Patent application title: PORCINE CMP-N-ACETYLNEURAMINIC ACID HYDROXYLASE GENE

Inventors: Chihiro Koike (Pittsburgh, PA, US)
IPC8 Class: AA01K67027FI
USPC Class: 800 17
Class name: Swine
Publication date: 02/19/2009
Patent application number: 20090049562

Abstract:

The present invention provides porcine CMP-N-Acetylneuraminic-Acid Hydroxylase (CMP-Neu5Ac hydroxylase) protein, cDNA, and genomic DNA regulatory sequences. Furthermore, the present invention includes porcine animals, tissues, and organs, as well as cells and cell lines derived from such animals, tissues, and organs, which lack expression of functional CMP-Neu5Ac hydroxylase. Such animals, tissues, organs, and cells can be used in research and in medical therapy, including in xenotransplantation, and in industrial livestock farming operations.

Claims:

1-66. (canceled)

67. A targeting vector for homologous recombination in a somatic cell comprising a marker sequence and a sequence homologous to a porcine genomic CMP-N-acetylneuraminic-acid (CMP-Neu5Ac) hydroxylase sequence, wherein said homologous sequence is sufficient to provide targeted insertion of the selectable marker sequence into a target CMP-Neu5Ac gene in a host.

68. The targeting vector of claim 67 wherein said vector comprises:i. a first nucleotide sequence comprising at least 17 contiguous nucleotides of the porcine genomic CMP-Neu5Ac hydroxylase sequence;ii. a second nucleotide sequence comprising at least 17 contiguous nucleotides of the porcine genomic CMP-Neu5Ac hydroxylase sequence; andiii. a marker sequence;wherein said first and second nucleotide sequences do not overlap.

69. The targeting vector of claim 68 wherein the selectable marker gene is green fluorescent protein.

70. The targeting vector of claim 68 wherein the first nucleotide sequence represents a 5' recombination arm.

71. The targeting vector of claim 68 wherein the second nucleotide sequence represents a 3' recombination arm.

72. The targeting vector of claim 68 wherein the first or second nucleotide sequence is homologous to Intron 5 of porcine genomic CMP-Neu5Ac hydroxylase sequence.

73. The targeting vector of claim 68 wherein the first or second nucleotide sequence is homologous to Intron 6 of the porcine genomic CMP-Neu5Ac hydroxylase sequence.

74. The targeting vector of claim 68 wherein the first or second nucleotide sequence comprises at least 50 contiguous nucleotides of the porcine genomic CMP-Neu5Ac hydroxylase sequence.

75. The targeting vector of claim 68 wherein the first or second nucleotide sequence comprises at least 100 contiguous nucleotides of the porcine genomic CMP-Neu5Ac hydroxylase sequence.

76. The targeting vector of claim 68 wherein the first or second nucleotide sequence comprises at least 150 contiguous nucleotides of the porcine genomic CMP-Neu5Ac hydroxylase sequence.

77. A cell transfected with the targeting vector of claim 67.

78. The cell of claim 77 wherein at least one allele of a porcine CMP-Neu5Ac gene has been rendered inactive via homologous recombination.

79. A porcine animal comprising the cell of claim 78.

80. The animal of claim 79 wherein at least one allele of a porcine CMP-Neu5Ac hydroxylase gene has been rendered inactive via homologous recombination.

81. An organ obtained from the animal of claim 80.

82. A tissue obtained from the animal of claim 80.

83. The organ of claim 81 wherein the organ is selected from the group consisting of heart, lung, kidney and liver.

84. A method to produce genetically modified cells comprising: (a) transfecting a porcine cell with the targeting vector of claim 67; and (b) selecting a transfected cell in which at least one allele of a porcine CMP-N-acetylneuraminic-acid (CMP-Neu5Ac) hydroxylase gene has been rendered inactive.

85. The method of claim 84 further comprising: (c) transferring the nucleus of the selected transfected cell into an enucleated oocyte to produce an embryo; and (d) allowing the embryo to develop into a non-human animal wherein at least one allele of a porcine CMP-Neu5Ac hydroxylase gene has been rendered inactive.

Description:

CROSS REFERENCE TO RELATED APPLICATIONS

[0001]This application claims priority to U.S. Provisional patent application Ser. No. 60/476,396, filed Jun. 6, 2003.

FIELD OF THE INVENTION

[0002]The present invention provides porcine CMP-N-Acetylneuraminic-Acid Hydroxylase (CMP-Neu5Ac hydroxylase) protein, cDNA, and genomic DNA regulatory sequences. Furthermore, the present invention includes porcine animals, tissues, and organs, as well as cells and cell lines derived from such animals, tissues, and organs, which lack expression of functional CMP-Neu5Ac hydroxylase. Such animals, tissues, organs, and cells can be used in research and in medical therapy, including in xenotransplantation, and in industrial livestock farming operations. In addition, methods are provided to prepare organs, tissues, and cells lacking the porcine CMP-Neu5Ac hydroxylase gene for use in xenotransplantation.

BACKGROUND OF THE INVENTION

[0003]The unavailability of acceptable human donor organs, the low rate of long term success due to host versus graft rejection, and the serious risks of infection and cancer are the main challenges now facing the field of tissue and organ transplantation. Because the demand for acceptable organs exceeds the supply, many people die each year while waiting for organs to become available. To help meet this demand, research has been focused on developing alternatives to allogenic transplantation. Dialysis is available to patients suffering from kidney failure, artificial heart models have been tested, and other mechanical systems have been developed to assist or replace failing organs. Such approaches, however, are quite expensive. The need for frequent and periodic access to dialysis machines greatly limits the freedom and quality of life of patients undergoing such therapy.

[0004]Xenograft transplantation represents a potentially attractive alternative to artificial organs for human transplantation. The potential pool of nonhuman organs is virtually limitless. Pigs are considered the most likely source of xenograft organs. The supply of pigs is plentiful, breeding programs are well established, and their organ size and physiology are compatible with humans. Therefore, xenotransplantation with pig organs offers a potential solution to the shortage of organs available for clinical transplantation.

