4602 4690 42 6045881J1 3906 4391 42 5896842H1 4192 4449

42 2741443H1 4643 4700 42 gll65520 3908 4221 42 g2713617 4193 4682

42 6620633H1 3565 3910 42 g2537466 3908 4007 42 1630325H1 4197 4431

Table 2 (cont.)

1630138H1 4197 4420 42 gl486975 4319 4697 42 2210296H1 1391 1628

4229783H1 4203 4496 42 g892196 4324 ■ 4703 42 2210403F6 1391 1868 g4136910 4219 4695 42 g3279131 4329 4701 42 4031020H1 1497 1753

2292673H1 4219 4483 42 g2358649 4331 4696 42 g2112520 1547 2048 g4269943 4221 4690 42 g843378 4349 4695 42 1655312T6 1596 2108 g4739630 4223 4695 42 3622954H1 4349 4654 42 3174512H1 1612 1856 g4736707 4226 4698 42 6839954H1 4349 4707 42 1723245T6 1636 2109

2626005H1 4229 4505 42 g2140547 4355 4698 42 2210403T6 1636 2109

2625829H1 4229 4468 42 g678534 4357 4690 42 g5393042 1674 2150 gl481868 4234 4694 42 2319411H1 4376 4640 42 3413243H1 1686 1938

5017059H1 4234 4484 42 6772602H1 1 519 42 g4174736 1701 2153 g3281238 4236 4692 42 6772602J1 8 525 42 6338656H1 1709 2147

4505368H1 4236 4512 42 6880022H2 89 573 42 2406763H1 1745 1982 g3144087 4242 4695 42 gl957521 270 750 42 g5639058 1815 2150 g5858526 4245 4695 42 6930168H1 405 575 42 3243872F6 1850 2227 g2713666 4259 4696 42 3531464H1 629 926 42 3243872H1 1850 2046 g3421998 4261 4699 42 1723245F6 735 1178 42 7076585H1 1955 2471

6396625H1 4265 4510 42 1723245H1 735 947 42 3899958H1 1959 2225 g4333743 4268 4690 42 7172590H1 768 1332 42 5902403H1 1960 2272 g5527375 4277 4695 42 6942842H1 786 1130 42 5902568H1 1960 2263 g4329772 4283 4698 42 6828957J1 844 1493 42 7013892H1 2058 2334 gl891693 4284 4696 42 6880022J1 878 1539 42 3596766H1 2065 2361 g3741927 4287 4699 42 1866114H1 917 1169 42 3596766F6 2065 2323 g4187402 4288 4694 42 7098620H1 966 1536 42 961692H1 2131 2331 gl744997 4288 4689 42 g3758210 1033 1436 42 g2884006 2191 2658 g917141 4291 4673 42 4895760H1 1062 1163 42 6419411H1 2203 2420 g3244774 4292 4695 42 1655312F6 1125 1572 42 6483672H1 2218 2734 g3648187 4292 4601 42 1655312H1 1125 1359 42 6064745H1 2218 2518 g3839663 4294 4698 42 6308462H1 1153 1635 42 5111344H1 2218 2483 g2106394 4294 4690 42 6313582H1 1154 1238 42 5199520H1 2218 2466 g4270115 4296 4690 42 4192005H1 1159 1335 42 6268649H1 2232 2513 g4089300 4300 4696 42 1928561H1 1195 1462 42 4030823H1 2231 2492 g4988925 4303 4672 42 6828957H1 1307 1778 42 2531619H1 2243 2492 g6027944 4304 4690 42 6595762H2 1350 1934 42 2493928H1 2244 2566 g3751446 4306 4695 42 5425831H1 1374 1520 42 1835162T6 2247 2699 g3163418 4309 4690 42 6595762J1 1379 1955 42 1835162R6 2247 2638 g3869704 4315 4695 42 3454330H1 1389 1640 42 1835162H1 2247 2491 g3423446 4316 4690 42 2210403H1 1391 1657 42 gl986374 2255 2573

Table 2 (cont.)

42 6914575J1 2280 2839 42 5680812H1 3305 3517 43 5005344H1 389 662

42 g3052903 2356 2756 42 70591287V1 3310 3916 43 1851313T6 390 928

42 g3099254 2357 2756 42 1599669F6 3328 3855 43 3167557H1 390 693

42 g5837122 2360 2749 42 1599669H1 3328 3556 43 735311H1 389 615

42 6991132H1 2405 2945 42 3944108H1 3328 3452 43 g943247 408 585

42 1295850H1 2523 2759 42 473931H1 3348 3586 43 gl062500 409 716

42 g5811286 2592 2753 42 2260945H1 3350 3614 43 70300862D1 410 722

42 7178785H1 2599 2951 42 6438815H1 3377 3988 43 2184742H1 413 706

42 g892202 2629 3026 42 1337442H1 3388 3651 43 728410R6 434 773

42 5405377H1 2641 2861 42 1468618H1 3392 3519 43 728410H1 434 686

42 3798053H1 2667 2900 42 4340801H1 3406 3589 43 gl664931 443 828

42 3243517H1 2670 2924 42 6952811H1 3419 4094 43 2368303H2 442 694

42 1871338F6 2714 3141 42 70591139V1 3437 4158 43 699622H1 447 647

42 1871338H1 2714 2830 42 6737173H1 3473 4057 43 6774559H1 447 966

42 g2030276 2756 3095 42 2408518H1 3482 3732 43 4976546H1 448 662

42 g4989487 2757 3221 42 5101625H1 3516 3651 43 7353452H1 473 998

42 g831781 2776 3012 42 3555394H1 3536 3863 43 g4084403 481 840 o ² 816801H1 2796 3046 42 2401170H1 3545 3820 43 1715928H1 500 747 o 42 100914H1 2977 3152 42 5101725F9 3545 3607 43 1300651H1 501 739

42 g3174505 3012 3221 42 gl486974 3552 3873 43 201520H1 504 832

42 6879635J1 3027 3604 43 4762482F8 1 578 43 4987575H1 503 758

42 g880203 3043 3367 43 4762482F9 1 675 43 202340H1 505 905

42 g706026 3042 3351 43 70300728D1 225 828 43 1308775H1 517 785

42 g3360412 3078 4696 43 70300734D1 251 716 43 4128110H1 519 708

42 g770838 3097 3247 43 70300231D1 257 795 43 871027H1 527 769

42 6914575H1 3109 3678 43 70300221D1 261 801 43 gl300912 530 771

42 g697357 3109 3483 43 70300270D1 261 716 43 1657105H1 529 711

42 gl891750 3173 3577 43 4767039H1 292 569 43 1254981H1 530 775

42 gl481321 3183 3582 43 4219425H1 295 598 43 1255176H1 530 762

42 3212095H1 3195 3473 43 70300328D1 297 876 43 1855454H1 536 795

42 g2046501 3221 3602 43 1892972H1 310 579 43 6774559J1 539 1216

42 665620H1 3231 3408 43 gl201811 320 676 43 g6132872 538 971

42 3214669H1 3234 3491 43 7057207H1 329 967 43 1341435H1 545 792

42 6589976H1 3241 3736 43 7058929H1 329 919 43 957179H1 585 868

42 7033558H1 3248 3852 43 3979505H1 336 624 43 2137224H1 586 867

42 5544513H1 3249 3452 43 3031026H1 339 654 43 2078670H1 600 863

42 2851066H1 3257 3527 43 2926473H1 346 611 43 6051601J1 600 854

42 5659979H1 3285 3558 43 1866123H1 360 607 43 6051601H1 600 854

Table 2 (cont.)

3084378H1 601 830 44 4582451T9 3739 4167 44 3077509H1 4191 4269

6102879H1 600 798 44 4321119H1 3740 4001 44 g5635105 4214 4374

123181H1 602 823 44 2159154H1 3752 4023 44 5718794H1 4217 4285 g2038744 609 848 44 5155185H1 3754 3999 44 4833360H1 4231 4430

5183851H1 610 867 44 70381521D1 3765 3826 44 995064H1 1 306

6199560H1 623 886 44 2854981H1 3769 4031 44 7183605H1 164 706

2299212H2 638 922 44 70378943D1 3773 3826 44 1945549H1 288 517

6755996H1 674 1299 44 5806161H1 3794 4073 44 7383801H1 294 751 g5363964 677 970 44 g4243139 3812 4278 44 6549205H1 308 754

109199H1 681 860 44 1880015H1 3830 4095 44 2832846T6 341 754 g990884 686 970 44 g4598394 3847 4270 44 6819064J1 435 810 g3161907 693 1069 44 g6439575 3851 4269 44 3280967H1 504 754 g6476617 699 969 44 3021981H1 3862 4151 44 2397313H1 607 834

1957314H1 740 829 44 g6476034 3867 4269 44 6830025J1 746 1064 g3004317 743 968 44 g3086570 3870 4268 44 6053477H1 762 1329

1661047H1 746 993 44 g3416423 3873 4269 44 4348719H1 775 1035

1660543H1 746 988 44 6733021H1 3879 4269 44 g3163362 788 1129

4972478H1 745 951 44 gl695458 3881 4269 44 4248617H1 798 1030 g4569699 770 969 44 5292403H2 3899 4146 44 6940669H1 802 1101 g3861537 770 863 44 5341347H1 3905 4148 44 6886338J1 801 1162 g3846933 773 944 44 1712455H1 3948 4152 44 5623119H1 819 987

4399877H1 784 904 44 g5513470 3963 4374 44 3597238H1 820 1104 g6041377 785 927 44 g3446060 3964 4374 44 914670H1 825 1091 g4599313 793 942 44 g4568404 3968 4269 44 915108H1 825 1131 g3848897 793 896 44 g4876405 4001 4385 44 5339305H1 846 919 g3848961 793 885 44 g4435068 4003 4374 44 5701708H1 880 1160

4212211H1 3429 3720 44 2270005H1 4019 4269 44 gl985651 889 1175

610669H1 3437 3709 44 g4301776 4027 4374 44 679430H1 900 1165

7102970H1 3515 4027 44 g2240627 4054 4374 44 3767690H1 961 1253

2885307H1 3534 3793 44 2410679H1 4059 4276 44 429994H1 993 1269

3714143H1 3548 3827 44 gl231923 4061 4272 44 4425802H1 1013 1275

70742997V1 3622 4221 44 211813H1 4104 4184 44 3768769H1 1017 1287

4072957H1 3629 3729 44 gl784545 4139 4276 44 2358712H1 1069 1330

2693562T6 3659 4246 44 6180170H1 4157 4273 44 2359316H1 1069 1331

70382494D1 3665 3772 44 2587751H1 4168 4275 44 2835111H1 1097 1370

70387993D1 3665 3825 44 g819902 4171 4386 44 5875970H1 1119 1401

2361176H1 3692 3955 44 1530352H1 4173 4375 44 5505305H1 1125 1342

4531511H1 3738 3987 44 2555081H1 4180 4269 44 3000263H1 1149 1444

Table 2 (cont.)

6782153H1 1160 1671 44 7060429H1 1745 2323 44 1435636H1 2620 2842

6053477J1 1203 1692 44 6955408H1 1748 2290 44 g2023037 2631 2947

3157719H1 1215 1498 44 6332331H1 1747 2192 44 70743767V1 3351 3875

3765631H1 1235 1519 44 6420565H1 1756 2147 44 3162341H1 2638 2911

1908860T6 1257 1675 44 70741619V1 3350 3955 44 1257054H1 2641 2874

4551786H1 1265 1463 44 6773924H1 1756 2263 44 1258294H1 2641 2863

4521416H1 1288 1531 44 3490671H1 1759 1926 44 6375444H1 2652 2922

3031440H1 1303 1442 44 5633425H1 1760 2016 44 3781848H1 2700 3010

890596H1 1315 1574 44 2171658H1 1759 1959 44 2772194H1 2706 2957

2991495H1 1356 1617 44 4840412H1 1770 2029 44 4633723H1 2723 2985

764400H1 1367 1610 44 5639607H1 1839 1967 44 023904H1 2728 2988

4906007H2 1395 1663 44 2512143H1 1858 2174 44 2763883H1 2738 2984

7267741H1 1469 1999 44 3243167H1 1970 2205 44 g3400659 2748 3194

6769245H1 1503 2048 44 2371305H1 1981 2202 44 4574816H1 2780 3041

997621R6 1575 1956 44 71303275V1 2021 2416 44 3882424H1 2796 3066

7328544H1 1580 2183 44 71130980V1 2217 2338 44 5687093H1 2819 3075

2832846H1 1580 1808 44 7213740H1 2222 2436 44 g920527 2832 3168

2860343H1 1580 1826 44 6332191H1 2329 2863 44 5281394H1 2844 3007

2830834H1 1580 1807 44 4730102H1 2375 2634 44 449764H1 2846 3059

2860379H1 1580 1847 44 1519940H1 2397 2598 44 4140731H1 2864 3170

3374480H1 1588 1863 44 1932345H1 2461 2718 44 g897406 2874 3188

6623866J1 1592 2173 44 4631720H1 2467 2747 44 g2254156 2935 3169

3077919H1 1614 1907 44 5516438H1 2467 2720 44 gl641497 2981 3180

3739575H1 1614 1877 44 4631626H1 2468 2655 44 3223084H1 2993 3290

4959060H1 1628 1875 44 g772275 2472 2763 44 1801096H1 2999 3085

4739571H1 1632 1886 44 6073520H1 2478 2745 44 3766823H1 3028 3310

5076688H1 1633 1891 44 4973296H1 2483 2621 44 454112H1 3070 3289

688318H1 1634 1905 44 5086726H1 2488 2*742 44 2661320H1 3075 3277

2445716H1 1664 1914 44 6701387H1 2488 2948 44 2688727H1 3091 3328

6044677H1 1665 1972 44 5687234H1 2488 2753 44 4595028H1 3292 3552

1386547H1 1665 1891 44 gl967335 2488 3017 44 70741735V1 3312 3923

2005094H1 1670 1929 44 6073522H1 2490 2745 45 6572570J1 1 436

6329762H1 1714 2197 44 4793022H1 2502 2616 45 g4435582 1 380

2898215H1 1710 2021 44 2228536H1 2505 2721 45 4345534F6 21 269

2243695H1 1728 1968 44 4590907H1 2507 2780 45 6073452H1 72 231

899794H1 1731 1996 44 4548974H1 2527 2743 45 4345534H1 105 269

5826773H1 1740 2266 44 3464267H1 2598 2832 45 7204038H1 148 663

518068H1 1739 1966 44 3492779H1 2605 2877 45 6981431H1 294 825

Table 2 (cont.)

