LIMKs as modifiers of p53 pathway and methods of use

Abstract

Human LIMK genes are identified as modulators of the p53 pathway, and thus are therapeutic targets for disorders associated with defective p53 function. Methods for identifying modulators of p53, comprising screening for agents that modulate the activity of LIMK are provided.

Description

REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional application of U.S. patent application Ser. No. 10/161,453, filed Jun. 3, 2002, which claims priority to U.S. provisional patent application No. 60/296,076 filed Jun. 5, 2001, No. 60/328,605 filed Oct. 10, 2001, and No. 60/357,253 filed Feb. 15, 2002. The contents of the prior applications are hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] The p53 gene is mutated in over 50 different types of human cancers, including familial and spontaneous cancers, and is believed to be the most commonly mutated gene in human cancer (Zambetti and Levine, FASEB (1993) 7:855-865; Hollstein, et al., Nucleic Acids Res. (1994) 22:3551-3555). Greater than 90% of mutations in the p53 gene are missense mutations that alter a single amino acid that inactivates p53 function. Aberrant forms of human p53 are associated with poor prognosis, more aggressive tumors, metastasis, and short survival rates (Mitsudomi et al., Clin Cancer Res 2000 October; 6(10):4055-63; Koshland, Science (1993) 262:1953).

[0003] The human p53 protein normally functions as a central integrator of signals including DNA damage, hypoxia, nucleotide deprivation, and oncogene activation (Prives, Cell (1998) 95:5-8). In response to these signals, p53 protein levels are greatly increased with the result that the accumulated p53 activates cell cycle arrest or apoptosis depending on the nature and strength of these signals. Indeed, multiple lines of experimental evidence have pointed to a key role for p53 as a tumor suppressor (Levine, Cell (1997) 88:323-331). For example, homozygous p53 "knockout" mice are developmentally normal but exhibit nearly 100% incidence of neoplasia in the first year of life (Donehower et al., Nature (1992) 356:215-221).

[0004] The biochemical mechanisms and pathways through which p53 functions in normal and cancerous cells are not fully understood, but one clearly important aspect of p53 function is its activity as a gene-specific transcriptional activator. Among the genes with known p53-response elements are several with well-characterized roles in either regulation of the cell cycle or apoptosis, including GADD45, p21/Waf1/Cip1, cyclin G, Bax, IGF-BP3, and MDM2 (Levine, Cell (1997) 88:323-331).

[0005] Eukaryotic LIM proteins contain LIM domains, highly conserved cysteine-rich structures containing two zinc fingers (Mizuno, K. et al. (1994) Oncogene 9: 1605-1612, 1994). Zinc fingers usually function by binding to DNA or RNA. However, it is believed that the LIM motif mediates protein-protein interactions. LIM kinase (LIMK) belongs to a small subfamily of kinases with a unique combination of two N-terminal LIM motifs and a C-terminal protein kinase domain. These LIM motifs and kinase domains are linked by a proline-serine-rich region containing several putative casein kinase and map kinase recognition sites (Mizuno, K. et al. (1994) supra). LIM kinases and their pathway proteins are believed to contribute to Rho-induced reorganization of the actin cytoskeleton (Maekawa et al. (1999) Science 285: 895-898).

[0006] LIM kinase 1 (LIMK1) contains a serine/threonine kinase with two LIM domains. It mediates signaling from Rho to the actin cytoskeleton via phosphorylation of cofilin, is involved in T cell chemotaxis, is activated during mitosis, and may regulate cell cycle progression. LIMK1 lacks a signal peptide and putative transmembrane domains, and therefore it may be a component of an intracellular signaling pathway and is likely involved in brain development (Tassabehji, M., et al. (1996) Nature Genet. 13: 272-273). LIMK1 demonstrates 95% homology with the murine LIMK1 gene and therefore the function of this gene should also be highly conserved (Proschel, C., et al. (1995) Oncogene 11: 1271-1281). Limk1 is expressed in the central nervous system during embryogenesis (Proschel, C., et al. (1995) supra). LIMK1 has also been identified as a potential activator of serum response factor, which regulates transcription of many serum-inducible and muscle-specific genes (Sotiropoulos, A., et al. (1999) Cell 98: 159-169). LIMK1 has been identified as a candidate for the unexplained neurologic features of William's syndrome (Tassabehji, M. et al. (1996) supra).

[0007] LIM kinase 2 (LIMK2), a second member of the LIMK family, has a domain structure similar to LIMK 1 with a serine/threonine protein kinase with two LIM motifs (Okano, I. et al. (1995) Science 285: 895-898). It also phosphorylates cofilin and regulates Rho family-dependent actin cytoskeletal rearrangement. LIMK2 has two alternative transcripts, LIMK2a and LIMK2b. Both forms of LIMK2 are expressed in a wide variety of tissues, with placenta showing the highest expression levels (Osada, H. et al. (1996) Biochem. Biophys. Res. Commun. 229:582-589). LMK2a contains two LIM domains, a PDZ domain, and a kinase domain. LIMK2b has only 1.5 LIM domains, which is thought to be involved in protein-protein interactions; the PDZ domain was originally recognized in a family of proteins related to the Drosophila lethal discs-large tumor suppressor gene product Dlga which functions in in protein-protein interactions targeting the protein to the submembranous compartment. Several studies have shown that LIMK2a (63 kD protein) resides in the cytoplasm and nucleus while the LIMK2b (58 kD protein) is found mainly in the cytoplasm (Okano, I. et al. (1995) supra).

[0008] Testis-specific protein kinase (TESK) is a probable member of the LIMK subfamily of serine/threonine protein kinases, and has strong similarity to rat Rn.7006, which is expressed specifically in testicular germ cells and may have a role in spermatogenesis. The protein kinase of the human TESK1 is structurally similar to both LIMK1 and LIMK2 (Toshima, J. et al. (1995) J. Biol. Chem. 270: 31331-31337). Testis-specific kinase 2 protein kinase (TESK 2) is a member of the LIMK/TESK subfamily of serine/threonine protein kinases, and may play a role in spermatogenesis. TESK2 exhibits dual specific protein kinase activity on both serine/threonine and tyrosine. It is predominantly expressed in the testis and prostate (Rosok, O. et al. (1999) Genomics 61: 44-54).

[0009] The ability to manipulate the genomes of model organisms such as Drosophila provides a powerful means to analyze biochemical processes that, due to significant evolutionary conservation, has direct relevance to more complex vertebrate organisms. Due to a high level of gene and pathway conservation, the strong similarity of cellular processes, and the functional conservation of genes between these model organisms and mammals, identification of the involvement of novel genes in particular pathways and their functions in such model organisms can directly contribute to the understanding of the correlative pathways and methods of modulating them in mammals (see, for example, Mechler B M et al., 1985 EMBO J. 4:1551-1557; Gateff E. 1982 Adv. Cancer Res. 37: 33-74; Watson K L., et al., 1994 J Cell Sci. 18: 19-33; Miklos G L, and Rubin G M. 1996 Cell 86:521-529; Wassarman D A, et al., 1995 Curr Opin Gen Dev 5: 44-50; and Booth D R. 1999 Cancer Metastasis Rev. 18: 261-284). For example, a genetic screen can be carried out in an invertebrate model organism having underexpression (e.g. knockout) or overexpression of a gene (referred to as a "genetic entry point") that yields a visible phenotype. Additional genes are mutated in a random or targeted manner. When a gene mutation changes the original phenotype caused by the mutation in the genetic entry point, the gene is identified as a "modifier" involved in the same or overlapping pathway as the genetic entry point. When the genetic entry point is an ortholog of a human gene implicated in a disease pathway, such as p53, modifier genes can be identified that may be attractive candidate targets for novel therapeutics.

[0010] All references cited herein, including sequence information in referenced Genbank identifier numbers and website references, are incorporated herein in their entireties.

SUMMARY OF THE INVENTION

[0011] We have discovered genes that modify the p53 pathway in Drosophila, and identified their human orthologs, hereinafter referred to as LIMK. The invention provides methods for utilizing these p53 modifier genes and polypeptides to identify candidate therapeutic agents that can be used in the treatment of disorders associated with defective p53 function. Preferred LIMK-modulating agents specifically bind to LIMK polypeptides and restore p53 function. Other preferred LIMK-modulating agents are nucleic acid modulators such as antisense oligomers and RNAi that repress LIMK gene expression or product activity by, for example, binding to and inhibiting the respective nucleic acid (i.e. DNA or mRNA).

[0012] LIMK-specific modulating agents may be evaluated by any convenient in vitro or in vivo assay for molecular interaction with a LIMK polypeptide or nucleic acid. In one embodiment, candidate p53 modulating agents are tested with an assay system comprising a LIMK polypeptide or nucleic acid. Candidate agents that produce a change in the activity of the assay system relative to controls are identified as candidate p53 modulating agents. The assay system may be cell-based or cell-free. LIMK-modulating agents include LIMK related proteins (e.g. dominant negative mutants, and biotherapeutics); LIMK-specific antibodies; LIMK-specific antisense oligomers and other nucleic acid modulators; and chemical agents that specifically bind LIMK or compete with LIMK binding target. In one specific embodiment, a small molecule modulator is identified using a kinase assay. In specific embodiments, the screening assay system is selected from a binding assay, an apoptosis assay, a cell proliferation assay, an angiogenesis assay, and a hypoxic induction assay.

[0013] In another embodiment, candidate p53 pathway modulating agents are further tested using a second assay system that detects changes in the p53 pathway, such as angiogenic, apoptotic, or cell proliferation changes produced by the originally identified candidate agent or an agent derived from the original agent. The second assay system may use cultured cells or non-human animals. In specific embodiments, the secondary assay system uses non-human animals, including animals predetermined to have a disease or disorder implicating the p53 pathway, such as an angiogenic, apoptotic, or cell proliferation disorder (e.g. cancer).

[0014] The invention further provides methods for modulating the p53 pathway in a mammalian cell by contacting the mammalian cell with an agent that specifically binds a LIMK polypeptide or nucleic acid. The agent may be a small molecule modulator, a nucleic acid modulator, or an antibody and may be administered to a mammalian animal predetermined to have a pathology associated the p53 pathway.

DETAILED DESCRIPTION OF THE INVENTION

[0015] Genetic screens were designed to identify modifiers of the p53 pathway in Drosophila in which p53 was overexpressed in the wing (Ollmann M, et al., Cell 2000 101: 91-101). The CG6027/cdi/tsk gene was identified as a modifier of the p53 pathway. Accordingly, vertebrate orthologs of these modifiers, and preferably the human orthologs, LIMK genes (i.e., nucleic acids and polypeptides) are attractive drug targets for the treatment of pathologies associated with a defective p53 signaling pathway, such as cancer.

[0016] In vitro and in vivo methods of assessing LIMK function are provided herein. Modulation of the LIMK or their respective binding partners is useful for understanding the association of the p53 pathway and its members in normal and disease conditions and for developing diagnostics and therapeutic modalities for p53 related pathologies. LIMK-modulating agents that act by inhibiting or enhancing LIMK expression, directly or indirectly, for example, by affecting a LIMK function such as enzymatic (e.g., catalytic) or binding activity, can be identified using methods provided herein. LIMK modulating agents are useful in diagnosis, therapy and pharmaceutical development.

Nucleic Acids and Polypeptides of the Invention

[0017] Sequences related to LIMK nucleic acids and polypeptides that can be used in the invention are disclosed in Genbank (referenced by Genbank identifier (GI) number) as GI#s 11421438 (SEQ ID NO:1), 8051614 (SEQ ID NO:2), 8051616 (SEQ ID NO:3), 565279 (SEQ ID NO:4), 10439425 (SEQ ID NO:5), 2078469 (SEQ ID NO:6), 8051617 (SEQ ID NO:7), 8051619 (SEQ ID NO:8), 15341773 (SEQ ID NO:9), 13928783 (SEQ ID NO:10), 5454109 (SEQ ID NO:11), 14739649 (SEQ ID NO:12), 15080032 (SEQ ID NO:13), 1805594 (SEQ ID NO:14), 6005895 (SEQ ID NO:15), 18549250 (SEQ ID NO:16), 15207800 (SEQ ID NO:17), and 14042344 (SEQ ID NO:18) for nucleic acid, and GI#s 11421439 (SEQ ID NO:19), 4505001 (SEQ ID NO:20), 2078472 (SEQ ID NO:21), 5031869 (SEQ ID NO:22), 2499660 (SEQ ID NO:23), 5454110 (SEQ ID NO:24) and 6005896 (SEQ ID NO:25) for polypeptides.

[0018] LIMKs are kinase proteins with kinase domains. The term "LIMK polypeptide" refers to a full-length LIMK protein or a functionally active fragment or derivative thereof. A "functionally active" LIMK fragment or derivative exhibits one or more functional activities associated with a full-length, wild-type LIMK protein, such as antigenic or immunogenic activity, enzymatic activity, ability to bind natural cellular substrates, etc. The functional activity of LIMK proteins, derivatives and fragments can be assayed by various methods known to one skilled in the art (Current Protocols in Protein Science (1998) Coligan et al., eds., John Wiley & Sons, Inc., Somerset, New Jersey) and as further discussed below. For purposes herein, functionally active fragments also include those fragments that comprise one or more structural domains of a LIMK, such as a kinase domain or a binding domain. Protein domains can be identified using the PFAM program (Bateman A., et al., Nucleic Acids Res, 1999, 27:260-2; http://pfam.wustl.edu). For example, the LIM domains of LIMK from GI# 4505001 (SEQ ID NO:20) are located at approximately amino acid residues 80 to 136 and 139 to 198 (PFAM 00412). The LIM domains of LIMK from GI# 5031869 (SEQ ID NO:22) are located at approximately amino acid residues 12 to 69, 72 to 129 (PFAM 00412). Further, the kinase domains of LIMK from GI#s 4505001, 5031869, 5454110 and 6005896 (SEQ ID NOs: 20, 22, 24, and 25, respectively) are located at approximately amino acid residues 394 to 652 for GI# 4505001, 310-518 for GI#5031869, 57 to 314 for GI#5454110, and 62 to 117 and 120 to 289 for GI#6005896, respectively (PFAM00069). Methods for obtaining LIMK polypeptides are also further described below. In some embodiments, preferred fragments are functionally active, domain-containing fragments comprising at least 25 contiguous amino acids, preferably at least 50, more preferably 75, and most preferably at least 100 contiguous amino acids of any one of SEQ ID NOs:19, 20, 21, 22, 23, 24, or 25 (a LIMK). In further preferred embodiments, the fragment comprises the entire kinase (functionally active) domain.

[0019] The term "LIMK nucleic acid" refers to a DNA or RNA molecule that encodes a LIMK polypeptide. Preferably, the LIMK polypeptide or nucleic acid or fragment thereof is from a human, but can also be an ortholog, or derivative thereof with at least 70% sequence identity, preferably at least 80%, more preferably 85%, still more preferably 90%, and most preferably at least 95% sequence identity with LIMK. Normally, orthologs in different species retain the same function, due to presence of one or more protein motifs and/or 3-dimensional structures. Orthologs are generally identified by sequence homology analysis, such as BLAST analysis, usually using protein bait sequences. Sequences are assigned as a potential ortholog if the best hit sequence from the forward BLAST result retrieves the original query sequence in the reverse BLAST (Huynen M A and Bork P, Proc Natl Acad Sci (1998) 95:5849-5856; Huynen M A et al., Genome Research (2000) 10:1204-1210). Programs for multiple sequence alignment, such as CLUSTAL (Thompson J D et al, 1994, Nucleic Acids Res 22:4673-4680) may be used to highlight conserved regions and/or residues of orthologous proteins and to generate phylogenetic trees. In a phylogenetic tree representing multiple homologous sequences from diverse species (e.g., retrieved through BLAST analysis), orthologous sequences from two species generally appear closest on the tree with respect to all other sequences from these two species. Structural threading or other analysis of protein folding (e.g., using software by ProCeryon, Biosciences, Salzburg, Austria) may also identify potential orthologs. In evolution, when a gene duplication event follows speciation, a single gene in one species, such as Drosophila, may correspond to multiple genes (paralogs) in another, such as human. As used herein, the term "orthologs" encompasses paralogs. As used herein, "percent (%) sequence identity" with respect to a subject sequence, or a specified portion of a subject sequence, is defined as the percentage of nucleotides or amino acids in the candidate derivative sequence identical with the nucleotides or amino acids in the subject sequence (or specified portion thereof), after aligning the sequences and introducing gaps, if necessary to achieve the maximum percent sequence identity, as generated by the program WU-BLAST-2.0a19 (Altschul et al., J. Mol. Biol. (1997) 215:403-410; http://blast.wustl.edu/blast/README.html) with all the search parameters set to default values. The HSP S and HSP S2 parameters are dynamic values and are established by the program itself depending upon the composition of the particular sequence and composition of the particular database against which the sequence of interest is being searched. A % identity value is determined by the number of matching identical nucleotides or amino acids divided by the sequence length for which the percent identity is being reported. "Percent (%) amino acid sequence similarity" is determined by doing the same calculation as for determining % amino acid sequence identity, but including conservative amino acid substitutions in addition to identical amino acids in the computation.

[0020] A conservative amino acid substitution is one in which an amino acid is substituted for another amino acid having similar properties such that the folding or activity of the protein is not significantly affected. Aromatic amino acids that can be substituted for each other are phenylalanine, tryptophan, and tyrosine; interchangeable hydrophobic amino acids are leucine, isoleucine, methionine, and valine; interchangeable polar amino acids are glutamine and asparagine; interchangeable basic amino acids are arginine, lysine and histidine; interchangeable acidic amino acids are aspartic acid and glutamic acid; and interchangeable small amino acids are alanine, serine, threonine, cysteine and glycine.

[0021] Alternatively, an alignment for nucleic acid sequences is provided by the local homology algorithm of Smith and Waterman (Smith and Waterman, 1981, Advances in Applied Mathematics 2:482-489; database: European Bioinformatics Institute http://www.ebi.ac.uk/MPsrch/; Smith and Waterman, 1981, J. of Molec.Biol., 147:195-197; Nicholas et al., 1998, "A Tutorial on Searching Sequence Databases and Sequence Scoring Methods" (www.psc.edu) and references cited therein; W. R. Pearson, 1991, Genomics 11:635-650). This algorithm can be applied to amino acid sequences by using the scoring matrix developed by Dayhoff (Dayhoff: Atlas of Protein Sequences and Structure, M. O. Dayhoff ed., 5 suppl. 3:353-358, National Biomedical Research Foundation, Washington, D.C., USA), and normalized by Gribskov (Gribskov 1986 Nucl. Acids Res. 14(6):6745-6763). The Smith-Waterman algorithm may be employed where default parameters are used for scoring (for example, gap open penalty of 12, gap extension penalty of two). From the data generated, the "Match" value reflects "sequence identity."

[0022] Derivative nucleic acid molecules of the subject nucleic acid molecules include sequences that hybridize to the nucleic acid sequence of any of SEQ ID NOs:1 through 18. The stringency of hybridization can be controlled by temperature, ionic strength, pH, and the presence of denaturing agents such as formamide during hybridization and washing. Conditions routinely used are set out in readily available procedure texts (e.g., Current Protocol in Molecular Biology, Vol. 1, Chap. 2.10, John Wiley & Sons, Publishers (1994); Sambrook et al., Molecular Cloning, Cold Spring Harbor (1989)). In some embodiments, a nucleic acid molecule of the invention is capable of hybridizing to a nucleic acid molecule containing the nucleotide sequence of any one of SEQ ID NOs:1 through 18 under stringent hybridization conditions that comprise: prehybridization of filters containing nucleic acid for 8 hours to overnight at 65.degree. C. in a solution comprising 6.times. single strength citrate (SSC) (1.times.SSC is 0.15 M NaCl, 0.015 M Na citrate; pH 7.0), 5.times. Denhardt's solution, 0.05% sodium pyrophosphate and 100 .mu.g/ml herring sperm DNA; hybridization for 18-20 hours at 65.degree. C. in a solution containing 6.times.SSC, 1.times. Denhardt's solution, 100 .mu.g/ml yeast tRNA and 0.05% sodium pyrophosphate; and washing of filters at 65.degree. C. for 1 h in a solution containing 0.2.times.SSC and 0.1% SDS (sodium dodecyl sulfate).

[0023] In other embodiments, moderately stringent hybridization conditions are used that comprise: pretreatment of filters containing nucleic acid for 6 h at 40.degree. C. in a solution containing 35% formamide, 5.times.SSC, 50 mM Tris-HCl (pH7.5), 5 mM EDTA, 0.1% PVP, 0.1% Ficoll, 1% BSA, and 500 .mu.g/ml denatured salmon sperm DNA; hybridization for 18-20 h at 40.degree. C. in a solution containing 35% formamide, 5.times.SSC, 50 mM Tris-HCl (pH7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 .mu.g/ml salmon sperm DNA, and 10% (wt/vol) dextran sulfate; followed by washing twice for 1 hour at 55.degree. C. in a solution containing 2.times.SSC and 0.1% SDS.

[0024] Alternatively, low stringency conditions can be used that comprise: incubation for 8 hours to overnight at 37.degree. C. in a solution comprising 20% formamide, 5.times.SSC, 50 mM sodium phosphate (pH 7.6), 5.times. Denhardt's solution, 10% dextran sulfate, and 20 .mu.g/ml denatured sheared salmon sperm DNA; hybridization in the same buffer for 18 to 20 hours; and washing of filters in 1.times.SSC at about 37.degree. C. for 1 hour.

Isolation, Production, Expression, and Mis-expression of LIMK Nucleic Acids and Polypeptides

[0025] LIMK nucleic acids and polypeptides, useful for identifying and testing agents that modulate LIMK function and for other applications related to the involvement of LIMK in the p53 pathway. LIMK nucleic acids and derivatives and orthologs thereof may be obtained using any available method. For instance, techniques for isolating cDNA or genomic DNA sequences of interest by screening DNA libraries or by using polymerase chain reaction (PCR) are well known in the art. In general, the particular use for the protein will dictate the particulars of expression, production, and purification methods. For instance, production of proteins for use in screening for modulating agents may require methods that preserve specific biological activities of these proteins, whereas production of proteins for antibody generation may require structural integrity of particular epitopes. Expression of proteins to be purified for screening or antibody production may require the addition of specific tags (e.g., generation of fusion proteins). Overexpression of a LIMK protein for assays used to assess LIMK function, such as involvement in cell cycle regulation or hypoxic response, may require expression in eukaryotic cell lines capable of these cellular activities. Techniques for the expression, production, and purification of proteins are well known in the art; any suitable means therefore may be used (e.g., Higgins S J and Hames B D (eds.) Protein Expression: A Practical Approach, Oxford University Press Inc., New York 1999; Stanbury P F et al., Principles of Fermentation Technology, 2.sup.nd edition, Elsevier Science, New York, 1995; Doonan S (ed.) Protein Purification Protocols, Humana Press, New Jersey, 1996; Coligan J E et al, Current Protocols in Protein Science (eds.), 1999, John Wiley & Sons, New York). In particular embodiments, recombinant LIMK is expressed in a cell line known to have defective p53 function (e.g. SAOS-2 osteoblasts, H1299 lung cancer cells, C33A and HT3 cervical cancer cells, HT-29 and DLD-1 colon cancer cells, among others, available from American Type Culture Collection (ATCC), Manassas, Va.). The recombinant cells are used in cell-based screening assay systems of the invention, as described further below.

[0026] The nucleotide sequence encoding a LIMK polypeptide can be inserted into any appropriate expression vector. The necessary transcriptional and translational signals, including promoter/enhancer element, can derive from the native LIMK gene and/or its flanking regions or can be heterologous. A variety of host-vector expression systems may be utilized, such as mammalian cell systems infected with virus (e.g. vaccinia virus, adenovirus, etc.); insect cell systems infected with virus (e.g. baculovirus); microorganisms such as yeast containing yeast vectors, or bacteria transformed with bacteriophage, plasmid, or cosmid DNA. A host cell strain that modulates the expression of, modifies, and/or specifically processes the gene product may be used.

[0027] To detect expression of the LIMK gene product, the expression vector can comprise a promoter operably linked to a LIMK gene nucleic acid, one or more origins of replication, and, one or more selectable markers (e.g. thymidine kinase activity, resistance to antibiotics, etc.). Alternatively, recombinant expression vectors can be identified by assaying for the expression of the LIMK gene product based on the physical or functional properties of the LIMK protein in in vitro assay systems (e.g. immunoassays).

[0028] The LIMK protein, fragment, or derivative may be optionally expressed as a fusion, or chimeric protein product (i.e. it is joined via a peptide bond to a heterologous protein sequence of a different protein), for example to facilitate purification or detection. A chimeric product can be made by ligating the appropriate nucleic acid sequences encoding the desired amino acid sequences to each other using standard methods and expressing the chimeric product. A chimeric product may also be made by protein synthetic techniques, e.g. by use of a peptide synthesizer (Hunkapiller et al., Nature (1984) 310:105-111).

[0029] Once a recombinant cell that expresses the LIMK gene sequence is identified, the gene product can be isolated and purified using standard methods (e.g. ion exchange, affinity, and gel exclusion chromatography; centrifugation; differential solubility; electrophoresis, cite purification reference). Alternatively, native LIMK proteins can be purified from natural sources, by standard methods (e.g. immunoaffinity purification). Once a protein is obtained, it may be quantified and its activity measured by appropriate methods, such as immunoassay, bioassay, or other measurements of physical properties, such as crystallography.

[0030] The methods of this invention may also use cells that have been engineered for altered expression (mis-expression) of LIMK or other genes associated with the p53 pathway. As used herein, mis-expression encompasses ectopic expression, over-expression, under-expression, and non-expression (e.g. by gene knock-out or blocking expression that would otherwise normally occur).

Genetically Modified Animals

[0031] Animal models that have been genetically modified to alter LIMK expression may be used in in vivo assays to test for activity of a candidate p53 modulating agent, or to further assess the role of LIMK in a p53 pathway process such as apoptosis or cell proliferation. Preferably, the altered LIMK expression results in a detectable phenotype, such as decreased or increased levels of cell proliferation, angiogenesis, or apoptosis compared to control animals having normal LIMK expression. The genetically modified animal may additionally have altered p53 expression (e.g. p53 knockout). Preferred genetically modified animals are mammals such as primates, rodents (preferably mice), cows, horses, goats, sheep, pigs, dogs and cats. Preferred non-mammalian species include zebrafish, C. elegans, and Drosophila. Preferred genetically modified animals are transgenic animals having a heterologous nucleic acid sequence present as an extrachromosomal element in a portion of its cells, i.e. mosaic animals (see, for example, techniques described by Jakobovits, 1994, Curr. Biol. 4:761-763.) or stably integrated into its germ line DNA (i.e., in the genomic sequence of most or all of its cells). Heterologous nucleic acid is introduced into the germ line of such transgenic animals by genetic manipulation of, for example, embryos or embryonic stem cells of the host animal.

[0032] Methods of making transgenic animals are well-known in the art (for transgenic mice see Brinster et al., Proc. Nat. Acad. Sci. USA 82: 4438-4442 (1985), U.S. Pat. Nos. 4,736,866 and 4,870,009, both by Leder et al., U.S. Pat. No. 4,873,191 by Wagner et al., and Hogan, B., Manipulating the Mouse Embryo, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., (1986); for particle bombardment see U.S. Pat. No., 4,945,050, by Sandford et al.; for transgenic Drosophila see Rubin and Spradling, Science (1982) 218:348-53 and U.S. Pat. No. 4,670,388; for transgenic insects see Berghammer A. J. et al., A Universal Marker for Transgenic Insects (1999) Nature 402:370-371; for transgenic Zebrafish see Lin S., Transgenic Zebrafish, Methods Mol. Biol. (2000);136:375-3830); for microinjection procedures for fish, amphibian eggs and birds see Houdebine and Chourrout, Experientia (1991) 47:897-905; for transgenic rats see Hammer et al., Cell (1990) 63:1099-1112; and for culturing of embryonic stem (ES) cells and the subsequent production of transgenic animals by the introduction of DNA into ES cells using methods such as electroporation, calcium phosphate/DNA precipitation and direct injection see, e.g., Teratocarcinomas and Embryonic Stem Cells, A Practical Approach, E. J. Robertson, ed., IRL Press (1987)). Clones of the nonhuman transgenic animals can be produced according to available methods (see Wilmut, I. et al. (1997) Nature 385:810-813; and PCT International Publication Nos. WO 97/07668 and WO 97/07669).

[0033] In one embodiment, the transgenic animal is a "knock-out" animal having a heterozygous or homozygous alteration in the sequence of an endogenous LIMK gene that results in a decrease of LIMK function, preferably such that LIMK expression is undetectable or insignificant. Knock-out animals are typically generated by homologous recombination with a vector comprising a transgene having at least a portion of the gene to be knocked out. Typically a deletion, addition or substitution has been introduced into the transgene to functionally disrupt it. The transgene can be a human gene (e.g., from a human genomic clone) but more preferably is an ortholog of the human gene derived from the transgenic host species. For example, a mouse LIMK gene is used to construct a homologous recombination vector suitable for altering an endogenous LIMK gene in the mouse genome. Detailed methodologies for homologous recombination in mice are available (see Capecchi, Science (1989) 244:1288-1292; Joyner et al., Nature (1989) 338:153-156). Procedures for the production of non-rodent transgenic mammals and other animals are also available (Houdebine and Chourrout, supra; Pursel et al., Science (1989) 244:1281-1288; Simms et al., Bio/Technology (1988) 6:179-183). In a preferred embodiment, knock-out animals, such as mice harboring a knockout of a specific gene, may be used to produce antibodies against the human counterpart of the gene that has been knocked out (Claesson M H et al., (1994) Scan J Immunol 40:257-264; Declerck P J et al., (1995) J Biol. Chem. 270:8397-400).

[0034] In another embodiment, the transgenic animal is a "knock-in" animal having an alteration in its genome that results in altered expression (e.g., increased (including ectopic) or decreased expression) of the LIMK gene, e.g., by introduction of additional copies of LIMK, or by operatively inserting a regulatory sequence that provides for altered expression of an endogenous copy of the LIMK gene. Such regulatory sequences include inducible, tissue-specific, and constitutive promoters and enhancer elements. The knock-in can be homozygous or heterozygous.

[0035] Transgenic nonhuman animals can also be produced that contain selected systems allowing for regulated expression of the transgene. One example of such a system that may be produced is the cre/loxP recombinase system of bacteriophage P 1 (Lakso et al., PNAS (1992) 89:6232-6236; U.S. Pat. No. 4,959,317). If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of "double" transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae (O'Gorman et al. (1991) Science 251:1351-1355; U.S. Pat. No. 5,654,182). In a preferred embodiment, both Cre-LoxP and Flp-Frt are used in the same system to regulate expression of the transgene, and for sequential deletion of vector sequences in the same cell (Sun X et al (2000) Nat Genet 25:83-6).

[0036] The genetically modified animals can be used in genetic studies to further elucidate the p53 pathway, as animal models of disease and disorders implicating defective p53 function, and for in vivo testing of candidate therapeutic agents, such as those identified in screens described below. The candidate therapeutic agents are administered to a genetically modified animal having altered LIMK function and phenotypic changes are compared with appropriate control animals such as genetically modified animals that receive placebo treatment, and/or animals with unaltered LIMK expression that receive candidate therapeutic agent.

[0037] In addition to the above-described genetically modified animals having altered LIMK function, animal models having defective p53 function (and otherwise normal LIMK function), can be used in the methods of the present invention. For example, a p53 knockout mouse can be used to assess, in vivo, the activity of a candidate p53 modulating agent identified in one of the in vitro assays described below. p53 knockout mice are described in the literature (Jacks et al., Nature 2001;410:1111-1116, 1043-1044; Donehower et al., supra). Preferably, the candidate p53 modulating agent when administered to a model system with cells defective in p53 function, produces a detectable phenotypic change in the model system indicating that the p53 function is restored, i.e., the cells exhibit normal cell cycle progression.

Modulating Agents

[0038] The invention provides methods to identify agents that interact with and/or modulate the function of LIMK and/or the p53 pathway. Such agents are useful in a variety of diagnostic and therapeutic applications associated with the p53 pathway, as well as in further analysis of the LIMK protein and its contribution to the p53 pathway. Accordingly, the invention also provides methods for modulating the p53 pathway comprising the step of specifically modulating LIMK activity by administering a LIMK-interacting or -modulating agent.

[0039] In a preferred embodiment, LIMK-modulating agents inhibit or enhance LIMK activity or otherwise affect normal LIMK function, including transcription, protein expression, protein localization, and cellular or extra-cellular activity. In a further preferred embodiment, the candidate p53 pathway-modulating agent specifically modulates the function of the LIMK. The phrases "specific modulating agent", "specifically modulates", etc., are used herein to refer to modulating agents that directly bind to the LIMK polypeptide or nucleic acid, and preferably inhibit, enhance, or otherwise alter, the function of the LIMK. The term also encompasses modulating agents that alter the interaction of the LIMK with a binding partner or substrate (e.g. by binding to a binding partner of a LIMK, or to a protein/binding partner complex, and inhibiting function).

[0040] Preferred LIMK-modulating agents include small molecule compounds; LIMK-interacting proteins, including antibodies and other biotherapeutics; and nucleic acid modulators such as antisense and RNA inhibitors. The modulating agents may be formulated in pharmaceutical compositions, for example, as compositions that may comprise other active ingredients, as in combination therapy, and/or suitable carriers or excipients. Techniques for formulation and administration of the compounds may be found in "Remington's Pharmaceutical Sciences" Mack Publishing Co., Easton, Pa., 19.sup.th edition.

[0041] Small Molecule Modulators

[0042] Small molecules, are often preferred to modulate function of proteins with enzymatic function, and/or containing protein interaction domains. Chemical agents, referred to in the art as "small molecule" compounds are typically organic, non-peptide molecules, having a molecular weight less than 10,000, preferably less than 5,000, more preferably less than 1,000, and most preferably less than 500. This class of modulators includes chemically synthesized molecules, for instance, compounds from combinatorial chemical libraries. Synthetic compounds may be rationally designed or identified based on known or inferred properties of the LIMK protein or may be identified by screening compound libraries. Alternative appropriate modulators of this class are natural products, particularly secondary metabolites from organisms such as plants or fungi, which can also be identified by screening compound libraries for LIMK-modulating activity. Methods for generating and obtaining compounds are well known in the art (Schreiber S L, Science (2000) 151: 1964-1969; Radmann J and Gunther J, Science (2000) 151:1947-1948).

[0043] Small molecule modulators identified from screening assays, as described below, can be used as lead compounds from which candidate clinical compounds may be designed, optimized, and synthesized. Such clinical compounds may have utility in treating pathologies associated with the p53 pathway. The activity of candidate small molecule modulating agents may be improved several-fold through iterative secondary functional validation, as further described below, structure determination, and candidate modulator modification and testing. Additionally, candidate clinical compounds are generated with specific regard to clinical and pharmacological properties. For example, the reagents may be derivatized and re-screened using in vitro and in vivo assays to optimize activity and minimize toxicity for pharmaceutical development.

[0044] Protein Modulators

[0045] Specific LIMK-interacting proteins are useful in a variety of diagnostic and therapeutic applications related to the p53 pathway and related disorders, as well as in validation assays for other LIMK-modulating agents. In a preferred embodiment, LIMK-interacting proteins affect normal LIMK function, including transcription, protein expression, protein localization, and cellular or extra-cellular activity. In another embodiment, LIMK-interacting proteins are useful in detecting and providing information about the function of LIMK proteins, as is relevant to p53 related disorders, such as cancer (e.g., for diagnostic means).

[0046] An LIMK-interacting protein may be endogenous, i.e. one that naturally interacts genetically or biochemically with a LIMK, such as a member of the LIMK pathway that modulates LIMK expression, localization, and/or activity. LIMK-modulators include dominant negative forms of LIMK-interacting proteins and of LIMK proteins themselves. Yeast two-hybrid and variant screens offer preferred methods for identifying endogenous LIMK-interacting proteins (Finley, R. L. et al. (1996) in DNA Cloning-Expression Systems: A Practical Approach, eds. Glover D. & Hames B. D (Oxford University Press, Oxford, England), pp. 169-203; Fashema S F et al., Gene (2000) 250:1-14; Drees B L Curr Opin Chem Biol (1999) 3:64-70; Vidal M and Legrain P Nucleic Acids Res (1999) 27:919-29; and U.S. Pat. No. 5,928,868). Mass spectrometry is an alternative preferred method for the elucidation of protein complexes (reviewed in, e.g., Pandley A and Mann M, Nature (2000) 405:837-846; Yates J R 3.sup.rd, Trends Genet (2000) 16:5-8).

[0047] An LIMK-interacting protein may be an exogenous protein, such as a LIMK-specific antibody or a T-cell antigen receptor (see, e.g., Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory; Harlow and Lane (1999) Using antibodies: a laboratory manual. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press). LIMK antibodies are further discussed below.

[0048] In preferred embodiments, a LIMK-interacting protein specifically binds a LIMK protein. In alternative preferred embodiments, a LIMK-modulating agent binds a LIMK substrate, binding partner, or cofactor.

[0049] Antibodies

[0050] In another embodiment, the protein modulator is a LIMK specific antibody agonist or antagonist. The antibodies have therapeutic and diagnostic utilities, and can be used in screening assays to identify LIMK modulators. The antibodies can also be used in dissecting the portions of the LIMK pathway responsible for various cellular responses and in the general processing and maturation of the LIMK.

[0051] Antibodies that specifically bind LIMK polypeptides can be generated using known methods. Preferably the antibody is specific to a mammalian ortholog of LIMK polypeptide, and more preferably, to human LIMK. Antibodies may be polyclonal, monoclonal (mAbs), humanized or chimeric antibodies, single chain antibodies, Fab fragments, F(ab').sub.2 fragments, fragments produced by a FAb expression library, anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above. Epitopes of LIMK which are particularly antigenic can be selected, for example, by routine screening of LIMK polypeptides for antigenicity or by applying a theoretical method for selecting antigenic regions of a protein (Hopp and Wood (1981), Proc. Natl. Acad. Sci. U.S.A. 78:3824-28; Hopp and Wood, (1983) Mol. Immunol. 20:483-89; Sutcliffe et al., (1983) Science 219:660-66) to the amino acid sequence shown in any of SEQ ID NOs:19, 20, 21, 22, 23, 24, or 25. Monoclonal antibodies with affinities of 10.sup.8 M.sup.-1 preferably 10.sup.9 M.sup.-1 to 10.sup.10 M.sup.-1, or stronger can be made by standard procedures as described (Harlow and Lane, supra; Goding (1986) Monoclonal Antibodies: Principles and Practice (2d ed) Academic Press, New York; and U.S. Pat. Nos. 4,381,292; 4,451,570; and 4,618,577). Antibodies may be generated against crude cell extracts of LIMK or substantially purified fragments thereof. If LIMK fragments are used, they preferably comprise at least 10, and more preferably, at least 20 contiguous amino acids of a LIMK protein. In a particular embodiment, LIMK-specific antigens and/or immunogens are coupled to carrier proteins that stimulate the immune response. For example, the subject polypeptides are covalently coupled to the keyhole limpet hemocyanin (KLH) carrier, and the conjugate is emulsified in Freund's complete adjuvant, which enhances the immune response. An appropriate immune system such as a laboratory rabbit or mouse is immunized according to conventional protocols.

[0052] The presence of LIMK-specific antibodies is assayed by an appropriate assay such as a solid phase enzyme-linked immunosorbant assay (ELISA) using immobilized corresponding LIMK polypeptides. Other assays, such as radioimmunoassays or fluorescent assays might also be used.

[0053] Chimeric antibodies specific to LIMK polypeptides can be made that contain different portions from different animal species. For instance, a human immunoglobulin constant region may be linked to a variable region of a murine mAb, such that the antibody derives its biological activity from the human antibody, and its binding specificity from the murine fragment. Chimeric antibodies are produced by splicing together genes that encode the appropriate regions from each species (Morrison et al., Proc. Natl. Acad. Sci. (1984) 81:6851-6855; Neuberger et al., Nature (1984) 312:604-608; Takeda et al., Nature (1985) 31:452-454). Humanized antibodies, which are a form of chimeric antibodies, can be generated by grafting complementary-determining regions (CDRs) (Carlos, T. M., J. M. Harlan. 1994. Blood 84:2068-2101) of mouse antibodies into a background of human framework regions and constant regions by recombinant DNA technology (Riechmann L M, et al., 1988 Nature 323: 323-327). Humanized antibodies contain .about.10% murine sequences and 90% human sequences, and thus further reduce or eliminate immunogenicity, while retaining the antibody specificities (Co MS, and Queen C. 1991 Nature 351: 501-501; Morrison S L. 1992 Ann. Rev. Immun. 10:239-265). Humanized antibodies and methods of their production are well-known in the art (U.S. Pat. Nos. 5,530,101, 5,585,089, 5,693,762, and 6,180,370).

[0054] LIMK-specific single chain antibodies which are recombinant, single chain polypeptides formed by linking the heavy and light chain fragments of the Fv regions via an amino acid bridge, can be produced by methods known in the art (U.S. Pat. No. 4,946,778; Bird, Science (1988) 242:423-426; Huston et al., Proc. Natl. Acad. Sci. USA (1988) 85:5879-5883; and Ward et al., Nature (1989) 334:544-546).

[0055] Other suitable techniques for antibody production involve in vitro exposure of lymphocytes to the antigenic polypeptides or alternatively to selection of libraries of antibodies in phage or similar vectors (Huse et al., Science (1989) 246:1275-1281). As used herein, T-cell antigen receptors are included within the scope of antibody modulators (Harlow and Lane, 1988, supra).

[0056] The polypeptides and antibodies of the present invention may be used with or without modification. Frequently, antibodies will be labeled by joining, either covalently or non-covalently, a substance that provides for a detectable signal, or that is toxic to cells that express the targeted protein (Menard S, et al., Int J. Biol Markers (1989) 4:131-134). A wide variety of labels and conjugation techniques are known and are reported extensively in both the scientific and patent literature. Suitable labels include radionuclides, enzymes, substrates, cofactors, inhibitors, fluorescent moieties, fluorescent emitting lanthanide metals, chemiluminescent moieties, bioluminescent moieties, magnetic particles, and the like (U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241). Also, recombinant immunoglobulins may be produced (U.S. Pat. No. 4,816,567). Antibodies to cytoplasmic polypeptides may be delivered and reach their targets by conjugation with membrane-penetrating toxin proteins (U.S. Pat. No. 6,086,900).

[0057] When used therapeutically in a patient, the antibodies of the subject invention are typically administered parenterally, when possible at the target site, or intravenously. The therapeutically effective dose and dosage regimen is determined by clinical studies. Typically, the amount of antibody administered is in the range of about 0.1 mg/kg--to about 10 mg/kg of patient weight. For parenteral administration, the antibodies are formulated in a unit dosage injectable form (e.g., solution, suspension, emulsion) in association with a pharmaceutically acceptable vehicle. Such vehicles are inherently nontoxic and non-therapeutic. Examples are water, saline, Ringer's solution, dextrose solution, and 5% human serum albumin. Nonaqueous vehicles such as fixed oils, ethyl oleate, or liposome carriers may also be used. The vehicle may contain minor amounts of additives, such as buffers and preservatives, which enhance isotonicity and chemical stability or otherwise enhance therapeutic potential. The antibodies' concentrations in such vehicles are typically in the range of about 1 mg/ml to about 10 mg/ml. Immunotherapeutic methods are further described in the literature (U.S. Pat. No. 5,859,206; WO0073469).

[0058] Nucleic Acid Modulators

[0059] Other preferred LIMK-modulating agents comprise nucleic acid molecules, such as antisense oligomers or double stranded RNA (dsRNA), which generally inhibit LIMK activity. Preferred nucleic acid modulators interfere with the function of the LIMK nucleic acid such as DNA replication, transcription, translocation of the LIMK RNA to the site of protein translation, translation of protein from the LIMK RNA, splicing of the LIMK RNA to yield one or more mRNA species, or catalytic activity which may be engaged in or facilitated by the LIMK RNA.

[0060] In one embodiment, the antisense oligomer is an oligonucleotide that is sufficiently complementary to a LIMK mRNA to bind to and prevent translation, preferably by binding to the 5' untranslated region. LIMK-specific antisense oligonucleotides, preferably range from at least 6 to about 200 nucleotides. In some embodiments the oligonucleotide is preferably at least 10, 15, or 20 nucleotides in length. In other embodiments, the oligonucleotide is preferably less than 50, 40, or 30 nucleotides in length. The oligonucleotide can be DNA or RNA or a chimeric mixture or derivatives or modified versions thereof, single-stranded or double-stranded. The oligonucleotide can be modified at the base moiety, sugar moiety, or phosphate backbone. The oligonucleotide may include other appending groups such as peptides, agents that facilitate transport across the cell membrane, hybridization-triggered cleavage agents, and intercalating agents.

[0061] In another embodiment, the antisense oligomer is a phosphothioate morpholino oligomer (PMO). PMOs are assembled from four different morpholino subunits, each of which contain one of four genetic bases (A, C, G, or T) linked to a six-membered morpholine ring. Polymers of these subunits are joined by non-ionic phosphodiamidate intersubunit linkages. Details of how to make and use PMOs and other antisense oligomers are well known in the art (e.g. see WO99/18193; Probst J C, Antisense Oligodeoxynucleotide and Ribozyme Design, Methods. (2000) 22(3):271-281; Summerton J, and Weller D. 1997 Antisense Nucleic Acid Drug Dev.:7:187-95; U.S. Pat. No. 5,235,033; and U.S. Pat. No. 5,378,841).

[0062] Alternative preferred LIMK nucleic acid modulators are double-stranded RNA species mediating RNA interference (RNAi). RNAi is the process of sequence-specific, post-transcriptional gene silencing in animals and plants, initiated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. Methods relating to the use of RNAi to silence genes in C. elegans, Drosophila, plants, and humans are known in the art (Fire A, et al., 1998 Nature 391:806-811; Fire, A. Trends Genet. 15, 358-363 (1999); Sharp, P. A. RNA interference 2001. Genes Dev. 15, 485-490 (2001); Hammond, S. M., et al., Nature Rev. Genet. 2, 110-1119 (2001); Tuschl, T. Chem. Biochem. 2, 239-245 (2001); Hamilton, A. et al., Science 286, 950-952 (1999); Hammond, S. M., et al., Nature 404, 293-296 (2000); Zamore, P. D., et al., Cell 101, 25-33 (2000); Bernstein, E., et al., Nature 409, 363-366 (2001); Elbashir, S. M., et al., Genes Dev. 15, 188-200 (2001); WO0129058; WO9932619; Elbashir S M, et al., 2001 Nature 411:494-498).

[0063] Nucleic acid modulators are commonly used as research reagents, diagnostics, and therapeutics. For example, antisense oligonucleotides, which are able to inhibit gene expression with exquisite specificity, are often used to elucidate the function of particular genes (see, for example, U.S. Pat. No. 6,165,790). Nucleic acid modulators are also used, for example, to distinguish between functions of various members of a biological pathway. For example, antisense oligomers have been employed as therapeutic moieties in the treatment of disease states in animals and man and have been demonstrated in numerous clinical trials to be safe and effective (Milligan J F, et al, Current Concepts in Antisense Drug Design, J Med. Chem. (1993) 36:1923-1937; Tonkinson J L et al., Antisense Oligodeoxynucleotides as Clinical Therapeutic Agents, Cancer Invest. (1996) 14:54-65). Accordingly, in one aspect of the invention, a LIMK-specific nucleic acid modulator is used in an assay to further elucidate the role of the LIMK in the p53 pathway, and/or its relationship to other members of the pathway. In another aspect of the invention, a LIMK-specific antisense oligomer is used as a therapeutic agent for treatment of p53-related disease states.

Assay Systems

[0064] The invention provides assay systems and screening methods for identifying specific modulators of LIMK activity. As used herein, an "assay system" encompasses all the components required for performing and analyzing results of an assay that detects and/or measures a particular event. In general, primary assays are used to identify or confirm a modulator's specific biochemical or molecular effect with respect to the LIMK nucleic acid or protein. In general, secondary assays further assess the activity of a LIMK modulating agent identified by a primary assay and may confirm that the modulating agent affects LIMK in a manner relevant to the p53 pathway. In some cases, LIMK modulators will be directly tested in a secondary assay.

[0065] In a preferred embodiment, the screening method comprises contacting a suitable assay system comprising a LIMK polypeptide with a candidate agent under conditions whereby, but for the presence of the agent, the system provides a reference activity (e.g. kinase activity), which is based on the particular molecular event the screening method detects. A statistically significant difference between the agent-biased activity and the reference activity indicates that the candidate agent modulates LIMK activity, and hence the p53 pathway.

[0066] Primary Assays

[0067] The type of modulator tested generally determines the type of primary assay.

[0068] Primary Assays for Small Molecule Modulators

[0069] For small molecule modulators, screening assays are used to identify candidate modulators. Screening assays may be cell-based or may use a cell-free system that recreates or retains the relevant biochemical reaction of the target protein (reviewed in Sittampalam G S et al., Curr Opin Chem Biol (1997) 1:384-91 and accompanying references). As used herein the term "cell-based" refers to assays using live cells, dead cells, or a particular cellular fraction, such as a membrane, endoplasmic reticulum, or mitochondrial fraction. The term "cell free" encompasses assays using substantially purified protein (either endogenous or recombinantly produced), partially purified or crude cellular extracts. Screening assays may detect a variety of molecular events, including protein-DNA interactions, protein-protein interactions (e.g., receptor-ligand binding), transcriptional activity (e.g., using a reporter gene), enzymatic activity (e.g., via a property of the substrate), activity of second messengers, immunogenicty and changes in cellular morphology or other cellular characteristics. Appropriate screening assays may use a wide range of detection methods including fluorescent, radioactive, colorimetric, spectrophotometric, and amperometric methods, to provide a read-out for the particular molecular event detected.

[0070] Cell-based screening assays usually require systems for recombinant expression of LIMK and any auxiliary proteins demanded by the particular assay. Appropriate methods for generating recombinant proteins produce sufficient quantities of proteins that retain their relevant biological activities and are of sufficient purity to optimize activity and assure assay reproducibility. Yeast two-hybrid and variant screens, and mass spectrometry provide preferred methods for determining protein-protein interactions and elucidation of protein complexes. In certain applications, when LIMK-interacting proteins are used in screens to identify small molecule modulators, the binding specificity of the interacting protein to the LIMK protein may be assayed by various known methods such as substrate processing (e.g. ability of the candidate LIMK-specific binding agents to function as negative effectors in LIMK-expressing cells), binding equilibrium constants (usually at least about 10.sup.7M.sup.-1, preferably at least about 10.sup.8 M.sup.-1, more preferably at least about 10.sup.9 M.sup.-1), and immunogenicity (e.g. ability to elicit LIMK specific antibody in a heterologous host such as a mouse, rat, goat or rabbit). For enzymes and receptors, binding may be assayed by, respectively, substrate and ligand processing.

[0071] The screening assay may measure a candidate agent's ability to specifically bind to or modulate activity of a LIMK polypeptide, a fusion protein thereof, or to cells or membranes bearing the polypeptide or fusion protein. The LIMK polypeptide can be full length or a fragment thereof that retains functional LIMK activity. The LIMK polypeptide may be fused to another polypeptide, such as a peptide tag for detection or anchoring, or to another tag. The LIMK polypeptide is preferably human LIMK, or is an ortholog or derivative thereof as described above. In a preferred embodiment, the screening assay detects candidate agent-based modulation of LIMK interaction with a binding target, such as an endogenous or exogenous protein or other substrate that has LIMK-specific binding activity, and can be used to assess normal LIMK gene function.

[0072] Suitable assay formats that may be adapted to screen for LIMK modulators are known in the art. Preferred screening assays are high throughput or ultra high throughput and thus provide automated, cost-effective means of screening compound libraries for lead compounds (Fernandes P B, Curr Opin Chem Biol (1998) 2:597-603; Sundberg S A, Curr Opin Biotechnol 2000, 11:47-53). In one preferred embodiment, screening assays uses fluorescence technologies, including fluorescence polarization, time-resolved fluorescence, and fluorescence resonance energy transfer. These systems offer means to monitor protein-protein or DNA-protein interactions in which the intensity of the signal emitted from dye-labeled molecules depends upon their interactions with partner molecules (e.g., Selvin P R, Nat Struct Biol (2000) 7:730-4; Fernandes P B, supra; Hertzberg R P and Pope A J, Curr Opin Chem Biol (2000) 4:445-451).

[0073] A variety of suitable assay systems may be used to identify candidate LIMK and p53 pathway modulators (e.g. U.S. Pat. No. 6,165,992 (kinase assays); U.S. Pat. Nos. 5,550,019 and 6,133,437 (apoptosis assays); and U.S. Pat. No. 6,020,135 (p53 modulation), among others). Specific preferred assays are described in more detail below.

[0074] Kinase assays. In some preferred embodiments the screening assay detects the ability of the test agent to modulate the kinase activity of a LIMK polypeptide. In further embodiments, a cell-free kinase assay system is used to identify a candidate p53 modulating agent, and a secondary, cell-based assay, such as an apoptosis or hypoxic induction assay (described below), may be used to further characterize the candidate p53 modulating agent. Many different assays for kinases have been reported in the literature and are well known to those skilled in the art (e.g. U.S. Pat. No. 6,165,992; Zhu et al., Nature Genetics (2000) 26:283-289; and WO0073469). Radioassays, which monitor the transfer of a gamma phosphate are frequently used. For instance, a scintillation assay for p56 (lck) kinase activity monitors the transfer of the gamma phosphate from gamma--.sup.33P ATP to a biotinylated peptide substrate; the substrate is captured on a streptavidin coated bead that transmits the signal (Beveridge M et al., J Biomol Screen (2000) 5:205-212). This assay uses the scintillation proximity assay (SPA), in which only radio-ligand bound to receptors tethered to the surface of an SPA bead are detected by the scintillant immobilized within it, allowing binding to be measured without separation of bound from free ligand.

[0075] Another example of antibody based assays for protein kinase activity is TRF (time-resolved fluorometry). This method utilizes europium chelate-labeled anti-phosphotyrosine antibodies to detect phosphate transfer to a polymeric substrate coated onto microtiter plate wells. The amount of phosphorylation is then detected using time-resolved, dissociation-enhanced fluorescence (Braunwalder A F, et al., Anal Biochem 1996 Jul. 1;238(2):159-64).

[0076] Apoptosis assays. Assays for apoptosis may be performed by terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling (TUNEL) assay. The TUNEL assay is used to measure nuclear DNA fragmentation characteristic of apoptosis (Lazebnik et al., 1994, Nature 371, 346), by following the incorporation of fluorescein-dUTP (Yonehara et al., 1989, J. Exp. Med. 169, 1747). Apoptosis may further be assayed by acridine orange staining of tissue culture cells (Lucas, R., et al., 1998, Blood 15:4730-41). An apoptosis assay system may comprise a cell that expresses a LIMK, and that optionally has defective p53 function (e.g. p53 is over-expressed or under-expressed relative to wild-type cells). A test agent can be added to the apoptosis assay system and changes in induction of apoptosis relative to controls where no test agent is added, identify candidate p53 modulating agents. In some embodiments of the invention, an apoptosis assay may be used as a secondary assay to test a candidate p53 modulating agents that is initially identified using a cell-free assay system. An apoptosis assay may also be used to test whether LIMK function plays a direct role in apoptosis. For example, an apoptosis assay may be performed on cells that over- or under-express LIMK relative to wild type cells. Differences in apoptotic response compared to wild type cells suggests that the LIMK plays a direct role in the apoptotic response. Apoptosis assays are described further in U.S. Pat. No. 6,133,437.