[0005]Host rejection of such cross-species tissue remains a major concern in this area. The immunological barriers to xenotransplantation have been, and remain, formidable. The first immunological hurdle is "hyperacute rejection" (HAR). HAR is defined by the ubiquitous presence of high titers of pre-formed natural antibodies binding to the foreign tissue. The binding of these natural antibodies to target epitopes on the donor organ endothelium is believed to be the initiating event in HAR. This binding, within minutes of perfusion of the donor organ with the recipient blood, is followed by complement activation, platelet and fibrin deposition, and ultimately by interstitial edema and hemorrhage in the donor organ, all of which cause failure of the organ in the recipient (Strahan, et al. (1996) Frontiers in Bioscience 1, pp. 34-41).

[0006]Some noted xenotransplants of organs from apes or old-world monkeys (e.g., baboons) into humans have been tolerated for months without rejection. However, such attempts have ultimately failed due to a number of immunological factors. Even with heavy immunosuppression to suppress HAR, a low-grade innate immune response, attributable in part to failure of complement regulatory proteins (CRPs) within the graft tissue to control activation of heterologous complement on graft endothelium, ultimately leads to destruction of the transplanted organs (Starzl, Immunol. Rev., 141, 213-44 (1994)). In an effort to develop a pool of acceptable organs for xenotransplantation into humans, researchers have engineered animals that produce human CRPs, an approach which has been demonstrated to delay, but not eliminate, xenograft destruction in primates (McCurry, et al., Nat. Med., 1, 423-27 (1995); Bach et al., Immunol. Today, 17, 379-84 (1996)).

[0007]In addition to complement-mediated attack, human rejection of discordant xenografts appears to be mediated by a common antigen: the galactose-α(1,3)-galactose (gal-α-gal) terminal residue of many glycoproteins and glycolipids (Galili et al., Proc. Nat. Acad. Sci., (USA), 84, 1369-73 (1987); Cooper, et al., Immunol. Rev., 141, 31-58 (1994); Galili, et al., Springer Sem. Immunopathol, 15, 155-171 (1993); Sandrin, et al., Transplant Rev., 8, 134 (1994)). This antigen is chemically related to the human A, B, and O blood antigens, and it is present on many parasites and infectious agents, such as bacteria and viruses. Most mammalian tissue also contains this antigen, with the notable exception of old world monkeys, apes and humans. (see, Joziasse, et al., J. Biol. Chem., 264, 14290-97 (1989). Individuals without such carbohydrate epitopes produce abundant naturally occurring antibodies (IgM as well as IgG) specific to the epitopes. Many humans show significant levels of circulating IgG with specificity for gal-α-gal carbohydrate determinants (Galili, et al., J. Exp. Med., 162, 573-82 (1985); Galili, et al., Proc. Nat. Acad. Sci. (USA), 84, 1369-73 (1987)). The α-galactosyltransferase (α-GT) enzyme catalyzes the formation of gal-α-gal moieties. Research has focused on the modulation or elimination of this enzyme to reduce or eliminate the expression of gal-α-gal moieties on the cell surface of xenotissue.

[0008]The elimination of the α-galactosyltransferase gene from porcine has long been considered one of the most significant hurdles to accomplishing xenotransplantation from pigs to humans. Two alleles in the pig genome encode the α-GT gene. Single allelic knockouts of the α-GT gene in pigs were reported in 2002 (Dai, et al. Nature Biotechnol., 20:251 (2002); Lai, et al., Science, 295:1089 (2002)).

[0009]Recently, double allelic knockouts of the α-GT gene have been accomplished (Phelps, et al., Science, 299: pp. 411-414 (2003)). WO 2004/028243 to Revivicor Inc. describes porcine animal, tissue, organ, cells and cell lines, which lack all expression of functional α1,3 galactosyltransferase (α1,3-GT). Accordingly, the animals, tissues, organs and cells lacking functional expression of α1,3-GT can be used in xenotransplantation and for other medical purposes.

[0010]PCT patent application WO 2004/016742 to Immerge Biotherapeutics, Inc. describes α(1,3)-galactosyltransferase null cells, methods of selecting GGTA-1 null cells, α(1,3)-galactosyltransferase null swine produced therefrom (referred to as a viable GGTA-1 null swine), methods for making such swine, and methods of using cells, tissues and organs of such a null swine for xenotransplantation.

[0011]One of the earliest known xenoantigens other than gal-α-gal is an epitope that Hanganutiu Deicher antibodies recognize, and which have long been associated with serum disease. The epitope has been identified as N-glycolylneuraminic acid (Neu5Gc), a member of the sialic acid family of carbohydrates. Among carbohydrates, sialic acids are abundant and ubiquitous. Sialic acid is a generic designation used for N-acylneuraminic acids (Neu5Acyl) and their derivatives. N-Acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are two of the most abundant derivatives of sialic acids.

[0012]The Neu5Gc epitope is located in the terminal position in the glycan chains of glycoconjugates. Due to this exposed position, it plays an important role in cellular recognition, e.g. in the case of inflammatory reactions, maturation of immune cells, differentiation processes, hormone-, pathogen- and toxin binding (Varki, A., Glycobiology, 2, pp. 25-40 (1992)).

[0013]Glycoconjugates containing Neu5Gc are immunogenic in humans. In healthy humans, Neu5Gc is not detectable, although Neu5Gc is abundant in most mammals. The lack of Neu5Gc in man is due to an exon deletion in the human gene that prevents the formation of functional enzyme (Chou, H. H., et al. Proc. Natl. Acad. Sci. (USA), 95, pp. 11751-11756 (1998); Irie, A., et al. J. Biol. Chem., 273, pp. 15866-15871 (1998)). Thus, Neu5Gc-containing glycoconjugates act as antigens and can induce the formation of antibodies. Historically, the antibodies have been referred to as Hanganutziu-Deicher (HD) antigens and antibodies (Hanganutziu, M., CR Soc. Biol. (Paris), 91, p. 1457 (1924); Deicher, H., Z. Hyg., 106, p. 561 (1926)). Hanganutziu-Deicher antigens are detectable in many human tumors (colon carcinoma, retinoblastoma, melanoma and carcinoma of the breast) as well as in chicken tumor tissues (Higashi, H., et al. Cancer Res., 45, pp. 3796-3802 (1985)). Although the amount of antigen in tumors is very small (usually less than 1% of the total amount of sialic acid, often in the range of from 0.01 to 0.1%), it is capable of inducing the formation of Hanganutziu-Deicher antibodies (Higashihara, T., et al., Int Arch Allergy Appl Immunol., 95, pp. 231-235 (1991)). This immunological reaction is a potential barrier to xenotransplantation of Neu5Gc-containing pig organs to humans.

