AU2018206754A1 - Sequences for detection and identification of methicillin-resistant Staphylococcus aureus (MRSA) of MREJ types xi to xx - Google Patents

Abstract

Described herein are novel SCCmec right extremity junction (MREJ) sequences for the detection and/or identification of methicillin-resistant Staphylococcus aureus (MRSA). Disclosed are methods and compositions based on DNA sequences for the specific detection of MREJ sequences designated types xi, xii, xiii, xiv, xv, xvi, xvii, xix, and xx for diagnostic purposes and/or epidemiological typing.

Description

BACKGROUND OF THE INVENTION

Field of the Invention [0001] The present invention relates to novel SCCmec right extremity junction sequences for the detection of methicillin-resistant Staphylococcus aureus, and uses thereof for diagnostic and/or epidemiological purposes.

Description of the Related Art [0002] The coagulase-positive species Staphylococcus aureus is well documented as a human opportunistic pathogen (Murray et al. Eds, 1999, Manual of Clinical Microbiology, 7th Ed., ASM Press, Washington, D. C). Nosocomial infections caused by S. aureus are a major cause of morbidity and mortality. Some of the most common infections caused by S. aureus involve the skin, and they include furuncles or boils, cellulitis, impetigo, and postoperative wound infections at various sites. Some of the more serious infections produced by S. aureus are bacteremia, pneumonia, osteomyelitis, acute endocarditis, myocarditis, pericarditis, cerebritis, meningitis, scalded skin syndrome, and various abscesses. Food poisoning mediated by staphylococcal enterotoxins is another important syndrome associated with S. aureus. Toxic shock syndrome, a community-acquired disease, has also been attributed to infection or colonization with toxigenic S. aureus.

[0003] Methicillin-resistant S. aureus (MRSA) emerged in the 1980s as a major clinical and epidemiologic problem in hospitals (Oliveira et al., 2002, Lancet Infect Dis. 2:180-9). MRSA are resistant to all β-lactams including penicillins, cephalosporins,

-12018206754 18Jul2018 carbapenems, and monobactams, which are the most commonly used antibiotics to cure S.aureus infections. MRS A infections can only be treated with more toxic and more costly antibiotics, which are normally used as the last line of defense. Since MRSA can spread easily from patient to patient via personnel, hospitals over the world are confronted with the problem to control MRSA. Consequently, there is a need to develop rapid and simple screening or diagnostic tests for detection and/or identification of MRSA to reduce its dissemination and improve the diagnosis and treatment of infected patients.

- 1A 2018206754 18 Jul 2018 [0004] Methicillin resistance in S. aureus is unique in that it is due to acquisition of DNA from other coagulase-negative staphylococci (CNS), coding for a surnumerary β-lactam-resistant penicillin-binding protein (PBP), which takes over the biosynthetic functions of the normal PBPs when the cell is exposed to β-lactam antibiotics. S. aureus normally contains four PBPs, of which PBPs 1, 2 and 3 are essential. The low-affinity PBP in MRSA, termed PBP 2a (or PBP2’), is encoded by the choromosomal mecA gene and functions as a β-lactam-resistant transpeptidase. The mecA gene is absent from methicillin-sensitive S. aureus but is widely distributed among other species of staphylococci and is highly conserved (Ubukata et al., 1990, Antimicrob. Agents Chemother. 34:170-172).

[0005] Nucleotide sequence determination of the DNA region surrounding the mecA gene from S. aureus strain N315 (isolated in Japan in 1982), led to the discovery that the mecA gene is carried by a novel genetic element, designated staphylococcal cassette chromosome mec (SCCmec), which is inserted into the chromosome. SCCzzzec is a mobile genetic element characterized by the presence of terminal inverted and direct repeats, a set of site-specific recombinase genes (ccrA and ccrB), and the mecA gene complex (Ito et al., 1999, Antimicrob. Agents Chemother. 43:1449-1458; Katayama et al., 2000, Antimicrob. Agents Chemother. 44:1549-1555). SCCmec is precisely excised from the chromosome of S. aureus strain N315 and integrates into a specific S', aureus chromosomal site in the same orientation through the function of a unique set of recombinase genes comprising ccrA and ccrB. Cloning and sequence analysis of the DNA surrounding the mecA gene from MRSA strains NCTC 10442 (the first MRSA strain isolated in England in 1961) and 85/2082 (a strain from New Zealand isolated in 1985) led to the discovery of two novel genetic elements that shared similar structural features of SCCmec. The three SCCmec have been designated type I (NCTC 10442), type II (N315) and type III (85/2082) based on the year of isolation of the strains (Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336). Hiramatsu et al. have found that the SCCmec DNAs are integrated at a specific site in the chromosome of methicillinsensitive S', aureus (MSSA). The nucleotide sequence of the regions surrounding the left and right boundaries of SCCmec DNA (i.e. attL and afrR, respectively), as well as those of the regions around the SCCmec DNA integration site (i.e. attBscc which is the bacterial chromosome attachment site for SCCmec DNA), were analyzed. Sequence analysis of the attL, attL. attBscc sites revealed that attBscc is located at the 3’ end of a novel open reading frame (ORF), orfX. orfX encodes a putative 159-amino acid

-22018206754 18Jul2018 polypeptide that exhibits sequence homology with some previously identified polypeptides of unknown function (Ito et al., 1999, Antimicrob. Agents Chemother. 43:1449-1458). Two new types of SCCmec, designated type IV and type V were recently described (Ma et al., 2002, Antimicrob. Agents Chemother. 46:1147-1152, Ito et al., 2004, Antimicrob Agents Chemother. 48:2637-2651, Oliveira et al., 2001, Microb. Drug Resist. 7:349-360). Sequence analysis of the right extremity of the new SCCmec type IV from S. aureus strains CA05 and 8/6-3P revealed that the sequences were nearly identical over 2000 nucleotides to that of type II SCCmec of S', aureus strain N315 (Ma et al., 2002, Antimicrob. Agents Chemother. 46:1147-1152; Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336). To date, sequence data for the right extremity of the SCCmec type IV from S. aureus strains HDE288 and PL72 is not publicly available (Oliveira et al., 2001, Microb. Drug Resist. 7:349-360).

[0006] Methods to detect and identify MRSA based on the detection of the mecA gene and S. aureus-specrRc chromosomal sequences have been described. (Saito et al., 1995, J. Clin. Microbiol. 33:2498-2500; Ubukata et al., 1992, J. Clin. Microbiol. 30:1728-1733; Murakami et al., 1991, J. Clin. Microbiol. 29:2240-2244; Hiramatsu et al., 1992, Microbiol. Immunol. 36:445-453). However, because the mecA gene is widely distributed in both S. aureus and coagulase-negative staphylococci, these methods are not always capable of discriminating MRSA from methicillin-resistant CNS (Suzuki et al., 1992, Antimicrob. Agents. Chemother. 36:429-434). To address this problem, Hiramatsu et al. developed a PCR-based assay specific for MRSA that utilizes primers that hybridize to the right extremities of the 3 types of SCCmec DNAs in combination with primers specific to the 5. aureus chromosome, which corresponds to the nucleotide sequence on the right side of the SCCmec integration site (US patent 6,156,507, hereinafter the “507 patent”). Nucleotide sequences surrounding the SCCmec integration site in other staphylococcal species (e.g., 5¹. epidermidis and & haemolyticus') are different from those found in 5*. aureus. Therefore, this PCR assay is specific for the detection of MRSA.

[0007] The PCR assay described in the “507 patent” also led to the development of MREP typing (mec right extremity polymorphism) of SCCmec DNA (Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336; Hiramatsu et al., 1996, J. Infect. Chemother. 2:117-129). The MREP typing method takes advantage of the fact that the nucleotide sequences of the three MREJ types differ at the right extremity of SCCmec DNAs adjacent to the integration site among the three types of SCCmec. Compared to type I, type III has a unique nucleotide sequence while type II has an

-3 2018206754 18 Jul2018 insertion of 102 nucleotides to the right terminus of SCCmec. The MREP typing method described by Hiramatsu et al. uses the following nomenclature: SCCmec type I is MREP type i, SCCmec type II is MREP type ii, and SCCmec type III is MREP type iii.

[0008] Because SCCmec types II and IV have the same nucleotide sequence to the right extremity, the MREP typing method described above cannot differentiate the new SCCmec type IV described by Hiramatsu et al. (Ma et al., 2002, Antimicrob. Agents Chemother. 46:1147-1152) from SCCmec type II.

[0009] The phrase MREJ refers to the mec right extremity junction « mec right extremity junction ». MREJs are approximately 1 kilobase (kb) in length and include sequences from the SCCmec right extremity as well as bacterial chromosomal DNA to the right of the SCCmec integration site. Strains that were classified as MREP types i-iii correspond to MREJ types i-iii. MREJ types iv, v, vi, vii, viii, ix, and x have been previously characterized (Huletsky et al., 2004, J Clin. Microbiol. 42:1875-1884; International Patent Application PCT/CA02/00824).

[0010] The embodiments described herein relate to the generation of SCCmec right extremity junction sequence data that enables the detection of more MRSA strains in order to improve NAT assays for detection of MRSA. There is a need for developing more ubiquitous primers and probes for the detection of most MRSA strains around the world.

SUMMARY OF THE INVENTION [0011] Provided herein are specific, ubiquitous and sensitive methods and compositions for determining the presence and/or amount of nucleic acids from all methicillin-resistant Staphylococcus aureus (MRSA) strains. Methods, compositions and kits are disclosed that enable the detection and quantification of novel MREJ types xi-xx.

[0012] Some aspects relate to a method to detect the presence of an MRSA bacterium in a sample comprising bacterial nucleic acids. MRSA strains have SCCmec nucleic acid insert comprising a mecA gene. The SCCmec insert renders the MRSA bacterium resistant to methicillin. The SCCmec is inserted into the bacterial DNA at the 3' end of the open reading frame orjX, creating a polymorphic right extremity junction (MREJ). At least one primer and/or probe specific for MRSA strains is provided, wherein the primer or probe hybridizes to a polymorphic MREJ nucleic acid of MREJ types xi to xx. The primer(s) and/or probe(s) are annealed with the nucleic acids of the sample. Annealed primer and/or probe indicates the presence of MREJ.

-42018206754 18Jul2018 [0013] In preferred embodiments, more than one primer and/or probe is provided. The primers and/or probes can anneal to the MREJ nucleic acids under substantially the same annealing conditions. The primers and/or probes can be at least 10 nucleotides, 12 nucleotides, 14 nucleotides, 16 nucleotides, 18 nucleotides, 20 nucleotides, 25 nucleotides, or 30 nucleotides in length. The probes and primers can be used together in the same physical enclosure or in different physical enclosures.

[0014] IN SOME EMBODIMENTS, THE PRIMERS AND/OR PROBES ANNEAL WITH ANY ONE OF THE NUCLEIC ACIDS OF SEQ ID NOS: 15,16, 17, 18, 19, 20, 21, 25, 26, 39,40, 41, 42, 55, AND 56. IN SOME EMBODIMENTS, THE PRIMERS AND/OR PROBES ALTOGETHER CAN ANNEAL WITH MREJ TYPES XI TO XX, SUCH AS SEQ ID NOS: 15, 16, 17,18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, AND 56.

FOR EXAMPLE, IN SOME EMBODIMENTS, THE PRIMERS AND/OR PROBES

LISTED IN TABLE 4 ARE USED TO DETECT MRSA BACTERIA COMPRISING

THE FOLLOWING MREJ NUCLEIC ACID: TABLE 4

Primer/Probe SEQ ID NOs:	To Identify MREJ type
30,31,32,33,34, 44, 45, 76	xi
30,31,32,33,35,44, 45, 62	xii
29,30,31,32,33,44, 45, 76	xiii
29,30,31,32, 33,44, 45, 59	xiv
24,30,31,32,33, 4, 45, 62	XV
36, 44	xvi
4,30,31,32,33, 44, 45,62	xvii
7,30,31,32,33,44, 45,59	xviii
9,30,31,32,33,44, 45,59	1 xix
8,30,31,32,33,44, 45,59	xx

[0015] In some embodiments, primers and/or probes are provided that anneal under stringent conditions to more than one MREJ type strain. For example, in preferred embodiments, SEQ ID NOs: 31, 32, 33 are provided for the detection of MREJ types xi to xv and xvii to xx.

[0016] In further embodiments primers and/or probes are provided in pairs for the detection of at least one MRSA having MREJ of types xi to xx. Accordingly, in some embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 34/45, 34/30, 34/76, and 34/44 are provided for detection of MREJ type xi.

-52018206754 18Jul2018

In other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 35/45, 35/30, 35/62, and 35/44 are provided for detection of MREJ type xii. In yet other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 29/45, 29/30, 29/76, and 29/44 is provided for detection of MREJ type xiii. In still other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 29/45, 29/30, 29/59, and 29/44 is provided for detection of MREJ type xiv. In other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 24/45, 24/30, 24/62, and 24/44 is provided for detection of MREJ type xv. In yet other embodiments, the oligonucleotides of SEQ ID NOs: 36 and 44 are provided for detection of MREJ type xvi. In still other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 4/45, 4/30, 4/62, and 4/44 is provided for the detection of MREJ type xvii. In yet other embodiments, at least one pair of oligonucleotides selected from the group consisting of 7/45, 7/30, 7/59 and 7/44 is provided for the detection of MREJ type xviii. In other embodiments, at least one pair of oligonucleotides selected from the group consisting of 9/45, 9/30, 9/59 and 9/44 is provided for the detection of MREJ type xix. In yet other embodiments, at least one pair of oligonucleotides selected from the group consisting of SEQ ID NOs: 8/45, 8/30, 8/59, and 8/44 is provided for the detection of MREJ type xx.

[0017] In some embodiments, at least two pairs of primers are provided for the detection of more than one MREJ type.

[0018] In other preferred embodiments, the primers and/or probes listed in Table 5 are provided together to detect MRSA bacteria comprising the following MREJ nucleic acid:

TABLE 5

Primer/Probe SEQ ID NOs:	To Identify MREJ type
51,30,31,32, 33	xi
52, 30,31,32, 33	xii
29, 30,31,32, 33	xiii
29, 30,31,32, 33	xiv
24, 30,31,32, 33	xv
36,44	xvi
4,30,31,32,33	xvii

-62018206754 18 Jul 2018

7.30.31.32.33

9.30.31.32.33

8.30.31.32.33 xviii xix xx [0019] In further embodiments, the methods described above further comprise providing primers and/or probes specific for a determined MREJ type, and detecting an annealed probe or primer as an indication of the presence of a determined MREJ type.

[0020] In yet other embodiments, primers and/or probes specific for the SEQ ID NOs listed in Table 6 are provided to detect MRSA bacteria comprising the following MREJ nucleic acid:

TABLE 6

Primer/Probe SEQ ID NOs:	To Identify MREJ type
17, 18, 19	xi
20	xii
15, 25, 26	xiii
16	xiv
56	XV
21	xvi
55	xvii
39, 40	xviii
41	xix
42	xx

[0021] In some embodiments, the primers are used in an amplification reaction, such as polymerase chain reaction (PCR) and variants thereof such as nested PCR and multiplex PCR, ligase chain reaction (LCR), nucleic acid sequence-based amplification (NABSA), self-sustained sequence replication (3SR), strand displacement amplification (SDA), branched DNA signal amplification (bDNA), transcriptionmediated amplification (TMA), cycling probe technology (CPT), solid-phase amplification (SPA), nuclease dependent signal amplification (NDSA), rolling circle amplification, anchored strand displacement amplification, solid phase (immobilized) rolling circle amplification, Q beta replicase amplification and other RNA polymerase medicated techniques.

[0022] In preferred embodiments, PCR is used to amplify nucleic acids in the sample.

-7.2018206754 18Jul2018 [0023] In other embodiments, oligonucleotides of at least 10, 12, 14, 16, 18, 20, 25, or 30 nucleotides in length which hybridize under stringent conditions with any of nucleic acids of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56, and which hybridize with one or more MREJ of types selected from xi to xx are also provided.

[0024] In other embodiments, primer and/or probe pairs are provided for the detection of MRSA of all of types xi to xx. For example, in certain embodiments, the primer pairs (or probes) listed in Table 7 are provided:

TABLE 7

Primer/Probe SEQ ID NOs:	To Identify MREJ type:
34/45, 34/30, 34/76, 34/44	xi
35/45, 35/30, 35/62, 35/44	xii
29/45, 29/30, 29/76, 29/44	xiii
29/45, 29/30, 29/59, 29/44	xiv
24/45, 24/30, 24/62, 24/44	XV
36/44	xvi
4/45, 4/30, 4/62, 4/44	xvii
7/45, 7/30, 7/59, 7/44	xviii
9/45, 9/30, 9/59, 9/44	xix
8/45, 8/30, 8/59, 8/44	xx

[0025] In further embodiments of the method described above, internal probes having nucleotide sequences defined in any one of SEQ ID NOs: 31, 32, and 33 are provided.

[0026] In still other embodiments, primers and/or probes used detection of MREJ types xi to xx are used in combination with primers and/or probes capable of detecting MRSA of MREJ types i to x, such as for example those primers and or probes disclosed in co-pending International Patent Application PCT/CA02/00824.

[0027] Other aspects of the invention relate to nucleotide sequences comprising at least one of the nucleic acids of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56, or the complement thereof. Further embodiments relate to fragments of the nucleic acids of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56, wherein the fragments comprise at least 30, 50,100, 150, 200, 300, or 500 consecutive nucleotides of the nucleic acids of SEQ ID NOs: 15, 16, 17, 18, 19,

-82018206754 18 Jul 2018

20, 21, 25, 26, 39, 40, 41, 42, 55, and 56, or the complements thereof. Further aspects relate to vectors comprising the nucleic acid sequences of SEQ ID NOs: 15, 16, 17, 18,

19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56, as well as host cells, such as E. coli host cells, comprising vectors comprising the nucleic acid sequences of SEQ ID NOs: 15, 16, 17,18,19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56.

[0028] Still other aspects relate to oligonucleotides that are at least 10, 12,14,

16, 18, 20, 25 or 30 nucleotides in length that anneal to any one of SEQ ID NOs: 15, 16,

17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56. For example, some embodiments are oligonucleotides that comprise the sequence of any one of SEQ ID NOs: 31, 32, or 33. Yet other embodiments relate to oligonucleotides that are at least 10, 12, 14, 16, 18, 20, 25 or 30 nucleotides in length that anneal to only one of SEQ ID NOs: 15, 16, 17, 18, 19,

20, 21, 25, 26, 39, 40, 41, 42, 55, and 56.

[0029] Yet other aspects relate to kits comprising primers and/or probes. The primers and/or probes can be at least 10, 12,14, 16, 18, 20, 25, or 30 nucleotides in length and hybridize with any one of the nucleic acids of MREJ type xi to xx. Further embodiments relate to kits comprising primers and/or probes that are at least 10, 12, 14, 16, 18, 20, 25, or 30 nucleotides in length and hybridize with any one of the nucleic acids of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56. Some embodiments relate to kits that comprise primer pairs. For example, in some embodiments, the kits comprise the following primer pairs:

Primer/Probe SEQ ID NOs: 34/45, 34/30, 34/76, 34/44 35/45, 35/30, 35/62, 35/44 29/45, 29/30, 29/76, 29/44 29/45, 29/30, 29/59, 29/44 24/45, 24/30, 24/62, 24/44 36/44

4/45, 4/30, 4/62, 4/44 7/45, 7/30, 7/59, 7/44 9/45, 9/30, 9/59, 9/44 8/45, 8/30, 8/59, 8/44

To Identify MREJ type:

xi xii xiii xiv xv xvi xvii xviii xix xx

-92018206754 18Jul2018

BRIEF DESCRIPTION OF THE DRAWINGS [0030] Figure 1 depicts the SCCmec right extremity junctions. Shown are the positions and orientations of the primers used to sequence the novel MREJ types xi to xx. SEQ ID NOs.: 4, 24, 27-30, 36, 43-45, 50-57, 78-86 were used to sequence MREJ types xi, xii, xiii, xiv, xv, xvi, xvii, xviii, xix, and xx. Arrows and numbers below indicate the positions of primers and their respective SEQ ID NOs. Walk indicates the positions where the DNA Walking ACP (DW-ACP) primers from the DNA Walking SpeedUp Kit (Seegene, Del Mar, CA) have annealed on the SCCmec sequence.

[0031] Figure 2 depicts the SCCwec right extremity junction and the position of the primers (SEQ ID NOs.: 4, 7-9, 24, 29-36, 44, 45, 59, 62, 73) developed in the present invention for detection and identification of novel MREJ types xi, xii, xiii, xiv, xv, xvi, xvii, xviii, xix, and xx. Amplicon sizes are listed in Table 11. Numbers in parenthesis under MREJ types indicate MREJ SEQ ID NOs. Arrows indicate the positions of primers and the numbers below indicate their respective SEQ ID NOs. Dark bars and numbers below indicate the positions of probes and their respective SEQ ID NOs. Deletion in MREJ type xvi indicates the position of the 269-bp deletion in orfX.

[0032] Figure 3 illustrates a multiple sequence alignment of 19 representative MREJ types i to ix and xi to xx comprising the orfX. the integration site, and the first 535 nucleotides of the SSC/nee right extremity. MREJ types i to ix sequences are from copending International Patent Application PCT/CA02/00824 SEQ ID NOs.: 1, 2, 232, 46, 50, 171, 166, 167 and 168, respectively. SEQ ID NO: 18 corresponds to MREJ type xi, SEQ ID NO: 20 corresponds to MREJ type xii, SEQ ID NO: 15 corresponds to MREJ type xiii, SEQ ID NO: 16 corresponds to MREJ type xiv, SEQ ID NO: 56 corresponds to MREJ type xv, SEQ ID NO: 21 corresponds to MREJ type xvi, SEQ ID NO: 55 corresponds to MREJ type xvii, SEQ ID NO: 39 corresponds to MREJ type xviii, SEQ ID NO: 41 corresponds to MREJ type, and SEQ ID NO: 42 corresponds to MREJ type xx.

DETAILED DESCRIPTION OF THE INVENTION [0033] Methicillin-resistant Staphylococcus aureus (MRSA) pose a serious health threat to individuals and the need for rapid and simple methods for the detection, identification, and quantification of MRSA is readily apparent.

[0034] Disclosed herein are novel DNA sequences and DNA arrangements present in MRSA strains that allow for the detection of MRSA that were undetectable using previously available methods. The novel DNA sequences and DNA arrangements

-102018206754 18 Jul 2018 are present at the SCCmec region of MRSA DNA. MRSA strains comprise an SCCmec insert that comprises a mec A gene. The SCCmec is inserted into the bacterial DNA at the 3' end of the orfX open reading frame. The insertion of the SCCmec into the bacterial DNA creates a polymorphic right extremity junction, hereinafter referred to as MREJ standing for «mec right extremity junction». MREJ regions include sequences from the SCCmec right extremity, as well as chromosomal DNA adjacent to the right SCCmec integration site. Embodiments of the invention relate to the novel MREJ sequences and arrangements disclosed herein, which can be used as parental sequences from which primers and/or probes useful in the detection and identification of MRSA described below are derived. Other aspects of the invention relate to novel primers and/or probes derived from the novel MREJ sequences, as well as kits comprising primers and or probes that hybridize to MREJ types xi to xx, for the detection of MRSA.

[0035] Also disclosed herein are methods providing for the detection of the presence or absence of an MRSA strain in a sample that includes nucleic acids. At least one primer and/or probe that is specific for MRSA strains and that anneals to an MREJ nucleic acid of types xi to xx, disclosed herein, is provided. The primer(s) and/or probe(s) can be annealed to the nucleic acids of the sample. The detection of annealed primer(s) and/or probe(s) indicates the presence of an MRSA of the MREJ type that hybridizes to the primer(s) and/or probe(s).

Primers and Probes [0036] As used herein, the terms primer and probe are not limited to oligonucleotides or nucleic acids, but rather encompass molecules that are analogs of nucleotides, as well as nucleotides. Nucleotides and polynucleotides, as used herein shall be generic to polydeoxyribonucleotides (containing 2-deoxy-D-ribose), to polyribonucleotides (containing D-ribose), to any other type of polynucleotide which is an N- or C-glycoside of a purine or pyrimidine base, and to other polymers containing nonnucleotidic backbones, for example, polyamide (e.g., peptide nucleic acids (PNAs) and polymorpholino (commercially available from the Anti-Virals, Inc., Corvallis, Oreg., as Neugene™ polymers), and other synthetic sequence-specific nucleic acid polymers providing that the polymers contain nucleobases in a configuration which allows for base pairing and base stacking, such as is found in DNA and RNA.

[0037] The terms nucleotide and polynucleotide include, for example, 3'deoxy-2',5'-DNA, oligodeoxyribonucleotide N3'—*P5' phosphoramidates, 2'-O-alkylsubstituted RNA, double- and single-stranded DNA, as well as double- and single-11 2018206754 18 Jul 2018 stranded RNA, DNA:RNA hybrids, and hybrids between PNAs and DNA or RNA. The terms also include known types of modifications, for example, labels which are known in the art, methylation, caps, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.), with negatively charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), and with positively charged linkages (e.g., aminoalklyphosphoramidates, aminoalkylphosphotriesters), those containing pendant moieties, such as, for example, proteins (including nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), those with intercalators (e.g., acridine, psoralen, etc.), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.), those containing alkylators, those with modified linkages (e.g., alpha anomeric nucleic acids, etc.), as well as unmodified forms of the polynucleotide or oligonucleotide.

[0038] It will be appreciated that, as used herein, the terms nucleoside and nucleotide will include those moieties which contain not only the known purine and pyrimidine bases, but also other heterocyclic bases which have been modified. Such modifications include methylated purines or pyrimidines, acylated purines or pyrimidines, or other heterocycles. Modified nucleosides or nucleotides will also include modifications on the sugar moiety, e.g., wherein one or more of the hydroxyl groups are replaced with a halogen, an aliphatic group, or are functionalized as ethers, amines, or the like. Other modifications to nucleotides or polynucleotides involve rearranging, appending, substituting for, or otherwise altering functional groups on the purine or pyrimidine base which form hydrogen bonds to a respective complementary pyrimidine or purine. The resultant modified nucleotide or polynucleotide may form a base pair with other such modified nucleotidic units but not with A, T, C, G or U. For example, guanosine (2amino-6-oxy-9-beta-D-ribofuranosyl-purine) may be modified to form isoguanosine (2oxy-6-amino-9-beta-D-ribofuranosyl-purine). Such modification results in a nucleoside base which will no longer effectively form a standard base pair with cytosine. However, modification of cytosine (l-beta-D-ribofuranosyl-2-oxy-4-amino-pyriinidine) to form isocytosine (l-beta-D-ribofuranosyl-2-amino-4-oxy-pyrimidine) results in a modified nucleotide which will not effectively base pair with guanosine but will form a base pair with isoguanosine. Isocytosine is available from Sigma Chemical Co. (St. Louis, Mo.); isocytidine may be prepared by the method described by Switzer et al. (1993) Biochemistry 32:10489-10496 and references cited therein; 2’-deoxy-5-methyl-122018206754 18 Jul 2018 isocytidine may be prepared by the method of Tor et al. (1993) J. Am. Chem. Soc. 115:4461-4467 and references cited therein; and isoguanine nucleotides may be prepared using the method described by Mantsch et al. (1975) Biochem. 14:5593-5601, or by the method described U.S. Pat. No. 5,780,610 to Collins et al. The nori-natural base pairs referred to as κ and π, may be synthesized by the method described in Piccirilli et al. (1990) Nature 343:33-37 for the synthesis of 2,6-diaminopyrimidine and its complement (l-methylpyrazolo[4,3]-pyrimidine-5,7-(4H,6H)-dione. Other such modified nucleotidic units which form unique base pairs have been described in Leach et al. (1992) J. Am. Chem. Soc. 114:3675-3683, or will be apparent to those of ordinary skill in the art.

[0039] Primers and/or probes can be provided in any suitable form, included bound to a solid support, liquid, and lyophilized, for example.

[0040] Specific binding or annealing of the primers and/or probes to nucleic acid sequences is accomplished through specific hybridization. It will be appreciated by one skilled in the art that specific hybridization is achieved by selecting sequences which are at least substantially complementary to the target or reference nucleic acid sequence. This includes base-pairing of the oligonucleotide target nucleic acid sequence over the entire length of the oligonucleotide sequence. Such sequences can be referred to as fully complementary with respect to each other. Where an oligonucleotide is referred to as substantially complementary with respect to a nucleic acid sequence herein, the two sequences can be fully complementary, or they may form mismatches upon hybridization, but retain the ability to hybridize under the conditions used to detect the presence of the MRS A nucleic acids.

[0041] A positive correlation exists between probe length and both the efficiency and accuracy with which a probe will anneal to a target sequence. In particular, longer sequences have a higher melting temperature (T_m) than do shorter ones, and are less likely to be repeated within a given target sequence, thereby minimizing promiscuous hybridization.

[0042] As used herein, T_m and melting temperature are interchangeable terms which refer to the temperature at which 50% of a population of double-stranded polynucleotide molecules becomes dissociated into single strands. Formulae for calculating the T_m of polynucleotides are well known in the art. For example, the T_m may be calculated by the following equation: T_m =69.3+0.41 x.(G+C)%-6- 50/L, wherein L is the length of the probe in nucleotides. The T_m of a hybrid polynucleotide may also be estimated using a formula adopted from hybridization assays in 1 M salt, and commonly

- 132018206754 18Jul2018 used for calculating T_m for PCR primers: [(number of A+T) x 2°C +(number of G+C) x 4°C], See, e.g., C. R. Newton et al. PCR, 2nd Ed., Springer-Verlag (New York: 1997), p. 24. Other more sophisticated computations exist in the art, which take structural as well as sequence characteristics into account for the calculation of T_m. A calculated T_m is merely an estimate; the optimum temperature is commonly determined empirically.

[0043] Primer or probe sequences with a high G+C content or that comprise palindromic sequences tend to self-hybridize, as do their intended target sites, since unimolecular, rather than bimolecular, hybridization kinetics are generally favored in solution. However, it is also important to design a probe that contains sufficient numbers of G:C nucleotide pairings since each G:C pair is bound by three hydrogen bonds, rather than the two that are found when A and T (or A and U) bases pair to bind the target sequence, and therefore forms a tighter, stronger bond. Preferred G+C content is about 50%.

[0044] Hybridization temperature varies inversely with probe annealing efficiency, as does the concentration of organic solvents, e.g., formamide, which might be included in a hybridization mixture, while increases in salt concentration facilitate binding. Under stringent annealing conditions, longer hybridization probes, or synthesis primers, hybridize more efficiently than do shorter ones, which are sufficient under more permissive conditions. Preferably, stringent hybridization is performed in a suitable buffer under conditions that allow the reference or target nucleic acid sequence to hybridize to the probes. Stringent hybridization conditions can vary for example from salt concentrations of less than about 1 M, more usually less than about 500 mM and preferably less than about 200 mM) and hybridization temperatures can range (for example, from as low as 0°C to greater than 22°C, greater than about 30°C and (most often) in excess of about 37°C depending upon the lengths and/or the nucleic acid composition of the probes. Longer fragments may require higher hybridization temperatures for specific hybridization. As several factors affect the stringency of hybridization, the combination of parameters is more important than the absolute measure of a single factor. Stringent hybridization conditions refers to either or both of the following: a) 6 x SSC at about 45°C, followed by one or more washes in 0.2 x SSC, 0.1% SDS at 65°C, and b) 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50°C or 70°C for 12-16 hours, followed by washing.

[0045] In the methods described herein, detection of annealed primers and/or probes can be direct or indirect. For example, probes can be annealed to the sample being

-142018206754 18Jul2018 tested, and detected directly. On the other hand, primers can be annealed to the sample being tested, followed by an amplification step. The amplified products can be detected directly, or through detection of probes that anneal to the amplification products.

[0046] In some embodiments, more than one primer and/or probe is provided. For example, some embodiments relate to methods for detecting a plurality of MRSA strains comprising MREJ types xi to xx. A plurality of primers and/or probes may be used in reactions conducted in separate physical enclosures or in the same physical enclosure. Reactions testing for a variety of MRSA types can be conducted one at a time, or simultaneously. In embodiments where the plurality of primers is provided in the same physical enclosure, a multiplex PCR reaction can be conducted, with a plurality of oligonucleotides, most preferably that are all capable of annealing with a target region under common conditions.

[0047] In some embodiments, a plurality of primers and/or probes that are specific for different MREJ types are provided in a multiplex PCR reaction, such that the type of the MREJ can be determined. The primers and/or probes used for detection can have different labels, to enable to distinguish one MREJ type from another MREJ type. As used herein, the term label refers to entities capable of providing a detectable signal, either directly or indirectly. Exemplary labels include radioisotopes, fluorescent molecules, biotin and the like.

[0048] Although the sequences from orjX genes and some SCCmec DNA fragments are available from public databases and have been used to develop DNA-based tests for detection of MRSA, the novel sequence data disclosed herein enable the detection of MRSA of MREJ types xi to xx, which heretofore were not detected using the assays known in the art. These novel sequences, which are listed in Table 8, could not have been predicted nor detected by PCR assays developed based on known MREJ sequences of MRSA (US patent 6,156,507; International Patent Application PCT/CA02/00824; Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336; Huletsky et al., 2004, J Clin. Microbiol. 42:1875-1884; Ma et al, 2002, Antimicrob. Agents Chemother. 46:1147-1152; Ito et al, Antimicrob Agents Chemother. 2004. 48:2637-2651; Oliveira et al, 2001, Microb. Drug Resist. 7:349-360). Accordingly, the novel MREJ sequences improve current NAT assays for the diagnosis of MRSA as they enable the skilled artisan to design of primers and probes for the detection and/or identification of MRSA strains with MREJ types xi to xx.

- 152018206754 18Jul2018

Design and Synthesis o f Oligonucleotide Primers and/or Probes [0049] All oligonucleotides, including probes for hybridization and primers for DNA amplification, were evaluated for their suitability for hybridization or PCR amplification by computer analysis using publicly and commercially available computer software, such as the Genetics Computer Group GCG Wisconsin package programs, and the Oligo™ 6 and MFOLD 3.0 primer analysis software. The potential suitability of the PCR primer pairs was also evaluated prior to their synthesis by verifying the absence of unwanted features such as long stretches of one nucleotide and a high proportion of G or C residues at the 3' end (Persing et al., 1993, Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.). Oligonucleotide amplification primers were synthesized using an automated DNA synthesizer (Applied Biosystems).

[0050] The oligonucleotide sequence of primers or probes may be derived from either strand of the duplex DNA. The primers or probes may consist of the bases A, G, C, or T or analogs and they may be degenerated at one or more chosen nucleotide position(s), using a nucleotide analog that pairs with any of the four naturally occurring nucleotides. (Nichols et al., 1994, Nature 369:492-493). Primers and probes may also contain nucleotide analogs such as Locked Nucleic Acids (LNA) (Koskin et al., 1998, Tetrahedron 54:3607-3630), and Peptide Nucleic Acids (PNA) (Egholm et al., 1993, Nature 365:566-568). Primers or probes may be of any suitable length, and may be selected anywhere within the DNA sequences from proprietary fragments, or from selected database sequences which are suitable for the detection of MRSA with MREJ types xi to xx. In preferred embodiments, the primers and/or probes are at least 10, 12, 14, 16, 18, 20, 25, or 30 nucleotides in length.

[0051] Variants for a given target microbial gene are naturally occurring and are attributable to sequence variation within that gene during evolution (Watson et al., 1987, Molecular Biology of the Gene, 4^th ed., The Benjamin/Cummings Publishing Company, Menlo Park, CA; Lewin, 1989, Genes IV, John Wiley & Sons, New York, NY). For example, different strains of the same microbial species may have a single or more nucleotide variation(s) at the oligonucleotide hybridization site. The skilled artisan readily appreciates the existence of variant nucleic acids and/or sequences for a specific gene and that the frequency of sequence variations depends on the selective pressure during evolution on a given gene product. Detection of a variant sequence for a region between two PCR primers may be achieved by sequencing the amplification product. On

-162018206754 18Jul2018 the other hand, to detect sequence variations that overlap with primer hybridization site, amplification and subsequent sequencing of a larger DNA target with PCR primers outside that hybridization site is required. Similar strategy may be used to detect variations at the hybridization site of a probe. Insofar as the divergence of the target nucleic acids and/or sequences or a part thereof does not affect significantly the sensitivity and/or specificity and/or ubiquity of the amplification primers or probes, variant MREJ sequences are contemplated, as are variant primer and/or probe sequences useful for amplification or hybridization to the variant MREJ.

[0052] Oligonucleotide sequences other than those explicitly described herein* and which are appropriate for detection and/or identification of MRSA may also be derived from the novel MREJ sequences disclosed herein or selected public database sequences. For example, the oligonucleotide primers or probes may be shorter but of a length of at least 10 nucleotides or longer than the ones chosen; they may also be selected anywhere else in the MREJ sequences disclosed herein or in the sequences selected from public databases. Further, variants of the oligonucleotides disclosed herein can be designed. If the target DNA or a variant thereof hybridizes to a given oligonucleotide, or if the target DNA or a variant thereof can be amplified by a given oligonucleotide PCR primer pair, the converse is also true; a given target DNA may hybridize to a variant oligonucleotide probe or be amplified by a variant oligonucleotide PCR primer. Alternatively, the oligonucleotides may be designed from MREJ sequences for use in amplification methods other than PCR. The primers and/or probes disclosed herein were designed by targeting genomic DNA sequences which are used as a source of specific and ubiquitous oligonucleotide probes and/or amplification primers for MREJ types xi to xx. When a proprietary fragment or a public database sequence is selected for its specificity and ubiquity, it increases the probability that subsets thereof will also be specific and ubiquitous. Accordingly, although the selection and evaluation of oligonucleotides suitable for diagnostic purposes requires much effort, it is quite possible for the individual skilled in the art to derive, from the selected DNA fragments, oligonucleotides other than the ones listed in Tables 9,10 and 11 which are suitable for diagnostic purposes.

[0053] The diagnostic kits, primers and probes disclosed herein can be used to detect and/or identify MRSA of MREJ types xi to xx, in both in vitro and/or in situ applications. For example, it is contemplated that the kits may be used in combination with previously described primers/probes detecting MRSA of MREJ types i to x. It is also contemplated that the diagnostic kits, primers and probes disclosed herein can be

- 172018206754 18 Jul 2018 used alone or in combination with any other assay suitable to detect and/or identify microorganisms, including but not limited to: any assay based on nucleic acids detection, any immunoassay, any enzymatic assay, any biochemical assay, any lysotypic assay, any serological assay, any differential culture medium, any enrichment culture medium, any selective culture medium, any specific assay medium, any identification culture medium, any enumeration culture medium, any cellular stain, any culture on specific cell lines, and any infectivity assay on animals.

[0054] Samples may include but are not limited to: any clinical sample, any environmental sample, any microbial culture, any microbial colony, any tissue, and any cell line.

DNA Amplification [0055] In some embodiments, an amplification and/or detection step follows the annealing step. Any type of nucleic acid amplification technology can be used in the methods described herein. Non-limiting examples of amplification reactions that can be used in the methods described herein include but are not restricted to: polymerase chain reaction (PCR) {See, PCR PROTOCOLS, A GUIDE TO METHODS AND APPLICATIONS, ed. Innis, Academic Press, N.Y. (1990) and PCR STRATEGIES (1995), ed. Innis, Academic Press, Inc., N.Y. (Innis)), ligase chain reaction (LCR) {See, Wu (1989) Genomics 4:560; Landegren (1988) Science 241:1077; Barringer (1990) Gene 89:117), nucleic acid sequence-based amplification (NASBA), self-sustained sequence replication (3SR)(&e, Guatelli (1990) Proc. Natl. Acad. Sci. USA, 87:1874), strand displacement amplification (SDA), branched DNA signal amplification bDNA, transcription-mediated amplification (TMA)(See_; Kwoh (1989) Proc. Natl. Acad. Sci. USA 86:1173), cycling probe technology (CPT), nested PCR, multiplex PCR, solid phase amplification (SPA), nuclease dependent signal amplification (NDSA), rolling circle amplification technology (RCA), Anchored strand displacement amplification, solidphase (immobilized) rolling circle amplification, Q Beta replicase amplification and other RNA polymerase mediated techniques (e.g., NASBA, Cangene, Mississauga, Ontario). These and other techniques are also described in Berger (1987) Methods Enzymol. 152:307-316; Sambrook, Ausubel, Mullis (1987) U.S. Pat. Nos. 4,683,195 and 4,683,202; Amheim (1990) C&EN 36-47; Lomeli J. Clin. Chem., 35:1826 (1989); Van Brunt, Biotechnology, 8:291-294 (1990); Wu (1989) Gene 4:560; Sooknanan (1995) Biotechnology 13:563-564.

-182018206754 18Jul2018 [0056] In preferred embodiments, PCR is used to amplify nucleic acids in the sample. During DNA amplification by PCR, two oligonucleotide primers binding respectively to each strand of the heat-denatured target DNA from the microbial genome are used to amplify exponentially in vitro the target DNA by successive thermal cycles allowing denaturation of the DNA, annealing of the primers and synthesis of new targets at each cycle (Persing et al, 1993, Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.).

[0057] Standard amplification protocols may be modified to improve nucleic acid amplification efficiency, including modifications to the reaction mixture. (Chakrabarti and Schutt, 2002, Biotechniques, 32:866-874; Al-Soud and Radstrom, 2002, J. Clin. Microbiol., 38:4463-4470; Al-Soud and Radstrom, 1998, Appl. Environ. Microbiol., 64:3748-3753; Wilson, 1997, Appl. Environ. Microbiol., 63:3741-3751). Such modifications of the amplification reaction mixture include but are not limited to the use of various polymerases or the addition of nucleic acid amplification facilitators such as betaine, BSA, sulfoxides, protein gp32, detergents, cations, and tetramethylamonium chloride.

Detection of Nucleic Acids [0058] Detection of amplified nucleic acids may include any real-time or postamplification technologies known to those skilled in the art. Classically, the detection of PCR amplification products is performed by standard ethidium bromide-stained agarose gel electrophoresis, however, the skilled artisan will readily appreciate that other methods for the detection of specific amplification products, which may be faster and more practical for routine diagnosis, may be used, such as those described in co-pending patent application W001/23604 A2. Amplicon detection may also be performed by solid support or liquid hybridization using species-specific internal DNA probes hybridizing to an amplification product. Such probes may be generated from any sequence from the repertory of MREJ nucleic acids disclosed herein, and designed to specifically hybridize to DNA amplification. Alternatively, amplicons can be characterized by sequencing. See co-pending patent application W001/23604 A2 for examples of detection and sequencing methods.

[0059] Other non-limiting examples of nucleic acid detection technologies that can be used in the embodiments disclosed herein include, but are not limited to the use of fluorescence resonance energy transfer (FRET)-based methods such as adjacent hybridization of probes (including probe-probe and probe-primer methods) (See, J. R.

-192018206754 18Jul2018

Lakowicz, “Principles of Fluorescence Spectroscopy, Kluwer Academic / Plenum Publishers, New York, 1999), TaqMan probe technology (See, European Patent EP 0 543 942), molecular beacon probe technology (See, Tyagi et al., (1996) Nat. Biotech. 14:303308.), Scorpion probe technology (See, Thewell (2000), Nucl. Acids Res. 28:3752), nanoparticle probe technology (See, Elghanian, et al. (1997) Science 277:1078-1081.) and Amplifluor probe technology (See, U.S. Pat. Nos: 5,866,366; 6,090,592; 6,117,635; and 6,117,986).

