Isolated human kinase proteins, nucleic acid molecules encoding human kinase proteins, and uses thereof

The present invention is in the field of kinase proteins that are related to the rho/rac-interacting citron kinase 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.

Protein Kinases

Kinases regulate many different cell proliferation, differentiation, and signaling processes by adding phosphate groups to proteins. Uncontrolled signaling has been implicated in a variety of disease conditions including inflammation, cancer, arteriosclerosis, and psoriasis. Reversible protein phosphorylation is the main strategy for controlling activities of eukaryotic cells. It is estimated that more than 1000 of the 10,000 proteins active in a typical mammalian cell are phosphorylated. The high energy phosphate, which drives activation, is generally transferred from adenosine triphosphate molecules (ATP) to a particular protein by protein kinases and removed from that protein by protein phosphatases. Phosphorylation occurs in response to extracellular signals (hormones, neurotransmitters, growth and differentiation factors, etc), cell cycle checkpoints, and environmental or nutritional stresses and is roughly analogous to turning on a molecular switch. When the switch goes on, the appropriate protein kinase activates a metabolic enzyme, regulatory protein, receptor, cytoskeletal protein, ion channel or pump, or transcription factor.

The kinases comprise the largest known protein group, a superfamily of enzymes with widely varied functions and specificities. They are usually named after their substrate, their regulatory molecules, or some aspect of a mutant phenotype. With regard to substrates, the protein kinases may be roughly divided into two groups; those that phosphorylate tyrosine residues (protein tyrosine kinases, PTK) and those that phosphorylate serine or threonine residues (serine/threonine kinases, STK). A few protein kinases have dual specificity and phosphorylate threonine and tyrosine residues. Almost all kinases contain a similar 250-300 amino acid catalytic domain. The N-terminal domain, which contains subdomains I-IV, generally folds into a two-lobed structure, which binds and orients the ATP (or GTP) donor molecule. The larger C terminal lobe, which contains subdomains VI A-XI, binds the protein substrate and carries out the transfer of the gamma phosphate from ATP to the hydroxyl group of a serine, threonine, or tyrosine residue. Subdomain V spans the two lobes.

The kinases may be categorized into families by the different amino acid sequences (generally between 5 and 100 residues) located on either side of, or inserted into loops of, the kinase domain. These added amino acid sequences allow the regulation of each kinase as it recognizes and interacts with its target protein. The primary structure of the kinase domains is conserved and can be further subdivided into 11 subdomains. Each of the 11 subdomains contains specific residues and motifs or patterns of amino acids that are characteristic of that subdomain and are highly conserved (Hardie, G. and Hanks, S. (1995) The Protein Kinase Facts Books , Vol I:7-20 Academic Press, San Diego, Calif.).

The second messenger dependent protein kinases primarily mediate the effects of second messengers such as cyclic AMP (cAMP), cyclic GMP, inositol triphosphate, phosphatidylinositol, 3,4,5-triphosphate, cyclic-ADPribose, arachidonic acid, diacylglycerol and calcium-calmodulin. The cyclic-AMP dependent protein kinases (PKA) are important members of the STK family. Cyclic-AMP is an intracellular mediator of hormone action in all prokaryotic and animal cells that have been studied. Such hormone-induced cellular responses include thyroid hormone secretion, cortisol secretion, progesterone secretion, glycogen breakdown, bone resorption, and regulation of heart rate and force of heart muscle contraction. PKA is found in all animal cells and is thought to account for the effects of cyclic-AMP in most of these cells. Altered PKA expression is implicated in a variety of disorders and diseases including cancer, thyroid disorders, diabetes, atherosclerosis, and cardiovascular disease (Isselbacher, K. J. et al. (1994) Harrison's Principles of Internal Medicine , McGraw-Hill, New York, N.Y., pp. 416-431, 1887).

Calcium-calmodulin (CaM) dependent protein kinases are also members of STK family. Calmodulin is a calcium receptor that mediates many calcium regulated processes by binding to target proteins in response to the binding of calcium. The principle target protein in these processes is CaM dependent protein kinases. CaM-kinases are involved in regulation of smooth muscle contraction (MLC kinase), glycogen breakdown (phosphorylase kinase), and neurotransmission (CaM kinase I and CaM kinase II). CaM kinase I phosphorylates a variety of substrates including the neurotransmitter related proteins synapsin I and II, the gene transcription regulator, CREB, and the cystic fibrosis conductance regulator protein, CFTR (Haribabu, B. et al. (1995) EMBO Journal 14:3679-86). CaM II kinase also phosphorylates synapsin at different sites, and controls the synthesis of catecholamines in the brain through phosphorylation and activation of tyrosine hydroxylase. Many of the CaM kinases are activated by phosphorylation in addition to binding to CaM. The kinase may autophosphorylate itself, or be phosphorylated by another kinase as part of a “kinase cascade”.

Another ligand-activated protein kinase is 5′-AMP-activated protein kinase (AMPK) (Gao, G. et al. (1996) J. Biol Chem . 15:8675-81). Mammalian AMPK is a regulator of fatty acid and sterol synthesis through phosphorylation of the enzymes acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase and mediates responses of these pathways to cellular stresses such as heat shock and depletion of glucose and ATP. AMPK is a heterotrimeric complex comprised of a catalytic alpha subunit and two non-catalytic beta and gamma subunits that are believed to regulate the activity of the alpha subunit. Subunits of AMPK have a much wider distribution in non-lipogenic tissues such as brain, heart, spleen, and lung than expected. This distribution suggests that its role may extend beyond regulation of lipid metabolism alone.

The mitogen-activated protein kinases (MAP) are also members of the STK family. MAP kinases also regulate intracellular signaling pathways. They mediate signal transduction from the cell surface to the nucleus via phosphorylation cascades. Several subgroups have been identified, and each manifests different substrate specificities and responds to distinct extracellular stimuli (Egan, S. E. and Weinberg, R. A. (1993) Nature 365:781-783). MAP kinase signaling pathways are present in mammalian cells as well as in yeast. The extracellular stimuli that activate mammalian pathways include epidermal growth factor (EGF), ultraviolet light, hyperosmolar medium, heat shock, endotoxic lipopolysaccharide (LPS), and pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1).

PRK (proliferation-related kinase) is a serum/cytokine inducible STK that is involved in regulation of the cell cycle and cell proliferation in human megakaroytic cells (Li, B. et al. (1996) J Biol. Chem . 271:19402-8). PRK is related to the polo (derived from humans polo gene) family of STKs implicated in cell division. PRK is downregulated in lung tumor tissue and may be a proto-oncogene whose deregulated expression in normal tissue leads to oncogenic transformation. Altered MAP kinase expression is implicated in a variety of disease conditions including cancer, inflammation, immune disorders, and disorders affecting growth and development.

The cyclin-dependent protein kinases (CDKs) are another group of STKs that control the progression of cells through the cell cycle. Cyclins are small regulatory proteins that act by binding to and activating CDKs that then trigger various phases of the cell cycle by phosphorylating and activating selected proteins involved in the mitotic process. CDKs are unique in that they require multiple inputs to become activated. In addition to the binding of cyclin, CDK activation requires the phosphorylation of a specific threonine residue and the dephosphorylation of a specific tyrosine residue.

Protein tyrosine kinases, PTKs, specifically phosphorylate tyrosine residues on their target proteins and may be divided into transmembrane, receptor PTKs and nontransmembrane, non-receptor PTKs. Transmembrane protein-tyrosine kinases are receptors for most growth factors. Binding of growth factor to the receptor activates the transfer of a phosphate group from ATP to selected tyrosine side chains of the receptor and other specific proteins. Growth factors (GF) associated with receptor PTKs include; epidermal GF, platelet-derived GF, fibroblast GF, hepatocyte GF, insulin and insulin-like GFs, nerve GF, vascular endothelial GF, and macrophage colony stimulating factor.

Non-receptor PTKs lack transmembrane regions and, instead, form complexes with the intracellular regions of cell surface receptors. Such receptors that function through non-receptor PTKs include those for cytokines, hormones (growth hormone and prolactin) and antigen-specific receptors on T and B lymphocytes.

Many of these PTKs were first identified as the products of mutant oncogenes in cancer cells where their activation was no longer subject to normal cellular controls. In fact, about one third of the known oncogenes encode PTKs, and it is well known that cellular transformation (oncogenesis) is often accompanied by increased tyrosine phosphorylation activity (Carbonneau H and Tonks NK (1992) Annu. Rev. Cell. Biol . 8:463-93). Regulation of PTK activity may therefore be an important strategy in controlling some types of cancer.

Activated Rho GTPases trigger distinctive kinase cascades. In particular, the Rho-binding serine/threonine kinase (ROCK) binds to Rho, and its kinase activity is moderately stimulated by this association. The citron molecule (Madaule et al., 1995), a specific interactor of Rho and Rac, shares a significant degree of structural homology with ROCK; however, its lack of a kinase domain raised the question of its biologic function. By PCR of a mouse primary keratinocyte cDNA library, Di Cunto et al. (1998) identified a novel serine/threonine kinase, CRIK (citron Rho-interacting kinase), belonging to the myotonic dystrophy kinase family. CRIK can be expressed as at least 2 isoforms, one of which encompasses the previously reported form of citron in almost its entirety. The long form of CRIK is a 240-kD protein in which the kinase domain is followed by the sequence of citron. The short form, CRIK-SK (short kinase), is an approximately 54-kD protein that consists mostly of the kinase domain. CRIK and CRIK-SK proteins are capable of phosphorylating exogenous substrates as well as of autophosphorylation, when tested by in vitro kinase assays after expression into COS-7 cells. CRIK kinase activity is increased several-fold by coexpression of constitutively active Rho, while active Rac has more limited effects. Kinase activity of the endogenous CRIK is indicated by in vitro kinase assays after immunoprecipitation with antibodies recognizing the citron moiety of the protein. When expressed in keratinocytes, full-length CRIK, but not CRIK-SK, localizes into corpuscular cytoplasmic structures and elicits recruitment of actin into these structures. The previously reported Rho-associated kinases ROCK1 and ROCK2 are ubiquitously expressed. Northern blot analysis of mouse tissues revealed a restricted pattern of expression limited to keratinocytes, brain, spleen, lung, kidney, and an especially strong signal in testis. No expression was detectable in heart, liver, or skeletal muscle. The CRIK protein contains a kinase domain, a coiled-coil domain, a leucine-rich domain, a Rho-Rac binding domain, a zinc finger region, a pleckstrin homology domain, and a putative SH3-binding domain. Di Cunto et al. (1998) reported cloning the human homolog of the CRIK kinase domain. They stated that the human homolog of citron is contained within a PAC clone mapping to chromosome 12q.

Di Cunto et al. (2000) generated mice deficient in citron kinase by targeted disruption. Citron-K−/−mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with dramatic depletion of microneurons in the olfactory bulb, hippocampus, and cerebellum. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Di Cunto et al(2000) concluded that citron-K is essential for cytokinesis in vivo, in specific neuronal precursors only. Moreover, they suggested a novel molecular mechanism for a subset of human malformation syndromes of the central nervous system. For a review, see Di Cunto et al., J Biol Chem Nov. 6, 1998;273(45):29706-11; Di Cunto, et al., Neuron 28:115-127, 2000; Madaule et al., FEBS Lett . 377:243-248, 1995; Nagase et al., DNA Res . 6:63-70, 1999.

Kinase proteins, particularly members of the rho/rac-interacting citron kinase 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 kinase proteins. The present invention advances the state of the art by providing previously unidentified human kinase proteins that have homology to members of the rho/rac-interacting citron kinase subfamily.

The present invention is based in part on the identification of amino acid sequences of human kinase peptides and proteins that are related to the rho/rac-interacting citron kinase 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 kinase activity in cells and tissues that express the kinase. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system.

FIG. 1 provides the nucleotide sequence of a cDNA molecule or transcript sequence that encodes the kinase 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system.

FIG. 2 provides the predicted amino acid sequence of the kinase 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.

FIG. 3 provides genomic sequences that span the gene encoding the kinase 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. 148 SNPs, including 6 indels, have been identified in the gene encoding the kinase protein provided by the present invention and are given in FIG. 3 .

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 kinase protein or part of a kinase protein and are related to the rho/rac-interacting citron kinase 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 kinase peptides and proteins that are related to the rho/rac-interacting citron kinase subfamily, nucleic acid sequences in the form of transcript sequences, cDNA sequences and/or genomic sequences that encode these kinase 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 kinase 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 kinase proteins of the rho/rac-interacting citron kinase subfamily and the expression pattern observed. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. 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 rho/rac-interacting citron kinase family or subfamily of kinase 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 kinase family of proteins and are related to the rho/rac-interacting citron kinase 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 kinase peptides of the present invention, kinase 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 kinase 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 kinase 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 kinase 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. For example, a nucleic acid molecule encoding the kinase 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 kinase 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 kinase peptides of the present invention can be attached to heterologous sequences to form chimeric or fusion proteins. Such chimeric and fusion proteins comprise a kinase peptide operatively linked to a heterologous protein having an amino acid sequence not substantially homologous to the kinase peptide. “Operatively linked” indicates that the kinase peptide and the heterologous protein are fused in-frame. The heterologous protein can be fused to the N-terminus or C-terminus of the kinase peptide.

In some uses, the fusion protein does not affect the activity of the kinase 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 kinase 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 kinase peptide-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the kinase 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 kinase 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(l):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 kinase peptides of the present invention as well as being encoded by the same genetic locus as the kinase peptide provided herein. As indicated by the data presented in FIG. 3, the map position was determined to be on chromosome 12 by ePCR.

Allelic variants of a kinase 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 kinase peptide as well as being encoded by the same genetic locus as the kinase 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. As indicated by the data presented in FIG. 3, the map position was determined to be on chromosome 12 by ePCR. 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 kinase 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 kinase protein of the present invention. SNPs were identified at 148 different nucleotide positions in introns and regions 5′ and 3′ of the ORF. Such SNPs in introns and outside the ORF may affect control/regulatory elements.

Paralogs of a kinase peptide can readily be identified as having some degree of significant sequence homology/identity to at least a portion of the kinase 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 kinase peptide encoding nucleic acid molecule under moderate to stringent conditions as more fully described below.

Orthologs of a kinase peptide can readily be identified as having some degree of significant sequence homology/identity to at least a portion of the kinase 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 kinase 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 kinase 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 kinase peptide. For example, one class of substitutions are conserved amino acid substitution. Such substitutions are those that substitute a given amino acid in a kinase 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 kinase 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 kinase 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 kinase 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 kinase peptide. Such fragments can be chosen based on the ability to retain one or more of the biological activities of the kinase 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 kinase 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 kinase 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 glutarnic 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 kinase 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 kinase peptide is fused with another compound, such as a compound to increase the half-life of the kinase peptide (for example, polyethylene glycol), or in which the additional amino acids are fused to the mature kinase peptide, such as a leader or secretory sequence or a sequence for purification of the mature kinase 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 kinase-effector protein interaction or kinase-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.

Substantial chemical and structural homology exists between the rho/rac-interacting citron kinase protein described herein and mouse Cirton Rho-interacting kinase(CRIK) (see FIG. 1 ). As discussed in the background, mouse CRIK are known in the art to be involved in phosphorylating exogenous substrates as well as autophosphorylation., and have be may play a role in central nervous system s. Accordingly, the rho/rac-interacting citron kinase protein, and the encoding gene, provided by the present invention is useful for treating, preventing, and/or diagnosing disorder related to the cytokinesis and massive apoptosis.

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, kinases 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 kinase. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte. A large percentage of pharmaceutical agents are being developed that modulate the activity of kinase proteins, particularly members of the rho/rac-interacting citron kinase 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. 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 kinases that are related to members of the rho/rac-interacting citron kinase subfamily. Such assays involve any of the known kinase functions or activities or properties useful for diagnosis and treatment of kinase-related conditions that are specific for the subfamily of kinases that the one of the present invention belongs to, particularly in cells and tissues that express the kinase. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte.

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 kinase, as a biopsy or expanded in cell culture. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. In an alternate embodiment, cell-based assays involve recombinant host cells expressing the kinase protein.

The polypeptides can be used to identify compounds that modulate kinase activity of the protein in its natural state or an altered form that causes a specific disease or pathology associated with the kinase. Both the kinases 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 kinase. These compounds can be further screened against a functional kinase to determine the effect of the compound on the kinase 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 kinase 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 kinase protein and a molecule that normally interacts with the kinase protein, e.g. a substrate or a component of the signal pathway that the kinase protein normally interacts (for example, another kinase). Such assays typically include the steps of combining the kinase protein with a candidate compound under conditions that allow the kinase 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 kinase 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 kinases or appropriate fragments containing mutations that affect kinase 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) kinase activity. The assays typically involve an assay of events in the signal transduction pathway that indicate kinase 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 kinase protein dependent signal cascade can be assayed.

Any of the biological or biochemical functions mediated by the kinase 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 kinase can be assayed. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte.

Binding and/or activating compounds can also be screened by using chimeric kinase 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 kinase. 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 kinase 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 kinase (e.g. binding partners and/or ligands). Thus, a compound is exposed to a kinase polypeptide under conditions that allow the compound to bind or to otherwise interact with the polypeptide. Soluble kinase polypeptide is also added to the mixture. If the test compound interacts with the soluble kinase polypeptide, it decreases the amount of complex formed or activity from the kinase target. This type of assay is particularly useful in cases in which compounds are sought that interact with specific regions of the kinase. Thus, the soluble polypeptide that competes with the target kinase 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 kinase 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 kinase-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 kinase-binding protein and a candidate compound are incubated in the kinase 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 kinase protein target molecule, or which are reactive with kinase 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 kinases 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 kinase protein activity identified according to these drug screening assays can be used to treat a subject with a disorder mediated by the kinase pathway, by treating cells or tissues that express the kinase. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. These methods of treatment include the steps of administering a modulator of kinase 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 kinase 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 kinase and are involved in kinase activity. Such kinase-binding proteins are also likely to be involved in the propagation of signals by the kinase proteins or kinase targets as, for example, downstream elements of a kinase-mediated signaling pathway. Alternatively, such kinase-binding proteins are likely to be kinase 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 kinase 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 kinase-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 kinase 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 kinase-modulating agent, an antisense kinase nucleic acid molecule, a kinase-specific antibody, or a kinase-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 kinase 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. The method involves contacting a biological sample with a compound capable of interacting with the kinase 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 kinase 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 pharmacogenomic 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 kinase protein in which one or more of the kinase 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 kinase 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. Accordingly, methods for treatment include the use of the kinase 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 kinase 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 kinase/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 phycoerythrin; 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 kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte. 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. 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 the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. 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 kinase 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 kinase 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 kinase 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 5KB, 4KB, 3KB, 2KB, or 1KB 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 kinase 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 transcription, 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 kinase 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. As indicated by the data presented in FIG. 3, the map position was determined to be on chromosome 12 by ePCR.

FIG. 3 provides information on SNPs that have been found in the gene encoding the kinase protein of the present invention. SNPs were identified at 148 different nucleotide positions in introns and regions 5′ and 3′ of the ORF. Such SNPs in introns and outside the ORF may affect control/regulatory elements.

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. 148 SNPs, including 6 indels, have been identified in the gene encoding the kinase protein provided by the present invention and are given in FIG. 3 .

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. As indicated by the data presented in FIG. 3, the map position was determined to be on chromosome 12 by ePCR.

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 kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte. 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 kinase 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 kinase protein, such as by measuring a level of a kinase-encoding nucleic acid in a sample of cells from a subject e.g., mRNA or genomic DNA, or determining if a kinase gene has been mutated. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte.

Nucleic acid expression assays are useful for drug screening to identify compounds that modulate kinase 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 kinase gene, particularly biological and pathological processes that are mediated by the kinase in cells and tissues that express it. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system. The method typically includes assaying the ability of the compound to modulate the expression of the kinase nucleic acid and thus identifying a compound that can be used to treat a disorder characterized by undesired kinase nucleic acid expression. The assays can be performed in cell-based and cell-free systems. Cell-based assays include cells naturally expressing the kinase nucleic acid or recombinant cells genetically engineered to express specific nucleic acid sequences.

The assay for kinase 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 kinase 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 kinase 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 kinase mRNA in the presence of the candidate compound is compared to the level of expression of kinase 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 kinase nucleic acid expression in cells and tissues that express the kinase. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte. Modulation includes both up-regulation (i.e. activation or agonization) or down-regulation (suppression or antagonization) or nucleic acid expression.

Alternatively, a modulator for kinase 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 kinase nucleic acid expression in the cells and tissues that express the protein. Experimental data as provided in FIG. 1 indicates expression in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system.

The nucleic acid molecules are also useful for monitoring the effectiveness of modulating compounds on the expression or activity of the kinase 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 kinase nucleic acid expression, and particularly in qualitative changes that lead to pathology. The nucleic acid molecules can be used to detect mutations in kinase 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 kinase 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 kinase 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 kinase protein.

Individuals carrying mutations in the kinase 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 kinase protein of the present invention. SNPs were identified at 148 different nucleotide positions in introns and regions 5′ and 3′ of the ORF. Such SNPs in introns and outside the ORF may affect control/regulatory elements. As indicated by the data presented in FIG. 3, the map position was determined to be on chromosome 12 by ePCR. 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 kinase 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 kinase 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 94/16101; Cohen et al., Adv. Chromatogr . 36:127-162 (1996); and Griffin et al., Appl. Biochem. Biotechnot . 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 (1988); Saleeba et al., Meth. Enzymol . 21 7:286-295 (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 (1992)), 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 kinase 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 kinase protein of the present invention. SNPs were identified at 148 different nucleotide positions in introns and regions 5′ and 3′ of the ORF. Such SNPs in introns and outside the ORF may affect control/regulatory elements.

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 kinase 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 kinase protein. An antisense RNA or DNA nucleic acid molecule would hybridize to the mRNA and thus block translation of mRNA into kinase protein.

Alternatively, a class of antisense molecules can be used to inactivate mRNA in order to decrease expression of kinase nucleic acid. Accordingly, these molecules can treat a disorder characterized by abnormal or undesired kinase 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 kinase protein, such as substrate binding.

The nucleic acid molecules also provide vectors for gene therapy in patients containing cells that are aberrant in kinase 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 kinase protein to treat the individual.

The invention also encompasses kits for detecting the presence of a kinase nucleic acid in a biological sample. Experimental data as provided in FIG. 1 indicates that kinase proteins of the present invention are expressed in the brain glioblastoma, uterus tumor, colon, normal nervous system, tumor nervous system by a virtual northern blot. In addition, PCR-based tissue screening panel indicates expression in a pooled tissues such as brain, heart, kidney, lung, spleen, testis, leukocyte. For example, the kit can comprise reagents such as a labeled or labelable nucleic acid or agent capable of detecting kinase nucleic acid in a biological sample; means for determining the amount of kinase nucleic acid in the sample; and means for comparing the amount of kinase 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 kinase 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 WO95/25 1116 (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 kinase 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 kinase gene of the present invention. FIG. 3 provides information on SNPs that have been found in the gene encoding the kinase protein of the present invention. SNPs were identified at 148 different nucleotide positions in introns and regions 5′ and 3′ of the ORF. Such SNPs in introns and outside the ORF may affect control/regulatory elements.

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 kinase 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 enterokinase. 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 kinases, 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 kinases, 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 kinase protein or peptide that can be further purified to produce desired amounts of kinase 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 kinase protein or kinase protein fragments, such as those described above as well as other formats known in the art. Thus, a recombinant host cell expressing a native kinase protein is useful for assaying compounds that stimulate or inhibit kinase protein function.

Host cells are also useful for identifying kinase 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 kinase protein (for example, stimulating or inhibiting function) which may not be indicated by their effect on the native kinase 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 kinase protein and identifying and evaluating modulators of kinase 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 kinase 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 kinase 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'Gorman et al. Science 251:1351-1355 (1991). If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein 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, I. 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, kinase 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 kinase protein function, including substrate interaction, the effect of specific mutant kinase proteins on kinase protein function and substrate interaction, and the effect of chimeric kinase proteins. It is also possible to assess the effect of null mutations, that is, mutations that substantially or completely eliminate one or more kinase 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.

