Isolated nucleic acid molecules encoding transferase enzymes

The present invention is in the field of enzyme proteins that are related to the transferase enzyme subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.

Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the transferase subfamily.

Transferases

The novel human protein, and encoding gene, provided by the present invention is related to transferases in general, specifically sulfotransferases and tyrosylprotein sulfotransferases in particular. Furthermore, the protein of the present invention may be an alternative splice form of tyrosylprotein sulfotransferase 1 (Genbank gi4507665); see the amino acid sequence alignment provided in FIG. 2 . The C-terminal sequence is not covered by the genomic sequence, suggesting an additional coding exon.

Tyrosylprotein sulfotransferases are important for catalyzing tyrosine O-sulfation, which is a widespread posttranslational modification that occurs in all multicellular organisms and tissues. The tyrosine O-sulfation reaction involves transferring sulfate from 3′-phosphoadenosine 5′-phosphosulfate to tyrosine residues within acidic motifs of polypeptides (Ouyang et al, Proc Natl Acad Sci U S A Mar. 17, 1998;95(6):2896-901). Tyrosine O-sulfation is important in protein-protein interactions in a wide variety of physiological systems, particularly those systems involved in inflammation and hemostasis (Ouyang et al., Proc Natl Acad Sci U S A Mar. 17, 1998;95(6):2896-901). Sulfation of tyrosine residues in P-selectin glycoprotein ligand 1 (PSGL-1), a leukocyte adhesion molecule, is required for binding of PSGL-1 to P-selectin on activated endothelium (Ouyang et al., Proc Natl Acad Sci U S A Mar. 17, 1998;95(6):2896-901). Tyrosylprotein sulfotransferases are integral membrane glycoproteins that are located in the trans-Golgi network with the catalytic site oriented towards the trans-Golgi network lumen. This position allows tyrosylprotein sulfotransferases to catalyze the tyrosine O-sulfation reaction on proteins that pass through the trans-Golgi network, such as plasma membrane and secretory proteins. Tyrosine O-sulfation facilitates protein-protein interactions between such proteins as secretory proteins, cell surface receptors, and plasma membrane proteins. For a further review of tyrosylprotein sulfotransferases, see Beisswanger et al., Proc. Nat. Acad. Sci. 95: 11134-11139, 1998.

Due to their importance in regulating protein-protein interactions, particularly in inflammation, hemostasis, and other important physiological processes, novel human tyrosylprotein sulfotransferase proteins/genes, such as provided by the present invention, are valuable as potential targets for the development of therapeutics to treat inflammatory, hemological, and other disorders. Furthermore, SNPs in tyrosylprotein sulfotransferase genes, such as provided by the present invention, are valuable markers for the diagnosis, prognosis, prevention, and/or treatment of such disorders.

Using the information provided by the present invention, reagents such as probes/primers for detecting the SNPs or the expression of the protein/gene provided herein may be readily developed and, if desired, incorporated into kit formats such as nucleic acid arrays, primer extension reactions coupled with mass spec detection (for SNP detection), or TaqMan PCR assays (Applied Biosystems, Foster City, Calif.).

Enzyme proteins, particularly members of the transferase enzyme subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the transferase enzyme subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.

The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the transferase enzyme subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus.

FIGS. 1A through 1B provides the nucleotide sequence of a cDNA molecule that encodes the enzyme protein of the present invention. (SEQ ID NO: 1) In addition, structure and functional information is provided, such as ATG start, stop and tissue distribution, where available, that allows one to readily determine specific uses of inventions based on this molecular sequence. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus.

FIGS. 2A through 2C provides the predicted amino acid sequence of the enzyme of the present invention. (SEQ ID NO:2) In addition structure and functional information such as protein family, function, and modification sites is provided where available, allowing one to readily determine specific uses of inventions based on this molecular sequence.

FIGS. 3 A through 3 CCC provides genomic sequences that span the gene encoding the enzyme protein of the present invention. (SEQ ID NO:3) In addition structure and functional information, such as intron/exon structure, promoter location, etc., is provided where available, allowing one to readily determine specific uses of inventions based on this molecular sequence. As illustrated in FIG. 3, SNPs were identified at 71 different nucleotide positions.

General Description

The present invention is based on the sequencing of the human genome. During the sequencing and assembly of the human genome, analysis of the sequence information revealed previously unidentified fragments of the human genome that encode peptides that share structural and/or sequence homology to protein/peptide/domains identified and characterized within the art as being a enzyme protein or part of a enzyme protein and are related to the transferase enzyme subfamily. Utilizing these sequences, additional genomic sequences were assembled and transcript and/or cDNA sequences were isolated and characterized. Based on this analysis, the present invention provides amino acid sequences of human enzyme peptides and proteins that are related to the transferase enzyme subfamily, nucleic acid sequences in the form of transcript sequences, cDNA sequences and/or genomic sequences that encode these enzyme peptides and proteins, nucleic acid variation (allelic information), tissue distribution of expression, and information about the closest art known protein/peptide/domain that has structural or sequence homology to the enzyme of the present invention.

In addition to being previously unknown, the peptides that are provided in the present invention are selected based on their ability to be used for the development of commercially important products and services. Specifically, the present peptides are selected based on homology and/or structural relatedness to known enzyme proteins of the transferase enzyme subfamily and the expression pattern observed. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. The art has clearly established the commercial importance of members of this family of proteins and proteins that have expression patterns similar to that of the present gene. Some of the more specific features of the peptides of the present invention, and the uses thereof, are described herein, particularly in the Background of the Invention and in the annotation provided in the Figures, and/or are known within the art for each of the known transferase family or subfamily of enzyme proteins.

Specific Embodiments

Peptide Molecules

The present invention provides nucleic acid sequences that encode protein molecules that have been identified as being members of the enzyme family of proteins and are related to the transferase enzyme subfamily (protein sequences are provided in FIG. 2, transcript/cDNA sequences are provided in FIG. 1 and genomic sequences are provided in FIG. 3 ). The peptide sequences provided in FIG. 2, as well as the obvious variants described herein, particularly allelic variants as identified herein and using the information in FIG. 3, will be referred herein as the enzyme peptides of the present invention, enzyme peptides, or peptides/proteins of the present invention.

The present invention provides isolated peptide and protein molecules that consist of, consist essentially of, or comprise the amino acid sequences of the enzyme peptides disclosed in the FIG. 2, (encoded by the nucleic acid molecule shown in FIG. 1, transcript/cDNA or FIG. 3, genomic sequence), as well as all obvious variants of these peptides that are within the art to make and use. Some of these variants are described in detail below.

As used herein, a peptide is said to be “isolated” or “purified” when it is substantially free of cellular material or free of chemical precursors or other chemicals. The peptides of the present invention can be purified to homogeneity or other degrees of purity. The level of purification will be based on the intended use. The critical feature is that the preparation allows for the desired function of the peptide, even if in the presence of considerable amounts of other components (the features of an isolated nucleic acid molecule is discussed below).

In some uses, “substantially free of cellular material” includes preparations of the peptide having less than about 30% (by dry weight) other proteins (i.e., contaminating protein), less than about 20% other proteins, less than about 10% other proteins, or less than about 5% other proteins. When the peptide is recombinantly produced, it can also be substantially free of culture medium, i.e., culture medium represents less than about 20% of the volume of the protein preparation.

The language “substantially free of chemical precursors or other chemicals” includes preparations of the peptide in which it is separated from chemical precursors or other chemicals that are involved in its synthesis. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of the enzyme peptide having less than about 30% (by dry weight) chemical precursors or other chemicals, less than about 20% chemical precursors or other chemicals, less than about 10% chemical precursors or other chemicals, or less than about 5% chemical precursors or other chemicals.

The isolated enzyme peptide can be purified from cells that naturally express it, purified from cells that have been altered to express it (recombinant), or synthesized using known protein synthesis methods. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. For example, a nucleic acid molecule encoding the enzyme peptide is cloned into an expression vector, the expression vector introduced into a host cell and the protein expressed in the host cell. The protein can then be isolated from the cells by an appropriate purification scheme using standard protein purification techniques. Many of these techniques are described in detail below.

Accordingly, the present invention provides proteins that consist of the amino acid sequences provided in FIG. 2 (SEQ ID NO:2), for example, proteins encoded by the transcript/cDNA nucleic acid sequences shown in FIG. 1 (SEQ ID NO: 1) and the genomic sequences provided in FIG. 3 (SEQ ID NO:3). The amino acid sequence of such a protein is provided in FIG. 2. A protein consists of an amino acid sequence when the amino acid sequence is the final amino acid sequence of the protein.

The present invention further provides proteins that consist essentially of the amino acid sequences provided in FIG. 2 (SEQ ID NO:2), for example, proteins encoded by the transcript/cDNA nucleic acid sequences shown in FIG. 1 (SEQ ID NO:1) and the genomic sequences provided in FIG. 3 (SEQ ID NO:3). A protein consists essentially of an amino acid sequence when such an amino acid sequence is present with only a few additional amino acid residues, for example from about 1 to about 100 or so additional residues, typically from 1 to about 20 additional residues in the final protein.

The present invention further provides proteins that comprise the amino acid sequences provided in FIG. 2 (SEQ ID NO:2), for example, proteins encoded by the transcript/cDNA nucleic acid sequences shown in FIG. 1 (SEQ ID NO: 1) and the genomic sequences provided in FIG. 3 (SEQ ID NO:3). A protein comprises an amino acid sequence when the amino acid sequence is at least part of the final amino acid sequence of the protein. In such a fashion, the protein can be only the peptide or have additional amino acid molecules, such as amino acid residues (contiguous encoded sequence) that are naturally associated with it or heterologous amino acid residues/peptide sequences. Such a protein can have a few additional amino acid residues or can comprise several hundred or more additional amino acids. The preferred classes of proteins that are comprised of the enzyme peptides of the present invention are the naturally occurring mature proteins. A brief description of how various types of these proteins can be made/isolated is provided below.

The enzyme peptides of the present invention can be attached to heterologous sequences to form chimeric or fusion proteins. Such chimeric and fusion proteins comprise a enzyme peptide operatively linked to a heterologous protein having an amino acid sequence not substantially homologous to the enzyme peptide. “Operatively linked” indicates that the enzyme peptide and the heterologous protein are fused in-frame. The heterologous protein can be fused to the N-terminus or C-terminus of the enzyme peptide.

In some uses, the fission protein does not affect the activity of the enzyme peptide per se. For example, the fusion protein can include, but is not limited to, enzymatic fusion proteins, for example beta-galactosidase fusions, yeast two-hybrid GAL fusions, poly-His fusions, MYC-tagged, HI-tagged and Ig fusions. Such fusion proteins, particularly poly-His fusions, can facilitate the purification of recombinant enzyme peptide. In certain host cells (e.g., mammalian host cells), expression and/or secretion of a protein can be increased by using a heterologous signal sequence.

A chimeric or fusion protein can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different protein sequences are ligated together in-frame in accordance with conventional techniques. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and re-amplified to generate a chimeric gene sequence (see Ausubel et al., Current Protocols in Molecular Biology, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST protein). A enzyme peptide-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the enzyme peptide.

As mentioned above, the present invention also provides and enables obvious variants of the amino acid sequence of the proteins of the present invention, such as naturally occurring mature forms of the peptide, allelic/sequence variants of the peptides, non-naturally occurring recombinantly derived variants of the peptides, and orthologs and paralogs of the peptides. Such variants can readily be generated using art-known techniques in the fields of recombinant nucleic acid technology and protein biochemistry. It is understood, however, that variants exclude any amino acid sequences disclosed prior to the invention.

Such variants can readily be identified/made using molecular techniques and the sequence information disclosed herein. Further, such variants can readily be distinguished from other peptides based on sequence and/or structural homology to the enzyme peptides of the present invention. The degree of homology/identity present will be based primarily on whether the peptide is a functional variant or non-functional variant, the amount of divergence present in the paralog family and the evolutionary distance between the orthologs.

To determine the percent identity of two amino acid sequences or two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In a preferred embodiment, at least 30%, 40%, 50%, 60%, 70%, 80%, or 90% or more of the length of a reference sequence is aligned for comparison purposes. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”). The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.

The comparison of sequences and determination of percent identity and similarity between two sequences can be accomplished using a mathematical algorithm. ( Computational Molecular Biology , Lesk, A. M., ed., Oxford University Press, New York, 1988 ; Biocomputing: Informatics and Genome Projects , Smith, D. W., ed., Academic Press, New York, 1993 ; Computer Analysis of Sequence Data, Part 1, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994 ; Sequence Analysis in Molecular Biology , von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer , Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991). In a preferred embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ( J. Mol. Biol . (48):444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at http://www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (Devereux, J., et al., Nucleic Acids Res. 12(1):387 (1984)) (available at http://www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. In another embodiment, the percent identity between two amino acid or nucleotide sequences is determined using the algorithm of E. Myers and W. Miller (CABIOS, 4:11-17 (1989)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.

The nucleic acid and protein sequences of the present invention can further be used as a “query sequence” to perform a search against sequence databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. ( J. Mol. Biol. 215:403-10 (1990)). BLAST nucleotide searches can be performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to the nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to the proteins of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al. ( Nucleic Acids Res. 25(17):3389-3402 (1997)). When utilizing BLAST and gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

Full-length pre-processed forms, as well as mature processed forms, of proteins that comprise one of the peptides of the present invention can readily be identified as having complete sequence identity to one of the enzyme peptides of the present invention as well as being encoded by the same genetic locus as the enzyme peptide provided herein. The gene encoding the novel enzyme of the present invention is located on a genome component that has been mapped to human chromosome 7 (as indicated in FIG. 3 ), which is supported by multiple lines of evidence, such as STS and BAC map data.

Allelic variants of a enzyme peptide can readily be identified as being a human protein having a high degree (significant) of sequence homology/identity to at least a portion of the enzyme peptide as well as being encoded by the same genetic locus as the enzyme peptide provided herein. Genetic locus can readily be determined based on the genomic information provided in FIG. 3, such as the genomic sequence mapped to the reference human. The gene encoding the novel enzyme of the present invention is located on a genome component that has been mapped to human chromosome 7 (as indicated in FIG. 3 ), which is supported by multiple lines of evidence, such as STS and BAC map data. As used herein, two proteins (or a region of the proteins) have significant homology when the amino acid sequences are typically at least about 70-80%, 80-90%, and more typically at least about 90-95% or more homologous. A significantly homologous amino acid sequence, according to the present invention, will be encoded by a nucleic acid sequence that will hybridize to a enzyme peptide encoding nucleic acid molecule under stringent conditions as more fully described below.

FIG. 3 provides information on SNPs that have been found in the gene encoding the enzyme of the present invention. SNPs were identified at 71 different nucleotide positions. Some of these SNPs that are located outside the ORF and in introns may affect gene transcription.

Paralogs of a enzyme peptide can readily be identified as having some degree of significant sequence homology/identity to at least a portion of the enzyme peptide, as being encoded by a gene from humans, and as having similar activity or function. Two proteins will typically be considered paralogs when the amino acid sequences are typically at least about 60% or greater, and more typically at least about 70% or greater homology through a given region or domain. Such paralogs will be encoded by a nucleic acid sequence that will hybridize to a enzyme peptide encoding nucleic acid molecule under moderate to stringent conditions as more fully described below.

Orthologs of a enzyme peptide can readily be identified as having some degree of significant sequence homology/identity to at least a portion of the enzyme peptide as well as being encoded by a gene from another organism. Preferred orthologs will be isolated from mammals, preferably primates, for the development of human therapeutic targets and agents. Such orthologs will be encoded by a nucleic acid sequence that will hybridize to a enzyme peptide encoding nucleic acid molecule under moderate to stringent conditions, as more fully described below, depending on the degree of relatedness of the two organisms yielding the proteins.

Non-naturally occurring variants of the enzyme peptides of the present invention can readily be generated using recombinant techniques. Such variants include, but are not limited to deletions, additions and substitutions in the amino acid sequence of the enzyme peptide. For example, one class of substitutions are conserved amino acid substitution. Such substitutions are those that substitute a given amino acid in a enzyme peptide by another amino acid of like characteristics. Typically seen as conservative substitutions are the replacements, one for another, among the aliphatic amino acids Ala, Val, Leu, and Ile; interchange of the hydroxyl residues Ser and Thr; exchange of the acidic residues Asp and Glu; substitution between the amide residues Asn and Gln; exchange of the basic residues Lys and Arg; and replacements among the aromatic residues Phe and Tyr. Guidance concerning which amino acid changes are likely to be phenotypically silent are found in Bowie et al., Science 247:1306-1310 (1990).

Variant enzyme peptides can be fully functional or can lack function in one or more activities, e.g. ability to bind substrate, ability to phosphorylate substrate, ability to mediate signaling, etc. Fully functional variants typically contain only conservative variation or variation in non-critical residues or in non-critical regions. FIG. 2 provides the result of protein analysis and can be used to identify critical domains/regions. Functional variants can also contain substitution of similar amino acids that result in no change or an insignificant change in function. Alternatively, such substitutions may positively or negatively affect function to some degree.

Non-functional variants typically contain one or more non-conservative amino acid substitutions, deletions, insertions, inversions, or truncation or a substitution, insertion, inversion, or deletion in a critical residue or critical region.

Amino acids that are essential for function can be identified by methods known in the art, such as site-directed mutagenesis or alanine-scanning mutagenesis (Cunningham et al., Science 244:1081-1085 (1989)), particularly using the results provided in FIG. 2 . The latter procedure introduces single alanine mutations at every residue in the molecule. The resulting mutant molecules are then tested for biological activity such as enzyme activity or in assays such as an in vitro proliferative activity. Sites that are critical for binding partner/substrate binding can also be determined by structural analysis such as crystallization, nuclear magnetic resonance or photoaffinity labeling (Smith et al., J. Mol. Biol. 224:899-904 (1992); de Vos et al. Science 255:306-312 (1992)).

The present invention further provides fragments of the enzyme peptides, in addition to proteins and peptides that comprise and consist of such fragments, particularly those comprising the residues identified in FIG. 2 . The fragments to which the invention pertains, however, are not to be construed as encompassing fragments that may be disclosed publicly prior to the present invention.

As used herein, a fragment comprises at least 8, 10, 12, 14, 16, or more contiguous amino acid residues from a enzyme peptide. Such fragments can be chosen based on the ability to retain one or more of the biological activities of the enzyme peptide or could be chosen for the ability to perform a function, e.g. bind a substrate or act as an immunogen. Particularly important fragments are biologically active fragments, peptides that are, for example, about 8 or more amino acids in length. Such fragments will typically comprise a domain or motif of the enzyme peptide, e.g., active site, a transmembrane domain or a substrate-binding domain. Further, possible fragments include, but are not limited to, domain or motif containing fragments, soluble peptide fragments, and fragments containing immunogenic structures. Predicted domains and functional sites are readily identifiable by computer programs well known and readily available to those of skill in the art (e.g., PROSITE analysis). The results of one such analysis are provided in FIG. 2 .

Polypeptides often contain amino acids other than the 20 amino acids commonly referred to as the 20 naturally occurring amino acids. Further, many amino acids, including the terminal amino acids, may be modified by natural processes, such as processing and other post-translational modifications, or by chemical modification techniques well known in the art. Common modifications that occur naturally in enzyme peptides are described in basic texts, detailed monographs, and the research literature, and they are well known to those of skill in the art (some of these features are identified in FIG. 2 ).

Known modifications include, but are not limited to, acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent crosslinks, formation of cystine, formation of pyroglutamate, formylation, gamma carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination.

Such modifications are well known to those of skill in the art and have been described in great detail in the scientific literature. Several particularly common modifications, glycosylation, lipid attachment, sulfation, gamma-carboxylation of glutamic acid residues, hydroxylation and ADP-ribosylation, for instance, are described in most basic texts, such as Proteins—Structure and Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York (1993). Many detailed reviews are available on this subject, such as by Wold, F., Posttranslational Covalent Modification of proteins , B. C. Johnson, Ed., Academic Press, New York 1-12 (1983); Seifter et al. ( Meth. Enzymol. 182: 626-646 (1990)) and Rattan et al ( Ann. N. Y Acad. Sci. 663:48-62 (1992)).

Accordingly, the enzyme peptides of the present invention also encompass derivatives or analogs in which a substituted amino acid residue is not one encoded by the genetic code, in which a substituent group is included, in which the mature enzyme peptide is fused with another compound, such as a compound to increase the half-life of the enzyme peptide (for example, polyethylene glycol), or in which the additional amino acids are fused to the mature enzyme peptide, such as a leader or secretory sequence or a sequence for purification of the mature enzyme peptide or a pro-protein sequence.

Protein/Peptide Uses

The proteins of the present invention can be used in substantial and specific assays related to the functional information provided in the Figures; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its binding partner or ligand) in biological fluids; and as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state). Where the protein binds or potentially binds to another protein or ligand (such as, for example, in a enzyme-effector protein interaction or enzyme-ligand interaction), the protein can be used to identify the binding partner/ligand so as to develop a system to identify inhibitors of the binding interaction. Any or all of these uses are capable of being developed into reagent grade or kit format for commercialization as commercial products.

Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include “Molecular Cloning: A Laboratory Manual”, 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E. F. Fritsch and T. Maniatis eds., 1989, and “Methods in Enzymology: Guide to Molecular Cloning Techniques”, Academic Press, Berger, S. L. and A. R. Kimmel eds., 1987.

The potential uses of the peptides of the present invention are based primarily on the source of the protein as well as the class/action of the protein. For example, enzymes isolated from humans and their human/mammalian orthologs serve as targets for identifying agents for use in mammalian therapeutic applications, e.g. a human drug, particularly in modulating a biological or pathological response in a cell or tissue that expresses the enzyme. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus. A large percentage of pharmaceutical agents are being developed that modulate the activity of enzyme proteins, particularly members of the transferase subfamily (see Background of the Invention). The structural and functional information provided in the Background and Figures provide specific and substantial uses for the molecules of the present invention, particularly in combination with the expression information provided in FIG. 1 . Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. Such uses can readily be determined using the information provided herein, that which is known in the art, and routine experimentation.

The proteins of the present invention (including variants and fragments that may have been disclosed prior to the present invention) are useful for biological assays related to enzymes that are related to members of the transferase subfamily. Such assays involve any of the known enzyme functions or activities or properties useful for diagnosis and treatment of enzyme-related conditions that are specific for the subfamily of enzymes that the one of the present invention belongs to, particularly in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus.

The proteins of the present invention are also useful in drug screening assays, in cell-based or cell-free systems. Cell-based systems can be native, i.e., cells that normally express the enzyme, as a biopsy or expanded in cell culture. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. In an alternate embodiment, cell-based assays involve recombinant host cells expressing the enzyme protein.

The polypeptides can be used to identify compounds that modulate enzyme activity of the protein in its natural state or an altered form that causes a specific disease or pathology associated with the enzyme. Both the enzymes of the present invention and appropriate variants and fragments can be used in high-throughput screens to assay candidate compounds for the ability to bind to the enzyme. These compounds can be further screened against a functional enzyme to determine the effect of the compound on the enzyme activity Further, these compounds can be tested in animal or invertebrate systems to determine activity/effectiveness. Compounds can be identified that activate (agonist) or inactivate (antagonist) the enzyme to a desired degree.

Further, the proteins of the present invention can be used to screen a compound for the ability to stimulate or inhibit interaction between the enzyme protein and a molecule that normally interacts with the enzyme protein, e.g. a substrate or a component of the signal pathway that the enzyme protein normally interacts (for example, another enzyme). Such assays typically include the steps of combining the enzyme protein with a candidate compound under conditions that allow the enzyme protein, or fragment, to interact with the target molecule, and to detect the formation of a complex between the protein and the target or to detect the biochemical consequence of the interaction with the enzyme protein and the target, such as any of the associated effects of signal transduction such as protein phosphorylation, cAMP turnover, and adenylate cyclase activation, etc.

Candidate compounds include, for example, 1) peptides such as soluble peptides, including Ig-tailed fusion peptides and members of random peptide libraries (see, e.g., Lam et al., Nature 354:82-84 (1991); Houghten et al., Nature 354:84-86 (1991)) and combinatorial chemistry-derived molecular libraries made of D- and/or L-configuration amino acids; 2) phosphopeptides (e.g., members of random and partially degenerate, directed phosphopeptide libraries, see, e.g., Songyang et al, Cell 72:767-778 (1993)); 3) antibodies (e.g., polyclonal, monoclonal, humanized, anti-idiotypic, chimeric, and single chain antibodies as well as Fab, F(ab′) 2 , Fab expression library fragments, and epitope-binding fragments of antibodies); and 4) small organic and inorganic molecules (e.g., molecules obtained from combinatorial and natural product libraries).

One candidate compound is a soluble fragment of the receptor that competes for substrate binding. Other candidate compounds include mutant enzymes or appropriate fragments containing mutations that affect enzyme function and thus compete for substrate. Accordingly, a fragment that competes for substrate, for example with a higher affinity, or a fragment that binds substrate but does not allow release, is encompassed by the invention.

The invention further includes other end point assays to identify compounds that modulate (stimulate or inhibit) enzyme activity. The assays typically involve an assay of events in the signal transduction pathway that indicate enzyme activity. Thus, the phosphorylation of a substrate, activation of a protein, a change in the expression of genes that are up- or down-regulated in response to the enzyme protein dependent signal cascade can be assayed.

Any of the biological or biochemical functions mediated by the enzyme can be used as an endpoint assay. These include all of the biochemical or biochemical/biological events described herein, in the references cited herein, incorporated by reference for these endpoint assay targets, and other functions known to those of ordinary skill in the art or that can be readily identified using the information provided in the Figures, particularly FIG. 2 . Specifically, a biological function of a cell or tissues that expresses the enzyme can be assayed. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus.

Binding and/or activating compounds can also be screened by using chimeric enzyme proteins in which the amino terminal extracellular domain, or parts thereof the entire transmembrane domain or subregions, such as any of the seven transmembrane segments or any of the intracellular or extracellular loops and the carboxy terminal intracellular domain, or parts thereof, can be replaced by heterologous domains or subregions. For example, a substrate-binding region can be used that interacts with a different substrate then that which is recognized by the native enzyme. Accordingly, a different set of signal transduction components is available as an end-point assay for activation. This allows for assays to be performed in other than the specific host cell from which the enzyme is derived.

The proteins of the present invention are also useful in competition binding assays in methods designed to discover compounds that interact with the enzyme (e.g. binding partners and/or ligands). Thus, a compound is exposed to a enzyme polypeptide under conditions that allow the compound to bind or to otherwise interact with the polypeptide. Soluble enzyme polypeptide is also added to the mixture. If the test compound interacts with the soluble enzyme polypeptide, it decreases the amount of complex formed or activity from the enzyme target. This type of assay is particularly useful in cases in which compounds are sought that interact with specific regions of the enzyme. Thus, the soluble polypeptide that competes with the target enzyme region is designed to contain peptide sequences corresponding to the region of interest.

To perform cell free drug screening assays, it is sometimes desirable to immobilize either the enzyme protein, or fragment, or its target molecule to facilitate separation of complexes from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay.

Techniques for immobilizing proteins on matrices can be used in the drug screening assays. In one embodiment, a fusion protein can be provided which adds a domain that allows the protein to be bound to a matrix. For example, glutathione-S-transferase fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtitre plates, which are then combined with the cell lysates (e.g., 35 S-labeled) and the candidate compound, and the mixture incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads are washed to remove any unbound label, and the matrix immobilized and radiolabel determined directly, or in the supernatant after the complexes are dissociated. Alternatively, the complexes can be dissociated from the matrix, separated by SDS-PAGE, and the level of enzyme-binding protein found in the bead fraction quantitated from the gel using standard electrophoretic techniques. For example, either the polypeptide or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin using techniques well known in the art. Alternatively, antibodies reactive with the protein but which do not interfere with binding of the protein to its target molecule can be derivatized to the wells of the plate, and the protein trapped in the wells by antibody conjugation. Preparations of a enzyme-binding protein and a candidate compound are incubated in the enzyme protein-presenting wells and the amount of complex trapped in the well can be quantitated. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the enzyme protein target molecule, or which are reactive with enzyme protein and compete with the target molecule, as well as enzyme-linked assays which rely on detecting an enzymatic activity associated with the target molecule.

Agents that modulate one of the enzymes of the present invention can be identified using one or more of the above assays, alone or in combination. It is generally preferable to use a cell-based or cell free system first and then confirm activity in an animal or other model system. Such model systems are well known in the art and can readily be employed in this context.

Modulators of enzyme protein activity identified according to these drug screening assays can be used to treat a subject with a disorder mediated by the enzyme pathway, by treating cells or tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. These methods of treatment include the steps of administering a modulator of enzyme activity in a pharmaceutical composition to a subject in need of such treatment, the modulator being identified as described herein.

In yet another aspect of the invention, the enzyme proteins can be used as “bait proteins” in a two-hybrid assay or three-hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos et al. (1993) Cell 72:223-232; Madura et al. (1993) J. Biol. Chem. 268:12046-12054; Bartel et al. (1993) Biotechniques 14:920-924; Iwabuchi et al. (1993) Oncogene 8:1693-1696; and Brent WO94/10300), to identify other proteins, which bind to or interact with the enzyme and are involved in enzyme activity. Such enzyme-binding proteins are also likely to be involved in the propagation of signals by the enzyme proteins or enzyme targets as, for example, downstream elements of a enzyme-mediated signaling pathway. Alternatively, such enzyme-binding proteins are likely to be enzyme inhibitors.

The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for a enzyme protein is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a enzyme-dependent complex. the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) which is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene which encodes the protein which interacts with the enzyme protein.

This invention further pertains to novel agents identified by the above-described screening assays. Accordingly, it is within the scope of this invention to further use an agent identified as described herein in an appropriate animal model. For example, an agent identified as described herein (e.g., a enzyme-modulating agent, an antisense enzyme nucleic acid molecule, a enzyme-specific antibody, or a enzyme-binding partner) can be used in an animal or other model to determine the efficacy, toxicity, or side effects of treatment with such an agent. Alternatively, an agent identified as described herein can be used in an animal or other model to determine the mechanism of action of such an agent. Furthermore, this invention pertains to uses of novel agents identified by the above-described screening assays for treatments as described herein.

The enzyme proteins of the present invention are also useful to provide a target for diagnosing a disease or predisposition to disease mediated by the peptide. Accordingly, the invention provides methods for detecting the presence, or levels of, the protein (or encoding MRNA) in a cell, tissue, or organism. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. The method involves contacting a biological sample with a compound capable of interacting with the enzyme protein such that the interaction can be detected. Such an assay can be provided in a single detection format or a multi-detection format such as an antibody chip array.

One agent for detecting a protein in a sample is an antibody capable of selectively binding to protein. A biological sample includes tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject.

The peptides of the present invention also provide targets for diagnosing active protein activity, disease, or predisposition to disease, in a patient having a variant peptide, particularly activities and conditions that are known for other members of the family of proteins to which the present one belongs. Thus, the peptide can be isolated from a biological sample and assayed for the presence of a genetic mutation that results in aberrant peptide. This includes amino acid substitution, deletion, insertion, rearrangement, (as the result of aberrant splicing events), and inappropriate post-translational modification. Analytic methods include altered electrophoretic mobility, altered tryptic peptide digest, altered enzyme activity in cell-based or cell-free assay, alteration in substrate or antibody-binding pattern, altered isoelectric point, direct amino acid sequencing, and any other of the known assay techniques useful for detecting mutations in a protein. Such an assay can be provided in a single detection format or a multi-detection format such as an antibody chip array.

In vitro techniques for detection of peptide include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations and immunofluorescence using a detection reagent, such as an antibody or protein binding agent. Alternatively, the peptide can be detected in vivo in a subject by introducing into the subject a labeled anti-peptide antibody or other types of detection agent. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. Particularly useful are methods that detect the allelic variant of a peptide expressed in a subject and methods which detect fragments of a peptide in a sample.

The peptides are also useful in pharmiacogenomic analysis. Pharmacogenomics deal with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See, e.g., Eichelbaum, M. ( Clin. Exp. Pharmacol. Physiol. 23(10-11):983-985 (1996)), and Linder, M. W. ( Clin. Chem. 43(2):254-266 (1997)). The clinical outcomes of these variations result in severe toxicity of therapeutic drugs in certain individuals or therapeutic failure of drugs in certain individuals as a result of individual variation in metabolism. Thus, the genotype of the individual can determine the way a therapeutic compound acts on the body or the way the body metabolizes the compound. Further, the activity of drug metabolizing enzymes effects both the intensity and duration of drug action. Thus, the pharmacogenomics of the individual permit the selection of effective compounds and effective dosages of such compounds for prophylactic or therapeutic treatment based on the individual's genotype. The discovery of genetic polymorphisms in some drug metabolizing enzymes has explained why some patients do not obtain the expected drug effects, show an exaggerated drug effect, or experience serious toxicity from standard drug dosages. Polymorphisms can be expressed in the phenotype of the extensive metabolizer and the phenotype of the poor metabolizer. Accordingly, genetic polymorphism may lead to allelic protein variants of the enzyme protein in which one or more of the enzyme functions in one population is different from those in another population. The peptides thus allow a target to ascertain a genetic predisposition that can affect treatment modality. Thus, in a ligand-based treatment, polymorphism may give rise to amino terminal extracellular domains and/or other substrate-binding regions that are more or less active in substrate binding, and enzyme activation. Accordingly, substrate dosage would necessarily be modified to maximize the therapeutic effect within a given population containing a polymorphism. As an alternative to genotyping, specific polymorphic peptides could be identified.

The peptides are also useful for treating a disorder characterized by an absence of, inappropriate, or unwanted expression of the protein. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. Accordingly, methods for treatment include the use of the enzyme protein or fragments.

Antibodies

The invention also provides antibodies that selectively bind to one of the peptides of the present invention, a protein comprising such a peptide, as well as variants and fragments thereof. As used herein, an antibody selectively binds a target peptide when it binds the target peptide and does not significantly bind to unrelated proteins. An antibody is still considered to selectively bind a peptide even if it also binds to other proteins that are not substantially homologous with the target peptide so long as such proteins share homology with a fragment or domain of the peptide target of the antibody. In this case, it would be understood that antibody binding to the peptide is still selective despite some degree of cross-reactivity.

As used herein, an antibody is defined in terms consistent with that recognized within the art: they are multi-subunit proteins produced by a mammalian organism in response to an antigen challenge. The antibodies of the present invention include polyclonal antibodies and monoclonal antibodies, as well as fragments of such antibodies, including, but not limited to, Fab or F(ab′) 2 , and Fv fragments.

Many methods are known for generating and/or identifying antibodies to a given target peptide. Several such methods are described by Harlow, Antibodies, Cold Spring Harbor Press, (1989).

In general, to generate antibodies, an isolated peptide is used as an immunogen and is administered to a mammalian organism, such as a rat, rabbit or mouse. The full-length protein, an antigenic peptide fragment or a fusion protein can be used. Particularly important fragments are those covering functional domains, such as the domains identified in FIG. 2, and domain of sequence homology or divergence amongst the family, such as those that can readily be identified using protein alignment methods and as presented in the Figures.

Antibodies are preferably prepared from regions or discrete fragments of the enzyme proteins. Antibodies can be prepared from any region of the peptide as described herein. However, preferred regions will include those involved in function/activity and/or enzyme/binding partner interaction. FIG. 2 can be used to identify particularly important regions while sequence alignment can be used to identify conserved and unique sequence fragments.

An antigenic fragment will typically comprise at least 8 contiguous amino acid residues. The antigenic peptide can comprise, however, at least 10, 12, 14, 16 or more amino acid residues. Such fragments can be selected on a physical property, such as fragments correspond to regions that are located on the surface of the protein, e.g., hydrophilic regions or can be selected based on sequence uniqueness (see FIG. 2 ).

Detection on an antibody of the present invention can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoeyrthrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125 I, 131 I, 35 S or 3 H.

Antibody Uses

The antibodies can be used to isolate one of the proteins of the present invention by standard techniques, such as affinity chromatography or immunoprecipitation. The antibodies can facilitate the purification of the natural protein from cells and recombinantly produced protein expressed in host cells. In addition, such antibodies are useful to detect the presence of one of the proteins of the present invention in cells or tissues to determine the pattern of expression of the protein among various tissues in an organism and over the course of normal development. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus. Further, such antibodies can be used to detect protein in situ, in vitro, or in a cell lysate or supernatant in order to evaluate the abundance and pattern of expression. Also, such antibodies can be used to assess abnormal tissue distribution or abnormal expression during development or progression of a biological condition. Antibody detection of circulating fragments of the full length protein can be used to identify turnover.

Further, the antibodies can be used to assess expression in disease states such as in active stages of the disease or in an individual with a predisposition toward disease related to the protein's function. When a disorder is caused by an inappropriate tissue distribution, developmental expression, level of expression of the protein, or expressed/processed form, the antibody can be prepared against the normal protein. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. If a disorder is characterized by a specific mutation in the protein, antibodies specific for this mutant protein can be used to assay for the presence of the specific mutant protein.

The antibodies can also be used to assess normal and aberrant subcellular localization of cells in the various tissues in an organism. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. The diagnostic uses can be applied, not only in genetic testing, but also in monitoring a treatment modality. Accordingly, where treatment is ultimately aimed at correcting expression level or the presence of aberrant sequence and aberrant tissue distribution or developmental expression, antibodies directed against the protein or relevant fragments can be used to monitor therapeutic efficacy.

Additionally, antibodies are useful in pharmacogenomic analysis. Thus, antibodies prepared against polymorphic proteins can be used to identify individuals that require modified treatment modalities. The antibodies are also useful as diagnostic tools as an immunological marker for aberrant protein analyzed by electrophoretic mobility, isoelectric point, tryptic peptide digest, and other physical assays known to those in the art.

The antibodies are also useful for tissue typing Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. Thus, where a specific protein has been correlated with expression in a specific tissue, antibodies that are specific for this protein can be used to identify a tissue type.

The antibodies are also useful for inhibiting protein function, for example, blocking the binding of the enzyme peptide to a binding partner such as a substrate. These uses can also be applied in a therapeutic context in which treatment involves inhibiting the protein's function. An antibody can be used, for example, to block binding, thus modulating (agonizing or antagonizing) the peptides activity. Antibodies can be prepared against specific fragments containing sites required for function or against intact protein that is associated with a cell or cell membrane. See FIG. 2 for structural information relating to the proteins of the present invention.