[0077] Cell proliferation and cell cycle assays. Cell proliferation may be assayed via bromodeoxyuridine (BRDU) incorporation. This assay identifies a cell population undergoing DNA synthesis by incorporation of BRDU into newly-synthesized DNA. Newly-synthesized DNA may then be detected using an anti-BRDU antibody (Hoshino et al., 1986, Int. J. Cancer 38, 369; Campana et al., 1988, J. Immunol. Meth. 107, 79), or by other means.

[0078] Cell Proliferation may also be examined using [.sup.3H]-thymidine incorporation (Chen, J., 1996, Oncogene 13:1395-403; Jeoung, J., 1995, J. Biol. Chem. 270:18367-73). This assay allows for quantitative characterization of S-phase DNA syntheses. In this assay, cells synthesizing DNA will incorporate [.sup.3H]-thymidine into newly synthesized DNA. Incorporation can then be measured by standard techniques such as by counting of radioisotope in a scintillation counter (e.g., Beckman L S 3800 Liquid Scintillation Counter).

[0079] Cell proliferation may also be assayed by colony formation in soft agar (Sambrook et al., Molecular Cloning, Cold Spring Harbor (1989)). For example, cells transformed with LIMK are seeded in soft agar plates, and colonies are measured and counted after two weeks incubation.

[0080] Involvement of a gene in the cell cycle may be assayed by flow cytometry (Gray J W et al. (1986) Int J Radiat Biol Relat Stud Phys Chem Med 49:237-55). Cells transfected with a LIMK may be stained with propidium iodide and evaluated in a flow cytometer (available from Becton Dickinson).

[0081] Accordingly, a cell proliferation or cell cycle assay system may comprise a cell that expresses a LIMK, and that optionally has defective p53 function (e.g. p53 is over-expressed or under-expressed relative to wild-type cells). A test agent can be added to the assay system and changes in cell proliferation or cell cycle relative to controls where no test agent is added, identify candidate p53 modulating agents. In some embodiments of the invention, the cell proliferation or cell cycle assay may be used as a secondary assay to test a candidate p53 modulating agents that is initially identified using another assay system such as a cell-free kinase assay system. A cell proliferation assay may also be used to test whether LIMK function plays a direct role in cell proliferation or cell cycle. For example, a cell proliferation or cell cycle assay may be performed on cells that over- or under-express LIMK relative to wild type cells. Differences in proliferation or cell cycle compared to wild type cells suggests that the LIMK plays a direct role in cell proliferation or cell cycle.

[0082] Angiogenesis. Angiogenesis may be assayed using various human endothelial cell systems, such as umbilical vein, coronary artery, or dermal cells. Suitable assays include Alamar Blue based assays (available from Biosource International) to measure proliferation; migration assays using fluorescent molecules, such as the use of Becton Dickinson Falcon HTS FluoroBlock cell culture inserts to measure migration of cells through membranes in presence or absence of angiogenesis enhancer or suppressors; and tubule formation assays based on the formation of tubular structures by endothelial cells on Matrigel.RTM. (Becton Dickinson). Accordingly, an angiogenesis assay system may comprise a cell that expresses a LIMK, and that optionally has defective p53 function (e.g. p53 is over-expressed or under-expressed relative to wild-type cells). A test agent can be added to the angiogenesis assay system and changes in angiogenesis relative to controls where no test agent is added, identify candidate p53 modulating agents. In some embodiments of the invention, the angiogenesis assay may be used as a secondary assay to test a candidate p53 modulating agents that is initially identified using another assay system. An angiogenesis assay may also be used to test whether LIMK function plays a direct role in cell proliferation. For example, an angiogenesis assay may be performed on cells that over- or under-express LIMK relative to wild type cells. Differences in angiogenesis compared to wild type cells suggests that the LIMK plays a direct role in angiogenesis.

[0083] Hypoxic induction. The alpha subunit of the transcription factor, hypoxia inducible factor-1 (HIF-1), is upregulated in tumor cells following exposure to hypoxia in vitro. Under hypoxic conditions, HIF-1 stimulates the expression of genes known to be important in tumour cell survival, such as those encoding glyolytic enzymes and VEGF. Induction of such genes by hypoxic conditions may be assayed by growing cells transfected with LIMK in hypoxic conditions (such as with 0.1% O2, 5% CO2, and balance N2, generated in a Napco 7001 incubator (Precision Scientific)) and normoxic conditions, followed by assessment of gene activity or expression by Taqman.RTM.. For example, a hypoxic induction assay system may comprise a cell that expresses a LIMK, and that optionally has a mutated p53 (e.g. p53 is over-expressed or under-expressed relative to wild-type cells). A test agent can be added to the hypoxic induction assay system and changes in hypoxic response relative to controls where no test agent is added, identify candidate p53 modulating agents. In some embodiments of the invention, the hypoxic induction assay may be used as a secondary assay to test a candidate p53 modulating agents that is initially identified using another assay system. A hypoxic induction assay may also be used to test whether LIMK function plays a direct role in the hypoxic response. For example, a hypoxic induction assay may be performed on cells that over- or under-express LIMK relative to wild type cells. Differences in hypoxic response compared to wild type cells suggests that the LIMK plays a direct role in hypoxic induction.

[0084] Cell adhesion. Cell adhesion assays measure adhesion of cells to purified adhesion proteins, or adhesion of cells to each other, in presence or absence of candidate modulating agents. Cell-protein adhesion assays measure the ability of agents to modulate the adhesion of cells to purified proteins. For example, recombinant proteins are produced, diluted to 2.5 g/mL in PBS, and used to coat the wells of a microtiter plate. The wells used for negative control are not coated. Coated wells are then washed, blocked with 1% BSA, and washed again. Compounds are diluted to 2.times.final test concentration and added to the blocked, coated wells. Cells are then added to the wells, and the unbound cells are washed off. Retained cells are labeled directly on the plate by adding a membrane-permeable fluorescent dye, such as calcein-AM, and the signal is quantified in a fluorescent microplate reader.

[0085] Cell-cell adhesion assays measure the ability of agents to modulate binding of cell adhesion proteins with their native ligands. These assays use cells that naturally or recombinantly express the adhesion protein of choice. In an exemplary assay, cells expressing the cell adhesion protein are plated in wells of a multiwell plate. Cells expressing the ligand are labeled with a membrane-permeable fluorescent dye, such as BCECF, and allowed to adhere to the monolayers in the presence of candidate agents. Unbound cells are washed off, and bound cells are detected using a fluorescence plate reader.

[0086] High-throughput cell adhesion assays have also been described. In one such assay, small molecule ligands and peptides are bound to the surface of microscope slides using a microarray spotter, intact cells are then contacted with the slides, and unbound cells are washed off. In this assay, not only the binding specificity of the peptides and modulators against cell lines are determined, but also the functional cell signaling of attached cells using immunofluorescence techniques in situ on the microchip is measured (Falsey J R et al., Bioconjug Chem. 2001 May-June;12(3):346-53).

[0087] Primary Assays for Antibody Modulators

[0088] For antibody modulators, appropriate primary assays test is a binding assay that tests the antibody's affinity to and specificity for the LIMK protein. Methods for testing antibody affinity and specificity are well known in the art (Harlow and Lane, 1988, 1999, supra). The enzyme-linked immunosorbant assay (ELISA) is a preferred method for detecting LIMK-specific antibodies; others include FACS assays, radioimmunoassays, and fluorescent assays.

[0089] Primary Assays for Nucleic Acid Modulators

[0090] For nucleic acid modulators, primary assays may test the ability of the nucleic acid modulator to inhibit or enhance LIMK gene expression, preferably mRNA expression. In general, expression analysis comprises comparing LIMK expression in like populations of cells (e.g., two pools of cells that endogenously or recombinantly express LIMK) in the presence and absence of the nucleic acid modulator. Methods for analyzing mRNA and protein expression are well known in the art. For instance, Northern blotting, slot blotting, ribonuclease protection, quantitative RT-PCR (e.g., using the TaqMan.RTM., PE Applied Biosystems), or microarray analysis may be used to confirm that LIMK mRNA expression is reduced in cells treated with the nucleic acid modulator (e.g., Current Protocols in Molecular Biology (1994) Ausubel F M et al., eds., John Wiley & Sons, Inc., chapter 4; Freeman W M et al., Biotechniques (1999) 26:112-125; Kallioniemi O P, Ann Med 2001, 33:142-147; Blohm D H and Guiseppi-Elie, A Curr Opin Biotechnol 2001, 12:41-47). Protein expression may also be monitored. Proteins are most commonly detected with specific antibodies or antisera directed against either the LIMK protein or specific peptides. A variety of means including Western blotting, ELISA, or in situ detection, are available (Harlow E and Lane D, 1988 and 1999, supra).

[0091] Secondary Assays

[0092] Secondary assays may be used to further assess the activity of LIMK-modulating agent identified by any of the above methods to confirm that the modulating agent affects LIMK in a manner relevant to the p53 pathway. As used herein, LIMK-modulating agents encompass candidate clinical compounds or other agents derived from previously identified modulating agent. Secondary assays can also be used to test the activity of a modulating agent on a particular genetic or biochemical pathway or to test the specificity of the modulating agent's interaction with LIMK.

[0093] Secondary assays generally compare like populations of cells or animals (e.g., two pools of cells or animals that endogenously or recombinantly express LIMK) in the presence and absence of the candidate modulator. In general, such assays test whether treatment of cells or animals with a candidate LIMK-modulating agent results in changes in the p53 pathway in comparison to untreated (or mock- or placebo-treated) cells or animals. Certain assays use "sensitized genetic backgrounds", which, as used herein, describe cells or animals engineered for altered expression of genes in the p53 or interacting pathways.

[0094] Cell-Based Assays

[0095] Cell based assays may use a variety of mammalian cell lines known to have defective p53 function (e.g. SAOS-2 osteoblasts, H1299 lung cancer cells, C33A and HT3 cervical cancer cells, HT-29 and DLD-1 colon cancer cells, among others, available from American Type Culture Collection (ATCC), Manassas, Va.). Cell based assays may detect endogenous p53 pathway activity or may rely on recombinant expression of p53 pathway components. Any of the aforementioned assays may be used in this cell-based format. Candidate modulators are typically added to the cell media but may also be injected into cells or delivered by any other efficacious means.

[0096] Animal Assays

[0097] A variety of non-human animal models of normal or defective p53 pathway may be used to test candidate LIMK modulators. Models for defective p53 pathway typically use genetically modified animals that have been engineered to mis-express (e.g., over-express or lack expression in) genes involved in the p53 pathway. Assays generally require systemic delivery of the candidate modulators, such as by oral administration, injection, etc.

[0098] In a preferred embodiment, p53 pathway activity is assessed by monitoring neovascularization and angiogenesis. Animal models with defective and normal p53 are used to test the candidate modulator's affect on LIMK in Matrigel.RTM. assays. Matrigel.RTM. is an extract of basement membrane proteins, and is composed primarily of laminin, collagen IV, and heparin sulfate proteoglycan. It is provided as a sterile liquid at 4.degree. C., but rapidly forms a solid gel at 37.degree. C. Liquid Matrigel.RTM. is mixed with various angiogenic agents, such as bFGF and VEGF, or with human tumor cells which over-express the LIMK. The mixture is then injected subcutaneously(SC) into female athymic nude mice (Taconic, Germantown, N.Y.) to support an intense vascular response. Mice with Matrigel.RTM. pellets may be dosed via oral (PO), intraperitoneal (IP), or intravenous (IV) routes with the candidate modulator. Mice are euthanized 5-12 days post-injection, and the Matrigel.RTM. pellet is harvested for hemoglobin analysis (Sigma plasma hemoglobin kit). Hemoglobin content of the gel is found to correlate the degree of neovascularization in the gel.

[0099] In another preferred embodiment, the effect of the candidate modulator on LIMK is assessed via tumorigenicity assays. In one example, xenograft human tumors are implanted SC into female athymic mice, 6-7 week old, as single cell suspensions either from a pre-existing tumor or from in vitro culture. The tumors which express the LIMK endogenously are injected in the flank, 1.times.10.sup.5 to 1.times.10.sup.7 cells per mouse in a volume of 100 .mu.L using a 27 gauge needle. Mice are then ear tagged and tumors are measured twice weekly. Candidate modulator treatment is initiated on the day the mean tumor weight reaches 100 mg. Candidate modulator is delivered IV, SC, IP, or PO by bolus administration. Depending upon the pharmacokinetics of each unique candidate modulator, dosing can be performed multiple times per day. The tumor weight is assessed by measuring perpendicular diameters with a caliper and calculated by multiplying the measurements of diameters in two dimensions. At the end of the experiment, the excised tumors maybe utilized for biomarker identification or further analyses. For immunohistochemistry staining, xenograft tumors are fixed in 4% paraformaldehyde, 0.1M phosphate, pH 7.2, for 6 hours at 4.degree. C., immersed in 30% sucrose in PBS, and rapidly frozen in isopentane cooled with liquid nitrogen.

Diagnostic and Therapeutic Uses

[0100] Specific LIMK-modulating agents are useful in a variety of diagnostic and therapeutic applications where disease or disease prognosis is related to defects in the p53 pathway, such as angiogenic, apoptotic, or cell proliferation disorders. Accordingly, the invention also provides methods for modulating the p53 pathway in a cell, preferably a cell pre-determined to have defective p53 function, comprising the step of administering an agent to the cell that specifically modulates LIMK activity. Preferably, the modulating agent produces a detectable phenotypic change in the cell indicating that the p53 function is restored, i.e., for example, the cell undergoes normal proliferation or progression through the cell cycle.

[0101] The discovery that LIMK is implicated in p53 pathway provides for a variety of methods that can be employed for the diagnostic and prognostic evaluation of diseases and disorders involving defects in the p53 pathway and for the identification of subjects having a predisposition to such diseases and disorders.

[0102] Various expression analysis methods can be used to diagnose whether LIMK expression occurs in a particular sample, including Northern blotting, slot blotting, ribonuclease protection, quantitative RT-PCR, and microarray analysis. (e.g., Current Protocols in Molecular Biology (1994) Ausubel F M et al., eds., John Wiley & Sons, Inc., chapter 4; Freeman W M et al., Biotechniques (1999) 26:112-125; Kallioniemi O P, Ann Med 2001, 33:142-147; Blohm and Guiseppi-Elie, Curr Opin Biotechnol 2001, 12:41-47). Tissues having a disease or disorder implicating defective p53 signaling that express a LIMK, are identified as amenable to treatment with a LIMK modulating agent. In a preferred application, the p53 defective tissue overexpresses a LIMK relative to normal tissue. For example, a Northern blot analysis of mRNA from tumor and normal cell lines, or from tumor and matching normal tissue samples from the same patient, using full or partial LIMK cDNA sequences as probes, can determine whether particular tumors express or overexpress LIMK. Alternatively, the TaqMane is used for quantitative RT-PCR analysis of LIMK expression in cell lines, normal tissues and tumor samples (PE Applied Biosystems).

[0103] Various other diagnostic methods may be performed, for example, utilizing reagents such as the LIMK oligonucleotides, and antibodies directed against a LIMK, as described above for: (1) the detection of the presence of LIMK gene mutations, or the detection of either over- or under-expression of LIMK mRNA relative to the non-disorder state; (2) the detection of either an over- or an under-abundance of LIMK gene product relative to the non-disorder state; and (3) the detection of perturbations or abnormalities in the signal transduction pathway mediated by LIMK.

[0104] Thus, in a specific embodiment, the invention is drawn to a method for diagnosing a disease in a patient, the method comprising: a) obtaining a biological sample from the patient; b) contacting the sample with a probe for LIMK expression; c) comparing results from step (b) with a control; and d) determining whether step (c) indicates a likelihood of disease. Preferably, the disease is cancer, most preferably a cancer as shown in TABLE 1. The probe may be either DNA or protein, including an antibody.

EXAMPLES

[0105] The following experimental section and examples are offered by way of illustration and not by way of limitation.

[0106] I. Drosophila p53 Screen

[0107] The Drosophila p53 gene was overexpressed specifically in the wing using the vestigial margin quadrant enhancer. Increasing quantities of Drosophila p53 (titrated using different strength transgenic inserts in 1 or 2 copies) caused deterioration of normal wing morphology from mild to strong, with phenotypes including disruption of pattern and polarity of wing hairs, shortening and thickening of wing veins, progressive crumpling of the wing and appearance of dark "death" inclusions in wing blade. In a screen designed to identify enhancers and suppressors of Drosophila p53, homozygous females carrying two copies of p53 were crossed to 5663 males carrying random insertions of a piggyBac transposon (Fraser M et al., Virology (1985) 145:356-361). Progeny containing insertions were compared to non-insertion-bearing sibling progeny for enhancement or suppression of the p53 phenotypes. Sequence information surrounding the piggyBac insertion site was used to identify the modifier genes. Modifiers of the wing phenotype were identified as members of the p53 pathway. CG6027/cdi/tsk was an enhancer of the wing phenotype. Human orthologs of the modifiers are referred to herein as LIMK.

[0108] BLAST analysis (Altschul et al., supra) was employed to identify Targets from Drosophila modifiers. For example, representative sequences from LIMK GI#5454110 (SEQ ID NO:24) and GI#6005896 (SEQ ID NO:25) share 59% and 54% amino acid identity, respectively, with the Drosophila. CG6027/cdi/tsk.

[0109] Various domains, signals, and functional subunits in proteins were analyzed using the PSORT (Nakai K., and Horton P., Trends Biochem Sci, 1999, 24:34-6; Kenta Nakai, Protein sorting signals and prediction of subcellular localization, Adv. Protein Chem. 54, 277-344 (2000)), PFAM (Bateman A., et al., Nucleic Acids Res, 1999, 27:260-2; http://pfam.wustl.edu), SMART (Ponting C P, et al., SMART: identification and annotation of domains from signaling and extracellular protein sequences. Nucleic Acids Res. 1999 Jan. 1;27(1):229-32), TM-HMM (Erik L. L. Sonnhammer, Gunnar von Heijne, and Anders Krogh: A hidden Markov model for predicting transmembrane helices in protein sequences. In Proc. of Sixth Int. Conf. on Intelligent Systems for Molecular Biology, p 175-182 Ed J. Glasgow, T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, Calif.: AAAI Press, 1998), and clust (Remm M, and Sonnhammer E. Classification of transmembrane protein families in the Caenorhabditis elegans genome and identification of human orthologs. Genome Res. 2000 November;10(11):1679-89) programs. For example, the LIM domains of LIMK from GI# 4505001 (SEQ ID NO:20) are located at approximately amino acid residues 80 to 136 and 139 to 198 (PFAM 00412). The LIM domains of LIMK from GI# 5031869 (SEQ ID NO:22) are located at approximately amino acid residues 12 to 69 and 72 to 129 (PFAM 00412). Further, the kinase domains of LIMK from GI#s 4505001, 5031869, 5454110 and 6005896 (SEQ ID NOs: 20, 22, 24, and 25, respectively) are located at approximately amino acid residues 394 to 652 for GI# 4505001, 310-518 for GI#5031869, 57 to 314 for GI#5454110, and 62 to 117 and 120 to 289 for GI#6005896, respectively (PFAM00069). Still further, the PDZ domains of LIMK from GI#4505001 (SEQ ID NO: 20) and GI#5031869 (SEQ ID NO: 22) are located at approximately amino acids 165-257 and 131-217, respectively (PFAM 00595).

[0110] II. High-Throughput In Vitro Fluorescence Polarization Assay

[0111] Fluorescently-labeled LIMK peptide/substrate are added to each well of a 96-well microtiter plate, along with a test agent in a test buffer (10 mM HEPES, 10 mM NaCl, 6 mM magnesium chloride, pH 7.6). Changes in fluorescence polarization, determined by using a Fluorolite FPM-2 Fluorescence Polarization Microtiter System (Dynatech Laboratories, Inc), relative to control values indicates the test compound is a candidate modifier of LIMK activity.

[0112] III. High-Throughput In Vitro Binding Assay.

[0113] .sup.33P-labeled LIMK peptide is added in an assay buffer (100 mM KCl, 20 mM HEPES pH 7.6, 1 mM MgCl.sub.2, 1% glycerol, 0.5% NP-40, 50 mM beta-mercaptoethanol, 1 mg/ml BSA, cocktail of protease inhibitors) along with a test agent to the wells of a Neutralite-avidin coated assay plate and incubated at 25.degree. C. for 1 hour. Biotinylated substrate is then added to each well and incubated for 1 hour. Reactions are stopped by washing with PBS, and counted in a scintillation counter. Test agents that cause a difference in activity relative to control without test agent are identified as candidate p53 modulating agents.

[0114] IV. Immunoprecipitations and Immunoblotting

[0115] For coprecipitation of transfected proteins, 3.times.10.sup.6 appropriate recombinant cells containing the LIMK proteins are plated on 10-cm dishes and transfected on the following day with expression constructs. The total amount of DNA is kept constant in each transfection by adding empty vector. After 24 h, cells are collected, washed once with phosphate-buffered saline and lysed for 20 min on ice in 1 ml of lysis buffer containing 50 mM Hepes, pH 7.9, 250 mM NaCl, 20 mM-glycerophosphate, 1 mM sodium orthovanadate, 5 mM p-nitrophenyl phosphate, 2 mM dithiothreitol, protease inhibitors (complete, Roche Molecular Biochemicals), and 1% Nonidet P-40. Cellular debris is removed by centrifugation twice at 15,000.times.g for 15 min. The cell lysate is incubated with 25 .mu.l of M2 beads (Sigma) for 2 h at 4.degree. C. with gentle rocking.

[0116] After extensive washing with lysis buffer, proteins bound to the beads are solubilized by boiling in SDS sample buffer, fractionated by SDS-polyacrylamide gel electrophoresis, transferred to polyvinylidene difluoride membrane and blotted with the indicated antibodies. The reactive bands are visualized with horseradish peroxidase coupled to the appropriate secondary antibodies and the enhanced chemiluminescence (ECL) Western blotting detection system (Amersham Pharmacia Biotech).

[0117] V. Kinase Assay

[0118] A purified or partially purified LIMK is diluted in a suitable reaction buffer, e.g., 50 mM Hepes, pH 7.5, containing magnesium chloride or manganese chloride (1-20 mM) and a peptide or polypeptide substrate, such as myelin basic protein or casein (1-10 .mu.g/ml). The final concentration of the kinase is 1-20 nM. The enzyme reaction is conducted in microtiter plates to facilitate optimization of reaction conditions by increasing assay throughput. A 96-well microtiter plate is employed using a final volume 30-100 .mu.l. The reaction is initiated by the addition of .sup.33P-gamma-ATP (0.5 .mu.Ci/ml) and incubated for 0.5 to 3 hours at room temperature. Negative controls are provided by the addition of EDTA, which chelates the divalent cation (Mg2.sup.+ or Mn.sup.2+) required for enzymatic activity. Following the incubation, the enzyme reaction is quenched using EDTA. Samples of the reaction are transferred to a 96-well glass fiber filter plate (MultiScreen, Millipore). The filters are subsequently washed with phosphate-buffered saline, dilute phosphoric acid (0.5%) or other suitable medium to remove excess radiolabeled ATP. Scintillation cocktail is added to the filter plate and the incorporated radioactivity is quantitated by scintillation counting (Wallac/Perkin Elmer). Activity is defined by the amount of radioactivity detected following subtraction of the negative control reaction value (EDTA quench).

[0119] VI. Expression Analysis

[0120] All cell lines used in the following experiments are NCI (National Cancer Institute) lines, and are available from ATCC (American Type Culture Collection, Manassas, Va. 20110-2209). Normal and tumor tissues were obtained from Impath, UC Davis, Clontech, Stratagene, and Ambion.

[0121] TaqMan analysis was used to assess expression levels of the disclosed genes in various samples.

[0122] RNA was extracted from each tissue sample using Qiagen (Valencia, Calif.) RNeasy kits, following manufacturer's protocols, to a final concentration of 50 ng/.mu.l. Single stranded cDNA was then synthesized by reverse transcribing the RNA samples using random hexamers and 500 ng of total RNA per reaction, following protocol 4304965 of Applied Biosystems (Foster City, Calif., http://www.appliedbiosystems.com/).

[0123] Primers for expression analysis using TaqMan assay (Applied Biosystems, Foster City, Calif.) were prepared according to the TaqMan protocols, and the following criteria: a) primer pairs were designed to span introns to eliminate genomic contamination, and b) each primer pair produced only one product.

[0124] Taqman reactions were carried out following manufacturer's protocols, in 25 .mu.l total volume for 96-well plates and 10 .mu.l total volume for 384-well plates, using 300 nM primer and 250 nM probe, and approximately 25 ng of cDNA. The standard curve for result analysis was prepared using a universal pool of human cDNA samples, which is a mixture of cDNAs from a wide variety of tissues so that the chance that a target will be present in appreciable amounts is good. The raw data were normalized using 18S rRNA (universally expressed in all tissues and cells).

[0125] For each expression analysis, tumor tissue samples were compared with matched normal tissues from the same patient. A gene was considered overexpressed in a tumor when the level of expression of the gene was 2 fold or higher in the tumor compared with its matched normal sample.

[0126] Results are shown in Table 1. Data presented in bold indicate that greater than 50% of tested tumor samples of the tissue type indicated in row 1 exhibited over expression of the gene listed in column 1, relative to normal samples. Underlined data indicates that between 25% to 49% of tested tumor samples exhibited over expression. A modulator identified by an assay described herein can be further validated for therapeutic effect by administration to a tumor in which the gene is overexpressed. A decrease in tumor growth confirms therapeutic utility of the modulator. Prior to treating a patient with the modulator, the likelihood that the patient will respond to treatment can be diagnosed by obtaining a tumor sample from the patient, and assaying for expression of the gene targeted by the modulator. The expression data for the gene(s) can also be used as a diagnostic marker for disease progression. The assay can be performed by expression analysis as described above, by antibody directed to the gene target, or by any other available detection method. TABLE-US-00001 TABLE 1 breast . . colon . . lung . . ovary GI#1805594 0 11 . 3 30 . 0 13 . 1 7 (SEQ ID NO: 14) GI#6005895 3 11 . 1 30 . 2 13 . 2 7 (SEQ ID NO: 15)

[0127]

Sequence CWU 1

1

25 1 3332 DNA Homo sapiens 1 gcgccgagcc ggtttccccg ccggtgtccg agaggcgccc ccggcccggc ccggcccggc 60 ccgcgccctc cgcccccgcc tccccgggcc ggcggcggtg ggcgagctcg cgggcccggc 120 cgcccccagc cccagccccg ccgggccccg ccccccgtcg agtgcatgag gttgacgcta 180 ctttgttgca cctggaggga agaacgtatg ggagaggaag gaagcgagtt gcccgtgtgt 240 gcaagctgcg gccagaggat ctatgatggc cagtacctcc aggccctgaa cgcggactgg 300 cacgcagact gcttcaggtg ttgtgactgc agtgcctccc tgtcgcacca gtactatgag 360 aaggatgggc agctcttctg caagaaggac tactgggccc gctatggcga gtcctgccat 420 gggtgctctg agcaaatcac caagggactg gttatggtgg ctggggagct gaagtaccac 480 cccgagtgtt tcatctgcct cacgtgtggg acctttatcg gtgacgggga cacctacacg 540 ctggtggagc actccaagct gtactgcggg cactgctact accagactgt ggtgaccccc 600 gtcatcgagc agatcctgcc tgactcccct ggctcccacc tgccccacac cgtcaccctg 660 gtgtccatcc cagcctcatc tcatggcaag cgtggacttt cagtctccat tgaccccccg 720 cacggcccac cgggctgtgg caccgagcac tcacacaccg tccgcgtcca gggagtggat 780 ccgggctgca tgagcccaga tgtgaagaat tccatccacg tcggagaccg gatcttggaa 840 atcaatggca cgcccatccg aaatgtgccc ctggacgaga ttgacctgct gattcaggaa 900 accagccgcc tgctccagct gaccctcgag catgaccctc acgatacact gggccacggg 960 ctggggcctg agaccagccc cctgagctct ccggcttata ctcccagcgg ggaggcgggc 1020 agctctgccc ggcagaaacc tgtcttgagg agctgcagca tcgacaggtc tccgggcgct 1080 ggctcactgg gctccccggc ctcccagcgc aaggacctgg gtcgctctga gtccctccgc 1140 gtagtctgcc ggccacaccg catcttccgg ccgtcggacc tcatccacgg ggaggtgctg 1200 ggcaagggct gcttcggcca ggctatcaag gtgacacacc gtgagacagg tgaggtgatg 1260 gtgatgaagg agctgatccg gttcgacgag gagacccaga ggacgttcct caaggaggtg 1320 aaggtcatgc gatgcctgga acaccccaac gtgctcaagt tcatcggggt gctctacaag 1380 gacaagaggc tcaacttcat cactgagtac atcaagggcg gcacgctccg gggcatcatc 1440 aagagcatgg acagccagta cccatggagc cagagagtga gctttgccaa ggacatcgca 1500 tcagggatgg cctacctcca ctccatgaac atcatccacc gagacctcaa ctcccacaac 1560 tgcctggtcc gcgagaacaa gaatgtggtg gtggctgact tcgggctggc gcgtctcatg 1620 gtggacgaga agactcagcc tgagggcctg cggagcctca agaagccaga ccgcaagaag 1680 cgctacaccg tggtgggcaa cccctactgg atggcacctg agatgatcaa cggccgcagc 1740 tatgatgaga aggtggatgt gttctccttt gggatcgtcc tgtgcgagat catcgggcgg 1800 gtgaacgcag accctgacta cctgccccgc accatggact ttggcctcaa cgtgcgagga 1860 ttcctggacc gctactgccc cccaaactgc cccccgagct tcttccccat caccgtgcgc 1920 tgttgcgatc tggaccccga gaagaggcca tcctttgtga agctggaaca ctggctggag 1980 accctccgca tgcacctggc cggccacctg ccactgggcc cacagctgga gcagctggac 2040 agaggtttct gggagaccta ccggcgcggc gagagcggac tgcctgccca ccctgaggtc 2100 cccgactgag ccagggccac tcagctgccc ctgtccccac ctctggagaa tccaccccca 2160 ccagattcct ccgcgggagg tggccctcag ctgggacagt ggggacccag gcttctcctc 2220 agagccaggc cctgacttgc cttctcccac cccgtggacc gcttcccctg ccttctctct 2280 gccgtggccc agagccggcc cagctgcaca cacacaccat gctctcgccc tgctgtaacc 2340 tctgtcttgg cagggctgtc ccctcttgct tctccttgca tgagctggag ggcctgtgtg 2400 agttacgccc ctttccacac gccgctgccc cagcaaccct gttcacgctc cacctgtctg 2460 gtccatagct ccctggaggc tgggccagga ggcagcctcc gaaccatgcc ccatataacg 2520 cttgggtgcg tgggagggcg cacatcaggg cagaggccaa gttccaggtg tctgtgttcc 2580 caggaaccaa atggggagtc tggggcccgt tttcccccca gggggtgtct aggtagcaac 2640 aggtatcgag gactctccaa acccccaaag cagagagagg gctgatccca tggggcggag 2700 gtccccagtg gctgagcaaa cagccccttc tctcgctttg ggtctttttt ttgtttcttt 2760 cttaaagcca ctttagtgag aagcaggtac caagcctcag ggtgaagggg gtcccttgag 2820 ggagcgtgga gctgcggtgc cctggccggc gatggggagg agccggctcc ggcagtgaga 2880 ggataggcac agtggaccgg gcaggtgtcc accagcagct cagcccctgc agtcatctca 2940 gagccccttc ccgggcctct cccccaaggc tccctgcccc tcctcatgcc cctctgtcct 3000 ctgcgttttt tctgtgtaat ctatttttta agaagagttt gtattatttt ttcatacggc 3060 tgcagcagca gctgccaggg gcttgggatt ttatttttgt ggcgggcggg ggtgggaggg 3120 ccattttgtc actttgcctc agttgagcat ctaggaagta ttaaaactgt gaagctttct 3180 cagtgcactt tgaacctgga aaacaatccc aacaggcccg tgggaccatg acttagggag 3240 gtgggaccca cccaccccca tccaggaacc gtgacgtcca aggaaccaaa cccagacgca 3300 gaacaataaa ataaattccg tactccccac cc 3332 2 3271 DNA Homo sapiens 2 gcgccgagcc ggtttccccg ccggtgtccg agaggcgccc ccggcccggc ccggcccggc 60 ccgcgccctc cgcccccgcc tccccgggcc ggcggcggtg ggcgagctcg cgggcccggc 120 cgcccccagc cccagccccg ccgggccccg ccccccgtcg agtgcatgag gttgacgcta 180 ctttgttgca cctggaggga agaacgtatg ggagaggaag gaagcgagtt gcccgtgtgt 240 gcaagctgcg gccagaggat ctatgatggc cagtacctcc aggccctgaa cgcggactgg 300 cacgcagact gcttcaggtg ttgtgactgc agtgcctccc tgtcgcacca gtactatgag 360 aaggatgggc agctcttctg caagaaggac tactgggccc gctatggcga gtcctgccat 420 gggtgctctg agcaaatcac caagggactg gttatggtgg ctggggagct gaagtaccac 480 cccgagtgtt tcatctgcct cacgtgtggg acctttatcg gtgacgggga cacctacacg 540 ctggtggagc actccaagct gtactgcggg cactgctact accagactgt ggtgaccccc 600 gtcatcgagc agatcctgcc tgactcccct ggctcccacc tgccccacac cgtcaccctg 660 gtgtccatcc cagcctcatc tcatggcaag cgtggacttt cagtctccat tgaccccccg 720 cacggcccac cgggctgtgg caccgagcac tcacacaccg tccgcgtcca gggagtggat 780 ccgggctgca tgagcccaga tgtgaagaat tccatccacg tcggagaccg gatcttggaa 840 atcaatggca cgcccatccg aaatgtgccc ctggacgaga ttgacctgct gattcaggaa 900 accagccgcc tgctccagct gaccctcgag catgaccctc acgatacact gggccacggg 960 ctggggcctg agaccagccc cctgagctct ccggcttata ctcccagcgg ggaggcgggc 1020 agctctgccc ggcagaaacc tgtcttcgca aggacctggg tcgctctgag tccctccgcg 1080 tagtctgccg gccacaccgc atcttccggc cgtcggacct catccacggg gaggtgctgg 1140 gcaagggctg cttcggccag gctatcaagg tgacacaccg tgagacaggt gaggtgatgg 1200 tgatgaagga gctgatccgg ttcgacgagg agacccagag gacgttcctc aaggaggtga 1260 aggtcatgcg atgcctggaa caccccaacg tgctcaagtt catcggggtg ctctacaagg 1320 acaagaggct caacttcatc actgagtaca tcaagggcgg cacgctccgg ggcatcatca 1380 agagcatgga cagccagtac ccatggagcc agagagtgag ctttgccaag gacatcgcat 1440 cagggatggc ctacctccac tccatgaaca tcatccaccg agacctcaac tcccacaact 1500 gcctggtccg cgagaacaag aatgtggtgg tggctgactt cgggctggcg cgtctcatgg 1560 tggacgagaa gactcagcct gagggcctgc ggagcctcaa gaagccagac cgcaagaagc 1620 gctacaccgt ggtgggcaac ccctactgga tggcacctga gatgatcaac ggccgcagct 1680 atgatgagaa ggtggatgtg ttctcctttg ggatcgtcct gtgcgagatc atcgggcggg 1740 tgaacgcaga ccctgactac ctgccccgca ccatggactt tggcctcaac gtgcgaggat 1800 tcctggaccg ctactgcccc ccaaactgcc ccccgagctt cttccccatc accgtgcgct 1860 gttgcgatct ggaccccgag aagaggccat cctttgtgaa gctggaacac tggctggaga 1920 ccctccgcat gcacctggcc ggccacctgc cactgggccc acagctggag cagctggaca 1980 gaggtttctg ggagacctac cggcgcggcg agagcggact gcctgcccac cctgaggtcc 2040 ccgactgagc cagggccact cagctgcccc tgtccccacc tctggagaat ccacccccac 2100 cagattcctc cgcgggaggt ggccctcagc tgggacagtg gggacccagg cttctcctca 2160 gagccaggcc ctgacttgcc ttctcccacc ccgtggaccg cttcccctgc cttctctctg 2220 ccgtggccca gagccggccc agctgcacac acacaccatg ctctcgccct gctgtaacct 2280 ctgtcttggc agggctgtcc cctcttgctt ctccttgcat gagctggagg gcctgtgtga 2340 gttacgcccc tttccacacg ccgctgcccc agcaaccctg ttcacgctcc acctgtctgg 2400 tccatagctc cctggaggct gggccaggag gcagcctccg aaccatgccc catataacgc 2460 ttgggtgcgt gggagggcgc acatcagggc agaggccaag ttccaggtgt ctgtgttccc 2520 aggaaccaaa tggggagtct ggggcccgtt ttccccccag ggggtgtcta ggtagcaaca 2580 ggtatcgagg actctccaaa cccccaaagc agagagaggg ctgatcccat ggggcggagg 2640 tccccagtgg ctgagcaaac agccccttct ctcgctttgg gtcttttttt tgtttctttc 2700 ttaaagccac tttagtgaga agcaggtacc aagcctcagg gtgaaggggg tcccttgagg 2760 gagcgtggag ctgcggtgcc ctggccggcg atggggagga gccggctccg gcagtgagag 2820 gataggcaca gtggaccggg caggtgtcca ccagcagctc agcccctgca gtcatctcag 2880 agccccttcc cgggcctctc ccccaaggct ccctgcccct cctcatgccc ctctgtcctc 2940 tgcgtttttt ctgtgtaatc tattttttaa gaagagtttg tattattttt tcatacggct 3000 gcagcagcag ctgccagggg cttgggattt tatttttgtg gcgggcgggg gtgggagggc 3060 cattttgtca ctttgcctca gttgagcatc taggaagtat taaaactgtg aagctttctc 3120 agtgcacttt gaacctggaa aacaatccca acaggcccgt gggaccatga cttagggagg 3180 tgggacccac ccacccccat ccaggaaccg tgacgtccaa ggaaccaaac ccagacgcag 3240 aacaataaaa taaattccgt actccccacc c 3271 3 3332 DNA Homo sapiens 3 gcgccgagcc ggtttccccg ccggtgtccg agaggcgccc ccggcccggc ccggcccggc 60 ccgcgccctc cgcccccgcc tccccgggcc ggcggcggtg ggcgagctcg cgggcccggc 120 cgcccccagc cccagccccg ccgggccccg ccccccgtcg agtgcatgag gttgacgcta 180 ctttgttgca cctggaggga agaacgtatg ggagaggaag gaagcgagtt gcccgtgtgt 240 gcaagctgcg gccagaggat ctatgatggc cagtacctcc aggccctgaa cgcggactgg 300 cacgcagact gcttcaggtg ttgtgactgc agtgcctccc tgtcgcacca gtactatgag 360 aaggatgggc agctcttctg caagaaggac tactgggccc gctatggcga gtcctgccat 420 gggtgctctg agcaaatcac caagggactg gttatggtgg ctggggagct gaagtaccac 480 cccgagtgtt tcatctgcct cacgtgtggg acctttatcg gtgacgggga cacctacacg 540 ctggtggagc actccaagct gtactgcggg cactgctact accagactgt ggtgaccccc 600 gtcatcgagc agatcctgcc tgactcccct ggctcccacc tgccccacac cgtcaccctg 660 gtgtccatcc cagcctcatc tcatggcaag cgtggacttt cagtctccat tgaccccccg 720 cacggcccac cgggctgtgg caccgagcac tcacacaccg tccgcgtcca gggagtggat 780 ccgggctgca tgagcccaga tgtgaagaat tccatccacg tcggagaccg gatcttggaa 840 atcaatggca cgcccatccg aaatgtgccc ctggacgaga ttgacctgct gattcaggaa 900 accagccgcc tgctccagct gaccctcgag catgaccctc acgatacact gggccacggg 960 ctggggcctg agaccagccc cctgagctct ccggcttata ctcccagcgg ggaggcgggc 1020 agctctgccc ggcagaaacc tgtcttgagg agctgcagca tcgacaggtc tccgggcgct 1080 ggctcactgg gctccccggc ctcccagcgc aaggacctgg gtcgctctga gtccctccgc 1140 gtagtctgcc ggccacaccg catcttccgg ccgtcggacc tcatccacgg ggaggtgctg 1200 ggcaagggct gcttcggcca ggctatcaag gtgacacacc gtgagacagg tgaggtgatg 1260 gtgatgaagg agctgatccg gttcgacgag gagacccaga ggacgttcct caaggaggtg 1320 aaggtcatgc gatgcctgga acaccccaac gtgctcaagt tcatcggggt gctctacaag 1380 gacaagaggc tcaacttcat cactgagtac atcaagggcg gcacgctccg gggcatcatc 1440 aagagcatgg acagccagta cccatggagc cagagagtga gctttgccaa ggacatcgca 1500 tcagggatgg cctacctcca ctccatgaac atcatccacc gagacctcaa ctcccacaac 1560 tgcctggtcc gcgagaacaa gaatgtggtg gtggctgact tcgggctggc gcgtctcatg 1620 gtggacgaga agactcagcc tgagggcctg cggagcctca agaagccaga ccgcaagaag 1680 cgctacaccg tggtgggcaa cccctactgg atggcacctg agatgatcaa cggccgcagc 1740 tatgatgaga aggtggatgt gttctccttt gggatcgtcc tgtgcgagat catcgggcgg 1800 gtgaacgcag accctgacta cctgccccgc accatggact ttggcctcaa cgtgcgagga 1860 ttcctggacc gctactgccc cccaaactgc cccccgagct tcttccccat caccgtgcgc 1920 tgttgcgatc tggaccccga gaagaggcca tcctttgtga agctggaaca ctggctggag 1980 accctccgca tgcacctggc cggccacctg ccactgggcc cacagctgga gcagctggac 2040 agaggtttct gggagaccta ccggcgcggc gagagcggac tgcctgccca ccctgaggtc 2100 cccgactgag ccagggccac tcagctgccc ctgtccccac ctctggagaa tccaccccca 2160 ccagattcct ccgcgggagg tggccctcag ctgggacagt ggggacccag gcttctcctc 2220 agagccaggc cctgacttgc cttctcccac cccgtggacc gcttcccctg ccttctctct 2280 gccgtggccc agagccggcc cagctgcaca cacacaccat gctctcgccc tgctgtaacc 2340 tctgtcttgg cagggctgtc ccctcttgct tctccttgca tgagctggag ggcctgtgtg 2400 agttacgccc ctttccacac gccgctgccc cagcaaccct gttcacgctc cacctgtctg 2460 gtccatagct ccctggaggc tgggccagga ggcagcctcc gaaccatgcc ccatataacg 2520 cttgggtgcg tgggagggcg cacatcaggg cagaggccaa gttccaggtg tctgtgttcc 2580 caggaaccaa atggggagtc tggggcccgt tttcccccca gggggtgtct aggtagcaac 2640 aggtatcgag gactctccaa acccccaaag cagagagagg gctgatccca tggggcggag 2700 gtccccagtg gctgagcaaa cagccccttc tctcgctttg ggtctttttt ttgtttcttt 2760 cttaaagcca ctttagtgag aagcaggtac caagcctcag ggtgaagggg gtcccttgag 2820 ggagcgtgga gctgcggtgc cctggccggc gatggggagg agccggctcc ggcagtgaga 2880 ggataggcac agtggaccgg gcaggtgtcc accagcagct cagcccctgc agtcatctca 2940 gagccccttc ccgggcctct cccccaaggc tccctgcccc tcctcatgcc cctctgtcct 3000 ctgcgttttt tctgtgtaat ctatttttta agaagagttt gtattatttt ttcatacggc 3060 tgcagcagca gctgccaggg gcttgggatt ttatttttgt ggcgggcggg ggtgggaggg 3120 ccattttgtc actttgcctc agttgagcat ctaggaagta ttaaaactgt gaagctttct 3180 cagtgcactt tgaacctgga aaacaatccc aacaggcccg tgggaccatg acttagggag 3240 gtgggaccca cccaccccca tccaggaacc gtgacgtcca aggaaccaaa cccagacgca 3300 gaacaataaa ataaattccg tactccccac cc 3332 4 3262 DNA Homo sapiens 4 gcgccgagcc ggtttccccg ccggtgtccg agaggcgccc ccggcccggc cgcccccagc 60 cccagccccg ccgggccccg ccccccgtcg agtgcatgag gttgacgcta ctttgttgca 120 cctggaggga agaacgtatg ggagaggaag gaagcgagtt gcccgtgtgt gcaagctgcg 180 gccagaggat ctatgatggc cagtacctcc aggccctgaa cgcggactgg cacgcagact 240 gcttcaggtg ttgtgactgc agtgcctccc tgtcgcacca gtactatgag aaggatgggc 300 agctcttctg caagaaggac tactgggccc gctatggcga gtcctgccat gggtgctctg 360 agcaaatcac caagggactg gttatggtgg ctggggagct gaagtaccac cccgagtgtt 420 tcatctgcct cacgtgtggg acctttatcg gtgacgggga cacctacacg ctggtggagc 480 actccaagct gtactgcggg cactgctact accagactgt ggtgaccccc gtcatcgagc 540 agatcctgcc tgactcccct ggctcccacc tgccccacac cgtcaccctg gtgtccatcc 600 cagcctcatc tcatggcaag cgtggacttt cagtctccat tgaccccccg cacggcccac 660 cgggctgtgg caccgagcac tcacacaccg tccgcgtcca gggagtggat ccgggctgca 720 tgagcccaga tgtgaagaat tccatccacg tcggagaccg gatcttggaa atcaatggca 780 cgcccatccg aaatgtgccc ctggacgaga ttgacctgct gattcaggaa accagccgcc 840 tgctccagct gaccctcgag catgaccctc acgatacact gggccacggg ctggggcctg 900 agaccagccc cctgagctct ccggcttata ctcccagcgg ggaggcgggc agctctgccc 960 ggcagaaacc tgtcttgagg agctgcagca tcgacaggtc tccgggcgct ggctcactgg 1020 gctccccggc ctcccagcgc aaggacctgg gtcgctctga gtccctccgc gtagtctgcc 1080 ggccacaccg catcttccgg ccgtcggacc tcatccacgg ggaggtgctg ggcaagggct 1140 gcttcggcca ggctatcaag gtgacacacc gtgagacagg tgaggtgatg gtgatgaagg 1200 agctgatccg gttcgacgag gagacccaga ggacgttcct caaggaggtg aaggtcatgc 1260 gatgcctgga acaccccaac gtgctcaagt tcatcggggt gctctacaag gacaagaggc 1320 tcaacttcat cactgagtac atcaagggcg gcacgctccg gggcatcatc aagagcatgg 1380 acagccagta cccatggagc cagagagtga gctttgccaa ggacatcgca tcagggatgg 1440 cctacctcca ctccatgaac atcatccacc gagacctcaa ctcccacaac tgcctggtcc 1500 gcgagaacaa gaatgtggtg gtggctgact tcgggctggc gcgtctcatg gtggacgaga 1560 agactcagcc tgagggcctg cggagcctca agaagccaga ccgcaagaag cgctacaccg 1620 tggtgggcaa cccctactgg atggcacctg agatgatcaa cggccgcagc tatgatgaga 1680 aggtggatgt gttctccttt gggatcgtcc tgtgcgagat catcgggcgg gtgaacgcag 1740 accctgacta cctgccccgc accatggact ttggcctcaa cgtgcgagga ttcctggacc 1800 gctactgccc cccaaactgc cccccgagct tcttccccat caccgtgcgc tgttgcgatc 1860 tggaccccga gaagaggcca tcctttgtga agctggaaca ctggctggag accctccgca 1920 tgcacctggc cggccacctg ccactgggcc cacagctgga gcagctggac agaggtttct 1980 gggagaccta ccggcgcggc gagagcggac tgcctgccca ccctgaggtc cccgactgag 2040 ccagggccac tcagctgccc ctgtccccac ctctggagaa tccaccccca ccagattcct 2100 ccgcgggagg tggccctcag ctgggacagt ggggacccag gcttctcctc agagccaggc 2160 cctgacttgc cttctcccac cccgtggacc gcttcccctg ccttctctct gccgtggccc 2220 agagccggcc cagctgcaca cacacaccat gctctcgccc tgctgtaacc tctgtcttgg 2280 cagggctgtc ccctcttgct tctccttgca tgagctggag ggcctgtgtg agttacgccc 2340 ctttccacac gccgctgccc cagcaaccct gttcacgctc cacctgtctg gtccatagct 2400 ccctggaggc tgggccagga ggcagcctcc gaaccatgcc ccatataacg cttgggtgcg 2460 tgggagggcg cacatcaggg cagaggccaa gttccaggtg tctgtgttcc caggaaccaa 2520 atggggagtc tggggcccgt tttcccccca gggggtgtct aggtagcaac aggtatcgag 2580 gactctccaa acccccaaag cagagagagg gctgatccca tggggcggag gtccccagtg 2640 gctgagcaaa cagccccttc tctcgctttg ggtctttttt ttgtttcttt cttaaagcca 2700 ctttagtgag aagcaggtac caagcctcag ggtgaagggg gtcccttgag ggagcgtgga 2760 gctgcggtgc cctggccggc gatggggagg agccggctcc ggcagtgaga ggataggcac 2820 agtggaccgg gcaggtgtcc accagcagct cagcccctgc agtcatctca gagccccttc 2880 ccgggcctct cccccaaggc tccctgcccc tcctcatgcc cctctgtcct ctgcgttttt 2940 tctgtgtaat ctatttttta agaagagttt gtattatttt ttcatacggc tgcagcagca 3000 gctgccaggg gcttgggatt ttatttttgt ggcgggcggg ggtgggaggg ccattttgtc 3060 actttgcctc agttgagcat ctaggaagta ttaaaactgt gaagctttct cagtgcactt 3120 tgaacctgga aaacaatccc aacaggcccg tgggaccatg acttagggag gtgggaccca 3180 cccaccccca tccaggaacc gtgacgtcca aggaaccaaa cccagacgca gaacaataaa 3240 ataaattccg tactccccac cc 3262 5 2456 DNA Homo sapiens 5 cagctgaccc tcgagcatga ccctcacgat acactgggcc acgggctggg gcctgagacc 60 agccccctga gctctccggc ttatactccc agcggggagg cgggcagctc tgcccggcag 120 aaacctgtct tgaggagctg cagcatcgac aggtctccgg gcgctggctc actgggctcc 180 ccggcctccc agcgcaagga cctgggtcgc tctgagtccc tccgcgtagt ctgccggcca 240 caccgcatct tccggccgtc ggacctcatc cacggggagg tgctgggcaa gggctgcttc 300 ggccaggcta tcaaggtgac acaccgtgag acaggtgagg tgatggtgat gaaggagctg 360 atccggttcg acgaggagac ccagaggacg ttcctcaagg aggtgaaggt catgcgatgc 420 ctggaacacc ccaacgtgct caagttcatc ggggtgctct acaaggacaa gaggctcaac 480 ttcatcactg agtacatcaa gggcggcacg ctccggggca tcatcaagag catggacagc 540 cagtacccat ggagccagag agtgagcttt gccaaggaca tcgcatcagg gatggcctac 600 ctccactcca tgaacatcat ccaccgagac ctcaactccc acaactgcct ggtccgcgag 660 aacaagaatg tggtggtggc tgacttcggg ctggcgcgtc tcatggtgga cgagaagact 720 cagcctgagg gcctgcggag cctcaagaag ccagaccgca agaagcgcta caccgtggtg 780 ggcaacccct actggatggc acctgagatg atcaacggcc gcagctatga tgagaaggtg 840 gatgtgttct cctttgggat cgtcctgtgc gagatcatcg ggcgggtgaa cgcagaccct 900 gactacctgc cccgcaccat ggactttggc ctcaacgtgc gaggattcct ggaccgctac 960 tgccccccaa actgcccccc gagcttcttc cccatcaccg tgcgctgttg cgatctggac 1020 cccgagaaga ggccatcctt tgtgaagctg gaacactggc tggagaccct ccgcatgcac 1080 ctggccggcc acctgccact gggcccacag ctggagcagc tggacagagg tttctgggag 1140 acctaccggc gcggcgagag cggactgcct gcccaccctg aggtccccga ctgagccagg 1200 gccactcagc tgcccctgtc cccacctctg gagaatccac ccccaccaga ttcctccgcg 1260 ggaggtggcc ctcagctggg acagtgggga cccaggcttc tcctcagagc caggccctga 1320 cttgccttct cccaccccgt ggaccgcttc ccctgccttc tctctgccgt ggcccagagc 1380 cggcccagct gcacacacac accatgctct cgccctgctg taacctctgt cttggcaggg 1440 ctgtcccctc ttgcttctcc ttgcatgagc tggagggcct gtgtgagtta cgcccctttc 1500 cacacgccgc tgccccagca accctgttca cgctccacct gtctggtcca tagctccctg 1560 gaggctgggc caggaggcag cctccgaacc atgccccata taacgcttgg