4

1

1515

Human

1

ggggagatgt tgaagttcaa atatggagcg cggaatcctt tggatgctgg tgctgctgaa 60

cccattgcca accgggcctc caggctgaat ctgttcttcc aggggaaacc accctttatg 120

actcaacagc agatgtctcc tctttcccga gaagggatat tagatgccct ctttgttctc 180

tttgaagaat gcagtcagcc tgctctgatg aagattaagc acgtgagcaa ctttgtccgg 240

aagtattccg acaccatagc tgagttacag gagctccagc cttcggcaaa ggacttcgaa 300

gtcagaagtc ttgtaggttg tggtcacttt gctgaagtgc aggtggtaag agagaaagca 360

accggggaca tctatgctat gaaagtgatg aagaagaagg ctttattggc ccaggagcag 420

gtttcatttt ttgaggaaga gcggaacata ttatctcgaa gcacaagccc gtggatcccc 480

caattacagt atgcctttca ggacaaaaat cacctttatc tggtcatgga atatcagcct 540

ggaggggact tgctgtcact tttgaataga tatgaggacc agttagatga aaacctgata 600

cagttttacc tagctgagct gattttggct gttcacagcg ttcatctgat gggatacgtg 660

catcgagaca tcaagcctga gaacattctc gttgaccgca caggacacat caagctggtg 720

gattttggat ctgccgcgaa aatgaattca aacaagatgg tgaatgccaa actcccgatt 780

gggaccccag attacatggc tcctgaagtg ctgactgtga tgaacgggga tggaaaaggc 840

acctacggcc tggactgtga ctggtggtca gtgggcgtga ttgcctatga gatgatttat 900

gggagatccc ccttcgcaga gggaacctct gccagaacct tcaataacat tatgaatttc 960

cagcggtttt tgaaatttcc agatgacccc aaagtgagca gtgactttct tgatctgatt 1020

caaagcttgt tgtgcggcca gaaagagaga ctgaagtttg aaggtctttg ctgccatcct 1080

ttcttctcta aaattgactg gaacaacatt cgtaactctc ctcccccctt cgttcccacc 1140

ctcaagtccg acgatgacac ctccaatttt gatgaaccag agaagaattc gtgggtttca 1200

tcctctccgt gccagctgag cccctcaggc ttctcgggtg aagaactgcc gtttgtgggg 1260

ttttcgtaca gcaaggcact ggggattctt ggtagatctg agtctgttgt gtcgggtctg 1320

gactcccctg ccaagactag ctccatggaa aagaaacttc tcatcaaaag caaagagcta 1380

caagactctc aggacaagtg tcacaaggta tttatttccg cagccggcct ccttccttgc 1440

tccaggatcc tcccgtccgt atatgccaag ggatccgccc ggggccgctg ctggctctga 1500

gccgcctgat ccgta 1515

2

497

Human

2

Met Leu Lys Phe Lys Tyr Gly Ala Arg Asn Pro Leu Asp Ala Gly Ala

1 5 10 15

Ala Glu Pro Ile Ala Asn Arg Ala Ser Arg Leu Asn Leu Phe Phe Gln

20 25 30

Gly Lys Pro Pro Phe Met Thr Gln Gln Gln Met Ser Pro Leu Ser Arg

35 40 45

Glu Gly Ile Leu Asp Ala Leu Phe Val Leu Phe Glu Glu Cys Ser Gln

50 55 60

Pro Ala Leu Met Lys Ile Lys His Val Ser Asn Phe Val Arg Lys Tyr

65 70 75 80

Ser Asp Thr Ile Ala Glu Leu Gln Glu Leu Gln Pro Ser Ala Lys Asp

85 90 95

Phe Glu Val Arg Ser Leu Val Gly Cys Gly His Phe Ala Glu Val Gln

100 105 110

Val Val Arg Glu Lys Ala Thr Gly Asp Ile Tyr Ala Met Lys Val Met

115 120 125

Lys Lys Lys Ala Leu Leu Ala Gln Glu Gln Val Ser Phe Phe Glu Glu

130 135 140

Glu Arg Asn Ile Leu Ser Arg Ser Thr Ser Pro Trp Ile Pro Gln Leu

145 150 155 160

Gln Tyr Ala Phe Gln Asp Lys Asn His Leu Tyr Leu Val Met Glu Tyr

165 170 175

Gln Pro Gly Gly Asp Leu Leu Ser Leu Leu Asn Arg Tyr Glu Asp Gln

180 185 190

Leu Asp Glu Asn Leu Ile Gln Phe Tyr Leu Ala Glu Leu Ile Leu Ala

195 200 205

Val His Ser Val His Leu Met Gly Tyr Val His Arg Asp Ile Lys Pro

210 215 220

Glu Asn Ile Leu Val Asp Arg Thr Gly His Ile Lys Leu Val Asp Phe

225 230 235 240

Gly Ser Ala Ala Lys Met Asn Ser Asn Lys Met Val Asn Ala Lys Leu

245 250 255

Pro Ile Gly Thr Pro Asp Tyr Met Ala Pro Glu Val Leu Thr Val Met

260 265 270

Asn Gly Asp Gly Lys Gly Thr Tyr Gly Leu Asp Cys Asp Trp Trp Ser

275 280 285

Val Gly Val Ile Ala Tyr Glu Met Ile Tyr Gly Arg Ser Pro Phe Ala

290 295 300

Glu Gly Thr Ser Ala Arg Thr Phe Asn Asn Ile Met Asn Phe Gln Arg

305 310 315 320

Phe Leu Lys Phe Pro Asp Asp Pro Lys Val Ser Ser Asp Phe Leu Asp

325 330 335

Leu Ile Gln Ser Leu Leu Cys Gly Gln Lys Glu Arg Leu Lys Phe Glu

340 345 350

Gly Leu Cys Cys His Pro Phe Phe Ser Lys Ile Asp Trp Asn Asn Ile

355 360 365

Arg Asn Ser Pro Pro Pro Phe Val Pro Thr Leu Lys Ser Asp Asp Asp

370 375 380

Thr Ser Asn Phe Asp Glu Pro Glu Lys Asn Ser Trp Val Ser Ser Ser

385 390 395 400

Pro Cys Gln Leu Ser Pro Ser Gly Phe Ser Gly Glu Glu Leu Pro Phe

405 410 415

Val Gly Phe Ser Tyr Ser Lys Ala Leu Gly Ile Leu Gly Arg Ser Glu

420 425 430

Ser Val Val Ser Gly Leu Asp Ser Pro Ala Lys Thr Ser Ser Met Glu

435 440 445

Lys Lys Leu Leu Ile Lys Ser Lys Glu Leu Gln Asp Ser Gln Asp Lys

450 455 460

Cys His Lys Val Phe Ile Ser Ala Ala Gly Leu Leu Pro Cys Ser Arg

465 470 475 480

Ile Leu Pro Ser Val Tyr Ala Lys Gly Ser Ala Arg Gly Arg Cys Trp

485 490 495

Leu

3

tacacctagc aatagtcata gaatgcacaa atcttcaatg ttagcaaata atgccaaact 60

tttttttcaa atttcaaaga gattgtatcc atttacacgc ctacgggtac tgtataagtg 120

tgtgtacttc cacatcttcg caaacactgt cacatccttt tgttgttgtt gttctcgaat 180

ttgagtgtta ttctttctca ctgtgacttt atttttcata ttttctgatt atgaacgagg 240

ttgacaactt tcacacattt gttggtcatc tggatttcct ttttggtgaa gtgcctgttt 300

aagtatctcg tctataattt attttaaagt gtcctttcag acagtctcaa tgactgtcac 360

caactccttg cagggcagtc agcccggaga tagagtaatc aaggtaggtt gaagtcaagc 420

tcaaaacatt cgctgcctca gctgtagcag aggaccactg ggcttcccca ggtaacaagt 480

acttctacct tagccacatg agagagaaag aagaccaggc agagcagcct ggctgccttc 540

ctccttgcag gtggccgaga gcaggggaca gcgccctggc gacctcctca gggatcctag 600

attaacagtc gcgtcctcaa acgcagcatc ctgcgtaacc gccaatttca aacttccaag 660

acctgccctg ctgattttgc ccttcccttt ttcccgttgg tcgcgagtca aaggaagatg 720

caatttgatt ggctctcccc ttcactttcc tccatgcctt tagggacatg ggcggggcct 780

ggctgagacg cccatgtcta tcataggagc ggagacgctg attggtccaa acacggctga 840

gacccgcccg cgccgttcct cgggttcaaa cgcggcggcg ggaggcgcgg ggcggaacag 900

atcgcagacc tgggggttcg cagagcgtga gtctgatccc ccagacccaa ttctaccgca 960

cccggctctg caaggccagg ggagggccgc ctccacccat acaagtcccg ggtttccctc 1020

ccgccccggg gagggcggcg attccacccc cagggctgcg ggaggcctgg agggtcttcc 1080

ggggctagct gtgcgcgcgc ccaccttcct tgggagccga ggggtcagcc gagtggtgct 1140

ggggcaggag gcttgctcct cccctaaacc aggcggagtg ctttgtctct tcagctctgc 1200

ctcctgtcag cactaactgc attattctgc ccagtgtagt cggccggttc cttattatct 1260

gcgtgaactt agccatttac ttaacctctc tgtttcagcg tattcatacc ccgtgcccac 1320

cccatcacct catgatgccc ccgcctcttt cgctctgctc cagtccgtct ggcctcgctg 1380

ttgctggaga ggccaggtcc tgcctcagtg cttttggctt ggctgtttcg tttgccacgg 1440

atgtctttct ttccccagat atcaacatgg cttgctggtc attcgcttca ggtcttcaag 1500

tcttgggtca aatggtggct tctcagtgaa gtcttatttg accacactaa aaattgcacc 1560

atctcacccc cattgtcctt ttcttgctcg attttgtttt taccccatag cacttaacac 1620

cttacaacaa gctatatatt ttgcttattt cagtcattca tttaataact attcgcacct 1680

atttgtgtgc caggctatgt gtgcccccac tgcatggggg caaacatctc tgcccttgtg 1740

gagcttccat tctaaggggg gagataataa acacatttat aagtaagaga gtatgtcaga 1800

taagtgtatc atctcctgtc acagtgagtt aaaatctggt gtttaatctc catgattaga 1860

ctgagcttcc taaaactgga gtggtagctg attttcacct ccttgtccct gatatcttga 1920

gggagatcag gatctctcag gcccttcctg ctcaaaacat aggacacact tgacttttct 1980

gatatccttt cagcgccagt ggggagatgt tgaagttcaa atatggagcg cggaatcctt 2040

tggatgctgg tgctgctgaa cccattgcca gccgggcctc caggctgaat ctgttcttcc 2100

aggtaacagc ctaccctgcc aactttgctc acctgtgtgt gtccttggaa tctccttgtc 2160

actcaccttt gcttttattt atttgtttat ttatttagag tctcagtctc tcaggctgga 2220

gtacagtggt gcaatctcag ctcactgcaa cctccgcctc ctgggttcaa gcgattctcc 2280

tgcctcagcc tccagagtag ctgggactac agccgcctgc caccacaccc ggctaaattt 2340

tgtatttttc tttttagtag agacggggtt tcaccatgtt ggccaggcta gggtcgaact 2400

cctgacctca agtgatccac ctgccttggc ctcctaaagt gctgggatta caggcatgaa 2460

ccgtgcccag cttgctttta ttataggacc agggataata ttttagggga aattctgttt 2520

tgttttgttt gaaacaaggt cttctgtcga ctctaggcct gtgccaccat gcctggctaa 2580

ttttttaatt ttttgtaggg atggggtctc actgtgttgc ccaggctgat atagaacacc 2640

tgacttcaag tgagcctctt gccttggcct cccaaagcac tggggttata ggtgtgagcc 2700

actgcacctg gccctctatt tagagtttta tatgcactga ttcttttgga aaaaagacac 2760

tgtgcagaag tagatagctg aacttgcctt agaagggaga tcttttcata tttctcacac 2820

tttacacttc tgtactaaag tttattcatt cattgattga ttggttgctt gcaagacagg 2880

gtcttgctct gtggctcagg ctggagtgca ttggcacaat cacggcttac tgcagccttg 2940

acctcctggg ctcaaacgat cctcccactt cagcttcctg agtagctggg accacaggtg 3000

tgtgccacca tacctggcta atttttgtat tttttgtaga gatgaggttt caccatgttg 3060

cccaggcagg tctcgaattc ctgggctcaa gtgatctact tgtcacagct tctgcaagtg 3120

ttgggcttac aggcataagc ccctgtacca gggcaagttt gtccttttat tgaagaaaga 3180

aaaataaatg aacaaagatg ctttttaaaa ctacaatttc tgtgggtata atcctattca 3240

ttttcattgc agggatgttt attttttaag attttttttt tttttttttg agacagagtc 3300

ttcgctgtcg cccaggctgg agtgcagtgg cgcgatctcg gctcactgca ggctctgccc 3360

cccggggttc acgccattct cctgcctcag cctcccacgt agctgggact acaggcgccc 3420

gtcacctcgc ccggctaatt ttttgtattt ttagtagaga cggggtttca ctgtgttagc 3480

caggatggta ttttttaaga ttttaaaaaa agttttgatg aataccacac ctgtttaacc 3540

ctcattcctc tcaagataca catttctgtc accccagatg cgttaaaact taatatcata 3600

agattacttc caaatagatt tttaattctt ttgtttctga tgtatgtgga acactggtga 3660

agtagaaatc cttgtttgat ttatgtattc gtaagtcagg gggacaatag agaccatgaa 3720

gatttagaat tgaatcccag tcccagcact agttagctgc attactttgg gtgagtcagt 3780

taccttttct gagtccattt gctattcttt aaaataggtt gtagcctgta atgccagtat 3840

tttcggaggc tgaggcgggc ggattacttg aggtcacggg ttcgagacca gcctggacaa 3900

cgtggtgaaa ccctgtctct actaaaaata tagaaaatta gctgggcatg gtggtcgcat 3960

gtacctgtaa tcccagctac ttgaaaagct gaagcaggag aatcatttga acccgggagg 4020

cggaggttgt cgtgagccga gatggtgcac tgcactccag cctgggcgac agagtgggta 4080

agactccatc tcaaaacaaa acaaaacaaa agaaaacaaa aaaaataaca tagaggttgt 4140

agtacctaat ccacagggtt gttgtgagga ttagatgaga tattcgattt aaagcactta 4200

gcaccttgcc tggctcttag taaactcctt ataaaaaatg gtaattattg ttaatactca 4260

gcatagaata gtattagtta taatattaat actaaatttg tttccttaat agtaattata 4320

tttgggaagg tagttatgta ggatacctgt aagatgatga atgatgaagt attcttgata 4380

actttttttt tttttccaaa atattggtat tgggtgttta aacagatgag agtggaaaca 4440

aattgaaagc ttaggttttt ctgtgggacc atccccatca gcattttaag tcttgacata 4500

tctttcacaa atgaatagtc tgtctttaac cttagatggc tggagtgctg ccacgtttca 4560

gcccctttat catgctactt taaaatatct ccaacttgct gggcgtggtg gctcacgcct 4620

gtaatcctag caatttggga ggctgaggtg ggtggattgc ttgaggtcag gagttcgaga 4680

gcagcccggg caacatggtg agcccctccg tttctactaa aaacacaaaa aatagctgac 4740

tgtgatggtg tgtgcctgta gtcccagcta ctcgggaggc tgaggcagga ggatcacttg 4800

agccctagag gcagaggttg cagtgagcta agattgtgcc actgcacttc agcacttcag 4860

cctaggcgac agagcaagac cctgtaaatt aaaaaaaaaa aaaaaaagaa aaggaaaaaa 4920

atttccaact tattaagggc ttatagtgtg ctgattatgt aatagttatg gcttccaatg 4980

tgtctggcat agaactggca tgtttctgag tatctcactt cagcctcatg acagaggtaa 5040

ggactatttt taatttaaac tttaaatagg aggcaacagg ccaggtgtgg tggctcacac 5100

ctgtaatccc agtactttgg gaggctgagg caggtggatt gcttgagtcc aagagttcaa 5160

gactagcctg ggcaaaatgg tgaaacccca tctctacaaa aaatataaat aattagtcag 5220

gcatggcggt gtgtgcctgt agtcccagct actcaggagg ctgaggtggg ggcatctctg 5280

gggccccgga ggcagaggtt gtagtgagtt gagattgcaa cactgcactc cagcctgggc 5340

aacagaacga gaccctgttt ctaaataaat acataaatag gaggcaacag atatagacag 5400

atatggaggt aggtaaggcc ttgcccaaga tcatacacgt tgggttttgc agatgaggcc 5460

aagatcagac tccatctttg gttggtctga ctccaaaggc tgaccacata gccattgggc 5520

cacagcacct gtgcacgtca gaatttatta agtatatctt gtatttagtc attataacag 5580

gaagacttat gggtaaaccc tcagttcatc tctttttaat gctgagatcc ccctgcccag 5640

taaagctatt attgcaagta tagtatatac ctatcatttg ccttgagtta tcaggtaagg 5700

atgctgtttg ttcttttccc atatagtgct gtttgaatga ggttgagata cagtagcaat 5760

tttgttttcc attcaggtga gtaccttaga ctgagtgtca ttttgtcttt tttacttcta 5820

ctcaacagga tttcctgaca tgttcgaggt cagtgattgt cagactttct gagccagcaa 5880

aatttcccaa attgctgggt agacacaggt tttccaactt tttattttgc caagtaagga 5940

tatataaaaa aaaaataaaa agaaagacct attattttct ggcccttgta tttcataaag 6000

ggcattttaa gaaacaacaa gacaggaaga acatcatctc agaataaagg accattttta 6060

aatttgaata catttagttt tataaaaaag atatcatgtg gtgttcattt tttctcattt 6120

cactgcaggc tgttgaaaac tttgttaaga accagtacta tatttgggaa cccctgcttt 6180

aattgatcta aactcttgaa gaatagaaga aacaaagcat tttatttttc tgagttactg 6240

gcaactatta ctaaagtgac agatatggtg gccttgaatg cagtgcttcc caaacctgat 6300

tgaggtctga ctctcttggg gaccagggtc tcattctgtt gcccaggctg gagtgtggca 6360

gcacaatctt ggctcactgc agcctttact tcttgggctc aagtgatcct tctacctcag 6420

tctcacaagt ggctaggact acaggaccat ggcactacac ctggctaatt tttttttgtt 6480

tgtttgtaga gatgggatct cgctgtgttg ccctggctgg tcttgaactc ctgggctcaa 6540

gtgatcctcc caccttggcc tcccaaagtg ctagtattcc aggtgtgagc cacctctccc 6600

tgctggggaa cttgttaata aaacagattc taggctacag tctggaaaat tctaattcat 6660

ttggttgtgg gggagggggg cataggacca gagaatgtgt ttgtttgttt gtttgttttt 6720

cttaaattct ccagtgctgt tgtgattcaa atgcagccgg tctgtttctg ttatcaagtg 6780

ctgtgtaaca aagcactcac aaagtttaaa gcaacaatga tttatttttt cttaggattc 6840

tgtgggttgg ctggactcag ctaggtagtt ctgcttcatc ctgtgatgtc agctggggtc 6900

acttgtgggg ctacattcag ctgggattat gtctgggact ggaacatgtg ggtgctgact 6960

gctggctggg gcaccttagt gtttctcaca tggcctctct tctccatgag gtctttcagt 7020

agtatagccc aggactcgta actttttttt tttttttaag acagactgtc gccctgtcgc 7080

ccaggctgga gtgcagtggc acgatctctg ctcactgcaa cctccgcctc ctgggttcaa 7140

gcaattctcc tgccccagcc tcccgagtag ctgggattac aggcacgtgc ctccacgccc 7200

ggctaatgtt tgcattttta gtagagatgg ggtttcacca cgttggtcag gctggtctcg 7260

aacttctgac ctcgcgatcc gcctgcctcg gcctcccaaa gtgttggaat tacaggtgtg 7320

agccactgca cctggctgac tcgtaacttt ttttgtaagt aataaatatt ttaggctttg 7380

tgggtcctgt agtctctgtt gcaaccactc aacttggcca tggtagcaca aaagcagcta 7440

aagacaatat gtaaatgatg ggtgtagctg tgttccagta aaacttataa aaagtccgtg 7500

ggctggattt ggtccaaggg ctacagattg cacacccctg gtctagccca agcatctgtg 7560

catggtggct ggcttcccaa aagtggaagc tgctaagctg cctttttttt tttttttttt 7620

ttttttgaga gggagtctca ctgtgttgcc taggctggag tgcggtggtg tgatctcggc 7680

tcactgcaac ctccatctcc cgggtgcagg caattctcat gcctcaacct cccaggtagc 7740

tgggattacg ggtgcctacc accacgcctg gctaattttt gtattttggt agagacaggg 7800

tttcaccatg ttggccaggc tggtctcaaa ctcctgacct caagtgatcc acccgtcttg 7860

gcctcccaaa gtgctgggat tacagatgtg agccaccgtg tctggccgct tgacaagctt 7920

cttaaaggca ctgccctgaa ctggcacagt gtcacttgtg tcacattctt ttggttgaag 7980

agagtctcag agatggcaca gattcaaagg caggagaaat agactccagc gcttaaagta 8040

aggagtagca tgtgcctaca gaattggagg aactgttgga ggccatcttt gaagagagac 8100

caccactatc catggcttgg cacgtgggaa tcactgctct ataccagggt tgcagactca 8160

tgtctttggg ggccaggcag tgagtataaa tgagtcaagt gggccagttg gaagatggag 8220

tcagacctgc agtgaactcc caaacacatc tgctaccggg aggggcagca ttactcagct 8280

ccagctcagc gtcatcaggc aggaaggcga ggcagtgttg ccggatgtgc cagtgtttca 8340

aaagaagcca gagactccat ttttattttt ttgtatggaa tctcctgatt ttgaaatatt 8400

ggcagataat tcaaattatc ttaaacacta caggccaaac aaaacatatc tgtgggctag 8460

agacagtctg ccagtttgta actatttctc cagatcatga gtaaatttgg ctttacgatg 8520

gtcactcagt tcttattact ctaggttgtt caaatgaatt aaaaaagctg aaattatatg 8580

aataaacccc tgggcacaca tgaaagaagt gaaaaaccca ttgtttccta ttgtagaaac 8640

atggaagcat gtcagagcca gaggatccag aggaaatatt ctcactagcc tcagaccctc 8700

aggagtgagg gagcttttct tgttaatggc cacgcttgtg cagttttcct tcccaggtgc 8760

tggtgaaaga aacccacagt cttggaatca tggaagtgat accataatga ctgtcagttg 8820

acgttgcttt aaagaatgaa gccacagaat tgtgctgtta gcatgtcgtg agcagttagt 8880

tgagttggtg gcttgtaatt tactctgtgt ggatgttatt gatcaaagct tttcattatt 8940

gacagtgtct ccatctgctg tttgctgttt ttaggggaaa ccacccttta tgactcaaca 9000

gcagatgtct cctctttccc gagaagggat attagatgcc ctctttgttc tctttgaaga 9060

atgcagtcag cctgctctga tgaagattaa gcacgtgagc aactttgtcc cggaagtgta 9120

agtttgggga actttttctt gaaaactgtc ctgagagaga aaaactagaa agatgcttga 9180

ggcagaatga gttactggtt gatagtagtc ggtaagaact ctggttctat ataagacaga 9240

tccaggttca aattcaggct gcacctctta tagctgggag accaggtaag ttgggcttct 9300

tggttgcaag cgacaaactt aattcaaaga ctgaatttag gccaggtgca atggctcata 9360

cctataatct cagccctttg ggaagctgag gtgggtgaat cgcttgagcc caggagttca 9420

agaccagctt gggcaacatg gtgaaacccc atctctacaa aaaatacaaa aattagctgg 9480

gtatggtggc ttgcacccgt ggtcccagct gctgaggagg ctgaggtggg aggatcactg 9540

gagcccggga ggttgaggct caatgagctg tgattgtgcc attgcactcc agtctgggtg 9600

acagagtgag accctgtgtg aataaaagag tgaatttatt ggctcatgaa actgagaaat 9660

ccaggaatga gttaagtttt agctttaggc atagctagtt ccagagacct caataatatc 9720

ccgtggccct gtccttatac tcactcaggg ctgactttct attaggcaga gtaggcacgg 9780

tgcttaggat ctgtgatatt taattttaat gaatttaatt acttttaatt aactgaatta 9840

aattttaatt tgttttaaaa ttataggaaa aatgaatata ataatgtata atgattctgg 9900

attacattca tctttatact aatgtagtca taaaatataa tttttgtttt ttttggagac 9960

agagtcttgc cctattaccc aggctggatt gcagtggtat atcatggctc actgcagttt 10020

caaccttcta ggctcaagca atccttccac cccagtggct gggactacag gctcacacta 10080

ccacgcccag ctaatttttg cttttttctc tgtagagata gggtcttact atgttaccca 10140

ggctggtttc aaactccagg cttgaagcag tcttcctgcc tcagcctccc aaagctttgg 10200

gattacaggt gtgagccacc atgcctggcc ccataaaata taatttttga attctttttt 10260

gtttttaatg gaggaagggg ctgaggaagg caaaagtacc tagggcctat gaagtcatat 10320

attggccttg ccttcaccct gtttctgact ttgcttgact tccatgtgat gaggcagttg 10380

gctgttagtg tcccagtttc atactcttac attagtgttt ttcaaccagt gggtgatttg 10440

acgttttcgg ttgtcagagc tagttggggg tggtggtgtg tgagtttggg gggaagggtc 10500

ctactgtcag ttaatgggtg aggccagaga tgccaccaaa caccttacag tgcacaaagc 10560

agcccccata acacagaatt atgtagccca caatgccaac agtgctgaat ttgagaaacc 10620

ccaccttgta caacattgct gtgcaaccaa ccaccctaaa tattactgac ttaaaacaat 10680

agtcactgtg gctgggcgcg gtggctcatg cgtgtaagcc cagcgctttg ggaggctgag 10740

gcggcggatc acttgaggtc aggagttcca gaccagcctg gccaacatgg tgaaaccttg 10800

tctctactaa aaatacaaga attagctgaa tgtggcagcg ggcgcctgta atcccagcca 10860

tttgggaggc agaggcagga gaatcgcttg aacctgggag gtggaggttg cagtgagcca 10920

agatctcacc attgcactcc agcttgggca atgagtgaga ctctgtctta aaaaaaaaaa 10980

aaagttattg tattacctct tgtgtgtgta ggttaattgg actcagctgg ggattcctct 11040

gctctgtatt acattggcca ggattgcagt cacctggggc tctcctgggc tggaatgtgt 11100

gagagggctt actcagtgtt tggtgccctg gcttggaggc tgggcccagc tgggcctctc 11160

tctcttcatg aagtttcagg gccttttgct gtccacatgg cacctctatg tggtctccaa 11220

atcagaagtc aaggaactac agcctgtgat gcctattttg taaagaaggt tttactggaa 11280

cacagcccta cccatgtgtt tgtacagtgc ctatggctgc tttcacatca taacagcatt 11340

ttatttcatt ttatttattt ttttttgaga caaagtctca ctctggctgg agtgcagcag 11400

cacaatcata gctcactgca gcctccaact cttgggctca agcaatcctc ctgtctcagc 11460

ctcctcagta gctagtacta caggcccatg ccaccactaa tggctaattt tttaattttg 11520

tgtagagatg ggaccttgtg agattgccta ggctggtctt gaactcctgg cctcaagaaa 11580

tcctcccacc ttggcctccc aaaatgcttg gattacaggc atgagccact gtgcccagcc 11640

cacaacagca tttgagtagt tgtgatagag accaaatggc ctacaaagcc caaaatagtt 11700

cctgtttggc ccatttcgaa aaggcttgct gacctctgag ctacatggtc tctctagcag 11760

gacagcctcg acggtagctc aggtttccaa aacacaaaag tggaagctgc caggctttct 11820

taggggttat cctaggaggg acataggatc tctttgactg cattttattg tttgatgcat 11880

gctctggggc tgctcaaatt ccacctgaga ggaaactaca caaggtcatg aatcccaaga 11940

ggactggggc attgggtgct atttttggag actggctacc acaccctgcc caatggtaat 12000

cttcccttat ctagattaat acaaccccag ggaagattct aacttggctc tgctttgggt 12060

catttgcctc cctggaggtg aggtgttgtg atcggttttg ttggaatgcc caaaggggtc 12120

agggcagtgt gattaccagg acctcatgga atgggggatg cgtggttatg caaaggagcc 12180

ggggatgctg ggtagaaaaa aaatcagcat atgttcacta tagtgctctt cagtatttta 12240

catgtacttt gttctcagtt ttctcatctg taaaatagga ataatgtata tccttttttt 12300

tttttttttt ttggagtctt gctctgttgt ccaggctgga gtacagtggc acaatctcag 12360

ctcactgcaa cctccgcatc ccgggttcaa gtgattctcc tgcctcagcc tcctcagtag 12420

ctgggactac aggcgtgcac caccacactc agctagtttt tgtattttta gtagagatgg 12480

ggtttcgcca tgttggccag gctggtctca aactcctgac ctcaagtgat ctgcctgcct 12540

cggcctccga aagtgctgga attacaggca tgagccacca cgcccattgg gaataatgta 12600

tatctaatga ggctgtgttg gaattgaatg agttaatgca cagaccagat ttgtcatgtt 12660

gcctggccca taggagacaa taaatggtac ccagtattaa taactgtgaa tgtcaacaac 12720

atttaatata ttgtatatct tcaaaatgta cttgaggtat ttgttcatca ttctgttttt 12780

gtttgaataa gctcgtgcct tctttttgtg aatatttaaa tttataagta gcgagtggga 12840

ggggaaggaa gttatgtgat gaggctagct tactgagcca tctgcaggca ccttcattag 12900

tcttgagact gtcctctggt tacttaacag cagtgaatta tctagaatca tttagtgatc 12960

agaagacttg gtttagtgga atgtagattt ttttctaata gacccctctt ccagggaaat 13020

gtttcatatt tttgaagagg tttcctgggg agtgtttaag aggccatgat tgaaaatggg 13080

tgattacatt agtgtgtttt ctattcctcc cctttttgag tttctgtttt ggaatgtaag 13140

ctttgttttt ctacgtggag aagggtccct cagctgcttc tgcccaggtt ttttgaatct 13200

tcctataggg atggagattt tctttgggga ctgttagaga aaatggaata gagtgtagct 13260

ctgaaggaga aggatgtctc cagcagaagt acctctagcc ttgggccaag ggagggaagg 13320

gaagggaacg agcatctggg aaccagggaa gggatttttg tctttcttaa ttactcttac 13380

atccccagtg cccaaaatag tgtctggcat atgttaagtc cttagtaaat acttgttgaa 13440

tgagtgtatg ctcagtgaac aaaataaatg gcaaacatta agcacagtat cagataattt 13500

gtgtaaaaaa tatacagcag tgttatacta aaacttgcac agaggccagg tgcagtggct 13560

cacgcctgta atcccagcac tgggaggccg aggtgggcag atctttgagc tcaggagttt 13620

gagaccaacc tgggcaacat gctgaaaccc tgtctataca aaaaatacaa aaagtagctg 13680

gggcatgggg acgcacatct gtggtcccag ctacttggga ggctgaggct ggagtaattg 13740

cttgaagctg ggaggtggag gttgcagtaa gccaagattg tgccactgca ccccagcctg 13800

ggtgacagag taagaccctg tctcaaaaca caaaacaaca cccccttcaa aaaaaatcca 13860

aaaccaccac cacaacaaaa aaacttacac agaaaagtgt tgataattgt caaaattggg 13920

ctgttattgg caatttgaca gtagctgaat tactaccatt tgagctatat tcactataga 13980

taagatcttc aatatattta caactttagt actaatggga aaatgataac ttttgaaaag 14040

tttttttttt ttcttattgc aaacaataca caatacaatg ttaaatatag aaggttaaac 14100

gtgcatctga gtctgtttgg gctgcgataa tagatacctt agacttggca atttataaac 14160

aatagaaatt cattgctgac agttgtgaag actgggaagt ccaagatcaa ggcgccagcg 14220

aatctggtat ctggtgatgg ctccctgctt caaaaatggc gccttcttgc tgcatcttca 14280

cctggcagaa ggggcaaaca tgagtccttc agcttctttt tttttttttt tctatgttta 14340

aaacttttgg tccggcgtgg tggctcatgc ctgtaatcct agcactttgg gaggccgagg 14400

caggtgcatc atgaggtcaa gagatcgaga ccatcctggc caacatggtg aaaccccccc 14460

gtctctatac taaaaataca aaaattagcc aggcatggtg gcgtgtgctt gtagtcccag 14520

ctactcagga ggctgaggca ggagaattgc ttgaacctgg gaggcagagg ttgcagtgag 14580

ccaagattgc gccactgcac tccagcctgg caacagagta agactccgtc tcaaaacaaa 14640

caaacaaaaa aaacaaaaaa aaacttttat tttaggttca tgggtaaatg tacaggtttg 14700

ttatgtaggt aaacttgtct tggggtttgt tatagattat ttcgtcaccc aggtactaag 14760

cctagtaacc aatagttatt ttttcagatt gtcctccctc ctcccaccct ctgtcctcta 14820

gtaggctcca atgtctgttg ttcccttctt agtgtccttg tgttctcatc ctttagctcc 14880

catttatatg tgagaacatg tggtatttgg ttttctgttc ctgcattagt ttgctaagga 14940

taatgtcagc ctcttttttt tttttttttt tttttttgat acagagtctc gctctgttgc 15000

ccaggttgga gtgcagtggt gcgatcttgg ctcactgcaa cctctgcctc ccgggttcaa 15060

gtgattctct tgccttagcc tcctgagtag ctgggactac aggtgcgcac caccatgcca 15120

ggctaatttt tgtattttag tagagatagg gtttcaccat gctggccacg ctggtctcca 15180

actcttgacc ttgtgatccg ccggcctcgt ctttttccca aagtgctgag attacaggtg 15240

tgagtcactg cacccggccc aatgtcagcc tcttttttag ggaagtgatt taatcacttc 15300

cctaaaagtc ctacctcgtt tttttttttg gttttttctt tttttttttt tttttttttt 15360

ttttttttta ggtagagtct tgctctgtca cccaggctgg agtgcagtgg tgcgatcttg 15420

gctcactgca acctccacct cctgagttca agcaattctc ctgcctcagc ctcctgagta 15480

gctgggatta taggtgcctg ccaccacgcc tggctaattt ttttgtattt ttagtagagt 15540

tggggtttca ccatgttggc caggctggtc ttgaactcct gacctcaagt gatctgccca 15600

aaatgctggg attacaggcg ggagccactg tggccagccc ctgcaagtcc tacctcttaa 15660

tagtattaca ctggggatta catttcaaca tgaattttgt aggggcgagg ggcacaaacg 15720

tttagaatat agcacatcac atacatagtg agagaaaaat ccctcaaaat cttacctgag 15780

acaatcactg ccaacagatt gctgtatagt gtgccaattt tgtttgtgtg tgtgtgtgcc 15840

ttaaaaatat ttattatgga aatttaaaaa cgtaccccaa ggtggccagg tgtagggctc 15900

acgcctgtaa tcctggcact ttgggagccc gaggtgggtg tattacttga ggtcaggagt 15960

ttgagaccag cctggccaaa atggtgatac cagtctccta aaaatacaaa aattagccgg 16020

gtgtggtggg cacctgtagt tccagctact cgggagacca agtcatgaga attgcttgaa 16080

ccctggaggc agaggttgca gtgagccaag accatgccac tgcactccag ccagggtgac 16140

agagtgagac tccatcctag taaacaaaca aacaaacaaa caaaccaact aaccaaccag 16200

gataaaactc cctgtctgta aggagtatgt gttctaatgg atactgagcc atcttgttct 16260

gtttaacatg tgcctaatgt tcttttatat gggcggactt gtaggttgtt tcaacttttc 16320

tgttgatgaa cctttaggtg gtttctgatt atttttgtgt tacaacagtt ttcatcattc 16380

acatctttgt atgcatcttt tttgagcaca tgtgcaagta tttctgtgga caatggatga 16440

ttcctagaaa ttgaaagttt ggattactgt gttccaaaaa aggaagcaat acacccagct 16500

atgttggctt ttgctcttgg gtccagatga ttatctgaca aagttattct ctgattgcat 16560

tttcttttct tttcttttct tttttttttt tgagatggag tttcgctctt gttgcccagg 16620

ttggagtgca atggcgcgat cttggctcac tgcaacctct gcctcccagg ttcaagcgat 16680

tctcctgcct cagcctccta agtagctggc attgcaggca tgcgccacga cacctggcta 16740

attttttgta tttttagtag agatgggatt tctccatatt ggtcaggctg gtcttgaact 16800

cttgacctca ggtgatccac ccgcttcagc ctcccaaagt gctgggatta caggcgtgag 16860

ccacagtgcc tggccctctg actgcatttt cacagtgttt tgggtcctta tctctacctc 16920

agtacctcaa tattcagtgc ccactgggcc cttagatact gcagctaaaa gtgcacaggg 16980

gtggagtgat gtgacggttt tggggtcaca gaagcagctg gtatagagag aagttgtgaa 17040

gttttttttt tttttcctga gacagagtct cgctgtatcc cctaggctgg agtgcagtgg 17100

cttgatctcg gctcactgca acctctgtct ccctggttca agtgattctt atgcctcagc 17160

ctcccgagta gctgggatta taggcatgtg tcaccatacc cagctaattt ttgtgttttt 17220

agtagagatg gggtttcacc atgttggcca ggctggtctt gagctcctga cctcaggtga 17280

tccgcccacc tgggcctccc aaagtgctgg gattacaggc ctgagccatt gcgcctggtc 17340

tttttttttt ttttttaagt aatcataggc ttgaatgtag cctctcatct gttcacctta 17400

ataatccaaa agcctttaga taaagaaatg gagatttgga atggcttctc agaattccaa 17460

gagagtattg tcatggtttt gcctgcaaag caccgtggtc tgtctccttg tgcagttgag 17520

aaagctggtg gtcgccactg acaggcccag agttattaag ttggacactg ctttaagcaa 17580

ctttgtaaac aatccaaggc atactagaga attaggagag attggctttg tgtatgagca 17640

ataacaaaat caagttcaat ccagcaagtt tttggggaat tataattcaa aactcaaata 17700

cttgatctgg aagaaacttg gaaagaggga aggaagacag gcttgttaca gcattgtcag 17760

ggtaaaagga aaataccgtg cagcttttaa ttttgcttct tcatggcatt ccccatgtag 17820

gtgccctaga tttgtttttt acagtggtca cgacttcatg tggatccacc caccactctt 17880

gcctggttcc ccaagggacc aagggaaggt gtattcagga tgattgctga agtgaggggt 17940

ggggtctgtg gctgagaaga ctctcaatac cgcggcactc attataagcc tctgacacag 18000

gagatttcaa ctccacccgt gcaacaaagg aacagggtgg gcaagagtag ttacagttgc 18060

aggctgagtg cgatggttca tgcctgtaat cccagtgctt tgggaagcca aggtgggagg 18120

attgcttgag tctaggagtt tgagaccagc ctgggtgaca taatgagacc ctacctgtac 18180

aaaaaaattt taaaaattag ccagattggt ggtgtgcgcc tatagtccca gctactctgg 18240

agaatgaggt gggtgagggt cccttgagtc caggagttcg aggctgcagt gagttatgat 18300

tctatgattt caccactgca ttccagcctg ggcgacagag caagattgtg ttcttttttt 18360

tttttgagac ggagtctcac tctgtcaccc aggctgaagt gcagtggtac gatctctgct 18420

cactacaacc tgcacctccc aggttcaagt gattctctcc ctcagcctcc cgagcagctg 18480

agattaaaag cggccgcttg tgtgcagcta atttttgtat tgttagtaga gatggggttt 18540

catcatgttg gtcaggcttg tcttgaactc ctgacctcag gtgatccacc cgcctcgccc 18600

tcccaaaatg ctgggattac aggcgtgagc tactgcgccc agccatttgt gtctcttaaa 18660

aaaaaaacta agaaaatgaa aaaaatgaca ttggccaatt cattaaaatg ccactcactg 18720

actgtggtat gaaatggctt tccctttgat ggaccgagtc tgtctcattg tgtgagccac 18780

ttgcagggct gagtatgact ctggaatgta gctcctaacc ttatctgctg cccagccatt 18840

gaaatggcca tcccttccag ttcccagaag attccagtgt gtgtttggga ttttaagaca 18900

gtctcttggt cttcagtgtg gcatctttct gccggatttt ccaggataat tttgattata 18960

agcattgcat tgcccttggt gtgtaatgcc tgtgtatgat gctgttccct tgtaacgtgc 19020

aggattaaat ttttgggtca gccactgctg ctccccttca ttcctgcagg tcattagagt 19080

catcgtacat ttagcgatgt ctcagatcag tgtatctaga gtgttaataa acatgttaga 19140

ttccaaatct actgtccatt taatccatac ttcatacgtt gaggatctct gactgaaaga 19200

ttagacttgg aaaaataata agactgtatg gtaagaaaac tatagttgca aatccatttg 19260

gacatgtagt atgtcagccc tgcagagcag atgtcagaac cccatttagt tctctgagtg 19320

ctaagccctt ctgcccacca cgctgttttt tttttttgag atggagtctc gctctgtcac 19380

tcaggctgga gtgcagtggt gtgatctcgg ctcactgcaa gctctgtctc ccaggttcac 19440