The invention also encompasses kits for using antibodies to detect the presence of a protein in a biological sample. The kit can comprise antibodies such as a labeled or labelable antibody and a compound or agent for detecting protein in a biological sample; means for determining the amount of protein in the sample; means for comparing the amount of protein in the sample with a standard; and instructions for use. Such a kit can be supplied to detect a single protein or epitope or can be configured to detect one of a multitude of epitopes, such as in an antibody detection array. Arrays are described in detail below for nuleic acid arrays and similar methods have been developed for antibody arrays.

Nucleic Acid Molecules

The present invention further provides isolated nucleic acid molecules that encode a enzyme peptide or protein of the present invention (cDNA, transcript and genomic sequence). Such nucleic acid molecules will consist of, consist essentially of, or comprise a nucleotide sequence that encodes one of the enzyme peptides of the present invention, an allelic variant thereof, or an ortholog or paralog thereof.

As used herein, an “isolated” nucleic acid molecule is one that is separated from other nucleic acid present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′ and 3′ ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. However, there can be some flanking nucleotide sequences, for example up to about 5 KB, 4 KB, 3 KB, 2 KB, or 1 KB or less, particularly contiguous peptide encoding sequences and peptide encoding sequences within the same gene but separated by introns in the genomic sequence. The important point is that the nucleic acid is isolated from remote and unimportant flanking sequences such that it can be subjected to the specific manipulations described herein such as recombinant expression, preparation of probes and primers, and other uses specific to the nucleic acid sequences.

Moreover, an “isolated” nucleic acid molecule, such as a transcript/cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. However, the nucleic acid molecule can be fused to other coding or regulatory sequences and still be considered isolated.

For example, recombinant DNA molecules contained in a vector are considered isolated. Further examples of isolated DNA molecules include recombinant DNA molecules maintained in heterologous host cells or purified (partially or substantially) DNA molecules in solution. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the isolated DNA molecules of the present invention. Isolated nucleic acid molecules according to the present invention further include such molecules produced synthetically.

Accordingly, the present invention provides nucleic acid molecules that consist of the nucleotide sequence shown in FIG. 1 or 3 (SEQ ID NO: 1, transcript sequence and SEQ ID NO:3, genomic sequence), or any nucleic acid molecule that encodes the protein provided in FIG. 2, SEQ ID NO:2. A nucleic acid molecule consists of a nucleotide sequence when the nucleotide sequence is the complete nucleotide sequence of the nucleic acid molecule.

The present invention further provides nucleic acid molecules that consist essentially of the nucleotide sequence shown in FIG. 1 or 3 (SEQ ID NO:1, transcript sequence and SEQ ID NO:3, genomic sequence), or any nucleic acid molecule that encodes the protein provided in FIG. 2, SEQ ID NO:2. A nucleic acid molecule consists essentially of a nucleotide sequence when such a nucleotide sequence is present with only a few additional nucleic acid residues in the final nucleic acid molecule.

The present invention further provides nucleic acid molecules that comprise the nucleotide sequences shown in FIG. 1 or 3 (SEQ ID NO:1, transcript sequence and SEQ ID NO:3, genomic sequence), or any nucleic acid molecule that encodes the protein provided in FIG. 2, SEQ ID NO:2. A nucleic acid molecule comprises a nucleotide sequence when the nucleotide sequence is at least part of the final nucleotide sequence of the nucleic acid molecule. In such a fashion, the nucleic acid molecule can be only the nucleotide sequence or have additional nucleic acid residues, such as nucleic acid residues that are naturally associated with it or heterologous nucleotide sequences. Such a nucleic acid molecule can have a few additional nucleotides or can comprises several hundred or more additional nucleotides. A brief description of how various types of these nucleic acid molecules can be readily made/isolated is provided below.

In FIGS. 1 and 3, both coding and non-coding sequences are provided. Because of the source of the present invention, humans genomic sequence (FIG. 3) and cDNA/transcript sequences (FIG. 1 ), the nucleic acid molecules in the Figures will contain genomic intronic sequences, 5′ and 3′ non-coding sequences, gene regulatory regions and non-coding intergenic sequences. In general such sequence features are either noted in FIGS. 1 and 3 or can readily be identified using computational tools known in the art. As discussed below, some of the non-coding regions, particularly gene regulatory elements such as promoters, are useful for a variety of purposes, e.g. control of heterologous gene expression, target for identifying gene activity modulating compounds, and are particularly claimed as fragments of the genomic sequence provided herein.

The isolated nucleic acid molecules can encode the mature protein plus additional amino or carboxyl-terminal amino acids, or amino acids interior to the mature peptide (when the mature form has more than one peptide chain, for instance). Such sequences may play a role in processing of a protein from precursor to a mature form, facilitate protein trafficking, prolong or shorten protein half-life or facilitate manipulation of a protein for assay or production, among other things. As generally is the case in situ, the additional amino acids may be processed away from the mature protein by cellular enzymes.

As mentioned above, the isolated nucleic acid molecules include, but are not limited to, the sequence encoding the enzyme peptide alone, the sequence encoding the mature peptide and additional coding sequences, such as a leader or secretory sequence (e.g., a pre-pro or pro-protein sequence), the sequence encoding the mature peptide, with or without the additional coding sequences, plus additional non-coding sequences, for example introns and non-coding 5′ and 3′ sequences such as transcribed but non-translated sequences that play a role in tanscription, mRNA processing (including splicing and polyadenylation signals), ribosome binding and stability of mRNA. In addition, the nucleic acid molecule may be fused to a marker sequence encoding, for example, a peptide that facilitates purification.

Isolated nucleic acid molecules can be in the form of RNA, such as mRNA, or in the form DNA, including cDNA and genomic DNA obtained by cloning or produced by chemical synthetic techniques or by a combination thereof. The nucleic acid, especially DNA, can be double-stranded or single-stranded. Single-stranded nucleic acid can be the coding strand (sense strand) or the non-coding strand (anti-sense strand).

The invention further provides nucleic acid molecules that encode fragments of the peptides of the present invention as well as nucleic acid molecules that encode obvious variants of the enzyme proteins of the present invention that are described above. Such nucleic acid molecules may be naturally occurring, such as allelic variants (same locus), paralogs (different locus), and orthologs (different organism), or may be constructed by recombinant DNA methods or by chemical synthesis. Such non-naturally occurring variants may be made by mutagenesis techniques, including those applied to nucleic acid molecules, cells, or organisms. Accordingly, as discussed above, the variants can contain nucleotide substitutions, deletions, inversions and insertions. Variation can occur in either or both the coding and non-coding regions. The variations can produce both conservative and non-conservative amino acid substitutions.

The present invention further provides non-coding fragments of the nucleic acid molecules provided in FIGS. 1 and 3. Preferred non-coding fragments include, but are not limited to, promoter sequences, enhancer sequences, gene modulating sequences and gene termination sequences. Such fragments are useful in controlling heterologous gene expression and in developing screens to identify gene-modulating agents. A promoter can readily be identified as being 5′ to the ATG start site in the genomic sequence provided in FIG. 3 .

A fragment comprises a contiguous nucleotide sequence greater than 12 or more nucleotides. Further, a fragment could at least 30, 40, 50, 100, 250 or 500 nucleotides in length. The length of the fragment will be based on its intended use. For example, the fragment can encode epitope bearing regions of the peptide, or can be useful as DNA probes and primers. Such fragments can be isolated using the known nucleotide sequence to synthesize an oligonucleotide probe. A labeled probe can then be used to screen a cDNA library, genomic DNA library, or mRNA to isolate nucleic acid corresponding to the coding region. Further, primers can be used in PCR reactions to clone specific regions of gene.

A probe/primer typically comprises substantially a purified oligonucleotide or oligonucleotide pair. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 20, 25, 40, 50 or more consecutive nucleotides.

Orthologs, homologs, and allelic variants can be identified using methods well known in the art. As described in the Peptide Section, these variants comprise a nucleotide sequence encoding a peptide that is typically 60-70%, 70-80%, 80-90%, and more typically at least about 90-95% or more homologous to the nucleotide sequence shown in the Figure sheets or a fragment of this sequence. Such nucleic acid molecules can readily be identified as being able to hybridize under moderate to stringent conditions, to the nucleotide sequence shown in the Figure sheets or a fragment of the sequence. Allelic variants can readily be determined by genetic locus of the encoding gene. The gene encoding the novel enzyme of the present invention is located on a genome component that has been mapped to human chromosome 7 (as indicated in FIG. 3 ), which is supported by multiple lines of evidence, such as STS and BAC map data

FIG. 3 provides information on SNPs that have been found in the gene encoding the enzyme of the present invention. SNPs were identified at 71 different nucleotide positions. Some of these SNPs that are located outside the ORF and in introns may affect gene transcription.

As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences encoding a peptide at least 60-70% homologous to each other typically remain hybridized to each other. The conditions can be such that sequences at least about 60%, at least about 70%, or at least about 80% or more homologous to each other typically remain hybridized to each other. Such stringent conditions are known to those skilled in the art and can be found in Current Protocols in Molecular Biology , John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. One example of stringent hybridization conditions are hybridization in 6×sodium chloride/sodium citrate (SSC) at about 45 C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 50-65 C. Examples of moderate to low stringency hybridization conditions are well known in the art.

Nucleic Acid Molecule Uses

The nucleic acid molecules of the present invention are useful for probes, primers, chemical intermediates, and in biological assays. The nucleic acid molecules are useful as a hybridization probe for messenger RNA, transcript/cDNA and genomic DNA to isolate full-length cDNA and genomic clones encoding the peptide described in FIG. 2 and to isolate cDNA and genomic clones that correspond to variants (alleles, orthologs, etc.) producing the same or related peptides shown in FIG. 2 . As illustrated in FIG. 3, SNPs were identified at 71 different nucleotide positions.

The probe can correspond to any sequence along the entire length of the nucleic acid molecules provided in the Figures. Accordingly, it could be derived from 5′ noncoding regions, the coding region, and 3′ noncoding regions. However, as discussed, fragments are not to be construed as encompassing fragments disclosed prior to the present invention. The nucleic acid molecules are also useful as primers for PCR to amplify any given region of a nucleic acid molecule and are useful to synthesize antisense molecules of desired length and sequence.

The nucleic acid molecules are also useful for constructing recombinant vectors. Such vectors include expression vectors that express a portion of, or all of, the peptide sequences. Vectors also include insertion vectors, used to integrate into another nucleic acid molecule sequence, such as into the cellular genome, to alter in situ expression of a gene and/or gene product. For example, an endogenous coding sequence can be replaced via homologous recombination with all or part of the coding region containing one or more specifically introduced mutations.

The nucleic acid molecules are also useful for expressing antigenic portions of the proteins.

The nucleic acid molecules are also useful as probes for determining the chromosomal positions of the nucleic acid molecules by means of in situ hybridization methods. The gene encoding the novel enzyme of the present invention is located on a genome component that has been mapped to human chromosome 7 (as indicated in FIG. 3 ), which is supported by multiple lines of evidence, such as STS and BAC map data

The nucleic acid molecules are also useful in making vectors containing the gene regulatory regions of the nucleic acid molecules of the present invention.

The nucleic acid molecules are also useful for designing ribozymes corresponding to all, or a part, of the mRNA produced from the nucleic acid molecules described herein.

The nucleic acid molecules are also useful for making vectors that express part, or all, of the peptides.

The nucleic acid molecules are also useful for constructing host cells expressing a part, or all, of the nucleic acid molecules and peptides.

The nucleic acid molecules are also useful for constructing transgenic animals expressing all, or a part, of the nucleic acid molecules and peptides.

The nucleic acid molecules are also useful as hybridization probes for determining the presence, level, form and distribution of nucleic acid expression. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus. Accordingly, the probes can be used to detect the presence of, or to determine levels of, a specific nucleic acid molecule in cells, tissues, and in organisms. The nucleic acid whose level is determined can be DNA or RNA. Accordingly, probes corresponding to the peptides described herein can be used to assess expression and/or gene copy number in a given cell, tissue, or organism. These uses are relevant for diagnosis of disorders involving an increase or decrease in enzyme protein expression relative to normal results.

In vitro techniques for detection of mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detecting DNA includes Southern hybridizations and in situ hybridization.

Probes can be used as a part of a diagnostic test kit for identifying cells or tissues that express a enzyme protein, such as by measuring a level of a enzyme-encoding nucleic acid in a sample of cells from a subject e.g., mRNA or genomic DNA, or determining if a enzyme gene has been mutated. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus.

Nucleic acid expression assays are useful for drug screening to identify compounds that modulate enzyme nucleic acid expression.

The invention thus provides a method for identifying a compound that can be used to treat a disorder associated with nucleic acid expression of the enzyme gene, particularly biological and pathological processes that are mediated by the enzyme in cells and tissues that express it. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus. The method typically includes assaying the ability of the compound to modulate the expression of the enzyme nucleic acid and thus identifying a compound that can be used to treat a disorder characterized by undesired enzyme nucleic acid expression. The assays can be performed in cell-based and cell-free systems. Cell-based assays include cells naturally expressing the enzyme nucleic acid or recombinant cells genetically engineered to express specific nucleic acid sequences.

The assay for enzyme nucleic acid expression can involve direct assay of nucleic acid levels, such as mRNA levels, or on collateral compounds involved in the signal pathway. Further, the expression of genes that are up- or down-regulated in response to the enzyme protein signal pathway can also be assayed. In this embodiment the regulatory regions of these genes can be operably linked to a reporter gene such as luciferase.

Thus, modulators of enzyme gene expression can be identified in a method wherein a cell is contacted with a candidate compound and the expression of mRNA determined. The level of expression of enzyme mRNA in the presence of the candidate compound is compared to the level of expression of enzyme mRNA in the absence of the candidate compound. The candidate compound can then be identified as a modulator of nucleic acid expression based on this comparison and be used, for example to treat a disorder characterized by aberrant nucleic acid expression. When expression of mRNA is statistically significantly greater in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of nucleic acid expression. When nucleic acid expression is statistically significantly less in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of nucleic acid expression.

The invention further provides methods of treatment, with the nucleic acid as a target, using a compound identified through drug screening as a gene modulator to modulate enzyme nucleic acid expression in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus. Modulation includes both up-regulation (i.e. activation or agonization) or down-regulation (suppression or antagonization) or nucleic acid expression.

Alternatively, a modulator for enzyme nucleic acid expression can be a small molecule or drug identified using the screening assays described herein as long as the drug or small molecule inhibits the enzyme nucleic acid expression in the cells and tissues that express the protein. Experimental data as provided in FIG. 1 indicates expression in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, hippocampus, and fetus.

The nucleic acid molecules are also useful for monitoring the effectiveness of modulating compounds on the expression or activity of the enzyme gene in clinical trials or in a treatment regimen. Thus, the gene expression pattern can serve as a barometer for the continuing effectiveness of treatment with the compound, particularly with compounds to which a patient can develop resistance. The gene expression pattern can also serve as a marker indicative of a physiological response of the affected cells to the compound. Accordingly, such monitoring would allow either increased administration of the compound or the administration of alternative compounds to which the patient has not become resistant. Similarly, if the level of nucleic acid expression falls below a desirable level, administration of the compound could be commensurately decreased.

The nucleic acid molecules are also useful in diagnostic assays for qualitative changes in enzyme nucleic acid expression, and particularly in qualitative changes that lead to pathology. The nucleic acid molecules can be used to detect mutations in enzyme genes and gene expression products such as mRNA. The nucleic acid molecules can be used as hybridization probes to detect naturally occurring genetic mutations in the enzyme gene and thereby to determine whether a subject with the mutation is at risk for a disorder caused by the mutation. Mutations include deletion, addition, or substitution of one or more nucleotides in the gene, chromosomal rearrangement, such as inversion or transposition, modification of genomic DNA, such as aberrant methylation patterns or changes in gene copy number, such as amplification. Detection of a mutated form of the enzyme gene associated with a dysfunction provides a diagnostic tool for an active disease or susceptibility to disease when the disease results from overexpression, underexpression, or altered expression of a enzyme protein.

Individuals carrying mutations in the enzyme gene can be detected at the nucleic acid level by a variety of techniques. FIG. 3 provides information on SNPs that have been found in the gene encoding the enzyme of the present invention. SNPs were identified at 71 different nucleotide positions. Some of these SNPs that are located outside the ORF and in introns may affect gene transcription. The gene encoding the novel enzyme of the present invention is located on a genome component that has been mapped to human chromosome 7 (as indicated in FIG. 3 ), which is supported by multiple lines of evidence, such as STS and BAC map data. Genomic DNA can be analyzed directly or can be amplified by using PCR prior to analysis. RNA or cDNA can be used in the same way. In some uses, detection of the mutation involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g. U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran et al., Science 241:1077-1080 (1988); and Nakazawa et al, PNAS 91:360-364 (1994)), the latter of which can be particularly useful for detecting point mutations in the gene (see Abravaya et. al., Nucleic Acids Res. 23:675-682 (1995)). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers which specifically hybridize to a gene under conditions such that hybridization and amplification of the gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. Deletions and insertions can be detected by a change in size of the amplified product compared to the normal genotype. Point mutations can be identified by hybridizing amplified DNA to normal RNA or antisense DNA sequences.

Alternatively, mutations in a enzyme gene can be directly identified, for example,. by alterations in restriction enzyme digestion patterns determined by gel electrophoresis

Further, sequence-specific ribozymes (U.S. Pat. No. 5,498,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site. Perfectly matched sequences can be distinguished from mismatched sequences by nuclease cleavage digestion assays or by differences in melting temperature.

Sequence changes at specific locations can also be assessed by nuclease protection assays such as RNase and S1 protection or the chemical cleavage method. Furthermore, sequence differences between a mutant enzyme gene and a wild-type gene can be determined by direct DNA sequencing. A variety of automated sequencing procedures can be utilized when performing the diagnostic assays (Naeve, C. W., (1995) Biotechniques 19:448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94116101; Cohen et al., Adv. Chromatogr. 36:127-162 (1996); and Griffin et al., Appl. Biochem. Biotechnol. 38:147-159 (1993)).

Other methods for detecting mutations in the gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA duplexes (Myers et al., Science 230:1242 (1985)); Cotton et al., PNAS 85:4397 (988); Saleeba et al, Meth. Enzymol. 217:286-295 (1992)), electrophoretic mobility of mutant and wild type nucleic acid is compared (Orita et al., PNAS 86:2766 (1989); Cotton et al, Mutat. Res. 285:125-144 (1993); and Hayashi et al., Genet. Anal Tech. Appl. 9:73-79 (992)), and movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (Myers et al., Nature 313:495 (1985)). Examples of other techniques for detecting point mutations include selective oligonucleotide hybridization, selective amplification, and selective primer extension.

The nucleic acid molecules are also useful for testing an individual for a genotype that while not necessarily causing the disease, nevertheless affects the treatment modality. Thus, the nucleic acid molecules can be used to study the relationship between an individual's genotype and the individual's response to a compound used for treatment (pharmacogenomic relationship). Accordingly, the nucleic acid molecules described herein can be used to assess the mutation content of the enzyme gene in an individual in order to select an appropriate compound or dosage regimen for treatment. FIG. 3 provides information on SNPs that have been found in the gene encoding the enzyme of the present invention. SNPs were identified at 71 different nucleotide positions. Some of these SNPs that are located outside the ORF and in introns may affect gene transcription.

Thus nucleic acid molecules displaying genetic variations that affect treatment provide a diagnostic target that can be used to tailor treatment in an individual. Accordingly, the production of recombinant cells and animals containing these polymorphisms allow effective clinical design of treatment compounds and dosage regimens.

The nucleic acid molecules are thus useful as antisense constructs to control enzyme gene expression in cells, tissues, and organisms. A DNA antisense nucleic acid molecule is designed to be complementary to a region of the gene involved in transcription, preventing transcription and hence production of enzyme protein. An antisense RNA or DNA nucleic acid molecule would hybridize to the mRNA and thus block translation of MRNA into enzyme protein.

Alternatively, a class of antisense molecules can be used to inactivate mRNA in order to decrease expression of enzyme nucleic acid Accordingly, these molecules can treat a disorder characterized by abnormal or undesired enzyme nucleic acid expression. This technique involves cleavage by means of ribozymes containing nucleotide sequences complementary to one or more regions in the mRNA that attenuate the ability of the mRNA to be translated. Possible regions include coding regions and particularly coding regions corresponding to the catalytic and other functional activities of the enzyme protein, such as substrate binding.

The nucleic acid molecules also provide vectors for gene therapy in patients containing cells that are aberrant in enzyme gene expression. Thus, recombinant cells, which include the patient's cells that have been engineered ex vivo and returned to the patient, are introduced into an individual where the cells produce the desired enzyme protein to treat the individual.

The invention also encompasses kits for detecting the presence of a enzyme nucleic acid in a biological sample. Experimental data as provided in FIG. 1 indicates that the enzymes of the present invention are expressed in humans in the placenta, neuroblastoma cells, liver, brain, T-cells from T-cell leukemia, and fetus, as indicated by virtual northern blot analysis. In addition, PCR-based tissue screening panels indicate expression in the hippocampus. For example, the kit can comprise reagents such as a labeled or labelable nucleic acid or agent capable of detecting enzyme nucleic acid in a biological sample; means for determining the amount of enzyme nucleic acid in the sample; and means for comparing the amount of enzyme nucleic acid in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect enzyme protein mRNA or DNA.

Nucleic Acid Arrays

The present invention further provides nucleic acid detection kits, such as arrays or microarrays of nucleic acid molecules that are based on the sequence information provided in FIGS. 1 and 3 (SEQ ID NOS:1 and 3).

As used herein “Arrays” or “Microarrays” refers to an array of distinct polynucleotides or oligonucleotides synthesized on a substrate, such as paper, nylon or other type of membrane, filter, chip, glass slide, or any other suitable solid support. In one embodiment, the microarray is prepared and used according to the methods described in U.S. Pat. No. 5,837,832, Chee et al., PCT application WO95/11995 (Chee et al.), Lockhart, D. J. et al. (1996; Nat. Biotech. 14: 1675-1680) and Schena, M. et al. (1996; Proc. Natl. Acad. Sci. 93: 10614-10619), all of which are incorporated herein in their entirety by reference. In other embodiments, such arrays are produced by the methods described by Brown et al., U.S. Pat. No. 5,807,522.

The microarray or detection kit is preferably composed of a large number of unique, single-stranded nucleic acid sequences, usually either synthetic antisense oligonucleotides or fragments of cDNAs, fixed to a solid support. The oligonucleotides are preferably about 6-60 nucleotides in length, more preferably 15-30 nucleotides in length, and most preferably about 20-25 nucleotides in length. For a certain type of microarray or detection kit, it may be preferable to use oligonucleotides that are only 7-20 nucleotides in length. The microarray or detection kit may contain oligonucleotides that cover the known 5′, or 3′, sequence, sequential oligonucleotides which cover the full length sequence; or unique oligonucleotides selected from particular areas along the length of the sequence. Polynucleotides used in the microarray or detection kit may be oligonucleotides that are specific to a gene or genes of interest.

In order to produce oligonucleotides to a known sequence for a microarray or detection kit, the gene(s) of interest (or an ORF identified from the contigs of the present invention) is typically examined using a computer algorithm which starts at the 5′ or at the 3′ end of the nucleotide sequence. Typical algorithms will then identify oligomers of defined length that are unique to the gene, have a GC content within a range suitable for hybridization, and lack predicted secondary structure that may interfere with hybridization. In certain situations it may be appropriate to use pairs of oligonucleotides on a microarray or detection kit. The “pairs” will be identical, except for one nucleotide that preferably is located in the center of the sequence. The second oligonucleotide in the pair (mismatched by one) serves as a control. The number of oligonucleotide pairs may range from two to one million. The oligomers are synthesized at designated areas on a substrate using a light-directed chemical process. The substrate may be paper, nylon or other type of membrane, filter, chip, glass slide or any other suitable solid support.

In another aspect, an oligonucleotide may be synthesized on the surface of the substrate by using a chemical coupling procedure and an ink jet application apparatus, as described in PCT application WO95/251116 (Baldeschweiler et al.) which is incorporated herein in its entirety by reference. In another aspect, a “gridded” array analogous to a dot (or slot) blot may be used to arrange and link cDNA fragments or oligonucleotides to the surface of a substrate using a vacuum system, thermal, UV, mechanical or chemical bonding procedures. An array, such as those described above, may be produced by hand or by using available devices (slot blot or dot blot apparatus), materials (any suitable solid support), and machines (including robotic instruments), and may contain 8, 24, 96, 384, 1536, 6144 or more oligonucleotides, or any other number between two and one million which lends itself to the efficient use of commercially available instrumentation.

In order to conduct sample analysis using a microarray or detection kit, the RNA or DNA from a biological sample is made into hybridization probes. The mRNA is isolated, and cDNA is produced and used as a template to make antisense RNA (aRNA). The aRNA is amplified in the presence of fluorescent nucleotides, and labeled probes are incubated with the microarray or detection kit so that the probe sequences hybridize to complementary oligonucleotides of the microarray or detection kit. Incubation conditions are adjusted so that hybridization occurs with precise complementary matches or with various degrees of less complementarity. After removal of nonhybridized probes, a scanner is used to determine the levels and patterns of fluorescence. The scanned images are examined to determine degree of complementarity and the relative abundance of each oligonucleotide sequence on the microarray or detection kit. The biological samples may be obtained from any bodily fluids (such as blood, urine, saliva, phlegm, gastric juices, etc.), cultured cells, biopsies, or other tissue preparations. A detection system may be used to measure the absence, presence, and amount of hybridization for all of the distinct sequences simultaneously. This data may be used for large-scale correlation studies on the sequences, expression patterns, mutations, variants, or polymorphisms among samples.

Using such arrays, the present invention provides methods to identify the expression of the enzyme proteins/peptides of the present invention. In detail, such methods comprise incubating a test sample with one or more nucleic acid molecules and assaying for binding of the nucleic acid molecule with components within the test sample. Such assays will typically involve arrays comprising many genes, at least one of which is a gene of the present invention and or alleles of the enzyme gene of the present invention. FIG. 3 provides information on SNPs that have been found in the gene encoding the enzyme of the present invention. SNPs were identified at 71 different nucleotide positions. Some of these SNPs that are located outside the ORF and in introns may affect gene transcription.

Conditions for incubating a nucleic acid molecule with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the nucleic acid molecule used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification or array assay formats can readily be adapted to employ the novel fragments of the Human genome disclosed herein. Examples of such assays can be found in Chard, T, An Introduction to Radioimmunoassay and Related Techniques , Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G. R. et al., Techniques in Immunocytochemistry , Academic Press, Orlando, Fla. Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of Enzyme Immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology , Elsevier Science Publishers, Amsterdam, The Netherlands (1985).

The test samples of the present invention include cells, protein or membrane extracts of cells. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing nucleic acid extracts or of cells are well known in the art and can be readily be adapted in order to obtain a sample that is compatible with the system utilized.

In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention.

Specifically, the invention provides a compartmentalized kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the nucleic acid molecules that can bind to a fragment of the Human genome disclosed herein; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound nucleic acid.

In detail, a compartmentalized kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers, strips of plastic, glass or paper, or arraying material such as silica. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the nucleic acid probe, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound probe. One skilled in the art will readily recognize that the previously unidentified enzyme gene of the present invention can be routinely identified using the sequence information disclosed herein can be readily incorporated into one of the established kit formats which are well known in the art, particularly expression arrays.

Vectors/Host Cells

The invention also provides vectors containing the nucleic acid molecules described herein. The term “vector” refers to a vehicle, preferably a nucleic acid molecule, which can transport the nucleic acid molecules. When the vector is a nucleic acid molecule, the nucleic acid molecules are covalently linked to the vector nucleic acid. With this aspect of the invention, the vector includes a plasmid, single or double stranded phage, a single or double stranded RNA or DNA viral vector, or artificial chromosome, such as a BAC, PAC, YAC, OR MAC.

A vector can be maintained in the host cell as an extrachromosomal element where it replicates and produces additional copies of the nucleic acid molecules. Alternatively, the vector may integrate into the host cell genome and produce additional copies of the nucleic acid molecules when the host cell replicates.

The invention provides vectors for the maintenance (cloning vectors) or vectors for expression (expression vectors) of the nucleic acid molecules. The vectors can function in prokaryotic or eukaryotic cells or in both (shuttle vectors).

Expression vectors contain cis-acting regulatory regions that are operably linked in the vector to the nucleic acid molecules such that transcription of the nucleic acid molecules is allowed in a host cell. The nucleic acid molecules can be introduced into the host cell with a separate nucleic acid molecule capable of affecting transcription. Thus, the second nucleic acid molecule may provide a trans-acting factor interacting with the cis-regulatory control region to allow transcription of the nucleic acid molecules from the vector. Alternatively, a trans-acting factor may be supplied by the host cell. Finally, a trans-acting factor can be produced from the vector itself. It is understood, however, that in some embodiments, transcription and/or translation of the nucleic acid molecules can occur in a cell-free system.

The regulatory sequence to which the nucleic acid molecules described herein can be operably linked include promoters for directing mRNA transcription. These include, but are not limited to, the left promoter from bacteriophage λ, the lac, TRP, and TAC promoters from E. coli , the early and late promoters from SV40, the CMV immediate early promoter, the adenovirus early and late promoters, and retrovirus long-terminal repeats.

In addition to control regions that promote transcription, expression vectors may also include regions that modulate transcription, such as repressor binding sites and enhancers. Examples include the SV40 enhancer, the cytomegalovirus immediate early enhancer, polyoma enhancer, adenovirus enhancers, and retrovirus LTR enhancers.

In addition to containing sites for transcription initiation and control, expression vectors can also contain sequences necessary for transcription termination and, in the transcribed region a ribosome binding site for translation. Other regulatory control elements for expression include initiation and termination codons as well as polyadenylation signals. The person of ordinary skill in the art would be aware of the numerous regulatory sequences that are useful in expression vectors. Such regulatory sequences are described, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual. 2nd. ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., (1989).

A variety of expression vectors can be used to express a nucleic acid molecule. Such vectors include chromosomal, episomal, and virus-derived vectors, for example vectors derived from bacterial plasmids, from bacteriophage, from yeast episomes, from yeast chromosomal elements, including yeast artificial chromosomes, from viruses such as baculoviruses, papovaviruses such as SV40, Vaccinia viruses, adenoviruses, poxviruses, pseudorabies viruses, and retroviruses. Vectors may also be derived from combinations of these sources such as those derived from plasmid and bacteriophage genetic elements, e.g. cosmids and phagemids. Appropriate cloning and expression vectors for prokaryotic and eukaryotic hosts are described in Sambrook et al., Molecular Cloning: A Laboratory Manual. 2nd. ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., (1989).

The regulatory sequence may provide constitutive expression in one or more host cells (i.e. tissue specific) or may provide for inducible expression in one or more cell types such as by temperature, nutrient additive, or exogenous factor such as a hormone or other ligand. A variety of vectors providing for constitutive and inducible expression in prokaryotic and eukaryotic hosts are well known to those of ordinary skill in the art.

The nucleic acid molecules can be inserted into the vector nucleic acid by well-known methodology. Generally, the DNA sequence that will ultimately be expressed is joined to an expression vector by cleaving the DNA sequence and the expression vector with one or more restriction enzymes and then ligating the fragments together. Procedures for restriction enzyme digestion and ligation are well known to those of ordinary skill in the art.

The vector containing the appropriate nucleic acid molecule can be introduced into an appropriate host cell for propagation or expression using well-known techniques. Bacterial cells include, but are not limited to, E. coli , Streptomyces, and Salmonella typhimurium . Eukaryotic cells include, but are not limited to, yeast, insect cells such as Drosophila, animal cells such as COS and CHO cells, and plant cells.

As described herein, it may be desirable to express the peptide as a fusion protein. Accordingly, the invention provides fusion vectors that allow for the production of the peptides. Fusion vectors can increase the expression of a recombinant protein, increase the solubility of the recombinant protein, and aid in the purification of the protein by acting for example as a ligand for affinity purification. A proteolytic cleavage site may be introduced at the junction of the fusion moiety so that the desired peptide can ultimately be separated from the fusion moiety. Proteolytic enzymes include, but are not limited to, factor Xa, thrombin, and enteroenzyme. Typical fusion expression vectors include pGEX (Smith et al, Gene 67:31-40 (1988)), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amann et al., Gene 69:301-315 (1988)) and pET 11d (Studier et al., Gene Expression Technology: Methods in Enzymology 185:60-89 (1990)).

Recombinant protein expression can be maximized in host bacteria by providing a genetic background wherein the host cell has an impaired capacity to proteolytically cleave the recombinant protein. (Gottesman, S., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128). Alternatively, the sequence of the nucleic acid molecule of interest can be altered to provide preferential codon usage for a specific host cell, for example E. coli . (Wada et al., Nucleic Acids Res. 20:2111-2118 (1992)).

The nucleic acid molecules can also be expressed by expression vectors that are operative in yeast. Examples of vectors for expression in yeast e.g., S. cerevisiae include pYepSec1 (Baldari, et al., EMBO J. 6:229-234 (1987)), pMFa (Kurjan et al., Cell 30:933-943(1982)), pJRY88 (Schultz et al., Gene 54:113-123 (1987)), and pYES2 (Invitrogen Corporation, San Diego, Calif.).

The nucleic acid molecules can also be expressed in insect cells using, for example, baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., Sf 9 cells) include the pAc series (Smith et al., Mol. Cell Biol. 3:2156-2165 (1983)) and the pVL series (Lucklow et al., Virology 170:31-39 (1989)).

In certain embodiments of the invention, the nucleic acid molecules described herein are expressed in mammalian cells using mammalian expression vectors. Examples of mammalian expression vectors include pCDM8 (Seed, B. Nature 329:840(1987)) and pMT2PC (Kaufman et al., EMBO J. 6:187-195 (1987)).

The expression vectors listed herein are provided by way of example only of the well-known vectors available to those of ordinary skill in the art that would be useful to express the nucleic acid molecules. The person of ordinary skill in the art would be aware of other vectors suitable for maintenance propagation or expression of the nucleic acid molecules described herein. These are found for example in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning. A Laboratory Manual. 2nd, ed, Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.

The invention also encompasses vectors in which the nucleic acid sequences described herein are cloned into the vector in reverse orientation, but operably linked to a regulatory sequence that permits transcription of antisense RNA. Thus, an antisense transcript can be produced to all, or to a portion, of the nucleic acid molecule sequences described herein, including both coding and non-coding regions. Expression of this antisense RNA is subject to each of the parameters described above in relation to expression of the sense RNA (regulatory sequences, constitutive or inducible expression, tissue-specific expression).

The invention also relates to recombinant host cells containing the vectors described herein. Host cells therefore include prokaryotic cells, lower eukaryotic cells such as yeast, other eukaryotic cells such as insect cells, and higher eukaryotic cells such as mammalian cells.

The recombinant host cells are prepared by introducing the vector constructs described herein into the cells by techniques readily available to the person of ordinary skill in the art. These include, but are not limited to, calcium phosphate transfection, DEAE-dextran-mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, lipofection, and other techniques such as those found in Sambrook, et al. ( Molecular Cloning: A Laboratory Manual. 2nd, ed, Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989).

Host cells can contain more than one vector. Thus, different nucleotide sequences can be introduced on different vectors of the same cell. Similarly, the nucleic acid molecules can be introduced either alone or with other nucleic acid molecules that are not related to the nucleic acid molecules such as those providing trans-acting factors for expression vectors. When more than one vector is introduced into a cell, the vectors can be introduced independently, co-introduced or joined to the nucleic acid molecule vector.

In the case of bacteriophage and viral vectors, these can be introduced into cells as packaged or encapsulated virus by standard procedures for infection and transduction. Viral vectors can be replication-competent or replication-defective. In the case in which viral replication is defective, replication will occur in host cells providing functions that complement the defects.

Vectors generally include selectable markers that enable the selection of the subpopulation of cells that contain the recombinant vector constructs. The marker can be contained in the same vector that contains the nucleic acid molecules described herein or may be on a separate vector. Markers include tetracycline or ampicillin-resistance genes for prokaryotic host cells and dihydrofolate reductase or neomycin resistance for eukaryotic host cells. However, any marker that provides selection for a phenotypic trait will be effective.

While the mature proteins can be produced in bacteria, yeast, mammalian cells, and other cells under the control of the appropriate regulatory sequences, cell-free transcription and translation systems can also be used to produce these proteins using RNA derived from the DNA constructs described herein.

Where secretion of the peptide is desired, which is difficult to achieve with multi-transmembrane domain containing proteins such as enzymes, appropriate secretion signals are incorporated into the vector. The signal sequence can be endogenous to the peptides or heterologous to these peptides.

Where the peptide is not secreted into the medium, which is typically the case with enzymes, the protein can be isolated from the host cell by standard disruption procedures, including freeze thaw, sonication, mechanical disruption, use of lysing agents and the like. The peptide can then be recovered and purified by well-known purification methods including ammonium sulfate precipitation, acid extraction, anion or cationic exchange chromatography, phosphocellulose chromatography, hydrophobic-interaction chromatography, affinity chromatography, hydroxylapatite chromatography, lectin chromatography, or high performance liquid chromatography.

It is also understood that depending upon the host cell in recombinant production of the peptides described herein, the peptides can have various glycosylation patterns, depending upon the cell, or maybe non-glycosylated as when produced in bacteria. In addition, the peptides may include an initial modified methionine in some cases as a result of a host-mediated process.

Uses of Vectors and Host Cells

The recombinant host cells expressing the peptides described herein have a variety of uses. First, the cells are useful for producing a enzyme protein or peptide that can be further purified to produce desired amounts of enzyme protein or fragments. Thus, host cells containing expression vectors are useful for peptide production.

Host cells are also useful for conducting cell-based assays involving, the enzyme protein or enzyme protein fragments, such as those described above as well as other formats known in the art. Thus, a recombinant host cell expressing a native enzyme protein is useful for assaying compounds that stimulate or inhibit enzyme protein function.

Host cells are also useful for identifying enzyme protein mutants in which these functions are affected. If the mutants naturally occur and give rise to a pathology, host cells containing the mutations are useful to assay compounds that have a desired effect on the mutant enzyme protein (for example, stimulating or inhibiting function) which may not be indicated by their effect on the native enzyme protein.

Genetically engineered host cells can be further used to produce non-human transgenic animals. A transgenic animal is preferably a mammal, for example a rodent, such as a rat or mouse, in which one or more of the cells of the animal include a transgene. A transgene is exogenous DNA which is integrated into the genome of a cell from which a transgenic animal develops and which remains in the genome of the mature animal in one or more cell types or tissues of the transgenic animal. These animals are useful for studying the function of a enzyme protein and identifying and evaluating modulators of enzyme protein activity. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, and amphibians.