[0060] In preferred embodiments, molecular beacons are used in postamplification detection of the target nucleic acids. Molecular beacons are single stranded oligonucleotides that, unless bound to target, exist in a hairpin conformation. The 5' end of the oligonucleotide contains a fluorescent dye. A quencher dye is attached to the 3' end of the oligonucleotide.. When the beacon is not bound to target, the hairpin structure positions the fluorophore and quencher in close proximity, such that no fluorescence can be observed. Once the beacon hybridizes with target, however, the hairpin structure is disrupted, thereby separating the fluorophore and quencher and enabling detection of fluourescence. (See, Kramer FR., 1996, Nat Biotechnol 3:303-8.). Other detection methods include target gene nucleic acids detection via immunological methods, solid phase hybridization methods on filters, chips or any other solid support. In these systems, the hybridization can be monitored by any suitable method known to those skilled in the art, including fluorescence, chemiluminescence, potentiometry, mass spectrometry, plasmon resonance, polarimetry, colorimetry, flow cytometry or scanometry. Nucleotide sequencing, including sequencing by dideoxy termination or sequencing by hybridization (e.g. sequencing using a DNA chip) represents another method to detect and characterize the nucleic acids of target genes.

MREJ nucleic acids [0061] The MREJ fragments disclosed herein were obtained as a repertory of sequences created by amplifying MRSA nucleic acids with novel primers. The amplification and sequencing primers, the repertory of MREJ sequences, and the oligonucleotide sequences derived therefrom for diagnostic purposes, disclosed in Tables 8-11 are further objects of this invention.

[0062] Aspects of the invention relate to nucleic acids, in particular nucleic acid sequences from DNA fragments of SCCmec right extremity junction (MREJ), including sequences from SCCmec right extremity and chromosomal DNA to the right of the SCCmec integration site in MRSA types xi to xx. Some embodiments relate to the

-202018206754 18 Jul 2018 parental sequences of MREJ types xi to xx from which primers and/or probes specific for the MREJ type xi to xx strain are derived. Thus, some embodiments relate to the nucleotide sequence of SEQ ID NO.T5, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, or 56 or the complement thereof. Other embodiments relate to DNA fragments and oligonucleotides, such as primers and probes. For example, some embodiments relate to nucleic acids comprising at least 10, 20, 30,40, 50, 75, 100,150, 200, 250, 300, 350, 400, 450, 500, 600, 700, or 800 consecutive nucleotides of the nucleic acids of SEQ ID NO: 15, 16,17,18,19, 20, 21, 25, 26, 39,40, 41, 42, 55, or 56.

[0063] The scope of this invention is not limited to the use of amplification by PCR, but rather includes the use of any nucleic acid amplification method or any other procedure which may be used to increase the sensitivity and/or the rapidity of nucleic acid-based diagnostic tests. The scope of the present invention also covers the use of any nucleic acids amplification and detection technology including real-time or postamplification detection technologies, any amplification technology combined with detection, any hybridization nucleic acid chips or array technologies, any amplification chips or combination of amplification and hybridization chip technologies. Detection and identification by any nucleotide sequencing method is also under the scope of the present invention.

EXAMPLE 1: Evaluation of Previously Described MRS A Diagnostic Amplification

Assays [0064] Initially, the literature taught that five types of SCCmec right extremity sequences (SCCmec types I-V) are found among MRSA strains, based on DNA sequence homology (See, Ito et al., 1999, Antimicrob. Agents Chemother. 43:1449-1458; ICatayama et al., 2000, Antimicrob. Agents Chemother. 44:1549-1555; Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336; Ma et al., 2002, Antimicrob. Agents Chemother. 46:1147-1152; Ito et al, 2004, Antimicrob. Agents Chemother. 48:26372651). SCCmec DNAs are integrated at a specific site of the chromosome of a methicillin-sensitive Staphylococcus aureus (MSSA), named orJX. Generally, each SCCmec type has a unique nucleotide sequence at the right extremity of the SCC/nec cassette. The exception to this rule is seen with SCCmec types II and IV, which exhibit nearly identical sequence over 2000 nucleotides. However, SCCzwec type II has an insertion of 102 nucleotides to the right terminus of SCCmec type I. Strains classified as SCCmec types I - III fall under the category of MREJ types i-iii.

-21 2018206754 18Jul2018 [0065] Recently, we analyzed the MREJ regions of several MRSA strains. We described seven new sequences at the right extremity junction of SCCzwec from MRSA that we named MREJ types iv, v, vi, vii, viii, ix, and x (Huletsky et al., 2004, J Clin. Microbiol. 42:1875-1884; International Patent Application PCT/CA02/00824).

[0066] We designed a real-time MRSA-specific multiplex PCR assay having primers that target the SCCmec portion of MREJ types i, ii, iii, iv, v, and vii with a primer targeting the & aureus orJX. Three molecular beacon probes (MBPs) specific to the orJX sequence were used for detection of all sequence polymorphisms identified in this region of the orJX sequence (Huletsky et al., 2004, J. Clin. Microbiol. 42:1875-1884). The oligonucleotide of SEQ ID NO: 30, which hybridizes to the 5¹. aureus orJX, and the oligonucleotides of SEQ ID NOs: 36, 70, 71, 72, and 74, which hybridize to the SCC/nec portion of MREJ types i, ii, iii, iv, v, and vii were used in the PCR reaction. Oligonucleotides of SEQ ID NOs: 31, 32, and 33, which hybridize to S. aureus orJX were used as probes. The specificity and ubiquity (i.e., the ability to detect all or most MRSA strains) of the PCR assay was verified using a panel of 569 reference and clinical strains of methicillin-sensitive S', aureus (MSSA) and 1657 different MRSA strains from 32 different countries and which include well-known epidemic clones.

[0067] A list of the strains tested and used to build the repertories of MREJ nucleic acids and oligonucleotides derived therefrom disclosed herein is presented in Table 1. The S. aureus clinical isolates used in this invention are part of the SENTRY program collection and several supplier’s collections. These S. aureus reference strains or clinical isolates originate from 32 countries: African countries (n=15), Albania (n=2), Argentina (n=50), Australia (n=71), Austria (n=2), Belgium (n=10), Brazil (n=78), Canada (n=607), Chile (n=42), China (n=70), Denmark (n=33), Egypt (n=l), Finland (n=12), France (n=50), Germany (n=47), Greece (n=7), Ireland (n=5), Israel (n=19), Italy (n=61), Japan (n=62), Mexico (n=l), The Netherlands (n=179), Poland (n=33), Portugal (n=24), Singapore (n=20), Slovenia (n=12), Spain (n=31), Sweden (n=10), Switzerland (n=13), Turkey (n=28), United Kingdom (n=22), and United States (n=528). Confirmation of the identification of the staphylococcal strains was performed by using the MicroScan WalkAway Panel type Positive Breakpoint Combo 13 when required (Dade Behring Canada Inc., Mississauga, Ontario, Canada). When needed, the identity was reconfirmed by PCR analysis using S. awreus-specific primers and mecA-specific primers (SEQ ID NOs.: 50, 60, 61, 63) (Martineau et al., 2000, Antimicrob. Agents Chemother. 44:231-238). The data from the assay is presented in Table 2.

-222018206754 18 Jul 2018 [0068] Among the 569 MSSA strains tested, 26 strains were misidentified as MRSA based on the PCR assay. Of the 1657 MRSA strains tested, 1640 were specifically detected with the PCR assay whereas 23 of these MRSA strains, representing a broad variety of origins were not detected by the assay. Thus, the specificity and ubiquity (i.e. the ability to detect all or most MRSA strains) of this PCR assay was verified. Four of these 23 MRSA strains, CCRI-9208, CCRI-9770, CCRI-9681, and CCRI-9860, which were not detected in the above assay have previously been shown to harbor the MREJ types vi, viii, ix, and x, respectively (International Patent Application PCT/CA02/00824).

[0069] The 19 remaining MRSA strains that were not detected in the assay were analyzed further. PCR was performed on the genomic DNA from each strain, using a primer targeting the sequence at the SCCzwec right extremity of MREJ types vi, viii, or ix in combination with a primer targeting the S’, aureus orfX. Specifically, each PCR reaction contained the oligonucleotide of SEQ ID NO:65, which anneals to MREJ type vi, the oligonucleotide of SEQ ID NO :75, which anneals to MREJ type viii, or the oligonucleotide of SEQ ID NO:29, which anneals to MREJ type ix, in combination with the oligonucleotide of SEQ ID NO:30, which is a X awrewi-specific primer. MREJ type x was previously shown to have a deletion of the complete orfX and a portion at the right extremity of SCC’/zzec type II (International Patent Application PCT/CA02/00824). Therefore, the oligonucleotide of SEQ ID NO:77, which anneals to orf22 in the S', aureus chromosome, and the oligonucleotide of SEQ ID NO:73, which anneals to orf27 located in SCCwec type II were used in a PCR reaction to detect MREJ type x. Two out of 19 strains, CCRI-11879 and CCRI-12036, were shown to harbor MREJ type ix with these PCR primers. However, 17 MRSA strains were not detected with primers targeting MREJ types vi, viii, ix, and x suggesting that these strains harbor new MREJ types (Tables 2 and 3).

EXAMPLE 2: Sequencing of Novel MREJ Types from MRSA [0070] To further characterize the MREJ region of the 17 MRSA strains from which DNA was not amplified with primers that allow the detection of MREJ types i to x, the nucleotide sequence of MREJ for 15 of these 17 MRSA strains was determined. First, a primer that anneals to mecA (SEQ ID NO.: 50) and a primer that anneals to the 5’ end of orfX (SEQ ID NO.:44) were used together in a PCR reaction to amplify MREJ fragments of MRSA. The strategy used to select these primers is illustrated in Figure 1. Four identical PCR reactions, each containing 100 ng of purified genomic DNA were

-232018206754 18Jul2018 performed. Each PCR reaction contained IX HERCULASE™ DNA polymerase buffer (Stratagene, La Jolla, CA), 0.8 μΜ of each of the oligos of SEQ ID NOs.: 44 and 50, 0.56 mM of each of the four dNTPs and 5 units of HERCULASE™ DNA polymerase (Stratagene, La Jolla, CA) with 1 mM MgCL in a final volume of 50pl. PCR reactions were subjected to cycling using a standard thermal cycler (PTC-200 from MJ Research Inc.) as follows: 2 min at 92 °C followed by 35 or 40 cycles of 10 sec at 92 °C for the denaturation step, 30 sec at 55 °C for the annealing step and 15 min at 68 °C for the extension step.

[0071] The four PCR reactions were pooled. 10 pL of the PCR reaction was resolved by electrophoresis in a 0.7% agarose gel containing 0.25pg/mL of ethidium bromide. The amplicons were then visualized with an Alpha-Imager (Alpha Innotech Corporation, San Leandro, CA) by exposing to UV light at 254 nm. The remaining PCRamplified mixture (150-200 pi, total) was also resolved by electrophoresis in a 0.7% agarose gel and visualized by staining with methylene blue (Flores et al., 1992, Biotechniques, 13:203-205).

[0072] Of the 15 strains tested, the following eight yielded amplification products ranging from 12-20 kb in length with SEQ ID NOs.: 44 and 50 as primers: CCRI-11976, CCRI-11999, CCRI-12157, CCRI-12198, CCRI-12199, CCRI-12719, CCRI-9887, CCRI-9772. The amplification products were excised from the agarose gel and purified using the QIAquick™ gel extraction kit (QIAGEN Inc., Valencia, CA). The gel-purified DNA fragments were used directly in sequencing reactions. Both strands of the MREJ amplification products were sequenced by the dideoxynucleotide chain termination sequencing method using an Applied Biosystems automated DNA sequencer (model 377 or 3730x1) with their Big Dye™ Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, Foster City, CA). 425-495 ng of the gel-purified amplicons were used in sequencing reactions with SEQ ID NO.: 44, which was used for the amplification reaction. Based on the sequence information generated from the reactions with SEQ ID NO:44, internal sequencing primers were designed and used to obtain sequence data from both strands for a larger portion of each amplicon preparation. Specifically, the oligonucleotides of SEQ ID NOs.: 43 and 45 were used to sequence MRSA strains CCRI-11976 and CCRI-11999; SEQ ID NOs.: 43, 45, and 51 were used to sequence MRSA strains CCRI-12157, CCRI-12198, and CCRI-12199; SEQ ID NOs.: 43, 45, and 52 were used to sequence MRSA strain CCRI-12719; SEQ ID NO.: 24 was used to sequence MRSA strain CCRI-9887, and SEQ ID NOs.: 4, 45, and 57 were used to

-242018206754 18Jul2018 sequence MRSA strain CCRI-9772 (Figure 1, Tables 9 and 11). The sequences of the 8 strains described in Table 3 are presented as SEQ ID NOs.: 15,16,17, 18, 19, 20, 55, and 56 (Table 8).

[0073] To ensure that the determined sequence did not contain errors attributable to the sequencing of PCR artifacts, two independent preparations of the gelpurified MREJ amplification products originating from two independent PCR amplifications were sequenced as described above. For most target fragments, the sequences determined for both amplicon preparations were identical. Furthermore, the sequences of both strands were 100% complementary thereby confirming the high accuracy of the determined sequence. The MREJ sequences determined using tire above strategy are described in the Sequence Listing and in Table 8.

[0074] A different set of oligonucleotide primers (described in Oliviera et. al.) was used to further analyze the 17 MRSA strains that did not yield amplification products with primers for detection of MREJ types i-vii (Oliveira and de Lencastre. 2002, Antimicrob. Agents Chemother. 46:2155-2161). Two strains, (CCRI-12382 and CCRI12383), harbored SCCmec type III and contained sequences specific to the yccr complex. Another strain, (CCRI-12845), harbors SCCmec type II.

[0075] To determine the MREJ sequences of strains CCRI-12382 and CCRI12383, a primer targeting the \\tccr complex sequence located in SCCmec type III (SEQ ID NO.: 27) was used in combination with a primer targeting the 5’end of orfX(SEQ ID NO.: 44) to amplify MREJ fragments of these two MRSA strains (Table 10 and Figure 1). Four identical PCR reactions, each containing 100 ng of purified genomic DNA were performed. Each PCR reaction contained IX HERCULASE™ DNA polymerase buffer (Stratagene, La Jolla, CA), 0.8 μΜ of each of the 2 primers (SEQ ID NOs.: 27 and 44), 0.56 mM of each of the four dNTPs and 5 units of HERCULASE™ DNA polymerase (Stratagene, La Jolla, CA) with 1 mM MgCL in a final volume of 50 μΐ. The PCR reactions were cycled using a standard thermal cycler (PTC-200 from MJ Research Inc., Watertown, MA) as follows: 2 min at 92°C followed by 35 cycles of 10 sec at 92°C for the denaturation step, 30 sec at 55°C for the annealing step and 15 min at 68°C for the extension step.

[0076] The PCR reactions were pooled and 10 μΐ of the PCR-amplified mixture was resolved by electrophoresis in a 0.7% agarose gel containing 0.25 pg/ml of ethidium bromide. The amplicons were then visualized with an Alpha-Imager (Alpha Innotech Corporation, San Leandro, CA) by exposing to UV light at 254 nm. The

-252018206754 18 Jul 2018 remaining PCR-amplified mixture (150-200 pi. total) was also resolved by electrophoresis in a 0.7% agarose gel and visualized by staining with methylene blue as described above. For these two MRSA strains, an amplification product of ~ 8 kb was obtained. The PCR amplification products were excised from the agarose gel and purified as described above. The gel-purified DNA fragment was then used directly in the sequencing protocol as described above. The sequencing reactions were performed by using SEQ ID NO.: 44 (also used in the amplification reaction) and 425-495 ng of the gel-purified amplicons for each reaction. Subsequently, different sets of internal sequencing primers were used to obtain sequence data from both strands and for a larger portion of the amplicon (SEQ ID NOs.: 28, 30, and 43) (Figure 1, Tables 9 and 11). The sequence of the MRSA strains CCRI-12382 and CCRI-12383 described in Table 3 which were sequenced using this strategy are designated SEQ ID NOs.: 25 and 26, respectively (Table 8).

[0077] To sequence the MREJ fragment of strain CCRI-12845 (SCCmec type II) PCR amplification was performed using the oligonucleotide of SEQ ID NO:44, which anneals to the 5’ end of orfX in combination with the oligonucleotide of SEQ ID NO:53, which anneals to the the SCCraec right extremity of MREJ type ii. 1 pL of a purified genomic DNA preparation was transferred directly into 4 tubes containing 39 pL of a PCR reaction mixture. Each PCR reaction contained 50 mM KC1, 10 mM Tris-HCl (pH 9.0), 0.1% Triton X-100, 2.5 mM MgCl₂, 0,4 pM of each of the oligonucleotides of SEQ ID NO.: 44 and 53, 200 pM of each of the four dNTPs, 3.3 pg/pl of BSA (Sigma-Aldrich Canada Ltd) and 0.5 unit of Taq DNA polymerase (Promega, Madison, WI) coupled with the TagStart™ Antibody (BD Bisociences, San Jose, CA). PCR reactions were performed using a standard thermocycler (PTC-200 from MJ Research Inc., Watertown, MA) as follows: 3 min at 94°C followed by 40 cycles of 5 sec at 95 °C for the denaturation step, 1 min at 58°C for the annealing step and 1 min at 72°C for the extension step. An amplification product of 4.5 kb was obtained with this primer set.

[0078] The amplification products were pooled and 10 pi of the mixture were resolved by electrophoresis in a 1.2% agarose gel containing 0.25pg/ml of ethidium bromide. The amplicons were then visualized with the Alpha-Imager. Amplicon size was estimated by comparison with a 1 kb molecular weight ladder (Life Technologies, Bethesda, MD). The remaining PCR-amplified mixture (150 pi, total) was also resolved by electrophoresis in a 1.2% agarose gel and visualized by staining with methylene blue

-262018206754 18 Jul 2018 as described above. The PCR reaction yielded a 1.2 kb amplification product. The band corresponding to this specific amplification product was excised from the agarose gel and purified as described above. The gel-purified DNA fragment was then used directly in the sequencing protocol as described above. The sequencing reactions were performed using the oligonucleotides of SEQ ID NOs.: 44 and 53 as well as one internal primer (SEQ ID NO.: 54) and 10 ng/100 bp per reaction of the gel-purified amplicons (Figure 1, Table 10). The MREJ sequence of strain CCRI-12845 is designated as SEQ ID NO.: 21 (Table 8).

[0079] To determine the MREJ sequences of the 4 last MRSA strains (CCRI12524, CCRI-12535, CCRI-12810, and CCRI-12905), the oligonucleotide of SEQ ID NO: 44 was used in combination with each of the four DNA Walking ACP (DW-ACP) primers from the DNA WALKING SPEED UP™ Sequencing Kit (Seegene, Del Mar, CA) according to the manufacturer’s instructions on a PTC-200 thermocycler. The DWACP primer system (DW ACP-PCR™ Technology) enables one to obtain genuine unknown target amplification products up to 2 kb. A first amplification product obtained with one of the DW-ACP primers was purified using the QIAQUIK™ PCR purification Kit (QIAGEN Inc., Valencia, CA). The purified PCR product was re-amplified using the DW-ACP-N primer in combination with the oligonucleotide of SEQ ID NO:30, which anneals to orfX under manufacturer recommended PCR conditions. The PCR-amplified mixture of 4 different 50-pL PCR reactions were pooled and resolved by electrophoresis in a 1.2% agarose gel. The amplicons were then visualized by staining with methylene blue as described above. Amplicon size was once again estimated by comparison with a 1 kb molecular weight ladder. An amplification product of 1.5 to 3 kb was obtained. The amplification product was excised from the agarose gel and purified as described above and the DNA was then used directly in the sequencing protocol as described above. 10 ng of purified DNA for every 100 bp of the amplicon was used in sequencing reactions using the oligonucleotides of SEQ ID NO.: 30 and DW-ACP-N. The MREJ sequences from MRSA strains strains CCRI-12524, CCRI-12535, CCRI-12810, and CCRI-12905 (described in Table 3) are designated SEQ ID NOs.: 39, 40, 41, and 42 (Table 8).

(0080] CCRI-12376 and CCRI-12593 described in Table 3 were not sequenced but rather characterized using PCR primers and shown to contain MREJ type xiii using specific amplification primers.

-272018206754 18 Jul 2018

EXAMPLE 3: Sequence Analysis of Novel MREJ types xi-xx [0081] The sequences obtained for 15 of the 17 strains non-amplifiable by the MRSA-specific primers detecting MREJ types i to x previously described were compared to the sequences available from public databases. In all cases except MRSA strain CCRI12845, the orfX portion of the MREJ sequence had an identity close to 100% to publicly available sequences for orfX. CCRI-12845 has a deletion in orfX (SEQ ID NO.: 21) (described below). While the orfX portion of most MREJ fragments (SEQ ID NOs.: 1520, 25-26, 39-42, 55-56) shared nearly 100% identity with publicly available 5. aureus orfX sequences, with the exception of strain CCRI-12845, the DNA sequence within the right extremity of SCCzwec itself was shown to be different from those of MREJ types i, ii, iii, iv, v, vi, vii, viii, ix, and x (International Patent Application PCT/CA02/00824; US patent 6,156,507). The DNA sequence within the right extremity of SCCmec of CCRI12845 was similar to that of MREJ type ii (see below). Thus, ten different novel MREJ sequence types are reported herein: MREJ types xi to xx.

]0082] The sequences within the right extremity of SCCmec obtained from strains CCRI-12157, CCRI-12198, and CCRI-12199 (SEQ ID NOs.: 17, 18, and 19) were nearly identical to each other, and different from those of MREJ types i, ii, iii, iv, v, vi, vii, viii, ix, and x (Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336; Ma et al., 2002, Antimicrob. Agents Chemother. 46:1147-1152, Huletsky et al., 2004, J. Clin. Microbiol. 42:1875-1884, International Patent Application PCT/CA02/00824, US patent 6,156,507). These new sequences were designated as MREJ type xi (SEQ ID NOs.: 1719). A BLAST™ search revealed that the first 86 bp of the SCCmec portion of MREJ type xi exhibited 87% identity with an unknown sequence of Staphylococcus epidermidis strain SRI (GenBank accession number AF270046). The remainder of the MREJ sequence was shown to be unique, exhibiting no significant homology to any published sequence.

[0083] The sequence obtained at the right extremity of SCCmec from strain CCRI-12719 (SEQ ID NO.: 20) was different from MREJ types i to x as well as from MREJ type xi. The new MREJ type was designated as MREJ type xii. When compared with GenBank sequences using BLAST™, the sequence at the right extremity of SCCmec of MREJ type xii exhibited 100 % identity with the sequence found at the right extremity of the SCCmec type V recently described (Ito et al., 2004, Antimicrob. Agents. Chemother. 48:2637-2651; GenBank accession number AB121219). The sequence also

-282018206754 18 Jul 2018 exhibited 85% identity with a 212-nucleotide region of the Staphylococcus epidermidis RP62a putative GTP-binding protein sequence.

[0084] The sequences within the right extremity of SCCmec obtained from strains CCRI-11976, CCRI-12382, and CCRI-12383 (SEQ ID NOs.: 15, 25, and 26) were 100% identical to each other, different from MREJ types i to x as well as from MREJ types xi and xii. The new MREJ sequences were designated as MREJ type xiii (SEQ ID NOs.: 15, 25, and 26).

[0085] The sequence within the right extremity of SCCmec obtained from strain CCRI-11999 (SEQ ID NO.: 16) was also different from MREJ types i to x as well as from MREJ types xi, xii, and xiii, and consequently, was designated as MREJ type xiv. A BLAST™ search of the MREJ types xiii and xiv sequences showed that a portion of the SCCmec of these two MREJ types was identical to that of MREJ type ix. Indeed, the SCCmec portions of MREJ types ix and xiv were preceded by one and two consecutive 102 bp insertions, respectively, when compared to MREJ type xiii. The rest of the MREJ types ix, xiii, and xiv sequences were 99.9% identical to each other. These sequences exhibited identities ranging from 97% to 100% (for the highest BLAST scores) with noncontiguous regions (in varying sizes of 1535 to 1880 nucleotides) of the SCC cassette without mecA harboring the chromosome recombinase genes of the methicillinsusceptible strain S', epidermidis ATCC 12228 (GenBank accession number BK001539). The sequence of the 102-pb insertion was 99-100% identical to that found in MREJ type ii.

[0086] The sequence obtained within the right extremity of SCCmec from strain CCRI-9887 was different from MREJ types i to x as well as from MREJ types xi to xiv and was therefore designated as MREJ type xv (SEQ ID NO.: 56). A BLAST search of the sequence obtained within the SCCmec portion of MREJ type xv revealed that this DNA fragment exhibited identities ranging from 92% to 96% (for the highest BLAST scores) with non-contiguous sequences (in varying sizes of 342 to 618 nucleotides) of the SCC cassette (which do not contain mecA) of the methicillin-susceptible S. aureus strain M (GenBank accession number U10927). Although the sequence of MREJ type xv has been described, the localization of this sequence downstream of orfX in a MRSA strain has heretofore not been described. The CCRI-9887 MREJ sequence also exhibited 94% identity with a 306-nucleotide region of strain Staphylococcus haemolyticus JCSC1435 located near the orfX sequence.

-292018206754 18Jul2018 [0087] The sequence obtained for MREJ from strain CCRI-12845 (SEQ ID NO.: 21) revealed that the MREJ fragment of this strain has a deletion of nucleotides 165 to 434 of orfX (269-bp fragment), whereas the sequence at the right extremity of SCCmec (328 nucleotides) had identities ranging from 99.8 to 100% with that of MREJ type ii available in public databases. Although the MREJ sequence obtained from this strain exhibited a high level of identity with known MREJ sequences, the presence of a 269-bp deletion within orfX had heretofore never been described. As one of the oligonucleotides used in the initial PCR amplification assay described above falls within this 269 bp deletion, the deletion in orfX explains why this MRSA strain was not or could not have been detected with primers and probes previoulsy described to detect MRSA (US patent 6,156,507 and International Patent Application PCT/CA02/00824). The novel MREJ sequence of this strain was designated as MREJ type xvi.

[0088] The sequence obtained at the right extremity of SCCmec from strain CCRI-9772 was different from MREJ types i to x as well as from MREJ types xi to xvi. The new MREJ type was designated as MREJ type xvii (SEQ ID NO.:55). A BLAST™ search against the GenBank database revealed that the SCCmec portion of MREJ type xvii sequence exhibited 100% identity with the sequence at left of the SCCmec junction of 5. aureus strain CA05 (JCSC 1968) (GenBank Accession number AB063172) harbouring SCCmec type IV (Ma et al., 2002. Antimicrob. Agents Chemother. 46:11471152). The genetic organization of MREJ type xvii is similar to the region downstream of orfic in MSSA. Although the sequence itself has been described previously, the localization of this sequence downstream of orfX in a MRSA strain has heretofore never been described.

[0089] The sequences obtained from the right extremity of SCCmec from strains CCRI-12524 and CCRI-12535 were nearly identical to each other but were different from MREJ types i to x as well as from MREJ types xi to xvii and were therefore designated as MREJ type xviii (SEQ ID NOs.:39 and 40). A BLAST search against GenBank sequences revealed a 100% identity with a 487-nucleotide region of the SCCmec cassette of Staphylococcus haemolyticus JCSC 1435. The remainder of the sequence was shown to be unique, exhibiting no significant homology to any published sequence.

[0090] The sequence obtained from strain CCRI-12810 was different from MREJ types i to x as well as from MREJ types xi to xviii and was designated as MREJ type xix (SEQ ID NO.:41). When compared with GenBank sequences using BLAST, the

-302018206754 18Jul2018

SCCmec portion of MREJ type xix sequence exhibited 100% identity with a 597nucleotide region of unknown function of strain ATCC 25923 which is located at the left of SCCmec (GenBank accession number AB047239). This result has been observed with four other MRSA strains for which the SCCmec sequences have been published: MRSA252, 85/3907, 85/2082, and MR108 (GenBank accession numbers: BX571856, AB047088, AB037671 and AB096217, respectively). The genetic organization of MREJ type xix is similar to the region downstream of orfa in MSSA. Although the sequence itself had been described, the presence of this DNA fragment downstream of orjX had heretofore never been described.

[0091] The sequence obtained at the right extremity of SCCmec from strain CCRI-12905 was different from MREJ types i to x as well as from MREJ types xi to xix and was designated as MREJ type xx (SEQ ID NO. :42). When compared with Genbank sequences using BLAST, the SCCmec of MREJ type xx sequence exhibited 100% and 99% identities with two non-contiguous sequences (respectively 727 and 307 nucleotides long) downstream of orfK of the methicillin-susceptible S. aureus strain NCTC 8325 (GenBank accession number AB014440). The genetic organization of MREJ type xx is similar to the region downstream of orfx in MSSA. The localization of this sequence downstream of orfX in a MRSA strain has heretofore never been described. Identity i

levels ranging from 98% to 100% with non-contiguous fragments (in varying sizes of 91 to 727 nucleotides) was found with 11 MRSA strains for which the SCCmec sequences have been published: N315, NCTC 10442, COL, USA300, Mu50, 2314, 85/4231, 85/2235, JCSC 1978, PL72, HDE 288 (GenBank accession numbers: BA000018, AB033763, CP000046, CP000255, BA000017, AY271717, AB014428, AB014427, AB063173, AF411936, AF411935, respectively). These identical fragments are located downstream of the mecA gene towards (or even downstream) the left insertion point of SCCmec.

EXAMPLE 4: Sequence comparison of new MREJ types xi to xx [0092] The sequences of the first 500-nucleotide portion of the SCCmec right extremity of all new MREJ types (xi to xx) were compared with each other and with those of the previously described MREJ types i to ix using GCG software programs Pileup and Gap (GCG, Wisconsin). Table 12 depicts the identities at the nucleotide level between the SCCmec right extremities of the 10 novel MREJ types (xi to xx) with those of the MREJ types previously described (i to ix) using the GCG program Gap. MREJ type x was

-31 2018206754 18Jul2018 excluded from this comparison since this MREJ sequence is deleted of the complete orfX and of the SCCmec integration site as well as ~ 4 kb at the right extremity of SCCmec when compared to the right extremity of SCCmec type II. The SCCmec right extremity of MREJ types ix, xiii, and xiv differed by only one and two 102-bp insertions present in MREJ types ix and xiv, respectively. However, the rest of these three sequences showed nearly 100% identity (Figure 3). Although the SCCmec portion of MREJ type xvi is nearly 100% identical with that of MREJ type ii, the deletion of nucleotides 165 to 434 of orjX in MREJ type xvi has never been described previously. The SCCmec right extremities of all other new MREJ types showed identities ranging from 38.2 to 59.5% with each other or with MREJ types i to ix. The substantial variation between the novel MREJ sequences and the previously described sequences, from which the prior detection assays were based, explains why the right extremities of the novel MREJ types xi to xx disclosed in the present invention could not have been predicted nor detected with MREJ primers previously described (US patent 6,156,507; International Patent Application PCT/CA02/00824; Ito et al., 2001, Antimicrob. Agents Chemother. 45:1323-1336; Huletsky et al., 2004, J Clin. Microbiol. 42:1875-1884; Ma et al, 2002, Antimicrob. Agents Chemother. 46:1147-1152; Ito et al, Antimicrob Agents Chemother. 2004. 48:2637-2651; Oliveira et al, 2001, Microb. Drug Resist. 7:349-360).

EXAMPLE 5: Selection of Amplification Primers from SCCmec/or/Y Sequences of

MRSA with MREJ types xi to xx [0093] Upon analysis of the 10 new MREJ types xi to xx sequence data described above, primers specific to each new MREJ type sequence were designed (Figure 2, Tables 9 and 11). Primers specific to MREJ type xi (SEQ ID NO.: 34), MREJ type xii (SEQ ID NO.: 35), MREJ types xiii and xiv (SEQ ID NO.: 29) (also detect MREJ type ix but each of MREJ types ix, xiii, and xiv has a different amplicon length), MREJ type xv (SEQ ID NO.: 24), MREJ type xvii (SEQ ID NO.: 4), MREJ type xviii (SEQ ID NO.: 7), MREJ type xix (SEQ ID NO.: 9), MREJ type xx (SEQ ID NO.: 8), were each used in combination with a primer specific to the 5¹. aureus orjX(SEQ ID NO.: 30) and tested against their specific MREJ target. For the detection of MREJ type xvi, a primer targeting MREJ types i, ii, and xvi (Table 10) was used in combination with a primer targeting the & aureus orjX (SEQ ID NO.: 44). MREJ types i, ii, and xvi can he distinguished from each other by their different amplicon length.

-322018206754 18Jul2018 [0094] Oligonucleotides primers found to amplify specifically DNA from the target MRSA MREJ types were subsequently tested for their ubiquity by PCR amplification (i.e. ubiquitous primers amplified efficiently most or all isolates of MRSA of the target MREJ type). The specificity and ubiquity of the PCR assays were tested either directly with bacterial cultures or with purified bacterial genomic DNA. The specificity of the primers targeting MREJ types xi to xx was also verified by testing DNA from MRSA strains harboring all other MREJ types.

[0095] 1 μΐ of a treated standardized bacterial suspension or of a genomic

DNA preparation purified from bacteria were amplified in a 20 μΐ PCR reaction mixture. Each PCR reaction contained 50 mM KC1, 10 mM Tris-HCl (pH 9.0), 0.1% Triton X100, 2.5 mM MgCl₂, 0.4 μΜ of each of MREJ type xi primer (SEQ ID NO.: 34), MREJ type xii primer (SEQ ID NO.: 35), MREJ types xiii and xiv primer (SEQ ID NO.: 29), MREJ type xv primer (SEQ ID NO.: 24), MREJ type xvi (SEQ ID NO.: 36), MREJ type xvii primer (SEQ ID NO.: 4), MREJ type xviii primer (SEQ ID NO.: 7), MREJ type xix primer (SEQ ID NO.: 9), or MREJ type xx primer (SEQ ID NO.: 8) which were each used in combination with 0.4 μΜ of a & aureus-specific primer (SEQ ID NO.: 30 or SEQ ID NO.: 44 for MREJ type xvi), 200 μΜ of each of the four dNTPs (Pharmacia Biotech, Piscataway, NJ), 3.3 μg/μl of BSA (SIGMA, St. Louis, MO), and 0.5 U Taq polymerase (Promega, Madison, WI) coupled with TbgStart™ Antibody (BD Biosciences, San Jose, CA).

[0096] PCR reactions were then subjected to thermal cycling: 3 min at 94°C followed by 40 cycles of 60 seconds at 95°C for the denaturation step, 60 seconds at 55°C for the annealing step, and 60 seconds at 72°C for the extension step, then followed by a terminal extension of 7 minutes at 72°C using a standard thermocycler (PTC-200 from MJ Research Inc., Watertown, MA). Detection of the PCR products was made by electrophoresis in agarose gels (1.2 %) containing 0.25 pg/ml of ethidium bromide.

[0097] Each of the MRSA strains harbouring a specific MREJ target was specifically detected with their specific MREJ primers and there was no cross-detection with non targeted MREJ types.

[0098] This invention has been described herein above, and it is readily apparent that modifications can be made thereto without departing from the spirit of this invention. These modifications are under the scope of this invention, as defined in the appended claims.

-33 2018206754 18Jul2018

Table 1. Reference Staphylococcus aureus strains used in the present invention

Strain number	Strain number	Strain number
collections (Type designation)
653 8b	BM10827(C)	54511 (Turku IE6)
13301b	3717 (EMRSA-GRlb)	54518 (Turku IIE7)
232351’	97S97 (Belgian epidemic clone la)	6,974 (Helsinki I El)
25923*’	359/96 (Berlin epidemic EMRSA IVc)	62176 (KotkaElO)
27660*’	792/96 (Berlin epidemic EMRSA IVd)	62305 (mecA- Tampere I El2)
29737*’	844/96 (Berlin epidemic EMRSA IVb)	62396 (Helsinki IIE2)
29213b	1966/97 (Hannover area EMRSA IIIc)	75541 (Tampere ΠΕ13)
29247b	2594-2/97 (S. German EMRSA lib)	75916 (Helsinki VE5)
33591	131/98 (S. German EMRSA II d2)	76167 (Kemi El7)
33592	406/98 (N. German EMRSA I cl)	98442 (Helsinki VI El 9)
33593	408/98 (N. German EMRSA I c2)	98514 (Helsinki VIIE20)
43300	872/98 (Hannover area EMRSA Illb)	98541 (LohjaE24)
BAA-38 (Archaic)0	1155-1/98 (S. German EMRSA II c)	M307 (EMRSA-3)
BAA-39 (Hungarian )“	1163/98 (S. German EMRSA II dl)	90/10685 (EMRSA-15)
BAA-40 (Portuguese)0	1869/98 (N. German EMRSA I d)	98/14719 (EMRSA-15/b4)
BAA-41 (New York)0	HS 2 (I)	96/32010 (EMRSA-16)
BAA-42 (Pediatric)0	AO 17934/97 (II)	99/579 (EMRSA-16/a3)
BAA-43 (Brazilian )°	98/10618 (EMRSA-15/b2)	5 (El)
BAA-44 (Iberian)0	98/26821 (EMRSA-15/b3) .	3680 (EMRSA-GR1)
41787 (Sa 501 V)°	98/24344 (EMRSA-15/b7)	3713 (EMRSA-GRla)
38266 (11)°	99/1139 (EMRSA-16/a2)	98S46 (Belgian epidemic clone 3b)
8325b	99/159 (EMRSA-16/al4)	97S96 (Belgian epidemic clone la)
11939 (EMRSA-1)0	6(D)	97S98 (Belgian epidemic clone lb)
	13 (A1)	97S99 (Belgian epidemic clone 2a)
ian epidemic MRSA (Type designation)1*	14 (A1)	97S100 (Belgian epidemic clone 2b)
A-l	18(A)	97S101 (Belgian epidemic clone 3a)
A-2	25 (P)	134/93 (N. German EMRSA I)
A-3	30 (G)	1000/93 (Hannover area EMRSA ΙΠ)
A-4	33(F)	1450/94 (N. German EMRSA la)
A-5	54(B)	825/96 (Berlin epidemic EMRSA IV)
A-6	60 (A)	842/96 (Berlin epidemic EMRSA IVs)
	80(E)	2594-1/97 (S. German EMRSA II a)
IONY collection of European epidemic MRSA	98 (C)	1155-2/98 (S. German EMRSA II)
designation)6
(B)	162(A)	1442/98 (Hannover area EMRSA Ilia)
(A)	920 (B)	N8-890/99 (Sa 543 VI)
(A)	95035 (A)	N8-3756/90 (Sa5441)
(B)	97121 (B)	9805-01937 (V)
(B)	BM10828 (C)	AK 541 (IV)
(B)	BM10882(C)	ON 408/99 (VII)
(A)	37481 (Seinajoki E 14)	AO 9973/97 (III)

-342018206754 18 Jul 2018 “ All S. aureus strains are resistant to methicillin except where otherwise indicated.

^b These S. aureus strains are sensitive to oxacillin (MSSA).

⁰ Informations on these strains and type designation based on pulse-field gel electrophoresis are from (6).

^d Information on these strains and type designation based on pulse-field gel electrophoresis are from (47).

^e Information on these'strains and type designation based on pulse-field gel electrophoresis are available at http://www.phls.co.uk/inter/harmony/menu.htm.

-352018206754 18 Jul

Table 2. Evaluation of the MRSA-specific primers targeting MREJ types i to x using DNA from a variety of methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains.

Staphylococcus aureus strains3 (number)	PCR results
Positive (%)	Negative (%)
MRSA (1657)	1640(99)	17(1)
MSSA (569)	26 (4.6)	543 (95.4)
a MRSA, methicillin-resistant	Staphylococcus aureus',	MSSA, methicillin-sensitive

Staphylococcus aureus. Reference S. aureus strains used are listed in Table 1. The origin of the 5. aureus clinical isolates is described in the text.

-362018206754 18 Jul 2018

Table 3. Origin of 17 MRSA strains not amplifiable using primers targeting MREJ types to x.

Staphylococcus aureus strain designation:
Original	CCRP	Origin
6-9637	CCRI-12157	Tempe, USA
15-3967	CCRI-12198	New York, USA
15-3972	CCRI-12199	New York, USA
91 2290	CCRI-12719	Australia
SSI 757	CCRI-11976	Houston, USA
255 D	CCRI-12382	Brazil
1061	CCRI-12383	Brazil
232 D	CCRI-12376	Brazil
6881	CCRI-12593	Spain
5109	CCRI-11999	Wilmington, USA
BK793	CCRI-9887	Cairo, Egypt
21 1 8424	CCRI-12845	Japan
SE46-1	CCRI-9772	Toronto, Canada
1059	CCRI-12524	Italy
1016	CCRI-12535	Italy
816867	CCRI-12905	Rennes, France
20 1 6060	CCRI-12810	Taiwan, China

^a CCRI stands for Collection of the Centre de Recherche en Infectiologie.

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Table 8: Novel Staphylococcus aureus MREJ^a nucleotide sequences

SEQ ID	5. aureus strain designation Original	CCRI0	Sequence3,0
15	SS1757	CCRI-11976	MREJ type xiii
16	5109	CCRI-11999	MREJ type xiv
17	6-9637	CCRI-12157	MREJ type xi
18	15-3967	CCRI-12198	MREJ type xi
19	15-3962	CCRI-12199	MREJ type xi
20	91 2290	CCRI-12719	MREJ type xii
21	21 1 8424	CCRI-12845	MREJ type xvi
25	255 D	CCRI-12382	MREJ type xiii
26	1061	CCRI-12383	MREJ type xiii
39	1059	CCRI-12524	MREJ type xviii
40	1016	CCRI-12535	MREJ type xviii
41	20 1 6060	CCRI-12810	MREJ type xix
42	816867	CCRI-12095	MREJ type xx
55	SE46-1	CCRI-9772	MREJ type xvii
56	BK793	CCRI-9887	MREJ type xv

^a MREJ refers to mec right extremity junction and includes sequences from the SCCmec right extremity and chromosomal DNA to the right of the SCCmec integration site.

^b Sequence refers to the target gene ^c CCRI stands for Collection for the Centre de Recherche en Infectiologie

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Table 9. Novel PCR amplification primers developed to detect MREJ types xi - xx

Originating target DNA MREJ type	Originating target DNA SEQ ID NO	Oligo Position3	Oligo SEQ ID NO
MREJ type xvii	55	954b	4
MREJ type xviii	40	1080	7
MREJ type xx	42	987b	8
MREJ type xix	41	581b	9
MREJ type xv	38	624	23
MREJ type xv	56	566b	24
MREJ type ix, xiii, xiv	15	756b	28
MREJ type xi	17	615b	34
MREJ type xii	20	612b	35
MREJ type xv	56	457	48
MREJ type xv	56	564b	49
MREJ type xi	17	956b	51
MREJ type xii	20	1053b	52
MREJ type xvii	55	415	57
MREJ type xvii	55	558	58

^a Position refers to nucleotide position of 5' end of primer ^b Primer is reverse-complement of target sequence

-392018206754 18 Jul 2018

Originating DNA

Table 10. Other amplification and/or sequencing primers and probes found in the sequence listing

>EQ ID	Position3	SEQ
40	Source	Target
27	Oliveira and de Lencastre, 2002, Antimicrob. Agents Chemother.	SCCnrec
29	46:2155-2161 SEQ ID NO.: 109b	MREJ types ix, xiii, and	652°	29
30	SEQ ID NO.: 64b	xiv or/%	325	18
31	SEQ ID NO.: 84b	or/A	346c	18
32	SEQ ID NO.: 163b	or/T	346c	20
33	SEQ ID NO.: 164b		-	-
36	SEQIDNO.:66b	MREJ types i, ii, and xvi	574c	21
43	SEQ ID NO.: 159b	orjX	367c	18
44	SEQ ID NO.: 132b	orjX	98	38 -
45	SEQIDNO.:70b	orjX	401	18
50	SEQ ID NO.: 69b	mecA	6945c	22
53	Oliveira and de Lencastre, 2002, Antimicrob. Agents Chemother.	SCCmec	.
54	46:2155-2161 SEQ ID NO.: 56b	MREJ types i and ii		-
60 61 62	SEQ ID NO.: 152d SEQ ID NO.: 153d This patent	putative membrane protein putative membrane protein orjX	193	20
63	SEQ ID NO.: 81b	mecA	6798	22
65	SEQ ID NO.: 204b	MREJ type vi	642c	191b
66	SEQ ID NO.: 115b	MREJ types ii, viii, ix,	514	167b

-402018206754 18 Jul 2018

73	This patent	xiii, xiv MREJ type x	1913c	69
74	SEQ ID NO.: 112b	MREJ type vii	503	189'
75	SEQ ID NO.: 116b	MREJ type viii	601	167'
76	This patent	orfX	193	17
77	This patent	orf22 (MREJ type x)	3257	69
78	This patent	SCCmec	22015	88
79	This patent	SCCmec	22100	88
80	This patent	SCCmec	21296	88
81	This patent	SCCmec	21401	88
82	This patent	SCCmec	22713	88
83	This patent	SCCmec	2062	87
84	This patent	SCCmec	1280	87
85	This patent	SCCmec	1364	87
86	This patent	SCC/wec	718	87

^a Position refers to nucleotide position of the 5’ end of primer (on the target sequence). ^b SEQ ID NOs from International Patent Application PCT/CA02/00824. ^c Primer is reverse-complement of target sequence.