gccattctcc tgcctcagcc tcccaagtag ctgggactac aggtgctcac caccatgccc 19500

agctaatttt ttgtatgttt ttggtagaga cggggtttca ctgtgttagc caggatggtc 19560

tggatctcct gaccttgtga tccacccgct tcggcctccc aaagtgctgg gattacaggc 19620

gtgagccact gctcctggcc cccacgcctt tttttttttt tggagacaga gtttcactct 19680

gtcacccaga ttggagtgct gtggcacaat ctcagctcat tgtgtcctct gcctcccagg 19740

ttcaagtgat tcttgtgcct cagcctcctg agtaggtgga attacaggcg tgcaccacaa 19800

cacctggcta atttttgtat ttttagtaga gatggggttt caccatgttg gccaggctgg 19860

tctcgatctc ctgacctcca gtgatccact tgcctaggcc tcccaaagtg ttgggattac 19920

aggcgtcagc caccatgcct ggacccctct gcccctttaa gcactgccac atattagatc 19980

tacgaaggct ttatggatac aatccaagga agatgaacct tgggctagtg ggataaaact 20040

aagcgcatgt agttagaatg gaatgatctg gaaaccaggt cccaagttgg tctaaattag 20100

actcatgttg actatgtcac actgtaaacc agtctaaatg ctaataagca tgcttgacca 20160

aacactgccc tgcagccttc agagaggaag aaggaaaaca taatttgtat cctctctccc 20220

tattttctga gtctatggga ttcaaattgt agctgccatg gaaactgtac tttggaattt 20280

ctagagccct taattttaac ttaacatata aaaacacttt tgtactgatt ttataattat 20340

tcatgatgga tgagaaagtg aatgtctttg acagtgaggg aagctatccg aatgctattt 20400

tctttttttt ttttctttca taaagatgca tatatttgca tgctttattt acctggggct 20460

aactcttgca tcttttgcag attccgacac catagctgag ttacaggagc tccagccttc 20520

ggcaaaggac ttcgaagtca gaagtcttgt aggttgtggt cactttgctg aagtgcaggt 20580

ggtaagagag aaagcaaccg gggacatcta tgctatgaaa gtgatgaaga agaaggcttt 20640

attggcccag gagcaggtag gaggatttta acatcatgct tttccacttt ctgtaccgga 20700

gtgttcattg caaagacgat aatctgctgc actggcgtct aggatcaagc acgttttcct 20760

ctgtgactct atatttaatt atagttgggg caaaaaggtc tctcatgttc ttagctcatc 20820

ttcttgaact gatgttggct aattttgaag gctcacaaat tcctcttgat gtatcatgtt 20880

tctatcgttg taatttattt cagaaccaag gtggcctttt agctaatgaa tttaagatga 20940

tcttttatga ccattagctg aggactcagg atatacatat ggtggggtga atcagattgc 21000

ttttgtacac gctttaggta tttgtgttgt gggcatatgg atttggtttt aaaacaggcc 21060

tttgaagaaa tcaaataaca ttctttgtta tgtggctagg gagttgcttg tttgagagca 21120

ggtagaacgt tatctttttt gttgtggtat ttttctttct tttaaacaag gctactgtct 21180

ctagacatat tgattcattt gctgtgtttt agagagatgg ccgtcagcct tggaattcag 21240

agagtaattt attacttaca gacattttag tgcacatgat atgtctgata atgtacccag 21300

ctctgcagga agcttgcaaa aggaatagaa gtcccatggt tgctattttc agtgtttaaa 21360

aacaaccttg gaaagtggag gaaaaatgca aatgtataaa gcaggtgctt accagctaaa 21420

gtatcacaga agtgggagag caattagcaa attaattaac gatgatgtga ggggagatgt 21480

tgtgggtgag caagggacag ttagggacag ttctcaccga tggggggaaa tgtaggttct 21540

cggcagagag aagtgatgag aacatgttgg gtagaagtgt gacattctgg agtactagaa 21600

tgctatgcaa gtgtgtgtgt gtgggtgtgt gtgtgtgttc agtggttcag aacagactgg 21660

gaaatggcga aatgaggaca tttgggtggg gagggggaaa tgggtgggaa actcaagaac 21720

ctttttttaa aaaattgtgg taaaatatat ataacataaa gtgtaccatt ttaaccattt 21780

ttaaatgtgc aactgagtgg tattcagtgc attcatgatg ttgtacaacc atgaccgctc 21840

tccatttcta gaatttttct atcatcccaa acagaaactc tctatccatt atacaatacc 21900

tccccattcc cccaagaacc agtttttgaa ttgcagttta ctttgtgagg ctgttgggga 21960

ttatttaggc ctctggaagg aggaggttgg gatcagagtc tggccctgtg gacttcaatg 22020

actttgtgtg gcctccaatc agagaagcag cggagggcag gaagctgctt gtcagaatct 22080

gagagtgatg tggcttcttt gtttagcaat aaaatgtgag cacataatag aaaggaaaag 22140

tgacaggaca tggcagataa tttggaagag aggagtggaa gatgctcact cagcctccca 22200

gctcctgaga aagaactgtg tctcatcagt tcatactacc tgagcatctg ttgtatctgg 22260

tgtgtttcta ggtcctggag aagaggcatt acgtgtagcc ctgaccttgt gatgcttatg 22320

tttttgatgg gaaatagtgc gtgtaaaaag aaaataatcc aacaggccac acggcaggca 22380

aacaatagag atattcaaat aggtatacct tcctccaggt gaatggcctg aaatgaccgt 22440

gtggaagtgt gggctggggg cttataaaat tatacacata caggcgctaa ctaaagccgc 22500

ctattcattc cttaagagga tgcatagaaa agaaaagtag ggtccttaac tgagccattt 22560

ggaatttaag ggcatgagag aagccagcac aagcagtgaa gggaaggaaa agaagtgccc 22620

gagaggaggg agggatgctg ttctgcagac aaggcctgcc gcctgggaga ggcccgcacg 22680

cccacccagg gttctctgac agctggaagg ggtcttcaga gactgtttat attttattta 22740

tttatttatt tatttatttt gagacagagt ctctgtcacc caggctggag tgcagtggtg 22800

cgatctcagc tcactgcaag ctccgcctcc caggttcaca ccattctcct atctcagcct 22860

cccgagtagc tgggactaca ggcgcctgcc acaatgcccg gctaattttt ttgtaatttt 22920

agtagagacg gggttttacc tcgttagcca ggatggtctt gatctcctga cctcatgatt 22980

cgcccacctc ggcctcccaa agtgctggga ttacaggtgt gagccactgt gcctggccga 23040

ctgtttctac tattttagag agagggtctc actgtcatct gtgctggaat gcagtgatgc 23100

agtcatagct cactgcaccc tcaaactcct gggcttaagc gaccctcccg cctcagcctc 23160

ttaagtagct gggaccatag gcatgtgctg ccacacccag ttaactttat tatttattta 23220

tttatttaga gaatgagtct cattctgttg cccaggctag aggtgcagtg gcacgatctc 23280

ggctcactgc aaccccgcct cccaggttca agcgattctt cttgctcagc ctcctgaata 23340

gctgggatta caggcacctg ccaccacacc tggctaattt ttgtattttt agtgcagagg 23400

ggggggtttc accatgttgg tcaggctggt ctcgaactcc tgaccttgtg atctgcctgc 23460

ctcggcctcc caaagtgctg ggattacagg cgtgagccac cgtgcccggc ccactttatt 23520

attttaaaaa cattgtttta tttttatttt tttgagacag agtccgctgg agttcagtgg 23580

ccggatctca ctcactgcaa cctctgcctc ctgggttcaa gtgattcttg tgcttcagcc 23640

tctctagtag ctgggactac aggcgggtgc caccatgcct ggctaatgtt ttttgtatct 23700

ttttagtaga gacggggttt tgcccatgtt ggccaggctg gtctcgaact cctgacctca 23760

agtgatctgc ccactttagc ctctcaaagt acttgggatt acaggcgtga gccactgtgg 23820

ctagccccca gctaacttta aaaaaaaatt ttgtgggccg ggtgcagtgg ctcacgcctg 23880

taatcccagc actttggagg ccaagcaggg cggatcactt gaggtcggga gtttgagacc 23940

agcctgacca acatggagaa accctgtctc tactaaaaat acaaaaaatt agccgggtgt 24000

ggtggtgcat gcctgtaatc ccagctactt gggagctgag gcaggagaat tgcttgaatc 24060

tgggaggcag aggttgcagt gagcttagat cacgccactg cactacagcc tgggcaacaa 24120

gagcgaacac tccgtctcaa aaaaaaaaaa taaattatgt agaggtggga tctccctatg 24180

ttgcccggac tggtcttgaa ctcctggcct caagtgatcc ttccatctcc ccctcccaaa 24240

gtgttgggat tacaggcatg agccacccct cctggctgag actgcttatt ttatttattt 24300

ttaatttttt ttgttttgag actgcttatt ttaatggaag cttcaggggt cagacggggt 24360

cagacagagt cattggtgag caagcaaagg tgtagactgt tcagttcagc cttccttgga 24420

caccttttat gtgccagaca aaagaaggat cagcatatca ggtgcagtaa attattgggg 24480

ttatgttggt gtttcccaaa tgtgttagat ttatccctgg tagtgttaaa tctcatgatt 24540

ttaggtagta tatggacaac ctatgtaaaa acatttaata gtttaatatt aactagcata 24600

tcaaaacctg tgactttgct cacgcctgta atcccagcac tttgggaggc caaggcggga 24660

ggatggtttg ggcccaggag tttgaggcca gcctaggtaa catggtgaga ccctgtctct 24720

aaaacaaaac aaaacaaaac aaacaaacaa acaaataaac aaatcccctg taacttgttc 24780

taacaataac ctaaacaatt ttttatttaa aattaaataa aaaaattgaa acagtaacca 24840

tttttttttt tttttttgga gacagagtct tgctttgtca cctagtctag agtgcagtgg 24900

cacaatctct gctcactgca acctctgcct tcaaacaatt ctcctgcctc aggcttctga 24960

gtaggtggga ttgattacag gtgcactcca ccatgcccag ctaatttttg tatttttagt 25020

agagacgggg tttcaccatg ttggctaggc tagtcttgaa ctcctgacct gcagtagtcc 25080

acgtgccttg gcctcccaaa gtgctgggat tacaatcaca aatttataga aaagttgcaa 25140

gtaccatgta gtcagggttc ttaagagaaa tggaaccagt aggagataga tatataatca 25200

tctcctagga ttataagttg acacataaga ctaaccgtca catacagtat aaacaacttt 25260

ttttcttaaa ccatttgata gatacacaca cactgatata catagaatat atatacacac 25320

acacagaatg tatatacaca tagaatatat gtgcatacag aatatataca cagaaatata 25380

tatgtacaca tgcatagaat atatttacat atatatgcat atatataatt tatttatttt 25440

aagcagttga tttatacagt ttttgttttt gttttttttt tgagacagag tctcactctg 25500

tcacccaggc tagagtgcag tggcgagatc tcagctcact gcaacctctg cccccgggtt 25560

ccagtgattc tcctgcctca gctccacaag tagcacacca ccatgcccag ctaatttttg 25620

tatttttttt agtagagacg aggtttcatc atgttggcca ggctggtctc gaactcctga 25680

cctcaagtga tccgcccgcc ttggcctccc aaagtgctgg gatttcaggc gtgagccacc 25740

acacctggct cccataatgt cttttagaat aaaacgatcg agttgaggat cacacgtgac 25800

acttaattgt cctgtctctt tagtctcctt caatctggag cagttctttg atttttcctg 25860

gactctcatg accttgacaa ttctgatgat tataggccag ttattttgta aaatttgaat 25920

ttgtctgatg ttgcttatgt ttagatttag ggtcttggtc tttggccgga atatctcaga 25980

caagatgctc tgttcttatt gcatcagagc agaagactct ctgtttcagt tgatcacatt 26040

tatgttgatg ctcactttga tcacttgatt aaggtggtgt cagttatgcc tttctacttg 26100

tagggttact ccttcctcct tcgtgatttt atttatttta tttttcttag agacagggtc 26160

ttgcttggtt gcccaagctg gagtgcagtg gtgggatctt ggctcactgc agccttgaac 26220

tcctgggctc aagtaatcca cctgccacag cctcctgagt aactgggact gtaagcgaac 26280

accaccacac ccagctactt tttgtattgt agagatgggg tctcactgtg ttgtccaggc 26340

tggtctgtaa ctcctggcct caagcagtct tccggccttg gcctcccgaa gtgctgggat 26400

tacaggcatg agccactgca cccagcctcc tttgtaatta aaaaagtatt ttatggggag 26460

ttactttcaa gtgatggaaa tattttatat ctatgtggac ttggattttc ctatttcagt 26520

cagtgagtta taatccattt ctgtcactag ttttatactt aaattgttcc caacttggcc 26580

actgagaacc tttttaggtt agcttttgtg tccttttcac atgtctccaa gattcattga 26640

atactttcct gctttctggt atagcaagat gttcaggttc ttttggtact tttactttct 26700

ctgccctggc tctggcatca gtcatttctc agaggagccc tgtgcctttc agtggacaat 26760

ggtgtttaga ggccaagatc tggacattgg gtgttttcat tgctaccggt gtgtcactac 26820

tcccagaccc ctttcagtgg acagcactaa ggaatacaca tacgtatata caatatatcc 26880

acctacacat gtgcgtgcac tcacacacac acatatacat tacatctata tttgtgtatc 26940

catgtctata tattgaaaat tgtggctggg cacagtggct tatgccttta atctcagcat 27000

tttgggaggc tgaggcaaga ggatcacctg aagccaggag ttcaacacca gcttgggaaa 27060

cagagagaga ctctgtctct acaaaaataa aaagggaaaa ccatgagttc acacccgtgc 27120

ccccagttcc aatccaactt cacagggttc attttagttt tcaccctttc catgtttgta 27180

attctcttct ctgacattat acccttaata tgtttactta ttttatgcat ctgtatgcat 27240

ccaatctact gtctttgttg gtatcccacc tccccttggt gggtccagat aatctgctct 27300

gggttgccct ttcacgtgga tgtcttcctt accctgtgtg ggcctgtgat actgggctgc 27360

ccccacacat gagtgctgcc ctcctcacgt tgcttgggac ggcactgtgt cctgggccac 27420

catgactttt ctcataacta gcgtggatgc ttaccttgtt ccacaccagt gaatggcttc 27480

aggaagagaa gaggaagaga aaaatattta catttaaaga aaggtagttt aaagaaatat 27540

gttaggtaaa gaattgagca ggtaatatac ggagctggca aaaattgtga ccaaagtagg 27600

tgaatgattg agatttatgc aattctgggc taagtgacag ccccttccct ttcccttccc 27660

ttccccttcc cttccctttt cttccctttc ccttcccttt ccttcccttt cccttcccct 27720

tcccttccct ttccttccct ttccctcttc ttccttcctt ccttctgttt tcttttccct 27780

tctttccttt gccttttttt tttttttaaa gctagaaaca tcagtttagg cataaagaca 27840

gaggaaaagg cttctttttc ctctcacagt tctttataat tgtctaagca gtttcttttt 27900

tccctaggtt tcattttttg aggaagagcg gaacatatta tctcgaagca caagcccgtg 27960

gatcccccaa ttacagtatg cctttcagga caaaaatcac ctttatctgg tgagtcttta 28020

catctgtctc tctggaatta gcctagcact ctgacactca gatgcctgtg gtagaactga 28080

atgttgttct tgcccatgtg gtctcattca tgcaaagact ttcttacctt acaggtgtct 28140

ccctggtttc ctcgttataa agatcaagag ctaacccatt tagaaacagc ctcattgggc 28200

tgaacgtggt ggctcacgcc tgtaatccca gcattttggg aggccgaggc gggtggatca 28260

cgaggtcagg agatcaagac catcctggct aacacagtga aaccccgtct ctactaaaaa 28320

tacagaaaaa ttagccgggc atggtgtcgg gtgcctgtag tcccagctac tcaggtggct 28380

aaggcaggac aatcgcttga acctgggaag cggagcttgc agtgagccga gattgcgcca 28440

ctgcactcca gcctgggtga cagagcaaga ctctatctca aaaaaaaaaa aaagaaaaaa 28500

aaagaaacag cctcattgac agttggatat tgtagctgtg gctttcaggc aataataggg 28560

aatcatttat tggggaatag tctgtcatta tgtataagat aatcttgctt taatttttaa 28620

aaacttcctg tgttagcttg cttaggatta aaaaaatgat aatagtgcat ggttgttata 28680

agaaaatgca aacactgcag acatgcatga agttgaaggg aaagcccccc attttctttt 28740

ccttttcttt ttttttgaga cagagtctcg ctttgtcacc caggctggag tgcggtggca 28800

ctatctcggc tcactgcaat ctccacctcc caggttcaag agattcttct gcctcagctt 28860

ccctagtagc tgggattaca ggcacgtgtc accacgccca actaattttt gtatttttag 28920

tagagatggg gttttaccac gttggccggg ctggccgcaa actcctgacc tcaaatgatc 28980

cacctgcctc ggcctcccaa agtgttgtga ttacaggagt gagccactgt gcccggcctc 29040

tccgttttat tttctaatcc tcctccctag gggaagaaat gttaaatggt tacataagct 29100

ttccctttct gacccttaac tgtgctctgt aggagcatgg tgggggatgt ttcttttctt 29160

ttcttctttt tttgagacca ggtctcactt tgccacccag gctggagttc agtggcatga 29220

acatggctca ctgcagcctc gacttcctgg gctccagcaa acctcccacc tcagcctccc 29280

gggcatacac cactgtgcct ggctaatttt tgtattttta gtagagacgg ggttttgcca 29340

tgttgcccag gctggtttcg aagtcctgag ctcaagagat cttcctgcct tggccttcca 29400

aagtgctggg attacaggtg tgagccacca tgcccagctc cggtggggga tatttctata 29460

tccacatgtg tatagtttac tttataaaaa tggtatgtta ctctgtgctt ggctctccag 29520

cttgctgttg cctttcacca gtgtatccca gacatccttt cttccttgtc agtaacgcag 29580

gtctacttta ttctttgagc agtggcataa ttttccctga tgtgtatata tcataagtta 29640

gagaatgcta aaattcattt tggggccttg tttaggttct tgagggatta aattcctaaa 29700

tttaacaagt gtatcctgga aacaattttt gttcctgatt cagcccttaa aagaggacta 29760

tcatgttacc ttgaatggag ataaacaggc tcacgtaaga gaaaagggta agagggatga 29820

actcccactt atcttaaact tctactggcc cgtttttggg gaatttgctg cttttattcc 29880

tgacctaaaa taaataagtt tatgtgtctt ggtttcatat tagttgagaa cccagtgcct 29940

ggagagaagt tttccttgtc ctctgagtga ggacattcac atatgaatct attggcagac 30000

tggctttgac tgaccacacg tgccttcaga accaatgcca cagctcttag gtttatggcc 30060

tgaaacaccc tttccttaca tattgcctta gaaactttcc ttccttgaga catggggcat 30120

ggaaccctca ccttcacaga tgaccttggt gtgtttctag ggttgctggt gttccaggac 30180

atctgttgca gatgcagtat ttaccttgtg ctctctgcat cataagcagc ttctcatgtt 30240

tgaatgtatt aacagacttt taattttttt tatttttgag acaaagtctc actctgtcac 30300

ccaggctagt gttacccagg ctggagtgca atggctcaat ctcagctcac tgcaacctcc 30360

acctcctggg ttcaagcgat tctcttgcct cagcctcccg agtagctggg attacaggtg 30420

catgacacca cgccctgcta atttttgtat ttttagtaga gacggggttt cgccatgttg 30480

gtggggctgg tctcaaactc ctgacctcag atgatctgcc cgccttggcc tcccaaagtg 30540

ctgggattac aggcgtgagc cactgcgcct tttcttttca ttttttttct gagatggagt 30600

ctttctctgt caccaggctg gagtacagtc atgcaatctc agctcactgc aacttccacc 30660

tcctgggtta aagtgattct cctgtcttag cctcctgtgt agctgggact acaggcgtgt 30720

gccactgtgc ccagctaatt tttatatttt tagtagagac ggggttttgc catgtgggtt 30780

aggctggtct tgaactcctg acctcaggtg atccacccgt cttggcctcc caaagtgctg 30840

gggttatagg cgtgagccac tgtgcccagc ctcaggcttc tttattaaga agaagttcgg 30900

gccaggtgtg gtggcttaca cctgtaatcc cagcaatttg ggaggccgag gtgggcagat 30960

caggaggtca ggagatcgag accatcctgg ctaacatggt gaaacctcgt ctctactaaa 31020

aatataaaaa attaggcagg tatggtggcg ggtgcctgta gtcccagcta ctcgggaggc 31080

tgagggagga gaacggtgtg aacctgggag gcggagcttg cagtgagccc agattgtgcc 31140

agtgcactcc agcctgggtg acagagcgag gctccgtctc aagaaaaaaa aaaaagacgt 31200

tcccttgaaa caacagggct tttgtttgtt ttggtttgtg tttgtttgtt attgttgttt 31260

tagatacgta tttttttctt tctttttttt ttttaagtga tgatgtctct gttgcagtgg 31320

catgatcata gctcactgta acctcaaatt gcagggctca agtgattctc ctgcttcacc 31380

ttcctgatta gctgggacaa caggtacaaa ccaccatgcc tagcgaattt ttaaattttt 31440

catagagact agggtctcac tatgttgcct aggctggttt cgaactcctg gccccaagtc 31500

atcctcctgc cttggcttcc caaattgttg ggatcacagg catgaatcac cacacccagc 31560

ctatttttag atattttaat tcgagctcta caggaggttt agaacactag cttgtgaaga 31620

taaacttcat tttcaaggcc acacagaatc taagtggtcc tggaattagg aagggctttg 31680

attttttgga ccaaagttga gagtccacag ttttctggtc taccttgcac tgctccataa 31740

actcatattt cttttctctg agctgaagag ctccccttct tggtgtctag tctcaggcaa 31800

cttattctta aaagtaagca ttattgaaat gctttgggat tttcacatca tcaaggtcca 31860

ttttggtaga ggcactgaca gattttgagt gttctgtgtg aaggaactca gttgaggatt 31920

tagtggtcca tgtggcaggc tactgctcag tagcttcagg gaaaccactg cttgcctccc 31980

ctgtggccag tgaggatgat cagaggagtc ccagcaggaa tgcccaaatg tagttttctt 32040

acatgttgat gggagtgcat tgtttcatgt ctaaacagtt ctcaaatcac atcttcagga 32100

gggtactatc tgggcacttt gataatttct cactttgatg tcaccgttct tattaccatc 32160

acctagtttt gtcatagtag aaataacttt cctttttctg tgtgtgtgtg tgtgtgtgtg 32220

tgtgtgtgtg tgtgtgtgtt ttgagatgga gtcttgccgt gttgcccagg ctgtagtgca 32280

gtggcgtgtt ctcggctcac tgcaacctct gcctcccggg ttctcctgcc tcagcctccc 32340

gagtagttgg gattacaggc gtgtgacacc acgcctggct catttttgta ttttcagtag 32400

agatggggtt tcaccacttt ggccaggctg gtcttgaact cctgaccttg tgatccgccc 32460

accttgacct cccaaagtgc tgggattgca ggtgtgagcc accacgcctg gctttttttt 32520

tttttttttt tgagacagag tcttgctctg ttgcccaggc tggagtgcag tggcgggatc 32580

ttggctcact gcagcctcca cctcctaggt tcaagcaatt cttctgcctc agcctcctga 32640

gtagctggga ttacaggtgc ccaccaccat gtccggcaaa tttttgtatt tttagtagag 32700

acagggtttc accatgttgg ccaggctggt ttctaactcc tgaccccagg tgatccgcct 32760

gcctcagcct cccagagtga tggaattaca ggcatgagcc actgcgcctg gccacctttg 32820

tcttcttagt tgtggattta actgctgtgg acatctgctt gggcatagcc ttcccggagt 32880

acctcttgga ttgggactgt ctgtgggttt ctgtgctagg acaggctccc agatgtagga 32940

ggcttcccca atgatctcac cactggcatc ggcatcctta gcttctactc agcttttcca 33000

tctgccatct tgcaagatgg aaggttgttt tgtttttgtt tttgtttttt ggtttatttt 33060

ttttgagata gagtctcgct ctgttgccaa ggctggagtt cagtggcgca atctcggctc 33120

agtgcaacct ccacctcctg ggttcaagtg attcacctgc ctcagcctct ggagtagctg 33180

ggattacagg cgcgtgccac catgttcgtt taattttttg tatttttagt agagacgggg 33240

tttcaccgtg ttagccagga tggtctcgat cttctgacct catgatccgc ctgcttcagc 33300

ctcccagagt gctgggatta caggcgtgag ccaccgtgcc cagcctagga gggttcttaa 33360

tgcagctgtt ttttggagtt ctggttgcct cagcacactg ctacttgggt caatgacatt 33420

tttactccct tgttttgtag ctcaattggg tattactgat gggattttgt aattattaat 33480

attttcttgt ctccattttc ttctcaagta ctttgttgct tttgagtaaa atgcttgcta 33540

agggtatagt tttcacataa aagctcaaat ttagcatgga aattaagata tgctcatacg 33600

tctgccatcc cttatctgta attctgaaat acctagagtt ctgaataacc tcaaattctt 33660

ttgttacttg tttatcagca aaacctgatt tgaactcagt ttttggcaaa acttgatcca 33720

agctctctta aggctctttt tagtctttat tcattccctt tagtgtgact tcccattttg 33780

ctataaaatt atgagtgtgt ttgattacaa ggtgatgtcc cagaccctac tgagggtgtt 33840

acataatata aactgtatgt atggctgggc gcggtggctt atacctgtaa tcccagcaac 33900

tttgggaggc cgaggcgagc ggataacctt agttcaggag ttcaagccca gcctggccaa 33960

catggtgaaa ccccgtctct actaagaata caaaaattag ccaggcatga tggtgggcgc 34020

ctgtaatccc agctactcct taggctgagg caggagaatc acttgaaccc aggaggtgga 34080

ggttgcagtg agccaaggtc atgccactgc actccagcct gggcgacaaa gcaagaatct 34140

gtctcaaaaa aaaaaaaaaa aaagtgtgtg taccacttta cctttctaaa atctgaaaaa 34200

ttctgaatct ggaaacccat tctgcttcaa gataaatgga tcctagattt atatcggtac 34260

cgtacagtcc tgaaattcca tcctatctat tggccacttt tacatcaaca aacctttgaa 34320

gtttggggaa acttacatat cacgctccct tggcagttga acattattta tttattttga 34380

gatggagtac tcgctttgcc caggctggag tgcagtggcg cgatcttggc tcactgcaac 34440

ctctgcctcc cgggttcaag caattctcct gcctcagcct cctgagtagc tgggattata 34500

ggcatgcaac accatgccca gctaattttt gtctttttag tagagacggg gtttcactat 34560

gttaaccagg ctgttctcga actcctgacc ttgtaatctt ccctcctcgg cctcccaaag 34620

tgctggaatt acaggcgtga accaccacgc ctggccctga agatacattt taaatcaatg 34680

aaaaaaacaa caggattcta cctcctatgg tatatccctc ctggctgtct cttctctcca 34740

gtcttgcctc tgctgtgtgg gtttcaggca tccatcttct ctactctgaa ttactgtgat 34800

aacctctgaa gtattttccc tgccatctgt ctggcccttc tcccaggtct tccacatact 34860

gcagccaagt cagcccgctg ttgaaaccct tcaagactcc ctgctgtcct ctggatgaag 34920

tccagactct tccacgtgac ttaccaggcc tttcttgcac ttgtccccag ccacttactg 34980

tttctctctt tctaccttaa catcctgaac ttcctttggt tctttgacct tgcctctgac 35040

ctttttccat gctgttcact ctttccctgt tcaccttgct aactcctctt tctctttctg 35100

ggttggatca gatttcactt cttccagaag cccttcctag accctatact tctggaatgg 35160

cgccttttga ctgtacgctc attgcaccct gtacttctcc tttatgagtg ggtgctggtc 35220

tgtcccacta ggctacttca tccataaagg gagagtagag ctttaccaag tcaatgctta 35280

agcaatattt attggatgaa tgtgtgatta atttcataga aatttgatgt gcattcaaat 35340

ttacttattg tattacggaa cttgcattat attctcagtg gagttatttt ctttcacgtg 35400

tgtaattcaa gatagactca gtgagatttt caaaatttgg aatgcagtgc aaggaaattg 35460

aacttgagtt cttttgcatt ttgatggtta aaaatttccc atttgtggtg acataccaca 35520

ataagccagt gaatgtggct tattgttttc tggtctatag aaaattgtcg caaactctgt 35580

cataatgtct ggttctatat aacaaagcta gtcctgtatt ctgcatgtgg ctgatggaaa 35640

cagtgctctg ttgatctggt tcatgaagaa atctgttcaa ttctgcataa cagatgcctt 35700

catcagtgtc cttccatgaa ggagctgatc ttcacaaaga acacatagtt ttgcatccca 35760

ccacttgcag tatttttttt tttttttttt tttttttgag atgcagtctc gctctgtcac 35820

cctggctgga gtgcagtggc atgatctcag ctcagtgcaa cctctacctc ctgggttcaa 35880

ttgattctcc tgcctcagcc tcctgagtag ctgggattac aggcgcacac caccatgcct 35940

ggctaatttt tgttgtttta gtagagacgg agtttcacca tattggtcag gctggtctca 36000

aactcttgac ctcatgatct gcctgccttg gcgtcccaaa gtgttgggat tacaggcgtg 36060

agtcactgtg ccctgccagt attgttttgt ctaaattatt tgtgctgatg tttttcctac 36120

tgtggttttc ttcagattac ccttgctctg agcctgcaat tgactcatga acttcttttc 36180

catgttctaa ccttacaatg acttccttgt gttcactcca aatgtttttc cctggttgca 36240

tgtagagatg tattagctaa ggtacatgct tagctgctgt atcaaagaga ccctaatgta 36300

caacccaggc tggtagagca gctctgctgt atgtgttaat tcagggaccc aggttccttc 36360

catgttgtga ctcccccctt ccttaggatg ttgtcttctt ttacatggct gaagttgggc 36420

catttcatgt ctctgttcca gctgcctggt aggaaaaaag aacagaaatt cagagtaagc 36480

aaattctttt tctatagatg gatgcggaag ttggacacat catttcctct cacattttct 36540

cggccagaac gtagtcatgt gactgcacgt ctagctgcta aggagactgg gaatttactg 36600

tcggctgtgt ggcctctgtc aagctaaaat tcttattact gtggaataag ggaaggatgg 36660

atttgggggc acaattaata gtctgtcaca gaggctaaaa cagctgcttt tggctgggca 36720

cggtggctca cacatgtaat ttcagcactt tgggaggccg aggcaagtgg atcacttgag 36780

atcaggaatt tgagaccagc ctggccaaca tggtgaaacc ctgtctctcc taaaaatata 36840

gaaattagcc gggcatggtg gcgggtacct gtaatccgag ctactccaga ggttgaggca 36900

ggagaattgc ttgaacctgg aaggcagagg ttgcagtgag ccaagatggt gccactgcac 36960

tccagcctgg gcgacagagc aagactccat ctcaaaaaaa aaaaaaaagg ttaaataaac 37020

agctgctttt gtaggtgata caaggtacag ctaagctttg aagccaggcc tgtagtttca 37080

ccttccatat tcttactcaa ggcattatac ttctggatct gaaaccactg gatctgatgc 37140

cctgcttggg atgagttctt tatattatct tgctttcaac ccacacctgt gtaattttat 37200

gggcagcgtt tgtttcctat ataggaacaa tttgaaagtg ggctgtttct aggctttcat 37260

gaatagcagg ctatgctgtc attgggaatc tggagggagt taatgaacac aacttcattg 37320

tttactttag tgaaatgtgg cagcttatga tagttttgac agtgagacat gtgctgtttt 37380

gatctctcag ctaagattat ctgatttttc aggcatgtct caaaactcac caggcctgct 37440

cacatgctgc tgcttctgaa gccagggttt ggaaaccagc tgcccatcag aatgaggctg 37500

tgacttagaa tattggttct tgttttatta ccattccttg tttggtctct ccagagtcac 37560

tggccttttc cgcttcaatt ttcttatcgg tgaaatgaga tattaattcc tcttattgac 37620

ttcaattcaa ttgctgagtg tattgttgcc tttgggaagt tctttgagtt ttctgtgcct 37680

ttgaaatagt tgtttttttt tattctggtg ttttgaggca tgtttcaagt gagtgcattt 37740

acacttctac cattttagga gccacaattc agttatgttg tcccagcttg cttggcccca 37800

tccccagagt ttctgattca gtaggtctgg ggtggggccc aataatttgc atttcttctt 37860

cttttttcga gacagagtct gactgtgtca tccaagctgg agtgcagtgg cacgatcgta 37920

gctcattgta gcctcaaact cctgggctca agccgtcctc ccacctcacc ctcctgagta 37980

gctgggacta taggcatata ctaccatgcc ctgccacctt tttaattttt tgtaaggatg 38040

ggggtctcac tgtgttgctc aggctggtct tgaattcctg ggctgaagtg atcctcctgc 38100

ttcagcctcc ccaaatgccg gcattcctgg catgagccac tgcacttggc caagactttg 38160

catttctaac tagtttccag gtaatgctgc tgctggtgta gggacctcat tttgagaacc 38220

attgttctat agctgtagct atagttagtt tctggttata gcttcttcct tttgtccctt 38280

cagtaatagt gtacacatcc gaaatccctg tccttgctct ttcaggccca ggcatggtat 38340

ctggtcctct tctgttgcta gccctggggt gcttcatcat cccaagttta tttttcttct 38400

cctaacctga acctttgtaa atagcccctt ccctaatgaa cgtcctcaat tccctgtttt 38460

gcgtgtcctg tctgtttctt ggcaagactc tggatgattc agtactcaat gaggattttt 38520

cgcatagatg gatgaaacag gctgggtttc atgttttcta agataaaggt gcttctctct 38580

ttttctcttg gtcactttga ccaagaagaa aataacagag tttttattct caagaagaat 38640

aatatcgggg ccactctgct cagaggccac tctgctttga ggaccccttc tctcctccct 38700

catgccaaag atcaggaaca ttgggcagag cggataacga tgccgccagc gtcattacat 38760

tttcacggca ctttcagttg tgctgagcgt gcaaacattt caaggagaca tttctaagag 38820

gtggctagca cagcatgcct ctaatgccct atgtgaattg gaatagagta ctaaagaact 38880

gttcaatatt caccccatcc ccgcatatgc aagcatgcac gtgggttcat tgtatatgtg 38940

tgtgtgcacg tgtgcacaga cacatttgtc cttcgtttca aatgcaacac aatggatgga 39000

aattgccttc ctggtactgg ggtatggatg caaacaccaa cagagaagca gccgctactt 39060

ccaaactgaa cacatgtgag atttgccctt taattagcat ctgcagctgc tgccatcaga 39120

agggtctgtc tctgttggcc tgaaagtctt tgctttaaaa gagcaagtcc attatagctc 39180

caagccaggc tcgtctgtca gctgctgtgc tttctctgcc atcagcgggg ttgccacatt 39240

gttttgggct gtttcactct aggactcttt cctcctcctg tgcccccagc ctttgattac 39300

catgccttgg tgatcctcat ttgggtgacc tgcagctgct cattgtgtgt gcaggagaca 39360

tctccagtcc ttgtaaggag ggaagatcac tggcttcagt gctgatggac tggttatttt 39420

ccagcccttt gtcgtcagtg atcttgtctt gatatgcaga aaggctccag gtagtcactg 39480

aaaaaaatat aagcagcaga ggtgatggct atatgaaagt cacgtttcat caagggcatt 39540

gctgctatgg aaactttcaa ttcacttgga gtagggagcc atattggttc cacagcctcc 39600

tcagcagtgg gtcccaacac agtgctgggc tagctgcctc tgaatcaccg cagtagctcc 39660

ttttactata gattcctggg tcccacccat ggaatgtgat ccatgaagtc tggggttatt 39720

ccctggaatc ctttaagctc cctaagtggt tgggatggga aagagatatg ctttatgtta 39780

ctatacttct tattattatt attttaaaat tcttgccggg cgcagtggct cacacctgta 39840

atcccagcac attgggagac cgaggcgggt ggatcacttg aggtcaggag ttcgagactg 39900

gcctggccaa catgatgaaa tcccgtctct actaaaaata caaaaattag ctgggcatgg 39960

tggcgcatga ctgtagtccc agccactccg gaggctgagg caggagaatc gcttgaaccc 40020

gggaggcaga ggttgcagtg agccgagatc gtggcactgc actccagcct gggtaacaga 40080

gtgagacttc atctcaaaaa aaacccaaaa aaacaaaact ctttttcatt ataccggaac 40140

gtcagcttta tggagtcggg gattttttct gttttattca ctgctgtttc cctaacatct 40200

agaatagtgg ctggcacgat aggcactcaa gtattgattt agatgagtct attttatttt 40260

cttttaaatt tttaattttt attagaggtg gggtctggct ttgttgccca agctggtctc 40320

aaaactcctg gcctcaagcg attgtactgc ctcagcctcc caaagggcta ggataggcat 40380

gagccaacat gcctggcttg tcttattttt aacaagcact tctggtgatt ctgatggaca 40440

atcaggcttg ggaagttcta acctagagga cctacagttg tcttggggta gaagccaagg 40500

ctatcctggt ttttagaatc agtgccttac tgggcatctc tgaagagtaa aagtcaggga 40560

cagagttaca tttttggaca aaaccagatg ctgtgaatgg actcttggtc acaacctggg 40620

tggcgacttg gtccttaact tcttcatcat tttctgctga ccctgttctt tggttcacag 40680

caagtcacct gataagaaga ctcaaagact gctagtttgt tactttagat gatgcttttg 40740

gaacctcttg gtaccatttt aacaatccaa acgtatttta tgaaagcact caagtcctgg 40800

gtctttattg tatctttaag ctctaacagc atgatgattg aataagctgt ggttggccac 40860

acacaagcca tcttccccat ggcctccatt catactagaa tgagcagcta taccccagta 40920

gtatagtttt gggatatggg taacatcttg ggatagccac atttacttag taaatgtctg 40980

gcttacattc tcctaatggt gcactgttgg aatttttggt gtggtaacct ggaatagtgt 41040

tggtgggtca agtttgatta gcatctttga taaggacccg gtctatttag aggtttgtca 41100

ttgagtgtgt ctgttttggc ctcatgttgt gaagcatgct gtgtagcagc tgttgtaatt 41160

tttgttgctt gttttctcaa tcaaccctgg ttttgaagaa atgggaagtt gttccactct 41220

tagactgatc tgacttggga ggggattttc agttcaggaa gttggatctt ctgaatggaa 41280

gcaaagaata catgtctttt tgccacttta caagctggct cttgttttct gaactatttt 41340

actggtcatt gcaaatagaa tgtcaggagt agctgccaaa tactaagttg tgttcagttt 41400

gtcagttctt aagagttgcc ggtggctgct ctgctatgcg tatgactttc tcagccttaa 41460

acttacaagc catactgttt ttttcacatc tttaatacag ccataggaaa tttataactg 41520

tggcgtgtcg tcataaatat gcattgttct tattttaaga catttcagta ctaaaagtat 41580

aagtacttct gttattatct gtgaatttct ttccttcttc tttttttgga tatttaagac 41640

cttttcgatg tcaatatata tttaaaacag acatataaat tagcattcac ccacataccc 41700

agggcctatg gagaaccagg ttgggatgag tgggtgagct acaggcagcc aggtggctcc 41760

tgtgggctcc tcgaggactg gggtgagtaa ctaatgtctg ctaggaactt gggggaaaga 41820

aggtgtgtat gttaggtgct gcccccttct aagtgttcct cttgttcata attgattttt 41880

tttttttttt tttttttttt tttagaagga gtctcgctct gttgccaggc tggagtgcag 41940

tggtgtgatc tcagctcact gcaacctctg cctcccgggt tcaagtgatt ctcctgcctc 42000

agcctcccga gtagctggga ctacaggcat gcaccaccat gcccagctaa tttttgtatt 42060

ttnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 42960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 43980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 44940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 45960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46560