A transgenic animal can be produced by introducing nucleic acid into the male pronuclei of a fertilized oocyte, e.g., by microinjection, retroviral infection, and allowing the oocyte to develop in a pseudopregnant female foster animal. Any of the enzyme protein nucleotide sequences can be introduced as a transgene into the genome of a non-human animal, such as a mouse.

Any of the regulatory or other sequences useful in expression vectors can form part of the transgenic sequence. This includes intronic sequences and polyadenylation signals, if not already included. A tissue-specific regulatory sequence(s) can be operably linked to the transgene to direct expression of the enzyme protein to particular cells.

Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in 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 in Hogan, B., Manipulating the Mouse Embryo , (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986). Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the transgene in its genome and/or expression of transgenic mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene can further be bred to other transgenic animals carrying other transgenes. A transgenic animal also includes animals in which the entire animal or tissues in the animal have been produced using the homologously recombinant host cells described herein.

In another embodiment, transgenic non-human animals can be produced which contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, see, e.g., Lakso et al. PNAS 89:6232-6236 (1992). Another example of a recombinase system is the FLP recombinase system of S. cerevisiae (O'Corman et al. Science 251:1351-1355 (1991). If a cre/IoxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein is 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.

Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, 1. et al. Nature 385:810-813 (1997) and PCT International Publication Nos. WO 97/07668 and WO 97/07669. In brief, a cell, e.g., a somatic cell, from the transgenic animal can be isolated and induced to exit the growth cycle and enter G o phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyst and then transferred to pseudopregnant female foster animal. The offspring born of this female foster animal will be a clone of the animal from which the cell, e.g., the somatic cell, is isolated.

Transgenic animals containing recombinant cells that express the peptides described herein are useful to conduct the assays described herein in an in vivo context. Accordingly, the various physiological factors that are present in vivo and that could effect substrate binding, enzyme protein activation, and signal transduction, may not be evident from in vitro cell-free or cell-based assays. Accordingly, it is useful to provide non-human transgenic animals to assay in vivo enzyme protein function, including substrate interaction. the effect of specific mutant enzyme proteins on enzyme protein function and substrate interaction, and the effect of chimeric enzyme proteins. It is also possible to assess the effect of null mutations, that is, mutations that substantially or completely eliminate one or more enzyme protein functions.

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

<160> NUMBER OF SEQ ID NOS: 4

<210> SEQ ID NO 1

<211> LENGTH: 1781

<212> TYPE: DNA

<213> ORGANISM: Human

<400> SEQUENCE: 1

ggcggcttcg gttgcgggtc ggaacggcgc tgctctgcgg ggccggtcca gg

#ctggcagc     60

tgccggcgct tggcggtgag ggcgggctcc cgagtggccc cccaccgaag gc

#ggcgcggc    120

ggctcctcac tcatcccaga tgttggttat ctttctgaag tagactgtcc at

#ggcctgaa    180

cattttccga aaatcatttt gagcaaaata tctgtttaat aacaagataa cc

#acatcaag    240

atggttggaa agctgaagca gaacttacta ttggcatgtc tggtgattag tt

#ctgtgact    300

gtgttttacc tgggccagca tgccatggaa tgccatcacc ggatagagga ac

#gtagccag    360

ccagtcaaat tggagagcac aaggaccact gtgagaactg gcctggacct ca

#aagccaac    420

aaaacctttg cctatcacaa agatatgcct ttaatattta ttggaggtgt gc

#ctcggagt    480

ggaaccacac tcatgagggc catgctggac gcacatcctg acattcgctg tg

#gagaggaa    540

accagggtca ttccccgaat cctggccctg aagcagatgt ggtcacggtc aa

#gtaaagag    600

aagatccgcc tggatgaggc tggtgttact gatgaagtgc tggattctgc ca

#tgcaagcc    660

ttcttactag aaattatcgt taagcatggg gagccagccc cttatttatg ta

#ataaagat    720

ccttttgccc tgaaatcttt aacttacctt tctaggttat tccccaatgc ca

#aatttctc    780

ctgatggtcc gagatggccg ggcatcagta cattcaatga tttctcgaaa ag

#ttactata    840

gctggatttg atctgaacag ctatagggac tgtttgacaa agtggaatcg tg

#ctatagag    900

accatgtata accagtgtat ggaggttggt tataaaaagt gcatgttggt tc

#actatgaa    960

caacttgtct tacatcctga acggtggatg agaacactct taaagttcct cc

#agattcca   1020

tggaaccact cagtattgca ccatgaagag atgattggga aagctggggg ag

#tgtctctg   1080

tcaaaagtgg agagatctac agaccaagta atcaagccag tcaatgtagg ag

#ctctatca   1140

aaatgggttg ggaagatacc gccagatgtt ttacaagaca tggcagtgat tg

#ctcctatg   1200

cttgccaagc ttggatatga cccatatgcc aacccaccta actacggaaa ac

#ctgatccc   1260

aaaattattg aaaacactcg aagggtctat aagggagaat tccaactacc tg

#actttctt   1320

aaagaaaaac cacaggtact gtgtctgctt tttcctcctg atgtatacta ga

#ttggctct   1380

tgcattgaag taatattttt aaagagataa tgaaattaaa aagacagaaa ca

#agaaaacc   1440

aaaaagaaaa gaagaaaagg gatagtgata tgtgctgggg aagaaagatc ag

#cgtctggg   1500

acttgttgat tttaacaata atttaacaca gtcttaattt cagagagctc ag

#tgtctccc   1560

aaaaccaggg aaatacttta ttgataacca aattctgatt gcttgaggtc ct

#gcacaagc   1620

cgcccagtgg gtaaagctgc tccagcgttc cagtgcctaa tttgaaataa aa

#atgttcag   1680

cgaccctctc tgttcctaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa

#aaaaaaaa   1740

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a

#

# 1781

<210> SEQ ID NO 2

<211> LENGTH: 376

<212> TYPE: PRT

<213> ORGANISM: Human

<400> SEQUENCE: 2

Met Val Gly Lys Leu Lys Gln Asn Leu Leu Le

#u Ala Cys Leu Val Ile

1               5

#                10

#                15

Ser Ser Val Thr Val Phe Tyr Leu Gly Gln Hi

#s Ala Met Glu Cys His

20

#            25

#            30

His Arg Ile Glu Glu Arg Ser Gln Pro Val Ly

#s Leu Glu Ser Thr Arg

35

#        40

#        45

Thr Thr Val Arg Thr Gly Leu Asp Leu Lys Al

#a Asn Lys Thr Phe Ala

50

#    55

#    60

Tyr His Lys Asp Met Pro Leu Ile Phe Ile Gl

#y Gly Val Pro Arg Ser

65

#70

#75

#80

Gly Thr Thr Leu Met Arg Ala Met Leu Asp Al

#a His Pro Asp Ile Arg

85

#                90

#                95

Cys Gly Glu Glu Thr Arg Val Ile Pro Arg Il

#e Leu Ala Leu Lys Gln

100

#           105

#           110

Met Trp Ser Arg Ser Ser Lys Glu Lys Ile Ar

#g Leu Asp Glu Ala Gly

115

#       120

#       125

Val Thr Asp Glu Val Leu Asp Ser Ala Met Gl

#n Ala Phe Leu Leu Glu

130

#   135

#   140

Ile Ile Val Lys His Gly Glu Pro Ala Pro Ty

#r Leu Cys Asn Lys Asp

145                 1

#50                 1

#55                 1

#60

Pro Phe Ala Leu Lys Ser Leu Thr Tyr Leu Se

#r Arg Leu Phe Pro Asn

165

#               170

#               175

Ala Lys Phe Leu Leu Met Val Arg Asp Gly Ar

#g Ala Ser Val His Ser

180

#           185

#           190

Met Ile Ser Arg Lys Val Thr Ile Ala Gly Ph

#e Asp Leu Asn Ser Tyr

195

#       200

#       205

Arg Asp Cys Leu Thr Lys Trp Asn Arg Ala Il

#e Glu Thr Met Tyr Asn

210

#   215

#   220

Gln Cys Met Glu Val Gly Tyr Lys Lys Cys Me

#t Leu Val His Tyr Glu

225                 2

#30                 2

#35                 2

#40

Gln Leu Val Leu His Pro Glu Arg Trp Met Ar

#g Thr Leu Leu Lys Phe

245

#               250

#               255

Leu Gln Ile Pro Trp Asn His Ser Val Leu Hi

#s His Glu Glu Met Ile

260

#           265

#           270

Gly Lys Ala Gly Gly Val Ser Leu Ser Lys Va

#l Glu Arg Ser Thr Asp

275

#       280

#       285

Gln Val Ile Lys Pro Val Asn Val Gly Ala Le

#u Ser Lys Trp Val Gly

290

#   295

#   300

Lys Ile Pro Pro Asp Val Leu Gln Asp Met Al

#a Val Ile Ala Pro Met

305                 3

#10                 3

#15                 3

#20

Leu Ala Lys Leu Gly Tyr Asp Pro Tyr Ala As

#n Pro Pro Asn Tyr Gly

325

#               330

#               335

Lys Pro Asp Pro Lys Ile Ile Glu Asn Thr Ar

#g Arg Val Tyr Lys Gly

340

#           345

#           350

Glu Phe Gln Leu Pro Asp Phe Leu Lys Glu Ly

#s Pro Gln Val Leu Cys

355

#       360

#       365

Leu Leu Phe Pro Pro Asp Val Tyr

370

#   375

<210> SEQ ID NO 3

<211> LENGTH: 116592

<212> TYPE: DNA

<213> ORGANISM: Human

<220> FEATURE:

<221> NAME/KEY: misc_feature

<222> LOCATION: (1)...(116592)

<223> OTHER INFORMATION: n = A,T,C or G

<400> SEQUENCE: 3

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn     60

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn    120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn    180