^d SEQ ID NOs from WO96/08582.

-41 2018206754 18Jul2018

Table XI. Length of amplicons obtained with primer pairs for MREJ types xi - xx

Oligo Pair (SEQ ID NO)	Target DNA	Amplicon length3
24/30	MREJ type xv	265
24/44	MREJ type xv	603
24/45	MREJ type xv	189
24/62	MREJ type xv	397
28/30	MREJ type xiii, xiv	464 (type xiii); 668 (type xiv)
28/44	MREJ type xiii, xiv	802b(type xiii); 1006b (type xiv)
28/45	MREJ type xiii, xiv	388 (type xiii); 592 (type xiv)
28/76	MREJ type xiii	596 (type xiii)
29/30	MREJ type xiii, xiv	267 (type xiii); 471 (type xiv)
29/44	MREJ type xiii, xiv	605b (type xiii); 809b (type xiv)
29/45	MREJ type xiii, xiv	191 (type xiii); 395 (type xiv)
29/59	MREJ type xiv	605
29/76	MREJ type xiii	399
34/30	MREJ type xi	328
34/44	MREJ type xi	661b
34/45	MREJ type xi	247
34/76	MREJ type xi	455
35/30	MREJ type xii	311
35/44	MREJ type xii	649b
35/45	MREJ type xii	235
35/62	MREJ type xii	443
36/44	MREJ type xvi	348b
4/30	MREJ type xvii	690
4/44	MREJ type xvii	968b
4/45	MREJ type xvii	614
4/62	MREJ type xvii	822
7/30	MREJ type xviii	780b
7/44	MREJ type xviii	1119b
7/45	MREJ type xviii	704
7/59	MREJ type xviii	912b
8/30	MREJ type xx	1076b
8/44	MREJ type xx	1415b
8/45	MREJ type xx	1000
8/59	MREJ type xx	1208b
9/30	MREJ type xix	657b
9/44	MREJ type xix	996b
9/45	MREJ type xix	581
9/59	MREJ type xix	789b

^a Amplicon length is given in base pairs for MREJ types amplified by the set of primers ^b Amplicon length is based on analysis by agarose gel electrophoresis

-422018206754 18 Jul 2018

Table 12. Percentage of sequence identity for the first 500 nucleotides of SCCmec right extremities between 19 types of MREJ^a,b

	i	iid	iii	iv	V	vic	vii	viii	ix'
i		100	44,4	39,1	40,4	42,9	43,2	41,5	42,4
iia	-	-	44,4	39,1	40,4	42, 9	43,2	41,5	42,4
iii	-	-	-	40,1	45, 8	45,0	44,4	42,3	49, 9
iv	-	-	-	-	45,2	40,3	41,6	42,1	42,7
V	-	-	-	-	-	45,0	41,3	46,5	43,8
vic	-	-	-	-	-	-	45,1	40,8	43,2
vii	-	-	-	-	-			42,8	44,8
viii	-	-	-	-			-		41,1
ixf	-			-
xi	.			-
xii	-	-	-		-		-	-	-
xiii	-	-
xiv®	-	-	-	-					-
XV		-		-			-
xvi	-			-	-	-	-		.
xvii	-	-							-
xviii	-	-				-		-	-
xix	-	-		-	-	-	-	-	-
XX

xi	xii	xiii	xiv®	XV	xvi	xvii	xviii	xix	XX
41,1	40,2	42,4	42,4	42,1	100	42,1	44,1	42,5	40,4
41,1	40,2	42,4	42,4	42,1	100	42,1	44,1	42,5	40,4
45,7	44,9	49,9	49,9	48,8	44,2	43,1	46,7	43,5	45,3
42,7	38,2	42,7	42,7	39,0	42,1	39,6	40,3	37,2	41,4
41,2	43,6	43,8	43,8	41,7	43,3	42,3	49,8	43,3	39,8
43,8	42,0	43,2	43,2	44,2	42,9	39,4	43,4	42,2	45,8
42,7	42,0	44,8	44,8	46,7	42,5	43,2	44,7	41, 1	41, 9
41,1	41, 9	41,1	41,1	37,6	52,2	40,9	41,2	42,4	39,1
46,0	42,5	100	100	43,4	44,1	40, 9	45,0	40,6	42,9
-	48,0	46,0	46,0	45, 9	43,2	40,5	47, 1	41, 8	43,6
-	-	42,5	42,5	47,6	39,2	43,3	43,7	44,7	45,6
-	-	-	100	43,4	44,1	40,9	45, 0	40,6	42, 9
-	-	-	-	43,4	44,1	40,9	45,0	40,6	42,9
-	-	-	-	-	43,6	41, 5	47,5	42,5	43,8
-	-	-	-	-	-	41,9	45,4	45,1	45,7
-	-	-	-	-	-	-	40,0	43,3	42,5
-	-	-	-	-	-	-	-	43,4	45,7
-		.	-		-	-	-		45,5

^a First 500 nucleotides refers to the 500 nucleotides within the SCCmec right extremity, starting from the integration site of SCCmec in the Staphylococcus aureus chromosome as shown on Figure 3.

^b Sequences were extracted from International patent application PCT/CA02/00824 (SEQ ID NOs.: 1, 2, 232, 46, 50, 171, 166, 167 and 168 for types i to ix, respectively). MREJ type x was excluded from the sequence comparison because it is deleted from the completed orfX, the integration site, and part of the SCCmec right extremity. Sequences for types xi to xx were extracted from SEQ ID NOs.: 18, 20, 25,16, 56,21, 55,39,41 and 42, respectively.

^c Sequence from the SCCmec right extremity of MREJ type vi is limited to 371 nucleotides.

^d The first 102 nucleotides from the SCCmec right extremity of MREJ type ii were excluded from the sequence comparison.

“ The first 206 nucleotides from the SCCmec right extremity of MREJ type xiv were excluded from the sequence comparison.

^f The first 102 nucleotides from the SCCmec right extremity of MREJ type ix were excluded from the sequence comparison.

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Claims (54)

1. WHAT IS CLAIMED IS:

   1. A method of detecting the presence of a methicillin-resistant Staphylococcus aureus (MRSA) strain in a sample comprising nucleic acids, wherein the MRSA strain comprises an SCCznec insert comprising a meek gene inserted in bacterial nucleic acids, and wherein the insertion of said SSC/wec insert in the bacterial nucleic acids generates a polymorphic right extremity junction (MREJ), said method comprising:

   providing at least one primer and/or probe that is specific for MRSA strains, wherein the primer and/or probe anneals to at least one polymorphic MREJ nucleic acid of types xi to xx;

   annealing the nucleic acids of the sample with the primer(s) and/or probe(s), wherein annealed primer(s) and/or probe(s) indicate the presence of an MRSA strain in the sample; and detecting the presence and/or amount of annealed probe(s), or detecting the amount of an amplification product produced through annealing of the primers to the nucleic acids, as an indication of the presence and/or amount of MRSA.
2. 2. The method of Claim 1, wherein the providing step further comprises providing a plurality of primers and/or probes that can anneal with at least one MREJ type selected from MREJ type xi, xii, xiii, xiv, xv, xvi, xvii, xviii, xix, and xx.
3. 3. The method of Claim 2, further comprising a DNA amplification step, wherein the DNA amplification is PCR, LCR, NABSA, 3SR, SDA, bDNA, TMA, CPT, SPA, NDSA, rolling circle amplification, anchored strand displacement amplification, solid phase (immobilized) rolling circle amplification, or Q beta replicase amplification.
4. 4. The method of Claim 2, wherein the plurality of primers and/or probes can anneal with at least four MREJ types selected from MREJ type xi, xii, xiii, xiv, xv, xvi, xvii, xviii, xix, and xx.
5. 5. The method of Claim 2, wherein the primers and/or probes anneal under common annealing conditions.
6. 6. The method of Claim 5, wherein the primer and/or probes are provided in the same physical enclosure.
7. 7. The method of Claim 1, wherein the primers and/or probes are at least 10, 12, 14, 16, 18, 20, 25, or 30 nucleotides in length.

   -442018206754 18Jul2018
8. 8. The method of Claim 1, wherein the primers and/or probes are capable of annealing to at least one of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56.
9. 9. The method of Claim 2, wherein at least one primer and/or probe of the plurality of primers and/or probes is capable of annealing to each of SEQ ID NOs: 15, 16, 17, 18, 19, 20, 21, 25, 26, 39, 40, 41, 42, 55, and 56.
10. 10. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 51, 30, 31, 32, and 33 for the detection of MREJ type xi.
11. 11. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 52, 30, 31, 32, and 33, for the detection of MREJ type xii.
12. 12. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 29, 30, 31, 32, and 33 for the detection of MREJ type xiii.
13. 13. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 29, 30, 31, 32, and 33 for the detection of MREJ type xiv.
14. 14. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 24, 30, 31, 32, and 33 for the detection of MREJ type xv.
15. 15. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 36 and 44 for the detection of MREJ type xvi.
16. 16. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 4, 30, 31, 32, and 33 for the detection of MREJ type xvii.
17. 17. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 7, 30, 31, 32, and 33 for the detection of MREJ type xviii.
18. 18. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 9, 30, 31, 32, and 33 for the detection of MREJ type xix. '
19. 19. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 8, 30, 31, 32, and 33 for the detection of MREJ type xx.
20. 20. The method of Claim 2, wherein the plurality of primers and/or probes comprises SEQ ID NOs: 51, 30, 31, 32, and 33 for the detection of MREJ type xi,

    SEQ ID NOs: 52, 30, 31, 32, and 33 for the detection of MREJ type xii,

    SEQ ID NOs: 29, 30, 31, 32, and 33 for the detection of MREJ type xiii SEQ ID NOs: 29, 30, 31, 32, and 33 for the detection of MREJ type xiv,

    -452018206754 18Jul2018

    SEQ ID NOs: 24, 30, 31, 32, and 33 for the detection of MREJ type xv SEQ ID NOs: 36 and 44 for the detection of MREJ type xvi,

    SEQ ID NOs: 4, 30, 31, 32, and 33 for the detection of MREJ type xvii,

    SEQ ID NOs: 7, 30, 31, 32, and 33 for the detection of MREJ type xviii,

    SEQ ID NOs: 9, 30, 31, 32, and 33 for the detection of MREJ type xix, and

    SEQ ID NOs: 8, 30, 31, 32, and 33 for the detection of MREJ type xx.
21. 21. The method of Claim 10, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 34, 44, 45, and 76 for the detection of MREJ type xi.
22. 22. The method of Claim 11, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 34, 44, 45, 52, and 62 for the detection of MREJ type xii.
23. 23. The method of Claim 12, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 33, 44, 45, and 76, for the detection of MREJ type xiii.
24. 24. The method of Claim 13, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 44, 45, and 59 for the detection of MREJ type xiv.
25. 25. The method of Claim 14, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 4, 45, and 62 for the detection of MREJ type xv.
26. 26. The method of Claim 16, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 44, 45, and 62 for the detection of MREJ type xvii.
27. 27. The method of Claim 17, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 44, 45, and 59 for the detection of MREJ type xviii.
28. 28. The method of Claim 18, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 44, 45, and 59 for the detection of MREJ type xix.

    -462018206754 18 Jul 2018
29. 29. The method of Claim 19, wherein the plurality of primers and/or probes further comprises the primers and/or probes of SEQ ID NOs: 44, 45, and 59 for the detection of MREJ type xx.
30. 30. The method of Claim 20, further comprising the primers and/or probes of SEQ ID NOs: 34, 35, 44, 45, 52, 59, 62, 76.
31. 31. The method of claim 21, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs : 34/45, 34/30, 34/76, and 34/44, for the detection of MREJ type xi.
32. 32. The method of claim 22, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs : 35/45, 35/30, 35/62, and 35/44, for the detection of MREJ type xii.
33. 33. The method of claim 23, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 29/45, 29/30, 29/76, and 29/44, for the detection of MREJ type xiii.
34. 34. The method of claim 24, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 29/45, 29/30, 29/59, and 29/44, for the detection of MREJ type xiv.
35. 35. The method of claim 25, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 24/45, 24/30, 24/62, and 24/44, for the detection of MREJ type xv.
36. 36. The method of claim 26, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 4/45, 4/30, 4/62, and 4/44 for the detection of MREJ type xvii.
37. 37. The method of claim 27, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 7/45, 7/30, 7/59, and 7/44 for the detection of MREJ type xviii.
38. 38. The method of Claim 28, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    -472018206754 18Jul2018

    SEQ ID NOs: 9/45, 9/30, 9/59, and 9/44 for the detection of MREJ type xix.
39. 39. The method of claim 29, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 8/45, 8/30, 8/59, and 8/44 for the detection of MREJ type xx.
40. 40. The method of claim 30, wherein the primers are provided in pairs, wherein the primer pair is selected from the group consisting of:

    SEQ ID NOs: 34/45, 34/30, 34/76, and 34/44 for the detection of MREJ type xi; SEQ ID NOs: 35/45, 35/30, 35/62, and 35/44 for the detection of MREJ type xii; SEQ ID NOs: 29/45, 29/30, 29/76, and 29/44 for the detection of MREJ type xiii; SEQ ID NOs: 29/45, 29/30, 29/59, and 29/44 for the detection of MREJ type xiv; SEQ ID NOs: 24/45, 24/30, 24/62, and 24/44 for the detection of MREJ type xv' SEQ ID NOs: 36/44 for the detection of MREJ type xvi;

    SEQ ID NOs: 4/45, 4/30, 4/62, and 4/44 for the detection of MREJ type xvii;

    SEQ ID NOs: 7/45, 7/30, 7/59, and 7/44 for the detection of MREJ type xviii;

    SEQ ID NOs: 9/45, 9/30, 9/59, and 9/44 for the detection of MREJ type xix; and

    SEQ ID NOs: 8/45, 8/30, 8/59, and 8/44 for the detection of MREJ type xx.
41. 41. The method of claim 40, further comprising probes having the following sequences:

    SEQ ID NOs: 30,31, and 32 for the detection of MREJ types to xi to xx.
42. 42. The method of Claim 40, wherein said probes and primers are used together.
43. 43. The method of Claim 42, wherein said probes and/or primers are used together in the same physical enclosure.
44. 44. The method of Claim 1, further comprising detecting an annealed probe and/or primer as an indication of the presence of a determined MREJ type from type xi to xx.
45. 45. The method of Claim 44, wherein the method of detection is selected from the group comprising: agarose gel electrophoresis, fluorescence resonance energy transfer, TaqMan probe, molecular beacon probe, Scorpion probe, nanoparticle probe, Ampliflour probe, chemiluminscense, potentiometry, mass spectrometry, plasmon resonance, polarimetry, colorimetry, flow cytometry, scanometry, and DNA sequencing.
46. 46. A nucleic acid selected from the group consisting of:

    SEQ ID NOs: 17, 18, 19 (MREJ type xi);

    -482018206754 18 Jul 2018

    SEQ ID NO: 20 (MREJ type xii);

    SEQ ID NOs: 15, 25,26 (MREJ type xiii);

    SEQ ID NO: 16 (MREJ type xiv);

    SEQ ID NO: 56 (MREJ type xv);

    SEQ ID NO: 21 (MREJ type xvi);

    SEQ ID NO: 55 (MREJ type xvii);

    SEQ ID NOs: 39, 40 (MREJ type xviii);

    SEQ ID NO: 41 (MREJ type xix); and

    SEQ ID NO: 42 (MREJ type xx), or the complement thereof.
47. 47. An oligonucleotide of at least 10 nucleotides in length which hybridizes under stringent conditions with a nucleic acid of Claim 46.
48. 48. An oligonucleotide pair selected from the group consisting of: oligonucleotides comprising the sequences of SEQ ID NOs: 34/45, 34/30, 34/76, and 34/44, for the detection of MREJ type xi, oligonucleotides comprising the sequences of SEQ ID NOs: 35/45, 35/30, 35/62, and 35/44 for the detection of MREJ type xii, oligonucleotides comprising the sequences of SEQ ID NOs: 29/45, 29/30, 29/76, and 29/44 for the detection of MREJ type xiii, oligonucleotides comprising the sequences of SEQ ID NOs: 29/45, 29/30, 29/59, and 29/44 for the detection of MREJ type xiv, oligonucleotides comprising the sequences of SEQ ID NOs: 24/45, 24/30, 24/62, and 24/44 for the detection of MREJ type xv, oligonucleotides comprising the sequences of SEQ ID NOs: 36/44 for the detection of MREJ type xvi, oligonucleotides comprising the sequences of SEQ ID NOs: 4/45, 4/30, 4/62, and 4/44 for the detection of MREJ type xvii, oligonucleotides comprising the sequences of SEQ ID NOs: 7/45, 7/30, 7/59, and 7/44 for the detection of MREJ type xviii, oligonucleotides comprising the sequences of SEQ ID NOs: 9/45, 9/30, 9/59, and 9/44 for the detection of MREJ type xix, and

    -492018206754 18Jul2018 oligonucleotides comprising the sequences of SEQ ID NOs: 8/45, 8/30, 8/59, and

    8/44 for the detection of MREJ type xx.
49. 49. An oligonucleotide comprising the sequence of SEQ ID NO: 31, 32, or 33.
50. 50. A kit comprising a plurality of primers and/or probes, wherein the primers and/or probes are at least 10, 12, 14, 16, 18, 20, 25, or 30 nucleotides in length, and wherein the primers and/or probes hybridize under stringent conditions to at least one of the nucleic acids of Claim 46, and wherein the plurality of primers and/or probes hybridizes with at least one MREJ of types selected from xi to xx.
51. 51. The kit of Claim 50, further comprising primers and/or probes, which hybridize with one or more MREJ of types selected from i to x.
52. 52. The kit of Claim 51, further comprising primer pairs, wherein the primer pairs comprise the nucleotide sequences of SEQ ID NOs:

    30/36 for the detection of MREJ type i;

    30/36 for the detection of MREJ type ii;

    30/70 for the detection of MREJ type iii;

    30/71 for the detection of MREJ type iv;

    30/72 for the detection of MREJ type v;

    30/65 for the detection of MREJ type vi;

    30/74 for the detection of MREJ type vii;

    30/75 for the detection of MREJ type viii;

    30/29 for the detection of MREJ type ix;

    73/77 for the detection of MREJ type x;

    34/45, 34/30, 34/76, 34/44 for the detection of MREJ type xi;

    35/45, 35/30, 35/62, 35/44 for the detection of MREJ type xii;

    29/45,29/30, 29/76, 29/44 for the detection of MREJ type xiii;

    29/45, 29/30, 29/59, 29/44 for the detection of MREJ type xiv;

    24/45, 24/30, 24/62, 24/44 for the detection of MREJ type xv ;

    36/44 for the detection of MREJ type xvi;

    4/45, 4/30, 4/62,4/44 for the detection of MREJ type xvii;

    7/45, 7/30, 7/59, 7/44 for the detection of MREJ type xviii;

    9/45, 9/30, 9/59, 9/44 for the detection of MREJ type xix; and

    -502018206754 18 Jul 2018

    8/45, 8/30, 8/59, 8/44 for the detection of MREJ type xx.
53. 53. The kit of Claim 51, further comprising probes, wherein the probes comprise the nucleic acid sequence of SEQ ID NOs: 31, 32, 33.

    -51 1/7

    2018206754 18 Jul 2018

    Figure 1.

    Junction

    MREJ Types xiii and xiv mecA

    45 43 44

    MREJ Type xi mecA orfX orfX

    45 43 44 mecA MREJ Type xii orfX

    50 52 45 43 44 mecA MREJ Type xvii orfX

    50 4 57 45 44

    2/7

    2018206754 18 Jul2018

    Junction

    Figure 1 (continued).

    2993644

    100506 mecA MREJ Type XV

    50 83 85 84

    86 24 44

    MREJ Type xvi orfX
54. 54 44

    MREJ Types xviii, xix,

    XX orfX

    30 44 —►—► walkwalk

    3/7

    2018206754 18 Jul 2018

    MREJ Type xiii (IS, 25, 26)

    MREJ Type ix (IS, 25, 26)

    MREJ Type xiv (IS, 25, 26)

    MREJ Type xi (17, 18, 19)

    MREJ Type xii (20)

    MREJ Type xv (56)

    100 pb

    Figure 2,

    Junction

    SCCmec | _orfx

    29 45 | 30 76 44

    31, 32, 33 | 30

    45 + 30 59 44

    31, 32 , 33

    OF tr

    45 (. 30 59 44

    31, 32 ,33

    45 a 30 76 44

    31, 32, 33

    A 30

    I I II· '1 .

    32, 33

    32,

    4/7

    2018206754 18 Jul 2018

    MREJ Type xvi (21)

    Junction

    SCCmec orfX

    deletion

    MREJ Type xvii (55)

    31,32, 33

    MREJ Type xviii (39, 40)

    45 | 30 59 44 ' ¹ 31 _r 32 or 33

    MREJ Type xix (41)

    100 bp

    5¾¾¾¾¾¾¾¾¾¾

    MREJ Type xx (42)

    31, 32 or 33

    Figure 2 (continued).

    5/7

    2018206754 18Jul 2018.

    Γϋ (1)

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    -Η

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    0 0 0 0 0 0 0 0 0 0 0 0

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    0 0 0 0 0 0 0 0 0 0 0 0 «J rtj >Jj s£ rtj < < Ρζ ρζ r$ ρζ raj

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    000000000000 pC pC PC kC pfi pC < ffi PC fiC r£ ρζ

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    0 0 0 0 0 0 0 0 0 0 0 0 pC pC pC rf rC pC pC kC rt pC pi pC p£ pc PC tf, «2 ρζ ja! rf, ρξ ft, 5; rij

    0 0 0 0 0 0 0 0 0 O 0 0

    B B B B B B B B B Eh Eh B

    B B b B B b B B B B B B rfFCKCBCpCpCpCjiCiiCKCrfri: PC PC PC PC *C FE PC KG PC PC PC PC

    0 0 0 0 0 0 0 0 0 0 0 0 ρζ < < *ί < ρζ ρζ Ρζ PC PC pC pC ssssdessssss 0 0 0 0 0 0 0 0 0 0 0 0

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    0 0 0 0 . -0 0 0 0 0 0 0 0

    000000000000 BBBBBBBBBBBB BBBBBBBBBBBB < pC pC . *£ *C -pC - pC #i pC pC < pC

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0 000000000000 gggggggggggg

    000000000000 pCkC-pCkC<pCpCpCkCpC<pC

    000O000000O0 «ζκξρζρζρζρζρζκζρζ^ρζρζ BBBBBBBBBBBB BBBBBBBBBBBB pC pC pC < fC < :FC < <=C PC pC pC 000000000000 pCpCkCpCpCpCpCfCfC-pCpCpC BBBBBBBBBBBB BBBBBBBBBBBB pCpCkCkCpCpCpCfCpCpCkCpC 000000000000 BBBBBBBBBBBB 000000000000 pC < pc < ρζ pC pC < *aj sc < pC

    0 0 0 0 0 0 0 0 0 .0 ο ο pC pC PC pfi pC pC pC pC fC_ fC .< pC

    0 0 O EMO O EMO EMO 0 0 0 0 0 0 0 0 0 0 0 0 0 0

    B B B B B B B B B B B B pC .pC pC pE . pC pC f£ pC pC -PC pC .PC pC -PC pc pC PC pC «C PC PC PC pC PC

    000000000000 < Ρζ PC «* ρζ pC: fC ρζ pC pC pC

    000000000000 000000000000 111 llllllill

    B B B B B B B B B B B B

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0

    FCFCFirCKCpSFCpCFCFiBCFC BBBBBBBBBBBB 0 0 0 0 0 0 0 0 0 0 0 0 pCpCpiRCrfJpCpCpCrilPCpCrt pC pC pC pC pC rf rf pC pC Ρζ pC pC pC <3 >3 fiC PC PC PC f£ PC PC PC

    00000000 0 0 0 0 0000000 U 00 0 0

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0

    0 0 0 0 0 0 0 0 0 0 0 0 ρζρζρΐίΪΡζΡίΡίρίΛίΡΕτϊρΐ; PC PC PC PC PC PC fX PC PC PC «C PC

    0 0 0 g 0,

    0 <3 0 0 0

    B E-ι Eh B B B B Fh Eh B B B rrinimmOmO ίϊίΙΓίϊΐϊίίίϊΓΠϊϊϊ ίϊΠϊΠΐΐίϊϊϊϊΐϊίίϊ

    6/7

    2018206754 18 Jul 2018

    -,-/7,77,4-,-,//-,4¾¾¾¾¾

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    -,-,7,4/44-, >, /7/474/7, •ι-ι ·|—t ·η ·η ό ·η ·π ·γί ·ι~> ·π ·η ·η ·γ—> ·ι—ι ·γί ·η ·π ·η ·η

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    2018206754 18 Jul 2018 ! ·η ·η ·γ~ι ·π ·.

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    2018206754 18 Jul 2018

    GENOM.O57CPl.TXT SEQUENCE LISTING <110> Huletsky, Ann

    Giroux, Richard <120> SEQUENCES FOR DETECTION AND

    IDENTIFICATION OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) OF MREJ TYPES xi to XX <130> GENOM.O57QPC <150> 11/248,438 <151> 2005-11-11 <160> 88 <170> FastSEQ for windows Version 4.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 1 gcaggaacaa acagatgaag a 21 <210> 2 <211> 19 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 2 tcggctctac cctcaacaa 19 <210> 3 <211> 19 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 3 tcgcagggat ggtattgaa 19 <210> 4 <211> 19 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 4 caccctgcaa gatatgttt 19 <210> 5 <211> 25 <212> DNA <213> Artificial Sequence

    Page 1

    GENOM.O57CPl.TXT

    2018206754 18 Jul 2018

    <220> <223> synthetically prepared nucleic acid sequence <400> 5 . ttcgttgaaa gaagagaaaa ttaaa <210> 6 <2U> 27 <212> DNA <213> Artificial sequence <220> <223> synthetically prepared nucleic acid sequence <400> 6 gctttttttt ctttattatc aagtatc <210> 7 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 7 aatggaattt gttaatttca taaat <210> 8 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> synthetically prepared nucleic acid sequence <400> 8 ttccgaagtc ataatcaatc aaatt <210> 9 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> synthetically prepared nucleic acid sequence <400> 9 ttccgaagct aattctgtta ata <210> 10 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 10 aggcgttaaa aatcctgata ctg <210> 11 <211> 22 <212> DNA <213> Artificial Sequence

    Page 2

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <220>

    <223> synthetically prepared nucleic acid sequence <400> 11 aagccaattc aatttgtaat gc 22 <210> 12 <211> 22 <212> DNA <213> Artificial sequence <22O>

    <223> Synthetically prepared nucleic acid sequence <400> 12 aacccctcct ctgtaattag tg 22 <210> 13 <211> 21 <212> DNA <213> Artificial sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 13 agcggtggag tgcaaataga t 21 <210> 14 <211> 23 <212> DNA <213> Artificial sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 14 ttgctggaca tcaacagtat cat 23 <210> 15 <211> 4149 <212> DNA <213> Staphylococcus aureus <400> 15 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa ttaaaccaca atccacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgag 420 caagtgtata gagcatttaa gattatgcgt ggagaagcat atcataagtg atgcggtttt 480 tattaattag ttgctaaaaa atgaagtatg caatattaat tattattaaa ttttgatata 540 tttaaagaaa gattaagttt agggtgaatg aatggcttat caaagtgaat atgcattaga 600 aaatgaagta cttcaacaac ttgaggaatt gaactatgaa agagtaaata tacataatat 660 taaattagaa attaatgaat atctcaaaga actaggagtg ttgaaaaatg aataagcaga 720 caaatactcc agaactaaga tttccagagt ttgatgagga atggaaaaaa aggaaattag 780 gtgaagtagt aaattataaa aatggtggtt catttgaaag tttagtgaaa aaccatggtg 840 tatataaact cataactctt aaatctgtta atacagaagg aaagttgtgt aattctggaa 900 aatatatcga tgataaatgt gttgaaacat tgtgtaatga tactttagta atgatactga 960 gcgagcaagc accaggacta gttggaatga ctgcaattat acctaataat aatgagtatg 1020 tactaaatca acgagtagca gcactagtgc ctaaacaatt tatagatagt caatttctat 1080 ctaagttaat taatagaaac cagaaatatt tcagtgtgag atctgctgga acaaaagtga 1140 aaaatatttc taaaggacat gtagaaaact ttaatttttt atctcctaat tacactgaac 1200 aacaaaaaat aggtaatttc ttcagcaaac tcgaccgcca gattgagtta gaagaagaga 1260 aacttgaact cttagagcaa caaaagcgtg gatatattca gaagattttt tctcaagatt 1320

    Page 3

    2018206754 18 Jul2018

    GENOM.057CPl.TXT taagatttaa agatgaaaat ggaaacagtt atcctgattg gtctattaaa aagattgaag 1380 atatttctaa agttaataaa gggtttactc caaatacaaa aaatgataaa tactgggatg 1440 aattaaatga aaattggtta tctatagcag gtatgacaca gaaatatttg tataaaggaa 1500 ataaaggaat tactgaaaaa ggtgcatcaa agcatgtaaa agtagataaa gatactctaa 1560 taatgagttt taaattgact ttaggtaagt tagctatagt aaaagagcct atctatacaa 1620 atgaagctat atgccatttc gtatggaaag aaagtaatgt taatactgag tatatgtact 1680 actatttaaa ttctataaat ataagtactt ttggtgcaca ggcagttaaa ggagtaacat 1740 taaataacga tgcaattaat agtattatag taaagttacc agtgatacaa gaacaaaata 1800 aaatagcata ctttttcaat aaattagata aattaattga aaaacaatct tctaaagtag 1860 aattattaaa acaacgcaaa caaggatttt tacagaaaat gtttgtttaa ttcttataaa 1920 gttctattat gtaaaatatt aaatagagat aacattatga aagcgagccc aagacataaa 1980 gtttttgaat aaataaaaaa gataatttct atcaaattaa tatagaaatt gtctttttta 2040 taaatttttt gattattttt agctgattga gctgttactt ttcttataat aagtgctatt 2100 agcacaaatc ctagttctct tttggctttg tttattcctc ttacggacat tcgagtgaaa 2160 cccattttaa ttttattaga agtaatttag gtttgaaccc acctaaataa atatatgagt 2220 tattttttta tgctacaaaa tatattcaga tttcaataat gacataaaat aggcatcttt 2280 atatttacct ttagtgtaga attgctcttt gagtaatcct tctgttttaa atccttgtga 2340 ctcgtatata tgcacagctt ttttgttatc tgtatcaaca tatagataaa ttttgtgcat 2400 gtttaatata tcgaatgcat aatttatcgc tttttcgaat gcgaattttg cataaccttt 2460 accactgaac tcaggtttaa taattatttg tatttcacaa ttacgatgga tgtaattaat 2520 ttctactaat tcaacaatac ctacgacttg attttcatct tcaacaataa aacgtctctc 2580 tgattcatct aataaatgct tatcaaataa atattgaagt tccgttaagg attcatatgg 2640 ttcttcaaac caataagaca taatagaata ttcattattt aattcatgaa caaaaagtaa 2700 atcactatac tctaatgctc ttagtttcat aattccactc ccaaaatttt ctcatatatt 2760 tgcattataa atataaataa cgaataagtc atcattcact gtgaatactc tattttaaca 2820 attcaccaca tactaattct cattttcttg ttattctcga tttattactc ttactatgaa 2880 acctataaaa ttctcacatt tgtttgtatt aagaataaat acgtcgatag taacaataaa 2940 aaaataaata ataaagcatc cctcaccgta aaagtgaagg atgctctagt tttattgaaa 3000 tatacatttc attttgttaa ataattatta ataatatttt gaaaatcatt attacgtgaa 3060 atcttcatag attttatcaa gtatttcttt gccttcaatt gctgtgaagt gatgtaccaa 3120 tctattttta caatcatatg taattttgtg acgctaggta attagtaatt gttcgtcagt 3180 ctgattgtat agtatcaagt ttcatagata atactctttg attttaatgt ccactttgac 3240 gtgctttaag attgagtata tacataatgt cattgtggaa tgttaaaaat cctacaaatg 3300 tttattcatc tgcaggattt ttaaatctcc aagaataaaa atcatcatag gacaactgga 3360 ttattgtttg gataaataac gtaaacaata attaggtact attatttatt tttgtttatt 3420 ctttttccta acaaaataaa gaaaagaata aacgcaattg ttaaaaatat gtgtcctaaa 3480 ccagcaatac cagcaatagc aggacttaca cttagatctt taatggtaga aataccgttc 3540 acgaattgca ttgccacagt aacaagcaca cctaaatggt atatataaaa gaaactgtta 3600 aacagctttg tatgagttgt taatttgaat tggccctcga taatcatgaa aattaagaac 3660 ataattgtac ctagtactaa taaatgtgta tgtgtaacat ttaattgaga aaaaccgcta 3720 aaatcttccg cttttgtcat ttctctataa aatagaccac ttaataaccc taatagtgta 3780 tagagcgctg aactatacat taatcttttc attttaattc cccctatttt taattacgag 3840 ataagtatag cggtagttta tgaactgagt atgaacttac aacaaaaaaa ttaatgaagt 3900 actttacaat aaactcaatt tattagatgg tggagggacg aaaaaggatt ttagaaaaat 3960 aaattaatat atttttattt tgataagtaa taattaataa tatcttggaa atcattgtta 4020 agtattgttg taatacaatc gtcattcata aaatcttcat agtttttatc aagaatttct 4080 tcatcttcga tagatgtgaa atgattagct aaccctttta taatttaagt gtaatttgtg 4140 aatctaaac 4149 <210> 16 <211> 4353 <212> DNA <213> Staphylococcus aureus <400> 16 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa ttaaaccaca atccacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgag 420 caagtgtata gagcatttaa gattatgcgt ggagaagcat atcataaatg atgcggtttt 480 ttcagccgct tcataaaggg attttgaatg tatcagaaca tatgaggttt atgtgaattg 540 ctgttatgtt tttaagaagc atatcataaa tgatgcggtt ttttcagccg cttcataaag 600 ggattttgaa tgtatcagaa catatgaggt ttatgtgaat tgctgttatg tttttaagaa 660 gcatatcata agtgatgcgg tttttattaa ttagttgcta aaaaatgaag tatgcaatat 720

    Page 4

    2018206754 18 Jul 2018

    GENOM.057CPl.TXT taattattat taaattttga tatatttaaa gaaagattaa gtttagggtg aatgaatggc 780 ttatcaaagt gaatatgcat tagaaaatga agtacttcaa caacttgagg aattgaacta 840 tgaaagagta aatatacata atattaaatt agaaattaat gaatatctca aagaactagg 900 agtgttgaaa aatgaataag cagacaaata ctccagaact aagatttcca gagtttgatg 960 aggaatggaa aaaaaggaaa ttaggtgaag tagtaaatta taaaaatggt ggttcatttg 1020 aaagtttagt gaaaaaccat ggtgtatata aactcataac tcttaaatct gttaatacag 1080 aaggaaagtt gtgtaattct ggaaaatata tcgatgataa atgtgttgaa acattgtgta 1140 atgatacttt agtaatgata ctgagcgagc aagcaccagg actagttgga atgactgcaa 1200 ttatacctaa taataatgag tatgtactaa atcaacgagt agcagcacta gtgcctaaac 1260 aatttataga tagtcaattt ctatctaagt taattaatag aaaccagaaa tatttcagtg 1320 tgagatctgc tggaacaaaa gtgaaaaata tttctaaagg acatgtagaa aactttaatt 1380 ttttatctcc taattacact gaacaacaaa aaataggtaa tttcttcagc aaactcgacc 1440 gccagattga gttagaagaa gagaaacttg aactcttaga gcaacaaaag cgtggatata 1500 ttcagaagat tttttctcaa gatttaagat ttaaagatga aaatggaaac agttatcctg 1560 attggtctat taaaaagatt gaagatattt ctaaagttaa taaagggttt actccaaata 1620 caaaaaatga taaatactgg gatgaattaa atgaaaattg gttatctata gcaggtatga 1680 cacagaaata tttgtataaa ggaaataaag gaattactga aaaaggtgca tcaaagcatg 1740 taaaagtaga taaagatact ctaataatga gttttaaatt gactttaggt aagttagcta 1800 tagtaaaaga gcctatctat acaaatgaag ctatatgcca tttcgtatgg aaagaaagta 1860 atgttaatac tgagtatatg tactactatt taaattctat aaatataagt acttttggtg 1920 cacaggcagt taaaggagta acattaaata acgatgcaat taatagtatt atagtaaagt 1980 taccagtgat acaagaacaa aataaaatag catacttttt caataaatta gataaattaa 2040 ttgaaaaaca atcttctaaa gtagaattat taaaacaacg caaacaagga tttttacaga 2100 aaatgtttgt ttaattctta taaagttcta ttatgtaaaa tattaaatag agataacatt 2160 atgaaagcga gcccaagaca taaagttttt gaataaataa aaaagataat ttctatcaaa 2220 ttaatataga aattgtcttt tttataaatt ttttgattat ttttagctga ttgagctgtt 2280 acttttctta taataagtgc tattagcaca aatcctagtt ctcttttggc tttgtttatt 2340 cctcttacgg acattcgagt gaaacccatt ttaattttat tagaagtaat ttaggtttga 2400 acccacctaa ataaatatat gagttatttt tttatgctac aaaatatatt cagatttcaa 2460 taatgacata aaataggcat ctttatattt acctttagtg tagaattgct ctttgagtaa 2520 tccttctgtt ttaaatcctt gtgactcgta tatatgcaca gcttttttgt tatctgtatc 2580 aacatataga taaattttgt gcatgtttaa tatatcgaat gcataattta tcgctttttc 2640 gaatgcgaat tttgcataac ctttaccact gaactcaggt ttaataatta tttgtatttc 2700 acaattacga tggatgtaat taatttctac taattcaaca atacctacga cttgattttc 2760 atcttcaaca ataaaacgtc tctctgattc atctaataaa tgcttatcaa ataaatattg 2820 aagttccgtt aaggattcat atggttcttc aaaccaataa gacataatag aatattcatt 2880 atttaattca tgaacaaaaa gtaaatcact atactctaat gctcttagtt tcataattcc 2940 actcccaaaa ttttctcata tatttgcatt ataaatataa ataacgaata agtcatcatt 3000 cactgtgaat actctatttt aacaattcac cacatactaa ttctcatttt cttgttattc 3060 tcgatttatt actcttacta tgaaacctat aaaattctca catttgtttg tattaagaat 3120 aaatacgtcg atagtaacaa taaaaaaata aataataaag catccctcac cgtaaaagtg 3180 aaggatgctc tagttttatt gaaatataca tttcattttg ttaaataatt attaataata 3240 ttttgaaaat cattattacg tgaaatcttc atagatttta tcaagtattt ctttgccttc 3300 aattgctgtg aagtgatgta ccaatctatt tttacaatca tatgtaattt tgtgacgcta 3360 ggtaattagt aattgttcgt cagtctgatt gtatagtatc aagtttcata gataatactc 3420 tttgatttta atgtccactt tgacgtgctt taagattgag tatatacata atgtcattgt 3480 ggaatgttaa aaatcctaca aatgtttatt catctgcagg atttttaaat ctccaagaat 3540 aaaaatcatc ataggacaac tggattattg tttggataaa taacgtaaac aataattagg 3600 tactattatt tatttttgtt tattcttttt cctaacaaaa taaagaaaag aataaacgca 3660 attgttaaaa atatgtgtcc taaaccagca ataccagcaa tagcaggact tacacttaga 3720 tctttaatgg tagaaatacc gttcacgaat tgcattgcca cagtaacaag cacacctaaa 3780 tggtatatat aaaagaaact gttaaacagc tttgtatgag ttgttaattt gaattggccc 3840 tcgataatca tgaaaattaa gaacataatt gtacctagta ctaataaatg tgtatgtgta 3900 acatttaatt gagaaaaacc gctaaaatct tccgcttttg tcatttctct ataaaataga 3960 ccacttaata accctaatag tgtatagagc gctgaactat acattaatct tttcatttta 4020 attcccccta tttttaatta cgagataagt atagcggtag tttatgaact gagtatgaac 4080 ttacaacaaa aaaattaatg aagtacttta caataaactc aatttattag atggtggagg 4140 gacgaaaaag gattttagaa aaataaatta atatattttt attttgataa gtaataatta 4200 ataatatctt ggaaatcatt gttaagtatt gttgtaatac aatcgtcatt cataaaatct 4260 tcatagattt tatcaagaat ttcttcatct tcgatagatg tgaaatgatt agctaaccct 4320 tttataattt aagtgtaatt tgtgaatcta aac 4353 <210> 17 <211> 1100 <212> DNA <213> Staphylococcus aureus