gtgcgtggga 1620 gggcgcacat cagggcagag gccaagttcc aggtgtctgt gttcccagga accaaatggg 1680 gagtctgggg cccgttttcc ccccaggggg tgtctaggta gcaacaggta tcgaggactc 1740 tccaaacccc caaagcagag agagggctga tcccatgggg cggaggtccc cagtggctga 1800 gcaaacagcc ccttctctcg ctttgggtct tttttttgtt tctttcttaa agccacttta 1860 gtgagaagca ggtaccaagc ctcagggtga agggggtccc ttgagggagc gtggagctgc 1920 ggtgccctgg ccggcgatgg ggaggagccg gctccggcag tgagaggata ggcacagtgg 1980 accgggcagg tgtccaccag cagctcagcc cctgcagtca tctcagagcc ccttcccggg 2040 cctctccccc aaggctccct gcccctcctc atgcccctct gtcctctgcg ttttttctgt 2100 gtaatctatt ttttaagaag agtttgtatt attctttcat acggctgcag cagcagctgc 2160 caggggcttg ggattttatt tttgtggcgg gcgggggtgg gagggccatt ttgtcacttt 2220 gcctcagttg agcatctagg aagtattaaa actgtgaagc tttctcagtg cactttgaac 2280 ctggaaaaca atcccaacag gcccgtggga ccatgactta gggaggtggg acccacccac 2340 ccccatccag gaaccgtgac gtccaaggaa ccaaacccag acgcagaaca ataaaataaa 2400 ttccgtactc cccaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaca aaaaaa 2456 6 128978 DNA Homo sapiens 6 gatcctactt cgcactcaca aatatggcca taataaaaaa ggaaaaaaat caacaacatc 60 cttgttggca aggatgtgga aaaattagaa tcctcataca ttgctggtgg gatgtaaact 120 ggtacagcca ccagtacctg actacagcca taccaccacg aacatgtcca atcttgtcta 180 aactttgatg tggaaaaact gatacggaaa gtagtttgat cagccgggca cagtggctca 240 cgtctgcaat ctcagaactt tggggagctg aggggggtgg atcacctgag gttgggagat 300 gaagaccagc ctggccaaca tggcaaaacc tgtctctact aaaaatacaa atttttgtat 360 ttttagtaga gccgggtgtg gtggctcaca cctgtaatcg cagctgctcg tgaggctgag 420 gcaggagagt catttgaacc caggaggcgg agattgcagt gaaccaagat cacatcactg 480 cactccagcc tgggtgacag agcgagactc catctcaaaa aaaaaaaaaa aaagaaaaag 540 aaaagaaaat agtttgatgg ttcctcgaaa agttaaacac agaataacca gcaatgccac 600 tcctaggtat atactcaaaa gaaatgaaaa caggtatcaa acaaaaacct gtacatgaat 660 attcatagta gcattattca taatagccaa aaggtggaaa caactcaaat gtccaccaac 720 tgatgactag ataaacaaaa tatggtacat ccatacacag gaatattatt cagccataaa 780 aagaaatgct gatacatgct acaacttaga tgaaccttca aaacatcatg cttagtagaa 840 gaagccagac acaaaaggtt gcatatagta tgattccatt tacataaaat gtctggaata 900 ggcatatcca tagaaataca aagagatcag tatttacttg gaacacttgg gacaataaca 960 aataaaataa taaaaatttt aaaaaagagt ccaggcgcag tggctcacgc ctgtaatccc 1020 agcactttgg gaggccaagg tgggtggatc ataaggtcag gagatcgaga ccgtggtgaa 1080 accccgtctc tactaaaaat acaaaaaatt agccgggcac gctggcgggc gcctgtagtc 1140 ccagctactc gggaggctga ggcaggagaa tggcgtgaac ctgggaggcg gagcttgcag 1200 tgagccgaga tcatgccact gcactccagc ctggctgaca gagcgagact ccgtctcaaa 1260 ataataataa caataataat aataataata ataataatta ttattattat tatttaaaaa 1320 agaaggagat cagaggttgc cagagggtga ggagaaagga aaatgaagag tggctgccaa 1380 caggtactag gtttctccca tctgagtact aaccagactc aaccctgctt agcttctgag 1440 atcagacaag attgcacatg ttcagggtgg tatggctgta gacaggtacc agcgtttctt 1500 tttggggtga tgaagtgttc tggaattaga tagcggtgat ggttacacaa ccttgtgaat 1560 atacagacat gagccacata atgatgtttc agtcaacaga ccgcatatat gacagtggtc 1620 ctataacaca gtggtcccca acctttttgg caccagggac tggtttcatg gaagacaatt 1680 tttccatgga ctgggggtga tggggggatg gtttcaggat gaaactgttc cacctcagat 1740 catcaggcat tagttagatt cttggaagga gtgcgcaacc tagatcccta gcatgtgcag 1800 ttcacaatag ggttcacact cctattagaa tctaatgtca ccactgatct gacaagaggc 1860 agagctcaga tggtaatgtt tgctcacctg ctgctcacct cctgctgtgc tactgggttc 1920 ctaactggcc acagccctgg ggtttgggga tccccgctat aagattataa taccatattt 1980 ttactgtacc ttttctatgt ttagatacac taatacttat cattgtgtta aagttgccta 2040 tagtatttag tacagttaga tgctgtacag gtttgtagcc tgagatcagt aggttacacc 2100 atatagccta gatatgtagt aggctgtccc gtctaggttt gtgtaattat actctatgat 2160 gtttgcatga cgcatttctc agaacctatc cttgttgtta agtgacgcac aggtactaac 2220 aactactgaa ctgtatgctg taaaatgatg aatttcatga tatgtgaatt gtatctcaat 2280 agaaaagagc atttataaag tttttgttgc taaatttatt tactttcggt aaattttctt 2340 ttaaaagatg tctatgtttt actgtcttcg tggtgctggg acataactga catctgaagc 2400 cttgaatgcc tctctttgca aactcatttg ttactactca gttaccatct cacctccaat 2460 acccaactgc ataccaaacc tctagccatt actagaacac atactctgag ctctgccata 2520 ctttagcgcc tgcacacatg ctgtttcttc tgctcagaaa cttttgtgcc ttctgtccat 2580 cccatccaag cctgtttttc aatgcccaac acaaatgtca ctggtaccct gaaacttcaa 2640 ctcctccttg ccccatctca gaaaatgtaa ctttctgtat tcttctctct gtatattcct 2700 ctaaagtggt atttcttata ctataccata atgacctggt cccatatttg tcctcttctt 2760 ccctcttcat cccagactgg gaccacaagg aggtagaact ttttctgttt tttttttttt 2820 ttgagacaga gtcttgctct gtcgccaggc tggagtgcaa tggcacgatc tcggctcact 2880 gcaacctctg cctcccgggt tcaagtgatt ctcctacctc agcctcccca gtagctggga 2940 tttcaggcgc acatcaccat gcccagctaa tttttgtatt tttagtagag acgggatttc 3000 accatgttga ccgggatggt ctcgatctct tgtcctcgtg atccgcccgt ctcagcctcc 3060 caaagtgttg ggattacggc catgagccac tgcgcccggc cggaggtaca actttcttag 3120 tcaatcttga gcaccagtgt agtgcttaga atcgggtagt gagagaagct aacatttact 3180 gaatgcctaa gaagtccagg gcacataaca gtcttcacaa ccatcctgtg aagtacgtat 3240 taccctatcc attttacaga taaagaaact tgagtttcaa gaaaggtata cctaaggtca 3300 ttcaacttgt taaatgatgg aatggaggag ttgagaccag attggacttc tgcctctttt 3360 tttttttttt ttttttttga gacaggctgg agtgcagtgg tgtgatctca gctcactgca 3420 agctctgcct cccaggttca cgccattctc ctgcctcagc ctcccaagta gctgggacta 3480 caggcgcctg ccaccacgcc cggctaattt tttctacttt tagtagagac ggggtttcac 3540 cgtgttagcc aggatggtct caatctcctg acctcgtgat ctgcccacct cggcctccca 3600 aagtgctggg attacaggcg tgagcgaccg cgcccagccg aacttctgcc tcttaaatcc 3660 agggttctcc ctgtcagtac agtgaggtgg taactagcaa aagctatgag atatgactgc 3720 ctgggtacat atcccagctc tttcacttat ctttgtggct ttacgcaaat tacttaacct 3780 ctttatgatt gtttcttcat ttgtaaaagg aagataataa cagtgcctat atatagggtt 3840 tttatgaaga ataaatgaga tagtatatat aaagcactta gaacagtatc tggcacatac 3900 taggtgctca ataaatgtta gcgatgacat ttattactgt cccacattga gctggtgttt 3960 gttaaacact ggatgactgg ataaaatgta catctttcat gcagagattg ctcgattatc 4020 catttcactg attcaggatc agagtctctt aagaatccag agaggggatg ttgaagccct 4080 aagaagtaaa aacactaaaa tgataacatt ttgacctttt gaaaactctt tgaagtggca 4140 atggccacaa aattgagcgg aaaccaaaca tattcagccc catttccaga taaattggat 4200 ttgctaaacc actcagaata acaagagcaa gaattagatg ttcagctaag ctctagcttc 4260 tgatcctaga tggtggcaat aacaacgata gtattaatga taatagcaga aactcttaat 4320 atgtgtgagg cattcttcta aatgctttac atatattaat ttaatgttca tcggagcaga 4380 ttctcctact gtatccaaga gatcagaaat tcagagcaaa aagcagattg ctgcctgata 4440 gcagatccac tctaggaatg gggagatttt ctcataaatc taatgactgg tgaaagtgac 4500 aagaggttag tccactcagt gttggaaagg acaagatcct agaaagtgga aatgctccac 4560 tattgcttta gggggaacag cctggctaca actgggcaga ctttctatta ctaacatcag 4620 gataataggg aagctcctgc caatgctgca tagaactaag aacacttagc agtgatggct 4680 gacttccaac tgagccatta aggtaagtgt agaagaaagc tccaggtaga aatatctttg 4740 ggaactcaga gaacacactg agtgtttgaa gctggtactt aatctattat tgaactcaga 4800 gtttgccatt ctggggccaa tttgagtcca cttatgacac ctcccacagc actgctcatt 4860 tctgttaact gggcttcaca gagggtgaga agggcagcaa tcagatcata taattgggcc 4920 tcattgtaat aaaatgttga tttctgttgt ccttggactt ccttccagcc acaatcactc 4980 tatgatcttg tctgagattc tttttccttt ctctctccat tttgctgact gtaatggaat 5040 aatagcagaa gctctcaatc tgtatgagga atatatatga agaatgtgta acattcactg 5100 tgtttcctaa tagatgaatt atctaaagga cacctcttaa gaagagatga gatggagcca 5160 actgtcagaa aaaaaaatgg gtgaagaaag tttcaaggag aagactccac agagcagaat 5220 gggaaagatg gccaggagaa aagtgagata ataaaaggaa aagcagtccc tgacacagaa 5280 ggtactcaac agctatttgc tgactgaaag aataaacact aataagagaa tgaaatacca 5340 ggattataaa gagggaacaa agatattttc ccatctactt tgttgttacc ccacccagga 5400 tatatttagg ttggtgcaaa agtaattgcg gtttttgaat cgttaataga ttaacatcta 5460 atttatgtat tgtttacata catacaaata caaactacaa ccatatatga tacatttaaa 5520 gtaatacgct aggcacagtg gtgcatatct atagtcccag ctgaggtggg aagactgctt 5580 gagcatagga gttcaagtcc ccttgggcaa catagcaaga ccctgtctct aaacaaagaa 5640 aacaaaaaaa gtgaagtaat taatgccaaa cattgcaatc agggtttggt gcacttgaaa 5700 tacacaaatg agtgttttta catgctgaag acacagcaac caacaactgg ggctaaagtg 5760 ctgcattcct aaagttaacc cacagagcct atcatgccat gccaaagttc actgctccgg 5820 ctccaaaccg gggactttcc tttcctattt cctctcccta acagcttaga gctactggac 5880 tccatccttg aactcctctg tttactaaaa atgttcttta taagctatga aatctggatt 5940 tgaggtctgg tttcttactt caactttgca actcatttcc caccccgagt tcacacaatc 6000 tcaaaatgtt catgaatttt atggctagac ctaaagcttc tttgtgcctt cctgccagcc 6060 tgcctttgtt ttggtacctt ctagcctatc ctcactcact tgagttttta ctctaatttt 6120 ctgtccagtc ttcccaccac tagtccccta tcaaattgct tgctggacat ttctatatac 6180 atagcttgct tgtccttacg tcaaattcaa aactaccaag agcaaatcca atgtgtgttc 6240 ccacatcagc tcccctttct cacctccctg gtatggttac tgaccaatta gaatgaatgt 6300 ccaaccactc agaatgccac aggcaatagg ccaaatcagt gtactgggtc caatgtcagc 6360 cctgtccata atccttctac ccagctaaac ttggaggaat tgtctgttct cacagtctcc 6420 cttcttcatc tcttattcct tccataatcc atacattttt agccctcctt ccttatcata 6480 aaaattcctc ctgacaaggt caccaatggc cttcttgttg ctaaaaccaa ttaattcttt 6540 ttagctttta tttcacttga tcatccttgg taacatttaa caatgctgac cattccctcc 6600 tccctgaaac actctcctta gcttctctga cattatactc ttctggttgc aatccagtca 6660 cctctggtgg tgccttctca gcctccccca aacctgcttt tcctcaggtt tcttatctca 6720 gtgaaagtca ccaccatccc ctaagctcct aaaccagaaa ccgaattcct tattcttctt 6780 atttgcttct aaccttcctt cagtcatgga atcctgctta ttcttagttt gcttctcttc 6840 actgcctaca tttttttttt ttttttttga gatggagtct cgctctgtcg cccaggctgg 6900 agtgcagtgg catgatctca gctcacggca acctccgcct ccctggttca agtgattcgt 6960 ctgtctcagc ctcccgagta gctgggacta caggcacgtg ccaccaggcc cggctaattt 7020 ttgtattttt agtagagaca gggtttcacc atattggcca ggctggtctc aaactcctga 7080 cctcgtgatc cgcccgcctc ggcctcccaa agtgctggga ttacagacgt gagccactgt 7140 gaccagcctt cactgcctac atttttaaag cacttaaata tgtgctaggc aggtgtgttc 7200 taagtgattt atcctcacaa taagcccata aggtaaattt tattatctcc aattttcaga 7260 ttaggtaaca gaggcaaaga gtggttaaat aacttgcata aagtcacata actactaagt 7320 ggcagagcag gattcaaacc caggtggcct gactcaattc tggatccagg tcactatcct 7380 atctcactga aatctctgca acagcctcct tggtttccag ccttccatca tggatggctt 7440 ccctgtagcc acagtgatct ttgttaaaac agaagtctga ctcttgctac tcttttgcat 7500 gaaaatcttt actggctctt tattgccttc agaataaagt ctacactcaa tatgacattc 7560 agggacctcc ataacctagc cagaaagtgt atacttcttt ggcttcatgt ttttggtttt 7620 tggccccatt ttaaccacga ccctaaaagc tccactagca caatgatagc ctatacttcc 7680 aggtttctgc actgtttgat gtgccaagaa cactctttcc caccttcaca ttcgacgact 7740 tctgataagc cttttctgat ttcctaagac cagggtatat gcctctcctg tgagctccca 7800 cagctcccag ttctaattct cactgtagca tttatttcac tgtgttatat gattctacta 7860 cccatctact aatattaata tctgctttat cacaagattg tgagcttcct gagaatggga 7920 actgtgtagg attcactgtt gtatcctcag tactcactgc tgcctacctg gtgcacggta 7980 ggcaatattc atttaatgaa taaaacttta ttgtctatat cacactcttt aacacttact 8040 tatataatgc cctatattga ttttattttc atatgtgtta gcctgatctt tataaccaga 8100 atgtcagttt cttgaaagat agcaattata cccagtactt cttttataaa tttatttact 8160 cttaggctgg gtgcagtggc tcacgcctat aatcgccaaa ttttgggagg ctgaggcagg 8220 aggatcactt gagtcgagga gtttgaggtc agcctgggta tagtgagacc tcatctctat 8280 aaaaaataag caagattagc tgggcatggt ggcatgcacc tgtggtccca gctattcagg 8340 agagctgagg tgggacggct tgagctccag agcctgaggc tacagtaagc catgatcatg 8400 ccactccagc ctcggtgaca aagcgagatc ctgtctcata aaagaaaaaa aaattatctt 8460 tagagatggg gtctcactct gtcccccagg atggagtgca gtgtcatgat catagctcac 8520 tgcagccttg aactcttggg ctcaagagat cctcccacct cagcctccca agtagcgggg 8580 actacaggtc tgtgctgcca tgcccagctg attcttttat ttgcagagat gggggtctca 8640 ctatgttgcc caggctggtc ttgaacttct gacctcaagc aatactcctg cctcagcctc 8700 ccaaaatgtt ggaattatag gcaaaaccca ccatgcctgg cctataccta gtacttacaa 8760 gttaggaggt actcacaaaa attcctgata acagctaaca tttattcagg gatcaatgaa 8820 tgtcaacaat ccaatgattt tggtaatttt tctctctctc tctgcctccc tccatatgag 8880 gaaactgagc catagtttag tagcttgcct aagatgacat agctaggaag caacagagct 8940 gggatttgaa tcctcatgtt ggtgcctgca ttcttaacca ctatgataac aggctaagaa 9000 agcttaaaat tatagatgct aagtaactta cctaagatct ttttaaacat ttaaaaagtt 9060 ttttttttcc tttgttagta ggcaaggaac taagatcata gtgcagtgct aagactagaa 9120 cccaagtatt ttcaaaggct acgctcggct gggcgtggtg gctcatgcct ataataccag 9180 cactttggga ggctgaggtg ggtggatcac gaggtcagga gtttgagatc agcctggcca 9240 acatggtgaa accccatctc tactaaaaat acaaaaaata gctgggcgtg gtggcgggtg 9300 cctgtaatcc cagttattcg ggaggctgag gcaagagaat ctcgcttgaa cctgggaggc 9360 ggaggttgca gtgagccaag atcgcaccac tgcactccag tctgggcgac agagcgagac 9420 tctgtctcaa aaacaaaaac aaaaacaaaa aaaaacccca aagcctacgc tcataaatta 9480 tttggtatac tgcttctcct actttaaaag tcagtactaa gctcatactg ggtgttaata 9540 cattttaaaa ctgcaaatcc agtttactga aattggagaa tatcagatcc ccttccaaga 9600 gaggcataat tgtagcttac tgggtgaatt caccttttat attgacagtc tagccttatg 9660 aaccaattaa gtttgtagtt tctgcattct tcctgtgaca ctgaagactg ttttcatcaa 9720 tgtgaaaacc atgttatcta agctaaatca aaatccactc tcattcagaa tttattcttc 9780 cttttatttc tcaacaccag tgacatgttc ccaagttctc tgcctttgtg gctccttagt 9840 ttccagtgtg gaatgtctta tttctgaaag caacctgtga ttgacaagcc ttcttggcta 9900 ttctgtagtt taccctaaaa aaaatctgtt ctctctgtcg gctcattaga ctgcttttcc 9960 ttacatggta ctctgctttt cccctttatt tcaagcattt attaaaacta aactatgtac 10020 caagcataca caaaatggat ataacctaac tctttgaagg ctacacttca aagaaacagc 10080 cttggtgttt acatattttg actagaatat tatttcccta acaagctgca taaaaccatt 10140 cctgctcagt ttgtaattat acaccaaaat attgagcaca atttcagtag ctacttctac 10200 agcacatcat ataaagtgaa ttgctggagc caactcatta ggtcttattc caaagatttt 10260 taccaacact ttggccctct tttgctgaca aaaaaggatt cttaagcctt ttaacagctt 10320 tataacttcc ttattagagt tcactcacta acatatcctg ttaacaaaat gaagtgccca 10380 tccttcttgg gaaacactct ggagaatatt tcctgatttc atcgcacagc tttgtctctg 10440 gattagtaat catctaatac gaaactgagg atatgagtat tatgtttcac aatgttgtct 10500 tcaaggatat aaacaactca aaatttaagt atttgagtag cactgtatca cattattatt 10560 gccgtgatat tttcagaaga aatctgaagt ctgcgctaac tacaggccat aaaatatggc 10620 catcttgccc caataaatgg agcaaagttc aaatctggat catcagaaaa agacaagagg 10680 cacatttcta aaccaaatct gattgccttg aggaaggaag gtactgaacc tgttagagta 10740 catctctgaa ggactgagaa tcaagtcctt cattccctcg ccccctaaaa aaatccaatc 10800 aatcatgctg ataaatgtct tagttacagg ggagaaaaaa tagacatgac taagctgaaa 10860 aaaatcttct ggctttgtat cttttctagg cagtgctgtt cctgataaga cacatgacac 10920 aaaatatggt tttgctgagt atcaaggtaa gttagggaaa atagtatttt ttaaatagga 10980 aaattagatg acaacagcaa caggtaaaga agccttgggc ttctgaggta gaaatactag 11040 catccctaca taggcatggt agataatctg aaactagtac aagtgctggc ctgttatagc 11100 ctgtctctac cgtaatcaga gggaaaagta ttacaatcca gcaaaagtag cccttcaaaa 11160 tctaaggagg agcatttcat cagatatcaa taaatgaacc ctcgctgcat acaaaggcaa 11220 tacattacgt gctgagtgac caacttcaaa gaaccttctg ctgttctgaa atttaaaact 11280 actctcattt cctcaagcct gtattttatg taatgaaaca aaatgcacat catatgtctc 11340 ctgctgcact gtaagagtaa acataggacc cctcccacca aaaattgtgc aaagagccct 11400 tccccttcag ctttttgcta tagaaatatc ctactacttc cctgaaaata gtatatgctt 11460 tctttggcaa gtggaatatc accctgttac tctctccctt actctgcttc actttttttc 11520 gcataacgct taagattacc taatatttta catgtttatc atgtctctcc caattagaat 11580 ataagcttca tgagggcaga gatttcaaat attttgttca cagatgtatt cccagtatct 11640 acaactatat ttagcatgta gcagattctc aaaaatattt gtaaaattaa taaaatttaa 11700 aaatccctat tatattggaa ttgttaaatt aaaaaaaaat tttggccagg cgcagtggct 11760 cacacctata atcccagcac cttaggaggc caagacaggc ggattacgag gtcaggagat 11820 cgagaccatc ctggctaaca cagtgaaacc ccgtctctac taaacaaaat acaaaaaatt 11880 agccgggcgt ggtggcgggc gcctgtagtc ccagctactc gggaggctga ggcagaatgg 11940 cgtgaaccca ggaggcggag cttgcagcga gccgagatgg cgccactgca ttccagcctg 12000 ggcaacagag caagactctg tctcaaaaaa aataaatttt ttttttaaga cagggtctct 12060 ctttgttgcc caagctggag tgcagtggca tgatcacagg tcactgcagc ctccaactcc 12120 tgaactcaaa tgatcctccc acctcagtag gtgggactac agatgagtgc caccacacct 12180 acctattttt ttttttttgt agagatgagg gtcttattat gttgcccagg ctggtctcaa 12240 actcctgggc tcatcctccc accttggcct cccaagtgct gggatttaca agtgtgagcc 12300 actatacctg gccaaatttt aaaatgctac cgtatctgtg tatgaatatg tgtgaataaa 12360 tttacagact ctagggtgta attcacaggg tagaccaagt caagagtcag aggatcagaa 12420 gcttgggtgg ggagatagga gagtgattgc aaaaacaaag caatctatct tattaaatgg 12480 acgaaaggga tcaaacatta tcagtaaact attttaaaga gtgaattaaa tgtatctctc 12540 tatcctttct atgagtgtag tgaattcaga ttcacctcag attagttgaa ttgacactag 12600 ttttcttccc tgataaagct tttaaaattt atttagtaaa gtggccaggc atggtggctc 12660 acacctgtaa tcccagaact ttgggaggcc aaggtgggtg gatcacctga ggtcaggagt 12720 ttgagaccag cctggccaac atggtgaaac cccatctcta ctaaaaaaat acaaaaaaaa 12780 atttagccag gcgtggtggc gcacaccttt aatcccagct acttgggagg ctgaggcagg 12840 agaattgctt gaacctggga ggtggaggtt gcagtaagcc gagatggtgc cactgcactc 12900 cagcctggga gacagagact ctgtcccccc cacccaaaaa aaaattagtt gttttcctcc 12960 ttaaattaca gcctgcaaga ttgaaacaga gtttccccat ttctattttg ggatctgact 13020 gagtcacaag gtagtcttga cgaatcactc tgctctatct ctcagtttac tgaggctgcc 13080 tgggaacttg agctgtcagc caaacaggaa gaagggccct tctgcctact ccaaaaggcc 13140 tcagtcaaat ggatatggtg agatttaatg atggatataa attacagcaa atggatttcc 13200 tatagggtga gggaaaaaaa aaaaagcaaa cattttactt aaattcctct atacaattta 13260 gggctggcag aaagggtaga ctattacaat gtagctgagc aaatttttcc atgtttgcat 13320 aacatgtgtt ttcaactaaa gatactcctt ctatagtcct actatataca acaccccaaa 13380 aaacctcaaa tgtaagaaaa agcaatgtga cagatttgac cctggccaag ttacactgtt 13440 tttttttttt tttttttttt tttttttttt taagtgtcag tgttcataaa ggcccttttt 13500 ctttttcaag gatgggtata aagtgttact cggccgaacg cggtggctca cacctgtaat 13560 tccaacactt tgggaggccg aggcaggtgg attacgaggt caggagttca agaccagtct 13620 ggccaacaca gtgaaacccc cgtctctatt aaaaatacaa aaaattagct gggttgtggt 13680 ggtgtgcccc tgtcacaagg tagtcttgac gaatcactct gctctctctc tcagtttact 13740 gaggctgcct gggagctgtc agccaaacag gaagaagggc ccttctgcct aactccaaaa 13800 ggcctaagtc aaatggatat ggtgagattt aatgatggat ataaattaca gcaaatggat 13860 ttcctataga gtgagggaaa aaaaaaatcc agctactccg gagactgagg cagaattgcg 13920 agaacccggc aggtggttgc agtgagccga gattgtgcca ttgcactcca gcccgggcga 13980 cagtgtgaaa ctctgtctca aaaagaaaag aaaagaaaaa aaaaaaaact attactccac 14040 tccccaccag aaactcttat tttttccccc ctatgtggtc atgaattcct cctgggtgca 14100 tagctcccta agttgttctg tgttttagtg cttataattt cccacatccc atgatgcccc 14160 ttgatagaat tattttttct

gtactcacac aaatggaaac agaagagatg aaaaaccctg 14220 gggatgcggc ctcgcaggtc tcaaactgat cggctgctaa gcacaacctg catatctctt 14280 ggctgagttc ctttcttggc tcagttagat tttgcatgac ctaggaggct taggacccag 14340 ggggcgcctt tcagctgaaa aacagctcgc gctgcagcaa gctagctggg aagctcccag 14400 ttctaaagag aggctgttta ccagaacagc ataacaaggg caggtctgac tgcaaggctg 14460 ggactgggag gcagagccgc cgccaagggg gcctcggtta aacactggtc gttcaatcac 14520 ctgcaagacg aaggaggcaa ggatgctgtt ggcctgggta caagcattcc tcgtcagcaa 14580 catgctccta gcagaagcct atggatctgg aggtgagatt acaatctttc ctttccgcag 14640 caacttcatg aaacagaagg ggtaaagccc cctatttccc aaacagggcc aggatgacag 14700 gaaacgaagc gtttagccgg tttctgttgt cccgtgaaag cttttccacc cctcctttcc 14760 ttgtcagggg cttgcagctc catctttgcc attaagaaca aaggcaagaa gccactttct 14820 ctctgccttt ccttgctcat gagtggatgg agcttggggg ttcatctccc ctactcccca 14880 agtcctgttc tttctaagcc ctttgcatgg tgtggtcctc cttccccagc ctccttctgt 14940 ggttctcctg cagaggggag tgggagcttg gagtctcatc cagtcagcga tgaggccggt 15000 ttcctccgtt tgaggctgtc ttgaatcttt tgcctgacgg agtcaaggct cctggagaat 15060 tctcctggga gggagtattt gccttttaaa cgggcagaag gtggccgtat ccgtgaagga 15120 ggaaacaccg gagtttatgt aacgtggcca ttacaacaca gggacaaatg tcacgtctgg 15180 gcgccccccg tcccaaaact cccagctcct caaagggacc ctaagccagg cctcctcctc 15240 tccatctcct cctccaaagt ggtcacaagt tcaagagtaa caacgctttg cacttctgca 15300 gcgctttcca ggtttcaaaa ataaataaaa cctaacagtc tctgagcgtt gactggggga 15360 caggcacagg ctgggggctt cacaccctga ggtgtgcgtg gagttggggg gggggggtgc 15420 gtggggcgtg ggggtgttgc cacgagagga gagggaggcc cagcagggcc cggggtcccc 15480 taaccaggct gaggttcagc ccgggtggtc ccggctcccc tgtccgccac gctgggcgtc 15540 ttccgttcgc tgcccgctat tctgtgtccg ggggcttctt ttcctcacag gctgtttctg 15600 ggacaacggc cacctgtacc gggaggacca gacctccccc gcgccgggcc tccgctgcct 15660 caactggctg gacgcgcaga gcgggctggc ctcggccccc gtgtcgggta agtgtcctcc 15720 gggggacggc cccggggctg gcgggcggcg gccgcgttcc cggtgccagc cccggcacac 15780 atttccttct ctcctctctt aggggccggc aatcacagtt actgccgaaa cccggacgag 15840 gacccgcgcg ggccctggtg ctacgtcagt ggcgaggccg gcgtccctga gaaacggcct 15900 tgcgaggacc tgcgctgtcc aggtacctgc ccgggacccc gggaatcccc gctcctggcg 15960 ctgacaggaa gcggctgaga cactcgtggc gcacgtgcgg ccgcgcgatg ccggccggcc 16020 ccgctccgcc tccgcgccgt ccgattggcc agggctgtct ccaggccgcg gggctcaaag 16080 cctattggcc gccgccgcca ctcgtatgag ctcatccgcc gcgagcgctt gtaaacaact 16140 gcgcggggcg aggctggggt gaggctaggt ctctccgccg cgcgtcctga ggagtggctt 16200 ttggcccctc agcgtttatt gaccgtttgc ggagcgtctg cagtgtgcta gacccacact 16260 gctcacaacc ccagctcccc aacctcccct gacacacacc gcgggaagaa gtcgtttgag 16320 gcatctgagc ttcagagaag ttaagcgatt taccaaaggc aatggcaggg gacagatttg 16380 aattcacgtt tcttagattc cagagcgcag gctttttgct cccaaagcag caagagagtt 16440 ttctaggttt aaatgggata atcaaaataa agcatttatt ttttattttt tattttttga 16500 gacggagtct cgttctgtca cccaggctgg agtgcagtgg cgcaatttcg gctcactgca 16560 acttccgcct tccgcgttac agtgattctc ctgcctcagc cgcttgagta gctgggataa 16620 caggcgtgca ccaccacgcc cagctaattt ttgtattttt agtagagacg gggtttcacc 16680 atgttggccg ggctgctctc taactcctga cctcaggtga tccgaccgtc tggcctccca 16740 aagtgctggg attacaggcg tgagccaccg ctcccggcac aaagtaaaac attttaccta 16800 aggactggca cagagcgtac gcttagatgt gagctgctca aaggaagcat gggttgtttc 16860 ctgaagtaga agtgggggga atcccctgca gaagaacgca accgagaggg gccttgggaa 16920 atagcaagga tttggacaga taaagacgtg ggaggtagga gagaagccct tccctacggc 16980 cttcctctct catttgcctt gtccctgaga tggttcagcc ctctcaggcc tgatcttacc 17040 tctggggcag aatttgactt tgggttgtgt gtggggggaa attcttaggt gacccacctt 17100 catctaccct aacactcagg ccaggttcag ctgtggaatt cactcagggc agtccctgat 17160 gagagctgtt tcccacctca tctccagaga ccacctccca ggccctgcca gccttcacga 17220 cagaaatcca ggaagcgtct gaagggccag gtgcagatga ggtgcaggtg ttcgctcctg 17280 ccaacgccct gcccgctcgg agtgaggcgg cagctgtgca gccagtgatt gggatcagcc 17340 agcgggtgcg gatgaactcc aaggagaaaa aggacctggg aactctgggt atgacggtcc 17400 cccacccctg ccctcgttgg gattcatcaa gagatgtcat ttgctgattg tctagggtgt 17460 ggctaatggg accttgtgtc ctatccttgg caggctacgt gctgggcatt accatgatgg 17520 tgatcatcat tgccatcgga gctggcatca tcttgggcta ctcctacaag aggtcagtag 17580 cttctcttct gggccctctt aggaggaggg gaggaaggta cacaaagtca aactttgtgg 17640 ctttcttacc caaaaggaag caagatgttg aaaatcagct caagatgtag agacttggtc 17700 ctagtcttta tctgctgacc ttggacaaac cctttccttt ggtgccttta cacctcactt 17760 aaaagccttg tgagggatgt tcttgttccg cattttacaa atgaagaagc ctctgtcaga 17820 gacttgctca aagtcacata gcctaggagt ggcagaacct ggattcagac ccagctcttt 17880 tgatagcaaa ttccctgctg tctgatccca catgcctggc attgaagtga gtggcactgc 17940 agaaatcagg cttgacactg attgcaggga ccttaagacc aaattctttc tgtgagttat 18000 aaaattctgc tactagaaaa ggtttccagc cactgttgca gttgaggctt aaatttcctg 18060 agctataagc agtgggatct cctctgctag ggaagaaaaa agtgagttgg agaacagaaa 18120 gtctgtttgc cactcttcac cacgtgtgag aaagccaaag aggctacttg tgaaactcaa 18180 ggacatgacc tgtggctggg acagcaggag aagaatgctt attttgaaag gtcccacgag 18240 atgtccgtca gtgactggtg catgatggta agccagactg gcattcatct ttacagcact 18300 ggctgattgt ggaaaattat ttgccattct tgggcaaaat cgggggattt gacttctagc 18360 cctgggtgtc tgtaatattc tcctctgtgg tctgagaaaa cttcctgtga ggaaagtgac 18420 acagtagcct gcatttttcc ttcctttcct ccctccctcc ctcccttcct tccttcccct 18480 ttctttcctt cctttctttg attttttttt ttcagggtct cgctctattg cctaggcttg 18540 agtgcagtgg tgcgatcacg gctcactgca gcctcaacct cccagggcgc aagtaattac 18600 ccccacccac ccccactgag tagctgggac tacaggcatg tcccaccatg cctggctgat 18660 ttttaatttt tttatagaga cagggtctca ctgtgttgcc caggctagtc tcaaactcct 18720 gggctcaagc agtcctccta cctcagcctc ccaaagtgta taggcatgaa ccaccatgcc 18780 tggcatgcag cctgcatttt ccagtgatga gggccatgtc tgagcccaca gcctcagtgg 18840 atcacccagc agggcatctt taaaggcctt gtagtcaacc tcctcattac agatgaaaaa 18900 ggggaagttt gggtataata ataacagcag tagcaaacat gtaccgtatg ccagacactg 18960 cttgaagcac atgctttaac tcataatcac ccttatgagg taaatgctgt catctccaat 19020 ttacagatga ggaaactgag gcaagagggg attatatacg ttacctgagg ttacacacct 19080 agcatttggt ggagagaagt cctttaacta gctatctctg tgaccctggg caaattgctt 19140 caatttccta ctccacatca tggtgtggag ctatggcttt tgactactta gctcagggtg 19200 tggcacatag taggtggtca gtaaatgatg gctgtttttc ttttctataa aatgtgtggc 19260 tgggcgtggt ggctcacacc tgtaatccta gcactttggg aggccgaggc gggcagatca 19320 tgaggtcagg agttcgagac cagcctggcc aacatagtga aatcctgtct ctactaaaaa 19380 tacaaaaaat tagccaggcg tggtggcggg cacttgtaat cccggctact tgggaggctg 19440 aggcaggaga atcgcttgaa cctgggaggc tgaggttgca gtgagccgag attgtgccac 19500 tgcactccag cctgggcgac agagccatac tccgtctcaa aaaaaaaaaa aaaaaaatgt 19560 aggtaatgga ccaggcgtag tggctcacac ctgtaatcct agcactttgg gaggcagagg 19620 tgggtggatc gcttgagccc aagagttcga gaccagcatg ggcaacatgg caaaaccctg 19680 tctctacaaa aaaatacaaa aattagccag gcatggtggt gggcgcctgt agtcctagtt 19740 actaaggagg ctgagatggg aggatcacct gagcctggga agtcgctatg gtgagccatg 19800 attgtgccac tgcactccag cctgggtgac agagtgagat gctgtctcaa aaaaaaaaaa 19860 aaaaaaaaaa aagtgggtaa tggactagta ctctctgatt tcttatgatg caggaagcag 19920 aggtccagag agggaaagta ttgacttgag aggacatcct gacgcccagt ctgaggttgt 19980 ttcccacaat gggatgcttg acatgcaggt ccagggacac ctgcttgttc atttcagagt 20040 taatgacata gtggccctgg ccttacaatt cataagcaga cctaagccac attggctgag 20100 tttagtcctt gaactatctc ctttttcctc agccacccaa cagcatttgg ctgtcctgca 20160 atcctgtgac agtttccagg ccttccaggt gcttgaactg actaaacatt cttaattctg 20220 agctcagttc tggtgtccag tggaagtctt ttttcttcta gatttgttcc tctaggctgt 20280 cacgagactg ccctgaggcc taaaatttat tttcctgtaa actcagggca aggcacccag 20340 tcatcagact ccccgtcact aacgaccaga tcaccccttt cttcagcaga actgctctga 20400 gaacagactg tacaacagga aaccgcatgt gggcttaaaa acaagcttgc agccttcatc 20460 tcttcctaaa gtcagagagc agagtgtcct gaaaagagct gtaggttgag tgtgggttca 20520 ggtgccctct gagccttggt atcttgtctg ttaaatgggg atatatcctc cctccacatc 20580 tacccatcta agattataag tattaaatgt aaacagaaac aatagcacac caatcaggta 20640 ataatcacaa tagcagccaa catttatttc atgctttctt aataagtaag gccctactgt 20700 atgctcttcc ctgattatct ttttttctta attttttttt ttttgagaca gagtctcgct 20760 gtgtcggctc actgcaaccg ccgcctcctg ggttcaagtg attctcctgc ctcagcctcc 20820 cgagtagctg ggattagagg cacccgccac catgtcctgc taatttttgt atttttagta 20880 gagacggggt ttcaccatgt tggccaggct ggtcttgaac ttctaacctc aggcaatcca 20940 cccgcctcgg cctcccaaag tgttgggatt ataggcatga gccactgcac ccagcctcct 21000 gattaccttg actaagcctc acaaccacac taggagcact gttagatttt acagtgagga 21060 gctgagacct agcagagtta agtacaatgg ccaggctaca cagctagtaa tgtatgtctg 21120 aggagtatta gtatctccag caagtccagt gaggccaagt agcctcatgt aaatttgctt 21180 tgaattgcaa aggaaagtag gaaaaataga aatttaaaaa aaggctgggt ttaaagtcag 21240 aagaaacaag atctagttct ggaactttca cctattctgg atgtgacact ggacaagtta 21300 tttaccttct ctggacctca atttcttcat ctgtactgta agggggttag atatggtgat 21360 actcccaact ctatttccta aaaagacaat attgccggtg ctaagactgg gttcaaatcc 21420 cagctctgcc atttgcttga acaaatagtg taacttctct gcatctgcct tcctatctat 21480 gaaacagatc aaaatagata ccacataggt tgtgaggatg aaattggaca gtatagttta 21540 ggcatacaat tggtgttcta tagcctggga gaggaagttg gaggcagcat acagtagggc 21600 cttacttatt aagaaagcag gaaataaatg ttggctgctc ttgtgattat tacctgtagc 21660 tgccttggga acttttcctg agcagcagtg tggcacagca ctgcctctga ctgggaaaat 21720 agcagcggct cagagtaata attgaagacg acctgtgtag tctgaatgag gtctgtggtg 21780 cttccatact ctgggagagg aagttggagg taggcagcag cttcctctac acctgctctc 21840 tctggccagc tcagctccca gtcccaccct ggccttggag caagcagtca gggtaggtac 21900 tgtaagcctt gagctctgcc aaaggccatg aggcttgcct aatgggatgg agcttttccc 21960 tggctgggat gggtgggcag gcaccaggct tcctcttagg gagggagggc tgtaaatggg 22020 ggtgggtggg agctcagcct ggccgggtct ttgtcctggt agtctaggcc acgaggttca 22080 aatggccagt ctgtgactga ggagctaagt gtactgtctg cactagcttc agagggaggt 22140 cttattttct gataaaaagg ggagggaaaa actgtaagtc aacaccactc cactccctta 22200 ggagaggaac taagtcagtg aacaagcctt ttgttctttc ttggctgcca cacaacaccc 22260 aggctaacca ccccctaccc ccaagcagtg agaaggggct aggctgcctg atggtcagtg 22320 tagcaggcct agtggcctct caaaggtcac ccaagggagc tgggagcagc cactgcatct 22380 ctaggactca caggcaccat taacagcagg cacatgggat tgagtgtgct tccaggcttc 22440 caaatggatg agactaatcc agactagtgc cagcatctgc tttctttacc cttgactgct 22500 cttccagccc tgctctgcct cattaataca aattgatttt tttcccctaa agacttgtat 22560 atgatgcagc ctggccatta gcagcagctc agctggccac aggtaaagga ggttgctgag 22620 gaaagcaagg cgcggaagtt aaactcaaaa gcctcagttt cttcatctat aaaacaggga 22680 ttaggctggg tgtggtggct cacgcctgta atcccagcac tttgggatgc tgaggcgggt 22740 ggatcacctg agatcgggag ttcgagacca gcctgaccac catggagaaa ccccatctct 22800 actaaaaata caaaatactc tgggcgtggt ggcgcatgcc tgtaatcctg gctacttggg 22860 aggctgaggc aggagaatcg cttgaacctg agaggcagag gttgcagtga gccgagattg 22920 tgccattgta ctccagcctg ggcaaaaagc acgaaactcc atctccaaaa aaaaaagcct 22980 gtagctgaca tttagtagat gcttattaaa agtaataagc atctctggga ggctgtctca 23040 cagcaggatg atcaggtcag ttttctggac aactttatgg gttaggtccg aagttcagat 23100 agttctctgg gtctctgggg ctgaaagaac aaaactgtgt cttgctttaa gagtctctat 23160 ctggccaggt gcagtggctc acgcctgtaa tcccagtact ttggggggtg ggaggatcgc 23220 ttgagcccag tagtttgaga ccagcctagg caacatgttg agaccctgtc tcaaccataa 23280 aaaaaaaaaa aaagtctctg tcctttactt tattttcatt gagccccggt gaagctgtat 23340 gaagtccata ctgctgtcac cctattttac agatggagaa cctaagacca gaggtgcagg 23400 agcttcttgt tgagtttaac gccgtcttgc agaatggata tcctagaatc ctggacctga 23460 gtttgggtcc tggctcagcc actgatttgt tgtgacaatg gcaagctgct gctcttgctg 23520 agcctcaggg atgctatcta atgagcaaag ctatgcagga ggcatagcct gaatgtttgt 23580 ttgttttttt cctgccaggg ggaaggattt gaaagaacag catgatcaga aagtatgtga 23640 gagggagatg cagcgaatca ctctgccctt gtctgccttc accaacccca cctgtgagat 23700 tgtggatgag aagactgtcg tggtccacac cagccagact ccagttgacc ctcaggaggg 23760 caccaccccc cttatgggcc aggccgggac tcctggggcc tgagcccccc cagtgggcag 23820 gagcccatgc agacactggt gcaggacagc ccaccctcct acagctagga ggaactacca 23880 ctttgtgttc tggttaaaac cctaccactc ccccgctttt ttggcgaatc ctagtaagag 23940 tgacagaagc aggtggccct gtgggctgag ggtaaggctg ggtagggtcc taacagtgct 24000 ccttgtccat cccttggagc agattttgtc tgtggatgga gacagtggca gctcccacag 24060 tgatgctgct gctaagggct tccaaacatt gcctgcaccc ctggaactga accagggata 24120 gacggggagc tcccccaggc tcctctgtgc tttactaaga tggcctcagt ctccactgtg 24180 ggcttgagtg gcatacactg ttattcatgg ttaaggtaaa gcaggtcaag ggatggcatt 24240 gaaaaaatat atttagtttt taaaatattt gggatggaac tccctactga cctctgagaa 24300 ctggaaacga gtttgtacag aagtcagaac tttgggttgg gaatgagatc taggttgtgg 24360 ctgctggtat gcttcagctt gctggcaatg atgtgccttg acaaccgtgg gccaggcctg 24420 ggcccaggga ctcttcctgt ttcataagga aaggaagaat tgcactgagc attccactta 24480 ggaagaggat agagaaggat ctgctccgcc tttggccaca ggagcagagg cagacctggg 24540 atgccccagt ttctcttcag ggatggatag tgacctgtct tcattttgca caggtaagag 24600 agtagttagc taacctatgg gaattatact gtggggcctt gtgagctgct tctaagaggc 24660 taacctggaa actaagctca gaggcaaggt aataaagcac ttcagggctt gctccccaag 24720 tgggcctgat ttagcaggtg gtcctgcggg cgtccaggtc agcaccttcc tgtagggcac 24780 tggggctagg gtcacagccc ctaactcata aagcaatcaa agaaccatta gaaagggctc 24840 attaagcctt ttggacacag gaccccagag aggaaaaagt gacttgccca aggtcgtaag 24900 caagctactg gcatggcaag agcccagctt cctgacggag cgcaacattt ctccactgca 24960 ctgtgctagc agctcagcag ggcctctaac ctgtgatgtc acactcaaga ggccttggca 25020 gctcctagcc atagagcttc ctttccagaa cccttccact gcccaatgtg gagacgggtt 25080 agtggggctt tctatggagc catctgcttt ggggacctag acctcaggtg gtctcttggt 25140 gttagtgatg ctggagaaga gaatattact ggtttctact tttctataaa ggcatttctc 25200 tatatacatg ttttatatac ctcattctga cacctgcata tagtgtggga aattgctctg 25260 catttgactt aattaaaaaa aaaaaaagac tccacattgc caagtttttg aggggtaaca 25320 ggaaccctcc gtgtaagttg agaagctttg ggttaccttg tcaacaccta tgtggcaagc 25380 tctgggcctt ttcttcattc atcctcgccc tgttactgga aagtgacaac tgcagcctgt 25440 gtccagattt ttttttttga gatggagttt ggctcttgtt gcacaggctg gagtgcaatg 25500 gcatgatctc gcctcactgc aacctctgcc ttgtgggttc aagcgattct cctgcctcag 25560 cctccagagt agctgggatt acaggtatgt gccaccacac ctggctaatt tttgtatttt 25620 tagtagagac ggggtttcac catgttggtc aggctgttct caaactcttg atctcaggtg 25680 atccacctgc tgaggcctcc caaagtgctg agattacagg ctagagccac cgtgcccggc 25740 ttgtgtgtcc agattatcat catcaggaat ctttcaggtt gaagcaggaa agacaggtgt 25800 gcaggcgtcc caacaaggtg gttggtcatt gcaaatcctc tccccttcag caattgtttc 25860 caaggtggag gtagttaaaa tgaatatcta gacagccctt gttaaaggct ggagtgcggc 25920 aggggttggg tggtgggtga cgggggtggt gctgcagcag ccaaaggggg aataactgca 25980 gaggaggaag ggtcactggg ctgcctgcag cagccctggg ctgaggaagt tccctgcaag 26040 gtgactacta tgactccaga agaaaagata ccaacaggag tgtctcctgg acttttagca 26100 agggatttca gccacaggtt atcagcctca ggaacaccca gatgacctct gcccatgccc 26160 agccattgct ctgtggttct gccagcaatg cgtactccag atcatcagtt tttttcggga 26220 accatattct gtccttaagt tggattcttc aagctttgag agtgcctggg agaaaacacc 26280 tttgggttta cagatttata ttgtgcccaa ggccccacta accagatagc attgtccttc 26340 ccaatggtca ctcttctacg acatccccca catgcagaag caagaagaaa ctggtcttct 26400 cctctcaagc acttgtaaag aaacacaagg ggtggggtga cttgcattca tttcttccca 26460 ttgcaaaggt ggcacccagc actgaggaaa gcaagccagg atacccaggc tatggaagta 26520 ttcatataga gaggatgaaa gggtagggct cctaaggaat gactcagctg gcatgtgaga 26580 gccaggccag gaaaaggtca tagtcagtca cacctgctgc aaggaagggg ctgcctcagg 26640 tgggatgtac atattctcta gagcagatgg gtgtctgctt gagggtttta gacttgggtg 26700 catgaaaact ctctgctatg gggagtttgt gtgggctagg ccagaaggtg gctagcagac 26760 cctctacatt tatgtccctg agccaatcat gttttcactc tccatattgc cagttatgtt 26820 aactgcttaa tttatttagt ctgatcaatg gcccagttca ggcccaccac tcctacactt 26880 gctggggaca gccaggaaac aaccagccac acaatgctga actgtgctgc tgctgggagt 26940 ccagggctca gccctaaagc aagcttgcaa acttcacaca taagtacagt ctatatagca 27000 agtaaactct gaccagagat gacatctggt cccacaactc atcaggtcta tgtacaatat 27060 ttcacatacc acccaataga taagataata ttaacagcaa ccactctcct ttatcaattc 27120 cccctgctcc aatacaacca ccacacattg cattaatacc ccaaacccat tcccaattta 27180 ttaaatatgg tgcaagctca tagacactta gaagaggcaa atctagttgt gatgaagagt 27240 tcctagagct ctgggagcca agatggaggt tttccagtac ctgcacatgt ggctcaggag 27300 gatgctgccc aggagctaat gagttgggag agcaaacatg ggaggtagaa gtcagatggc 27360 ccagctcagg gagctatctc tctcagcatc tcagctttga gactctgcca ccacctcttc 27420 ccagcccaag ctgctgccta aaccaggcat gttgaagggt gagcagtggt tgccatgaag 27480 ccaagaccaa gagattgctg agactcccac tcccctccct cagactctag gcctgtgaca 27540 agccacactg tcctccagaa cccatcgagc tttaggcaaa atgttttagg catctgacta 27600 aggagcccac ccgagtatga gtaacagaag ccaagatctg agctttctag agggcagggc 27660 ctctttctag tcccccagcc tcttcctttg cttgtgactg tttgtttcag acagaaagga 27720 tgttgtccgt aagttctcag ccagtctcca gtattaagtt tgaaaacatg aggtggaggc 27780 ttcctctcac attgatgtgg tccctgggct ggctagagcc agtgagcagg taaacagaag 27840 ccagcccttt ctctaactcc tggcctgttc caccacatat taagggactc ttcaaaacct 27900 actccctcaa ccttgctcca ggaaggacag gatctggagt agaaaggggg agcatcactg 27960 actttttcac accctttgag ccatcagtct ttctttcgtc cacacacttg aagtcctcct 28020 gcacccagct ggactagtga cttcagagtt cacaggcagg ttcaccctgg gatcctgccc 28080 agcaggtcca ggtcacgctg attagtgtaa gcaagagcct cccacaatcc actgccaggg 28140 agttcctggg tggattcgag taacagattc ctcctggccc aaaggccagg ggtttttttc 28200 ttcttcacag ctttcaggca agtattggat ttacagacag taactaggcc ccagaacctg 28260 tggagataca tttccctggt gctgcgccca cttgcctcct ggggaggtaa taggaatggc 28320 ttgttctgct tctaaacatt ccgccaatcc acaggaagcc cggacggccc tgctcacagc 28380 aggaatgggg cacagagggg caatgctggc tgtagaacac ccccctgcag ggggctgggc 28440 cagggctagg gaggtgagtc ccgggtcagg ccgtactgca tgctcacagt gtggtccaac 28500 tcctccagct ctgcaggcag cgggatgccc agctccccca ggtacaggga gagggcctca 28560 aaggagtcct ccaatttcga gaatgctggt ctagaaggaa aagaggtaaa ttagaggcag 28620 gtggaacatg agcagggcca tggggtgggt ggaagggatc taggctcagc tacttcctgg 28680 ttgtataacg tcaggcaaac tccttcacct agtagtgcct ctgtgagaaa tgggcataat 28740 gttaccggta cctcatatat ttgctataaa gattaggtaa cactataaca aggctggact 28800 agctggagtt aatacttaaa aacaatagga gaaaaacttc cctcccatat cttagagaaa 28860 atgcagttat caaaggtgga atcggaaaca ccaggctcct agtgccacgg aaatggcttg 28920 gctgccccgg aagcctaaga cagctcaggc ttactcctcc tcctccatgt ttatgcttaa 28980 atgtcatgtc acctcagtga ggcctgctct gacgaccata tttaaaattg caactggtac 29040 cctgaacaat cgtctttact tgtcttgact ctttttccat agcatctgcc acattctaat 29100 attcaatata gtttacttat tgtatctact gtatgataca gtagatacca tgctagaatc 29160 tatgttctat gagggtaagc acctttattt tgttcgctgc tgtaacccaa gtgtttagaa 29220 ctgtacctag cacacagtag