2630960F6 730 1090 45 gl784513 1726 1848 47 1993688F6 1652 2097

2630960H1 730 965 45 2223448H1 1760 1896 47 1993688H1 1652 1899

609082H1 802 1065 45 g6505941 1763 2406 47 666099H1 1670 1895 g564302 805 1003 45 2660260H1 1785 2032 47 g3423957 1725 2098 gll39137 837 1181 45 4857157H1 1816 2022 47 g3241592 1770 2104

2554584H1 957 1231 45 3242659H1 1933 2154 47 1479372H1 1175 1422

2555307H1 957 1233 45 g823764 2079 2417 47 2761062H1 1178 1443

6990332H1 984 1308 45 6572570H1 2278 2762 47 2761062R6 1178 1435 g781616 1020 1332 45 6924120H1 2500 3013 47 6001120H1 1235 1723

5904340H1 1041 1335 45 6168506H1 2644 2967 47 6977932H1 1414 1612

5901269H1 1041 1283 45 6987381H1 2657 3220 47 7033269H1 1452 1982

5893679H1 1042 1343 45 3508325H1 2828 3116 47 3466972H1 1462 1719

5904340F6 1057 1609 46 7061915H1 1 477 47 5016835H1 1842 2094

6937534H1 1070 1684 46 g2155606 172 658 47 4774836H1 1845 2099

6092295H1 1129 1391 46 g2381480 353 4979 47 4229676H1 1889 2098 gl398375 1133 1551 46 g2842283 794 1156 47 4254348H1 1999 2098

6917411H1 1143 1733 46 g2034110 827 1154 47 2708491F6 715 1057

3142603H1 1278 1440 46 gll09149 1845 2143 47 6953084H1 1 555

3142603F6 1279 1701 46 gll67026 1888 2061 47 5373405H1 1 224 g4985474 1317 1751 46 5610451F6 2289 2861 47 5373405F8 21 542

5099033H1 1339 1615 46 5610451H1 2289 2532 47 3942701H1 129 421

4147460H1 1349 1541 46 gl969027 2438 2801 47 4340882H1 331 526

3142603T6 1395 1863 46 gll42377 2447 2779 47 4340882F6 331 807

3689942H1 1434 1717 46 gll51984 2615 3003 47 3323337H1 389 656 g4394682 1460 1909 46 g4242953 2628 2914 47 1479486F6 393 809 g3418148 1462 1908 46 gll09150 2745 2961 47 1479486H1 393 628 gl398292 1472 1885 47 6772168H1 1565 2062 47 1993010H1 423 703

6197152H1 1476 1923 47 2788543H1 1463 1697 47 3471007H1 621 893

2630960T6 1491 1867 47 5858122H1 1534 1797 47 3915086H1 658 817 g3424422 1526 1906 47 2705868F6 1563 1929 47 5373405T6 1566 209.3

5638207H1 1551 1833 47 5022301H1 1563 1833 47 3783242H1 1041 1328 g827423 1566 1771 47 2705868H1 1564 1835 47 2708491H1 716 1011

1299193F6 1583 1900 47 4340882T6 1795 2060 47 6307323H1 787 1123

6073452T6 1583 1862 47 1479486T6 1569 2058 47 551890H1 881 1067

1299193H1 1583 1777 47 2761062T6 1568 2057 47 4492287H1 882 1261

1299193T6 1583 1857 47 2705868T6 1581 2056 48 70572210V1 884 1469

2107254H1 1590 1866 47 3468165H1 1577 1844 48 70572495V1 955 1286 g560355 1684 1900 47 1993688T6 1645 2057 48 70571926V1 754 1202

Table 2 (cont.)

48 70571502V1 745 1349 48 70569223V1 248 856 49 4631337H1 679 753

48 70569574V1 826 1486 48 70570943V1 250 912 49 1971904H1 712 971

48 70570142V1 836 1398 48 70571295V1 259 821 49 1971904F6 712 1114

48 70570141V1 844 1193 48 70568330V1 355 1012 49 g3989039 765 832

48 70570482V1 849 1305 48 70568216V1 363 1033 49 g4004553 765 832

48 70569465V1 855 1274 48 2237351F6 363 725 49 732931H1 765 972

48 70569269V1 556 1188 48 2905811H1 1091 1408 49 2235515T6 807 1469

48 70569417V1 559 1188 48 70568512V1 1109 1378 49 1514627T6 814 1176

48 70570991V1 584 1118 48 2522478F6 1137 1449 49 4080269H1 870 1146

48 70569428V1 571 1259 48 2522478F7 1137 1471 49 6832335H1 897 1445

48 70568632V1 620 1317 48 2522478H1 1137 1402 49 4116133H1 949 1215

48 70572355V1 635 1302 48 2522389H1 1137 1396 49 2258867H1 950 1206

48 70564434V1 639 1062 48 70570776V1 1149 1704 49 4492763H1 962 1540

48 70571851V1 657 1264 48 70570912V1 1149 1797 49 1386487H1 1074 1292

48 70570748V1 704 1295 48 70569442V1 1176 1474 49 4431852H1 1082 1334

48 7003760H1 729 1123 48 2450339T6 1168 1666 49 3599043H1 1121 1403

48 70563349V1 947 1323 48 70568046V1 1222 1524 49 1313052H1 1130 1364

48 70570762V1 960 1527 48 70572193V1 1248 1704 49 4825915H1 1179 1465 o 48 70571845V1 969 1601 48 5494475H1 1250 1538 49 1578741H1 1199 1411

^"^ 48 6866835H1 983 1631 48 70569585V1 489 1228 49 6521182H1 1240 1806

48 70562712V1 984 1298 48 70568685V1 490 914 49 5506584H1 1243 1449

48 6157305H1 993 1269 48 70568639V1 500 1181 49 3905468H1 1244 1490

48 5516852H1 1028 1312 48 70568617V1 505 1145 49 5718792H1 1246 1761

48 2450339F6 1 224 48 70568629V1 528 1239 49 2211706H1 1251 1517

48 2450339H1 1 135 49 7260572H1 1 542 49 g4523198 1435 1853

48 6854122H1 5 557 49 2839721H2 23 287 49 3818989F6 1449 1915

48 7081863H1 20 596 49 2839721F6 77 411 49 3818989H1 1449 1668

48 2237351H1 363 650 49 4705119F8 77 655 49 6942236H1 1467 2063

48 70569676V1 378 981 49 4705119H1 77 277 49 g2219561 1488 1811

48 70552498V1 387 1058 49 3843861H1 193 497 49 gl712378 1488 1668

48 70563545V1 416 639 49 4542028F8 230 721 49 1974505F6 1535 1853

48 3460952H1 24 248 49 4542028H1 229 502 49 1974505H1 1535 1668

48 70569565V1 210 797 49 7337215H1 396 581 49 6978865H1 1547 1936

48 g4703329 426 774 49 5727315H1 491 1020 49 gl856293 1557 1943

48 70570223V1 438 1185 49 ■ 4880713H1 564 798 49 6839538H1 1559 2161

48 70570920V1 440 898 49 2843763H1 603 866 49 6073945H1 1564 1765

48 70570781V1 440 897 49 3097805H1 670 819 49 g2537789 1605 1892

48 70567983V1 475 904 49 4631337F6 678 737 49 3818989T6 1753 2232

Table 2 (cont.)

49 4631337T6 1759 2243 49 1312172H1 2140 2324 50 70801138V1 2037 2684

49 g4684927 1775 2271 49 1514627H1 2190 2269 50 70801844V1 2074 2737

49 2364406H1 1776 1931 50 2638422T6 1 140 50 70803750V1 2156 2834

49 g4188351 1787 2267 50 2638422F6 1 373 50 70802422V1 2157 2719

49 g3412954 1794 2267 50 6981422H1 7 572 50 6854011H1 2187 2549

49 g5590415 1794 2272 50 g4148173 53 490 50 70802774V1 2212 2605

49 1974505T6 1795 2231 50 2638422H1 113 373 50 70803192V1 2204 2760

49 g3647432 1802 2269 50 6768020J1 195 727 50 70799608V1 2284 2822

49 g3330983 1815 2271 50 7359784H1 207 757 50 6311222H1 2340 2883

49 g4261154 1829 2269 50 g6199167 365 749 50 70799712V1 2430 3039

49 1781695H1 1833 2127 50 5900048H1 409 699 50 70803364V1 2588 2975

49 1781695R6 1833 2266 50 6989532H1 559 1155 50 70804594V1 2646 3250

49 g3932044 1843 2267 50 70803892V1 654 1303 50 70801808V1 2683 3255

49 4243158H1 1857 2235 50 70800990V1 720 1318 50 70800968V1 2688 3348

49 1514627F6 1888 2269 50 70803809V1 835 1513 50 3462322F6 2749 3282

49 g3415551 1879 2269 50 70804202V1 838 1520 50 70803000V1 2775 3325

49 g3108736 1910 2274 50 70802115V1 859 1472 50 3462322H1 2963 3283

*-*. ⁴⁹ gl550011 1918 2269 50 6307959H1 872 1397 50 g2882851 3179 3525 o 49 g3921822 1920 2273 50 70804306V1 1070 1567 50 7067268H1 3180 3742

^ 49 g4330608 1923 2269 50 70803140V1 1088 1463 50 5119843F6 3186 3640

49 g5630278 1926 2272 50 70804898V1 1133 1715 50 6984347H1 3214 3705

49 g2189478 1928 2260 50 70800978V1 1132 1618 50 5119843H1 3375 3640

49 g4073608 1929 2276 50 70804775V1 1147 1612 50 gl874645 3618 4111

49 g4109783 1929 2271 50 7056347H1 1181 1581 51 7228427H1 1 573

49 g4392501 1929 2260 50 70801141V1 1186 1827 51 7091223H1 358 648

49 1971904T6 1930 2232 50 70803370V1 1405 1947 51 5996621H1 456 977

49 gl856294 1940 2269 50 70799868V1 1417 1961 51 3784279H1 556 862

49 g3095415 1941 2271 50 70804130V1 1516 2035 51 2858090F6 603 820

49 g5630271 1944 2272 50 g3162700 1645 1978 51 2858090H1 603 682

49 546355H1 1961 2220 50 70805243V1 1687 2355 51 6756153H1 771 1318

49 g3896543 1970 2269 50 70804667V1 1765 2369 51 5967687H1 773 1194

49 1781695T6 1983 2229 50 70800147V1 1774 2372 51 7101263H1 1029 1223

49 g2219452 2007 2269 50 70802731V1 1850 2545 51 5972491H1 1076 1457

49 g6463319 2010 2273 50 70801205V1 1863 2516 51 g317931 1290 1685

49 gl722646 2038 2269 50 70802853V1 1885 2354 51 g317603 1313 1685

49 g5326403 2077 2269 50 70804916V1 1896 2382 51 5877835F6 1348 1872

49 652012H1 2089 2352 50 70799899V1 1936 2639 51 5877835H1 1348 1630

49 g3756725 2122 2272 50 70803805V1 2003 2638 51 6756153J1 1704 2225

Table 2 (cont.)