    Page 5

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <400> 17 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa ttaaaccaca atccacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgag 420 caagtgtata gagcatttaa gattatgcgt ggagaagcgt atcacaaata aaactaaaaa 480 ataagttgta tataacttat tttgaaattg gttaagtata taatatctcc aataaaatgt 540 agttaactta cgataatgct gaactatagc tttgtaaact aaaatgtaaa taattacaat 600 caaattgcaa caatatagtt caagaatgct acaatttgag gacagattga tagcattaat 660 ccctttaaaa tgaagctagg agataactta cattatgatt agtaaacaaa taaaggattt 720 acgaaagcaa cataattata ctcaagaaga gctagctgaa aaattaaata cttcaagaca 780 aacaatttct aaatgggaac aaggtatttc agaaccagac ttaattatgc ttatgcaatt 840 gtcacaatta ttttctgtta gtacagacta tctcattaca ggaagtgaca atattattaa 900 aaaagataat aaaagctatt atgaaatgaa tttttgggca tttatgtctg aaaaatggtg 960 ggtaattatt attatagtaa tcataatttg tggaacaata ggacaaattt tttcaaacta 1020 atgtaagtat ctctcaaata ttttgggagg ttttattatg aaaatcaaaa aattattaaa 1080 gacattatta attattttat 1100 <210> 18 <211> 1109 <212> DNA <213> Staphylococcus aureus <400> 18 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa tcaaaccaca atcaacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgaa 420 caagtgtaca gagcatttaa gattatgcgt ggagaagcgt atcacaaata aaactaaaaa 480 ataagttgta tataacttat tttgaaattg gttaagtata tagtatctcc aataaaatgt 540 agttaactta cgataatgct gaactatagc tttgtaaact aaaatgtaaa taattacaat 600 caaattgcaa caatatagtt caagaatgct acaatttgag gacagattga tagcattaat 660 ccctttaaaa tgaagctagg agataactta cattatgatt agtaaacaaa taaaggattt 720 acgaaagcaa cataattata ctcaagaaga gctagctgaa aaattaaata cttcaagaca 780 aacaatttct aaatgggaac aaggtatttc agaaccagac ttaattatgc ttatgcaatt 840 gtcacaatta ttttctgtta gtacagacta tctcattaca ggaagtgaca atattattaa 900 aaaagataat aaaagctatt atgaaatgaa tttttgggca tttatgtctg aaaaatggtg 960 ggtaattatt attatagtaa tcataatttg tggaacaata ggacaaattt tttcaaacta 1020 atgtaagtat ctctcaaata ttttgggagg ttttattatg aaaatcaaaa aattattaaa 1080 gacattatta attattttat tatgttttg 1109 <210> 19 <211> 1159 <212> DNA <213> Staphylococcus aureus <400> 19 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa tcaaaccaca atcaacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgaa 420 caagtgtaca gagcatttaa gattatgcgt ggagaagcgt atcacaaata aaactaaaaa 480 ataagttgta tataacttat tttgaaattg gttaagtata tagtatctcc aataaaatgt 540 agttaactta cgataatgct gaactatagc tttgtaaact aaaatgtaaa taattacaat 600 caaattgcaa caatatagtt caagaatgct acaatttgag gacagattga tagcattaat 660 ccctttaaaa tgaagctagg agataactta cattatgatt agtaaacaaa taaaggattt 720 acgaaagcaa cataattata ctcaagaaga gctagctgaa aaattaaata cttcaagaca 780 aacaatttct aaatgggaac aaggtatttc agaaccagac ttaattatgc ttatgcaatt 840

    Page 6

    2018206754 18 Jul 2018 gtcacaatta ttttctgtta gtacagacta aaaagataat aaaagctatt atgaaatgaa ggtaattatt attatagtaa tcataatttg atgtaagtat ctctcaaata ttttgggagg gacattatta attattttat tatgttttgt gctatggcat attgtgagc <210> 20 <211> 1125 <212> DNA <213> Staphylococcus aureus <400> 20 accattttag ctgtagggaa actaaaagag gaaaaacgtt taggcccata caccaagata ccagaaaata tgagcgacaa agaaattgag ctagccaaaa tcaaaccaca atccacagtc tcttccgaag gattggccca agaattgaac gtattcgtca ttggcggatc aaacggcctg gcactatcat ttagcaaaat gacattccca caagtgtata gagcatttaa gattatgcgt acggattgtg tataatatat tttaaatata gaaaatgtta gttataaatc attcgataat aatatatttt ttggaagaaa tgggagtgga ctagataatg aaaaaagtgt tatctttaat gttgaagaaa tagatggtgt gaatttggtt caaattaagc atttaaatag cgctataaat agtgaactta agcattcaaa agaaagaatt gctagagaaa gatttgaaat aggtagtaat gatccagtta atgcttttta tagttggaag actattgaat ctttagatga attagaagaa aatataaaaa caccaatttt agcttttgat <210> 21 <211> 818 <212> DNA <213> Staphylococcus aureus <400> 21 aatattggaa gcaagccata gcagaatatg acatcataga agttccagac gaaaaagcac aagtgtatag agcatttaag attatgcgtg tcagccgctt cataaaggga ttttgaatgt tgttatgttt ttaagaagct tatcataagt cctccgcagt ctttcatttc aagtaaataa tagtgaagca aagttctagc tttgagaaaa ggtaaaatat aaataagtac atattgaaga gggaatttca aatgatagac aactttatgc ccaataatgt agttaaaaaa tctgattggg atgataagtt acccaagcag ttaaaagtgc ggaaggttgc tactgggaac tatagtaaag taacaaaaga aacaaaggat ggatattatt gcatatactt atcttgaatc aaggatggtc <210> 22 <211> 27 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nuc' <400> 22 aacaggtgaa ttattagcac ttgtaag

    GENOM.O57CPl.TXT tctcattaca ggaagtgaca atattattaa 900 tttttgggca tttatgtctg aaaaatggtg 960 tggaacaata ggacaaattt tttcaaacta 1020 ttttattatg aaaatcaaaa aattattaaa 1080 attgtctgtt attgtgcaaa atatttcaat 1140 aaatattgga agcaagccat agcagaatat 60 gacatcatag aagttccaga cgaaaaagca 120 caagtaaaag aaaaagaagg ccaacgaata 180 attacattag aaatacaagg aaagatgcta 240 caacgcatga cccaagggca aagcgacttt 300 cacaaggacg tcttacaacg cagtaactat 360 catcaaatga tgcgggttgt gttaattgaa 420 ggagaggcgt atcataaata aaactaaaaa 480 aaaaggattg attttatgtt aaataaatta 540 tacactagtg aagatgattt gactaaagta 600 aaaagctcat taagtgaatg gttaagaaga 660 actggttact taaaaaataa tattgaagaa 720 attggagaag aatctataaa tcatagtgac 780 agtttagaaa attttattac tcggaaaaat 840 tacaataaaa tgaafatcag actaaatgaa 900 gtggttaagc agaagaggaa tgctgacaaa 960 aaaaatgcta acgatataat tcaagagatg 1020 agaataacaa gaaaagaagt cttattaaat 1080 tataatgatt ttagt 1125 aaaaacgttt aggcccatac accaagatag 60 cagaaaatat gagcgacaaa gaaattgagc 120 gagaagcata tcataaatga tgcggttttt 180 atcagaacat atgaggttta tgtgaattgc 240 aatgaggttc atgatttttg acatagttag 300 tagcgaaata ttctttatac tgaatactta 360 ttctttctgc aactaaatat agtaaattac 420 aaatgagaca taatatattt tataatagga 480 aggtccttaa attaattaaa gagaaacgta 540 ataaaggtga tctatataaa actttagtcc 600 atataaaaga agataaatat tcagttgtag 660 ttccttggat ttcaatatat gatgagaata 720 tggtatatct ttttcatccg gaaggagaag 780 aaagataa 818 eic acid sequence <210> 23 <211> 24

    Page 7

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 23 gagcggattt atattaaaac tttg 24 <210> 24 <211> 24 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 24 gttgccatag attcaatttc taag 24 <210> 25 <211> 1081 <212> DNA <213> staphylococcus aureus <400> 25 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa tcaaaccaca atcaacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgaa 420 caagtgtaca gagcatttaa gattatgcgt ggagaagcat atcataagtg atgcggtttt 480 tattaattag ttgctaaaaa atgaagtatg caatattaat tattattaaa ttttgatata 540 tttaaagaaa gattaagttt agggtgaatg aatggcttat caaagtgaat atgcattaga 600 aaatgaagta cttcaacaac ttgaggaatt gaactatgaa agagtaaata tacataatat 660 taaattagaa attaatgaat atctcaaaga actaggagtg ttgaaaaatg aataagcaga 720 caaatactcc agaactaaga tttccagagt ttgatgagga atggaaaaaa aggaaattag 780 gtgaagtagt aaattataaa aatggtggtt catttgaaag tttagtgaaa aaccatggtg 840 tatataaact cataactctt aaatctgtta atacagaagg aaagttgtgt aattctggaa 900 aatatatcga tgataaatgt gttgaaacat tgtgtaatga tactttagta atgatactga 960 gcgagcaagc accaggacta gttggaatga ctgcaattat acctaataat aatgagtatg 1020 tactaaatca acgagtagca gcactagtgc ctaaacaatt tatagatagt caatttctat 1080 c 1081 <210> 26 <211> 1054 <212> DNA <213> Staphylococcus aureus <400> 26 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 60 gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa tcaaaccaca atcaacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgaa 420 caagtgtaca gagcatttaa gattatgcgt ggagaagcat atcataagtg atgcggtttt 480 tattaattag ttgctaaaaa atgaagtatg caatattaat tattattaaa ttttgatata 540 tttaaagaaa gattaagttt agggtgaatg aatggcttat caaagtgaat atgcattaga 600 aaatgaagta cttcaacaac ttgaggaatt gaactatgaa agagtaaata tacataatat 660 taaattagaa attaatgaat atctcaaaga actaggagtg ttgaaaaatg aataagcaga 720 caaatactcc agaactaaga tttccagagt ttgatgagga atggaaaaaa aggaaattag 780 gtgaagtagt aaattataaa aatggtggtt catttgaaag tttagtgaaa aaccatggtg 840 tatataaact cataactctt aaatctgtta atacagaagg aaagttgtgt aattctggaa 900

    Page 8

    2018206754 18 Jul 2018

    GENOM.057CPl.TXT aatatatcga tgataaatgt gttgaaacat tgtgtaatga tactttagta atgatactga 960 gcgagcaagc accaggacta gttggaatga ctgcaattat acctaataat aatgagtatg 1020 tactaaatca acgagtagca gcactagtgc ctaa 1054 <210> 27 <211> 22 <212> DNA <213> Artificial sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 27 ttcttaagta cacgctgaat eg 22 <210> 28 <211> 24 <212> DNA <213> Artificial sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 28 taatttcctt tttttccatt cctc 24 <210> 29 i <211> 24 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 29 tgataagcca ttcattcacc ctaa 24 <210> 30 <211> 19 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 30 ggatcaaacg gcctgcaca 19 <210> 31 <211> 37 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 31 cccgcgcgta gttactgcgt tgtaagacgt ccgcggg 37 <210> 32 <211> 37 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence

    Page 9

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <400> 32 cccgcgcata gttactgcgt tgtaagacgt ccgcggg 37 <210> 33 <211> 37 <212> DNA <213> Artificial Sequence <22O>

    <223> synthetically prepared nucleic acid sequence <400> 33 cccgcgcgta gttactacgt tgtaagacgt ccgcggg 37 <210> 34 <211> 24 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 34 caaattgtag cattcttgaa ctat 24 <210> 35 <211> 24 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 35 ctcccatttc ttccaaaaaa tata 24 <210> 36 <211> 29 <212> DNA <213> Artificial Sequence <22O>

    <223> Synthetically prepared nucleic acid sequence <400> 36 gtcaaaaatc atgaacctca ttacttatg 29 <210> 37 <211> 1256 <212> DNA <213> staphylococcus aureus <400> 37 gctgtaggga aactaaaaga gaaatattgg aagcaagcca tagcagaata tgaaaaacgt 60 ttaggcccat acaccaagat agacatcata gaagttccag acgaaaaagc accagaaaat 120 atgagcgaca aagaaattga gcaagtaaaa gaaaaagaag gccaacgaat actagccaaa 180 attaaaccac aatccacagt cattacatta gaaatacaag gaaagatgct atcttccgaa 240 ggattggccc aagaattgaa ccaacgcatg acccaagggc aaagcgactt tgtattcgtc 300 attggcggat caaacggcct gcacaaggac gtcttacaac gcagtaacta cgcactatca 360 ttcagcaaaa tgacattccc acatcaaatg atgcgggttg tgttaattga gcaagtgtat 420 agagcattta agattatgcg tggagaagca tatcataaat gatgcggttt tttcagccgc 480 ttcataaagg gattttgaat gtatcagaac atatgaggtt tatgtgaatt gctgttatgt 540 ttttaagaag catatcataa gtgatgcggt ttttattaat tagttgctaa aaaatgaagt 600 atgcaatatt aattattatt aaattttgat atatttaaag aaagattaag tttagggtga 660 atgaatggct tatcaaagtg aatatgcatt agaaaatgaa gtacttcaac aacttgagga 720 attgaactat gaaagagtaa atatacataa tattaaatta gaaattaatg aatatctcaa 780 agaactagga gtgttgaaaa atgaataagc agacaaatac tccagaacta agatttccag 840

    Page 10

    2018206754 18 Jul 2018

    GENOM.O57CPl.TXT agtttgatga ggaatggaaa aaaaggaaat taggtgaagt agtaaattat aaaaatggtg 900 gttcatttga aagtttagtg aaaaaccatg gtgtatataa actcataact cttaaatctg 960 ttaatacaga aggaaagttg tgtaattctg gaaaatatat cgatgataaa tgtgttgaaa 1020 cattgtgtaa tgatacttta gtaatgatac tgagcgagca agcaccagga ctagttggaa 1080 tgactgcaat tatacctaat aataatgagt atgtactaaa tcaacgagta gcagcactag 1140 tgcctaaaca atttatagat agtcaatttc tatctaagtt aattaataga aaccagaaat 1200 atttcagtgt gagatctgct ggaacaaaag tgaaaaatat ttctaaagga catgta 1256 <210> 38 <211> 23 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 38 gaggaccaaa cgacatgaaa ate 23 <210> 39 <211> 756 <212> DNA <213> Staphylococcus aureus <400> 39 tgacattccc acatcaaatg atgcgggttg tgttaattga gcaagtgtat agagcattta 60 agattatgeg tggagaagcg tatcacaaat aaaactaaaa aataggttgc gcataatata 120 attagaaagg aattagacat aaattaggag tccttcacag aatagegaag gactcccatt 180 aaatatatta tggtgtaaag aaatcacaaa tcaafatata tacttaatac catatattaa 240 cttgtactat tataaagtac gacatcagta ttaggtatca ctttgaacac atgaatttca 300 ttatcacttt tattattcac aaaaaatttt ccaattctca attactgaat tatgtgtata 360 catgttgtta aaaattaata aaggatattt atgtttgttt aaagcatatc acaagtgatg 420 cggtttttta taaagattta cttgttagtg attttgataa aaatgcttaa tactatttca 480 ataatatgta tttaaaaatt agattaatag tatttaaett caaatggcct cgtataaact 540 catagcaaat taacgtaaat caatgaaata aaatgaaaac aatttcaaga atacattata 600 aacataaagt atacaaaaaa taaatgagcg tatttgttta aacgtataca ctcattttta 660 ttaaattaat ttattatatt ttacgattgt tatttatgaa attaacaaat tccatttttg 720 atagtgaaat taaaagcttt atcacttatt attgat 756 <210> 40 <211> 771 <212> DNA <213> staphylococcus aureus <400> 40 tgacattccc acatcaaatg atgcgggttg tgttaattga gcaagtgtat agagcattta 60 agattatgeg tggagaagcg tatcacaaat aaaactaaaa aataggttgc gcataatata 120 attagaaagg aattagacat aaattaggag tccttcacag aatagegaag gactcccatt 180 aaatatatta tggtgtaaag aaatcacaaa tcaatatata tacttaatac catatattaa 240 cttgtactat tataaagtac gacatcagta ttaggtatca ctttgaacac atgaatttca 300 ttatcacttt tattattcac aaaaaatttt ccaattctca attactgaat tatgtgtata 360 catgttgtta aaaattaata aaggatattt atgtttgttt aaagcatatc acaagtgatg 420 cggtttttta taaagattta cttgttagtg attttgataa aaatgcttaa tactatttca 480 ataatatgta tttaaaaatt agattaatag tatttaaett caaatggcct cgtataaact 540 catagcaaat taacgtaaat caatgaaata aaatgaaaac aatttcaaga atacattata 600 aacataaagt atacaaaaaa taaatgagcg tatttgttta aacgtataca ctcattttta 660 ttaaattaat ttattatatt ttacgattgt tatttatgaa attaacaaat tccatttttg 720 atagtgaaat taaaagcttt atcacttatt attgataatt ttgactgcat c 771 <210> 41 <211> 680 <212> DNA <213> staphylococcus aureus <400> 41 ttcagcaaaa tgacattccc acatcaaatg atgcgggttg tgttaattga acaagtgtac 60 agagcattta agattatgeg tggagaagcg tatcataagt ageggaggag ttttttacct 120

    Page 11

    2018206754 18 Jul 2018

    GENOM.057CPl.TXT tgtgacttat cataaagtac gatgtttatg taagtgatta tcattattta agcaggtttt 180 tcaaattaaa taataacaag aataaaatgc acttagcgac attgaaattt attaatctag 240 taaactaata gatttataga aaattttatt tgcaagggga taattttgaa aagtagtatt 300 ttctatcttt ccataataca ttgtaattac aacggagggg atattgtgat gaagtgtata 360 gataaaacgt gggttagcta ttataaagaa ttagctgata agttaacaga ttatcaaaat 420 aaacgttatg aattaattga aatagtgaag gaagtatata aaaaaacggg aataaaattc 480 cctactttag caagtgataa tgtattgatg gacatagatc cttttacaat atttgcatta 540 tttaataaaa attccatgag agaaactaat aaggtaaaaa tattaacaga attagcttcg 600 gaattgaata ttaagtccaa aattccgtca gtttttgaca gtattccaac agtcaataat 660 ctgaatgcta catattataa 680 <210> 42 <211> 1119 <212> DNA <213> Staphylococcus aureus <400> 42 gacattccca catcaaatga tgcgggttgt gttaattgag caagtgtata gagcatttaa 60 gattatgcgt ggagaggcgt atcataagta aaactaaaaa attctgtatg aggagataat 120 aatttggagg gtgttaaatg gtggacatta aatccacgtt cattcaatat ataagatata 180 tcacgataat tgcgcatata acttaagtag tagctaacag ttgaaattag gccctatcaa 240 attggtttat atctaaaatg attaatatag aatgcttctt tttgtcctta ttaaattata 300 aaagtaactt tgcaatagaa acagttattt cataatcaac agtcattgac gtagctaagt 360 aatgataaat aatcataaat aaaattacag atattgacaa aaaatagtaa atataccaat 420 gaagtttcaa aagaacaatt ccaagaaatt gagaatgtaa ataataaggt caaagaattt 480 tattaagatt tgaaagagta tcaatcaaga aagatgtagt tttttaataa actatttgga 540 aaataattat cataatttaa aaactgacaa tttgcgagac tcataaaatg taataatgga 600 aatagatgta aaatataatt aaggggtgta atatgaagat taatatttat aaatctattt 660 ataattttca ggaaacaaat acaaattttt tagagaatct agaatcttta aatgatgaca 720 attatgaact gcttaatgat aaagaacttg ttagtgattc aaatgaatta aaattaatta 780 gtaaagttta tatacgtaaa aaagacaaaa aactattaga ttggcaatta ttaataaaga 840 atgtatacct agatactgaa gaagatgaca atttattttc agaatccggt catcattttg 900 atgcaatatt atttctcaaa gaagatacta cattacaaaa taatgtatat attatacctt 960 ttggacaagc atatcatgat ataaataatt tgattgatta tgacttcgga attgattttg 1020 cagaaagagc aatcaaaaat gaagacatag ttaataaaaa tgttaatttt tttcaacaaa 1080 acaggcttaa agagattgtt aattatagaa ggaatagtg 1119 <210> 43 <211> 24 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 43 cattttgctg aatgatagtg cgta <210> <211> <212> <213> 44 23 DNA Artificial sequence <220> <223> synthetically prepared nucleic acid sequence

    <400> 44 gaggaccaaa cgacatgaaa ate 23

    <210> 45 <211> 21 <212> DNA <213> Artificial sequence <22O> <223> Synthetically prepared nucleic acid sequence Page 12

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <400> 45 atcaaatgat gcgggttgtg t <210> 46 <211> 26 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 46 aaacgaaaat actggtgaag atatta <210> <211> <212> <213> 47 25 DNA Artificial sequence <220> <223> Synthetically prepared nucleic acid sequence

    <400> 47 ttgcctttct caagtcttta caact

    <210> 48 <211> 20 <212> DNA <213> Artificial sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 48 cgaggagaag cgtatcacaa <210> 49 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 49 agttgccata gattcaattt ctaaggt <210> 50 <211> 27 <212> DNA <213> Artificial Sequence <22O> <223> Synthetically prepared nucleic aci d sequence <400> 50 aacaggtgaa ttattagcac ttgtaag <210> 51 <211> 26 <212> DNA <213> Artificial sequence <22O> <223> synthetically prepared nucleic aci d sequence <400> 51

    Page 13

    GENOM.057CPl.TXT

    2018206754 18 Jul2018 ctattgttcc acaaattatg attact <210> 52 <211> 26 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 52 cttcttttct tgttattctt tcttct <210> 53 <211> 20 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 53 ctaaatcata gccatgaccg <210> 54 <211> 20 <212> DNA <213> Artificial Sequence <22O>

    <223> Synthetically prepared nucleic acid sequence <400> 54 atgctctttg ttttgcagca <210> 55 <211> 1073 <212> DNA <213> Staphylococcus aureus <400> 55 tattggaagc aagccatagc agaatatgaa aaacgtttag gcccatacac atcatagaag ttccagacga aaaagcacca gaaaatatga gcgacaaaga gtaaaagaaa aagaaggcca acgaatacta gccaaaatca aaccacaatc acattagaaa tacaaggaaa gatgctatct tccgaaggat tggcccaaga cgcatgaccc aagggcaaag cgactttgta ttcgtcattg gcggatcaaa aaggacgtct tacaacgcag taactatgca ctatcattta gcaaaatgac caaatgatgc gggttgtgtt aattgaacaa gtgtatagag catttaagat gaggcgtatc ataagtgatg cttgttagaa tgatttttaa caatatgaaa agcttaaaca atttgtttat ctaagtactt atttaataat tgattgaact ccaggctgtc tggtaaattg agaagttggg ttttggagcg tataaatgat taaaattcaa tttgaggagt aggagattat gtcgaatata aaaacaacac cgtaggacta gaaaaagaca acgataagct atttgattat ataactgaat aaacacgcct gaaaaccggg aagcaaaagt tgttattgaa gaaaggttac taaatatgaa ttagatcaaa tgacaccaga gtatggaata caaaaaggca aggtcatgca gatgttgtaa tatttcatga ttctaaagat aaatctcaag aataatagta gagtgtaaaa gaaagaatcg cagggatggt attgaacaat tcttgcaggg tgtgagtctg cagaatacgg cgtttggttt aatggagaag tataaaacga ttgaaaaaag caccacattg gaaaacagta tttaatatac <210> 56 <211> 2031 <212> DNA <213> Staphylococcus aureus <400> 56 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat Page 14 caagatagac 60 aattgagcaa 120 cacagtcatt 180 attgaaccaa 240 cggcctgcac 300 attcccacat 360 tatgcgtgga 420 tagctgtgga 480 gtgattggca 540 agaattaata 600 tagagacgtc 660 tagagattca 720 ataaagaata 780 gtgttagaat 840 agaatattaa 900 taaaaacata 960 atatagtata 1020 cga 1073 agcagaatat 60

    2018206754 18 Jul 2018

    GENOM.057CPl.TXT gaaaaacgtt taggcccata caccaagata gacatcatag aagttccaga cgaaaaagca 120 ccagaaaata tgagtgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 180 ctagccaaaa tcaaaccaca atccacagtc attacattag aaatacaagg aaagatgcta 240 tcttccgaag gattggccca agaattgaac caacgcatga cccaagggca aagcgacttt 300 gttttcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 360 gcactatcat tcagcaaaat gacattccca catcaaatga tgcgggttgt gttaattgaa 420 caagtgtaca gagcatttaa gattatgcga ggagaagcgt atcacaaata aaactaaaaa 480 atagattgtg tataatataa aaggagcgga tttatattaa aactttgaat tcaaaaatta 540 ttgaaaggga agctacctta gaaattgaat ctatggcaac taatacattg aaaataaacc 600 cggatattaa ttcaaacgat acaaaaatgt ctttcgatgg agaattggaa gtgtatgatt 660 ctgaaaattt gagtaaaaaa aatttcgttg gaaaaataca agttcaagtt aaaggaaagg 720 aagtagctaa aagaggaggt aaggttattc atcgaagtaa tgtcaaaatg aatgatttaa 780 aggcatacca acgagaaggt ggtgtgtatt actttgtcgt gtatttaatc gttgagaata 840 aaaaagttgt tgagaagcag gtttatggta aacaattaca tcaattagat ttacaatttt 900 tactgcaaaa aaagcagaaa agcgtcacta taaaaatgta tgaaattgaa aatgaaaaaa 960 ttttatataa taattgcgta aaatatataa atgaaaagag attacaaaat caagtaggtc 1020 aagttaaagt aaagaacata gaaaaagctt tatcatatat agctacacct gaaaatattg 1080 tgatggatca tagaggttta ccattaaatg atttttatgg ctatataaaa attaattcat 1140 ctgaattaga tgtaactata ccagatggag tattaagtat ggaaaaagta aaaagagtga 1200 acaaaaagca gataataaaa gaaggcaagt tattatttga aggtatggta ggtattgaaa 1260 cttcaaagga gtccatctct ataactatag atgatatttt caaaattcaa acatttgaaa 1320 gtgataacaa aagtatatat acaatgttac catttaaaaa attaaatata gccgaacaat 1380 cttttaatgt tataaacgaa ttgtcgaaag gcggcgaatt ctttttggat caaatccaat 1440 tagtaatcca accttttgaa attaatatta ttgaaataaa agaaacaata aataagttga 1500 atattaaatt atcagagtat agtaacttgc tttcgtttga tgtgagtcta aaatctacag 1560 aatttgataa gcagatgaat gagataaaag gtttattaga attattggaa tataaaaatt 1620 ttaaagattt taaaatgcat aataatggat actataaaat gaagttttgt ggaaaattta 1680 tattattatt taaagacaat acatcattgt ataatgtcta ctctaatgac tttgtagata 1740 gatttgaggc tgttacaaaa gaaagagttg tacagatgcc aattgtttac acattaacaa 1800 gagatatgat tgtagatgta ctgaattttg atataaatgt tattaaagaa tgtattgaat 1860 cagataaaat tgctattcaa tctgacatta aatgggagaa attaaataac tttgcattag 1920 aattaatcgc agcctatgat gaaactcaaa gaaccgattt attagaatta gctgaatatg 1980 tattaaataa tttgctgaat tttgataatg ataaaatatt tatgaactta a 2031 (

    <210> 57 <211> 22 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 57 cgtggagagg cgtatcataa gt <210> 58 <211> 22 <212> DNA <213> Artificial sequence <220> <223> synthetically prepared nucleic acid sequence

    <400> 58 gctccaaaac ccaacttctc aa 22

    <210> 59 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 59 gccaaaatta aaccacaatc cac

    Page 15

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <210> 60 <211> 30 <212> DNA <213> Artificial sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 60 aatctttgtc ggtacacgat attcttcacg <210> <211> <212> <213> 61 30 DNA Artificial sequence <22O> <223> Synthetically prepared nucleic acid sequence

    <400> 61 cgtaatgaga tttcagtaga taatacaaca

    <210> 62 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 62 gccaaaatca aaccacaatc cac <210> 63 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 63 attgctgtta atattttttg agttgaa <210> 64 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> synthetically prepared nucleic acid sequence <400> 64 tattgcaggt ttcgatgttg a <210> 65 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 65 tcaccgtctt tcttttgacc tt <210> 66 page 16

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <211> 23 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 66 cagcaattcw cataaacctc ata 23 <210> 67 <211> 26 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 67 caggcatagc tatatatgat aaagca 26 <210> 68 <211> 26 <212> DNA <213> Artificial Sequence <220>

    <223> synthetically prepared nucleic acid sequence <400> 68 atgcctttaa atcattcaca ttgaca 26 <210> 69 <211> 4340 <212> DNA <213> staphylococcus aureus <400> 69 cttcatatga cgtctatcca tttatgtatg gcatgagtaa cgaagaatat aataaattaa 60 ccgaagataa aaaagaacct ctgctcaaca agttccagat tacaacttca ccaggttcaa 120 ctcaaaaaat attaacagca atgattgggt taaataacaa aacattagac gataaaacaa 180 gttataaaat cgatggtaaa ggttggcaaa aagataaatc ttggggtggt tacaacgtta 240 caagatatga agtggtaaat ggtaatatcg acttaaaaca agcaatagaa tcatcagata 300 acattttctt tgctagagta gcactcgaat taggcagtaa gaaatttgaa aaaggcatga 360 aaaaactagg tgttggtgaa gatataccaa gtgattatcc attttataat gctcaaattt 420 caaacaaaaa tttagataat gaaatattat tagctgattc aggttacgga caaggtgaaa 480 tactgattaa cccagtacag atcctttcaa tctatagcgc attagaaaat aatggcaata 540 ttaacgcacc tcacttatta aaagacacga aaaacaaagt ttggaagaaa aatattattt 600 ccaaagaaaa tatcaatcta ttaactgatg gtatgcaaca agtcgtaaat aaaacacata 660 aagaagatat ttatagatct tatgcaaact taattggcaa atccggtact gcagaactca 720 aaatgaaaca aggagaaact ggcagacaaa ttgggtggtt tatatcatat gataaagata 780 atccaaacat gatgatggct attaatgtta aagatgtaca agataaagga atggctagct 840 acaatgccaa aatctcaggt aaagtgtatg atgagctata tgagaacggt aataaaaaat 900 acgatataga tgaataacaa aacagtgaag caatccgtaa cgatggttgc ttcactgttt 960 tattatgaat tattaataag tgctgttact tctcccttaa atacaatttc ttcattttca 1020 ttgtatgttg aaagtgacac tgtaacgagt ccattttctt tttttatgga tttcttattt 1080 gtaatttcag cgataacgta caatgtatta cctgggtata caggtttaat aaatttaacg 1140 ttattcattt gtgttcctgc tacaacttct tctccgtatt taccttcttc tacccataat 1200 ttaaatgata ttgaaagtgt atgcatgcca gatgcaatga tacctttaaa tctactttgt 1260 tctgcttttt ctttatctat atgcatatat tgaggatcaa aagttgttgc aaattggata 1320 atttcttctt ctgtaatatg aaggcttttt gttttgaatg tttctcctac tataaaatca 1380 tcgtatttca tatatgtctc tctttcttat tcaaattaat tttttagtat gtaacatgtt 1440 aaaggtaagt ctaccgtcac tgaaacgtaa gactcacctc taactttcta ttgagacaaa 1500 tgcaccattt tatctgcatt gtctgtaaag ataccatcaa ctccccaatt agcaagttgg 1560 tttgcacgtg ctggtttgtt tacagtccat acgttcaatt cataacccgc ttcttttacc 1620 atttttactt ttgctttagt aagtttggca tcttcagtgt ttactatttt agcattacag 1680 taatctaaaa gtgttctcca gtcttcacga aacgaagttg tatggaatat aactgctctg 1740

    Page 17

    2018206754 18 Jul 2018

    GENOM.057CPl.TXT ttatattgtg gcatgatttc ttctgcaagt ttaacaagca caacattaaa gcttgaaatg 1800 agcacttctt gattctgatt taagtttgtt aattgttctt ccacttgctt aaccatactt 1860 ttagaaagtg ctagtccatt cggtccagta atacctttta attctacatt taaattcata 1920 ttatattcat ttgctatttt tactacatca tcgaaagttg gcaaatgttc atctttgaat 1980 ttttcaccaa accaagatcc tgcagaagca tctttaattt catcataatt caattcagtt 2040 atttccccgg acatatttgt agtccgttct aaataatcat catgaatgat aatcagttgt 2100 tcatcttttg taattgcaac atctaactcc aaccagttta taccttctac ttctgaagca 2160 gctttaaatg atgcaattgt attttccgga gctttactag gtaatcctct atgtccatat 2220 acagttagca tattacctct ccttgcattt ttattttttt aattaacgta actgtattat 2280 cacattaatc gcacttttat ttccattaaa aagagatgaa tatcataaat aaagaagtcg 2340 atagattcgt attgattatg gagttaatct acgtctcatc tcatttttaa aaaatcattt 2400 atgtcccaag ctccattttg taatcaagtc tagtttttcg gttctgttgc aaagttgaat 2460 ttatagtata attttaacaa aaaggagtct tctgtatgaa ctatttcaga tataaacaat 2520 ttaacaagga tgttatcact gtagccgttg gctactatct aagatataca ttgagttatc 2580 gtgatatatc tgaaatatta agggaacgtg gtgtaaacgt tcatcattca acggtctacc 2640 gttgggttca agaatatgcc ccaattttgt atcaaatttg gaagaaaaag cataaaaaag 2700 cttattacaa atggcgtatt gatgagacgt acatcaaaat aaaaggaaaa tggagctatt 2760 tatatcgtgc cattgatgca gagggacata cattagatat ttggttgcgt aagcaacgag 2820 ataatcattc agcatatgcg tttatcaaac gtctcattaa acaatttggt aaacctcaaa 2880 aggtaattac agatcaggca ccttcaacga aggtagcaat ggctaaagta attaaagctt 2940 ttaaacttaa acctgactgt cattgtacat cgaaatatct gaataacctc attgagcaag 3000 atcaccgtca tattaaagta agaaagacaa ggtatcaaag tatcaataca gcaaagaata 3060 ctttaaaagg tattgaatgt atttacgctc tatataaaaa gaaccgcagg tctcttcaga 3120 tctacggatt ttcgccatgc cacgaaatta gcatcatgct agcaagttaa gcgaacactg 3180 acatgataaa ttagtggtta gctatatttt tttactttgc aacagaacca tattttatgt 3240 gttgttgttt gtggtgcatt agcagcaaac attcgtggtg aaagtgatgc tgttttagca 3300 tttgataatt tgaatgttgc tgattgagtt ggtttttgtg ttgaggcttg ttgtgcatct 3360 acgtcgcgcg tttcgtttac tgttgttgaa actgctgtag atggtttgtt agatggtgcg 3420 ttggatgtta ctttgttgtt tgtatcatca gctgttccct gtactgatgc tgatacgttg 3480 gttgccgctt cttcaccaga ttgatgagcc gcttcctttg ttggcgttac ttgttgctta 3540 tctgttgttg ctgcttgtgc tttcattggt gtatgctgct cagccgcgtt cgagacatgc 3600 cataatccca tcacactaaa aagcaaaacg agccatacac ttgttttaag taataaagct 3660 ttcatttcgt tccctccatt aactgtcata caccaatata ttatcataat ccttatatta 3720 aaatgtttga ttttatgtaa attatttata aattacattt aatatcgaat tattttacac 3780 atttcaatca atccgattca actcaacaac agccatttcc caccaacaac ataaaaaagc 3840 acccgataaa gtcgtttcac agcagtgcgg aactttatcg gatgactctc atttatattg 3900 tatatattgg tgttggaata gctttatccg tatcacatag caatacttct ttttccgtat 3960 caatatcgtg ttcgttcaat acttggccaa cactcatacg cgccaaatct ttcatattat 4020 tatcttgtga taaatgcgat aagtaaatac gtttcgtgtt acctgtaatc acgtctgtca 4080 tcgcatgacc cgcatcctca ttagatacat gacccatatc gcctaaaatg cgttgtttcg 4140 tcttccatgg ataacgacac attctcaaca tatcgacgtc atgattactc tcaaaaataa 4200 atgcatcgct gccacgtatc atacctttca tacgatcaga cacgtaaccc gtatctgtta 4260 aaatcgtaaa cttcttatag ttattatgga aaatataaaa ttgcggatct atcgcatcat 4320 gtgacacgtt aaacgattca 4340 <210> 70 <211> 29 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 70 atttcatata tgtaattcct ccacatctc 29 <210> 71 <211> 29 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 71 caaatattat ctcgtaattt accttgttc 29

    Page 18

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <210> 72 <211> 29 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 72 ctctgcttta tattataaaa ttacggctg <210> 73 <211> 22 <212> DNA <213> Artificial sequence <220> <223> synthetically prepared nucleic acid sequence <400> 73 caagctccat tttgtaatca ag <210> 74 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 74 cactttttat tcttcaaaga tttgagc <210> 75 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> synthetically prepared nucleic acid sequence <400> 75 acaaactttg aggggatttt tagtaaa <210> 76 <211> 23 <212> DNA <213> Artificial sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 76 gccaaaatca aaccacaatc aac <210> 77 <211> 23 <212> DNA <213> Artificial sequence <220> <223> synthetically prepared nucleic acid sequence <400> 77 accacgaatg tttgctgcta atg <210> 78 Page 19

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <211> 25 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 78 acgcaattgt taaaaatatg tgtcc <210> 79 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> synthetically prepared nuclei c aci d sequence

    <400> 79 tggcaatgca attcgtgaac 20

    <210> 80 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 80 ttccactccc aaaattttct ca <210> 81 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 81 aatcgagaat aacaagaaaa tgaga <210> 82 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Synthetically prepared nucleic acid sequence <400> 82 ttggcgaaca gttgctagtt <210> 83 <211> 26 <212> DNA <213> Artificial sequence <22O> <223> Synthetically prepared nuclei c acid sequence <400> 83 tctctttata atttgagctt ggttga <210> 84 <211> 24 Page 20

    GENOM.057CPl.TXT

    2018206754 18 Jul 2018 <212> DNA <213> Artificial sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 84 tggaaaaagt aaaaagagtg aaca <210> <211> <212> <213> 85 24 DNA Artificial sequence <220> <223> Synthetically prepared nuclei c acid sequence

    <400> 85 tggttataga aatggactcc tttg 24 <210> 86 <211> 22 <212> DNA <213> Artificial Sequence <220>

    <223> Synthetically prepared nucleic acid sequence <400> 86 acccggacat taattcaaac ga 22 <210> 87 <211> 46392 <212> DNA <213> Staphylococcus aureus <400> 87 aaaatatcaa aaactgcaaa aaatattggt ataataagag ggaacagtgt gaacaagtta 60 ataacttgtg gataactgga aagttgataa caatttggag gaccaaacga catgaaaatc 120 accattttag ctgtagggaa actaaaagag aaatattgga agcaagccat agcagaatat 180 gaaaaacgtt taggcccata caccaagata gacagcatag aagttccaga cgaaaaagca 240 ccagaaaata tgagcgacaa agaaattgag caagtaaaag aaaaagaagg ccaacgaata 300 ctagccaaaa tcaaaccaca atcaacagtc attacattag aaatacaagg aaagatgcca 360 tcttccgaag gattggccca agagttgaac caacgcatga cccaagggca aagcgacttt 420 gtattcgtca ttggcggatc aaacggcctg cacaaggacg tcttacaacg cagtaactac 480 gcactatcat tcagcaaaat gacatttcca caccaaatga tgagggttgt gttaattgag 540 caagtgtaca gagcgtttaa gattatgcgt ggagaagcgt atcataaata aaactaaaaa 600 ataggttgtg tataatataa aaggagcgga tttatattaa aactttgaat tcaaaaatta 660 ttgaaaggga agctacctta gaaattgaat ctatggctac aaatacattg aaaataaacc 720 cggacattaa ttcaaacgat acaaaaatgt cttttgatgg agaattggaa gtgtataatt 780 ctgaaaattt gagtaaaaaa atttcgttgg aaaaatacaa gttcaagtta aaggaaaaga 840 agtacctaaa agaggaggta aggttattca tcgaagtaat gtcaatgtga atgatttaaa 900 ggcataccaa cgagaaggtg gtgtgtatta ctttgtcgtg tatttaattg ttgagaacca 960 agtttatggt aaacaattac atcaattaga tctacaactt ttactgcaaa aaaaatagaa 1020 aactgtcact ataaaaatgt gtgaaattta aaatgaaaaa aattatataa taactgttta 1080 aaatatataa atgaaaagcg attacaaaac caagtagatc aagttaaagt aaagaaaaaa 1140 gaaaatgctt tatcatatat agctatgcct gaaaatattg tgatggatca cagaggttta 1200 ccattaaatg atttttatgg ctatataaaa attgattcat ctgaattaga tgtaactata 1260 ccaaacgaag tattaagtat ggaaaaagta aaaagagtga acaaaaagca gataacaaaa 1320 gaaggtaaat tattatttga aagtatggta ggtattgaaa cttcaaagga gtccatttct 1380 ataaccatag atgatatttt caaaattcaa acatttgaaa gtgataataa aagtacatat 1440 acaatgttac catttaataa attaaatata gccgaacaat cttttaatgt tataaacgga 1500 ttgtcgaaag ttggctaatt cttttttgat gaaattcaat tagtaataga acttttgaaa 1560 ttaatattaa tgaaataaaa gaaacaataa ataaattaaa aattaagtta tcagagtata 1620 gtaacttgct ttcgtttaat gtgagcctaa aacctacaga atttgataag caaatgaatg 1680 aaataaaagg tttattagaa ttattggaat ataaaaaatt taaagataat acatcattat 1740 ataatgtata ttctaatgaa tttatggata gatttgaagc tattacaaaa gaagaatctg 1800