gcattcaata ctgtatatat atatttttta ataaattaaa 29280 gatatttaga atgacaagag gtattagaaa acaaatactg tgtagcttca caatttctcc 29340 tcaagctttt acactggtgt tactgaagga ctgcggtcct tggcctataa aggaacaagg 29400 tatagattct cccaccagaa aatttcaact ctaatgtgga ccgctggaaa tcattttttt 29460 tttttttttt gagctgcacc aaaggcgtac cctacctcgc tttattaaag ggcccgtgcc 29520 gcagagtcaa tataaaaaca caaagtccca tcagtttaat aacaataaaa aaatccaaaa 29580 gtggaaaact gagggggcag gggaagagac ccctgggcca ggggcacgag gagccctgct 29640 catggaacca ggcctggccg cagggtcccc cggtattgct gttgctacga ggtcgggggg 29700 tagcgattgt cctatgggag ccaccgttcg cctgggtcgg ggaccctcac ttcttctggg 29760 gtgtgctcag cttctgcatg gcccggatct tgtccagcag gccagagatg aaggcctctg 29820 tgggtttgta acagtcaacc agcagctcct tgaccctgga agcccaggca tcgtcactct 29880 ccatgtccag gagctcatcc acgtcaatct ctagttctga gatctcctct tcctggcagt 29940 cgtagaggcg cgtgagctgc tccaggatcc actcctctag gttgaggtgc ttccgtagct 30000 ccttggggtc atacttgatg gtgaccttcc cttggcgcct cactgggccc tcatcatccg 30060 cgcagcccgg gccctctcct gcggccccgg ggggggctct gaaagtagat gcgtggtcct 30120 tggccgccac tgcctggcct gggggccggg gccggggccg ccaacgccgc gccccccgcg 30180 gtgccgctgt ccgccacggc ggcctccggg gccacgtgcg cgcgtggggc ccctccttgt 30240 gccgccgcct ccgtgacgcc cgccggctgg ctcaggttag ctcgccggct ccgcggcgag 30300 ggcggcggcg ggggcgcccg ggggcagctg cagcatgcgg agcccccggg cctggcctgg 30360 tcgcgccccg ccccctcccc gccgatccgc ccgccctttg tcccctgcgg ccgccgccgg 30420 ggctgccgcc gccgaagcgc tttctctatc cggaaaccat ttttaaataa agattatgtc 30480 ccaactggtt atcctgggag ggtggagttg ggggtgagga gaatgttgag ggatatattg 30540 gttaagggag attacagaag acgtatttcc tgtgctataa actttggtaa tgtttgaact 30600 tgtttttaaa agaaacatga tttttgatgg caggaaaaga accccatttt tgagacagag 30660 tttcactctt gttgccgagg ctggagtgca atggcgtgat atcggctcac tgcaacctcc 30720 gcccctgggt tcaagcaatt ctcctgcctc agcctcccaa gtagctgggg ttacaggcac 30780 ctgccaccat gcctggctaa gttttgtatt tttagtagag atggggtttc accatgttgg 30840 ccaggctggt ctcgaactcc agacctcagg tgatccacca gcctcagcct cccaaagtgc 30900 tgggattaca ggtgtgagcc atcgcgccca gccagattct cgttttttaa ccacacactt 30960 gaaaagacct agggtaactt tggtaataat gaaattatta cctgagaaga ataaaggtaa 31020 ttttgaaaat acttcctcaa aggagaaatt agctaaatgc ataaaactgc tcactgtagt 31080 taaataccta ttgtaaagag aaactggaaa aacctgaaca tctacattac aatatgttca 31140 gacagtctct caatagaatt tcatgttgtc gacaaaaatg ataaacagga agactggata 31200 gtaaacacaa gggaaatgca gggcaaaata cagaactatt tactataaaa aaaagtatat 31260 gtgtagatat ggacagggga atatcgaaag atgaatacac ttactgtatt caaatggttt 31320 gggtgaattt ccttctttta aactttcttt taatggctgt gtttctgtgt cctatccaga 31380 ttacttgctg ctatgtcttt acctctctct tctccaacct gtacatatgt gttgtcagat 31440 ggctcagggg ttgacagcca cattcttgac ctcaaggctt ctctcacccc tgtgcttgca 31500 gagggctcag gggtggcctt agacagaggc aaacgtccca ggaccctgtg agctgggaga 31560 aaaaggcagg ataccaacct gctctcaggc tccagtctgc agcagatggc ggccagcggg 31620 aagaaggccg ggggacaatc tgtgggaaca aacttctccc agaaaagctt cacgttgagg 31680 ccaaagtcca gtgttcgggg aaggcagtca ggatctgcat acacctgccc aatgatctgt 31740 agggtaagaa gacagctgtt tacaaaggac tacagaggcc acagatactt ggcaagggaa 31800 agggatgctg ggatgtggac aggaagaatg gcagaagagg aggtggtaaa ataggttaga 31860 gagctctccc caatccccaa tcatctctcc aaatcttact aatccagacc tgtatccact 31920 gagagctggg ttactgaaga ggactaagaa ggggcttcac tgcagaagcc aagtgttcca 31980 aatcagcatc tgctcctagc ttccactcat cctaccctgc cttgtctgtg tctccttgtg 32040 gctgtgtgtg tgtgccagag ttaaggctct atgaggtgct ggatctgatt catgtctgaa 32100 accctctggc accagcccag tgctctgaac agaggtgttc aattaatatt aaagaaaaca 32160 attttttaaa acaaatcttc cttcatggcc aggcacggta gctcatgcct gtaatctcag 32220 cactttggga ggctgaagcg ggtggatcac ctgaggtcag gcatttgaga ccagcctggc 32280 caatatggcg aaaccctgtc tctactgaaa atacaaaaat tagccaggcg tggtggcgca 32340 cacctgtagt cccagctact tgggaggctg aggcaggagg attgcttgaa cctgggaggc 32400 ggaggctgca gtgagccaag attgcacctc tgcactccag cctgggtgac agagtgaaac 32460 tccatctcaa aaacaaaaac aaaaacaaaa cattccttca ttatcctaac catcccttgt 32520 ctctcctctc ctctacccct cacaactttg taggaattac agaaggcttt gaatgtgtgt 32580 gtgtttgagt cgctgagata tgctgtcacc tgactaaact cctaaaggta ggaatctttc 32640 caagattcct cactctgtcc acgtggtacc tggcacaggg ctgacacttc ctagagtggc 32700 tacttctact tgaagggaac tgagaagggc tacatttggc ccaagagcta gctagacagc 32760 cacatgaaca gtctcttgcc cttccttctg gaattctgag tctcatctgc cccttatcga 32820 ccatgtgcaa gccactgccc tcttccaagc ctcagtttcc tcaactaaaa aaaaaaaaaa 32880 aaaaacctgg ccgggcgagg tagctcacgc ctattaattc cagcactttt agaggctgag 32940 gcaggcggat cacctgaggt ccggagttca agaccagcct ggccaacatg gtgaaaccct 33000 gtctctacta aaaatacaaa aattagccgg gcatggtggt gtgtgccggt agtcccagct 33060 acttgggagg ctgaggcagg agaatcactt gaacccagaa ggcagaggtt gcagtgagcc 33120 cagattgtgc cactgcactc cagcctgggc aacgaagtga ggctccatct aaaacaaaaa 33180 aaccctgcca gtccttctct taagaccaat gaaacacgaa cgtggcaaag atgtgcagat 33240 gcgttataaa ccataaaacc ctacacccat gttgatttta gtcaagctag tcatccctag 33300 gaggagatgc cccagttccg agggaaggca gagctgctag gcctgctgcc tcgggcatgg 33360 ccttggtgcc agagctcacc tcacagagaa cgatcccaaa ggagaagata tccaccgtct 33420 catcatagct ctttccttgg ggaacacagg agagcacact gttaagttta catcccttac 33480 ctgctctgca ctgggtctag ggtcaatcta agccacagct aagaactagg gctagaacag 33540 gttctgtagg gacaccccac aggctgtcct gcgcagacac cacctgaaaa tagtccttcc 33600 tcagctgtag gtgaactgcc ttggagagcc cttataacat aacactgcct aggatgaaac 33660 tgcacgttaa agtggaaaag aaccagacta gggttcatct agcctctgcc attaggcagc 33720 tgtatgctcc taggcaattc actgaacttc tctgggcctc agactccaaa atggattgta 33780 ttcagaccat ttctgaggcc tcacaaccct gatttcaaga atcccaacca gcatctctgg 33840 ttggtttgag cattatccac cagagggcac cacacttcag ttctcaccat ggagagagaa 33900 ggctaaagct gggacaatag cctgagctct tagcgatccc tgaggcacaa atgccacagt 33960 cagaactcac cttatccccc atgatgggac actgatcagt tcccagcccc ctgagctcag 34020 gagctaaatc gtgaggcccc acctggcaag ggaaaaatat cctcagctct gggtatccgg 34080 tcctacgctt cacaggcctc ccctggaatt cccagggctc tgatgcaagg gcagcatctg 34140 tcctccctct gcgggtgtcc cctccagggc ttcaggactc accgttcagc atctcagggg 34200 ccatccagta ggggtttccc accaccgtgt agcgcttctt gcggtcgttc ttgcgcaagg 34260 tgcgtttctt ggtggtggcc ttctccatgg gggccctttt cctctcttcc actatgagcc 34320 gtgacagccc aaagtctgcc accaccacag tcttgtcctg gtaggataaa agacaggtca 34380 ggacttcatg gggatgttct caaacctggc cctggggagg aagcataggc aagagaagcc 34440 actgagaagg ggagaaaagg tgtatagcaa gggagaatca gagcagaaag ctctatcaaa 34500 tagacacact caggccaggc acggtggctt ccacctgtaa tcccagaact ttgggaggcc 34560 aaggcgggtg aatcacctga ggtcaggagt tcaagaccag cctggccaac atggcaaaac 34620 cccgtctcta ctaaaaatac aaaaaaaaaa aaaaaaaaat tagctgggcg tggtggcaca 34680 cgcctgtagt cctagctact tgggaggctg aagcagaaga atcactagaa cccgggaggt 34740 agaggctgca gtaagccaag attgcaccac tgcactccag cctgggaaac agaatgagac 34800 tccatctaaa aaacaaaaca aaacaaaaca aaaaaacaga cacacttggc atttgtgttt 34860 ctgagggtct ggtatctgtg cacagcagac tcccagccca cagtgggttc atggcagagc 34920 cactggagcc ctggaggtga ggctcaggga cttggagagt ggaactcaga ggtgggacag 34980 ggggttgctt ttgtttttcc ctgtcctgtc ttattcctaa aatgatttca ggcagtggct 35040 agaaccagga taagacagaa aaaggcaagg tggaggcagt agatggggag acttggggga 35100 gacaagctct ttgaatagct acagggcagt catgtgggaa aggaatgaag attgcgtggt 35160 gtgggtctag agggcagagc cagggccagc cggtagacac ccaggaagcc agatagcaag 35220 tcagtaagac aaacaacatt gtaaccacca cagctgaggg gcagtgggag gaatgctggt 35280 ctcaaactgg tccctgtaaa tttactagct cggtggcctc aggctgaggc ttcaggtgcc 35340 accactgtaa aatggggtca gcaatgaact gttttacaag actactatgg ggcaaaagca 35400 ggtaaaatga cagggttttc tacatatagt caacaaactt ctgaagtccc ttctaatcaa 35460 attatttcaa aggttgctaa tgagagaagg tgaaattatg tctgtgtgtg tctcggagct 35520 cccagaggac agagaagggc attggaagaa gcaggaaggg aaagatagga gctcctaggc 35580 aacacctctg ccctctagcc agaggggaca agtcagcctc ctttgtgaca aggaagccag 35640 gaaggatagg accctggagg ccaggcccag agcagtggga cataccaact tgatgaggca 35700 gttgtgcgag ttcagatccc ggtggatgat gcacatagag tgcaaatagg cctggaacag 35760 aagcatgagc tgaggctaca gggccagcaa atcaactaga ccctgaatct ggaattgggc 35820 gccatagatg ctctcctacc aggccatgcc cacccagctt cagaacccaa cctggacaac 35880 agggccaggg cctcctatgg cctctccctt gtcccaatac caacaggaag cctggacttc 35940 ctctgcttcc ctgctgccat ctcctgccca tcctttggtt caccaatcac tagcacagtg 36000 gctggccaaa gccctcacag ctctctccta atgtccccaa cttcagaaaa ccctggccgt 36060 tgcagcaccc cctccacctc tacccatttt acttagatcc aggctgctcc ctcctcccca 36120 ctctcccaat ctctggcttg agccactttg gatccttcct gcctgcaaca gagaagtgac 36180 ttcttgctcc agctagctct gtctttcaga cattcacctc ctctaagact ccaccttccc 36240 cactgtctaa actttaagct ctcccccttc ctaccaaaat gtttgtcaac aaatttgttt 36300 gttatgtctc ctctccaggc ctccaccact gactcttacc actctcagga gcaacttcct 36360 ttctccttcc cttgcaaatg tagaaggagc cactccttgc tctccagccc cctgcaatac 36420 tactttcatc ccttaggctc ctggagctgc tcacacaccc agggagctct tcctgaatcg 36480 ctatagctca tgacctgcct gcctgcctgc ctgagggagt gctcctcaaa gactgtccac 36540 aactttccta tgctacctga tcctgagact cttgtgtgtc tgtttttttc ttccagcctt 36600 ttcagtgtca gccctgctca aagccatctc ctcttcacaa gctgagacac ccccaccagc 36660 tacatggatg cctcttctgt cccacagctc cagctgcccc ttctctgcag attaggtgac 36720 tagcagcctc tccctaagcc agtctcatgg agccagtttc ctgcccagaa gatgctgata 36780 ggttctgcta gcacagaaca gcagggatca atgctagctc ttcccaaacc agttgctcaa 36840 caatcatggc tatcccccat cccccaaatg tctggtaagt gacacctcaa gccactcgta 36900 actcctcctc ctcctcctcc tgttccctca ttgccaacca gtctctccat tctgactcca 36960 cccggcctcc caggctcctg tccccacagc cactacctta attcagaaat ttgaaatgtt 37020 tcattagccc cctatgcagg gctccattcc ctggaccctc cgcattccac cccaatgtac 37080 taaccatatc agtctctctt tttttttttt tttgagatga agtctcactc tgtcacccag 37140 gctggaatgc agtggtgtga tcttggctca ctgcaacttc tgcctcccag gttcaagcta 37200 ttctcctgcc tcggcctcct gagtagctgg gactacaggc gtgcaccacc acgcccagct 37260 aatttttgca tttttttctt tagtagaaac agggtttcac cagttggcca ggctggtctc 37320 aaactcctga cctcaagtga tccactcacc tcggcctccc aaaaaagtgc tgggattaca 37380 ggcatgagcc actgtgccag cccagactca ttttggaaaa accacagctc ttaagctttc 37440 ttgcttaaaa atcttttcct gccgggcatg gtggctcaca actgtaatcc caacactttg 37500 ggagggcgag gcaggaggaa tgcttgagcc caggagtttg agatcagcct gggcaacaaa 37560 gtgagaacct gtctctacca aaaaaaaaaa aaaaaaaaaa gaaaaaaaaa ttcaaaaaat 37620 taggtgtggt ggtacacacc tgtagtccag ctacttggga ggctaaggca ggaggattgc 37680 ttgagcccag gaggtcgaag ctgtagtgag ccatgatcgt gccactgcac tccagtctgg 37740 gcaacagagc aatatccttt ctcaaaacaa caacaacaaa aaaacctcct tcctgattca 37800 agccccagaa acaggaaaaa aaaacaaaaa aacaaacaaa caaacaaaca aaaaaaccaa 37860 aaagccagtc aaccaaaaaa ctcttttaca tttgtctcct atagtccaga ctccatagct 37920 taaaacacag cgaccttgat gtacccccaa actgttccag actactacta ttttcatgga 37980 cccccatgtg aagggcagtg gctaaagtct caggcttggc gaccagactg attagcccag 38040 gatcccagct ctgtcccttt ccagtccagc ttatctggaa accaaggttg tcatgaggaa 38100 taaacatgca catgcatgtt aatccctcag cccagtgcct agcatataga gggcactcag 38160 tacttgtcag ctgttattat ttctatgctt ggaatcattt gtttccaggt gaaatagatg 38220 attttctcct ctttcctccc aggtctttgc tcctgtcact tcaatcctgg tgcctctctg 38280 ccaataagaa ctttatccaa ttctgatcct tcagggctcc gctagaactc atttcccctt 38340 cattgatttc ctaggcagtg aggtgctcta gttggtctaa gggccctcag cacctgaata 38400 cctgtgatgg caagcccagg ccatctcagg ctacagtttg cctctccagt ttgccttgtc 38460 cgtgccctgt ttgcctttag agatgtgtaa ttctttgaaa acagggctgt gaactgagaa 38520 cagttggctg gggtcagttt cagtgacaca gacaaactca atgaatagct gctgacccag 38580 cccacacaag ttgcatagga aggggtctct accttccagt gaagcccaca attctcacac 38640 ctctccctac tctcgccctg ctggcaggtt tgttggtggg actcaccatt ccggaggcga 38700 ttcctttggc aaacctgacc ttctgctgcc aggggaacgg atcctgcaga atggggaatg 38760 attttcagag gctgttgagc cctgtcccac tcgtggtcca ggccccatgg gtcaatgtgg 38820 tctcccagtg aagcctccct gtgtatgctc agtcccaccc agcatggtcc tttggaggca 38880 aagcagggcc cctctgccct ttaagctcct agggtagtga tagcataggt gtctgacaac 38940 ccaccaaggc tcctggagac tatggggtgg tgtgctcacc atactgcgca gaaagtcctt 39000 cagtgtgccc ccctcaatgt actctgtcag gaggttcagc ttcttatcct tgtacagcac 39060 accaatgaac ttgagcacat tggggtggtc caggctgcgc atcactttca cctgggggtg 39120 ggggaagcca aggaaagctg gtggttaact tctcactgtc ttccttacct cttccctcca 39180 aggaatcagc ttgacaagtg ttaccacctg tatctcctac ctcctatctt gtgatatgac 39240 agggcactaa gatcaggatg agggaagacc accaccatat agatggagat ggcttcatag 39300 gccttaccct tggaactgca ttgggagaac tggggtggga gtggccaagt ggcttggagg 39360 gcaataccca gaccacaggt gtccccaact taagttactc catgaagtaa cttgggaggg 39420 gtagtgaaaa ctgtaaatgc ccaaggagtg tgagtgctca gggagctccc ctccaggctc 39480 ccttagcagg gcgttcaggt gaggattata acattgagtt gtactaaatt ggagtgtttt 39540 catgtccatc atcctcataa cctgagagct cttctgaacc ctgtatcttt tgttactgca 39600 tcccttgtac cctgtttgtg ttgcttttag taagtgttca ttgaacaaat aattacgctg 39660 taatttagag ggagtgggat attcctctag ggctcttttc tgcttagtct ttaagacagt 39720 aattccaaac tgtattttct cttgaagcca ttatttgtaa ggtcttctct cttccaatgg 39780 tgacaccaac ctcccgggcc ccctccatct tcttacctca gtcagaaaag ttttctgggt 39840 ctcctcatca catcgaatta actctttcat gaccatcact ttgcccgtgg ctttgtgtgt 39900 cacctacagg gagggtgact gttaatggtg ctgagaccag aggaagttct ggagaactgt 39960 ttgagaaaat ctatgcagct ggccatccca tcccttggag ggcacactga gccgggtcag 40020 aatgacagag ttcatgtgtg gaagatgcag cgtggagcaa catgggactc acacggaagc 40080 aaaccctctt tcctggagag ctgggcatgc acagaggaca ggcaagaacc cagaaaaggg 40140 aagtggggaa gaaggcagga ggggatgctg ccaagccaag caggggctct ggtcatttgg 40200 catagaagtg agtctcctga gtgaacagaa gtctgggggc aggaaggtca gtgccaaaga 40260 catgcaccag ggagctgggt ggatcggggg tgagctctcc agccctgctg cccccaagct 40320 gagacacacg tcttacctga ccccccctcc cagttctcag cagaagagga ggaggaggag 40380 agaaagagag aggttagtcc ctgagactgt tcaccaggga ggcaggagcc attcccctgt 40440 gtgctccttg tagcatgccc ggtactgagg tctgcaggca cctaacaaac acccactgac 40500 tggaggcagg agggccacag gcacagctca acccaacctg gatctccagg tccacaagct 40560 cactgtaaca gcaacattga ccttaggtgg cctgggtggg ggtgaaggat acctctcaca 40620 ccaacaccca aagccaggaa ggaggcctgg catcctgcat ggtgtggggt ggggccaagt 40680 gatgagaaat ccccgaaaga cagtgacaga gggactgggg gcagaagagc aaagcaattg 40740 ttgcctgcgc tcaccttgat agcctgccca aagaagccct tccccaggac ctccccatgg 40800 attaggtcac agggccggaa gatctgctgt gaatagctgc tggaacaacg aagggattct 40860 gagcggctga tgtcacggct gaacagcagg ggctcctttg gggagctggg gccaggggac 40920 ttggagatac tgttactgcg cctgaagatg aggaaagacg ggagtaggga tgtgtagtcc 40980 tcagagaccg gccaagaaac cctggaggga ggaaacttag gggcacctgt tcattccaat 41040 gtctatagtt tagatgttat tattggggaa caggggctct tacatcagat gtatcatttt 41100 ggggttgctg acatcagtca tttatttaag catagtaaaa acacattcaa aatgggaact 41160 ctgcatacat cacacataga acaattaact agattctact agctgataat gctcagtatg 41220 tgacatatat gacaacactg tagatggtaa ttcaccatct cccatatctg cttgatttaa 41280 gtactaactg gtttagagtg atagttatac tagtatccaa aaaatgagca aatgggattt 41340 tttttttttg agacagagtc tcgctctgtc aaccaggctg gagtgcagtg gtgtgatctt 41400 ggctcactgc aacctctgtc tccctagttc acctgagtct catgcctccg cctcctgagt 41460 aactgggact acaggcatgt gccaccaggc ccggctagtt attgttatta ttattatttt 41520 tgagacagag tctcgctctg tcgcccaggc tgaagtgcaa tggcacgatc tcggctcact 41580 gcgacctccg ccttccaggt tcaagcgatt ctcctgcctc agcctcccaa gtagctggga 41640 gtataggtgc acgccaccac gcccggctaa tttttttttt tttttttttt tttttgatgg 41700 agtctcactc tgtcgcccag gctggagtgc aacggcggga tctccactca ctgcaacctc 41760 tgcctcccag gttcaagaga ttctcctgcc tcagcctccc aagtagctgg gattacaggc 41820 gtgtgccacc acaaccgaat aatttttgta tttttttagt agagatgggg tttcaccatg 41880 ttggctaggt tggtctcgaa ctcctgatct cgcgatccat ctgtctcggc ctccctaagt 41940 gctgggatta caggcgtgag ccaccacacc cggccctaat ttttgtattt ttagtagaga 42000 tggggtttca ccatattggc caggctagtc tcaaactcct gaccttgtga ttcgcccacc 42060 tcggcctccc aaagtgctgg gattataggc gtgagccact gcgcccagcc taattattgt 42120 atttttagta gagatagggt ttcaccatgt tggccaggct ggtctcaaac tcctgacctc 42180 aagtgatttg cccgcctcgg cctcccaatg tgctgggatt acaggcgtga gccaccgtgc 42240 ctggccagca aatgggattt tggatgatat tttgcacatc tttgtacctg tccatgtttc 42300 ctgaatttta agatgataaa cacgtatgat ttttacagca ataaagtcac tatgtttaca 42360 ttttcaaaag cggtcgataa tagtcatggt caatgactgt tattttcact tactgaagaa 42420 ggaacaagaa ggttgaagtc cacagcactg caggtgaaca gccctgcgaa ctttctctct 42480 ggggtatgct cctgctttac ttgggctacc cagagaggac tgacgctgga tggctcttgg 42540 cttgtcccga cctacaggtt tacttaccct tgtccttttg ctctgcctcc tgctgaccat 42600 gcccaccaga gcacacaagg ctagctgccc ccctcctctg catggtggct ctacagatac 42660 ctggccactc ccaaatcttc ccttttccag gccatggatt tctagctctt ccctgccctc 42720 tgttgccctg cctcccacta atttcatcat actgaccaag gccaagaggc aatgggagtg 42780 agggcagcac tttaatgaga gggcactgtt tccaacacat gccagctgag agggctctaa 42840 cttactcagt ttgtttggtg aggagagtgg ataaaaaaaa acaaactttt ttttttggag 42900 acaaggtctc actctgttgc ccaagctgta gtacagtggt gtgatcaagg ctcactgcag 42960 tcttgaactc ctgggctcag gcaatcctcc tcctcagcct cttgagtagc tgggattaca 43020 ggcatgtgcc accatgccca gttaagtttt ttattctttg tagagacagg aatgtggccc 43080 aggctgctcc tgaactcctg gcctcaagca atcctccggc cttggcctcc caaagtgctg 43140 ggattacagg tgtgagccac agtgccctgc ccatctaatt aaaaacaatt attattatta 43200 tttttttttt gtagagacag tgtctcacta tgttgctcag gctggtctca aactcctgtg 43260 ttcaagccat cctccgacct aggcctccca gagtgttggg attacaggca tgagccacgg 43320 tgcctggcca agaacctgat tcttagtgat actaagaatg tgtcacgttt actgaacact 43380 gtccctatgg cagcactata caactttatg tccttttcca catttaatcc ttacataatt 43440 ggtgagacag ccacctttat cttaccatct tatgtcacag atgcagaaac aggctcagag 43500 agatgaagtg atttgtgaag ggaggagctc agcctgaagc cccagtaggg tatcagtatt 43560 tctgcctggg agccagtgct cttgacttct tttctgtaag tctccctact tggggcttcc 43620 actcaaggca acttctcctt ccccatggac ctggcagaat ctggggtttg ggggttgttg 43680 gtccctcaag tctaaaaaaa acgttcattc atcttttgct ttattgtttt caaagtcttt 43740 ctacacaatt tattcaatcc tatctgtgcc cctactccag gctctgagct ccatgctttc 43800 tccataggcc atgttgccct tcagggttta gcatcactgc ctcctgtcca gcttaggagt 43860 tcagtggaca gagactgact ctcaggtttc taaggaaacc tggcagacag ctgggtccgc 43920 acaggctctg gctgtaaact gtgatcccca caggggcagc tgggtcagca caatcctcat 43980 agtctgtccc tggccagctg gttcctttcc taactctgca ggcttctgaa agccagctca 44040 gcttcatccg agagacagac ataggacaga acagagccag ggtgggaggt ggcaccttag 44100 ggaacgtctc ctcagtgtcc cctccagatt ctccttggtg tccagggtgc tgagggcgtg 44160 ggggtgtccg gcattctgca tgtgaggagc gagccgggcc tccagccgca gctggtccag 44220 gcgttgggag acggggtcat gttcaatcaa cagctgaagt gtctggctcg tctggctaat 44280 tgcatcctcc acctgtggcc

aagagcagta taaagctccc acaggctgcc ccatcccagg 44340 ccacccatgg ccaacccaga tgactcaggc acagtgtggc cagtgctcaa cttgtctaat 44400 ggtggccttt agctgccagt ggcctcacag tgccctctgc ctggcatcct gtcagctctc 44460 ccgtccatca accatccctg ctaccctggg aacctgttac gctgaaatag gtcaccagtg 44520 gtcacaggct caatgctaag acaaagagat gggctggggg taggaaaagg taaaggctac 44580 agcctgattt ctcagaggat ctgttccatg tcccaccctc acaagacaga ttagacacac 44640 actctacctc ctccactcga agtgtgcgga cgggggtccc attgatctcc aggatgcggt 44700 ccccagggtg gatggcgttt cgattgttgg gactgatgtg catccggttg accctgggcc 44760 agacaagagt tgaggcaggg taaagatgtc ctaaaaacct gcttgaccaa ttctgcttgt 44820 gcagggaagg tttaccaggt cccaggccac cagtggcccc taaggggccc aggataccca 44880 cacagaaagg caacaccttt tccaggatgc cccatctcag tgaagggaat tgccactcac 44940 cctgtggcct aagccagaaa cttgaacatc atcttcccaa tctggagttc cctcatctct 45000 cctactccca tctctaagaa ctctgccttc tttccatcat tgtagttatt cacatctctt 45060 acctggatca cggtaatagc ttctattttt tttttaaact ttgtttttaa tttttatttg 45120 agatggcatc ttactctgtc atccaggctg gagtgcagtg gcatgatctg ggctcactgc 45180 aacctccacc tcccaggctc aagcaattct catgcctcag cctcctgagt aactgggatt 45240 acaggcgcgc accaccatac ccagctaatt tttttgtact ttttgtagag atggggtttt 45300 gccatgttgg ccaggctaat cccaaactct tttttttttt tgagatggag tctcgctctg 45360 tcgctcaggc tggagtgcag tggcgtgatc tctgctcaca gcaagctccg cctcctaggt 45420 tcatgccatt ctcctgcctc agcctcccga gtagctggga ctacaggcgt ccgccaccat 45480 gcccggctaa tttttgtact tttagtagag acggggtttc attgtgttag ccaggatggt 45540 cttgatctcc tgaccttgtg atccgcccac ctcggcctcc caaagtgctg ggattacagg 45600 cgtgagccac tgcgcctggc ctaatcccaa actcttgacc tcaagcaatc tgcccacctt 45660 ggcctcccaa agtgctggca ttacaggcgt gagccactat gtctacgtct ggacttttct 45720 tttaattaag aaaaacagag acggggtctt gctatgttgg ccaggttggt cttcaactcc 45780 tggcctcaag caatcctccc acctcagcct cccaaagtgc tgagattaca ggcatgaacc 45840 accatgccca gcctacaata gcttcctaac tagtctctat acctttaggc tttcccctct 45900 ccaatccaac ctccatacca gtgatccttc taaaatgtta acttggtcac aacaccttgc 45960 tgcttaaact ctcaatggat ctgctggatt ttcataatcc aggccctcta tacttaacag 46020 ccccttttct ggccacactc aacctacatc agacatgatt aagactccta cttttggaga 46080 aatgcttctc cctctgccct gaacacaatt ccctctcctc ttcatctaat aaggttgtag 46140 aacagacctt agctcctcct gacttcccaa actctagtat ctttcacctg ctgtgcaagc 46200 actagcctag tgtccaacac atggtagata cacaatcaat atttacatgg taagcggcca 46260 gaggtacgac attactggta ttagatagac acagactctt tctccatctg gtctctggcc 46320 tgaatctagg atagggtctt aacttctttt gggccatgga ccacattttc tccattcatt 46380 ctctcgactg acaaaataat aatcaatcaa ctcctactat atgccaggta ctcttccaag 46440 ccctgggcat gcagcactga ataagacagc aagtttcttc tggaatttac attctagtgg 46500 aggggataga agataaacaa ctaatacaca taatcaagcc agatgatttc aaagagcaaa 46560 catgacctga aacctgacac ctgaaaggtg agtgattctt gccttaagta tcgggtagga 46620 agtagcctgg gcagagagaa cagtaagtgc caaggcccag gtacggttac agcatagtgg 46680 ggtccaggag aaagatatga gatgagaata aagggagttc tgcatgagac tttggaggtc 46740 taagccctct gaggcccatt tacagactct gctcaagaac ccctgctgaa gggttctcaa 46800 aatacttact ctttcacttg cacagtggtg gcgtagttgg agcaggcact ctccacggac 46860 acggagaagc cccgcctgcc ttcagtggtg gccggcatgg agatgagcgt gacagagtag 46920 ggcagctgct cctgaacaga ctctgtggag agtctctcaa acatgggtgc cagcaccacc 46980 tcattgtggc acttcccact ggggagaggg cacagggggg aataagatgc tagagtccca 47040 cacagaagcc ccccagcaac cactgcacca tgtggcttta agcaacagta cccatagtct 47100 cactaccacc ctctttgtca tgattctagc tggctgctca gaatgaggag cctgggttct 47160 cagggtgggc tgggactggg ggtgctgagc tagatctgca gcaagtggta tatttggaaa 47220 aacactggcc tgggttgggg tgagatggtc tgggttctct tcactctacc tttgactcac 47280 aatgagaacc ttgcccttgt actattctat tccatgggcc ccaggctgac ttcttttatc 47340 aaccaaggtg gttggacagg gtgagctcta aggggtcttt gactttaatg ttctgggatc 47400 gtccttgaag agtgcctccc actgggagga ttgcagggca gagtgaagac attttcaagg 47460 ttggtaagga aaaagggtag agacatgtgt aaatcattct gcttacaagt taaagagctg 47520 gttaagagca ctgctgtggt aagaatccaa tgctctgact accctaacac tccttctgcc 47580 caactcaccc tgccactgtc cctccccgcc agccactctt atatgggaga ggatagacaa 47640 aggaccacta tcttaccagt agagggtggc atgctgcacc agtgcatatg catccccatc 47700 ctcaatgatc accttgcagc tcatacaggc aaagcactct gggtggtact tgaactcccc 47760 agccacctgt gagcaggtgg ggagaagggt gtacaaaggg aggaaggaag tgagttatca 47820 ctgttgctgg agtgaggaca ggggtgggtg aatgacctcc aagcaaggcc cccgtcaaaa 47880 tccactcttt cactctctgc cctagagctt ccaaaggaag tgtcagattg gtacctcctg 47940 tcatttctga gactgcacaa aactgttttg gtctcagtta tgagaagaaa tccccagaag 48000 taatcatccc cactaaaaaa gatcagttct tccaatacag ggttggcaag tctgtcacta 48060 tgcttaaagt cgtttgtcca gagcaggtat aggaggtagc ccctctctct gccagcctat 48120 tccagagtct ccttttctga ttccctaaag acaacctaag tatatcctcc tctcagcctg 48180 taacactctc cttggaggtc cttatccaac tatattgtgt ctcctctctg cctgcctctc 48240 ctcccactcc caacgttcaa ctattaagtc tttgagggaa ggatcttacc tttcacttag 48300 taggtgctca attgatacct gctagttgaa tgaatgaata aataaaggga gatgccctgg 48360 ctgatggaaa gactaaaaga ttaacaggcc acagggaact ggaagcactg tcaatggact 48420 ctgaagacca agaggggcag atatgaaggg attcactcac cataaaaggc cctgtcatca 48480 gcagggagca cccatgacag aactccccaa acttccccca gtagtccttg gggcagtaga 48540 gcttcccatc cttctcatag taccagttgg tgagggaatc ctggcattct gaacacctga 48600 aaggcaagac aagaactgaa attctcctgg atccctggaa ccaggccaca taagctgtcc 48660 ctggttccta ggtatgacaa caaaatggac agtcctcttt gatccaaagc caagatgggg 48720 caaagttaca gccttgtgct atctccccaa gggaagctgg ttcagactga acaaggcccc 48780 agaaaccagc tctgtgttgc ctgcctcagt ggacagacta gtgtttcata acctctttgg 48840 gtcttggggc cctctgagaa tttgataaaa gccaagaagc ctcccctaga aaaatgaata 48900 tataaagaag atgtgtatat aatttaggtg ggggacaggg tgtatatata aaggattctc 48960 tgaaacctat ttatggcacc agttaaggat ctctggtctt gacagatact tcaatgaaca 49020 aaagcagttt aatcatctcc actcttcaaa actgacccat caccaacagc gttaccaatg 49080 taatgttctt gccaaaaata cgttaagtat aaaaaaacta atcaggcaaa tctagaatgt 49140 gggttattct ataagaataa ccggtcttga ctcttctaaa aagtcatggg gagaagaaaa 49200 ggcacagatt ttaaaaaccc tagagacaca gcaaccaaat acaatgcctc aaacttggat 49260 tcaaatttag attaaaaaag gaaacagcca tgaacatttt ttggaacaac tgaggaaata 49320 tggatttgga ctataatatt atattgtaaa attgccgtga attttcttag atgtaatgat 49380 atctgactta tataggagaa ttcttagcag aaacatattg aactgttcaa gggtaaaatc 49440 aagatgcctt taagttactc tgaaatagtt cagcaaaaat aaataaataa aagtatacag 49500 atagagggag agagatatat acaaagtggc ataacattaa caaatcatga atctatgtga 49560 aaggtatgta ggtgttcttt gaactacatt ttcaactttt ctatatattt gaattttttt 49620 tcaaaataaa atattgggga agaaacccaa cattctatta gcactgtgta agatgtacat 49680 gttagatcca tagctcgctg ggcggggtgg ctgatgcctc taatcccagc actttgggag 49740 gctgaggtgg gaggatcact tgagcccagg agttcaagac cagcctgggc aacatagtaa 49800 gaccccgtct ctaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaatcta tagctccctt 49860 ctcccctaat gacctggcta tgaagctcca cctctcaaaa gtctggtgtg ttctcaggac 49920 ttacctgcac agacaacctc ttcctccctt ctgagcttcc caacacacac agctaagagc 49980 tccctggcct gctgagccca tgccatctct ttccttctag ctccttcttt tccctattct 50040 tgttgtcaag gccttgcacc ttccacagtg gccacattct tgcttccaag aggtttgaac 50100 attgcttggt ttgaatcttg atcctgccac ttactagtta catcatcttg ggcaagatat 50160 tttacttctc tggcctagtt tcctcatcta taaaatgaac tgctgtgaaa attaatggaa 50220 ataatatgta ttaaaaatat agagagcagc tgggcacagt ggcttatgct tataatccca 50280 gcactttggg aggccgaggc gggtggatca cttgaagtca ggagttcgag accagcctgg 50340 ccaacatggt gaaacctggt ctactaaaaa tacaaaaaat tagctgggcg tggtggcatg 50400 cacctataat cccagctact cgggaggctg aggcaggaga atcactggaa cccaggaggt 50460 ggaggttgca gtgagtcgag atcacgccac tgcactccag cctgggtgac agagtcagac 50520 tctgtctcaa aaaacattat agctagctag ctagctagct agagatagct tatataaaag 50580 tcctaatata ggcagggcgc ggtggctcac acctgtaatc ccagcacttt gggaggctga 50640 ggcgggcaga tcacaaggtc aggagttcaa gaccagcctg gccaacatgg tgaaaccctg 50700 tctctactaa aaatacaaaa attagccggg cgtggtggcg tgcactggta gtcccagcta 50760 ctcaggaggc tgaggcagga gaatcgcttg aacctgggaa gcggaggttg tggtgaccca 50820 aaattgcacc actgcactcc agcctggaca acagagcaag attccgtctc aaaaaaaaaa 50880 aaaaaaaaaa aaaaaaaaaa aaaaaaaaga cccaatatag tagaaactca gtatgtgtta 50940 acttctatta aagatgatga caatgtaatg gcagctcact ttatcagcca cttactgtca 51000 ctagctggac aacttctctt agtagctttc tctcattgaa aataactaat agcatcctat 51060 tactacaaag agccaatgtg aagaggaaat aagctaatgt atgagagaaa gccttttgcc 51120 aggcaagtgc attattataa cttgctaagc actgcagata taaaagataa atacacaggg 51180 caccctactt cacctttcat gagcttatga agagttgagg aagagaaagt ctaaataaaa 51240 ctcaacaatg caaggtgaga ggccacagtg agttctacta cttctgagca ctgcgggagg 51300 tagagaagag gggcaggaat gagttgaagc agctgagcta gggaagtcta gagaagcaag 51360 tccctgagaa tccctttatc tttctggagt gcccaattcc tcctgggtgc tcaacaaaca 51420 ctgatggcta tttttaccct atagcttttc ctacttgtct tatggaaggg gaacttcagg 51480 gtcttaaggg ctgggtatgg catgaagagt atggctgtga agtgtctcaa aactgcacag 51540 tgaggttgga ggcagagggg aagactgttc ttggtatgtg gctcacactc ctctcaatat 51600 aagatacatg tgggatgagc tctaaatgag gaggagagag atatgggttc aagttcttgg 51660 gtgctaaatt gccttggaca agcccctttc cctctctggg ttgtttcccc acctgtgaaa 51720 caagaggaca aacaataccc tgggtcccct taactctgtg catatctgtg tttttcccta 51780 gatgatctga ggttctaatc ttagcaccac catttaccac ctaagtgatc ttgggctagc 51840 cccttcactt ctcatttgtg aaatggcaat gtcatcacct actttcaagg tagcagtgag 51900 gattttttct tttttctttt tttttttgag atggaatttt gctcttatcg cccaggctgg 51960 agtgcagtgg cacaatctcg gctcactgca acctctgctt cccgagttca agtgattttc 52020 ccacctcagc ctcctgagta gctgggatta ctggcgcatg ccaccacacc cggctaattt 52080 ttctattttt agtagagacg gggtttcccc atgttggtga ggctggtctc gaactcccga 52140 cctcaagtga tctgcccgcc ttggcctccc gaagtgctgc gattacaggt gtgagccact 52200 atgcctggcc tgcagtgagg attaaatgtg gttctgaaga actatggggt gcccaacaga 52260 gggctggcag taggagcagg ggcttccttc ttgcctcctg ccttctgact tagaagttcc 52320 tgggcaacca tctttcttct tcactagact gttagctccc tgaggacaaa aacagcatcc 52380 cacttactct tggtagactc agcaccaagc aaaggacctg gaagagcaaa gccttaacaa 52440 atatttccaa actgaaaatg gtaggagtgg caagaaccag tagcccaggt aggggagcac 52500 aagggttcca tggctcctgg tcaccaggtc cttcttttct tctgtgtgca gacttatttg 52560 cacccaaatg caggcctggg ctctgttacg cccttgcaat ggtatgtgcg ccgcagggca 52620 tgggagcacc agaacacacc ctcctttcca ttgccaatat cctgcttttg tttgctgcaa 52680 gtagctctgg ccaggcccag gagagggagc agggagacaa acaagtacag gcatgcagga 52740 gacagccagg ccagcctgct gggaagaaca cctggctgga gagcaacgtc accagtccac 52800 atatctgtgt caaggaatgc ctttaaaggg cacagccagc tatgtggcca aagtcactgc 52860 cacacatgtc tctgaagaac tggaaggtga acagctgaca ggagggctgg gtatggatcc 52920 ctaagctgtg ttttgccaca gaacacaact gggttctcag accacttaag aagttgccat 52980 ggtagacttc agagttctag cttagctatc aattaacagc tactatttat tgaatgccag 53040 ccataatcca ggtcctatat gaggtacctt atttatatta tctctaatcc tgacaaccct 53100 acggtagcag gattatccct gttttacaga agactgaaaa gcagagttaa agtcaaatca 53160 ttctgcaaag ctgcccaata cataattgat ggagctggaa tgtgaagcta tgtgtgcttg 53220 gctgcaaagc cacatccact gtactatgtc accggagtga gacagcacat ctcaacagct 53280 gagcctcagg attctcacct gtgaaaataa ggaagctgga gccctgacag ctcaagaccc 53340 tttgagtgtt aacacttcgt gatgcttctc ctttagccca agtactgaat gttaaatagc 53400 acaattctcc tccttcatat acttcacagt gttcaattcc ccagcagtct ctgttctttt 53460 aaacaaagaa cccagaacac actttggaac tgtaaggtgc tactcgaaca tgtcccacct 53520 cagatgctta gaggccatgg acatcatacg ttcttcccaa agccaaggct gtttttctac 53580 ctttcaattt ttggaagttt caagtgaaag tcaaaatctg ccctggctgt aggtagaaga 53640 gtacccagct gggaggtggt aaagctgagg tctgaaccag tcatcccact gtcctgagga 53700 gccagagtga attgagctga aatcctcagg ttaggggaga tcacctagag gcctacatac 53760 gctgaggcta tgcctaagga caacctccaa aactcatctt ccaaaacatt actgaggggt 53820 tctgagggct tgggcagata caaagtgcat ggaaccctga tggtcagttc agtgggtcaa 53880 cccagatcca cacagagacc ttttgagtca gcagagaaca tatgagtttt ttaaaaaaga 53940 taatcagttg agattttctc tttcaagacc tggatccata ttccttctct gccatttacc 54000 atctgtgtca cccaaggcca gttacttcat gactctgagc ctcagtttcc tcacttgtac 54060 attgctaata atatcttatg gggttatgag aattaaatta tgtacagatg tcttgcatga 54120 tgcctggctc acagaaggta gccagtaagt gttcatttct ttccctcccc aatttgagac 54180 caccaagggc aaatgcagac agaccccttt ttctcctatg cctagcaata tggacctgct 54240 tctcagccca gaatgaaaca gatttctgta agtgaaaaag aaaggtccta aaatgacctt 54300 tatttatcta tccaaataga aatcaacttt tttttttttt ttttaagaga cagagtctta 54360 ctctgtcacc caggctggag tgcagtggca caatcattgc tcactgtagt ctgacctccc 54420 aggctcaaga gatcctcctg cctcagcctc ctgagtagct gggactacag gtgcacacca 54480 ccatgcctgg ctaatttttt attttttgta gagacagggt ctccctatgt tgcccaggct 54540 ggtcttaaac tcctggactc aggtgatcct ccagccttgg cctcccaaag tgctgggatt 54600 acaggaagga gccaccaagc ccagctgaaa tcaattgatt ctaatagatt tctaataatt 54660 aggaaatagt tactgtgcat ctaggatgtg taagaacaag caggcaaggt gctgtgctga 54720 gagaagccaa gtgagataag atagaggccc agccctcact tacatccaaa ttcttcagac 54780 aaaaatgttt acaggtaaat tctcaacctt atggggtaaa agaaccagtc attattgcag 54840 tggatttaca catgttaaag cataagccct cccatgtcct gaggaaggcc tggctggatg 54900 gtcatccctt aacctcccag tgaacagcca gttgtagaga agcttctttc agcccctagc 54960 ctctgaattg agtgggctga aggagagaat gggaagctcc ctccaccaca gcctgagggc 55020 acctggagag caccacaact ggggatgcca acttttcccc agggcccaga agggcagata 55080 tgacaggggc ctagagagac tctgttccat aagagctcag tcaaaaatcc ctttattact 55140 cctccttcct gcagatccta tagactgaaa cagtctgcca attaagctgt aattattatg 55200 gaatatgtta ttgttgtttt aaaaaattaa ccaaacacat aatgaagcct acgaacagca 55260 agaaataagt gttgctagag tgcactgatt cagttccaac caaaaaccag gaagactgta 55320 gtttcaagta ttttgtgtag ttgtactgca gttaaagaca gggcctccat tatttggcaa 55380 ataatggaaa agagcttgtg tgcctctgag gagccacata agttgcagag ctgggaacca 55440 ttcacctgat ccaagtcctt catttttcag ataaggaaaa gagtcccaga ggacctaagg 55500 cacctgccaa aggttactgt gaagctgggc agagttatgc ataatttttt ccctttaaac 55560 atggattgct ttggaacaca aaggttcatt tgttttcttc aagagataat gtgtaaaccc 55620 aagctcatta aatcagtatt ggacattaag tgaaattcta taaaaagaaa aatgctttaa 55680 agatgtccga caaaagccac tccctaattt acctcttttg taaattccaa tttgaggtat 55740 tttcttactt ggaagcacag tggtaattgc agctcacttc tcacgctagt gtggtaggaa 55800 agacagtgca ttctctgctg agtatgtatg gcctgtcagg caggggtgta tgggacacag 55860 aagttgtatt cttcattccc ttgctccctc ttcctccctc acatgtcacg cctgatcatg 55920 tccccatgga atctggttgc gtcactttcc ttgcaaccac agccccagaa ctcccataga 55980 ctttgtactc ccccagaggc ctagggtcaa gaacttaatt tgtttcacag aatccagcaa 56040 ggaccctgtt caggagccca agaagtctag cttctacttt ctgccaagga tgaaactgag 56100 gcccaaagag gagcccttga ggatatccta taataaaaga gggaggggct aatggcagaa 56160 acagctttct gaccaggtag tgatgtggta acggatacct gggagagcag agggtctggg 56220 tggtccctcc ctggggggaa agagccctgt gtggcagcta tctcttcaga agtgacttca 56280 ggaatgtggc ctcttatttg gggaagggaa gaatgtctac gaaagtcagt cagtaccccc 56340 cagactctag ctgggcaaac ggagcttggg ggtaggggca agaagatcag gttctccaga 56400 aagcctggga cagaacaaga caaacggcag gtggacttgg gtggcattag tggtctggcc 56460 cttaaaggtt caggttgaga gttcactatc tgctctagct tctcctcttc ctgagaagtt 56520 gtgtcctccc tggcttccct gcctctccaa gggtaaaagg ggtatagttc ctggctccta 56580 aaggaacaac ccttctccta agctgccttc ccaggattaa gagaaattaa tgaggacctg 56640 aaatgtggct acttcaacac ttggcatctt aattccacat gtaaaagctt tctcctaaac 56700 tcaagatcaa tttccattgg ctctttagaa aacaatctca gccacacctt caacaagtca 56760 ggcaaactat cccttttttt actctctgct aggagaggaa aacaaacctg agaatttcct 56820 ctccactagg agaagaaaac aaacctgcag ccccctgaag gatgagagaa agtcaggaag 56880 acagaaaaag ctgcccagtg aggctccata tgttaactct gttgaaactg gttgcctcat 56940 ctgtaaaatg gggatatata atctctttag gctgttgaga gattaaagga taaagtgtct 57000 agcagggcgc ttggtagagt cagcattgag gaccagttcc cttccccctt ccccctgtcc 57060 agacacttcc cagcaatcta ccagggtccg gtcattccac aaaaccacat ggtgcactgc 57120 ttttctgccc agggcctggc cacctgacta gtatcccggc agcaagatct gggcactgga 57180 cctagcttag agaagccaga agggaaaagt cgaccaggac cactggtgag ggggaggcag 57240 cctttttgga acaacaggct gctcccaaag aatgaaaaca aaccccaccc tagcctggaa 57300 tggctccatt cagaagggac ccagagggcc agaaaccccc tggggagttt ctatgggagg 57360 tggagtgggg caatgagcaa agaaagccag gttagaggta gagtttccac atctccctct 57420 gagaagcccc acagagagag gctcgtggag gtacttaggc ctagggactg aggaggtgtg 57480 ggggctggcc cagcagctca ggaacactct aaagcccatt gctccagtct tagaagcact 57540 cgcccaggtc tttccccagc aactacattc acctgggagc tcagaagccc ttcaaggcca 57600 gaggcaaatg tgcctgccat taagagaaca aacgtttata aggtgcctac tgtgtaccag 57660 gctacccaca cccaggactt gccagtttcc acagtttggc aaaacctgcc catcctgctt 57720 gttgggacaa attcctgggc aggcagcatg gcccgcaggt aagacatgtg agagctggaa 57780 acagcactct atttgggcta ttccccccgg aagcagtaac atctacaatg ggcaggtcag 57840 tggcatcttt tggaggctcc ttcaggtttg tctgggatag aaggggagct ggagctccct 57900 aagaagttcc ttctgggtat atccctcccc tcaccacttc caggacataa tgggggtacc 57960 tcacaaggcc gattctcctt gggtataacc tccgctggct tctgcccggc agaaccgatg 58020 gtaaaggact aagtgagaag gagatttagg gagaccaccc tcctctcagg accaggggcc 58080 aggagagatg gagaggggaa ctcggagacc aactcaccga aacaggtctc tggaggtgaa 58140 gtaagccggg actgacaagt aactccccat cttcttccca caccagatag acaggctcag 58200 ctgcaaatcc gtctgtgact gcctcaggcc ggctgtagat ggccaccatg acaggcccgg 58260 ggctcccggc acctctggct gcaggcaggc tgccctgagc tcacctctcc ctccggagca 58320 gctgcgggag cctgaggact ccaggccact tggcccccag cagattccca caggggctca 58380 tggctgggat ggctcctccc tagttctcag aagctcaggc ggcccctctg gactccgaga 58440 aaacgacctc tctgtggagg ctacacacac actggcattc ttgagcaggg gccggtgact 58500 agctaagaaa gaagcgctgc tgtcaagtta gccttcttct tcagtcccac ccctgaatga 58560 gggagggagg gaggaagagg aggggctccc gcagaaccga ggtgtgtggt tggagcagct 58620 gttaggaaac agaccttgca ggcaaggggt ggagctgggc tggatcgagg ctgcaggcag 58680 gcgctgcaga caataactgg gaccaattga gcgtccatcc tgagctcagg gaagggcaag 58740 gcaggataga gtgtgaacat atctggcccc agatgtcctc aagcagagga gctgcctaca 58800 ggacagtaat tctgcttgga ggtggaaaaa aaaaaaaagc agaggatgcc aggtccagga 58860 agagccacac cagacggggg gacctctggt aggagagaca ggtccagaga gccatcctag 58920 ctctgagctg ccatctgttc tgtcctggca ctagggctcc cattcattcc ctccctctgc 58980 ctgtcctggg gacagcctca agagctgacc aatgggaggt gccacttcca ctccagggca 59040 gggctgtgtt gcaaataagg aaacaaggcc cagagtatta acctacacct gatgtgtctc 59100 catgtggcaa acactatatg cactctttta tttctctgag acaggaatta ttcccactct 59160 acagacaaga aaagtgaggt acagagagat taggtaactc actcaaggtc aaaaagggag 59220 tcagtggcag ggctggaatt taaatgtagg ctcatgtgac tctagagctg gagctctccc 59280 actaccaggc ttcattctgg ctctttaagg agaaaaatct tttccaaagc tctctgcaaa 59340 taggatggag cccaggttac