nnnnnnnnnn nnnnnnnnnn agattctgct cggtagcagg ctggacacac ag

#gcagggtt    240

tctatgttgt agttcttttc caggaaacct cagtctttgc tcttaaagcc tt

#tacctgtt    300

agatgaggcc ttcctgtatt atggagggta atccacttta ctagaaatct gt

#tgatttaa    360

gtgttaatca catctaaaat ataccttcac agacatatct agattggtgt tt

#gatcaaac    420

aactggacac caaagtctag ccaagttgac acataaaatt aactgtcaca ct

#tgccttct    480

gaggattcag ggtaaattat tttggtgtac atgtagtctg gttgctgtct gt

#ttcccact    540

gtataccctt gctctagcta aactagcagc tccagctgtt tcatatacat gc

#ttctgctt    600

ttgcacatcc atgtctttgg tcatagtgta cctgcagcat ggagtgcttc ct

#gtgtccag    660

atcttacctg tccttctgag gattagatca cagatactta tacatacaat tt

#tgtttgca    720

gcctatacac tagctttcct aaacttcttc ctgtcaccta attatgctgt gt

#tctgtctt    780

gccattgtgc ttttgcacac aagttccttt ggtttagaat atccctccct ct

#gtcttttc    840

tttcttaaag agacagggtc tcagtgtggg ctggtctcga actcctgagc tc

#aaatgatc    900

ctcccatctc ggtctcccaa agagctgtga ttacaggcgt aagctgctgc ac

#ctggtcct    960

tccttcctac tttctgtaaa acttttacag cttcctcagg tcaattacat gc

#tccttttc   1020

attatgctcc cattgtccct ttgcgtattt ccacggaggc actcatcaca tt

#ttattgtt   1080

attgtttaca tatctgtctg tcaaaaggct ttgttttcca acagcagaag tt

#actatact   1140

gttttccttt tcaaagttgg tcctcagtcg agcctatctg gtctgtagta cc

#taaataaa   1200

ttgtgggata ataaactgaa tctctgttaa agatttggaa gttgtttcat at

#ttcttcta   1260

taatttctca ttgttagaat gtggagataa tgactgcttg gagataaagc aa

#gtctgaat   1320

agcagagatc agccttgggt tggactccag acattcttgg gcttattaaa ta

#tttggttg   1380

actcactgat agaaatagtt ttatttattt tccattcttt accaggtaca ta

#gcttcaaa   1440

attacttcat taacaaaagc tgtttctgat tataaacatt gatttatttt ta

#ctcaaatt   1500

tgtatatact gtatatactg agtaaaacaa attttactca tttgtttttg tt

#ttgttttg   1560

ttttgttttg tttttttgag acagagtctt gctttgttgc ctaggctgga gt

#gcagtggc   1620

atgatctcag ctcactgcaa gctctgcctc ctggattcat gccattctcc tg

#cctcagcc   1680

tcccgagtag ctgggactac aggcacccgc caccatgccc agctaatttt tt

#ttgtattt   1740

ttttttagta gagatggggt ttcaccgtgt tggccgggat ggtctccatc tc

#ctgacctc   1800

gtgatccgcc cgcctcggcc tcccaaagtg ctgggattac aggtgtgagc ca

#ccgcgccc   1860

ggtctcaatt ttgttttaag aatatcaaag aatccaagac tgtttcagct tc

#tttctacc   1920

taaaatgcag tggtgataac tggtgactga tttgtaagca atctcaatgt aa

#tgataaat   1980

aaccttttcc tttctctact agatgttggt tatctttctg aagtagactg tc

#catggcct   2040

gaacattttc cgaaaatcat tttgagcaaa atatctgttt aataacaaga ta

#accacatc   2100

aagatggttg gaaagctgaa gcagaactta ctattggcat gtctggtgat ta

#gttctgtg   2160

actgtgtttt acctgggcca gcatgccatg gaatgccatc accggataga gg

#aacgtagc   2220

cagccagtca aattggagag cacaaggacc actgtgagaa ctggcctgga cc

#tcaaagcc   2280

aacaaaacct ttgcctatca caaagatatg cctttaatat ttattggagg tg

#tgcctcgg   2340

agtggaacca cactcatgag ggccatgctg gacgcacatc ctgacattcg ct

#gtggagag   2400

gaaaccaggg tcattccccg aatcctggcc ctgaagcaga tgtggtcacg gt

#caagtaaa   2460

gagaagatcc gcctggatga ggctggtgtt actgatgaag tgctggattc tg

#ccatgcaa   2520

gccttcttac tagaaattat cgttaagcat ggggagccag ccccttattt at

#gtaataaa   2580

gatccttttg ccctgaaatc tttaacttac ctttctaggt tattccccaa tg

#ccaaattt   2640

ctcctgatgg tccgagatgg ccgggcatca gtacattcaa tgatttctcg aa

#aagttact   2700

atagctggat ttgatctgaa cagctatagg gactgtttga caaagtggaa tc

#gtgctata   2760

gagaccatgt ataaccagtg tatggaggtt ggttataaaa agtgcatgtt gg

#ttcactat   2820

gaacaacttg tcttacatcc tgaacggtgg atgagaacac tcttaaagtt cc

#tccagatt   2880

ccatggaacc actcagtatt gcaccatgaa gagatgattg ggaaagctgg gg

#gagtgtct   2940

ctgtcaaagt gagtagaaga tacgtttttt attttgactc tatatttagc ta

#ataatgat   3000

ctatacatat gtatgtatgt gttttatgta tatatgtgtg tatgttcctg tg

#tgtatata   3060

tagaaactga agaccttttc tggaacagat acagcttcat tgatgaggtt tc

#ttttttta   3120

ttaattctct actagtttat tacagatgtt cacttattta tacttcattt tt

#tcatttat   3180

atatcgtggc cctctttatt tgtttgatgg atacaaaccc accttacagg cg

#gtgaaaag   3240

ccttcttcag ggtctcagac cttaatgcca atcattcagt tttagtggct tc

#tgatttct   3300

aatttctaga tattgttgtt aatgaggata gttggctttt gtgtggatta ag

#gttaaaat   3360

caggaagtgc atatatcatg ttaatgagca catagtgaat tataagcatt tt

#gaaatttt   3420

tagtggtaga gaaaaataaa agcttcgtct aacctaatct cttcatttta tg

#gacaagaa   3480

gactgagtca cagtaagatt aaaacgattt gttcagattt agatggcaag gc

#cagaattc   3540

gaatctgtgc cttggtctca atgaggtcgt gcttttctcc gtggcatttt ac

#tacgtgtt   3600

gtgcttcctt tgtcatctga aggatataac ctctcttatt ttttacaaaa gg

#ctagagaa   3660

tctccaaaat ttggaagcct aatccataca agaagttcct tggattcaaa ac

#ttctcaaa   3720

tgatgatttt tagcattttg cttcttttct tatgaagtga caactagtat ac

#cctctaac   3780

ctgtcttgat gacttatata cctggaatga ggatataaaa atggaaacta ct

#attaaatt   3840

caggtagcat ctcttcatga agaagagttg gctataacta aattttattt tt

#gttttttt   3900

tcttttatca aagtaatata taacacctgt aaaaaagaaa tatataaggt gt

#tatatata   3960

catatataaa aagaaatata aaaggtgtta tatatacttt ttatcaaagt aa

#tatataac   4020

acctgtaaaa aatactttcc ttgtgtgccc ttcttacttt caccaaggaa ta

#tctgctta   4080

attttttttt gctgtataga acttgtatag taaatagatt tcttatgtag at

#aatctcaa   4140

aggaacagct gcctgcctgt accaagcttt caattattga ttataagtta tg

#acatacca   4200

tcattgtagt ggctctaggt tgtttttatt gattcaaaga aaatttcagc tc

#tggctact   4260

ctgattgcag tttattatta tttccagata atagactata attgattttt aa

#tcacctgt   4320

attaggtatt tcagtctttg tgcttgtatg ttggcccggc accgatgcca cc

#tacatctg   4380

ctaatataaa aggaggccat tagaccacca gcctcttcag tagggattaa ag

#agatatgc   4440

ttaagttaaa ttttggtgct aatcaggaag agaacatttt gtgtatatac tt

#gctatgtt   4500

taaggtaaac ataaaggcca agaaaattca tagaaattat attatgaatt aa

#tgaatttt   4560

agaaagtaaa gagatgttac ttagcatttc agtatgtgga atggaggccc tg

#taaggctc   4620

tatgtttttt caaaaattaa catgtcacaa tcatgagtag aacctaccat gc

#ttattcca   4680

agatttttgc attggggtct ttctagtttg gggctattat ggatcaaagt tg

#ctaagaac   4740

gttcttgtac attacttttg gtggatatag cattcatttc ttttaggtat at

#accaatga   4800

atagaattgc tggatgacaa ggggtgtgtg tgtgtgtgtg tgtgtttgtg tg

#tgtgtgtg   4860

tgtgtttaac agatactttc taacagtttt ccaaagtgtc tctatcattc at

#gtatggct   4920

gtactgtaaa tgaacatgtt ctagttgcct cacatcttta ccaacacttg gt

#attttagt   4980

cttttctggt aggctacaat tgttttttaa aacttaaaag caaaataata tt

#tgaacccc   5040

tttttgaaag aaaatcttac ccagaattcc aatataaaac aagagctgct tt

#ggttgagg   5100

tgagtctaaa ctagaccata tttccttctt ttgtttttga gatggagtct ct

#ctgtgtca   5160

tccaggctgg agtgcagtgg catgatctct gctcactgca acctccatct cc

#caggctca   5220

ggtgatcctc ccatctcagc ctcccgagta gctgggatta caggcacgca tc

#accatgcc   5280

cagctaattt tttttttttt ttttttgtat ttttggtaga gccccatgtt gg

#ccagactg   5340

gtctcaaact cctgagttca ggcaatccat gtacctcagc ctcccagagt ac

#tggggtta   5400

caggtgtgag ccactatgcc tggccagcca tacttctttt ttaaagattg aa

#tccctact   5460

ctcaaaaact gctttttggg gaataaggca gaaaatacaa aattattaca ta

#gtgccaag   5520

ttgtaaatat cccatgttca ttataataaa gaatttattg cccacagtca gt

#catcctgt   5580

gtgcttttcg ttttttaaac atttttattc tgggaaattt tttttttttt tt

#ttttttct   5640

tcgagacgga gtcttgctct gtcgcccagg ctggagtgca gtggcatgat ct

#cggctcac   5700

tgcgagctcg gcctcccagg ttcacgccat tctcctgcct cagcctcctg ag

#taggtggg   5760

actataggtg ccccccacca cgcccagcta atttttttat ttttattttt ag

#tggagaca   5820

gggtttcgcc atgttagcca ggatggtctc gatctcctga cctcgtgatc tg

#cctgcctc   5880

ggcctcccaa agtgctggga ttacaggcgt gagccaccgc gcctggccga aa

#attgttta   5940

aagtaaatat tttaatactt agttcagtat tacttagtat tacaatactt aa

#atatttag   6000

gcagccttga aggtttgaag atgtcaccag atggcctagg gatacttgta ga

#agctgttg   6060

aaaatagaga tatcaggaga ccttcacagt tctgcctctt atcttgttaa tt

#tttgagag   6120

ttaaccttta ctttgcttag aaatttccag ttatttacag tcagggtggc at

#ctcttgcg   6180

tctctgggct gttccagtta cagaaaagtc agaggctcct gctcaagtat ct

#tgaaaaga   6240

aagcagaagt aaagtttgag gctatttacg ttgccctctt ctcatggttt gt

#ggaatttt   6300

ttgtggaatt ttagttgtct ccatcaggga acttttggga agttacaaga gc

#gtacagtt   6360

acttctgtta ttaaactcat tatgatacca tgaaattacg tggaacaaat aa

#aagtcaag   6420

tttgctaggt caaaagagca aatccagaaa agcagattaa tgtaacagtg ac

#gcttagac   6480

aacaagtaca ggaatcacaa ctacaattca gagacgagtt cttatctaca ct

#tagggcag   6540

aaagagaata tagcaactat taaacacaaa taaattagaa tgaaaaagat aa

#tagtagtg   6600

ataagtacaa gagaacaaat aagaacatga aaactgacac cctacagctt ct

#aataagta   6660

aagcagacaa aaaatcctct aaatcagatc aaaagcaaag aaagactgaa ta

#aatgagtg   6720

aaaataatgt aaaaaggttt ttggaaatgg agacattttt gaggaagtag ga

#agaataat   6780

tagtaattta ttaaattcat aactttcttt ttaatataga aagtgaaatt ta

#gttttgtt   6840

aaagaaaaaa ttattcagtg atacctgcta aggcatgagg cagtgtttat tt

#agcaccac   6900

tgcaggaggt acagggacca ctgcagtcgg gtcttgcagt ggggaataga ga

#ttggactt   6960

aactctgaat acagcatggg caagtgagaa tttgtagcca gagagtaagg tg

#agggtcag   7020

tggatggaaa attactacga ggaaacatca ggggtcaggg gcattctggc ta

#aatttacc   7080

tgataggatt ctcactgaag acaggccggg gtgatcagac atcacctgga gg

#gtggtgga   7140

ggatgagaaa cccgatcaga tcctgagagt gattagatat caagggtagg ag

#gttgcttg   7200

ctaaactgcc ttagcagggt tactttgcta aaactggatt ttataaagaa gt

#gcacagat   7260

ggtcctagga gaaggttcag gagcctgact gaagtttggt cacacaaaga at

#ctttgtca   7320

gtttggaaac ttaaaattct tatgtcttat gggattaaca gaaagataac tc

#aatagcca   7380

cttgaaattc ttctgaaatt taaggataac aagaatattt tgagcaagtg aa

#gagaatga   7440

cagaccatat tcacaaagat atgagcatta atagcatgga aaattaacag ca

#ggcaaatt   7500

aggatcacct gagctctact agctcagtct gaaatatccc agaagaattt ta

#taaatatt   7560

acatgtggtg ttttgttttt gtttttgttt tcatgaagct atcagagaac aa

#gtctgttt   7620

atttgtgaaa acttctcctt tgtgaagcac tgcctaagga tgctattggg ct

#attggggt   7680

tgggtctttt ttggtttttt ttttggagac agggtcttgc tccatcaccc ag

#gctggagt   7740

atagtggcaa gattgtagct cactgcagcc ttgaactcct gggttcaaat ga

#tcttccca   7800

ccttagcttc ctgttagtag ctgggattac aggtgcatgc catcatgcct gg

#ctaatttt   7860

tttttttttt tttttttttt ttttttgggg gagacagggt ctcactatgt gt

#tacccagg   7920

ctggattcga actcctggcc tcaagcagtc ttcctgccat ggcctcccaa ag

#tgctggga   7980

ttaccgctgt gagctgccat gcccagcctc cttttacaag ctatattgaa ga

#gagaagtg   8040

actgagacat cttagctgga gaggaggaat tgaataaaca agggatacaa gt

#gacagagt   8100

aaaatgggct gtgaaaggaa atcagagagc tgatgaaaca ttgcatttca aa

#gtgtgtca   8160

gggaaagatt gagaagaagc agaaccagaa catgaattaa taaggcaaca tt

#tgtacttt   8220

tcttggagaa tatagcaatt ggtagcaaaa attagaagtt ggatatcaga tc

#atttatta   8280

gtttgattag atttctctac aaatagtaga gatccaaaat aacaaagatt tc

#caaataat   8340

gactactatg tagaaggcag accagggctg ctttgtcagc tttgcagtca tc

#tggcattt   8400

aggctgcttc cagcttttgt ctccatcatc cccaggatcc aagttggagc gc

#cagtcatt   8460

tcatctacat tctaagcagc acagcagggg tggatgtgtg taaaacaaat gg

#cgtttagt   8520

attttttgag gatatttctt agaagcttcc aggtagtact tcttgctttt ca

#ctggccat   8580

aactggggtt ccttttacta agaaaaatca attggatatt gggataggca ga

#tagtagtc   8640

tctgctacat tattgagcac ctactatgtg ccagacactg tgttagctcc tt

#gagataaa   8700

aggtctttgc cttaaaggaa catatgatct aatagaagac ttagattcat at

#ataatgca   8760

gggttaagaa ctatggtcac cactgcttct tcattggtga ataattaaaa ac

#aaacaaaa   8820

agaggccagg cacccagtgg ctcacacctg taatcccagc actttgggag gc

#tggggtgg   8880

gcagatcacc tgagggcagt agttcaagac cagcctgacc aacatggtga aa

#ccccatct   8940

ctactaaaaa tacaaaaatt agccaggggt ggtggcccat gcctgtaaac cc

#agctactc   9000

gggaggctga ggcaggagaa tcacttgaac ctgggaggtg gaggttccag tg

#agctgagg   9060

tcgtgccact gcactccagc ctgggtgaca gagcaaaact ctgaacaaca ac

#aacaacaa   9120

caaagaacta tggaaaacca aggagaggtg cctaacccag tctgaggtgt tc

#agagaggt   9180

catcttgggc aatgtgtcat gaaactgagc cctaaagaag ggtttcctca ag

#cttggtat   9240

gacattttag tcagataatt atttgttgtg gcagccatcc aagatgatca ac

#agataaag   9300

ggaagcgcat ttagttttga cttagggaat attgtgctcc ctgggtgacc ca

#tggttaag   9360

gcgctgtagt tcttccttga ctgtccagaa tgtctttcct tttccttagc ca

#atgagcca   9420

cccaagaaat gttactcctg ggagaagcct gtgcctaact gtggtttaca ga

#attcaaag   9480

ggaagaggta gtatggagga ctccttgtgg cttcactcct ggcccaaccc ag

#ggcctcaa   9540

aaggacctaa ggaacaacta cgccctgtta tgcctgacct atggacccta cc

#ctcttgac   9600

catataatgg aagtcagcta agcttagtcc cacctggacc tagaacatgg tg

#tttgtttc   9660

ccataggtga atatattttt gaaaaatata tttttgaaaa ataagtaaaa ca

#aaaccaaa   9720

tcaggaaata atcattgaga agttacaata tgaacacctt aacaaagatg ag

#taacaatg   9780

tggtgttttt tgctagagag ttcatttcca ggcaggaagt agtgtgaaac aa

#ggtttgag   9840

agaaatgatg cggaccaggc tttggagggc cttatatttt aagctaaaga ta

#ttgaattt   9900

taagccagtt gccttcagac ttctcttatt agtggagcac cctttttttc aa

#gtgaaatc   9960

ttgttcggaa ccttggtaga tgatgtactt ggaagtgaag tggccctcct tt

#aggcagca  10020

tttaattttg gttggattta acaaagaaaa ctgaagtgaa gctcatggaa tt

#gcaaaact  10080

acaattttgt ttttaaaaga aaaacattga ttgtaatgtg taaaatttac aa

#aactgata  10140

cacttttaat tgggattata ttggtttata aaaacattta gtgttttttt tt

#tttttttt  10200

tgagacagag tctcgcactg tcttctgggc tggagtgcaa tggcatgatc tc

#ggctcact  10260

gcaacctctg cctcacgagt tcaagtgact cttctgcctc agcttcctga gt

#agctggga  10320

ttgcaggtgc gtgccaccac acccagctaa tttttttttt gtgtgtgtgt tt

#ttaataga  10380

gatggggttt caccatgtta gccaggatgg ccttgatctc ctgacctcat ga

#tccgcctg  10440

cctcggcctc ccaaagtgct gggattatag gcgtgagcca ccgtgcctgg ct

#caaaacat  10500

ttagttttaa taggcatttt agggtatgtc ttagtccatt tgggctgcta ta

#acaaaata  10560

ccacaaactg ggttcttaca aacacagaag ttgatttctc gcagttttgg ag

#gctgggat  10620

gtccaagatc aggcactgat ggattcagca tctagtaagg gcctgctgtc tg

#gttcatag  10680

atggcacctt gtgtcctcac atggtaaagg aggtgaagaa tctctccctg gc

#ctcttttg  10740

taagtgcact aataaggaca cttcccaagt tcccatctcc taatacagtc ac

#attggtga  10800

ttaggtttta acatgaattt ggggggacac aaacattcag tccataatga gg

#tataaaac  10860

ttagaagatt cctgtttttt ttaaaaaaat tctttttttt ttttaagatt ta

#aaatgtaa  10920

gcctagttca gagtattttg ccaagatgaa gtgtagggca aattggatct tt

#aagtagag  10980

taacctatta cattgattaa ctactgtcaa agaaaagcca agcacatcaa gg

#gaattatg  11040

gttggtaccc atccagatat tatacatgaa ttcatggttc ctccttggtc ct

#tttctgaa  11100

ttacctgtct aatgaagaat tatttcattg tttttgaaaa catccttaca tt

#tcctcatt  11160

gctgaaaatc atgttttcaa acatcaacca ttcatcacaa tcacatacag aa

#cctttaaa  11220

agacctaaaa tttctgattc aggaggtctg ggataggccc aagaacttgc gc

#ttctaaca  11280

ggtttcccgg tgatgctaat gttcctggcc tgatttcact ttgagaacca ct

#gcttaaaa  11340

tcatgctacg ttttgtttgc ttcatttgtg gactcagact ttcttgcccc ta

#cagcctgg  11400

gctgcagcca cactgaaata attgtagcta caattattgc cacaccattt at

#ttaatcag  11460

ttcctttgaa tgtgttgttt cctgtgcctg caacaccttt ctctcacttc at

#ttcttcat  11520

ctgaccaact catggttgta tttcaagatt tagttcaggt ttcctttccc ta

#aggaagat  11580

ctctccaagg cccccctctg tctgggatgt acttcctatg ctttcatgag ac

#acttggca  11640

aatggaaaag ggttgatact ttgaagctgg ctagactttg tttaaagtct tt

#cattgaca  11700

ctaactggtt ttgtaacatt gcatcaaata ctatctctct ccgtgtctcc at

#tttcttat  11760

ctataaaaca gggaagatgg tgatgatggt aatgatacca tccaacatct ac

#tgaacatt  11820

tgttatgtgc caggcagtat gctgagctct ctgtgtgcct tatctcattt ag

#tttttata  11880

tttacccttt cacactcacc cataggtgcc ttaaacatct taattttata ga

#tgagggac  11940

ttgaggctcc cagaagttga ggagcttgtc ctccgtccca cagttggaag at

#ggtagagc  12000

caggctgtgg actcaggtct ttgtcttcat ctatactttt agctcttgtt gt

#atatactt  12060

acagcattta tgaagacaaa ctaaaacagt gtgacagtgg ctaagcacac gt

#tttagagt  12120

cagacagaca taggttcaaa tcctagcact gtcctttatt gattatgtga cc

#ttgagtga  12180

gttatttggt tttgtctagt cttggttatc tcatctttcc tttagttttc tt

#atcctgga  12240

aatgggaatg ataatatgtt agatccccct tatctgcaga tgatatgttc ca

#agacccca  12300

gtggatgccc gaaaccccac tgatggtacc gagccctata tatactatgt tt

#tttcctgt  12360

gcatatatac ctgtggttaa tttataaatc aagcacagta agattaacag ca

#gtaactaa  12420

ttataaagta gaacaattat aacaatatgc cagtattact acttttgagc tt

#tatggcca  12480

tgattaagtt aaacaagagt tacttcaacg taagcactgc gatactgcta ca

#gtccatct  12540

gataacagag ggctactaag tgactaatgg tgggtagtga gtgtacattg ca

#tggacgtg  12600

ttgaacaaag ggatgattta catcccagtc tagacagagt gagacaatgt ta

#gatttcat  12660

catgctactg agaatgacat gcaatttaaa acttatgagt tgtttatttc tg

#gagtttcc  12720

catttaatgt tttcagacca cagttgactg cagagaacta cctgaaactg tg

#gataaagg  12780

cttactgaaa tagtatccat taaggatgat aataataact atccataggg tt

#gtcgtgag  12840

gatttagtta gaatgactat aaagccctta gccaagtgcc tggtatataa tg

#agaggttg  12900

aaaatgttac ctgttgtctt tattattata ataataagga tgataataat ac

#cgattgca  12960

gatgatggta agtagtattt atagagttgt gagaattaaa ttactacaaa gc

#ctttagaa  13020

tagcacctgg cacatagaaa ttgttcaaag tggtacttat tagtatgtta tt

#tttattgt  13080

cgaacgctta tgcactgttc ccctccctct ccccatccca aaataatgag tg

#tgaaacac  13140

ctaggttagt agcaagtgca ccacaggctt ttgttaatgt tcttacacat gc

#tcctgtaa  13200

gcttgtttag ggcaaaggta gtcttgaagt catgaaatgt ttgtctcaat ga

#agcaaagt  13260

aagcacccga tttgaatagc tctagtagga aactaacatg gcaggttggg aa

#tgctggca  13320

ttacagtaac aataatctct gaaactactt ggaggtgacc tttgatattt ca

#ttgtcatg  13380

ttttcccttt ttcctttgtt tctttgttta gtttgcctgt tggtaaactt ta

#tataaatg  13440

ggatcatggt ctgtgttttt ttcggtcagg ttcttttttt ttttctctgg cc

#taacattt  13500

tcttttgaga tttacctgtg ttgtggtata tagctatatc atcagtttta at

#tgccaaaa  13560

tactattctc tggtataata tagattattt atacattttt actattgatg aa

#catttgga  13620

ttgtttttag tttggagcta aggacatttt tgaaggtgtt tccttcaaga gt

#ttctctaa  13680

gatatacact ttggattaga atagctggat tatgagcagt atgcatattc ca

#cttgtttt  13740

tcttttttgt tttttgagat ggagtctcgc tctgtcgccc aggctagagt gc

#agtggtgc  13800

gatctcggct cactgcaagc tccgcctccc gggttcacgc cattctcctg cc

#tcagcctc  13860

ccaagtagct gggactacag gcgcctgcca ccacacccgg ctattttttt gt

#atttttta  13920

gtagagacag ggtttcactg tgttaatcag gatggtctcg atctcctgac ct

#cgtgatct  13980

acccgcctcg gcctcccaaa gtgctgggat tacaggcttg agccaccgcg cc

#cagccttt  14040

tttttttttt tttgagacgg agtctcgctc tgtcgcccag gctggagtgc ag

#tggcgcga  14100

tctctgccca ctgcaagctc acaccattct cctgcctcag tctcccaagt ag

#cagggact  14160

gcaggcgccc accaccatgc ccggctaatt ttttgtattt ttagtagaga cg

#gggtgtta  14220

gccaggatga tctcgatctc ctgaccttgt gatccgccca cctcggcctc cc

#aaagtgct  14280

gggattacag gcgtgagcca ccgtgcccgg ccagtagctt atcttttaac tt

#ccttttta  14340

atatcttttt tgtcaatgac ctcactttaa cagaattaag aaaaataaga aa

#aatctttt  14400

gatgaattta agttttaaac ttgtatttac caatcttttt ctttagaatt tt

#ttgtaaaa  14460

aaattcttcc atactctgag gtcataaaaa tagtttccca tgttttttcc aa

#aacttaaa  14520

acaaatttct tttcatgtta atctggaatt tattaatcaa tatggaattt at

#tttcttgt  14580

gtgaggtgca gattcatttt catatttttt ctataaagat gaccagtttc cc

#ggaaccat  14640

ctatggaaat acagtcagta ctttggatcc atgggttcca catccataga tt

#caactaac  14700

ctcaggtcaa aaacattcag gggggaaaaa ttccacagag ttcccaaaat ta

#caacttga  14760

gcttgccatg tgctgaatac tacattgaat ctacgtgaat gaagtgatgt gt

#gggcatcg  14820

ttaggttagg tattataagt aatctagaga tgatttaaag tataagggaa ga

#tgtatgta  14880

ggttatatgt aaatactgtg ccattttata tgagagattt gggcatctgt gg

#attttggc  14940

atttgtgggg agtccagaaa cctaggggat tgtcctaatg acatgcagta cc

#agctaggt  15000

taaacatcag gtttccatgt atgcattatt cttttagtga gatcgctttc tt

#tttttttt  15060

ttttttttga gacagagtct cactctgttg cccacgctgg agtgcagtgg ca

#cgatctca  15120

gctcactgca acctccgcct cctgggttca agcgattctc atgcctcaat tc

#tcccgagt  15180

agctgggact acaggcgtgt gccaccatgc ctggctaatt ttttgtattt tt

#agtagaga  15240

cgggatttca ccgtgttaac caggatggtc tctctctcct gaccttgtga tc

#cgcccacc  15300

ctggcctccc aaagtgctgg gattacaggc atgagccact gcacccagtc aa

#gaaatcct  15360

tcttcactta gtctatccta atgccatata ccactctatt ttaattactg ca

#gttttaga  15420

aaatgtcttc gagttagcca ggcgcggtgg cttatgccta taatcccagc ac

#tttgggag  15480

gctgaggtgg gcggatcact tgaggtaagg agttataccc cagcctggcc aa

#cacggtga  15540

aacgccatca ttaccaaaaa ataaaaatta gctgggcatg gtagcgggca cc

#tttagtcc  15600

cagggaatgg aggcagaagt tgcagtgatc caagattgta ccactgcact cc

#agcctggt  15660

tgacagagtg agactctgtt tcaaaaaaaa aaaaaaaaaa aaagaaagaa ag

#aaaatggc  15720

ttagaatcta atagggtaat ctccctgctt agttcttctc taggaatgtc ta

#ggctgttt  15780

ttaaaccctt tggtcctccg tatatatttt aaaatcaact tgcctgattt ca

#tgaaaaat  15840

cagactaaat ttacattgaa cctgtaggta atttggggga ggattgccat tc

#ttaaaata  15900

ttaagccatt ctatccataa tacagtgggc ctctcctttt atttaggtcg tc

#tacaatat  15960

cctttgatgg tattgtattt tataatgttc ttcataaaag tattgtactt ta

#tttgataa  16020

gtttattatt cagtaccttc ttttcattgg taatgtaaat atgtgtattg tt

#tttattta  16080

tttaagttat tcatttattc ttttgggatg gagtctcact gtgttgccca gg

#gtagagtg  16140

cagtggtgcg atctcagctc actgcaacct ccgcctcccg gattcaggag at

#tctcctgc  16200

ctcagcctcc cgagtcgctg ggattgcaag tgtgagccac caagcctggc ta

#atttttgt  16260

atttttagta gagacagggt tttgccatgt tttccaggct ggtctcaaac ta

#ctgaactc  16320

aggtgatgca ctcgcctcag cctcccaaag cgttgggatt ataggcacaa gc

#caccatgc  16380

ccagccagat atgtgtattg tttttaaatg ttcttttagt tgctggtgta ta

#taattgta  16440

aatgactttt gtatatctat atcccgcagc tttcctaatg ttttgtggtt tt

#gcctaggc  16500

taggacttct aatagtagta agcaacctta ttttaaaaca gttgttgttg cc

#aggcgtgg  16560

tggctcacgc ctgtaatccc agcactttgg gaggccaagg cgggtggatc ac

#gaggtcag  16620

gagatcgaga ccatcctggc taacatggtg aaaccccgtc tctactaaaa at

#acaaaaaa  16680

ttagccgggc gtggtggcgg gcgcctgtag tcccagctac tcgggaggct ga

#ggcaggag  16740

aatggagtga acccaggagg cggagcttgc agtgagcgga gatcatgcca tg

#cactccag  16800

cctgggtgac agagcgagac aacgtctcaa aaaaaaaaaa aaaaaaaagt tg

#tttttaag  16860

tggggacagt ttgttcccta ggggacattt ggcaatgtct ggagactttt tg

#gtcatcac  16920

agttggggaa gtggaggtga tactgctggc ctcaaataga aagaggccag gg

#tgttgcta  16980

aacatcctgc aattatagga cagctactac aacaaagaat ttattcagcc cc

#aaatgtca  17040

gctgtgccaa ggttgagaaa ctgtatttta aagggaatgc cttaaacaat at

#tttattat  17100

tatgcagaat tccaaacaca aaaataaatt ggtaaacaga attcccaata cc

#aacagtta  17160

actattgtag gccagtattt aactcctttc cttcccccaa cttctgctga at

#tattttaa  17220

aacaaataca agatatcaca tcattccatc tgtaaatact tctctgtgtg tc

#actaaagt  17280

agaggttccc aaattatggt ttcagaatac ccaaaaaatc cttcagaccc tc

#ccagaaga  17340

tctccaaggc taaaactatt ttcacaatgg tactaagatg ttatttgaat tt

#tcattctg  17400

ttgacatttg tgctgatagt gcaaaagagt tgaaaattgt ggatgcctta gc

#acaaatca  17460

aggctctggc accaaactgt acttagtggt cattgtactt ttagtactgt ca

#aattctct  17520

tctgcttaaa aaaaaaacca actagattta agtaagaatg tgattcatga ag

#cagtacag  17580

ttttttttag tcttctacct aatggtttta gtgatcattg atgaatcatt gc

#ccagacct  17640

actattttat taagtctggc caaatggtgg tagtctaatt taaaatttcc tt

#ctgtattc  17700

attaatgata tttttctata aagaagactg tgcttatacc aactgtttag tt

#actcctaa  17760

atatcctttg tgtaggaaat ggaggaaaat gatttattta ttttttccca ga

#acagagtt  17820

cactctaaag ggaatatgtt taatgaattt tgttgtattt attttaatgt ac

#attattgg  17880

tatatgctgt tagttttctt tctctttgtt gatatctttt atcaagttaa ag

#aatttctc  17940

ttctatttct agttcactaa gagttttcaa agttaatgga tattgtattc at

#tttccatt  18000

gctgtgtagt aagttacccc agaatttagt ggctgaaaac aacaaacata aa

#agtttctg  18060

tgtgtcagga atatggacac agcatagctg gatcttctgc ttcagagtcc ct

#cacaaggc  18120

tgcatcaggg ctcgactggg gaaggaatga tttcctagtt catgtggtat tt

#ggcaagat  18180

tcagttcctt ctctgtctta ggtggagggc cttagtttct tgctgtgtgt tt

#ctgtatat  18240

ggctacttaa catggcagca ggcaaacaag aagagccaga gaaagtaaag aa

#gatggaag  18300

ttacatcttt tccagcctta tctcagaagt gacatcctat cacttttgcc at

#attcatga  18360

gaatcaaatt cctaggccca gctaaaatca agtagacggg attacacgaa gg

#taggaata  18420

tcaggagttg ggaaccatca ggtgctattt tagaagcagc cttccagcct gc

#cctgtggc  18480

ccccaatgac tcatgtctct tgcatatggc cctcttaatt tgccccttcc tc

#caggtctc  18540

caaaagtctc attctgttac agcatcagct caaagtccag aatcttgtca tc

#taaatcag  18600

gtccagttgt gagtgaggct tatgggtgaa gtttcttttt tttcttgaga ca

#gcatctca  18660

ctctgttgcc taggctggag tgcagtggcg cagtcatggc tcactgcagt ct

#caacctcc  18720

tgggttcaag tgatcctcct gccccagcct cctgagtagc tgggattaca gt

#tgtgtgcc  18780

accacacctg gctaattttt ttatttttag tggagatagg gtttcgctat gt

#tgcccagg  18840

ctggtttcaa actcctgggc tcagcccccc aaagtgctag gattacaggt gt

#gagccact  18900

gcacctggcc aaagttttta aaatacagtt ccttgtgtac agttccattc ag

#tctgtaga  18960

aatgtgacat taaagataca agttatcctc ccttccctat atccagtata ca

#agggtgga  19020

acaggcatgg gataatagac attcctgttt aaaggaggga aaataggagg ca

#cagaagtg  19080

ttactagtcc atatcaattc tgaaatccag ccaggatgtt agaagttcct tg

#attccacc  19140

tctgagttat tcttcctttt tcatgaaagg tagcatgtgt tagcagctgt gt

#agtttttt  19200

attagtctgc ttcctgccag tagaattttg ggagtctagt gacctctttt cg

#tgttatac  19260

tatttctggg tttttttggt ccagcctggc agtgttgctg ctgatataat tt

#tctcaaaa  19320

actttgtcag tcctttgtga aactcactgg tgttcattcc attgggtaat ag

#tcacaccc  19380

acgaatctaa ggtacaccct tctttacttt gtgatctttc tcagatggct ga

#gggacaat  19440

gttcttaagt ttcctagagc ccctgttgtt gagtcgcgag gacctattag gc

#acaccctt  19500

aatttcttta aagagccctt tgtatgacag aattactggg aaccattttc ca

#agtagccc  19560

accacaaagg ttgtattttg tcaaattgaa ggagtcatct gactttcctt aa

#tcataagc  19620

tacaaatata ataagctaca ttaatagatt ttctaatatt tatttaactt tg

#aatttctg  19680

gaaaaaaccc aacttggtaa tgatttatca tctgagcttt gtttttggct tt

#ggtatgct  19740

aatttttggc ttaggatttt tatatctatt tcatgagtga cactgacctg ta

#attttccc  19800

ttttcttact ctctatgtct gttttttttt aatatagtta tgcttccctt ac

#aaattact  19860

tttgattgtc ttttccctca attttggatc acattttcct gatgctctca tt

#tgagtaat  19920

tttggagtta tattttgtgt ttctaagtcc tgttaaaatc cttggaagaa tg

#ctgatttt  19980

atttttgttt tggtagactg tcaggctggt taggttctaa accacaagtt tt

#ctcacctg  20040

tgaatagtat ttccagtatc agttcaaaga ctgtgctatg ctactttggg tc

#tttcctat  20100

ccacagacca tttattagtt agtttggagc tttggcaaca gtttatattt ta

#atttattc  20160

tcagagcctt tgctgtgctt ccctgaatct ctcttatgtg tgagctagaa gt

#tgtgctgg  20220

ttcatgtgca aaattacggg aaaccctttc tctggctcat cttttcctgg at

#tccccaca  20280

tctctctggc tcacagaggc tcctttcatt gttattctag tcagacgttt gg

#atttcttt  20340

cagagcttta gctgcctgcg atgcgtttct gtatggctgg tgccaccctt ag

#ggtgaaga  20400

gctcagaaaa agtgttaaaa ataatgagaa tgattcttac gctccttaga cc

#actgtggt  20460

ctttcccaat tatttttgcc tgaaatgagg ggttttgccc agagtttttg ct

#gctcacat  20520

ttgtgcatag tgtggactta tggttctaat tttattctaa ggatctttat at

#ttctcagg  20580

gttttttgtt ttgttttttg aaaaagtctt agtttcttag caggttattt tt

#ggtttatt  20640

taattctggg ttggcaataa ttttctctta gtgttttgaa gatattattc ca

#ccatccac  20700

tagttgcagt ggttgctgtt gaaaaacctg ctgtcaataa ttgtcaggcc tt

#tgttatat  20760

gtcatttctc tgaccacttt aagctcttta tcttttgtgt attttgtttt ta

#ttactgta  20820

ttttgtgagt aggtgtggat tccttttttt gtttagcttg gtaaatgctc tt

#cttgtaaa  20880

tataatttta gtttctttag acaacatagg gctatttaaa ttgtttctta ag

#tgagcttt  20940

ggtagtttgt ctttcaagga atttgttcat ttcctctaag ttgttgaatt ta

#tgggcata  21000

aagttgttca taatccttat tatcattttc aatccataga atctgtagtg at

#ctgtagaa  21060

ccttgcattc ctgaaatcag taatttttac ttggaacgtg ttgagctctt tg

#gatcagtg  21120

agttttatag tttatataaa atttggaaaa ttgtgtactt tttttttcca aa

#tttttttt  21180

ctcttctttc tcctttcctt caggactcca attacacata tatgagactg tt

#ggaaatgt  21240

ttccatagtt cactgatttt tttcaatttt attttcaaaa ataggctttg tt

#ttttatag  21300

cagttctgga ttcatggcaa acttgaacag aaagtgtaga gagttcccat at

#atgactta  21360

tccacacaca tgcactgcct accccaatat cagtatccta ctggtatatt ta

#ttacaatc  21420

gatgaattta tattgacaca ttattataac ccaaagtcca tagtttacat ta

#acgttcac  21480

tcttggcatt gtatattctg tgggttttga caaatgtata ctaccatata tc

#taccattt  21540

tagtatcata cagaatattt taactgtcct aaaaatcctc cgtgttcccc ct

#atttatcc  21600

tttccttttt cagccccttg gcaaccactg attttttatt ctagccatag tt

#ttgccttt  21660

tccagaatgt catggagttg gaatcataca gtatgtattc ttttcagatt gg

#gctctttc  21720

acttagtaat atgctcttta ctccatgtcg tctcatgtct tgatagttta tt

#tcttttta  21780

gcactgctgt caatacagct taagtatctc ttatccgaaa tgcttggact ag

#aagtgttt  21840

ccaattttgg attattttgg attttgaaat atttgcatat acctgattag at

#ctacttga  21900

gaatgggata taagtctaaa tatgaaattc atttatgttt catattacac ct

#tatgcaca  21960

tagcccaagg tgattttata caatattttg aataattttg ttaatgaaac aa

#agtctgtg  22020

ttaagtatgt gtggaatttc ccacttgtgg agtcaatgtg aatgtcacaa aa

#tttcgtat  22080

tttggagcat ttcagatttt tagattaggg atgctcaacg tgtacttgaa tg

#actgtact  22140

ccataataac tgtggaataa tctgtggaat aactgtttta atgcatttgg ta

#attctaac  22200

atctgtgtta tttaaaaatg agtatttttc tcattacgag ttgtgtttcc ct

#gtttattt  22260

gcatgcctga taatatttgg atgccagatg ttgtaaattt tacttttttg gt

#tgctggat  22320

attttttgtt tgttttattt ttgtttgctg gatatttttg tagttctgca aa

#tattcttg  22380

agctttgttc tgggatgcag ttaacttact tgaccagttt gatctttggg gt

#ttttgctt  22440

ttatgatttg ttaggtgagt ctgaagaaat acttagtctg tgcctgatta tt

#ccctatta  22500

ctgagtcaag acctggctga gtactctact aatatccaat aaattatgag tt

#tgtccact  22560

ctgggtggta agagcaagca ctattccttg ttctatgtga gttctgggca ca

#gttccctg  22620

taaattcgtt ctttccattt agcacatctc cagaattctc tctgtataca gc

#tctctcct  22680

ctttgattct ctggcctgaa aactccaacc aggactttca gctccatttc tc

#aacttaga  22740

gtctgctggg ctctgcctgg gacccccttc ttataccaca gtctggatat tt

#tctcaagg  22800

cagtaagctg gggcaattat ggggatcact tttttcccca tttctcggga aa

#cagtcttc  22860

ttcattgccc ctaatatcca gtgttttgaa aattgttgtg caacgtatat tg

#tctttttt  22920

tttttttttt ttggttcttt cgggttggat tactttgaag cctttcattt at

#agatattt  22980

caatatggtc ctttgaaaga taagcactct ttactttttt ctgaaacctt tt

#atattatc  23040

tgaactcatc acgtgtgggc agcactgtgt tgctgtgttc atgaaacatt ta

#taagttat  23100

gtactagttt gctttatttc ccagtatatc agttttgttc agtaacaatc at

#ttgataga  23160

ttagtgctca cctttaaatt ttttaaaatt ttgggcagct gatggctatg tg

#tgttatct  23220

cctatttctt tatgttatcc tggattcaga gccatagaat actacctaga tt

#ctttagga  23280

aagtctttgt gtgcctgaca ttctgtttat cattttcata tatttaaaaa aa

#tatattta  23340

atacatgtat ttttccataa aatatatgtt gtcatattgg gttcagatct tg

#gctttacc  23400

acttactgac tgtgggacct tgaatcagat acctaacctt tgtatgcctc at

#tttcttca  23460

tgtgtaaaat ggtgatagta atggcattta cgtcataggg ttgttaataa gg

#tttaaatg  23520

cattaataat atgtaaagag cttaggatag tatctggcat ctaagtgcta ta

#aatgtgtg  23580

ttagctctta ttatttttac cacaactacc accaccactg catatattac tg

#ctagtgtc  23640

catgccagga gaaccatgtc tgttccctag gtggcatatg ggtgtgtgta tg

#taaagatg  23700

aggtgactgt gtggtcttgt gctgctctct ctgagccctc cttggcctct gg

#agtaatag  23760

tattgctgtc cacctggtca atgtgtcctg ctgataagtg ctgttgcagt ct

#gtggtcag  23820

caaatggtcc agtggttctc cttgcttcac tggcctcacc ttggctcatg ct

#gactctga  23880

ggtttgggtg tcatattctt taagccctgg acctgggcag taagacaaat ag

#cccttagt  23940

tactgaatct ctttgcctcc cctggggcaa aaccctgtcc ttcagtgatt tt

#gctagcag  24000

aatccccacc tcccttcctc ttctttcatt gggcatacag aaaatttggg at

#gcctttta  24060

tgccttgtgg gagccagaga actctggata actaaatcca tgccctcctt cc

#tcctaacc  24120

cttctatgtt gatgattccg cccccacatt ttcattaagg gtcatcttgt gt

#agcagtct  24180

cctcccagaa ccccaaatgg gagatggatc aaagatgcct gtttttttag ct

#ttttcttc  24240

catctgccta gcatgtcttt tcccttttgg aactctatcc tggagagagg ag

#atgagaac  24300

agacttgtgt cactgctgct tccttcccac tgttctcttc tcctgtcatg aa

#gacaccag  24360

aagtctaggc cgggtagact ttccatttcc tcttccactt tcctttgggc at

#gatggcag  24420

gtgtgatact gggaaggggg aatctgcttg ctgataagga aatgtgtgtt gg

#gagatatt  24480

ttaaaaaata taatccttgg ctgggtgcgg tggctcatgc ctgtaatccc ag

#cactttgg  24540

gaggccgagg tgggcagatc acctgaggtc aggagttcaa gaccagcctg gc

#caacatgg  24600

tgaaacccca tctctgctaa aaatacaaaa aaattagcca ggtgtggtgg ca

#tgtgcctg  24660

tagtcccagc tactggggag gctgaggtac tagaatcgct tgaacctgag tg

#gtggaggt  24720

tgcagtgagc ccagatcgtg ccactgcact ccagcctggg tgacagagtg ag

#actccatc  24780

tccataaaaa aataaaaaat aaaaaaataa aaaaataaaa taaaatatta tc

#cttgttaa  24840

acaggttaaa gggaaaaaga atattttagg gtaaaggtgg gggtgccagt tt

#agatggga  24900

attagggaag gtttctctga ggacataaca cttgaacaat ttcaaggctg tt

#ttgtagta  24960

ttgacaaaat ttaatactag gatcaagatt gcttgtgcac aaagccaaaa ga

#tgggctct  25020

cttatgccct cttcttccca tactgcagtt agtacattct gttttctgca gt

#ggtaactc  25080

tttctggcct aattgctcag tttctcgtac tagtctctgt aacacattta tt

#ctgcttat  25140

cactatagag tcctagtatg tagaggctga caaaaacctg aggcaatatt tc

#ttcaagca  25200

agctaccggt ttcagaacca tctggaacac ttaaaattgc tcctctcgaa cc

#cactccag  25260

tgtcataatt actaacagtt tcatttggaa tctgatactg ttgaatttat ca

#tattactt  25320

gaggacgagc agtttgttat tgttatcttt ttagccacac agcattgtaa at

#tctaagta  25380

aatgcttgat aaattgattt attaggaagc taggagagag gcatttcaag tg

#gtttaaaa  25440

agttttgcta tttgggggtg acatcagcaa aagcggcaca gtaaagaagt gt

#aaaatttt  25500

acccttccat aagagcgaca gaagaactgg caacacctgt cagaatcaac tt

#tttcagaa  25560

ctctagaaat taaccaaaga cttgaaaaaa agtgtgaaga gtgctcattc ac

#aaaaaatg  25620

gctgaatctt agtaagaata gtgagcttac ccaagcccca ttccctgttc ca

#tgtgtcag  25680

ctggggctga aataacagcc tgtgtttctg tactggaggg agcagaacag ac

#ctcattgt  25740

aagtatttgt tttgccttct taggtggatc cctggatgaa tgacttcaaa ac

#cttgtctc  25800

tatttctcct gactcagaac tgccctactt ctgagatcgg ggaggacagt ag

#ttatcaag  25860

aaacatttac agacaaataa tttagtcatt gcttcctgaa tcaagaaata ac

#aatggggg  25920

caaacagtag actaactaaa gagcctagga gcagagattg ggaatgagat gt

#ctatgaga  25980

gctttgaaaa gcttcacata ttcccaagaa tgtagaaggc cacatgcttg gc

#aaggactg  26040

tatgcatgcc cagggaagac ttctacctct cgctgatctt gaggctctgt ga

#aagcagga  26100

agtgaagcct aaggcagagt tagaagctac ctggctaagt agtgaaggtg ta

#tcccaaac  26160

ctacccagag cccttctgca aagacagaca ggttttttgg ttccaagcat tt

#aaggcagt  26220

ctgttcagtt gttagctggc cattaagcta acagaataga gactccagtg ac

#tgcacata  26280

acaaggaata cagattttac agaattagtt ttgataagtc ttgaaacaaa ca

#actacaac  26340

aataagcagc aacaaaaaat tctggagagg ggagagaatc tgattcccag ag

#ttgccaca  26400

ttataagatt taaaatgtct agtgtttaac aaaaaagtgt aagatatgaa ac

#acaacaag  26460

aaaaaaagcc atgaatagaa attgtccctg aggaagccca gacgttagaa tt

#tctagaca  26520

aacactttat attagctatt taaaataatt cttcaagagc taaagaaaac ca

#tatcttaa  26580

acaaaacaaa acaaaacaaa aaacccaaaa acctaactga aagtttgaga ac

#agtgtctc  26640

accaattgag aatatcaaca aaaagataga aattatgaac taaaccagat ag

#acaagcat  26700

ggtaactgaa atgaaaaatt tgcttctagg gcccatcagg agatttgaac ag

#gaagaaga  26760

aagaaatttg aaggtagttc tattgacttt atctaatttg aagaacagaa aa

#ggaaaaaa  26820

gtaattagga aatataaata gagcctaaag agacctgtgg gataccatca ag

#tgtaccaa  26880

catacacatg acaggaatct cagaaggaga ggagagatgg tggggcagaa gg

#atatttga  26940

agaaataatg ggccaggtgc agtggctcat gcctgtaatc ccagaacttt gg

#gagaccaa  27000

aacaggcagg tctcttgagc ccaagagttt gagaccagcc tgcgcaacag cg

#tgaaaccc  27060

tgtctctaca aaaaatacaa aaattaacca tacgtgatga catgtgcctg ta

#gtcccagc  27120

tactcaggag gctgaggttg gaggatcact taagcccagg aggccatggc tg

#cagtgagc  27180

tgtgattgca ctactgcact gcagactgga cgacagtgtg gaaccctgtc tc

#aaaaaaaa  27240

aaaaagaaaa aagaaaaaaa gggaaaggga agtgaaatag tggctaaaac cc

#caaatttg  27300

atggaaaagc atgcatttat gcatacaaga agctcagtaa actccaagca gg

#ataaaacc  27360

agagattcac agctagacac atcataatca aactgttgaa agccaaagat ag

#aatcttta  27420

aagcggcaag agaaaagcag ctcatcatgt acagggtaac ctcagtaaga tg

#aacagcag  27480

acttctcacc agaaactatg gtgcccagaa ggcaatgggt tgatgtactc ac

#atccctga  27540

aaggaaaaag cccaacaaaa actaccatat ctggcaaaac tccccttgag aa

#atgaaaga  27600

gaaagaagat attcctcata aaccaaaact gtgagaattg tagctagcag ac

#ctgcctac  27660

aacaaatgct aaggggaatt cttccagctg aaatcaagat gcactagatg gt

#aactcaaa  27720

tctgcatgaa agaataaaga acatgggtca agttaactac atcggttaac tt

#agcactgg  27780

cccaagctgg ttcccagaaa aaggagaccg tccaataatc aactgccaga gg

#acaggaag  27840

gatgaaacca tatttttctc tcctcttcac tttcaggagc cctgcacact tc

#ccatattt  27900

cagtatataa tttttgagta aattagcaag gtgagatctt ttcaccagtc ta

#attctact  27960

aaaaaaaaaa aaaagtaggc ttagtattat tagtccatag ggaatgcagt tt

#aaaaccac  28020

agtgagatac ccctctatat tcaccagaat ggttaatatt aaatgaatgg ac

#attacaga  28080

gtaatggcaa ggataatgtt ggtaggagtt aaactagtat aaccatttgg gg

#aaactata  28140

tattatggct acttagcaaa acatgcctag cttataaccc tacaaatcca ct

#cctacata  28200

tattcacaac ataaagaagt tatacacttt aaaaattaca ctaaaagact ta

#cagaagaa  28260

tatttatagc agcactattc atagtaatag ctgaaagcta gaaatggatc ca

#agtaccta  28320

tcaacagggg gatgtataaa taaaatacat tatattcatg caattagata tt

#actcagca  28380

ataaaaagaa gcaaaccagt gatacataca acatggttga agctcagaaa ta

#tactaagt  28440

gtacacagcc agctgcaaat aagtatatac tgtaggtttc catttatatg aa

#gttcaaaa  28500

gtagctaaaa ccaatctttt gtgatagtag ttagaatagt ggttattctg gg

#gggctgac  28560

tgggaggcaa cacaaaagag actgttgagg ggctagaaat gatcactgtc ct

#atctaggt  28620

ggtggttaca tggctgtata tataaaattt tgagttacac acttcagaca gt

#gttgctgt  28680

taagatctgt gtatactcca tattatgaaa gataattttt aggatcttaa aa

#aaaatctt  28740

gattgctctg tcagtgttat tgaaatcaag gatgtataat attatcaagt tc

#aatcatcc  28800

taaaaggaaa ttcaattata gtttcatttt tgtaactgtt aaaagcatta ag

#atataaac  28860

atgttaaaca attctccttt gagacataaa cataaaaaca ggtctactga tg

#agtctgtt  28920

gattacccta ttgcatttta gccaatgttt aaatatttgg tcatgtatgt ta

#ttcttgaa  28980

gtgcagaatg tgcttagggt aattattagc aacatttaac caaattggtt ct

#gttatttc  29040

acgctggagg accagagcag gatgagtcag taaggggact tttgagaaat ga

#aatgtcag  29100

tgtttttgca accatttgta ggccataaaa aaaaaaaatc agatttgttc tt

#acaaagaa  29160

tgcaggactg gccaaacacc aagatgttgc tacacagaga gaataaaaca ac

#cagagaca  29220

aaaccacagc agaactgctt tcatccccaa attgcagaat aagtactgag at

#atgaccga  29280

gaaacagggg agagaaaggg taaacagtgg aggaaagaga tttttttgac ct

#tatgctaa  29340

ctattaatct gaagctagaa atgctgattt tatctgaaaa attagagctt tc

#cacagtta  29400

ttcatttatt caacaaatat ttgttaaact tccattatgt acctagaatc at

#cctgggcg  29460

cataagatgg agcagcagac aaaacaaaaa ttcctgccct tatggaacat at

#attggggg  29520

agggggtgtg gcagaaatgc atacacatat tgtacatgta gcaatgaggt ta

#gattagat  29580

ggctactttt tctctttctt tccttctttc cttcctttcc ttcctttcct tc

#cttccttt  29640

cgtccttttt ttttgacagg gtttccatct atcacccagg ctggagtgca gt

#ggtacagt  29700

cttggctcac tgcaacctcc tcctctcggg ctgaagtgat tctcctacct ca

#gcctccca  29760

agtagctggg attacaggca tgtgccacca cgcccagcta atttttacat tt

#ttagtaga  29820

gatgaggttt tgccatgttg cccaggctgg tcttgaactc ctgacctcaa gt

#gatccacc  29880

cacctcagcc tctcaaagtg ctgggattac aggtgtgagc cactgcaccc gg

#ccaaggtg  29940

gctacttttt aaagtatgcc atagtttagc cttcaactat atatgcctta tg

#gaacctcc  30000

agtttaatgc tgctgttgat acccctctta gattttctaa tgagaccttc ct

#cagcactt  30060

taataatgaa atctactata tgactcaagg ttgatgtgtc ttactcagtg gc

#aaagaaca  30120

gaataagaaa tagatccaaa catatcggaa tttaagacag tggaatgata tc

#ttacagaa  30180

aggagtcagg gtattgggtc ctaaaatcaa cacagatcaa agctgaaatt aa

#taaaatag  30240

agaaaaatag aataggataa ataaaaacca aaatcaattc tttgggatgg tc

#agtagaaa  30300

tgtaaaccct ttgcaatatt gatgaaaata aaagtgaata tgtatcataa ag

#gatgagga  30360

aagagaaata atcacaactg taaacgattt tttttttttt tgagacagaa tc

#ttactctg  30420

ttgcccaggc tggagtgcct ggctcactgc aacctctgcc tctcaggttc aa

#ttgattct  30480

cctgccttag cctcctgagt agctgggatt acaggcacgc gccaccacgc ct

#agctaatt  30540

tttgtatttt tagtagagac aggatttcac catgttggcc aggctgaact cc

#tgacttca  30600

ggtgatccgc ctgccttggc ctcccaaagt gctgaggtta caggggcgtg ag

#ccaccacg  30660

cccggcctat aaaagacatt tttaaaaaat gataggagaa tacaagaaag ta

#catttgta  30720

atacatttga aagtctagaa acagtggctg atttttgaag atagatggag ag

#cttcagta  30780

ggttgattag caccaaagag attaaacggt gattaagaga tatcatttaa aa

#aggaagag  30840

atgatacaca actgaattat ttctaatcag tggagaacag atgagtccga tg

#ctatttaa  30900

gctattttag tagatggaaa actccccatt cattttccaa agctatgatt ta

#atgtcaga  30960

acccaataga aattacataa aagaaaactt tagattagtt ttcttatgca tg

#cagatgct  31020

aaaaccataa ataaaatacc agtaaataga attcagcagt gtagcaaaaa ct

#gatcagct  31080

attatgacca aatagttttt atttcagcaa caaaagaata gttcactact ag

#aaaaatct  31140

gtcaacagaa tgtactacat caataaatta aaggagaaaa ccatatgatc at

#atcattca  31200

gtgctgaaaa ggctctgggt acaattcagt tgtcattcat aataaaagct ct

#taagaagg  31260

aacaggaaaa acactaccta gatatagtaa agactgcact caacatgttt tt

#actaagca  31320

tccattatat gcccagtaat attccagcag ttaacagaca aaacatttag ag

#ccatctca  31380

ttttttaaaa aagaaggagt tgaatgttta gtttgtcaga tggtaataag cg

#ctttgaaa  31440

taagaaataa agcagggaat aggaggttgc caagagctga gatgtaggaa tt

#gtcaggga  31500

aggactcatt ggtaaggtga tatttgagta gagaactgta ggagagcaag tc

#aacaaagc  31560

aggcaaaaat tccagccatc atgtatccta cggtctcatg gtgggggagg gg

#gcaataca  31620

aaaaacatga taaaaacata tagcatatta gaaggttata gtggaaaaaa gg

#aaaaacag  31680

aggaaagtaa aggggaccag ggcccagagg attttgaagg tcagattata aa

#gttagtag  31740

tctcattgag aaggtgatat ctgagcaaag tctcaaagga ggtgagggag tt

#agccaagt  31800

agatattaca ggaaggagtg ctccaggcag agagaagagt cacagtaaag ta

#gctatcaa  31860

gagaccacgc ctggcctagt caaggaccta caaagatgtc aataggactg ga

#gtagagtg  31920

aacaagggag tgtgtgaagg tcaggttatt ttatgtggga ccttgtagac ca

#ctggaagg  31980

actattttaa aaattacctt aatgaatttt tataaggcaa acactcttat aa

#ctattacc  32040

catgttaaga aatagaacca tatcagtcag tccagaagct ttttcatgta cc

#ctatccca  32100

aactaagtcc cctcctcttc tcccaaacta tccactattt tggcaccttt ag

#aaatcact  32160

tactctgctt ctttatactt ttattaccca aatgtgcatt tagacattgt ag

#cttattct  32220

tactcattaa aaataatttg acaagtcttc tcttttaatc gacagatttc ca

#agtgatcc  32280

attcctttct ttaccataca ctattttttg aagaacccaa gctatttagc ct

#gtaaagtt  32340

attcacaatc tgaattttgc tgattggaaa attgtgcagt tttgcaatcg aa

#ctgctgat  32400

tatccagcat gttcttctga attctctact tcctgtaaat tgatcgctga gc

#ccagaggc  32460

ttaatcacac tcaaggtctt atttggtgag gctatataca ttatgtgtgg tt

#gtcatttt  32520

tcttgtgatt ttagcagcca ttgatcctca gtgcctagat tcatcaattt gt

#tgactatt  32580

gtaaagtgct gatattctaa ttctgatctc ttttctacat cttacttgga ac

#aattttat  32640

gaagagacat atccttgcct ctatattttt tggttgccca gggttacagc tt

#ttcatata  32700

caaaaagcat aataaatact tgattctttt gcttttttgg ggccagtttt ca

#agataatg  32760

gtttggttcc ttttcatctt cccaagagac caattttata tgtttctatc tg

#ttgcaatt  32820

agcattttta ttgagttcaa attgttcctt ctctggccac tagatgcttc ta

#cacattac  32880

ctcctgagta cttttgctgt gacctcagtt gtgtctgata gcttccttgc ta

#cctggtat  32940

gataacatct ggtgtgacaa gatagtacat gctcagctga gcttagtgat ca

#gctgggac  33000

tacaggtgcc cgccgccacg cccggctaat ttttgtattt ttagtagaga cg

#gggtttca  33060

ccctgttagc caggatcatc ttgatctcct gatctcgtga tctgcccgcc tc

#agcttccc  33120

aaagtgctgg gattacaggc gtgagccacc gtgcctggct tgtttatttt at

#atcagtgc  33180

aagttggtac cctttgacct acatctcccc atttcctccc atttctgccc ct

#ggtaacca  33240

ccatcctact ctgctttgat gtgttttact tttttagatt ctgcatataa gt

#gagatcat  33300

acagtatttg tctttctgtg tctaatttat ttcacttagc ataatgtcct cc

#aggtttat  33360

ccatgttgtt acaaatggca gtgtctcctt tttaaaggct gcataatatt tc

#attgtgag  33420

tatatattaa tccatatata tgtatatatc catatccata tcgtatatgt at

#caccattt  33480

ctttagccat tcatccctac attttaggat tttttttttt cattttagga ca

#ttttcaaa  33540

ggattgtaaa aattctaaaa agagaatacg caacagatta ttctttggat ta

#tagagcct  33600

aaactatttg ctgtctagtc ttttacagaa aaaatttgct gacatacact ct

#agtagatt  33660

cttcagaaag tgtctgtggg aacaatattc tctgagtttg taactttgat aa

#cagctgct  33720

ctgtgccttt tatactttta caagtcattt ttcctggatg taagattctt gg

#cttatttt  33780

tcttccatat gtatattaaa tagattgttc aatttcttct gggggaaaaa ag

#tattgata  33840

ttctacaaga aaagaaaatt agaagccagt atttctggtg aatatagatg ca

#aaaatcct  33900

caacaaaata ttaggaaaca aaattcatca gcacatttat aaggatcatt ca

#ccataatc  33960

aaatgggact tatatttggg atacaaaggt gattcaaaat aatgcaaatt aa

#taaatgcg  34020

atataccaca tttacagaat gaaggacaaa aatcgtatga tcacctcaat ag

#atgcagaa  34080

aaggcatttg acaaaattca gcatcttttc atgataaaaa ctctcaacca aa

#ttagatac  34140

agaaggaagg tatgtcaaca caataaagac tatcataagc ccacagctga ca

#tcatcctc  34200

agtggtgaaa agttgaaagc ttttcctgca agatcaggaa caagacagaa ta

#cccactct  34260

caccccaatt cttttttttt ttttttttct gagacatggt ttcactctgt tg

#cccaggtt  34320

ggaaggcagt agtgcaatca cagctcactg cacctcctcc tccgggctca ag

#caatcctt  34380

ccacctcagc ctcccaagta gctgggacta caggcacata ccctcatgcc tg

#gctaattt  34440

ttgtatattt tatagagttg gggttttgcc atgttgccca ggctagtctt aa

#actcctag  34500

gctcaagcag tccactcacc ttgccctcct aaagtgctgg gattacgggt gt

#gagccact  34560

gtgcttggcc ttactctcac cacttctgtt cagtacagta ctggagtcct ag

#ccagagca  34620

attaagcaag agacagaaat aaaaggcatc cacatcagaa aggaagaaac ta

#aattgtct  34680

ctatttgctg atgacatgat cttacatata gaaagtccta aagactccac ca

#aaaattgt  34740

tagaactagt taatgaattc agtaaaattt caagatacaa agtcaacatt ca

#aaaatcag  34800

tagtgtttct atacactaac aatgaactgt ccaaaaaaga aatgatgaaa ac

#aatctcat  34860

tcacaatagc taccaaaaaa aagacttatg aataaattta aaatttaatc aa

#ggaggtga  34920

aagacttgta cactaagaac tataaaacac tgatgaaaga aactgaacac ac

#taataaat  34980

ggaaacatat cctgtattcg tggattggaa tattgtttaa atggccacac ta

#cctaaaat  35040

gatctataga tttcaataca atccctatca aaatttcaat gacattttca ca

#gaaataga  35100

aaaagcactt gtaaaattta tgtagaacta caaaaagccc caaatagtca aa

#gcaatctt  35160

gatagaaaag aacaaagctg gatgcatcac agtatttgac ttcaaaatat ac

#tgtaaagc  35220

tatagtaatc agaatagcat ggtactggca taaaaacaga catataaacg aa

#tggaactg  35280

aatagagagc ccccagaaat aaacccacat atttatggtc agttgatctt aa

#gggtgcca  35340

agaatacaca atagggaaaa gacagtctct taaataatgt tgggaaaact gg

#atatccac  35400

atgagaagaa tgaagttaga ctcttacctc acatcatata caacaaccaa ct

#caaaatgg  35460

atcaaagttt tatcttggaa aaaaaaaatt ttttttttct tttgagacag gg

#tctcactc  35520

tgtcacccag gctggagtgc agtggtgtga tcttggctca ctgcaacctc cg

#ccttctgg  35580

gttcaagcga ttctctcacc tgagccttcc tagtagctgg gactgcaggc at

#gtgccacc  35640

atgcccaact aatttttgtt gttgttttct tttttctttc ttttcttttt tt

#tttctttg  35700

gtagagacgg ggtttcacca tgttggccag gctggtcttg aactcctgac ct

#taagcaga  35760

cccaccttcc agctgggcgc ggtggctgac gcctgtaatc ccagcacttt gg

#gaggccga  35820

ggcgggtgga tcacaaggtc aggagatcga gaccatcctg gctaacacgg tg

#aaacccca  35880

tttctactaa aaatacaaaa aattagtcag gtgtggtggt gggtgcctgt aa

#tcccagct  35940

actcaggctg aggcaggaga atggcgtgaa cccgggaggt ggagcttgaa gt

#gagcgttg  36000

agatcgcgtc actgcactcc agcctgggcg acagagtgag actccgtctg aa

#aaaaaaaa  36060

aaagatccac tcggcctctc aaagtgctgg gattacaggc atgagccacc tg

#tacctggc  36120

ctcaaaatgg attaaaggtt taaatgtaaa acctgaaact gtataactat ca

#gaagaaga  36180

cataagggaa aagctctgtg acattggtct gggcaatgaa tttttggatt tg

#acctcaaa  36240

agcactggca acaaaaacaa aaatggtcat atgggattat gtcaaacaaa aa

#agctctgc  36300

acagtaaagg aaactatcaa cagagtgaag agacaaccta tagaatgggt tg

#atatattt  36360

gcaaaccata tatctgatat ggagttaata tccaaaatat ataaggaact ca

#attcggca  36420

agaaaacaaa tctaaaaaaa tgggcaaaga acctgataga catttatcaa aa

#gaagacat  36480

acaaatggcc aacagttata tgaaaaaaat gcttagcatc gctaatcatc ag

#agaaatgc  36540

aaattaaaac tacagtgtac ctcatacctg ttagaatggc tattataaaa aa

#gataggcc  36600

aggtgcagtg gctcacacct gtaatccctg cactttggga ggccgaggtg gg

#tggatcac  36660

gaggtcagga ggtcgagacc atgctggcta acacggtgaa accccatctc ta

#ctaaaaat  36720

acaaaaaatt agccaggtgt ggtggcgggt gcctgtagtc ccagctactt gg

#gaggctga  36780

ggcaggagaa tggcgtgaac ccgggaggca gagcttgcag taagccaaga tt

#gagccact  36840

gcactccagc ctgggtgaca gagcgagact ccgtctcaaa gaaaaaataa aa

#aaaaataa  36900

aaaaagataa caagtgttgg caaagatgtg gagaaaaggg agacctatac ac

#tgttggtg  36960

agactgtaac ttggtacagc cgttatggaa aacaacatgg aggttcctca aa

#aaattgaa  37020

aatagagcta ccatatgatc cagcaatccc actaccaggt atgtacccaa ag

#gaattgaa  37080

atcagaatgt ggtagatata cctgcactca catgttcatt acagcactat tc

#acaatagc  37140

caagatatca acccaagcat ccattcacag atgaatggat aaaaagaaaa tg

#cggcatac  37200

atacacaatg gaatactatt tagcctttaa aaggaggaaa tcttgtcatt tg

#caacatcg  37260

ttaataaacc tgtagaacat tattgtaaat gaaataagcc aggcatggaa ag

#acaaatac  37320

ttgggatctt atttctatgt agaacctaaa aaagtcaaat tcatagaagc aa

#gagtagaa  37380

tggtggttan nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn  37440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn  37500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#nnnnnnnn  37560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nn