[0014]The Neu5Gc epitope is formed by the addition of a hydroxyl group to the N-acetyl moiety of Neu5Ac. The enzyme that catalyzes the hydroxylation is CMP-Neu5Ac hydroxylase. Thus, the expression of the CMP-Neu5Ac hydroxylase gene determines the presence of the Neu5Gc epitope on cell surfaces. Purification studies of CMP-Neu5Ac hydroxylase in mammals have shown that it is a soluble, cytosolic oxygenase that is dependent on cytochrome b5 and cytochrome b5 reductase (Kawano, T., et al., J. Biol. Chem., 269, pp. 9024-9029 (1994); Schneckenburger, P., et al., Glycoconj. J., 11, pp. 194-203 (1994); Schlenzka, W., et al., Glycobiology, 4, pp. 675-683 (1994); Kozutsumi, Y., et al., J. Biochem. (Tokyo), 108, pp. 704-706 (1990); and, Shaw, L., et al. Eur. J. Biochem., 219, pp. 1001-1011 (1994)).

[0015]Another important feature of Neu5Gc is that it acts as an adhesion molecule for pathogens, allowing for entry into the cell (Kelm, S. and Schauer, R., Int. Rev. Cytol, 179, pp. 137-240 (1997)). This causes disease and economic losses in certain livestock species. Specifically, enterotoxigenic Escherichia coli with K99 fimbriae infect newborn piglets by binding to Neu5Gc in gangliosides such as Nue5Gcα2→3Galβ1→4Glcβ1→1' ceramide [GM3(Neu5Gc)], N-glycolylsialoparagloboside and GM2(Neu5Gc) attached to intestinal absorptive and mucus secreting cells, causing a potentially lethal diarrhea (Malykh, Y., et. al., Biochem. J., 370, pp. 601-607 (2003); Kyogashima, M., et al., (1993); Teneberg, S., et al., FEBS Letters, 263, pp. 10-14 (1990); Isobe, T., et al., Anal. Biochem., 236, pp. 35-40 (1996); Lindahl, M. and Carlstedt, I., J. Gen. Microbiol., 136, pp. 1609-1614 (1990); King, T. P., et al., Proceedings of the 6^th International Symposium on Digestive Physiology in Pigs, pp. 290-293, (1994)). Pig rotavirus infects pig newborns causing diarrhea by binding to GM3(Neu5Gc). Pig transmissible gastroenteritis coronavirus infects pigs via entry into glycoconjugates containing α2,3-bound Neu5Gc (Schultz, B., et al., J. Virol., 70, pp. 5634-5637 (1996)).

[0016]CMP-Neu5Ac hydroxylase has been isolated from mouse liver and pig submandibular glands to homogeneity and characterized (Kawano, T., et al., J. Biol. Chem., 269, pp. 9024-9029 (1994); Schneckenburger, P., et al., Glycoconj. J., 11, pp. 194-203 (1994); and, Schlenzka, W., et al., Glycobiology, 4, pp. 675-683 (1994)).

[0017]Schlenzka, et al. (Glycobiology, Vol. 4, pp. 675-683 (1994)) purified the enzyme from pig submandibular glands using ion exchange chromatography, chromatography with immobilized triazin dyes, hydrophobic interaction chromatography and gel filtration. Schneckenburger et al. (Glycoconj. J., Vol. 11, pp. 194-203 (1994)) isolated the CMP-Neu5Ac hydroxylase from mouse liver. Both the CMP-Neu5Ac hydroxylase from pig submandibular glands and the one from mouse liver are soluble monomers having a molecular weight of 65 kDa. Their catalytic interactions with CMP-Neu5Ac and cytochrome b5 are very similar to one another. The activity of these enzymes seems to be dependent on an iron-containing prosthetic group.

[0018]JP-A 06 113838 describes the protein and DNA sequences of murine CMP-Neu5Ac hydroxylase, as well as a monoclonal antibody that specifically binds to the hydroxylase.

[0019]PCT Publication No. WO 97/03200A1 to Boehringer Manheim GMBH discloses a partial cDNA for the porcine CMP-Neu5Ac hydroxylase. This application discloses a cDNA sequence beginning in the middle of Exon 8 of the CMP-Neu5Ac hydroxylase gene (further disclosed as GenBank accession number Y15010).

[0020]Martensen, L., et al. (Eur. J. Biochem., Vol. 268, pp. 5157-5166 (2001)) discloses a full length amino acid sequence of porcine CMP-Neu5Ac hydroxylase.

[0021]PCT Publication No. WO 02/088351 to RBC Biotechnology discloses a partial cDNA and genomic sequence (exons 7-11 as well as partial genomic sequence surrounding each exon) of porcine CMP-NeuAc hydroxylase. In addition, methods are provided to generate porcine cells and animals lacking the CMP-NeuAc hydroxylase epitope, optionally, in combination with other genetic modifications, such as inactivation of the alpha-1,3-galactosyltransferase gene and/or insertion of complement proteins.

[0022]It is an object of the present invention to provide genomic and regulatory sequences of the porcine CMP-Neu5Ac hydroxylase gene.

[0023]It is an object of the present invention to provide the full length cDNA, as well as novel variants of the CMP-Neu5Ac hydroxylase gene.

[0024]It is another object of the invention to provide novel nucleic acid and amino acid sequences that encode the CMP-Neu5Ac hydroxylase gene.

[0025]It is yet a further object of the present invention to provide cells, tissues and/or organs deficient in the CMP-Neu5Ac hydroxylase gene.

[0026]It is another object of the present invention to generate animals, particularly pigs, lacking a functional CMP-Neu5Ac hydroxylase gene.