tctcattcac tcactattca ctgagtgttc acatgcagaa 59400 caccatccat tggcctcagt ggacagtgga gcttcttcta cttgtcctgt gataaccatg 59460 cttttcaaac tgaaaaatgg ggcatgaggg agaaaaaggc ctggggtgcc aaaagggatt 59520 gataagccta ggtatctgga atgggagccc acctgaacag cccccagttg tgacgatgac 59580 caaaccagag cctaccatgt agaaagccct tgtctccctg cctgcaggat tgtaaaggaa 59640 aaagcaaggc tgctggagga aaccagaaca ctcagatctc actactggat ttggggcagt 59700 gacatcagct ctcccttacc aggcacacac cgctcaccat tgtaaagagc cagaagtcac 59760 cgtgcagctt ctatctctta ctgtgaacca tggcaggaaa gtctgataaa gatggtagat 59820 ggggttacaa gggagccttt tcccattcca ccaactggac acagggacaa caatgcatgt 59880 gataagagca catgggtttg aatactgtta agaagctacc atttattgag cagttaatat 59940 cttctaggcc ctgtgttaag tgcttagcat ttattatcca tcatgtttaa attgccagta 60000 aaaggaggaa acgtcatcag cctcatttaa cagattagga aataggttct gaggggttat 60060 gtcactattc tcaagacaaa tagctgataa gtggtgaggg tgtttttttt ttttgttttt 60120 ttttttttga gtcagggtct ctctctgtca ctcaggctgg agtgcggtga tgccatcatg 60180 gctcactaca atcttgacct cgaccttctg gactcaagtg atcctctcac ctcagcctcc 60240 agagtagctg ggactacaga tgcgtgccat cacacccagc tgtgaggctg agtttcaaac 60300 ctggtacata tggctctaga gcacaggtca aggcactttt tctgtaaagg gccagagagc 60360 aaatatctta ggctctgcag gccatacaga ctgtcgtggc cactcaattg tgtcattata 60420 gggcaaaagc agccatatat aaaacataaa ctaagggaca tggctatgtt ccaacagata 60480 tttacttatg gaaagatttt tttctttttt ttttttttct tttgagattc agtctcacac 60540 tgttgccctg gctaaagtgc agtggtataa acatggttca ttgtagtctc aaccacctaa 60600 gctcaagtga tcctcctacc taagcctcca gtgcatcctg ggaccacacg tgctggccac 60660 catacccagc gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgcgtgcgt gcgtgtgtcg 60720 gagtctcgct ctgttgccca ggctgcagtg tagtgtcgcg atcttggctc actgcaacct 60780 ccgcctccca ggttcaagca attctcttgt ctcagcctcc caagtagctg ggactacagg 60840 cgcatgccac catgctcggc taatttttgt gtttttagta cagacagggt ttcaccatat 60900 tggtcaggct ggtcttgaac tcctgacctc aggtgatcca cttgcctcgg cctcccaaag 60960 tgctgagatt ataggtgtga gccactgcgc ccggccctgg cttatttttt tttatttttt 61020 gtagagacag ggtctcactt tgttgcccag gctgggacac tgatatttga gtttcatgta 61080 atttccacat gtcacaaagc attcttttgc tttttttccc ctaaccatta aaaatcacag 61140 gtcatatagg ccaggcatag tggctcatgc ctataatccc agcattcgag aggccaagga 61200 gggaggactg cttgaagcca gaagtttgag accagcctgg gtaacaaacc aagaccctat 61260 ctctactaaa aaaatcagtc aatcaggcca gtcatggtgg ctcacgcctg taatcccagc 61320 actttggaag gctgaggcgg gcagatcacc tgaggttgga agttcgagac tagcctgacc 61380 aacatggaga aaccctgtct ctactaaaaa tacaaaaatt agccaggcgt ggtggcacat 61440 gcctgtaatc ccagctactc gagaggctga gacaggagaa tcgcttgaac ccaggaggca 61500 gaggttgcgg tgagctgagt tcgtgccatt gcattccagc ctgggcaaca agagtgaaac 61560 tctgtctcaa aaagaaaaaa aaaatcaatc aatcacaggc cgtattaaaa taggcaatgg 61620 gccatagctt gccggcctct gttctagaac cacagagctc aaccactctg tttactacct 61680 ctaatagtga agaacagctc ttggtgtttg tgcagagctc agccatatct atctatctat 61740 accacgaaga caccacactc tagccccaga ggcagccaga agaaggaagc actgaacagg 61800 tgctcaccct gtattaaaca ttgcttgcag cactacttgt atgaatgaat tttaaccccc 61860 actattccac agtgctgtga tttttctctt tacagataaa gcaactgagg tacagggagg 61920 ttaaatcact tgcctgaggt cactcagctg taaatgtgag aagtgaagcc aggatttgaa 61980 cccagactag acattataga caacgttcta ccatgctata ccaaagctca gcctgggccc 62040 agagccagac tgtctgggtt tgaatgcgac aatgcactgc atgtaagccc ttggcacaaa 62100 gtctgggaca cattaaaggt tgataaatgt tagccattaa tatcattaag actattgtta 62160 caactactgt gggctagcta tgtggccttt agcaagtcac tctctctgtc tgggccttgg 62220 ttaggtctct aaatagctcc cagcatcaac atttttcacc cctatgaggt tgcagagggc 62280 tctctatttt ccttgggtct caagttgagt ttaaactctt gagcaggagg tcaggatcct 62340 agccgagggg acacacaagg gccacagagg aggtgaggtg ggctggaagt ggggaaataa 62400 catacgggat actgaaaggg ctgcccagct ggagagctgg gagcaatctt tctcccagcc 62460 acacagacaa ctatttctca ccaaaaatct attatgttcc cctgtaattc aatcaggcaa 62520 gaagggggcc ccaaattaag tctgggacta gcaaattatc ttttaattgt accctctgat 62580 ttccatgtga tgaacacagt actaatggaa gaatatgcaa gccacaaaga gactgaggcc 62640 agggagccta tgagcataac tcctcttgac atttcacaca gctctgctgt tccagcggcg 62700 acgggctcag tgagtcggtg tctaggaatg tgagcaggag gctgcaggcg ctctcctctc 62760 cccctactcc tcttacaaag gacttggtgg gtgggtgggg aataagtgag aggacatctc 62820 aatgccatga aaactgcctc cccctggaag aggaacagcc ttctccccat gtcctgagtt 62880 gaagcagaag cccctcccag gtggaatcca tttgacctcc aaaaattcag acttcaggag 62940 gaacctttga aggattgatc accagatgtg ataagctgct ggctgctcag acccaagtgt 63000 gtggttcctc agagccaact tcaaagggcc caagccaccc atcactggga gatgaaatgt 63060 cacactggag gatatatttc accctcccac ccttggaaac tggtcctgga tagaaaactg 63120 ctcttctagg tcctcagagc agctggcaga acattcatca gttatggctg ccagaggcaa 63180 ctgcaggaat cctttgactg gcaattatag tagggataaa atggcaggag aggtgttaat 63240 ctccagcaca tttcataagt tggaaacctg gcacggagct gaacaaactg actccttaga 63300 accagctgag gcacaggtct tcaaagcgtc tgtgacaggc tggagaacaa tagccttcat 63360 aaccggcagc cccaagtgaa tgttcaggca aggtgtggta agtgaatgaa tcaccccaac 63420 cttttgtcgg aagaaagctc tggtcaaaca attcaaaacc caagaaactg tttgtgtgaa 63480 gccctctatt ggctgggagg actccaatca aggaagagaa tttttgagga ctccgaagcc 63540 tccaaatact gaaaggtaag cattaccacc cccatctact aaccatcttt cgtgccccac 63600 tcctcccctc ttccaaatca ctttctacat tatagcagca gtcatccttc taaaacaagg 63660 gtcccgggca ggcatggtgg ctcatgcctg taatcccagc actttgggag gctgaggcag 63720 gcagatcact tgaggtcaag tgttcgtgac caacctggcc aacatggaga aactccatct 63780 ctgctaaaaa tacaaaatta gctggatgtg gtggtgtgtg cccgtaatcc cagctactgc 63840 ggaggctgag gcaagagaat cgcttgaacc cgggaggcgg aggttgcggt gagccaagat 63900 catgccattg cacaccagcc taggtgacag agccagactc cgtctcaata aataaataaa 63960 taaaatgtcc cagcaattcc cagcttcaca gggttatgag cattaaatga gaacatatgt 64020 gaacaagctc acttcagtat ctggctcatg gaactcagtc agtgttttac agagtgagag 64080 tttagtatct gctactcctg taatgtgatg tcatgttcac aaacaccagg taaaagacaa 64140 tatttggcat ctatcttagg tatcatggaa agagaaaaga atttggcatc tggatagaac 64200 tttagagatt tagtctaatc ctttgtttta cagttcatga acttgaaact aggaatggag 64260 aattggaagc ccaagacata tgaggatacc aagtcacatg aaatgtgttc agattttcag 64320 actgggagaa ttatttccca atatattgaa aaaagaaaat atgttggcac agtgatggaa 64380 ccattgttag taactttgga gaaactggag aatgggtgca atatctccaa agtgtaatgt 64440 tccatatcta ctatatacca ggcgctgggg atgtattcat gaaataaaaa tggagatagc 64500 taactggccc agttttcaaa aaggaggaaa aacatactgg aaaaaggaag ccttatgatc 64560 cttttgcttt gattccttca cataaattct aggcagatga tggaataagt ggacagtaag 64620 cacttagaaa aggagctgat catcaggagt cagcagtagt gaaatagtag tgactagtta 64680 gacttgactt catgttttca ctgggttact catcatgaga ccttatcttg gatttccaca 64740 ggcatttgat aaactctttc ctgatatcca gacagtaaga atgtgggcag gaaatctaga 64800 aaaatcagat acaagaactc aacataccca gcaatttgag gctctaaact gtagaggcag 64860 gattcctgaa taccttgcta gagctcacat tgaggaaagg gcatgggatt tgagctcaga 64920 aaacttttct tttaatttca gtgctgccct tcccagcagc ataaacttgg ataaattatt 64980 taacatctct gggcttccct tgtcctgctt gtgctatatt cctcaagagg ttgttgcagg 65040 aactgaacta gatgatgagt acaaaagccc tctgtaaact gaagatgcat tataaacatt 65100 agttattatc actgttctag tgctatagtt gctcatcatg ggggtcctga atcataggtt 65160 tctttactag gcatctgtgg acacctggta tgggccaggc ctatgctggg cactgacagt 65220 acctagtgcc tgccttcacg tagtttgatc tggtgataga cagatatggc cacagggtcc 65280 ttcctgggtg tgatgtgctt ggagacacat tgaaggaacc cttcccagag gagaatgaat 65340 gctgtgtcag agcagggcct ggaaaaagga ggagaagaca gcacctgcag gagatgtagg 65400 aggctgtaaa aggagttaag agagcaaagg tttgggggac tcccagggag ccttatgtgg 65460 tgagtcatca atggagtaca gcaggaggtg accagagccg ttcctgaggg aactaaggtt 65520 cacagagaag gttgctgttt aaggtcacag gtctaggaac tgacaaagct ggagtttgac 65580 ccaagtcttt ggactccagg tccaacatac taaaactgcc tcaaataact attttattct 65640 tgccatttga tttacagtaa tatttctgaa agtgtaacta aaggaatagc agcattggac 65700 cctctggtca gcttgttgaa aatcaagatt cctgagtccc acttcagata tacagaatca 65760 gaatcgctga gactggggct aagaatctgc attttaaaca agccccagtg tttctgatcc 65820 acactaacaa ttgaaaacca atgcttttct ttttcctaag tgcttttcca cttgatttca 65880 ttttattctc acaataaccc tcagaggcag gcaggataga tcactatcat taccttgtta 65940 caaacgagaa aatgaatgta cagatagctt gttcatcttc ttatcctgaa cgtagcttaa 66000 taaataaatg tttggtgatt gacattttgt taagccttgg ctaagtagag actttcacct 66060 tcctggtgcc actcttaccc atttgtaacc ccacagtagc tgcctctctc tttccttggt 66120 gacgcggcag tggtgctcac gttatggtat aaaaaggtga ttctaggcca ggcgcggtga 66180 ctcacacctg taatcccagc actttgggag gctgaagcag gcagatcaca aagtcaggag 66240 atcgagacca tcctggccaa cacggtgaaa ccccgtctct actaaaacac ataaaattag 66300 ccaggagtgg gggtgtgcgc ctgtagtaac agctcctcgg gaggctgagg caggggaatc 66360 acttgaaccc ggaaggtgga gattgcagtg agctgagatt gtgccactgc actccagcct 66420 ggcgacacag cgagactcca actcaaaaaa aaaaaaaaag tgattctaga agatagcgtc 66480 attccatgaa agtgctatct ctggaactaa aacaaatttc aaacaaacaa acgtgaggga 66540 tgacattagc caacttcaga aacggtgctt ctgcaagagt cagtgctact gatggcagtg 66600 gagcaccctc tgatctcagc aaaatctcta tagggcatca tcaggaagtc atgaccagaa 66660 tacagctgac acacaaaaga aaacaacctt aactcaagtc tggcatgaga tgctgagggt 66720 tttttttgta atcgtaagca gtatggagaa agaatttgtt agcacacttc cagcactgcc 66780 catgggagaa gggactctag cttttggggg aaaaatgaaa aacacggcaa aataagcaca 66840 gcaggttgct acagttgcag aaggcatgcc attccttgag gccctggttt tgatggttta 66900 agacttaggg atgacattta cagactgagg tcttagtcta cataagtttg agcttatctt 66960 atcacctcaa aagataagct cttgcctaaa agaatattgt agagcgaaga gatggtaatg 67020 gtgcatactg gatggacttt attcaagtgt ccaaagagtc gttcaacaaa tacatcattc 67080 acccagcaaa cactctgagc acccactaca ttctaggcac tttgctaagc tctgggatac 67140 aaagacaaac tagatacggc tccacacttg gagaatttca cactctaaga gtgatgctag 67200 atgtgtaaac aaatactgaa atggatataa ctgaggtatg aagagaataa cgaagagaat 67260 aacaaagaga gaagaagtct ctgattggtg gggagaggta tgggtggatt tggcgggggg 67320 ctcctccaca gaagatggga tggtattggc agactctaat aggctgattg ccaggcagta 67380 acaggcattc tggcctgaag gaacaacatg tgcaaatgca ctgaggcata aagagtatgg 67440 tatgctcata taacgctgag caggtctgta agctctagtg catggcacat atgggcagca 67500 attagacagg aggccagaat ggtggaagag agtaggggca gagcactaaa gaccaagtct 67560 gctaggctaa agagttgcct acaggcagtg aagagctatc agaggtattt aagcaagcag 67620 tgatttttaa cagaacgcaa agctgaaatg ccaaagagaa tgctgatctt tagttgccag 67680 tttggctctc tgaatgggta taaatgccta aagtctacag ttggccgtgt atatgcccat 67740 gtgaaatttg ctggccaact agtgttcact aacagcagag tatgcctttg tcctggggcc 67800 acatctctac tgccttgtca ttttaacagc tgatatttgt ctatatgggc tgtaagcaca 67860 taagcatgga attgcaaccc cttatagata atcatccact gttgctccat gatactaatt 67920 agaaaattga atgtctaaca ttgagtaaca aatgctgtgt tgacagggac atccttctcc 67980 aggctgcact gggaaaaatg cttcggatat ctcaagaaat ctctaggcaa ttcaaggaaa 68040 aaagccctcg tctggcaggg aacacctgaa aaatcaccct ggttaacaga aaatctgcgt 68100 gtgatcttag gcaagccatt aaatctctct gggcttcaac ttcttcctct gtaaaaggaa 68160 ggagttaggt gagcaaaaaa ttccataccc attacaggtc aatgcttaaa gaagcaacga 68220 ggaaggaggt gtgatcaaag gaaggttgac tggtggacca cccagagaac tcttcaaggc 68280 tgatgttttc ttggtgaatg accctaatct aggcctagct tttggccttt caggtttttg 68340 accttcctaa tgtccaaaga ggtgtagaca ttctgtgatg gttctgacct aaccatttat 68400 caaaccctct gtacacttat gaattgacta ttaaaatcag aacactcata tcccctatac 68460 aggtactact tccagaccct tcctgttatt aagtatccca ggaagctgaa ttaggcatca 68520 gaaggttgct ctgtgagcat ggacttaaaa taaagggaaa tgagtagcca ctgaaagaaa 68580 tttcatcctg gcagtggtga gtcagccaaa ctagcccagg ttgccacaaa ggaccctatt 68640 ctggtgacca aatctagatt cagcatcttt atctgaatac agtactagtt ttgcttcact 68700 aacttttcac tttctgtttc attgctggcc acttatttat tatattggtt ttggtttttt 68760 tttttttttt ttgagacagt gtctccctct gtcacccagg ctgaagtgca gtggcacaaa 68820 ctcggctcac tacaacctcc acctcctggg ttcaagcaat tctcctgcct cggcctccca 68880 agtagctggg attacaggga cctgccatca tgcctggcta atttttgtac tttttttttt 68940 ttttagcaga gacagggttt caccatgttg gccaggctag tctcgaactc ctgacctcaa 69000 atgatctgcc cacctcggcc tcccaaagtg ctgggattac aggtgtgagc cactgcgctc 69060 ggccttatat tggtttttaa actaagtttt aattgaaaaa aataactact tctttagata 69120 tgtgcgacaa tcaccaattc acacatatta ttcagccctg gcagacattt gcctctctag 69180 taactaataa caaagaacaa acattcatga gtgctctgtg aatagtgttc ccagtgctac 69240 acacactttt attcacagta atactgtgag ggtaggttgt aaggaggtag gtagtaagtt 69300 tgtatctcca tttcttcttt tttttttttt ttgagacgga atctcactct actggagggc 69360 agtggcgcga tctcagcaca ctgcaacctc catctcccag gttcaagcta ttctcctgcc 69420 ttagtctcct aagtagctgg gattacaggt gcctgccatc gtgcctggct aatttttgta 69480 attttagtag agacaaggtt tcaccatgtt ggccaggctg gtctggaact cctgacctca 69540 ggtgatccgc ccgcctcgac ctcccaaagt gctgggatta caggcgcgag ccaccgcgcc 69600 caacctccat tttttttttt ttttttgaga cagagtcttg ctctgtcgcc caggctggac 69660 tgcagtggcg cgatctcagc tcactgcaag ctccgcctcc cgggttcacg ccattctcct 69720 gcctcagcct cctgagtagc agggactaca ggtgcctgcc accatgcctg gctaattttg 69780 tgtattttta gtagagacgc ggtttcactg tgttagccag gatggtctcg atctcctgac 69840 cttgtgatcc gcccccctcg gcctcccaaa gtgctgggat tacatgcgtg agccaccgtg 69900 cctgctggcc tccatatttt tttattttat tttattttat tttattttat tttatgttta 69960 tttatttatt gagacagagt ctcgctctgt ctcccaggct ggagtgcagt gacatgatgt 70020 tggcccactg caacctccgc ctcctgggtt caagcgattc tcgtgcctca gcctccaagt 70080 gagtagctgg gactacagga gcatgccacc atgcctggct aatttttgta ttttcagttg 70140 agatggggtt tcaccatgtt ggccaggcta gtctcgatct cctgacctca agtgatccac 70200 ctgccttggc ctcccaaagt gctgggatta ctggcgtgag caaacgcgcc tggctcgttt 70260 cttttttttt ttttttttga gatagggtct tgctctgtca tccaggctgg catgtagtgg 70320 tgcagtcatg gttcactgca gcctcaacct cctgggctca agcaatcctc tcgcctcagc 70380 ctcctgagta gctgggacca caggcatgag ccaccatgcc tggctaaatt tttgattttt 70440 tgtggggatg aggtcttgct ctgttaccca gactgatctt gaaactcctg agttcaagca 70500 atcctcccgc ctaggcctcc caaagtgctg atattataag tgtaagccct gcacccagcc 70560 tgtatctcca gtttgttttt tttttttttt tttagactga gtctagctct tgtcacccag 70620 gctggagtgc agtggtgcaa tcctggctca ctacaacctc tgccttccag gttcaagtgt 70680 ttctcccgcc tcaggctcct gggtagctgg gattacaggc acccgccatc atgcctggct 70740 aatttttgta tttttgtaga gacagggttt caccatgttg gccaggctgg tcttgaactt 70800 ctcacctcag gtgatctgcc cacctcggcc tcccaaagtg ctgggattat aggcatgagc 70860 cactacgcct ggcctctcca ttttctagat gagaaaaatg aagcacacaa agggcaagta 70920 acttgcccaa agtacacaga taataaaagg cagaaccagg atttgaaact aagcaatctg 70980 gttctagagt gtgctcttaa ctacaacaca atactgcttt cattacttgt ggatctaatt 71040 agttcaactc acagaggaca aacttcattt ccaacttctt gggggaactg ccaacctatc 71100 caccccactc cccatcataa atcacctata agtaaaagat actatgcaag tattccattt 71160 tttccactct atattgaata tatatcttta gttaatgcca tctttcaaat atacaattta 71220 agaaaacaaa atgaaacaaa acaaacttac gattggaatt gaaatttttc agatttcagg 71280 gcaattcata atcagtttgg tggctagagt agctgaactc attcttcctc tcttgccctc 71340 ctctccggag gtacctaggg cttgttcctg cctggattgt agctacagag aagtgcagct 71400 caagacctgc tgctggaaag aaggactcct ggggtcagct tctctggctt ctactcacta 71460 tgggatagct cctctgaggg caaaagacaa agctttaact tatcaccctg acacttgcag 71520 gcaattttct aaaacaaccc aatgtccgga actgattccg tcttgccatt tacagtaact 71580 gcagccacgg tggctgctat aggaaggatg tggggaaggg gaaggggaag ggcagggaaa 71640 agcctgactt acatcatatc tcttggccac ctctagcaat tcattcaaca aatatccctc 71700 ctatgccaac aatatgctca gtgctgacac aatgaggggc aaaaacccca cagtccatga 71760 ccaaattgtt ctattagagg tcttaagata tcattaagga gatgatcaca tgaataaatg 71820 tgagattaaa actacttttt taaaaaaagc ctcaaaggaa aggtctatga aaacataaaa 71880 cagggaccta acctattttt cagggtgagg aattacttct atatttctct gagccatcca 71940 ggtaaagatc taaacgataa gcaggagtta agtgaacaga gtaagggggc attctaggca 72000 gagggagcag aatgaacaaa gcccttgtca gaaggagggc ctgtccagaa gagaggtgag 72060 gctgaagtgc agggagcagg aggttgtgga gatgtggaga gaggccacat tacggagggc 72120 tctactgtag gccaaattaa ggaatttttt tttttttttt tttttttgag atggagtctt 72180 actctgtcac caggctggag tgcagtggcg tgatctgggc tcactgcaac ctctgcctcc 72240 caggttcaag tgattctcct gcctcagcct cccaagtagc tgggactaca ggcacacgcc 72300 accacgacca gctaattttt gtatttttag tagagatggg gtttcaccat gttggccagg 72360 atggtctcaa tctcttgact tcatgatctg cctgcctcgg cctcccaaag tgctgagatg 72420 ataggtgtga gccaccgcgc ctggccaagt taaggatttt ggtctttatc caagaacact 72480 gggaagttgt ggaagtatac aaggtaggag agacaacaca gagtgacaca gtcaagtttt 72540 tttttgtttt tttttttttt aagatcactc cttccagcca ggtgcagtgg ctcacacctg 72600 taatcccagc actttgggag gccgaggcag gtggatcact tgaggtcagg agttcgagac 72660 tagcttggcc aacatggcaa aaccccatct ctactaaaaa tataaaaatt agctgggtat 72720 gggggccggt gccttaatcc cagctacttg ggaggctgag gcaggagaat tgcttaaacc 72780 cgggaggcag aagttgcagt gagccgaaat tgtgccactg cactccagcc tggggaacag 72840 agtgagactc tgtctaaaac aaaacaaaac aaacaacaaa aatcactcct tccaactgct 72900 ctatagagaa cagattaggg ggtgcagagt ggctgtggga gatgaggcta ttgcagacat 72960 ccaggtgaga tgatggtagc ttggagcagg gtggtggtgg gagaaaagga aagaagtaaa 73020 cctaccaaaa tataatttag agataaaact gataggcttg gatatgcagg atgagagaga 73080 acaggtatca aggattccta ggtttctggc ttaggcactg ggtggatggt ggtgcctctc 73140 aatgacatac atgtttcagt ggaagaggag ccagttttag ggggaagagt gaaagtccag 73200 caaagtctag agaagagagt ctgaagtgcc tggaagacat tcaaatggac aagccaggtt 73260 gatagtacaa catatgggtc tagaactcag tggaaaggtt taggctggag atactgattt 73320 tagggtcatc agtgtgtgga ggacaatgga aggaagtcat gagtgtgtgt aagactgcct 73380 aaggagaaaa cagcacgcct gaaggaatgg taacatccca gagctggaca aagaaggata 73440 agcaaacagg tattaccaga gaggtaagag aaaaccagga gagtgtggaa tgtcatgaaa 73500 gccaagggaa gagaacattt caagactgac agatactaat aataaatgct aacatctgtt 73560 aagtcccagt catggccaga cattctgctc aggactttga atacatgatt gaatttaatg 73620 ttaacaactt tttgaggtgg gagccatttc ccttttcata gacaaggaaa ctgtggcaaa 73680 gaatggttaa gcagctgact catggtcagg tggctggtaa gtgaagctgg catttaagct 73740 caagcagcct gactccgaac tttatccact tttctctaat acaaccctta gtgcagtttg 73800 ggaggtcata taagatgaag cctgaagagt ggtcggtaga cagactgatg aagctgttat 73860 tcggaatatt actaaaggaa tgttgtttca ggggagaaac agaatgaaag ccaggctgga 73920 gcccatggtt aggaatgctc catgacattc tctatttcca gctgtcttag ggaaccagtt 73980 aagagaccag gccaggtgcc gtggctcata cctgtaatcc caacactttg tgaggcccag 74040 gtgggaggat ctcgagccca ggagtttgag accagcctgg gcaacagagc aagaccctgt 74100 ctctacaaaa aattaaaaaa aaattagctg ggcatggtag tgtgtgcctg tagtcccagc 74160 tactcaggag gattgtttaa gcctgggaga ttgaggctat agtaagctat catcatgcca 74220 ctgcactcca gcctgggcaa tagagcaaga cctatctcaa aaataaataa gctaattaat 74280 gaattaatta agaggccagg ctagtatgcc aactccgtat cccccacagt gcctaatttg 74340 atgactttta tatatagcaa atgacgcttg atatatttgg atagttaata taagatgcac 74400 aatgttgcca tgtgctgctg

ctaatccttc acattaaacc attctaatgt tttcagagtc 74460 cttgatcatc acaactactc catgagatgg atttctttta tgacatttta cagataagaa 74520 actgaggctc acaggggcta aggaacttgc ccacagttac acagttagcc tagctcaact 74580 aagactcaaa tcagattttc tgtctccaag tctactgttt tttttttttt tttctcctgg 74640 gagtcctagt ggaaagcaga ctctcttggg agccagggag acctgagttc aaatatcatc 74700 tgtgtgaccc tggacaagtt actccaaacc tttctgggcc ttcctgtttt agtataaaat 74760 gggggttgca ctggccaggc acagtggctt acttccgtaa tcccaagcac tttgggaggc 74820 tggggcagga ggatcgctgg agttcaagac cagcctgggc aacatagtat taataagacc 74880 ttgtttctac ttaaaataaa aaaaaatggc aaggtgtggt ggcacgcctg tagtccaagc 74940 tgcttgcaag gctgaggtgg gaggattgct tgagctcagg aggttgacac tgcagtgaac 75000 tatgattgta ccagtgcact gtagcctgga caacagagca agaccctgtc tcaaaaaaag 75060 gtgggggttg cagggttatt atgaagattg aatcagataa tctaagtgag gttcttaata 75120 caacgtttaa ttaatatcag ttatctatct ctggcctcat ctctctccat ttttctacct 75180 ctgcctccta tagaagctgt gaaacatctg tgggtcctta gttctctctt ctcaaagtaa 75240 agagcaggat taaggcacat tcaagctcat atgctgctgc tacatcctag gagtaccact 75300 ctgtggtcag gctggagtct cttgtagggg cagaggaaga accagatgtc tgcccttcct 75360 tcctctgtca ggcaggcccc agccccctgt ccaatagcca gccttaatga tctacgggct 75420 ggctgtttcc taaaagataa actggacaaa tgagtaaaca ccttctggag aaggccacag 75480 ccagaatcaa aggtttaggt tagtaagtgt ggcagcaaca tcaacagcat aacagcagat 75540 ggcagggttg ctccactgac tctacatcag gagcctgaga cccagaagaa agttaacagc 75600 acttttgttg acattataga gtccatgaag cctttaaact aacacccttc aatgttatct 75660 gacactacca gtgtgtggca ggcagggtga gggctcttta ccccatatta tataagagga 75720 aactgagcct cagtgaggtt aagaaatatg cttgcattca agaatgccaa gagactcttg 75780 caggcaagga gtaagaatgc ctgagttcaa atctcagcta tgctacctat tagctctgtg 75840 actttaaaca agtaacctcc atttccctat tctcgaagta ggtaagacta gtactacatt 75900 ttattaagtc attgtaagga ttaaatgtgc tatgcatgtc gtatgctcag gagggtgtct 75960 ggcacagagt actcaataag tggtacctat tactgtaatt atgattctac caggcttgct 76020 tagatgggga tgaggggaga gaaaatgaat gtggctttca gcatcacaga aagtaccctg 76080 ctgtcagcca acatattaca acacagtctc tggttgctac gtgtgttatt tcttcactgg 76140 ccttcctgga gtcactaaat ttagcggaaa tggtctgttg cctgatgcag tgaccacagt 76200 cttctatctg cattagccct ttcccagagt ataggtatta gtaaccgctt ttcaaaagtg 76260 aaagctcaaa tagtcttatg tttgcaatcc tgagaaagga agtcctgaaa gttcccagga 76320 gccttaagag cggtggattt tccttctgat aatgctgcta ggaaccaggt caagcaatag 76380 agacccacgc tggggccatc aagactaata ggggtagctt ttcttccctc ctcctaagcc 76440 aaacaccttt gatcagggtg aacggacaat catcaaaaaa gttgtcaagg tcctctggct 76500 tgctaacatg ccaagaggcc aggtcaccat tgatagctcc acactttaac ctcagctaca 76560 aatgacatgc tctctggcta ctctcctggc ctctcctaag gagagagagc caggtccaga 76620 gaacatcaga aaggattgcc ccagatacag aattaatggc actgctcaag gaaaggaaag 76680 agaggtaact cagagtttta aaaaaggcct actgggctgg tccaagtaca atagtgttta 76740 caagtaattg atcactacca gttaccgatt tctttgttcc ttttccactc ccacaatttc 76800 acttcactag cctaaaaaaa aaaaaaaaaa gaaagaaaga aagaaagaaa aaaaagaaaa 76860 gaaaaaaagg aaaaaaaaga ggcctgttgg gaaggcttgg gaggactagt cagccatatg 76920 tccaggagat ccaaaagatt ctggccagct gcctaatcgc accagcacaa ttactgacag 76980 agctactttc agttttgtca ctggcctcca ttgcacagtc tgaggttcca gctttaagta 77040 gcttcctgtt gtcctgggca cctgagggtc tgtcggaagg ctaacagagg caggattatg 77100 gatgtggctg cagacagaag aatggggtaa tgtaagggag agatgagggg aggagtttag 77160 gatggacccc agcaatttct ccattcaata tccagcccca ccctgtgact aggaaaacaa 77220 aggtactggg ggaaggggag aagaaaagtc atttccttta ttgtaactgt agcccagctg 77280 ggtaagagca aggctggaag ggggccttga agaatgaatt tctctgagta gcacagaggg 77340 agagtcctcc tcccagcagg cctgcactac tcaggtactc taaattcatc agagaaacac 77400 tggcaagctg gcgtgggaga gatcttacaa gaccattcag gttgatgccc catgttcctc 77460 aaaacccagg ttatctctgg ggtcagacaa atacaatcct tcctagccct gaagattttc 77520 ctccaactgg ggcaaaagtc aaattagatc caaaagacag tcactctccc cagggcaaat 77580 taccaggctc tatctgaggg cgccgtgaca tccagtttga atttaccagg ggaaagctca 77640 gaagtcagga gatgtgctcc ttcagcacag ctggattaga gtctctgtcc tcaaggtaaa 77700 gctgcaacta ggagacagaa cctagatact ctacttcctc cacgggaatg atatttggct 77760 tgattgtgtc agggtagttc aaagttgccc ttaatccctg gggctccaca tcagatcacc 77820 aatgaatgtg taataagaga aatgtataca tataggtgta tatagacaca cactcacaac 77880 ataatataaa gtgacagtta ctgattatta agggtttttt ttttcatttg ttttgttttg 77940 agacaggggt ttcactctgt cccccagctg gatggagtac agtggcatga tcacagctca 78000 ctacagcctt gatatccctg ggctcaggta atcatcgctc ctcagcttcc caagtagctg 78060 ggactacagg tgtgtgccat cacgcctggc taatattttt gtattttttg tagaggtgga 78120 gttttgccat gttggccagg ctggtctcaa actcctgggc tcatgggctc aagcgatcct 78180 tctgcctcgg cctcccagag tgctaggatt acaggcataa gccaccacgt ccggccctat 78240 taagagtttt ctatatgtca gatgctatgc tagccacttt atataggtta tcacatttaa 78300 tcctccctaa caaccatgtg gcatgagtaa tattcttatc ctcattttac agattggtgc 78360 ctgaagctca gggaagtcac ttaaggctag ttaataaatt gcaaagccag gatttaaaac 78420 catagtctca ttccatagcc tgtactcttg gtggtggttg tttttttgcg atggagtttc 78480 cctcttgttg cccaggctag actgtaatgg cacaatctcg gctcactgca acttctgctt 78540 cccggattca agcgattctc ctgcttcagc ttcccaagta gctgggatta caggcatgtg 78600 ccaccatgcc aagctaattt ttttctgtat ttagtagaga tggggtttca ccatgttggt 78660 caggctggtc tcgaattcct gacctcaggt gatccacctg ccttggcctc ccaaagtgct 78720 gggattacag gcgtgagcca ccacgcctgg cctgcctgta ctcttatcta ccatgctaac 78780 gtgtctactt cctctttatg tatttgtgta catatgttat ctttctgtct ctatctcaca 78840 cacacacaca cacacacaca cacacgcacg cacagagcta acaagctagc atctgactag 78900 acctacaaat gacccaagag ttcagtgcta gggccagctc ttgtcatcca tggcctgagc 78960 aagtcttttt ggtttcaggc ctcatctgtg atatgaatgg gttataccat atagtgggtg 79020 gtttcttcta gttctgaagt tttttagctc taagagaatc cagaaattcc aaagattaac 79080 ttgctctacc ctgtcctgct tattttggat agaaaatatt catacacata ggaaaacagc 79140 aagaatatga acatatgggt tacatgccaa ggcgagaccc aatctgtgaa ctcattgggt 79200 tttgacgtta cttattagtc ccagctataa aatgaaagga ccagccaaag gctttaacta 79260 taaggtccct tacagctctg acattctctg ctcctgtcat actaaatgga acagaaaaga 79320 cagaatcaac ttccctggga gtaaaagggg caagaaccaa ggcaataaga tccacagaaa 79380 agacttgaga gctctgagtt atagctgaaa ggaaaggata ataatgatgg ttgctttcca 79440 actcttccag aggccagacg tctccaggcc aatcccctat atggttccca gggaagaggc 79500 aagtgtttaa aggtcaactc aattacttgg tataagcaca gggatgtttt acaacaagag 79560 ctatgtgcag gagctggaat ctacagcaca aggtgcctgc ctagtctatc tcattctcag 79620 gatataggca cagccctacc acttcagacc ttgggggcca ggcatgccca tccagcctct 79680 ggagtggact gctcttcttt ccaccaacaa atttcaacta ttttacgttg tgaagaatat 79740 aaagacaagt tcccaccctt gagaattcca atccgatggg aggaaggaat aaccattcac 79800 tgggtgtcta ccatgtactg gatacactgc atatattatt tcattcaatc tcaacaagat 79860 tattaccatc cattttccag atgaagaaac tgagcctcag acagcaggaa caaatctgat 79920 ttgaagtctg tataattttt aagaaactga gctgcctaca aaaataatgt agctataggc 79980 agggcgcggt ggctcatgcc tgtaatccca acattttggg aggccgaggc aggcggatca 80040 cctgaggtca ggagtttgag accagcctgg ccaacaaggt gaaaccccgc ctctactaaa 80100 aatacaaaaa ttagctgggc gtggtggcag gtgcctggag tcccacctac taggggggct 80160 gaagcaggag aattgcttga actcgggggg cagaggttgc agtgagccaa gatcacatca 80220 ctgtacacca gcctgggcga cagagcgaga ctctgtctca ataataataa caataataat 80280 aataatgtag ctataataaa gctagtaaca aaaagtagga acctagggag gcaacctgtg 80340 gtgaggaaga gctggctctg ccaaccacac taaaaacaac tcttggctgg gcacagtggt 80400 tcacgcctgt gattccagca ctttgggagg tcgaggtggg tgcatcattt gaggtcagga 80460 gttcaagacc agcctgacca acatgttgaa acccccgtct ccactaaaat acaaaaatta 80520 gctgcgcatg gtggcaggtg cctgtcatct cagctactca ggaagctaag gcagaaaaat 80580 cacttgaacc cagcaggcag agattgcagt gagccgagat tgcaccactg cactccagcc 80640 tgggcaacag caagaatccc tctcataaaa taaaataaaa taaaataaaa taaaataaaa 80700 taaaataaga atacaaacaa ctcttgaagt acctgcataa tctgtagtgc agccacagga 80760 aagtcactct tcctgggcct cagtttcctc acccataaag tgagggatat gggacaaccc 80820 tggaaagggc tcctctcatc cccccaccct gcctccagct ggcccattta tggctcttcc 80880 aatttaacct gggttcaggg gggccacact tgaggtttgg tcatgagctc ttccttggta 80940 cattcctttc cccaccctaa gattgaaatt ctcaactcag aagcttgttt ctgtgttttc 81000 catcagaaca tgaaatagtg cttggcccat agtacactgg taaagatggg aggataggcc 81060 cacctaccgg aagcaagagc cgtgccaggt ttcgttgaca gtcctgtacc atatctggct 81120 tggagcaatg tggtccccac agcctggaca cctccagaca tcttcacctg cacacaaaac 81180 caagaggttg agaggcccaa agtagcagga ggcaaaggga caggattcct accatgtaga 81240 ataagactga gttaacagca tctcatttga aagggttagg ccaatgctct gctagatgca 81300 cagtttctgc ctccacaaga tctctggtaa gcacttgtcc aacctctgct catctctcca 81360 gggacaagga actcatggcc tcaaaagtag tctcattcca ttttctaaaa atggttctga 81420 ttatcctttt ttctactgaa acaaaacttg cctttttcta gaactttcag cctttgctta 81480 tagctctgag aagaagaaac gaacacaatc tccttctttt cagtgtcagc ccttcctatg 81540 actattccca gccaacagcc agaaacttct ctctgggtta aacatgttac tgccttttcc 81600 tattcctcaa aagccctgtt ttttcagatt tttccatcac ctaatccaag agctcattta 81660 ctcaaccaac attgaataaa ttggtcctct agatcagcag tcctcaacct ttttggcacc 81720 aggggccaat ttttccacgg accctaggct gggggttggg gggcgggggg atggttttgg 81780 tatcaaactg ttccaactca gatcatcagc cattagtgag attctcataa ggagcatgca 81840 acccagatcc cttgcatgtg cagttcacaa tagggttcac actcctatga gaatctaatg 81900 ccaccactga tctgacagga ggcagagctc aggcagcaat gctcactggc ccgccgctca 81960 cctcctgctg tgcagcctgg ttcctaacag gctacagacc cgtaccagtt ggcggtccag 82020 gggctgggga cccctgttct agatacaaag ctctttgtat gttggaggct gttagattac 82080 ataatctctg ctccttaaga agcaaatcca ctggaaaaga actgctcttt catgttgttg 82140 atttttcact tggatgttat ttcagagata gaaccaagta ttattttagt tcagaaaaag 82200 aaaagtaatg ggtataaaag gggaagaaca aatatttaat gaatgcctcc tatatgccaa 82260 gaactctgct aggtgctttc atagacctaa tctcatttaa ttctcaaaat aatcctgtga 82320 cacaggtatt attatattca cttaatggat aggaaaatta aaacttgagg cagggggcag 82380 ggttgactag ctaagtggtg gatctagcat tcatactcag gtctggctca ttctaaagct 82440 tctgctcttt ccattctacc atgtcaactc ttgttcactc caatgagggg aaccaggaaa 82500 gtctttgtag aggaagctga cacttgagct gagccttgca agatagggaa gacttaccta 82560 tcactggctg agaaaggagg gtgaagggtt gtgtgagctc agagaccagc atagacaaaa 82620 gcacagagtc ggtccatgtt cctccaaaaa gagaggcctc aaacaaaata caatactcct 82680 ggtatggctc agatgtcaac ttcttgaaat aaagaggaca gctgagatca agctgtggta 82740 cctgactcag ccctagaaag caggacaagg ttgttacaag actcccttgt gcgctctgtg 82800 tatgcagctt tgttctctct gggtaactac agactgccac aggcacagtg acagtcaccg 82860 aaccctgttt cacaggcaca ggggccatga atagacaaag cacagctcct ggcacttcaa 82920 gattgctcaa catcattctg gagcagccaa tgtacacagt tgtccccctc gttccccaga 82980 gaagagttaa acaagctggc aagaggcctt aaaacaccac ctcaacccac ccattccact 83040 cttctcatgc ctcagtaata ggatatatat atgcccatca ctcattcttc ctgggtctaa 83100 aatcctcaga ctccttgtca agaggggcct ttttggtttt agggtgacag tggtcacaga 83160 gtatgccatc tctctcacaa actccaaggc agaaagtctg agagactcac tcaaaccaat 83220 cccaggttgg gttacggaca gtggacaaga caatgaatta gtgagagatt ttaatgaaca 83280 caaacatcca aatgaatctt ccaagttttg gaaatatttt tggaactctt acatgtaaga 83340 gctttcaggg tcagtttatg agctgccatg ccccaccccc agcacatctc attattttag 83400 agccacacct tgtttcttgt ttttactttt taacccaaaa ttaagtctgt aacctgacca 83460 cccacttact caacaattca atctcttggc tctgaatgat ttctatttcc aaaattcaaa 83520 caggatcagg actttccacc atgaggatat tcaagataac ttgttattgc cataccctcc 83580 agagcttgcc ctgctttctc cagtcttgag aaacccaaag acattcaatc aacacatact 83640 ttagtacctg ctttgggtta agcatgaaag acccgaaatc aagaccctct actctctcct 83700 ctcatatcca cctggtttca ctttccaaat gtctctctag cccttccctg tccttcaccc 83760 cagccctact tcagattttt ggcttctttt ccctatctgc tgtactcagc tggctcatcc 83820 acactgcaag ctatctcagc tctgggttag actccccagt gtccacggaa caaaggctgg 83880 gctactcggt atgacacccc tgttctggat cccattccat cttacttctt agaagaagtg 83940 cacttttagt tatctttaca gcacccctct ccctcactgg ctcctcctta tcttttaaat 84000 aagttcaagt cactgccatc aaaaaaacct ctggtactct cgcttcagca gcacatacat 84060 taaaattgga ctgagacaca gaaggttagc atggcccctg cgcaaggatg acatgcaaac 84120 tcgttaagtt ttaaaatcta atttagtttt aaaatctaat tttaaaaaaa accaaaccac 84180 tggatccttt tctcctctag ctaccatcct tgtttctccc cttcacagcc acatgtatga 84240 aaaagttgtc ttgggaggcc aaggtgggtg gatcacttga ggtcaggagt ttgagaccag 84300 cctggccaac atggtaaaac cccacctcta ctaaaactac aaaaattggc tgggcatggt 84360 ggtgcacgcc tgtagtccca gctactcagg aagctgaggc aggagaatcg cttgaaccca 84420 ggaggtggag gttgcagtaa tctcgccact gcactcacgc ctgggcaaca gagcgagact 84480 ctgtctcaaa aaaaaaaaaa aaaaaaaaaa aaaagaggct gggcacggtg gctcatgcct 84540 gtaatcccag tactttggga ggctgaggcg ggtggatcac ctgaggtcgg gaatttgaga 84600 ccagccatga ccaacatgga gaaaccacat ctctaccaaa aatacaaaat tagccaggca 84660 tggtggtgca tgcctgtaat cccagctact caggaggctg aggcaggaga atggcttgaa 84720 cccgggaggc agaggttgca gtgagctgag atctcgccat tgcactccag cctgggcaag 84780 agtgaaactc caactcaaaa aaaaagaaaa aagaaaaaaa gttgtctaca catcgctgcc 84840 ctcatttcct cacttcccac tttctgcata atgcactgca atctggcttc cacccccacc 84900 atttctctga aactgtctca ccaaggtcaa cagtaacagt aactgcttat tgctaaattc 84960 aatggacccg cttcagtcat tctttcagca aatatttatt gcatgccaac tatgcatctg 85020 acactgtgtt ggggaaagag gagcaaacaa gagagagatt aaacacaaag caaatattaa 85080 acaataatat aattatttat tgagggccgg gcgcagtggc tcacgcctgt aatcccagca 85140 ctttgggagg ctgaggcagg tggatcacaa ggtcaggagt tcgagaccag cctggccaat 85200 atggtgaaac cttgtctcta ctacaaatac aaaaattagc caggcatggt ggtgggcgcc 85260 tgtagtccca gctactcagg aggctgaggc aagagaattg cttgaacctg gtaggcggag 85320 gttgcagtga gccaagatca ttccactgca ttccagcttg ggcgacagag cgagactctg 85380 tctcaaaaaa taataattat tattattatt tatttataat tggggcaagt ggtacgaaga 85440 tatcaagttc ataactagga aaagggcggg cggccaaagt attccttgag gaagtaattt 85500 ccaagctgag ctctaaagga tgaatacaaa ttaacggggc aaaaaagggg ggaaggaagg 85560 ctaacactgg agagggggga catgtgcaaa ggccctgggg caggaacaaa aacttctcac 85620 acatcattaa agttggcttt tgctacctcc aaagggctag caaaccatgt ctggcccctg 85680 gtctgctaca atccttcaat aaacagttac tgaaagagca aatggtcctt acaatgtggt 85740 cccaaaggac ccttctctct caccattcct tacaaaagaa tgctctagtt acattttgac 85800 ctattttcta ttcctgccac ttttattcat gtacttgcat cctgacattc acacctccag 85860 ttattctcta tgtataagct tctctatctt ttcccttaat caaaaaaaaa attttttttt 85920 ttgaaacaga gttttgcttt tgttgcccag gctggagtgc aatggcacaa tctcggctca 85980 ccacaacctc cgcctcccag gttcaagtga ttctcctgcc tcagcctccc gagtatagct 86040 gggattgtgg gcatgcgcca cgacgcccgg ctaattttgt atttttagta gagacggagt 86100 ttctccatgt tggtcaggct ggtctcaaac tcccaacctc aggtggtctg cccacctcgg 86160 cctcccaaag tgctgggatt acaggcgtga gccactgctc ccggcccctt aatcaaattt 86220 ctatcctttc tttaaagttc cctaaaatca ggcagtgttt gtttcatttt gtctatacct 86280 attttacata atttgttatt taattacagt tcactgcata tgtttctctc tccttcagtc 86340 cctctctctc cactctcctc ccccacaccc cattcagaga actaaggtgt aagaactgta 86400 tctttattat gttcttatct ccagggccta accttgggcc tggtgcaaaa cagacattcc 86460 tttgtgtggt gaacccaact gaaaatttgg atccaactgc cagctataaa agcaatttcc 86520 aaagataagt tccaaaggtc agcacagatg attccactgg aataactgtt ctggctccca 86580 gattacctat gagtagtctc atgtggataa acctggcctc agtttacctg ttatgcattc 86640 acactgcttt tctgttagga agtacctgag caaagatatt cacccaaagc acacagcctc 86700 ctacgcccag accctcttca agagaacact cttgacttct ttagctctct tacagtctta 86760 aaaattcatt gatctattct cttaccacct ttattctagg aaatgtaaaa gaaatgtaat 86820 actgtaatgc aaagtcttag ggatttctgt gaagcctagt ggaggatcaa tccaaagtcc 86880 agtcagcctg ggaagttctt tcttaagaaa atatctcatt gtaccaggct gttcattctc 86940 tccctctata gtgtttacct ctcatatttg cagacttatc aacagtggct actgattgtt 87000 aagagtccag aaaagagccg ggcgtggtgg ctcacgcctg taatcccagc actttgggag 87060 gccgaggcgg gtggatcacg aggtcaagag atcaaggcca tcctggctaa cacggtgaaa 87120 ccctatctct actaaaaaat acaaaaaatt agccgggcat ggtgatgggc gcctgtagtc 87180 ccagctactc gggaggctga agcaggagaa tggcatgaac ccgggaggtg gagcttgcag 87240 tgagccgaga tcgtgccact gcgctccagc ttgggcgaca gagccagact ctgtctcaaa 87300 aaaataaaat aaaataaaaa aaagaagagt ccagaaaagg agcttgattt aagtaaatgt 87360 tcacagtacc ttcaaacaat aaaggaccct tattaggtgt ttaataaaca gaaaactgtg 87420 ttttcagtta ttattggaat ttgttgcttt taataagtgc aactgtgcaa cgtaaggtga 87480 gcactgcaac aaatgtctca ttataggggt tctcaccttt aagacctttt caatcttggt 87540 ataaaataca ttcactttac attcacttta tgaatgcttc tctctcccaa cttaattagc 87600 aatgtggccc tcaaacaaat gtgaatccac tggggcaggc gccaaaaaaa aaagaaggaa 87660 aatagacttg cctaaccacc acaaagctac tgaaagatgg tccaggaggg attcaaaccc 87720 atgctcagag actaccatgc cagtcatatt tttaataccc tatgcagcct cagacaagtt 87780 gagacttgct caagaacaca cagctattca gtggaagggt tggcctggta tcccagctca 87840 gagccaatgc agtccccaca atgttcacct taaatttggt ctaagagctt ggtttctgca 87900 aatgagtcct ttttaggctt caaaatggtg agaaatcctc aagcactgag agctcatgag 87960 actctaatgc ctagcttaaa tcaacatcct atcctttcat ttaaaaaaat ctttgaagct 88020 tctcacgttc caccagacaa cgagaaccag gaacaaaact cagccaattc agtgcagcat 88080 aaaacaagta tggtaacccc tgggcccctt gggaactggc gggtcaggtg tataaatccc 88140 acttgttctg ggacaaagca gaaagcagaa gggcagggca gcagctgctg gggaaaagcc 88200 aagagaaaaa gatcacattt taatgaagtg actatcaaaa agactaacag taaggattaa 88260 catgcctcta gatactctcc ctgtaaccca aagggttttc ttcctcacta gcttaccaaa 88320 ttttaccaaa aggagtgtct caggaaaaaa aaagattaga tgatttttaa aagagctttc 88380 gagcttctct aaaccttgga ttgttctttt gtaaaaggag ggatcaagtg atttcttcca 88440 gctctgagag actgacacca aaccaagggc ctctcctttt tcaggttaag gcacagacac 88500 aggtatctca gaaagtttcc ttcttgctgt tattctcttc ttcccttctt tggtttattt 88560 ggaaaaattt gtgaggggta aatgtatgtg tgtttgaaac ctgaatctgt cactgtttgc 88620 ctctgtgtcc ttgggcaaat tatttgacct ctctgagctt gtctcctaat ctttaaaaag 88680 aggataatac cacctgcttt acaggattac caagtggatt aatagaaata atgtaataga 88740 tgtgaaaata tctcccatgg tgccaggcac ttagttggac cgatttgtga ctaacttctc 88800 ttccttcctg cgtgtgtatc taggaagttg gctggggaaa aggttaagct gaatacagaa 88860 acttctaaaa tctgaaggga aggttttcaa aacaaactca gcaaactttt ttctatgtgc 88920 ccatgtacaa ggcacagagt aggccaggaa ttactggggc ccttggtgtg tactcatggg 88980 gtgtgaagga catggatata cacagaaata acatgtcaga gagggacaaa ccaggtgcta 89040 caggcaaggc aaactcagta cattaacaaa atacactgca gtgacaaatg agacagatgg 89100 ttcttatgtc tttcaggcca cccagactgc aacttccaac cagaagttca ctcaactgtg 89160 aatgagtagg cattttctta tctatggagg gcctataaaa atatctttat cagagaactg 89220 gttaaccaat tgatatattc tcatacagca gttctctgcc agttgtcaat gatagaggaa 89280 aaaaactact ttatgccaga caatgtccta agcactacgc aagtatgagc taactgaata 89340 caaagatccc atgagatcag gactagtctt aaagaactat tattgttctc attttacgga 89400 agaggaaact gaaatactca gctaataaat gtttgagctg ggattagacc acaggtctag 89460 tctccaaagc ctgtcttttt