#atatttta  37620

aaacatgtta tatattcagt tttcatcagt ttaaaaaact taatttaaaa aa

#aaaaagtt  37680

ttgatgttga aaagtctgat ctaattttct tctcctatag gtaatttgga ta

#cctatact  37740

ttgcctagat actcaaatat tttttcttta aagtgcaata attttaatat gt

#tttgttgg  37800

tcatcatata gcagatattc tcagatatac catgtgttct gtcaatatat ag

#attaaaaa  37860

aactttttaa aaataatgtt ttcttaaatt ttggttttta gtatttgctg tg

#ttcccttt  37920

gattctcttc ttcaaagact cctatttttc attaaagact ttttttgcct gt

#taatattt  37980

ttcactttct tttgaattgt tttatttctt cttaaatttt aaaaacattt ca

#tatatata  38040

tatatatgta tttttttgag gcagagcctc actttgtctc ccaggctgga gt

#gcagtggt  38100

gtgatctcgg ctcattgcaa cctctgcctc ctgggttcaa gtgattctcc tg

#cgtcagcc  38160

tctcaagtag ctgcgagtac aggcatgtgc catcatgcct ggctaatatc tt

#ctattttc  38220

aattagttta aattggaaag cttttaaatc tttgaaggca ttctatttca ct

#tataattt  38280

cttttaagat tctcttgtat ttattaactc ttgtcttcct tctagtttag tt

#tatttttg  38340

taatgatttt tccttccatt tctaaattcc tgagctctat caccttattt ct

#aatatgat  38400

ttatgtatca ttttctcagt gtcttttagc ttgttttaaa atagtaagtt ac

#aattttaa  38460

tgttttgtgg gcatgtcttt ttttctctat aggaatgttc ttcttcttct ct

#gttttctt  38520

ttaacaactc tttatggtat ttgaccaaat acttttttgt cactcatttt ta

#ctgaaaaa  38580

cagttttctc aagcttttgg gaggaggaat agttcaagct gtctttatta at

#ttcatagc  38640

tctccatctc ctgttttttg gttttgttct ggtaaagcgt taaataatat gg

#tggcttgc  38700

tttctgagac ttcctgactc catagcctcc cctcgcttgt atcggggcct tc

#tctttcct  38760

ttgtctctgt caccattgta attagcccaa ttctgattct cctcccagaa gt

#ttctaatt  38820

gcgatgtcct gtcctggaaa ggagctttgg ctggttggtt tcaagttcat gt

#ttcccatc  38880

tttctctggc ccctttgaga acctaccagt ggcccttata gtcacttttt gg

#tttgatga  38940

aacccttccc aatttcaact ggtgttctca aatagatctg ctctgatttt ta

#gagtttgg  39000

tttatggctg ctgtggtgtt tcccattctc agttttcaga tgcgttgttg ct

#tctttttc  39060

tttcaccaca ttaacattca ttccatgagg ggattgtggt tactgttggt tg

#tctccacg  39120

aacttgtatt ttggagtttg tgagctactt tgtcatctag ttttgttgtc ca

#tggtgttt  39180

tagttttgtt attggattac tttgcatgtt tttagggaat gatttggtga ga

#tgaaaact  39240

attcagaata gttttttcta tttggatgat ctcatcaaat catcccctaa at

#ctatacaa  39300

atcaggaaat ctattcaaat aggaaaaact attctgtgat tactcagatt cc

#ctctcatt  39360

tccagtgcct agtcactctg agtgactagg gagtcattgc aggattttga gc

#aatggagt  39420

gacatgacct gactggtgtt ttaaaggctc tgtctggtga tagactgaga at

#agaccata  39480

gaaatgtaga ggaagaagta gggggaccta ttagaagaat gttgcagaaa ta

#ggctgggt  39540

ggatcacttg aggtcaggag tttgagacca gcctggccaa catggcgaaa cc

#ctgtctct  39600

actaaaaata caaaaattag ctgggtgtgg tagtgggtgc ctgtaatccc ag

#ctactcag  39660

gaggctgagg ctggagaatt gcttgagccc atgaggtgga cgttgcagtg tg

#ctgagatt  39720

gtgccactgc actccagcct gggcaacaag aatgtgactc catctcaaaa aa

#aaaaaaaa  39780

aaaaaaaaaa aaaaattgca gaaatccagg tgagagatgt ttgcttggac tt

#ggggagca  39840

gcagtggagt taatgagaag tggccagatt tgcatatatt ttgaggtata gt

#tgataaga  39900

tttcctgatg gatttgatgt gaagtatgag agaatgtagt tgaaaaataa ct

#ctggtttt  39960

gtcctgagca actgtaagaa tggagttgct tttaactgag attagaaggc tg

#aggctgcc  40020

gtgcgggtaa ggtagacttt aggggtgaca taaagagctc agtttggact at

#gttgagct  40080

tgagatagtt attagacttc tgagtgaaga tactcttcgt gattctgcga gt

#cccatgac  40140

agcatgaggt aaaaaaagaa agacattggg ccgggcgcag tggctcacgc ct

#gtaatccc  40200

agcactttgg gaggtcgagg tgggcggatc acgaggtcag gagattgaga cc

#atcctagc  40260

taacacggtg aaaccccatt tctactaaat atacaaaaaa gtagctgggc tt

#ggtggcgg  40320

gcgcctgtag tcccagctac tgggaggctg aggcaggaga atggcgtgaa cc

#tgggaggc  40380

ggagcttgca gggagccgag atcgcaccac tgcactccag cccactgcac tc

#cagcctgg  40440

gtggcagaac gagattccgt ctcaaaaaaa aaaaaagttt atcatagaaa at

#tggaaaat  40500

atggataagt taggtaagaa aataaaaatc atgctgcatt gtaaacattc tg

#atatgatt  40560

ctaaacatac atataacatg catttagaac acatcgcttt tttctttcca ac

#ttttaggt  40620

tcagggagta catgcacagg tttgctaccg gtaaattgtc tgtcacgggg gt

#ttggtgta  40680

cagattgttt catcacccag gtaataagca tagtactcta tgggtagttt tt

#cgatcctc  40740

accttcctcc caccctcgac ccttaagtag gcccaagcgt ctgttgttcc cc

#tttgtatc  40800

tatgtgtgct cagtgcttag ctagcactta taagtgagaa catgcagtat tt

#ggttttct  40860

gttcatgtat taattcgctt aggataatgg cctccaactc catccatgtt gc

#tgcaaagg  40920

acactatttc atttttttat agctgtgtag tattccatgg tgtatatcta cc

#acattttc  40980

atcatccagt ccactgttgt gggcatttag gttggttcca tgtcttagct at

#tgtgaaca  41040

gtgttgcgat gaacatacag ttacatgtgt ctttatagta gaacgattta ta

#ttcctgtg  41100

ggtatatatc cagtaagggg gttactgggt ctaatggtag ttctgagttc tt

#tgagaaat  41160

cttcgaactg ctgtccacag tggctaaact aatttacatt cccaccagca ga

#tataagca  41220

tactcttttc tttgttttgt tttgttttaa aactaaagct tattctggcc aa

#tttactct  41280

actattttct aataacagct catagatcag aaacggtctt tgttttaaac tt

#tcctatcc  41340

atatgaaaca caatgatgtt ggggtaagag gggccttttc tctaaatgaa aa

#tacaatac  41400

ttattctgta caattctaga gggcccagag atgtggaaat aatgtatttg ta

#agaattat  41460

attaaacaat ctttatttga taaatagtac cttacaatcc taatgctatc ta

#tcaagctt  41520

cagtaagagc aatttcagca tcaagtaatg aacagtagct aaactgacaa ga

#gatcaatc  41580

aaaagggctt taaatggagc agcaccagct gatgtgctgc taaggctctg gg

#cattcagg  41640

actctcctat ggggaaaacg gaatcaaacc agcaggtgct ctggacctaa gc

#cttcacat  41700

cgtgacctgc ctccctcctg ggggtgtggt ggcccacagt ccccctggca tt

#tctcggcc  41760

cttgtgggct gcagacggaa atcctggcac caaaggacag cttgggaaag gc

#tgaaactt  41820

gacctcacag tcaactggct tctgcctatt gtggtcattt tctttccaga gc

#acctagag  41880

cactcgcaca gtggacgtgg aagccaccca gcattcttgg gctgttttct ca

#tagaagag  41940

gaccttcctc taagcattgg aagcgtcttt ctccaattcc tgggccagat ct

#tgggccat  42000

cttcttgtag gtcatgggtc tgacacacat ggttcaagtt ttcgtggcta tt

#gtgaatgg  42060

gattgtgttt ttgatttagc tctcagctcg gatattgttg gtgtatggaa at

#gctatttt  42120

tgtacaatga ttttgtatcc tgaaacttta ctgaagttgt ttatcagatc ta

#gaagcttt  42180

tgggcagaga ctgtggggtt ttctaggtat aaagtcatat cgtctgcaaa ta

#tggaagat  42240

agttgacttc cactcttcct ggatgccttt atttttctta ctactctatc ta

#ggacttcc  42300

agtactgtgt tgagtaggag tggtgagaga gggcatcctg gtcttattct gg

#ttctcaat  42360

gggaatactt ccagtatggt atgcttccag cagcacatca actggtgctg ct

#ccctttaa  42420

agcacttttg attgatctct tgttagttta gctattgttc attacttgat gc

#tgaaattg  42480

ctcttattga agtttgatag atagcattag aattgtaagg tactatttat ca

#aataaaga  42540

ttgtttaata taattcttac aaatacataa tttccacatc tgtgggccct cc

#agaacatt  42600

tcagcatgtt ctggatgttg gctgtgggtt tgtcatagat atcacttatt gt

#tttgaggt  42660

atgttccttc gatgcctagc ttgttgagag tttttaacat gaagggatgc tg

#aattttat  42720

tgaaagcatt ttctgtgtct atcgagatga tcatgtagtt tttgtcttta gt

#tctgttta  42780

tgtgatgaat cacatttatt ggtttgtgta tgttgaaccc accttgcatc cc

#agggataa  42840

agcctacttg attgtggtgg attagctttt gatgtgcttc tagtctctgt tt

#cctagtat  42900

ttttgttgag gatttttgca tctgtgttca tcagggatat tggcctgaag tt

#ttcttttt  42960

ttgttgtatc tctgataggt tttggtgtca gaatgatgct gacctcatag aa

#taagttgg  43020

caaggagtcc ctcttcctga atttttggga atagtttcag taggtttggt ac

#aaggtctt  43080

ctttatacat ctgatagagt ttggttatga atccctcctg tctagggctt tt

#tctggttg  43140

gtaggttttt tagtactaat tcaatttagg aactcattat tggtctgtag aa

#cacatttt  43200

cacaaagttg aatttctatt gtatatacat tttaaaatct tctttcacaa ga

#catgacct  43260

gagcattttc taatagtgaa agtctttgaa aacatggttt ttaatggtat tt

#cattacat  43320

gttttactgt aataaaccta accacttgga ttatgtactc tttcactcat tc

#ctttttgc  43380

atatctgttc catcccctat gctttaatat ggaggatttg gtttcttgta gt

#agttgctg  43440

ggtatcataa ttcagacctg tggtttggca gtcagcctgg ctgtagtgtt ta

#actgagtc  43500

tcgtggaaga tccatgctta aaatgaatgt cgtggagaat tgtattcacc tc

#agtcattc  43560

aagactttgg catagacccc attccttgag gaggagttgc cgccactgtg ac

#tgccacag  43620

acggaaggaa gcctgggcag ttgggactgg ggagaacttg ctgagtcaca ga

#tatcttgt  43680

ctcagtgtgc atgggccgtg tgtattgaaa tgtaccagtc tgtgaggcac ta

#tgttttga  43740

ggtctcagta agctaaaggg gtgtagaatg gtatctagtt cataccgtag ta

#tgctttag  43800

atctaagtgt tggttaattc tgtaaggact gaaggaatag gggagattta at

#gagctcct  43860

tgcagtctgc aggttattat cgagaaaaga aaattaggct ctcagttcca gg

#cccatttc  43920

cctctaatca ctgtgtcctt ttgaacaaaa gttggcaaac tttttctgta aa

#gggccaga  43980

tatttttagc tttgcaggcc atatgatttc tgttgtaagc attgagctct tc

#tgttatag  44040

agcaaaagca gccataggca gtacaggaac aaatggccat ggttatgttc ta

#gtaaaact  44100

ttatttacat aacaggcagc aggccagatt ggagcaatag ttgtcaactc ct

#gctttgaa  44160

aatgttttgg aaactgtgtc tccgtctgtt agtggtcatt atcctcagtc tc

#ttaggatc  44220

agagtttttc ttagattaca aaactggatc atacagacct gacttccagg tc

#tgcgttct  44280

ctccactaca ctttgctgcc tcttagaaaa acataagcta aataactaga ac

#ccatggaa  44340

agagggaaaa gtgaagccca gagagctgat gcgggactaa gaggcaactc tg

#agagtttc  44400

aatgtggaat gtttgtgtgg ctccccaacc agaccgtgac ctccttgaag at

#tgggactg  44460

catcgtatct tgttctcatt ttctatttta ttttaatgat ctatcctttg gg

#ttgaacga  44520

atgtgtttct tgaacccgat aagtgcaaca ctgagtaaac acttgtttct tt

#tctccctt  44580

ccatcctccc aacttagtag cttcaataca ttcttagctc tcctcacttg ct

#attctcta  44640

accataccac gtggctgggc acggtggctc atgcctgtag tcccagcact tt

#gggaagcc  44700

gaggtgggca gatcacctga ggtcaggagt tcaagaccag cctggccaat gt

#ggcaaaac  44760

cccactaaaa atacaaaaat taactgggta tggtggtggc ctgtaatccc ca

#gctactca  44820

ggaggctgag gcaggagaat cgcttgaacc caggaggcag aggttatagt gt

#gctgagat  44880

tgcgtcactg cactccagcc tgggtgacag agcaagagtc cgtctcaaaa aa

#caaaaaca  44940

aaaaaaaccc caggttatct ccatgaatgt gaatattgat gtggtccttc tg

#tcaggaag  45000

acatcacctg agaccacaca cagaaagcct atttttcctt aggatacagt cc

#tacatcag  45060

ggttgacaaa gtttttttgt aagggttaga tagtaaatat tttagatttt gc

#aagccata  45120

tggtctcttc ctcagctact caactctgcc gttgtactac aagagcagcc at

#agacaatc  45180

tatacatgaa tgagtgtggc tgtgttccag taaactttac ttatggatat tg

#atactcag  45240

atttcacatg attttcatgt gtaatgaaat gtgattattt ttatttaaaa ca

#ttaaaaat  45300

gtaaaagcca ttttttgctt gcaggccaga caaaaacagg cagtgtgagt ca

#atttaatt  45360

taatgtgtga ctcatagatg ctaacccttg ccttagctgc ttagtaactt gc

#cctagtca  45420

tgtgttaccc catgaaaaga atggcctact tctgtcatat tgtctctaac ct

#ctgtcatt  45480

tcatttatga tgctatgtat tatgtgtacc tttgtctctc ttgctggatt ct

#gagtatct  45540

tgagaggtag gccatggcct agtcagtcat ctttgtatcc ttaatatcaa ac

#ccacatag  45600

tgggtattta agaagtgact gttgaatttg aattttatgc ttgatatata ta

#aaatgtca  45660

tttctgctga tcttaaagag aaacacttga ctgatatgca taggtttccc at

#gttcttcc  45720

ccttgagagg ccatagttaa ctgcatttgc tgctagcggc tcttgtaaac tc

#agtggtta  45780

tacagcaaag cctttgcaaa gtcttttatt ttagagctct ttttcagaca ag

#aaatgatt  45840

atactttttc ttcaaatcat ttattcaatc ataatgataa atatggcttt ca

#ctattctg  45900

atgaagcaga gctaccatca gtgtgaaata ataatagccg ttgtttagtg ag

#catctact  45960

acattccagt caattcagat tttttctcta gatttttggt gaccttctga tt

#actattaa  46020

tttacatttt tttttattgt tctctacatg tcaaacaaaa caaagcaaca at

#atcaaaaa  46080

cccacatgct ttttcttcat actgtctata ttattgaatg acagacaaac at

#ctgtcctt  46140

caagtcaaat attaattaat catagactcc tttctcttct tcttcacccc gc

#cttatcta  46200

attggccact gtcttagctt tttttttttt ttttttttta aagatggagt ct

#taccctgt  46260

tgcctagtct ggagtgcagt ggtgtgatct cggttcaccg caacctccat ct

#cctgggtt  46320

caagcaattc tcctgcctca gcctcccaag tagctgggat tacagacatg ca

#ccaccaca  46380

cctggctaat ttttgtattt ttagtagaga tgggatttcg ccatgttggc ca

#ggatggtc  46440

tcgaactcct gacctcaaat aatccaccca ctttggtctc ccagtgtctt ag

#cagtttta  46500

aaaattatct ttggaatttg tctcatctct atttctaatt catttaatct aa

#ttgaagcc  46560

ttaatcattt cttttcttcc aacatgttga gcatctgttc tgattttcct ga

#ccccactt  46620

gcctcattct ccaattattc ttcccatagt tatcagcact gaatgctaat aa

#taatactt  46680

tgttcatatc agttgttatt aaaactcttc acttattcct tattatcttc aa

#ggtaagcc  46740

cagcttccca gtcatgacat acaagactct atgtgtgacc ccaatactta ac

#acagatgt  46800

gtttcagaat tcagaatttt ttggatttta gaaaagtaat acggtttatg ca

#atacatat  46860

ataacatcct ctgctcattc ctgaacactg atgggagtga atggcaggtg ct

#tttaataa  46920

ttacgctgag gtaaattatg ctaggtgtaa actggacctg tcctgggcaa ac

#gaggatgt  46980

tctttacaca gtttaagaat gtcaagcaaa gaacattagg gatgaagcaa ta

#cagggaga  47040

atagatagag tgaagggagc agtgggttaa gtggagtcct ggagaaatat tt

#gaaaaggg  47100

agaaaggaat gtggctcctg aggtaggagg gaaacctgga gcaggtagcc cc

#acagaagc  47160

ccagggaaga ggcattgttt ttctattatt ttggaagcag atccccttta gg

#agactcct  47220

catcagataa tgattattca ctaagaggtt atattcttaa ttaaaagggc ct

#ttaccttt  47280

tcttagaata ctatgtttga ataacttttt atgtattacg atataaaagt ct

#cttttaag  47340

catttctgtt ttatagtcat ttggccaaaa tctaattcag atccagctta aa

#tccaaatg  47400

tcatttgatg ctacatttta tcctgaggtt gctagttatt tagtcaaata ta

#gtgagtat  47460

aatcactaca ggcttagagt aaatttccat gtcaagaggt agaacacatt ta

#ttctgtaa  47520

tattgaatcc tgtaatattg aaaatcaaaa acagcccttt tttttcttct gt

#agaaaata  47580

agatttttaa ggaaggcagc aggaaaatag aacaagtgaa tattttacgt tc

#ttagtggt  47640

ttatggttgg cagttttccc ccaacatttt gttacgaaaa gttaaaatgt ac

#agaagaat  47700

tgaaagactt atacccacca gctagattgt gccattaaca tgttgctgta tt

#tactttat  47760

cactgtccat ctctctgacc atctatttgt ccctctttcc atccatcagt ct

#gtcttttt  47820

tttggtaagc atttcaagta agttgactgg caatttttct aagcagctgt at

#ctttattt  47880

tgttactgtt tttttcctgg atgttgtaat tacagtgtca agacatttaa ta

#atgcacat  47940

gtttcagcta acccttttcc caatttctag aaatctgaga ttgccaataa tc

#cctgtcaa  48000

tcttaaatta ttttttaatt ctggtaaata gtgtcaaacc tgattagtgc cc

#tctttctc  48060

aattgttttg taatccagac aactgttagt cattaaaaca taatttatag tg

#gttttaaa  48120

gcatgatttt ctaaaaaatt ttaaataaat atttattcat attatgttgt tt

#tcagagtg  48180

gagagatcta cagaccaagt aatcaagcca gtcaatgtag gagctctatc aa

#aatgggtt  48240

gggaagatac cgccagatgt tttacaagac atggcagtga ttgctcctat gc

#ttgccaag  48300

cttggatatg acccatatgc caacccacct aactacggaa aacctgatcc ca

#aaattatt  48360

gaaaacactc gaagggtaag tgagattttt taaagcaact gagaaaacta ga

#ttttgaat  48420

ttgggatctg aatacgtttt tttcttattt tatttcttgc tatttaatga tc

#agaaaaat  48480

atattttttt ttttttcatt tatttttatt ttattttatt ttattttttt ta

#ttatactc  48540

taagttttag ggtacatgtg cacattgtgc aggttagtta catatgtata ca

#tgtgccat  48600

gctggtgcgc tgcacccact aatgtgtcat ctagcattag gtatatctcc ca

#atactatc  48660

cctcccccct cccccaaccc caccacagtc cccagagtgt gatattcccc tt

#cctgtgtc  48720

catgtgatct cattgttcaa ttcccaccta tgagtgagaa tatgcggtgt tt

#ggtttttt  48780

gttcttgcaa tagtttactg agaatgatgg tttccagttt catccatgtc cc

#tacaaagg  48840

atatgaactc atcatttttt atggctgcat agtattccat ggtgtatatg tg

#ccacattt  48900

tcttaatcca gtctatcatt gttggacatt tgggttggtt ccaagtcttt gc

#tattgtga  48960

atagtgccgc aataaacata cgtgtgcatg tgtctttata gcagcatgat tt

#atactcat  49020

ttgggtatat acccagtaat gggatggctg ggtcaaatgg tatttctagt tc

#tagatccc  49080

tgaggaatcg ccacactgac ttccacaatg gttgaactag tttacagtcc ca

#ccaacagt  49140

gtaaaagtgt tcctatttct ccgcatcctc tccagcacct gttgtttcct ga

#ctttttaa  49200

tgattgccat tctacctggt gtgagatgat atctcatagt ggttttgatt tg

#catttctc  49260

tgatggccag tgatgatgag catttcttca tggttttttg gctgcataaa tg

#tcttcttt  49320

tgagaagtgt ctgttcatgt ccttcgccca ctttttgatg gggttgtttg tt

#tttttctt  49380

gtaaatttgt ttgagttcat tgtagattct ggatattagc cctttgtcag at

#gagtagga  49440

tgcgaaaatt ttctcccatg ttgtaggttg cctgttcact ctgatggtag tt

#tcttttgc  49500

tgtgcagaag ctctttagtt taattagatc ccatttgtca attttgtctt tt

#gttgccat  49560

tgcttttggt gttttggaca tgaagtcctt gcccacgcct atgtcctgaa tg

#gtaatgcc  49620

taggttttct tctagggttt ttatggtttt aggtttaacg tttaaatctt ta

#atccatct  49680

tgaattgatt tttgtataag gtgtaaggaa gggatccagt ttcagctttc ta

#catatggc  49740

tagccagttt tcccagcacc atttattaaa tagggaatcc tttccccatt gc

#ttgttttt  49800

ctcaggtttg tcaaagatca gatagttgta gatatgcggc attatttctg ag

#ggctctgt  49860

tctgttccat tgatctatat ctctgttttg gtaccagtac catgctgttt tg

#gttactgt  49920

agccttgtag tatagtttga agtcaggtag tgtgatgcct ccagctttgt tc

#ttttggct  49980

taggattgac ttggcaatgc gggctctttt ttggttccat atgaacttta aa

#gtagtttt  50040

ttccaattct gtgaagaaag tcattggtag cttgatgggg atggcattga at

#ctgtaaat  50100

taccttgggc agtatggcca ttttcacgat attgattctt cctacccatg ag

#catggaat  50160

gttcttccat ttgtttgtgt cctcttttat ttccttgagc agtggtttgt ag

#ttctcctt  50220

gaagaggtcc ttcacatccc ttgtaagttg gattcctagg tattttattc tc

#tttgaagc  50280

aattgtgaat gggagttcac ccatgatttg gctctctgtt tgtctgttgt tg

#gtgtataa  50340

gaatgcttgt gatttttgta cattgatttt gtatcctgag actttgctga ag

#ttgcttat  50400

cagcttaagg agattttggg ctgagacgat ggggttttct agataaacaa tc

#atgtcgtc  50460

tgcaaacagg gacaatttga cttcctcttt tcctaattga atacccttta tt

#tccttctc  50520

ctgcctgatt gccctggcca gaacttccaa cactatgttg aataggagca gt

#gagagagg  50580

gcatccctgt cttgtgccag ttttcaaagg gaatgcttcc agtttttgcc ca

#ttcagtat  50640

gatattggct gtgggtttgt catagatagc tcttattatt ttgagatacg tc

#ccatcaat  50700

acctaattta ttgagagttt ttagcatgaa gggttgttga attttgtcaa ag

#gccttttc  50760

tgcatctatt gagataatca tgtggttttt gtctttggct ctgtttatat gc

#tggattac  50820

atttattgat ttgtgtatat tgaaccagcc ttgcatccca gggatgaagc cc

#acctgatc  50880

atggtggata agctttttga tgtgctgctg gattcagttt gccagtattt ta

#ttgaggat  50940

ttttgcatca atgttcatca aggatattgg tctaaaattc tcttttttgg tt

#gtgtctct  51000

gcctggcttt ggtatcagaa tgatgctggc ctcataaaat gagttaggga gg

#attccctc  51060

tttttctatt gattggaata gtttcagaag gaatggtacc agttcctcct tg

#tacctctg  51120

gtagaattcg gctgtgaatc catctggtcc tggactcttt ttggttggta aa

#ctattgat  51180

tattgccaca atttcagagc ctgttattgg tctattcaga gattcaactt ct

#tcctggtt  51240

tagtcttggg agagtgtatg tgtcgaggaa tgtatccatt tcttctagat tt

#tctagttt  51300

atttgcgtag aggtgtttgt agtattctct gatggtagtt tgtatttctg tg

#ggatcggt  51360

ggtgatatcc cctttatcat tttttattgt gtctatttga ttcttctctc tt

#tttttctt  51420

tattagtctt gctagcggtc tatcaatttt gttgatcctt tcaaaaaacc ag

#ctcctgga  51480

ttcattgatt ttttgaaggg ttttttgtgt ctctatttcc ttcagttctg ct

#ctgatttt  51540

agttatttct tgccttctgc tagcttttga atgtgtttgc tcttgctttt ct

#agttcttt  51600

taattgtgat gttagggtgt caattttgga tctttcctgc tttctcttgt ag

#gcatttag  51660

tgctataaat ttccctctac acactgcttt gaatgcgtcc cagagattct gg

#tatgtggt  51720

gtctttgttc tcgttggttt caaagaacat ctttatttct gccttcattt cg

#ttatgtac  51780

ccagtagtca ttcaggagca ggttgttcag tttccatgta gttgagcggc tt

#tgagtgag  51840

attcttaatc ctgagttcta gtttgattgc actgtggtct gagagacagt tt

#gttataat  51900

ttctgttctt ttacatttgc tgaggagagc tttacttcca actatgtggt ca

#attttgga  51960

ataggtgtgg tgtggtgctg aaaaaaatgt atattctgtt gatttggggt gg

#agagttct  52020

gtagatgtct attaggtctg cttggtgcag agctgagttc aattcctggg ta

#tccttgtt  52080

gactttctgt ctcgttgatc tgtctaatat tgacagtggg gtgttaaagt ct

#tccattat  52140

taatgtgtgg gagtctaagt ctctttgtag gtcactgagg acttgcttta tg

#aatctggg  52200

tgctcctgta ttgggtgcat aaatatttag gatagttagc tcctcttgtt ga

#attgatcc  52260

ctttaccatt atgtaatggc cttctttgtc tcttttgatc tttgttggtt ta

#aagtctgt  52320

tttatcagag actaggattg caacccctgc ctttttttgt tttccatttg ct

#tggtagat  52380

cttcctccat ccttttattt tgagcctatg tgtgtctctg cacgtgagat gg

#gtttcctg  52440

aatacagcac actgatgggt cttgactctt tatccacctt gccagtctgt gt

#cttttaat  52500

tgcagaattt agtccattta tatttaaagt taatattgtt atgtgtgaat tt

#gatcctgt  52560

cattatgatg ttagctggtg attttgctca ttagttgatg cagtttcttc ct

#agtctcga  52620

tggtctttac attttggcat gattttgcag cggctggtac cggttgttcc tt

#tccatgtt  52680

tagcgcttcc ttcaggagct cttttagggc aggcctggtg gtgacaaaat ct

#ctcagcat  52740

ttgcttgtct ataaagtatt ttatttctcc ttcacttatg aagcttagtt tg

#gctggata  52800

tgaaattctg ggttgaaaat tcttttcttt aagaatgttg aatattggcc cc

#cactctct  52860

tctggcttgt agggtttctg ccgagagatc cgctgttagt ctgatgggct tt

#cctttgag  52920

ggtaacccga cctttctctc tggctgccct taacattttt tccttcattt ca

#actttggt  52980

gaatctgaca attatgtgtc ttggagttgc tcttctcgag gagtatcttt gt

#ggcgttct  53040

ctgtatttcc tgaatctgaa cgttggcctg ccttgctaga ttggggaagt tc

#tcctggat  53100

aatatcctgc agagtgtttt ccaacttggt tccattctcc acatcacttt ca

#ggtacacc  53160

aatcagacgt agatttggtc ttttcacata gtcccatatt tcttggaggc tt

#tgctcatt  53220

tctttttatt cttttttctc taaacttccc ttctcgcttc atttcattca tt

#tcatcttc  53280

cattgctgat accctttctt ccagttgatc gcatcggctc ctgaggcttc tg

#cattcttc  53340

acgtagttct cgagccttgg ttttcagctc catcagctcc tttaagcact tc

#tctgtatt  53400

ggttattcta gttatacatt cttctaaatt tttttcaaag ttttcaactt ct

#ttgccttt  53460

ggtttgaatg tcctcccgta gctcagagta atttgatcgt ctgaagcctt ct

#tctctcag  53520

ctcgtcaaaa tcattctcca tccagctttg ttctgttgct ggtgaggaac tg

#cgttcctt  53580

tggaggagga gaggcgctct gcgttttaga gtttccagtt tttctgttct gt

#tttttccc  53640

catctttgtg gttttatcta cttttggtct ttgatgatgg tgatgtacag at

#gggttttc  53700

ggtgtagatg tcctttctgg ttgttagttt tccttctaac agacaggacc ct

#cagctgca  53760

ggtctgttgg aatacactgc cgtgtgaggt gtcagtgtgc ccctgctggg gg

#gtgcctcc  53820

cagttaggct gctcgggggt caggggtcag ggacccactt gaggaggcag tc

#tgcccgtt  53880

ctcagatctc cagctgcgtg ctgggagaac cactgctctc ttcaaagctg tc

#agacaggg  53940

acacttaagt ctgcagaggt tactgctgtc tttttgtttg tctgtgccct gc

#ccccagag  54000

gtggagccta cagaggcagg caggcctcct tgagctgtgg tgggctccac cc

#agttcgag  54060

cttcccggct gctttgttta cctaagcaag cctgggcaat ggcgggcgcc cc

#tcccccag  54120

cctcgctgcc gccttgcagt ttgatctcag actgctgtgc tagcaatcag cg

#agattccg  54180

tgggcgtagg accctctgag ccaggtgtgg gatatagtct cgtggtgcgc cg

#tttcttaa  54240

gccggtctga aaagcgcaat atttgggtgg gagtgacccg attttccagg tg

#cgtccgtc  54300

acccctttct ttgactcgga aagggaactc cctgacccct tgcgcttccc ag

#gtgaggca  54360

atgcctcgcc ctgcttcggc tcgcgcacgg tgcgcacaca cactggcctg cg

#cccactgt  54420

ctggcactcc ctagtgagat gaacccggta cctcagatgg aaatgcagaa at

#cacccgtc  54480

ttctgcgtcg ctcacgctgg gagctgtaga ccggagctgt tcctattcgg cc

#atcttggc  54540

tcctcctccc ccagaaaaat attttgaatt agaaaaattt gggcctagtg gc

#ctggcacg  54600

ctggctcatg cctgtaatcc cagcactttg ggaggtcgag gcgggtggat ca

#caaggtca  54660

ggagatcgag accatcctgg ctaacacggt gaaacccctt ctctactaaa ta

#cacaaaaa  54720

attatccagg cgtggtggtg ggcgcctgta gtcccagcta cttgggaggc tg

#tggcagga  54780

gaatggcatg aacccgggag gcagagcttg cagtgagtag agatcacgcc ac

#tgcactcc  54840

agcctggatg acagagcgag actccatctc aaaaaaaaaa aagaaaaact tg

#ggcccagc  54900

atagggctga cacctgtagt ttcagcactt tggaaggccg agatgcgagt ga

#gcccagga  54960

tttcaagact agcctgggca acatagtgag acccccatct ctacaaagaa ta

#taaaaatt  55020

atccaggcat ggtggcacat gactctagtc ccagctactt gggaggctga gg

#tgggagga  55080

ttgattgagc ctgagaggtc aaggctgcag tgagctgaga gtatgccact gt

#actgtagc  55140

ctgggtgaca gagcaagacc ccgtctcaaa ataagaaaaa agaatgaaga aa

#aattatat  55200

ttgtagaatg ctttcttatc agcagtcttc cactgcattt taaggataac tg

#gctcgttg  55260

gggatagttc ttagggtatt ttgctcagtt tctaggaatg atactcactg tt

#gggagatt  55320

tattctcagc caattactgc agatctgcat aaacaccata attattagtg ac

#cttacttc  55380

tgatttcttt ctttctgtaa atctaatagc cactttactt ttaaaccttt gt

#ttagatga  55440

ggcataattt ttggatacct aaaagctaaa cattggttac actagaaaaa tt

#attaaaca  55500

ctagccttct gattaagaga aagttgctat taaagtgaca ttacagtttt ta

#ttttaata  55560

agttatgctc acgtctttac aatatattat ttcagaaagt gctgaaaatt ca

#gagctaga  55620

ttatatagcc taccagttga gtctatttca aatcagatct tatacattct tt

#tctttatt  55680

gcagtaagat atatttaaca taaaatttac cactctgaca ctttttaaag tg

#cacaattc  55740

agtggcatta aatacattca cattgttgtg caactgtcac caccgtccat ct

#ccagaaca  55800

ttttttgtct tcccaaactg aaattctgta cccatactct tcattgcctg gt

#ccctgtca  55860

actgcagttt tttgtgtcac ttgtatatat tcttttttga aactacattt ca

#aataagac  55920

aaccatgcta gcataagttc actgataggc tatttgattc caaggtgaaa at

#tccttggc  55980

tttgtctgaa ttctcttgtt tatatcagtg tccttccctc cctacaacca ta

#taaccgta  56040

tcatgttttt attctgtctt ttgataactt taattgacaa atttatgcca ca

#tttatttc  56100

atgagattaa tttctatgtg aattcctttc tcttaggtat tacttttatt tc

#cccttttc  56160

aattcattat tagcagctat atgggaagag ctgccttctt gtaaaccatc ac

#atatgagg  56220

gcaaattaaa aaaaacaata atcgctatcc tctttacact ttttatatat at

#ataaatat  56280

ttccattata aaaatataag ctcattatat gaaacttaca aaattcaaag ga

#taagagaa  56340

taaaaatcac ctgtaatgtt cccacctaga cacatacaca tattattctt tt

#ttattttc  56400

ttatttattt acacatatta ttcttaatat tttgatgtat tttctctcct ct

#gcattatg  56460

ttaaacaaag gtaagattac gtatatcatc ttacctttat atacacagtt tt

#gtatccag  56520

tccttttaat attcacgagc attttcccat tgtgtgcatg ctttttaaac at

#aattttta  56580

tagttataaa ccttcataga agccacctta aattctttct gaagcacagt ag

#taaatgaa  56640

tgaataaatc aacaaacaaa atacatttcc ctggtagatg ttctacaatt ga

#ttttacca  56700

ttttgttgtt taccgttttc tctttgacaa attgtgctgc agtgaacatc tt

#tgcagata  56760

ctcaatttta ggattttttt tttaaggtag gatcaataaa aatagaacta aa

#ccagggta  56820

aagtatctga gatttttaaa aggtgtttga tatctattga tactaaaaaa cc

#tttgggct  56880

ggccacagtg gctcacgcct gtaatgccag cattttggga ggctgaggtg gg

#tggatcac  56940

ttgagctcag gagttcaaga ccagcctgga caacgtggca aaaccccatc tc

#tacaaaaa  57000

atacaaaagt tagccaggtg tggtggcaca tgcctctggt ttcagctgct tg

#ggaggctg  57060

aggtgagagg attgcttgag cccagaattt tgaggttaca gtgagctgag at

#tgtgccac  57120

tgcactccag cctgggtgat ggagcgagat cctgtctcaa gaaaacaaaa ac

#aaaaaaca  57180

aacaaacaaa aaacctttga actgccagca taattgaggt aatttatttt ag

#atttttgt  57240

tggttttaat agatttcatt gattaatgta attgaacatt ttccagttat ta

#gctatatg  57300

tatatattct tttatgaact aagtttttac tttatttatt tgagacagag tc

#ttgctctg  57360

ttggcacaat cttggcttac tgcaacctgt gtctcctggg ttcaagtgat ga

#ttctcttg  57420

cctcaggtgg gattataggc acatgctacc acgcctggct aatttttttt aa

#ttttttat  57480

ttttagtaaa gttagggttt cgttgtgttg gcctggctga tctcaaactc ct

#gacctcaa  57540

gtgatctacc tgccttggcc tcccaaagtg ctaggattac atgagccact ct

#ttaaagtt  57600

ttatatgtat taaagttttg tgagctcttt gtaattggta attcatagct at

#ctcctttg  57660

cacaatagtg aaagggtttt ttattaccaa gatacatgta caatgctatt tt

#gagggttc  57720

ttaggcagta gacattatag ttttcctaca tgcaaattgg cttggctaga tt

#atcctttg  57780

ctttcttgag tggtgggttg ggaagaatgc tatggtttga atccatgtga ct

#aaagaatc  57840