1806404F6 1823 2286 52 70694835V1 2853 3313 52 1322784H1 1427 1657

1806404H1 1823 2078 52 g2821799 1953 2224 52 70255841V1 1459 1963

1806342H1 1823 2101 52 70257206V1 1975 2202 52 6799978H1 1476 2078

5877835T6 1912 2353 52 g3154360 2000 2215 52 70257425V1 1481 1644

1806404T6 1926 2353 52 70249502V1 2056 2215 52 7007871H1 74 670

1284836F6 10 356 52 70696280V1 2123 2801 52 70252822V1 87 505

1284836H1 10 255 52 3737128T6 2868 3297 52 6496939H1 102 663

4831767H1 8 274 52 g3645644 2896 3264 52 70248840V1 695 1099

70249801V1 11 180 52 5175059H1 2901 3163 52 70252852V1 121 517

70248113V1 10 351 52 70250389V1 2145 2215 52 70254883V1 704 1215

70252775V1 18 504 52 70692131V1 2910 3294 52 70257807V1 135 301

3613968H1 43 353 52 70691832V1 2912 3295 52 70258095V1 135 301

70255782V1 710 1161 52 70691710V1 2152 2757 52 70247658V1 165 301

70693658V1 2319 2959 52 70693686V1 2952 3295 52 70252777V1 170 520

3934733H1 2328 2628 52 g4535021 3028 3301 52 70252891V1 182 663

70696721V1 2349 2664 52 1711081F6 2152 2641 52 70252829V1 186 718

70697189V1 2352 2883 52 70697119V1 2152 2630 52 70252868V1 207 662

70693987V1 2387 2733 52 70693270V1 2152 2608 52 6575878H1 231 787

70693793V1 2392 2906 52 70696536V1 2152 2729 52 70252913V1 231 747

70691748V1 2402 2965 52 70692071V1 2152 2630 52 70252807V1 238 771

70695598V1 2575 3130 52 1711081H1 2152 2385 52 70254964V1 277 800

70701933V1 2584 2746 52 70693128V1 2193 2699 52 70250751V1 384 687

6571494H1 2608 3105 52 1854271H1 2311 2580 52 5097321F6 390 883

70696700V1 2618 2974 52 70255440V1 1097 1598 52 5097321H1 390 657

70694905V1 2652 3207 52 70254994V1 1119 1647 52 70250298V1 404 684

70698828V1 2656 2912 52 70254806V1 1141 1680 52 70252721V1 418 757 g3898245 2680 3119 52 2057866H1 1170 1417 52 70248985V1 515 677

3737128F6 2701 3256 52 70254564V1 1204 1732 52 70247676V1 516 759

3737128H1 2701 3001 52 2348065F6 1277 1691 52 70249928V1 525 996

70694991V1 2719 3251 52 2348065H1 1277 1496 52 70255416V1 541 1010 g2933892 2734 3208 52 gl694359 1300 1481 52 70249098V1 555 646

70695524V1 2779 3272 52 6799978J1 1302 1898 52 70248520V1 558 889

70255499V1 1937 2215 52 70255800V1 1339 1716 52 70248316V1 561 888

70696984V1 2787 3244 52 70250827V1 1343 1523 52 70258290V1 582 873

70695420V1 2799 3015 52 70257217V1 1351 1740 52 70252961V1 665 1255

70694656V1 2806 3295 52 3856416H1 1357 1598 52 5097673H1 680 937

70696762V1 2811 3295 52 70255611V1 1378 1879 52 70252728V1 1 443

70692751V1 2837 3295 52 70248591V1 1394 1596 52 70252939V1 1 545

Table 2 (cont.)

70252948V1 1 536 52 70256133V1 42 575 53 2137575F6 383 773

70252942V1 1 545 52 70246781V1 48 269 53 2137575H1 383 643

70252875V1 1 500 52 70252880V1 49 438 53 6914654H1 411 921

70252809V1 1 438 52 70256162V1 53 635 53 4008767H1 413 687

70252971V1 1 441 52 70252834V1 54 503 53 041252H1 446 640

70252862V1 1 395 52 70255234V1 57 594 53 1537441H1 532 777

70252977V1 1 341 52 5317447H1 1845 2072 53 2829631T7 652 1120

2640403H1 1 250 52 5315839H1 1845 1988 53 2502234H1 674 921

2640465H1 1 257 52 3727579T1 1851 2179 53 3278811T6 716 965

70252968V1 1 207 52 g3070073 1873 2179 53 4957707H1 760 932

70252879V1 1 218 52 70255218V1 1540 2114 53 6768050J1 779 1398

70253339V1 1 129 52 70257386V1 1596 1780 53 6768050H1 860 1424

70252864V1 1 458 52 1284836T6 1607 2170 53 4775909H1 911 1113

70252944V1 8 517 52 3727547H1 1615 1913 53 4147184H1 1023 1259

70252854V1 7 417 52 5095010H1 1615 1891 53 6757024H1 1051 1701

4830790H1 854 1092 52 70255952V1 1645 2175 53 2441247H1 1284 1514

70248055V1 879 1376 52 5097869H1 1645 1892 53 6757024J1 1368 1874

4999054H1 896 1140 52 7344776H1 1680 2203 53 1400881H1 1376 1605

4999939H2 910 1196 52 70256309V1 1737 2099 53 1401450F6 1376 1884

70258363V1 912 1079 52 70254641V1 1742 2215 53 1401450H1 1376 1621 gl525795 981 1309 52 70257103V1 1743 1851 53 3556941H1 1546 1834

70255663V1 1009 1544 52 70250099V1 1751 1924 54 g3405927 1 245

3616714H1 1011 1327 52 70249987V1 1752 1925 54 4061048T8 1 543

70257537V1 1046 1393 52 2348065T6 1755 2187 54 5961372H1 217 755

70255304V1 1064 1516 52 70254831V1 1756 2215 55 6595513H2 1 455

70254849V1 1078 1548 52 5002821H1 1757 2001 55 g3237891 1 431

70255814V1 1077 1499 52 70256296V1 1762 2215 55 gl406421 1 383

4513535H1 756 1022 52 6783161H1 1766 2374 55 g5863035 1 313

70248026V1 769 1215 52 70249593V1 1789 1980 55 g2714241 1 468

70255094V1 780 1277 52 5095212H1 1791 2023 55 7069348H1 10 209

70257552V1 805 1219 52 5867448H1 1794 2079 55 70834691V1 13 578

70252896V1 813 1400 52 70257289V1 1818 2014 55 71219243V1 13 540

70246987V1 815 1027 52 5317679H1 1845 2082 55 4906280F6 13 523

70248642V1 834 1228 53 2836841H1 1 268 55 70832787V1 13 476

2640465T6 834 1360 53 6552443H1 18 593 55 4906280H2 13 256 gl525794 844 1078 53 6914654J1 187 694 55 g680955 14 384

70248207V1 851 1020 53 2928638H1 280 548 55 70822785V1 13 105

70255236V1 42 594 53 3278811F6 367 979 55 7339618H1 35 589

Table 2 (cont.)

55 5970464H1 50 599 55 7099404H1 1272 1774 56 2342785T6 795 1371

55 70833853V1 72 632 55 6818682H1 1320 1676 56 70564198V1 779 1223

55 6772419J1 93 664 55 70831777V1 1325 1840 56 588426T6 771 1207

55 71220574V1 156 731 55 2767081H1 1674 1918 56 5096743H1 881 1110

55 g2433743 185 324 55 5633412R8 1703 1788 56 70566592V1 819 1438

55 072410H1 202 432 55 6988282H1 1716 2079 56 70668498V1 855 1353

55 gl441845 234 323 55 5675457H1 1736 2001 56 2653741H1 840 1122

55 71220458V1 256 858 55 1621977H1 1746 1826 56 gl962977 845 1314

55 71220313V1 258 856 55 g6476364 1821 2213 56 588426R6 842 1207

55 2897226F6 308 762 55 gll46532 1850 2203 56 6803050H1 887 1254

55 gl406525 312 723 55 5966829H1 1871 2436 56 1297330T6 931 1073

55 2897226H1 310 585 55 1721129T6 1893 2173 56 70567006V1 903 1458

55 3903661H1 326 619 55 7236449H1 2047 2275 56 70562861V1 917 1563

55 2897226T6 341 869 55 6825137H1 2074 2522 56 4408168H1 1000 1255

55 5280549H1 418 688 55 656980H1 2237 2477 56 70564258V1 942 1569

55 7164092H1 442 978 56 70563822V1 1350 1929 56 4083330H1 1008 1286

55 71219526V1 554 1144 56 6140441H1 1312 1552 56 70662295V1 965 1066 g5527320 587 981 56 70674104V1 1320 1499 56 70662354V1 1055 1155 o 55 71219762V1 614 1143 56 70567008V1 1333 1494 56 70562675V1 982 1511

°° 55 71219779V1 691 849 56 g882792 2005 2419 56 588426H1 1048 1279

55 6618366J2 702 1289 56 g6047387 729 1139 56 5620393R8 1017 1245

55 1479279F6 837 1300 56 g3033883 803 1144 56 70564166V1 1034 1599

55 1479279H1 837 1005 56 g4111129 828 1047 56 g573475 1052 1378

55 71220581V1 879 1134 56 g2397417 733 1106 56 70669958V1 1053 1323

55 1648685H1 895 1132 56 g2690499 829 1097 56 70570002V1 1041 1456

55 4631458H1 912 1183 56 g2620172 734 1066 56 g882849 1056 1327

55 2733185H1 990 1256 56 gll87613 797 982 56 70663697V1 1058 1346

55 g2111602 998 1417 56 g5741320 737 1193 56 6706725H1 1062 1567

55 g685314 1017 1332 56 g3765855 737 1063 56 70668887V1 1062 1559

55 1721129F6 1104 1449 56 g6142132 833 1040 56 883631H1 1055 1298

55 1721129H1 1104 1300 56 g3770103 842 1154 56 4376346H1 1074 1327

55 5742466H1 1118 1413 56 g6462630 796 965 56 g5674715 1063 1301

55 3902467H1 1118 1398 56 70666243V1 781 1320 56 g882957 1080 1329

55 3902459H1 1118 1371 56 70669273V1 737 1186 56 g5837269 1068 1291

55 6918681H1 1176 1725 56 4590906H1 799 983 56 70670665V1 1082 1462

55 762794R1 1211 1711 56 344501H1 740 1113 56 70662627V1 1090 1644

55 762794F1 1221 1711 56 5464077H1 770 1030 56 70658327V1 1099 1239

55 762794H1 1222 1451 56 1989939H1 775 1044 56 70565737V1 1112 1707

Table 2 (cont.)

56 6459664H1 1122 1708 56 201433H1 1807 2142 56 g4988332 2176 2411

56 6459764H1 1156 1331 56 4799413H1 1966 2233 56 g564908 2177 2411

56 70566802V1 1118 1858 56 200319H1 1807 2154 56 3590745H1 2330 2634

56 6459772H1 1206 1358 56 1262834H1 2017 2252 56 476150H1 2331 2602

56 g766175 1134 1200 56 1989939T6 1856 2152 56 1577439H1 2440 2654

56 70563249V1 1142 1653 56 g822901 2079 2419 56 g2347702 2176 2413

56 2175353F6 1138 1346 56 4046894F8 1 602 56 g4124357 2097 2417

56 2175353H1 1138 1388 56 5622335H1 34 306 56 g882958 2124 2419

56 70564319V1 1146 1662 56 5620393F8 37 506 56 3791454H1 2139 2415

56 70564161V1 1148 1705 56 5620393H1 37 310 56 4905965H2 2176 2361

56 3957616H2 1158 1372 56 6746680H1 45 629 56 g6473997 2176 2415

56 3958977H1 1159 1445 56 7184188H1 87 506 56 6141362H1 1555 1901

56 70566156V1 1159 1550 56 2839152F6 95 550 56 4597106H1 1559 1853

56 70664157V1 1189 1428 56 1727562F6 97 507 56 70564268V1 1362 1678

56 729045H1 1194 1422 56 2839152H1 95 383 56 70564413V1 1378 1930

56 195736R6 1195 1438 56 3386005H1 95 350 56 3553956H1 1381 1537

56 195736H1 1195 1400 56 70564762V1 97 598 56 70669318V1 1404 1644

56 729045R6 1195 1424 56 1727562H1 97 312 56 1241441H1 1429 1701 o

V 56 1297330F6 1202 1653 56 5044068H1 105 379 56 1297330H1 1489 1643

56 6751614H1 1206 1810 56 5044068F6 105 555 56 70565761V1 1509 2000

56 5493653H1 1206 1481 56 70566005V1 148 570 56 4857906H1 1550 1860

56 6735456H1 1230 1348 56 2452790H1 183 403 57 g5664193 1 377

56 5552258H1 1248 1342 56 7156278H1 232 814 57 g2619178 5 333

56 653456H1 1276 1418 56 70565482V1 441 1010 57 6441247H1 12 543

56 4703350H1 1276 1348 56 6630501U1 445 1010 57 453769H1 184 377

56 70566134V1 1331 1923 56 70565168V1 457 1122 57 3762476H1 235 538

56 70563519V1 1299 1861 56 5044068R6 519 939 57 6729757H1 348 910

56 6631102H1 1301 1782 56 70565572V1 549 1013 57 3116387F6 383 761

56 2006255H1 1302 1513 56 70563167V1 589 1157 57 3116387H1 384 664

56 195736T6 1736 2373 56 4414516H1 597 862 57 5661301H1 391 644

56 70565915V1 1589 2352 56 70564872V1 599 1148 57 gl977456 394 782

56 1687411H1 1659 1891 56 2187472H1 651 928 57 3496148F6 397 981

56 3497631H1 1707 2009 56 70563453V1 669 1239 57 70139347V1 397 887

56 3930656T9 1884 2275 56 70564150V1 678 1265 57 3496148H1 397 675

56 1727562T6 1874 2376 56 70564317V1 705 1376 57 1008165H1 455 761

56 70562875V1 1935 2413 56 70562729V1 718 1328 57 6518018H1 464 1031

56 3255274H1 1776 2026 56 70562680V1 726 1288 57 4177624H1 490 696

56 70565475V1 1935 2345 56 70564226V1 742 1421 57 826356H1 517 846

Table 2 (cont.)