[0027]It is yet a further object of the present invention to provide cells, tissues and/or organs deficient in the CMP-Neu5Ac hydroxylase gene for use in xenotransplantation of non-human organs to human recipients in need thereof.

SUMMARY OF THE INVENTION

[0028]The full length cDNA sequence, peptide sequence, and genomic organization of the porcine CMP-Neu5Ac hydroxylase gene has been determined. To date, only partial cDNA and genomic sequences have been identified. The present invention provides novel porcine CMP-Neu5Ac hydroxylase protein, cDNA, cDNA variants, and genomic DNA sequence. Furthermore, the present invention includes porcine animals, tissues, and organs, as well as cells and cell lines derived from such animals, tissue, and organs, which lack expression of functional CMP-Neu5Ac hydroxylase. Such animals, tissues, organs, and cells can be used in research and in medical therapy, including xenotransplantation. In addition, methods are provided to prepare organs, tissues, and cells lacking the porcine CMP-Neu5Ac hydroxylase gene for use in xenotransplantation.

[0029]One aspect of the present invention provides the full length cDNA of porcine CMP-Neu5Ac hydroxylase. The full length cDNA is shown in Table 1 (SEQ ID No 1) and the full length peptide sequence is provided in Table 2 (SEQ ID No 2). The start codon for the full-length cDNA is located in the 3' portion of Exon 4, and the stop codon is found in the 3' portion of Exon 17. Nucleotide and amino acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to SEQ ID Nos 1 or 2 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 15, 17, 20, 25 or 30 nucleotide or amino acid sequences of SEQ ID Nos 1 or 2 are also provided. Further provided is any nucleotide sequence that hybridizes, optionally under stringent conditions, to SEQ ID No 1, as well as, nucleotides homologous thereto.

[0030]In one embodiment, nucleic acid and peptide sequences encoding three novel variants of CMP-Neu5Ac hydroxylase are provided (Tables 3-8, FIG. 2). SEQ ID No 3 represents the cDNA of a variant of the gene, variant-1, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15a, 16, 17, and 18. SEQ ID No 5 represents the cDNA of a variant of the gene, variant-2, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 12a. SEQ ID No 7 represents the cDNA of a variant of the gene, variant-3, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11 and 11a. SEQ ID Nos 4, 6 and 8 represent the amino acid sequences of variant-1, variant-2 and variant-3, respectively. Nucleotide and amino acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to SEQ ID Nos 3-8 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 15, 17, 20, 25, or 30 nucleotide or amino acid sequence of SEQ ID Nos 3-8 are also provided. Further provided is any nucleotide sequence that hybridizes, optionally under stringent conditions, to SEQ ID Nos 3, 5 and 7, as well as, nucleotides homologous thereto.

[0031]A further embodiment provides nucleic acid sequences representing genomic DNA sequences of the CMP-Neu5Ac hydroxylase gene (Table 9, FIG. 1). SEQ ID Nos 10-28 represent Exons 1, 4-11, 11a, 12, 12a, 13-15, 15a, 16-18, respectively, and SEQ ID Nos 29-45 represent Introns 1a, 1b, 4-15, 15a, 16, and 17, respectively. SEQ ID No. 9 represents the 5' untranslated region of the CMP-Neu5Ac hydroxylase gene. SEQ ID No. 46 (Table 10) represents the genomic DNA and regulatory sequence of CMP-Neu5Ac hydroxylase.

[0032]In another embodiment, the genomic sequence of the porcine CMP-Neu5Ac hydroxylase gene is represented by SEQ ID No. 47. SEQ ID No. 47 represents the 5' contiguous genomic sequence containing 5' UTR, Exon 1 and a portion of intronic sequence located 3' of Exon 1 (Table 11).

[0033]In another embodiment, the genomic sequence of the porcine CMP-Neu5Ac hydroxylase gene is represented by SEQ ID No. 48. SEQ ID NO. 48 represents a contiguous genomic sequence containing intronic sequence located 5' to Exon 4, Exon 4, Intron 4, Exon 5, Intron 5, Exon 6, Intron 6, Exon 7, Intron 7, Exon 8, Intron 8, Exon 9, Intron 9, Exon 10, Intron 10, Exon 11, Intron 11, Exon 12, Intron 12, Exon 13, Intron 13, Exon 14, Intron 14, Exon 15, Intron 15, Exon 16, Intron 16, Exon 17, Intron 17, and Exon 18 (Table 12). In addition, nucleotide sequences that contain at least 2775, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500 or 10,000 contiguous nucleotides of SEQ ID NO. 48 are provided, as well as nucleotide sequences at least 80, 85, 90, 95, 98, or 99% homologous to SEQ ID NO. 48.

[0034]In another embodiment, the genomic sequence of the porcine CMP-Neu5Ac hydroxylase gene is represented by SEQ ID No. 49. SEQ ID NO. 49 represents contiguous genomic sequences containing Intronic sequence 5' to Exon 4, Exon 4, Intron 4, Exon 5, Intron 5, Exon 6, Intron 6, Exon 7, Intron 7 and Exon 8. Further, nucleotide sequences that contain at least 1750, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10000, 11000, 12000, 13000, 14000, 15000, 16000, 17000, 18000, 19000, or 20000 contiguous nucleotides of SEQ ID NO. 49 are provided, as well as nucleotide sequences at least 80, 85, 90, 95, 98, or 99% homologous to SEQ ID NO. 49.

[0035]In another embodiment, the genomic sequence of the porcine CMP-Neu5Ac hydroxylase gene is represented by SEQ ID No. 50. SEQ ID NO. 50 represents contiguous genomic sequences containing Exon 12, Intron 12, Exon 13, Intron 13, Exon 14, Intron 14, Exon 15, Intron 15, Exon 16, Intron 16, Exon 17, Intron 17, and Exon 18 are provided. Nucleotide sequences that contain at least 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10000, 11000, 12000, 13000, 14000, 15000, 16000, 17000, 18000, 19000 or 20,000 contiguous nucleotides of SEQ ID NO. 50 are provided, as well as nucleotide sequences at least 80, 85, 90, 95, 98, or 99% homologous to SEQ ID NO. 50.