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT tacaaatgcc aattgtgtac acattaacaa gagatatgat tgtaaatgta ctaaattttg 1860 atataaatgt tattaaagaa tgtgttgaat cagataaaat cgctattcaa tctggcatta 1920 aatgggagaa actaaataat tttgcattag aattaatcgc agcctatgat gaaactcaaa 1980 gaatcgattt attagaatta gctgaatata tattaaataa tttgctgaat tatgataatg 2040 ataaaatgtt tatgaacttg atcaaccaag ctcaaattat aaagagaaga aaaagtatgg 2100 tagattaaaa attgttaagc gacttatttg aattgaaaga taaattagtt gatatttata 2160 aggttgatat gaagaaattt caaaaaaatt ctggggaaag tgaaagggca gcttatagtt 2220 tcaatggtat tgcttttgat atattatgtg tcttattaaa taatatgaca gatgataata 2280 taccaaaagc aattacggat gaagatgtaa ggctgagaaa agatgcgata aaaaatattg 2340 atattaccca atatgcgaat tttattaaaa atgttaagaa tgatatagat aaaattgaat 2400 ttaaaccatt aaagttacat atacatgcac aaaaagcata ccaagatgta aaaaggtgtt 2460 tgattcaggc agtaaaataa acgataagtt acaattagct tctgaagtaa tgagtcaatt 2520 acctatagat aaacaagtgg aattaagtga caaaattgca cttgctataa atgaagttgt 2580 ttactcaaca ttttcagaaa gtaaatataa tgaacgaatt gatgaacaca atcaaacgag 2640 tgaaaagtca agtcaatatg attttcgata taattatttt gtaaatcaat taatagataa 2700 tgtaataaca gaagatatag atgaagagaa agcatttata tatgatagaa atgaacaatt 2760 agattggtta ttagttaaga tactaaataa agttcaaaga gctgcggatg gatggggaat 2820 gagaaatgct aaacttcatc acagaacaca aacatttaga gatatggaac attatttcct 2880 cagagatata tcgaaaatga tagataaaga gcttaacaaa aaggaaaact taaataagca 2940 atctaaaaaa tatgacttcg ataataagat aaaggtcata aatgacaata ttgagttttt 3000 taatgaagat gaacaaatta gaaaacattt actagagtta cgcaagcgat tagactttca 3060 ttctgcagca gtattagata agaaaaatca ttcacacata gggaatgaaa tgttccaata 3120 ttttatggat gatatgcagc aagttgtaac attgatagac cgatacatta ataagactga 3180 acattataat gatatgaaaa atggctatat taatgaatat aaatcatttt ataatgctta 3240 taataatgaa attgaagtga ctaagacgca cgaaaataac atcccaatgg caatgttaat 3300 gaagcaattt aagaatcaac tgttaaaaag aaggaataac cgaaaaagct ctaattgaag 3360 ttaagtagaa atttaataaa taattggtaa gctcaatccc tcatataaag ggattgagct 3420 tatttgcttg gtgggaattt ttttgaattt ttttgccact tcatcaacga cctctattta 3480 gtattaagat tgtcttgtca aaacgttttg aacaaatttt aagttgaaag tgagcgcgcc 3540 actttcaacc ataaaggaga agatttacat ggagacaaga gacaaactga tgtcgttgac 3600 tcagagtaac aaaatacagc aatggttaat ggacaaatca tctaaccaag atgaggttca 3660 acaattgcag caaccaattc agtcagccag ctagatcaac aatataatgc acttttagct 3720 gatgaaaaag ctaagttaga ccaatacgtg gaagtacatc aaggattgga atcattaaag 3780 gaagagattg aatcagaacc tattacgatt aatatcgata aattacccga tatcaaagca 3840 acaatgcttg aaagagccaa gaatgatgaa cattctgata agatcgaaaa gctatttgaa 3900 aggttagaac aggcattaag tggtacgaat cgattatata cgcaattatc gttgattggt 3960 acacgaacac atagaattac aactaaaaat tttaatcttc aaggcttacc taaagcagtt 4020 caacatacga ttttaccttc aaaatttaag aaggtgtata caatcgattt caactcattt 4080 gaaccttcgg ttgttgcgta catgactcaa gattcaaaac tgattgactt tttaaatcag 4140 aaagacggac tgtatgacgc attgctaagt gaattaggct tatcagatga gctacgagta 4200 tttgttaaac gtgcatttat tggttcgttt ctatttggcg gcaacttcca tagccctaaa 4260 ttcaagttga aacattatgt aagtgaagtg caatggttgg atgcggtcag ccaatttaca 4320 aaagtcattg aacttaagaa acaaatcgaa gagcataaaa ccatgcctat gccttacggc 4380 attgaacatg atatgagcgc attttaaggt agcagtatta tggcatttta tgtacaaact 4440 gtagcgagtt atattttcaa acacattcta ttggaagttt ataaagcgca gtgtacacaa 4500 aagagctttc aaatcatttt gccaattcat gatgccatta tgattgagtg cgacgatgaa 4560 gaaacagccc aaagtgtagc ccaactaatg aaaagtaaag ctaataaatt gtttaatggt 4620 gagtttgcgc acgtgacagt ggaagcatta ggaggtgtaa gcaatgaata atgatagagg 4680 tcaaagttta caaattccaa aatgcacctc actaacagaa ggctatatat acgttgcttc 4740 attatattct gtaatccaaa cagatttcaa tggtgatgtt aaacaccagt ttacgtatga 4800 aataaagata gatcagaaag ttatttatgt gaatcgtagt atttcaaaag atgctaccga 4860 taagcagtta tcaattactg attggcttaa acgtcatagt aattatagtt ccactcatga 4920 gaattataac ccttacattg atagaaagca tttaatctat gtgggtgtca atataacgga 4980 aactattatg ttcaagatgt agcaccatta gatggatttg gaggggtatt gtaatgaatc 5040 atattttaga aatgttaata aaattattaa aagtgggtat ggaggcaatc gaccgtaaag 5100 gtctgattgc catcctaaca agtagtattg gaaatgatga aatggatgat tctgaacaag 5160 ctgtaatggt gtataacgag cttatcgata aactacagct taacattcct aaagatgtcg 5220 actatagacc taacatatac agttattttg gtattcaaaa aaagccaaat gacacaatat 5280 tagtggaaat gatgataagt atttttaata tcaagcgttt tgattcagag ttgtttgttt 5340 tcaaagataa aggttggcaa aaggtaaatg aagatgaatt gcaaggactg atatctaaaa 5400 tgatacaagt gttgctagtt gattataagc cctcgttaag tattctaaag aatgtagtgg 5460 ttggcttaca aaattcaata gatgtagaag aactagttga gaataaacag tccattgcat 5520 gcggtcataa catgtttaat ctagacgcat ttgaagtggt tgaaaattct ataaagattt 5580 tctccgcaac acggttgaat ttagagttgg ttaaaagtga tgtcataact gaaaaaacac 5640 ctccacattt taatcgatac atgttagagt ttgctaattt tgattctgat ttacagtact 5700 ttctttttca acatatagcg gtgcttctta cagctaacac aaagtatcgc agagccttac 5760 tattatatgg tggatctaag aatgggaaat ccgtagttat taatttagtt aggtcatttt 5820

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    2018206754 18 Jul 2018 tctacagcga agacattgtg tctaaagcac agagcttggt gggtaaaaaa cttatggcaa aaaagattgt aaatgactta aaaaagttag aaggtaaaac acaagttgaa actactttgg gacttaattt tccatctgct catgcgaagg gtgaatatta tgttgaaaaa gctgaccctg aagaaatctt tctttacttg atgtatgtgt acctccaaaa tgatcgtgtt actgaaattt ttgtttctag taaatcagca agtattgaaa aacttataaa aatcaaacca ggatcacgaa aatgaagaaa taaaggtgag ttctcaggtt actcaaacca aactatacaa tggctacgat gataaaaaag agattcatga tatttcggaa gaaaatataa cagacgatga ggcattagat tttgacgatg aataatgaac aaattgaagc agaacgtatc aataaaggta agtactcata tgaaattata aatatatatt atccatatga tctaataaaa ggagcggtac attatgagta catctgagca atctgaacgt ggttattcaa aagttgtgaa aaatttcccg ggttatgact gtaaaaatat tgaaggtcgt ccggcaatga aaattgaaat ggtattaagt tggaaattga ttaatattat tcatgaattc aaagagcttg ttgatacatc caatgcttct ggagaagtac tagaacgttc aacactgatc agtaatgtca gagaggctat tacagataga gtgctcggtt aaaatgattt ggttatcgat gaaaatgaag acttggatca taataaagga ctcaaagcca gtactattaa ttaaaagcca ttttcagttt tctataaagg ttatgtcaga ttcaataacc gcaaaagtga taaaaatgat gtgatattgg aagaggtatt tgaccaagtt catgaaaaat ctattggtgg agatttctac cttcgtgggc tggtatgtcg tcggacttat tataaaacga attacatttg ttctttattc aatcgttcag atgctgaagt cgtcgaacgt gtaatcaatg atgtgattaa aaagattgcg tcaaatgtga aaacagaaat aaaatatgat attgatagtc aacaagaacg attattggaa ttgttcttag ctaaacaaag tcaaatgaat caacagttag aacaagcata tcaatcacaa gctgaaatac ttttaatgat aacacgattc agtgtgtatt aacttatgaa aatgttaatt gattcgattg tacgatataa aattgatgaa agtcttatcc ttttatgccc aaattccaat tcgaaatata taccactttt accacttagt tattagtgaa tatatatcat ctaaatgata tatcacatgt aacaatgaca ttagaactac aactcaaaca ggatgaaaag tgggaatgtg aatctatcga atatgtaagg cttggggcac tcagtaataa tacacttcac gaaagtaata tctacccttt catcggctat atcgatgaaa atcacgatat gccacttttg gatcaacgat acttactaac aaattacaca attagtaatc acaatactaa aacgaaagga agtctcttat gaatagatat actgcattac aacatcaatt atggcaattt gaactagaag caatagatta ttttcatgta tatgtaaaac acaaacaaga acgtcctgag aaagatctca atattaataa ggtctacatt ctatgtcatg ttactacccg aagaatatta atgtacatta gaaactgaag caatatttag aaaacatggg acaatgataa aaagataatt ggaacgaaaa aattagattt aacgactcaa gaatttggtt ccatcaattt tgtgaatcta aaacatttag aaaccctcta tgatgcctat gcagccaagg agtcagatga agtaatagaa caactcatta accccgaaag ctcgtcgcaa

    GENOM.057CPl.TXT ttaacgagct ttaaggccgt tttgacaaag 5880 gtgacgaaat tggggaatca aggattcaag 5940 tatctgttga accagtacac gttgatcgta 6000 atttaaaact tgcttttggt acaaatgcaa 6060 cactagagcg tcgaattgct gttattccat 6120 acttaattga aaagttacag gatgaaaaga 6180 ataagcaaat tgtaaaaaat gatatcgagt 6240 ctcatgattg gttaaatttt ggatatgaat 6300 atcagaaagc gtgtattaat ttactcagaa 6360 tcaaagtatc cgagttaaat acaagttatt 6420 attaaacagt taattcaagc aaactttgat 6480 tattggattg atttaggttg gaaagaagcc 6540 aaagataata ttatttcatt agataaaaat 6600 gaagagaatt tagactttga ttgggaggac 6660 atttgtagaa gtgtttgtgc ctatcataga 6720 tgattaagtg gtaaaagtga taaaaagaaa 6780 tgttacaaga ccgatggtct gtagcaataa 6840 agaaaattgc actgtactca cgtgtaagta 6900 tccatgaaca agagcaagtg ctcatcaaag 6960 atgagacata tactgactca ggcatttcag 7020 aacgtctatt acaagatgtt aaggataata 7080 atcgtatttc tcgctcaatg agagacgtgt 7140 acgtaagtta tcaatcgatt tctgagaata 7200 tcgttacaat gtttgggttg ataggatcaa 7260 aaatgtcgat gaatgctaaa gcacgtagtg 7320 acaagttgaa actcaatcca cttacacaga 7380 ctaatatcgt acgtgaaatt ftcgatttat 7440 ttacatcagt actgaatcaa aaggggtatc 7500 atggtgttaa atatattttg aataatccag 7560 atcaaaattg ggctgtacag cgaagaagtg 7620 tcaaaggtaa acatgaagcc attataagtg 7680 tagcttctaa aagttttaaa ccgggcagac 7740 tcaataaatg tccagagtgt ggcaataata 7800 aaaagtcgaa agaacggaca atcaaacgct 7860 ggagttctgc ctgtcatagt aatacgatca 7920 ttcatctaaa tcgtattttg tctcaaccgg 7980 tagaaaaact gaaacaaaag catagtaaac 8040 tagaaaaaca aaaagcaaaa gttaaaacac 8100 atgatgaaat ggacagtgaa attttaaaag 8160 aagtattaga ccagcaaatt aaagaagcaa 8220 ccaattttga taagttaaaa ggacgactca 8280 ttagaaaagc cacacccgaa gctaaaaatc 8340 aaattacgac agataaacag gtgaaactag 8400 ctcaatcttt gaaaaaagat tgggggtctt 8460 tggtcaaaat gattatttca tcaaccaaat 8520 aaaagtgaga gaaatgaaat aaaaatcaaa 8580 atacatcaac caaatacatt aggaggttat 8640 ctatataacc aatttattca acctaccaaa 8700 ggaaatcgct gatgatatcc tacctgacca 8760 aatacttcaa acctatacct actactctga 8820 cattctctac tatcagaaac agctcatagc 8880 ggatttctta tacctacaca acaccatcat 8940 aggaggacaa taatatgcat aaatatatca 9000 gtgaaatcat catttggatg aaagagtcag 9060 atcacccgtg gtatcgccaa caacttacct 9120 gtagcacaac gtgaaaacga acagtccaag 9180 ttccagttca acatgcacaa taatcaatta 9240 tatgtcaaaa ttcataaagc gaattattcg 9300 atccgagaat atgatgtaga ctttttctta 9360 ataggaggca tcaatcatgc agaatataca 9420 tgacgataat caacatcgtt acttactcaa 9480 tcagttataa cttgttatcc aaattttgaa 9540 ctaattatga acaaagttgt agaaatggat 9600 tactctaata ttacaacacc gattaatttc 9660 gataagcata cagatattca aattatgaag 9720 atgttgaaac cacataagaa gaaagtgaaa 9780 gtggatatat aaacaaaaca ctatttaaaa 9840

    Page 23

    2018206754 18 Jul 2018 taattataca aaagcgaagg tatttaatgt actaatataa aaattacatt cgagaaatta taaatttata aaagtagtga aattatgaga tttgatgaca atattataga tatcgttgtt tggaaatgat gaaatgttaa ataaagaact tgttaaggga gtaaaatatg acattaccaa atgtgtattt cttgtagtac aagtaggact agtatatctt gaaattttag ggtcttattt cggtaaagat gtagcaaaaa ttatagaaaa ataattatta aaaatagaac atttcctacc atattttttc taacgaaact agaatacacc ggtatagtcg tattttgtca ctttccaata atctgaaaaa aattttcaaa gattttctta aacttgtttt ttaacatata acttaaagga tacgaaagca gatcatggat aagtacaccc gttataatat tgaacaagat aaaagttaaa atatttatta tattgctcca aaattaaacc cataaaacat catgcaaata aacgaagtaa taatgaaaat cgatcaacaa taacaatcgt atctaaatac aatcaaaaac ttttaaatct aattaattta acaattaatt tgggagatct agatacccaa taaatagaac cacagtataa aatctttaaa caaatgaagt aataattgag ttatttgtta catagcattt cgatgtaaaa tttgcaaaat atacagggga ttatatataa atatggaaag tacaattgat ttatctgaat tattaataat attaccactt ttaggtctgc tagatgtaaa gtaccaagct tctactcaaa aaattatggc acaagaagtt caaagtaata ttaaaagccc acgtattcta gataaggttt gtgagatatc aagtatgtta accgttacca atgttgaaag taaaagtggt agtaattcag ttagtgatga agtgcctgat attatgaatg ataatacagg aaaacaagtt gcaccaaaac taggattggt tatcgcatta ttaataattt aaacagaaga agaagttgaa aatgaattgg ttgattaagg agggttttat ctatggcaaa tcatgataaa cctaaatcga cgataagtga gttttctaat gctgaaaatg aaataaaaag tggtaagagc atactttcgg caaacattgc attaattata gatggagata tgagaaagcc taatagtggg ctatctaatt taattattaa aactagagta gagaatttaa acgttttaac attaattgct tctagcaaat ttgcaactat cattgtgata gacacacctc cgattaatac agtaaaaaat tgtgtgcttg tcatagatgc agcgaaaggt ttacttacta aagccggtgg gccaattgat aaaaattcta gctactatta atacataatc atattttggt tgatgtagat gagttgctta aacaagccca aagtgaaaat cttcataaga gatatagtaa tgatattgaa aataactcag aaataaaaaa attaggactt acggatcaaa ttatagaagg tataaaaaat tatttgttaa tagaatttcc tagcaatgag gagttacaaa caatgggata tattccaatc gttcaaaatt tagatttact atttgaatta gcttcttcat tattgggaga ttttgggaat gatagtaatt tagcacattt tattgcatca atgctaaaac agttgtttaa tgatagaaag tatttaaaaa acgggaagtt agttttaaca caagattata agcagaaaaa atggtttggt aaagtgacaa gtatttctgc gaaattgcga attgttacat tttcagtatt tttaggatat tcaatagatt tattagtatt atcatctgtt tatgtattta atttatatca tcgagcgtgg gttttaaaag cggttacaag ttcaatagtg agtgaaagtc catttctaag gttatatttt

    GENOM.057CPl.TXT attttaataa gaaaaagcaa gaaaaaattg 9900 tattaaacgg aaaacaagtg atttgttgca 9960 acgtatagct gtattgattg ctacatttat 10020 gtatggagct atggcgataa gtatatttgg 10080 taattcactg caagaagcga tatgaaagta 10140 atttattaaa ttattattaa tgcaattttt 10200 tgtatctgga ggtagtgttc tacttgcagt 10260 taaaaggatt tttacaatta aatggccact 10320 ttactttggt gaacctgtat aaatcagaga 10380 tttcatagta ggaaatgttc tatttaattt 10440 tactttgata acttaattaa cataagtaga 10500 tttacaaact atcttcaaag tcaatgcttt 10560 aaatttacga aggaatgact tattgtgaaa 10620 gataatatat tggattgtgt ataccgattg 10680 aaagtaatta agtatgatta taaatcgaaa 10740 atatgtattt tatgtatgat attttggctg 10800 gttactttta gcaatatctt aaattttaat 10860 gttgttaatg aattttgatc gctttgaaat 10920 atcaatcgtc acacgagcat taaatgaaaa 10980 atattgattt aatttcaatg tttgattttc 11040 atatcaaaga cattaataaa atgaaattaa 11100 attatatcag tatgcttata taatttttga 11160 aaaagtgtag ttaaattatt tttcttgaaa 11220 ttcacttttt ataagtaaat ttaaaaagag 11280 tggaaaacaa gaaaggaaaa taggaggttt 11340 tattaggaag agtaagaaaa aatatgaaat 11400 taattagtgc aataatttct tttttctttt 11460 tattagtgaa tcaaaaagga aatgactcac 11520 ttcaactagt aaacacatat tcagagatag 11580 ctaaagaatt agatgataaa tattcacgta 11640 accaagcaga gtctcaagta ttaaatattg 11700 aaaaaattgc taataaaata gcagaagtat 11760 ttgataatgt ttctgtttta tctacagcgg 11820 ctatggttaa tttagttgtt ggtttagtaa 11880 ttataaaaga agtgtttgat aaacgtatta 11940 tgatacctgt actgggttca atccaaaaat 12000 aaagaaaagc actatatcac cactatatgt 12060 aaaatttaga ggtattcgat caaatatcat 12120 cttgttgata acttctgaaa aatccgcatc 12180 agtaacatat gcacaggcag gttacaaaac 12240 tacacaacat tatatctttg atttgcctaa 12300 taaaactaca tatagcgatt caattaaaga 12360 agcaggacca acaccgccta atccttcaga 12420 atttaatgaa cttttgaatc attatgactt 12480 agtaacggat gctcaagtat atgcgcgaat 12540 tgaaaaaaat aataagagtg aagttaagaa 12600 gaaagtatta ggcgcagttt taaataaaat 12660 ctactatgga gaagattaag aatggttgat 12720 gatggaccaa aaagcattaa tgaagcaatt 12780 gtaacagata tagttgcaac acctcaccat 12840 aaagtgaaaa taaaattaaa tgaattaaaa 12900 aatttatatg ttggacaaga gattcgtata 12960 aaagagattg aaggaattaa tgaatctagg 13020 attccttatt atacgaatca attattctat 13080 attgcgcatc cagaacggaa taaagcgata 13140 ataaatggtg gtgcattaag tcagattaca 13200 aacataagaa aattatcatt aaaaatgata 13260 gatgcacata gtataacaaa tcgacctttt 13320 ttaaaagctt attatgagga attagaaagt 13380 aatgaaagaa tttccaaaca gataccaact 13440 cttttataga aaaagtgagt gaggggatta 13500 tttttaatat taattattat agattcgttt 13560 gcaatattag aaccgtattt taaaggatat 13620 atattgttgg tatcacatca tatattcgca 13680 gagtatgcga gtgtaagtga attgatgtca 13740 gtaacacttt tattagtttc attacttata 13800 ataacgtgga tgatgcattt gctattgatt 13860

    Page 24

    2018206754 18 Jul 2018 ggtggctcta gattgttttg gcgggtttat aaaaaagcca cattagtagt aggggctgga ttaagaagcc aagatatgcg tatgcaacca caaaaaatga ctattactga acgtgttaaa ctagtaaaaa aatttagaat aaaaaagatt aggttaaatg aaattaataa aatatgtaat aatatagaag atgtgttatc tggagaatta gaagatttac ttggaagaga tccagttgaa acgaataaaa caatattggt aactggagct caagtaagta aatttgatcc tcaaaaaatt tattcaattc atcaagaatt aagtaaaact atagctgatg tacaaaataa aacacgtatt gctgtttatc atgctgcagc acataagcat gctattagaa. ataatatttt aggtactaaa gtaagtaaat ttgtaatgat ttcaacagat gcaacaaaac gcattgctga aatggtaata agttttgtag cagtaagatt tggaaatgtg tttaaaaatc aaattgaatc aggtggtccg tatttcatga ctataccaga agcatcaaga ggtggcgaag tatttgtgct agacatgggt aatttaatac ggttgagcgg taaaaaagaa agaccaggag aaaaattata tgaagaatta gtatatgaaa aaatttatag aggcaaagtt attgtggaag atttaataaa taatttctca taaatataaa atgtatattg gagttttaaa ataaattttg ttacagtatt atttagtata ataggtttta gagttgttac aatatcatta ctttacaaaa aaagaaaagg ttttttatta tttggtgtat ttgtaacaaa tatattttta ttatcttggt attatataaa tacatctaat acttttacaa ttttaagtaa ttttattagt tttgatatta aaagtaaagg aaataattta ggatttacta tacaatttct tttttatatt ggagattatg taagtagcat acaagaatta tcaattggga ttgcatttgc attttctaat attatattaa ctccccaagt gttatttttt tatccaattc tatctgcact tggagtgtta atgataatta caattgtttt tacattattt aatatggata gtagctcaat tgaaaaggtt ataggctaca cactgcgccc tttaggttat atagtttatg gcaaaagtta cttagcacct gggttacaac ctgtaaacta tgaaatggtt atgggtttta atgtaatagc agaagcgtat gtaatggtgt tattagtgct tttactttgg ctgtcaatgg gtactgcaat tgtaagtgta ttcgtacctg catacatatt aattatcatt agttatttaa aaaaagaaac gaaggccgat tgttgctaat atactgtctg cattgtgcaa aggaacacct gaggatgtag gacgttataa tttatttata tccctgaaaa taaggtctgt tgaatatata tcagcaattt tatcattaaa tgtttatgta ttaggaaatg gtgatttaac atttgaaaat ataaaagaag taccttatgg actcggaatc tcaatgggta tttataatat ttctttttca cacaacttga atatggcact atttgctatt atcgatagat ggtatctaag taacaacatt gcaaagttta aggagatttt tgcgttagga tcattaaata caggaattcc atatacatta ggtatatttt ctacaattgc aaattcaatc agtcaagttt ttttacccaa aattgaattt gaaaagttaa ctagaaaaat ctcggtaata ttgagtttgt ttttaggtga atatggtgaa aataatataa tattaatcat tggtattttt ttggggacaa ctataatagc ttctctaata ctattgtttt gtattttgat tttattaggt gctgctttaa ctattactat ctatttttac aaaaggatat tttgaggtgg

    GENOM.057CPl.TXT agaaggtatt ttattgataa cgctgtcgaa 13920 caaggcggat ctgttttaat tcgtgaaatg 13980 gttttagctg ttgatgacga taaaaacaaa 14040 gttcaaggtt atgttgaaga tataccggaa 14100 attattgcta taccgacatt aagccaaaaa 14160 attgagggcg ttgaattatt taaaatgcct 14220 gaagtcaata atttgaaaaa agtagaagta 14280 ctagacatgg cattaatttc aagagaatta 14340 ggaggatcaa taggttcaga aatttgcaga 14400 attttgttag gacatggaga gaacagtatt 14460 tatggaaata gaattgaatt tgttcctgtt 14520 ttagaagtca tgaatgaatt taagccatat 14580 gtaccattaa tggaatacaa ccctcatgaa 14640 aatgtagctg agtctgcaaa agaaggagaa 14700 aaagctgtaa atccatctaa tgtaatggga 14760 caaagtttaa atgaagataa ttctaagaca 14820 cttggatcaa gaggatcggt catacctcta 14880 gttacagtaa ctcaccctga aatgacacga 14940 cttgtattac aggccggggc attggcacaa 15000 aaaccagtta aaatagttga tttagctaag 15060 gaagatattg gtattgaatt ttcagggatt 15120 ttaaataaaa atgaaattca tccgcagcag 15180 gaccactata ttaaaacgga agttgatttg 15240 aaagagaagc tcttaaagat agcaaataga 15300 atgaaactaa agtacaaagt aattttaatt 15360 tttacattca tcggttattt aaataacttg 15420 tgtataacta tagctatgac cgtgtactta 15480 gtttatttaa tatatttatt tttaactaat 15540 gccaatcctt tagtggagta tcacggtgat 15600 ttgtttagca ttgctacttt tgcgatatta 15660 gtgtttagca aaataaatcc aagtagaaag 15720 ttctactaca caggaatatt atttatcatt 15780 ataactggtc gattagcaat taatacttat 15840 ccaatgtata cgtacggtat attctttttt 15900 gtaaaaaaaa cacatattaa atatctagta 15960 ttaataaccg gaaatagggg agaagtattt 16020 atagtaagga attataaaat taaatggtgg 16080 tttgtaatac catttattaa agtctttaga 16140 gatataaatt ggttttcttc acttgttgaa 16200 gtaactaggt ggattgacgg tggggaaagc 16260 attcaaaata tattttcata tattatacca 16320 ggttacggtt ttaggtatag actacctggt 16380 tacaatggtg caattgttgg agtattgatt 16440 aaatttacaa attttaaatc ttttgaaatg 16500 ttaatcaata atataagaaa cgcattttca 16560 gtaatagtga ttatattgct gtttatagat 16620 taaagtggtt aaaaatttta attatatgtt 16680 atttttaatt ttactagtaa tagttagatt 16740 ttatgcttta gttataactg ctccaatttt 16800 aattgtcacg aatgataaat atagtccaaa 16860 tattattact ttaatatttg ttgcaatttt 16920 tactatatta atagtatcgt taataaaatt 16980 aatatatcaa aaaaatgaga gtctcaaatt 17040 actaagttta attttgtttt atattatata 17100 tttattttta gtaatatcct gtatattctc 17160 taagtattat aatataaaac tacactataa 17220 tattcttaca atacctcttg ctttttcaag 17280 tagaatagta ttagaaaatc tatttggaaa 17340 gtatgtactg gtaatcggtg ggttattcgc 17400 attaagaaaa ttatataaag atgaaaaaaa 17460 ggtgtttatt ggaattttta ttggtatgtg 17520 ggccttgtta tcattgttat ttggtaaaga 17580 tctttctttt ggtttgcttt ttatactcag 17640 cactggaaag tataatgtga attacaaaat 17700 atttagtttc ttattaatac caaaatattc 17760 ttcacaattc gttgctttaa taagctatta 17820 aaaatatgaa aaaattattt ttaaagttaa 1788Q

    Page 25

    2018206754 18 Jul 2018 tgaaaaggaa tctatctgaa gataagataa gtaggttttt aagtgttgat agatcaacat gaaatcatgt aacaataact agtggtgtaa tttttagaaa aaaatatcct gagatagata ttttcatagg gattaattca ataattttgc taggtgctgg gagtgtggta acgaaagatg ctgccaaaaa aattaaaagt atagaggcct acacaaaaaa acttaattat aatgaaaaga ataggtataa ttaatgatta aagttatgca agaattaaga actatggata caatgaaact tgctacatca ggaaaaaggg gcgaattaga acattattta gatattaaaa aatttagttt gaaaaatata gatgttgtac atagtcacat ttctttttca gcaaatgtaa gaaatagaat agaacaatat aataaaataa gaaaagctag ctttagtacg aaaatcttat atgtaagtaa actttttccg aaaaaacata aaactattta aaattttaaa aaagaggaaa atagttttat ccaattattt ttgttagatg taatagaaat aattactttt gttggcaata ttcaaactga tgaaagaggt ttaaataaaa atattaaggt tttaaaaacg agtgaatatt ttttgtttcc gatagaagcg catcatcaca attgtattgt agtaaatcaa tattttaaag actcttcatt ctcaactatc aaaaagctaa tttcaaggaa ttttgatatc aatatgacta cacaagaatt gatgaaggga ttgattttca tgaaaatatt acatcttgcg aaaaaactaa ttaaacaagg tgattattat tcagtttctt tgaaagagga cacttttaat aaagtgaaat tagaaaatta acaaccagaa gtagtagtta atttagctgc tccaaggacg tatattgatt ctaatattgt gcattttaat attcaaaatt taatttatgc ttctaaacca tttagcactt cggataatat taaaaaatca aatgagctaa tggcacatac aggattgaga tttttcacag tatatggtcc atttacaaaa gcaatcgtaa atgatcaagc gagagacttt acttacgtgg atgatattgt agcgtcccct aataaagaat ggtcaggggc atataaagtc tacaatattg ggaacaacag tatagagaat aaattaggca aagaagctag tgtacctgaa acttatgcaa atgtagatga aactacaatt caagatggtg taaataaatt atgaagaaaa agggtgtttt aatatgcaat aatataaaga taattattac tcaataggct ccatttttga taaaatgctc ataaattcaa ttaataaatc gaatggagaa aaagtgaatt aatctctaat ttttaaacat aaaaaaatat gtgatggtgt tttaattagg gtaccaagtg aaaaaatcaa taaaccttat atggtggaag ttcatggatc aatatttgga aaaattttat cagtgaaaaa tgctagcata gcgatttatg cttgtaacgg gaaagagttt aaaggcattt agaatttaga tattgggaat aaaattaaaa ataaaggaca taacgtagct ataaaatcaa ttgaattaga atttgtgggt gatgggccca acaatgttga aaataatgtt atatttaaag attggtttag aaatttagat ttgtatattc caattgtgga agcaatagga aatggagtgc cggatagtgt taacaaagaa tatttgttta taattaatag atctattttg tctaagcaat aaaatatttc aggttacaac ctggaaaata attataaaaa aataataaat gatttttatt tatatatata atcattcacc aataattttc atattcatga aacaaagata tactaaacat tgtaatgatt tatttgaact tcaaaatcaa aaaaatagtg aattttattc tgaaataatt

    GENOM.057CPl.TXT ggaaattggg tgtacaagtt ggaaatgatt 17940 ttggatctga gccttacctg attcaaatag 18000 aatttgctac ccatgatggt ggggtatgga 18060 attttcatag aatatttatc ggtaataatg 18120 caggagtaac aataggaaat aatgttgtag 18180 tacctgataa tgtaattatt ggtggtaatc 18240 atgaaactaa aatattagaa aatgcggatt 18300 agatatattt attaaataaa ttcaaagaga 18360 tatatttagc agaatgaatc gtggcggtgc 18420 attaaatagg gagtttgagt ttcatgtatg 18480 tgatgaatta gaatctatgg gtattacgat 18540 tcctttcaag ttcataaagt tattgaaaaa 18600 actttttatg agtggattga ttcaattact 18660 aacacacttt agaacttcca aagatagtaa 18720 aaataaagta ctgaaagcca ttatagaaat 18780 tatagcaaat aggaatttaa tctcaatgaa 18840 caatggattt gaaataagta atataaacaa 18900 ttatgtcggt aggttcattc atactaagaa 18960 tttaaaaaaa gaatttaata ctaacattga 19020 ttatggaaaa aaattcttga gtatagcaaa 19080 tattggagaa gtgaataacc cattagatta 19140 tagtgaatta gagggattac cgggagcatt 19200 tatatcttcg aatataaaag aaaattctga 19260 tgaattagaa ttaattccaa aaacttgggc 19320 aaagcatata agttttaatg attctaatgt 19380 aaaagaaatt tatatgagta aaactttata 19440 aatcacaggt acagcaggtt ttattgggtc 19500 tcattacgtt ataggtgtag atagcataaa 19560 tagattaaaa tcaataggga aagagaattt 19620 tgacgattta tctaaagtat ttgtagatga 19680 tcaagcaggt gttagataca gtattgagaa 19740 cggttttatg aacattttag aatgcagtag 19800 ttcatctagt tctgtttatg gtgcaaatac 19860 tgatcatccg ttaagtttat atgcagcaac 19920 gtatagtcat ttatacaatt tacctacaac 19980 atgggggaga ccagatatgg cgctatttaa 20040 tatagacgtc tataatcacg gaaatatgat 20100 tgaagcaatt agtaggcttg ttaagaaacc 20160 cgaccctgac cctggttcct catatgcacc 20220 tccagttaga ttgatggaat ttgtagaggc 20280 gaaaaactac atggatttac aaccaggaga 20340 cttgtttaga gatattgatt tcaaaccaga 20400 tgttgattgg tacttagaat attataaaaa 20460 tactctttgt acatgatttc ccagttgaaa 20520 tctctcacaa aatttggaat cgatatttaa 20580 gagtgaaaaa tgtagataat ggggaaatta 20640 tcaaaacaat agatagctat aaatcaccta 20700 ttgaagccct tacaatttct atcaagaaaa 20760 ttttaggatt tattgcagct ctaatatgta 20820 tagttggtgc agcatttgac gcatattggt 20880 cgttacctat ggaatattta caaaaaaatg 20940 taactaagaa atatttgagt aacaaatatc 21000 caaacgtaca atctgtagaa aaatttaata 21060 ttggacttat tggatctacg tttgttgatt 21120 taagtaattt ggtgaatgaa ggttataaca 21180 gtaagaaatt tatggaaatg gctaaaaaat 21240 gtaaaattta tgacaagaca gcgttaaata 21300 aaccaagttt aacagaggga cattgtcgag 21360 ctacattagc gtctaatgct ggtggtaatt 21420 aaccaaaaga tgtagttaaa ttaacaaaac 21480 atcgagaaga aaatgtttta gaaaacaaaa 21540 ttcaaataga aagagaaaaa gcactactta 21600 tagcgaaagg aataaataaa aatgcttaat 21660 caaaatttaa tggtttcaat aaagggtaaa 21720 tattatgaag aaataaagag acttagagag 21780 agatttgaag aattttataa ttatatcaaa 21840 aaaaaaaata atctaagcgg taaaaaaatc 21900

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT actgttgcaa atataaacca attgcctgaa attacgaaag atgatattag aaaaaatgtt 21960 gataaaatta ttactaaaaa gaaaaataaa cttataaaaa tgggcactgg cggttcgact 22020 ggtaaaagta tggtttttta tactaatgca tatgatatgt ctagaaaaat agcttacctt 22080 gattatttta aagaacaaca tggggtatat aaaggtatga aaagagttag tgtaggtggt 22140 agaaaaattg taccaattaa acaaaaaaag aaagtatttt ggcgatataa taaaccacta 22200 aatcaattaa tgatatctgc ttatcatgct gatggtgaaa atcttaaata ctacattaaa 22260 aaattaaata aatttcagcc tgaaactttg gatggctata ctacagttat tcataggatt 22320 gcgagatata ttttagataa caatatagaa ttaagtttta caccaattgc tatttttcct 22380 aatgcagaaa ctttaactga tttaatgagg gatgatattg aaaaagcttt taattgtcca 22440 gtgcgtaatc aatatgcttc ttctgaagga gcacctttta ttacagaaaa caaagaaggc 22500 gaactagaaa ttaatgtagc tactggagtg tttgagtgta aacaaattca tggtaatatc 22560 tatgaattaa tagtgacagg tttttatact actactacac cattattgag gtataaaatc 22620 ggagattcag tagaattaga aaatgagctt cccgtaaatt atcaacaaaa agatataaaa 22680 attaaaagaa ttatcggtcg taacaatgat tttttacagt ctagagaaaa aggaattgta 22740 actaatgtga atttgtcaac agcaataaga tttgttgaga atgatgttat tgaatcgcaa 22800 tttgtacaga atgatattga taacattatt gtgtatttag taattagtaa tgatgcggat 22860 aaaaataata ttataaagaa attaaaatat gagttgaaat tcaggtttgg tacaaatact 22920 aatttccatt ttgaatttgt taataagata ccatcaacac ctggtggaaa aaaaagattt 22980 gcaattaata acattaaata aggggataag aaaatgaata gaaatattgc agtagtaggt 23040 ttaggttatg taggtttacc agtagctgta acttttggga ataaacataa agtaatcgga 23100 tttgatatta atgaatcaag aattaaagaa ttaaaaaata attatgatag aacaaatgaa 23160 gtaacagaaa ataaattaaa aaacacgaat atagaatata cttcaaatgc agaagatttg 23220 aaaaaggctg attttattat tatagctgtg ccaacaccaa tcgataagca taataaacct 23280 gatttattac cattattaaa agccagtgaa actgttggga aggtaattac tccagacaca 23340 atcgttgtat atgaatctac agtttatcct ggcgcaacag aagaagaatg tgtacctgta 23400 ttggaaaaat attctggact cgtttgtggt aaagattttt ttgttggtta ctcacctgaa 23460 agaattaatc ctggggataa ggtacatact tttgaaacca ttactaaggt tgtatctggc 23520 caaacgcttg aagtattaga aatagttgca gacgtatata gttcagtagt cacagcagga 23580 gttcataaag catcttctat taaagtagca gaagcagcaa aagtcattga aaacacacaa 23640 cgtgatgtaa atattgccct aatgaatgaa ttggcaatta tttttgataa attagatata 23700 gatactaacg aggtattaaa agcttcagga acaaaatgga acttcttgaa ttttaaacca 23760 ggattagtag ggggacattg cattggtgtg gacccatatt atttaacaca taaagctcag 23820 gaagttgggc accatcctga agtgatttta gcaggtagaa gaataaatga taatatggct 23880 aaatatattg cttctaacgt tattaaagag ttattgaagc aaggattaga agtacaagga 23940 gcaacagtta atgtgctagg tcttacattt aaagagaatt gtccggattt aagaaataca 24000 aaggttattc atattattga agaactgaaa gagtatggat taaacgtaac agtgaatgat 24060 gttgaagcgg ataaaaatga agctaaaaag ttctttggtt tagatttgat agatacaaaa 24120 gaattaaaaa tggtggatgt agtgttattt gcagtgccac ataaagacta tatggaaaat 24180 aaaaaggatt atatcaattt agttaaagat tgtggcatag tgtttgacat taaaggcata 24240 atcaatagtg atgaacttaa tgtaagtcaa cgattatgga gattataagt gtaaaattac 24300 attgtgaggt tttgtatgaa aaatcaaaaa atatttcatt tagttactgt ttctaagagt 24360 attccactta tgagaggaca aatagaattt ttaagaaaaa aaaatatgga tgttcacatt 24420 gtttcgagtg atggtaagga attaaagcag tatgataatg aaatagctca tgttatacct 24480 atgaaaagag atatagcatt attcagtgat ttaaagtcat tattaaaaat gatattacta 24540 tttcacaaag aaaaaccatt tattgttaat tctggtactc caaaagcagg attaatagga 24600 acaatagctg cgtttattac ccaaagacct attagaatat atactgtgag aggtttaagg 24660 cttgaaacag ttaaaggatt caaatatttt gtattgtatt tgatggaaaa gatagcaatg 24720 ttttgtgcaa ctgatataat agcaatttct gaaagtttaa agcataaaat tattacatct 24780 aatttggcta aggaaaataa aattactgtt ttgggatttg gtagttctaa tggtatacaa 24840 tttgaaaaat tccaattaga taacaataaa ttagaagaaa aataccataa attattaaat 24900 gataattttg ttattggcta tgtaggaaga attgtaaaag ataaaggtat acatgaatta 24960 attcagtcat ttaaaattat tgtaagtaaa ggatataatg tcaaattgct tgttattggt 25020 agtttagaga cagaaaattc tattgatgaa tctgactatt tatttttaac tcaaaatcct 25080 aatgtagtac taatcaagca tgtttcagat ccaatttcat tttataataa tatgaatgta 25140 tttgtttttc caactcatag agaagggttt ggaaatgtta gtatagaggc tcaagcactt 25200 gaagtgccag taattactac taatgttaca ggcgctattg atactgtagt aaatggagaa 25260 actggattta ttgttgaaaa aggtgacttt aaagcaatcg ctgaaaaaat tgaaaaatta 25320 attaatgacg agagtttaag agaaactatt ggtcataatg gaagaaagag agtggaaaat 25380 aaattttcaa gccaaattat atgggaagaa ttggaaagta tgtacaatac ttttctaaaa 25440 gaaagtgagg gaaagtaatg aaaagaatat ttgatatatt tagttcatta tatgcaatta 25500 ttatattttt gccgctgctc tttctagtgt ctattgcaat taaaatagag tctaaaggtc 25560 cgattgtatt taaacaggac cgaccaggcg taaagaacaa attatttaaa atttataaat 25620 ttagatctat gagacaagat accccaaatg tagcaactga taggttagac cctgcagatt 25680 atattacaaa aactgggaag ttcattagaa aaacatcatt agatgaatta ccacagttat 25740 ttaatatttt aaaaggtgat atggcagtag ttgggcctag acctgcttta tataatcagt 25800 atgaacttat tgaaaaaaga actaatgtaa atgttcattt ggttaagcca ggattaactg 25860 gcttagcaca agttatgggc agagataaca atacggacga ccaaaaagtt caatatgata 25920

    Page 27

    2018206754 18 Jul 2018 agttttatgt tgaaaaccaa tctttcaaat aaaacactat atcttctgaa ggggttagtc aaatggattt gtaggtaatc aatttcaatt tagagtcagt ttgaaaaata atgattggaa cattcattta gcagcattgg ttcataataa gaatacgaat taccatttaa ctagagaact tcaatttata ttttttagta ctatgggtat atgtgaaatc actcaattaa ctccatataa gttagcagaa agagatattc aaaaattaat accgccaatg atatatggta aaaagggacc aaatttatca agaatatttc ccaaatatca cttatataaa catattttac acttattgaa gaatatggaa tatatgaaca ctaatactgc atcgagtgaa cttatagaaa ttccagtgcc aaatattgcg aacaaaatat atggaaattt aataaataat atgcattttg acaattttaa aattatatga taaaagattt gttatgataa tgttataatt ataccaatat tattattatt gttttaaata gcttaattaa tgatctacta ttttcgatta atgtgaaagg tcaaaaaata cactaaaatt gtcggtagag gtacataaga atcgtacatg gcagtaaaat ctattgaaaa tgcaacgatt aatttagatg gtgatgaaca gtgagtaaca gtgattttta tccccaatta tggatggtaa agaatcttca gcgtttatac gaggaaatag acaagcgaga caacagcacg tccaacctct atcatgagaa ccaattcaat gtcgacttca ttacttctat cctggtgata atttgaattt aaataaaatt ttagtaaaca tatagattaa aatatatgga aacacagatg cagcatttga gttttggagg agttggtatt atatctaatt gaattggcac atataattta tgaagaaaag ctattttagc catttataca ctaatatggg gaggcgtatc ataagtaggg atttggctaa aaaagactag ctgttcatta cagttttcat gtgtgtattt ttaaatgcca gtctagaatt gttgtaccaa tttacataat tttcaaattg catttgtttt acaaattctg ctgcgttatc ataaggacaa tctttggtac gaacttcatc tatcaaatga ttattaaatt tttattctgc tgattgcttt tgatactata ccaacaattt ttctattaaa tagatctata acttttacgt atgttaaatc acttactaat tcattcaaat gatttttaat ttgtcttgta ttatgattgc acgttctacg tttgaatcat tagaatcata ataggtactt cttggtattt attgatgtgc attcttttga atgacttcta taaaatatcg ttctccattt ttatatgttg ttcttcatct gataaattat cttgatgatt ccattttcct aacacctagg aatgaaacct cgattttctt tctcttgtca taataaaatc ctcatagaat ttgtccaatt aagtgtagac acttcttgct ttttatgatt aacttagcaa attacttaat atatatttat taccattaga catcagattt ttctttccat gcatgaggtg aaaactcata aagggcaggt cttaaccttt ttcgaccctc tgataaacgt gtaacacctg catctttata tagttccttt gataaagaaa ttcgttagga attgcttcat taagactctc agatgattcg atgccaaaaa aattatatag attatttgct tcaactacca aggaattttt aactttcgcg aatttattta ttcttttaat taaataattt tcatttttat atttaaattt catatcgtca aatattaatt gaattttaga cctatatata agtggatttc tacataatta atctttcaaa aatgtacctc ataaaaagaa ttctttatta ctaaatacac tttaacacat