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nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 52020

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nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54780

nnnnttctaa taactgtgct ttctactaca ttaagcctat tttttttttt tttttttttt 54840

tttgagatgg agtcttgctc tgttacccag gctggagtgc agtggcacaa tatcggctca 54900

ctgcaaccct gcctcctggg ttcaagcgat tttcctgcct cagcctcctg agtagctggg 54960

atcacgggtg cccaccacca tgcctggcta atttttgtat ttttagtaga gatggggttt 55020

caccatgttg gctaggctgg tcttgaactc ttgaccttag gtgatccgcc tgcctcggcc 55080

tcccaaagta ttgggattac aggcatgagc cactgtgcct agcctgtgaa gctcatttct 55140

taaggctctg ataaatgtat atgttttagt ttcaaccaaa aggaaaagga acgtatttcc 55200

tagatttttg tatctcacct aattttcatc tttctggaat gcttaataca tatttttatg 55260

tacatacatt atttgttatt cttgagcctc ctcttgagtg aaaatttccc cttagatgac 55320

tcttggagct aatttatttc cttcccttta gctcactcac tcattcaatc attcaataac 55380

gagtgcgtta tcataccagg tactgttagg tagcaggttt acagggatga gcagaagaag 55440

caggccctct ctgccttctt tctttttcat cacactgaaa tcacagcgca ttgtgtgtgt 55500

gcaaaagtag agtgcagagg gaacatgcag aaaggagtta taggatagaa aaggtagcca 55560

aggaaagcag caagaacagc atgatttgtt cagggatctt taaatagctc atcattgttg 55620

gacagcaaag ggagagatgg ggaacgtggc aagatgagat gagaagggga gccggggtca 55680

agccatggag gacgctgaac ccctacaaag gaactaagcc tattgatgtg aacaggccac 55740

ttattttggg aacacgcctt tggtccaaag ggaagagggc acgaaacttc cttctctaaa 55800

aaacaaaaaa aaagaaactt gcatatatga gaaatacttt cttcactttg cagcatgaga 55860

aacggaatcc ctactaagga aataattctc ttattttttt tggaacagcg gtttttgaaa 55920

tttccagatg accccaaagt gagcagtgac tttcttgatc tgattcaaag cttgttgtgc 55980

ggccagaaag agagactgaa gtttgaaggt ctttgctgcc atcctttctt ctctaaaatt 56040

gactggaaca acattcgtaa ctgtaagtag ggctgttttc cttaatttgg gatgttggga 56100

ttatgaaaca ctcaagagag atctgagatt gttctggccc aaagaagctt ctgtaaatta 56160

cataaataaa ggctttaatt atctacagga gtagtaaagg ctaatgatgt agctgtcttt 56220

gagtaataat tctgccttaa aattgtttgt gtagaactgg gtcatttatc aaactctgtg 56280

tttatgtggc ctttagaata ttatccctca gtaagttaga ggcacagatt aatggagttt 56340

gaaggttgtc acttggtttg acacagtttc ttccaaaaaa gtggatctag gtatttcatt 56400

cacatatcag gaaaaagact cagattaggc aacatgccca ggttgttctg ctaatggctg 56460

agtttaaaca aaaaccataa acacctccct gtgtttattc atttgtttcc ctcgataata 56520

tttgtctttg ctcacaagca tgtaaaacct ataatgtata tgcacagtag attcattcat 56580

acatcacttt ttataatcag ttagtgcaaa ctgaatgaat tcattaaaaa caaagacctg 56640

gtttattatc aacagaaacc acacaatgct cttttttctt ttaccagttg gtgatctttt 56700

aaaaatcctt ttaattcttg gatgtgttgt tgattgaatg tgttctactg aatgatcagc 56760

acggattaga gccagtagga aagcagttat cctgtttgag tatgtgtttt gtttttggtg 56820

atggagggag gttgggaaat ggaatctgtt tctaggtgtc aaaaccaggc ttctgattgg 56880

agatgtgtta taattataat tgcttgcacc ttcagctagg acatagtatg gtaaaaaatc 56940

agtattgtcc agttgtaaac cattttgatg gtttctctaa ccttctgctg aaatatttaa 57000

gtaggtagca tttccataaa tctttcttgg caaatgtttt tattattcgg gtggccacat 57060

tgctttattt ttctaaataa atagacatct ccccccaaat ctccaaggtt cagaccttct 57120

aatcagtaat atattttcag ggcattcttc cttttatgct tttagaaaga tgtaatagac 57180

tttcttttag atgctgttca agtacttaat cttttcttgt cttgcctttt tatctctgta 57240

atcttcttga ataagcagtt aatttttttt attcatgaac ctgctgatca tgtctaagaa 57300

tgtatctcca cttaagtaag tcagtgaatg gtgattacct gagtagagtt aaagtagtcc 57360

cccaccctcc tatctgtggc acatatgttc caagtctccc agtggatgtg tgaaactgat 57420

gatagtactg aaacccatct accttttttc ctgtgcatac atacctatgt tatataaagc 57480

ttaacttata aattaggcat aatatatttg actcccagct cccagtgtag tggctctgaa 57540

gactcacaaa atgtatttgc tttaaaaaat tctttttttt ttttttgaga cggagttttg 57600

ctcttgttgc ccaggctgga gtgcagtggt gcgacctcag ctcactgcaa cctccgcctc 57660

ttgggttcaa gcgattctcc tgcctcagcc tcccaagtag ctgggattat aggcatgcac 57720

caccacaccc agctaatttt ctatttttcg tagaaacggt ttttccatgt tggtcaggct 57780

gatcttgaac tcctgacctc aggtgatctg cctgcctcgg ccttccaaag tgctgggatt 57840

acaggtgtga gccaccacgc ctggccaaaa aattctttta atttaagtaa atctttattt 57900

atttactttt gagacagagt ctcactctgt gggccaggca ggaatgcagt ggtgtgatca 57960

cggctcactg cagcctcgac ctcccatgct caagcagtcc tcccacctca gcctcctaag 58020

tagctaggac tacaggtgtg tgccatcaca ctctgctaat ttttttgtat ttgtagagac 58080

gcggtttcac caggttgccc aggctggtct tgaactcctg agctcaagtg atcctcctgc 58140

tttggcctcc caaaatactg ggattacagg cgtgagccat tgcacccagc cctaatttta 58200

ataaatcttt tattttggaa tagtattaga tttatagaaa agttgcaaag atagtatgga 58260

agagttccca catacccttc acccagtttt ccccaacgtt aactcttttt tatatttatt 58320

tatttatttt ttgagacaca gtcttcccgt cgcccaggct ggagtgtggt ggcacgatct 58380

cggctcactg caacctccgc ctcctgggtt caagtgattc ttctgcctca gcctccgagt 58440

agctgggacc acaggtgtgc gccaccatgc ccggctactt tttgtatttt cagtagagac 58500

agggtttcac catgttggtc aggctgatct caagctcctg acctcaggtg atctgcctac 58560

cttagcctcc caaagtgctg ggattacaga catgagccac cgcacccagc ccccagtgtt 58620

aactcttaca taacagtgtc actgtctaag tgtttgaaaa actatttgtc aaaactaata 58680

ttggtacatt attgttaact acacttcaga ctttttttgg attttaccaa ttctcccact 58740

catgtccctt ttctgtttca ggaatcaatc cgtggtacca tattgcagtt agggtgttta 58800

tatttgatgg gactggtcct agtttagata cttagtgtag ctcagccagc aggtgggatc 58860

ttcatgccca ccgaggattg gtattgtgtt ttcctggtgg ttttatggca tttccgacta 58920

tgcagagagg catggtatta acttcagtgt ctcctagcaa attttcctgt ttttcaccaa 58980

cctctgatcc ctgcattatt tgcaatcaac tcagagattt gtgattgaaa acattgcttg 59040

actccatgct ctttaagcta ttttctaact aggtaactgt aacataaatt atgcttttat 59100

ctagcactgt ttttcataaa cacatgttga gtgattttca tcaaccgaaa tacttcgaat 59160

cattaagttt cccaagttca tggatgctgc ttaaatgcct ggtggttcca ggctgtcgaa 59220

tatttctgcc ttctgcaata agagattgtc ccttgttaaa agcaacatta gcctttgtgc 59280

ggtttcaccc ccaattcttc tttttcttgt tgtaaccaat gaaaggaagt actgcttaac 59340

acagcaggta ataatcttct aaaactcatt atctcaagag gtggtcctgg caggatatat 59400

aaatgcaatt taagaaaggt cttggcaaat ttatgaatga cagaactggg agtggctacc 59460

gagagaaact aggatgcgcc tttgctttga cactgaggtc aggcgtagct tctgtaccct 59520

cctgggtcct gcctcttggg gttgctgcag gcagcacccc atgaaccagg catctgaccc 59580

agttccagga tacttattct tccagcaagt cgaacactct gtgatgagtg actgccatgc 59640

tcatgggtca ccaggctctc attattctgt ttcatttcca gcctcccaca agattggttt 59700

ttcagctgct tatttattat tatcattatt tcaaggctgc tttccaagtt tcagtggggg 59760

gtttcctaag cgtaccagct gccctggttg tgcagttccg gtgatgtttc agatgctggg 59820

ccggattctg gctgtaccca gcctgatctt tctgggcttc aggaaagctg aagccaatca 59880

gagctcctct ttcatgcctt tgggattatg cttaccttgc ctggcatcgt gtacctgctc 59940

ccatccatgg gaaagttttg ctgtctggta ctgtcttcta tcaacatctt ttaagatatc 60000

ttcccccgag gcatcgtgat gtcaacggaa ccagcacact tgtacgtttt atgcaagact 60060

gccatatctc aacagtgaga aatgcataat ggaagtggtg atcacggatt atttcctagg 60120

acattatggc taatgcgcta gagaactcgg atggtctgtt gcgtctgaca tgggcttttt 60180

ctcttgagtt gtctttcttt tgctattctc tgaaagaaac aattcttgcc acatgatcct 60240

gatttttcag gtcctcagca tttgttagca gaaagtacac tttgtttcca tccggcagtg 60300

actcagtggt ggtcccatgc tgatgaaacg ctgagatagt cttcttccaa ataggtatcg 60360

ttttgattgt tgctgcttat ttgctagctg gccctcaata gtgacaatga aacctcaagt 60420

gtataatatg gttgctcagt aatcctgagg gaagacagtc tttggtttgg gggataggga 60480

ttctgtgcct acttagcttc aggtgaaagt cttacaaatt tttgtgtgta gaaataagca 60540

ccatgtacct ccttgggttt tttctttttt tttctagtcc tttagtatgg tcaacaatat 60600

tgtttaggga gtacctattc tgtgctaacc actaggcatt caagtatatt acactatgct 60660

ccttcaaaac acttctgtca aatgtaagga ttattatacc cattttacag atgtggttac 60720

tgtggtaact tggccaaggt catagggcaa gtgaataagg gattctggat ttgggtggag 60780

gtctgtgtga ttccaaagcc catgctcttt ctacaatact atatatgcct ttgcataagt 60840

tattgttatt agtaataata tttgtgatga tggcaaataa taaaccatgt cacactagag 60900

agtgatttaa tctctaggtc tatttaagaa catttggaat tgcaggaatt ggattttttt 60960

ttttttttaa gtgatggagt cttgccatct ttgcccaggc tggtctcaaa cttgtgggct 61020

caagtgatca tcctccctct gcctcccaaa gtgatgggat tacagatatg agccaccatg 61080

cccagcctag aattgcagga atttttgaat tgatgattca ttctgatatt tgaatttcta 61140

cagtatgtta agtgcaatgt caggtgctgg tgctgtggct ccattgatga acacatttgg 61200

gtatggccct accttcattg aatttagagt ctaagagcct aaccggtctt ttgcttgaat 61260

agagctgtag tcctgttaaa ttgctgtacc tccaaatggt gggaagttta atgcttcgta 61320

ggcctcccct cactagttta ctgaaccaca tgtgcttgat ttttttttga gatggggtct 61380

cgctctgttg cccaggccgg agtgcagtgg cgtgatctcg gctcactgca agctccgcct 61440

cccaggttca cgccattctt ctgcctcagc ctcccgagta gctgggacta caggtgcccg 61500

ccaacacgcc cggctaattt ttttgtattt ttagtagaga cagggtttta ccatgttagc 61560

caggatggtc tcggtctgct gacctcgtga tccacctgcc tcagcctccc aaagtgctgg 61620

gattacaggc atgagccact gtgcctggcc ccacatgtgc ttgattttaa gcaaaataca 61680

gactataggc tgtgacctgg tgatctcttc cccacataca gcatcctgct aacctataac 61740

tctccccatg tctcagatct agcctgggaa aggacaatgt tggatcgatg gcccacttct 61800

aatcttggga tttctaatct caagatgagt tgagaagact caggatgtgt cctgttttct 61860

gtttatttag aacagggttt ctcagccttg gcactgttga catttggggc cagataattc 61920

tttgctgtgg gggctgttgt gtgaattgca ggatgttgaa cagcatcgct gtgctttctc 61980

catggatacc agtagcaccc tccccctgca gttgcaacaa ccaaaaatga ctctagacat 62040

tgcccagtct ccccttgggg gctacagtca ccttcagttg agaaccattg atttagaaga 62100

attggccagg ttattatcag gagagggaac atcacagtaa tctgaatctc tcaatactgc 62160

cactgttact gttaacgaac agcaaaacta ttacgtggag gcagtaggac cttgctactc 62220

agagtgtggt ccgtggaccg gcagcatcgg aatcatctag gagcttgtta gagcttcaga 62280

gactcaggcc tactgagtca gaagctgcat tttaataagg atccccaggg gatttctgtg 62340

catattagag ttgtgaagcc ctgcaagagg aagaaattgg atgctagcct cagagtttct 62400

tgctcatctt tgtgggtctt cctcgttttg tcttcgggct taaggtatgg ggaggccact 62460

ttttggctca ggactcctat gggtgaatgg gactgcttag aactgctggg ttttaggcct 62520

tgctttgagg aatttaaagc ttttctctta gatggacatt acatcgttca tatacttcaa 62580

aatggtggtt tgacctaatc tctgccttct gatagcaaaa agatatttcc ttgactccct 62640

gaaccccact ttactgttgt cccatattgg attttaatta agggtggaat aagtattctt 62700

cactaacatg tttatacatg tatgatatta ccatgccatt tattgagtgc ctagtatgtg 62760

ccaggagctc tgcaaagtgc tttatgctta ttattgttcc atttattctt ccccaaacct 62820

ctgtgaggca ggtcctatca ctagtccaca atacaaatga ggtcatggag cccgaagttg 62880

gcagtggtag gaatcaaact caggtctccc tgactctaaa ttctctttgc ctttgttttt 62940

ttgaaaaagt ggtatagccc atagcagaaa attcacatta tacagaaggt tatacggcga 63000

aaaatgcctc cttcccaccc cacgctcaac ccctctccct caagcgaacc actattgtca 63060

gtttctcata gaactttcca gaatattcta tgctcctata acactagcac aacctatcct 63120

cttaacaaca tctttatgct gcctcccaag aattcagtaa tttttttttt tttgagatgg 63180

agttttgctc tagttgccca ggctggagtg caatggcgtg atctcggctc attgcaacct 63240

ctgcctccca cgttcaagtg attctcttgc ctcagcctcc cgagtagctg ggattacagg 63300

catgcgccac tatgcttggc taattttgta tttttagtag agatggggtt tctccatgtt 63360

ggtcaggctg gtcttgaact cccaacctca ggtaatccgc ccacctcggc ctcccaaagt 63420

gttgagatta caggcgtgag ccaccgcacc tggccaaatt cagtaatttt tattggcagg 63480

ttattttccc gcatcattga aatgaatgaa gcaatcttta tacttcattc atttaagcat 63540

ggccctacca tgcttatcct tcgaatctgc cactcagcca ttggtttctg ataagcagtg 63600

ctcttctcaa atgaaaaccc cttatggctt tttttttttt ttaaacaagg ccacaggtga 63660

tatcatgatt ttgacattat tttttcattt attttgttta gtgtcctgcc tttagaattg 63720

cattatctca atggcttgtg catttagtgt gtgtgtgtgt gtgtgtgttg tgtgtgtgtg 63780

tgtgtggtat gtgagcacgc acatatttgt tttgggccct tttttttttt ttttttgaga 63840

cagagtcttc ctctgtcagc caggctggag tgcagtggca caatctcggc tcactgcaac 63900

ttctgcctcc tgggttcaag caattctcct gcctcagcct cccacgcagc tgggattaca 63960

ggcatgcgcc accacgcctg gctaattttt ttgtattttt agtagagacg ggtttcaccg 64020

tgttggccag gctggtctcg aactcctgac ctcaggtaat ccgcccgcct cggcctccca 64080

aagtgctggg attacaggcg tgatgttttg ggccttttaa agttcatctt gtttgtgtat 64140

tcatttgttt ggggcctttt aaagttcttc ttgtttgagg cttcctgtca tttgaagggt 64200

tatctggtca tgttttgttt tctaagctag ttccatgagg atcatagata tgcttctctg 64260

ttaggcttgg ttggccctta aacttgtctt ccttttggac actcacttac ttcaggggca 64320

ggaggaagtg aggaagagga gttgggtctg tttggagtat cagcatggac gggaagggga 64380

gcaagaggga tgggatggta aagtagtgat ggtagaaatt caacttacta gaccaggagc 64440

gtgtgggcgc cacctactaa aacaaaaaag gaataatgaa gagctatagt cagtagctct 64500

tataatctct tatgggatat gtaggcaaat atttatgtgt ctcttcgggg ctgttctgtt 64560

tttagaaggt aaatgattgg taagaaaaaa taggccaaaa agagctaaat gcttatgaat 64620

taggattata ggattttccc ccactagtct gaatttagaa gctacttcca gagatgtcaa 64680

aaatatgtaa tattctactt tattccaaga taaattgagg gcaacttatt ctagaaataa 64740

ttgcaatatt aaaaatataa caatgaataa atagagaaat ctagatgaaa ggagtatgag 64800

gatagggaaa taaagttagg gttgaaagta aaaacaagga agttcctgtt aagttgccaa 64860

aggaagaatg atttgggact ctcagtctcc cagtgaccaa agcagaaagg agaatataaa 64920

cagttacaag agccccagtc gcatgaaaaa aaagtccaga atgctctgct cagaggagac 64980

ccaattttct gaatactgag ccctgaggaa tttcaccact gggtttccca taaatgagac 65040

cccctgtgac ctggtgggcc ccatccctcg gaagtgtacc ctggcatttc cataggactg 65100

cttccttctg ggcctcttag tgcaagccag cagtgcaatg ccacatccaa gtttggtaaa 65160

tcaattctaa gtgagataaa ttaatgcctt ttttggggga agatgggaaa cagagtgggt 65220

ttgttggaga gcccataaat tggagtcttc aacccttaaa ttctcacttg cgggaaaacc 65280

tttcacaacc aagcaaacgt ggaaatgatt tggccaaaga ttcaaaatta tattaaacat 65340

ctgggactat attcagcagc caactttcta atcaattcta tgagtgtggt gattgcagtt 65400

atgctcattt tctgagggtg aagtttggat agaactaaaa agggcggttg gcaggaatca 65460

aaagagatga aagcctcagg acaaagagtt agaggcccag gtggttcatg actgagagtt 65520

tggaaatgat ttctggtgtc tcacttcaga gaaaataaat atagccaact ctgttcatcc 65580

gtggtgatgg aacattcaac tacagcactg gcagtttggg atctaagacc acccttccag 65640

cacttcaaaa ttctgactta taaaggacac acacaaagaa cagatagcca gatagagacc 65700

aaaataccca ctttattctt ggcagggcaa gcacccagta agctctgatg cagggctctg 65760

gtaaatttgc ccatcctacc aacagagaag aatggtggcc tcccctcatg aacggggtcg 65820

gaggggggcc ttgccacaac agggggcctg atggaaataa gggggacaag agtgttcggt 65880

tggttgagtg cctgctatgc ctgtgcctag gcagtaaaag gggaagtttt aagtttggcc 65940

cttactttca agacatagta attctacctt ctagtaaaac atggccaaat aaatgtctgc 66000

ttttcatgag ccagataacc tccttcttct ttattggagg agtgagtaga agggtgagac 66060

tagccgggtg cgatgtctcc aacctgggcg aaagagcaag actccatctc aaaaaaaaaa 66120

aaaaaaatta agaataaatc ttttcactgt tggagaaaag ttttgagagg ccgaggtgag 66180

aggatcactt gaggccagga gtttgagact agcctgggca acatagcaag acccctgtct 66240

ctatcaaaaa ataataataa aaaaagctag ctgggtatgg tggtgtgcac ctgtaatccc 66300

agctacttgg gaggctgagg tgggaggatt gcttgagccc aggagttcaa gcttatagtg 66360

aactatgatt gcacccctgc actccctcct gggcatcaga gtgagacact gtctctaaaa 66420

aaaaaaagtt ggagaaaagg atactaaaga gataaaaggg tactaaagag atcgggaagg 66480

cagcaaagaa tgaatctagt ctgatgtgtt attgggtgta cgtaattcat ggcggaaggt 66540

gctgaaaggg aaggttgcct gggcctacag caagcaggtg ctgatgaact agctcctttg 66600

ctattactta aatgtgtcct ggttgggcca gatgtggtgg ctcacacctg taatcccagc 66660

actttgggag gccaaggcgg acggatcact tgaggtcagg agttcgagac cagcctggcc 66720

aacatggtaa aaccccgtct ctactaaaaa tacaaaaaaa gtatccaggc atggtggcag 66780

gtgcttgtaa tcccagctac ttgggaggct gaagcatgag aattccttga acccgggagg 66840

tggaggttgc agtgagccga gatcatgcca ctgcacttcc aacctgggca aaagagcaag 66900

actgagttct caaaaaaaaa aaaaaaaaaa attcctgggg aatatccacc agggtgaaaa 66960

attgggtata tccaaattca gctttgcaaa gaaatgcact catgactagt tgcaatttga 67020

aacgttcctc ttctgagtat ttctagccta tgtaggtgtt tcacagattg ctgagtacct 67080

agactgagag ggagagaaaa aaacaaagta aagctaaaat gttaagaagt ctggttaaag 67140

tgcaatccag aagtgaggga aagcatctct aaaagtatga atctttgggg aaacataact 67200

tgattaccaa aaacttaata ttaagcagcc tcataggaac atggcttttg ggtatggcga 67260

gagccagcta gagctcacat ctccattgaa atccaccacc agagaggtta tctgcctagt 67320

tgttggcagc cagaccctgg cattgtttag attgattgat ggaaggctac tttgggaatg 67380

ctggcttcct tattcattga ctttaaagac agcattgtaa aaattgatca ccagcccaaa 67440

tcaatgttac cctgaagtat ttttatgact ttttggggag gcaaagagat gggataattt 67500

ttgatttatt taagtctatt gcaaactgga actcctttgt cttctttttg aactaccttt 67560

tttgtttttt tgagagagag tcttgctttg ttacccagac tagaaagcag tgatgcagtc 67620

acagctgact gcagccttga cctcccagac tccgatgatc ctcccatctc tcccatgtgc 67680

atcaccacac ccggctaatt ttttgtattt tttgtagaga cagggttttg ccatgttgcc 67740

caggctggtc ttgaactcct agactgaagt gatccacctg ctttggcctc ctaaaatgct 67800

gggattacaa gtgttagcca ccaggcccgg tcttgaactt cgtatataca gtgtgttgtg 67860

tgggcaagtc atgcctgacc acttcctagt gggaggggag aaactagagg gcttgcctga 67920

ggctttaggc aatgtaatct gttctcttgg gatcaattac ttatgcatat ttagtagcca 67980

gctctatttg ctgatcacct aatctgttct cttcgttcat tcccatgaga cttcgatatg 68040

ggatatcttc ctcttcttcc cattgcagcc ttttctctca gagttgttcc catgataaga 68100

actcccatca aaatctctgc tctaacatca gttgtcagat tttgccactt tttttttttt 68160

tttttttctg agatgatgga atctcactct gctgcccagg ctggaggcag tgccaccatc 68220

tcggctcatt gcaacctctg tctcccgggt ttgagggatt ctcctgcctc agcctcccga 68280

gtagctgaga ttacaggagc accccaccac tccaggctaa tttttgtatt ttttttagta 68340

gagatgggct ttcaccatat tggccaggtt ggtctcaaac tcctgacctt aaatgatctg 68400

cctgtctctg cttcccaaag tgctgggatt acaggtgtga gccactacgc ccagccacat 68460

tttgttactt ctttctgtaa cctgaatgtg gaaaaactca ctgtctttcc tccactctca 68520

caccataact gtcaacacca cagaagactt ctgtgaccaa atatgtggtc accaccaagc 68580

aagcagtaag ttctgcagtg gacaccacta ggcgtcctcc agttcagttc tggcactatc 68640

cgcctggaga tagggctcaa tcccacaggt ggaggtctca gtccccaaga atgtcccctc 68700

ttcaggcacc agttgcaagt ccaggcctct ggaacttctc gctgactggc ttcaaattgg 68760

ggttcctgca gccccctctt tgagttcaat taattggcta gagctgctca cagaacttgg 68820

gaaaacacat ttactggttt attctaaagg acattgcaaa ggataaagat gaagaaatgc 68880

atagggcgag gtatggggga agggttgcga gcttccacgc cctccctggt cgccctccag 68940

gaacctccac gtgttcagct atccggaagc tctccaaact ctgtcctctt gggacctttc 69000

atggagacgc cattggatag gcatgatcaa caaccatgta gaaatgggat tgcacgaaaa 69060

ggctatgatc taatcctcat aggctgagtg gggaatccca gcaaggcctg tttgttcaga 69120

tccttctgta gcattcattc ctccaggtta tggggcagga ccccttctga aatggggtct 69180

tctgacctac aatcagacaa ggcagaggaa atttctttat ggccagctcc aagtcagaaa 69240

ggtgggggaa gattagagtc ctgccttgag cagatgaaag gagggctgga ggaggtcaga 69300

gagagagaga ttctgttttt caaggcctgc ttctaaagcc taaagcaccc ctaaataaca 69360

aaagattgta acaaggacta tgggagtcat aagccaggaa ccgtggatga aaacctatat 69420

atatgtatat atatatctca taataattca aacctgtctc ctgttaatcc catcctctct 69480

gtttctgtta tcatttcctt agtgtagatc tgcctaagtg tagaatttgt agaatttgtc 69540

atgttgacta ttgtagactt gtcttttaga gtttctagca ctagcctctt ccacccatca 69600

ctattgagat gattgtatcc gtctcagtac tgacactaac ccagcactct ggttttacat 69660

ctgtcaatcc atcaagactt cactttcact ttcttccctg cctcattatt cactatgctc 69720

ttgggccatt gctctggctt ctggggcttt tctaaagtag cacttttccc cactccagcc 69780

catgaagata ccttttaacc agctcttgag attaaatccc ctccgtgaca ctttcctgca 69840

ggaacttgca aaaaagtact gcattcccca ctggcaaaac ttgccatcag ccagtttatg 69900

tattctctgc ttttcacacc catatcttga cctctgaaca acacacatat tctcctcttc 69960

atttatttca cagttctgtc ttcataacat tgataagtat gatcacatta gcgctctaga 70020

ttttaagcaa ctggaagata gctatttttt tggtactctt cctttaaatt tgaacatagt 70080

gtctaattag tcaattaaca tttttttaaa agggcgaggg acatcatggt agagagaacg 70140

aagttgaacg tgtttttggt tgaatattag cgcatgccca ctgtattcta ggcacagtcc 70200

tgattcatta tatcatcaca caataattat ttatgtgcct tcatccttta tgacacagtg 70260

ctggctctta ttcatctccc atttctgcaa tccatggtga tgattaaaag tcttaggagt 70320

tttacgaggc tcagtatttt ttttttttaa tatgctagtt cttcatgaat acattgggta 70380

ctctgaagca tatcatttcc tgggtttcct gaagtggtat gttgcgtgga atggcacatt 70440

aggtctaaat aattatcccc tatgtaaggt tcttgttttt cattcattct cttaaaaaat 70500

agatattaaa cattaaataa ggacagccag gtattgtttg aggtgttagt gggctatgct 70560

aaaaaatcaa aggtgggaat gaggcagctg gagctcaaag gagcatgtta gaaggagtcc 70620

caagaggaca aatccatttg gttcttcttt ccttgttttt tttcgaatat ttttgaggat 70680

gataattttt ttcccctcaa aagcttttaa tgaatgttag gattaaaaaa gagagagaga 70740

gaatttatag aagagaaatt aactatagct cctaaaatag ctctttgttt ctgaaagcct 70800

tgattctgct atctatttta taactgaaac aaaaacaaaa acaaaaacaa aaaacaacct 70860

caagaagtta cttgtatagc ctctgccact aaggagactg tgttctgatg ttacctcaaa 70920

caggctgatt tattaaaata tttaaaaata tatatggaaa tatttttttc tatttttttt 70980

tttagtggct tttcccagtg aacaataggt cttactatat gatttcttat ttgtcattag 71040

tgaatgtggt gggtatgtgg cagctggggg agctgatgat tttataatac tgtatcagaa 71100

atgattagtg taggtactta ttaacatatt tctcagacag aacaatcttg acttttaaaa 71160

cctcttcatt taattcaaac atcaagtacc ctgtttgtgg cctgtgttat gttaggtgct 71220

ctctttacaa gacctatttt cttgctattt aattatatat ttgcttagca aatatttact 71280

ctgcacctac taggtacctg gcactgtgct gtgtactgag gtgccatgtg tacctccatc 71340

aacatagact caagatcaat atgatttcag tgaactaaaa atacctttat tgaagcaaaa 71400