ttttttttct gagacggagt ctcgctctgt cacccaggct 89520 ggagtgcggt ggtgcaacct cggctcactg caacctctgc ctcccaggtt caagcaattc 89580 tctgcctcag cctcccgagt agctgggatt acaggcacct gcccccatgc ccggctaatt 89640 tttgtatttt agtagagatg gggtttcacc atcttggcca gactggtttg aactcctgac 89700 cttgtgatcc acccacctca gcctcccaaa gtgctgggat tacaggcgtg agccactgca 89760 cctggctcaa agcctgtctt taactacatt ttagactttc tttcctggac aaaacaaatt 89820 acaggcagaa agacatgata aaaaagaatc ccagaaagaa tgttcaagga acactttaat 89880 gaaaccaggc attggtttca tgttctagtt actattcaat gtaaattaat aggtaaaata 89940 gtctaattct ttctactata taaaaataga taaaggatga gaaagaaggt agacttgtaa 90000 gagactgcta cagtttcagg tcctctcatt gaaatgagat gtgtgtgatg gtgggcccta 90060 tcagacccgc tcaaggttac actaacaaga aggcagccct gttctgggaa tcagctcagc 90120 ctccagaaga tgcagaaaat ccaccatgaa tgtggaaagc ctaatacagc cccttgatca 90180 tgacggattt ttatttagtt ttgaaatctt gtggtcattt tggaccctac cctgctccat 90240 cacatatcca ggaccatcca agtcaccctg gcctgcctat gtcaggaggc atcttttatt 90300 ggttggtgcc ttcttcattg ctaccactaa gacctcatct cagggcccac tatacccacc 90360 tccagattgg tggccctgtg cccacatcat gagtcttcct ttctctaaac ctacggtgcc 90420 tactgtagac tagaaacttc caaaatcctc agcctggcat taaaccctct agtccggttg 90480 cacccacatt ctcagctgta ccttccactt cctatgaatc ttccacctcc caatccttgc 90540 ctctaccaca cgtatttgct accctttatg aagacctgaa acttgcctac ttttgtctcc 90600 tactcccaaa gtttcttccc tactaagata tcatcttccc caccttcttt aagcctattt 90660 aagatttctc aagtcttacc cacttcaaga agtattccct aaccaaaact gatggccacc 90720 ctggataccc tgctattctt taaacatgcc aaacacattc cctgacaact cacttcttct 90780 atccccttac cctacttcac ttctcttcaa tggatttatc cctgaatatg atgttcatac 90840 atttacttgc tgtctatctc tccccaccag aacatacact acatgaggga agggatttgg 90900 tctatcttgt tccttgctgt atccctaggg gccaaaagag tttagcacat agcaggaact 90960 caatatatat ttgtggaata aatgtttgaa gagaattctc cctcatcttt gaaattctat 91020 aatgttatca tacgcaagcc ttataacagc ttgtcttatc aatttttttc ttttttttaa 91080 gagatgggga tcttgctatg tagcccaggc tggagtgcgg tggcttttca caggcgcaat 91140 cccactactg atcagcatgg cagttttgtt ttttgcctta attaccttaa ctagacagta 91200 agtttctcag aggcacaaac tatatataac tcatttccac aaatacttat taagggctta 91260 ccatgtgcca gaccctgtac gtcttaagca gcctggaata ctggaaagaa cactgcagaa 91320 gtcttacctt ggttctggct ctaccactag ttgagtgacc ctggacaact ccgttttttt 91380 tccctgagcc tcagtttctt cataggtaaa acaaggagac tatacattat ctcaaaactc 91440 tctcctggct ctaacacctg ttaaaattta taagaggtaa aacttggtcc tgcccagtgc 91500 cacagacatc acaggcactc agtaaatatt tgatttgtta tcgattctcc ggttacacga 91560 ggaatctgag gtgtctcaga acatggtttg aatggaataa caagtgaaag tttaagtccc 91620 acttccttct cagactccat agtcaacttc attctgcttt ttgtgctaca gagaggagga 91680 agcactaaac ttgaagttgg aaaatatgaa ctctgaccac cactgctcat ttagctatgg 91740 aaccttgtca tttctgggcc tgtctcctca tctataaaaa agccatactt ggctgggcat 91800 ggtggctcac gcctataatc ctagcatttt gggagtccaa ggcgggtgga ctgcctgagc 91860 tcaggagttt gagaccagcc tgggcaacat ggtaagaccc cgtctctaat aaaaatacaa 91920 aaaattagct gggcgtggta gcacttgcct gtagtcccag ctactcagga agctgaggca 91980 gaagattcac ttgaacctgg gaggtggagg gtacagtgag tctggatcgc gccactgtac 92040 tccagcatgg gcaacagagc aagactcttc ctccccaccc cctacaaaaa aatcaaaaaa 92100 ccatattgac ctcccagctc caaggctcaa aggcactaca tgccttccta ccctagggcc 92160 tttttatgct gtttcctctg cctggaatgc tctgtgagct ttttttgcca ggctaacttt 92220 tacttatctc caggggtcag cataaacttg catttttaag aaaagtattc ccttcaaaaa 92280 aaaaaaaagt agaggatggg catggtggtt catgcctgta atcccagcac tttgggaggt 92340 tgagacagga ggatggcttg aaaccaccgt gggcaacata gtgagaccct gtctctacca 92400 aaacagaaaa aaaagtagag aaaaccctca cccctggtgc actcttacag cacttatctc 92460 aattgtttac cttaactatt atagcattta ttgcaattgt tacaattatt tattgtccat 92520 ctctaggatt attaagcacc acaaagccaa gaactatgtc accactgtac tcagcatttg 92580 gctaagtata tgacacagaa gaatccaaca aatattcttt gaatgaaaga aagaatgcat 92640 aaactaatgc atctagaggc tttatgcctc tagactattg tactgtgaaa cctttcacaa 92700 ttttctaaga aacagggttc aagacaggca acctatatta cacagctgtt agaaaaagtt 92760 actggaaatc ggccgggtgc ggtggctcac gcctgtaatc ccagcacttt gggaggccga 92820 agcgggcgga tcacaaggtc aggagttcaa gaccagcctg gccaatatgg tgaaacccca 92880 tctctactaa atataccaaa aaaattagcc gggcgtggtg gcgggcccct gttgtcccag 92940 ctactcggga ggctgaggta ggagaatcgc ttgaacccgg gaggcagagg ttgcaatgag 93000 ccaagattgt gccactgcac cccagcctgg gcgacagagc aagactccat ctaagaaaaa 93060 aaaaaaaaag ttactggaaa tcattcgagt tgaaggactc tgtaagctta aaaaaaatct 93120 tttttaagag acaaggtttt gtttttaaga gatgaagtct cgctatattg cccaagctgg 93180 tctcaaactc ctggactcaa gcgatcctcc tgccctgccc tcccaaagtg ctgggattac 93240 aggcatgagc caccacgccc agcctaaaaa aatttgtttt aggcatttcc acccctagct 93300 ctctccagaa gtctgttatc accagtgaag agaaaatccc atgctccctt gctgaggaag 93360 tgacccactg gtagcccagt ccttgcattc aagatgaagg aagtgactgt ccacagacgg 93420 aaagccagga agcagggggc agatagccag cccccctcca cctcaatacc ctcttgccgc 93480 ctctccaaag cttctggacg ctgaccctgg tggacccaga ggtgggccac ccacacaggt 93540 ggctgggaaa cataggagac agaaggttcc tactgctggg ggaaaagatg gggaaggcag 93600 gaagctgcag ggtggtgtgt gaggtggcgg ggaggtgact gcaggtgcaa ctaacccaac 93660 tctgaagcta cccttcaccc ttagacaact cttccttcca ggaggtgttt ggccgaatcc 93720 ctctagtctt tagtctagag aggccaaggg agcttccaca ggaggactca gaaccccagg 93780 tggcctactt tcgccacctg tagcagagat ctttgggccc caaaaagaat ggtccgatct 93840 ctccttaccc ttagtcctgt cctaaacctc aaggggctcc atactccctt attttctgca 93900 aagagctccc agccccgggg gactcccaga caccaagatg cccgcgagaa gccttgggtc 93960 ttggcaggga agtcacatcc tccatttccc tcagaaaacc cagaacccgg ggtaactctc 94020 ctaattgtcc tgaaccctag aggatcctgt actcctcaaa ttccacagag cttccactat 94080 aagagaaccc catgcttttc aacttcctta aaaagggtta atttgggggt ctgcggccgc 94140 caggtccctc caaaaagctg gattcctggc agacccagaa tctcttcctc cccgggacct 94200 caactcgcgg gaagcctccc aacccgcctg cccctcggag ccctctgtct ccaggatgcc 94260 ctgcctcccc attcccggag tcccaccctc caaatgcctg gggagcgctg tgcccacccc 94320 gcctcccagc ttttctgagg agctcggacc cacgaggacc caaccagccc gaaacccccg 94380 agagacagcc ggtttccctc aggcgccatg gaaccggact tcggagataa cagcgggaca 94440 gggcggagca gcccttcctt acccgccagc gcggacatgg tcccgggagc gcggaaatgg 94500 ggaggaggag gcgggggaca cagcagctcc cctcagttcc ctacaactcc cctcagctcc 94560 tgccgccgcc gcctcaggcg cgggaagacc acagccccag gcgcgaacgg gatgcaccgc 94620 ctacggcgcc ctgggaggac caaaccacac ctggcacagg ggactgcccg ccgacgcccc 94680 gccccgccgc tctcaggcct cgctcccgag acgcggcccc gccccctggc tctggctcgg 94740 gctctgcagc ggccctggcg ccccctagtg cgagcggcgt cccctcgagg tgctcccgcc 94800 ggtaaggttg attctgcggg ggccggaagt ctcaacacgg atgacagtcc gcacccatct 94860 agtcgccctc atttacagat agggaaagtt aaggatcaga ggctaagttc gactacattg 94920 aaatggcgtc gctcattagg aggagagccg ggatgggagc ccaggcctgc taactgccag 94980 ttcagagctc tttccagtag tgtttggaat caggaatatt acaatggagg agccaggtct 95040 atcccacaaa cagctttgag gatggacttt tcttagaagc ttctagctca gagaaaccac 95100 ttctctgcgc cactatgagt aagctgacag taaataatct ctaagtcaaa gacagttgga 95160 ggcgaccaac cagcattcca ggagcagatc ctcagccagg ccaattaggt ttagcgcagg 95220 acgctggagc ttgtgcgccg cattggaaga cgagcactcc cctgcaggaa catgggccta 95280 ccattcccag gtcttccaac ctttcaaaac atgccaaaaa tccagatatt taggtgaaat 95340 ttgccacttt taaaaaatgt tgatagcatc aaaaagttct taaaatgcca tgtagaccaa 95400 atgaaacaca cctggccact agatttgccc tgtgggctgc cagtttacaa tcttctatga 95460 ggaggaggga ttacaggact aagagttagg acagctgact gggttatggc agctgctagc 95520 tggctgagta gctttgagaa ccacttccgc tcattaggtt tggaaggaga ttggggtcct 95580 ctgtgtgatt aagatattaa tacatcatca gccaggccag ctggtccctg atgacccacc 95640 ctcccatcag attctctcac gctgggtctt tcacaattgt catttcctta catcagattt 95700 agatcacagg aaacatgtcc aaatgaccag aaagaggatg gagcccaggg aaatggattc 95760 tgtcccctcc acccccaccc ctgaccaaag acaaagttca acccagctgc ctctggtccc 95820 agcagttggg taagcaaagg caaaggcaaa gacaaaggcg agcacaattc tcttccttcc 95880 tgctctaatt caaaccggat gccggtcaga tttttctctt ctgggtgtgg caggtggctc 95940 acgatgtcct gagtgtgcac aaagtgctgg ggaggagggc tctgtcccat ttccgttaat 96000 tcctgggaac tcttttcagt actcagtttt gtagtttctg aggaaatcat tatagtaaac 96060 acaagattgt gtattgaatt aaagtgacag gaatccagag actctcctga caagctgcct 96120 catggctagc aaacagggga cagggacttt ccccatcctt cctacagaaa gatgtaacac 96180 tgtattttcc caggcaacaa agcactggca tcctgggaac caaaacctcc tgggtgtctt 96240 ccctctccct ccgttccaca ccaaggcacc caggtctatc tcttctccct cctcattctc 96300 tctcacattc cacttcctcc tacctccagc ctcatggtct tcaccagcag ggagctgggg 96360 aatagccaag tcccccaagt tcctcccagg gaagttcagg cgactctgag aaacacaagt 96420 tgaaaatgta atggaaggga atagctttct atagaaatgc tatagccaag agatatattt 96480 ttaatatgga cccaaagaac attccagaaa tcacttgtga actcaagggg gacttctgga 96540 gggtagagaa agcctgggca gggagtagac caactgagtt tcaatagcac ccaggttacc 96600 tgtccacagt ttgtttcact ggccatagct tggtcagtcc ctagggccag atcctgccag 96660 ccgcctcaca gtcaactctc tgagcctagg atcctgaaac ctggaccttg aaaaacaact 96720 caaggttctg ccctcttgaa ggtactggtc cactggtacc caaccagact tgcccagtgt 96780 cacttccact tgcttcaaac tgagccagtc tctgccctcc ctgaatcatc ctacccaaaa 96840 ctgactgtgt taatcttcca aaagtatgtt tctggacctg tcatctctct gttcaaaacc 96900 cttcaacagc accccactgc ctacaaaata aaagccaaac cagtcctcat gagctgacta 96960 catctcaccc tgcggacttg tctccctatt cccttcactc caggactctg ctttttcctg 97020 agcacatcct gccttgcgcc acctgccatt cctacaacaa ccagctctcc aggttctctg 97080 taattttgtg ccccactctg cccagagtgc agtcttgttt ctcaactcta aatgatatag 97140 tggcatctgt aacatcacaa agtaggacta ccagacatta agtgcctcca ggtaagacgc 97200 accaagtata tactatcacc tatgacgtag tcttacaaaa caaaaataat aagcttgaat 97260 ctggtcaagc ttctagatct aacaaccaac ttacaggaaa tacatggaga agaggagctt 97320 aataacattt ccatgatgca aatagcaaaa atgatgctgt gggaaatgca acaggacaaa 97380 taacctagtt tctttaacag ataaactgca gagtagaaaa aatttcatag acaggccagg 97440 caaggtggct cacccctgta atcctagcac tttgggaggc tgaggcgggt ggatcatgag 97500 gtcaggagct tgagaccatc ctggctgaca tggtgaaacc ccgtctgtac taaaaataca 97560 aaaaaaatta gccgggcgtg gtggcgggca cctgtagtct cagctacttg ggaggctgag 97620 gcaggagaat tgtgtgaacc caggaggtgg agcttgcagt tagccgagat cccgccactg 97680 cacttcagcc tgggcaacag agcgagactc tgtcacacaa acacacacac aaaaaaacaa 97740 aaaattagcc aggcatgatg gcgggcgcct gtagtcccag ctaccaagga ggctgaggca 97800 tgagaatcac ttgaacccgg gagacggggg ctgtagtgag ctgggatcgc atcactgcac 97860 tccagtctgg gcggcaagtg aaactctgtc tcaaaaaaaa aaaaaaaaaa aattcagaga 97920 caaataatag caatgtatga aactgatttg gatctcaatt gaaactacac aagttatgag 97980 acaactaggg aaatctgaac aatgtgattg gatatgatga ttttaagaaa ttttttaaag 98040 gtattttgct tttttttttt ttttgagatg gagtcttgct ctgtcgcccc gactggagtg 98100 cactggtgcg atctcggctc actgcaacct ctgcctcccg ggttcaagcg attctcctgc 98160 ctcagtctcc cgagttgctg agactacagg cgcctaccgc tacgcctggc taattttttg 98220 tattttagta gagacggggt ttcactatgt tgcccaggtt ggtctcaaac tcctgagctc 98280 tggcaatccg cccgcctcac cctcccaaag tgctaggatc acaggtgtgt gccatcgtgc 98340 ccggcatatt ttgcttgttt ttaaaatact tgagatgcat atcgaaatac ttaataaatg 98400 acatgactgg ggtttgtttc cgaatagttc agacagtggg agaggaacag cgtgcgggag 98460 gtatagatgc aacaagactg atctgagttg atagttactg gagttgggtt atggctacat 98520 ggaggcttta ttgtcctgtt ctactactgt tttttttttt ttttccccat cgaaaacaaa 98580 aacctaaggc cgggcatggt ggcttaaacc tgtaattcca acactttggg aggctgaggt 98640 gggagaacct actgagaccg ggagttccag gctgcagtaa gctgtgatca caccactgca 98700 ctctagccag ggcacccgag taagaccctg tttctaaaag ggtctgttgc cctggctgga 98760 atgcactagc atgatcacaa ctcactgcag ccttgacctc ccaggctcag gtgatcttcc 98820 cacctcagcc tccctcccgg gtagctggga ccacaagcat gcaccactgt gcctggctaa 98880 tattttttat ttttgtagag atggagtctc cctgtgttgc ccaggctggt ctcaaactct 98940 tggcctcaag cgatcctccc acctcagcct cacaaagtgc tggggtttgt aggtgtaagc 99000 caccatgcct ggcctaaaat taaaatcttt caaaaaaaaa aaaaaaacct ggtcttttct 99060 cattgggctt atgagctcct gaagttccct cacctttgca ttccccactg tatcttggta 99120 ctattcaatt tgataactgt tagatcaaaa tctaagagga agaaaaaaag ctcttttcag 99180 aggaattact tgtagctctg gcatgttggg aaggctgagg ctgggccaga tttgtaacct 99240 cagcaacatc ttccatctca cactacaccc tgctactaag gaaccttagg gagggacaca 99300 ccttctgctc gagagagagg acttggctga cagcccacct gccctgttac taaacagatg 99360 gagagacgct gacagtgagt aacctgattg ttctaaaggc tctgataagt gacaagctaa 99420 gctctattgt ggcagcttgt cacttacgaa gctcaggaat gccatgtact tgtcaggact 99480 ggggctgcct gtcagacagg ttttatattg ggcaaggctg tgtatgaagc caggcctcca 99540 gcctacattt atcatctcta attatcaata gtcgtttaaa gactttcttt cctttttttt 99600 aagagacagt ctcgctttgt cacccaggct ggagttcagt ggcatgatca tagctcaatg 99660 cagccttgaa actcagggct caagcaatcc tcttgcctca gcctccagag taactaggac 99720 tacaggcata agtcatgccc agcttctttg aagactttcg ttctcagtgt gacattacgg 99780 aggatgcaca ggagcctcca ggagggcata ccagtgtgac tactccccac ccactcgccc 99840 tccacaacac agacaagaag tccaagctca tagtaatgta aaaccatttg tttaattcta 99900 aatcaaatca ctttcacaac agtgaaaatt agtgactggt taaggtgtgc cactgtacat 99960 atcatcattt tctgactggg gtcaggacct ggtcctagtc cacaagggtg gcaggaggag 100020 ggtggaggct aagaacacag aaaacacaca aaagaaagga aagctgcctt ggcagaagga 100080 tgaggtggtg agcttgccga gggatggtgg gaagggggct ccctgttggg gccgagccag 100140 gagtcccaag tcagctctcc tgccttactt agctcctggc agagggtgag tggggaccta 100200 cgaggttcaa aatcaaatgg catttggcca gcctggcttt actaacaggt tcccagagtg 100260 cctctgttgg ctgagctctc ctgggctcac tccatttcat tgaagagtcc aaatgattca 100320 ttttcctacc cacaactttt cattattctt ctggaaaccc atttctgttg agtccatctg 100380 acttaagtcc tctctccctc cactagttgg ggccactgca ctgagggggg tcccaccaat 100440 tctctctaga gaagagacac tccagaggcc cctgcaactt tgcggatttc cagaaggtga 100500 taaaaagagc actcttgagt gggtgcccag gaatgtttaa aatctatcag gcacactata 100560 aagctggtgg tttcttccta ccaagtggat tcggcatatg aaccacctac tcaatacttt 100620 atattttgtc tgtttaaaca ctgaactctg gtgttgacag gtacaaagga gaagagatgg 100680 ggactgtgaa gaggggaggg cttccctcat cttcctcaag atctttgttt ccataaacta 100740 tgcagtcata attgagaaaa agcaatagat ggggcttcct accatttgtt ggttattgct 100800 ggggttagcc aggagcagtg tggatggcaa agtaggagag aggcccagag gaaagcccat 100860 ctccctccag ctttggggtc tccagaaaga ggctggattt ctgggatgaa gcctagaagg 100920 cagagcaaga actgttccac caggtgaaca gtcctacctg cttggtacca tagtccctca 100980 ataagattca gaggaagaag cttatgaaac tgaaaatcaa atcaaggtat tgggaagaat 101040 aatttcccct cgattccaca ggagggaaga ccacacaata tcattgtgct ggggctcccc 101100 aaggccctgc cacctggctt tacaaatcat caggggttgc ctgcttggca gtcacatgct 101160 tccctggttt tagcacacat acaaggagtt ttcagggaac tctatcaagc cataccaaaa 101220 tcagggtcac atgtgggttt cccctttcct tgcctcttca taaaagacaa cttggcttct 101280 gaggatggtg gtcttttgca tgcagttggg ctgacctgac aaagccccca gtttcctgtg 101340 gcaggttctg ggagaggatg cattcaagct tctgcagcct aggggacagg gctgcttgtt 101400 cagttattac tgcctcggag ctccaaatcc caccaaagtc ctgactccag gtctttccta 101460 atgcacagta gtcagtctca gcttcggcag tattctcggc tgtatgttct ctggcagaga 101520 gaggcagatg aacatagttt tagggagaaa gctgatggga aacctgtgag ttaagccaca 101580 tgtctcacca ggaataattt atgccaggaa accaggaagt cattcaagtt gttctctgag 101640 gccaaagaca ctgagcacag cccagagcca ataaaagatc tttgagtctc tggtgaattc 101700 acgaagtgac cccagcttta gctactgcaa ttatgatttt tatgggacag caatttcttg 101760 catctctaca gaggaagaag agggggagtg ggaggggaag gaaagagaac agagcggcac 101820 tgggatttga aaggggaacc tctctatctg aggagccccc actggcttca gaagcaactt 101880 accaaggggt atttaaagac atgaaaattt ccagaaatac catttggtgc atccctttgt 101940 ttctgtaata ttaaactcag gtgaaattat actctgacag tttctctctt tctgcctctt 102000 ccctctgcag agtcaggacc tgcagaactg gctgaaacaa gatttcatgg tgtcacccat 102060 gagagatgac tcaatgccaa ggcctgaagt tatagagtgt ttacagcggt ggcgatattc 102120 aggggtcatc gccaactggt ctcgagttcc aaagctctga tgaagaaaca agactccttg 102180 atgtgttact gatcccactg attccaggag tcaagattag ccaggaagcc aaacaccagg 102240 agttggggtg gcacgtcacc agtccagagc cctgccacgg atgtaggcag gagcccagca 102300 ttaggcaatc aggagccaga acatgatcac cagggccaca aataggaaga ggcgtgacag 102360 gaactgctcg tccacatact ggggtgtccc agggacagct ggagagacag aaaggagaaa 102420 acaggctatt agaacactgc agctatgcac actgcccact caggccagaa gttgacagca 102480 tcaatcttta tctctttaca acatcagaat cctacacaca aaaagatttc tttttttttt 102540 ttttgaaatg tagtctcgct ctgttgccca ggctagagtg cagtggcacg atctcagctc 102600 actgcaacct ccgcttccca ggttcaagcg attctcctgc ctcagcctcc taagtagctg 102660 ggattacagg tgtgcgccac caagcctggc taatttttgt atttttagta gagacggggt 102720 ttcaccatgt tggtcaggct ggtctcgaac tcctgacctt gtgatccgcc tgcctcagcc 102780 tccaaaagtg ctgggattac aggcatgagc caccatgcct ggcctttttt tttttttttc 102840 tttttgaggt ggagttttgc tcttgttgcc caggctggag tgcaatggca cgatctcggc 102900 tcactgcaac ctccacctcc taggttcaag cgattctgct gcctcagcct cctgagtagc 102960 tgggattaca ggcacgcacc accacacccg gctaattttt tttttgtatt tttagtagga 103020 acagggtttc accatgttag ccaggctggt ctcaaactcc tgacctcaga tgatccgccc 103080 acctcagcct cccaaagcgt tggcattaca ggcatgagcc atcgcgccca gccaaaaaaa 103140 atttctaaac cccaaataat atcaggcaaa atgaaactat gtggaacaat aacaataagg 103200 acaagacacg gtccaattta tcataaaagg tttggcctgc acatgcaaat aaaccaggtg 103260 attaacagga aactcttgca ggaaataatg aaagcaagcc tactatttgt taagtatctt 103320 ctatctgcta agtgttttgt acatgttatt atttggtgga tattattatt tccattttga 103380 gtaggaagca gctgaaacat aggtttgagg tgacctgttc aagattgaaa ggctcagaaa 103440 ttagtggcag agctctgcag cctctccaca cactgcctct caagggcccc acagggattg 103500 ccttcctttt ccagaagaga actaggatcc agacaggcaa aatgacttgt ttttcaaggt 103560 agaggcagaa ctggggtgag aacctaagtc tccactcctc tctgctttag gaaaagctac 103620 catttagagc tccctgtcct gactttgggg gaaggaggat aaaagaatct gtgtccagga 103680 tgggcaaatt gtaccaagca tgacaaggga aaactgtgac tgtggcaggg ggataaagta 103740 atccagagtc tagcctggct gtggaactct gcttagctgg ggaatccaag gttagccttc 103800 gaccaggtta gaaggatgca agctatcagg caggttcttg ctggcttcac aggaatttgc 103860 cctttcttca gggcagagta caccctatct tttggggtat acttcctctg aaaaacaaat 103920 gtgaacagag gataaacctt caaggcagat aaagtaagaa agggcatccc cagggccggg 103980 cgcggtggct cacgcctgta atcccagcac attgggaggc ccaggcgggc ggatcacgag 104040 gtcaggagat cgagaccatc ctggctaaca cagtgaaacc ctgtctctac aaaaaaatac 104100 aaaaaaatta gccaggcgtg gtggcaggcg cctgtagtcc cagctactcg ggaggctgag 104160 gcaggagaat ggcgtaaacc tgggaggtgg aacttgcagt gagccgagat tgtgccactg 104220 cactccagcc tgggggacag agcgagactc catctcaaaa aaaaaaaaaa aaaaaaaaag 104280 gcattcccaa gatatcttgg tgctgagatt cctcagctag atgctctgat ggattcacga 104340 agacagacag gcaggcaggc aggcagtcaa gaaagactta tagatcacct gctgtgtacc 104400 aaggaccagg gtggggatga gaataactgg gatgacccag ttaccatctt tagggcataa 104460 gctcttggcg tgaaccacac aatggtcact tctgtaccat atgctgtgtc cagtgcacat 104520 gaagctccaa caagtgcagg

cagagctcaa ccgatcatgg catctctgca ggctccacag 104580 taaggatctt ggcttgggtg tcagactgtg ataagagttc aaggcaccca cctcatagag 104640 gtggcttgca cctatagagc aagggctcta taccgaatgc ggatggcact ttcaagcagt 104700 aggagggaga actgcagcag cagttggtag acctaggcat ggttcccaca gggctgaggc 104760 tgcttctgac cagcctcatg ttgtgtcctg aaggaagcta gacagagatg ccagagaatg 104820 gagatgcctt cactccttat gggtcatctc acatttccag gcccccaaat ggtcaaagtg 104880 ggaagtaaat gtgcagaact aggcttttcc tcagctgagt atcacttaca gttttccatt 104940 ttatagacat ggggtatgtc ttggtaacat tactgagcat tttctgatct gttaaacgca 105000 gctaatcaca cacctgttcc atagggtggt tgtgatgatc ccctgagctt ggaatggaaa 105060 gtgctatata tatgcatgcc taatagttgg taagtgctca gcattgttac catgtctgta 105120 agtgatctaa aaacagctta agatattttg aaaaggctga ttatccatgt agtgacaatt 105180 atctgtaact tatatactgc tgaattccaa ggagctttca agcaatatta ctaagatatc 105240 ttcctaattt ctcaaggaaa tagggtctta cctggaggag gccgcccatc atttatatta 105300 aatgctgtgg caaatatccc aaagggaaat gccccaattc caaaagacat ctggaagcca 105360 ccatctccaa atccaaatcc ttgaaatccc tgtgtggaag aaaggcaatt aagggcagga 105420 gaatcaggca ggtttctcct gtgcctgtca aaactcaaca tacctcacgt tgtcttgcat 105480 gtggcacctg cctcttctcc ctaccttgtg ccacatgttt cgaaggtggg ggacagcttt 105540 tcctcccata tataccctga agtagaggaa ctctggcaag ccctctgccc ttttagcctt 105600 agcttccagc taagaatcta tgaatgggcc aaaaaggact ggctctgacc cagtgtgaaa 105660 cactctgctg acataagtca gcactcacag ggcttgagga tattttccat agtcccacat 105720 tagctagtaa caccttctac atgctttata ggagcaatat tgacagccac ccctgtgccc 105780 aagggaacat caaacaagct acacattatc tttaatagca aaaatgttga aactctaatt 105840 agccaacaat ggaagtcatg atcaaaatct tgatacatgc attcaaagaa ccattaccct 105900 gacttaagcg gtaacactga acaactcttg tgaccaagtt atcagacaaa attgtttgaa 105960 cactgtggtc acaactacat gacaatatgt aggtatatgg acaagttacg gattaaaatt 106020 tcttttaata ctgttacata gaatttttac attttaaaac actataatgt tttctggtta 106080 taaaagtaat atatacttgc tataagaaac tcacatatta cagaaataat tgacagagtc 106140 agagatcttc tattcacctt cccacttcgc agccactcca ctttacctct gaaataacca 106200 ctatcagcag tttggtatat caccctcagt tttctttcca tgtgcatgtt ctacactgca 106260 tcatctttca catgaaaaga ttcagcagga acaatactgt gaataaataa ctcccttttt 106320 taaagcgtga gctctgtgct aggcaccatg ttaagcacta ggacatataa atcatgttta 106380 atttttacat tggcttcatc tgcatttcac agatgaccaa actgaggctt ggagaggtga 106440 aataacttga ccaaggagta cagtttagat ctaaaactag gtcaatttga tctgaaaaca 106500 catgcttttc tttttctttt cttttttttt gagacagggt ctcgctctgt caccaagcct 106560 ggagtgcaat ggtgcaatca tggctcactg tagactcaac ctcccaggct caagcaatgc 106620 tcccatctca gcctcttgag tagctgggac cacaggtgta cccctccatg ctttgctaat 106680 ttttaaattt tttgtacaga tagggtctca ctttgttgct caggctggtc tcaaactcct 106740 gggctcaagt gatcctccca cctcagcctc ccaaagtgct gggattagag gccagagcca 106800 ctgtgcccgg ccttcatgct cttaattact gtgcgcatct ttcaaatatt tttttctctt 106860 cccctgcacc cctgatgaga ggtttagaac aaatgatttt aaaaataata aaaagcagac 106920 agactattgg gtcaaatgct cttcacaaag agctcaatgg ccttcattta tgagtttttt 106980 gcaagtcaca aaaatagctg ctctccatca cacactgatc agcctggcat ctagttccaa 107040 acttcttgcc agatggcatc acctataaag cctaacagct gacttaatga gagggcaaac 107100 ctaaagggag ggaaaacaaa gagtttccat ctcctcaata caaaatgcct cctactcagt 107160 tcatggttga atctaatggc tcctgggact gaggctgcct tacttgggaa ggtgcaattg 107220 tttcatcagg aaccacagat tcattcagtg caatcctgag gactaaccgt tctgcttccc 107280 ttctagcaac atctttatga tctcaccagt ccatacattt ggtgggatta tgttcctggg 107340 ccagagtatg caaaaaaaca tcgctagtag ctgcaggtgc ttataaatgc tagaggtatg 107400 cactttggtc aacaaggcca gggcctctgg cttctggggg cctctgattc ctgcattagt 107460 tgctaatgct ctgtaggaaa ccaaaaccta ggaatgttaa agtggtgtca cctggtggtc 107520 aagagcagag acttcaatac cagccagatc tgggtttcag cactgtacgt gtggccctgg 107580 acagatcact ttacctatct gggcctcagt ttcctcctcc gttaaatgag ttgatgtgag 107640 gcttaaatga gatcatgcat ataaagctct taacatatag ttatttccat atagtaacca 107700 ttcaacaagt gttcactgct agtattatta ttaagggtaa tccggagaag agaaccttaa 107760 tttctttctt tctttttttt tttttttgag acagagtctt gctctgtcgc caaggctgga 107820 gtgcagtggt gtgatctcag ctcactgcaa cctctgcctc ccgagttcaa gtgattctcc 107880 tgtttcagcc tcccgagtag ctgggactac aggcacatgc caccacaccc ggctaatttt 107940 tatgttttta agaaagcaga gacagggttt caccatattg gtcaggctgg tctcgaattc 108000 ctgacctcag gtgatccacc cgcctcagcc tcccaaagtg ctgagattac aggtgtgagc 108060 caccacgccc agccgagaac cttaatttct ttcaagatcc ctgactcaat aatcctactc 108120 ctggaaatcc taataaaatg ccattattca aactcaaaaa aaaaaaaaaa aaaaaaaaaa 108180 aagaaagtgg cagtgcgcgg tggctcacgc ctgtaatccc agcactttgg gaggccaagg 108240 agggcggatc atctgagctt gggagttcga gaccagcctg accaacatgg agaaacctcg 108300 tctctactaa aaatacaaaa attagctggg catggtggcc catgcctata atcccagcta 108360 ctctggaggc tgaggcagaa gaattgttta aacccgggag gcagaggctg tggtgagccg 108420 agatcgcact actacactcc agttgggcaa caagagtgaa acttcatctc aaaaaaaaaa 108480 aaaaaaaaaa aagtgtgcaa agatggttat tgtagcatta tttaaacagc aaaatgggga 108540 aacaactaaa aggtccttcg atgaggaaaa cccaaattac aatgaaccaa aactcaatgg 108600 gttcccagca atagcatgga aaaataaaaa ataataaaaa actcaatagg ataaatggca 108660 gcctaaataa taaagaggac acttcagagc atcatggaaa acctgccaaa attaaatttt 108720 aaagcaaaca gaatggtgat ggctacataa aaatacatat gcacagccta cagatgaaga 108780 gaacatgagg atatgagaat atacttgttc tgggctcttg gcaatggtgg gtaaatattt 108840 tgcttttaaa atttctttaa cattttaaca gaattttttt aagagtaaca tttgatgtaa 108900 atatgcaaaa aatgtaaatg tttttgttcc tagccactag accactagag acaaatgtgc 108960 aatttttttt tagccagtaa tcttacttct aagaatttat cctaagccag gtacagtggt 109020 tcacgcctgt aatcctaaca ctttgggagg ctgaggtggg aggattgctt gagcccagga 109080 gttagagacc agcctgggca acatagtgag accttgtttc tacccaaaca aaacaaaaca 109140 aaaaaaagaa agacaaaaaa aaactcaaaa aactagctgg gcatggtgcc gtgcacctgt 109200 ggtcccagct acatgggagg ctgaggtaga ctgagcccag gaggtcgagg ctacagtgaa 109260 ctgtgatcac accactgcac tccagcctgg gctacagagt gagaccctgt cttatcctaa 109320 taaaataata atgaacatgc tcacaaattt atctgtaagt tcatcaggat tttttttaac 109380 ttggaaaaag aaagccgcta atgtctaaca aaggattgaa ttatgttaaa tccacacaac 109440 taaatgctaa acagctagtt agtaaaatat tgctggcaat gtaaaatctc aagataatac 109500 taaaagactc ccactcacac aaagaaggta ctaagtatct gtagaacaaa tgaaatttta 109560 agagagggtt acaaaacagg agccacatat tgtaaaaaac aaaaaacaaa aactgtaaaa 109620 agtatacaca catctgtaaa atacacgcac agatttgtaa aatttgtgtg tatatataat 109680 tatagaaaaa tggaaaagaa aatagaacca aaatgtttcc agtggttacc tctggattgg 109740 tgtggttata agtgattttt ttccccctct tttcctttct gtattttaca agttttcctt 109800 tacttttata atcaaggaga aaaattgtaa ggctaagaag gaaacttcta aagccatcag 109860 ctcatttgta gaagcttctc ctagaatgtt cctcacccct ctattctccg gctctggcct 109920 ctgtccttga ggacgaggag gggtcttctc tctgaaacag aaatggtgta aaataagtct 109980 attacaaatt gctttgagtt gctccctgtg aggacctgga gctctttacc aacagggtca 110040 gggccatagc ctctttcttg tccaggacat gaacttatgc cagattaatt ctccaaatac 110100 gaactcttca ttctacctgc aactgttctt cccacgtgta tagagaacca gggagaaaat 110160 caactcgtta tgagatattc accagattgc actacagcct actcctctta cagagatcct 110220 gactcagatc ggttaggaat catggccaga tgccttccct gggcctgtta cagataacag 110280 aaatcccaaa tccatactgg aacagagggt gggttgtcag cagtaagggc tgaggttcat 110340 ggtttctctg accttcccct attaacttca gctctatctc ctactattct tgggcaaata 110400 cccaatgcta ttatttttga gtctcacccc ctcaaatcac tcaacccatg aatactcaat 110460 tgagggctta gttatacaat aagcattatg caggatgctg taatactgat gacagaccca 110520 acccttgaag tgttcatggt ttcaaggggg ataaagccag tcatatgaca ctgtggtggg 110580 aactgggtga gagcaactaa tgtgaagaag acagaccact tcaaggaaga gggaacttta 110640 gggctgctca taagagatga gtagaagtta gaggagcagg tgggggtaga ggggtagctt 110700 gagcaggact ggggagggaa gaaggcagaa gagagagcaa atacacaggc tgataaatgt 110760 gaaagagcaa gtccctttaa gagaaagtct aatatgtcgg gtacacagca tatgctaggg 110820 tagctggata aaggtaagag attcttctgg agagcttggg gatgccagac catgaagggc 110880 tctcaatact tgtgtttgtt gaatgctgga cccatgcaca tctccatttc tagaaatccc 110940 aaactccaca aagtcaccca gatcctgttt cccctcccgc catgctttat acatcactga 111000 tgcagcaacc ctgctccctg gagcctctcc tgctacatat cctgcttccc aggttgcaga 111060 aatgctcttt cacagggctc tgcacacttg tgattgtgat gtctgttcac tgctgggtcc 111120 tagcaagtgg caacttggat cccctctctt ccctcccctc ctagctgact ctcatctgga 111180 tgagactgct tcgaaaccaa gagatcatct agtactaagt aaagggtggg gttaggggat 111240 gctgaatggg agtgaattca catccaaggg gagaagtggt tgggagaggc atcctgagtc 111300 ctcacctggg gtcctgttgc ccagtgctgc cccttccata gagggggatg accttgtctc 111360 ggctgatgcc agctttgcaa acaggacaca cctgtctgtt aggtctggtc tccaaccact 111420 gcaaacagga gagaaaaatg catgtggatg gcccaagacc caccagagtg atcagccaga 111480 gccaccagaa caacacaggc cagaggcctc aaactgggaa acaccagcat gagcagggaa 111540 catctcaagg aacctgactc ccattccttc tcctaccatt cagcaaatac ctaccagtgg 111600 taaaatcaaa attgccttta aatatcatca taattggccg ggtgcggtgc tcatgcctgt 111660 aatcccagcg ctttgggagg cggaggtggg tggatcacct gaggtcagga gttcaagaga 111720 agcctggcca acaaggtgaa accccgtctc tactaaaaat acaaaaatta gccagacatg 111780 gtggcgcatg cctgtagttc cagctactcg ggaggctgag ggaggagaat cgcttgaacc 111840 cgggaggcgg aggttgcagt gagccgagat tgcaccactg cattccagcc tgggcaacag 111900 agcaagactc tgtctcaaaa aaaagaaaaa aaatcatcac aattaggctt cttcatgctt 111960 tgtttctctc tagggcctcc tagcaacaca gggggaggga aactgcaagt ctggggctgt 112020 caagtctgac atgcccagcc tcaatttagg ctgctggtgt aagtacagca aactttaaat 112080 ccccaccttc ccagtaggag caactgtatt ttcctgtcag tcatattctt ctttctgtga 112140 tttctcattt ttttttcccc agacagagtc ttgctctgtc acccaggctg gagtgtagtg 112200 gcatgatctc aggtcactgc aacccctgcc tcctgggttc aagcaattct cctgtctcag 112260 ccttccaagt agctgggatt acaggcgccc accactgcgc ccagctaatt tttgtatttt 112320 tagtagagac agggtttcac catgttggcc aggctggtct caaactcctg acctcgtgat 112380 cttcctccct tggtctgcca aagtgctggg atcacaggca tgagccaccg cgcccggcca 112440 atttctcatt tttatagcat tttcccaaca actgtgtatc ccaggcatca gaatcaggag 112500 ataagctgat cattttctgg tgacttacca catgctaaag gataggtttt gctcattatc 112560 taaatttgct taatgctttt tgtgtacttt cattgatttt ttgcattcac ctatttcttt 112620 caatataaaa aaaatcccgt tttgggtttc tcaggccctt tcactggtta cattaaaatt 112680 ttttgtttag gccaggcgcg gtggctcacg cttgtaatcc cagcactttg ggaagctgag 112740 gcgggtggat cacctgaggt cagcagttca agaccagcgt ggggaacatg gtgaaactcc 112800 gttgtctcta ctaaaaagac aaaaaaacta gccgggtgtg gtggtgtgca cctgtaatcc 112860 cagctaccca ggaggctgag gcacaagaat cgcttgaacc cgggaggcgg aggttccagt 112920 gagccgagat ctcaccattg cactctagcc tgggcgacag aatgagactg tctcaaaaaa 112980 aaaaaaaaat taattttctt aaaaaaacaa gtgataaaaa atgtttttgg tttgtttttg 113040 tttgtttttt gcttgttttt gatttttttt tcggtttttt ggtttttttt ctcgaaacag 113100 agtctcacta tgtcacccag gctggagtgc agtggtgcaa tctcagctca ctgcaacctc 113160 tgcctcccag attcaagcga ttctcgtgcc tcagcctccc tagtagctcg gactataggc 113220 gtgcaccacc acgcccagct aatttttata ttttttgtag agacggggtt ttgccatatt 113280 ggccaggctg ttctcaaact ccttgcctca agtgatccac ctgccttggc ctccctacgt 113340 gctggaatta taggtgtgag ccaccacacc cggccaaaat gtgtttttat agacattcta 113400 taaacatgaa tctaggactt cagggctgag gagatggcag cactgaatga ttttatttac 113460 tactcttact gttcatagct ccaaaactta atgtgttatg tgttcttcat aaactcatag 113520 tcaatatgta ctaccaggtc ccgctgggga cagaatgtgc agccctgttc ccaccttctt 113580 tctcccatcc agattctgaa gctttagcag tctggaactt ctgtcctccc ccacattccc 113640 aggccaccta cgagtgtggt actctactgc tgacgaccag ggagactttc agcaggctgt 113700 gattattcac agccacttgt gaatgccagg cccagctctg tctcaccaag taggtgctaa 113760 agctaggaaa atagactttt ctctcctcac aaaagctctt tgttgacacc aaaaaaattt 113820 tccccttcct aatattttca taacctttaa gggctggggg actgttgata tgataggagg 113880 cactgtttta atagaagcag aatctcaaaa ataaaaagga cctaactaac atactatcaa 113940 tccaatccaa tttataaatg agtaactgag atccaaaaag gccctctgtg gcagaattag 114000 gaccatcccg atttcatcaa gtgtctgtca gtggacaggt atgtaaagaa ggctgtgggg 114060 gtaagtaagc aaatgagccc acaagcaggg cagattgcag cttctgaaag cagtctcctg 114120 agactagggc tctcttgtgc aaccagagct gatgaaagac aaagtaaaat gaaatgcatc 114180 ttacctgatg taaacacggc caactgccag agtccccagg gcaaccagtc atcaaggaga 114240 aggagaaaag gggaaaggaa gaaaaatgtt ttcattagca gaaacacttg atgggtggag 114300 tggtagtagc agaatgagaa aacaggagta aactatggag cactgcatgc ccattgaggt 114360 tctgtaggga ttactggtat cggaaattaa aaaaaaactg gggtaaaaat cacagaaaat 114420 aaataacgca atggagataa gaccccagcc tctgcccctg agatctcagt atatgtgaaa 114480 tccccagggc tcagaccaca cagacccagc ttctctacaa atcaccctgt gagaggttac 114540 aacatctgaa ggaatccaat aaaagctaag gacaccctgt gcaaaaaatt gatgggggca 114600 ttcacataca catgtactac acactatttt acactcaatt tcagtgggtt catagtctcc 114660 tcgggctcac aagggatgtg tggactctca ggtagtccag atccagttta acaaaatctt 114720 caggctgtcc tcatccttga gaactctcct agcaggaagc agcttaaaag ttcaggtcta 114780 ctctaaaagc atctttaagt aatagaaagg atggggatgc tacttgacag aaagggttac 114840 cttcagctta gagagctgct gtccaatctc tctccatttt caaatgagga aaccaaagct 114900 cagaaacata aaatgaactg catcaggatt aaaaaaaaaa gtctcctgac ttctagttca 114960 ttgccctttc tataatctaa caccacatac aaaaaaaaaa tgatatctac agaattgaaa 115020 gaaaagtatt caactccact tttttttttt tttttttttg agacgaagtt ttgttcttgt 115080 tgcccaagct ggagtgcagc tcactcagct cactgcaacc tccacctccc aggttcaagc 115140 gattctcctg tctcagcctc ctgagtagct gggattatag gtgtgtgcca ccacgcccag 115200 ctaatttttt gtatttttag cagaaacggg gtttcaccgt gttagtcagg ctggtctcaa 115260 actcctgacc tcaggtgatc cgcccacctt ggcctcccaa agtgctggga ttaaaggtgt 115320 gagccaccgt gtctggccca catttttaat ttctttctct cgtttattta gttaacacat 115380 atctactgtg tacctactat gtaggccagg acagtggaaa atgcaggcat ggcttctgta 115440 cctcacatac caagtatctt tagctgagta cactttgaac tcaaaggata gttccttttc 115500 caattcctga accacagttt agcttcacaa accaaataca caatcttcct ggccataaca 115560 tctgactcca acattaatct tgcaatgtca ttctaaactg agtggagaat aaccccaaat 115620 catggcagat ctccactggc aagttccctt aaagactcta ggggagaagt ggaggtgaat 115680 gaatgaccct caggggaaag tcaggcttta taacaacgac cattcctccc atttattaag 115740 caacgatagt catgtatcac tgaacgacag ggataattct gagaaatgtg tcattaggca 115800 atttcatcat tgtgagcatc acagagtgta cttacacaaa cctagctgaa atagcttact 115860 acacacctag gctacatagt atagcctatt gctcctaagc tacaaacctg aatagcatgt 115920 gagtatcata ggtaactgta acagagtggt aaatatttgt gtatttaaac atacctaaca 115980 tagagccaag gtgtggtggc tcatgcctgt aatcccagca ctttgggagc tgaggtgggc 116040 agattatttg aggtcaggag ttcgagacca gcctggccaa catggtgaaa ccccatctct 116100 attaaaaata caaaaactag ccatgtgtgg tggcacatgc ctgtaatccc agctacatag 116160 gaggctgaag cacgagaatc acttgaacct gggaggtgga ggttgcagtg agctgagatc 116220 gtgctactca atctggagtg ctactgcact ccagcatggg tgacgcagtg agactccatc 116280 tcaaaaaaaa ccaaaaacca ggctgggcgt ggtggctcac gcctgtaatc ccagcacttt 116340 ggaaggctga ggcggttgga tcacctgaga tcaggagttc aagaccagcc tggccaacat 116400 ggtaaaaccc cgtctctact aaaaatacaa aaattagtca ggtgtggtgg cacgtatgtg 116460 taatcccagc ttctcgggag gctgaagcag gagaatcgtt tgaacctggg aggcagaggt 116520 tgcagtgagc caagatcacg ccactgcact ccagcctggg caacagagtg agactcctca 116580 aaaaaacaac aaacaaacaa acaaaaaatc caacatacct aacacagaaa aggtaacgca 116640 ctgctctata acattttaaa atcactagat tataggaact tttcaggtcc atcatcatct 116700 tatggaaccg ctgttggata tgtaatccat tgttgaccaa aatgtcatta tgtactgcat 116760 gactgtactg tgtgccacgc tgtggctgaa taccttttca tttcttaatg tcactggacg 116820 gtcacattaa cctatgaggc agtaccatca tctccatctt acagatgagg aaaccaaagt 116880 acagggaagc tagcagattt gctcagggat gcaccatcca gactggaagc atctgtttca 116940 ttttagagtc tgtgttcttt ccaatggcat tctgccttta aaaaaaaaat tgatagcagg 117000 catggtggct cacaccagta atcccagcac tatgggaggc cgaggcgggc agataacgag 117060 gtcagaagat cgagaccatc ctggccaaca tggtgaaaac ctctctctac taaaaataca 117120 aaaattagct gggtgcacct gtaatcccag ctacccggga ggctgaggca ggagaattgc 117180 ttgaacttgg gaggcagaga ttgcagtgag ccgagattgt gccactgcac tccagcctgg 117240 tgacaaagca agacttcgtc tctaaaaaaa aaaaaaaaaa tttgacacag ggccaggcat 117300 ggtggctcac gcctgtaatc ctagcacttt gggaggtcgg ggtgggcaga tcacttgagg 117360 tgaggagttt gaaaccagct tggccagcat ggcgaagccc catctctact aaaaatacaa 117420 aaagaaaatt agccgggcgt ggtggtgcat tcctgcagtc ccagctactt gggaggctga 117480 gacaggagaa ccacttgagc ccaggaggca gaggttgcaa gtgagccaag actgcaccac 117540 tgtactccag cctgggcaag agagcaaggc tgtctccaca aaaaaaaaaa aaaaaaaaaa 117600 aaaaaagata tacaacagct gtacatttaa atatatgtat agttaatata tacataaaat 117660 acataattta taatcttaaa atttataatt ataaaattta ataaatacat acacaaacac 117720 aaacacacac acacacacac acacacacac attttttttt tgagacagag tcttgctcca 117780 tcacccaggc tggagtgcag tggcgcgatc tcagctcgct gcaagctctg cctcccgggt 117840 tcacgccatt ctcctgcctc agcctcccca gcagctggga ctacaggtgc actccaccac 117900 acccggctaa tttttttttt tttttttttt tagtagaaac gggtttcacc gtgttagcca 117960 ggatggtctc gatctcctga ccttgtgatc cgcccacctt ggcctcccaa agtgctggga 118020 ttacaggcgt gagccaccgc gcccagccca gaatatatat atatttttaa gagacagggt 118080 ctctctctgt cgcctagact ggagtgcagt gatacaatca tagctcactg tagcctcgaa 118140 ttcctgggct caagccttcc tcccacctca gtctcccgag tagctaggac tacaggtacc 118200 gccaccatgc ctgactagtt ttaaacatag tggggcctca ctatgttgcc cagactcatc 118260 ttgcactcct gggctcaagt gatcctccca ccatggcctc tcaaagtgtt tggattacag 118320 gtgtgagcca ctgagcccag ccataatagc tgtacacatt ttttatgtta tatgtgataa 118380 tttgatacat tcacataatc aaatcagggg tatcctgtct ttgaattctt aattttgtca 118440 atcatttcaa gtcctggttt tacgataccc tgaagtatcc tgaatttcta ggagaatgtg 118500 gatcacaaca gcttttacac aagatggtaa ttagggcaag agcctcaaga acaaaaatct 118560 ctgctccatt ctatttattc accaataaat tgatgtttta cgctgttgcc aacttaaaat 118620 cccttaaata ttgtttaaac ggccttttct tcacacgatt tctctgctca aaaatattca 118680 ttacctctat gtccctttag tcgaatctgg gtttgataat ctggctcaac actactgtaa 118740 ccattatttt tcctaacact cccagaccct catccagagt gctgtgagag gtatacagta 118800 gcctcaaggg tctcagatga gtccaacagt gcatgtgcct gtccctagaa actccctgcc 118860 ttggagtgac acacacaccc ttcgccttta cctagcattt tttgatcgac ctttcaaggt 118920 tcagctcaaa atctcaagac aaaaaaaaac acacacacac acacaaaaaa ccaaaatccg 118980 accttcacct agcacctagg ttctcagagc cagaaagggc tcctgtaacc gtcaaggctg 119040 gaacagacac cgaccttgac acttcatttt gatgagtgta tctatctata tataaacata 119100 aaatatagta acaattatag tcatagctaa cacatagtat ttactgcaag ctatgtgctc 119160 ttctaagcct tttacatatt ttgagtcatt taatgcttgc aaacgaccct gtaaaatgag 119220 gcagaatgtg tgtaagtacc ttgtccaagg tcaaacagga aggtggcaga gtcaagcttc 119280 aaaaggagga agcccagttc cacagtcctt gcttataacc attatgctat actgcctcta 119340 ggctcagcac agcaagtagc aggtagtaag tgctcactaa atggtaagta ttattacttt 119400 agagatgggg agaacgagct tagagtggag acaggatttg cccaaggtca tccagctcat 119460 tggtagcaga gctgggatgg gaactcaggt ctcttgtccc ttgagcctga gtgtattccc 119520 aaagtgagca ggaagcattc tgctccaaac cacccagggc cacaggcttt ccaaacttgg 119580 caatgtgctc tctggggtgg