tatttcatac acacttgtgg tttttgaaag gatttcaaaa tacccactga aa

#taaaaaaa  57900

cacccaccct ttcccccccc cccccccgtc tctgcctatc tttaaagtga ca

#gataattt  57960

tgaggaagaa aagatgaagt gtgaactata gtggtgtttt tgggcctttt gt

#ggtaatgc  58020

atacaaactg acagtcttgt cttgtgaggg taggtttcat aagacctttt tg

#caaactaa  58080

atcctgtgta tcttcaaagc ttttttgcct gtaataagtc agatgctaat gt

#atccagca  58140

ctgatgatca tgaggttttt gtaaagcagt gcttgaaaag agattgttga cc

#gttagcta  58200

tgatatgaga tgggccccag agaaagaggt ggctggcgaa ggtgttttcc tt

#agttatgg  58260

ggtgagagtg ggagaaaaat aacattttga ctgagaatat aggatttata tc

#tctaagcc  58320

taaaaatact gggttggttt tttttttttt tttttttttt tggtacaatt ct

#gggtagtc  58380

tgcaagtaat attgagtcag cacattttag ggacatatta cccaatattg aa

#tggataat  58440

catgcttcat ggttactgtg actcacatag taaattggta atgaaacgtt aa

#catatttt  58500

ataccctgtc ccaccatagt ctctaatcct aaaattatag tatatttcag ta

#aatggtgc  58560

tgtctaggtt acatcgtcag ccttcttgca tagattctta accttttaga ct

#taggaact  58620

tatttgagaa tttgatgaat cctgtggatc cccacctcag aaatacagac ac

#atgaatac  58680

acagatttca ctcacaattt cagtggatac atagatatac cagaagtcca tc

#agattaag  58740

gactcctatt agccacaatt tcagtggatg catgtgtgcc agaagcctga ca

#gattaagg  58800

actcctattt tatagtctcc ttgctcaagc tcatccactc atagggcttt ca

#ttacagcc  58860

tatttgctga ttatcataaa tctgtatttc ctagtgggtc tctttcctga gc

#cctaggtt  58920

cattatttcc aactgtcttc tgtatgtgtc caccgaaatg ctctcaagga cc

#tcaaattc  58980

aaagtccaaa attgaattta ttttctaaac ttgttccctg agaggcagaa gc

#taggtgga  59040

attgttcatt aaactgagca ggaatccacc ttgagagtgg ggatgatgct gt

#gctcatct  59100

atacttgcgg tacctatgag ccagagagca gatttgagga acagagtcct ca

#gggcacat  59160

ggctcaaacc ccaaaacaat tcaagaacct ggttgctaaa gttagagagc tg

#aaaagcag  59220

atccaattta tgaatggaat atttagttgg aaacctgagt agatagtact ga

#ggaagagc  59280

aagtgatcaa atggaaaagc atgtaccaag gtgcagaacc cacagtaaca ga

#caagaaga  59340

aacatgaaaa tgaagtcagc tgggggacag gggttagatt aaatccctaa ac

#caaacaac  59400

aaaaagctgc agcagcagtt ggaattgata ttcttacatt aaaggtaaag cc

#tggaatga  59460

atgcatactt gtgttttctg gttcctatac tcagcaaaaa ctgcttgttc ct

#gttttttt  59520

ctatctccat acatagcatg cttattcacc cagttaccca aattaggtct cc

#tcacttaa  59580

aattcatgaa tgactccact gttactacag gatagagtct agacttctta ga

#atgacatt  59640

tacttttcta gtatttgggt attttctcat tatctttttg ttgttgattt ct

#aatgtgac  59700

cattatggtc agagaacact cattatggtt tgtttcagtc ctttgaaata ta

#ttgaatat  59760

tgttttatgg ccagtatatg gtcttatgtg atcagttgaa aaaatatgta tt

#ctgtgatt  59820

gttgcagagt tctgtaaata tcagtgaggt caagaaattt tatagtgttg tt

#acagtcta  59880

aatcttattt gattttttgg tctgctttat taatgttggg aaaattatga at

#ttttcaaa  59940

ttttccttac atttctagca attttgtttc atgtatttag gatctatatt at

#tgggaaca  60000

cacccattta gaccttcttg aagaagtaac tcttttgtaa ttatgaaata tt

#tctcttta  60060

tctctgctgt taccctctga aagtctactt tatctgatat gaatatagcc ca

#acagtgtt  60120

tttatgtata ctatatacat ggtatatttt cccgattctt ttacttttaa tc

#tgtgtctt  60180

tatatagctg gctttgtttg ttaatccagt tttatagtct ctgcctttta aa

#tggagagt  60240

taatccactt acatttaatg taattattca tctgattgga tttaaaacta cc

#atcttgct  60300

atttgttttt tatttggatc atctattttt gtttctttgt ttctcttttc ct

#gccttctt  60360

ttggattaat cttttttggt attccatttt atatattatc tcctcttttt ag

#ctatacct  60420

cttctttttg ttttgttttt gcttatagtg gttactgtaa gacatgggct gc

#acattttt  60480

tatattgtaa aaatccagat agtaggccgg gtgcagtggc tcacacctgt aa

#tcccagca  60540

ctttgggagg ctgaggcagg tggatcacaa ggtcaggaga tcgagaccat cc

#tggctaac  60600

atggtgaaac ccccgtctct actaaaaata caaaaagaat tagctgggct tg

#gttgtggg  60660

cacctgtagt cccagctact tgggaggctg aggcaggaga atggcatgaa cc

#tgggaggt  60720

ggagcttgca gtgagctgtg atcactccac tgcactccag cctgggcaac ag

#agcgagac  60780

accgtctcaa aaaaaaaaaa aatccagata gtaaatatat tatgctttgt gg

#gccacagt  60840

tgggctcttt gttctttact tgaagatcca gattttcatc tggcatcatt tc

#tctttagc  60900

ctgatgcact tcctttagca gttcttatag taaagacatg ttgactacta at

#gctcttag  60960

gttttttttt ttttttttaa tttgaaaatg tgtttgtttt ttttttaatt tg

#agaatatt  61020

ttgctggaca tagagttcta ggctattggt cgttttgtat tttttttaac tt

#tcaacatt  61080

aaaaagatac tattttattg gcttcccatg tttttgatga aagtcagctg ac

#attcttat  61140

gaatgtaatt ttttttcttt gactgctata agatttttcc ctatttttgg tt

#ttcagcag  61200

tttgattata atataccaaa ttcgtagctc cgttctactg ccatctcctg tg

#tgggcctc  61260

agttttgatt agtttttatt agcctacctt tgaattcatt gatcccttct tt

#ttctgtgt  61320

ccagtctgct gttaaaccca tctggtgact tcttcatttc agatcattta tt

#tttcagtt  61380

ctagaatttc cctttctctg ctggaattct ttgctcttta cccattctgt tg

#atcttttc  61440

ctctaaatta tttaacatat tcataataac ttttaaagtc ttcatccacg ga

#tctctccc  61500

tgttgacttt gtttctttat tatgggttat aggcacacct tggagagact gt

#gggtttgg  61560

ttccagacca ccaaaataaa gtgaatatcc caataaagca agtcacacat aa

#tttggttt  61620

cccagtacat ataaaagtta tacactacat tgtagtctgt tcagtctgta gt

#agcattgt  61680

gtcaaaagaa aacacaatgc atatgcctta atttaaaata ctttattgct aa

#aaaaaaaa  61740

tgctagcaat catccaagcc ttcagcaagt cataatcatt ttgctggtgg ag

#actcttac  61800

ctccatgttg atgactgcta gaccattcag ggtggtggtt gctaaagatt gg

#ggtgacta  61860

tagcaatttg ttttgttatg taatattcta tatcctttgc tgtcttttca ac

#aatattca  61920

cagcatcttc accaggagta gattccatct caagaaccac tttctctgct ca

#ttcttaag  61980

aagcaactca ttcattcaag ttcaatcata agattgtagc aattcaacca ca

#tcttcagg  62040

ctcacttcta gttatagttc ttttgctatt tctaccacat ctgcagttcc tt

#cctccact  62100

gaagtcttga acctctcaat gtcatccgtc tgattcttcc aaattcctgt ta

#acattgaa  62160

attttgacct cctcccatga attacgaatg ttcttaatgg catctaaaat ga

#tgaaccct  62220

ttccagaagg tttgcagttg actttgtgca aatccatcag aggagttggt at

#ctatggca  62280

gctatagtct taagaaatgt atttcttaaa taataatctt gacagggcca gg

#tgcagtgt  62340

cttaaacctg taatcccagc actttgggag gccaaggtgg atggatcacc tg

#aggtcagg  62400

agttcaagac cagcctggcc aacatggcga aactccatct ctactaaaaa ta

#caaaaatt  62460

agctgggtgt ggtggcgcat gtgtgtaatc ccagccactc aagaggctga gg

#caagagaa  62520

tcgcttgaac cggggaggga gaggttgcag tgagccaaga ttatgccact gc

#actccagc  62580

ctgggtgaca gagcgagact ccatctcaaa aaaaaaaaca aaaaacaaaa cc

#aacttgac  62640

agtagaaatt actccttgat ccgtggacta cagaatggat actgtgttag ca

#agcatgaa  62700

aacagcattc atctccttgt atatctctat cagaactcat gggtgacaag gt

#gcattgtc  62760

aacgagcaat agtattttgt gagaaatctt ttttcctaag caataggtct ca

#acagtggg  62820

ctgaaaattg catttttatg ttatggagat agcttctttc cttaatcttc at

#aaacaaac  62880

aacctctact agcctccaac ttttcctctc acagccttta taaaattgaa ga

#gaattagg  62940

gccttgctct ggattaggct ttggcttaag ggaatgtcat ggctggcttt at

#ctgtctag  63000

tccactaaaa cttttgccat gtctacagta agactctcac tttcttacca ct

#tgtgtgtt  63060

cattggagta gcacttgaat ttacttcaag aacttttcct ttgtattcac aa

#cttgacta  63120

tttgatgcaa gaggcctggc tttcagctta tcttggcttt caacatacct tc

#ctcactaa  63180

gcttgattgt ttctagcttc tgacttaaag tgagagatat gcgactattc ct

#ttcgtttg  63240

gacacttaga gcccattgtt ggattattaa tcggcctttt ttcaatatca at

#gtgtcaca  63300

ggaacagggg aggcccaagg gagagggaga gagatggggg aacaaacagc ca

#gttggtgt  63360

agcagtcaga acatacacaa cattgattaa gttaattatg ttatatgggc tt

#aggatcgt  63420

ggcaccccaa aacaattaca tggtaacatc aaagatctct gatcgcacat ca

#ccgtaaca  63480

gatacaataa tgaagaaggt tcaaatattg caagaattac cacagtgtca ta

#aagagaca  63540

tgaagggagt gcatgttgtt ggaaaaatgt caccaacaga cttgctcacc ac

#aggattac  63600

cacacacctt caatttgtaa aaaacacaac atctgcaaag cacaatgaaa tg

#aggtatgc  63660

ctgtactcat ttgcttcttc acatgtctta gaagttttaa ctgcatactg ga

#ccttttgt  63720

ataacagagg ggtagagaat gaactaggta atactttttg ttttattttt gt

#taaagaga  63780

gcagttcttt cctccagcag gtagctaagg tgatcactca aatttgacag tg

#aatcaagc  63840

tgagctgggg ctgagcagta gctttaattg atttcagttt gcctctggat tc

#aaatgaga  63900

ttaaggaaat ttgactttta gcccaacctt agctttctat atcatttaga cg

#aggggttc  63960

atttctttga ttttagcaag attgcagctg ggaggcagtt gggttgaaga tt

#aaattaat  64020

ttactttacc tctggattgc aactatagca gggccctgga acccaagcac ca

#cacagcat  64080

tgggagatct ctttctgtct ctcactgtgc tcccaccagc acttactaag at

#tctcttgt  64140

agtattacat gtaattgtca ggtcaagaga tttgttttta cacttgggac tc

#tttcagat  64200

tctaattaat cataccagtc cacagtctca ctaaaagttt ggcttgtttc ag

#caaaatct  64260

ttccacctat gggagacctc cttttctgcc cacttgtacc cagacaggca at

#tgattcaa  64320

ggtagctaga aacaggcttt tgtttctctg tgaagaactc atccttctcc ag

#aaattggc  64380

tcagttagac ttcttggcat tcatttactg ctttttcatg gctttacaga aa

#agtatgaa  64440

gtttagttta tctggtgttt tcttgttttg atgagagcag tggtcttttg gg

#atcagctg  64500

cattcaaacc aggttggaac gctttagaat gatggcatta agattctttg cc

#ttctgctt  64560

tcaaccttcc ttttcaacct catctctttt tattctttta accacaccac ag

#tgcctccc  64620

tttcattccc acagcacatt gtatacctcc atacctttgt tccttctgcc tt

#gattgtcc  64680

ttcttctcat cttacaactt tgtcctttga aactcaactc acatgacacc tc

#ttctgtgc  64740

cacagatcct cctgctacaa tgtacctacc tttacttgtg tactttcaca tt

#atattgtg  64800

atgatttata ttatatgctg ctgcttttaa actaaggaca tgccagacat gc

#cttcatct  64860

gaaaatgtta atatagttca aagtgttgct atagtctttg tttagttaaa gt

#aacaactt  64920

tctggtctga aaaaaaaaag actatgcatc ccttcaacag aataagatag tt

#ttaaaagt  64980

aatgatatgg gagcatctct taagatatgg tcagtgttat gttttaccat tt

#gtatttag  65040

aaaaacagct gtgtgtgtat gtatgtatgt atgtatgtat gtatgtatgt at

#gtatgtat  65100

taatttattt tgaaacggag tctcattctg tcacccaggc tggagttcag tg

#gtgcgatc  65160

tctgctcact gcaacccccg cctcctgggt tcaagcaatt ctcccacctc ag

#cccctaga  65220

gtagctggtg ttacaggtgc atgccaccat gcctggctaa tttttatatt tt

#tagtagtg  65280

acagggtttc accaagttgc ccaggctggt ctgaagctgc tgacctcagg cg

#atctgctc  65340

accttggcct ctcaaagtgc tgggattaca ggcgtgagtc actgcacctg gc

#ttgtatat  65400

gtagtttttt aaaaaaataa ataagtaaag acttttcaag gacaaagata tc

#atttgcat  65460

tttgtagcct gagtgccagt aatacttgac aattacttga tgctcaataa aa

#tgattctt  65520

attagcaaaa taaaccttac acgtagaaaa agaatatgcc aggaaccaag aa

#aagggata  65580

ttcagatatg aggctcttgg agttacggct cagctcacaa ggattctgcc gt

#aggtgaga  65640

aatgctccat tacccagagg caaagcccca gaggttgtgg cagcacttta tg

#actatgta  65700

tcagtctggg ctcagtcagg gaaacattga gccactgtta agtgttatag ga

#gtgagggg  65760

tttaatatag taattaaggc ctatgcaaat atgggaggac tagagaagtg aa

#ggtctgca  65820

cgttttttat tgtatactgg acacgttgtt tacaatagga gtagggaatg ag

#ctggatac  65880

agctacagtt ggaagaccag aggaataggc actgatgact gaaacctgca gc

#tctagaga  65940

gggcagagaa gtgctaggaa actgcctctc gctgccaaag taggactcag tg

#tgggatcc  66000

caaggaaagg tctgtgaaga ctgccacggg gataaagtgg agctttagga ga

#ggccagtg  66060

gagcgactgc atctgactgc cctgacctct taaaaataat ggcttctact tc

#atttccac  66120

cttctaaaac tcacagaagc ctctgaccca gaaccacaca gggaaaggaa tt

#ctgggaga  66180

cttaattttc tgtcctagac aacagtggtg gtggtgccag ttgaccatcc ag

#cataggcc  66240

attcctttgc cagcctggct tacatacaca cctacttaaa ccatatttaa ct

#gccagata  66300

aagctaaatg ctctgcttaa catgttgtaa ctatcgctta gcaaactgaa aa

#catgctaa  66360

gcactccctc aaagaggaga tgctgtattt catattgtgc tttgtacatt tc

#tggctgat  66420

atgaatgtat tccactagct gagtcacatc ccctctttga tatcctaaaa ct

#tacatata  66480

ctgagataca gagttagcca tttccttttt ttttttttct tggcaaggtc tt

#gttctgtc  66540

acccaggctg cagtgcagtg gcgccatcat agctcactgc atccagaatc tc

#ctgggccc  66600

aagcgatccg cctgccttag cttcttgact ataggtgtgc accaccacac ct

#agctaaat  66660

tttttttatt tttaactttt tgtagagaca agaggtatca ctgtgttgcc ca

#ggctgctc  66720

ttgaactcct ggcctcaagc aatcctgttg ccttagcctc tcaacgtgtt ag

#gattatag  66780

gcatgaacca ccgtgcccag ccagagtcaa tacaccttat attagagagt at

#tattagac  66840

agggaaaagt ggaaaaaaga attcgttaat atattcagta tatattcata tc

#aaagcaaa  66900

gaagaatatc tgccaaacta ttgtagttct cattttctgt acctttcatg tg

#atcatggc  66960

aggtatctgt catttctttc ttcctctagc cattccatgt tcctttggtc ct

#cagtagtc  67020

acctcagatg gtctttgttc tttgcctggt ggggtggcct aaaccttcat tc

#tggggtgt  67080

atgtaccaat aaatggccat attgttttgc tctaatatcc cgttaacttt cc

#ataataaa  67140

caagtgtaat agaaaatcct aggttccagg caatttcttt ccttcttcca tt

#gagtattt  67200

ttttcccatt gtgtatttta aacttggttc ttccttgata atcgggatca at

#cagcctag  67260

ctattatagt acctgcctta cttgtctttg gctaagtggc atgaggagca ag

#aagtgctg  67320

agttaacagt ctcagctctc tgttcagtgg aaataatgtt gtgtctcccc ca

#aagaagca  67380

cttctccctt gaggattaag acctgtaaac tgggagagcc cacagctgct gc

#gagttttc  67440

ttttggggaa ggattttgat aatatttagt gaatataggg ctatttcgat tt

#tcttgttc  67500

ttgtatcaat tttgataaat tgtatttttt aaagtaattt ggccatttca ct

#taagttgt  67560

caaatttgtt ggcaggaagc tgcagtattt tcttagagtc cttctaatct tt

#gtcaaatt  67620

gatagtgata acttttctat tcctcatgtg atgacccctt gattccgcct ct

#gtccacac  67680

ctgttagtga ttccctccac ctgaatgtgg acaggacctg tgacttgctt gg

#aacgaata  67740

gaatacaaca aaggcgatgg gagatatgtg attgcatgat tatattatat aa

#gattacag  67800

cactggactg gctggagtgt gcacgtctct ctctctctct ctctggacat aa

#agactgtt  67860

atcttgtata gactctgggt tcctttataa tactcttgtg aatgcattta ct

#tttgtttt  67920

agcaggcaat caactcaggt aggctggatt atacattgtt ttgccttttg ca

#ggcagtga  67980

ttcaaatccc aattcagtta tcaaagcaaa gcctttgcta aactggtttg gg

#tttgtcct  68040

gtgcatgtgt gattcagagg ttaaggtgag acccgtgtag gtgcatacat aa

#aagtggag  68100

agctccttca cctgctgttt ctgctccagg agtttgctct gactccctgt ct

#ttctttgg  68160

ctcctttccc tgcttgctct gaccagaaag aaaacaattc ctatcagagt tt

#tagccacc  68220

tacgtgtgct gcttagtgac tgaagctgtc ccaccctcaa ggaaaaactt ga

#tgagaaaa  68280

aaataaacaa acagaaaact caccctgtaa ggtcacttct ccaacttttt ac

#ttccctcc  68340

acaatctgcc tgcttttatt tactttccag atcctcatat agttttttgt tt

#tgttttgt  68400

tttgctgtgt tttgagatgg agtttcactc ttggtgccca ggctggagtg ca

#gtggcaca  68460

atcttgtctc actgaaacct ccccctcccg ggttgaagcg actcttttgc ct

#cagcctcc  68520

tgagtagctt gggattacgg gcagccgcca ccatgcacgg ctaatttttg gt

#atttttag  68580

tagagacagg gtttcaccat gttggccagg ctggtcttga actcctgacc tc

#aggtgtcc  68640

cacccacttc agcctcccca cagtgctggg attacaggtg tgagccaccg cg

#cctggccc  68700

aaggtagtta ttttttaaaa gtttgctcaa actttatagt tgtaattaga gg

#gaggaaca  68760

actttatggg atgtaggtgg cttaacctca ccataatgga accaaaactc ca

#cttcattc  68820

actttttttt tttagatgga gtctcgctct gtctgcagtg atgagatctc gg

#ctcactgc  68880

aaggtccgcc tccccgggtt catgccattc tcctgcctca gcctcctgag ta

#gctgggac  68940

tacaggcgtc tgccaccacg cccggctagt ttttttgtat ttttagtaga ga

#cggggttt  69000

caccgtgtta gccaggatgg tctcgatctc ttgacttcgt gatccgcccg cc

#tcggcctc  69060

ccaaagtgct gggattacag gtgtgagcca ctgcgcccgg cccacttcat tc

#actttaaa  69120

atgaagtact tgaccagaag cagtactgtt tagaatgcca ttatggtgaa ta

#agatattt  69180

tgtaagggaa aggatgctgg tttttgacag aaatgttgtg ggcagagaag ga

#aatcttca  69240

ttgagtaaaa gcagtgtcct ttttagatgg aagcggtcca gtgtgatcat cc

#tgctacag  69300

atggctgccc agaccccctg ggagcagcgc tttattgggg caccattgtt gg

#cctctcct  69360

gttggcaggt tggacactta gccatgattg ttgccaggtc agccttgaca gg

#tggaagcc  69420

tgtgtcactg agcacatgca tgaccttcat tcctgttgct ctcacagtag ga

#tatgaact  69480

ttgttcatta gcgttctgag caagggaaac agtggctgat aaaataatga gt

#cattttgt  69540

ccacttggtt attgagagcc tcctctgctg agattataca ttggtcatca tt

#tacatggg  69600

acacaaatac cctcacactt tgtcctgttt gagaatagtt tattgacata gc

#tcttttct  69660

atatcttacc acaagtttcc caaccttatt ctaagtttct gaatttccag tc

#aaaccatc  69720

tgctgctgac cacaaatcag tgtggattcg tatttatagc catcactcct tt

#gacacaaa  69780

atgtgcagtc atgtacactg cttcgagtgt atgatgagca gcctaagcga ct

#tgggcaac  69840

ttggtagcca gtggtaaagt gttcagtcct tactaaatcc tagtagcaag ca

#agggctct  69900

ttctcaaaag ggagagtaat gatctccaga agttagcata gctttgctct aa

#aatcctag  69960

ggttctatac tgtgatttac ctctagggcc tgccatacct ccacacatca ct

#catgaagt  70020

atcatcctgt atcttaagtt tttgttggcg atactaatct ctgcagttcc tc

#taggaatg  70080

cagtattact tttggtgtaa tattttggta gagagaggca gctctaatgt aa

#cccctgag  70140

gtatggcttt agtatgctac ccatctctgt tagtcctagg gacaccatca cc

#aatcagcc  70200

accaccagag atctctacag ctcacaccat tctcttttcc tactctacct ct

#gcgtgtgc  70260

ttataaagta tagccatgtg cccattgttt ctgtcatgaa gcgtcaccag tt

#ggctgctg  70320

tgactcagag atcttttcat ccttcccttg ggttcaggga atctatttct ct

#gacagcct  70380

ttcccattgt tatttctagc ctgcagcgaa caagcactaa agagcttttt ag

#ggatgttg  70440

ttgccccctt caccaatgta tttctcaaag gcttggtaaa ggagtgagtt ct

#ctagacat  70500

tcctgggatg tagttaggag atcagtgaac agatcagtca tacgtattaa at

#acacccca  70560

gtattcctta ttttctaacc ttttgaataa attttatttt gagactgagt tt

#tgctcctg  70620

ttgcccaagc tggagtgcaa tggcactgtc tcagctcatt gcaacctctg cc

#ttccgggt  70680

tcaagcactt ctcctgctca gtctcctcag tagctgggat tacaggtgcc cg

#acaccatg  70740

cccagctaat ttttgtattt ttagtagaga cagggtttca ccatgttggt ca

#ggctggtc  70800

ttggaactcc tgacctcagg tgatccaccc accttggcct cccaaagtgc tg

#ggattaca  70860

ggcatgagcc actgcacctg gcttgaacaa cttttattta cagtatacca ag

#gaggttct  70920

ggcatctaag cttcatttaa tgtaagccac tgatggatcc aggttttggc ca

#accaggtg  70980

aggaaattgt tagagttatt ccctgattac tcaagccaat atactgcatc ca

#aaatatct  71040

ggttaatgta ctcatatatt gataaatttg accaagtcca acgttacatt cc

#ttcttgtc  71100

tggtctaaca ttcttaggat tcattgctac acacttccta ggtttctgca ag

#tacaaatg  71160

ggcaaaatct agcacaatga ccctagccct ctgagggtca cagcaggttg gt

#tcaggagt  71220

aggaacctga cccaacacag gcaaataaag gtctttccct gggactgtga aa

#tggtacca  71280

agggaagaaa ggtggtttct ctctggtagg gagggccact ggatataagg ca

#caggaact  71340

gttgctggaa gcgttagaca ctgctgactg cttgttcctt tttccctgtt ag

#taaagact  71400

attcctttaa aaaaccaaaa aaggtagata aaaatgccag atattcattt tc

#ccatatac  71460

tcttgtgggt ggaatgacca cttgaccatt tttttgtagc cagtgataca ta

#aggagatt  71520

tttttttaac agggaaaaaa agagcttaca aattttatgt gcacatgtgt gc

#atgggagt  71580

tatacaattc ttttaaaaaa aaaactcaaa tggctagatg attgacactt tt

#gtaccacc  71640

ctgagataca gaaagaatag gggcttggat catggccaaa caagttatgg tg

#gcaaaaca  71700

ggttatggga ggaagagaag accacctttg cctggctagc aaaggtagtc tt

#gaactctc  71760

acaggcagca gccctcagaa agaatggata gtagccagtg ataaatgttt ct

#agcagacc  71820

tttaaaggtg ttagactctc agttaatcat tcttaggtct ggataaggag at

#gtttgcta  71880

gggattttct gggagagatt tagctttctg agaaaataaa gaattgtgtg aa

#aagagctt  71940

actctttcct tcctgctttt gaacattgct gtgaaagaac attatgctta gc

#cctgctgc  72000

agccactttg tgatcctaag agaagttatc atcaataaca cactgaaggt ga

#cagaagga  72060

agattagggc agaggcttcc cttgatttct gggcttagga ctgtccatcc ac

#ctcatgtc  72120

tggacttctt gttatgtgtt tgacatactt gtactcagtt attctattac cg

#tgtgttca  72180

ctgcaaatgg ggtcgtgttc ctcagtgtgt aagggaataa agccaaccca tc

#gagagaag  72240

cagagccaaa gaggtcaagg gagtgtctgg caggggttga ggtcctggtt ct

#ggttgccc  72300

atgaagatca tttccagctc tgcccttgcc acagttccag gaaacatttc cc

#tttttgac  72360

tgtattactt gaattgggtt tctgggctgt agtaggaata ttccaactaa ta

#ccatactg  72420

ggtaaatttg aagtatgata aattttaagc tacttctcac tttatttctt gt

#gcctaaat  72480

ttgaagagta tttatttatt tatttattta tttatttatt tatttattta tg

#agacaggg  72540

tctcgctctg ttgcccagag tgctctggaa tgcagtggca cgatcatagc tt

#actgcagc  72600

cttgacttct tgggctcagg tgatcctccc accttggcct cccaaagttc tg

#ggattata  72660

ggcatatagg catgagccac tttgtctggc ctaaatttta gttaaagaaa tt

#cttatctc  72720

attctttcag aattttcata ggccttcaaa gcaacaacca tggagttaaa tt

#catttcct  72780

caacttggca ggattttttt tttcccctat tgaagtattt tgtctttttt tt

#gtgtgtgt  72840

gtgacagggt ttcactcttc gctctgttgc ccaggctgga gtgcagtggc at

#gatgatag  72900

ctcactgtag ccttaaactc ccctgggctc aagccatcct cccacctcag ct

#ccctgagt  72960

agctgagacc ataggcatgc accactatgc ccaactaatt attgtatttt tt

#gtagagac  73020

aagatgtcac catattaccc aggctggcct caaactcctg agctcaagtg at

#tcacctgg  73080

cccggcctcc caaagtgctg ggattacagg agtgagccac tgtgcccagc ca

#ttttgttt  73140

tattttgaaa gaaggctgaa ttgattcctg caggcattct gtaaagaata ta

#taaggaag  73200

ttcaaagtag cacattttac catctctcag aatacctcag tctttcttct ga

#tgcatcac  73260

tttaaggctt cgattattaa acaagcaatt actaaacagt tgctttttgg aa

#tactacct  73320

tctagtgctt caggagatgc aaagatctgg cttgtatcca ggaagaaaat ac

#aggtaatt  73380

ggattggaga gagaagacat gccatagaag aaaatgaaat aataataaga tg

#ggagaaga  73440

atttttactg tgttttaaag ggttaaaaac tgttggaaac ctaaaaattt gt

#ccacagga  73500

cgaggctgaa agtctgagac taccccacag gaatagcctt gtcaaggcct ga

#ttgtgccc  73560

tttgactcat ccttcaaagt caaacctttc tcatcttctc tcccagcttt gg

#cactgtca  73620

ttccataagt gtatcccaat aatttgtgtt ttctgccaga aatccttttg gg

#gctaatga  73680

gtttcatgca cttgtatttg ctgtgtaaag taggttttcc tatacttgta ct

#taccagat  73740

taaatgtcaa aggatccagc tctttgttgg ttttgtgtac aagcacaaat tg

#cacttgct  73800

catgccattc agaatttcgt acattttagt tgtcttttac aactgtaatc cc

#atctgaag  73860

gtctatggga aattcagttc cttaagaaat aggttcccct catccttctc tt

#tctgcctt  73920

cattagtgag agtacttttt gagagcaaga gaacatttgc agtgaagagg tt

#tagttgga  73980

tagctattta tacagttttc cttggaattt taaagaatga aataatttct ct

#ttatgtca  74040

gcaaatgcct attctgaaca ttcagaatga ctgttctgaa cagtaatgtt ta

#actcttaa  74100

aaaacatggt atttataaat gagaatataa taaatcagta ttagaagtca tt

#ttttaccc  74160

catgctctaa ttcaggagaa aataggagat acttataggt taacttggtg tc

#tgattacc  74220

agtgcctgat ataatttctc caattccctt tttaaaaatc tattaaaata tc

#gttaattt  74280

aaaaaatccc tttaaaatga agatatgaaa agctctatgc taaagaatag gg

#aaattttc  74340

cactaagtcg atcattgatt gtattgtggc ttttccttaa acccaaagat ta

#cccaaaga  74400

ttactgtaga agtgacacta cgaaaaatca aattaatgat agggagagta ta

#cattagat  74460

gctcttccag aatgtccagc aaaagaccag agatgaagat tgatagatga ga

#gaaaatga  74520

tacctatgaa agaaaaaaat agagatttaa ctggtgacta atagatgtct gc

#aaaggagc  74580

caacagaagt ggaacaaaag catggatcaa atgtctcatt gtggaagact tt

#ccagggtt  74640

gaaaatgacc tgaagaataa aagagctcac tgtattctaa agaacattat ga

#aaacgtgt  74700

ctgtacctag acatattttg ctggttttct tttgatttta aggatcctga aa

#aaaaaaaa  74760

aatcctgcat atatcaaggc acaaaaaaat gagctttcaa caaagaaaca aa

#aatgatgc  74820

tggtagccag gcgcggtggc tcatgcctgt aatcccagca ctttgggtgg cc

#aaggtggg  74880

cagatcacaa ggttaggagt ttgagaccag cctggccaac atggtgaaac cc

#tgaatcta  74940

ctgaaaatac aaaaaattag ctgggtgtgg tggcatgtgc ctataatccc ag

#ctactcgg  75000

gaggctgagg caggagaatc atttgaactc gggaggcgga ggttgcagtg ag

#ccaagatc  75060

atgccataac tctccagctt gggtgacagg gcgagacttg atctcaaaaa aa

#ataaaata  75120

ataaaataaa ataaacaaat tatgctggct acaaaatttt cttttgcaaa ta

#ctaaatgt  75180

tggaaaatga tggagcagtg ggcagtgatc cttagcttat gtggtctttg aa

#ctccctgc  75240

agtaatattt ggacctctat gtcttgatgc aagttgattt tcctgggaat ag

#aatctata  75300

tcgttcctca tattttccag gatttcatga aacaaagagt taagaactac ag

#tagtggag  75360

caatattcat ggtgcttttt ctttttcttt tgaaataatt aaaaacttac ag

#aaaggctg  75420

taagaataat acagagaaat cctgtgtatt ctttcccaaa ttcatgtgtt tg

#tcttctct  75480

ctctttctct ctccttataa aatatttcaa tgttgttagt tatctcaaaa tg

#gactttgt  75540

agtttttttt tcctccccta ccagtacagg tttcagtcta agatcacatc at

#atatatag  75600

ttttatattg ttttagtttt ctttatctgt aacagtttct cagatgctct ct

#gtcttcca  75660

tgatactgat atttttttga agaatgctgg caggttattt tacagtgttc ct

#cattctgg  75720

gtttgtctga tgtttcctct tgattattat tcgggttatg catatgaggc ca

#caatacta  75780

ggtaaattgt gtggtttcat tctcaaggta tccacatctg aaggcgtatg at

#gttcatct  75840

gtcacaccgt tgatgttaat ttcgatctca tggtaaatgt gttttttcgg tg

#tctccact  75900

ctatggttac ttttttatcc ctttcaatta aaaaacaatc agtggtcggg ca

#ctgtggct  75960

catgcctatg atcccaacac tttgggaggc agaggcagga ggatcgctta ag

#cccaggaa  76020

ctcaagacca gcctgggcaa catagggaga ccccatctct actggactgg tg

#gcatgtgc  76080

ctcttgtccc agctgcagga ggctgaggtg ggaggattgt ctgagcccag ga

#tgtcaagc  76140

ctgcagtgag ctgagattgc accactgcac tccagcctga gtgacagagt ga

#gaccctgt  76200

ctcaaaaata aataaattaa ttaaaaataa aaacgatcaa tgtggaaaaa ac

#ttgaagac  76260

tgtgcaaata gccatatgtt gcttaacgat gggaatacat tgtgaaaaat gt

#gttattag  76320

gtgattctgt cattgtgcaa acaccatagg gtgtacttac ataaatttag at

#ggtatagc  76380

ctgctacata gctaggctat atggtttagc ctattgttct taggctacaa aa

#ctgtacag  76440

cttgttactg tactgaatat tgtaggcagt tgtaacacta tgataagtat ta

#tataaaca  76500

tgtctaaaca taggaagata cagtaaaaat acagaattat aatcttatgg ga

#ccactgtc  76560

ataagtgtgg tttattactg accaaaatgt cattatgtgg cacatggctg ta

#tcttgctt  76620

ttcatcaggc tttacactct agatgagcat ccattgatta ttcttaccca ca

#ccaatggt  76680

acagttatga tagttggaaa atgctgcttt tttccaactc cactactccc tc

#catttcat  76740

ggtattctaa tgaatgatca ttgtcacaaa attcaacacc taattgtatc tg

#ttatgata  76800

atgaaaagaa acaaatgacc cattcaaaac agttcagttg aaaagagttt at

#caaaggaa  76860

tgacttaaca cggtgtggcc acagtaaggg aatcaacaag gaatggtgaa gc

#acccagta  76920

actagcaaca gtgggaagcc attgccaccc ttagacctgc ggaggcaaag gg

#agggcaca  76980

tggttatcag gctcgtgaaa ctggaattca tagaggagga accacctaca gg

#tgctgtgt  77040

ctctagagaa aaacagccac tgtcagcaca gaggcaaggt tgagacaaag ct

#gggggaat  77100

cagctgagtt cttcctgctg ctgctctgac ctgttagtag tgctcacggt tg

#cccagtca  77160

taagccaaag gacaagaaag cctgggtgat gcaatctgga gagcttgacc tc

#ctggggca  77220

cagaaggtgt tggggggttg tgggaatggt agtataacca gcacactagc ta

#agatttta  77280

ttaatgtgac aagacaagaa aaagatctct gatgcgcaag aactgaatgg ag

#agttcaga  77340

tcatgttctt agatgggaag attgaatagt ataaatatct tggttcttgc ca

#catgaatt  77400

tgtctactta attccaacag tctaatggaa ttacggaggg agtaggggtg at

#ggtggggt  77460

aacattgtta aaatgattct aagttcaatc aggcaagaat aacaagaaaa aa

#aaattcgg  77520

gccaggtgcg gtagcacacg cctgtaatcc cagcactttg ggaggccaaa gc

#aggcagat  77580

cacctgaggt ctggagttcg agaccagcct gaccaacatg gagaaaccct gc

#ctctacta  77640

aaaatacaaa attagccagg catggtagca catgcctgta atcccagcta ct

#cgggaggc  77700

tgaggcagga gaatcgcttg aactcaggat gcggaggttg cggtgagcca aa

#ttcatgcc  77760

attgcactcc agcctgggca acaagagtga aactccatct caaaaaaaaa aa

#aaaaattc  77820

tgatttcact gcgtaatttt aaaaataata ttttaatttt gttttgaact aa

#atatttta  77880

aaattatttg tgttcataaa ttatttagaa ttgtttttaa gggttttcta ag

#ttacattt  77940

ttgttactcc tttctgactt aaatataata tagttaaaga atattatcta aa

#tgatacta  78000

attctgtaaa atgttgttga agcttaatga tctaagacgg gtcagttttt gt

#gaatctta  78060

ctgtgtgtgt gttcctgaga aggatgtgta ttcactaatt aatgggtgct gg

#gttttatt  78120