aaaaatcaca ttttgtaagg atcaaaaaag agacatttta tataaggtac aagaaataga 71460

agaattatat ccccaagata tatgtgataa catacttgtt agtttttgga cgtgaccaga 71520

ttttacacaa tccttaaaaa atgcagcaac cagattttaa agtagttctc taatctctct 71580

ttctgtgccc cattagatgt atattggatc ttctcattct gtctttgtct tttgacctct 71640

catgttttcc gtctctttgt ctctgtgtgt tgcattgtac acaaatgctt cttgaactgt 71700

ggtgtgcaca tgaatcacct ggggaccttg ttacaacgta ggttctgatt ccatgggtat 71760

ggggcagggc ctgagattct tagagaatta aattctaacc agctcctgag tggtggtgat 71820

aatgccagtg tgtagaccat agcttaagta tcaaggttct atgtgattcc ctcagatcta 71880

actgctagtt cactaagttt ctcttcagct gtatctagtc tgctatttaa catattcagt 71940

gaatttttaa ccttaaattc aagaacaaga ctttttattt ctggaagttc agtttggttc 72000

ctttcaaatg tacctggttc tttttcaaag tgtcatgttc tttgataaga atttctacta 72060

atttaccttg ataataaaaa tttgtttcat ggctcatttt agattgttct tttatctgca 72120

gtttttggag ggctaattct cccatttctt gtatctgttg ttgcacccgt aaggtgtagt 72180

tgttgatttt tactttttaa ttgtgaattt atttctggta gggattggaa ggaggttgtt 72240

ggggtggggg tggggtgggg agaaaatcct gtgtgccctg ggttgcaaaa acacccctac 72300

aagttgttct ccacttgcat ctgccagtgc tccaagggct cagtgatcct ggaccagtag 72360

tcatgataat ttcttgaatt gtaacaggat actgtaaatg tggacactct acctgaggtt 72420

actgcttctt tctatctgct ttatttcctt cccactgaag ggccctggac aagggtaaac 72480

atctcatcac tttctgggtg gcagaatatt tccagttccc ccacttcttt ttggcttaag 72540

gctgtggctt tttcctctgc ctgaatgtgg ccctaagaag cccttctttt caaactttcc 72600

tgttgtactt gaccgactag ctgtctagag gtttatatcc ctagctttta atctttgctg 72660

tgaatatctt acctgttacc agctagtata tttcacattg acttctcttt cctttttttt 72720

tttttttttt tttttgagac ggtgtttcgc tcttgttccc caggctggag tgcagtggca 72780

cgatcttggc tcactgcaac ctccacctcc caggttcaag cgattctctt gcctcagcct 72840

cccaagtagc tgggactaca ggcatgcacc atcacatctg gctaattttt ttgtattttt 72900

aatagagatg gggttttacc atgttggcca ggctggcctt gaactcctga cctcaggtga 72960

tccacctgcc tcgccctccc aaggtgctgg gattacaggc atgagccact gtgcctggcc 73020

tacttcttct tccttttaac ttgaagatta tctgcccctt tttctaatct taaccgcatt 73080

aagctggctt tgagcatggc aagagtttta tagatgaatc ttattttata gtacaggatt 73140

tcaaaatcat aattatttca ctgagggtgg cttttaccct ccattaatta tacttctcac 73200

tcagaaatgg aattctattt tggtctccta aagataaatt agtatatagt ggaaaggaat 73260

tataaagttc tgctaggaat taaatgatat gattaacaca aacatccaca tggatgtgtc 73320

tctgccctgt gcaggaaaga tgaacattca gtacagattc tgctctatgt cactagcttt 73380

caagacctgc aggttctctc ctaagcatgc aattcctgtg agcagtagca ataatagcag 73440

gtcatatttg tggagtgatt actgtatgct aagaactgtg gtaaacactt ttatatggat 73500

tattttattt aaacctccta atagtccatt gaaatagata ttgccatgtt gaaaactgag 73560

gttcagagag gttaagtgac ttacccagtg tcacagaact agtaagtggt gcagctggga 73620

tttgaactga gattccagaa caattgccat taaccacttt gcttccatat tagtatcatc 73680

tgcaaatctc tctccataaa tttcctcagt ctttatctga gtttccttat ttcaggaagg 73740

aaaacttctg tttttgatcc ttatgaaata caatttccat taaaactttt tttttttgct 73800

attaaaaaag gtaccggata attgaaacca gactggattt gagcctgtgt tgatggaagt 73860

acacatggga tgtgggctga agtgttcaat ctaatttttc tttccatcag ctaattttta 73920

aagtattaag caagtagatt ctgacactaa cagggaagat ttaaattctc ttgagagact 73980

ggaggtgtta aataattttc tggtagtgca cattttacat cttaaatctt cctcactctc 74040

ccacctcatc tcaatgtacc tgaagctctg ggaatgttct tttgtacttc tcaggaacag 74100

ccagacctct ggcttcatct cctctcccct ccacatccct ttcctgctcc aattacttcc 74160

cagcgccact tggatgttgt tgtcatcggg gaactttgga aacagccaga tttttttgga 74220

gtctgtaagc agaaaacaga ctgcttgctg ctcatatctg gcacccagct ttgtccagaa 74280

aacgaggagt taaaaagaag tctgggctgt gaagggctgt gacaactgtc ctagggggag 74340

ctctagcgag ccctggcggg cagtgactca tgctgctctg tcactgggat cagcactggc 74400

ccctggcagg caggcggcag ccaggtgggg ttccagccag agcacgcacg cacggagccg 74460

ggagcatgca gcctgcactg cgggggatgt gatgctcggc tctaactcgc ctggctggcc 74520

cgccacggac gcctcagctt gcaaccatgg taacgtttct ggcgggggac acccccggga 74580

gcccaccgcg atgggcagcc tcctggtgac tgatggacga gtgtccacct cccagaccga 74640

gagcgcttag taggtcggag gaagtggaga ggatgtaaca cgcccccagc cgggagtgaa 74700

gccctgagga ggtaggagcc gcatatgtcc atccgtgcat tcccaccgtc agcgcgcagg 74760

ggtgctgtag atcaccggta ggaactttat ttggctggtg cttcattatg ctgattaaac 74820

tgcagtggat ttgatgggca tgattgcgct ggggaagatg cataatgaac taaaaaaaaa 74880

aaaaagtggt taataagatc tcggagtcga cttgtccggg tatgaatgaa gtagactgca 74940

gtggtatcct aacaggagtt ccagaacctc acacatccct tttcctggtc cttcctctta 75000

tcccggttaa tccacgaaat gtagaagttc catcttattt caacgattag tgctaatcat 75060

taataattta gacctgtctg gaggagggaa tccataggtt taggtctcct agcatcctgg 75120

cactagccag cagctgctct gtaggagcct tctggaaaca gcaggaagga gcggcttccc 75180

cacgagttcc ccaagtgctt tcgttggccc aagtgctttc gttggcccaa gtgacctgtt 75240

tgagtttgct cttcagttta ccccaggcgg gaaggcagcc tgtctgcggg ttggtggcca 75300

tgttggcaga gaaggggtta atctcttgtt gctgtaggag ccgaggttgc gagctagatt 75360

gaaagcaggc gctgcagtgc catcgccagc gccgaaggag taagacgatc ttctccgcaa 75420

cagtgttgaa tccggctgaa attttttttc ctccccgcct cctttcttgt ttttctttaa 75480

ccagctcctc cccccttcgt tcccaccctc aagtctgacg atgacacctc caattttgat 75540

gaaccagaga agaattcgtg ggtttcatcc tctccgtgcc agctgagccc ctcaggcttc 75600

tcgggtgaag aactgccgtt tgtggggttt tcgtacagca aggcactggg gattcttggt 75660

agatctgagt aagtgaaaat ttgactttct aaagggacct gcattgatgc aaggcttttg 75720

gagccaaagg tggtggtggg ggggtggggg aataggtggg gggagtgcag tggagggaag 75780

ctgctagtca cctgcattgg gaaagcagtc tacctgttag ggctttgcgg gggtagcctg 75840

ttaatattct cattttgcag tgtgtaaggt acctgttcct gtctgtggta tgataattgt 75900

caattgggta ctttgggtta gttttccaat ctttggtctt ctttaaaggg gagagagtgg 75960

gagatttcca gcagtgcaga tccccggtca aaggagaaat gtgcaggagt taagatgagc 76020

tgcccatcta tctaaccatc tatgtatctg tctctcaagt gggtggatgg gggttgctat 76080

cttggctgta taaagaatcc taaaaacctt gtctcataag ctagaggttt cctgatgggt 76140

ttaactgagc tgcaagtggc tgaaccagag ctctaacaga gagatggtgc tcggctcctc 76200

tccaagtatg ctgcaagatc agggatctgg cagctgagcc tctctgagct ggtggagcgc 76260

tggcagccag agaaagcccc gttactgtga gccaccagga gggagtgtga tgtagccgag 76320

tcattgattc acagaaactg ggcttcatag ggggaaaaaa aaccaggaga ctagaaaatg 76380

gaaatataaa tatcactgta aacctcttga tctggtaggt ctttctccat tctcataaaa 76440

gctattgaaa aatgcattaa cagagcactt ggaattagag ggtcgaggct tccaggagcc 76500

tcctggaatt tctgtaaaat gcagtagctt ctgtggatgt gggaggtcag tatcttgcct 76560

cattctctca tgatacaatg acattctgtt ttcagaggag tgagttcccc agaagatctt 76620

ggactgatgg tgttatttgc cagccaccct ggtccctgca ctttcaggtt ctcagagggt 76680

aatgttgggt tagttgctgc ccacttagga gacgagcaga atttgatatt cttcttggca 76740

gcatctttcc ctctttgtgg tatttgtagc ttagatatcg atttataggg atgttatgtt 76800

ggttcctgga tggtgtctcc ctatgggtgc tattttgaca gtaacgttcc tgaaaagatt 76860

tcagagtgtt gtggggaatt gggcatttga tacgaaataa ggttgtgggc tgtgattgaa 76920

tgtgagggag gtttttatgt tgcaagatgt tgaagtggtc tttcttgatc ccctctctgg 76980

gggctgggtt tcaaattcag gttggatttt ggtagtgtta gatgtgcctc tctgtctgat 77040

ttgctccaca accccaaagc aatctggatg gtggtgggag aggcagagtg ctaactagct 77100

gttgaatgtg ccatcagatg ggtttgaaac ggctcagcag gattgggagg ttttgccatt 77160

ggcatcaaag agcagggcag aagcggaggc ctgatgttga aggatgcatg gttagtgggc 77220

agtataacct tgacacacgc agcacactga aggtcacacg tcgtactgga aggacgtgtg 77280

gagagttcta gttctggtta gcagtgggct ggctgggtca gaatgcaagc ttgcttgggt 77340

gttggtcagt gatctgaaag acgagggagg attcgaggga gttagatttc aggggaaaag 77400

gcagaatgat atgggagatc ttaggcattg caattaatct gaagcagtgt gtgattaatt 77460

gcttattttt caggaagact tgaatgacat ctttctgttt ctcacagaaa gctcagttta 77520

gggagctctc tgacagggac atctcagtat taaggctgag gcactcgata aatatttgtt 77580

gatttaattt acctatgatc ctttcctcca gaagtgttta tattgcttat tgtatttgaa 77640

gatgtgctat ctcacctctg gtagtttaaa ctatatcctt agagcacaaa acgagctgct 77700

gttcctgacc caacagaatg tttaataaga ttcttatttc aaaaaaggtc catgcaaata 77760

aaactgtgta tttcttattt ggacgatggc atcagagtat tcctatcatt ggggaacttt 77820

aacgtttttt caaagcttgg caacggggtt ggaatcagaa agattttctt tcatcttgcg 77880

tcttgttatg tgttattgct attggacttg gctactctgc tgtaggcagc cctgtgggtg 77940

atacctacaa gcatcatttt agaaattcat ccacctgttg gatgtagatg accctggaca 78000

tatcagattg tgattaatta gaaatctaat aaaagagagg cagtgatgaa attacttagc 78060

agctcctgca gttttattga caaaatttac ttggagagag ggggagacat tttctggggg 78120

taccaccttt gctgccagcg accctgtgtt tcttcctgag tttctttttc ttttctcacc 78180

attttcagca tcacaggttt ttatttacac acattgatta cctgtgctgt tactcattct 78240

tcacaccact gaggaaattg cagatgctgc tgtactgtgc taggtaaatt gacctcagat 78300

ttgttaccag tgaattgaat gaaatgttca gaggtggagc tgaatgaacg aggagttttt 78360

gtggagaaat tggcagtgag aatgatttaa attctgtgat agctcctcgt tttttgggat 78420

ccttattttg ggaccccaga ctatttttaa gccattgagt gcatcattat tttaggctga 78480

gcaagaatct tgatgacagc gtttcaatgg ctgaggcgta gtgggagttc cttgcagctt 78540

gagttggtgg gagctggaga gtttctagag aactaggttt ggttgtcttt ggggtggggt 78600

tatggtgaaa ttagtcttgg agagtgagta gctgtctgat gcttcttttc ctttttaacc 78660

agcaagagcc caaaccaaat ccccaagctc tgaatgcctg gctgttcctc tcagcctttc 78720

tttgcttgaa cttgacaata gtagggtagt aacaggaaac agcatgttaa agttttaaaa 78780

ataaaataga tctcagctct tttccttccc attagcaagg ggtacattta tttaggtttt 78840

tccttctaga ttgaggcact gcctcattta agttcttggt gaagccatgc atttctgcaa 78900

accataagta taaactctag aacgggggtg tccaatcttt tggcttcctt gggccacatg 78960

ggaagaagaa gaattgtctt gaggcacaca taaaatacac taatgatagc tgatgagcta 79020

aaaaaaaaaa aaaactcata aagttttaag aaagcttaca aacttgtaag ttttgagcca 79080

cattaaaaac catcctgggc tgcatgcagc ccccggggcc ttgggttgga caagcttgct 79140

gtagaaggta aaaatcagtt ggttttatgt ttttgtttta aacatgctgg ttgtatgctt 79200

ttggaagagt tggggaacac tgagggtaat gggatcttga tggggctgga atttgtggga 79260

agatggtgtc tgggtaggct gtttttagga aggggcactc tcttcctttt gattcagaga 79320

tttttccttt cttttcgggt ggttctgaaa acacagcgat ggatccaggc attcaaacac 79380

catggaggaa ggaagagtgg ctgttgccat tgcttcccga gttttctggg aaccagtttt 79440

tggtgcctct tccttgctct actggggctt ctctgcatgt cagtttcttc aactgcgaag 79500

tggaaggaca gcgatacttt tcttacagga cttttgcggg gatggatgaa atacgtaaaa 79560

cacttggtct agtacctggc acatggaaaa gccttggtaa atgttcactg ttgttatttt 79620

tgttattact aatacactag tccatgtatg tatagtgtcc tcctatacac accaagagaa 79680

tatggaaagg actcagcaat gattaggtag tccaaagtca taccagattg gaaaccaagc 79740

ttcccaggcc ctgggacttt tctgctagag acacttcacg gttctgacca actacaaaga 79800

gttaatatgc agttgccaaa tacctgttgg taaaaggtgg atgttgggga ggagtggatt 79860

ggggaacaga attagaaggt ccagtcccag aatgggtacc ttcccatcaa gttgaacaag 79920

tcaaaacagg ttatgttgaa acaactgaga gaaagtaaag caaacaccat tgctgcagaa 79980

tatcatggta caaattggac atctttggga gttagcggag taaggcaaaa tccagtgagg 80040

gacgcttaat gggtaatgcc aattcacaat tcttgttaaa ttacattgct gatcttcctt 80100

ggaatgtctg tccattcccc caagtagact gtgatctcaa ggcaaggctg ggtcttattc 80160

atcctggttt tcctggagca gtaaatactt gtgctgggac tgggcttata agcatactaa 80220

tggaaagtaa aatatttggg ttggtttttt aaaaagacag tggatttgga tcagtggaga 80280

ggaaggtaga gggaatttca ggtgggcagg gtgctaacaa cagcccatcc ttacagggca 80340

ccaactgtgt tctaggctgt gttccaacca ctttacacag atgaattcat ttaaattgca 80400

caaccagccc aagaggaagg taccattatt attctcattt tggatgtgag gaaactgagg 80460

cgtggggaga tcaaacaact tgcctaaagt tatgtagctt tgagtggctt agctgagatt 80520

tgaaccctgt gggtataaac gccacagatg ggaaatttgt gtggggtacc caggttcatg 80580

tgcttgttag aagtggaagc tatttgtaga gaatcacgaa tgatgaggtt ggggcagggt 80640

gtgatgggag ctgacaggca ggtctaaatg ctgggattca ttttcagtct ctgtgtttat 80700

tgagtaggta gacggtatag ctcttggatt tctcagattt tttcctcttt tcatttagag 80760

actcttatct ggtgtgtgtg tgcccgcaca catacataaa cccacgcgta tatactcttt 80820

ccctgaatgt tcttatttgc taaagcttaa gcttggcaaa gagaggaaac tgcactgacc 80880

ttactctcca ccatatcttc aggctgatca tacacaagtt gcttaataag catttggtta 80940

atccatctaa atcattctta tggctgcaac tctcattttg ttgatgactc tactatctat 81000

gtctattcac atctacattt tgtacttttg tttgcctccc atctgtcctg ggatggctga 81060

taccagtgga agacagcctg aactctccaa tcagtcctgt ttccttttta tgaaatactt 81120

ggaggttgga ggatcttccc ttaaaaagtg ttttcctttc tacatccagc caaaggctct 81180

tggtccttgt gcttgctacc tagatcccta ttggaaagag tcttgcctgc aatttgattt 81240

tttaaatagc agcaataaca gagtcgtctc tgctacacga agacatgcat ctgctgtatt 81300

tcccagacaa gttcaaaaac cttaactagc ttctgcccat ggttattgct ctcaagtgcc 81360

ttgtgttgtt cccatcccct cattatctgg attagatgtt taacatttgc ctgtgtgtgt 81420

tgtgttggat tttctcctct cctcttgctc attcaatttc ttccttctct tagccaagca 81480

cagcttgttc tcctacttgc cttattctgt tctctattta gactgtgcgt gcctgccttg 81540

cagccctggc aggaccattc caccgccttc tcatttgtct taaagatacc tttaggaaat 81600

ctaatccaga caatcctagc ccagtcctga agattaggct ccagaagatc tgtcaagtgt 81660

gttttttgct ggcctacaca tgctaatttg catggttgcc tgggatccct taagaagaca 81720

gtcattgact aaatggcgct acatgttccc aagctctgcg ccagtctggc aactcttcct 81780

ttgtctacgt gaatttctcc tagttctttc tgctttgctt gctgttcatc tcctgacctc 81840

tctccgacaa acttcctgaa agaagagcct gcactcaaca cctctttttt ccacctcttc 81900

aacaatactg aaatgactgt ctcagaagcc gttgattgta cctaaccacc aaatctggtg 81960

atttccatct caccacgtga taccattaat actacctttc ttcgagacaa cgttctactt 82020

tcttctcttc tgtattatgg acacttggtt tccctcctac ctctctgact gtcattctca 82080

ctcttttgtg gctgccatca ggctcttgca atgtacgtac catctcctca agttccatcc 82140

tcagttatct ttctagttgg ttcttggtga tctcattcag ttccttgact ttagttctta 82200

cctccccatg gcctcctccc atcgtacact gtgttcctca tcaccaggat gttttaccag 82260

tttctcacca tcccatcctc tgttcccttc ctacatagac agacccactc gctcactcag 82320

taagccacta ggtgctagtt ttggcttctt cattttatgt aagaaactac caccttccct 82380

acccttctag gcaagaaagc tgagtcatcg taaattcttt tctgcctccc ccgccatccc 82440

atcagttgcc aatttctcca agtggtgcct ctaggatgcc acttgcatcc atacccatct 82500

ttcttcctca ttggcaccca tcatggactc ttgcttggtc tggtgcagta gcctcctcag 82560

tgattccctt gcctctggtt ttcctggctg taatccattc tccacaaagg gtggaattct 82620

tccaaagcat aggttggatg atgtcattca ccggcttaca ccttcaacag catcccagtg 82680

tgctcataat taatggctgc tcctgaactt ggtattcagt cttggtatgc caagacccca 82740

gcctgccggc tcatttgtgt ctcctcatcc cctactgaat cacttcaata gtgttgtctg 82800

gccaagctgt tcaaggctca ttaaggacag gaccaggtct tccttctttt gcctgaaaca 82860

gtgccttgcc cctggcaggt cttcaatgaa catttgttga attgaattag actaaaatgg 82920

ccagggatta taccaattcc ttctgcacag tgtagacaac tgctaatgga acctgttttc 82980

tgtagagcac ttcttgtgtt cccagaacta tgcgagtact ttatgtgcat tatctcatta 83040

aatcatcaca atctcactgt aactctatga ggtagctgat attatcccca ttttacaaat 83100

gaagacactg attcaggaag attagattat tttcctgagg ttctgaaggt agaaacacat 83160

ctaagacttg gagcaatatc tggttgcctc tagaccactg tactatctac cctgcctcta 83220

agagccatga ctttgctaga ttatgcagga gttatggact tgtctaatag taaaggtaaa 83280

agaattggtt ttaatgagaa tctactcttc taggtactat tctgagtgcc tgacaagcat 83340

tctcatgtag acccagcaat aactcattat tttacagata gagaaaatga tgatcatgat 83400

gcttgggtta cttcttaggt tcactcagct cacatctggc agagggtggt caacttttcc 83460

aagttttaac ttatttattt atttattttg agacagagtc tcattctgtt gcccacgctg 83520

gagtacggtg acacaatctc agcttattgc aacctccgcc tcccaggttc aagcgattct 83580

tgtgcctcag cctcccgtgt agctgggatt acaggtgcct gccaccacgc ccagctaatt 83640

ttgtttttgt atttttagta gaggctgggt ttcaccatgt tggccaggcc tgtcttgaac 83700

tcctgacctc aagtgatctg ccagcctcgg cctcccaaag tgttgtgatt acagatgtga 83760

gccaccacgc ctggctcaac ttttaacttt agaactgata taaacatgcc tatttttttg 83820

ggactgactg tagcataccc attcaaagtc caggctttgg aatcagacag acgtgggctg 83880

aactcagggt ttcacccctt gcttgttgtg tgaatgagac atttcactgc tttcagcctc 83940

aattccctca tctgtaaagt ggaaggtgta aggtcgccta tctgataggt ttgccatggg 84000

gatatgaagc acacttagtg ttggtgccat gagtagaatg agtgttcatt tcatatttgt 84060

taatgttatt taggtccgag gatgggtatg gggtgctttg gactctcttt ttctccctgc 84120

ttccgcctta taaagacatc ttgctggttt ctgcccattg agagaatcca gctccacgtg 84180

gggggcctga cagatgtcct aatatctcca tccaattttt tactctgaat ggagtctgtg 84240

atgtatcact tcaacctgca ctttctataa aatgctctcc aggcttctgg taggatccag 84300

tgccagtggg aagtgtgcat gttcccagcc tagatgtcac atgctcccac ccaccctgga 84360

agcacttggg tatcccctgg atgggtaagt ctgtgtgtca ttgtgccatt cctgtctcag 84420

aaccaatgct gggcatctct acttgcaggt gctggaaagc tttttcatgc cagcatacat 84480

gcagcacact tctcattttg gattccttta tcccacggtg acctttaaac tggctgcctg 84540

ggggcacaga agtactagca caccattcac ttatttattc attcattcat tcattcattc 84600

attcactcaa caaatatatt gttctagtcc ttaaggcaca actctgagca agacaggtaa 84660

ggtctttact ctcaagaagc tagcatttgg tggggagaaa caaaggagaa ataactactg 84720

tgcacatgtg aggcaattgc agatggtggt ctgcagaatt gggattgaga ctgcctgggg 84780

gtggccactt tagactgggt ccgcaaggaa aggttctctg agctgagcat gagtatttgt 84840

tcaagaaggc tgagttgcat cccaaggtga cacagctttt aagcccacac tgagcagctc 84900

tgaggtccta ggggctgttc gagaacctgg gatatagcac tgactatgag acaaaaatcc 84960

ctgtcttcat ggagcttaca tgatgggggc agattcacat tcattcattt gttcattaat 85020

tcattaattc attcagctat ttgagagcct actatgtgcc aagcactttc taggcactgg 85080

agaagtaaca gtgaatgcaa aggagcaagc atccctgccc acacagagtg cattcttcca 85140

gaatatcaat aaggagtcgg ttagcaaaaa taagtgggaa gagtattcca gagagaggaa 85200

aaaagggcaa aggccctgag gctgccacta acctatgggt gctcaatgaa cagaaggcat 85260

gtttgggtag ggggtactta aggatacaca aggaacatgg tctgagctga ggtcatcagg 85320

gcctttaggt atggactttg ctctaaattg cactgagtag gaagcttttg caggattttg 85380

aatagggtca tggaatatct gggtcttatt tcacaaagtg tgcctctgac cattgtgtgg 85440

agggtggata gtgagggaca agagttggat ccagggaggt aagtgtggtt attgcagtca 85500

tcccaggtga gaggcaatga aattaacctg caaagtgagg cactggctta gaggtgggaa 85560

ctgaattaaa aatcatggga ctagctattc ttttattaat agcatgattt ttgataaatg 85620

attctggagc tacatattaa tcatttcaaa gcaagtgctc taatttaact agagaccact 85680

gctggttgtg tgtgtgagtg catatgtgtg tatgtatatg agtatgtgtg gtgtgtgtca 85740

gtatgtatat gtgtgtatgg tatatatata aatatatata ttgtgtgtgg tgggggaggg 85800

ggggtgcccc aaagctagac agactctgac tgtctttagg ggaatagtgt ttttgatatt 85860

tccaggtgtt cctgatgggc accattgtta ttttatttta tttttatttt atttttgaga 85920

cggagtctca ctctgtcgcc aggctggagt gcagtggcgc tatctcggct caagacaacc 85980

tccgcctccc aggttcaagc aattctcctg cctcagcctc ccgagtagct aggactacag 86040

gtgcgtgcca ccacacccgg ccaccattgt gtattttaaa gtgtgcttat aaaattagtt 86100

cagagccaga tgtggtggcc cacgcctgta atccaagcac tttgggaggc cgaggcgggt 86160

ggatcatgag gtcaggagac cgagaccatc cttgccaacg gggtggtgaa accccatctc 86220

tactaaaaat acaaaaaaat tagctgggta cagtggcgcg tgcctgtagt cccaactact 86280

ccggaggaca aggcaggaga attgcttgaa cctgggaggt agaggttgca gtgagccgag 86340

atcgcaccac tgcactccag cctggtgaca gaacaagact ccatctctaa ataaataaat 86400

aaaacaagtt cacaaatttc ggaatgctca atcttaaaag ccagtatatt tttggaaacg 86460

gaatgctgat gagtttttta ttttttgcag catattacat cttgcagttg catgtatttt 86520

tagtgctgtt ggccagcact aaaggtgggg ccctcagctg agctaatttt gagtcccctc 86580

attttggctt caagtatact cattcttggt tttcccaaga atatctggga tttgtgatct 86640

gtgttatctg tggtttggtg tcgtattttg caggcatagg gtcctattcc taagggaata 86700

aatggatggc ttgatgctta agcacgaact taatcatcgc agtagtgatt aaagagtatt 86760

caacatgtac acttgcttgt aggaaggagt acacattgta ttctcttttg atatgcaata 86820

ttttattcat agccctatta agtaattttt tttaacaaag ttatatggat tatttacagg 86880

tacatcacgg gaaaactgca ttttataatt ttcactgaaa tgttgaggtt acatgtaaag 86940

caatttttat gtcatatctg atacatttta agaaaacatg tcttcctgtt acagcggtaa 87000

tgaccatgcc tgctctttct tctgtgtcat atgccattat ccctattaat actctttggg 87060

cttctataat tataaagcag atgtgtatat cagggagaga tgttgatttc agagtaagtt 87120

tttctagaaa atagaagctg gaaaaaaaag gaaaacccaa acttggcttc gtgctcgaag 87180

agacagcact gctgtgtgtg ggcgggtggc tgcgtgcacc cgctgctcag aagtgccttt 87240

tctctccatg gggataactg gctgtgtatc cgagatgtgg ccaggagtag gcaagcaacg 87300

tgtgggcagg ctgcatgttc ttttattagc atcttcattg tactgcatct cgtcgagccc 87360

agagcatgaa ctggcctggg tttctaatat ctaccctgct tcccacctaa ttactcccct 87420

gaaccctaaa gtgagggagg gagagttgct cttgtggggt gagctttccc tggggtggct 87480

gtgaaccaac ctggcatgtg gatgttcttg ggtatccaga gctgtcctgg actcaggctt 87540

ggagtcagct tcttagcact gaatgcagcc agtcatggat ggaggtcact gtatctcaca 87600

tgttccgctc tccctttcct ccatgacctt gcccctctga gcctctgtag cacttttctt 87660

gagtgtgtcc aaggccatct agctaagaag tagcagaaat gggatttgaa gccatgactg 87720

tttggtgata gagcctcagc tttgaactgg ggttctactg cctggcaccc ctgcacaaat 87780

catggtaacg tggtaggaga acatagaggt atagggcaag cccctcctta atgccatgaa 87840

taatacccat cttataggat tgtggggagg actcagtgaa gtaacccgtg aagcactaaa 87900

cacgtgcctg acacgtgctc aataaatgag cacttgtcct gatgacaaag gtcgtggcat 87960

taattctctc tcctaggttg ttacttcctt gaggacagga attgtggctt ccttaatggc 88020

cactgcagca gagtttctca agttggcact attgacattt tgggctggat aattcttgtt 88080

gtgggagctg tcctgtggat tgtaggatgt tgagcagcat ctttggcctc tacccgctac 88140

atattaatag cacccctagt catgaaaata aaatgtctag acattgccaa actgcccctg 88200

ttgagaacca ctggtctgca ggtatctctc atggggatca cagggctttt atattctctt 88260