[0036]In further embodiments, nucleotide and amino acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to SEQ ID Nos 9-45, 46, 47, 48, 49 and 50 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 15, 17, 20, 25, 30, 50, 100, 150, 200, 300, 400, 500 or 1000 contiguous nucleotide or amino acid sequences of SEQ ID Nos 9-45, 46, 47, and 48 are also provided. Further provided is any nucleotide sequence that hybridizes, optionally under stringent conditions, to SEQ ID Nos 9-45, 46, 47, 48, 49 and 50, as well as, nucleotides homologous thereto.

[0037]Another aspect of the present invention provides nucleic acid constructs that contain cDNA or variants thereof encoding CMP-Neu5Ac hydroxylase. These cDNA sequences can be derived from Seq ID Nos. 1-8, or any fragment thereof. Constructs can contain one, or more than one, internal ribosome entry site (IRES). The construct can also contain a promoter operably linked to the nucleic acid sequence encoding CMP-Neu5Ac hydroxylase, or, alternatively, the construct can be promoterless. In another embodiment, nucleic acid constructs are provided that contain nucleic acid sequences that permit random or targeted insertion into a host genome. In addition to the nucleic acid sequences the expression vector can contain selectable marker sequences, such as, for example, enhanced Green Fluorescent Protein (eGFP) gene sequences, initiation and/or enhancer sequences, poly A-tail sequences, and/or nucleic acid sequences that provide for the expression of the construct in prokaryotic and/or eukaryotic host cells.

[0038]In another embodiment, nucleic acid targeting vectors constructs are also provided wherein homologous recombination in somatic cells can be achieved. These targeting vectors can be transformed into mammalian cells to target the CMP-Neu5Ac hydroxylase gene via homologous recombination. In one embodiment, the targeting vectors can contain a 3' recombination arm and a 5' recombination arm that is homologous to the genomic sequence of a CMP-Neu5Ac hydroxylase. The homologous DNA sequence can include at least 15 bp, 20 bp, 25 bp, 50 bp, 100 bp, 500 bp, 1 kbp, 2 kbp, 4 kbp, 5 kbp, 10 kbp, 15 kbp, 20 kbp, or 50 kbp of sequence homologous to the CMP-Neu5Ac hydroxylase sequence. In another embodiment, the homologous DNA sequence can include one or more intron and/or exon sequences. In a specific embodiment, the DNA sequence can be homologous to Intron 5 and Intron 6 of the CMP-Neu5Ac hydroxylase gene (see, for example, FIGS. 6-8). In another specific embodiment, the DNA sequence can be homologous to Intron 5, a 55 bp portion of Exon 6, and Intron 6 of the CMP-Neu5Ac hydroxylase gene, and contain enhanced Green Fluorescent Protein sequence in an in-frame orientation 3' to the 55 bp portion of Exon 6 (see, for example, FIGS. 10 and 11).

[0039]Another embodiment of the present invention provides oligonucleotide primers capable of hybridizing to porcine CMP-Neu5Ac hydroxylase cDNA or genomic sequence, such as Seq ID Nos. 1, 3, 5, 7, 9-45, 46, 47 or 48. In a preferred embodiment, the primers hybridize under stringent conditions to SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47 or 48. Another embodiment provides oligonucleotide probes capable of hybridizing to porcine CMP-Neu5Ac hydroxylase nucleic acid sequences, such as SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, or 48. The polynucleotide primers or probes can have at least 14 bases, 20 bases, preferably 30 bases, or 50 bases which hybridize to a polynucleotide of the present invention. The probe or primer can be at least 14 nucleotides in length, and in a preferred embodiment, are at least 15, 20, 25, 28, or 30 nucleotides in length.

[0040]In another aspect of the present invention, mammalian cells lacking at least one allele of the CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein are provided. These cells can be obtained as a result of homologous recombination. Particularly, by inactivating at least one allele of the CMP-NeuAc hydroxylase gene, cells can be produced which have reduced capability for expression of functional Hanganutziu-Deicher antigens.

[0041]In embodiments of the present invention, alleles of the CMP-Neu5Ac hydroxylase gene are rendered inactive according to the process, sequences and/or constructs described herein, such that the resultant CMP-Neu5Ac hydroxylase enzyme can no longer generate Hanganutziu-Deicher antigens. In one embodiment, the CMP-Neu5Ac hydroxylase gene can be transcribed into RNA, but not translated into protein. In another embodiment, the CMP-Neu5Ac hydroxylase gene can be transcribed in an inactive truncated form. Such a truncated RNA may either not be translated or can be translated into a nonfunctional protein. In an alternative embodiment, the CMP-Neu5Ac hydroxylase gene can be inactivated in such a way that no transcription of the gene occurs. In a further embodiment, the CMP-Neu5Ac hydroxylase gene can be transcribed and then translated into a nonfunctional protein.

[0042]In a further aspect of the present invention, porcine animals are provided in which at least one allele of the CMP-Neu5Ac hydroxylase gene is inactivated via a genetic targeting event produced according to the process, sequences and/or constructs described herein. In another aspect of the present invention, porcine animals are provided in which both alleles of the CMP-Neu5Ac hydroxylase gene are inactivated via a genetic targeting event. The gene can be targeted via homologous recombination. In other embodiments, the gene can be disrupted, i.e. a portion of the genetic code can be altered, thereby affecting transcription and/or translation of that segment of the gene. For example, disruption of a gene can occur through substitution, deletion ("knock-out") or insertion ("knock-in") techniques. Additional genes for a desired protein or regulatory sequence that modulate transcription of an existing sequence can be inserted.

[0043]In another aspect of the present invention, porcine cells lacking one allele, optionally both alleles of the porcine CMP-Neu5Ac hydroxylase gene can be used as donor cells for nuclear transfer into enucleated oocytes to produce cloned, transgenic animals. Alternatively, porcine CMP-Neu5Ac hydroxylase knockouts can be created in embryonic stem cells, which are then used to produce offspring. Offspring lacking a single allele of the functional CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein can be breed to further produce offspring lacking functionality in both alleles through mendelian type inheritance. Cells, tissues and/or organs can be harvested from these animals for use in xenotransplantation strategies. The elimination of the Hanganutziu-Deicher antigens can reduce the immune rejection of the transplanted cell, tissue or organ due to the Neu5Gc epitope.