6441415H1 554 1059 57 469801R6 1232 1464 57 g3804418 1702 2137

4539787H1 619 878 57 70138703V1 1237 1803 57 1814612T6 1704 2141

70142580V1 634 1044 57 817498H1 1266 1558 57 3879011H1 1725 2014

6710170H1 649 1209 57 817306R1 1266 1836 57 g3145312 1767 2184

6203306H1 668 1199 57 817306H1 1266 1484 57 g5658515 1767 2183

70131575V1 692 1096 57 6440332H1 1269 1829 57 g4896513 1777 2189

7362891H1 712 1260 57 4226121H1 1286 1563 57 g3041462 1783 2183

2798030F6 720 1287 57 2888006H1 1291 1565 57 1268321F6 1789 2170

2798030H1 720 971 57 5326773H1 1333 1512 57 1268321H1 1789 2040

2659046H1 723 968 57 4827817H1 1343 1622 57 2798030T6 1790 2144 gl748057 740 899 57 2837990H1 1343 1585 57 4855273H1 1844 2031

1832131H1 748 960 57 181567H1 1351 1537 57 3947216H1 1844 2020

4822509H1 763 1012 57 064652H1 1351 1526 57 2232569H1 1859 2088

6980545H1 771 1103 57 1566979H1 1353 1562 57 g6507253 1866 2134

5219156H1 843 1062 57 5489077H1 1372 1494 57 2244523H1 1863 2114

5767782H1 859 1315 57 70132097V1 1377 1687 57 2044580H1 1880 2159

5644717H1 859 1095 57 g853275 1388 1725 57 g4088814 1891 2181

6917456H1 880 1413 57 6132302H1 1388 1663 57 1268321T6 1903 2130

3788651H1 923 1087 57 2744049H1 1388 1648 57 4850944H1 1927 2158

4571245H1 925 1203 57 826818H1 1400 1733 57 1492447H1 1928 2134

3436728H1 928 1087 57 3467063H1 1437 1705 57 g5658077 1940 2134

2231388F6 953 1455 57 70133770V1 1439 1833 57 gl211221 1951 2196

2231388H1 953 1202 57 3449015H1 1463 1629 57 621406H1 1954 2171

5040546H1 956 1087 57 3121922H1 1463 1773 57 g852913 1962 2111

70133707V1 976 1464 57 2538144H1 1485 1813 57 2231388T6 1974 2142

2113640H1 977 1226 57 70136427V1 1488 1931 57 gll55579 2012 2197

6583623H1 1015 1355 57 2008648H1 1506 1685 57 2245140H1 2088 2172 g2004410 1019 1322 57 3145660T6 1511 2119 57 3496148T7 1537 2094

4314146H1 1020 1302 57 70136864V1 1526 1925 57 6175211H1 1541 1824 g2010211 1020 1353 57 469801T6 1526 2094 57 1814612F6 1548 2013 gll89835 1027 1229 57 3116387T6 1579 2142 57 1814612H1 1548 1801

70131494V1 1104 1537 57 4760891H1 1610 1891 57 2370362H1 1551 1807

2737895H1 1123 1333 57 1572810T6 1637 2138 57 2372634H1 1551 1793

6443615H1 1123 1627 57 3917658H1 1652 1962 57 70131661V1 1563 1852

666344H1 1123 1300 57 g5764969 1660 2134 58 2174866H1 1 146

70143472V1 1128 1500 57 6752149H1 1663 2144 58 2698567H1 1 197

4112076H1 1170 1444 57 g5232494 1668 2138 58 5541622H1 1 194

469801H1 1232 1464 57 g3835399 1696 2137 58 2930567F6 33 479

Table 2 (cont.)

2930567H1 33 338 58 653612R6 1252 1492 58 gl977012 1938 2287

4982447H1 269 540 58 6325601H1 1252 1547 58 1811076T6 1938 2221

6255850H1 303 576 58 653612H1 1252 1494 58 2589380H1 1968 2238

6258186H1 303 577 58 653612T6 1253 1462 58 2552865H1 1968 2215

5721674H1 321 908 58 2667659H1 1309 1395 58 g2631458 1972 2243

4152487H1 322 596 58 2206550H1 1293 1492 58 5573308H1 1982 2232

4028078H1 339 611 58 6598025H1 1340 1850 58 g6439334 2088 2250

7279087H1 343 928 58 3928253H1 1315 1633 58 3732638H1 2100 2243

3097754H1 343 649 58 3928196H1 1316 1628 58 3736212H1 2116 2249

5668252H1 343 574 58 5039319T9 1355 1949 58 gl629446 2143 2250

5538912H2 342 416 58 3414970H1 1347 1620 58 g3891127 2146 2250

2816646H1 349 612 58 1743113H1 1381 1664 58 6131388H1 2153 2243

2816646F6 349 871 58 g2115578 1382 1750 59 3625376H1 2752 2845

2610076H1 349 585 58 71042069V1 1422 2060 59 g5675476 2517 2963

2777845H1 349 580 58 5691992H1 1409 1710 59 g3146172 2594 2958

3293887H1 350 593 58 2816646T6 1435 2011 59 3274786H1 2616 2858 gl753994 350 559 58 71041726V1 1509 2118 59 1953692H1 111 344

3355981H1 351 608 58 4689116H1 1522 1787 59 6539166H1 198 716 g29167 376 691 58 2936253H1 1524 1803 59 2133241F6 229 647

2476803H1 387 650 58 3528601T6 1552 2014 59 2133241H1 229 494

2476803F6 387 595 58 5203894H1 1559 1823 59 6365336H1 335 613 gl646650 406 767 58 3415070T6 1578 2015 59 1676569H1 375 591

3796918H1 778 1068 58 5423080H1 1583 1854 59 g2881893 461 513

7217683H1 812 1267 58 5422280H1 1583 1828 59 6812474H1 525 1081

5608991H1 821 1011 58 g434100 1753 2008 59 4934590H1 525 609

1811369F6 853 1303 58 1811369T6 1780 2215 59 045505H1 526 755

1811369H1 853 1163 58 6489437H1 1800 2249 59 2670704F6 598 980

71041470V1 943 1602 58 gl751419 1841 2048 59 2670704H1 598 846

4514405H1 957 1207 58 g2541732 1845 2055 59 003688H1 628 941

3860484H1 982 1279 58 g5530419 1870 2049 59 6812474J1 792 1344

6708640H1 1017 1588 58 3212650T6 1875 2026 59 2185753H1 923 1155

207612H1 1015 1241 58 3118422H1 1882 2049 59 1665259H1 1333 1552

3461827H1 1088 1182 58 3002323F6 1882 2047 59 5193614H1 1718 1967

6753368J1 1105 1745 58 3118368T6 1885 2009 59 4378244H1 1994 2271 gl629548 1195 1610 58 830827R1 1897 2249 59 70742391V1 2036 2610

7156421J1 1209 1390 58 830827H1 1897 2160 59 419872H1 2167 2379

7156421H1 1209 1374 58 997447H1 1899 2151 59 171741R1 2186 2661

7202481H1 1235 1816 58 6506368H1 1903 2249 59 171741H1 2186 2362

Table 2: (cont.) g2009473 2197 2490 60 g3230679 2327 2520 60 2291932H1 1506 1759 g2189171 2227 2329 60 g717890 2461 2535 60 530715H1 1531 1754 g6330101 1 2954 60 60201999D1 2508 2561 60 7090888H1 1628 1769

2669204T6 5 463 60 750787H1 2258 2510 60 g3086021 1626 2047

5951559H1 34 348 60 667235H1 2263 2515 60 71228809V1 1628 2200

3942253H1 2231 2521 60 g561290 2289 2520 60 60202364B1 1657 2134

042842H1 2237 2480 60 g714831 2246 2557 60 60202363B1 1657 2096

2656261H1 2243 2497 60 70818421V1 673 1279 60 2291932T6 1669 2269

1971006F6 2319 2789 60 g869715 675 1023 60 60202367B1 1665 2041

1971006H1 2319 2583 60 4745248H1 1 238 60 3335250T6 1672 2184

2667143T6 2341 2911 60 748982H1 675 914 60 70870682V1 1770 2476

001227H1 2373 2728 60 70869543V1 746 1291 60 70869072V1 1785 2476

3716845H1 2374 2648 60 70838362V1 773 900 60 70867264V1 1828 2445

6514287H1 2382 2935 60 70837422V1 778 1013 60 70868309V1 1828 2491

4120983H1 2404 2640 60 71229105V1 787 1469 60 6841962H1 1858 2421 g4189206 2487 2958 60 70870484V1 807 1465 60 70870157V1 1978 2569 g2278337 2503 2957 60 70869894V1 829 1508 60 6855669H1 2008 2520

71229143V1 621 1253 60 70839431V1 828 1138 60 6885209J1 2001 2441

6983112H1 624 904 60 70837620V1 868 1305 60 746910R6 2044 2520 g570318 633 919 60 g565684 918 1102 60 746910T6 2045 2516

7046749H1 452 1052 60 71221539V1 985 1416 60 746910H1 2044 2281

70868787V1 465 1132 60 70869173V1 992 1418 60 6844175H1 2075 2520

753174H1 355 544 60 71229615V1 1005 1492 60 2568562H1 2123 2362

4318873H1 153 369 60 70867752V1 1053 1804 60 g4393425 2130 2563

71230534V1 162 657 60 70870784V1 1013 1466 60 g4109519 2140 2520

7322168H1 165 793 60 71229687V1 1038 1742 60 g2694947 2170 2520

6992614H1 233 746 60 70870712V1 1032 1587 60 g2703845 2174 2520 g778569 676 1011 60 70870207V1 1036 1656 60 g3884077 2176 2520

744829H1 675 915 60 gl025621 1047 1385 60 g3278030 2179 2569

7158869H1 1 478 60 gl059514 1047 1284 60 4705947H1 2239 2398

3335250F6 28 397 60 71229437V1 1156 1803 60 5266308H1 635 795

70870096V1 657 1340 60 g714830 1131 1442 61 6803748H1 1 281

70869315V1 674 1384 60 70870012V1 1147 1778 61 6803748J1 185 681

744829R1 675 1254 60 4311224H1 1231 1528 61 7179441H1 281 837

3335250H1 28 270 60 70869086V1 1284 1849 61 6993211H1 431 958

7077668H1 130 662 60 2292421R6 1498 1606 61 990041H1 585 938 g518739 2296 2520 60 71229131V1 1473 2098 61 2647312H1 2235 2464

60202000D1 2303 2520 60 2292254R6 1506 1988 61 5303648H2 2242 2538

Table 2 (cont.)