ctctgtctct ctctctccct ctctgggtgt ctctctctct cacacacacg cttagagaag 88320

gtggttaaaa aaaattttgt tgaagtttga gaattttgag aacaaaggaa aaattttgga 88380

aggcatttta atgaacagat agactctgtc ccattccatg gtcaacagaa tttcataatt 88440

agatagtttg tttactgcaa ctctgcaccc cattgcccat cattttagag ttccaaccag 88500

ttagaggatt tttcttgcaa actttcctta aagcagtgat agtatcagct ctttaaataa 88560

tactatgctt gatgaagtgg tacttttcgg gataatttga gaccagccga cttgctgctt 88620

gaagaggaca gggctatatt tggtaataat atatatgtga taatatgtat gtaatattat 88680

tataatgtaa tatacaataa tatttggtgt aactggtgac tctgaggcca gtctttgatc 88740

gaacctctca agctatgatt tacattatgg tcaatgttag cataatgcaa ttatcagcaa 88800

tcacttgctg ttgctttgaa agtcagaagg atggctaata aaaatcttag aaaaagaaaa 88860

caggctgggc gcagtggctc acccctgtaa tcccagcact ttgggaggct gaggcgggca 88920

gatcatgagg tcaggagatc gagaccatcc tggccaacat ggtgaaaccc catctgtact 88980

agaatacaaa aaaaaaaaaa aaatttgctg ggcgtggtgg cgtgcgcctg tagtcccagc 89040

tactcgggag ctgagtcagg ggaatcgctt gaacccggga ggtggaggtt gcagtgagcc 89100

gagattgtgc cactgcactc cagcctggtg acagagtgag actccgtctc aaacaaaaca 89160

aaacaaaaca aaaaacaaaa aaagaaaatc ttagaaaaag aaaataaatt gtaatatttc 89220

agaatatttg ttggggagga tatgtgtgct caagaaatat atactgagaa cttaccattg 89280

atgctagaga ttgaattgcc ccatgtctac atgaaaaatg aatagaatat aaacatttta 89340

aattgagcca tgtctatctg tattatattt cttttataga aattcatgga aatggtatat 89400

tttaactgaa ttattaacac tggggacaat aggctttaat cattatctaa tacctgtacg 89460

ttgttttgaa attcatagcc caccaccatt aatttcaaaa ttgggttctt actcaaagag 89520

tgatgaaaag gcaccagtac caaatggtct ggccaaaatg ctacatggaa ctaaatgctg 89580

gggatggtca tacaatgagt tttaagtggc tagaccctaa atcagaagca ctttcttcta 89640

attagcacca tggttcttaa tcctttctgt acattacaat cgctcagcag cttaatacaa 89700

atgttgcttc ccggggccac actccacatc tttctgactc tctgatttaa ttggtccgaa 89760

tggggcctat acatcaggtg ttttttaaaa ggtctccaag tgattctaat gtgtacctgc 89820

attgaggacc agggaaggtg taggaagcct gataaccttt actctccagc ctcatcctcc 89880

aatcccatga ttgtttatgg gattgttgct acacacccag cttagtcata gcattcttac 89940

tctagctttt ttttagatgc aatttttatt tattcttaaa gaaaaagatt tctttagcac 90000

ctttattcta aagagctctt aattgctgtg cttagaactt ctaaacagtg agcatttgtc 90060

aaacatagaa tagcagaatg aaggggttgg acctcgggtg aggagggctg tcgcatggtc 90120

tctttcgagt gccggcgggt gggggctgca catctcctcg cttctgggcc cattgataag 90180

tgacctaaaa gtgcctttcg ttttttttgg tggggggtga aaaagcaatc tgttttgtac 90240

ccacagcggt gcactttaaa caggaagccc tactggggcc agccttctat gtgtcattaa 90300

gtttttcacg ccacatccta cctatcatca tgcacccatg tcatcgttct tttaaagggt 90360

gccagttttt tgcttaagca caaggagctg tgacctgtgt tgtcatccct gatgcatgtc 90420

atgcatgtga cttcatgaca tgtgggtgac ttttgatctc tgaaggacca gggacccagt 90480

ctgtggatca ccactctctc cgtgggtggt ttgggtcttg ttctctagcc cacccagcca 90540

ggtgcaatta ggaataaagg aaatagcaaa ggaattttgc tcaaggccat gccaagcatt 90600

tcatctcata tgaaaaggaa aagagagaga gtgtgtgtgt gttggctaga tttaggtaga 90660

aaacaggctg gtgagaagcg tagaacttgg ttaaaatttc tagccaaaag taagattttt 90720

aaaaagattt atttctggat ccaatccctg ttgcccattt ctatgaataa tcaccatttg 90780

ttttaatgtg aataatagca cacagcaaat tcagccccct gagttttacc attttaagca 90840

attgctttag gcccgtgagg catgtactat ttatgaagtt gcatgggtag taatggaaaa 90900

cacaacaatg acagtagtaa caggtgacat ttgtcgaaca cttgcagtgt gccaggcact 90960

gtgctgagag cattacatgc attatttcat ttaatccttc caagaactct ttgaagtagg 91020

ttggtaatta tggccatttt acaattgagg aaactgaggt tcggagatgt caaataacta 91080

gtcagtggtg ggggtcagat ttttcttttt tttttaaatt tatttgcttt tttttttttt 91140

ttttttgaga cggagtctca ctctgttgcc caggctgagt gctgtggtgc catcttggct 91200

cactgcaagt tccgcctccc gggttcacgc cattctcctg cctcagcctc cggagtagct 91260

gggactacag gcgcccacca ccaggcctgg ctaatttttt gtatttttag tagagacgag 91320

gtttcaccgt gttagccagg atggtctgga tctcctgacc tcgtgatccg cttgcctcgg 91380

ccccccaaag tgctgagatt acaggcatca gccaccgcgc ccggcctatt tgtttttttt 91440

tttaagagac aaggtcttgc tgtgttaccc agactggagt gcagtggtac aatcgtagct 91500

cactgtagcc ttgaactcct gggctcgagc gatcctccca ccccagcctc ccacgtagct 91560

gggactagag gcatgagcca ctatgcccga ctcattttta aacatttttt atagagacgg 91620

ctgggtgtgg tacctgtaat cccagcactt tgggagactg aggcgggcgg attgcttgag 91680

cccaggaatt tgagaccagc ctgggcaaca tggagaaacc ccgtgtctac aaaaaataca 91740

aaaatcagct gggtgtggtg gtgcgtgcct gtagttccag ttactgggga ggctgaggta 91800

agagaatcac ttgagtctgg gaagtcgagg ctgcagtgac ctgggaccac cgcactccag 91860

cctgggcatc ggagtgagac tgtctttcaa aaaataattt atttatttat tttaaaaata 91920

gagacagggt attgctgtgt tgcccaggcc cgtcttgaac ttctggcctc aagtgatcct 91980

tctgcctcgg cctcccaaag tgttgagatt ataggcatgt gccactgtgc ccagcctgag 92040

attttgaaca gaggagcatg atgctgggcg ttgactcatt tggctgtgag tgtggaaagc 92100

tgtcactgga gtacagcaag tcagcactat caagccagcc cttgtcattg ccaggagctg 92160

cggggagaga ggtgttttgc attgctgcag ggaactgacc tcttttagtc agggaagtag 92220

tttgggcagt agaaagcaga acttgcacct gctggtaaga tctgagtggt cactgacaac 92280

cagctctgca accctgttac cagggcaaca aagatgggcc caggggtagt ggtgggctct 92340

gccacatctc tctgtgcata agaacctttg gccacttgct ctggccttgt ctttcaccaa 92400

tcccagtgtt catatccagt gtaccaacca ctgagggcag ctgtcctgga atctgtctct 92460

catctctgcc cataattaac tgcttctggg cacagtgcat gagttacata gatgagtgtg 92520

ggtaagtttg ccctttctgt ggggggagca tccttttggt ccactctcag gagggcatcc 92580

tatgttattt ttgtgatatt ttcctaagag ttgtataagc aagtgcatca agccaacttg 92640

tctaccccag ctccctcttg agaccagcag aaactattta tcaactggca gtttacgtaa 92700

cctctctggg cctcaatttc ctcatataaa atgaggataa taaatcgtat ctgctcatag 92760

agttgctgtg gggagtaaag agttcaaatg tatctgtcag tgaaggaaaa aagaaaaaaa 92820

aacaaaaaca aagagttcaa atatatctag cgttcaaaca gaaccaggta tgcagccagt 92880

gcccaatagg tgtatgagtt tcctatggcc aatgtaacaa atgaccacaa acttagtggc 92940

ttaaaacaac acacatttat tattttacag ttctggaggt cagaagtcta agatgatgcc 93000

aggcttggtg gctcaagcct gtaatcccag cactttggga ggctgaggtg gcaggatcac 93060

ttgaggtcag gagttccaga ctagcctagc caacatggtg aaaccccatc tctactaaaa 93120

atacaaaaat tagtcaggca cggtcacgag cacctgtaat cccaactact caggaggctg 93180

aggcaggaga attgcttgaa cccaggaggt ggaggttgca gtgagccgag gttgcagtga 93240

gccgaggttg caccactgca ctccagcctg ggcaacagaa cgcgaccctg tttccaagaa 93300

aaaaaaaaag tccgggatga gttttactgg gctgagatca gtgtagacaa ggctgccctc 93360

tctctggagg ctctagggca gaatctgttt ccttgtcttt tccagcttct agaggttgcc 93420

tgcattcctt ggcttgtggc cccttcctcc gtgttcaaag ccattggtgt aacatcttca 93480

ggtctctgtg actccgatcc ttgcttccat cttataagga tccttgtgat ttcattgtac 93540

ccatccagat atcccaggag aatctttcca tcccaagatc cataacttaa atcccatctg 93600

caaagtccct tttgccatgt gtggtaatat attcacagct tgcagagatc aggacatggg 93660

catctttggg aaacgggaag ggggcattat ttgacctaac atcaagagca tgagatgttt 93720

ttgtaaaatg aaacaaatgt tgcagcttcc taatgcagct tcttaggccc acctgcaggc 93780

ccccttgacg ttggtttttc tctacctagg tctgttgtgt cgggtctgga ctcccctgcc 93840

aagactagct ccatggaaaa gaaacttctc atcaaaagca aagagctaca agactctcag 93900

gacaagtgtc acaaggtatt tatttccgca gccggcctcc ttccttgctc caggatcctc 93960

ccgtccgtat atgccaaggg atccgcccgg ggccgctgct ggctctgagc cgcctgatcc 94020

gtagagagtg aggcgctcct gccttcgctg aagtcgcgcc tccagcagct cagagggaga 94080

tgaattcggg ccttgctgtt gctgtaaatc ctttaaatct aaaccagagg aggccctgga 94140

tttaaacagt ccgtttctca gcatgaccca gccagatgtc tgcttcttcc ggcaggtggc 94200

ctgggtcctc acctgtggct gagatacatc ccatctgctt tgagtgatgc gaagtctctc 94260

ttcctagtct tttaaaactc ctgcttatgt cactgcggcc actgtgttga ttacgctcaa 94320

cgtctcttaa cattcactgt tcctgcccag aggcaacgct ctggaaacta ataagtcact 94380

gcttgcctgg gactcctaag agtgcagacg aataaatatc tccttgccct gtcctggatt 94440

tgtcctctag atctttgcaa ggagatgggg ggggatcaag atggatttgg gataaaatta 94500

aagtgacgtc tgcaaaaaca aaacaaaaac aaaagcaaac aggtgaaaaa tgatgattgt 94560

ggcttccttg ctaactgggt tagagaagtg atcaagtgtg aaccgggact tgaatgagag 94620

gagtgactta gcatttggtg actgtcctta acgaagaact gtgcgctcct gggcgaagaa 94680

acaatggtat ttccatccca acttaacttt tggcgaatta gccttagccc agaccaccag 94740

gtggtttcgg aggctacttg agatgtgatt gctcctaatg aacctccacg ggccttttta 94800

acctgtcgat gtgtttattt cagatggagc aggaaatgac ccggttacat cggagagtgt 94860

cagaggtgga ggctgtgctt agtcagaagg aggtggagct gaaggcctct gagactcaga 94920

gatccctcct ggagcaggac cttgctacct acatcacaga atgcagtgtg agccttccct 94980

gaagccccct tcccttggag gtggcacttc ctgttgtgtg tgtctcatcc tgtttcatga 95040

tgactccatg aggcacatca cagccaatgg cagagagtag agagagggag agcacaaaag 95100

caagatctgt gttttgcaga gtagtgagag ccaggcgtaa ggtccccaag aaatgagatt 95160

ggactcattt ccagcagaaa gtgcaggtag acggctggta ccatggagtc tggagatggg 95220

agtaattcat ctttgccgca agttgcaaaa gatcttaaca tctcccatcc cagcctctgt 95280

ggtctgcgtt gtgtctgaca tgagcagcct tgagaaccag actcccaact atgtacaaga 95340

aaacttactt tcaatcttcc tgacatcaaa ttttccattg gccagaacca gtgtagtgac 95400

aagaaaatag ccttgaaaac ccagaccctc tgtcattatt taccatgtga ctttcatttt 95460

ttctttcctt cacaagagta gactgtcttc ttctccattg tcttgttaaa tttttcattc 95520

aggtgttttt taatgtgccc aattaaacag tctcaagaag ttgaatcaca catttctaaa 95580

gtttttttca caagggagag gaaatctata gaacgtggct gattaagaat aactgctatg 95640

tttccattcc agacttggct gcctttcagt ggtgggtgaa gttattcagc tatgtatttc 95700

agatatagat ttcagtgcca ttgaagcatt aagggattct tatggatgaa aggtgtccag 95760

gaaaaataag ccaggaggta gaaatagacc acttggagtc ttaaatgaca actgggcaga 95820

ggatatgaag tcattgctac tttgaaagag gcatatgtac tttagggccc acaaataact 95880

gtagaaaaca ctttgtagct atccacatgg tggctgtaat agctactggg tcttaatagg 95940

ttttagtcct gaacatgcaa gtaagtatct cctaggacag gtagatggtg gcaggagaca 96000

ggctgatgca gtttccggct ggactaattt ttgtattgtt agtagagatg gggtttcatc 96060

atgttggtca ggcttgtctt gaactcctga cctcaggtga tccacccgcc tcgccctccc 96120

aaaatgctgg gattacaggc gtgagctact gcgcccagcc atttgtgtct cttaaaaaaa 96180

aaactaagaa aatgaaaaaa atgacattgg ccaattcatt aaaatgccac tcactgactg 96240

tggtatgaaa tggctttccc tttgatggac cgaagtctgt ctcattgtgt gagccacttg 96300

cagggctgag tatgactnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 96960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 97020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 97080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnntcggcc 97140

tcccaagtgc tgggattaca ggcgtgagcc actgctcctg gcccccacgc cttttttttt 97200

ttttggagac agagtttcac tctgtcaccc agattggagt gctgtggcac aatctcagct 97260

cattgtgtcc tctgcctccc aggttcaagt gattcttgtg cctcagcctc ctgagtaggt 97320

ggaattacag gcgtgcacca caacacctgg ctaatttttg tatttttagt agagatgggg 97380

tttcaccatg ttggccaggc tggtctcgat ctcctgacct ccagtgatcc acttgcctag 97440

gcctcccaaa gtgttgggat tacaggcgtc agccaccatg cctggacccc tctgcccctt 97500

taagcactgc cacatattag atctacgaag gctttatgga tacaatccaa ggaagatgaa 97560

ccttgggcta gtgggataaa actaagcgca tgtagttaga atggaatgat ctggaaacca 97620

ggtcccaagt tggtctaaat tagactcatg ttgactatgt cacactgtaa accagtctaa 97680

atgctaataa gcatgcttga ccaaacactg ccctgcagcc ttcagagagg aagaaggaaa 97740

acataatttg tatcctctct ccctattttc tgagtctatg ggattcaaat tgtagctgcc 97800

atggaaactg tactttggaa tttctagagc ccttaatttt aacttaacat ataaaaacac 97860

ttttgtactg attttataat tattcatgat ggatgagaaa gtgaatgtct ttgacagtga 97920

gggaagctat ccgaatgcta ttttcttttt tttttttctt tcataaagat gcatatattt 97980

gcatgcttta tttacctggg gctaactctt gcatcttttg cagattccga caccatagct 98040

gagttacagg agctccagcc ttcggcaaag gacttcgaag tcagaagtct tgtaggttgt 98100

ggtcactttg ctgaagtgca ggtggtaaga gagaaagcaa ccggggacat ctatgctatg 98160

aaagtgatga agaagaaggc tttattggcc caggagcagg taggaggatt ttaacatcat 98220

gcttttccac tttctgtacc ggagtgttca ttgcaaagac gataatctgc tgcactggcg 98280

tctaggatca agcacgtttt cctctgtgac tctatattta attatagttg gggcaaaaag 98340

gtctctcatg ttcttagctc atcttcttga actgatgttg gctaattttg aaggctcaca 98400

aattcctctt gatgtatcat gtttctatcg ttgtaattta tttcagaacc aaggtggcct 98460

tttagctaat gaatttaaga tgatctttta tgaccattag ctgaggactc aggatataca 98520

tatggtgggg tgaatcagat tgcttttgta cacgctttag gtatttgtgt tgtgggcata 98580

tggatttggt tttaaaacag gcctttgaag aaatcaaata acattctttg ttatgtggct 98640

agggagttgc ttgtttgaga gcaggtagaa cgttatcttt tttgttgtgg tatttttctt 98700

tcttttaaac aaggctactg tctctagaca tattgattca tttgctgtgt tttagagaga 98760

tggccgtcag ccttggaatt cagagagtaa tttattactt acagacattt tagtgcacat 98820

gatatgtctg ataatgtacc cagctctgca ggaagcttgc aaaaggaata gaagtcccat 98880

ggttgctatt ttcagtgttt aaaaacaacc ttggaaagtg gaggaaaaat gcaaatgtat 98940

aaagcaggtg cttaccagct aaagtatcac agaagtggga gagcaattag caaattaatt 99000

aacgatgatg tgaggggaga tgttgtgggt gagcaaggga cagttaggga cagttctcac 99060

cgatgggggg aaatgtaggt tctcggcaga gagaagtgat gagaacatgt tgggtagaag 99120

tgtgacattc tggagtacta gaatgctatg caagtgtgtg tgtgtgggtg tgtgtgtgtg 99180

ttcagtggtt cagaacagac tgggaaatgg cgaaatgagg acatttgggt ggggaggggg 99240

aaatgggtgg gaaactcaag aacctttttt taaaaaattg tggtaaaata tatataacat 99300

aaagtgtacc attttaacca tttttaaatg tgcaactgag tggtattcag tgcattcatg 99360

atgttgtaca accatgaccg ctctccattt ctagaatttt tctatcatcc caaacagaaa 99420

ctctctatcc attatacaat acctccccat tcccccaaga accagttttt gaattgcagt 99480

ttactttgtg aggctgttgg ggattattta ggcctctgga aggaggaggt tgggatcaga 99540

gtctggccct gtggacttca atgactttgt gtggcctcca atcagagaag cagcggaggg 99600

caggaagctg cttgtcagaa tctgagagtg atgtggcttc tttgtttagc aataaaatgt 99660

gagcacataa tagaaaggaa aagtgacagg acatggcaga taatttggaa gagaggagtg 99720

gaagatgctc actcagcctc ccagctcctg agaaagaact gtgtctcatc agttcatact 99780

acctgagcat ctgttgtatc tggtgtgttt ctaggtacct ggagaagagg cattacgtgt 99840

agccctgacc ttgtgatgct tatgtttttg atgggaaata gtgcgtgtaa aaagaaaata 99900

atccaacagg ccacacggca ggcaaacaat agagatattc aaataggtat accttcctcc 99960

aggtgaatgg cctgaaatga ccgtgtggaa gtgtgggctg ggggcttata aaattataca 100020

catacaggcg ctaactaaag ccgcctattc attccttaag aggatgcata gaaaagaaaa 100080

gtagggtcct ttaactgagc ccatttgaat ttagggcctg agagaagcag cacaagcagt 100140

gaagggaaga aaaagaagtg cccgagagga gggagggatt ctgttctgca gacaaggcct 100200

gccgcctggg agaggcccgc acgcccaccc agggttctct gacagctgga aggggtcttc 100260

agagactgtt tatattttat ttatttattt atttatttat tntgagacag agtctctgtc 100320

acccaggctg gagtgcagtg gtgcgatctc agctcactgc aagctccgcc tcccaggttc 100380

acaccattct cctatctcag cctcccgagt agctgggact acaggcgcct gccacaatgc 100440

ccggctaatt tttttgtaat tttagtagag acggggtttt acctgcgtta gccaggtatg 100500

gtcttgatct cctgacctca tgattcgccc acctcggcct cccaaagtgc tgggattaca 100560

ggtgtgagcc actgtgcctg gccgactgtt tctactattt tagagagagg gtctcactgt 100620

catctgtgct ggaatgcagt gatgcagtca tagctcactg caccctcaaa ctcctgggct 100680

taagcgaccc tcccgcctca gcctcttaag tagctgggac cataggcatg tgctgccaca 100740

cccagttaac tttattattt atttatttat ttagagaatg agtctcattc tgttgcccag 100800

gctagaggtg cagtggcacg atctcggctc actgcaaccc cgcctcccag gttcaagcga 100860

ttcttcttgc tcagcctcct gaatagctgg gattacaggc acctgccacc acacctggct 100920

aatttttgta tttttagtgc agaggggggn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 100980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 101940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 102780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnntata tgtgcataca gaatatatac 102840

acagaaatat atatgtacac atgcatagaa tatatttaca tatatatgca tatatataat 102900

ttatttattt taagcagttg atttatacag tttttgtttt tgtttttttt ttgagacaga 102960

gtctcactct gtcacccagg ctagagtgca gtggcgagat ctcagctcac tgcaacctct 103020

gcccccgggt tccagtgatt ctcctgcctc agctccacaa gtagcacacc accatgccca 103080

gctaattttt gtattttttt tagtagagac gaggtttcat catgttggcc aggctggtct 103140

cgaactcctg acctcaagtg atccgcccgc cttggcctcc caaagtgctg ggatttcagg 103200

cgtgagccac cacacctggc tcccataatg tcttttagaa taaaacgatc gagttgagga 103260

tcacacgtga cacttaattg tcctgtctct ttagtctcct tcaatctgga gcagttcttt 103320

gatttttcct ggactctcat gaccttgaca attctgatga ttataggcca gttattttgt 103380

aaaatttgaa tttgtctgat gttgcttatg tttagattta gggtcttggt ctttggccgg 103440

aatatctcag acaagatgct ctgttcttat tgcatcagag cagaagactc tctgtttcag 103500

ttgatcacat ttatgttgat gctcactttg atcacttgat taaggtggtg tcagttatgc 103560

ctttctactt gtagggttac tccttcctcc ttcgtgattt tatttatttt atttttctta 103620

gagacagggt cttgcttggt tgcccaagct ggagtgcagt ggtgggatct tggctcactg 103680

cagccttgaa ctcctgggct caagtaatcc acctgccaca gcctcctgag taactgggac 103740

tgtaagcgaa caccaccaca cccagctact ttttgtattg tagagatggg gtctcactgt 103800

gttgtccagg ctggtctgta actcctggcc tcaagcagtc ttccggcctt ggcctcccga 103860

agtgctggga ttacaggcat gagccactgc acccagcctc ctttgtaatt aaaaaagtat 103920

tttatgggga gttactttca agtgatggaa atattttata tctatgtgga cttggatttt 103980

cctatttcag tcagtgagtt ataatccatt tctgtcacta gttttatact taaattgttc 104040

ccaacttggc cactgagaac ctttttaggt tagcttttgt gtccttttca catgtctcca 104100

agattcattg aatactttcc tgctttctgg tatagcaaga tgttcaggtt cttttggtac 104160

ttttactttc tctgccctgg ctctggcatc agtcatttct cagaggagcc ctgtgccttt 104220

cagtggacaa tggtgtttag aggccaagat ctggacattg ggtgttttca ttgctaccgg 104280

tgtgtcacta ctcccagacc cctttcagtg gacagcacta aggaatacac atacgtatat 104340

acaatatatc cacctacaca tgtgcgtgca ctcacacaca cacatataca ttacatctat 104400

atttgtgtat ccatgtctat atattgaaaa ttgtggctgg gcacagtggc ttatgccttt 104460

aatctcagca ttttgggagg ctgaggcaag aggatcacct gaagccagga gttcaacacc 104520

agcttgggaa acagagagag actctgtctc tacaaaaata aaaagggaaa accatgagtt 104580

cacacccgtg cccccagttc caatccaact tcacagggtt cattttagtt ttcacccttt 104640

ccatgtttgt aattctcttc tctgacatta tacccttaat atgtttactt attttatgca 104700

tctgtatgca tccaatctac tgtctttgtt ggtatcccac ctccccttgg tgggtccaga 104760

taatctgctc tgggttgccc tttcacgtgg atgtcttcct taccctgtgt gggcctgtga 104820

tactgggctg cccccacaca tgagtgctgc cctcctcacg ttgcttggga cggcactgtg 104880

tcctgggcca ccatgacttt tctcataact agcgtggatg cttaccttgt tccacaccag 104940

tgaatggctt caggaagaga agaggaagag aaaaatattt acatttaaag aaaggtagtt 105000

taaagaaata tgttaggtaa agaattgagc aggtaatata cggagctggc aaaaattgtg 105060

accaaagtag gtgaatgatt gagatttatg caattctggg ctaagtgaca gccccttccc 105120

tttcccttcc cttccccttc ccttcccttt tcttcccttt cccttccctt tccttccctt 105180

tcccttcccc ttcccttccc tttccttccc tttccctctt cttccttcct tccttctgtt 105240

ttcttttccc ttctttcctt tgcctttttt ttttttttaa agctagaaac atcagtttag 105300

gcataaagac agaggaaaag gcttcttttt cctctcacag ttctttataa ttgtctaagc 105360

agtttctttt ttccctaggt ttcatttttt gaggaagagc ggaacatatt atctcgaagc 105420

acaagcccgg gatcccccaa ttannnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 105960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 106440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnatggagt 106500

cttgctctgt tgtccaggct ggagtgcagt ggtgtgatct tggctcactg caacctccgc 106560

ctcctgggtt gaagcgattc tcctgcctca gccccctgaa tagctgggat tacaggcatg 106620

tgccaccacg cctggctaat ttttgtattt ttaatagaca cggggtttca ccatgttggt 106680

caggctggtc tcgaactcct gacctcaggt gatctgcatg cctaggcctc ccaaagtgct 106740

gggattacag gcatgagcca ctgcgcctgg ccaacttatt taactttttt gagacagggt 106800

ctcactctgt cacccaggct ggagtgcagt ggcatgatca tggctcactg cagcctcaaa 106860

ttgcagggct caagtgattc tcctgcttca ccttcctgat tagctgggac aacaggtaca 106920

aaccaccatg cctagctaat ttttaaattt tctgtagaga ctagggtctc actatgttgc 106980

ccaggctggt ttcgaactcc tgagctcaag agatcttcct gccttggcct tccaaagtgc 107040

tgggattaca ggtgtgagcc ccatgcccag ctccggtggg ggatatttct atatccacat 107100

gtgtatagtt tactttataa aaatggtatg ttactctgtg cttggctctc cagcttgctg 107160

ttgcctttca ccagtgtatc ccagacatcc tttcttcctt gtcagtaacg caggtctact 107220

ttattctttg agcagtggca taattttccc tgatgtgtat atatcataag ttagagaatg 107280

ctaaaattca ttttggggcc ttgtttaggt tcttgaggga ttaaattcct aaatttaaca 107340

agtgtatcct ggaaacaatt tttgttcctg attcagccct taaaagagga ctatcatgtt 107400

accttgaatg gagataaaca ggctcacgta agagaaaagg gtaagaggga tgaactccca 107460

cttatcttaa acttctactg gcccgttttt ggggaatttg ctgcttttat tcctgaccta 107520

aaataaataa gtttatgtgt cttggtttca tattagttga gaacccagtg cctggagaga 107580

agttttcctt gtcctctgag tgaggacatt cacatatgaa tctattggca gactggcttt 107640

gactgaccac acgtgccttc agaaccaatg ccacagctct taggtttatg gcctgaaaca 107700

ccctttcctt acatattgcc ttagaaactt tccttccttg agacatgggg catggaaccc 107760

tcaccttcac agatgacctt ggtgtgtttc tagggttgct ggtgttccag gacatctgtt 107820

gcagatgcag tatttacctt gtgctctctg catcataagc agcttctcat gtttgaatgt 107880

attaacagac ttttaatttt ttttattttt gagacaaagt ctcactctgt cacccaggct 107940

agtgttaccc aggctggagt gcaatgnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 108960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 109980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 110940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 111420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn atattgaatc tgtgcaaagt 111480