[0044]Alternatively, animals lacking at least one allele of the CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein can be less susceptible or resistant to enterotoxigenic infection and disease such as, for example, E. Coli infection, rotavirus infection, and gastroenteritis coronavirus. Such animals can be used, for example, in commercial farming.

[0045]In one aspect of the present invention, a pig can be prepared by a method in accordance with any aspect of the present invention. Genetically modified pigs can be used as a source of tissue and/or organs for transplantation therapy. A pig embryo prepared in this manner or a cell line developed therefrom can also be used in cell-transplantation therapy. Accordingly, there is provided in a further aspect of the invention a method of therapy comprising the administration of genetically modified cells lacking porcine CMP-Neu5Ac hydroxylase to a patient, wherein the cells have been prepared from an embryo or animal lacking CMP-Neu5Ac hydroxylase. This aspect of the invention extends to the use of such cells in medicine, e.g. cell-transplantation therapy, and also to the use of cells derived from such embryos in the preparation of a cell or tissue graft for transplantation. The cells can be organized into tissues or organs, for example, heart, lung, liver, kidney, pancreas, corneas, nervous (e.g. brain, central nervous system, spinal cord), skin, or the cells can be islet cells, blood cells (e.g. haemocytes, i.e. red blood cells, leucocytes) or haematopoietic stem cells or other stem cells (e.g. bone marrow).

[0046]In another aspect of the present invention, CMP-Neu5Ac hydroxylase-deficient pigs also lack genes encoding other xenoantigens, such as, for example, porcine iGb3 synthase (see, for example, U.S. Patent Application 60/517,524), and/or porcine Forssman synthase (see, for example, U.S. Patent Application 60/568,922). In another embodiment, porcine cells are provided that lack the α1,3 galactosyltransferase gene and the CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein. In another embodiment, porcine α1,3 galactosyltransferase gene knockout cells are further modified to knockout the CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein. In addition, CMP-Neu5Ac hydroxylase deficient pigs produced according to the process, sequences and/or constructs described herein, optionally lacking one or more additional genes associated with an adverse immune response, can be modified to express complement inhibiting proteins, such as, for example, CD59, DAF, and/or MCP can be further modified to eliminate the expression of al least one allele of the CMP-Neu5Ac hydroxylase gene. These animals can be used as a source of tissue and/or organs for transplantation therapy. These animals can be used as a source of tissue and/or organs for transplantation therapy. A pig embryo prepared in this manner or a cell line developed therefrom can also be used in cell-transplantation therapy.

DESCRIPTION OF THE INVENTION

[0047]Elimination of the CMP-Neu5Ac hydroxylase gene produced according to the process, sequences and/or constructs described herein can reduce a human beings immunological response to the Neu5Gc epitope and remove an immunological barrier to xenotransplantation. The present invention is directed to novel nucleic acid sequences encoding the full-length cDNA and peptide. Information about the genomic organization, intronic sequences and regulatory regions of the gene are also provided. In one aspect, the invention provides isolated and substantially purified cDNA molecules having one of SEQ ID Nos: 1, 3, 5 or 7, or a fragment thereof. In another aspect of the invention, DNA sequences comprising the full-length genome of the CMP-NeuAc hydrolase gene are provided in SEQ ID Nos 9-45, 46, 47, 48, 49 or 50 or fragments thereof. In another aspect, primers for amplifying porcine CMP-Neu5Ac hydroxylase cDNA or genomic sequence derived from SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 or 50 are provided. Additionally probes for identifying CMP-Neu5Ac hydroxylase nucleic acid sequences derived from SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 or 50, or fragments thereof are provided. DNA represented by SEQ ID Nos 9-45, 46, 47, 48, 49 or 50, or fragments thereof, can be used to construct pigs lacking functional CMP-Neu5Ac hydroxylase genes. Thus, the invention also provides a porcine chromosome lacking a functional CMP-NeuAc hydroxylase gene and a transgenic pig lacking a functional CMP-NeuAc hydroxylase protein produced according to the process, sequences and/or constructs described herein. Such pigs can be used as tissue sources for xenotransplantation into humans. In an alternate embodiment, CMP-NeuAc hydroxylase-deficient pigs produced according to the process, sequences and/or constructs described herein also lack other genes associated with adverse immune responses in xenotransplantation, such as, for example, the α1,3 galactosyltransferase gene, iGb3 synthetase gene, or FSM synthase gene. In another embodiment, pigs lacking CMP-Neu5Ac hydroxylase produced according to the process, sequences and/or constructs described herein and/or other genes associated with adverse immune responses in xenotransplantation express complement inhibiting factors such as, for example, CD59, DAF, and/or MCP.

BRIEF DESCRIPTION OF THE FIGURES

[0048]FIG. 1 represents the genomic organization of the porcine CMP-Neu5Ac hydroxylase gene. Closed bars depict each numbered exon. The length of the introns between the exons illustrates relative distances. (Open boxes also represent exons that appear in some variants (see FIG. 2); "start" and "stop" denote start and stop codons, respectively) The approximate scale is depicted in the bottom of the figure.

[0049]FIG. 2 depicts cDNA sequences of the CMP-Neu5Ac hydroxylase gene. Variant-1 contains exon 15a in place of exons 14 and 15. Variant-2 contains exon 12a, and variant-3 contains exon 11a. "Start" and "stop" denote the start and stop codons, respectively.

[0050]FIG. 3 illustrates four non-limiting examples of targeting vectors, along with their corresponding genomic organization. The selectable marker gene in this particular non-limiting example is eGFP (enhanced green fluorescent protein). eGFP can be inserted in the DNA constructs to inactivate the porcine CMP-NeuAc hydroxylase gene.

[0051]FIG. 4 illustrates transcription factor binding sites located within exon 1 (228 bp) and its 5'-flanking region spanning 601 bp.

[0052]FIG. 5 depicts oligonucleotide sequences that can be used for DNA construction of porcine CMP-Neu5Ac hydroxylase gene targeting vector.