aagtaggggt actgaccaga agaggtggcc acacaggctg 119640 atgacggcat ccttggctgt gtccaagcag atgttgcact cgaaagtgct gtcctgccct 119700 ccgctctcgc cagcgccatt gctgctccca ctgggccccc ctgcactgga gttctcagga 119760 gatgcagagg ccgagggccc cttgcttgcc atccttggct gtcagcgaag ctctgagtga 119820 agactttccc cagggaaatc ctaaaaggca gagaactctt gactgtccat ttctgcagcc 119880 ctctcccccc agcttccatg ccaacattcc tgtcttctct aggctccaga gctgattatg 119940 actgaatccc tgagcagact tcccaaagcg ctacagaaga caagagttgt agggcactac 120000 ccaaagggca gtgacccaga aacttctcat gaatatggtc cagaatatat cacacagata 120060 cgcaaactcc accaaataca gagcagcctc cagatggttc tccacaggaa ccaggacctt 120120 gtctcacttg tctttagatt cccccatgac aatcaaccca ggtgacaaat acatgctaca 120180 ttaaatggaa tgttcaggct gtccagcctc tatattgatg ggtgaatctg ctgaggcagg 120240 aaggttgtga ttgtcatatg ccagaacata tatatatatt tttaagagat ggagtttcac 120300 tctgtcgccc aggctggagt gcagtggcac aatcttggct cactgcaacc tctgcctccc 120360 aggttcaagt gattctcctg cctcagcctc ccgagtagct gggattacag gtgcctgcca 120420 ccacacctgg ctaatttttg tatttttagt agagatgggg tttcatcatg ttggccaggc 120480 tggtcttgaa ctcctgacct caggtgatcc acctgcctca gtttcccaaa gtgctaggat 120540 tacaggtgtg agccactgtg cccagcccat acgccagaat attaagaaat tcctgtaact 120600 atgaaaggat aggaagctaa taaggaccag aaagatcatc tggtccaagg tcttccatat 120660 tgcaatcttt ttcaatcctc cttctgccac attggaatac tattcacctt attttatcta 120720 aatatatcaa ctttttagcc tcagtacatt taaagaagag gtttatgtca ctgtaataaa 120780 tggaaaacca gtaatactta ccataagtaa aaaggttaat ataaaagtaa caaatgaaaa 120840 gtttaccctc ataccacctg acatcacctg gcacactcat actatgtttt ggacaatctt 120900 gatctggtcc aatttcttta ggaaactgca gttaccttgg ctagctgact aatgtggggc 120960 tgagactggg actcatggac accctgtttg caccgtacca ctacatacta aactggccac 121020 taaatgctgg tataaacaga ccactgttga ccaccacctc caagtcaaag aacccagcca 121080 ggagttgaac aagaaagagg ataaaaccaa caccaaggga tacccaggaa ttctggatgc 121140 acattaacaa tctgtcagga gccttatctg gccaccctca tcacctcaga aattccaagt 121200 aggaaatgtt cgctggctac cacagtcaga gaagtggagg cctggatact ggactcagcc 121260 tctagcttgc taggtggttc tgggaacctc cctttccctc tactgatcat aattttctca 121320 tctgtaaaat gaggcactgg actccctggt gtcctgggtg gccccctcca gctcttagac 121380 tgtgcctctc caggtcatct taacctactg ttacctccaa aacaagcggc cccttcacaa 121440 atttaggact taccactgga acaccagaag gtcaccctga tgtcagcttc cagagtatga 121500 gaagacaagg accaaaaaag ttacagcctt ctcagaccca gaaagcttcc tgccttcaca 121560 cggtggactc agagctctgg cctcatgagt atccctcacc acgataccag ctcagtgact 121620 tgagcagaga gaggaggcca gctcaccact ttttcactca gttacatcat tttacataat 121680 gtcccagaag ggtagctgga tgctggtggc accagtttcg tgcgctggcc tcggctccaa 121740 gaccttctct ctgaccttcc tcttcttcat attacatgtg ctctcttcat cttaggataa 121800 aacccacttt tgagggccac attactatct ttcctcatta ttccagctca acaatcaatc 121860 ctaagtaccc aacctatgtg tgtttctttt taaaaaaaaa aaaaaatctt aaaaaattaa 121920 aaattgctct ccctccccct ccccctccct ctcccctttg cacggtcctc gtctcccctt 121980 tgcacggtct ccctctgatg ccgagctgag gctggacagt actgccgcca tcttggctca 122040 ctgcagcctc cctgcctgat tctcctgcct cagcctgccg agtgcctggg attgcaggcg 122100 cgcgccgcca cacctgactg gttttcatat tttttggtgg agacggggtt ttgccgtgtt 122160 ggccgggctg gtctccagct cctgaccgcc agtggtctgc cagcctcggc ctcccgaggt 122220 gccaggattg cagacggagt ctcgctcact cagtgctcaa tgttgcccag gctggagtgc 122280 agtggcgtga tctcggatcg ctacaacctc cacctcccag ccgcctgcct tggcctccca 122340 aagtgccgag attgcagcct ctgcccggcc gccaccccat ctaggaagtg aggagcgtct 122400 ctgcctggcc gcccatcgtc tgggatgtga ggagcccctc tgcccagccg cccagtctgg 122460 gaagtgagga gcgcctctcc ccggcggtca tcccgtctag gaagtgagga gagtctctcc 122520 ctggccgccc atcctctggg atgtggggag cgcctctgcc ccgccacccc gtctgagatg 122580 tgaggagtgc ctctgccagg ccgcgacccc gtctgggaac tgaggagtgt ctctgcccca 122640 ccgccacccg tctgggaggt gaggagcgtc tctgacctgc caccctgtct gagaagtgag 122700 gagcccctct gcccggcagc cgccccgtcc gggaagtgag gagcgtctct gcccggcagc 122760 tgccccgtcc aggaggtggt gggcagcccc cgcccggcca gccgccccgt ccgggaaggg 122820 aggggcagcc cccgaccggc cagccgcccc gtccgggagg tggggggggg cagcccccgc 122880 ccggccagct gccccgtccg ggagctcggg gcagcccccg cctggacagc tgccccgtcc 122940 gggaggtggg agcccctctg cccggccgcc accccgtctg ggaggtgtac ccaacagctc 123000 attgagaacg ggccatgatg acaatagcgg ttttgtcgaa tagaaaaggg ggaaatgtgg 123060 ggaaaagaaa gagagatcag attgttattg tgtctgtgta gaaagaagta gacatagcag 123120 actccatttt gttctgtact aggaaaaatt cttctgcctt gggatgctgt taatctataa 123180 ccttaccccc aacccctgct ctctgaaaca tgtgctgtgt ccactaaggg ttaaatggat 123240 taagggcggt gcaagatgtg ctttgttaaa cagatgcttg aaggcagcat actcgttaag 123300 agtcatcacc actccctaat ctcaactacc cagggacaca aacactgcgg aaggcggcag 123360 ggccctctgc ctaggaaaac cagagacctt tgttcacatg tttatctgct gaccttccct 123420 ccactattgt cctatgaccc tgccaaatcc ccctctccga gaaacaccca agaatgatca 123480 ataaatacta aaattaaaaa aaaaaaaatt aaaaattatg catatagatt ttggaaagac 123540 aaccataaag tcagatcagt cacatcagcc tcctgatgtg atgcaacaga agtacacagc 123600 accaccaatg aaacatgttt gcgttaaaac tcagacactg atcaagcatc taaaatgaat 123660 taccagccag gcatggtggc tcacgcctgt aatcccagca ctttgggagg ccgaggcagg 123720 tggatacctg agatcaggag ttcaagacaa gcctggccaa catggtgaaa ccctgtctct 123780 actaaaaaca caaaaattag ctgggcatgg tggcacacac ctgtaatccc agctacttga 123840 gaagctgagg catgagaatc gcttgaaccc gggaggcgga ggttgcagtg aactgagatt 123900 gtgtcatcgc actccaacct gggtgacaag agagagactc catctcaaaa ataataataa 123960 taataataat aataataaat aaaataaatt acctatttac agaaaatatg gaggataggt 124020 gcaagtatta aacgactcca tgaagatgtc atcagccaaa tccagaatgt gggactttct 124080 acaggacaaa caataaagtt ctacaaaaaa taaatagcat ggacaggatt ggggttatag 124140 attgagatac gagatattcc aaccacttgt agtatgtggg tcttattgga acaagattca 124200 aacaaaccaa ctgtacaaag acacttgtga catgattgac aaaaactgtt tagcctaggt 124260 attactcgat atgaaggaat tattgttggc tgggcatggt ggctcatgtc tataattcca 124320 gcactttggg aggccaaggt aggtggatcg cttgagctca ggaggtggag accagcctgg 124380 gcaacatggt gaaaccctat ctctaccaaa acaaaataaa acaaaacaaa aattagctgg 124440 gtgtggtggt gcatgtctat ggtcccagct actccagagg ctgaggcagg agaatcgctt 124500 aagcttgcga ggcggaagtt gcagtgagcc aagattatac cactgcattc cagcctgagt 124560 gacatagtga ctctgtctca aaaaaaataa ataaataaaa ataaaaaatt agctgggtgt 124620 ggtggtacac acctgtagcc ccagacagtc aggaggctga ggtgggagga tcacttgggc 124680 ctgggaggtg gaggctgcag tgagccgtga ttgtgctgct gcactccagc ctgggtgaca 124740 gagtggaaac cctgtctcaa aaaaaaaaaa aaaaaaagga attactgtta attttgttgg 124800 gtataataat gatattgtgt tttttttttt aaacaaaacc tgatctgcta gagacacatt 124860 tttttaaata tatatatatt tttattatac tttaagttct agggtacatg tgcacaacgt 124920 gcaggtttgt tacatatgta tacatgtgct atgttggtgt gctgcaccca ttaactcgtc 124980 atttacatta ggtatacctc ctaatgctat cccttccccc tccccccacc ccacaacagg 125040 cccaggtgtg tgatgttccc cttcctgtgt ccaagtgttc tcgttgttca tttcccacct 125100 atgagtgaga acatgaggtg tttggttttt tgtccttgcg atagtttgct gagaatgatg 125160 gtttccagct tcatccacgt ccctacaaag gacatgaact catcattttt tatggctgca 125220 tagtattcca tggtgtatat gtgccacatt ttcttaatcc agtctaccat tgttggacat 125280 ctggcttggt tccaagtctt tactattgtg agtagtcccg caataaacat acgtgtgcat 125340 gtagagacac atatttttga agcaatacaa tgtttgggat ttgctttaaa atactccagg 125400 ggaaaaaaat aaaaatggag agaaaagatg aaacaagaac aaggaagttg gttgttgaag 125460 ctgggtgatg aatggaggtt cactgtaata gtctgtgtgt gtgtttgaaa attacaataa 125520 aaggtatttt ttttttcttt tttttgagat ggtctcgctc tgttgcccag gctggagtgc 125580 agtggtgcaa tcacagctca ctgcaagctc aacctcctgg gctcaagcaa tcccctgcct 125640 cagcctccca agcagctagg actacaggtg cacaccacca tgctcagcta atttttaaat 125700 tattttgtag aaacaaggtc tatgttgccc agggtagtct caaactcctg ggctcaagca 125760 attctcctgc ctcagcctcc cagtgagcca ccatgcctag ccccaataaa aggtattttt 125820 taaaaagatt aagttgtaga agagtatgta tataaactta tttgggtaaa aactaagtat 125880 gtatatgagt atgtatgtgt gtggatccat acacagacag acaggcagac acacacacac 125940 acacacacac acacacacac acacacacac agagagagag agaaaatgcc tagaaaatac 126000 acattaaacc atcaacagtt atttctggga ttataagggc taggagacat tgaattatta 126060 tattcttacc ctgtttcaat gttttataac aaataagtat tactttcaca agaacatttt 126120 taaaaaggaa atcataaaat gtgaagtatt ttacatatgt tacaataatg aatataggta 126180 ttagaaaatg gctttaggcc aggcatggtg gctcatgcct gtaaccctag tactttggga 126240 ggccaaggta ggaggattac ttatgcccag gagtttgagg ctgcagagag ctatgaatgt 126300 accactgcac tccagcctgg gcaattagag cgagactctg attgtattaa aaaaaaaaaa 126360 aaagtcttta acaatgtgga agaacatact caactgtatt actttttttt cttctttttt 126420 tttgagacaa gtctcagtct gtcacccaag ctggaatgca gtggtgtgat ctcggctcac 126480 tgcaacctcc acctcccggg ttcaagcaat tctccctgcc tcagcttcct gagtagctgg 126540 gcttataggt gcccaccacc acgcccagct aatttttgta ctttttagta gagacagggt 126600 ttcgccatgt tggccaggct gctcttgaac tcctgacctc aggtgatcca cccacctcag 126660 ccttccaaag tgctgggatt acacgtgtga gccactgcac ccggccttta catgtattac 126720 ttttgaaatc agtcaaaaga ataataatac ataaaatttc ctacccccca cccccccgcc 126780 atgttctggt ttccacccca tgttctggtt ttccccaatc ctgaaagttc tgagttcaag 126840 tcctggttcc atcactgact gtccatatgg ccacggtaga tctcttgatg atttgaatct 126900 cttttctcac ctgaaaagtg agagtatcat gcctcctaca tggctactga ggtggcctta 126960 tgaaataaca cagtgacctg gagggccctc caaggcagga cagggctgtt gctgttgggg 127020 aggcacacat ttcataccat gtaacctggt ccactgccac cccacttcgt ggacccaaca 127080 aagctgtgca tggcccatac tcctacacac aggcatgagg ggacaaccag gatcaaggta 127140 ggtgttggag taggaatggt taagggacag taacaggtca gctcagagtt tgcagggagt 127200 ggcagccttg tgccaggcca ggcactgaga caggcctgca tgtcccaact gtaggcaggc 127260 catatcactc tccttgtaaa tcttagtaga caccacatgg tccccaccca ggatctacag 127320 cctcatccta gcaggcactc aaatatttgc tgagtgagga tgggcacgca tgactgactt 127380 tggtcaactc ccagctggct ggtcaccaac ttttctttgt aacatattct gggccccaca 127440 gctgcatact catccctgga gccacctctt ctcaccttct cctacaccta tgcacaggaa 127500 tctcagtaca ccaaggtggc atggcagaaa tcagcagctt cccctgggga ttgtctactg 127560 agcacctaca gaaccatatg ggtctaccag gactgggaca gtggcccaaa acatagaggt 127620 tcctgatcgg ctcaggaact aggcagaaag agaatcaggt cctgagcata cctatatggc 127680 catcctgcta aaatttctca tggtccctgt agaagctata gactttcacc taaccacaga 127740 gcaaccttgt tgtggctagt tctgtgcctc tgtccctacc ctgaccattc ttttctcctg 127800 accagaatcc actctctagt tttcaaagca tttcacatct atcgctgcat tttatcctca 127860 tgccatttta cagatgagga cactgggcca gggacattag aggactgcct aaggccagga 127920 caccacgcaa tgccaaattc agacttccta acacaatatt cagcactctc ttcattctta 127980 tgtttttcta ttaacatgct gctttacaaa attaaatacc tggtttttgt cttccctcaa 128040 atttatcgtg caatgttgta acttttgtgc tgtttgaaat gagtacagag taaattaatc 128100 actcatccac ttattcattc aaccaaccag cagttttcca atgccaatta catttgaggt 128160 ctggtgctac caactgtgga ggagttacaa agaggaataa gaccaagttg aggtcttgga 128220 gtctagtaca ggagctgaag gcacatagat taattttaag aattctaaac aaggggctcc 128280 atcaaactca cctgtttttc ctttcgttgt tgtttttgcc tgtttttctt aaacaaagca 128340 tcctctcacc ccacgaaaga tctggttccc agatcccttc agagatttaa ataggatctg 128400 gacctagatc aggcctaaga atctgtatgc ttttaatgta gccctcactt tctaccctag 128460 atgattctct aattaacaga gttttggaaa cccagctcta gaagagggta cagctctatc 128520 aatagcacaa agcaatacca acaaaataca gtattttaga aggacagaaa cctcagggcc 128580 tatccagcta caatccacag ggactacaga gaggtcagat aaacttgggg ggtaagggac 128640 aaatctgctg aattcagatt aatcagcatt tagtccaact ggaacacagc tgatcatttt 128700 aagaaataag ttcacaccta gttttaaaaa acagtcctaa ctttgagatg tccagggcaa 128760 cacatgtggt gctgggacta acgcggattt gcaatactta atgatcctgt aggaacacag 128820 agcctggcgg ctgaagttga ctgacccagt atcttcaata tattaccttc ccagagctgg 128880 cctttggtct acttggtctg gcccacctca caggaattga gcaagaaaga gaacacgaga 128940 gttgaatatc cctgcaggaa ccaccaggga acttgatc 128978 7 3806 DNA Homo sapiens 7 ctcaagaatg ccagtgtgtg tgtagcctcc acagagaggt cgttttctcg gagtccagag 60 gggccgcctg agcttctgag aactagggag gagccatccc agccatgagc ccctgtggga 120 atctgctggg ggccaagtgg cctggagtcc tcaggctccc gcagctgctc cggagggaga 180 ggtgagctca gggcagcctg cctgcagcca gaggtgccgg gagccccggg cctgtcatgg 240 tggccatcta cagccggcct gaggcagtca cagacggatt tgcagctgag cctgtctatc 300 tggtgtggga agaagatggg gagttacttg tcagtcccgg cttacttcac ctccagagac 360 ctgtttcggt gttcagaatg ccaggattcc ctcaccaact ggtactatga gaaggatggg 420 aagctctact gccccaagga ctactggggg aagtttgggg agttctgtca tgggtgctcc 480 ctgctgatga cagggccttt tatggtggct ggggagttca agtaccaccc agagtgcttt 540 gcctgtatga gctgcaaggt gatcattgag gatggggatg catatgcact ggtgcagcat 600 gccaccctct actgtgggaa gtgccacaat gaggtggtgc tggcacccat gtttgagaga 660 ctctccacag agtctgttca ggagcagctg ccctactctg tcacgctcat ctccatgccg 720 gccaccactg aaggcaggcg gggcttctcc gtgtccgtgg agagtgcctg ctccaactac 780 gccaccactg tgcaagtgaa agaggtcaac cggatgcaca tcagtcccaa caatcgaaac 840 gccatccacc ctggggaccg catcctggag atcaatggga cccccgtccg cacacttcga 900 gtggaggagg tggaggatgc aattagccag acgagccaga cacttcagct gttgattgaa 960 catgaccccg tctcccaacg cctggaccag ctgcggctgg aggcccggct cgctcctcac 1020 atgcagaatg ccggacaccc ccacgccctc agcaccctgg acaccaagga gaatctggag 1080 gggacactga ggagacgttc cctaaggcgc agtaacagta tctccaagtc ccctggcccc 1140 agctccccaa aggagcccct gctgttcagc cgtgacatca gccgctcaga atcccttcgt 1200 tgttccagca gctattcaca gcagatcttc cggccctgtg acctaatcca tggggaggtc 1260 ctggggaagg gcttctttgg gcaggctatc aaggtgacac acaaagccac gggcaaagtg 1320 atggtcatga aagagttaat tcgatgtgat gaggagaccc agaaaacttt tctgactgag 1380 gtgaaagtga tgcgcagcct ggaccacccc aatgtgctca agttcattgg tgtgctgtac 1440 aaggataaga agctgaacct gctgacagag tacattgagg ggggcacact gaaggacttt 1500 ctgcgcagta tggatccgtt cccctggcag cagaaggtca ggtttgccaa aggaatcgcc 1560 tccggaatgg cctatttgca ctctatgtgc atcatccacc gggatctgaa ctcgcacaac 1620 tgcctcatca agttggacaa gactgtggtg gtggcagact ttgggctgtc acggctcata 1680 gtggaagaga ggaaaagggc ccccatggag aaggccacca ccaagaaacg caccttgcgc 1740 aagaacgacc gcaagaagcg ctacacggtg gtgggaaacc cctactggat ggcccctgag 1800 atgctgaacg gaaagagcta tgatgagacg gtggatatct tctcctttgg gatcgttctc 1860 tgtgagatca ttgggcaggt gtatgcagat cctgactgcc ttccccgaac actggacttt 1920 ggcctcaacg tgaagctttt ctgggagaag tttgttccca cagattgtcc cccggccttc 1980 ttcccgctgg ccgccatctg ctgcagactg gagcctgaga gcagaccagc attctcgaaa 2040 ttggaggact cctttgaggc cctctccctg tacctggggg agctgggcat cccgctgcct 2100 gcagagctgg aggagttgga ccacactgtg agcatgcagt acggcctgac ccgggactca 2160 cctccctagc cctggcccag ccccctgcag gggggtgttc tacagccagc attgcccctc 2220 tgtgccccat tcctgctgtg agcagggccg tccgggcttc ctgtggattg gcggaatgtt 2280 tagaagcaga acaagccatt cctattacct ccccaggagg caagtgggcg cagcaccagg 2340 gaaatgtatc tccacaggtt ctggggccta gttactgtct gtaaatccaa tacttgcctg 2400 aaagctgtga agaagaaaaa aacccctggc ctttgggcca ggaggaatct gttactcgaa 2460 tccacccagg aactccctgg cagtggattg tgggaggctc ttgcttacac taatcagcgt 2520 gacctggacc tgctgggcag gatcccaggg tgaacctgcc tgtgaactct gaagtcacta 2580 gtccagctgg gtgcaggagg acttcaagtg tgtggacgaa agaaagactg atggctcaaa 2640 gggtgtgaaa aagtcagtga tgctccccct ttctactcca gatcctgtcc ttcctggagc 2700 aaggttgagg gagtaggttt tgaagagtcc cttaatatgt ggtggaacag gccaggagtt 2760 agagaaaggg ctggcttctg tttacctgct cactggctct agccagccca gggaccacat 2820 caatgtgaga ggaagcctcc acctcatgtt ttcaaactta atactggaga ctggctgaga 2880 acttacggac aacatccttt ctgtctgaaa caaacagtca caagcacagg aagaggctgg 2940 gggactagaa agaggccctg ccctctagaa agctcagatc ttggcttctg ttactcatac 3000 tcgggtgggc tccttagtca gatgcctaaa acattttgcc taaagctcga tgggttctgg 3060 aggacagtgt ggcttgtcac aggcctagag tctgagggag gggagtggga gtctcagcaa 3120 tctcttggtc ttggcttcat ggcaaccact gctcaccctt caacatgcct ggtttaggca 3180 gcagcttggg ctgggaagag gtggtggcag agtctcaaag ctgagatgct gagagagata 3240 gctccctgag ctgggccatc tgacttctac ctcccatgtt tgctctccca actcattagc 3300 tcctgggcag catcctcctg agccacatgt gcaggtactg gaaaacctcc atcttggctc 3360 ccagagctct aggaactctt catcacaact agatttgcct cttctaagtg tctatgagct 3420 tgcaccatat ttaataaatt gggaatgggt ttggggtatt aatgcaatgt gtggtggttg 3480 tattggagca gggggaattg ataaaggaga gtggttgctg ttaatattat cttatctatt 3540 gggtggtatg tgaaatattg tacatagacc tgatgagttg tgggaccaga tgtcatctct 3600 ggtcagagtt tacttgctat atagactgta cttatgtgtg aagtttgcaa gcttgcttta 3660 gggctgagcc ctggactccc agcagcagca cagttcagca ttgtgtggct ggttgtttcc 3720 tggctgtccc cagcaagtgt aggagtggtg ggcctgaact gggccattga tcagactaaa 3780 taaattaagc agttaacata actggc 3806 8 3699 DNA Homo sapiens 8 taggcggtgc atcccgttcg cgcctggggc tgtggtcttc ccgcgcctga ggcggcggcg 60 gcaggagctg aggggagttg tagggaactg aggggagctg ctgtgtcccc cgcctcctcc 120 tccccatttc cgggctcccg ggaccatgtc cgcgctggcg ggtgaagatg tctggaggtg 180 tccaggctgt ggggaccaca ttgctccaag ccagatatgg tacaggactg tcaacgaaac 240 ctggcacggc tcttgcttcc ggtgttcaga atgccaggat tccctcacca actggtacta 300 tgagaaggat gggaagctct actgccccaa ggactactgg gggaagtttg gggagttctg 360 tcatgggtgc tccctgctga tgacagggcc ttttatggtg gctggggagt tcaagtacca 420 cccagagtgc tttgcctgta tgagctgcaa ggtgatcatt gaggatgggg atgcatatgc 480 actggtgcag catgccaccc tctactgtgg gaagtgccac aatgaggtgg tgctggcacc 540 catgtttgag agactctcca cagagtctgt tcaggagcag ctgccctact ctgtcacgct 600 catctccatg ccggccacca ctgaaggcag gcggggcttc tccgtgtccg tggagagtgc 660 ctgctccaac tacgccacca ctgtgcaagt gaaagaggtc aaccggatgc acatcagtcc 720 caacaatcga aacgccatcc accctgggga ccgcatcctg gagatcaatg ggacccccgt 780 ccgcacactt cgagtggagg aggtggagga tgcaattagc cagacgagcc agacacttca 840 gctgttgatt gaacatgacc ccgtctccca acgcctggac cagctgcggc tggaggcccg 900 gctcgctcct cacatgcaga atgccggaca cccccacgcc ctcagcaccc tggacaccaa 960 ggagaatctg gaggggacac tgaggagacg ttccctaagg cgcagtaaca gtatctccaa 1020 gtcccctggc cccagctccc caaaggagcc cctgctgttc agccgtgaca tcagccgctc 1080 agaatccctt cgttgttcca gcagctattc acagcagatc ttccggccct gtgacctaat 1140 ccatggggag gtcctgggga agggcttctt tgggcaggct atcaaggtga cacacaaagc 1200 cacgggcaaa gtgatggtca tgaaagagtt aattcgatgt gatgaggaga cccagaaaac 1260 ttttctgact gaggtgaaag tgatgcgcag cctggaccac cccaatgtgc tcaagttcat 1320 tggtgtgctg tacaaggata agaagctgaa cctgctgaca gagtacattg aggggggcac 1380 actgaaggac tttctgcgca gtatggatcc gttcccctgg cagcagaagg tcaggtttgc 1440 caaaggaatc gcctccggaa tggcctattt gcactctatg tgcatcatcc accgggatct 1500 gaactcgcac aactgcctca tcaagttgga caagactgtg gtggtggcag actttgggct 1560 gtcacggctc atagtggaag agaggaaaag ggcccccatg gagaaggcca ccaccaagaa 1620 acgcaccttg cgcaagaacg accgcaagaa gcgctacacg gtggtgggaa acccctactg 1680 gatggcccct gagatgctga acggaaagag ctatgatgag acggtggata tcttctcctt 1740 tgggatcgtt ctctgtgaga

tcattgggca ggtgtatgca gatcctgact gccttccccg 1800 aacactggac tttggcctca acgtgaagct tttctgggag aagtttgttc ccacagattg 1860 tcccccggcc ttcttcccgc tggccgccat ctgctgcaga ctggagcctg agagcagacc 1920 agcattctcg aaattggagg actcctttga ggccctctcc ctgtacctgg gggagctggg 1980 catcccgctg cctgcagagc tggaggagtt ggaccacact gtgagcatgc agtacggcct 2040 gacccgggac tcacctccct agccctggcc cagccccctg caggggggtg ttctacagcc 2100 agcattgccc ctctgtgccc cattcctgct gtgagcaggg ccgtccgggc ttcctgtgga 2160 ttggcggaat gtttagaagc agaacaagcc attcctatta cctccccagg aggcaagtgg 2220 gcgcagcacc agggaaatgt atctccacag gttctggggc ctagttactg tctgtaaatc 2280 caatacttgc ctgaaagctg tgaagaagaa aaaaacccct ggcctttggg ccaggaggaa 2340 tctgttactc gaatccaccc aggaactccc tggcagtgga ttgtgggagg ctcttgctta 2400 cactaatcag cgtgacctgg acctgctggg caggatccca gggtgaacct gcctgtgaac 2460 tctgaagtca ctagtccagc tgggtgcagg aggacttcaa gtgtgtggac gaaagaaaga 2520 ctgatggctc aaagggtgtg aaaaagtcag tgatgctccc cctttctact ccagatcctg 2580 tccttcctgg agcaaggttg agggagtagg ttttgaagag tcccttaata tgtggtggaa 2640 caggccagga gttagagaaa gggctggctt ctgtttacct gctcactggc tctagccagc 2700 ccagggacca catcaatgtg agaggaagcc tccacctcat gttttcaaac ttaatactgg 2760 agactggctg agaacttacg gacaacatcc tttctgtctg aaacaaacag tcacaagcac 2820 aggaagaggc tgggggacta gaaagaggcc ctgccctcta gaaagctcag atcttggctt 2880 ctgttactca tactcgggtg ggctccttag tcagatgcct aaaacatttt gcctaaagct 2940 cgatgggttc tggaggacag tgtggcttgt cacaggccta gagtctgagg gaggggagtg 3000 ggagtctcag caatctcttg gtcttggctt catggcaacc actgctcacc cttcaacatg 3060 cctggtttag gcagcagctt gggctgggaa gaggtggtgg cagagtctca aagctgagat 3120 gctgagagag atagctccct gagctgggcc atctgacttc tacctcccat gtttgctctc 3180 ccaactcatt agctcctggg cagcatcctc ctgagccaca tgtgcaggta ctggaaaacc 3240 tccatcttgg ctcccagagc tctaggaact cttcatcaca actagatttg cctcttctaa 3300 gtgtctatga gcttgcacca tatttaataa attgggaatg ggtttggggt attaatgcaa 3360 tgtgtggtgg ttgtattgga gcagggggaa ttgataaagg agagtggttg ctgttaatat 3420 tatcttatct attgggtggt atgtgaaata ttgtacatag acctgatgag ttgtgggacc 3480 agatgtcatc tctggtcaga gtttacttgc tatatagact gtacttatgt gtgaagtttg 3540 caagcttgct ttagggctga gccctggact cccagcagca gcacagttca gcattgtgtg 3600 gctggttgtt tcctggctgt ccccagcaag tgtaggagtg gtgggcctga actgggccat 3660 tgatcagact aaataaatta agcagttaac ataactggc 3699 9 2805 DNA Homo sapiens 9 gggaggagcc atcccagcca tgagcccctg tgggaatctg ctgggggcca agtggcctgg 60 agtcctcagg ctcccgcagc tgctccggag ggagaggtga gctcagggca gcctgcctgc 120 agccagaggt gccgggagcc ccgggcctgt catggtggcc atctacagcc ggcctgaggc 180 agtcacagac ggatttgcag ctgagcctgt ctatctggtg tgggaagaag atggggagtt 240 acttgtcagt cccggcttac ttcacctcca gagacctgtt tcggtgttca gaatgccagg 300 attccctcac caactggtac tatgagaagg atgggaagct ctactgcccc aaggactact 360 gggggaagtt tggggagttc tgtcatgggt gctccctgct gatgacaggg ccttttatgg 420 tggctgggga gttcaagtac cacccagagt gctttgcctg tatgagctgc aaggtgatca 480 ttgaggatgg ggatgcatat gcactggtgc agcatgccac cctctactgt gggaagtgcc 540 acaatgaggt ggtgctggca cccatgtttg agagactctc cacagagtct gttcaggagc 600 agctgcccta ctctgtcacg ctcatctcca tgccggccac cactgaaggc aggcggggct 660 tctccgtgtc cgtggagagt gcctgctcca actacgccac cactgtgcaa gtgaaagagg 720 tcaaccggat gcacatcagt cccaacaatc gaaacgccat ccaccctggg gaccgcatcc 780 tggagatcaa tgggaccccc gtccgcacac ttcgagtgga ggaggtggag gatgcaatta 840 gccagacgag ccagacactt cagctgttga ttgaacatga ccccgtctcc caacgcctgg 900 accagctgcg gctggaggcc cggctcgctc ctcacatgca gaatgccgga cacccccacg 960 ccctcagcac cctggacacc aaggagaatc tggaggggac actgaggaga cgttccctaa 1020 ggcgcagtaa cagtatctcc aagtcccctg gccccagctc cccaaaggag cccctgctgt 1080 tcagccgtga catcagccgc tcagaatccc ttcgttgttc cagcagctat tcacagcaga 1140 tcttccggcc ctgtgaccta atccatgggg aggtcctggg gaagggcttc tttgggcagg 1200 ctatcaaggt gacacacaaa gccacgggca aagtgatggt catgaaagag ttaattcgat 1260 gtgatgagga gacccagaaa acttttctga ctgaggtgaa agtgatgcgc agcctggacc 1320 accccaatgt gctcaagttc attggtgtgc tgtacaagga taagaagctg aacctcctga 1380 cagagtacat tgaggggggc acactgaagg actttctgcg cagtatggat ccgttcccct 1440 ggcagcagaa ggtcaggttt gccaaaggaa tcgcctccgg aatggcctat ttgcactcta 1500 tgtgcatcat ccaccgggat ctgaactcgc acaactgcct catcaagttg gacaagactg 1560 tggtggtggc agactttggg ctgtcacggc tcatagtgga agagaggaaa agggccccca 1620 tggagaaggc caccaccaag aaacgcacct tgcgcaagaa cgaccgcaag aagcgctaca 1680 cggtggtggg aaacccctac tggatggccc ctgagatgct gaacggaaag agctatgatg 1740 agacggtgga tatcttctcc tttgggatcg ttctctgtga gatcattggg caggtgtatg 1800 cagatcctga ctgccttccc cgaacactgg actttggcct caacgtgaag cttttctggg 1860 agaagtttgt tcccacagat tgtcccccgg ccttcttccc gctggccgcc atctgctgca 1920 gactggagcc tgagagcaga gccccccccg gggccgcagg agagggcccg ggctgcgcgg 1980 atgatgaggg cccagtgagg cgccaaggga aggtcaccat caagtatgac cccaaggagc 2040 tacggaagca cctcaaccta gaggagtgga tcctggagca gctcacgcgc ctctacgact 2100 gccaggaaga ggagatctca gaactagaga ttgacgtgga tgagctcctg gacatggaga 2160 gtgacgatgc ctgggcttcc agggtcaagg agctgctggt tgactgttac aaacccacag 2220 aggccttcat ctctggcctg ctggacaaga tccgggccat gcagaagctg agcacacccc 2280 agaagaagtg agggtccccg acccaggcga acggtggctc ccataggaca atcgctaccc 2340 cccgacctcg tagcaacagc aataccgggg gaccctgcgg ccaggcctgg ttccatgagc 2400 agggctcctc gtgcccctgg cccaggggtc tcttcccctg ccccctcagt tttccacttt 2460 tggatttttt tattgttatt aaactgatgg gactttgtgt ttttatattg actctgcggc 2520 acgggccctt taataaagcg aggtagggta cgcctttggt gcagctcaaa aaaaaaaaaa 2580 aaaatgattt ccagcggtcc acattagagt tgaaattttc tggtgggaga atctatacct 2640 tgttccttta taggccaagg accgcagtcc ttcagtaaca ccagtgtaaa agcttgagga 2700 gaaattgtga agctacacag tatttgtttt ctaatacctc ttgtcattct aaatatcttt 2760 aatttattaa aaaatatata tatacagtaa aaaaaaaaaa aaaaa 2805 10 3581 DNA Rattus norvegicus 10 gggctgtaga ggcctctgca cctcctcctc tggcctgagg ggggcatacc cgcgtctaca 60 gacgcggggc gcaacctgcc gaaaggggtc acaccgctgg gcgagagcta ggggaggagt 120 caccttgaga ggaggggtca caatgattag ccgagtcact ctgaaaggtc tcttttagtg 180 aaaggaacac aaagaggagg gggtgcagca ctaaggggct ctggatacac actgatgtgc 240 cagtgtcatc ccaaggaaag gtccccctga aggagagcgg gctccgaggg gcagcggcct 300 ttgagggggc gggatcctgt cgaggggtgg gctgtgacgg agggcggggc tttcttgcag 360 gtgcaggctt cccctaagag ggttattagg acaaagaagt aggagggtgg tcaccgggcg 420 gagcgcagga atctcaactt tactcagggg aatggagatg gagtgaggag gggtcgggcc 480 aggtcaggga tgcggaggcc agaggctccc tacagccctg ggtaccacga ccggagaaaa 540 caggtgttag cgagccccga gatttagggt gtcggggtca gaagcccctt gaaatgggca 600 gtcggagtgg ggcgcagact gggcaggcag cgggcttgat ccgtggagcc cagggcgcag 660 gagaattcgc gcctgcagtc aacccttaag tcgtcctgtt attcacgccc cggcctacgc 720 gccgggacgc acctgagggg gcgtggccgg gccacagctc gggctccaag gagttaaccg 780 cagacccggc cggccacgcc ccgggcaggc cgcgcagcct gagcccggcg gcgaagcgga 840 gcagcagccg cccgcgggga gcccgccgcc ggcgcccggg agcgccgccg ccgcccggcc 900 caggcccagg cccaggcccc gcgcagagcg gagagccgcg gcgttccacc aggcccaact 960 cgccggcgcg gcgggggcgg gcccaggacc ttcggcaggt cctcccggag tccgccgggc 1020 gggagtcccg gcacccggga tcaggttggg ccggcgccca tggcgagcgc ggcctgcccg 1080 ggtcccgggg atccggccat gtgaagcagg ccggggctgg gggcccggcc atggccgggg 1140 aacggccacc gctgcggggc cccgggcccg gagagactcc ggtggagggg ccggggggcg 1200 caggcggagg cccgggccgg ggccggccct cctcctaccg ggccctccgc agcgccgtgt 1260 ccagcctggc gcgcgtggac gatttcgact gcgcagagaa gatcggggct ggtttcttct 1320 ctgaggtcta taaggttcgg caccgacagt cgggacaagt catggtgctg aagatgaaca 1380 agctccccag taaccggagc aacactctaa gggaggtgca gctgatgaac cggctccggc 1440 atcctaacat cctcaggttc atgggggtct gtgtgcacca agggcagctg cacgcgctta 1500 cagagtatat gaatgggggt accctggaac agctgctgag ctccccagaa cccctctcct 1560 ggccagtcag gctccaccta gcactggaca ttgcacaagg cctacggtac ctacacgcca 1620 aaggtgtgtt tcaccgagac ctcacatcca agaactgtct ggtccgacgg gaagacggag 1680 gcttcacagc tgttgtgggt gacttcggac tggctgaaaa gatccctgtg tatagggaag 1740 gggcaaggaa ggagccattg gctgtggtgg gctccccata ctggatggcc ccagaggtgt 1800 tgcggggaga gctgtatgat gagaaggccg acgtcttcgc ctttgggatt gtcctctgtg 1860 agctcatcgc ccgagtacct gcagaccctg actacctacc ccgtactgag gactttggtc 1920 tggatgtgcc tgcttttcga actctggtgg gaaatgactg tccgctacct ttcctgcttc 1980 tggccatcca ctgctgcagc atggaaccca gcgcccgtgc cccttttact gaaattaccc 2040 agcacctgga acaaatcctg gagcagctgc ctgagcccac gcccctcgcc aagatgcccc 2100 ttgccaaggc tcccttgaca tacaatcagg ggtctgttcc aagaggaggt ccctctgcca 2160 cgcttcccag gtcagacccc cggctctccc gaagccggtc agacctcttc ctgccacctt 2220 caccagaatc accccccagt tggggggaca atctaacacg agtcaacccc ttctcactgc 2280 gggaagacct caggggtggc aagatcaaac ttctggacac accctgcaag ccggccactc 2340 cactgcccct ggtgccacca tcaccactga cctctaccca gctgcccttg gtggcctctc 2400 cagagtccct ggtccagcct gagactcccg tccgccgctg tcgttcactc ccttcatccc 2460 ctgagctccc ccgacggatg gaaactgcac tgccaggtcc tggcccgtcc cccgtgggcc 2520 cctcgactga ggaaaggatg gactgtgagg gcagcagccc tgagccagag cccccagggc 2580 cggctcccca gctgcctctg gctgtggcca ctgacaactt catcagtacg tgttcctcag 2640 cctctcagcc ctggtctgct agaccaggac cttccctcaa taataacccc cctgctgtgg 2700 tggtgaattc cccacaagga tgggcgaggg agccctggaa ccgggcacag catagccttc 2760 cccgggcagc agccctggag cggacagaac cctcaccacc cccatcagct ccccgggagc 2820 aggaggaggg gctgccctgc cctggctgct gcctcagccc cttcagcttt ggcttcctat 2880 ccatgtgccc ccgccctacc ccagctgttg cccgctaccg caacttgaac tgtgaggcgg 2940 gcagtcttct ctgccaccga gggcatcatg ccaagccacc cacacccagc ctgcagctgc 3000 ctggggcacg ctcttagcac tgaggcctgt gatctcaggc ttccaacctt ggccttcggg 3060 ataccctgta aggacagagt gcacttgctg gacaatgcca gccccagatg ggctgactgg 3120 ctcttctccc cgtatagggg agcctcagca tggtctcaat ggacagagca cttcctgtcc 3180 aacccctggg atcactggac tagacacagc attgctgaca cacaagacta acacgtgcaa 3240 aatatttaaa aatatttcaa taaaactgcc tggctggctc cgggccatcc atccactcag 3300 cggagcgccc tcccctgacc catctctagt tcgggaagtt cttaaggaag gtcaaagtct 3360 tttctggagg cttctttact cttcccaaga atagtttctg gagcagcttt caagcaagca 3420 gcaggtcgcc agaccagaat cagcccttag ctgggcgtgc ccaagagtga gggagtgctg 3480 gaggaatagc agtcttgaga attggcaggc cataggttaa ggatgtaggt cacaaggtct 3540 tgttcaagtg tctggaaaaa taaagcacca gtgagctccc c 3581 11 2443 DNA Homo sapiens 11 caccgccacc gcctggtcca ggcccaagcc caggccctgc gcggagcgga gcggcgcggc 60 gtccacccgg gcccagccag ccggcgcggc gggggcgggt ccaggatctt cggcggatct 120 tcggcggatc ttcggcggat cttccattct cagggcggga gccggagtcc gggcgcccgg 180 gatcgggctg ggcccgcgcc catggcaagc gcggcctgcc cgggccctgg ggaccctgcc 240 atgtgaggca ggcccgggct gggggcccgg ccatggccgg ggaacggccc ccactgcggg 300 gccctgggcc cgggcctgga gaggtgccgg gggaggggcc cccggggccg gggggcacgg 360 gcggaggccc gggccggggc cgcccctcct cctaccgggt tctccgcagc gccgtgtcta 420 gcctggcgcg tgtggacgat tttcactgcg cggagaagat cggggccggc ttcttctctg 480 aggtctacaa ggttcggcac cgacagtcag ggcaagtcat ggtgctgaag atgaacaagc 540 tccccagtaa ccggggcaac acactacggg aagtgcagct gatgaaccgg ctcaggcacc 600 ccaacatcct aaggttcatg ggagtctgtg tgcaccaggg acagctgcac gctcttacag 660 agtatatgaa tggggggaca ttggaacagc tgctcagctc ccctgaaccc ctatcctggc 720 cggtcaggct ccacctggcc ctggacattg cccgaggcct gcggtacctg cactccaaag 780 gtgtatttca ccgcgacctc acatccaaga actgtctagt ccgacgggaa gatcgaggct 840 tcaccgctgt cgtgggtgac ttcgggctgg ccgaaaagat tcctgtgtat agggaggggg 900 caaggaagga gccattggcc gtggtgggct ccccatactg gatggctcca gaggtgttac 960 ggggtgagct gtatgatgag aaggctgatg tctttgcctt cgggattgtc ctctgtgagc 1020 tcatcgcccg agtacctgca gaccctgact acctaccacg cactgaggac tttggcctgg 1080 atgtgcctgc tttccgaact ctggtggggg atgactgccc actgcctttc ttgctcctgg 1140 ccatccactg ctgcaacctg gaacccagca cccgtgcccc cttcaccgaa attacccagc 1200 acctggaatg gatcctggag cagctgcctg agccagcccc actcaccagg accgccctga 1260 cacacaatca gggctctgtt gcaagagggg gtccctctgc cacgcttccc aggccagatc 1320 cccggctttc ccgaagccgg tcagacctct tcctgccccc atcaccagaa tcacccccca 1380 actgggggga caatctgact cgagtcaacc ccttctcact acgggaagac ctcaggggtg 1440 gcaagatcaa gctcttagac acacccagca agccagtcct gcctcttgtg ccaccatcac 1500 cattcccatc cactcagctg cccttggtga ccactccgga gaccctggtc cagcctggga 1560 cacctgcccg ccgctgccgc tcactaccct catcccccga gctcccccgc cgtatggaga 1620 cagcactgcc aggtcctggc cctcccgctg tgggcccctc ggctgaagag aagatggagt 1680 gcgagggcag cagccctgag ccggaacctc cagggccagc gccccagctg cctctggctg 1740 tggccacaga caacttcatc agcacctgtt cctcggcctc ccaaccctgg tcccctagat 1800 caggacccgt cctcaataac aatcccccag ctgtggtggt gaactcccca caaggctggg 1860 ctggggagcc ctggaaccgg gcccagcata gcctgccccg ggcggcagcc ctggagcgga 1920 cagaaccctc gccaccccct tcagctcccc gggagcccga tgaggggctg ccctgtcctg 1980 gctgctgcct cggccccttc agctttggct tcctgtccat gtgcccccgc cccacaccag 2040 ctgttgcccg ctaccgcaac ctgaactgtg aggcgggcag tctcctctgc caccgagggc 2100 accacgccaa gccacccaca cccagcctgc agctgcctgg ggcacgctct tagcagtgga 2160 gcccgtggtc tcaggcctcc aactttggcc ttcaggacac cctgtaagaa cagagcacac 2220 ttgctggaca gtgccagttc cagatgggct gaccggctct tctccccgtg taggggagcc 2280 ccagcatgga ctcaagggac agagcacttc cagtcgaccc cccggctcgc gttcccgtgg 2340 ggatcactga accagacaca gcattgctga cacatgagac taacacgtgc aattatttaa 2400 aaagatttca ataaaactgc ctggctggct ccgggccgcc cct 2443 12 2421 DNA Homo sapiens 12 caccgccacc gcccggtcca ggcccaagcc caggccctgc gcggagcgga gcggcgcggc 60 gtccacccgg gcccagccag ccggcgcggc gggggcgggt ccaggatctt cggcggatct 120 tccattctca gggcgggagc cggagtccgg gcgcccggga tcgggctggg cccgcgccca 180 tggcaagcgc ggcctgcccg ggccctgggg accctgccat gtgaggcagg cccgggctgg 240 gggcccggcc atggccgggg aacggccccc actgcggggc cctgggcccg ggcctggaga 300 ggtgccgggg gaggggcccc cggggccggg gggcacgggc ggaggcccgg gccggggccg 360 cccctcctcc taccgggctc tccgcagcgc cgtgtctagc ctggcgcgtg tggacgattt 420 tcactgcgcg gagaagatcg gggccggctt cttctctgag gtctacaagg ttcggcaccg 480 acagtcaggg caagtcatgg tgctgaagat gaacaagctc cccagtaacc ggggcaacac 540 actacgggaa gtgcagctga tgaaccggct caggcacccc aacatcctaa ggttcatggg 600 agtctgtgtg caccagggac agctgcacgc tcttacagag tatatgaatg gggggacatt 660 ggaacagctg ctcagctccc ctgaacccct gtcctggccg gtcaggctcc acctggccct 720 ggacattgcc cgaggcctgc ggtacctgca ctccaaaggt gtatttcacc gcgacctcac 780 atccaagaac tgtctagtcc gacgggaaga tcgaggcttc accgctgtcg tgggtgactt 840 cgggctggcc gaaaagattc ctgtgtatag ggagggggca aggaaggagc cattggccgt 900 ggtgggctcc ccatactgga tggctccaga ggtgttacgg ggtgagctgt atgatgagaa 960 ggctgatgtc tttgccttcg ggattgtcct ctgtgagctc atcgcccgag tacctgcaga 1020 ccctgactac ctaccacgca ctgaggactt tggcctggat gtgcctgctt tccgaactct 1080 ggtgggggat gactgcccac tgcctttctt gctcctggcc atccactgct gcaacctgga 1140 acccagcacc cgtgccccct tcaccgaaat tacccagcac ctggaatgga tcctggagca 1200 gctgcctgag ccagccccac tcaccaggac cgccctgaca cacaatcagg gctctgttgc 1260 aagagggggt ccctctgcca cgcttcccag gccagatccc cggctttccc gaagccggtc 1320 agacctcttc ctgcccccat caccagaatc accccccaac tggggggaca atctgactcg 1380 agtcaacccc ttctcactac gggaagacct caggggtggc aagatcaagc tcttagacac 1440 acccagcaag ccagtcctgc ctcttgtgcc accatcacca ttcccatcca ctcagctgcc 1500 cttggtgacc actccggaga ccctggtcca gcctgggaca cctgcccgcc gctgccgctc 1560 actaccctca tcccccgagc tcccccgccg tatggagaca gcactgccag gtcctggccc 1620 tcccgctgtg ggcccctcgg ctgaagagaa gatggagtgc gagggcagca gccctgagcc 1680 ggaacctcca gggccagcgc cccagctgcc tctggctgtg gccacagaca acttcatcag 1740 cacctgttcc tcggcctccc aaccctggtc ccctagatca ggacccgtcc tcaataacaa 1800 tcccccagct gtggtggtga actccccaca aggctgggct ggggagccct ggaaccgggc 1860 ccagcatagc ctgccccggg cggcagccct ggagcggaca gaaccctcgc cacccccttc 1920 agctccccgg gagcccgatg aggggctgcc ctgtcctggc tgctgcctcg gccccttcag 1980 ctttggcttc ctgtccatgt gcccccgccc cacaccagct gttgcccgct accgcaacct 2040 gaactgtgag gcgggcagtc tcctctgcca ccgagggcac cacgccaagc cacccacacc 2100 cagcctgcag ctgcctgggg cacgctctta gcagtggagc ccgtggtctc aggcctccaa 2160 ctttggcctt caggacaccc tgtaagaaca gagcacactt gctggacagt gccagttcca 2220 gatgggctga ccggctcttc tccccgtgta ggggagcccc agcatggact caagggacag 2280 agcacttcca gtcgaccccc cggctcgcgt tcccgtgggg atcactgaac cagacacagc 2340 attgctgaca catgagacta acacgtgcaa ttatttaaaa agatttcaat aaaactgcct 2400 ggctggctcc gggccgcccc t 2421 13 2299 DNA Homo sapiens 13 ggcacgaggc cattctcagg gcgggagccg gagtccgggc gcccgggatc gggctgggcc 60 cgcgcccatg gcaagcgcgg cctgcccggg ccctggggac cctgccatgt gaggcaggcc 120 cgggctgggg gcccggccat ggccggggaa cggcccccac tgcggggccc tgggcccggg 180 cctggagagg tgccggggga ggggcccccg gggccggggg gcacgggcgg aggcccgggc 240 cggggccgcc cctcctccta ccgggctctc cgcagcgccg tgtctagcct ggcgcgtgtg 300 gacgattttc actgcgcgga gaagatcggg gccggcttct tctctgaggt ctacaaggtt 360 cggcaccgac agtcagggca agtcatggtg ctgaagatga acaagctccc cagtaaccgg 420 ggcaacacac tacgggaagt gcagctgatg aaccggctca ggcaccccaa catcctaagg 480 ttcatgggag tctgtgtgca ccagggacag ctgcacgctc ttacagagta tatgaatggg 540 gggacattgg aacagctgct cagctcccct gaacccctat cctggccggt caggctccac 600 ctggccctgg acattgcccg aggcctgcgg tacctgcact ccaaaggtgt atttcaccgc 660 gacctcacat ccaagggagg gggcaaggaa ggagccattg gccgtggtgg gctccccata 720 ctggatggct ccagaggtgt tacggggtga gctgtatgat gagaaggctg atgtctttgc 780 cttcgggatt gtcctctgtg agctcatcgc ccgagtacct gcagaccctg actacctacc 840 acgcactgag gactttggcc tggatgtgcc tgctttccga actctggtgg gggatgactg 900 cccactgcct ttcttgctcc tggccatcca ctgctgcaac ctggaaccca gcacccgtgc 960 ccccttcacc gaaattaccc agcacctgga atggatcctg gagcagctgc ctgagccagc 1020 cccactcacc aggaccgccc tgacacacaa tcagggctct gttgcaagag ggggtccctc 1080 tgccacgctt cccaggccag atccccggct ttcccgaagc cggtcagacc tcttcctgcc 1140 cccatcacca gaatcacccc ccaactgggg ggacaatctg actcgagtca accccttctc 1200 actacgggaa gacctcaggg gtggcaagat caagctctta gacacaccca gcaagccagt 1260 cctgcctctt gtgccaccat caccattccc atccactcag ctgcccttgg tgaccactcc 1320 ggagaccctg gtccagcctg ggacacctgc ccgccgctgc cgctcactac cctcatcccc 1380 cgagctcccc cgccgtatgg agacagcact gccaggtcct ggccctcccg ctgtgggccc 1440 ctcggctgaa gagaagatgg agtgcgaggg cagcagccct gagccggaac ctccagggcc 1500 agcgccccag ctgcctctgg ctgtggccac agacaacttc atcagcacct gttcctcggc 1560 ctcccaaccc tggtccccta gatcaggacc cgtcctcaat aacaatcccc