7236332H1 2251 2534 61 7124412H1 1803 2268 61 5345386H1 2069 2260

3606921H1 2256 2543 61 g650235 1811 2087 61 g4244699 2071 2541

4423382H1 2269 2538 61 3934148H1 1829 1983 61 3934148T6 2072 2496

1976495H1 2269 2526 61 6914591H1 1830 2173 61 3480660H1 2078 2301 g6400732 2279 2543 61 3934148F6 1838 2178 61 576039H1 2079 2319

6538345H1 2292 2509 61 5950691H1 1874 2208 61 g650236 2084 2482

1942829H1 2284 2540 61 5950591H1 1874 1946 61 2915418H1 2086 2383

1929606H1 2292 2537 61 7336402H1 1901 2467 61 g4664830 2100 2538

1794859H1 2312 2543 61 4000559H1 1959 2238 61 gl017329 2107 2465

6912812H1 961 1221 61 1570912F6 1974 2307 61 g704704 2107 2457

1602952F6 691 1143 61 1570912H1 1974 2184 62 1730307H1 320 543

3436025H1 691 925 61 7152207H1 1328 1863 62 1852850F6 344 904

3025993H1 921 1218 61 7152523H1 1375 1863 62 1852850H1 344 623

954323H1 2326 2529 61 684121H1 1431 1674 62 1786201H1 1224 1347

954323R1 2326 2529 61 1998986H1 1449 1545 62 5500430F6 4 384

954323T1 2326 2483 61 598762H1 1472 1718 62 3751387H1 26 298 g395758 2345 2528 61 2227505H1 1546 1793 62 6862090H1 34 606

5393045H1 2354 2470 61 3393621H1 1557 1854 62 6939856H1 42 508

1602953H1 691 793 61 3441995H1 1570 1822 62 1264746H1 209 445

1602952H1 691 779 61 g5528672 2232 2527 62 1730307F6 320 696

1602953F6 691 909 61 6992150H1 1037 1416 62 g2782908 1611 2044

1568974H1 1974 2177 61 4514493H1 1075 1162 62 4573617F6 1197 1548

6950168H1 1976 2470 61 1622836H1 1163 1292 62 4573617H1 1197 1460

6951183H1 1988 2470 61 2864609H1 1208 1358 62 g953428 863 1055

1510868H1 1997 2126 61 7259857H1 1220 1855 62 70576776V1 1251 1474

5511854H1 2007 2266 61 3551930H1 1220 1512 62 4516586H1 1279 1522 g2017578 2021 2249 61 1379503H1 1223 1458 62 1964843H1 856 1126

2225061H1 2036 2295 61 7154005H1 1283 1863 62 3508361F6 1 54

5685115H1 2039 2313 61 5297140H1 2150 2448 62 3277390H1 1484 1734

5503829H1 2046 2302 61 3984036H1 2152 2347 62 819859H1 1480 1708

6736816H1 2051 2433 61 g3048902 2160 2538 62 1852850T6 1436 2015

6914591J1 1587 2103 61 5297634H1 2177 2469 62 gl521345 1445 1556

7267538H1 1622 1800 61 5297140F8 2180 2460 62 1966204T6 1488 2046

6559545H1 1677 2237 61 g5367334 2217 2545 62 7183685H1 1516 2053

7287559H1 1703 2171 61 2569168H1 2218 2485 62 g5394325 1583 1905

6912812J1 1719 2352 61 g3842534 2219 2536 62 1540056H1 1599 1816

6714578H1 1791 2351 61 2449539H1 2228 2458 62 71013442V1 1295 1412

6384321H1 1791 2017 61 4947830H1 2067 2189 62 gl275357 1296 1768

Table 2 (cont.)

71008110V1 1299 1866 62 g5362837 1996 2101 63 70683980V1 270 750

3080148H1 1299 1445 62 g3434471 1757 2093 63 3925359H1 270 546 g772703 1305 1422 62 gl219640 1768 2096 63 3925359F6 270 448 g890466 1340 1492 62 g822861 1727 2124 63 70682278V1 270 429

3121030F6 1342 1806 62 g5634808 1758 2101 63 3531535H1 322 622

4562285H1 1351 1630 62 3121030T6 1613 2054 63 70680431V1 396 861

826668H1 1403 1691 62 1730307T6 1632 2053 63 1560619F6 422 805

6370579H1 1404 1660 62 820388H1 1644 1878 63 1560619H1 422 632

71008260V1 864 1019 62 70590209V1 1648 2093 63 3699779H1 467 637

2542469H1 909 1139 62 5266218T6 1655 2071 63 g6399045 695 1131 g766126 956 1040 62 5609530H1 1237 1422 63 70681329V1 709 873

1966137H1 863 1097 62 6222010U1 1248 1565 63 70708067V1 711 811

1966204R6 863 1107 62 3508361H1 1 297 63 2992541F6 780 1329

1966137R6 863 1325 62 71014845V1 611 896 63 2992541H1 781 1083

5500430R6 4 432 62 6618123J1 696 1329 63 70680523V1 889 1539

3121030H1 1342 1653 62 71008490V1 732 1116 63 1560619T6 958 1101

2128205H1 1702 1971 62 71009446V1 377 1047 63 70683064V1 971 1406

1966137T6 1663 2049 62 6221969U2 590 945 63 70684594V1 985 1592

6843171H1 1670 2093 62 4305106H1 1008 1298 63 70680581V1 1006 1548

4573617T6 1679 2086 62 1823430H1 1026 1243 63 70683735V1 1037 1587

71236524V1 1681 1927 62 gl958618 1021 1382 63 70682555V1 1322 1950 g!521346 1691 2093 62 3760149H1 1062 1376 63 70704188V1 1327 1535 g2030368 1694 2085 62 6221994U1 1073 1569 63 999076R1 1323 1695

4976812H1 1656 1926 62 gl976176 1153 1550 63 999076R6 1323 1695 g5630558 1769 2096 63 70684185V1 1354 1880 63 999076H1 1323 1568

4421852H1 1773 2020 63 70682617V1 1395 1806 63 6623832J1 1349 1520 g2946092 1782 2096 63 70707488V1 1460 1832 63 4378643F7 1825 2433

3324470H1 1798 2071 63 70683177V1 1461 1983 63 4379312F7 1825 2363

71236287V1 1829 2002 63 70707392V1 1462 1832 63 4379312H1 1825 2112 g820432 1839 2114 63 70680197V1 1465 1847 63 4378643H1 1826 2123 g2899828 1848 2096 63 70679832V1 1602 2217 63 70682506V1 1843 2439 g4224026 1850 2093 63 70681040V1 1625 2221 63 6623832H1 1843 2366 g890467 1850 2077 63 7282455H1 1636 2232 63 70708640V1 1901 2124 g3116690 1859 2093 63 70684191V1 1662 1801 63 3925359T6 1915 2464 g6476925 1890 2093 63 70687607V1 1721 2137 63 5100839T9 1935 2253

3508361T6 1912 2054 63 70680047V1 1742 2387 63 4378643T7 1966 2392 g518427 1917 2093 63 70679818V1 1769 2456 63 70682105V1 1968 2496

71013952V1 1980 2089 63 6543969H1 1780 2352 63 4071965T6 1989 2503

Table 2 (cont.)

5328012T6 2014 2458 64 g3430798 912 1371 64 g4264614 1185 1372

5328012F6 2021 2417 64 g5110040 919 1372 64 g5233294 1187 1372

4071965F6 1 359 64 g5590010 921 1377 64 3617375H1 222 428

4071965H1 1 295 64 1620383H1 543 765 64 7141668H1 231 698

7125750H1 1 395 64 g848117 553 822 64 5272669H1 248 468

70682403V1 270 773 64 2448547H1 572 801 64 2824332H1 248 536

5328012H1 2021 2275 64 838081H1 598 828 64 1521787H1 267 468 g3871281 2037 2485 64 1866438H1 678 930 64 g6472427 923 1374 g2934374 2056 2496 64 1283358H1 826 1062 64 g3679316 924 1372

1431377H1 2204 2445 64 g6504962 862 1372 64 g5768136 931 1372 g3047856 2222 2499 64 g4764556 888 1358 64 g5813683 939 1374 g4371425 2237 2496 64 g5675975 891 1372 64 1622824H1 938 1078

70686041V1 2264 2420 64 g5848125 902 1372 64 g2910940 939 1372 g4327870 2279 2496 64 g5764743 904 1374 64 g4390160 945 1371 g3134381 2279 2496 64 g5545082 905 1373 64 g6451090 953 1376

70684032V1 1100 1538 64 g5886738 906 1372 64 g5864498 957 1372

70684362V1 1110 1587 64 g4691015 907 1373 64 g6073735 960 1377

70682629V1 1151 1740 64 g4486385 908 1374 64 g6035456 963 1372

70683547V1 1185 1635 64 g4287684 909 1371 64 g4300047 971 1372

3832836H1 1163 1384 64 1520534H1 911 1135 64 g2782529 1004 1372

70684463V1 1170 1734 64 1647964H1 452 606 64 g3870189 1005 1373

70682920V1 1196 1755 64 1648365H1 452 624 64 g2555234 1032 1371

70703741V1 1215 1394 64 2054919H1 478 749 64 g6506601 1039 1372

70682638V1 1223 1736 64 2770417H1 478 698 64 g4073949 1047 1373

70682682V1 1223 1749 64 gl933783 493 719 64 g4435426 1050 1377

70682459V1 1249 1908 64 943317H1 501 752 64 g4298104 1051 1373

70681204V1 1257 1766 64 2796760H1 503 780 64 g5630151 1055 1376

70685069V1 1300 1653 64 2209885H1 503 669 64 g3750504 1074 1374

6931315H1 1291 1695 64 1348306H1 523 753 64 g4509918 1077 1372

3254414H1 69 317 64 1345963H1 523 741 64 g3884253 1079 1373

698585H1 70 286 64 2840447H1 536 670 64 g5590634 1087 1373

595891H1 74 292 64 3483204H1 1 253 64 g2874129 1097 1316

6175776H1 79 356 64 6178578H1 1 218 64 g2222026 1109 1373 g2159426 78 188 64 3574891H1 12 173 64 gl933727 1109 1374

657830H1 80 273 64 666288H1 1189 1371 64 g4331539 1123 1372

3457909H1 81 348 64 g6141365 1191 1372 64 g4987875 1124 1374

6301420H1 81 349 64 g6044743 1197 1372 64 3343619H1 1127 1372

3575481H1 85 394 64 2011575H1 1211 1303 64 g2913373 1132 1372

Table 2 (cont.)

64 4204339H1 1134 1372 64 3187627H1 315 615 65 1670914H1 609 863

64 g2115784 1144 1376 64 2768194H1 319 572 65 2682534H1 444 676

64 3999467H1 1144 1366 64 2814432H1 317 602 65 gl887075 233 454

64 g5325930 1150 1371 64 3729901H1 1212 1372 65 4888904H1 1 277

64 1497968T6 1155 1322 64 4194682H1 1236 1343 65 4888904F8 25 578

64 1491584F6 1162 1372 64 1288019H1 1266 1372 65 4888904F9 27 472

64 1491584H1 1162 1360 64 5225561H1 1266 1371 66 7266271H1 192 555

64 g4123527 1174 1372 64 5077632H1 1293 1376 66 7266415H1 192 764

64 g5233350 1181 1373 64 g2464354 1295 1371 66 4828047H1 658 939

64 g774782 31 202 64 g2986696 1218 1372 66 5506726H1 736 923

64 g766776 38 379 64 6795195H1 67 633 66 6491143H1 855 1416

64 1417835H1 44 296 64 2372795H1 379 601 66 5614913H1 984 1235

64 3390866H1 15 247 64 6945477H1 436 775 66 gl921859 1104 1499

64 3295609H1 67 345 64 6826837H1 64 366 66 5903582T6 1122 1468

64 1630345H1 69 301 64 6826837J1 64 366 66 g2437372 1135 1552

64 1630524H1 69 298 64 1418532H1 44 241 66 6037758H1 1141 1523

64 3359727H1 129 229 64 g4223892 52 551 66 g2112991 1169 1578

64 6149745H1 142 693 64 2855769F6 54 195 66 2075750F6 1372 1546 σ-* 64 6817217J1 162 754 64 7162693H1 55 632 66 5903582F6 1 473

64 g4606728 165 384 64 2855769H1 54 323 66 5903582H1 1 273

64 g2063565 171 590 64 3276579H1 54 314 67 70985136V1 1070 1350

64 1987618H1 188 407 64 6497645H1 57 708 67 70985260V1 1073 1455

64 6735147H1 85 195 64 3232792H1 58 353 67 70983054V1 1073 1558

64 552603H1 89 286 64 478616H1 65 358 67 71295531V1 1073 1453

64 1988618R6 91 498 65 2132236T6 1004 1401 67 3717638T6 1080 1571

64 1988618H1 91 316 65 2132236H1 1004 1263 67 70984050V1 1221 1738

64 6577808H1 91 254 65 gl887025 1093 1444 67 70986990V1 1372 1585

64 6432246H1 101 473 65 2086267H1 1132 1266 67 gl980540 1447 1629

64 3231513H1 101 331 65 6175915H1 1148 1402 67 g760823 1462 1594

64 2642693H1 100 322 65 g4876495 1204 1445 67 71295238V1 1066 1226

64 6265064H1 115 300 65 g5365413 1204 1445 67 71295235V1 1067 1708

64 3447578H2 124 390 65 2132236R6 1004 1434 67 3717638F6 762 1251

64 1746508H1 343 620 65 1667496H1 609 860 67 3717638H1 762 822

64 6817217H1 344 811 65 1300507F6 678 1121 67 71269157V1 1057 1278

64 7386534H1 350 837 65 1300507H1 678 918 67 70984218V1 1064 1297

64 5204331H1 367 623 65 1670894T6 892 1399 67 3365081H1 1 160

64 7240357H1 306 493 65 1300507T6 930 1415 67 6535437H1 18 468

64 2526407H1 306 556 65 1670894F6 609 1072 67 71295036V1 289 822

Table 2 (cont.)