    GENOM.057CPl.TXT tagatatgta tattatttat aaaaccataa 25980 actaatgaaa aatatattaa tcacagggaa 26040 attattaaat aatgataatt ataaagtcga 26100 gttttgttca tttgaaaatt atgacgtaat 26160 tcaacccaat gctaaaataa ttgattatat 26220 agctaaaaaa gctaaagatg acggtgtaag 26280 ttttggcatg aatggtttaa ttaataaaaa 26340 acctaaaagt gcatacgact attctaaatt 26400 tgatgacaaa tttgtggtaa atatcgttag 26460 gggtaatttc gctaaactta taaaagttgc 26520 taatgaaaga agtgttatac atatagataa 26580 gaatgaaaaa tctgatatca cacatccaca 26640 tttatcattg attagaaatc atttaggaaa 26700 aaatttcatt aataaaatta ttgaaaaatc 26760 aacatactca aaaaatatag acgatagaga 26820 tcaaactatt agtaaaactt taaaataaaa 26880 ataaatcgtt aacgaaaaaa taggcttaac 26940 tatagtaggt tttgttttta taaattaata 27000 gaaaaggcag gttcccattt ctattgacta 27060 gatgtgatca gtgctttacc tgagtacaca 27120 aaagattaat catgtgtatg tgtgttgtga 27180 attaattaat gtgccaattg gcattcatta 27240 ttactttatg gagtgaatgg tgtcgatgtt 27300 tcccttctct aaaggtcaaa aaataccaca 27360 gtaatagaaa agaagcgggt gctggtagtg 27420 ttattgaagc agttactaaa aaactatgaa 27480 taataaaggg gcaaaacacg ttaggtgttg 27540 atgaagatat tattcaagca tatcgagaca 27600 tcaattgctc atttagcggt tggtgttttt 27660 taaataacct ttttattaaa gttatactta 27720 aaatgaaact acaggcagtt ttgatttatg 27780 ttattataat tcgagtataa aagttaggaa 27840 tagctatgtt gtaaatattt agcaaaataa 27900 gggatgttga taagcttccc cttgttagtt 27960 tatttacatg gtatgtcaac attttttaga 28020 ctgacgtcaa atactttaat gaagaatgtg 28080 caaataattc tgtttctaac tgttctaagt 28140 ttttcattgc tttcatcgtt gcttccgcaa 28200 ttcatgaacg tttcatttta aatgtttcta 28260 ctttgcctct atcggtgtga aatagtttga 28320 tttgcgtcct tatttttaac tgcactgtaa 28380 aataaacata tgtagtgcca tgttcctgcg 28440 gcttccattg gttgctctct attaaaagct 28500 ccaagacctt tctattagaa ttaaaaatat 28560 ctttagtgat tttattatct tttcttttta 28620 ttaggacttt acatattgct ggtactgaat 28680 ttttcgtctc ataatcagct ctgcttgctt 28740 aacttctttg cgtaatttaa tcagctcttt 28800 gaacaaacct gtgtattgat gttgctttat 28860 aaccatttgt aacttaaact ctgaactaaa 28920 acctactttc ttaaattaac aatatctact 28980 gattcaaaat atcaaattta tatgtatagc 29040 aaaatacaaa tcaacaataa ataaaattta 29100 gtctgtttac agcatccttt ttgatttgtt 29160 aaaagttaaa tgtaatacta tggtcatcaa 29220 ttgctttttc atttcttctt tctgatcttt 29280 tacaataaat tttatccatt tctttgatat 29340 tattttttct ttacttgaat taacatttac 29400 ataaaaagga aatagccctt taccaaaact 29460 catactgtaa tcatctacta ttaatccatt 29520 catagttgac tctttataaa atgttaattg 29580 aaattttcct ttaaatctgc ggataaagac 29640 aaatgaatca ataatataat ccttatcacg 29700 caagtgtaaa ttgttcatag ttatctactc 29760 ttctcctagg aaccctaaaa tcggcattat 29820 taggttgata tcgactttaa tttactctct 29880 ttgtaaaatc ataatcattc actctaacat 29940

    Page 28

    2018206754 18 Jul 2018 agtaaaattc ataatttttt cttaagtata tgaatatact ttattcattt attagtcgaa ttaaattatt taatcttatt cttactcatc tcaaagacta acttaaagac tcttttataa acaaaatcat cacttataaa atgtgatccg aatattttgt ctataccgtc aaatttatta tattaaaata atattatagt attctacgca cttcagaatt aagttctttc cacattaatt aagtattaaa ataacttata ttatcctttt gcgaaaacct ttctctactt cctaaaaaag taagattgaa tacttgttgt attctattct taactaaagt actaacaata aataatacat taatagcgat tttattfgaa gttacacttg tttttttagg ttttatttct acataatttc ttttaatcat tcataatacc ccaatccctt aactgctaac tgtgggcttt agatttattt ctaatgtatt taatattatt tttagtattt cttatcagtt aataatggct ctatgtcaaa ggcaactaaa cattgcttaa cttccttttt taatattcga ttgcgtaaat gattgtaact ttttattttg ttatttatac cttctaaagg attttttata aagtatgcat gtttgtttag cgcttgagat aatggcatat gttttaattc aagtttgaat cgtaattgat tgatatattg taatatatac ttgacgatac ctttttgtgt atattcaaat gcctctaaat cttcttcagg cttattatat aaaggttgat tcgtcgttct ggtttaaaat actgttttat ggcggtttga cgtgctttta atgcgctttt acttttattt tttagtttag ataaatctga aagagtagca aattttaaaa tagacatgtt taaacaatca aaagtttatg gatagaacaa ttatatgtaa acttaattat cgcaatattt ggtctatata actttgatat ctacagaatt aataggagtg gaaagttaat tttgtaattg tatcaacaat atagccctgt taagggataa atgatataat ctattgactc aaagattaac aaacaaatcg tacaaaagaa caacaaatac aaattcttca cttattcgta aaatcgcttt taaataatga tattaaattc taatatgctt ggtgtcaaaa ttgctttttt aattgctgaa gcttccgttg atcgtttaaa gtgaatttca agataattat gacgtaggga cagtcattaa aatataaaag ataattaaat tttaaaaatt atagttacat gttgataagg gtcaactaaa ttaattatat tatactaatc actttgttat ttggttatag gacacaaaat gatccaaata taagtgaatt gcataatata tggtatttat ataatagtga tgacaaattt ttgagtcatg aattcattgt tgttaaaact gagttaaaag acagtacaat tatttttggc gtcaattatt ttgatcaatg tagtaatcaa ggagctggaa gcaaaaaaac gaacaatacc aataatagaa ttcagcctat tactctttct tttgatatca atattgataa taaagtgaga aataaattaa tttctaaaat tgaaacggga tacattaaat ttatagaaaa gccagaccct ggctttactc agtctaaata tgaatcagcc aaaacggaaa tagaagtgca atcaataata atttatggct agattaaagt cttggaaaag ttgctttttt taattacttc caaacaaaaa aggaggaaca ttacattcct aattttaacg tcttcgtcca tttgggcttc aattgattgt gtgttcatca attgatggcg atagatttta aagaatctac gcaaactctt gttaaacaat gataatgcaa tctcaacaga ggttcttttt caaaagcgaa tggattgtgg atgccatatt tttctgcaag ttcaagtcct

    GENOM.057CPl.TXT ttaattgtat attttcatat taaagtccaa 30000 tttttcatat ttcattaacc aactacctac 30060 atttcaaagt gttggatatg tctaagtttt 30120 tttctcatac ttgctccatc aaaggtaata 30180 tcatttattc ctgaaataag tgatttacat 30240 atacatcttt cataatccat gcccctataa 30300 ttgtattaaa tgatgttatt ggtgacattt 30360 gatatgaaga ttttatagca ttattctcat 30420 ttctaataat tccatacatt acttcattaa 30480 tgatttcttt atgaaagtaa atattgtgag 30540 tattatttct acagtcattt atcaaatttt 30600 tactatctaa actagaaatt ggatcatcta 30660 tactctcatg actaccataa ataaaattta 30720 tataggtcgc aatgttttga agcgaaattt 30780 attttaatta gtaaagacac tatatttatc 30840 ctgataatca aaattatgtc tgagatgtta 30900 aatctccccc atacttatga tacgcctctg 30960 ttggactgat aagttcaata ttggaagtta 31020 actttttgga gcgtaaagtt ttgaacataa 31080 tccataacca aaagatatac gtttaattaa 31140 accatttgat aaattgtaat aatcaaatgt 31200 tgtcttaatt gctcgttgga caaatgaatg 31260 gtgaataaag ccttcataat cattatgttt 31320 gtaggcgtca ttcagtgagt catcttgatc 31380 cttccattcc ttaaataaag cgactttacg 31440 ttttaataat aatttcgcat atcttttaaa 31500 taattcattc ataacagcga tgtcaatagc 31560 aaatatcgtt ttttagcggg ttaagaatat 31620 attctcatgt ttacgttctt catagcaatt 31680 gcttcaaaat ttgcatttat atctaaaaat 31740 aaagtgtgca ttgctaaatc atcattttca 31800 acatatttat ttaagtttta aaaaagtagg 31860 aatgaaatat gatttaagtg aagaaataat 31920 atcagtcgta taacagtaat tgcaatttgt 31980 ttttaaataa gattattagg taagtcataa 32040 agtgctatat aggaggcgat atcgtgatta 32100 ctaaaacctt tcacttgaag gtatgtatgt 32160 tgcaattaat aataagaaat tacaaatgag 32220 aatatgatgg aatacagcaa gacgaatatt 32280 cttctgatga attaaagcga cttggaaaag 32340 aagaggaagg atataaattc tatttccctt 32400 caaaaaagca tatatactat attaaaagtg 32460 gattattaaa gtgcaatttg ttgtaatata 32520 taagtgaata tatgttataa aataacaacg 32580 attcaagagg agtaatatga gaaaagtatt 32640 tagctattct ttgttggaag ctaaagcaga 32700 aaacaaatct agtcaatata cgggttcgtg 32760 tccagttaat gctaaaaaaa taaagctaag 32820 tccaataaat aaccctagtc attacgacta 32880 ggctagttca tttgatggga aagaagtcga 32940 ctatttttta aatgaaaata tacagtgtga 33000 ttgtatgtat ggtggtataa cattaaatga 33060 tgttgtaaaa gtttacgaga atgacagtgt 33120 agagactgta actattcaag agttagatta 33180 caatttatac catttaggtg gcacttcata 33240 tggtaatcga tattattggt atgatatgat 33300 tttgatgata tatcggggta atgaaacagt 33360 cttaactaaa aagtagacat agagcaactt 33420 aaataaaaat attttgatga attaaagcga 33480 tttaaaaagt aggtgcatta gtctttaata 33540 cctcaacctt tattactcat actataattc 33600 aaattcatct agaagtgctc ttgcttctgc 33660 aagttcgcta gcacctctta tgccacgcac 33720 gaattgtcgt atttcatctt tttcatattt 33780 tctaatagtt ccttgcttgt gtgttcacgt 33840 aaaatgcctc taccaatcat gacgccatca 33900 gtttttctat cgggaatatc accgttaatt 33960

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    2018206754 18 Jul 2018

    GENOM.057CP1.TXT gttaacaatg tatttggtgc aatttcgtca cgtaaatttt taatagcttc gattaattcc caatgtgcat ctactttact catttcttta cgtgtacgaa gatgaataga taaatttgca atgtcttgtt caaagacatg ctttaaccaa tctttccatt catcgatttc atagtagccg aggcgtgttt taacacttac cggaagccca cctgctttag ttgcttgaat aattttggca gcgacatcag gtcttaagat taagccggaa cccttaccct ttttagcaac atttgctaca ggacatccca tatttaagtc aataccttta aagcccattt tagctaattg aatactcgtt tcacggaact gttctggctt atctccccat atgtgagcga ccatcggctg ttcatcttca ctaaaagtta agcgtccgcg cacactatgt atgccttcag ggtggcaaca gctttcagta tttgtaaatt cagtgaaaaa cacatccggt ctagctgctt cacttacaac gtgtcgaaag acgatatctg taacgtcttc cattggcgcc aaaataaaaa atggacgtgg taattcactc caaaaatttt ccttcataat atatttatac cctctttata attagtatct cgatttttta tgcatgatga tattaccaca aaagacgaac ttatacaaaa ggaattttag ctgatacaac catttgaaag ggaagtctac gagtagtcta aaatgaatat tgtggttagt tgatcagtat acaaatcaag gattatcgta ttagattgtt cattattaat gatacactac ttattaatat gattcagaat tttctttagc tacatataca ataccgtgat ttttacgtta tcttataaca aagacaaatt tataaaggtg atattatgga agatttaaaa cactctttaa aaggtttagg ttggtatgac ttatttttta cagtacctat gtttctacta ttcgtgtatc tgccgaatta taatttcata actatattta ttaacattgt tattattatt ttcttttcca taggtttgat tttaactact catataatta taggtaacat taagaacaac tctaaatgat ttattaatac aaatatggtt aaacataaaa ctgaaggagc gattacaatg gcgactgaga aagatgtaaa tgatttattt ttaaatcatg tgaattcaaa tgccgttaaa actagaaaga tgatgggaga atatattatt tattatgatg gtgtggttat aggtggtttg tatgataata gattattggt caaggcgact aaaagtgcac gtcatcaatt tcaagataat acattagtat cgacgtatcc tggtgccaag gaaatggttt taattccaca ctttgtcaaa gtaacaactc taaatgattt atttgagctc ataaaaaatg atttgcaaaa gtgaagtgcg aatagagaga gaaataaaag cggataatat gtccgtcttc gccaccctta aaatatatta ttgtaccttt tatgaggtaa gtagctaaag gttgttcgaa ctaagcacta gtacttcatt ttctatttca attctttctt aatttgatta ggagatttcc tctcctttaa aggtcgttgc ttttagtaaa tttctttttg ctttgtatgt tcgaggtata tcattattaa aaaatgccta caattaatga ggactatagc aaatgtagta ccgataatga ttagaatgtt tttttgatat gatatcaact ccgatattgg taaggacata ggagcaatta caatttccaa acaaggtaca cgagtgccat tgaatatttt attcagatca aaagtacacg cactaaaata agcatttatt tctatgtaac ttacatcttt gatactacag aagttcatgc atatgttcaa tcgtctcata atttttaaat acccctgatt cccatagtta aatacattat tcaaatcgta attaaaacat agaagtattt gaatcaccat attcaacttt taagtttgta ctactatgaa gtaatctaac taccacttta gtcaatacaa atataacgga aagataatca agtgagtgct cattcagggg tgctcttttt tcatgtattt attgaacaaa aataaagatg cttaaggccc atttaaaaag ctacggaagt catttgagaa ataatatagt tacagtaaaa agttatacat aatatcttca tcagtgaaag ccctttaaaa tatagaactt tgatttaagt aagaaaaatt taattcatgt gatatttatg aatgtttaga ttaaagatga tatatactat taataacagt attacttgaa aattaactac cttgtatatt tgaatataat aatatgatgt gactgttttt atacaatcta atttaaaact aaactgccaa tattgaatat tatggggtat agacaagtta tatgtagcca ctttttgaga gtactttatt ataatagtct tgtagtcaat ttgcagtgac aagagctaaa aaagaatttt atgtaattgg ggacatgcaa agaatacaga caaaaccatt ttatgaaacc atttttgaag aaagaaatgt agaataacat acaaaaaaag tatatagagg gagttatttt catgcaaaat agaaatgatt ttatagaaaa actattagac agagctcaaa ttgaagaagg tatgcgtgta ctggatatag gttgtgcgac tggtgaggtc actcaattaa ttgcaaaacg tgtgggggcg aatggtgaag tcgtcggtgt tgatgtgaat gaatcattac ttaaaattgc aaatgaaaac aatcaatata acaatgtatc atatcaatat tctgatatat atcacttgcc agacactatg gggcattttg atgcgattgt tggtagaaga gtattgatgt acttaccaga tgctgaaaag tgtttacaaa ttttgaatca attttaaaat ctgagggtat attatgtttt caagaaagtg atgctattaa tacaggcgtt ggtgcagatg cactaccttt acatcaatcg gcaattcaat ggatttggga aacagtgaag caagaaggtg gcaatattca tattggtcaa aatttatata atttgtttaa taataatgga atgtatgttg tagattactt tgcagaggca gtgattcaaa cgtcaatgga taatgattta gcatggcttg tagatgtaat gctaccaaga atgaaagcgc atggtgtcat taatgatgat ttttcactag atgagtttaa atcaaacctt gaacatgaag caataaacaa tcaatgtgca tttatacgtg aaatggcgtt tggtattatc ggaaaagcgt agtttaaaaa acgctgaaag tagcatatta ttatcaacaa tgttttaatt tgtgaagtta ttaatggaat ttgaaatgac agcatttcta taggctaatc aagtgatact taattaccga gcaatttata cattttaaaa ggagtaaaat tgaataatga agaaatttaa caactggata ttaaatgcaa taagtggatc tcaaacagac aagaatggaa caactgaaga attaaaaggg gcaaaattta tcattttata tgcatattca atgctcgttt tgcttgcgtt agtaatttct aacatattca ttcacatttt ggagcctaaa ttatcaatca ccactcaaat catcatcgtt ttgattttaa ttgaatcact aattggacta cgtttcttgc aaagggtacg atgttaggcg tggcaaagat aaagaaaata agaaaaatag taaggatttc gttaaactaa aatcaatttt agtagcaatt ttatttacat cattggtgct gacagcaggc actgtagctg atatatacgg tttcactgac ttaggaaata ctagaagtga ttaatcgttt ggagcatagg tggtattata tttggcctcg

    Page 30

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    2018206754 18 Jul 2018 taagttacac aatggaagat aaaaaataac ccttttttaa cttatttatg taaagaacta ttcctataat acattgttaa aacatcaatt tatttgaaaa agatgtataa ttaatgtatt agtgtattaa gactttgttt ttaagtatca cagcacatgc gtcagattcg ttgagtaaaa aaagcaaaca tttaactgag attaatatgc taaaggatcc agtaaaatcg gtttgggcaa tgaagtcagg agtcaggttt tttgatatta cggttcatca cggcatggtt tatttgcatc aatattattt gagtgcctat ccaaatgaaa atagtgaccc taaagttatg aagacatttg acccgcaata tcagaatctt ttttacacag cgaaaggtaa aattgttcta ttcaatagaa gtgctgacac gtcaggtatt caatgggcag atggtaactt acatttacag gtacaagatg aagctgttaa aaatttattg gctaaagcaa tgaatttctt gagtgtggcg tctggaggca cacatataaa tcctgaaatt gcaaaaacga ggctgattgt tgactatgca ggatatccgt ttatagatag taataaataa ggattaaata gattctaatt attttcacta ctcgttttta tataaattga acagattttt tgtgaaattt aattgataaa tatatgtaat tcgaaaaagt atgataaaac gtgtaaataa attagtgctt atcactgctg gttgtgatat gggtaaagaa ttaagtatgt atccgattaa aaacctagag gatcaatttg ataaaaatga taaaggtaca aataagggtg aagctctgaa agttaaaggt agtgcaaaag gattttacta tgttaatgca gataataaaa tagaatatcc ggttaaaatg attaaagatg gaaacataaa aaaagaaatc acctttaaag atttgtcgaa gtacaaagat agttattcag ctaaatatca attaactaat agatatgata taccaacaaa taaagcgcca aaaggttcat cagttggata taaagacatt aatacttttt ttactgatag tctacatctt ataaagagta tgaaatcgat cccggaaaaa aaattagtgc ttggtattag tcttctgttt attggtaaag aagcggaaat taagaaaagt aaaaatctag aagatttata cgataaagaa gataaaggaa cgtggactat tagttctgaa aatataaaag gtatggtttt gaagttaaat tatgttaatg cgataaagaa ggatgaagat cctgttaaaa tggtcgataa taaaatcatt aaaaaagaaa tcgaaaactt taagttttta aagtacaaag atggcgatat atcatacaat caattaacca atgatgatta taatgtgaaa aataaagcac caaagttatt gttgaaaggt tataaagata ttgaatttac tttcgtggag agtttacatc ttaaaccgag tgaggataaa cgaatttcaa atatgttgct gtaaaataat gagggatagt atgcaacgtg attatttaat caaaaggctc aatggtttaa tgattggttt tgaaaataat atgacgcaat gcaacagtgg gtatcgattt caacttcaac aagatggcat tttagcagac aagtttgatg atgcgcattg aacaaagaat aaacatcaac tgagaaatat acataatgag ttgtctaaat tgactgagca gattcattat gtcccgcgta catatcattc gaatcaagta tgcgactata ttgagttaca aagcgaatat gttgggtggt cagagagcca tgtaggattc cagcatttct taaatacgac atatacagat gaaatgatta ctgatattgc ctttgcgaga acatttaaac acattacgca tccagcagtc actgaaaacc agcaatcggc attactttta aatgactaca ttgaagaaat

    GENOM.057CPl.TXT gataaggagt tggcgattat aaagctagct 38040 tcccgcgggt gtttaatcat atgtcaataa 38100 aaataagttt taaaatttta cccatatttt 38160 gaatatagaa agaatttgat attatgaaaa 38220 ttttagtagt gatgagtggt ttatatcatt 38280 gtccggaaaa ttggatgagt aaacttgatg 38340 caggctcaca tgatagtggc tcattcactt 38400 agactcaaga taaagattac cttacgcaaa 38460 gaggtagagc aagtgctgat aatataattt 38520 atgaattagg aaaatttctc gatgatgcta 38580 caattgtgat gtctatgaaa aaggactatg 38640 aagaggtttt tagagaatat tattataata 38700 gaagtaatgc gaaccctact ttaaaagaga 38760 tggggggcac atacataaag agtggttatg 38820 acaatgcgac atttgaaacg aaaattaata 38880 agtataaaga ttattacgat aagaaagtag 38940 aaacggatag taacaaagac aatgtatatg 39000 gcgcatttaa tagtacttat aactatgcat 39060 ttaaagcaaa tgggaaagct agaacgggtt 39120 ggcctggata tgatggtatc gtaagcaaaa 39180 atgacattaa gacgagtatg aaaatagtta 39240 ttttgaaaat aagtaataat tcaacaatat 39300 ttgataatat taaagtgaaa aagtgttata 39360 gaatcatttt aaaaagaaga gagtgatgaa 39420 ggtattagtc ttctgttttt agtcattagt 39480 gaggaaataa agaaaagttt tgaaaaaaca 39540 gatttataag ataaagaagg ttatcgtgat 39600 tggattattg gttctgaaat ggcaactcaa 39660 atggtcttat atatgaatag aaatacaaga 39720 gtaaagaaag atgaagatgg tagacctcag 39780 gtcgataata aaatcatccc tactaaagat 39840 gaaaacttta agttcttcgc gcaatatggt 39900 ggagatattt catataatcc agaggtaccg 39960 gatgattata atgtaaaaca attacgaaaa 40020 aagctgttgt tgaaaggttc gggagactta 40080 gaatttactt ttgtggagaa aaaaggggaa 40140 gaaccaagtg aggataaata atcatgacca 40200 gagagtgatg aaatgataaa acgtgtaaat 40260 ttagtcatca gtatcgctgc tggttgtggc 40320 tttgagaaga cattgagtat gtatccgatt 40380 ggttatcgtg atgacgaatt tgataaaaat 40440 atggcaattc agaaaaaggg agaagcatta 40500 agaaatacaa ggagtgcaaa aggattttat 40560 ggaagacctc aggataatca aatagaatat 40620 ccaacaaaag aaattaaaga tgacaacata 40680 gttcaatacg gtaactttaa agatttgtcg 40740 ccagaggtgc cgagttattc agctaaatat 40800 caattacgaa aaagatataa tataccaacg 40860 acaggtaatt taaaaggctc atcagttgga 40920 aaaaaaggtg aaaatatata ctttagtgat 40980 taacctcatt gtctcccaca cgattcaaca 41040 gtaaaataaa cgtattcata ttactgaatt 41100 tcgagtagaa actgagagta tgtcagattt 41160 tgttattaaa ggtgaggcac atatttatga 41220 cgacattttc atcattaacc accgcgactt 41280 catatgttat atccaattcc aaatgaaata 41340 tctatatttt cacttaacag atgcgaccac 41400 aatggcaaga ctggtttcaa cacatatccg 41460 acaacttgtg attcagttgc ttatgcatat 41520 gaaccaaagt atcttaaatg atgataaagt 41580 ttttcatgaa gatttaagcc tttcggaatt 41640 tctgtctaaa aagtttgcag aatcactagg 41700 gcgaattgag catgcgaaac tcgatttgac 41760 attgcaaaat ggcttttcaa gtgcagcgag 41820 tcaaacacct aaacagtatc gaggtgatcg 41880 acaacatgat tatcacgacc gtgaattgat 41940 gaatcatttc attgaagata ttgaaatgat 42000

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    2018206754 18 Jul2018

    GENOM.057CPl.TXT gaactataaa gagattacct ttcaaccaac caatcaacaa ctaaatcaat ttaatcatat 42060 cattcaagtg ggctatttga ggaatttgct caatacacag tatcaatcac agttgcttac 42120 atgtcatcat gattttcaag tcaatgaagt attagcatat gatgtgatgc catatatcat 42180 gaaaaagctc aatgcgccat tcacgtatga tgcagaaatt tcgaatatat tttatgatat 42240 tgatttgtgt ttagactttt tattagatca taattttagt ctgaccatgc atttggatta 42300 gtatgactca cgagattata tcgatgcatt caaagtattt atccatcacg ttgccctgca 42360 tgtcagtcat agaaaagatt tgaagttcaa cttgtatgtg acgacattgc acacgtcttt 42420 gattgaaatg attgattatt ttaaagcatt attccctaat ggtggcttgt acattcactt 42480 agatcaagct acggaaaggc agctaccatt gttgaaacga cttgagccac acatcgacca 42540 ttttgtattt gatgccaatt caaataatgc tgttgatttt aataaaatga atgatgatga 42600 atttaaaact gcaagtcaaa tgattattaa taaaacgaat taccttatcg atttaatgca 42660 tcgtcatcat ctaaagcgtc cactcatttt actcaattgg aatacattga cgggtgatac 42720 atttattaca aacggcgaat gttttagagg tggtatcatc attgagcaat tattaaaatt 42780 aagttctaaa gtagagggta tcgggtattg gttgaattat gacttgcacg tcagtcattg 42840 tagaaatgaa cgggattata tgaattctat tgaactgttt catcaatata atggaaaacg 42900 tccggtctat ttcacggcat tgctatttaa taaattaaca agcaatattt tatattctga 42960 tgatacatgt attgtcacgg gaactgattc aaattttcaa atattgttat atgatgcaaa 43020 gcattttaat ccgtacttag cgttggacaa tcaaatgaat atgcgtgcaa cggaaatgat 43080 ccatttgaac attaatgccc tggaagaagg tatgtataag attaaacatt ttaccttaga 43140 taaagaaaat ggtgcattat ttaatctttg gcgcaaacat catacgatac atggtatgga 43200 caaggactct atagattacg ttaatcgaat gagttttcca aaattagaag tgtacgatat 43260 agatatgacg gatacgctgg cattaaatat taaaatgatt acaaatggaa ttcacttaat 43320 tgaagtaaaa cgttacccaa gttcataaaa tgatcacaaa tcacaaattt tgatatacag 43380 aatttgtgat tttttatatt caaagttaaa attgcaaaaa attaatggtt aacatctctg 43440 ttgttggcaa tataaataat gattaatcat ttatgatgta actaaggaga tgaatgatat 43500 gaatcaacaa ttaattgaag ctttaaaatc aaaagaagac aaaatgattg agatcagacg 43560 ttatttacat cagcatccag aattatcttt tcatgaaggt gaaacggcga aatacatcgt 43620 tgaattttac aaagataaag atgtagaagt agaaacgaat gccggaccac gtggaattaa 43680 agtaacgatt gattcaggga gacctggtaa aacattagca atccgtgcag actttgatgc 43740 attacccatt actgaagata caggattgtc ttttgcatca caaaataaag gtgttatgca 43800 cgcatgtggt cacgatgcac atacagcata tatgcttgta ttagcagaga cgcttgctga 43860 aatgaaagat agttttacag gaaaggtcgt tgtgatacat caaccagctg aagaagtacc 43920 accaggtggt gctaaagcaa tgattgaaaa tggtgtatta gacggtgttg atcatgtatt 43980 aggcgtacac gtcatgagca caatgaaaac aggtaatgtg tattacagac ctggttatgt 44040 tcaaacagga cgcgcattct tcaaattgaa agttcaaggt aaaggtggtc atggttcatc 44100 accacatatg gccaatgatg ccattgttgc aggtagctac ttcgtcacag cgttacaaac 44160 agttgtatct agacgactaa gtccatttga aaccggcgtt gtcacaatcg gttcatttga 44220 cggtaaaggt caattcaatg tcattaaaga tgttgttgaa attgaaggtg atgtacgtgg 44280 attaacagat gctacaaaag caacaattga aaaagaaatt aaacgtttat caaaaggatt 44340 agaagcattg tatggtgtaa cttgcacatt agaatataac gatgattatc ctgcattata 44400 taatgatcca gagtttactg agtacgtggc taagacgcta aaagaagcag acctggaatt 44460 tggtgtcgaa atatgtgaac cacaaccacc ttcagaagac tttgcatatt atgctaagga 44520 acaaccaagt gcctttattt atacaggtgc agctgtggaa gatggtgaaa tttacccaca 44580 tcatcatcct aaatttacca tttcagaaaa atcattactt atttcggaag aagctgtagg 44640 gacagttgtt ttagattacc ttaaaggaga taactaacat gaatgaaacg tatcgcgggg 44700 gcaacaagtt aatcttaggt attgtattag gtgttattac attttggttg tttgcacaat 44760 cacttgtaaa tgttgtacca aatttacaac gaagttttgg tgcagatatt ggaacaatta 44820 gtattgcggt aagtctaacc gcactatttt caggcatgtt tgttgttgga acaggcggcc 44880 tagcagataa aattggacgc gtgaaaatga cgaatatcgg cttattatta agtattattg 44940 gttcagcatt aattattatt acaaatttac cagcattgct aattttaggt cgtattatac 45000 aaggcgtatc agcagcgtgt attatgcctt ccacattggc cattatgaaa acttattatg 45060 agggtgctga acgtcagcgt gccttaagct actggtctat cgtttcttgg ggtggaagtg 45120 gtatctgttc actcttcggt ggggcagttg cgacaactat gggttggaga tggattttca 45180 tcttctcaat tatcgttgcc gtactttcaa tgttactcat caaagggacg cctgaaacga 45240 aatcagaagt taccaataca cataaatttg acgttgcagg tctaattgtt ctagtagtta 45300 tgttgctaag tttaaacgtt gtcattacta aaggtgcagc acttggttat acatcattat 45360 ggttctttgg tttgattgca atcgtaattg tagcattctt tattttctta aatgttgaga 45420 aaaaataggt acatcatcgt taagaccaac aagtgcttca gaaacatttc gtgaatgata 45480 accgatacgt tcaagaacac caatcatatc gatatatagt aatccgcctt ttgttgtaca 45540 ttcaccacga ttaaggcgtt taatatgacc tttgcgtagt ttatgttcaa tattaaatga 45600 ttctctacta cgctctacaa tttcatcttt tttcgttttg tcataaacat ctaacatgtc 45660 gatggcttta tcaaatgact cagcaacatg gttgaataat ttatccatac cgcgttgtgc 45720 atcttctgta atgcgaatat cttcatcatg ttggcgtttt aattgagcga catactcttc 45780 tgttagctct gctactttta aaatagagcg attgacatca aacataactg ctaaacgctc 45840 aacgtctgcc ttcgtaatgg cttttgtaga aattctaact aaataatttc gaatactatc 45900 attgattgtt tcaacagctt ggtgcttttg ttcaagcttt ttgatcaatt ttttatcgtc 45960 ttttgtaatt tcgcgaatgt cttcaaacat tgataagaca atctgaccca cattttgtaa 46020

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    2018206754 18 Jul2018

    GENOM.O57CPl.TXT ttctttttga gtttcttgta atgcaacacc aggtgcgtga taaacaagat ctttgtttaa 46080 gtgctgaggt ttatagtcat cagcaatatc tttacctggg acaagctttg taactatcca 46140 tgctaaacct gctacaaatg gtaattgaat caaagtattt gttatgttga agataccatg 46200 tgatactgca atcgtcatcg ctggttttaa gtgccataca tcttgtaaca aactaatcaa 46260 atgaatcaca actggcaaga aaattgtgaa gataattacc ccgattaagt taaagatgac 46320 gtgtacaagc gccgcacgtt ttgcagcgat tgagccggct aaactagcta agatagctgt 46380 aatcgtggta cc 46392 <210> 88 <211> 57474 <212> DNA <213> staphylococcus epidermidis <400> 88 cgaagcatat cataaatgat gcggtttttt cacaatactt ttgttaaaat ataaagacaa taataaattc tcttattttt ccatttgaat cttcttcaga ttcaatatct acactatcta gtgtataaaa aaaatatata aaaggaatta ttaccttcct tattcaatag ctataaactt atatttttga atattaaata acaatcgtta aaaagtagat gtatataatg aaaaattatc acagcacatt tgttaaaatt attcatgata tatatgcata tgagaaaact atgctcttta agtttgcgat attcaatagt tatgccttat tgtttagata gtcttaataa tcaaactttt ggagattcaa atttgcatga cgaaataaaa tctaatgttt catcaaatcc tcaatattat gaatatatct tgtttatgga tagtgatgat aatgaaatca taaatgaaga acacgatttt tataccaaaa gtttaacttt caaggaaaac gaaaaaataa gaaagctact taccgatata attaataaac tatatgagct tgaattagta aaatttttag acaatattaa ttatcgttta ttcataatag atcatgaact aggatttgat tttgttatca aattatataa tttagtagat tttaaattaa tacataacga tagtattagt actaaaagct attataaatt attagcgtat aacttagcga gaaaattaaa aggttttgct ggtgaagatt ttcgaaactc atttaacaat ttactaaata aaccttcaaa aagactcaaa cctattaaga acggggaata cagaaaagcc tataatgctt atgaattttt gaaacctaaa aaaaattttt ttgcaaaatt gccaatacgt gggaaaaatt actctgatag ccctaaatca gataaattta aacatgtttg gattttgaat ttaaatgata aaaatgtgaa aattatcgat actgtcgcaa agtattttat actaaatatg gatcaaacta ttttatctac atggcatggc gataatgtaa cttcagcaag taaaagttat tgggattacc taattgctgc taataaatat tatcctactt caaatatttt aacttatggt aatcaagaat ataaaattaa ggttaaacaa gttctttatg ctcctacttg gagagatgat tcattaaatt tagacttaga acaaatgaga cttagaatgc attactttat atcagataga tttgattttt ctaaatataa tgatgtaaat acagattatt cttcagtttt ctttgattat acttatgact tagataaata taaagatgaa gatttaccag gaccgctttt atttgattca gaggttataa ataataatta taaagagaga ttagatgatg gaaaagcaac aaaaagagtc atgaaaaaat aaattaatag agcatccctt tgaaattaat ataagcttca ttctgataga ttaagtaccg ttgttacagc gtcatcatcc tagccgcttc atgaagaaaa ttagagttag atatttggaa atataaaaat aattaataat ctctatataa atttttttgc aaaaggacat ccaatttttt atttctaaca tcagtaagtc ataaaaagaa tcttaatttt ttcatagaaa aaaataacat ttattttaat attagtaaat agaatgtata acacttataa atatattatt aaaaagtagt aaaattaaaa tttacctttc tgtaaatttg atgtaaagat taaattataa gtattaggtg aacattttag ggaggaaaat aaagaaacag atacaaagat gtttaatgat aaagattttg aggtattatt tatacatgat aatattaatt ttaatcataa agttttagaa agaaatatag gtattaagga agctacgggt tacttacacc ctaattcgtt aatttatgcc gtggttaagc taggagtaaa aaaaactcac actcgaagtt tttataaacc tgaaatttcc aataaagaaa atgtatctaa tccagagttt aagcatagtt ataataatat taaacaaaat aaatctaatg ggttaataat taatagacaa acaactaaca gtttatatgg agatattccg agaataaaac agacaagagt aaaattatat tatccgtcac atacacaaaa atttaaagaa gataaagcat tgaattattg tcctaattta acaagagaat atttatatta tgtatgtaaa gtaaaaccaa tatattcaat tttacgagat atcaatttgc gtcataaatt ggaaattaat tataataggt caagaagaag agttaagttg aatgaaagat atagaaaaaa agttatacaa aaagatttga tcgtttatga aagtttttta atttttgaat atcttaaatc atctgagagc aataaagata ttttagaaga ttatccaata agatttagct gggaatattt ttattatgta agacagccca aatggttagt taaaaagaaa actcctttaa agagattagt atttgatatg aaacaagatt tttatcagca atcaagaaat agtgagcaaa ttttcgagag agcattcaaa tatcctcgaa atgatatctt aagtaattat aaattaaata tacctacaga taaaaaagtc gaatatcatg gagtaggtca atacaaattt caagaattgg gggaagaata tatcgtacta ttagatattt cagaatatga aggatttgcg gacctttata ttgtaagcga catattgatc gctaatctga agagacctat tttattctat ctgcgtggtt tctatataga tatggaaaaa tcggaagtta ttaataatat aaaaaatatt tacgaattat tttataataa attctgttta gttgaaaagg ttattaacta atatttttaa accgcaaagt gaaggatgct ctatttttgt tagtcattaa taattgtttg caaatcgtta ataaaatcct cgtagatttt atcaagaatt

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    3060

    2018206754 18 Jul 2018

    GENOM.O57CPl.TXT tattcctctt acagacattc gcgagaagtc cgttttaatt ttattagaag taattcaggt 3120 ttgaacctac ctaaatgaat atatgagtta tcttttatac tacaaaatat attcagattt 3180 caataatgac ataaaatagg catctttata tttaccttta gtgtagaatt gctctttgag 3240 taatccttct gttttaaatc cttgtgactc gtatatatga atagcttttt tgttatctgc 3300 atcaacatat agatagatct tgtgcatatt taaaatattg aatgcataaa ttatcgcttt 3360 ttcgaatgcg aattttgcat aacctttacc actgaactca ggtttaataa ttatttgtat 3420 ttcacaatta cgatggatgt aattaatttc tactaattca acaataccta cgacttgatt 3480 ttcatcttca acaataaaac gtctttccga ttcatctaat aaatgcttat caaataaatg 3540 ttgaagttcc gttaaggatt cataaggctc ttcaaaccaa taagacataa tagaatattc 3600 attatttaat tcatgaacaa aaagtaaatc actatattct aatgctctta gtttcataat 3660 tccactccca aaatcttcat atatatttgc attataaata taaataacga ataagtcatc 3720 atcactgtga acactttttt taacaattca tcacatatta attctcattt tcttattatt 3780 ctcgatttat tactcttact atgaaatcta taaaattctc atatttgttt atattaagaa 3840 taaatacgtc aatagtaaca ataaaaaata aataatagag catccctcac cgctaagtga 3900 aggatgctct agttttattg aaatatacat ttcattttgt taaataatta ttaataatat 3960 tttgaaaatc attattacgt gaaatcttca tagattttat caagtatttc tttgtcttca 4020 attgctgtga agtgatgtac caatcctttt ttacaatcat atgtaatttt gtgacgctag 4080 gtaattagta attgttcgtc agtctgattg tatagtatca agtttcatag ataatactct 4140 ttgattttaa tgtccacttt gacgtgcttt aagattgagt atatacataa tgtcattgtt 4200 gaatgttaaa aatcctataa atgtttattc atctgcagga ttttttaatc tccaagaata 4260 aaaatcatca taggacaact ggattattgt ttggataaat aacgtaaaca ataattaggt 4320 actattattt atttttgttt attctttttc ctaacaaaat aaagaaaaga ataaacgcaa 4380 ttgttaaaaa tatgtgtcct aaaccagcaa taccagcaat agcaggactt acacttagat 4440 ctttaatggt agaaataccg ttcacgaatt gcattgccac agtaacaagc acacctacat 4500 ggtatatata aaagaaactg ttaaacagct ttgtatgagt tgttaatttg aattggccct 4560 cgataatcat gaaaattaag aacataattg tacctagtac taataaatgt gtatgtgtaa 4620 catttaattg agaaaaaccg ctaaaatctt ccgcttttgt catttctcta taaaatagac 4680 cacttaataa ccctaatagt gtatagagcg ctgaactata cattaatctt ttcattttaa 4740 ttccccctat ttttaattac gagataagta tagcggtagt ttatgaactg agtatgaact 4800 tacaacaaaa aaattaatga agtactttac aataaactca atttattaga tggtggaggg 4860 acgaaaaagg attttagaaa aataaattaa tatattttta ttttgataaa taataattaa 4920 taatatcttg gaaatcattg ttaagtattg ttgtaataca atcgtcattc ataaaatctt 4980 catagatttt atcaagtatt tcttcatttt caatcgctgc gaaatgatgt actaatcctt 5040 ttacaattga tacataactt tgcgatgcta aacaactagc aactgtatgc caatctgatt 5100 gtttagtttc atggttcata gataatcatc ctttatttca atgtccattt ttgacgtgct 5160 ttaggattaa gcggatgcat aatatcattt gttgctggat ttatcaactt tttcaccttc 5220 tttttatgag gttttaacat ttccattacc tgtgatacac gttcaacgac agttggccgc 5280 ttcgcataag ctccataggc tagaatcact gtgtcacttt cacttatcgc tttcatcaag 5340 tgaatatcag tgtgctcatc atatggattt ttgatgtgtt tgagattttc tggactttta 5400 atattagaga atagatttac aagatataca gcgccatatt gttcagaatt agctaattgg 5460 ttgaggataa gaacagttgt gagatcgagt gataatacac cgtctaaatg aggatacatc 5520 gttatcactg tgcatgcagc tttcttttca tcccatgttt tcttgagtaa atagcggtgc 5580 tgttcatcat cgctaaatat ggcttctgtg tgtatcgtac ttttgattgt attcatcatc 5640 gtcacttcct ttagtattct tctggtaaaa gcatcacata ataaaaagcg tccacgtcat 5700 cttcacgaat gacgtagact ttcttaggta atgcattttg atttttttca tagtttgtat 5760 agtgatattc caatttgtat gtgggttgtt cttgttcatg cgtaactgac aacatattat 5820 catcttcttg tagtttgaaa atgtgtaggt aatcggtatg agagtggtta tctctttctt 5880 ttaccatatt ccaaagtatg atttgaaggt ctagagatag ttgttcacta atgcctcttg 5940 tgatgtatcg attgattttc atactatttg cctccatttt gcttttcttt catgatgtca 6000 atcacttcgt taatgactgt aacagatatt tgtgccactt tgatccaatt attcatggtc 6060 ctgacctcct tgttttagta aatgacgttc atcaataatg atattttgag tatctgtaag 6120 gtacagaaag tccatatcaa aatgatccag ataaccaata ctgatgagtt ggttattggc 6180 atacattaga aatggataga tacttagctc atgtagctca tcattatagt aggtataagt 6240 ctcgagtgtg agttgtacca gtggagaatc attaataaaa cgttccggta gaatattttc 6300 tgctgcttcc tccagcgctt cacattccca agcttcgtta ttagatagtt ggaataagtg 6360 ggtcatatat tgtttgagtt cttgagtgat ggttttcata ttattgcctc ctagatagtg 6420 taatagtgat gtagttcata tacatcattg agataatata tatttgattt gtcatttatt 6480 acgaatcccg gtgggaataa gagaaaattc catatgaaaa accgcttcaa accttggtat 6540 gacaaggaaa tcccgaaatt ccgcctgttt tgacgaacaa tcaactcatt atttataagt 6600 attgatgata gtggcgggtc tttacttcct tatatatatt atttatttat aaagaataac 6660 gggattttgg gattgtgctt gcacaatcct tctgcttctt cgaatctgca aatcccattc 6720 ctttcccgat aaaaaatcat cgtgggatgt tctttagcaa tttcaatata agcttcgtgt 6780 agtagtagat agatactgtc aattcgctct ctcattagat aagtgttatt gaaattgata 6840 aagagaattc tcaaaaattt ttagaaaaag aaagaggaag tatgtagata taaaatagat 6900 ttattaaata gtaagatata atgtttgcgg taaaaataaa gacgaagtgc tggaatacac 6960 ttcgtcgata ataaggtaat tgaagtctcg attattttaa attgatcatt ttaagcctac 7020 aaattcctct aatgtttcac cagatttgta cacttttgtc gccttctttt ttcctaaata 7080