cagctgtggt 1620 ggtgaactcc ccacaaggct gggctgggga gccctggaac cgggcccagc atagcctgcc 1680 ccgggcggca gccctggagc ggacagaacc ctcgccaccc ccttcagctc cccgggagcc 1740 cgatgagggg ctgccctgtc ctggctgctg cctcggcccc ttcagctttg gcttcctgtc 1800 catgtgcccc cgccccacac cagctgttgc ccgctaccgc aacctgaact gtgaggcggg 1860 cagtctcctc tgccaccgag ggcaccacgc caagccaccc acacccagcc tgcagctgcc 1920 tggggcacgc tcttagcagt ggagcccgtg gtctcaggcc tccaactttg gccttcagga 1980 caccctgtaa gaacagagca cacttgctgg acagtgccag ttccagatgg gctgaccggc 2040 tcttctcccc gtgtagggga gccccagcat ggactcaagg gacagagcac ttccagtcga 2100 ccccccggct cgcgttcccg tggggatcac tgaaccagac acagcattgc tgacacatga 2160 gactaacacg tgcaattatt taaaaagatt tcaataaaac tgcctggctg gctccgggcc 2220 gcccctatcc gctcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2280 aaaaaaaaaa aaaaaaaaa 2299 14 2443 DNA Homo sapiens 14 caccgccacc gcctggtcca ggcccaagcc caggccctgc gcggagcgga gcggcgcggc 60 gtccacccgg gcccagccag ccggcgcggc gggggcgggt ccaggatctt cggcggatct 120 tcggcggatc ttcggcggat cttccattct cagggcggga gccggagtcc gggcgcccgg 180 gatcgggctg ggcccgcgcc catggcaagc gcggcctgcc cgggccctgg ggaccctgcc 240 atgtgaggca ggcccgggct gggggcccgg ccatggccgg ggaacggccc ccactgcggg 300 gccctgggcc cgggcctgga gaggtgccgg gggaggggcc cccggggccg gggggcacgg 360 gcggaggccc gggccggggc cgcccctcct cctaccgggt tctccgcagc gccgtgtcta 420 gcctggcgcg tgtggacgat tttcactgcg cggagaagat cggggccggc ttcttctctg 480 aggtctacaa ggttcggcac cgacagtcag ggcaagtcat ggtgctgaag atgaacaagc 540 tccccagtaa ccggggcaac acactacggg aagtgcagct gatgaaccgg ctcaggcacc 600 ccaacatcct aaggttcatg ggagtctgtg tgcaccaggg acagctgcac gctcttacag 660 agtatatgaa tggggggaca ttggaacagc tgctcagctc ccctgaaccc ctatcctggc 720 cggtcaggct ccacctggcc ctggacattg cccgaggcct gcggtacctg cactccaaag 780 gtgtatttca ccgcgacctc acatccaaga actgtctagt ccgacgggaa gatcgaggct 840 tcaccgctgt cgtgggtgac ttcgggctgg ccgaaaagat tcctgtgtat agggaggggg 900 caaggaagga gccattggcc gtggtgggct ccccatactg gatggctcca gaggtgttac 960 ggggtgagct gtatgatgag aaggctgatg tctttgcctt cgggattgtc ctctgtgagc 1020 tcatcgcccg agtacctgca gaccctgact acctaccacg cactgaggac tttggcctgg 1080 atgtgcctgc tttccgaact ctggtggggg atgactgccc actgcctttc ttgctcctgg 1140 ccatccactg ctgcaacctg gaacccagca cccgtgcccc cttcaccgaa attacccagc 1200 acctggaatg gatcctggag cagctgcctg agccagcccc actcaccagg accgccctga 1260 cacacaatca gggctctgtt gcaagagggg gtccctctgc cacgcttccc aggccagatc 1320 cccggctttc ccgaagccgg tcagacctct tcctgccccc atcaccagaa tcacccccca 1380 actgggggga caatctgact cgagtcaacc ccttctcact acgggaagac ctcaggggtg 1440 gcaagatcaa gctcttagac acacccagca agccagtcct gcctcttgtg ccaccatcac 1500 cattcccatc cactcagctg cccttggtga ccactccgga gaccctggtc cagcctggga 1560 cacctgcccg ccgctgccgc tcactaccct catcccccga gctcccccgc cgtatggaga 1620 cagcactgcc aggtcctggc cctcccgctg tgggcccctc ggctgaagag aagatggagt 1680 gcgagggcag cagccctgag ccggaacctc cagggccagc gccccagctg cctctggctg 1740 tggccacaga caacttcatc agcacctgtt cctcggcctc ccaaccctgg tcccctagat 1800 caggacccgt cctcaataac aatcccccag ctgtggtggt gaactcccca caaggctggg 1860 ctggggagcc ctggaaccgg gcccagcata gcctgccccg ggcggcagcc ctggagcgga 1920 cagaaccctc gccaccccct tcagctcccc gggagcccga tgaggggctg ccctgtcctg 1980 gctgctgcct cggccccttc agctttggct tcctgtccat gtgcccccgc cccacaccag 2040 ctgttgcccg ctaccgcaac ctgaactgtg aggcgggcag tctcctctgc caccgagggc 2100 accacgccaa gccacccaca cccagcctgc agctgcctgg ggcacgctct tagcagtgga 2160 gcccgtggtc tcaggcctcc aactttggcc ttcaggacac cctgtaagaa cagagcacac 2220 ttgctggaca gtgccagttc cagatgggct gaccggctct tctccccgtg taggggagcc 2280 ccagcatgga ctcaagggac agagcacttc cagtcgaccc cccggctcgc gttcccgtgg 2340 ggatcactga accagacaca gcattgctga cacatgagac taacacgtgc aattatttaa 2400 aaagatttca ataaaactgc ctggctggct ccgggccgcc cct 2443 15 3016 DNA Homo sapiens 15 gaattcgcgg ccgctcgacg ctcagcagag ctaccagctg ccctgttggc ttcgctggtc 60 ggatcgtcct cctggccccg ccaaacaggc gagcggcccc gactgtgggg catggcagta 120 gtctcctcgt tctccgccgc cgctagccta gctgagtcgc cggcttctgc gctaggggct 180 cccaccgcct ccgcaggcta aggagccgct gccaccaacg agctgtgagg gttactatgc 240 tccctctttg ccgccgtctc ctcctcttgc ccgcgcaggc acccctctgg ctgctcagtc 300 ctgcctcagt gtcaaaccag aagagaagta aaattcaaca aaaatttatg tgtggagttc 360 cttcttaaaa gaagaaaaaa gtgattattt agactatgga tcggagcaaa cggaattcaa 420 ttgcaggatt tcctccacgt gtggagcgtc ttgaagagtt tgaaggaggt ggtggaggag 480 aaggaaatgt gagccaggtg ggaagagttt ggccatcttc gtatcgagct cttataagtg 540 ccttttccag actgacgcgt ttggatgatt tcacctgtga aaaaataggg tctggcttct 600 tttctgaagt gttcaaggta cgacaccgag cttctggtca ggtgatggct cttaagatga 660 acacattgag cagtaaccgg gcaaacatgc tgaaagaagt acagctcatg aatagactct 720 cccatcccaa catccttagg tatatcaact ccgggaacct ggaacagttg ctagacagta 780 acctgcattt gccttggact gtgagggtaa aactggccta tgacatagca gtgggcctca 840 gctaccttca cttcaaaggc atttttcatc gggacctcac atctaagaac tgcctgataa 900 agagggatga gaatggttac tctgcagtgg tagctgactt tggcctggct gagaagatcc 960 ccgatgtcag catggggagt gagaagctgg ccgtggtggg ttccccattc tggatggcac 1020 ctgaggttct ccgagatgag ccctataatg aaaaggcaga tgtgttctct tatggtatca 1080 tcctctgcga gatcatcgcc cgcatccagg ccgatccgga ctatcttccc cgcacagaga 1140 atttcgggct ggactatgat gctttccagc acatggtggg agactgtccc ccagattttc 1200 tgcaacttac tttcaactgc tgtaacatgg atcccaaact gcgcccatct tttgtggaga 1260 ttgggaagac cctggaggaa attctgagcc gcctacagga agaagagcag gagagggata 1320 ggaagctgca gcccacagcc aggggactct tggagaaagc acctggggtg aagcgactaa 1380 gctcactgga tgacaagatc ccccacaagt caccatgccc aagacgtacc atctggctgt 1440 ctcgaagcca gtcagatatc ttttcccgta agcccccacg tacagtgagt gtcttggacc 1500 catactaccg gccacgagat ggtgctgccc gcacccccaa agtcaaccct tttagtgctc 1560 gccaggacct catggggggc aagatcaagt tttttgacct gcccagcaag tctgtcatct 1620 ctctggtatt tgacctggat gcaccagggc ccggaactat gcccctggct gactggcagg 1680 agcccctggc cccacctatt cgccggtggc gttccttgcc tggttcgcct gagttcttgc 1740 atcaagaggc ttgtccattt gtgggccggg aagaatcgct atctgatggg cccccaccac 1800 gcctaagtag tctcaagtac agagttaaag agatcccacc attccgggca tctgccctac 1860 cagctgctca agcccatgag gctatggact gctccattct ccaggaagaa aatggttttg 1920 ggtccaggcc ccaggggacc agtccatgcc ctgcgggtgc ttctgaggag atggaggtag 1980 aagaaaggcc agcaggctca actccagcca ccttctccac ctcaggcata ggcctgcaaa 2040 cccagggaaa gcaggatggg tgagggggtt tagtccctgc ctcaccttgg ggatggacct 2100 tcagctgaaa ccatatggcc ccctaggtgc acagccttga ttcttccctg gagcctacag 2160 agcaggcagg ctaggccaag ccaggctcaa cttctgggct cccagtgccc attggctgtg 2220 tatgacggga ggcagcagtg agaggccttc ctagttaggg ccaacagctg ataccaagcc 2280 tctgaaatcc agcaaggagg tctgcctccc accagaccct ctccagtgta cttccccaga 2340 taggaccaga ggatgtctag ttctaggctg agctggcagg cagctattac cccggttctt 2400 tccccacccc aggtctgtct cttgcctttt cttggggcat ataagctact gagtggaaca 2460 tggagctgat caagaggccg taatggtcat ggctgtttcc agacctgaat attgggtgct 2520 tcttgccagt attctaagac atttgagtaa ttgctgtttg cacttactgc atggtcagac 2580 cacgtcacta catttctatg caaggggaca gcaaggcagc gtggtggtca tggctcttag 2640 ctaacctatt caaagacctt ttcctgttga ttaatctatt ttcatattta taaaggagtc 2700 ttaatgttct gccccataag actttcaacc ttgtggttgg gagtggggct ggttttgtag 2760 gccctagggc ctgcttctat gtatttatca acatgtgata cattcaattg gttaaatggt 2820 ttatacaggg actgatttgc ttcccttcct gccatggctg gagctttggg aacagtctgt 2880 ccttacagag ctgcaataag aaataaccaa agatgaagct ggtcaaatat tttcataact 2940 tgcttctgtt gatttttttt ttgtaaaact ttcccaagac attttcagac ttaaaaataa 3000 agtcagtgtt acaggt 3016 16 2280 DNA Homo sapiens 16 gtatatcaac tccgggaacc tggaacagtt gctagacagt aacctgcatt tgccttggac 60 tgtgagggta aaactggcct atgacatagc agtgggcctc agctaccttc acttcaaagg 120 catttttcat cgggacctca catctaagaa ctgcctgata aagagggatg agaatggtta 180 ctctgcagtg gtagctgact ttggcctggc tgagaagatc cccgatgtca gcatggggag 240 tgagaagctg gccgtggtgg gttccccatt ctggatggca cctgaggttc tccgagatga 300 gccctataat gaaaaggcag atgtgttctc ttatggtatc atcctctgcg agatcatcgc 360 ccgcatccag gccgatccgg actatcttcc ccgcacagag aatttcgggc tggactatga 420 tgctttccag cacatggtgg gagactgtcc cccagatttt ctgcaactta ctttcaactg 480 ctgtaacatg gatcccaaac tgcgcccatc ttttgtggag attgggaaga ccctggagga 540 aattctgagc cgcctacagg aagaagagca ggagagggat aggaagctgc agcccacagc 600 caggggactc ttggagaaag cacctggggt gaagcgacta agctcactgg atgacaagat 660 cccccacaag tcaccatgcc caagacgtac catctggctg tctcgaagcc agtcagatat 720 cttttcccgt aagcccccac gtacagtgag tgtcttggac ccatactacc ggccacgaga 780 tggtgctgcc cgcaccccca aagtcaaccc ttttagtgct cgccaggacc tcatgggggg 840 caagatcaag ttttttgacc tgcccagcaa gtctgtcatc tctctggtat ttgacctgga 900 tgcaccaggg cccggaacta tgcccctggc tgactggcag gagcccctgg ccccacctat 960 tcgccggtgg cgttccttgc ctggttcgcc tgagttcttg catcaagagg cttgtccatt 1020 tgtgggccgg gaagaatcgc tatctgatgg gcccccacca cgcctaagta gtctcaagta 1080 cagagttaaa gagatcccac cattccgggc atctgcccta ccagctgctc aagcccatga 1140 ggctatggac tgctccattc tccaggaaga aaatggtttt gggtccaggc cccaggggac 1200 cagtccatgc cctgcgggtg cttctgagga gatggaggta gaagaaaggc cagcaggctc 1260 aactccagcc accttctcca cctcaggcat aggcctgcaa acccagggaa agcaggatgg 1320 gtgagggggt ttagtccctg cctcaccttg gggatggacc ttcagctgaa accatatggc 1380 cccctaggtg cacagccttg attcttccct ggagcctaca gagcaggcag gctaggccaa 1440 gccaggctca acttctgggc tcccagtgcc cattggctgt gtatgacggg aggcagcagt 1500 gagaggcctt cctagttagg gccaacagct gataccaagc ctctgaaatc cagcaaggag 1560 gtctgcctcc caccagaccc tctccagtgt acttccccag ataggaccag aggatgtcta 1620 gttctaggct gagctggcag gcagctatta ccccggttct ttccccaccc caggtctgtc 1680 tcttgccttt tcttggggca tataagctac tgagtggaac atggagctga tcaagaggcc 1740 gtaatggtca tggctgtttc ccagacctga atattggggt gcttcttgcc agtattctaa 1800 gacatttgag taattgctgt ttgcacttac tgcatggtca gaccacgtca ctacatttct 1860 atgcaagggg acagcaaggc agcgtggtgg tcatggctct tagctaacct attcaaagac 1920 cttttcctgt tgattaatct attttcatat ttataaagga gtcttaatgt tctgccccat 1980 aagactttca accttgtggt tgggagtggg gctggttttg taggccctag ggcctgcttc 2040 tatgtattta tcaacatgtg atacattcaa ttggttaaat ggtttataca gggactgatt 2100 tgcttccctt cctgccatgg ctggagcttt gggaacagtc tgtccttaca gagctgcaat 2160 aagaaataac caaagatgaa gctggtcaaa tattttcata acttgcttct gttgattttt 2220 ttttttgtaa aactttccca agacattttc agacttaaaa ataaagtcag tgttacaggt 2280 17 3071 DNA Homo sapiens 17 gaattcgcgg ccgctcgacg ctcagcagag ctaccagctg ccctgttggc ttcgctggtc 60 ggatcgtcct cctggccccg ccaaacaggc gagcggcccc gactgtgggg catggcagta 120 gtctcctcgt tctccgccgc cgctagccta gctgagtcgc cggcttctgc gctaggggct 180 cccaccgcct ccgcaggcta aggagccgct gccaccaacg agctgtgagg gttactatgc 240 tccctctttg ccgccgtctc ctcctcttgc ccgcgcaggc acccctctgg ctgctcagtc 300 ctgcctcagt gtcaaaccag aagagaagta aaattcaaca aaaatttatg tgtggagttc 360 cttcttaaaa gaagaaaaaa gtgattattt agactatgga tcggagcaaa cggaattcaa 420 ttgcaggatt tcctccacgt gtggagcgtc ttgaagagtt tgaaggaggt ggtggaggag 480 aaggaaatgt gagccaggtg ggaagagttt ggccatcttc gtatcgagct cttataagtg 540 ccttttccag actgacgcgt ttggatgatt tcacctgtga aaaaataggg tctggcttct 600 tttctgaagt gttcaaggta cgacaccgag cttctggtca ggtgatggct cttaagatga 660 acacattgag cagtaaccgg gcaaacatgc tgaaagaagt acagctcatg aatagactct 720 cccatcccaa catccttagg ttcatgggtg tatgtgttca tcaaggacaa ttgcatgcac 780 ttacagagta tatcaactcc gggaacctgg aacagttgct agacagtaac ctgcatttgc 840 cttggactgt gagggtaaaa ctggcctatg acatagcagt gggcctcagc taccttcact 900 tcaaaggcat ttttcatcgg gacctcacat ctaagaactg cctgataaag agggatgaga 960 atggttactc tgcagtggta gctgactttg gcctggctga gaagatcccc gatgtcagca 1020 tggggagtga gaagctggcc gtggtgggtt ccccattctg gatggcacct gaggttctcc 1080 gagatgagcc ctataatgaa aaggcagatg tgttctctta tggtatcatc ctctgcgaga 1140 tcatcgcccg catccaggcc gatccggact atcttccccg cacagagaat ttcgggctgg 1200 actatgatgc tttccagcac atggtgggag actgtccccc agattttctg caacttactt 1260 tcaactgctg taacatggat cccaaactgc gcccatcttt tgtggagatt gggaagaccc 1320 tggaggaaat tctgagccgc ctacaggaag aagagcagga gagggatagg aagctgcagc 1380 ccacagccag gggactcttg gagaaagcac ctggggtgaa gcgactaagc tcactggatg 1440 acaagatccc ccacaagtca ccatgcccaa gacgtaccat ctggctgtct cgaagccagt 1500 cagatatctt ttcccgtaag cccccacgta cagtgagtgt cttggaccca tactaccggc 1560 cacgagatgg tgctgcccgc acccccaaag tcaacccttt tagtgctcgc caggacctca 1620 tggggggcaa gatcaagttt tttgacctgc ccagcaagtc tgtcatctct ctggtatttg 1680 acctggatgc accagggccc ggaactatgc ccctggctga ctggcaggag cccctggccc 1740 cacctattcg ccggtggcgt tccttgcctg gttcgcctga gttcttgcat caagaggctt 1800 gtccatttgt gggccgggaa gaatcgctat ctgatgggcc cccaccacgc ctaagtagtc 1860 tcaagtacag agttaaagag atcccaccat tccgggcatc tgccctacca gctgctcaag 1920 cccatgaggc tatggactgc tccattctcc aggaagaaaa tggttttggg tccaggcccc 1980 aggggaccag tccatgccct gcgggtgctt ctgaggagat ggaggtagaa gaaaggccag 2040 caggctcaac tccagccacc ttctccacct caggcatagg cctgcaaacc cagggaaagc 2100 aggatgggtg agggggttta gtccctgcct caccttgggg atggaccttc agctgaaacc 2160 atatggcccc ctaggtgcac agccttgatt cttccctgga gcctacagag caggcaggct 2220 aggccaagcc aggctcaact tctgggctcc cagtgcccat tggctgtgta tgacgggagg 2280 cagcagtgag aggccttcct agttagggcc aacagctgat accaagcctc tgaaatccag 2340 caaggaggtc tgcctcccac cagaccctct ccagtgtact tccccagata ggaccagagg 2400 atgtctagtt ctaggctgag ctggcaggca gctattaccc cggttctttc cccaccccag 2460 gtctgtctct tgccttttct tggggcatat aagctactga gtggaacatg gagctgatca 2520 agaggccgta atggtcatgg ctgtttccag acctgaatat tgggtgcttc ttgccagtat 2580 tctaagacat ttgagtaatt gctgtttgca cttactgcat ggtcagacca cgtcactaca 2640 tttctatgca aggggacagc aaggcagcgt ggtggtcatg gctcttagct aacctattca 2700 aagacctttt cctgttgatt aatctatttt catatttata aaggagtctt aatgttctgc 2760 cccataagac tttcaacctt gtggttggga gtggggctgg ttttgtaggc cctagggcct 2820 gcttctatgt atttatcaac atgtgataca ttcaattggt taaatggttt atacagggac 2880 tgatttgctt cccttcctgc catggctgga gctttgggaa cagtctgtcc ttacagagct 2940 gcaataagaa ataaccaaag atgaagctgg tcaaatattt tcataacttg cttctgttga 3000 tttttttttt gtaaaacttt cccaagacat tttcagactt aaaaataaag tcagtgttac 3060 aggtaaaaaa a 3071 18 3050 DNA Homo sapiens 18 agagagctac cagctgccct gttggcttcg ctggtcggat cgtcctcctg gccccgccaa 60 acaggcgggg ggagcggccc cgactgtggg gccatggcag tagtctcctc gttctccgcc 120 gccgctagcc tagctgagtc gccggcttct gcgctagggg ctcccaccgc ctccgcaggc 180 taaggagccg ctgccaccaa cgagctgtga gggttactat gctccctctt tgccgccgtc 240 tcctcctctt gcccgcgcag gcacccctct ggctgctcag tcctgcctca gtgtcaaacc 300 agaagagaag taaaattcaa caaaaattta tgtgtggagt tccttcttaa aagaagaaaa 360 aagtgattat ttagactatg gatcggagca aacggaattc aattgcagga tttcctccac 420 gtgtggagcg tcttgaagag tttgaaggag gtggtggagg agaaggaaat gtgagccagg 480 tgggaagagt ttggccatct tcgtatcgag ctcttataag tgccttttcc agactgacgc 540 gtttggatga tttcacctgt gaaaaaatag ggtctggctt cttttctgaa gtgttcaagg 600 tacgacaccg agcttctggt caggtgatgg ctcttaagat gaacacattg agcagtaacc 660 gggcaaacat gctgaaagaa gtacagctca tgaatagact ctcccatccc aacatcctta 720 ggttcatggg tgtatgtgtt catcaaggac aattgcatgc acttacagag tatatcaact 780 ccgggaacct ggaacagttg ctagacagta acctgcattt gccttggact gtgagggtaa 840 aactggccta tgacatagca gtgggcctca gctaccttca cttcaaaggc atttttcatc 900 gggacctcac atctaagaac tgcctgataa agagggatga gaatggttac tctgcagtgg 960 tagctgactt tggcctggct gagaagatcc ccgatgtcag catggggagt gagaagctgg 1020 ccgtggtggg ttccccattc tggatggcac ctgaggttct ccgagatgag ccctataatg 1080 aaaaggcaga tgtgttctct tatggtatca tcctctgcga gatcatcgcc cgcatccagg 1140 ccgatccgga ctatcttccc cgcacagaga atttcgggct ggactatgat gctttccagc 1200 acatggtggg agactgtccc ccagattttc tgcaacttac tttcaactgc tgtaacatgg 1260 atcccaaact gcgcccatct tttgtggaga ttgggaagac cctggaggaa attctgagcc 1320 gcctacagga agaagagcag gagagggata ggaagctgca gcccacagcc aggggactct 1380 tggagaaagc acctggggtg aagcgactaa gctcactgga tgacaagatc ccccacaagt 1440 caccatgccc aagacgtacc atctggctgt ctcgaagcca gtcagatatc ttttcccgta 1500 agcccccacg tacagtgagt gtcttggacc catactaccg gccacgagat ggtgctgccc 1560 gcacccccaa agtcaaccct tttagtgctc gccaggacct catggggggc aagatcaagt 1620 tttttgacct gcccagcaag tctgtcatct ctctggtatt tgacctggat gcaccagggc 1680 ccggaactat gcccctggct gactggcagg agcccctggc cccacctatt cgccggtggc 1740 gttccttgcc tggttcgcct gagttcttgc atcaagaggc ttgtccattt gtgggccggg 1800 aagaatcgct atctgatggg cccccaccac gcctaagtag tctcaagtac agagttaaag 1860 agatcccacc attccgggca tctgccctac cagctgctca agcccatgag gctatggact 1920 gctccattct ccaggaagaa aatggttttg ggtccaggcc ccaggggacc agtccatgcc 1980 ctgcgggtgc ttctgaggag atggaggtag aagaaaggcc agcaggctca actccagcca 2040 ccttctccac ctcaggcata ggcctgcaaa cccagggaaa gcaggatggg tgagggggtt 2100 tagtccctgc ctcaccttgg ggatggacct tcagctgaaa ccatatggcc ccctaggtgc 2160 acagccttga ttcttccctg gagcctacag agcaggcagg ctaggccaag ccaggctcaa 2220 cttctgggct cccagtgccc attggctgtg tatgacggga ggcagcagtg agaggccttc 2280 ctagttaggg ccaacagctg ataccaagcc tctgaaatcc agcaaggagg tctgcctccc 2340 accagaccct ctccagtgta cttccccaga taggaccaga ggatgtctag ttctaggctg 2400 agctggcagg cagctattac cccggttctt tccccacccc aggtctgtct cttgcctttt 2460 cttggggcat ataagctact gagtggaaca tggagctgat caagaggccg taacggtcat 2520 ggctgtttcc cagacctgaa tattggggtg cttcttgcca gtattctaag acatttgagt 2580 aattgctgtt tgcacttact gcatggtcag accacgtcac tacatttcta tgcaagggga 2640 cagcaaggca gcgtggtggt catggctctt agctaaccta ttcaaagacc ttttcctgtt 2700 gattaatcta ttttcatatt tataaaggag tcttaatgtt ctgccccata agactttcaa 2760 ccttgtggtt gggagtgggg ctggttttgt aggccctagg gcctgcttct atgtatttat 2820 caacatgtga tacattcaat tggttaaatg gtttatacag ggactgattt gcttcccttc 2880 ctgccatggc tggagctttg ggaacagtct gtccttacag agctgcaata agaaataacc 2940 aaagatgaag ctggtcaaat attttcataa cttgcttctg ttgatttttt tttttgtaaa 3000 actttcccaa gacattttca gacttaaaaa taaagtcagt gttacaggtg 3050 19 702 PRT Homo sapiens 19 Ala Pro Ser Arg Phe Pro Arg Arg Cys Pro Arg Gly Ala Pro Gly Pro 1 5 10 15 Ala Arg Pro Gly Pro Arg Pro Pro Pro Pro Pro Pro Arg Ala Gly Gly 20

25 30 Gly Gly Arg Ala Arg Gly Pro Gly Arg Pro Gln Pro Gln Pro Arg Arg 35 40 45 Ala Pro Pro Pro Val Glu Cys Met Arg Leu Thr Leu Leu Cys Cys Thr 50 55 60 Trp Arg Glu Glu Arg Met Gly Glu Glu Gly Ser Glu Leu Pro Val Cys 65 70 75 80 Ala Ser Cys Gly Gln Arg Ile Tyr Asp Gly Gln Tyr Leu Gln Ala Leu 85 90 95 Asn Ala Asp Trp His Ala Asp Cys Phe Arg Cys Cys Asp Cys Ser Ala 100 105 110 Ser Leu Ser His Gln Tyr Tyr Glu Lys Asp Gly Gln Leu Phe Cys Lys 115 120 125 Lys Asp Tyr Trp Ala Arg Tyr Gly Glu Ser Cys His Gly Cys Ser Glu 130 135 140 Gln Ile Thr Lys Gly Leu Val Met Val Ala Gly Glu Leu Lys Tyr His 145 150 155 160 Pro Glu Cys Phe Ile Cys Leu Thr Cys Gly Thr Phe Ile Gly Asp Gly 165 170 175 Asp Thr Tyr Thr Leu Val Glu His Ser Lys Leu Tyr Cys Gly His Cys 180 185 190 Tyr Tyr Gln Thr Val Val Thr Pro Val Ile Glu Gln Ile Leu Pro Asp 195 200 205 Ser Pro Gly Ser His Leu Pro His Thr Val Thr Leu Val Ser Ile Pro 210 215 220 Ala Ser Ser His Gly Lys Arg Gly Leu Ser Val Ser Ile Asp Pro Pro 225 230 235 240 His Gly Pro Pro Gly Cys Gly Thr Glu His Ser His Thr Val Arg Val 245 250 255 Gln Gly Val Asp Pro Gly Cys Met Ser Pro Asp Val Lys Asn Ser Ile 260 265 270 His Val Gly Asp Arg Ile Leu Glu Ile Asn Gly Thr Pro Ile Arg Asn 275 280 285 Val Pro Leu Asp Glu Ile Asp Leu Leu Ile Gln Glu Thr Ser Arg Leu 290 295 300 Leu Gln Leu Thr Leu Glu His Asp Pro His Asp Thr Leu Gly His Gly 305 310 315 320 Leu Gly Pro Glu Thr Ser Pro Leu Ser Ser Pro Ala Tyr Thr Pro Ser 325 330 335 Gly Glu Ala Gly Ser Ser Ala Arg Gln Lys Pro Val Leu Arg Ser Cys 340 345 350 Ser Ile Asp Arg Ser Pro Gly Ala Gly Ser Leu Gly Ser Pro Ala Ser 355 360 365 Gln Arg Lys Asp Leu Gly Arg Ser Glu Ser Leu Arg Val Val Cys Arg 370 375 380 Pro His Arg Ile Phe Arg Pro Ser Asp Leu Ile His Gly Glu Val Leu 385 390 395 400 Gly Lys Gly Cys Phe Gly Gln Ala Ile Lys Val Thr His Arg Glu Thr 405 410 415 Gly Glu Val Met Val Met Lys Glu Leu Ile Arg Phe Asp Glu Glu Thr 420 425 430 Gln Arg Thr Phe Leu Lys Glu Val Lys Val Met Arg Cys Leu Glu His 435 440 445 Pro Asn Val Leu Lys Phe Ile Gly Val Leu Tyr Lys Asp Lys Arg Leu 450 455 460 Asn Phe Ile Thr Glu Tyr Ile Lys Gly Gly Thr Leu Arg Gly Ile Ile 465 470 475 480 Lys Ser Met Asp Ser Gln Tyr Pro Trp Ser Gln Arg Val Ser Phe Ala 485 490 495 Lys Asp Ile Ala Ser Gly Met Ala Tyr Leu His Ser Met Asn Ile Ile 500 505 510 His Arg Asp Leu Asn Ser His Asn Cys Leu Val Arg Glu Asn Lys Asn 515 520 525 Val Val Val Ala Asp Phe Gly Leu Ala Arg Leu Met Val Asp Glu Lys 530 535 540 Thr Gln Pro Glu Gly Leu Arg Ser Leu Lys Lys Pro Asp Arg Lys Lys 545 550 555 560 Arg Tyr Thr Val Val Gly Asn Pro Tyr Trp Met Ala Pro Glu Met Ile 565 570 575 Asn Gly Arg Ser Tyr Asp Glu Lys Val Asp Val Phe Ser Phe Gly Ile 580 585 590 Val Leu Cys Glu Ile Ile Gly Arg Val Asn Ala Asp Pro Asp Tyr Leu 595 600 605 Pro Arg Thr Met Asp Phe Gly Leu Asn Val Arg Gly Phe Leu Asp Arg 610 615 620 Tyr Cys Pro Pro Asn Cys Pro Pro Ser Phe Phe Pro Ile Thr Val Arg 625 630 635 640 Cys Cys Asp Leu Asp Pro Glu Lys Arg Pro Ser Phe Val Lys Leu Glu 645 650 655 His Trp Leu Glu Thr Leu Arg Met His Leu Ala Gly His Leu Pro Leu 660 665 670 Gly Pro Gln Leu Glu Gln Leu Asp Arg Gly Phe Trp Glu Thr Tyr Arg 675 680 685 Arg Gly Glu Ser Gly Leu Pro Ala His Pro Glu Val Pro Asp 690 695 700 20 647 PRT Homo sapiens 20 Met Arg Leu Thr Leu Leu Cys Cys Thr Trp Arg Glu Glu Arg Met Gly 1 5 10 15 Glu Glu Gly Ser Glu Leu Pro Val Cys Ala Ser Cys Gly Gln Arg Ile 20 25 30 Tyr Asp Gly Gln Tyr Leu Gln Ala Leu Asn Ala Asp Trp His Ala Asp 35 40 45 Cys Phe Arg Cys Cys Asp Cys Ser Ala Ser Leu Ser His Gln Tyr Tyr 50 55 60 Glu Lys Asp Gly Gln Leu Phe Cys Lys Lys Asp Tyr Trp Ala Arg Tyr 65 70 75 80 Gly Glu Ser Cys His Gly Cys Ser Glu Gln Ile Thr Lys Gly Leu Val 85 90 95 Met Val Ala Gly Glu Leu Lys Tyr His Pro Glu Cys Phe Ile Cys Leu 100 105 110 Thr Cys Gly Thr Phe Ile Gly Asp Gly Asp Thr Tyr Thr Leu Val Glu 115 120 125 His Ser Lys Leu Tyr Cys Gly His Cys Tyr Tyr Gln Thr Val Val Thr 130 135 140 Pro Val Ile Glu Gln Ile Leu Pro Asp Ser Pro Gly Ser His Leu Pro 145 150 155 160 His Thr Val Thr Leu Val Ser Ile Pro Ala Ser Ser His Gly Lys Arg 165 170 175 Gly Leu Ser Val Ser Ile Asp Pro Pro His Gly Pro Pro Gly Cys Gly 180 185 190 Thr Glu His Ser His Thr Val Arg Val Gln Gly Val Asp Pro Gly Cys 195 200 205 Met Ser Pro Asp Val Lys Asn Ser Ile His Val Gly Asp Arg Ile Leu 210 215 220 Glu Ile Asn Gly Thr Pro Ile Arg Asn Val Pro Leu Asp Glu Ile Asp 225 230 235 240 Leu Leu Ile Gln Glu Thr Ser Arg Leu Leu Gln Leu Thr Leu Glu His 245 250 255 Asp Pro His Asp Thr Leu Gly His Gly Leu Gly Pro Glu Thr Ser Pro 260 265 270 Leu Ser Ser Pro Ala Tyr Thr Pro Ser Gly Glu Ala Gly Ser Ser Ala 275 280 285 Arg Gln Lys Pro Val Leu Arg Ser Cys Ser Ile Asp Arg Ser Pro Gly 290 295 300 Ala Gly Ser Leu Gly Ser Pro Ala Ser Gln Arg Lys Asp Leu Gly Arg 305 310 315 320 Ser Glu Ser Leu Arg Val Val Cys Arg Pro His Arg Ile Phe Arg Pro 325 330 335 Ser Asp Leu Ile His Gly Glu Val Leu Gly Lys Gly Cys Phe Gly Gln 340 345 350 Ala Ile Lys Val Thr His Arg Glu Thr Gly Glu Val Met Val Met Lys 355 360 365 Glu Leu Ile Arg Phe Asp Glu Glu Thr Gln Arg Thr Phe Leu Lys Glu 370 375 380 Val Lys Val Met Arg Cys Leu Glu His Pro Asn Val Leu Lys Phe Ile 385 390 395 400 Gly Val Leu Tyr Lys Asp Lys Arg Leu Asn Phe Ile Thr Glu Tyr Ile 405 410 415 Lys Gly Gly Thr Leu Arg Gly Ile Ile Lys Ser Met Asp Ser Gln Tyr 420 425 430 Pro Trp Ser Gln Arg Val Ser Phe Ala Lys Asp Ile Ala Ser Gly Met 435 440 445 Ala Tyr Leu His Ser Met Asn Ile Ile His Arg Asp Leu Asn Ser His 450 455 460 Asn Cys Leu Val Arg Glu Asn Lys Asn Val Val Val Ala Asp Phe Gly 465 470 475 480 Leu Ala Arg Leu Met Val Asp Glu Lys Thr Gln Pro Glu Gly Leu Arg 485 490 495 Ser Leu Lys Lys Pro Asp Arg Lys Lys Arg Tyr Thr Val Val Gly Asn 500 505 510 Pro Tyr Trp Met Ala Pro Glu Met Ile Asn Gly Arg Ser Tyr Asp Glu 515 520 525 Lys Val Asp Val Phe Ser Phe Gly Ile Val Leu Cys Glu Ile Ile Gly 530 535 540 Arg Val Asn Ala Asp Pro Asp Tyr Leu Pro Arg Thr Met Asp Phe Gly 545 550 555 560 Leu Asn Val Arg Gly Phe Leu Asp Arg Tyr Cys Pro Pro Asn Cys Pro 565 570 575 Pro Ser Phe Phe Pro Ile Thr Val Arg Cys Cys Asp Leu Asp Pro Glu 580 585 590 Lys Arg Pro Ser Phe Val Lys Leu Glu His Trp Leu Glu Thr Leu Arg 595 600 605 Met His Leu Ala Gly His Leu Pro Leu Gly Pro Gln Leu Glu Gln Leu 610 615 620 Asp Arg Gly Phe Trp Glu Thr Tyr Arg Arg Gly Glu Ser Gly Leu Pro 625 630 635 640 Ala His Pro Glu Val Pro Asp 645 21 638 PRT Homo sapiens 21 Met Ser Ala Leu Ala Gly Glu Asp Val Trp Arg Cys Pro Gly Cys Gly 1 5 10 15 Asp His Ile Ala Pro Ser Gln Ile Trp Tyr Arg Thr Val Asn Glu Thr 20 25 30 Trp His Gly Ser Cys Phe Arg Cys Ser Glu Cys Gln Asp Ser Leu Thr 35 40 45 Asn Trp Tyr Tyr Glu Lys Asp Gly Lys Leu Tyr Cys Pro Lys Asp Tyr 50 55 60 Trp Gly Lys Phe Gly Glu Phe Cys His Gly Cys Ser Leu Leu Met Thr 65 70 75 80 Gly Pro Phe Met Val Ala Gly Glu Phe Lys Tyr His Pro Glu Cys Phe 85 90 95 Ala Cys Met Ser Cys Lys Val Ile Ile Glu Asp Gly Asp Ala Tyr Ala 100 105 110 Leu Val Gln His Ala Thr Leu Tyr Cys Gly Lys Cys His Asn Glu Val 115 120 125 Val Leu Ala Pro Met Phe Glu Arg Leu Ser Thr Glu Ser Val Gln Glu 130 135 140 Gln Leu Pro Tyr Ser Val Thr Leu Ile Ser Met Pro Ala Thr Thr Glu 145 150 155 160 Gly Arg Arg Gly Phe Ser Val Ser Val Glu Ser Ala Cys Ser Asn Tyr 165 170 175 Ala Thr Thr Val Gln Val Lys Glu Val Asn Arg Met His Ile Ser Pro 180 185 190 Asn Asn Arg Asn Ala Ile His Pro Gly Asp Arg Ile Leu Glu Ile Asn 195 200 205 Gly Thr Pro Val Arg Thr Leu Arg Val Glu Glu Val Glu Asp Ala Ile 210 215 220 Ser Gln Thr Ser Gln Thr Leu Gln Leu Leu Ile Glu His Asp Pro Val 225 230 235 240 Ser Gln Arg Leu Asp Gln Leu Arg Leu Glu Ala Arg Leu Ala Pro His 245 250 255 Met Gln Asn Ala Gly His Pro His Ala Leu Ser Thr Leu Asp Thr Lys 260 265 270 Glu Asn Leu Glu Gly Thr Leu Arg Arg Arg Ser Leu Arg Arg Ser Asn 275 280 285 Ser Ile Ser Lys Ser Pro Gly Pro Ser Ser Pro Lys Glu Pro Leu Leu 290 295 300 Phe Ser Arg Asp Ile Ser Arg Ser Glu Ser Leu Arg Cys Ser Ser Ser 305 310 315 320 Tyr Ser Gln Gln Ile Phe Arg Pro Cys Asp Leu Ile His Gly Glu Val 325 330 335 Leu Gly Lys Gly Phe Phe Gly Gln Ala Ile Lys Val Thr His Lys Ala 340 345 350 Thr Gly Lys Val Met Val Met Lys Glu Leu Ile Arg Cys Asp Glu Glu 355 360 365 Thr Gln Lys Thr Phe Leu Thr Glu Val Lys Val Met Arg Ser Leu Asp 370 375 380 His Pro Asn Val Leu Lys Phe Ile Gly Val Leu Tyr Lys Asp Lys Lys 385 390 395 400 Leu Asn Leu Leu Thr Glu Tyr Ile Glu Gly Gly Thr Leu Lys Asp Phe 405 410 415 Leu Arg Ser Met Asp Pro Phe Pro Trp Gln Gln Lys Val Arg Phe Ala 420 425 430 Lys Gly Ile Ala Ser Gly Met Ala Tyr Leu His Ser Met Cys Ile Ile 435 440 445 His Arg Asp Leu Asn Ser His Asn Cys Leu Ile Lys Leu Asp Lys Thr 450 455 460 Val Val Val Ala Asp Phe Gly Leu Ser Arg Leu Ile Val Glu Glu Arg 465 470 475 480 Lys Arg Ala Pro Met Glu Lys Ala Thr Thr Lys Lys Arg Thr Leu Arg 485 490 495 Lys Asn Asp Arg Lys Lys Arg Tyr Thr Val Val Gly Asn Pro Tyr Trp 500 505 510 Met Ala Pro Glu Met Leu Asn Gly Lys Ser Tyr Asp Glu Thr Val Asp 515 520 525 Ile Phe Ser Phe Gly Ile Val Leu Cys Glu Ile Ile Gly Gln Val Tyr 530 535 540 Ala Asp Pro Asp Cys Leu Pro Arg Thr Leu Asp Phe Gly Leu Asn Val 545 550 555 560 Lys Leu Phe Trp Glu Lys Phe Val Pro Thr Asp Cys Pro Pro Ala Phe 565 570 575 Phe Pro Leu Ala Ala Ile Cys Cys Arg Leu Glu Pro Glu Ser Arg Pro 580 585 590 Ala Phe Ser Lys Leu Glu Asp Ser Phe Glu Ala Leu Ser Leu Tyr Leu 595 600 605 Gly Glu Leu Gly Ile Pro Leu Pro Ala Glu Leu Glu Glu Leu Asp His 610 615 620 Thr Val Ser Met Gln Tyr Gly Leu Thr Arg Asp Ser Pro Pro 625 630 635 22 638 PRT Homo sapiens 22 Met Ser Ala Leu Ala Gly Glu Asp Val Trp Arg Cys Pro Gly Cys Gly 1 5 10 15 Asp His Ile Ala Pro Ser Gln Ile Trp Tyr Arg Thr Val Asn Glu Thr 20 25 30 Trp His Gly Ser Cys Phe Arg Cys Ser Glu Cys Gln Asp Ser Leu Thr 35 40 45 Asn Trp Tyr Tyr Glu Lys Asp Gly Lys Leu Tyr Cys Pro Lys Asp Tyr 50 55 60 Trp Gly Lys Phe Gly Glu Phe Cys His Gly Cys Ser Leu Leu Met Thr 65 70 75 80 Gly Pro Phe Met Val Ala Gly Glu Phe Lys Tyr His Pro Glu Cys Phe 85 90 95 Ala Cys Met Ser Cys Lys Val Ile Ile Glu Asp Gly Asp Ala Tyr Ala 100 105 110 Leu Val Gln His Ala Thr Leu Tyr Cys Gly Lys Cys His Asn Glu Val 115 120 125 Val Leu Ala Pro Met Phe Glu Arg Leu Ser Thr Glu Ser Val Gln Glu 130 135 140 Gln Leu Pro Tyr Ser Val Thr Leu Ile Ser Met Pro Ala Thr Thr Glu 145 150 155 160 Gly Arg Arg Gly Phe Ser Val Ser Val Glu Ser Ala Cys Ser Asn Tyr 165 170 175 Ala Thr Thr Val Gln Val Lys Glu Val Asn Arg Met His Ile Ser Pro 180 185 190 Asn Asn Arg Asn Ala Ile His Pro Gly Asp Arg Ile Leu Glu Ile Asn 195 200 205 Gly Thr Pro Val Arg Thr Leu Arg Val Glu Glu Val Glu Asp Ala Ile 210 215 220 Ser Gln Thr Ser Gln Thr Leu Gln Leu Leu Ile Glu His Asp Pro Val 225 230 235 240 Ser Gln Arg Leu Asp Gln Leu Arg Leu Glu Ala Arg Leu Ala Pro His 245 250 255 Met Gln Asn Ala Gly His Pro His Ala Leu Ser Thr Leu Asp Thr Lys 260 265 270 Glu Asn Leu Glu Gly Thr Leu Arg Arg Arg Ser Leu Arg Arg Ser Asn 275 280 285 Ser Ile Ser Lys Ser Pro Gly Pro Ser Ser Pro Lys Glu Pro Leu Leu 290 295 300 Phe Ser Arg Asp Ile Ser Arg Ser Glu Ser Leu Arg Cys Ser Ser Ser 305 310 315 320 Tyr Ser Gln Gln Ile Phe Arg Pro Cys Asp Leu Ile His Gly Glu Val 325 330 335 Leu Gly Lys Gly Phe Phe Gly Gln Ala Ile Lys Val Thr His Lys Ala 340 345 350 Thr Gly Lys Val Met Val Met Lys Glu Leu Ile Arg Cys Asp Glu Glu 355 360 365 Thr Gln Lys Thr Phe Leu Thr Glu Val Lys Val Met Arg Ser Leu Asp 370 375 380 His Pro Asn Val Leu Lys Phe Ile Gly Val Leu Tyr Lys Asp Lys Lys 385 390 395 400 Leu Asn Leu Leu Thr Glu Tyr Ile Glu Gly Gly Thr Leu Lys Asp Phe 405 410 415 Leu Arg Ser Met Asp Pro Phe Pro Trp Gln Gln Lys Val Arg Phe Ala 420 425 430 Lys Gly Ile Ala Ser Gly Met Ala Tyr Leu His Ser Met Cys Ile Ile 435 440 445 His Arg Asp Leu Asn Ser His Asn Cys Leu Ile Lys Leu Asp Lys Thr 450 455 460 Val Val Val Ala Asp Phe Gly Leu Ser Arg Leu Ile Val Glu Glu Arg 465 470 475 480 Lys Arg

Ala Pro Met Glu Lys Ala Thr Thr Lys Lys Arg Thr Leu Arg 485 490 495 Lys Asn Asp Arg Lys Lys Arg Tyr Thr Val Val Gly Asn Pro Tyr Trp 500 505 510 Met Ala Pro Glu Met Leu Asn Gly Lys Ser Tyr Asp Glu Thr Val Asp 515 520 525 Ile Phe Ser Phe Gly Ile Val Leu Cys Glu Ile Ile Gly Gln Val Tyr 530 535 540 Ala Asp Pro Asp Cys Leu Pro Arg Thr Leu Asp Phe Gly Leu Asn Val 545 550 555 560 Lys Leu Phe Trp Glu Lys Phe Val Pro Thr Asp Cys Pro Pro Ala Phe 565 570 575 Phe Pro Leu Ala Ala Ile Cys Cys Arg Leu Glu Pro Glu Ser Arg Pro 580 585 590 Ala Phe Ser Lys Leu Glu Asp Ser Phe Glu Ala Leu Ser Leu Tyr Leu 595 600 605 Gly Glu Leu Gly Ile Pro Leu Pro Ala Glu Leu Glu Glu Leu Asp His 610 615 620 Thr Val Ser Met Gln Tyr Gly Leu Thr Arg Asp Ser Pro Pro 625 630 635 23 626 PRT Homo sapiens 23 Met Ala Gly Glu Arg Pro Pro Leu Arg Gly Pro Gly Pro Gly Pro Gly 1 5 10 15 Glu Val Pro Gly Glu Gly Pro Pro Gly Pro Gly Gly Thr Gly Gly Gly 20 25 30 Pro Gly Arg Gly Arg Pro Ser Ser Tyr Arg Val Leu Arg Ser Ala Val 35 40 45 Ser Ser Leu Ala Arg Val Asp Asp Phe His Cys Ala Glu Lys Ile Gly 50 55 60 Ala Gly Phe Phe Ser Glu Val Tyr Lys Val Arg His Arg Gln Ser Gly 65 70 75 80 Gln Val Met Val Leu Lys Met Asn Lys Leu Pro Ser Asn Arg Gly Asn 85 90 95 Thr Leu Arg Glu Val Gln Leu Met Asn Arg Leu Arg His Pro Asn Ile 100 105 110 Leu Arg Phe Met Gly Val Cys Val His Gln Gly Gln Leu His Ala Leu 115 120 125 Thr Glu Tyr Met Asn Gly Gly Thr Leu Glu Gln Leu Leu Ser Ser Pro 130 135 140 Glu Pro Leu Ser Trp Pro Val Arg Leu His Leu Ala Leu Asp Ile Ala 145 150 155 160 Arg Gly Leu Arg Tyr Leu His Ser Lys Gly Val Phe His Arg Asp Leu 165 170 175 Thr Ser Lys Asn Cys Leu Val Arg Arg Glu Asp Arg Gly Phe Thr Ala 180 185 190 Val Val Gly Asp Phe Gly Leu Ala Glu Lys Ile Pro Val Tyr Arg Glu 195 200 205 Gly Ala Arg Lys Glu Pro Leu Ala Val Val Gly Ser Pro Tyr Trp Met 210 215 220 Ala Pro Glu Val Leu Arg Gly Glu Leu Tyr Asp Glu Lys Ala Asp Val 225 230 235 240 Phe Ala Phe Gly Ile Val Leu Cys Glu Leu Ile Ala Arg Val Pro Ala 245 250 255 Asp Pro Asp Tyr Leu Pro Arg Thr Glu Asp Phe Gly Leu Asp Val Pro 260 265 270 Ala Phe Arg Thr Leu Val Gly Asp Asp Cys Pro Leu Pro Phe Leu Leu 275 280 285 Leu Ala Ile His Cys Cys Asn Leu Glu Pro Ser Thr Arg Ala Pro Phe 290 295 300 Thr Glu Ile Thr Gln His Leu Glu Trp Ile Leu Glu Gln Leu Pro Glu 305 310 315 320 Pro Ala Pro Leu Thr Arg Thr Ala Leu Thr His Asn Gln Gly Ser Val 325 330 335 Ala Arg Gly Gly Pro Ser Ala Thr Leu Pro Arg Pro Asp Pro Arg Leu 340 345 350 Ser Arg Ser Arg Ser Asp Leu Phe Leu Pro Pro Ser Pro Glu Ser Pro 355 360 365 Pro Asn Trp Gly Asp Asn Leu Thr Arg Val Asn Pro Phe Ser Leu Arg 370 375 380 Glu Asp Leu Arg Gly Gly Lys Ile Lys Leu Leu Asp Thr Pro Ser Lys 385 390 395 400 Pro Val Leu Pro Leu Val Pro Pro Ser Pro Phe Pro Ser Thr Gln Leu 405 410 415 Pro Leu Val Thr Thr Pro Glu Thr Leu Val Gln Pro Gly Thr Pro Ala 420 425 430 Arg Arg Cys Arg Ser Leu Pro Ser Ser Pro Glu Leu Pro Arg Arg Met 435 440 445 Glu Thr Ala Leu Pro Gly Pro Gly Pro Pro Ala Val Gly Pro Ser Ala 450 455 460 Glu Glu Lys Met Glu Cys Glu Gly Ser Ser Pro Glu Pro Glu Pro Pro 465 470 475 480 Gly Pro Ala Pro Gln Leu Pro Leu Ala Val Ala Thr Asp Asn Phe Ile 485 490 495 Ser Thr Cys Ser Ser Ala Ser Gln Pro Trp Ser Pro Arg Ser Gly Pro 500 505 510 Val Leu Asn Asn Asn Pro Pro Ala Val Val Val Asn Ser Pro Gln Gly 515 520 525 Trp Ala Gly Glu Pro Trp Asn Arg Ala Gln His Ser Leu Pro Arg Ala 530 535 540 Ala Ala Leu Glu Arg Thr Glu Pro Ser Pro Pro Pro Ser Ala Pro Arg 545 550 555 560 Glu Pro Asp Glu Gly Leu Pro Cys Pro Gly Cys Cys Leu Gly Pro Phe 565 570 575 Ser Phe Gly Phe Leu Ser Met Cys Pro Arg Pro Thr Pro Ala Val Ala 580 585 590 Arg Tyr Arg Asn Leu Asn Cys Glu Ala Gly Ser Leu Leu Cys His Arg 595 600 605 Gly His His Ala Lys Pro Pro Thr Pro Ser Leu Gln Leu Pro Gly Ala 610 615 620 Arg Ser 625 24 626 PRT Homo sapiens 24 Met Ala Gly Glu Arg Pro Pro Leu Arg Gly Pro Gly Pro Gly Pro Gly 1 5 10 15 Glu Val Pro Gly Glu Gly Pro Pro Gly Pro Gly Gly Thr Gly Gly Gly 20 25 30 Pro Gly Arg Gly Arg Pro Ser Ser Tyr Arg Val Leu Arg Ser Ala Val 35 40 45 Ser Ser Leu Ala Arg Val Asp Asp Phe His Cys Ala Glu Lys Ile Gly 50 55 60 Ala Gly Phe Phe Ser Glu Val Tyr Lys Val Arg His Arg Gln Ser Gly 65 70 75 80 Gln Val Met Val Leu Lys Met Asn Lys Leu Pro Ser Asn Arg Gly Asn 85 90 95 Thr Leu Arg Glu Val Gln Leu Met Asn Arg Leu Arg His Pro Asn Ile 100 105 110 Leu Arg Phe Met Gly Val Cys Val His Gln Gly Gln Leu His Ala Leu 115 120 125 Thr Glu Tyr Met Asn Gly Gly Thr Leu Glu Gln Leu Leu Ser Ser Pro 130 135 140 Glu Pro Leu Ser Trp Pro Val Arg Leu His Leu Ala Leu Asp Ile Ala 145 150 155 160 Arg Gly Leu Arg Tyr Leu His Ser Lys Gly Val Phe His Arg Asp Leu 165 170 175 Thr Ser Lys Asn Cys Leu Val Arg Arg Glu Asp Arg Gly Phe Thr Ala 180 185 190 Val Val Gly Asp Phe Gly Leu Ala Glu Lys Ile Pro Val Tyr Arg Glu 195 200 205 Gly Ala Arg Lys Glu Pro Leu Ala Val Val Gly Ser Pro Tyr Trp Met 210 215 220 Ala Pro Glu Val Leu Arg Gly Glu Leu Tyr Asp Glu Lys Ala Asp Val 225 230 235 240 Phe Ala Phe Gly Ile Val Leu Cys Glu Leu Ile Ala Arg Val Pro Ala 245 250 255 Asp Pro Asp Tyr Leu Pro Arg Thr Glu Asp Phe Gly Leu Asp Val Pro 260 265 270 Ala Phe Arg Thr Leu Val Gly Asp Asp Cys Pro Leu Pro Phe Leu Leu 275 280 285 Leu Ala Ile His Cys Cys Asn Leu Glu Pro Ser Thr Arg Ala Pro Phe 290 295 300 Thr Glu Ile Thr Gln His Leu Glu Trp Ile Leu Glu Gln Leu Pro Glu 305 310 315 320 Pro Ala Pro Leu Thr Arg Thr Ala Leu Thr His Asn Gln Gly Ser Val 325 330 335 Ala Arg Gly Gly Pro Ser Ala Thr Leu Pro Arg Pro Asp Pro Arg Leu 340 345 350 Ser Arg Ser Arg Ser Asp Leu Phe Leu Pro Pro Ser Pro Glu Ser Pro 355 360 365 Pro Asn Trp Gly Asp Asn Leu Thr Arg Val Asn Pro Phe Ser Leu Arg 370 375 380 Glu Asp Leu Arg Gly Gly Lys Ile Lys Leu Leu Asp Thr Pro Ser Lys 385 390 395 400 Pro Val Leu Pro Leu Val Pro Pro Ser Pro Phe Pro Ser Thr Gln Leu 405 410 415 Pro Leu Val Thr Thr Pro Glu Thr Leu Val Gln Pro Gly Thr Pro Ala 420 425 430 Arg Arg Cys Arg Ser Leu Pro Ser Ser Pro Glu Leu Pro Arg Arg Met 435 440 445 Glu Thr Ala Leu Pro Gly Pro Gly Pro Pro Ala Val Gly Pro Ser Ala 450 455 460 Glu Glu Lys Met Glu Cys Glu Gly Ser Ser Pro Glu Pro Glu Pro Pro 465 470 475 480 Gly Pro Ala Pro Gln Leu Pro Leu Ala Val Ala Thr Asp Asn Phe Ile 485 490 495 Ser Thr Cys Ser Ser Ala Ser Gln Pro Trp Ser Pro Arg Ser Gly Pro 500 505 510 Val Leu Asn Asn Asn Pro Pro Ala Val Val Val Asn Ser Pro Gln Gly 515 520 525 Trp Ala Gly Glu Pro Trp Asn Arg Ala Gln His Ser Leu Pro Arg Ala 530 535 540 Ala Ala Leu Glu Arg Thr Glu Pro Ser Pro Pro Pro Ser Ala Pro Arg 545 550 555 560 Glu Pro Asp Glu Gly Leu Pro Cys Pro Gly Cys Cys Leu Gly Pro Phe 565 570 575 Ser Phe Gly Phe Leu Ser Met Cys Pro Arg Pro Thr Pro Ala Val Ala 580 585 590 Arg Tyr Arg Asn Leu Asn Cys Glu Ala Gly Ser Leu Leu Cys His Arg 595 600 605 Gly His His Ala Lys Pro Pro Thr Pro Ser Leu Gln Leu Pro Gly Ala 610 615 620 Arg Ser 625 25 555 PRT Homo sapiens 25 Met Asp Arg Ser Lys Arg Asn Ser Ile Ala Gly Phe Pro Pro Arg Val 1 5 10 15 Glu Arg Leu Glu Glu Phe Glu Gly Gly Gly Gly Gly Glu Gly Asn Val 20 25 30 Ser Gln Val Gly Arg Val Trp Pro Ser Ser Tyr Arg Ala Leu Ile Ser 35 40 45 Ala Phe Ser Arg Leu Thr Arg Leu Asp Asp Phe Thr Cys Glu Lys Ile 50 55 60 Gly Ser Gly Phe Phe Ser Glu Val Phe Lys Val Arg His Arg Ala Ser 65 70 75 80 Gly Gln Val Met Ala Leu Lys Met Asn Thr Leu Ser Ser Asn Arg Ala 85 90 95 Asn Met Leu Lys Glu Val Gln Leu Met Asn Arg Leu Ser His Pro Asn 100 105 110 Ile Leu Arg Tyr Ile Asn Ser Gly Asn Leu Glu Gln Leu Leu Asp Ser 115 120 125 Asn Leu His Leu Pro Trp Thr Val Arg Val Lys Leu Ala Tyr Asp Ile 130 135 140 Ala Val Gly Leu Ser Tyr Leu His Phe Lys Gly Ile Phe His Arg Asp 145 150 155 160 Leu Thr Ser Lys Asn Cys Leu Ile Lys Arg Asp Glu Asn Gly Tyr Ser 165 170 175 Ala Val Val Ala Asp Phe Gly Leu Ala Glu Lys Ile Pro Asp Val Ser 180 185 190 Met Gly Ser Glu Lys Leu Ala Val Val Gly Ser Pro Phe Trp Met Ala 195 200 205 Pro Glu Val Leu Arg Asp Glu Pro Tyr Asn Glu Lys Ala Asp Val Phe 210 215 220 Ser Tyr Gly Ile Ile Leu Cys Glu Ile Ile Ala Arg Ile Gln Ala Asp 225 230 235 240 Pro Asp Tyr Leu Pro Arg Thr Glu Asn Phe Gly Leu Asp Tyr Asp Ala 245 250 255 Phe Gln His Met Val Gly Asp Cys Pro Pro Asp Phe Leu Gln Leu Thr 260 265 270 Phe Asn Cys Cys Asn Met Asp Pro Lys Leu Arg Pro Ser Phe Val Glu 275 280 285 Ile Gly Lys Thr Leu Glu Glu Ile Leu Ser Arg Leu Gln Glu Glu Glu 290 295 300 Gln Glu Arg Asp Arg Lys Leu Gln Pro Thr Ala Arg Gly Leu Leu Glu 305 310 315 320 Lys Ala Pro Gly Val Lys Arg Leu Ser Ser Leu Asp Asp Lys Ile Pro 325 330 335 His Lys Ser Pro Cys Pro Arg Arg Thr Ile Trp Leu Ser Arg Ser Gln 340 345 350 Ser Asp Ile Phe Ser Arg Lys Pro Pro Arg Thr Val Ser Val Leu Asp 355 360 365 Pro Tyr Tyr Arg Pro Arg Asp Gly Ala Ala Arg Thr Pro Lys Val Asn 370 375 380 Pro Phe Ser Ala Arg Gln Asp Leu Met Gly Gly Lys Ile Lys Phe Phe 385 390 395 400 Asp Leu Pro Ser Lys Ser Val Ile Ser Leu Val Phe Asp Leu Asp Ala 405 410 415 Pro Gly Pro Gly Thr Met Pro Leu Ala Asp Trp Gln Glu Pro Leu Ala 420 425 430 Pro Pro Ile Arg Arg Trp Arg Ser Leu Pro Gly Ser Pro Glu Phe Leu 435 440 445 His Gln Glu Ala Cys Pro Phe Val Gly Arg Glu Glu Ser Leu Ser Asp 450 455 460 Gly Pro Pro Pro Arg Leu Ser Ser Leu Lys Tyr Arg Val Lys Glu Ile 465 470 475 480 Pro Pro Phe Arg Ala Ser Ala Leu Pro Ala Ala Gln Ala His Glu Ala 485 490 495 Met Asp Cys Ser Ile Leu Gln Glu Glu Asn Gly Phe Gly Ser Arg Pro 500 505 510 Gln Gly Thr Ser Pro Cys Pro Ala Gly Ala Ser Glu Glu Met Glu Val 515 520 525 Glu Glu Arg Pro Ala Gly Ser Thr Pro Ala Thr Phe Ser Thr Ser Gly 530 535 540 Ile Gly Leu Gln Thr Gln Gly Lys Gln Asp Gly 545 550 555

Claims

1. A method of identifying a candidate p53 pathway modulating agent, said method comprising the steps of: (a) providing an assay system comprising a purified LIMK polypeptide or nucleic acid or a functionally active fragment or derivative thereof; (b) contacting the assay system with a test agent under conditions whereby, but for the presence of the test agent, the system provides a reference activity; and (c) detecting a test agent-biased activity of the assay system, wherein a difference between the test agent-biased activity and the reference activity identifies the test agent as a candidate p53 pathway modulating agent.

2. The method of claim 1 wherein the assay system comprises cultured cells that express the LIMK polypeptide.

3. The method of claim 2 wherein the cultured cells additionally have defective p53 function.

4. The method of claim 1 wherein the assay system includes a screening assay comprising a LIMK polypeptide, and the candidate test agent is a small molecule modulator.

5. The method of claim 4 wherein the assay is a kinase assay.

6. The method of claim 1 wherein the assay system is selected from the group consisting of an apoptosis assay system, a cell proliferation assay system, an angiogenesis assay system, and a hypoxic induction assay system.

7. The method of claim 1 wherein the assay system includes a binding assay comprising a LIMK polypeptide and the candidate test agent is an antibody.

8. The method of claim 1 wherein the assay system includes an expression assay comprising a LIMK nucleic acid and the candidate test agent is a nucleic acid modulator.

9. The method of claim 8 wherein the nucleic acid modulator is an antisense oligomer.

10. The method of claim 8 wherein the nucleic acid modulator is a PMO.

11. The method of claim 1 additionally comprising: (d) administering the candidate p53 pathway modulating agent identified in (c) to a model system comprising cells defective in p53 function and, detecting a phenotypic change in the model system that indicates that the p53 function is restored.

12. The method of claim 11 wherein the model system is a mouse model with defective p53 function.

13. A method for modulating a p53 pathway of a cell comprising contacting a cell defective in p53 function with a candidate modulator that specifically binds to a LIMK polypeptide comprising an amino acid sequence selected from group consisting of SEQ ID NOs:19, 20, 21, 22, 23, 24, and 25, whereby p53 function is restored.

14. The method of claim 13 wherein the candidate modulator is administered to a vertebrate animal predetermined to have a disease or disorder resulting from a defect in p53 function.

15. The method of claim 13 wherein the candidate modulator is selected from the group consisting of an antibody and a small molecule.

16. The method of claim 1, comprising the additional steps of: (d) providing a secondary assay system comprising cultured cells or a non-human animal expressing LIMK, (e) contacting the secondary assay system with the test agent of (b) or an agent derived therefrom under conditions whereby, but for the presence of the test agent or agent derived therefrom, the system provides a reference activity; and (f) detecting an agent-biased activity of the second assay system, wherein a difference between the agent-biased activity and the reference activity of the second assay system confirms the test agent or agent derived therefrom as a candidate p53 pathway modulating agent, and wherein the second assay detects an agent-biased change in the p53 pathway.

17. The method of claim 16 wherein the secondary assay system comprises cultured cells.

18. The method of claim 16 wherein the secondary assay system comprises a non-human animal.

19. The method of claim 18 wherein the non-human animal mis-expresses a p53 pathway gene.

20. A method of modulating p53 pathway in a mammalian cell comprising contacting the cell with an agent that specifically binds a LIMK polypeptide or nucleic acid.

21. The method of claim 20 wherein the agent is administered to a mammalian animal predetermined to have a pathology associated with the p53 pathway.

22. The method of claim 20 wherein the agent is a small molecule modulator, a nucleic acid modulator, or an antibody.

23. A method for diagnosing a disease in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with a probe for LIMK expression; (c) comparing results from step (b) with a control; (d) determining whether step (c) indicates a likelihood of disease.

24. The method of claim 23 wherein said disease is cancer.

25. The method according to claim 24, wherein said cancer is a cancer as shown in Table 1 as having >25% expression level.