71295290V1 321 570 69 g766638 710 999 69 70364017D1 651 1226

70985880V1 321 580 69 g564283 710 957 69 2295159R6 660 1121

70986588V1 321 517 69 5710302H2 721 969 69 70362705D1 645 882

71295432V1 604 822 69 4093587H1 1283 1553 69 70366027D1 651 1243

70985853V1 677 1325 69 70378136D1 1397 1884 69 70451316V1 1240 1648

2261815H1 654 822 69 7010739H1 1234 1657 69 1292366F1 1203 1595

71294916V1 670 1292 69 70365505D1 1359 1894 69 70378088D1 408 888

71296536V1 568 1197 69 70365928D1 1 611 69 7071779H1 410 731

70986118V1 545 822 69 6729581H1 1 416 69 70365775D1 1419 1922

70986361V1 546 1189 69 2998772F6 1 174 69 70378121D1 1386 1894

70985351V1 321 549 69 7172430H1 1 425 69 70446570V1 916 1260

3384358H1 328 499 69 2998772H1 1 75 69 70447538V1 1056 1507

71123582V1 328 431 69 70362802D1 17 511 69 2295159H1 660 911

70986562V1 379 822 69 2656315F6 17 568 69 5081872H1 690 891

70985543V1 397 824 69 2656315H1 17 245 69 g872874 709 1076

71295516V1 397 820 69 6179484H1 90 350 70 765092H1 184 414

70984072V1 397 734 69 6201177H1 105 612 70 6351315H2 235 422

71295044V1 397 763 69 70364249D1 1394 1894 70 765092R6 1 412

70986344V1 397 650 69 70451849V1 1414 1599 70 765092T6 37 412

70983024V1 510 1139 69 70451495V1 1418 1657 70 6351215H2 237 597

71294736V1 510 822 69 70446527V1 1443 1879 71 g4523614 641 887

70983429V1 646 1207 69 70378406D1 1447 1881 71 g3203614 1 374 g2884969 1 149 69 70364892D1 1466 1869 71 1485642H1 86 348

6702215H1 1 640 69 g723744 1686 1942 71 6963127H1 98 348

3524645H1 1160 1405 69 g749908 1756 1879 71 3599520H1 200 492

70365425D1 247 658 69 70377452D1 1767 1880 71 1485642T6 318 963

3030907F6 263 672 69 70366252D1 1787 1884 71 6954177H1 512 1103

3030907H1 263 558 69 70365521D1 1787 1893 71 g820653 538 876 g574359 341 660 69 661155T6 1787 1950 71 3214706H1 629 894

70378343D1 342 793 69 1292366F6 1203 1689 71 g5369990 637 887

70365801D1 372 867 69 1292366H1 1203 1452 71 1485642F6 86 661

2656315T6 1358 1946 69 70377916D1 1315 1657 71 1483336H1 86 391

70376806D1 1386 1894 69 70364727D1 1315 1657 72 183176R6 27 491 g770844 438 691 69 70366014D1 1315 1880 72 183176H1 27 251

6178165H1 499 799 69 70450434V1 1318 1850 72 2733388H1 110 339

6552117H1 584 1167 69 5675995H1 1317 1571 72 5616358H1 120 396

6552017H1 584 1047 69 70364614D1 1339 1894 72 71238219V1 165 770

70377552D1 1193 1657 69 70364566D1 1338 1894 72 g4762579 398 832

Table 2 (cont.)

72 71020348V1 429 1029 73 3449244H1 1427 1651 73 4829932H2 595 840

72 71019924V1 467 918 73 3521301H1 1274 1416 73 gl891400 596 1068

72 7104793H1 478 998 73 6511601H1 1280 1531 73 6368954H1 647 926

72 71019186V1 519 967 73 7060576H1 1283 1718 73 160137H1 660 901

72 4004284H1 525 792 73 gl424041 1315 1536 73 160137R6 664 1020

72 71020080V1 771 1365 73 g4523497 1231 1652 73 1968940H1 726 989

72 71238694V1 772 1352 73 gll93170 1237 1536 73 3899549H1 785 1048

72 71237183V1 791 1317 73 3051747H1 1272 1562 73 2667776H1 815 1045

72 71019222V1 822 1224 73 3996830H1 1513 1643 73 4871959H1 830 1026

72 71240267V1 868 1118 73 453660H1 1653 1728 73 2608521H1 904 1097

72 71240088V1 868 1118 73 355514H1 1212 1424 73 5433362H1 913 1091

72 71237170V1 1030 1386 73 g2899582 1156 1536 73 g2963571 1473 1662

72 g2358498 1 382 73 3802944H1 1179 1451 73 g2910204 1121 1536

72 183176R1 27 640 73 g5862645 1187 1536 73 g5592759 1126 1537

73 277677H1 1431 1536 73 4001379H1 1198 1339 73 1227022H1 1139 1269

73 3873445H1 946 1227 73 4819034H1 45 131 73 795156H1 1140 1383

73 6448059H1 968 1478 73 3725796H1 76 160 73 g748850 11 227

73 000843H1 1046 1539 73 gl273189 87 309 73 g678626 24 445

73 867412H1 1039 1238 73 g2141610 1148 1539 73 556041R6 270 622

73 160137T6 1041 1517 73 g4224292 1149 1536 73 6717668H1 277 609

73 1928767T6 1083 1496 73 gl861043 1153 1541 74 5947068H1 65 379

73 1928767R6 1099 1542 73 6074694H1 1113 1357 74 g673182 66 311

73 1928767H1 1099 1376 73 g2969771 1116 1536 74 70585819V1 66 223

73 2937207H1 1099 1339 73 2877117H1 1 139 74 g784700 81 171

73 5001393H1 1100 1297 73 gl934264 1321 1728 74 4071087H1 84 393

73 g5631970 1101 1539 73 816059R1 1351 1728 74 g3401588 316 738

73 5989817H1 1102 1292 73 816059R6 1351 1549 74 g3412723 338 732

73 g5747028 1103 1536 73 816059H1 1351 1589 74 g6038772 338 732

73 6074562H1 1113 1412 73 6716201H1 1400 1664 74 g784495 365 732

73 6074662H1 1113 1338 73 4439494H1 1412 1548 74 3346654H1 49 339

73 g2719198 1477 1539 73 2417379F6 342 682 74 70585937V1 67 573

73 5902113H1 1501 1728 73 2417379H1 342 509 74 2198034H1 54 310

73 4931449H1 1501 1770 73 433802H1 342 509 74 6559467H1 53 662

73 g673993 182 474 73 gl640167 342 492 74 2554485H1 55 292

73 gl267101 196 545 73 3723919H1 360 471 74 3213289H1 55 220

73 4826378H1 262 524 73 4443121H1 401 705 74 7154394H1 56 646

73 556057H1 270 478 73 6309581H1 458 948 74 999535H1 55 245

73 556041H1 270 479 73 2779428H1 473 715 74 2446468H1 58 303

Table 2 (cont.)

74 138735H1 61 441 74 70573192V1 282 565 75 1573637T6 1340 1773

74 70576514V1 117 242 74 g4070388 291 730 75 g4176290 1343 1817

74 5529836H1 83 260 74 70578389V1 295 439 75 g3765500 1344 1814

74 2642157H1 83 233 74 2584982H1 299 556 75 5032276H1 1380 1620

74 2854411H1 84 281 74 g3924424 317 650 75 g2569759 1383 1814

74 3394115H1 84 265 74 g4896209 440 747 75 g3433438 1386 1804

74 2457270H1 84 217 74 70590586V1 409 565 75 g2903602 1395 1814

74 7246868H2 85 171 74 4171532H1 427 728 75 2530791T6 1411 1773

74 5467726H1 91 265 75 g864641 472 730 75 2994433H1 1433 1644

74 5048151H1 112 277 75 g854955 498 853 75 gll48705 1461 1817

74 4055118T9 1 653 75 7018723H1 526 1079 75 g2903846 1465 1793

74 2571441H1 11 258 75 1634405F6 537 1019 75 gl880344 1474 1588

74 6297876H1 49 332 75 1634405H1 537 753 75 g777248 1484 1755

74 gl389377 68 470 75 2135762H1 598 889 75 g6450447 1495 1793

74 4621236H1 70 366 75 6754472H1 666 1291 75 g3753249 1527 1813

74 2718503H1 69 184 75 1573637F6 689 1107 75 g863905 1529 1804

74 g813048 71 501 75 1573637H1 689 906 75 g778854 1529 1795

74 g570365 71 376 75 000132H1 691 1122 75 g854914 1530 1773

74 5478847H1 74 317 75 gll64431 695 972 75 g5365595 1535 1816

74 g613447 81 330 75 2893510H1 729 1003 75 g778166 1662 1796

74 70589118V1 67 741 75 5687323H1 796 1064 75 g2269957 1680 1813

74 7344794H1 68 664 75 4369688H1 854 1120 75 g3056293 1703 1814

74 1649902F6 67 377 75 6130274H1 858 971 75 7341877H1 194 778

74 1384494H1 67 331 75 g778259 940 1189 75 6092377H1 332 608

74 1649839H1 67 311 75 5076483H1 1055 1318 75 3074534H1 1 263

74 1649902H1 67 310 75 3926443F6 1083 1488 75 3293881H1 38 284

74 6389250H1 68 379 75 3926443H1 1084 1284 75 439597R6 177 719

74 2729287T6 122 700 75 439597T6 1142 1776 75 439597H1 177 404

74 4055118T7 124 624 75 1634405T6 1166 1762 75 6558204H1 182 612

74 906915H1 132 286 75 2530791F6 1225 1590 75 062726H1 374 548

74 5621907H1 135 475 75 2530791H1 1225 1466 75 062712H1 374 541

74 gl281834 137 550 75 3926443T6 1285 1789 75 5565196H1 413 626

74 3773136H1 160 490 75 567711T6 1298 1783 76 1375031F6 785 1262

74 70588034V1 182 477 75 567711R6 1298 1759 76 1375031F1 784 1041

74 70588682V1 186 734 75 567703H1 1298 1551 76 2133064H1 763 1041

74 1649902T6 192 689 75 g2785236 1315 1793 76 6827035J1 1 659

74 70590189V1 243 734 75 g3649430 1318 1747 76 3507907H1 885 1175

74 g2908534 249 701 75 g2779890 1324 1813 76 114238H1 915 988

Table 2 (cont.)

76 128209H1 915 1030 76 70088685V1 2434 2683 76 70089240V1 1973 2539

76 6530747H1 1096 1708 76 gl489884 2497 2667 76 70090145V1 1973 2674

76 5291702H1 1127 1366 76 g4298447 2503 2666 76 70089170V1 1973 2538

76 1375031H1 784 1034 76 gl227527 2522 2669 76 70092550V1 1973 2489

76 684570H1 829 1046 76 g2836709 2227 2666 76 70092490V1 1973 2499

76 g2786676 2256 2677 76 404342H1 2229 2497 76 70089927V1 1973 2437

76 g959893 2259 2671 76 401524H1 2229 2445 76 70092932V1 1973 2447

76 g6033820 2259 2666 76 402039H1 2229 2426 76 70091424V1 1973 2516

76 2180264T6 2265 2625 76 401524F1 2229 2666 76 70090074V1 1973 2480

76 g6074973 2269 2673 76 70093923V1 2230 2654 76 70090511V1 1973 2426

76 gl507095 2273 2669 76 6912204J1 189 491 76 70092562V1 1973 2452

76 g5741986 2275 2672 76 6912204H1 191 490 76 70090451V1 1973 2487

76 g4004471 2278 2672 76 gll46598 386 763 76 70093155V1 1973 2333

76 gl201567 2280 2668 76 7338712H1 426 1013 76 70093381V1 1973 2335

76 g2786837 2282 2677 76 4951401H2 596 877 76 2180264F6 1973 2319

76 g6086742 2293 2671 76 3225692H1 728 993 76 70091927V1 1973 2286

76 70091053V1 2301 2666 76 2133064F6 763 1210 76 2180264H1 1973 2143

76 70092520V1 2230 2635 76 g2657310 41 563 76 70091191V1 1974 2497

G 6 600490H1 2233 2502 76 2081047F6 1132 1650 76 2956706H1 1982 2065

° 76 70090081V1 2238 2676 76 2081047H1 1132 1375 76 gl239260 1989 2120

76 g4985261 2241 2670 76 g2969649 1175 1525 76 g3658694 1993 2448

76 g3047609 2241 2666 76 873831H1 1198 1406 76 g2369409 1995 2221

76 g898301 2240 2666 76 5187690H1 1219 1495 76 gl489980 1995 2193

76 gll94822 2242 2669 76 4089635H1 1236 1369 76 2915268H1 1995 2189

76 g697708 2249 2675 76 6596535H1 1272 1417 76 5103731H1 1995 2143

76 g3245902 2242 2672 76 2581130F6 1301 1702 76 5083588H1 1995 2127

76 g3778060 2242 2672 76 2581130H1 1301 1552 76 g2036913 2011 2270

76 g3675008 2247 2672 76 gl994825 1382 1595 76 1375031T1 2047 2289

76 g3700953 2253 2680 76 7040047H1 1449 1702 76 70090620V1 2054 2455

76 70090551V1 2252 2654 76 6630452U1 1468 1702 76 1006083H1 2056 2329

76 70088450V1 2252 2654 76 6630374U1 1578 2150 76 gl315008 2071 2546

76 g4987033 2306 2666 76 4143678H1 1593 1692 76 70090041V1 2079 2597

76 7346532H1 2315 2669 76 g959892 1613 1702 76 2275715H1 2082 2355

76 gll95921 2333 2667 76 6903811H1 1646 2243 76 70089944V1 2092 2664

76 g3307378 2351 2673 76 4332838H1 1648 1702 76 gl507094 2121 2366

76 gl424265 2356 2666 76 g697795 1774 2119 76 2503051T6 2138 2254

76 gl994824 2368 2666 76 g704969 1774 2043 76 2871614H1 2143 2443

76 70092273V1 2369 2666 76 2888581H1 1951 2236 76 2081047T6 2151 2289

Table 2 (cont.)