    Page 34

    2018206754 18 Jul 2018 acgtaaatgc caaggttcat attgatatcc tataataaat ccataattat gggcattctt aaaactagca tatagatttt tatctgaatc ttgatgttca gaatagcctg gacgcgcact cttcacataa ttattatata gcttaacttg atataagtga atatcatctt tttgtgcacc ttttggattt tcacccggat tataagagga aattccatct gcatacgtcc gaccattctt atcgttattt tgggcttgat ttgtatgtgc ttcagattga tgtgaacaag ctgaaagtaa ttttttcata ttaatactcc ttttgctaat acatatactt tgagctctat atataatatt atataattta tattatgtta ccattaaata gttcattttt aatatcaaag tcacaaatat aaaatatttt tgattatgtt gatatcttta tatgctttga ctcctgttga aatcactaat aaccctagag gagcagtcgt gacaacaacg gataagaaag ttgatcctgc atcaacaaca gacattaatc atagtaaagt gagcttaaaa aaaatgtcac aattacctaa tttaactacc attgaacagt tactaaaaca agctgcctta gcagaacata tagatggaga tatttcaaaa ttattaggta tgaatcaaac gcactttact aaaccctatg aacccaaaaa atataaggat atggctattt taacaaatca cttattacgc ttggaaacag atactcaata caatcaacaa caatcactcg gcatgaaaaa tgtggatgga aatttagcat taaccgctaa aaaagatcaa cagccatatc ctagtgaaaa agctaaattt caaaacgcat ttaaaaatta tacgtatcgc gatggtaaaa cttacaacgt gaaagaagac aaatatgaat taaaaatatc ggaaaaaaac actaaagggg agcatattcc tagcgttaaa ttatttcaaa tcactttagc aattgtcggt gcgatcaaag tgtacataaa aaaatatagt agaacatgtg taacaaatgt ataaattaaa tatttttata taatttatat atttaaaata aagtattata ttttgaataa aggcgaagtg tttttattaa ttaatacttg tgtatcaatg tctagctgtt ttttcgtaca tttctagttg ggtgtgagac ctcagccagt ctgtgacatg ggggagtcaa attttccaac gtaatcgatt ctttcattcg ttcttatgtc atttattatt gtattatttt ttgaatttag attatcaccg ttatctttat cattttgctt gttctttatt tttttttatt gttcatatct ataacagtct cacttattaa agcgactgta gataatatag atataattta atcctatatt gcattaattt aataaaaagg ttggggtaaa aataaagacg tatcattgaa aacctgttta attacttcat ttttgtgatt gctgtctttt ctaatatcta taagttgaga ttttttcatt ttctcaatat tttttttggc attatatgag ggtttatctt gactcataat gtcattaagt tgcttatcat ttaagtccgg attatcctcg atggttttaa catattgttg ttgcttataa gcgatatcgt cttgattaac acgtgctaca acgcgttgaa tttgcttcat cacataatct tcaatcacat tggacccctt gttgcgaaaa ttactacatg ctttaagtgt attcgttgta ttgcttgctg taatgcctgt aagcagattt gttcctttgc ttttacgtat ttgtacttta ttccataaat cagctatcac tggtttatca ttaagccctt tcgcaaattg aattttgccg atatagaatg tactaaaagg tttacccttt ttagtgacat tacgatagcc atgtcctttg gcataggact gttggttaat cattagctcg tgtttactat

    GENOM.057CPl.TXT tgtgatgctt tctttgtttt taggatatct 7140 agctatccag cgtccttcct cagttttacc 7200 gacgccacca acatcaaatg taagacctgt 7260 atatttatct gctgcttttt taccatcacg 7320 tgtaggatag cttctatatc cacttatttt 7380 atcaaataat tgttttaagg ctttttgtgc 7440 gggtaaatca atatttttgt ttacaattaa 7500 aacaactttt tgatgcttct tttggttgtt 7560 agttttactt tcatttttgt cattgtggct 7620 taaagcgcta gtcatcaata ttacagataa 7680 acaaaaatat taaatgctaa atataacata 7740 taatatttta taatgattca attaatgcgt 7800 tacatgatac gagttgattt aaagtaagtc 7860 aaaatagaaa ttgaggaata tgaattgaaa 7920 ttttgttgta gttttttcac aaatactaca 7980 aattcaaaag cacaacttga tgaaggattg 8040 aatggacaaa tattatataa gtatcataag 8100 aagttgatga caatgctagt tatatatgac 8160 gacaaggtta aaatatctga gagatatcaa 8220 tttccattaa aaaaagggca aacatatacg 8280 aattctagta atgcagcaac gctagtatta 8340 ttcactgata gaatgaaccg tgaagcgcaa 8400 aatcccagtg gtgccaacaa taaaattata 8460 gaaactagct catatacgac agcaaatgat 8520 aagtatccta atattttaaa aatgactcaa 8580 ttacataaca cgaatttatc actgcctcat 8640 ttgaaaacgg ggacaagcaa agaaggatat 8700 ttaagagtga atacaaattt atttaatatc 8760 gcacgccaca aggttgctaa cgcactcacc 8820 aaagtgatat cgaaaggtgc acatcaaatt 8880 ttatatgatg tagtacctaa ggataacagt 8940 caactatcag ttaaatacaa tcgacaattt 9000 gtagaaccaa agtttaactt cttgtctgta 9060 ataatattgg tttctgtcat tgttattata 9120 aaaaattaaa ttaatttctt tttaagaaat 9180 gtagatgcaa ctttttgtgt taatattctc 9240 attatattat tcatatagta ctaaagatta 9300 ctacaaagca cttcgccata atatccagca 9360 tagatgtgcg ctagtttctt caacttctcc 9420 cttctcataa tatgatttat atcatattaa 9480 acattttttt catattgggc ttctttttga 9540 tcgtttttgg ttttgtgtat aacttctcca 9600 acgttattat ttgcattagg ttgagcaatt 9660 ctgtcatttc attcaacagg ctcttctttt 9720 tttggtagtt ttatgagctt gagagtcttg 9780 tgtaactaaa tactaacgat acaataatta 9840 gggaaaaata tttcttataa acctctctca 9900 aaaaaacata ccactgaaat tatattgtta 9960 aagtgctaag gagcacttcg tcgagaggaa 10020 tatcaagttt gagtgttaca taaaactgtt 10080 tgcgatcaat cactgctaag tacagtgctt 10140 tatgaaagac gtatcgcaat attttaccaa 10200 cattttgttg ttttttgagt tgattgattt 10260 atttttgaat cgacggcctg attactgatg 10320 tcaagttatt tagtttgatt cttacttcat 10380 gatgaagtga cgcacaatca acttgatttt 10440 tgactttatc acttttgact atttcgagta 10500 cagctcttac actgtttgcc gaacatactt 10560 aatagtaacg tatacgtttc ttggttccat 10620 ccataggtgc gccacattgg ggacagtgaa 10680 catggacttg gggtttttga ctgacttgtt 10740 cttgattaat aatgggggaa tgcttccctt 10800 tacgacgttt ttcactccaa tctttgtatt 10860 ggttagctaa tatatatgtg atagaactaa 10920 agcctttgtg attcaatgca ttggctattt 10980 cgaatatata ttttacaata ttagcttcat 11040 ctggtatttt gtcataacct agtggtaaat 11100

    Page 35

    2018206754 18 Jul 2018 tgccttgata atagccttct tgggcacgtc tgttattacg ttcgaattct gagaaactcg aagtattgac ttccatacgc tctgataaac cttcgacgat tttcagaaga tccgatgtat taacacaatc tatattgcct tcttttgcat tcataaattt acctgaaata ccacgatcag agtcacagta ttctttgatt tgattgattt gcatttctgt tgaaacacgt acatagatac tgttacatcc tttcttcatt tatgcaatcg gtggttcatt tttgaaatag attcctataa caatataggg gtacaatatg tttaacgtga gttgtatttg atgcccattt atagatgtag tttgttctct gaacgtttct gcatcaatga cttgagtcaa tatgtgatgt ttttctatgt cacctttaat ttttgtgtag atgcgttgat ctttatcttc aagtgtttgt gcattgatgc tcatgttttt aggacagacg tagtaacgta ttgtaagtgt tgcattacaa catgggcatt atgtctgttt ggtttgtttt tgcgatcgaa aaacaataga aggaaacata ttgtcgaatt aattaggatt gatgataatg ttacgaactt cttcttctaa taactgtgca attttcttat cagcctttac cgttggtgac tcattttgat aaccaaaagg tgcatgtgtt gtaatcaatc ttctgacttg ttctccaatg ttatccgatt gcttgagtcg gtcgaaagct tgatccatat gaacatggta cgtttgacat aatttgatga acctattaag acgataacag cataatatgt cttgtcgata cccactacga ttatctttgc tatgttgaat atgatgtttt tcggctattg attgttgttt catcgtactt tgacgtaaat ctttcacagt gataatatat atttatagat atgttgggcg tccatattag tcattcgttt atatctcgat aagttcatcc atgtttttca gattattcag tttgatgctt cacggttgta tcctgaaggg cctatcccct cattagcgga atttgccggt gtccaatttt gaattaacga aaactctaca tctaatttta gatggtaaaa tttgacactt cttttagttg tttggcgtcc taaggcgttg acaacattat taacatcttg aacgtttgca atcattttta cttcgatatg ctcaaacata tttttcaaag caccttcatc ttgaatgatg acatcgatag ctttatcagc ataatcaata aagtagtctc ttattttagc taatattttt gcagatgttg taatgactgc gcttttatca tctttcaatt tagcttcaaa aacttcatct tcacgattta taagatattt tagtgctaca gcttttttaa tattgtcagc aatctcgatg gttcttacac gtaatccatc ttctgacgtt gaaatgacag aagtacccca gtttgaacgt tgacgacctt gaccttcagt aaaagttgct gatgagagtt catcaaatac accttcaagt gcattacgtg tggcattcca agggttacca gcgactgata cagctaaaga acctgtaaaa ctaaaaatga ttccggcaaa cgtcactaag gcagaaatac caaatacgac ctcttttaga tacatgttaa accaattatc attatcacaa atggcgtcag atggagattt acttaacgat acaataggac caaacggtgt ggaaatgggt aattgattgc gcatttgttg ttcattaata ctaaatccat acttcattaa actagattca acaatttctt tttgatcttc tttagggtca ataaacttat tttcgataac cattcctcct ttttcttttg ggggcgtgtc tggtgaagga ttaaatgaaa ggttagtttg ttgctgttat ggtgtggatt aggacctgtt ttaccgataa taataaatgg aacacgtggc

    GENOM.057CPl.TXT tcgtttgccc cataaataca ttctcgacaa 11160 caagtatttg taacatgagt ttaccagaag 11220 tgaaaaattc gacattttgt ttatgcaaat 11280 tacgagctaa tcggtttgtt ttgtagatca 11340 ctttcaacat acgttggagc tcaggtctgt 11400 cgtatatatc tttgacctca aaatgatgga 11460 gtccatcgat actataacct tctgtgcttt 11520 cgacacgttt tgttttaagt tgttgcatta 11580 atgattgcat ggcttgattg acgatattga 11640 gatttttatc tttcgtaatg tgaatggttt 11700 aacgtttttg aataatattt tgaatggtgt 11760 tgcgttgcgg ttgttgacgt aatgattgcg 11820 tgccttgtgc caacttttct atcagttgtt 11880 ttctttgtct tttgatgcgt ttgtcaatcg 11940 tttgataaaa gtctcggcac acttctaata 12000 ctttaaaatc acagacaaag cgtgaagcat 12060 atgtatgatt cttttttcta atggtcatat 12120 tgattttttg tttgagttga ttatccgaag 12180 gtctctgcgc ttgctcatat atacttgtgg 12240 gaccatattg attgttgaca cgaccacaat 12300 gatagggttg tcgattgata tacgtgttat 12360 aaccatgacc tttaatgtaa taattgaata 12420 tgatgatgaa tgttccgttg tgataatcgt 12480 gaccttgctt tgctttttct tgaagcccat 12540 caagttcggc taaactgatg aagatattaa 12600 caaagtaacc atcatgtacg cttaagatat 12660 gttttaatgc atttttcaga ttacgatgca 12720 cacattgtcc ttgttgaatt aattgtgtta 12780 gtcctgattg tttgtcgcta taaaagttga 12840 cttcgatagc ttgtttctgt gctgcaagag 12900 agcctataac ttgtttcata tcggctcctc 12960 gaattgatat ataagcccaa catcaatgag 13020 gattgatttc ttcaattacc aaatcggcta 13080 ctccgttatt tgttctatct tcaatacgtc 13140 tgataaagac aatcagaaat cttcgtgaac 13200 tttaaaaagt tctttcgcag ctttgttatc 13260 cttatcttta gttaatccca ggatagatgc 13320 tacaagtgat tgttttttac cgctattatc 13380 acggtcagct aatatgaaac ctttatctct 13440 aaattgatga ttgtttagca tctgtttaaa 13500 gtcatctttt aatgagatta atccatagtt 13560 tgaaaactta cctctgtttt gtgctacaaa 13620 taatgagcgt tcagagattg tatgaccatg 13680 gatatcaata tctgtagcta aaacacgacc 13740 ataacgctta aacatacgat tgcctgtgtt 13800 ccaatctact tccttgtaaa accattgaat 13860 agctactaac ggtaaaacat gaccatagtt 13920 attggtcgca tttgtagtga attgttcatt 13980 gttttgagct gaatcattaa aaatactgtg 14040 attcttaggc gttttaactt ctccatgaac 14100 gatggagtac aataaccccg ttgtatctct 14160 aataggtata ccaaaattgt tactcaagta 14220 atttctaaag agagtttcat tacctttggt 14280 agctgcagtt gacttaccgg ttgaggattg 14340 ttcggtttca tgtttgtgct tcaggaaact 14400 tgctaattct aaaagaagag aacctttaac 14460 aaatgtacct ttaggagtta agtcataagc 14520 attatcaaat tctttagtag tatagatttc 14580 ttccagtata cctacccctt catataagta 14640 caacgcataa cctaaatctt ttgtatattt 14700 agatggcagt ttttgtgtcg ttaaaatatc 14760 gtctgtgata attagttttt cagtattagt 14820 gataggacct gcgatttcaa cttcagtagg 14880 tttataccaa cctttttttg atttgtatcg 14940 agccattagc aatcacctcc tttcgaaggg 15000 ttaagataaa ctaagtgacc gtgagtatcc 15060 gcatgtttta caaaatatgc gaaccaacgt 15120

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    2018206754 18 Jul 2018 ccaacatttt gttgtacagc ttttgaacat aatgtaaatt cttctccttc aggtaaattg tgctcgaatt tatctgattg attgaaatac taggaaaatt aaatatgcgc acaattaact catttgaaag cttgtaaaaa tatgttagaa tgacaaaata aaaaacgctg atttaacagc taaaagtagt cagaaggagt ggtgttatta tcttttatta atttatcatg atgttctttt tcttctaagt cttttggaga cactaggtca ttaggtgccg aagctctggt gtctcgatga cttacttttt cattttctaa aaagtttgta gtacttattt cagtgtttaa atcgtctatt ttatctttag aagtgatacc tttttcagtg atttctatat tactgtctac tagaaaatag tctctttgat cagtaatttc atgattgatg gaagaatcta tatctttgtc attgataccg tttgagagta tatcatataa tacaaataaa gatttaaagt ttgctatgtt tattcctaga aaattatttt tttcttgaat aaacatgtcg atcatattga tattttcttc aatcttgtca tatcttacta tatcacttat atttatggaa tttttattat cttgatctac agccctacat ttatcaatgt tcaaaattat gtctactaat ctcttattca taatatcact acctttatca gtagaagtac ttgatgagag gttagataaa aacttctaag actttttttc atatactaat aagtagtgta taaaaatgta tgcaaagaag ttttaatata aaatatttat aatattttat gcaacgagta attttacttt agttatatta gtttgttcct gtttttatat gtaaatacga ttgacttcga aatagaatat ttaatttcaa ataataaatt taatacaaga aaagagagaa cataaagata aagcagaatt attacatgat caagaagctt atttaatttt aggagtcgca gattcaaatc gaaaaaacca agaagaatta gcgggtaggc accccaagat ttcattaatg gtcattataa taaatcctaa aggatatgta caaaaaagta aaaaaaacaa aacagtcaat aaaaataccc caatagattc tactgcaagt cattttggtt tatatcctac tcctataaag aaatggatgc agaactcaac aggttatttt aaaaatgagg acattgaaga aaaagaaaat tataatcaaa tcaatagtaa cactttatac gttttatatg gttgccggtg tatctcttta gaactaggtg agataaattt taatatgcat attgaagaga cgatgcttta taatattcat gagaaatttg caatggataa atttttagaa aaggaacttt ttgaaaatta tatattagat gaaaataata aacgtgtatt tggaactgaa actaaaaaag taaaaacagt taaagtttta gaaaaattat tggttaatag gagaaaatca tagacttact ttcttcaaga agctcactca acattatgag agatagttct ataaatcaaa gggaatatat tagtacttta aatttagaag ttatagaaac gtatttgttt caatggaatc aaattaatag attaataaaa ataattaatg gaaaaataac taaaaatgaa agagaagtta aatttgatat tgaatatgta ttaaaagaat atccagagga cgcaattaca tctgcaaaat tagattctga aggagaaaaa tttaataata taagtaatat tatgaatctt tctcctggtg tgagtggaat gataaatgta attaacggtc cacatggtaa atcaaagaaa aattataggc acgcagcacg tacgataact gaatttcttt atgaatagca atcaaatata ttggttataa catatcataa gtgatgcggt ttttattaat aattattatt aaattttgat atatttaaag

    GENOM.057CPl.TXT tgtacatttg cacgactgtt caagtcatga 15180 aatgaaatac ctaatatttt cttttttaac 15240 atttaacttc ctcctactaa tgaactaaga 15300 ttcttaagtt cattttagcc aagaagttat 15360 attccgtact aaattaagat ggatttttgt 15420 gctttaaata aaaattaatc tgaagttata 15480 tcattataat aatctagtgc tttattgatt 15540 gttattttct ttggatattt gagttctttt 15600 ctatttaaaa ttaatgataa cagcatattt 15660 gtaatatatt ttgctaaatt actgtttata 15720 ctatttttca catgagcatc agcaattttg 15780 tcatctaaat aatattcaag aatctgaagt 15840 aaaatcttaa taatgataga tttgattcca 15900 agataataat tagtcagagc atgttcataa 15960 aaataatata agttctcttt gatacgatta 16020 tttttaaaaa agtgtagata aactgagttg 16080 ctttttggtt taaatacata tgattttcct 16140 gcgttgcaga atttattaaa attagttgta 16200 ttgtcattta attctgaact atgattttta 16260 ctatttaaat tttccatgca aagtatacta 16320 aaatctttag gagaacgatt taaagtatcc 16380 gaatcatcaa aaacttcttt gacatttatt 16440 gcattttgaa atttttcatt atatatgtct 16500 attataataa tatattatat cttaatattt 16560 acaccacatt tctctggtta gtaaaaacat 16620 aaattatatt ataaatattt ttgaaaataa 16680 gtgttttagt atagatttta aggcattcat 16740 attaaaaatg attatccttt caaaattttt 16800 taaagtagaa ttaatagtaa ttaaaggaac 16860 gaacgattga atagataaag aaggataaaa 16920 gaaggagagt attggatgtt aaagcataaa 16980 gggagttact gggattttaa agcagaatat 17040 ataatttgtt tatcaaataa cttgttgaat 17100 gataacggtc atattctggg ggttgcaggt 17160 atatcattta ttactggaaa aaaatttgct 17220 acatttgaat atgaagaaaa ggaaatcgat 17280 ccatactatc tggagagagc agaaaccgat 17340 gcaggtagca tttatacaag agttgaagat 17400 ccattagata cagaaatatt atggaaaatg 17460 aggttacaga attatttact aactcctgag 17520 catagtgaat cgccagagta tatagtatac 17580 tattttaatt tagtaagtcc attttatgcg 17640 tcatattacg aatttaaata tcatagtaca 17700 gattcaggta tctacacaac accagtacct 17760 agagatgata ctatttatta tcgttatttc 17820 ctttttatgt ataagggtga ttcgatggaa 17880 tgtgttttgg tttataaaag tgatgtagaa 17940 aattgggata aagttaatca gtcaattaat 18000 catttgtcac aacttgaaaa agaagatatc 18060 aaagatgaac ttgagaactt tagaacttga 18120 tgaaaaaatc aacactcatt gataaatttt 18180 gagaaattca gaataatttt attgatgcaa 18240 aatataacgg acaacgtaaa tcgttagcgt 18300 atgaagctga attttctaaa ttacttaatg 18360 tgtatatcca tgaagttgat gaagacgaag 18420 tattaggtta tgaatataat aaagatacag 18480 atttaagtac tattaaatct ttggcaataa 18540 gtaatagaat tgaaaaagag gcactaacgg 18600 cgatggttga gagtactttg aagcatattt 18660 atgaaacctt gagaggttta tataaaaaag 18720 gacataatga aaatactttt aaaacaattt 18780 tggacgaagt aaggaatgaa tatggtgacg 18840 ctgaaactag acatgctttt ctagcaatca 18900 tagcttcata taaaaagtaa aagctatttg 18960 aaaaccgcat catcaactga taagcagaag 19020 tagttgctaa aaaatgaagt atgcaatatt 19080 aaagattaag tttagggtga atgaatggct 19140

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    GENOM.057CPl.TXT tatcaaagtg aatatgcatt agaaaatgaa gtacttcaac aacttgagga attgaactat 19200 gaaagagtaa atatacataa tattaaatta gaaattaatg aatatctcaa agaactagga 19260 gtgttgaaaa atgaataagc agacaaatac tccagaacta agatttccag agtttgatga 19320 ggaatggaaa aaaaggaaat taggtgaagt agtaaattat aaaaatggtg gttcatttga 19380 aagtttagtg aaaaaccatg gtgtatataa actcataact cttaaatctg ttaatacaga 19440 aggaaagttg tgtaattctg gaaaatatat cgatgataaa tgtgttgaaa cattgtgtaa 19500 tgatacttta gtaatgatac tgagcgagca agcaccagga ctagttggaa tgactgcaat 19560 tatacctaat aataatgagt atgtactaaa tcaacgagta gcagcactag tgcctaaaca 19620 atttatagat agtcaatttc tatctaagtt aattaataga aaccagaaat atttcagtgt 19680 gagatctgct ggaacaaaag tgaaaaatat ttctaaagga catgtagaaa actttaattt 19740 tttatctcct aattacactg aacaacaaaa aataggtaat ttcttcagca aactcgaccg 19800 ccagattgag ttagaagaag agaaacttga actcttagag caacaaaagc gtggatatat 19860 tcagaagatt ttttctcaag atttaagatt taaagatgaa aatggaaaca gttatcctga 19920 ttggtctatt aaaaagattg aagatatttc taaagttaat aaagggttta ctccaaatac 19980 aaaaaatgat aaatactggg atgaattaaa tgaaaattgg ttatctatag caggtatgac 20040 acagaaatat ttgtataaag gaaataaagg aattactgaa aaaggtgcat caaagcatgt 20100 aaaagtagat aaagatactc taataatgag ttttaaattg actttaggta agttagctat 20160 agtaaaagag cctatctata caaatgaagc tatatgccat ttcgtatgga aagaaagtaa 20220 tgttaatact gagtatatgt actactattt aaattctata aatataagta cttttggtgc 20280 acaggcagtt aaaggagtaa cattaaataa cgatgcaatt aatagtatta tagtaaagtt 20340 accagtgata caagaacaaa ataaaatagc atactttttc aataaattag ataaattaat 20400 tgaaaaacaa tcttctaaag tagaattatt aaaacaacgc aaacaaggat ttttacagaa 20460 aatgtttgtt taattcttat aaagttctat tatgtaaaat attaaataga gataacatta 20520 tgaaagcgag cccaagacat aaagtttttg aataaataaa aaagataatt tctatcaaat 20580 taatatagaa attgtctttt ttataaattt tttgattatt tttagctgat tgagctgtta 20640 cttttcttat aataagtgct attagcacaa atcctagttc tcttttggct ttgtttattc 20700 ctcttacgga cattcgagtg aaacccattt taattttatt agaagtaatt taggtttgaa 20760 cccacctaaa taaatatatg agttattttt ttatgctaca aaatatattc agatttcaat 20820 aatgacataa aataggcatc tttatattta cctttagtgt agaattgctc tttgagtaat 20880 ccttctgttt taaatccttg tgactcgtat atatgcacag cttttttgtt atctgtatca 20940 acatatagat aaattttgtg catgtttaat atatcgaatg cataatttat cgctttttcg 21000 aatgcgaatt ttgcataacc tttaccactg aactcaggtt taataattat ttgtatttca 21060 caattacgat ggatgtaatt aatttctact aattcaacaa tacctacgac ttgattttca 21120 tcttcaacaa taaaacgtct ctctgattca tctaataaat gcttatcaaa taaatattga 21180 agttccgtta aggattcata tggttcttca aaccaataag acataataga atattcatta 21240 tttaattcat gaacaaaaag taaatcacta tactctaatg ctcttagttt cataattcca 21300 ctcccaaaat tttctcatat atttgcatta taaatataaa taacgaataa gtcatcattc 21360 actgtgaata ctctatttta acaattcacc acatactaat tctcattttc ttgttattct 21420 cgatttatta ctcttactat gaaacctata aaattctcac atttgtttgt attaagaata 21480 aatacgtcga tagtaacaat aaaaaaataa ataataaagc atccctcacc gtaaaagtga 21540 aggatgctct agttttattg aaatatacat ttcattttgt taaataatta ttaataatat 21600 tttgaaaatc attattacgt gaaatcttca tagattttat caagtatttc tttgccttca 21660 attgctgtga agtgatgtac caatctattt ttacaatcat atgtaatttt gtgacgctag 21720 gtaattagta attgttcgtc agtctgattg tatagtatca agtttcatag ataatactct 21780 ttgattttaa tgtccacttt gacgtgcttt aagattgagt atatacataa tgtcattgtg 21840 gaatgttaaa aatcctacaa atgtttattc atctgcagga tttttaaatc tccaagaata 21900 aaaatcatca taggacaact ggattattgt ttggataaat aacgtaaaca ataattaggt 21960 actattattt atttttgttt attctttttc ctaacaaaat aaagaaaaga ataaacgcaa 22020 ttgttaaaaa tatgtgtcct aaaccagcaa taccagcaat agcaggactt acacttagat 22080 ctttaatggt agaaataccg ttcacgaatt gcattgccac agtaacaagc acacctaaat 22140 ggtatatata aaagaaactg ttaaacagct ttgtatgagt tgttaatttg aattggccct 22200 cgataatcat gaaaattaag aacataattg tacctagtac taataaatgt gtatgtgtaa 22260 catttaattg agaaaaaccg ctaaaatctt ccgcttttgt catttctcta taaaatagac 22320 cacttaataa ccctaatagt gtatagagcg ctgaactata cattaatctt ttcattttaa 22380 ttccccctat ttttaattac gagataagta tagcggtagt ttatgaactg agtatgaact 22440 tacaacaaaa aaattaatga agtactttac aataaactca atttattaga tggtggaggg 22500 acgaaaaagg attttagaaa aataaattaa tatattttta ttttgataag taataattaa 22560 taatatcttg gaaatcattg ttaagtattg ttgtaataca atcgtcattc ataaaatctt 22620 catagatttt atcaagaatt tcttcatctt cgatagatgt gaaatgatta gctaaccctt 22680 ttataattta agtgtaattt gtgaatctaa acaactagca actgttcgcc aatctgattg 22740 tgtagtgtca tggttcatag ataatcctcc ctttatttta atgtccattt ttgacgtgct 22800 ttagggttaa gtggatgcat aacttcgttc gttactggat taatgagttt tttgactttc 22860 tttttatgag gttttaacat ttccatcact tgctcaacac gttcgacgac aacaggccgc 22920 ttcgcataag ctccataggc tagaatcact gtgtcacttt cactaatcgc tttcattaag 22980 tgaatgtctg tgtgtttgtc ataaggctct ttcctacgat tagtcaagta cttataatta 23040 aaataagcat tacttaacta aaccgttcat tttaattttt ttgaataagg tgttaaacta 23100 tatttaattg tacgtttggc taatgtggtg acatttgata atcgtacaat ttatgattca 23160

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    2018206754 18 Jul 2018 ttacaagata atgaattgtt tttaataatc gaggtttctc attaggctgc tttcttagtt aatgatgctg ccctcttatt atattcataa tattaccacg cttgttgatg gtatctctac tatcaatgcc aacaaaagca ttgagttgtt tctccccaat aatcatagct gtgcttagct caaaataatc gagttgttgt gctaattgaa gaatagattg ttttaattgt tgaataagta tatcgacatt aggatagctt tcttgagcaa ctttatccat tgacattccc ttatctgtag tgtcgatatc aagaaccatg tctggatgag ttgaatatcg actactaaat aatctttcta ggatctgaaa tttaagtcga ttttgttcat ctcttaattc aaagaatatt aactcatgta gtcctaaaca agcaagctta tgagcatctg tcgttttaaa tttggcttct aacggattca aaaatcgttc catacctctt gaatagatac ctaagtcatt caaatacttg agtaaataat actctttttg gaattttcca tttttataat caacacctaa gtaatcgata aaaaaacctc cttaaccttt ctcatttcat tttcctatac gaatttcaaa aggcgagagt aaagctgact tctggacagt ctacttctct ctataactat tagatttctt catagctaat cttagtatgt atattagaga atagatttac tagatataca ttgagaatga gaacagtggt aagatcgagt gttatcactg tacaagaggg tttcttttca tgttcatcgt cgctaaatat agcttctgtg cgttacccct tttaatattc ttctggtaaa tcttcacgaa tgacgtagac tttcttaggt tagtgatatt ccaatttgta tgcaggttgt tcatcttctt gcagtttaaa aatgtgtagg tttaccatgt tccaaagtaa gatttgaagg gtgatatatc gattgatgtt catactattt aatcacttcg ttaatgactg taacagatat gattccctcc ttgttttagt aaatgacgtt ggtagagaaa gtccatatca aaatgatcca cgtacataag aaatggatag atacttagct tgttgagtgt gagatgcgca agtagagaat ctgctgcttc ctcaagtgct tcacattccc gagttatata ttgtttgagt tcttgagtgg gtgatagtga tgtagttgat atacatcatt tacgaatccc ggtgggaata agagaaaatt taacaaggaa atcccggaat cccactcatt tattgatgat agggttgtgt ctctgcttcc cgggattttg ggattgtgct tgcacaatcc cctttcccgg taaaaaatca ttgtgggatg tagtcatgaa aaaaatgacg gcaatgactg aaagagaatt ctaaaaatgg ttagataaaa ttattcaata gttatatata aagtttgtgg ttcgtcgagt ggatggttat taaatagttg aacataaaat tgcttcttat gatgctcatc tagatatagt gatttcaact gagatttctc tagtacattc gcaatcatat cagcatcata tagttgatag atttgattat ttatttgatt ttttaatacg ctatctaagt caggtgagtc tgcttttatt tcttcacatt gtgactgttt gtctatttga cttttttcat ttaccttttc gataatttcc aatatctgat ccataacata ggcagaacaa acttttgaac ctttatttct tttcttagtg ccatctttta atgtattagt tttcggacat tttacaatcc cagtcagtag cttgcgactc tcttgacgtt taaactgtac cgcatgttta ccatcagcga taatcggttc ccagtgtcta tacttcgcaa actgtatctt ggtaatggac gaaatactaa aaggtttccc tgcgttcgca atcttacgat aaccatgacc

    GENOM.057CPl.TXT gatttataca agcaatgatg gcagtcttat 23220 tgtagtaata atcgacgaca tgattgtcat 23280 tcacccaaaa taaaagtttt ctcgcttttt 23340 agtgtgtatg acctgattga tatcgtttga 23400 tatttgattt aaatcgctta atatcaccaa 23460 taccaatacc aggtatcgaa tgaatatttt 23520 tcatggcatc atctaattgt ttgagatgat 23580 agcgtaattt ttcgactaga aaggaatgtc 23640 tcactcttaa ttgaagtgca tattttgtag 23700 aattgaatat atgtgtaatc agtacatcct 23760 taaagatttc tgcgatgttg agtgcaatga 23820 aaccagggaa tgtttgatgg agtaattcaa 23880 tctcgatttc tagatgaaaa cggacgcgtt 23940 taggtaagct gtctgtttgt ttaagcgtcg 24000 cctgatcagt tttccatgat cttagagcgc 24060 tttgaatata gttaatttga tttacacaac 24120 ctgtagattc aaaaatgagt tgtgggtggt 24180 tgtaaccatt tttattattc tggatgaaaa 24240 gtgcaactac actacttctt ttactaatat 24300 ctttgaataa ttgagaagct aaaaacttta 24360 acggtttcaa gaacccaaca tactacaaac 24420 tgttttttat acggatttaa aatccaagag 24480 aaaaaatagc tatgaaaaaa tctatcgtca 24540 ttaatatgtt taaggttttc aggtgtttta 24600 gcaccgtatt gttcagaatt agctaattgg 24660 gataatacgc catctaaatg tggatacatc 24720 tcccatattt tcttgagtaa gtagcggtgt 24780 tgtatcgtac ttttgattgt attcatatat 24840 agcatcacat aataaaaagc gtctacgcca 24900 aatgcatttt gattttttac atagtttgta 24960 tcttgttcat gtgtgattga gagtatattc 25020 taatctgtat gaggttgatt gtcccgttct 25080 tctagagata ggtgttcact aatgcctctt 25140 tcctccattt tgcttttctt tcataatgtc 25200 ttgtgccact ttgatccaat tattcatggt 25260 catcgataag cgtgttttta gtgtctgtga 25320 aataaccaat gctgatgagt tggtcattgg 25380 catgtagctc atcattgtag taggtataag 25440 tattaataaa acgttccggt agaatatttt 25500 atgtttcgtt gttagatagt tggaagagac 25560 ttgttttcat atcattgcct cctagatagt 25620 gggataatat atatttgatt tattatttat 25680 ccatataaaa acccgtgata aatgttggtg 25740 ttgacgaaca atcaactcat tatttataag 25800 ttatatatat tatttattta taaaaaataa 25860 ttctgcttct tcgaatctgc aaatcccatt 25920 ttctttagca atttcaatat aagcattgtg 25980 tttcattaga taagtgttat tgaaattgat 26040 taagtgaaag aatagcagtg tagttattgt 26100 caaaaataaa gacgaagtgc tagggagcac 26160 tttgattata tcattattta acttgagcgt 26220 ttttcttatg tcaatgcgat cgatgattgt 26280 taatttgtct atatctttga atattgcttg 26340 atgtggagct tctgcttgtt tatcttgttc 26400 caattcatct tggtagctaa gtattgttgg 26460 ttcaatagtt ttcgttaatg tatgcatttt 26520 ataggcaata tcatggttca aagaagagac 26580 aaccaattgc ttcaatacct ttttgctttt 26640 tttttctagt acatctgctc taacgctatt 26700 aaaattgcta catgagtaat atctgattct 26760 tgtattactt gcctccattg ctgcaccaca 26820 gtttgttcct ttgccgtgaa cttgtggttt 26880 tttatcccat aggtttctat caataatagg 26940 ctcattgagt ccttttcgtc ttttatcgct 27000 tccaatgtaa aaagggtttg agatgatgta 27060 tttcttagtc acataacctt tatgattcaa 27120 tttagcgtat gaatcaaaaa tatatttaac 27180

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    GENOM.057CP1.TXT aatattcgct tcatgttgat tgatcatgag ctctttttta ctgtcaggta ctttatcgta 27240 gcctagaggt aaattacctt gataataacc ttcaatagca cgttgtcttt ggccattgta 27300 gacattctct acaatcgtat tacgttcaaa ttctgcgaag ctggctaaaa tttggagcat 27360 caatttacct gttgaactgg caatttctat tttttcagtt agactaaaaa attcgacatt 27420 aatcttatac aattcctcga caatatttaa caaatctgag gtatttctag ctaaacgatt 27480 tgttttgtag accataatac aatctaattt accttcgttg gcatctttta acatacgttg 27540 taattctgga cgttgcattg ttttacctga tataccacga tcggtgtatt cattgacgac 27600 ttcatagcct tgaaattgac aatactctgt aagttgattc aattgacctt gaatactgta 27660 accatccgtt tgcatttcag tcgatacacg tgcatataat ccaatacgtt tctttttgag 27720 ttgtttcata ttacttcatt cctttcagga gttattaaat gtgattgttc aacgatattg 27780 agtggactgt ttttaaagta gattccttgt aattgtttag tttgagttat tttgatgcaa 27840 tcgataaaag gtgctatatc ctgtaaagtt attttatttt ttatgacata ttttaatttg 27900 tcatcgattt ggtaggttga ataagtagag taattctctt cacttttaca actagcagat 27960 aaacgtttga acgtttttac atcaatacga ttttgagcta gcttttcgat aagttgttct 28020 tgtgttagat gggtttcttt atgcttcatt tgttgctgtt ttaggacttt gagtattgtg 28080 ttattcaatc gtttatgaaa cgattgttct tcaaaatact ttttacaagt gtcgagcact 28140 tcactttcaa gttctggtgc attgatactt ttaaatgggc atgtacgata agcgtcattc 28200 atatttttag gacaaacata gtaacgtaga gaatagttct ctttttttat cgttaagttt 28260 gttaatgttg attgacagta aggacatttg attcgtcgct ttagcttatt tctagaattg 28320 gatcgattga gttgtttatg aatacgacgc tcttgtgctt cttcaaatgt atcaatatca 28380 ataataggtg gaacgatatc attaaacgtg ccatatttat tgatgacacg accgcaatag 28440 ttagggttca agagaatatt tctaacttga tagggcttac gaggaataag gttaggatta 28500 ctatccaaat gttgggaaat ctttttgtag cctagacctt gtaagtacca gcgataaacc 28560 gatttaactg tatacgcttc ttcttcttgt acaacaaaac aaccttttct ataacgatag 28620 ccaaacggag catgagttgt gattagctta ccttgtttgg ctttttctct aatcccattt 28680 tttgtttgtt cgctgatatt gtttgattcc atttccgcta gactcataag tatgttcaaa 28740 cgaaagcaat caaactcttt agacaaatca aaatatccat cgttaacact gatgattgtg 28800 atgtgatgct ttttacaaat ttcaaagaat tgtatggcat ttttcaaatt acgatgtagt 28860 cggttcaagc gatagcaaca caatacttta cattttccag acgtaattat ttctaccatt 28920 ttttgataac ctgaacgttt tgtatgtcga cctgttttct tatcatcata aaacgccaca 28980 ttagaccatc catattgctt agcggtatcc ataatgagcg atttttgagt agctaagctt 29040 tgttgtttga gtgtactttg acgtacataa gcaatcgctt cttccatgtt atacacctcc 29100 aaaaagataa tatatatttg tgagtaaatt agaatgaaag gtccaacgtg cttttaacac 29160 gttggaccgt cgtgattagt tatcgttctg tagctcttca acgactaaat cagctagtaa 29220 ttcaatcaat tcatccattt tatctactcc tgtacgattt catctttaag ttattaaaaa 29280 tcaattaaat catcgttctg ttttttccat gattcaagta tctttttgtt atccaagtta 29340 atttcagctt taataggttc agcatcttta gttagaccaa aaatagacgc atattttgaa 29400 tctagcttta aatggtaaaa gacaagtgac tgtttcttgc catagtcatc tttaactgct 29460 cttttcgtag ttattcgatc acggtcagat tcgataaatc ctttatccct tagtgcattc 29520 acaacattgt tgacatcttg gaaatgatgc tctatcaaca tattcttaaa tacagatgca 29580 atgattttaa cttcgatata atcatctttt aaggcaatta gtccatagtt ctcaatcata 29640 ttctttaatg ctgtatcatc agaaaactta ccacggtttt gtgctacaaa ttgcgtaatg 29700 acttcaatcg ctttatcagc cagtgatcgt tcagagactg tatgagcatg ataatcaata 29760 aagtagtctc ttattttagc gatatcaata tctgtagata aaacatgact aagaatcttg 29820 gccgaagtag tgatagccgc atagcgctta aacatacgaa taccagtatt atttgtttca 29880 tccttcaatt tatctttaaa ccaatgatgt aattcaaaaa cggatcaaaa aacaaaaggc 29940 cctagaaact aggagcacac ttacacaaga acaattgata gataaattag ctaaaggagc 30000 catcgatgca gaaacgttca gaaaacaatc tcaatcgtta cttcaacaat caaaaccaac 30060 actatcaata aatgagcaac aaattcaaag gtcttttgaa aatgtaattc aacaacactt 30120 cacgttaagc atgttatacc gatatattga tgaaattcat atttctaaaa acaaaagcct 30180 tgtgggaatc tatttcaaaa atgaaccgct aaacattgta aaccaagcta cgcaatcatc 30240 gattgcttaa ttaatgaaag gatgaaaaat atgaaagaaa tgaaaagaaa atctgtagga 30300 tgttatgtta gagtttcaac aatttctcaa gacattgata aatttagtat taatggtcaa 30360 attacacaaa taaaggaata ttgccaacag ggaaattatg aattgctata ctgataatta 30420 aaagtacccc cgatcgaacg aaaatatctt tttgatgact attagtgata attgtaattt 30480 tatccattaa tagatgaatg gattggaata atactaagcc tattgctatt ccaccgagta 30540 aaattaccca cccgcctaat tcaatacttt ccggaatcat ttcaaaaaat aataagccaa 30600 ttataaggcc tgcacataat gaataaataa agccatgacc actttgaaaa ccttccatta 30660 tccaagcgag tccaccgcca acaccaattc caagtgcgga agctaacgcc cgatcatcca 30720 tactgcactc atcccactat tcttaaaaag gctttgttta ttttactcta aaaaatcaaa 30780 acaaaatata tgaattcata ttaaatatta tttgactctt tattcagatg gttatatcat 30840 atatatgaac atatattaat atatgtagat aaatagtgat tattatatat aaggttttga 30900 attgaaacct aaagtgaggg aaggataatg gaagaaaaaa aggaattaga ggaagtaaat 30960 aataaggact tagatgatga aacattattt gtcgtatcgc aaacatttaa agcgttaggt 31020 gatcctacga gaatccggat tctccatttg ctcttttata aggagtattc ggtaaacggt 31080 attgctgaaa cgctacatct tagacaatca acagtttccc atcaattgcg gttcttgaaa 31140 aatttacggt tagtaaaatt ccgaagggaa ggcacaacat tgttttattc ccatgatgat 31200