ggtaggccag aagtcaaact tgacagttat gtagccctta attcatgcta at

#gttttgta  78180

tcattggtct gtaaataact gaaagagctg tgttgaaatc ttccactttg tg

#gatagatt  78240

tgttcatttc tctctaaagt tgtcaaattt tgctttattt tgaggctatt tt

#ttgagagc  78300

ttacaaattt agattcatta gcattttcta gcaaattgaa cattttattg ta

#acatacgg  78360

actatcacta aaaatgcttt ttgtcttaca gagtagaatt gctaaataaa at

#acaggatg  78420

ctcaattaaa tttgaatttc agataaatgt tgagtacttt tttagtataa gt

#atgttcta  78480

catattgcaa aaattattca tttttcacag gaacagaaaa ccagatacca cg

#tgttctca  78540

cttataaggg ggcactaaat gatgagaaca catggacaca tggcggagaa ca

#agacactg  78600

gggtgtactg gagggtggag ggtggaggag ggagaggatc aggaaacata ac

#taatgggt  78660

actaggctta atacctgggt gatgaaataa tctgtacagc aaacccccat ga

#catgagtt  78720

tacctataga acaaaactgt acatgttccc ctgaacttaa aataaaagtt aa

#caaaaaaa  78780

gtctggcatg gaaagacata aacatgcgtg gagctggttg tctctgatct tg

#caccactt  78840

gtgataaagt tgtttgtagt atttaatgaa tgtgttcaaa aatctgtatc tt

#tagttata  78900

tgtacttctt ggtcctaata ttactgattt gtgctaccta tacagttttg gt

#ggggggtt  78960

tgcttatttg ggggataacc ttactactgg tttgtctctc ttattagtct tt

#tcaagtaa  79020

tactttcttt ggctgtattc tgttgctcct tttctagctt gtttaattga ac

#atttaatt  79080

aaatattcat cattcctttt gaaaaaattg ttgtttatct gacattcaaa tt

#taactagg  79140

catcctatgt tttgtttgtt tttgctaaat ttgggagcct atttaaaaac ta

#ttttgttt  79200

gatactaata tagctatccc caatattttt tggttataat ttccctagta ta

#tcgttttt  79260

ataaatttca ttctttgagt ctttgtgttt taatgttttt tttttaatat cc

#tatagtca  79320

gaattgttag tctaatctta cctatgttgt ttttctagga agtgtagggc tt

#ttttattg  79380

ggattgcaga cctattgtcc cttttttaaa actatatttt caaatgcttt tt

#atttttcc  79440

cacttgtttt gtgcttttgt ggactgtttt ctttttgcat gattttaaaa aa

#attccatg  79500

ttctcttact attattttag acattacaca tatttattat tttgttaacc tt

#taaatatt  79560

actgtcaggc caggcacggt ggctcatgcc tgtaatccca tcactttggg ag

#gccaaagc  79620

gggtggatca cctgaggtca ggtgttccag accagcctgg ccaacatggc ga

#aaccccgt  79680

ctctactaaa aatataaaaa ttagccaggc ggggtggcag gcgcctataa tc

#acagctac  79740

tgagaaggct gagtcaggag aatcgcttga acctggaggc agaggttaca gc

#gagccgag  79800

atcatgccat tgtactcgag cctcggcgac agagcaagac tctttctcaa aa

#ataaataa  79860

ataaataaat atatattact gttcaaactc tacttgataa agttatttaa ta

#tttttaaa  79920

tccccacaca aacatcctaa ctctgataac taccctttta atgcttatgc ta

#ttactgat  79980

gaatatttaa gttctttttt taacactata tgttagacat catcattact gt

#tactttat  80040

atggacagta ttatgtttat gtatatgttt accatttccc atgctcacaa tt

#acttcttg  80100

catctaagat catctttctc agattggttt cctttttttt cccccaagta ca

#ttcttcag  80160

aatttttttt tttttttaga cgaagtctca ctctgttgtc aggctggagt gc

#agtggcac  80220

gatctcagct cactgcaacc tccccctcct gggttcaagg gattctcctg cc

#tcagcctc  80280

ccgagtagct cctactacag gtgcccgcca ccacgcctgg ccaatttttg ca

#tttttagt  80340

agagatgggg tttcaccatg ttgcccaggc tggtctcgat ctcctgacca tg

#tgactcgc  80400

cgccttggcc tctcaaagtg ctgggagtat aggcgtgagc caccacgccc ag

#cctagaag  80460

tttttttggt aaaggtaaat tgatggtaga ctcagacttt gcatatttgg ga

#atattttt  80520

acttcactct aattcttgaa atgttgtttt gttgaataga ctaggtttat ag

#taatcttc  80580

catcagcact ttgaagatat tttaacattt tctgggccct agttttgcaa tt

#gagaagtt  80640

actatcagcg tagttgctat ttctttgtgg gtgactttac tctctgattt tt

#aaggtctt  80700

ctttatataa ctgtattttc caattttact acaatatagc taactgtggc tt

#ttctcatt  80760

tatttgtttt gttttgtata tttatatgat ttcctgtatt ttatcagttc ta

#taaaattc  80820

tcgaccattt ttctttgaat atttcttctt ctccgttctc tccattttgt cc

#tttgaact  80880

ccagttattt gaatattaaa atgttgcatt ctgtcctcca gatagtttaa ca

#actctttc  80940

atgttttctg ccttcttacc tctatctgct agataatttc tttagatcaa tt

#gtctgatt  81000

cactcattct ttcttcatct gtttcatttg ctctttaacg tgtccagtat at

#tttaatta  81060

aaaatatata tgttgggtta tttttagcct gcctgctact ttaaaaaaat ac

#tcttttgt  81120

tccttttaaa acatcaaaag ttgatctgaa gtgtttcagc agttgaactc ct

#aggtcttc  81180

attgtcagcc tgctgtactt gttttcttca agaagataga tatctctaaa tg

#ttgtcata  81240

tccttttttg ttattgaatc aaagtagctg aatttgatag aagttcagtg tt

#gcattgtc  81300

cagatacaca gttttgaggt ttgaaagctt gaataagtgc cagtggactt ca

#tgcaaatg  81360

ctttatatat ttttcaccta atatattttg aatttcaaca agtaacacat tc

#tcttaaat  81420

actgacttga taggcaagtg agcatagcaa gcttcatctt ttagtgaaag tc

#cattgatc  81480

ctgtttcgta attggatgaa gagtgtccaa actattgcca gtagctttct gt

#tttcccat  81540

catttttcaa cccagaaata tttatttttc tttccaggga ggcattagca gt

#accctgga  81600

agctcccctc ctacccctcc aaattattcc ctcctcctct ttacttttct cc

#aaagataa  81660

tctctgtcct gaatcaaaaa tcgtccccgc ttcctggtag cacccgatct gg

#aagaaacc  81720

caaaatcacc taaccaaaac ctgaatcata taatagtctt ttctaatact ct

#tttactga  81780

gacattccac aattcccaat tatatgtgtt attccttgct gaaatgaata at

#gaacccaa  81840

catgtgcaac tacagctatg ttcctggtaa cctttggctg ggaggattga ca

#atattcat  81900

ttgtgtctgg tttctttctt tctttttttc tttttctttt tttttttttt tt

#ttttgaga  81960

cggagtcttg ctctgtcccc caggctggag tgcagtggca caatctcggc tc

#actgcaag  82020

ctccacctcc cgggttcact ccattctcct gcctcagcct cccgagttgc tg

#ggactaca  82080

ggcgcccgcc accatgcctg gctaattttt tgtattttta gtagaggcgg gg

#tttcacca  82140

tgttagccag gatggtctcg atctcctgac cttgtgatct gcccgcctcg gc

#ctcccaaa  82200

gtgctgggat tacaggcgtg agccaccgcg cccagcctgg tttctttctt tt

#taacattt  82260

tgtaagattc atgtttttgc atgtagtcat agtttttttt gtgtgtgtga tg

#gaatttca  82320

ctcttgttgc ccaggctgga gtgcaatgga gtgatctcgt ctcaccacaa cc

#tccgcctc  82380

ccaggttcaa gcgattctcc tgcctcagcc tcccgagtag ctggtattac ag

#acatgtgc  82440

caccacgccc ggctaatttt gcatttttag tagagatggg gcttcaccat gt

#tggtcagg  82500

ctggtctcaa actcctgacc tcaggtgatc tgcccgcctc agcctcccaa ag

#tgctggga  82560

ttacagttgt gagccaccgt gcccggcctt gttcattttt gttatttaat at

#tatgctat  82620

aattacataa ctatttggaa ctttttgact ctgttttaat gttgatacac ag

#tatctttg  82680

tacatatcat ttggtgaaca tgaataatgc atttttgttg ggagtatgcc tg

#ggagttat  82740

attgggagtt cccaagacca ctcatagtaa tcagaagtta tgattatgat ta

#tagttgat  82800

tacagcaaaa ggatatgaag taaaagtcaa gaaagggaaa aggcacatgg gc

#aaagtctg  82860

gaaggaacca gctgctcact ttccaatgtg ccctctcagt ggagtcagac ag

#gacatgtt  82920

tcatttcccc agcaacatgt gtgacaacac acacaaaatg tttccaatca ag

#gaagctca  82980

cctgagcttt tgtgtccaga gtttttatta ggggtcagtc atgacatagg ca

#tttggtat  83040

tacctgcaca actgacttca gggtcaggct ccagatcccc agagaaaaag ca

#ggtgtcaa  83100

ccataaatca cattgttagc ataaactatc tggttaaacc agtacagcat gg

#cccaaggc  83160

ctcagacaca tgaaacattt cttatcagac ataagattct atgataggag gc

#agccaata  83220

gccagtcctg aaaacaggcc tgtcttggga atgtgcaacc aggcctgctg ag

#ttaataaa  83280

cttttccagc agagattgaa aaggatgggt caaaggatat ctgtaggtac aa

#atttgaga  83340

gatagtgcca aagagttttt caaagtgatt atacctgttt actctctaac ca

#gcagatgt  83400

gtaagaactt cagttcttct actttgccaa taccttgtac agtttaatct tc

#taaaattg  83460

taattttctt cctcgtgtct attgatatct cattttggtt tacattttta tt

#tccttagt  83520

aactgagact gagcaccttt tcatatgtca ttgaccagta gcctatgttg tg

#aagtgcca  83580

gttcaggttc tttgcctggt tttcttttga atcatttgct tttttctcat tg

#atttttag  83640

gaattattta catgttttga tatgtacact tcatgtgtgt ttcaaataac tt

#ctcccatc  83700

tatctgcctt gccttttctc tctcttaagg ctgtcttttg aaaaatagaa gt

#taatttta  83760

atgtctaatt ttgtgatctt tttctttact gcttttggca taccatttaa ta

#aatctttt  83820

ttccaattca agtccttgga tatatcctcc tatgttatct aatgaaaagt tt

#attgcttt  83880

acctttctct tttagatctg taacctgcct ggaattgatt tcttttcatt gt

#ggtaagaa  83940

acacatgaca taaaatactc tcttaaagat ttacaactgt acatctcagt ag

#tgttaaac  84000

atatttacag tgttgtaaaa cagattcaga aactttttat cttgaaaaac gg

#aaaacttt  84060

atactcatta aacaataact ctccattctt cttctcccca ctcccctcct tg

#ctgctcct  84120

ggcagtccct attttacttt tgtctcgatt taagtacctc atgtggcatc aa

#atagtatt  84180

tgtctctttg tgactggctt gtttgagtta gcataatgtc ctcaagtttc at

#ccatgtta  84240

caggatgtga caggacttcc tttttaaggc tgcatagtat ttcattgtat gt

#ctgtacca  84300

cattttgttc atccattcat ctgttgatca atttgggttg cttccatttc tt

#ggctattg  84360

tgaatagtgc tgcagtgaac atgatgtgca gatatctctt tgagttcttg ct

#ttcagtta  84420

ttttgtgtat actcagaagt ggaattgctg aattatatgg gagttctatt tt

#ttattttt  84480

tcaggaagct gccgtactgt tactccatag cagctgcact attttacatc cc

#ttccagta  84540

gtgcacaaag gttccagttt tccacagctc accaacactt gttatttttt tt

#attttttt  84600

attttttatt tttttaaata gtagccattc taatggatat gaatggtaac tc

#attatggt  84660

tttgatttgc atttctctga tgattagtga tgttgagcat cttttcatat gc

#ttgttgtc  84720

tatttatgta tcatctttgg gaagaaatac tttgttcatt tttaattgga tt

#ttttgatt  84780

ttttgctgtg aattgtagaa gttctttatg taattctgaa tattaacccc at

#agcagata  84840

catgacttgc aaaattgtgt ttctttagag ttgatttctt taactttatt tt

#gattcttt  84900

aattgggcca tctatccaga ccaggctggt ctcggactcc tgagctcagg ca

#atcaaccc  84960

gtatcagcct tccaaagtgc tgggattaca ggcgtgagcc accctgcctg gc

#cgctgtgg  85020

atttttaaat aaacgtcctt tatcatgtta aagaagcttt cttctgttct ta

#gtttacta  85080

agtgttttgt tatgaagtga tgttgagttt tgcccagtgt ttttttctgt gt

#gtattgag  85140

atgatgtgtt tttctttata ttttattatt atgtattaca ctggatgatt at

#cttacatt  85200

gaaccaccct agcattcctg agataaatcc aaattgggct gcatcgaaac ta

#aaaacttt  85260

tgtattacaa atgttatgaa gaaagtgaaa agacaaccca cagatgctat ct

#agagattg  85320

gtatccagat tatataaaga attcttgcaa gtcaaataat aaaaatttac at

#cacccaat  85380

tagtagttta agtcagccag agttggttcc tcttgaatca cccaatttgt gg

#tgaattga  85440

aactataatc agatactact tcacacccac cgggatgctt ataataaaaa at

#acatggga  85500

aatagtacag tagttcctca aaaaattata gaattaccat ttgatccagc ag

#ttccactt  85560

ctgtgtatat atacaaaaga ggtcaaagca gggatacaga tatttgtgca cc

#agtgttca  85620

tagcagcact attcacaaca gtcagaaggt ggaaacaacc taaatgtcca tc

#tacagatg  85680

aatgggtaaa caaaatgtgg taaagatgga tcaatagatc acaaaggaat at

#tattcagc  85740

cttaaaaagg aatgaaattc tgatacatgc tacaataagg atgaaacttc aa

#gacactgt  85800

gctgggtgaa ataagccaga cacaaaagga caaatgttgt ataatttgac tt

#atggggta  85860

catagaatag gtcaattcat agagatagaa agtagaatgg aggttatcag gg

#gtggggta  85920

tgatttcatt cctgtaaagt tcagagttac tcttattgga ggaaaggata ca

#ttatgact  85980

agaaggaggg acaaggaagg ccactgggtc atcttctatt tctcaatctg tg

#tttactcc  86040

atagaatttg attgagctgt ttagctgtgg tttgcacatt ttcctttacg ta

#taaacttt  86100

ttacatatat acttttatta aaatctactt aaaatgggaa aaaaaaagat at

#ctagattt  86160

cagcttttaa atgctggtgc aatgatagcc attttcggct gggtgcagtg gc

#tcacacct  86220

gtaatcccag cactttggga ggctgaggca gctggatcac ctgaggtcag ga

#gttcaaga  86280

ccagcctggc taacatggtg aaactttgtc tctactaaaa attagccaaa cc

#tggtggtg  86340

ggttcctgta atcccagcta ctcgggaggc tgaggaagga gaattgcttg aa

#ctcgggag  86400

gcagaggttt tgcagtgatc caagactgtg ccactgcact ccagcctggg tg

#acagagta  86460

agactctgtc tcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaacaagaca aa

#acactcat  86520

atctgaaatg tggtttacat agaatgttct tccaggcaaa aaaaacaaga tt

#aaaattac  86580

tggttttgaa aatgtattct gttctttctt atatcaaagt cttgatgttg gt

#ggctagag  86640

agaacttctt aggttttcta cctgtattag tccgttttca tactgctata aa

#gaactgcc  86700

caagacgggg taatttataa aggaaagagg tttaattgac tcatagttca gc

#atggctgg  86760

ggaggcctca ggaaacttaa aatcatagta gaaggtcaag aggaagcaag gc

#actttctt  86820

cacaagtcac aaaggagaag tgctaagtga aggatgaaga gccccatata aa

#accatcac  86880

atctcgtgag aactcactca ctatcacgag gacagcatgg gggaacctct gc

#cgtgattc  86940

agtgacttcc acctggtctc tcccttgaca cgtggggatt atggggatta ta

#attcaaga  87000

ggagatttgg atggggacac aaagcctaac catatcacta ccatttttct tt

#tctttttt  87060

tttcatgcct ggattttttc gttgttccct catgaacatt ttaaagtgta at

#taagcaaa  87120

agagaatact atacaatggt ttttaacaat ttttttaagt ttcccccctc cc

#cccaagac  87180

agggtttccc aatgttgcct aggctggtct cgaactcctg gcctcaagtg at

#tctcccac  87240

ctcaccctcc taagtagctg ggactacaga catgtgccac tgtgcccagc tg

#cctataca  87300

gtgtttttat tttattttat ttttttaaga tggagtcttg ctttatcacc ca

#ggctggag  87360

tgcagtggca ttatcttggc ttaccgcaac ctctgcctcc cggattcaaa tg

#attctcct  87420

gcctaagcct cccaagtagc tgggattaca ggcacccgcc tccatgcctg gc

#taattttt  87480

gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcga ac

#tcctgagc  87540

tcgtgatctg cccgccttgg cctcccaaat tgctggggtt acaggcgtga gc

#caccatgc  87600

ctggccttta atttttttaa aaagtaaaac ttctttaatt ttcttctcgc aa

#gaattgaa  87660

tagaatgata gaatgaatgc cagtatttta taatgttgta tccagcaggt tg

#caatcagg  87720

gaggctccaa cagagtcact ttttctgtct ttttatgttc aatctatgct gt

#aaattggt  87780

ttcagaaact tctgtgagtc tatcaactgt aaaaatggag atgactatga aa

#ggatctta  87840

cgcttttatt cttctttgat ccacatgtct gtttgttcct ccatctagaa ta

#taaagatg  87900

attaagactc tacctgtctc ctttaagtcc agtgaagaag atagatttac aa

#ttaatggt  87960

aattcagtat aactgccgta agaacagggc attcagaatg ccctgtgagc tc

#agagatgg  88020

cgctactgta ttctcatgtt taaaggataa gtaaaagttc cccagtttga ga

#aaagaggg  88080

gaaaaggact ccagtgaaag gaaattgatg aaattactgt tgactttact tg

#tatatatt  88140

aactgtcttt cagtgtctct gaaaacttga tttgggacta tttcctttga ac

#agaaataa  88200

tagcattcct gcctgataaa tgtcctgtgg tcaaataata tgatttccta at

#cattctgc  88260

acactaaact tccccccacc aggaaatcaa tgccttaatg ctaaatttcc tc

#tgtactac  88320

tttctgtaag agtaagaggt tcctatttca cagtcacgac acattcccaa ct

#caattcac  88380

attccaatcc atcttgtcca acttcattga aagttgatac actgaaccat tt

#cctttact  88440

taaaagaaat agaattcttc ctaaattcta tctactgttg gaatagaaag aa

#tatcatgc  88500

ttctagactg actaattttt tttcttcttg atataagtat tgacaacatt ta

#ttcatttg  88560

tttctaggca gcacaagact gttgaacttt cctagaactg agtctgagat tt

#gcaaagct  88620

gccaaaatat tttgaaacaa atgaaaatat gtaaacatga atgttatcag ct

#gttttaca  88680

gtatttgtgt tttagagata atgagcatct ggtggaccac aggagcccag gg

#ggatttca  88740

aactccagat tcctttttgt gtaatcatat ctggctggag ttatttgttt tc

#tctgcatg  88800

tgaaactatc aagtcataat tcttcaaagg ggaatgttta ttgcattatt ta

#aaaataat  88860

aaattatatt actaaataaa taacagcagg ccaggcataa accaatgatg aa

#agtttgtc  88920

agaaactaag gcttctgatt aattctgtgc tctggactat aattggaagg aa

#ggattata  88980

ttagagttta caatgagttt acagaaagaa aggagaggga taaattatat tt

#agttcaca  89040

gtaaatctga attcagaacc cctggttgta agactagtct tttaaccttt ag

#agttaaaa  89100

aatgtatatg tacagctggg tgcagtggtt cacgcctgta atcctagcac tt

#tgggaggc  89160

caaggtgggt ggatcgcttg aacccaggag tttgagacca ggatgggcaa aa

#tggcaaaa  89220

ccctgactct ataaaaaata caaaaattag ctaggtgtgg tggcaggtgc cc

#atagtcct  89280

agctactcag gaggctgagg tgggaggatc ccttgagtct gggaggtcaa ag

#ctgcagtg  89340

agccgtgatt gtgctactgt actccagcct gggtgacaga gaaagaccct gt

#cttaaaaa  89400

aaaaaaaaag tgcgtgtgtg tgtgtgtgta tgtacgttga agaaaactat ga

#gaaaaagc  89460

aaaaatgtag agtccataat gcataatgtt gtgttaagca catagtttag tc

#attggtac  89520

atatttctgg agatggtcta aagatctatt ttttaaaaac tgattttagt ta

#aatcagag  89580

gttagcaaat cacagcctgc aggccaaatc tggcctatca tacattttgt tt

#gtctcttt  89640

gttgtgtttt tggtgttttt ttttctttct tttttttttc ctttcctttt tt

#tttttttt  89700

tttttttttt ttggagacag agtcttgctc tgttacccag accaggctgg ag

#tgcattgg  89760

tgcgatctca gctcactgca acctctgtct cccaggttca agcaattctc ct

#gcctcagc  89820

ctcctgagta gctgggatta taggtgtgca ccaccatgcc cagctaattt tt

#gtattttt  89880

agtagagatg gggttttacc atgttgccca ggctggtctc aaactcctga gc

#tcaggcaa  89940

tcttctcgcc ccagcctccc aaagtgctgg gattacagac gtgagccacc gc

#gcctggcc  90000

ctatcataca ttttggtaaa taaagtttta ttagaacata ctatgctcaa tc

#atttatat  90060

gttttgtgtg gctgcatttg ccctgcagca gtagagctga gtagttggaa ca

#gagactgt  90120

ggttcataca acctaaaata tttaccctgg cctttgttac agaataggtt gc

#taacctct  90180

gagtttctca gttttagccc attcacaaat gaaatagttt ttttttgttg tt

#ttttttga  90240

gacagcctca ctctgtcgcc caggctggag tgcagtggca tgatcttggc tc

#actgcaac  90300

ctctgcctct tgggttcaag caattctctt gcctaaacct cctgagaagt tg

#ggactata  90360

ggcacatgcc acaacgcctg gctaattttt gtatttttag tagagaccag gt

#ttcgccat  90420

gttgaccagg ctggtcttga actcctggca tcaagtgatc tgcctgtctt gg

#cctcccaa  90480

agtgctggga tcccagcctc tctctctctc tttctcactc tctctctctc cc

#gctctctc  90540

tctctctctc tctctctctc tctctctata tatatatata tttttttttt tt

#tttttttt  90600

ttttgagaca gggtctcatt ctgtcaccca ggctggagtg cagtggcata at

#cacagctc  90660

actgcagcct caaccccacg ggctcaagca attctcctgc ctcagcctcc ca

#agtagctg  90720

ggattacagg tgcgcacaac cacgcccagc taatacttgt atttttttgt ag

#agacgagg  90780

cttctccatg ttgtccaggc tgttctcgag ctcctggaac tcaagcaatc tg

#cctcaggc  90840

aggaatcctg aaattctggg attataggtg tgagccactt ctccctggcc ca

#caaatgac  90900

atattcctta taatctacta cagtgagctt tgcatggtta atatatttgt tg

#tgttgaaa  90960

ctatcttcct gattttttcc aattttttat agagaaacct ggaaagaata gt

#accataaa  91020

tacctatata ccctaacaga gaattattgt taaaattttg ccatatttgc tt

#tatcttct  91080

ctgtgcatat gtatactcac atggcttttt ttttattggt attagttgaa ag

#ttgcagat  91140

attatgcttc ctcagcgcat atccctaaga ataaaagcat tttcctcgac aa

#ctgattat  91200

gttaaaattt gaagacgtgt atgaggtttt tgtttgtgag ggctatatga ct

#ggcgtttc  91260

tccagtatat gacactttgt tcatccctat gttcctcttt ataaactgca ga

#aattctaa  91320

atataatgca ttagttgtct attgcttgca agtagtagac tgaatgatgg ct

#ccataaag  91380

atgtccactt ccattagata aagaaaatgt gtacatatac accatgaaat at

#tgcacagc  91440

cataacaaag agcgaaatca tgttctttgc agcagtttgg atggcgcttg ag

#gccattat  91500

cctaagtgaa ttaatgcaga aacagaaaac caagtacctc atgttctcac tt

#gtaagtga  91560

gaggtaaaca ctgggtacaa atggacataa agatggggac agtagacact gg

#gaatacaa  91620

gagggcagaa gagggaagga aaaataaggg ttgaaaaact acctattggg ta

#ctgtgctc  91680

actacctggg tgacaggttc aatcatatcc caaacttcag catcacacac ta

#tacccctg  91740

taacaaacct gcacatgtac cccctgaatc taaataaaag ttggaaaaac aa

#atcaaccc  91800

agatggccat ttcctaatcc ctggggtctg tgaatatgtt accttatctg gc

#aaaaggaa  91860

ctttacagat ggaattaagg aattttagat gaggagatta ccgatcatct gg

#tgggccta  91920

aagtaatcac cagggtcctc ataaaggaga ggcaagggag ttgaaggtag ag

#aaggggct  91980

ctgaagatgg gaagcagaat aagtgtagga aatgtgagct tgccacactg ct

#agtgttga  92040

agatggtgag gctaagaatt ttcacatcca ctttcaaaac cattgtgtcc tg

#gctccttt  92100

taaaccatct ttccctcaat ttctctgtcc tcttacatct tattgtaaac ac

#caagaaga  92160

aacctggcag ttaactttgc ttggaaatct ttttagctag accatctaat tc

#attcggca  92220

cattttctac cttccacatc actgtaaaat tgggttgcta aactttccac aa

#ctacctaa  92280

cagagatccc ttgcctccag tttctactca gatgttcctc acattcctta aa

#actcacag  92340

tccacctcct aacaatctaa aatctaccaa ctatcaattc ctggcaattt ag

#gctttacc  92400

gctcctctcc tgaaaggcct taaagtatta gaactgggcc ctattattag aa

#cctatttc  92460

ccagttctaa tattcctccc acatttttgg tatgtgtgac aatggaactt ta

#ctcctgat  92520

accaaaatct gtatgattta tatatgaagc ataacaaatt attctaaaac gt

#attaatgg  92580

cttaaatcaa caaacgtgtt gtctcatagg ttctgtggtt caggaatcca gg

#caaagcta  92640

cctagatgct tctagctcag gatctttcat gaagttgcag tcaagctgtc ag

#ctgggctg  92700

cagtcatcca aggctcagct gggagaggat ctgccttcaa gctctctcat gt

#gactgttg  92760

gcgggcctca ggttttcact ggctgttggc tggagatgcc agttatttgc ca

#catgagcc  92820

tctgtctacg gcagttgaca acatgcagct ggcctacctc agagcaagca ac

#caagcaag  92880

agagcaagat agagtgctca agacaaaaga taacagactt tttgtaactt aa

#tctcagaa  92940

gtaacatccc atcacttttg ccaaattctg gttgttagaa gccagtcact ag

#atctgtcc  93000

cacacttgaa gagggttaaa caaggtcatg ttcttcataa gattaatcca ag

#tacagaat  93060

tggcttaata acatttctga cgatttttcc tataacttgt aaaaccttgg ct

#atctgaaa  93120

cccttgggaa gtgaatcatc cttaaaagct aagtttctgg atagattttt ac

#catgaagg  93180

gaccaaatct taataatttg gagtagaatc acttctgcat ttgatcacaa ta

#tttcttgc  93240

cttttaaaat aaattactga tcattatttg aaattttatt tcatcaaaag aa

#aattagca  93300

attgtgtgtt ataaagagaa ggtgtctgtc ttctccttat gtagggtata ga

#actgttca  93360

tctctttact aaaaacttaa ggcttctgtc tgccttttat aatttctgtt tc

#tttctttg  93420

tttcatttgt tacctcttag ttatcagtac ttgcccattg ccttcctgtt ta

#ctgtatct  93480

agtaagttgc tgcaaaagta attgtgattt ttgtattaaa acaaatggca tt

#agattctc  93540

ataggagcac gaacactttt gtgaactgtg catgtgaggc atctcggttg tt

#cttgcctt  93600

atgagactct aatgcctgat gatctttcac tgtctccgat cacccccaga tg

#agaccctc  93660

tagttgcagg aaaacaagct cagggcttct actgattctg caatatagtg ag

#ttgtgtaa  93720

taatttcact atatattatg atgtaataat aacagaaata aagtgcacag ta

#aacgtaat  93780

gtgcttgaat catccggaaa ccatcccctc tgctggtcca tggaaagatt gt

#ttttcaca  93840

aaaccggccc caaagttggg gactactgct atagagaatt ggatctgcgg tc

#tacaagta  93900

atgttaatga catttatttt aagttgcact gagacttttg tttacatctt tt

#tttttttt  93960

ttgagatgag agtctcgttt gtgttgctca ggctggagtg caaggcacaa tc

#tcagctca  94020

ctgcaacgtc cgtctcctga gttcaagcga ttctcctgcc tcagcctccc ga

#gtagctgg  94080

gattacaggt gcccgccacc aagcccagct aattttttgt atttttaata ga

#gatggggt  94140

ttcaccatac tggttggcca ggctggtctt gaactcctga cctcaggtga tc

#cacccgcc  94200

tcggcctccc aaagtgctag gattacaggc atgagccaac atgcctggcc tg

#tttacatc  94260

ttaattatga attgttacta tagtcagccc tttgtatctg tggtttccac at

#ccatagat  94320

tcaactaacc atggactgaa aatatgtggg ggggaaatga tgcttacatc tg

#tactgaac  94380

gtgacggact ttgtcattat ttcctaaaaa atacaggata actatttaca ta

#gcatttgc  94440

attgtattag gtgttataag cagtctagag atgatttaaa gtatacagga gg

#atatgtgt  94500

atgttacgtg caaatactac accattttat ataaggcact tgagcacctg tg

#gattttgt  94560

tattcacagg ggatcctgga aacaatcccc tgtggatacc aagagatgac tg

#tatagggg  94620

aggccgtggt gacagatgaa gtggcactgg gcttagtaag ggtaagaaag ct

#aagagtgg  94680

cctgaggaca gatgacaaac atgacatatt gctcacttta gccaatgctc ag

#aatctctt  94740

aggtttttga aacttcacaa gcaatttagg caaactctcc tttcttctct at

#ctctgtat  94800

tctatgtaat cccacagttg aaggctgttc ttatagtgga attaattata cc

#tcactcca  94860

aaaacttgac cctgatttcc gtctacaaac ccaaagcagc aaatacaatt ta

#cttttata  94920

tttgaattat tttctttgta atggtgtctg ttgacagcca aagcctcttg ta

#tggaaaca  94980

taccaccact gccacaagta aaagctataa agcagtgtta aatactgtat at

#agagctca  95040

catttgtata tgcatttctt ttaggtctta tgtagtgtgt gtactgtgga ag

#atcgagaa  95100

agtgcgttag gttgttagac aaaagaccca gaaggcctgc tagagatgcc ac

#aggtggaa  95160

ctaagaaagc aatctctgtg tcactcaggc tttgagaaac ttccttcaga at

#cataaaac  95220

attagaactg ggaaggttaa aaaatcttta gtcttttttt cccagctcca gt

#ctcttgtg  95280

aataattaac agtaaagtta aagattatgg gaattacgtg cctccttttt tc

#ccttgcac  95340

aacatagaat ttgttttcta atagtagttt atttgttagc tttgcattcc ca

#taagtgat  95400

ggtttccagc cttggcaaac ccttgcagcc tccagccaca agtcccctgg ac

#ctcagaga  95460

atgtatatac tgtatgtgca ccctaataac atgtttcctt aaaactagta ct

#actggatc  95520

ctctaacttt agtacatgtc tttcatgtcc aacttttcag aggccgccaa ac

#tagcaacc  95580

ctaaactcat ttgtcactat caaaacataa tatacgaata tggaaagcta at

#ataaaaat  95640

ggtaagggac tgagccattt ggaaggtaac ttaatgtaag tgcctgaaaa ac

#agggatac  95700

aaaaaagcaa agggacaaga agcaagccag ttcaccctga accctacaaa tg

#tttgggaa  95760

ttagaaacat caagtattac aaattagggg aaacggatga agtctgatac ta

#aaaatagg  95820

gaggttgaca gtctgtgtag gaacagttag acttccagat ccttatctct at

#accccacc  95880

tccccctctg cagaagagat agattccctt agggaggaag aaaactagag aa

#aataaaga  95940

cactaggggg agagtgtgat gtcagcaaga tagtggaata aaagatacct gg

#catcactc  96000

ttcccacaaa aatgcaacta gaaattattc aggctgggcg cggtggctca ct

#cctgtaat  96060

cccagcatgt tgggaggccg aaacgtgtgg atcacttgag gtcaggagtt cg

#agaccagc  96120

ctggccaaca tggtgaaacg ccgtctctac taaaaataca agcattagct gg

#gcatggtg  96180

gtgggtgcct gtaatcccag ctactcagga ggctgagaca ggagaattgc tt

#gaactcgg  96240

gagttggagg ttgcagtgag ccaagatcat gccactgcac tccagcctgg gt

#gaaagagc  96300

gagactcctc tcaaaaaaaa aaaaaaaagt attcaaagac aagaatatca ac

#ctgagttc  96360

accagaactt ggggaagaag tggagaaacc tcctgggcca acaaaatttt tt

#gtaaaata  96420

agtggtcatt tcagactgtg ccaccccttc cccccaagct ggcataacac ca

#ctcaggga  96480

gaattttcct agccctgcag tttccaaggt gagaggaagg aattggaggt gt

#gtattcag  96540

tctcctcact ggtctgggaa tcttcccagg gagcccactc ccgtcccatc ag

#ggagagcc  96600

aggagagctg aactatctgg ggtaaagtgg ggacaaagag cagggcactg at

#tgtagcaa  96660

ctagtatatg gatcttgcag ctactctgta ctctaattag ccgagacacc ct

#attgacaa  96720

ggatggccag tgtcttagtg ccactggggt gtaatcagtg ggaaggcctg aa

#tccctggt  96780

cggattttcc acaaaactta gtgctcacat ggaaccttcc cgtggcccag aa

#acagctat  96840

aagattggga ttaagctggg catggcagct catttctgta atcccatttt gg

#gaggccaa  96900

gttgggtgga taatttgagc ccaggagttc aagaccagcc tgggcaacat ag

#caaaatcc  96960

cacttctacc acaaaaacaa aagttagctg catgtggtgg tacgtgcctg ta

#atcccagc  97020

tacttcagag gctgaagcaa agagtcgctt gagcctggga gacagaggtt ac

#agtgagcc  97080

aagatcgcac cactgaacgc cagcctgggc aacagagcaa aactgtgtct ca

#aaaaaaaa  97140

aaaaagttgg gattaacttc cagtgtacac ttaagcactt aagactttca ca

#gactggga  97200

aatgatgaca ggatagcaat atagttggag aacaatgttt acctttcggt gg

#tcactata  97260

agtcttcctg tctgtgaaac aatgtcaggg caagttagtt tagttttagt gc

#agtgtttt  97320

gaacggcagg gcaagttagt tctgttttag tgcaatgttt tgaatggcag gg

#caagttag  97380

tttagtttta gtgcagtgtt tcagttctga tgctcactgt aagtcttccc ca

#gaatggga  97440

agaaacaata ggccagtact taagctctca tactaagtaa aggcccgaaa tc

#accaaaga  97500

acacctgcaa aacctagaag aaatggctgt gtcctcaaat gtgcaagcat ca

#acataaac  97560

aagcaatgat tatgaaaact tagggaaata tgacaccacc aaaagaaacc aa

#caaagctc  97620

caccagtgga ctcagaagaa ttgaagatct atgaaatgtc agacagagaa tt

#cagaataa  97680

gcctctttaa aaagttcagt gaatctgcca ggcatggtgg cttacgcctg ta

#atcccagc  97740

actttgggag gccgaggtgg gcagatcacg aggtcagggg atcgagacca tc

#ctggctaa  97800

cacggtgaaa ccccatttct actaaaaata caaaaaataa gcagggcctg gt

#ggtgggca  97860

cctgtagtcc cagctactcg ggaggctgag gcaggagaat ggtgtgaacc ca

#ggaggcgg  97920

agcttgcagt gagctgagat tgtgccactg cactccagcc tgggagacag ag

#caagactc  97980

cgcctcaaaa aaaaaaaaaa tgttcaggga atcacaagaa aatagagata ga

#aaattaaa  98040

tgaaatttag aaagcaatcc atgtatgtag tgagaaattt gacaaagaaa ta

#gaaacaag  98100

aaaacaaata gaaatcctat ctataaacaa tacagtaact gaactggaat aa

#ctcattgg  98160

aaagctttag cagcagactt aatcaaataa aagaattggt gagcttcagg ac

#agaacata  98220

tgaaattacc cattcagagg agcaagaata aaaaagggta aagaagacct ac

#aagaattg  98280

tggaatacca tcaagcagac taacctctgc ataataggaa ttcctgaaga tg

#aggaagaa  98340