76 1543664H1 2164 2375 77 3331210F6 2781 3196 77 5924192H1 1784 2080

76 g3734766 2174 2672 77 3331210H1 2781 2955 77 7292851H1 1788 2312

76 2133064T6 2177 2289 77 2043050H1 2878 3139 77 1833479T6 1796 2354

76 g4175843 2179 2669 77 g678229 2896 3222 77 70935438V1 1825 2345

76 g2705950 2190 2669 77 g4186860 2906 3322 77 5205918H1 1835 2094

76 70092616V1 2190 2680 77 g561452 2927 3226 77 4710070H1 1851 2150

76 6017144H1 2186 2462 77 g817283 2954 3237 77 71040258V1 1855 2399

76 gl424317 2192 2665 77 gl242796 3055 3317 77 70936878V1 1868 2349

76 70092373V1 2191 2664 77 g678324 3120 3276 77 g876649 1880 2293

76 70091541V1 2202 2654 77 g671188 3142 3276 77 g570326 1880 2195

76 920317H1 2208 2457 77 5821129H1 3194 3328 77 g792017 1880 1970

76 920309H1 2208 2455 77 1414767F6 1261 1693 77 7252042H1 1893 2490

76 70091726V1 2216 2666 77 70407644D1 901 1138 77 5918594H1 1898 2195

76 gl317327 2225 2673 77 71042670V1 1006 1659 77 4308614H1 1922 2266

76 70089181V1 2228 2655 77 71039461V1 1032 1644 77 5775902H1 1951 2547

76 4592652H1 2227 2372 77 7290781H1 1077 1648 77 900678T6 1952 2320

77 5386182H1 2434 2533 77 71039094V1 1110 1784 77 1267888F1 1965 2533

77 5929032F6 2513 3092 77 71039976V1 1157 1628 77 1267888H1 1965 2211

77 5929032H1 2513 2807 77 71040172V1 1160 1738 77 gl991900 1988 2282

77 5928821H1 2513 2602 77 71042825V1 1179 1788 77 g946386 2032 2371

77 2404117R6 2533 2936 77 71042505V1 1191 1806 77 g891688 2079 2407

77 2247162H1 2533 2802 77 71041242V1 1224 1881 77 70947602V1 2088 2333

77 5845721H1 2532 2686 77 70938142V1 1261 1803 77 70947760V1 2095 2333

77 2404117H1 2533 2717 77 g574829 1615 1881 77 2524117H1 2129 2395

77 6274929H2 2557 3085 77 g767565 1616 1876 77 g943716 2133 2371

77 4839303H1 2572 2867 77 70937073V1 1646 2215 77 70935414V1 2153 2809

77 70936812V1 2588 3163 77 71041370V1 1653 2311 77 70938201V1 2175 2740

77 6559464H1 2597 3142 77 g947001 1665 2012 77 g953501 2230 2370

77 2404117T6 2613 3183 77 3334355H1 1666 1945 77 70937638V1 2264 2847

77 2424729H1 2630 2886 77 g705805 1704 1982 77 5207284H1 2273 2516

77 6557735H1 2666 3250 77 6763269H1 1740 2365 77 g823406 2281 2415

77 70936842V1 2716 3372 77 71041012V1 1745 2398 77 6747059H1 2291 2882

77 1414767T6 2737 3276 77 1254953H1 1759 1993 77 5108466H1 2305 2395

77 g5768528 2761 3225 77 6507931H1 1798 2269 77 750487H1 556 782

77 gl212489 2763 3057 77 1833479R6 1771 2216 77 6983706H1 37 535

77 659884H1 2764 3006 77 1833479H1 1771 2075 77 g2000717 382 570

77 3331210T6 2779 3276 77 6271456H2 1777 2341 77 6855956H1 517 998

77 4942039H1 2778 3048 77 3332037H1 1779 2041 77 g953502 1 212

Table 2 (cont.)

77 g2331234 1 2384 78 982079R6 2378 2741 78 2417475H1 1999 2100

77 7359814H1 27 485 78 982079H1 2378 2691 78 70858537V1 2011 2620

77 5351059H1 2335 2472 78 982079T6 2378 2744 78 70962120V1 2020 2649

77 70942966V1 2341 2513 78 4859367H1 1503 1670 78 g5595178 2416 2791

77 2152647H1 2383 2636 78 gl056444 1527 1812 78 g2569464 2421 2792

77 70941613V1 2429 2567 78 2881063H1 1478 1786 78 g2848983 2422 2790

77 1414767H1 1261 1503 78 4546751H1 1485 1761 78 gl507026 2424 2792

77 g769023 1271 1589 78 6219786H1 2241 2558 78 gl645469 2491 2786

77 71039996V1 1278 1834 78 5044584H1 1072 1352 78 70962041V1 2226 2750

77 71041640V1 1276 1859 78 5731888H1 1086 1332 78 2805557T6 2240 2753

77 661243H1 1311 1572 78 2668983H1 1013 1254 78 6307990H1 2241 2695

77 70845562V1 1318 1677 78 5869109H1 1423 1674 78 g3701921 2399 2789

77 g891480 1320 1516 78 4175935F6 1476 2104 78 70856260V1 1659 2200

77 71042682V1 1370 2012 78 71287876V1 1476 2061 78 71287735V1 1680 2356

77 6437672H1 1366 1900 78 71286863V1 1476 2009 78 71226071V1 1619 2077

77 g705704 1384 1755 78 70995743V1 1476 1941 78 70960213V1 1653 2205

77 71040965V1 1418 1876 78 4175935H1 1476 1769 78 1258447F6 1616 2083

77 4695010H1 1441 1721 78 70175363V1 1478 2039 78 5886340H1 1960 2108

77 70938843V1 1447 1894 78 2881063F6 1478 1993 78 5880788H1 1959 2089

77 71041816V1 1463 2053 78 1405756H1 1101 1358 78 5883358H1 1960 2230

77 71040541V1 1463 2021 78 6212807H1 1168 1473 78 5882287H1 1960 2207

77 4178826H1^" 1494 1762 78 6789736H1 1286 1749 78 70996202V1 1968 2079

77 2525545H1 1496 1726 78 g866161 2297 2612 78 5884261H1 1959 2100

77 70936642V1 1550 2202 78 4933985H1 2263 2430 78 5886308H1 1959 2238

77 71243429V1 1557 1786 78 g865342 2297 2641 78 70172850V1 1547 2052

77 6124654H1 1590 2086 78 70961841V1 2250 2783 78 70172946V1 1554 1896

77 6560433H1 1614 2187 78 6843570H1 124 268 78 5109345H1 1773 1894

77 g389618 1615 1914 78 5447930H2 212 443 78 70858458V1 1829 2390

77 960213H1 814 1101 78 6819333H1 375 837 78 70861427V1 1872 2034

77 g774455 786 1139 78 063360H1 575 793 78 gl645468 2153 2569

77 962582R6 795 1260 78 2717804H1 736 995 78 70857537V1 2132 2748

77 962582H1 795 849 78 1336510H1 542 798 78 70961205V1 2134 2784

77 g879553 796 1117 78 1336565H1 542 794 78 6465155H1 817 1387

77 4028250H1 574 833 78 2260777H1 522 781 78 3737993H1 865 1101

77 g572875 750 1009 78 6819333J1 525 1141 78 2805557F6 888 1348

78 1504601F6 383 747 78 1504601H1 383 641 78 2805557H1 888 1199

78 1258447H1 1616 1755 78 6935560H1 497 997 78 7166418H1 1 544

78 71225337V1 1618 2089 78 2260777R6 522 929 78 6845517H1 18 576

Table 2 (cont.)

78 7216754H1 109 637 78 71287317V1 2192 2816

78 g3895948 2405 2789 78 6376946H1 2205 2491

78 gl506843 2407 2792 78 3408549H1 2215 2526

78 g3934604 2413 2783 78 2461537H1 982 1199

78 71362378V1 1586 1776 78 2056939T6 2523 2754

78 71288334V1 1613 2200 78 3819114H1 2568 2764

78 71288102V1 2182 2787 78 767808H1 2576 2783

78 70858569V1 2361 2790 78 g3871569 2579 2783

78 981508H1 2378 2661 78 g5638296 2585 2789

78 g3280794 2348 2786 78 g2969829 2618 2783

78 g4900509 2359 2783 78 6368851H1 2678 2783

78 858094H1 2047 2315 79 4404143T6 1 604

78 71288239V1 2117 2721 79 3566814H1 199 382

78 2056939R6 2154 2463 79 5639354R6 465 918

78 2056939H1 2154 2430

78 1641318H1 2168 2384

78 1298674H1 2174 2448

G ⁷⁸ 1298674F1 2174 2342 w 78 70172181V1 1769 2279

78 5699556H1 1678 1913

78 7027634H1 1695 1971

78 71225035V1 1707 2313

78 71225177V1 1746 2398

78 70961047V1 1745 2324

78 1692282F6 1749 2316

78 1692282H1 1749 1985

78 1305007H1 1754 2002

.78 5887009H1 1958 2240

78 5889943H1 1958 2243

78 5888977H1 1958 2176

78 5884968H1 1959 2101

78 g2347469 1895 2202

78 2727193H1 1942 2100

78 2083456H1 1955 2102

78 70856801V1 1881 2488

78 2408695H1 2219 2334

78 1504601T6 2211 2755

78 1692282T6 2211 2740

Table 3

SEQ

ID NO: Tissue Distribution

1 Unclassified/Mixed - 71%, Endocrine System - 16%

2 Embryonic Structures - 82%, Nervous System - 18%

3 Germ Cells - 62%, Connective Tissue - 17%, Unclassified/Mixed - 16%

Endocrine System - 71%, Nervous System - 29% Nervous System - 76%, Endocrine System - 18% Endocrine System - 63%, Liver - 23%

Endocrine System - 29%, Hemic and Immune System - 24%, Exocrine Glands - 19% Endocrine System - 42%, Germ Cells - 19%

9 Endocrine System - 66%, Sense Organs - 21%, Nervous System - 11$

10 Germ Cells - 30%, Sense Organs 24%, Nervous System - 17% 11 Nervous System - 100% 12 Embryonic Structures - 18%, Pancreas - 17%, Hemic and Immune System - 17%

13 Exocrine Glands - 42%, Cardiovascular System - 21%, Respiratory System - 16%

14 Nervous System - 86% 15 Unclassified/Mixed - 17%, Sense Organs - 12% 16 Unclassified/Mixed - 2288%%,, EEmmbbrryyoonniicc SSttrruuccttuurreess -- 2200%%,, LLiivveerr - 16-i 17 Endocrine System 100% 18 Digestive System 57%, Hemic and Immune System - 29%, Nervous System - 14%

19 Unclassified/Mixed 90% 20 Exocrine Glands 50%, Respiratory System 38%, Nervous System 13%

21 Unclassified/Mixed - 20%, Connective Tissue - 10% 22 Sense Organs - 17% 23 Female Genitalia - 32%, Hemic and Immune System - 24%, Endocrine System - 20%