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    2018206754 18 Jul 2018 gaacatacta tgaatatgct aaaacaggcg gtaaaccagt aatgagtgtt aataataatt aaaaatatta taggcatatg aaaagggggt gaatggaaag cgttgtatga tatctcgaag agtgaatacg gttgataaat tcataggatg tcaattaacg tcctggttta gtaaagctta atttatttag aaaggtgata gaaatgaaaa atagccacga tcatagtcat gatcatgatc ttggcttagt gttggctata attgggcttt acatcttatt ttcaattgcc acaatcacag ttggagagac agttgaaaat actaaattaa taatgggatt agctgcaatc ggggcttctc tgatacttat tttttccggc gctcattttc gagaaattac taagctactc gaaatgaacc gaaacacaaa aattgttgat gtcagtgaat acggtgatca agttccaatt gatgggataa cttctattaa tggagaaagt ataccgaaag gtacgattaa tggaacaggt acttttacta tattctctaa aattttacaa ttagttagtc gtatcattca aaaattcgag cctaaatatg taatgttact tgctcctttt ctatttgatt tagtgctttt agtcgcagct tcaccgtgtg tgtctacaac atctaaccta gctaaaaaag cacaattagc ggatatagat gcaattgcct aacctaaagt aacaaattac tatttcactc ttatagtcgc ccttgaaaag gaatccaatc ttgaagttaa aaataaaata gacatcgaag gagattataa tggaaaaaat tatcgtattg aagagtatac ccagttcaat catgattggg cagaaaatga agaagttatt gggattatag aagaaacaat taattacttt aagaaacttg cggaaatgac gggaaaagct gtaggcgaac taatgcctga agataaatcc agaattatag ccatggttgg agatggtgtg aacgatgcac ctatgggggg cggtactgat gtggcagtag atttatctaa attagtacag tctcataaaa aaaatattat tttttcaatg gcagttgttg taactgatat tacaatcagt gtaattgttc atggacttcg attattaaga tctaaataat aagtgtggat tctacaatgt tcccataaca aagatgttat gagtaaaaac aatgccttgc aagcaattaa agagcatggg aagcataaaa acattcaaaa gttaaattga ctgtattaaa gcaagcgtcg agccaaagat aatgccagga gaaaggtttt accttctcta tgccaagaca tttgggcgtt tgtgaacggt aatcgcagga catcacaata aagttggcgg catttgttct ggccgtatta agtgatacag gagctgctat gagggtaaaa gaataaaagt aaggataact gcttattttt catcaaaatc aaaaacgttt gtaccgattt tttaacctta ttgtatcagt tttctctttt atcatacgtt tataaaaata aatagatcaa aataatcttc tggttaaaaa ttgtttgatt agattagacc ctaataagac ctttgaaaat gtaaggacca ttattattat gcgtaccaca aataaaacta aaaaaatgaa ttgaactttt ttggcaatga tgttaaggca gacataaagt tctaggataa gtgaaaaaag tcttttttat aatttttttg attattttca agtgccatca gcacaaattc tagttctctt gagtgaaatc caaaatggcc ttaataaatc gactgtagat ggtttttgtt tttgatttga ggacattctg aacaatcatc acattcatat atcatgacta taggcatatc ttttaaatcc atcgttaatt tcgtcataat ccccattttg tagttttatc ttttataaac atttcataag atgctttaga gtctttattc atccttgact

    GENOM.057CPl.TXT atcgatcacg cctgtcatca ctagtattcc 31260 cacgtcatta atattgttat atgatcatat 31320 tttgcaatgg atatggaaaa caaaaaaaca 31380 gaaagtgaga tgggtgtagc agagagggtt 31440 tattattgga tacaaaaagt ttggatgtgg 31500 ctgcgaatat attggaaccc gatatatcat 31560 atattcaaga gcaacaagca cacgaaagtc 31620 acggaaaaat gccaattatt tcatatttta 31680 ttttaagtga tgcaaattta ttaatacaaa 31740 ccggctacca tgtaattatt ctcgaaggaa 31800 agggaaaatt cactcctaat tctcatattc 31860 tgatagggag tttttgggaa ggaacccttt 31920 ttgaagatta cgctgaagga aaaagtaaaa 31980 caacgacagc taaattaatc ttacctgatg 32040 taaaagttgg agatcaactc caagtgctga 32100 ttttatccgg tactacctca attgatgaat 32160 agaagtctaa gggtgacgaa gtttttggaa 32220 tggaagtcac taaggaaaac aaggatactg 32280 aaaaccaaga taatcaaaca aaagctgcca 32340 ttaatatagt tttaatcgca ataccattag 32400 ggacatggtc gcaaagtgtt tacaggggat 32460 ctttggcagc agctactgta tctgtaacat 32520 gcgtgctttc aaaaggaagt acttacctat 32580 tcgataaaac aggaaccctt acgaacggag 32640 attctgtgaa cgaagaaaat attattgata 32700 acccactcgc taatgctatt ttagaaaaat 32760 ttactaatca aattggaaaa ggtctgacag 32820 gtaagcctac ttcttttgaa agtgcttctg 32880 catcagaagg aaagacggtt gtatacgtag 32940 ctctaatgga tattccgaat gagcatgcta 33000 gtatccacac gactttaatt actggtgatt 33060 aattgggaat agacgaagtt atcgctaatg 33120 aagaacaaaa agaaaaattt ggagttactg 33180 cggcccttgt taatgctgat gttggtatag 33240 aagtatctga tttggtttta atgcagaaca 33300 tttcctcaaa tatgggtcgt gttattaggc 33360 cctttttagt tgtcgttagt ttgttaggat 33420 atgaaggaag tactttagtt gttatactaa 33480 gaacgaatcg attgacatga atgaactttg 33540 ttggacacta aaaaacagag caatctaata 33600 ataccgtttt tatcatacgg gcggtcaaat 33660 tcataaacag tgacttaagg cagccagttt 33720 agtttcgaaa cgattaatat ccgtatgggg 33780 cagagcgtct ttttccgttc ttttaagtgg 33840 gtcccagagc taaaagggcc agttgctctt 33900 aggggatttt cccaaccgca cctggttttc 33960 gatattcttg ggaatactta cactatgaat 34020 tattgtaata ctgaatgctc tccgcctttt 34080 aggtaaagct gttcaatcaa aaattgaaca 34140 attataatac ctacacttgt tctgttaaat 34200 aatatcttga aacgaagtaa gcgactaaaa 34260 cacttttaag aacggtttga aaatttttga 34320 acctgtagat atgatttctc tcttaaattt 34380 gcattcaata tgtctacacg tgaatttagt 34440 aaaaacccca gtataaaacg atacgctgaa 34500 tattataatg atatattaac aattaaaagt 34560 aaaatgtatt gaagaaagtt aagagtttgg 34620 acaatttcta ttgaagtaat ataaaaattg 34680 gatcgttgag ctgttacatt tcttatatta 34740 ttgtcttttt tattcctcga acggacattc 34800 caaaaaacag gctccacatc aacttttttt 34860 agtttatact ttatacattg gtgtttcaga 34920 aatttaaagt ctcgtttaaa aactatattt 34980 tagtctttta ttattcggac aagtgaattc 35040 agtattaaga aatgtcactt ttatattttt 35100 ttatgagtgg cattcgatta aaatgataga 35160 caggttttga atactatttt tccatacaaa 35220

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT tgtatatcga ttggcatttg cctcaacttt cgtatcatca ataaaaatgg cttgatcatc tctaagattt tacttcaaac actgaatatg aaattgaata aataacgttt ctaataaagc atcactttgg gatttactct aaatcgatta atcgttttat aagaatgctt tagattttgt gacagccaca ccattcggat tctatcattg agcaattttt ctatcttacg tcctgaaaac acagattgtg tgtaggtata tagaactact tttaacatca tttttggata gtatgatgtt gcaccatgat aatgtctgaa ttcatcgaat tcagtctcgg gaattgtttc tacaatatca tttggggtga gtattatttg atgaaagctg aagataaaag ttagaataaa attactaaat atagatttga catctttata aattaagaat ttgtcaaaat aaagggaggc attctataga taatggtgaa tgatgatttt acgaatgagt tatatcaact tatagttcct atggatgata aaataaaaga aaacattgat gaagtattat ctttctacaa tattaatttc aaaaaatatt tatttagtat ctcttcgtta gtaacctttg aaaagtgtaa taaattacga ggaagaattg ctaaatatcc tatttttaca attttatatg aaaaagtaga atatgatgaa aaagggatta agattataat taatagtaaa attcttaatg acatacaaac gcatgtgagt catattccta atactactga aatttatttg gttaacttta ataacctaaa catttctgaa aaaacaaaga aagaattggt taaagaatta aataaaatgt ttaacgacca gaaaaaaaga aagttagccc atcaagttgt aaatattata gagataataa aattggatag tcatggtaag tctctaattg atatcggcta tttctattta ggtgctaaaa atagtgcttt aaagtttcaa aaaatacata ttcaagaaaa aatggactat cggggaaagt aatttcaaat cgatttgaat tattaagaga tatctatgat atagacatga atcaatttca accctatttt gataagaaag atagtaaaac aaaaagatca aattatgaat ttgatatgga gcaattcgaa tctataagta cattagtaga tttgttagag aattacccac ttcctaaaag tgaaaataat attaaacatt tagaaagtat taagaaaaat atatttagtg ataacgcaga tgaatacgaa aagtatttta atgaaggtat agataaactt aaagaaggtg catttgaatt acaaaagcaa ttatataacc agtatccatt tcaattactt atgcgatttc agtatgaatt aactgaatta attaagcata ttagtatgta ttttaaacaa gtaaatcagt caaatatata tgaagctacg actttatacg aaaaattaaa caattttatt ttaagaagtc tacttgagaa taactcagaa aaagttaatt ttaaaaactt tttgaatgga gtaaaatttg aagaatcaac aatcaatgca gatgaggaaa taattgttaa aaaatacaat gattttgtag ataatattga gtttaataaa gatgattttg ataaactata tgatcaatat gaggtgttta atagtataac taaattagtt acattaaatg aagatgaaat aaaatgggat catatatttg tatataaata taaattaaaa acccctttca ttgataaaat aatcattgat aacttgaaaa acattaaaag tcaatatatt gatagtaaaa ctatgttgga aagagaatac aataaaaatg gtaattttat ttttgatttt ttaaatttag caaaatgtaa agatgagaat gaattagatg aggaaataga tgagttactc ttcaatcttg ataatatagg taacagatta ctaaagaaag ttgtattagg tcactctaaa aatataaaat attcaaacgc actattaaaa gaaattcgga gaatgataaa ggttttaaat ttatattctt cacaaaaaaa tcaatccaac atggttgtca cttaccatca attgcaaaag agcgataatg aatttgataa tagaattaat ttacttacaa aggaattagt ttatctaaga gtaaagaaag aactttttaa taacagtaaa tatactcata atgatgatag atagacattt aatttgaata atgaataagt ttaagctaac tcaattgagt tagctttttt ggcttccccc tctttaatga attttgggga agctaacgat tagttctaaa aatgttgata aagtatatct tgtaacgtta ctaataaaga tttcccgggc aatcaaactt gggggtgagt ttaaaaatgg aaagcaaagt agttgtaaaa gtagaacatg ataacgataa attacgagtt gagctaaacg tttcgaaaag agatgacttt aactatcaaa tgcactttgc aataagtgaa cgtgcatatg cattactaac tgtaatgatt ggtagagcgt taatgttacc aagagggaca gtattctcat gctatgaaag gttctgttgc aaagttgaat ttatagtata attttaacaa aaaggagtct tctgtatgaa ctatttcaga tataaacaat ttaacaagga tgttatcact gtagccgttg gctactatct aagatatgca ttgagttatc atgatatatc tgaaatatta agggaacgtg gtgtaaacgt tcatcattca acggtctacc gttgggttca agaatatgcc ccaattttat atcgaatttg gaagaaaaag cataaaaaag cttattacaa atggcgtatt gatgagacgt acatcaaaat aaaaggaaaa tggagctatt tatatcgtgc cattgatgca gagggacata cattagatat ttggttgcgt aagcaacgag ataatcattc agcatatgcg tttatcaaac gtctcattaa acaatttggt aaacctcaaa aggtaattac agatcaggca ccttcaacga aggtagcaat ggctaaagta attaaagctt ttaaacttaa acctgactgt cattgtacat cgaaatatct gaataacctc attgagcaag atcaccgtca tattaaagta agaaagacaa ggtatcaaag tatcaataca gcaaagaata ctttaaaagg tattgaatgt atttacgctc tatataaaaa gaaccgcagg tctcttcaga tctacggatt ttcgccatgc cacgaaatta gcatcatgct agcaagttaa gcgaacactg acatgataaa ttagtggtta gctatatttt ttactttgca acagaacctc caatatcatt aaagcaacac cagaaactat gaaaacatca gcgagattaa agataggata atcaatgagc cgaaaatcaa ggctatctat tacttctcct ctaatcaagc ggtcaaaaaa gttccctaat gctccaccta gcaacagtga taaggcaaaa gagattcgtc ggttattcct tccttctgtt tgtaaataat aaatgatacc cagtacaaca attaacgtta caataataaa aaaccagcgt tgaccttgca aaattccaaa tgctgctcct ttatttcgaa gagaagtaat atggaatact ccttcccata aaggaatggt ttgacctatt tccattcatt tgacaatcgc agatttccat agttgatcaa tgattaaaac gatgactgca atgatatagt agatcctgat tctcctcctc caatattcat tattttaaag tataccatga tataacgaaa aaatgtatat tttattgttg caataaaacg ttatattatt tatactaata tatatacaaa taataatttg aatgttattt tatacactaa ttacagagga ggggttgttt tgagtattac ttccataaat

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    2018206754 18 Jul 2018 aaaaaagaac atgatttaga tggtataaaa atatttgacc cagaaaaggt tgagcgccgt tcacaattgt ttaaagtttt tgcggatgat caagaagatg aaatgtgtgt ctgtgatgta gcttcacacc acctacgtat gttacgtaat aagatagttt tttataggct agtaagtaat cagttgaagg aaaagaagta aatgtgatga aacaactcag tcctccgttt tacatgatgg attacctaag aaaagaccag tagataaaaa cactagggct taaatcttgt tttttctctg gaaatggaat gaattaaagt aaggagagtt tgtgttactc acaagtatag ctaatcttgt gtcccccaaa gctcttacat atttaatggc tattcttgat ctaatgccag aaggattaga aataggattt ttagtattat tttcctttca ctatgaaaca catgaggata aactcagtaa aatgaccatt catagtttct ttgatggggt tgaattaggt ttccttgtgt ttgttgctgt catttcttcg attgttcttg tagtatttaa agtactggct ttggctacta tatttggagg atttgcagct gaagtacttg gcgattcttt tgtttttcta tatgttgcag caacggactt aaaaactggt ctttacgttt tgcttggtgt aggagttgtt gggttggaat gaaaatatta aattaaacag aaaagttgag tttagtctta atcatttgac tatctatatg tgtggatata aatgaatatc ataatgagag atggccaaga aaagatacat tggttaatta agaaggaggt tagaggagaa atatgtctat cgtgttgatg ttgaaagaaa tgttaaaaaa attccgggag ccaaaatttc cgtttacgga gaagcaacgg agaaccttaa agtggctcca gaaaaaccta acaaaaatat atatcgtgtt gaagggtttt gaaatgttaa aaaaattccg ggagtagagg tttccgttta cggagaagca acgattgaag ttaaagtggc ctctgaaaaa cctgtacggc aggatgaaaa agaagaaaaa gtgccattct ccttattgat tgttttcgga tatctttcag ctacattatt atttgtagca tcgatgttaa tccaaaactt gttacgcttt gaatttgaca gtggtgcgat tataggagaa tgggcagaag gtgaagctct agaacgattt tctatggata atattgcacc taaagaggca cttgttagac atgatattgc agttggagat attatgattg ggatggttgt aagtgggtac tctgctgtta ctgttgaaaa agcggttgat gatgaagtat ttgaagtaga aataactaaa ttagtagaag tagaggaagc acagggagaa cgagcaccat attatactcc gatcatcatg atcatagctg ttggggctag ttgggaaaca tgggtttatc catgtgcgtt ggttatttcc accccgattt aaaagggtgt cctaataaaa ggtggcgttt ttgctttcga taaaacaggt actttgacaa tgttgaacaa acaggtagat gaaaatgaaa gttctcagca ccctcttgca tcagcaatca attcagatgt tgtgatagat gacttctctt tagacggaac gacctattat attggaagtc gttttgataa gaatttagag aaaaaagttg tggttgttgg aactgacaaa gaaatactag aatcaagtaa agaagtcatt caaaaactac ttaccggtga taataaaggt actgcgaatg ttcaggctga attaatgcct caggataaat acaacaacgt agctatgatt ggcgatggtg ctgttggaat tgcaatgggt ggagctggta cactaatggg agatgattta agaaaacttc taaacataat aaaagctaac attacttttg tggttattcc aggttggtta acactctgga

    GENOM.057CPl.TXT tcaaggggaa aagatgcttg tgagacattt 39300 cagcaggaag tcggtcaaac ggatggctta 39360 acacggttga aaattgttta tgcacttacg 39420 gcaacgatta ttggttctac gaatgctact 39480 atggggtttg ccgagtacca taaaaaaggg 39540 catgtgcatc accttatgca agaagcacta 39600 gtgttgggaa aaattagtta aaatgttaca 39660 aatgcagttg ctcaaaaata aaccataaaa 39720 atcatctcag gagatttaag acctggtatc 39780 aattgtaccc tgatggtcca aattatttgt 39840 tgtaatgttc tcatggactg tagtatctct 39900 tggaggattt attgtcgtga gaaaagaatg 39960 ttttagtgca ggttttcttt tatccatagg 40020 aaattcacct gaaaatggaa tctatatatt 40080 aagaatcctc acaactcatt ttcatttcgg 40140 aaaaacgggc ggtttaggtg cctttatcgg 40200 ctccattgtt gcgggattcg aagtaagcag 40260 attacttcat aaaataccag atggcttaac 40320 tgacaggaaa aaggcgttta ttgcctctgc 40380 agctttagta tggctactca gtgacacaga 40440 tgcaagaatt gctttgtcct tttcagcagg 40500 acttccagtt gttaatcaat ctgaaaatcg 40560 agccgttttc tatatagctt cttggatcat 40620 aaggaatagc cttgaataat cagttgagga 40680 gcaaaaaaag aaataaaata caatcaaata 40740 taataacaac agaacataac gtaatattca 40800 atataggaat tccacatgca ttgattgata 40860 tattaaatat gagtgaagca acgaagccat 40920 gattttcatg cgcaaactgt gcaggaaagt 40980 tagaggatgc aaaagtaaat tttggagcat 41040 ttgaagaatt agaaaaagca ggtgcctttg 41100 ggcggcaggc tccgcaagag gttaaaaaag 41160 catgcgcaaa ctgtgcagga aagtttgaaa 41220 atgcaaaagt aaattttgga gcatccaaaa 41280 aattagaaaa agcaggtgct tttgagaatc 41340 aagctacaca agagattaac caggaaaaag 41400 ataaaaagca cagtacttta ctctattcga 41460 tctttgttaa tggggatgag aacattgtta 41520 taggaggatt atcgcttttt aaagttggtt 41580 tgaaaacact tatgactgtt gcagttatag 41640 tttctgttgt tgtcatactc tttgcaatta 41700 aagcgagaca atcaattcga tcattaatgg 41760 gaaaaggtca agaaatgatg gttcatgtag 41820 tcaaacctgg tcaaaagatt gccatggacg 41880 atcaagctgc cattacaggt gagtcagtcc 41940 ttgcaggtac tctaaatgaa gaaggattac 42000 atacaaccat ttcaaaaatt attcatcttg 42060 ctcaagcctt tgtagaaaaa tttgcgaaat 42120 cgttagttgc tgtagttcca ccattattct 42180 aaggtttagc tgttttagtc gttggttgtc 42240 cgattgtttc agcaattgga aatgcagcga 42300 atttagaaga aatgggtgcc ttaaaggcca 42360 aaggtgtccc tgttgtaact gacttcaatg 42420 tgctatccat cattactgca ttagagtatc 42480 tgaaaagagc agaagaggcg aatatttctt 42540 ccattacagg aaaaggaatt aagggtactg 42600 caaaactatt taaggaactg tcaaactcta 42660 caactcttca aaatcaaggg aaaactgcta 42720 ctattattgc agtagcagat gaagtacgtg 42780 atcaacttgg catcaaaaat acaattatgc 42840 ccattggaag tcatgtcgga gtaaaagaag 42900 tggattatat taaacaattg aaatcggaat 42960 tcaatgatgc acctgcattg gcagcttcca 43020 ctgatacagc attagaaacg gcggacgttg 43080 cgtttacggt aaaactaagt cgaaaagcgc 43140 caattgctat taaatttatt gccttattat 43200 ttgcgattct ttcagatatg ggtgcaactc 43260

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT ttcttgtagc gttgaacagt ttacgactta tgcgagtgaa agattaagag taaaaagagt gtgggacata aagtcccagg ataagtaaaa aaagacaatt tctattgaaa taatatagaa attgtctttt ttattatttt tttgattatt ttcagctcgt tgagctgtta cttttcttat attaagtgcc attagcacaa atcctaattc tcttttggct ttatctatcc ctcgaacgga cattctagtg aaacccaaaa tagccttcat aaatccaaaa acaggctcca catcaatttt tctttgactg tagatggttt ttgtttttgg ttctgaaagc tttttattaa tttgggcttt aaaatattcc caattataat ttttcattat ttttttattt gtttttgaat tgaagttcat acattgttgt ttcagagggc attctgaaca atcatcacat tcatataatt taaagtctcg tttaaaacca tatttatcat gacgataggc atatctttta aatcctagtc ttttattatt cggacaaatg aattcatcgt taatttcgtc ataatcccaa ttttgagtat taaagatgtc acttttatat tttttagttt tatcttttat aaacattcca taagttatga gtggcgttcg attaaaatta tctataattg ccatataatt ggcttcgcta ccataacctg cgtcagctac aatatattca ggtaaatgac cgtaggtctc ttgtattgta tttaaaaaag gtatcattgt tcttgtatca gtcggatttt gatacacatc ataaaataaa acaaattgag aatttgtcgc tatttgtaaa ttataccccg gtttaagttg tccatttttc atatgatctg ttttagaata actatttcta tcctttaaaa tagatttttg gacttcgtat ttatgctttc gctgagagta atcattaatt tgctttttgt attttttaat tttagttctt ttgagccgta tttgttttct tattttagta catttttcat tatcgatatg ttggtttaaa tcttcgattt ctttatctaa atgactacca atcaaatcta tttcttcttt tgttaagtca ttatcatgat cttttttaat ctcaggtatg attttattta tcaccaattc atgatagagt gctttagagt tttcattcat tcttgactca tggttttgaa tactcttttt ccatacaaat gtatatcgat tggcatttgc ctcaactttc gtaccatcaa taaaaatggc ctgatcatca ataagatttt gtttcaaaca ctgactatga aattgaataa ataatgattc taataaagca tctactttgg gatttactct aaatcgatta atcgttttat aagaaggctt ttgattttgt gatagccaca tcattcggat actatcattg agtaattttt ctatcttacg tcctgaaaac acagattggg tgtaggcata taaaactact tttaacatca tttttggatg gtatgatgtt gcacctcgat gatgtctgaa ttcatcgaat tcagtctcgg gaattgtttc tacaatatca tttacatgtc gtgaaatatc atttgtgggg ataagaactg aagtttccat tggtagagta agttgagtca tgttataatc tttatacata aggcacctcg ttaatttagt ttagtgatgt ttattaaatt atacgaaagg gccttatttt tttaaagtat tttaatgtaa aattacatat gaatacaaag tattttggcg agactcttga gggaacagga caagctgaag actacaggct gaagctgtcc cctaagaaag cgagccaaca atacgaagta ttgtaaataa agaagccagt aaatgaattt atgaaaactc atttactggc tattttgata ggaattatgt cccaggccct tttaatcaaa atgtagatta ttttttataa attgtctaat aagagaagaa aaataggtga aaataagaaa aaggttagat acatattaca caactatatt cttgagtaca aatagtaatt atagttactt atcaaaggag gaatctagga tgactggaga agtgaaaaaa tatgtagacc ttttagtgat aggagcaggg tctggaggtt atgtggcggc aatacgtgct gcccagttag gaaaaaaggt ggtactggtt gataaggcgg agttaggagg agtttgcctt aatcgagggt gtatcccttc aaaagctctt attagtgcat ctgaacgagt caaacacatt aaacatgcca atacaatggg gcttaaggtt tcgggtgagg ttcaagttga tatgccagaa gtagtaaagt ggaaggacgg aatcgtgaac aagctaacag atgggattcg caccttgtta aaaggaaatg gtgtagaggt catcagtggg gaagcctatc tcactgaagc acatattgca aaaataaaaa tagaggacga ggaacagatt ttttcctaca aagatttaat tcttgcaata ggttctttgc cagtcgagtt aaaaagtatg ccatttgatc aaaaaagaat catttcttca acggaggcat tgcaactaca ggaagtaccc aatcatttag ttgtggtagg tggtggttat atcggtttag agttaggtac tgcttatgca aagtttgggg caaaagtgac catccttgag ggatcggata caattttgtc cgggacagat cctatcctaa caaaaacagt aaaacgtcat ttaaaggaaa ttggaatcac tgttataacg gatgcccttg ttcaaggtgg agaaaataca ggcgatgaag ttaacgtcca tgttcaagtt gatggaaagg aagaaattat tcaatgtgat tattgcttag tttctattgg gagaaaacca aacacaggta aaattggtct ggaaaatatc ggagtagtat tagacgacca aggatttatt aagataaata acaaatgtca aacaaacatt gaacatgttt atgcaatagg ggattgtgct ggtggtgacc tccttgctca taaagctagt tatgaagcaa agatagcagc cgaagtgatc agtggtcaaa atagtgtgat tgattttcaa gcgatgcctt ttgttatctt cagcgatcct gaagtagcct atacaggttt aacagagaag gaagcaaagg aaaaaggata cgaaacagta tccagtcgtt ttccattcca agcaaatgct agggcgttat ctgtctcgga tgcagatggc tttgtacaag ttgtagccga aaagaatacg aaaagagtgt taggagtaca gatggttgga ccagaggtat cctctctgat tgcagaggct gtttttgcga ttgaggctgg ggcaaatgcg gaagatctta gccttacgat tcatgctcat cctaccttac cagagccact tatggaagca gcagaaggtg tgatgggaca tgctacacat atgttgaata aaaagcaata atgtgaatgc aggccaacct gcactttttc ataagtgcag gttgaatttt tattaatgga tggagactca tgcacatttt gtattgatag atgtattact gtataaaatt cctgatggta tggattaatc actattcatg aatttctaat gaactgggtt aatacaaatt atgaaatata tcaaatcgtt tttctgactg tttatgaacg atgaaggagt tgatataaat gaatttaatt ttaactattc tctctgcttt aggttctttt atagtaacca atgtcgatga tatttttgtc ttgatgttac tgttctctca agcaaggtca caagctaaaa cgggtaacag tggaatagtt agcatggagt cgaaaggaaa ccgtatttat ccaagagata tagtcattgg ccaatatctt ggttttgcac ttttagtttt aatcagtctt ttagcaacat ttggagtaac actcattcct gatcagtggg

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    GENOM.057CPl.TXT taggtttgct aggattaata ccgatatatc taggagtaaa actctttata aagggtgaag atgaggatga aggtaacatt ctttccaact taaacaaatt taataagttc tatttaagtg tagcctttat cacattcgcc aatggcggag acaatattgg aatttatgtt ccattctttt ctaccttaaa taacaaccaa ctgataatta cagttgttac tttctttata atggttgctg tctggtgttt aattggctat cgtctagcaa ggttcagata tgtttctgaa acacttgaga aatacggccg ctggattatc ccaattgtgt ttataggatt aggaatatat attatggtgg agaacgaaac tttccgcgcc attttgagtt tagtgaatta aaaatttctc aaaagtacct ctgatttaca gtaggacttt gatatttaga gtaaatattt atcctctgac aaataattct atggatacgc tcatctatat tttgcttagc gtacaaaatt tccgaaatgt tggctgtacc ccaataagca attagaatat tatcaaaatt gttaattaag aatagccctc gaaaaaatcg ggggctttgc ttttggcata agacggccaa aacaaagccg aaccaaaagg agtgaatgtg atgtgcataa cgcacacaca tcacattcac attaaaacta aattcaaaat ggagggaaag tgaagattca ctttcccttt attttcattt ttagaattta tttttttgtg ttgaaacgct cacacgtaca atcaaagatt gtacttttaa caagcctact caatcttaca aggggcaata aaacttttta ggttctgttg caaagtaaaa aatatagcta accactaatt tatcatgtca gtgttcgctt aacttgctag catgatgcta atttcgtggc atggcgaaaa tccgtagatc tgaagagacc tgcggttctt tttatataga gcgtaaatac attcaatacc ttttaaagta ttctttgctg tattgatact ttgatacctt gtctttctta ctttaatatg acggtgatct tgctcaatga ggttattcag atatttcgat gtacaatgac agtcaggttt aagtttaaaa gctttaatta ctttagccat tgctaccttc gttgaaggcg cctgatctgt aattaccttt tgaggtttac caaattgttt aatgagacgt ttgataaacg catatgctga atgattatct cgttgcttac gcaaccaaat atctaatgta tgtccctctg catcaatggc acgatataaa tagctccatt ttccttttat tttgatgtac gtctcatcaa tacgccattt gtaataagct tttttatgct ttttcttcca aatttgatac aaaattgggg catattcttg aacccaacgg tagaccgttg aatgatgaac gtttacacca cgttccctta atatttcaga tatatcatga taactcaatg catatcttag atagtagcca acggctacag tgataacatc cttgttaaat tgtttatatc tgaaatagtt catacagaag actccttttt gttaaaatta tactataaat tcaactttgc aacagaacca tttgcgatac aacgaggcga cattagccgt taatttgctt aactgtagaa gatttaaaag aaccccttgc catatattta acaatgttgt ccgggataac aacacagtga atccaccgtt tagttaagat gatggatttt ttcaaactgt ggatgaggta cagagtttca ttagataaaa acagggaaaa cttattaaag agtgatttct gtgaggagga taatgatgac aaagaaatac gatcttattg tgattggtac aggttctgcg gggtcaatca cagcagcaaa atgtaataaa gccggctgga atgtagctat ggtagatgac aggccgtttg gaggcacgtg tgcactacgt ggatgtgacc caaaaaaggt tctacatggt gctgccgagc ttattgattg gaacaaacgg atggttaaga atggagtacc gtctgaagtc tccatcaact ggaaagatct tatgaatttt aaaagaacct ttacagatga tgtcccggaa aaaaaagagg aagcattgaa taaacaggga atcgatacgt atcatggcaa tgcatctttc gtgagtgagg acaaacttga agtgaataaa gaagtgctcg aggggagtca tttcttgatc gctagtggtg cgaaacctac ccctttaccc ataaaaggag aagaacatct tacttatagt gatgagtttt tggagttgga tgaattacca caaagaatcg tctttgttgg tggtgggtat atttcgtttg aatttgctca tatcgcggca cgtgctggat cagaagttca tattatccat cgaggtcaaa gacctttgga gaattttgat atagatcttg tagatatcct tttagaaaag tcgaaagaga ttggcataca ggtacatctt caacattccg ttgaatccat tgaaaaagaa caaggaaagt ttcatgtgta cgctcgaaaa aaagaggata taacgcggtt tgaagcagac attgttattc atggtgctgg acgggtccct gccttagata tgaatcttga aaaagggaat atagaaagga aaaaacatgg tgtccatgtt aatgagtatt tgcaaagtgt aagtaacccg aatgtctatg cagctggaga tgctgcagca acggatggct tgcccctcac acctgtagcc agtgcagatt ctcatgtcgt agcatctaat ttattgaaag ggaacagcaa aaaaattgaa tatcccgtga ttccatctgc tgtatttacc gtacctaaaa tggcatcggt aggtatgagc gaggaggaag ccaaaaactc tggccggaat attaaagtaa agcagaaaaa catctccgac tggtttacgt ataaacggac aaatgaggac tttgctgcgt ttaaagtgct aattgacgag gatagtgatc aagttgtcgg tgctcatttg attagtaatg aagccgatga actaattaac cactttgcaa cagccattcg ctttggaatt tcaaccaaag aattgaaaca aatgatattt gcctatccaa cggcagcttc ggacattgca cacatgttgt aagtttgcgt tttgtgagat gtttataaac cactttatcg tctaatcttg ttatatgatc ttagaatcaa aaagaaaata acttttttga cagccacatt tttcaacgga agaatgtggc ttcttggcgt gaagagcaga tatctttatt cttaaacttc taaaaaagct tatgtgaaca cttgataaat aaggtttttt atctgaccta ttttataaga ttattctata aaagaaaaaa taatgtatga cttgaccgtg tactatagta cagggtttat actttttatt gaggtgacaa tatggagatg aaaatcagtg aattggctaa agcgtgtgat gtgaataaag aaaccgttcg gtattacgag cggaaaggat tgatagccgg gcctcccaga aacgaatcag ggtatcgaat atattcagag gaaacagcag atcgggtacg gtttattaaa cgaatgaagg aattggattt ctcgctaaag gaaatccacc tgttgtttgg tgtggttgat caagatgggg agagatgtaa agatatgtac gcctttaccg ttcaaaaaac caaagaaatc gagcggaaag tgcaggattt gttacgaatc caacggttat tagaggaatt aaaagaaaag tgtccagatg aaaaggcgat atatacctgt cctattattg aaacgttaat gggagggcct gataaataaa tgggggaaga tttgaatgaa aaaacgcatt tccttcaccg ctataatgac ggtgttgtta atcggtttaa cagcttgtgg agcagaatct gataccgcga

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT atgaatcaaa ggttcaagac attcaaggaa atccagtcag cctacctaat gagaaaccca cactcattta ttttatggca acctggtgtc catcttgtat atacaatgag gaaatcttta aggaaattca tcaactaaac ccgaacgatg ttcaattgat cacagttagt ttagacccta acacagatac aaaagaaagc tttgcgaaat ttaaacagga ttatggcggg gattggcccc atgttttaaa gataggagtg gaattatgag tttttcgttt ctcttcattc tgaccgctgg aatggttgcg gcctttaatc cttgtggtat cgccttgctt ccttcttata tctcctattt aattggaggc gaaacaaagg atcattcgtt ccgctatgca atttttaaag gattagggct tggtggagcg atgaccacgg ggtttttaac gatttttgta ttggctggtt tgttgatagg aggattggga agcgcactaa cagggatttt tccgattctt tcattggtta tgggtatact cattgcttta ttggggttgg gcatgctatt tgggaagcat ttgccgatta aaataggatc ttttcaagtc aagccaggga aatggtctat ctatttttac ggaatagcct atgccgtgac atcacttggt tgtaccttgc cagcctttat gttggtggtc tctgcatcgc tgaatgacaa tagcgtaacg gccgtgatca tcaagttcat catctactcc cttggtatgg gaattgtggt gacagcgatc acgatggtct cattgatttc acgacaattg gtacagaagt ttctgcacaa ctatatgggt tctatccaaa aaatagcagc tgttgtgatt ttcctctccg gtttgtacat ggcttattac tggtatttcg gttctggtgg catttgtaca ttttaaaatc caaccgatca ggtgtaacaa aaaatagatg aaagatgtaa aaaagctaaa cgaacaaatt tcaagttagg ctataggcca tgtatgtacc ttaaccaaag aataaaattt ttttagaaag agtggtgaga atgatggatg agaatcgctc gaaaggtaac cgctggggtg tttgggcctt tttcggaata ttattggttc ctttattggt tcctttactt tgttgcgcag gaccgattct ccttgttgca ttagggagca caggtattgg tgccctcttt gctggtgcga caggaaattg gtggttgacc ggcatttttg cagcattggc cattgttatg attgctctga tcctcagcaa gttgttgaag aacaaataca attctcctga aggcaatgga aaaacaaaaa ataaaacgga ttgctgtacg cctccagaga gcgtggatcg gaaacatgag acaagataaa tatgagataa atgtacagaa ctgtctatca aactttaaat agaaagaggg attcaaatga ctcaaaattc atataaaata cccattcaag gcatgacatg cacaggctgt gaagaacatg taaccgaagc attggaacaa gccggagcta aagatgtttc ggccgatttc cgacgcggtg aggccatttt tgaactcagc gatgatcaga tcgaaaaggc taagcaaaat atttcggcag ccggctatca acccggagag gaagaaagcc agccctctga aaacagtgta gatttcaatc gggatggcga ttacgatctt ctgattattg gttccggcgg tgcggcgttt tctgcagcta tcaaggccaa tgaaaacggg gcgaaagtgg ccatggtaga acggggaacc gtcgggggga cctgcgttaa catcggttgt gtaccgtcaa aaaccatgct tcgtgccggt gaaataaacg gtctcgccca aaacaatccg tttaccggac ttcaaacgag taccggtgct gcggaccttg cccaattgac cgaacaaaaa gatggattag tcagtcaaat gcgtcaagaa aaatatatag acttgatcga agaatatgga tttgatctca ttcgtggcga ggcctcgttt atcgacgata agacgataca agtgaatgga caaaacatca cgtctaaaag ctttttaatc gcaacggggg cttctccggc tgttccggaa atcccgggaa tgaatgaggt tgattattta acaagtacat ccgcactcga attaaaagag gttccacaac gattggcagt gatcggttct ggctatatcg cagcggaatt aggtcaaatg tttcacaacc tcggaacaga agtgactctc atgcaaagaa gcgagcgtct gtttaaaacc tacgatcctg aaatttccga agccatcgat gaatccttaa ctgagcaagg acttaacctg atcactgggg tcacttatca aaaggttgag caaaacggta agtcgacaag catttatatt gaagtgaacg gtcaagaaca agtcatcgaa gccgatcaag tcctcgtggc aacaggaaga aagccgaaca cagagacttt aaaccttgaa tcagcaggtg tgaaaacagg gaaaaaaggc gaagtgctga ccaatgaata tttgcaaacg tcgaataacc gaatatatgc cgcgggcgat gtgaccctcg gtccgcaatt cgtttatgtt gcagcttatg aaggcgggat tgtggcaaat aatgcgttgg gtctagcgaa acgcaaaatc gatcttcgct ttgttcccgg cgtaaccttc accaatccat cgatcgccac agtcggcttg actgaacaac aggcaaaaga aaaaggttac gatgtcaaaa catcggtcct tccgttggac gctgtaccgc gggccttagt caatcacgaa acaacagggg tctataaact tgtagtcaac gcccaaaccc agaaattgat cggggcgcac attgtgagtg aaaatgctgg agatgtgatt tatgcggcaa cgttagcggt tcaatttgga ttgaccattg aagaccttac ggatagcttt gcgccttatt taacgatggc tgaaggatta aagcttgcag ccttgacgtt tgataaagac gtatcgaaat tatcttgttg tgcaggctaa tggttccttt tgattctaat gctatgttgc aggaggcact taaaacaatg aagtggagaa aatataagga ggaataagct tatgaaaaat atttcagaat tctcagccca acttaatcaa acttttgatc aaggggaagc cgtctctatg gagtggttat tccgtccgtt gctaaaaatg ctggcggagg gcgatccagt ccccgttgag gacatcgcgg cggagaccgg gaagcccgtc gaggaagtta agcaagtcct acagactcta cctagtgtgg aacttgatga gcagggccgt gtcgtcggtt atggcctcac actggtccct accccccatc gcttcgaggt tgatgggaag caactatatg catggtgcgc ccttgacaca cttatgttcc cagcactcat cggccggacg gtccacatcg cttcgccttg tcacggcacc ggtaagtccg tacggttgac ggtggaaccg gaccgcgttg taagcgtcga gccttcaaca gccgttgtct cgattgttac accagatgaa atggcctcgg ttcggtcggc cttctgtaac aacgttcact ttttcagttc accgagtgca gcccaagact ggcttaacca acaccctgag tcgagcgttt tgcccgttga agatgccttt gaactgggtc gccatttggg agcgcgttat gaggagtcag gacctactaa tgggtcctgt tgtaacattt aatcttaggc aattacgcct gcgtcaatct tggccttacg atgatgtcct gtaaccgaag ctctatctag tgaaaccaat tttatgggaa accaaataaa taaaaagatc aattgcttgt gcctatatcg gggagttaat aaagcgagaa agtggattct tgaatatagg

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    2018206754 18 Jul 2018

    GENOM.057CPl.TXT agtaaataag gtgccaaaat ggcaccttat ttaaaatatg taacgccaag gtctgccgta 55380 ttatattgca ttggaaaaag aaaaccttct gtataaggag atgttatatg atatttggta 55440 aactgttcgg cagtttgggc gtagaaagct tttgctcctt gaacatcacg tttgccagtt 55500 acaatgtcat ttaacaagtt taaagataaa aaattcatcg cttcctcatg acactttgct 55560 gatgcctcac ctgtagttcg atctaagtag acacttccat caaaagcggc aatcgcatca 55620 tataagtgta cgggcacttt ataatcgatg gtctgcttaa ggaaatcaag gtgaggggta 55680 gggaagttat gagggactgg atccttatat actatcgtgc gtttccatgg cccgctattg 55740 taccaaatta atcgtctcat tgttgcttcc tggggatatc catacttact aattatggtt 55800 tttgcccctt ccaacggtgg tccctgccaa taggacaaaa tgtgatttaa atgactatcc 55860 attgccatac ctcctaaaca tttgcctaaa agcattgtat gcccaataaa tgaattttag 55920 gtaaatgtat atttaatgat cggcagattg cagtaaataa cgaatgcctg caatgcaatt 55980 aacatgggat ttaacactgg acagtaattt ttttgctggg attttgctat cagatagctt 56040 ttcttagtga tgataggata tgttgaccaa attggccgtg agattggagg ggtggttttt 56100 atggttagtt gttgttcaat cgatccatac actgaattcg aagtcattat tattggtgcc 56160 ggggtgccgg aggtttctct tgcctttcat ttgacttcat acggcataag gacggcactt 56220 gcggatgaac agaacgtgga taacagatta aaggactttt taagaacttt tcaagaattg 56280 attgagcgcg attcgggtat gccgtgaacg ttacaggcaa taaaagaaga tatgcacctc 56340 atcctttttg acggtaccat tacccttgaa ggtgaacatg ctgtccgtat tgatgaacac 56400 aaaattcggg gggatcgtat ggtcgtacca tttgatacgt ttaaacaaat aggaaaacct 56460 agaaaccaaa acgacatcca ttttaaaaac gatccttttc aaagagttac gaatgattta 56520 tggatcacga atccctcatt gtcagaagtg gatcaagaac aaatatggca gactggagac 56580 tatttttcaa aacaccttca gaacattgaa taaatgaagg gttctgttgc aaagtaaaaa 56640 aatatagcta accactaatt tatcatgtca gtgttcgctt aacttgctag catgatgcta 56700 atttcgtggc atggcgaaaa tccgtagatc tgaagagacc tgcggttctt tttatataga 56760 gcgtaaatac attcaatacc ttttaaagta ttctttgctg tattgatact ttgatacctt 56820 gtctttctta ctttaatatg acggtgatct tgctcaatga ggttattcag atatttcgat 56880 gtacaatgac agtcaggttt aagtttaaaa gctttaatta ctttagccat tgctaccttc 56940 gttgaaggtg cctgatctgt aattaccttt tgaggtttac caaattgttt aatgagacgt 57000 ttgataaacg catatgctga atgattatct cgttgcttac gcaaccaaat atctaatgta 57060 tgtccctctg catcaatggc acgatataaa tagctccatt ttccttttat tttgatgtac 57120 gtctcatcaa tacgccattt gtaataagct tttttatgct ttttcttcca aattcgatat 57180 aaaattgggg catattcttg aacccaacgg tagaccgttg aatgatgaac gtttacacca 57240 cgttccctta atatttcaga tatatcacga taactcaatg catatcttag atagtagcca 57300 acggctacag tgataacatc cttgttaaat tgtttatatc tgaaatagtt catacagaag 57360 gctccttttt gttaaaatta tactataaat tcaactttgc aacagaacct tattgcatat 57420 ctttttagcc atatcactga tagggtgaag catatcataa atgatgcggt tttt 57474

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