cagctatcag tctgattgcc ctatcccaca aattgcatcc caggagatga ttagatgcaa 111540

taggtgaaag ttttcatgtt cctcagtggc attcagtgca tgaacaacca ttgtccacct 111600

aattcctctg catctacagc aagaaataga atttttgtgg agacttaaca tgctgtgtct 111660

tacttacata tgtatgcaaa aaaaaaaaaa aaagtcactt tttttctttt ttgagaccga 111720

gtcttgctct gtggcccagg ctggagcaca atcacggctc actgtaacct ccgctaccca 111780

ggttcaagtg attctcctgc ctcagcctcc ttgagtagct gggactacag gcacgtgcca 111840

ccatgcccag ctaatttttg tacttttagt agaaatgggg ttttgccatg ttggccaggc 111900

tggtctcgaa ctcctgacct caggtgatcc acctgtcttg gcctcccaaa gtgtgggatt 111960

acaggcgtga accaccaacg cctggccctg aagatacatt ttaaatcaat gaaaaaaaac 112020

aacaggattc tacctcctat ggtatatccc tcctggctgt ctcttctctc cagtcttgcc 112080

tctgctgtgt gggtttcagg catccatctt ctctactctg aattactgtg ataacctctg 112140

aagtattttc cctgccatct gtctggccct tctcccaggt cttccacata ctgcagccaa 112200

gtcagcccgc tgttgaaacc cttcaagact ccctgctgtc ctctggatga agtccagact 112260

cttccacgtg acttaccagg cctttcttgc acttgtcccc agccacttac tgtttctctc 112320

tttctacctt aacatcctga acttcctttg gttctttgac cttgcctctg acctttttcc 112380

atgctgttca ctctttccct gttcaccttg ctaactcctc tttctctttc tgggttggat 112440

cagatttcac ttcttccaga agcccttcct agaccctata cttctggaat ggcgcctttt 112500

gactgtacgc tcattgcacc ctgtacttct cctttatgag tgggtgctgg tctgtcccac 112560

taggctactt catccataaa gggagagtag agctttacca agtcaatgct taagcaatat 112620

ttattggatg aatgtgtgat taatttcata gaaatttgat gtgcattcaa atttacttat 112680

tgtattacgg aacttgcatt atattctcag tggagttatt ttctttcacg tgtgtaattc 112740

aagatagact cagtgagatt ttcaaaattt ggaatgcagt gcaaggaaat tgaacttgag 112800

ttcttttgca ttttgatggt taaaaatttc ccatttgtgg tgacatacca caataagcca 112860

gtgaatgtgg cttattgttt tctggtctat agaaaattgt cgcaaactct gtcataatgt 112920

ctggttctat ataacaaagc tagtcctgta ttctgcatgt ggctgatgga aacagtgctc 112980

tgttgatctg gttcatgaag aaatctgttc aattctgcat aacagatgcc ttcatcagtg 113040

tccttccatg aaggagctga tcttcacaaa gaacacatag ttttgcatcc caccacttgc 113100

agtnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113400

nnnnnnncct actgtggttt tcttcagaat tacccttgct ctgagcctgc aattgactca 113460

tgaacttctt ttccatgttc taaccttaca atgacttcct tgtgttcact ccaaatgttt 113520

ttccctggtt gcatgtagag atgtattagc taaggtacat gcttagctgc tgtatcaaag 113580

agaccctaat gtacaaccca ggctggtaga gcagctctgc tgtatgtgtt aattcaggga 113640

cccaggttcc ttccatgttg tgactccccc cttccttagg atgttgtctt cttttacatg 113700

gctgaagttg ggccatttca tgtctctgtt ccagctgcct ggtaggaaaa aagaacagaa 113760

attcagagta agcaaattct ttttctatag atggatgcgg aagttggaca catcatttcc 113820

tctcacattt tctcggccag aacgtagtca tgtgactgca cgtctagctg ctaaggagac 113880

tgggaattta ctgtcggctg tgtggcctct gtcaagctaa aattcttatt actgtggaat 113940

aagggaagga tggatttggg ggcacaatta atagtctgtc acagaggcta aaacagctgc 114000

ttttggctgg gcacggtggc tcacacatgt aatttcagca ctttgggagg ccgaggcaag 114060

tggatcactt gagatcagga atttgagacc agcctggcca acatggtgaa accctgtctc 114120

tcctaaaaat atagaaatta gccgggcatg gtggcgggta cctgtaatcc gagctactcc 114180

agaggttgag gcaggagaat tgcttgaacc tggaaggcag aggttgcagt gagccaagat 114240

ggtgccactg cactccagcc tgggcgacag agcaagactc catctcaaaa aaaaaaaaaa 114300

aggttaaata aacagctgct tttgtaggtg atacaaggta cagctaagct ttgaagccag 114360

gcctgtagtt tcaccttcca tattcttact caaggcatta tacttctgga tctgaaacca 114420

ctggatctga tgccctgctt gggatgagtt ctttatatta tcttgctttc aacccacacc 114480

tgtgtaattt tatgggcagc gtttgtttcc tatataggaa caatttgaaa gtgggctgtt 114540

tctaggcttt catgaatagc aggctatgct gtcattggga atctggaggg agttaatgaa 114600

cacaacttca ttgtttactt tagtgaaatg tggcagctta tgatagtttt gacagtgaga 114660

catgtgctgt tttgatctct cagctaagat tatctgattt ttcaggcatg tctcaaaact 114720

caccaggcct gctcacatgc tgctgcttct gaagccaggg tttggaaacc agctgcccat 114780

cagaatgagg ctgtgactta gaatattggt tcttgtttta ttaccattcc ttgtttggtc 114840

tctccagagt cactggcctt ttccgcttca attttcttat cggtgaaatg agatattaat 114900

tcctcttatt gacttcaatt caattgctga gtgtattgtt gcctttggga agttctttga 114960

gttttctgtg cctttgaaat agttgttttt ttttattctg gtgttttgag gcatgtttca 115020

agtgagtgca tttacacttc taccatttta ggagccacaa ttcagttatg ttgtcccagc 115080

ttgcttggcc ccatccccag agtttctgat tcagtaggtc tggggtgggg cccaataatt 115140

tgcatttctt cttctttttt cgagacagag tctgactgtg tcatccaagc tggagtgcag 115200

tggcacgatc gtagctcatt gtagcctcaa actcctgggc tcaagccgtc ctcccacctc 115260

accctcctga gtagctggga ctataggcat atactaccat gccctgccac ctttttaatt 115320

ttttgtaagg atgggggtct cactgtgttg ctcaggctgg tcttgaattc ctgggctgaa 115380

gtgatcctcc tgcttcagcc tccccaaatg ccggcattcc tggcatgagc cactgcactt 115440

ggccaagact ttgcatttct aactagtttc caggtaatgc tgctgctggt gtagggacct 115500

cattttgaga accattgttc tatagctgta gctatagtta gtttctggtt atagcttctt 115560

ccttttgtcc cttcagtaat agtgtacaca tccgaaatcc ctgtccttgc tctttcaggc 115620

ccaggcatgg tatctggtcc tcttctgttg ctagccctgg ggtgcttcat catcccaagt 115680

ttatttttct tctcctaacc tgaacctttg taaatagccc cttccctaat gaacgtcctc 115740

aattccctgt tttgcgtgtc ctgtctgttt cttggcaaga ctctggatga ttcagtactc 115800

aatgaggatt tttcgcatag atggatgaaa caggctgggt ttcatgtttt ctaagataaa 115860

ggtgcttctc tctttttctc ttggtcactt tgaccaagaa gaaaataaca gagtttttat 115920

tctcaagaag aataatatcg gggccactct gctcagaggc cactctgctt tgaggacccc 115980

ttctctcctc cctcatgcca aagatcagga acattgggca gagcggataa cgatgccgcc 116040

agcgtcatta cattttcacg gcactttcag ttgtgctgag cgtgcaaaca tttcaaggag 116100

acatttctaa gaggtggcta gcacagcatg cctctaatgc cctatgtgaa ttggaataga 116160

gtactaaaga actgttcaat attcacccca tccccgcata tgcaagcatg cacgtgggtt 116220

cattgtatat gtgtgtgtgc acgtgtgcac agacacattt gtccttcgtt tcaaatgcaa 116280

cacaatggat ggaaattgcc ttcctggtac tggggtatgg atgcaaacac caacagagaa 116340

gcagccgcta cttccaaact gaacacatgt gagatttgcc ctttaattag catctgcagc 116400

tgctgccatc agaagggtct gtctctgttg gcctgaaagt ctttgcttta aaagagcaag 116460

tccattatag ctccaagcca ggctcgtctg tcagctgctg tgctttctct gccatcagcg 116520

gggttgccac attgttttgg gctgtttcac tctaggactc tttcctcctc ctgtgccccc 116580

agcctttgat taccatgcct tggtgatcct catttgggtg acctgcagct gctcattgtg 116640

tgtgcaggag acatctccag tccttgtaag gagggaagat cactggcttc agtgctgatg 116700

gactggttat tttccagccc tttgtcgtca gtgatcttgt cttgatatgc agaaaggctc 116760

caggtagtca ctgaaaaaaa tataagcagc agaggtgatg gctatatgaa agtcacgttt 116820

catcaagggc attgctgcta tggaaacttt caattcactt ggagtaggga gccatattgg 116880

ttccacagcc tcctcagcag tgggtcccaa cacagtgctg ggctagctgc ctctgaatca 116940

ccgcagtagc tccttttact atagattcct gggtcccacc catggaatgt gatccatgaa 117000

gtctggggtt attccctgga atcctttaag ctccctaagt ggttgggatg ggaaagagat 117060

atgctttatg ttactatact tcttattatt attattttaa aattcttgcc gggcgcagtg 117120

gctcacacct gtaatcccag cacattggga gaccgaggcg ggtggatcac ttgaggtcag 117180

gagttcgaga ctggcctggc caacatgatg aaatcccgtc tctactaaaa atacaaaaat 117240

tagctgggca tggtggcgca tgactgtagt cccagccact ccggaggctg aggcaggaga 117300

atcgcttgaa cccgggaggc agaggttgca gtgagccgag atcgtggcac tgcactccag 117360

cctgggtaac agagtgagac ttcatctcaa aaaaaaccca aaaaaacaaa actctttttc 117420

attataccgg aacgtcagct ttatggagtc ggggattttt tctgttttat tcactgctgt 117480

ttccctaaca tctagaatag tggctggcac gataggcact caagtattga tttagatgag 117540

tctattttat tttcttttaa atttttaatt tttattagag gtggggtctg gctttgttgc 117600

ccaagctggt ctcaaaactc ctggcctcaa gcgattgtac tgcctcagcc tcccaaaggg 117660

ctaggatagg catgagccaa catgcctggc ttgtcttatt tttaacaagc acttctggtg 117720

attctgatgg acaatcaggc ttgggaagtt ctaacctaga ggacctacag ttgtcttggg 117780

gtagaagcca aggctatcct ggtttttaga atcagtgcct tactgggcat ctctgaagag 117840

taaaagtcag ggacagagtt acatttttgg acaaaaccag atgctgtgaa tggactcttg 117900

gtcacaacct gggtggcgac ttggtcctta acttcttcat cattttctgc tgaccctgtt 117960

ctttggttca cagcaagtca cctgataaga agactcaaag actgctagtt tgttacttta 118020

gatgatgctt ttggaacctc ttggtaccat tttaacaatc caaacgtatt ttatgaaagc 118080

actcaagtcc tgggtcttta ttgtatcttt aagctctaac agcatgatga ttgaataagc 118140

tgtggttggc cacacacaag ccatcttccc catggcctcc attcatacta gaatgagcag 118200

ctatacccca gtagtatagt tttgggatat gggtaacatc ttgggatagc cacatttact 118260

tagtaaatgt ctggcttaca ttctcctaat ggtgcactgt tggaattttt ggtgtggtaa 118320

cctggaatag tgttggtggg tcaagtttga ttagcatctt tgataaggac ccggtctatt 118380

tagaggtttg tcattgagtg tgtctgtttt ggcctcatgt tgtgaagcat gctgtgtagc 118440

agctgttgta atttttgttg cttgttttct caatcaaccc tggttttgaa gaaatgggaa 118500

gttgttccac tcttagactg atctgacttg ggaggggatt ttcagttcag gaagttggat 118560

cttctgaatg gaagcaaaga atacatgtct ttttgccact ttacaagctg gctcttgttt 118620

tctgaactat tttactggtc attgcaaata gaatgtcagg agtagctgcc aaatactaag 118680

ttgtgttcag tttgtcagtt cttaagagtt gccggtggct gctctgctat gcgtatgact 118740

ttctcagcct taaacttaca agccatactg tttttttcac atctttaata cagccatagg 118800

aaatttataa ctgtggcgtg tcgtcataaa tatgcattgt tcttatttta agacatttca 118860

gtactaaaag tataagtact tctgttatta tctgtgaatt tctttccttc ttcttttttt 118920

ggatatttaa gaccttttcg atgtcaatat atatttaaaa cagacatata aattagcatt 118980

cacccacata cccagggcct atggagaacc aggttgggat gagtgggtga gctacaggca 119040

gccaggtggc tcctgtgggc tcctcgagga ctggggtgag taactaatgt ctgctaggaa 119100

cttgggggaa agaaggtgtg tatgttaggt gctgccccct tctaagtgtt cctcttgttc 119160

ataattgagt tttttttttt tttttttttt ttttagaagg agtctcgctc tgttgccagg 119220

ctggagtgca gtggtgtgat ctcagctcac tgcaacctct gcctcccggg ttcaagtgat 119280

tctcctgcct cagcctcccg agtagctggg actacaggca tgcaccacca tgcccagcta 119340

atttttgtat ttttagtaaa gacggggttt caccatgttg gccagggtgg tctcgatctc 119400

ttgaccttgt gatccgcctg cctcggcctc ccaaagtgct gggattacag gtgtgagcca 119460

ctgtgcccag cccataaatc aaaatttttt cagcaattgt tatacaagtg gaaccttact 119520

cttcaaatgc aattgtccag tgtctggctt aatgtctgct gttgtcagaa accatgtgaa 119580

tggagtagat tcccaggtta taaggagccc ccagggagga tgcgcgagtc actggcttct 119640

ccaggggtct ctggtttggg gttgccttgg tgctgggcac acttcctgga gattttactg 119700

gaccagcctg aggcctttgg ggctctgtgc agatgctcta cttctgactt gtctagagct 119760

ttcttctaat tctggactaa aagcaagcag gagtttggag gatgatggtg agaattcaca 119820

tccccgagtt ggcttttgga atgcagtagt ttgtgagatt tagtgttttt tttaagaagt 119880

atattcagat cttgcctttt tcccagaaag catatgagac aacttccaag acatttatag 119940

catggctaat aaaatgggaa atcagggcga aggacaggag aactcaataa gggttaacat 120000

ggctacagcg attgtctaaa tgggttcttt ttgctggcca gagcagaaag gatcatgcag 120060

taaagtgggg gggaagaaag ggaattgaat ggtaggtgaa gacttcatgt tggtgccagg 120120

cactgtgcca ggccctccta ggaccttgtc ttactcaatc ctcacacagt gctgcaagag 120180

gattagtctt atccctgttt tagagaggat gaaactgaaa ggcagcgagg tgaagtcacc 120240

agcaggaggc tgaagccgcc caggctaact ggccttatag ctacctaggg actcaggaat 120300

atcacacctg tttatcatca aaaggagaaa ggatttcagt tccttggggt agaagagttt 120360

ctttttgcta atcaaacatt ttacttgagg cttcatattc ttcttcaaga tttttttcct 120420

gtgtatgtac caacacatgt aataattcct tgtttatttc aaaaaagggg ttgtacttta 120480

ttctttacaa gatttcactt tatattgtca tggacaattt tccatggcag tatgaataaa 120540

tggaatctgt ttgtttttaa tatctttgtc ttatcccatt gtttacatat gtcatatttt 120600

agccagtctc taactgatgg atagctgaat gatttccatg tttttttccc ctgttacaaa 120660

caatactgca aggaatctat ttatctttct atttatctgc aaactattgt aagtacctgt 120720

aaattgttag aagtggaatt actaggtcaa aggggatatt ttcacattta aattttgaat 120780

agaggctgtc agttgccttc cacactgact ataaaaggaa aagattgtat cacatttatt 120840

gcaagccttc tgtattctgc tgggtgctga ggggaataca gaaaggatat aagagtggtt 120900

gccctctagg aatatccgtc tacactgtac ctaatcctag ggaatgtctg gggtgtcaac 120960

ttgtgggtgg gaaagtgggt ggatttaatt caactgttca agcttgcctt gcaaacactg 121020

tgcatggtgt ctgggactag tctttcatta tattgattcc cctgggtaac agatgtaatt 121080

tccttagggc agggacttca tcctacatga cttacagcgt gccttacaca tcttctttgc 121140

tttgtggaga ccttgttatt ataacacgtc aggtgatatt cgaggatcta attgaggcat 121200

tccctatttt tgggtgtgtg aagaattaat aactttggca ttctatacag gtcatggaat 121260

atcagcctgg aggggacttg ctgtcacttt tgaatagata tgaggaccag ttagatgaaa 121320

acctgataca gttttaccta gctgagctga ttttggctgt tcacagcgtt catctgatgg 121380

gatacgtgca tcggtaagtg agactctggt agcattttta tgctgaggat tttcctgtgt 121440

cgcataagag ttcctgcatg gaaatgagtg gatgagtgat ttcaagatca agataacgcc 121500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 121980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 122940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 123720

nnnnnnnnnn nnnnaaaaaa ctgatgctag tgaaaatgca taatttaaga ggttagagaa 123780

gctgctcttc aaaatgcccc ccaagtctga gagttaaatc ctttacataa aggacaatat 123840

gtaaaatttt ctttttcttt tttctttttt tttgagacgg agtctcgctc tgtcccccag 123900

gctggagtgc agtggcgcga tctcggctca ctgcaagctc cgcccccctg ggttcacgcc 123960

attctcctgc ctcagcctcc cgagtagctg ggactgcaag cgcccgccac catgcccagc 124020

taattttttg tatttttagt agagacgggg tttcaccgtg ttagccagga tggtctcgat 124080

ctcctgacct cgtgatccac tcgcttcggc ctcccaaagt gctgggatta caggcataag 124140

ccactgcgcc cggctctttt ttttcttaaa ctgcttccag aaaagtggat attattaggt 124200

tgatgttaag aaaaggcttg gagttgcatt aactttttgc tttctagcat ctggcctgtc 124260

tgttctgcag acctgagacc tacttgagat aattttcttg gtgttcaggc ccttggaaaa 124320

ataagttccc tatgttgtcc agtgtcaaag tttctcaacc tcagcactat tctttttttc 124380

aggttatttt cttgtaatct gttcacttga tcattacatt aagaattaga ttatattgct 124440

ataactacaa agcattttat gttttaaaaa ttatgtacaa tttagaaaca ggcatgaaaa 124500

cttaggtatt aaatttagtg gaataaagca cagaaaaaaa gttaaaataa tgcagtttta 124560

tcacttagga ttaaacattt atatgggccg ggtgtagtgc ctcacacctg taatcccagc 124620

acgtttggag gtcgaggcgg gaggattgct ggagtttgag accagcctgg gcaacaaaat 124680

gagacctagt ctctacaaaa aatcaaaaaa ttagccagac atggtagtac atgcttgtag 124740

ctccagccac atgggaggcc aagacagtag gatcgctgga gcgaaggagg ttgaggctgc 124800

aatgaccgtg tttgcaccat tgcattccag cctgggcgac agaacaagac cctgtcttaa 124860

aacaaattta tatgctgcat tcgtgaaatt aaaaaaaaat catggattta gaaataaatt 124920

gaagcaaggt acattgacag tgtaacctca gcactactga cattttgatc tgaataattc 124980

tttgttgtgg gggatgcgct gtataagatg tttagctgca tccctgactc ctacctccta 125040

gatgccatta gcaccctccc ctccagatgt gataaccaaa aatgtctcta gacattgcca 125100

gatgtgcctg gggtaggagg gttgggggaa gtggggtttg agaaccctta gttgatcatg 125160

cctgcagtag gttgagaagc atcagaaagc taattaatta gacaggaata tgtgtttgca 125220

gtaagaaaac ctcagcaaac taatcaagtt ccaaagttac tgcttggtaa ataaatagga 125280

attaagaata agaccctatc tctgtgtctg gggtcattct cttcggagct cttggtggag 125340

agacagggtt cccagtttca attttttagt gcttcagact gcccttttca gttataattg 125400

taacaacctt cactccaggt ggggagcctc ccaggtttat ttacaacaag gctcaatctc 125460

tgattatttt ggtcaaggag atatgacact ctataccaca cacttgagaa tattgcctct 125520

ctttttctct tgagctttta gggttggaac gtgacaggca gataaggaat tttttgcatt 125580

aagtgcaaag tcctttttct tatagaagag caataatctg cacactagat caagtcaagt 125640

gtggatataa aattataatt tttgggggga tatttttaat agtggttttg ggttaaacat 125700

atttccttta aatgaaatgt ctgtaggcct aaagtaggtt ctaaatgttg cctgtactca 125760

tagtatacca tataaaatat aatccacatt tactggaact accatatatt acttacccca 125820

aatcaatcaa tcccttccct atcaccccca cgtaagatct tcgtattttg gatacctgtg 125880

aatcttagat ctgttcagtt ttccattatc cattgtctta tttcaagctt ctcattcaga 125940

atgttgcttt ggagtatttt ctgttagtaa acacagggcc tagtgactct aggacctgct 126000

gtgtgactta ggtcacccac ttcactttat tagaatctca aagaatggtg aacagctgag 126060

ttccaatctg tctcatttgg ctctcatgaa aacagtcata aggagattgt agataaacca 126120

cattatatag catagtaagt gataatcaac cccatttggc agttgcaacc ccacaagaga 126180

tagccctttt tagatttgtg taggagtgaa aagctttatt ttccacaaga ggaacgacat 126240

agtaagaact cctttccccc ctgcttctgc aggtatatgc ttatgcccta ggcaacttga 126300

tgggtaaagt taggtttaaa tagttttatt tgtaagctct tctcttctct tctcttctct 126360

tctcttctct tctcttctct tcttttcttt caagacagag tcttgctctg tcacccaggc 126420

tggagtgcag tgggcgacct tggctcactg caacctccgc ctcctgggtt caagagattc 126480

tcctgcctca gctccccgag tagctgggat tacaggtgcc cgccaccatg cctggctaat 126540

ttttgtattt ttagtagaga tggggtttca ccatgttgaa gcattttagg aaaggggtta 126600

ggaggaggaa gacannnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 126660

nnnnnnnnnn nnnnnntctc cccctttctc ccaaaatatg gcagactctt ctgtccccta 126720

gtcattctca tatagtcttc tgaacttgtt tattttcttc cctgttaata cagtaaaaat 126780

taactaagtt ggccaggagt ggtggcacat gcctgtaatc ccagcacttt gggaggccga 126840

ggcgagcaga tcacctgagg tcaggagttt gagaccagcc tggccaacat ggtgaaaccc 126900

tgtctctact aaaaaaaaat tgtaaaagtt agctgggtgt ggtggtgcgc acctgtagtc 126960

ccagctattc gggaggctga ggcaggagaa ttgcttgaac ccaggggctg gaggttgcag 127020

tgagccaaga tcgcgccact gcactctagc ctgggcgaca gagcagtctt taaaaaaaaa 127080

aaaaaattaa ctaagttaag tagtacttgg gccctatcag atagtgtcct cctgcaggca 127140

ggctgggccc ctactacagt ttcactttta atatctcacc gagattagct gactgaattg 127200

ccaccagagg agagtgaaag catattgcaa aatcataatc aggacatgtg agattatgtg 127260

ttgaacaggt ttaatgtgct tgggggtcag tgactaatgg gaacttagca gtcattaact 127320

gtcattaaaa acgtttgtta attactatta cacacttaga gatttgttaa ttaacaaaga 127380

gtaatgcctt tgctaatcac tattatgcac ttaagaggaa gccagtgggt atttttccct 127440

tcatagcttt ctagtacaaa ttaataaaat ttagaaaatt agaaaatgat tgtgcataaa 127500

tgtgtataat catgtatctg ttagggggca aaaattagtt ggggaattat ctttctttga 127560

taagtcttat cattagtttg aaaatggggc attggcaatt catactgttt ggctgggttg 127620

tcctgagaaa cactccccag tcaattctgt ttttgcaact ctttggttgt gaacaagtga 127680

ctgccctgtg agctgcaaat aaggagaact gaatattcct gaacagtctg tggcaataaa 127740

aatgaaatcc agtaagtgca aatggtatgt attcaacaat tgcgtagtta ggtcctgcaa 127800

ggtaattaga cataaaggat aagtatttaa tcaacaatat agtagcattt tcattaccta 127860

gtcaaatcaa gatgttacag ttttccttct cttgttttgt tatttaaaaa atatctattg 127920

tggccaggct ccgtggctca cacttgtaat cccagcactt tgggaggcca agatgggtgg 127980

atcacgaggt caagagatcg agaccatcct ggccaaacat agtgaaaccc cgtctctact 128040

aaaaatacaa aaattatctg ggtgtggtgg catgcacctg tagtcgcagt tactcgagag 128100

gctgaggcaa gagaattgct tgaacctggg aggaggaggt tgcagtgagc tgagatcgca 128160

gcactgcact ccagcctggt gacagagcga gactccatct cggaaaaaaa aaaaaatcta 128220

ttggttattg ttggtgcatt ttaaccaaaa ccctttagtt taaccctaac ctgtgctgag 128280

ctctttaaca tttacataca tattaaaaaa cagaatcagc ccagatttcc caacatatta 128340

agtcttctcc ttgacttaag ctactttcag ttcttcaagc ttaagtcacc ctgtggtttt 128400

gtcttaggcc aaatattttc ccctttgtct ccccttctgt ctatcaagcc aagcctgcct 128460

gtgggttttg gatagtgtga ccatctggct ttcttgaagg ggcacttaca ggggaagttt 128520

tattgcccaa accggtggac aatccatgtc aggaatgatt atatcacact gctttctggg 128580

tttagggctt ggaaaaacct gtatcagagc gtgggcccta gggaagaggt aaaaagagag 128640

gagagggaag aataggtctg tttcatataa cgagaaagtc tcatggcaga ggaatggatg 128700

agattcaagt tacaggctgg aagagcttca tccagaatca gccccgggga gaggagacct 128760

catcacgtcc tcactaaaca ttcactttcc tctccacacc cagttaaagt aaagcaaatt 128820

tacttccttg gtgaaaagcc cagccttcaa ggtatgtgga cttacccaca aaatctcttg 128880

gctcactcag tttcacttac catcgtttaa tgaggaaaaa gttcttttgt accatgtaac 128940

tgctgacctg agagaagccc attatgatat agagttatag gacagctggc caacacacta 129000

tatagctaaa atcagggcct ctctgttttg atggggagaa aagttagaga aggaatcttt 129060

agacttcaaa tttcatggct cagtaaaacg tcaaaataat tttgaagacc aaaggggttg 129120

ccagcttact aggctgccta gacaggggtg ggtatgaggg gaagaaagcc tgcttctttc 129180

atcaacagca tatccagaaa caaaggacat ttaaacacta aaaaagtcag aaggacaaat 129240

tctcagaaaa aaaggacagt cctttaaatg ggttacattt agctttataa aatgccctcc 129300

tgtattgtcc taatctttct ttgccaaggt caagtgcttg ggtgccattg gattataagc 129360

ccctgggttt ctgaacggtg ggggagggaa ccacaggaac aagggttagg ggtgaggaaa 129420

aagaactcat taaccttggg ccctgggtgg aagttaatta tcatgtcttg ccctgtgggt 129480

gggttgaagt aggaacgtta attccaaagg cagttttcca aatttttgaa cttgagattt 129540

gtaatattat cttgccagtt agccaccagt tctcttctct tttttctttt cttttcttac 129600

agtctcgctg tcacccaggc tgcagtgtaa tggcgcaatc ttggctcact gcaacctccg 129660

cctcccaggt tcaagcgatt cttgtgcctc agcctcccga gtagctggga ccacaggtgt 129720

gcaccaccac acctgactaa tttttgtatt tttaatagag atggggcttc accatgttgg 129780

ccatgctggt ctcaaactcc tggcctcaaa tgatccaccc accttggcct cccaaagtgt 129840

tgggattaca ggcatgggcc actgcacctg gccaactgcc agttttctag taatggttag 129900

gttgatattt tagattcatt tttagagttt attatcattt tgctgttatc ataagagaag 129960

ttccatcatg tcaataactt gtattaggaa agacatcttc cattcccggt atatccaact 130020

ctcattcgta taactgaagg ctgtgtgtat atcatcaaca attcttgccc ttttgccctt 130080

ggattgcatt atatgctgtg tgcttttttt tttttttaaa ttagtaaagc gtttgcattt 130140

cctgacagtg tgccacttga cagctggttt aagtgcctgg gagaatagta atcagtggca 130200

aatcagcttg tgtctgaaat gtggctgttg gcagtctact tgaggataat tgaaagtttg 130260

ctgtattcgt tttattgatg ggattctagg tgaatgccaa actcccgatt gggaccccag 130320

attacatggc tcctgaagtg ctgactgtga tgaacgggga tggaaaaggc acctacggcc 130380

tggactgtga ctggtggtca gtgggcgtga ttgcctatga gatgatttat gggagatccc 130440

ccttcgcaga gggaacctct gccagaacct tcaataacat tatgaatttc caggtaaaga 130500

gtccttagaa gatttcgaag tcacattgag aaacgttatt taaaaattgt gcgaatgagg 130560

ctgggccgtg ggtggctcat gcctgtaatc ccggcacttt gggaggccga ggtgggtgga 130620

tcacgaggtc aggagatcga gaccatcctg gctaacatgg tgaaacccca tctctactaa 130680

aaaatacaaa aaaattagcc agttgtggtg gtgggcgcct gtagtcccag ctannnnnnn 130740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 130800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 130860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 130920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 130980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 132960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 133980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 134400

nnnnnnnnnn nnattgcttt atttttctaa ataaatagac atctcccccc aaatctccaa 134460

ggttcagacc ttctaatcag taatatattt tcagggcatt cttcctttta tgcttttaga 134520

aagatgtaat agactttctt ttagatgctg ttcaagtact taatcttttc ttgtcttgcc 134580

tttttatctc tgtaatcttc ttgaataagc agttaatttt ttttattcat gaacctgctg 134640

atcatgtcta agaatgtatc tccacttaag taagtcagtg aatggtgatt acctgagtag 134700

agttaaagta gtcccccacc ctcctatctg tggcacatat gttccaagtc tcccagtgga 134760

tgtgtgaaac tgatgatagt actgaaaccc atctaccttt tttcctgtgc atacatacct 134820

atgttatata aagcttaact tataaattag gcataatata tttgactccc agctcccagt 134880

gtagtggctc tgcagactca caaaatgtat ttgctttaaa aaattctttt tttttttttt 134940

gagacggagt tttgctcttg ttgcccaggc tggagtgcag tggtgcgacc tcagctcact 135000

gcaacctccg cctcttgggt tcaagcgatt ctcctgcctc agcctcccaa gtagctggga 135060

ttataggcat gcaccaccac acccagctaa ttttctattt ttcgtagaaa cggtttttcc 135120

atgttggtca ggctgatctt gaactcctga cctcaggtga tctgcctgcc tcggccttcc 135180

aaagtgctgg gattacaggt gtgagccacc acgcctggcc aaaaaattct tttaatttaa 135240

gtaaatcttt atttatttac ttttgagaca gagtctcact ctgtgggcca ggcaggaatg 135300

cagtggtgtg atcacggctc actgcagcct cgacctccca tgctcaagca gtcctcccac 135360

ctcagcctcc taagtagcta ggactacagg tgtgtgccat cacactctgc taattttttt 135420

gtatttgtag agacgcggtt tcaccaggtt gcccaggctg gtcttgaact cctgagctca 135480

agtgatcctc ctgctttggc ctcccaaaat actgggatta caggcgtgag ccattgcacc 135540

cagccctaat tttaataaat cttttatttt ggaatagtat tagatttata gaaaagttgc 135600

aaagatagta tggaagagtt cccacatacc cttcacccag ttttccccaa nnnnnnnnnn 135660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn tatttattta tttatttttt 135720

gagacacagt cttcccgtcg cccaggctgg agtgtggtgg cacgatctcg gctcactgca 135780

acctccgcct cctgggttca agtgattctt ctgcctcagc ctccgagtag ctgggaccac 135840

aggtgtgcgc caccatgccc ggctactttt tgtattttca gtagagacag ggtttcacca 135900

tgttggtcag gctgatctca agctcctgac ctcaggtgat ctgcctacct tagcctccca 135960

aagtgctggg attacagaca tgagccaccg cacccagccc ccagtgttaa ctcttacata 136020

acagtgtcac tgtctaagtg tttgaaaaac tatttgtcaa aactaatatt ggtacattat 136080

tgttaactac acttcagact ttttttggat tttaccaatt ctcccactca tgtccctttt 136140

ctgtttcagg aatcaatccg tggtaccata ttgcagttag ggtgtttata tttgatggga 136200

ctggtcctag tttagatact tagtgtagct cagccagcag gtgggatctt catgcccacc 136260

gaggattggt attgtgtttt cctggtggtt ttatggcatt tccgactatg cagagaggca 136320

tggtattaac ttcagtgtct cctagcaaat tttcctgttt ttcaccaacc tctgatccct 136380

gcattatttg caatcaactc agagatttgt gattgaaaac attgcttgac tccatgctct 136440

ttaagctatt ttctaactag gtaactgtaa cataaattat gcttttatct agcactgttt 136500

ttcataaaca catgttgagt gattttcatc aaccgaaata cttcgaatca ttaagtttcc 136560

caagttcatg gatgctgctt aaatgcctgg tggttccagg ctgtcgaata tttctgcctt 136620

ctgcaataag agattgtccc ttgttaaaag caacattagc ctttgtgcgg tttcaccccc 136680

aattcttctt tttcttgttg taaccaatga aaggaagtac tgcttaacac agcaggtaat 136740

aatcttctaa aactcattat ctcaagaggt ggtcctggca ggatatataa atgcaattta 136800

agaaaggtct tggcaaattt atgaatgaca gaactgggag tggctaccga gagaaactag 136860

gatgcgcctt tgctttgaca ctgaggtcag gcgtagcttc tgtaccctcc tgggtcctgc 136920

ctcttggggt tgctgcaggc agcaccccat gaaccaggca tctgacccag ttccaggata 136980

cttattcttc cagcaagtcg aacactctgt gatgagtgac tgccatgctc atgggtcacc 137040

aggctctcat tattctgttt catttccagc ctcccacaag attggttttt cagctgctta 137100

tttattatta tcattatttc aaggctgctt tccaagtttc agtggggggt ttcctaagcg 137160

taccagctgc cctggttgtg cagttccggt gatgtttcag atgctgggcc ggattctggc 137220

tgtacccagc ctgatctttc tgggcttcag gaaagctgaa gccaatcaga gctcctcttt 137280

catgcctttg ggattatgct taccttgcct ggcatcgtgt acctgctccc atccatggga 137340

aagttttgct gtctggtact gtcttctatc aacatctttt aagatatctt cccccgaggc 137400

atcgtgatgt caacggaacc agcacacttg tacgttttat gcaagactgc catatctcaa 137460

cagtgagaaa tgcataatgg aagtggtgat cacggattat ttcctaggac attatggcta 137520

atgcgctaga gaactcggat ggtctgttgc gtctgacatg ggctttttct cttgagttgt 137580

ctttcttttg ctattctctg aaagaaacaa ttcttgccac atgatcctga tttttcaggt 137640

cctcagcatt tgttagcaga aagtacactt tgtttccatc cggcagtgac tcagtggtgg 137700

tcccatgctg atgaaacgct gagatagtct tcttccaaat aggtatcgtt ttgattgttg 137760

ctgcttattt gctagctggc cctcaatagt gacaatgaaa cctcaagtgt ataatatggt 137820

tgctcagtaa tcctgaggga agacagtctt tggtttgggg gatagggatt ctgtgcctac 137880

ttagcttcag gtgaaagtct tacaaatttt tgtgtgtaga aataagcacc atgtacctcc 137940

ttgggttttt tctttttttt tctagtcctt tagtatggtc aacaatattg tttagggagt 138000

acctattctg tgctaaccac taggcattca agtatattac actatgctcc ttcaaaacac 138060

ttctgtcaaa tgtaaggatt attataccca ttttacagat gtggttactg tggtaacttg 138120

gccaaggtca tagggcaagt gaataaggga ttctggattt gggtggaggt ctgtgtgatt 138180

ccaaagccca tgctctttct acaatactat atatgccttt gcataagtta ttgttattag 138240

taataatatt tgtgatgatg gcaaataata aaccatgtca cactagagag tgatttaatc 138300

tctaggtcta tttaagaaca tttggaattg caggaattgg attttttttt ttttttaagt 138360

gatggagtct tgccatcttt gcccaggctg gtctcaaact tgtgggctca agtgatcatc 138420

ctccctctgc ctcccaaagt gatgggatta cagatatgag ccaccatgcc cagcctagaa 138480

ttgcaggaat ttttgaattg atgattcatt ctgatatttg aatttctaca gtatgttaag 138540

tgcaatgtca ggtgctggtg ctgtggctcc attgatgaac acatttgggt atggccctac 138600

cttcattgaa tttagagtct aagagcctaa ccggtctttt gcttgaatag agctgtagtc 138660

ctgttaaatt gctgtacctc caaatggtgg gaagtttaat gcttcgtagg cctcccctca 138720

ctagtttact gaaccacatg tgcttgattt ttttttgann nnnnnnnnnn nnnnnnnnnn 138780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn ctcactgcaa 138840

gctccgcctc ccaggttcac gccattcttc tgcctcagcc tcccgagtag ctgggactac 138900

aggtgcccgc caacacggcc cggctaattt ttttgtattt ttagtagaga cagggtttta 138960

ccatgttagc caggatggtc tcggtctgct gacctcgtga tccacctgcc tcagcctccc 139020

aaagtgctgg gattacaggc atgagccact gtgcctggcc ccacatgtgc ttgattttaa 139080

gcaaaataca gactataggc tgtgacctgg tgatctcttc cccacataca gcatcctgct 139140

aacctataac tctccccatg tctcagatct agcctgggaa aggacaatgt tggatcgatg 139200

gcccacttct aatcttggga tttctaatct caagatgagt tgagaagact caggatgtgt 139260

cctgttttct gtttatttag aacagggttt ctcagccttg gcactgttga catttggggc 139320

cagataattc tttgctgtgg gggctgttgt gtgaattgca ggatgttgaa cagcatcgct 139380

gtgctttctc catggatacc agtagcaccc tccccctgca gttgcaacaa ccaaaaatga 139440

ctctagacat tgcccagtct ccccttgggg gctacagtca ccttcagttg agaaccattg 139500

atttagaaga attggccagg ttattatcag gagagggaac atcacagtaa tctgaatctc 139560

tcaatactgc cactgttact gttaacgaac agcaaaacta ttacgtggag gcagtaggac 139620

cttgctactc agagtgtggt ccgtggaccg gcagcatcgg aatcatctag gagcttgtta 139680

gagcttcaga gactcaggcc tactgagtca gaagctgcat tttaataagg atccccaggg 139740

gatttctgtg catattagag ttgtgaagcc ctgcaagagg aagaaattgg atgctagcct 139800

cagagtttct tgctcatctt tgtgggtctt cctacgtttt gtcttcgggc ttaaggtatg 139860

gggaggccac tttttggctc aggactccta tgggtgaatg ggactgctta gaactgctgg 139920

gttttaggcc ttgctttgag gaatttaaag cttttctctt agatggacat tacatcgttc 139980

atatacttca aaatggtggt ttgacctaat ctctgccttc tgatagcaaa aagatatttc 140040

cttgactccc tgaaccccac tttactgttg tcccatattg gattttaatt aagggtggaa 140100

taagtattct tcactaacat gtttatacat gtatgatatt accatgccat ttattgagtg 140160

cctagtatgt gccaggagct ctgcaaagtg ctttatgctt attattgttc catttattct 140220

tccccaaacc tctgtgaggc aggtcctatc actagtccac aatacaaatg aggtcatgga 140280

gcccgaagtt ggcagtggta ggaatcaaac tcaggtctcc ctgactctaa attctctttg 140340

cctttgtttt tttgaaaaag tggtatagcc catagcagaa aattcacatt atacagaagg 140400

ttatacggcg aaaaatgcct ccttcccacc ccacgctcaa cccctctccc tcaagcggaa 140460

ccactattgt cagtttctca tagaactttc cagaatattc tatgctccta taacactagc 140520

acaacctatc ctcttaacaa catctttatg ctgcctccca agaattcagt aatttttttt 140580

tttttgagat ggagttttgc tctagttgcc caggctggag tgcaatggcg tgatctcggc 140640

tcattgcaac ctctgcctcc cacgttcaag tgattctctt gcctcagcct cccgagtagc 140700

tgggattaca ggcatgcgcc actatgcttg gctaattttg tatttttagt agagatgggg 140760

tttctcccat gttggtcagg ctggtcttga actcccaacc tcaggtaatc cgcccacctc 140820

ggcctcccaa agtgttgaga ttacaggcgt gagccaccgc acctggccaa attcagtaat 140880

ttttattggc aggttatttt cccgcatcat tnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 140940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 141960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 142980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 143940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 144960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 145980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 146340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnaatt 146400

caaaacctgt ctcctgttaa tcccatcctc tctgtttctg ttatcatttc cttagtgtag 146460

atctgcctaa gtgtagaatt tgtagaattt gtcatgttga ctattgtaga cttgtctttt 146520

agagtttcta gcactagcct cttccaccca tcactattga gatgattgta tccgtctcag 146580

tactgacact aacccagcac tctggtttta catctgtcaa tccatcaaga cttcactttc 146640

actttcttcc ctgcctcatt attcactatg ctcttgggcc attgctctgg cttctggggc 146700

ttttctaaag tagcactttt ccccactcca gcccatgaag atacctttta accagctctt 146760

gagattaaat cccctccgtg acactttcct gcaggaactt gcaaaaaagt actgcattcc 146820

ccactggcaa aacttgccat cagccagttt atgtattctc tgcttttcac acccatatct 146880

tgacctctga acaacacaca tattctcctc ttcatttatt tcacagttct gtcttcataa 146940

cattgataag tatgatcaca ttagcgctct agattttaag caactggaag atagctattt 147000

ttttggtact cttcctttaa atttgaacat agtgtctaat tagtcaatta acattttttt 147060

aaaagggcga gggacatcat ggtagagaga acgaagttga acgtgttttt ggttgaatat 147120

tagcgcatgc ccactgtatt ctaggcacag tcctgattca ttatatcatc acacaataat 147180

tatttatgtg ccttcatcct ttatgacaca gtgctggctc ttattcatct cccatttctg 147240

caatccatgg tgatgattaa aagtcttagg agttttacga ggctcagtat tttttttttt 147300

taatatgcta gttcttcatg aatacattgg gtactctgaa gcatatcatt tcctgggttt 147360

cctgaagtgg tatgttgcgt ggaatggcac attaggtcta aataattatc ccctatgtaa 147420

ggggtcttgt ttttcattca ttctcttaaa aaatagatat taaacattaa ataaggacag 147480

ccaggnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 147960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 148980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 149880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnt tccttttttt tttttttttt 149940