[0053]FIG. 6 is a schematic diagram illustrating the production of a 3'-arm segment from the porcine CMP-Neu5Ac hydroxylase gene using primers pDH3 and pDH4, and its insertion into a vector (pCRII).

[0054]FIG. 7 is a schematic diagram illustrating the production of a 5'-arm segment from the porcine CMP-Neu5Ac hydroxylase gene using primers pDH1 and pDH2, followed by pDH2a, pDH2b, and pDH2c, and its insertion into a vector (pCRII) in which a 3'-arm has previously been inserted.

[0055]FIG. 8 is a non-limiting example of a schematic illustrating a targeting vector that can be utilized to delete Exon 6 of the porcine CMP-Neu5Ac hydroxylase gene through homologous recombination.

[0056]FIG. 9 represents oligonucleotide sequences used in generating a enhanced green fluorescent protein expression vector for use in a Knock-in strategy.

[0057]FIG. 10 is a schematic illustrating the insertion of a EGFP fragment with a polyA signal into the targeting vector pDHΔex6.

[0058]FIG. 11 is a schematic illustrating a knock-in vector for expression of eGFP.

[0059]FIG. 12 is a schematic illustrating homologous recombination resulting in a frameshift between the targeting cassette DNA construct (pDHΔex6) and genomic DNA.

[0060]FIG. 13 is a schematic illustrating homologous recombination resulting in a frameshift between the targeting cassette DNA construct (pDHΔex6) and genomic DNA.

DEFINITIONS

[0061]A "target DNA sequence" is a DNA sequence to be modified by homologous recombination. The target DNA can be in any organelle of the animal cell including the nucleus and mitochondria and can be an intact gene, an exon or intron, a regulatory sequence or any region between genes.

[0062]A "targeting DNA sequence" is a DNA sequence containing the desired sequence modifications. The targeting DNA sequence can be substantially isogenic with the target DNA.

[0063]A "homologous DNA sequence or homologous DNA" is a DNA sequence that is at least about 80%, 85%, 90%, 95%, 98% or 99% identical with a reference DNA sequence. A homologous sequence hybridizes under stringent conditions to the target sequence, stringent hybridization conditions include those that will allow hybridization occur if there is at least 85% and preferably at least 95% or 98% identity between the sequences.

[0064]An "isogenic or substantially isogenic DNA sequence" is a DNA sequence that is identical to or nearly identical to a reference DNA sequence. The term "substantially isogenic" refers to DNA that is at least about 97-99% identical with the reference DNA sequence, and preferably at least about 99.5-99.9% identical with the reference DNA sequence, and in certain uses 100% identical with the reference DNA sequence.

[0065]"Homologous recombination" refers to the process of DNA recombination based on sequence homology.

[0066]"Gene targeting" refers to homologous recombination between two DNA sequences, one of which is located on a chromosome and the other of which is not.

[0067]"Non-homologous or random integration" refers to any process by which DNA is integrated into the genome that does not involve homologous recombination.

[0068]A "selectable marker gene" is a gene, the expression of which allows cells containing the gene to be identified. A selectable marker can be one that allows a cell to proliferate on a medium that prevents or slows the growth of cells without the gene. Examples include antibiotic resistance genes and genes which allow an organism to grow on a selected metabolite. Alternatively, the gene can facilitate visual screening of transformants by conferring on cells a phenotype that is easily identified. Such an identifiable phenotype can be, for example, the production of luminescence or the production of a colored compound, or the production of a detectable change in the medium surrounding the cell.

[0069]The term "contiguous" is used herein in its standard meaning, i.e., without interruption, or uninterrupted.

[0070]The term "porcine" refers to any pig species, including pig species such as Large White, Landrace, Meishan, Minipig.

[0071]The term "oocyte" describes the mature animal ovum which is the final product of oogenesis and also the precursor forms being the oogonium, the primary oocyte and the secondary oocyte respectively.

[0072]The term "fragment" means a portion or partial sequence of a nucleotide or peptide sequence.

[0073]The terms "derivative" and "analog" means a nucleotide or peptide sequence which retains essentially the same biological function or activity as such nucleotide or peptide. For example, an analog includes a proprotein which can be activated by cleavage of the proprotein portion to produce an active mature polypeptide.

[0074]DNA (deoxyribonucleic acid) sequences provided herein are represented by the bases adenine (A), thymine (T), cytosine (C), and guanine (G).

[0075]Amino acid sequences provided herein are represented by the following abbreviations:

TABLE-US-00001 A alanine P proline B aspartate or asparagine Q glutamine C cysteine R arginine D aspartate S serine E glutamate T threonine F phenylalanine G glycine V valine H histidine W tryptophan I isoleucine Y tyrosine Z glutamate or glutamine K lysine L leucine M methionine N asparagine

[0076]"Transfection" refers to the introduction of DNA into a host cell. Cells do not naturally take up DNA. Thus, a variety of technical "tricks" are utilized to facilitate gene transfer. Numerous methods of transfection are known to the ordinarily skilled artisan, for example, CaPO₄ and electroporation. (J. Sambrook, E. Fritsch, T. Maniatis, Molecular Cloning: A Laboratory Manual, Cold Spring Laboratory Press, 1989). Transformation of the host cell is the indicia of successful transfection.

I. Complete cDNA Sequence and Variants of the Porcine CMP-Neu5Ac Hydroxylase Gene

[0077]One aspect of the present invention provides novel, full length nucleic acid cDNA sequences of the porcine CMP-Neu5Ac hydroxylase gene (FIG. 2, Table 1, Seq ID No 1). Another aspect of the present invention provides predicted amino acid peptide sequences of the porcine CMP-Neu5Ac hydroxylase gene (Table 2, Seq ID No 2). The ATG start codon for the full-length cDNA is located in the 3' portion of Exon 4, and the stop codon TAG is found in the 3' portion of Exon 17. Nucleic and amino acid sequences at least 90, 95, 98 or 99% homologous to Seq ID Nos 1 or 2 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 15, 17, 20 or 25 contiguous nucleic or amino acids of Seq ID Nos 1 or 2 are also provided. Further provided are fragments, derivatives and analogs of Seq ID Nos 1-2. Fragments of Seq ID Nos. 1-2 can include any contiguous nucleic acid or peptide sequence that includes at least about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90. 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 550, 600, 700, 750, 800, 850, 900, 1000, 5000 or 10,000 nucleotides.