24 Sense Organs - 15%, Embryonic Structures - 13% 25 Sense Organs - 43%, Unclassified/Mixed - 11% 26 Unclassified/Mixed - 16%, Embryonic Structures - 13%, Germ Cells - 13%

27 Respiratory' System - 43%, Nervous System - 21%, Female Genitalia - 21%

28 Liver - 33%, Germ Cells - 12% 29 Endocrine System - 31%, Germ Cells - 25%, Liver - 12% 30 Exocrine Glands - 29%, Germ Cells - 28% 31 Exocrine Glands - 18%, Cardiovascular System - 10% 32 Sense Organs - 23%, Embryonic Structures - 15%, Endocrine System - 15%

33 Sense Organs - 17%, Endocrine System - 11%, Skin - 10% 34 Musculoskeletal System - 86% 35 Connective Tissue - 16%, Embryonic Structures - 14%, Digestive System - 11%

36 Pancreas - 40%, Female Genitalia - 20%, Cardiovascular System - 16%

37 Respiratory System - 12%, Urinary Tract - 12% 38 Embryonic Structures - 53%, Digestive System - 17%, Nervous System - 12%

39 Digestive System - 40%, Nervous System - 32%, Nervous System - 28% 40 Exocrine Glands - 47%, Sense Organs - 21% 41 Connective Tissue - 60%, Unclassified/Mixed - 22% 42 Hemic and Immune System - 15% 43 Sense Organs - 21%, Female Genitalia - 13% 44 Hemic and Immune System - 18%, Female Genitalia - 17% 45 Embryonic Structures - 32%, Female Genitalia - 17% 46 Male Genitalia - 49%, Skin - 32% 47 Nervous System - 42%, Nervous System - 40%, Endocrine System - 14% 48 Digestive System - 41%, Nervous System - 15%, Liver - 14% 49 Exocrine Glands - 34%, Unclassified/Mixed - 22% 50 Nervous System - 57%, Unclassified/Mixed - 11% 51 Nervous System - 52%, Digestive System - 25%, Connective Tissue - 10%

52 Digestive System - 24%, Germ Cells - 22%, Exocrine Glands - 11% Table 3 (cont.) Endocrine System - 32%, Digestive System - 19% Embryonic Structures - 58%, Nervous System - 37% Female Genitalia - 18%, Nervous System - 18%, Embryonic Structures

- 18% Connective Tissue - 29%, Germ Cells - 22%, Liver - 13% Musculoskeletal System - 15%, Embryonic Structures - 11% Stomatognathic System - 27%, Urinary Tract - 11% Sense Organs - 25%, Endocrine System - 16% Exocrine Glands - 33%, Urinary Tract - 27%, Nervous System - 14% Endocrine System - 16%, Musculoskeletal System - 13% Exocrine Glands - 27%, Skin - 15%, Female Genitalia - 15% Female Genitalia - 36%, Urinary Tract - 22%, Digestive System - 22% Germ Cells - 16%, Endocrine System - 11%, Liver - 11% Pancreas - 24%, Unclassified/Mixed - 21%, Male Genitalia - 17% Endocrine System - 43%, Embryonic Structures - 14%, Unclassified/Mixed - 12% Embryonic Structures - 42%, Male Genitalia - 19%, Female Genitalia

- 19% Male Genitalia - 67%, Nervous System - 33% Urinary Tract - 50%, Endocrine System - 18% Respiratory System - 100% Skin - 43%, Nervous System - 19%, Nervous System - 19% Cardiovascular System - 35%, Nervous System - 27%, Male Genitalia

- 19% Female Genitalia - 12%, Germ Cells - 11% Male Genitalia - 28% Embryonic Structures - 30%, Urinary Tract - 22%, Respiratory System - 16% Musculoskeletal System - 16%, Respiratory System - 12% Nervous System - 35%, Male Genitalia - 31%, Germ Cells - 11% Stomatognathic System - 19%, Liver - 12%, Exocrine Glands - 11% Respiratory System - 38%, Female Genitalia - 38%, Male Genitalia - 25%

Table 4

Program Description Reference Parameter Threshold

ABI FACTURA A program that removes vector sequences and masks Applied Biosystems, Foster City, CA. ambiguous bases in nucleic acid sequences.

ABI PARACEL FDF A Fast Data Finder useful in comparing and annotating Applied Biosystems, Foster City, CA; Mismatch <50% amino acid or nucleic acid sequences. Paracel Inc., Pasadena, CA.

ABI AutoAssembler A program that assembles nucleic acid sequences. Applied Biosystems, Foster City, CA.

BLAST A Basic Local Alignment Search Tool useful in sequence Altschul, S.F. et al. (1990) J. Mol. Biol. ESTs: Probability value= 1.0E-8 or similarity search for amino acid and nucleic acid 215:403-410; Altschul, S.F. et al. (1997) less sequences. BLAST includes five functions: blastp, blastn, Nucleic Acids Res. 25:3389-3402. Full Length sequences: Probability blastx, tblastn, and tblastx. value= l.OE-10 or less

£ FASTA A Pearson and Lipman algorithm that searches for Pearson, W.R. and DJ. Lipman (1988) Proc. ESTs: fasta E value=1.06E-6 similarity between a query sequence and a group of Natl. Acad Sci. USA 85:2444-2448; Pearson, Assembled ESTs: fasta Identity= sequences of the same type. FASTA comprises as least W.R. (1990) Methods Enzymol. 183:63-98; 95% or greater and five functions: fasta, tfasta, fastx, tfastx, and ssearch. and Smith, T.F. and M.S. Waterman (1981) Match length=200 bases or greater; Adv. Appl. Math. 2:482-489. fastx E value=1.0E-8 or less

Full Length sequences: fastx score=100 or greater

BLIMPS A BLocks IMProved Searcher that matches a sequence Henikoff, S. and J.G. Henikoff (1991) Nucleic Probability value= 1.0E-3 or less against those in BLOCKS, PRINTS, DOMO, PRODOM, Acids Res. 19:6565-6572; Henikoff, J.G. and and PFAM databases to search for gene families, sequence S. Henikoff (1996) Methods Enzymol. homology, and structural fingerprint regions. 266:88-105; and Attwood, T.K. et al. (1997) J. Chem. Inf. Comput. Sci. 37:417-424.

HMMER An algorithm for searching a query sequence against Krogh, A. et al. (1994) J. Mol. Biol., PFAM hits: Probability value= hidden Markov model (HMM)-based databases of protein 235:1501-1531; Sonnhammer, E.L.L. et al. 1.0E-3 or less family consensus sequences, such as PFAM. (1988) Nucleic Acids Res. 26:320-322; Signal peptide hits: Score= 0 or Durbin, R. et al. (1998) Our World View, in a greater Nutshell, Cambridge Univ. Press, pp. 1-350.

Table 4 (cont.)

Program Description Reference Parameter Threshold

ProfileScan An algorithm that searches for structural and sequence Gribskov, M. et al. (1988) CABIOS 4:61-66; Normalized quality score≥GC motifs in protein sequences that match sequence patterns Gribskov, M. et al. (1989) Methods Enzymol. specified "HIGH' value for tha defined in Prosite. 183:146-159; Bairoch, A. et al. (1997) Nucleic particular Prosite motif. Acids Res. 25:217-221. Generally, score=1.4-2.1.

Phred A base-calling algorithm that examines automated Ewing, B. et al. (1998) Genome Res. sequencer traces with high sensitivity and probability. 8:175-185; Ewing, B. and P. Green (1998) Genome Res. 8:186-194.

Phrap A Phils Revised Assembly Program including SWAT and Smith, T.F. and M.S. Waterman (1981) Adv. Appl. Score= 120 or greater; CrossMatch, programs based on efficient implementation Math. 2:482-489; Smith, T.F. and M.S. Waterman Match length****** 56 or greater of the Smith- Waterman algorithm, useful in searching (1981) J. Mol. Biol. 147:195-197; and Green, P., sequence homology and assembling DNA sequences. University of Washington, Seattle, WA.

Consed A graphical tool for viewing and editing Phrap assemblies. Gordon, D. et al. (1998) Genome Res. 8:195-202. SPScan A weight matrix analysis program that scans protein Nielson, H. et al. (1997) Protein Engineering 10:1- Score=3.5 or greater sequences for the presence of secretory signal peptides. 6; Claverie, J.M. and S. Audic (1997) CABIOS 12:431-439.

TMAP A program that uses weight matrices to delineate Persson, B. and P. Argos (1994) J. Mol. Biol. transmembrane segments on protein sequences and 237:182-192; Persson, B. and P. Argos (1996) determine orientation. Protein Sci. 5:363-371.

TMHMMER A program that uses a hidden Markov model (HMM) to Sonnhammer, E.L. et al. (1998) Proc. Sixth Intl. delineate transmembrane segments on protein sequences Conf. on Intelligent Systems for Mol. Biol., and determine orientation. Glasgow et al., eds., The Am. Assoc. for Artificial Intelligence Press, Menlo Park, CA, pp. 175-182.

Motifs A program that searches amino acid sequences for patterns Bairoch, A. et al. (1997) Nucleic Acids Res. 25:217-221; that matched those defined in Prosite. Wisconsin Package Program Manual, version 9, page M51-59, Genetics Computer Group, Madison, WI.

Claims

CLAIMS What is claimed is:

1. An isolated polynucleotide comprising a polynucleotide sequence selected from the group 5 consisting of: a) a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79, b) a naturally occurring polynucleotide sequence having at least 90% sequence identity to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79, c) a polynucleotide sequence complementary to a), 0 d) a polynucleotide sequence complementary to b), and e) an RNA equivalent of a) through d).

2. An isolated polynucleotide of claim 1 , comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1-79. 5

3. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 1.

4. A composition for the detection of expression of secretory polynucleotides comprising at o least one of the polynucleotides of claim 1 and a detectable label.

5. A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 1 , the method comprising: a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction5 amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.

6. A method for detecting a target polynucleotide in a sample, said target polynucleotide o comprising a sequence of a polynucleotide of claim 1 , the method comprising: a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.

7. A method of claim 5, wherein the probe comprises at least 30 contiguous nucleotides.

8. A method of claim 5, wherein the probe comprises at least 60 contiguous nucleotides.

9. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 1.

10. A cell transformed with a recombinant polynucleotide of claim 9.

11. A transgenic organism comprising a recombinant polynucleotide of claim 9.

12. A method for producing a secretory polypeptide, the method comprising: a) culturing a cell under conditions suitable for expression of the secretory polypeptide, wherein said cell is transformed with a recombinant polynucleotide of claim 9, and b) recovering the secretory polypeptide so expressed.

13. A purified secretory polypeptide (SPTM) encoded by at least one of the polynucleotides of claim 2.

14. An isolated antibody which specifically binds to a secretory polypeptide of claim 13.

15. A method of identifying a test compound which specifically binds to the secretory polypeptide of claim 13, the method comprising the steps of: a) providing a test compound; b) combining the secretory polypeptide with the test compound for a sufficient time and under suitable conditions for binding; and c) detecting binding of the secretory polypeptide to the test compound, thereby identifying the test compound which specifically binds the secretory polypeptide.

16. A microarray wherein at least one element of the microarray is a polynucleotide of claim 3.

17. A method for generating a transcript image of a sample which contains polynucleotides, the method comprising the steps of: a) labeling the polynucleotides of the sample, b) contacting the elements of the microarray of claim 16 with the labeled polynucleotides of the sample under conditions suitable for the formation of a hybridization complex, and c) quantifying the expression of the polynucleotides in the sample.

18. A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence of claim 1, the method comprising: a) exposing a sample comprising the target polynucleotide to a compound, under conditions suitable for the expression of the target polynucleotide, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound.

19. A method for assessing toxicity of a test compound, said method comprising: a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of claim 1 under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of claim 1 or fragment thereof; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.

20. An array comprising different nucleotide molecules affixed in distinct physical locations on a solid substrate, wherein at least one of said nucleotide molecules comprises a first oligonucleotide or polynucleotide sequence specifically hybridizable with at least 30 contiguous nucleotides of a target polynucleotide, said target polynucleotide having a sequence of claim 1.

21. An array of claim 20, wherein said first oligonucleotide or polynucleotide sequence is completely complementary to at least 30 contiguous nucleotides of said target polynucleotide.

22. An array of claim 20, wherein said first oligonucleotide or polynucleotide sequence is completely complementary to at least 60 contiguous nucleotides of said target polynucleotide

23. An array of claim 20, which is a microarray.

5

24. An array of claim 20, further comprising said target polynucleotide hybridized to said first oligonucleotide or polynucleotide.

25. An array of claim 20, wherein a linker joins at least one of said nucleotide molecules to l o said solid substrate.

26. An array of claim 20, wherein each distinct physical location on the substrate contains multiple nucleotide molecules having the same sequence, and each distinct physical location on the substrate contains nucleotide molecules having a sequence which differs from the sequence of

15 nucleotide molecules at another physical location on the substrate.