ttttttgaga cggtgtttcg ctcttgttcc ccaggctgga gtgcagtggc acgatcttgg 150000

ctcactgcaa cctccacctc ccaggttcaa gcgattctct tgcctcagcc tcccaagtag 150060

ctgggactac aggcatgcac catcacatct ggctaatttt tttgtatttt taatagagat 150120

ggggttttac catgttggcc aggctggcct tgaactcctg acctcaggtg atccacctgc 150180

ctcgccctcc caaggtgctg ggattacagg catgagccac tgtgcctggc ctacttcttc 150240

ttccttttaa cttgaagatt atctgcccct ttttctaatc ttaaccgcat taagctggct 150300

ttgagcatgg caagagtttt atagatgaat cttattttat agtacaggat ttcaaaatca 150360

taattatttc actgagggtg gcttttaccc tccattaatt atacttctca ctcagaaatg 150420

gaattctatt ttggtctcct aaagataaat tagtatatag tggaaaggaa ttataaagtt 150480

ctgctaggaa ttaaatgata tgattaacac aaacatccac atggatgtgt ctctgccctg 150540

tgcaggaaag atgaacattc agtacagatt ctgctctatg tcactagctt tcaagacctg 150600

caggttctct cctaagcatg caattcctgt gagcagtagc aataatagca ggtcatattt 150660

gtggagtgat tactgtatgc taagaactgt ggtaaacact tttatatgga ttattttatt 150720

taaacctcct aatagtccat tgaaatagat attgccatgt tgaaaactga ggttcagaga 150780

ggttaagtga cttacccagt gtcacagaac tagtaagtgg tgcagctggg atttgaactg 150840

agattccaga acaattgcca ttaaccactt tgcttccata ttagtatcat ctgcaaatct 150900

ctctccataa atttcctcag tctttatctg agtttcctta tttcaggaag gaaaacttct 150960

gtttttgatc cttatgaaat acaatttcca ttaaaacttt ttttttttgc tattaaaaaa 151020

ggtaccggat aattgaaacc agactggatt tgagcctgtg ttgatggaag tacacatggg 151080

atgtgggctg aagtgttcaa tctaattttt ctttccatca gctaattttt aaagtattaa 151140

gcaagtagat tctgacacta acagggaaga tttaaattct cttgagagac tggaggtgtt 151200

aaataatttt ctggtagtgc acattttaca tcttaaatct tcctcactct cccacctcat 151260

ctcaatgtac ctgaagctct gggaatgttc ttttgtactt ctcaggaaca gccagacctc 151320

tggcttcatc tcctctcccc tccacatccc tttcctgctc caattacttc ccagcgccac 151380

ttggatgttg ttgtcatcgg ggaactttgg aaacagccag atttttttgg agtctgtaag 151440

cagaaaacag actgcttgct gctcatatct ggcacccagc tttgtccaga aaacgaggag 151500

ttaaaaagaa gtctgggctg tgaagggctg tgacaactgt cctaggggga gctctagcga 151560

gccctggcgg gcagtgactc atgctgctct gtcactggga tcagcactgg cccctggcag 151620

gcaggcggca gccaggtggg gttccagcca gagcacgcac gcacggagcc gggagcatgc 151680

agcctgcact gcgggggatg tgatgctcgg ctctaactcg cctggctggc ccgccacgga 151740

cgcctcagct tgcaaccatg gtaacgtttc tggcggggga cacccccggg agcccaccgc 151800

gatgggcagc ctcctggtga ctgatggacg agtgtccacc tcccagaccg agagcgctta 151860

gtaggtcgga ggaagtggag aggatgtaac acgcccccag ccgggagtga agccctgagg 151920

aggtaggagc cgcatatgtc catccgtgca ttcccaccgt cagcgcgcag gggtgctgta 151980

gatcaccggt aggaacttta tttggctggt gcttcattat gctgattaaa ctgcagtgga 152040

tttgatgggc atgattgcgc tggggaagat gcataatgaa ctaaaaaaaa aaaaaagtgg 152100

ttaataagat ctcggagtcg acttgtccgg gtatgaatga agtagactgc agtggtatcc 152160

taacaggagt tccagaacct cacacatccc ttttcctggt ccttcctctt atcccggtta 152220

atccacgaaa tgtagaagtt ccatcttatt tcaacgatta gtgctaatca ttaataattt 152280

agacctgtct ggaggaggga atccataggt ttaggtctcc tagcatcctg gcactagcca 152340

gcagctgctc tgtaggagcc ttctggaaac agcaggaagg agcggcttcc ccacgagttc 152400

cccaagtgct ttcgttggcc caagtgcttt cgttggccca agtgacctgt ttgagtttgc 152460

tcttcagttt accccaggcg ggaaggcagc ctgtctgcgg gttggtggcc atgttggcag 152520

agaaggggtt aatctcttgt tgctgtagga gccgaggttg cgagctagat tgaaagcagg 152580

cgctgcagtg ccatcgccag cgccgaagga gtaagacgat cttctccgca acagtgttga 152640

atccggctga aatttttttt cctccccgcc tcctttcttg tttttcttta accagctcct 152700

ccccccttcg ttcccaccct caagtctgac gatgacacct ccaattttga tgaaccagag 152760

aagaattcgt gggtttcatc ctctccgtgc cagctgagcc cctcaggctt ctcgggtgaa 152820

gaactgccgt ttgtggggtt ttcgtacagc aaggcactgg ggattcttgg tagatctgag 152880

taagtgaaaa tttgactttc taaagggacc tgcattgatg caaggctttt ggagccaaag 152940

gtggtggtgg gggggtgggg gaataggtgg ggggagtgca gtggagggaa gctgctagtc 153000

acctgcattg ggaaagcagt ctacctgtta gggctttgcg ggggtagcct gttaatattc 153060

tcattttgca gtgtgtaagg tacctgttcc tgtctgtggt atgataattg tcaattgggt 153120

actttgggtt agttttccaa tctttggtct tctttaaagg ggagagagtg ggagatttcc 153180

agcagtgcag atccccggtc aaaggagaaa tgtgcaggag ttaagatgag ctgcccatct 153240

atctaaccat ctatgtatct gtctctcaag tgggtggatg ggggttgcta tcttggctgt 153300

ataaagaatc ctaaaaacct tgtctcataa gctagaggtt tcctgatggg tttaactgag 153360

ctgcaagtgg ctgaaccaga gctctaacag agagatggtg ctcggctcct ctccaagtat 153420

gctgcaagat cagggatctg gcagctgagc ctctctgagc tggtggagcg ctggcagcca 153480

gagaaagccc cgttactgtg agccaccagg agggagtgtg atgtagccga gtcattgatt 153540

cacagaaact gggcttcata gggggaaaaa aaaccaggag actagaaaat ggaaatataa 153600

atatcactgt aaacctcttg atctggtagg tctttctcca ttctcataaa agctattgaa 153660

aaatgcatta acagagcact tggaattaga gggtcgaggc ttccaggagc ctcctggaat 153720

ttctgtaaaa tgcagtagct tctgtggatg tgggaggtca gtatcttgcc tcattctctc 153780

atgatacaat gacattctgt tttcagagga gtgagttccc cagaagatct tggactgatg 153840

gtgttatttg ccagccaccc tggtccctgc actttcaggt tctcagaggg taatgttggg 153900

ttagttgctg cccacttagg agacgagcag aatttgatat tcttcttggc agcatctttc 153960

cctctttgtg gtatttgtag cttagatatc gatttatagg gatgttatgt tggttcctgg 154020

atggtgtctc cctatgggtg ctattttgac agtaacgttc ctgaaaagat ttcagagtgt 154080

tgtggggaat tgggcatttg atacgaaata aggttgtggg ctgtgattga atgtgaggga 154140

ggtttttatg ttgcaagatg ttgaagtggt ctttcttgat cccctctctg ggggctgggt 154200

ttcaaattca ggttggattt tggtagtgtt agatgtgcct ctctgtctga tttgctccac 154260

aaccccaaag caatctggat ggtggtggga gaggcagagt gctaactagc tgttgaatgt 154320

gccatcagat gggtttgaaa cggctcagca ggattgggag gttttgccat tggcatcaaa 154380

gagcagggca gaagcggagg cctgatgttg aaggatgcat ggttagtggg cagtataacc 154440

ttgacacacg cagcacactg aaggtcacac gtcgtactgg aaggacgtgt ggagagttct 154500

agttctggtt agcagtgggc tggctgggtc agaatgcaag cttgcttggg tgttggtcag 154560

tgatctgaaa gacgagggag gattcgaggg agttagattt caggggaaaa ggcagaatga 154620

tatgggagat cttaggcatt gcaattaatc tgaagcagtg tgtgattaat tgcttatttt 154680

tcaggaagac ttgaatgaca tctttctgtt tctcacagaa agctcagttt agggagctct 154740

ctgacaggga catctcagta ttaaggctga ggcactcgat aaatatttgt tgatttaatt 154800

tacctatgat cctttcctcc agaagtgttt atattgctta ttgtatttga agatgtgcta 154860

tctcacctct ggtagtttaa actatatcct tagagcacaa aacgagctgc tgttcctgac 154920

ccaacagaat gtttaataag attcttattt caaaaaaggt ccatgcaaat aaaactgtgt 154980

atttcttatt tggacgatgg catcagagta ttcctatcat tggggaactt taacgttttt 155040

tcaaagcttg gcaacggggt tggaatcaga aagattttct ttcatcttgc gtcttgttat 155100

gtgttattgc tattggactt ggctactctg ctgtaggcag ccctgtgggt gatacctaca 155160

agcatcattt tagaaattca tccacctgtt ggatgtagat gaccctggac atatcagatt 155220

gtgattaatt agaaatctaa taaaagagag gcagtgatga aattacttag cagctcctgc 155280

agttttattg acaaaattta cttggagaga gggggagaca ttttctgggg gtaccacctt 155340

tgctgccagc gaccctgtgt ttcttcctga gtttcttttt cttttctcac cattttcagc 155400

atcacaggtt tttatttaca cacattgatt acctgtgctg ttactcattc ttcacaccac 155460

tgaggaaatt gcagatgctg ctgtactgtg ctaggtaaat tgacctcaga tttgttacca 155520

gtgaattgaa tgaaatgttc agaggtggag ctgaatgaac gaggagtttt tgtggagaaa 155580

ttggcagtga gaatgattta aattctgtga tagctcctcg ttttttggga tccttatttt 155640

gggaccccag actattttta agccattgag tgcatcatta ttttaggctg agcaagaatc 155700

ttgatgacag cgtttcaatg gctgaggcgt agtgggagtt ccttgcagct tgagttggtg 155760

ggagctggag agtttctaga gaactaggtt tggttgtctt tggggtgggg ttatggtgaa 155820

attagtcttg gagagtgagt agctgtctga tgcttctttt cctttttaac cagcaagagc 155880

ccaaaccaaa tccccaagct ctgaatgcct ggctgttcct ctcagccttt ctttgcttga 155940

acttgacaat agtagggtag taacaggaaa cagcatgtta aagttttaaa aataaaatag 156000

atctcagctc ttttccttcc cattagcaag gggtacattt atttaggttt ttccttctag 156060

attgaggcac tgcctcattt aagttcttgg tgaagccatg catttctgca aaccataagt 156120

ataaactcta gaacgggggt gtccaatctt ttggcttcct tgggccacat gggaagaaga 156180

agaattgtct tgaggcacac ataaaataca ctaatgatag ctgatgagct aaaaaaaaaa 156240

aaaaactcat aaagttttaa gaaagcttac aaacttgtaa gttttgagcc acattaaaaa 156300

ccatcctggg ctgcatgcag cccccggggc cttgggttgg acaagcttgc tgtagaaggt 156360

aaaaatcagt tggttttatg tttttgtttt aaacatgctg gttgtatgct tttggaagag 156420

ttggggaaca ctgagggtaa tgggatcttg atggggctgg aatttgtggg aagatggtgt 156480

ctgggtaggc tgtttttagg aaggggcact ctcttccttt tgattcagag atttttcctt 156540

tcttttcggg tggttctgaa aacacagcga tggatccagg cattcaaaca ccatggagga 156600

aggaagagtg gctgttgcca ttgcttcccg agttttctgg gaaccagttt ttggtgcctc 156660

ttccttgctc tactggggct tctctgcatg tcagtttctt caactgcgaa gtggaaggac 156720

agcgatactt ttcttacagg acttttgcgg ggatggatga aatacgtaaa acacttggtc 156780

tagtacctgg cacatggaaa agccttggta aatgttcact gttgttattt ttgttattac 156840

taatacacta gtccatgtat gtatagtgtc ctcctataca caccaagaga atatggaaag 156900

gactcagcaa tgattaggta gtccaaagtc ataccagatt ggaaaccaag cttcccaggc 156960

cctgggactt ttctgctaga gacacttcac ggttctgacc aactacaaag agttaatatg 157020

cagttgccaa atacctgttg gtaaaaggtg gatgttgggg aggagtggat tggggaacag 157080

aattagaagg tccagtccca gaatgggtac cttcccatca agttgaacaa gtcaaaacag 157140

gttatgttga aacaactgag agaaagtaaa gcaaacacca ttgctgcaga atatcatggt 157200

acaaattgga catctttggg agttagcgga gtaaggcaaa atccagtgag ggacgcttaa 157260

tgggtaatgc caattcacaa ttcttgttaa attacattgc tgatcttcct tggaatgtct 157320

gtccattccc ccaagtagac tgtgatctca aggcaaggct gggtcttatt catcctggtt 157380

ttcctggagc agtaaatact tgtgctggga ctgggcttat aagcatacta atggaaagta 157440

aaatatttgg gttggttttt taaaaagaca gtggatttgg atcagtggag aggaaggtag 157500

agggaatttc aggtgggcag ggtgctaaca acagcccatc cttacagggc accaactgtg 157560

ttctaggctg tgttccaacc actttacaca gatgaattca tttaaattgc acaaccagcc 157620

caagaggaag gtaccattat tattctcatt ttggatgtga ggaaactgag gcgtggggag 157680

atcaaacaac ttgcctaaag ttatgtagct ttgagtggct tagctgagat ttgaaccctg 157740

tgggtataaa tgccacagat gggaaatttg tgtggggtac cccagggttc atgtgcttgt 157800

tagaagtgga agctatttgt agagaatcac gaatgatgag gttggggcag ggtgtgatgg 157860

gagctgacag gcaggtctaa atgctgggat tccattttca gtctctgtgt ttattgagta 157920

ggtagacggt atagctcttg gatttctcag attttttcct cttttcattt agagactctt 157980

atctggtgtg tgtgtgcccg cacacataca taaacccacg cgtatatact ctttccctga 158040

atgttcttat ttgctaaagc ttaagcttgg caaagagagg aaactgcact gaccttactc 158100

tccaccatat cttcaggctg atcatacaca agttgcttaa taagcatttg gttaatccat 158160

ctaaatcatt cttatggctg caactctcat tttgttgatg actctactat ctatgtctat 158220

tcacatctac attttgtact tttgtttgcc tcccatctgt cctgggatgg ctgataccag 158280

tggaagacag cctgaactct ccaatcagtc ctgtttcctt tttatgaaat acttggaggt 158340

tggaggatct tcccttaaaa agtgttttcc tttctacatc cagccaaagg ctcttggtcc 158400

ttgtgcttgc tacctagatc cctattggaa agagtcttgc ctgcaatttg attttttaaa 158460

tagcagcaat aacagagtcg tctctgctac acgaagacat gcatctgctg tatttcccag 158520

acaagttcaa aaaccttaac tagcttctgc ccatggttat tgctctcaag tgccttgtgt 158580

tgttcccatc ccctcattat ctggattaga tgtttaacat ttgcctgtgt gtgttgtgtt 158640

ggattttctc ctctcctctt gctcattcaa tttcttcctt ctcttagcca agcacagctt 158700

gttctcctac ttgccttatt ctgttctcta tttagactgt gcgtgcctgc cttgcagccc 158760

tggcaggacc attccaccgc cttctcattt gtcttaaaga tacctttagg aaatctaatc 158820

cagacaatcc tagcccagtc ctgaagatta ggctccagaa gattctgtca agtgtgtttt 158880

ttgctggcct acacatgcta atttgcatgg ttgcctggga tcccttaaga agacagtcat 158940

tgactaaatg gcgctacatg ttcccaagct ctgcgccagt ctggcaactc ttcctttgtc 159000

tacgtgaatt tctcctagtt ctttctgctt tgcttgctgt tcatctcctg acctctctcc 159060

gacaaacttc nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 159960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161520

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161580

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161640

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161700

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161760

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161820

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161880

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 161940

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162000

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162060

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162120

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162180

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162240

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162300

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162360

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162420

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 162960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 163980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 164340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnatttca gagtaagttt ttctagaaaa 164400

tagaagctgg aaaaaaaagg aaaacccaaa cttggcttcg tgctcgaaga gacagcactg 164460

ctgtgtgtgg gcgggtggct gcgtgcaccc gctgctcaga agtgcctttt ctctccatgg 164520

ggataactgg ctgtgtatcc gagatgtggc caggagtagg caagcaacgt gtgggcaggc 164580

tgcatgttct tttattagca tcttcattgt actgcatctc gtcgagccca gagcatgaac 164640

tggcctgggt ttctaatatc taccctgctt cccacctaat tactcccctg aaccctaaag 164700

tgagggaggg agagttgctc ttgtggggtg agctttccct ggggtggctg tgaaccaacc 164760

tggcatgtgg atgttcttgg gtatccagag ctgtcctgga ctcaggcttg gagtcagctt 164820

cttagcactg aatgcagcca gtcatggatg gaggtcactg tatctcacat gttccgctct 164880

ccctttcctc catgaccttg cccctctgag cctctgtagc acttttcttg agtgtgtcca 164940

aggccatcta gctaagaagt agcagaaatg ggatttgaag ccatgactgt ttggtgatag 165000

agcctcagct ttgaactggg gttctactgc ctggcacccc tgcacaaatc atggtaacgt 165060

ggtaggagaa catagaggta tagggcaagc ccctccttaa tgccatgaat aatacccatc 165120

ttataggatt gtggggagga ctcagtgaag taacccgtga agcactaaac acgtgcctga 165180

cacgtgctca ataaatgagc acttgtcctg atgacaaagg tcgtggcatt aattctctct 165240

cctaggttgt tacttccttg aggacaggaa ttgtggcttc cttaatggcc actgcagcag 165300

agtttctcaa gttggcacta ttgacatttt gggctggata attcttgttg tgggagctgt 165360

cctgtggatt gtaggatgtt gagcagcatc tttggcctct acccgctaca tattaatagc 165420

acccctagtc atgaaaataa aatgtctaga cattgccaaa ctgcccctgt tgagaaccac 165480

tggtctgcag gtatctctca tggggatcac agggctttta tattctcttc tctgtctctc 165540

tctctccctc tctgggtgtc tctctctctc acacacacgc ttagagaagg tggttaaaaa 165600

aaattttgtt gaagtttgag aattttgaga acaaaggaaa aattttggaa ggcattttaa 165660

tgaacagata gactctgtcc cattccatgg tcaacagaat ttcataatta gatagtttgt 165720

ttactgcaac tctgcacccc attgcccatc attttagagt tccaaccagt tagaggattt 165780

ttcttgcaaa ctttccttaa agcagtgata gtatcagctc tttaaataat actatgcttg 165840

atgaagtggt acttttcggg ataatttgag accagccgac ttgctgcttg aagaggacag 165900

ggctatattt ggtaataata tatatgtgat aatatgtatg taatattatt ataatgtaat 165960

atacaataat atttggtgta actggtgact ctgaggccag tctttgatcg aacctctcaa 166020

gctatgattt acattatggt caatgttagc ataatgcaat tatcagcaat cacttgctgt 166080

tgctttgaaa gtcagaagga tggctaataa aaatcttaga aaaagaaaac aggccgggtg 166140

cagtggctca cccctgtaat cccagcactt tgggaggctg aggcggacag atcatgaggt 166200

caggagatcg agaccatcct ggccaacatg gtgaaacccc atctgtacta gaatacaaaa 166260

aaaaaaaaaa aatttgctgg gcgtggtggc gtgcgcctgt agtcccagct actcgggagc 166320

tgagtcaggg gaatcgcttg aacccgggag gtggaggttg cagtgagccg agattgtgcc 166380

actgcactcc agcctggtga cagagtgaga ctccgtctca aacaaaacaa aacaaaacaa 166440

aaaacaaaaa aagaaaatct tagaaaaaga aaataaattg taatatttca gaatatttgt 166500

tggggaggat atgtgtgctc aagaaatata tactgagaac ttaccattga tgctagagat 166560

tgaattgccc catgtctaca tgaaaaatga atagaatata aacattttaa attgagccat 166620

gtctatctgt attatatttc ttttatagaa attcatggaa atggtatatt ttaactgaat 166680

tattaacact ggggacaata ggctttaatc attatctaat acctgtacgt tgttttgaaa 166740

ttcatagccc accaccatta atttcaaaat tgggttctta ctcaaagagt gatgaaaagg 166800

caccagtacc aaatggtctg gccaaaatgc tacatggaac taaatgctgg ggatggtcat 166860

acaatgagtt ttaagtggct agaccctaaa tcagaagcac tttcttctaa ttagcaccat 166920

ggttcttaat cctttctgta cattacaatc gctcagcagc ttaatacaaa tgttgcttcc 166980

cggggccaca ctccacatct ttctgactct ctgatttaat tggtccgaat ggggcctata 167040

catcaggtgt tttttaaaag gtctccaagt gattctaatg tgtacctgca ttgaggacca 167100

gggaaggtgt aggaagcctg ataaccttta ctctccagcc tcatcctcca atcccatgat 167160

tgtttatggg attgttgcta cacacccagc ttagtcatag cattcttact ctagcttttt 167220

tttagatgca atttttattt attcttaaag aaaaagattt ctttagcacc tttattctaa 167280

agagctctta attgctgtgc ttagaacttc taaacagtga gcatttgtca aacatagaat 167340

agcagaatga aggggttgga cctcgggtga ggagggctgt cgcatggtct ctttcgagtg 167400

ccggcgggtg ggggctgcac atctcctcgc ttctgggccc attgataagt gacctaaaag 167460

tgcctttcgt tttttttggt ggggggtgaa aaagcaatct gttttgtacc cacagcggtg 167520

cactttaaac aggaagccct actggggcca gccttctatg tgtcattaag tttttcacgc 167580

cacatcctac ctatcatcat gcacccatgt catcgttctt ttaaagggtg ccagtttttt 167640

gcttaagcac aaggagctgt gacctgtgtt gtcatccctg atgcatgtca tgcatgtgac 167700

ttcatgacat gtgggtgact tttgatctct gaaggaccag ggacccagtc tgtggatcac 167760

cactctctcc gtgggtggtt tgggtcttgt tctctagccc acccagccag gtgcaattag 167820

gaataaagga aatagcaaag gaattttgct caaggccatg ccaagcattt catctcatat 167880

gaaaaggaaa agagagagag tgtgtgtgtg ttggctagat ttaggtagaa aacaggctgg 167940

tgagaagcgt agaacttggt taaaatttct agccaaaagt aagattttta aaaagattta 168000

tttctggatc caatccctgt tgcccatttc tatgaataat caccatttgt tttaatgtga 168060

ataatagcac acagcaaatt cagccccctg agttttacca ttttaagcaa ttgctttagg 168120

cccgtgaggc atgtactatt tatgaagttg catgggtagt aatggaaaac acaacaatga 168180

cagtagtaac aggtgacatt tgtcgaacac ttgcagtgtg ccaggcactg tgctgagagc 168240

attacatgca ttatttcatt taatccttcc aagaactctt tgaagtaggt tggtaattat 168300

ggccatttta caattgagga aactgaggtt cggagatgtc aaataactag tcagtggtgg 168360

ggtcagattt ttcttttttt tttaaattta tttgcttttt tttttttttt tttttttttg 168420

agacggagtc tcactctgtt gcccaggctg annnnnnnnn nnnnnnnnnn nnnnnnnnnn 168480

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168540

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168600

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168660

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168720

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168780

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168840

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168900

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168960

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169020

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169080

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169140

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169200

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169260

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169320

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169380

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169440

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169500

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169560

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169620

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169680

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169740

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169800

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169920

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 169980

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170040

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170100

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170160

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 170400

nnnnnnnnnn nnnnnnnnnn nnntggctta aaacaacaca catttattat tttacagttc 170460

tggaggtcag aagtctaaga tgatgccagg cttggtggct caagcctgta atcccagcac 170520

tttgggaggc tgaggtggca ggatcacttg aggtcaggag ttccagacta gcctagccaa 170580

catggtgaaa ccccatctct actaaaaata caaaaattag tcaggcacgg tcacgagcac 170640

ctgtaatccc aactactcag gaggctgagg caggagaatt gcttgaaccc aggaggtgga 170700

ggttgcagtg agccgaggtt gcagtgagcc gaggttgcac cactgcactc cagcctgggc 170760

aacagaacgc gaccctgttt ccaagaaaaa aaaaaagtcc gggatgagtt ttactgggct 170820

gagatcagtg tagacaaggc tgccctctct ctggaggctc tagggcagaa tctgtttcct 170880

tgtcttttcc agcttctaga ggttgcctgc attccttggc ttgtggcccc ttcctccgtg 170940

ttcaaagcca ttggtgtaac atcttcaggt ctctgtgact ccgatccttg cttccatctt 171000

ataaggatcc ttgtgatttc attgtaccca tccagatatc ccaggagaat ctttccatcc 171060

caagatccat aacttaaatc ccatctgcaa agtccctttt gccatgtgtg gtaatatatt 171120

cacagcttgc agagatcagg acatgggcat ctttgggaaa cgggaagggg gcattatttg 171180

acctaacatc aagagcatga gatgtttttg taaaatgaaa caaatgttgc agcttcctaa 171240

tgcagcttct taggcccacc tgcaggcccc cttgacgttg gtttttctct acctaggtct 171300

gttgtgtcgg gtctggactc ccctgccaag actagctcca tggaaaagaa acttctcatc 171360

aaaagcaaag agctacaaga ctctcaggac aagtgtcaca aggtatttat ttccgcagcc 171420

ggcctccttc cttgctccag gatcctcccg tccgtatatg ccaagggatc cgcccggggc 171480

cgctgctggc tctgagccgc ctgatccgta gagagtgagg cgctcctgcc ttcgctgaag 171540

tcgcgcctcc agcagctcag agggagatga attcgggcct tgctgttgct gtaaatcctt 171600

taaatctaaa ccagaggagg ccctggattt aaacagtccg tttctcagca tgacccagcc 171660

agatgtctgc ttcttccggc aggtggcctg ggtcctcacc tgtggctgag atacatccca 171720

tctgctttga gtgatgcgaa gtctctcttc ctagtctttt aaaactcctg cttatgtcac 171780

tgcggccact gtgttgatta cgctcaacgt ctcttaacat tcactgttcc tgcccagagg 171840

caacgctctg gaaactaata agtcactgct tgcctgggac tcctaagagt gcagacgaat 171900

aaatatctcc ttgccctgtc ctggatttgt cctctagatc tttgcaagga gatggggggg 171960

gatcaagatg gatttgggat aaaattaaag tgacgtctgc aaaaacaaaa caaaaacaaa 172020

agcaaacagg tgaaaaatga tgattgtggc ttccttgcta actgggttag agaagtgatc 172080

aagtgtgaac cgggacttga atgagaggag tgacttagca tttggtgact gtccttaacg 172140

aagaactgtg cgctcctggg cgaagaaaca atggtatttc catcccaact taacttttgg 172200

cgaattagcc ttagcccaga ccaccaggtg gtttcggagg ctacttgaga tgtgattgct 172260

cctaatgaac ctccacgggc ctttttaacc tgtcgatgtg tttatttcag atggagcagg 172320

aaatgacccg gttacatcgg agagtgtcag aggtggaggc tgtgcttagt cagaaggagg 172380

tggagctgaa ggcctctgag actcagagat ccctcctgga gcaggacctt gctacctaca 172440

tcacagaatg cagtgtgagc cttccctgaa gcccccttcc cttggaggtg gcacttcctg 172500

ttgtgtgtgt ctcatcctgt ttcatgatga ctccatgagg cacatcacag ccaatggcag 172560

agagtagaga gagggagagc acaaaagcaa gatctgtgtt ttgcagagta gtgagagcca 172620

ggcgtaaggt ccccaagaaa tgagattgga ctcatttcca gcagaaagtg caggtagacg 172680

gctggtacca tggagtctgg agatgggagt aattcatctt tgccgcaagt tgcaaaagat 172740

cttaacatct cccatcccag cctctgtggt ctgcgttgtg tctgacatga gcagccttga 172800

gaaccagact cccaactatg tacaagaaaa cttactttca atcttcctga catcaaattt 172860

tccattggcc agaaccagtg tagtgacaag aaaatagcct tgaaaaccca gaccctctgt 172920

cattatttac catgtgactt tcattttttc tttccttcac aagagtagac tgtcttcttc 172980

tccattgtct tgttaaattt ttcattcagg tgttttttaa tgtgcccaat taaacagtct 173040

caagaagttg aatcacacat ttctaaagtt tttttcacaa gggagaggaa atctatagaa 173100

cgtggctgat taagaataac tgctatgttt ccattccaga cttggctgcc tttcagtggt 173160

gggtgaagtt attcagctat gtatttcaga tatagatttc agtgccatga agcataaggg 173220

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 173280

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 173340

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 173400

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 173460

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn tgattctcct 173520

gcctcagcct cccgagtagc tgggactaca ggcatgcacc accatgccca gctaattttt 173580

gtatttttag taaagacggg gtttcaccat gttggccagg gtggtctcga tctcttgacc 173640

ttgtgatccg cctgcctcgg cctcccaaag tgctgggatt acaggtgtga gccactgtgc 173700

ccagcccata aatcaaaatt ttttcagcaa ttgttataca agtggaacct tactcttcaa 173760

atgcaattgt ccagtgtctg gcttaatgtc tgctgttgtc agaaaccatg tgaatggagt 173820

agattcccag gttataagga gcccccaggg aggatgcgcg agtcactggc ttctccaggg 173880

gtctctggtt tggggttgcc ttggtgctgg gcacacttcc tggagatttt actggaccag 173940

cctgaggcct ttggggctct gtgcagatgc tctacttctg acttgtctag agctttcttc 174000

taattctgga ctaaaagcaa gcaggagttt ggaggatgat ggtgagaatt cacatccccg 174060

agttggcttt tggaatgcag tagtttgtga gatttagtgt tttttttaag aagtatattc 174120

agatcttgcc tttttcccag aaagcatatg agacaacttc caagacattt atagcatggc 174180

taataaaatg ggaaatcagg gcgaaggaca ggagaactca ataagggtta acatggctac 174240

agcgattgtc taaatgggtt ctttttgctg gccagagcag aaaggatcat gcagtaaagt 174300

gggggggaag aaagggaatt gaatggtagg tgaagacttc atgttggtgc caggcactgt 174360

gccaggccct cctaggacct tgtcttactc aatcctcaca cagtgctgca agaggattag 174420

tcttatccct gttttagaga ggatgaaact gaaaggcagc gaggtgaagt caccagcagg 174480

aggctgaagc cgc 174493

4

494

Mus Musculus

4

Met Leu Lys Phe Lys Tyr Gly Val Arg Asn Pro Pro Glu Ala Ser Ala

1 5 10 15

Ser Glu Pro Ile Ala Ser Arg Ala Ser Arg Leu Asn Leu Phe Phe Gln

20 25 30

Gly Lys Pro Pro Leu Met Thr Gln Gln Gln Met Ser Ala Leu Ser Arg

35 40 45

Glu Gly Met Leu Asp Ala Leu Phe Ala Leu Phe Glu Glu Cys Ser Gln

50 55 60

Pro Ala Leu Met Lys Met Lys His Val Ser Ser Phe Val Gln Lys Tyr

65 70 75 80

Ser Asp Thr Ile Ala Glu Leu Arg Glu Leu Gln Pro Ser Ala Arg Asp

85 90 95

Phe Glu Val Arg Ser Leu Val Gly Cys Gly His Phe Ala Glu Val Gln

100 105 110

Val Val Arg Glu Lys Ala Thr Gly Asp Val Tyr Ala Met Lys Ile Met

115 120 125

Lys Lys Lys Ala Leu Leu Ala Gln Glu Gln Val Ser Phe Phe Glu Glu

130 135 140

Glu Arg Asn Ile Leu Ser Arg Ser Thr Ser Pro Trp Ile Pro Gln Leu

145 150 155 160

Gln Tyr Ala Phe Gln Asp Lys Asn Asn Leu Tyr Leu Val Met Glu Tyr

165 170 175

Gln Pro Gly Gly Asp Phe Leu Ser Leu Leu Asn Arg Tyr Glu Asp Gln

180 185 190

Leu Asp Glu Ser Met Ile Gln Phe Tyr Leu Ala Glu Leu Ile Leu Ala

195 200 205

Val His Ser Val His Gln Met Gly Tyr Val His Arg Asp Ile Lys Pro

210 215 220

Glu Asn Ile Leu Ile Asp Arg Thr Gly Glu Ile Lys Leu Val Asp Phe

225 230 235 240

Gly Ser Ala Ala Lys Met Asn Ser Asn Lys Val Asp Ala Lys Leu Pro

245 250 255

Ile Gly Thr Pro Asp Tyr Met Ala Pro Glu Val Leu Thr Val Met Asn

260 265 270

Glu Asp Arg Arg Gly Thr Tyr Gly Leu Asp Cys Asp Trp Trp Ser Val

275 280 285

Gly Val Val Ala Tyr Glu Met Val Tyr Gly Lys Thr Pro Phe Thr Glu

290 295 300

Gly Thr Ser Ala Arg Thr Phe Asn Asn Ile Met Asn Phe Gln Arg Phe

305 310 315 320

Leu Lys Phe Pro Asp Asp Pro Lys Val Ser Ser Glu Leu Leu Asp Leu

325 330 335

Leu Gln Ser Leu Leu Cys Val Gln Lys Glu Arg Leu Lys Phe Glu Gly

340 345 350

Leu Cys Cys His Pro Phe Phe Ala Arg Thr Asp Trp Asn Asn Ile Arg

355 360 365

Asn Ser Pro Pro Pro Phe Val Pro Thr Leu Lys Ser Asp Asp Asp Thr

370 375 380

Ser Asn Phe Asp Glu Pro Glu Lys Asn Ser Trp Ala Phe Ile Leu Cys

385 390 395 400

Val Pro Ala Glu Pro Leu Ala Phe Ser Gly Glu Glu Leu Pro Phe Val

405 410 415

Gly Phe Ser Tyr Ser Lys Ala Leu Gly Tyr Leu Gly Arg Ser Glu Ser

420 425 430

Val Val Ser Ser Leu Asp Ser Pro Ala Lys Val Ser Ser Met Glu Lys

435 440 445

Lys Leu Leu Ile Lys Ser Lys Glu Leu Gln Asp Ser Gln Asp Lys Cys

450 455 460

His Lys Val Ser Ile Ser Thr Ala Gly Leu Arg Pro Cys Ser Arg Ile

465 470 475 480

Leu Gln Ser Ile Tyr Ala Glu Gly Ser Ala Gly Gly His Cys

485 490