aagggtgtag aaagcatact taagcaaatc atggctgaaa aagtcccaaa tc

#tagagaaa  98400

gatgacactg tctaggtaca ggaagctcag tgatcagcaa ttaaaatcaa cc

#caaagaag  98460

agatacctat ggcacataac aatctggtta acaaaaatca aagacaaaga aa

#gattactc  98520

aaggcagcaa gagaaaagaa atgtgtccca ttcaacatac cccaatagag ct

#ttcagcag  98580

atatcccagc agaaaccctg taggccagca aagagtggaa tggtatattt ag

#agtgctga  98640

aggaaaagaa aaaaactgcc aagcaagaat actgtaccca gcaaagttac cc

#tttataaa  98700

cacaaaggca agataaagat ttttccagac aaacaaaagt tgagggaatt ca

#tcaacacc  98760

agacctgtct tacaaaaaat gctaaaggga gctgttcagt cagaaagtga ag

#gatgctaa  98820

tgggtaaaaa gaaagcatct aatggcatta aactcaccgg caaaagaaag aa

#aactcact  98880

ggtaaaagaa gacttctgaa aaattcagaa tattgtaata ctgcaaatgg ga

#tgagtaaa  98940

ccacttatat tttaagtatg aagactaaaa gacaaatttt tttttttttt tt

#tttttttt  99000

ttaagacaga gcctcgctct gtcactcaag ctggagagtg cagtggtgca at

#ctcagctc  99060

actgcaacct gcacctcctg ggttgaagtg attctcatgc ctcagcctcc ga

#gtaactgg  99120

gattacagat atgtgccaac acacctggct tatttttgta tttttagtag ag

#acagtatt  99180

tcacaatgtt ggccaggctg gtctcgaact cctgacctca ggtgatccgc cc

#acctcggc  99240

ctcctgaagt gctgggatta caggcttgag ccaccatgtc cggccgacaa aa

#ctattaaa  99300

aacagtaact acaacggtta tttaggagac aggacaattg tttaagcaat aa

#aaagatta  99360

aatcaaaaca tcaaaaagtc aaaatggcaa tggcggtgtt aaagtataga gt

#ttttgtta  99420

cttttctttg caaagttaag tgattatcag tttaaaataa cctattataa ga

#tttttttg  99480

taagcctcac agtaaccata aagcaaaaac ctataataga tacactaaaa at

#aaatagca  99540

caaaatcaaa gcacgctgct agagaaaatc acttaccata gaggaagaca gt

#aagagagg  99600

aaaataggaa gaaagaatct acaaagcaac caaaaacaag gaacagtatg gc

#agtagtaa  99660

acccttacct gtcagtaata actttgaata taaatggatt aaattcttca at

#taagagtg  99720

gcagaatgga ttaaaaaaca agacccatcc atatgctggc tacaagaaac tc

#acttcatc  99780

tgtaaagata agcacagact gaaagtgaag gtatggaaaa agataattta tg

#caaatgga  99840

aaccaaaaaa gagcaagaga gcctatagtt ttatcacata aaataaactt aa

#atcaagat  99900

ggttaaaaaa aagacaaggc cattatataa cgacaaaggg gtcagtacag ca

#agaggata  99960

taacaatggt aaatatatat acacccaaca ccagagcacc caaatatata aa

#gcaaatat 100020

taatagacct aaagagagag atagactgca atacagtaat actagggaac at

#ccacactt 100080

tcaatgtgaa cagatcatcc agacagaaaa gaaacaaaga aacgtagaca tt

#aaactgta 100140

ctctggacca aatggaccta acagatattt acagaacatt ccatccaaca gt

#tgcagaat 100200

acacattttt ctcaacagca catggaatat tctccaggat tgatcataca tt

#aggtcaca 100260

aaacaagttt taacaaattt ttaaaattga aattatattt atcttgtcac ag

#tggaataa 100320

aactagaaat ctataatcag aggaacattg gaaacagtac aaattaatgg aa

#attaaaca 100380

acaaatggac caatgaagaa attttaaagt aaattttaaa atttcttgag ac

#aaatgaaa 100440

atggaaacaa aataccaaaa cctatgggat acagcaaaag cggttctaag ag

#ggaagtgt 100500

atagcaataa acgtctatat caaaaaagta aaaagacttc aaataaccta ac

#gatacacc 100560

tcaaggaact agaaaagcaa aaccaaacaa acccccaatt ttttgttctt tt

#tttctccg 100620

tgaaaaaagg catctaaaaa acaaaccaat gttaatagaa agaaataata aa

#agagcaga 100680

agtaaatgaa accaagacta aaagaataca aagatcaatg aaatgaaaat gt

#ttttttga 100740

ataggtaatc aaaattggca aacctttcag aagactaagt gttggggggt gg

#tgggtggg 100800

gggagaagaa gacccaaata agcaaaacca gaggtgaaaa atgggacatt gt

#aagtgata 100860

ccaccgatat acaaaaagat cattagagac tactatgaac aactatacac ca

#aaaaattg 100920

caaagcctag aaggaatgtg taaattctct gacacataca acctaccaag at

#tgaatcag 100980

gaagaaacaa aagacctcaa caaaccaata atgagtaatg agattgaagc ca

#tataaaaa 101040

aagtctctca accaagaaaa gcccaggacc tgttgcttca ctgctaaatt ct

#gccagaca 101100

tttaaagagc taataccaat cctactcaaa ctcctcaaaa caaaaatttt tt

#tggaagag 101160

aagggattac ttcccaactc attctacaag ggcaacatta ccctgatacc aa

#aaccagac 101220

aggatgcaac aagaaaatga caggccaaca tccctgatga acacagatgc aa

#aaatcctc 101280

aacaaaatac taacaaacca agtgcaacaa tacattaaaa agatcatcct gg

#gatacgaa 101340

gaggggaaga acagacttac ttgagggtgg ggggttggag gaaggagagg at

#cagaaaaa 101400

atacctattc ggtactatgc ttattacctg agtgatgaaa taatctgtac ac

#caagcctc 101460

tgtgacacac agtttaccca cataacaaac cagcacatgt acccctcaac ct

#aaaaaaaa 101520

aaaaaaaaaa aatcatcatg ataaagtgga aatccgaggg atgcaaggat ga

#ttcagcat 101580

acccaaatca ataaacatag tacattacat taatacaatc aagaccaaaa ac

#catatgat 101640

gatttcaata gatgctcaaa aagcattcag tagaattcag catcccttct tg

#ataaaaat 101700

tctcaacaaa cggtatagaa ggaacatact tcggtgaggt gtagtggctc at

#gcctgtaa 101760

tcccagcaat ttgggaggct gaggtgagtg gatcccttga agtcaggagt tt

#gagaccag 101820

cctggcccac atggtgaaac cccatctcta ctaaaaatac aaagcctggg tg

#atagagcg 101880

agactttatc tcaaaaaaga aaaaaaaaag aaggaacata tctcaaacca ta

#tatgacaa 101940

acccacagct aatgtcatgt tcaacagtga aaagctgaat aatgaataat tt

#ttctctaa 102000

gattaggaac agacaaggat gcccactcta accacttctg ttcaacttag ta

#cttgaagt 102060

cctagcccaa gcaattaggc aagagaaaga aataaagggt acccaaattg ga

#aaggaaga 102120

aaccacatta tctttatttg cagataacat gatcctgtat ttagaaaaac ct

#gaagactc 102180

ctccaaaaac tgctagaact gataaacaaa ttcacttaag tttcatgata ca

#aaatcaac 102240

ataacaaaaa tctgtagcat ttctatacat caacagcaag caatctgaaa aa

#gaaatcag 102300

aaaagcaatc ccatttacat agctacaaaa aaaataaaat acctaggcat ga

#acttaacc 102360

aaataagtga agaatctctg tgatgaaaac tgtaaaagac tgatgacaga aa

#ttgaagag 102420

gacatataga aaatgaaaag atacttcata ctcatggatt agaagaatta at

#attgttat 102480

ggagttcgag accagcctgg ccaacatagt gaaaccccat ctctactaaa aa

#tagaaaaa 102540

ttagccaggc ctggttgtgg gtgcctataa tcccagctac tcaggaggct ga

#ggcaggag 102600

aatcacttga acctgggagg cagagggtgc accaagccga gatcatgcca ct

#gcactcca 102660

gcctgggtga cagagtgaga ctccgtctca aaagtcagta ttacccaaag ta

#atctacag 102720

agtcagtata atctctatca aaataccaat gacatttttc acagaaatag aa

#aaaaccta 102780

aaatttgtgt ggaatgacaa aagaccttga atacctaaag ctatcctgag ca

#gaaagaac 102840

aaagttggag acatctcact gcctgacttt gaataccaca aagctatggt aa

#ccaaaaca 102900

ccatggttct atatatatgt gcacacattt tatacacaca taggtatata aa

#acacctac 102960

aaatttttgt tttttgagac agagtctcgc tctgttgccc aggctggagt gc

#agtggcat 103020

gatcttggct cactgcaacc tccgcctcct gggttcaagc aattctctgc ct

#cagcctcc 103080

caagtagctg ggattgcagg cacccatcac aaatgcctgg ctaatgtttt tg

#tatttttg 103140

gtagagatgg ggtatcacca tcttggtcag gctggtcttg aactcctgac ct

#catgatcc 103200

acctgcctcg gcctcccaaa gtgctgggat tccaggtgtg agccaccgca ct

#cagcctag 103260

acctacaaaa ttatacttgg agaatcctga caaaaaggct ggctgagaaa gc

#acacccat 103320

aattatactc aactctcata tagagaactc tatttaactt tgtagtgctt ca

#tagccaag 103380

acttgccaga aattggcaga acatctctaa cataagagag accaaaagaa ag

#aaaaatgt 103440

acctcggaga taacaaaaac aatgtaataa gcaaaagaaa tcataaatga ac

#tgtaatta 103500

atattcttgt agaggtgagg tgaaggaaca agaataaatt gctattttct aa

#aacattca 103560

gaaagcttgg gaactaaaaa taggagagct gaaatttaaa atcagtgatt gg

#ataaagtt 103620

gagaaaatat cttagtaaaa caaaaagaaa aaacaagaga tgacttagag ag

#aaaagata 103680

agaaacttag aagcaaaatt caagttgtct gatgtttaac tgactggaat tc

#cagaaaaa 103740

gagaatagag aaaacgaaca gcaggatgtt atcaaaatga caatataaga gt

#agatggac 103800

atgtatctgt ttccaatacc actgagtgag gaaaataagc cacagtacca tg

#aaactgta 103860

gaacaccaag gacaaagaga agctgcaaaa actgaaaaat caactcttca at

#cagaaaat 103920

tgaggcttca gggcaaacca ttctcccaaa aactggaggg aatggtgcat ac

#tgagaatc 103980

acagattacc tccagaaacc tcaccagatt ctcagggtaa agagaaaaat ct

#cctcaagc 104040

tttaggtagg gagaagggga aatcatcatc ttgaaataag ccgtagcact cc

#ttagcaat 104100

ggtttgctct caaagtaaac tgtttaatca agcctaattg acatgtgctt ta

#ccagagcc 104160

taacagacct ggaggaagat gtgttagtcc atcttgcatt gctaaaaaag aa

#tacctgag 104220

actggtaatt tataaagaag aggggtttat ttggctcaca tttctgcaga ct

#gtacaaga 104280

agcatggcac cagcatctat ctgcttagct tctggtgagg cctcaggaag ct

#ttccctta 104340

tggtggaaca caaaggggaa caggcacagc acatggagag agagagagca ag

#agagagag 104400

gggagggagg tgccagactc ttgaacaacc agatctcgca ccaggtcttg cg

#tgaactat 104460

agttatagag taagaactca ctcacaagtg cagggacaac atcaagccat tc

#atgaggga 104520

tctggcccca tgacccaaac acttcccact aggccccacc ttcaacactg gg

#aatcacat 104580

ttcagcatga gttggagggg aaaaataccc aaagtgtatc agaagggaaa ca

#cccaactg 104640

cagccctctc tagccttcct gtcttaccta attggggaga agggaacctg ag

#aagcactt 104700

gtgaaagtca cggcccaggc acacaggctc actaaaagac tgagaactaa tt

#atgtgatt 104760

ataagacact ccccccacca cacacacctc accaccacac caatcagtct cc

#tgtgtaat 104820

gatagtggat tactgctaaa tgaactaatt ttcagaccct attctatttt aa

#taaggagt 104880

ctttagggaa acgaagaaat gatagataca aaaacaagga tgtgattgta ac

#aacgtggg 104940

tacagctgga ggccattatc ctaagtgaat taatgctgaa acaaaaaacc aa

#aaactaca 105000

tgttccgaac tcataagtgg gagctagaca ttgggtattc atggacataa ag

#atgggaac 105060

agtagacact gggtactgca agagacagga gagagggagg ggagaaaggg tt

#gaaaagct 105120

gcctattggg tactatgctc acgacctggg tagcaggatc agttgtaccc ca

#gacgtcag 105180

catcacacaa aatacccttg taacctgcac gtgtacccct gaatctaaaa ta

#aaaattga 105240

tttaaaaaag gacactaaag gaaatgtaac ctatacagct acacaaaaca gt

#aaacacaa 105300

cccaactctt agccagagaa acataaagcc tcaaacaaga ggacttttta cc

#gcagtttc 105360

ttctacccag tatatcatgt ctgctttcaa caaaaactta caagacatgc ta

#aaaggcaa 105420

aaatcaaagt tgcatgaggc ataacaagaa tcagaaccat tgccagactc at

#ttatggca 105480

gcgatttttg gaataatcag actggaaatt ttaaataagt atgattaata ta

#ctaaaggc 105540

tctaatggaa aaagtgaaca acatgcaaga aaggtgggta acataagcag ac

#aatagaaa 105600

ctctaagaaa gaacccaaaa gaaatactag aaataagcaa tactataaca ga

#aatgaaga 105660

atgcccttgg acttattgat agagtggaaa ggacaataga taacctggga aa

#gattcaat 105720

gagcttgaag atatgtcagt agaaagttcc aaaacttaaa ctgcaaagag aa

#aaaagaat 105780

aaatgacaga acatggcagg gcctggtggc tcacactgta tctccacact tc

#aggaggcc 105840

caggtgggaa gatcacttga gaccaagagt tgagggccag cctaggcaac ag

#agagagat 105900

ctgttgactc cacaaaaaat aaaaaggaaa agaataggat atccaaaaac tg

#tgggacag 105960

ttacaaaatt atatatattt aagtccttgc tttggctgaa cctaacacta aa

#attggaac 106020

aataccaaga agattgcaca acatggccct gtgcaaggat gatatgtaag gt

#catgaagc 106080

atagaaaaaa catttctaat tgtttttttt agatggagtc tcactctttc ac

#ctgagctg 106140

tagtgcagtg gcatgatctt ggctcactgc aacctctgct gcccagattc aa

#gcgattct 106200

cctgcctcag cctccagagt agctgggatt acaggtgtct accactgcgc ct

#ggctaatt 106260

tttgtaattt tagtggagat ggggtttcac catcttggcc aagctggtct tg

#aactcctg 106320

acctcgtgat ccacctgcct tggcctccca aagtgctggg attacaggtg tg

#aggcacct 106380

cacccagcca acatttctaa tttttttttt tttttttttt tagacatagt ct

#cactctgt 106440

cgcccaggct ggagtacagt ggggcaatct cggctcactg caagctccgc ct

#cctgggtt 106500

catgccattc ttctgcctca gcctccctag tagctgggac tacaggtgcc tg

#ccaacaca 106560

tccagctaat tttttatact ttttagtaga gacggggttt caccatgtta gc

#cgggatgg 106620

tctcgatctc ctgaccttgt gatccgcccg cctcggcctc ccaaagtgct gg

#gattacag 106680

gcgtgagcca ccgcgcctgg ccaatttttt aaaaaattaa aaaaaatatg tg

#tatgtaaa 106740

attgtgtaca cacgatggga ataacaaagg aaaagagaga aaggaataga ag

#aaccattt 106800

gaagtaataa tgactatttt caaaactaaa gacagatgcc aaaccacaaa tc

#cagtttag 106860

aaagttaaga aaacaagcaa gataaatacc aaatgccagg tgcggtggct ca

#cacctgta 106920

atcccagcat tttgggaggc cgaggtgggc agatcacttg aggtcaggag tt

#caagacca 106980

gcctggccaa catggtgaaa ccctgtctct actaaaaata gaaaaattag gc

#ctggtggc 107040

aggtgcctgt aatcccagct actcaagaga ctgaggcagg agaattgctt ga

#acctggga 107100

ggcagaggtt gcagtgagct gggcaccact gcactccagc ttgggcaaaa ga

#gtgagact 107160

ccatctccaa aaaaaaaaaa aaaaaaaaaa gataaataca agaaagtctg ta

#cccaggca 107220

cctaggcata tcataatcaa attgcagaaa atcaaagata acatcctgaa aa

#aacctaga 107280

ggaaaaaaaa cacctatgga gagtggagtg aaatatctct atatttatta tg

#tctttatt 107340

atgtttttaa ttatgttttt catttatttt tgtggttacc tggtaggtgt at

#atatttat 107400

ggggtacatg agatattttg atgcgggtat acaatatgta ataatcacat ca

#ggatgaat 107460

gaggtatctg tcacctcaag catttatcat tttcttgtat tacaaaccat ct

#agttatac 107520

tctagttgtt tttaaataaa tagttaatta ttgactgtag tcaccgtgtt gt

#gctatcaa 107580

atactagatt ttattccttc tatctaataa tatttttgta ccctataatt at

#cccctccc 107640

ccacccacct acccactacc cttcccagcc tttggtaacc attgttctac tc

#tctatttc 107700

catgagttca actgtcttaa tttttagctc ccacaaataa gtgagaacat gt

#aaagtttg 107760

tctttctata cctggcttat tttacttaac ataatgaccc ccacttccat cc

#atgttgtt 107820

gcagatgaca gggtcattct tttctatggc tgaatagtac atatatatat at

#atataata 107880

tttcctttat ccatttatct gttgatggac acttagattg atcccaaatc tt

#ggctattg 107940

tgaatagtgc tgcagcaaac gtgagaatgc agatatctcc ttgatttact ga

#tttccctt 108000

cttttgggta tattcctagt agtgggattg ctagatcata tggtagttcc at

#ttttagtt 108060

ttttgaggaa cctccatact gttctccatg gtggttgtac taatttatat tc

#ccaccaac 108120

agtgtaccag ggttcccttt tctccacatc ctcaccagca ttcgttattg cc

#tgtctttt 108180

ggataaaagc cattttaact gggatgagat gatatctcat tgtagttttg at

#ttgcatct 108240

ccctgatggt catgacgtaa tattgagtac cttttcatat acctgcttgc ca

#tttgtatg 108300

tctactttgt agtaatgtct attctgatct tttgcccatt ttttattgta tt

#attcgatt 108360

ttttattgac ttgtttgagc tctttattct ggttattagt ttcttgtcaa at

#ggatagtt 108420

tgcaaatatt ttcttccatt tgggggattg tcacttccct ttgttgattg ta

#tcctttgc 108480

tgcatagaag tttttacact tggcatgatc ccatttgtcc atttttgctt tg

#ggtgcctg 108540

tctttgtggg gtattactca agaaatcttt gctcagtgca atgtcctgga ga

#gttttcca 108600

aatgttttct tttagcagct tcatagtttg aggttttaga tttaagtatt ta

#attcattt 108660

tgatttgatt tttgtatatg gcaagagata ggggtctagt ttctttcttt ct

#tctttttt 108720

tcctttgctt tacttttttt tttttttttt tttttttttg agacagggtc tc

#actctgtc 108780

tcccaggctg gagtacagtg gtgtgatcac aactcattgc aacctccacc tc

#ccaggttc 108840

aagtaattct aatgcctcag cctcctgagt agctgggatt tcaggtatat gc

#caccatgc 108900

ctggctaatt tttgtatttt gagtagagac ggggtttcac catgttgccc gg

#gctggtct 108960

caaacttctg gcctcaagtg atccactggc cttgacttac taaagtgctg gg

#attatagg 109020

tgtgagccac catgtccagc aagtatctag tttcattcta ctacatatgg at

#atccagtt 109080

ttcccagcac catttattga agagactgtt ctttccccaa tgtatgttct tg

#gcacattt 109140

gttggtaatg agttctctgt agatgtgtgg atatgtttct gggttatctg tt

#cttttcca 109200

tcaatctgtg tgtctatttt tatgccagta ccatgctgtt ttggttacta ta

#actctgta 109260

gtataattcg aattcaggta atgttactcc accagtatta ttctttttgc tc

#aggatagc 109320

tttggttatt ctggatcttt tcatggttcc aggtaaactt tagaattgtt tt

#ttctattt 109380

ctgagtagaa gaattttatt ttattcatag ctattgtaaa tgggattact tt

#cttgactt 109440

ctttttcaga ttgttcactg ttggcacata aaaatgctac tgatttttgt at

#gttggttt 109500

tgtcttcttc aactttctga atttattagt tctaatagtt tttttggtgg ag

#tcttttgg 109560

tttttccaaa tataaggtta tattatctat aaacaaggat aatttgactt ct

#ttctttct 109620

agtttggatg ccctttcttt ctattttctt attactgtaa gacttacaga at

#gaaatatt 109680

taaagtattg aaagaaaaac cccaccaacc tatggtaact ccatgtttcc ag

#ttggtagt 109740

tgcttaggca aaacaccttg gagtcattct tgattctcct tgtccctcac at

#cccacatc 109800

ctatctgtta ggatatcgag atgtaataag aaaaaaaaaa ttgtaatcct cc

#ccttctta 109860

ccacctctat ttctatctcc ttggtccaag ccatcattat ctcttctctg ga

#ttattgct 109920

atagactcca tactacagtc taaacagagc aactagaatg attaaagtcc aa

#tctagtac 109980

tactacagaa gcttcccatt tcactacctg tctatgaatt acttaatttc tc

#tgtgtctc 110040

agttgcttca tctgttaaaa gagaataata cctcctcagg agattgtgtg at

#tgatgagg 110100

aggcacttac ttaataccaa cctgatgcac agaaaatagt aaagtttagc ga

#tttttttt 110160

attattttaa tttccaattt gcccttcaaa tcagaagctt agttttgtct ta

#ttcttcag 110220

tgcttgaggt gggagggttt gtagaaacat ttggcttctg aatacctagc tc

#attgctgt 110280

caagcagaat cctccatctt ttagtgcctg aaaatattca gatgtccaga aa

#cattaacc 110340

aaaggaaatt ccatttctag ctctgctgtt tgtataggca atgtagtggg tc

#agttttct 110400

gcactgtgta gaaattgctt tgtcagtgga aaatgttatt ttcgtcggtt tt

#acagttcc 110460

taacttttga ggcatttgtt ccctggagga tactaaaaga aggaaatctt ca

#gacagctg 110520

cccactgaat ttttgcgtga gcctttattt gatattttac ccagacccct tt

#tggttttt 110580

tattacagta acatcgcata cctaggtttt ttttttcttc ttcatataag cc

#ttacctat 110640

ctggaactgt cagtactagg aaggtactta tagtgttgaa tgttcccact ca

#tatttcct 110700

gttatgcctt atgcttttta taacaagcca aaaagaggaa gaaagatttc ac

#catagatt 110760

tgctaaaggc aatgtgggat gcaatgagtg tggtttaatg gaagagccct gg

#ggtgcggc 110820

ctctgagcct tgctctgcca ctgacacctg tatgactgcc tgggcttgag tt

#aaacgttc 110880

tgcataaatt ctagcagaag aggctagctc aaagaggaga ttcagtgtct ga

#atgtctga 110940

gagagtgtga aaataagaaa agttggctgg gcgccgtggc tcacacctgt aa

#tgcagcac 111000

tttgggaggc cgaggcaggc ggatcacctg aggtcaggag ttcaagacca gc

#ctgaccaa 111060

catggagaaa ccctgtctct attaaaaatt caaaaaagta gccaggcgtg gt

#ggtgcatg 111120

cctgtaatcc cagctactca ggaagctgag gcaggagaag tgcttgaacc tg

#ggaggcag 111180

aggttgtggt gagccaagat tgcgccattg cactccagcc tgggtgacag ag

#cgaaactc 111240

cgtctcaaaa caacaacaac aacaacaaca aagtcaagtc acttgagacc tc

#aacccact 111300

gacaagagaa gagggactgg ggcagaccca acctgaactg gttctgtaaa gc

#agccacgg 111360

cacagaccag agtggactgt gggcctgagc agtgtatgcc cctggggcct gg

#aaagtagg 111420

ggctgggact tcatttcttg aatagaggga gaaggaaaga cacttgagaa tc

#tggtaaaa 111480

acaaaaacaa caacaacaaa aaacccaaaa caaataaaac attctagtag ct

#tcaggccc 111540

tccactgggc atggtgtctt cttgacccac agacaatagg caggcaaagt ag

#atggaagc 111600

aagtgctaac atgatacaca gctcccaggg cttagacact tcccacctca gc

#aagctgga 111660

cccatccaag ctgtggtgtc agggtagaac aaatgattct ttttttcgag at

#ggagtttc 111720

gctcttgttg cccagtctgg agtgcaatgc tgagatcagc tcactgcagc ct

#ccgcctcc 111780

caggtttgag caattcacct gcctcagcct cctgagtagc tgggattaca gg

#cgcctgcc 111840

aacacgctca gctaattttt tgtattttaa gtagagatgg ggtttcacca tg

#ttggccag 111900

gctggtctcg aactcctgac ctcaggtgat ctgcccgcct tcgcctccca aa

#atgctggg 111960

attacaggca tgagctaccg cgcccagccg aacaaatgat tcttatatgt ag

#attcttta 112020

gggagcagct aagccagccc ccattgactg ggggagatga tggtagcttt ga

#gacactcc 112080

tagcagctgc agttttgtta tcctgcaccc tgttcacttt ccagggccat gc

#acctccac 112140

ggaaatacct tatctataag ccttgtgtct ctacttcagt ttaggtctcc ta

#gactgtaa 112200

cggagaacaa aaaaaaaaaa tagaccaagt tttaggcatt gcaggaaaaa aa

#agtgtgtt 112260

cattctctga gcctccgaag taatgcagct atatttataa gtggatcagt aa

#aaggagaa 112320

acttctttag gtttttagac ctgggattca gcattgagat tttctgtgct ct

#gaaggact 112380

atccagtaac tgtccttcca ataactttcc ttagtttctt gttacaatcg cg

#attccggt 112440

ggttatcaaa cttcttccta gtggattgct tttccactct tcattgacat ta

#cttgttcc 112500

caagtttttt tttgctgttg caaagtgttg aaataaacat ctttgtactt aa

#atgatata 112560

tgtgtaacag taaattttta acattaaacc actgacttaa ttcatttatt ga

#attttgtt 112620

gtagtatatc acacatacag tataccaatc atttatcaat aactgatgtg tt

#cacaaaat 112680

gaacacatgc tcataatcac tactgatatc aagacagaaa attaccagca cc

#ctggaagc 112740

ctctctcagc ttctctctct caatcactac cacctccttc ctacccaggg ca

#aacagtat 112800

cctgatttct aagatcattg atttgtttta cctacttagt agctttaaat tt

#tttaaatg 112860

aagatgtagt atattattct ttggaatctg gctccccacc tcctcatcat ta

#tgttgaga 112920

ttcatctgtg ttgttgctaa tgtagcagag ttcatttttt tgttactgta ta

#gtgtatca 112980

ttatatgcgt agatcacgtt ttttaattta ttctttctca ttgcactgtt ct

#gcaatgcc 113040

accttgccgt aaaccaggca tctgcatctg aggggctgtt tctggacctg tc

#attctgtt 113100

tcatcgatat atttatctat ccttgtgcca aaaccctact gtcttactta tg

#gctatatc 113160

attaacttag ctaatgttta gagctatgta atgtagataa ttgtagctgt at

#aatagtaa 113220

tgtatcgata tctggtagaa taagttcttc tactttgtta ttcttttaaa ac

#taccttga 113280

ctattcttgg ccctgtgtat ttccatataa cttttacaat caagttgaaa tt

#actccctc 113340

ccctccaaaa aaaaaaaaaa agcatgctag aattttgatt gggaattctt tg

#aggagaat 113400

ggctatcttt attatattaa atcttcctgt ccctgaaagt ggtatgtctg tt

#tatgtggg 113460

tctttaattt ctctcaatag tgttttatag ttttctgtgt taaggtttta ta

#tatctttt 113520

attgatttac tcttacatat tcagtgggct tttaaatgta ataaatggta tt

#tatcacaa 113580

atttatcata aagattccta attattgcat gtattagaaa catttttata ta

#ttaaagca 113640

taggttttta attataagat tttatgagat ttacggttta tatcatttta ag

#aatcactt 113700

aatattcaaa ttcaaatcac catgagaatt ctgggtaaat tgagaaaagt aa

#agttggat 113760

taaatccagg gttgtatcct tggagaattc aaaaggaacc aggaagagct tg

#ttcctaaa 113820

ctgcgtgagt tctgtgttgg ttgcttgaga gagattgcct agggcttgct tc

#ctctctca 113880

gctaaagtga ttgggatttg gcagtcaggg tgcttttgtt tttagggtac cc

#tgagccct 113940

ctcctagcca gcccacattt gtgagcactc ggtaaacaca gagcaggagg ga

#attacagt 114000

gaatggggat ttccctcagt gctgcccact ggctgctctt gaactgacag gc

#ttctttct 114060

cattctaaac tcaccagcag tggagcagta aacccggcca cggtcaggca tg

#gcacatgt 114120

cctgcaatga tggggactgg acctgttgcc ttaaactcac gcctgctttg tt

#tttccagg 114180

tctataaggg agaattccaa ctacctgact ttcttaaaga aaaaccacag gt

#actgtgtc 114240

tgctttttcc tcctgatgta tactagattg gctcttgcat tgaagtaata tt

#tttaaaga 114300

gataatgaaa ttaaaaagac agaaacaaga aaaccaaaaa gaaaagaaga aa

#agggatag 114360

tgatatgtgc tggggaagaa agatcagcgt ctgggacttg ttgattttaa ca

#ataattta 114420

acacagtctt aatttcagag agctcagtgt ctcccaaaac cagggaaata ct

#ttattgat 114480

aaccaaattc tgattgcttg aggtcctgca caagccgccc agtgggtaaa gc

#tgctccag 114540

cgttccagtg cctaatttga aataaaaatg ttcagcgacc ctctctgttc ct

#actctgtg 114600

tactgtacat ccttgcccct ttgacttttc tcatttggag cccagatgac tt

#atatatac 114660

acatagtcac tggcccctgg gaaggacagt gagagtttga aggattaaag cc

#agcatggt 114720

ggctcatgcc tgtaatccca gcaatttgtg agaccgaggt tggcagatca ct

#tgaagtcg 114780

ggagttcaag accagcatgg ccaacatggt gaaacctcat ctctactgaa aa

#tataaaaa 114840

ttagccgagt attgcagaat ttgcctgtaa tcccagctac ttgggaggct ga

#gggagaat 114900

cacatgaacc gggagttgga ggttgctgag ccaagattac accactgcac ta

#cagcctgt 114960

gtgacagaac aagactgcct caaaaaaaga aaaaattagc taggcatggt gg

#cgaggcct 115020

ctggtcccag ctacttggga ggctgaggca ggaggatcgc ttgagcccat ga

#ggtggagg 115080

ttgccatgag tttagattgt gccactgcac tccagcctgg gtgacagagt ga

#gaccctgt 115140

ctcaaaaata aaaaaaatta agcagattca gagttttccc tgtaacgtct tc

#tctcactg 115200

acttgcattc caatcctgtt tcctgggttg gaaagaaaca gggagtctca cg

#gctgacat 115260

gcctagagga gcccggcatc ctgcctctgg gcatcactgt catgcccata tg

#gaagtcag 115320

aaaaaatgga cactcatggc ctgagtgcag ccgacttccc tttccagcaa gg

#cgatgatg 115380

catgttgcct ccaggctgct gctgtcagtg attagcttgt caataggaag ag

#gagactca 115440

gttttgaact cagtttctga aagcgttcca gatagaggtt ggtgaagcaa ca

#gcacctca 115500

gagacttgtg tgaagtccag ttgcctgatg caagcctgga gtaaatgggc tg

#ccctctct 115560

gagggaagcc atgtctcaca ccagagttga agcctcttcc ttcctgaccc tt

#ttctgaaa 115620

acacttagcc gccagtaatt gatacatatg acttgagtgt ttcaaagtac tt

#tcaaggca 115680

tattcttatt cacatatatt tactattcat ccattcattc acttattcac ca

#attgttta 115740

cccagtgtct actatggtga ggaattagag taagtcctca ggagtcacgg gg

#gaaagaaa 115800

gacctcaagg agctcctgat ttatccagaa gaatccgacc acctcgtgca ga

#caagggga 115860

cacagagctc tgggcccagg ctgggcatga tgtcccagaa acctgggcag at

#tcatgaac 115920

agactgacac cggctgtgga aattggagcc agagaatatt ccaagaggct gt

#cttgaagg 115980

aatataaaat ccaaaagcgc ccaggtgcgg tggttcacgc ctgtaatccc ag

#cactttgg 116040

gaggcccagg tgggtggatt gcctgaggtc aggagttcaa gatctgttta gc

#caacacag 116100

tgacaccccg tctctactaa aaatataaaa taattagcaa gacttggtgg tg

#tgcgcctg 116160

taatcccagc ctgggtgaca gagcgagagt ctgtctcaaa aaaaaaaaaa aa

#aaaaaaaa 116220

aaaattccaa aagccggttt gcataacaaa tctgaagaag tcaagaaaag gt

#atttgaga 116280

ctaaaactaa agggacactc ctgcttcaca acatacctaa aaatatttcc aa

#atggattg 116340

cacacctaaa tgtgaaaggc aaaataatga aagttgttag aggatataga ag

#agccaggc 116400

atgaggctca cgcttgtaat cccagcactt tgggaggcag gcagattgct tg

#agtccagg 116460

cattcaaaac cagcctggga aacatagcca aacctcatct ctactaaaaa ta

#caaaaaat 116520

tagctgggtg tggtgcatgc ctgtagtccc agctacttgg gaggctgagg tg

#ggaggatc 116580

acctgagccc ca

#

#

#   116592

<210> SEQ ID NO 4

<211> LENGTH: 365

<212> TYPE: PRT

<213> ORGANISM: Human

<400> SEQUENCE: 4

Met Val Gly Lys Leu Lys Gln Asn Leu Leu Le

#u Ala Cys Leu Val Ile

1               5

#                10

#                15

Ser Ser Val Thr Val Phe Tyr Leu Gly Gln Hi

#s Ala Met Glu Cys His

20

#            25

#            30

His Arg Ile Glu Glu Arg Ser Gln Pro Val Ly

#s Leu Glu Ser Thr Arg

35

#        40

#        45

Thr Thr Val Arg Thr Gly Leu Asp Leu Lys Al

#a Asn Lys Thr Phe Ala

50

#    55

#    60

Tyr His Lys Asp Met Pro Leu Ile Phe Ile Gl

#y Gly Val Pro Arg Ser

65

#70

#75

#80

Gly Thr Thr Leu Met Arg Ala Met Leu Asp Al

#a His Pro Asp Ile Arg

85

#                90

#                95

Cys Gly Glu Glu Thr Arg Val Ile Pro Arg Il

#e Leu Ala Leu Lys Gln

100

#           105

#           110

Met Trp Ser Arg Ser Ser Lys Glu Lys Ile Ar

#g Leu Asp Glu Ala Gly

115

#       120

#       125

Val Thr Asp Glu Val Leu Asp Ser Ala Met Gl

#n Ala Phe Leu Leu Glu

130

#   135

#   140

Ile Ile Val Lys His Gly Glu Pro Ala Pro Ty

#r Leu Cys Asn Lys Asp

145                 1

#50                 1

#55                 1

#60

Pro Phe Ala Leu Lys Ser Leu Thr Tyr Leu Se

#r Arg Leu Phe Pro Asn

165

#               170

#               175

Ala Lys Phe Leu Leu Met Val Arg Asp Gly Ar

#g Ala Ser Val His Ser

180

#           185

#           190

Met Ile Ser Arg Lys Val Thr Ile Ala Gly Ph

#e Asp Leu Asn Ser Tyr

195

#       200

#       205

Arg Asp Cys Leu Thr Lys Trp Asn Arg Ala Il

#e Glu Thr Met Tyr Asn

210

#   215

#   220

Gln Cys Met Glu Val Gly Tyr Lys Lys Cys Me

#t Leu Val His Tyr Glu

225                 2

#30                 2

#35                 2

#40

Gln Leu Val Leu His Pro Glu Arg Trp Met Ar

#g Thr Leu Leu Lys Phe

245

#               250

#               255

Leu Gln Ile Pro Trp Asn His Ser Val Leu Hi

#s His Glu Glu Met Ile

260

#           265

#           270

Gly Lys Ala Gly Gly Val Ser Leu Ser Lys Va

#l Glu Arg Ser Thr Asp

275

#       280

#       285

Gln Val Ile Lys Pro Val Asn Val Gly Ala Le

#u Ser Lys Trp Val Gly

290

#   295

#   300

Lys Ile Pro Pro Asp Val Leu Gln Asp Met Al

#a Val Ile Ala Pro Met

305                 3

#10                 3

#15                 3

#20

Leu Ala Lys Leu Gly Tyr Asp Pro Tyr Ala As

#n Pro Pro Asn Tyr Gly

325

#               330

#               335

Lys Pro Asp Pro Lys Ile Ile Glu Asn Thr Ar

#g Arg Val Tyr Lys Gly

340

#           345

#           350

Glu Phe Gln Leu Pro Asp Phe Leu Lys Glu Ly

#s Pro Gln

355

#       360

#       365