TABLE-US-00002 TABLE 1 Full length cDNA CCCGACGTCCTGGCAGCGCCCAGGCACTGTTA Exons Seq ID No 1 TTGGTGCCTCCTGTGTCCACGCGCTTCCCGGC 1 & CAGGCAGCCCTGGCGGATCCTATTTTCTGTTC 4-18 CCCCGATTCTGGTACCTCTCCCTCCCGCCCTC GGTGCGCAGCCGTCCTCCTGCAGTGCCTGCTC CTCCAGGGGCGAAACCGATCAGGGATCAGGCC ACCCGCCTCCTGAACATCCCTCCTTAGTTCCC ACAGTCTAATGCCTTGTGGAAGCAAATGAGCC ACAGAAGCTGAAGGAAAAACCACCATTCTTTC TTAATACCTGGAGAGAGGCAACGACAGACTAT GAGCAGCATCGAACAAACGACGGAGATCCTGT TGTGCCTCTCACCTGCCGAAGCTGCCAATCTC AAGGAAGGAATCAATTTTGTTCGAAATAAGAG CACTGGCAAGGATTACATCTTATTTAAGAATA AGAGCCGCCTGAAGGCATGTAAGAACATGTGC AAGCACCAAGGAGGCCTCTTCATTAAAGACAT TGAGGATCTAAATGGAAGGTCTGTTAAATGCA CAAAACACAACTGGAAGTTAGATGTAAGCAGC ATGAAGTATATCAATCCTCCTGGAAGCTTCTG TCAAGACGAACTGGTTGTAGAAAAGGATGAAG AAAATGGAGTTTTGCTTCTAGAACTAAATCCT CCTAACCCGTGGGATTCAGAACCCAGATCTCC TGAAGATTTGGCATTTGGGGAAGTGCAGATCA CGTACCTTACTCACGCCTGCATGGACCTCAAG CTGGGGGACAAGAGAATGGTGTTCGACCCTTG GTTAATCGGTCCTGCTTTTGCGCGAGGATGGT GGTTACTACACGAGCCTCCATCTGATTGGCTG GAGAGGCTGAGCCGCGCAGACTTAATTTACAT CAGTCACATGCACTCAGACCACCTGAGTTACC CAACACTGAAGAAGCTTGCTGAGAGAAGACCA GATGTTCCCATTTATGTTGGCAACACGGAAAG ACCTGTATTTTGGAATCTGAATCAGAGTGGCG TCCAGTTGACTAATATCAATGTAGTGCCATTT GGAATATGGCAGCAGGTAGACAAAAATCTTCG ATTCATGATCTTGATGGATGGCGTTCATCCTG AGATGGACACTTGCATTATTGTGGAATACAAA GGTCATAAAATACTCAATACAGTGGATTGCAC CAGACCCAATGGAGGAAGGCTGCCTATGAAGG TTGCATTAATGATGAGTGATTTTGCTGGAGGA GCTTCAGGCTTTCCAATGACTTTCAGTGGTGG AAAATTTACTGAGGAATGGAAAGCCCAATTCA TTAAAACAGAAAGGAAGAAACTCCTGAACTAC AAGGCTCGGCTGGTGAAGGACCTACAACCCAG AATTTACTGCCCCTTTCCTGGGTATTTCGTGG AATCCCACCCAGCAGACAAGTATATTAAGGAA ACAAACATCAAAAATGACCCAAATGAACTCAA CAATCTTATCAAGAAGAATTCTGAGGTGGTAA CCTGGACCCCAAGACCTGGAGCCACTCTTGAT CTGGGTAGGATGCTAAAGGACCCAACAGACAG CAAGGGCATCGTAGAGCCTCCAGAAGGGACTA AGATTTACAAGGATTCCTGGGATTTTGGCCCA TATTTGAATATCTTGAATGCTGCTATAGGAGA TGAAATATTTCGTCACTCATCCTGGATAAAAG AATACTTCACTTGGGCTGGATTTAAGGATTAT AACCTGGTGGTCAGGATGATTGAGACAGATGA GGACTTCAGCCCTTTGCCTGGAGGATATGACT ATTTGGTTGACTTTCTGGATTTATCCTTTCCA AAAGAAAGACCAAGCCGGGAACATCCATATGA GGAAATTCGGAGCCGGGTTGATGTCATCAGAC ACGTGGTAAAGAATGGTCTGCTCTGGGATGAC TTGTACATAGGATTCCAAACCCGGCTTCAGCG GGATCCTGATATATACCATCATCTGTTTTGGA ATCATTTTCAAATAAAACTCCCCCTCACACCA CCTGACTGGAAGTCCTTCCTGATGTGCTCTGG GTAGAGAGGACCTGAGCTGTCCCAGGGGTGCC CAACAACATGAAAAAATCAAGAATTTATTGCT GCTACGTCAAAGCTTATACCAGAGATTATGCC TTATAGACATTAGCAATGGATAATTATATGTT GCACTTGTGAAATGTGCACATATCCTGTTTAT GAATCACCACATAGCCAGATTATCAATATTTT ACTTATTTCGTAAAAAATCCACAATTTTCCAT AACAGAATCAACGTGTGCAATAGGAACAAGAT TGCTATGGAAAACGAGGGTAACAGGAGGAGAT ATTAATCCAAGCATAGAAGAAATAGACAAATG AGGGGCCATAAGGGGAATATAGGGAAGAGAAA AAAATTAAGATGGAATTTTAAAAGGAGAATGT AAAAAATAGATATTTGTTCCTTAATAGGTTGA TTCCTCAAATAGAGCCCATGAATATAATCAAA TAGGAAGGGTTCATGACTGTTTTCAATTTTTC AAAAAGCTTTGTTGAAATCATAGACTTGCAAA ACAAGGCTGTAGAGGCCACCCTAAAATGGAAA ATTTCACTGGGACTGAAATTATTTTGATTCAA TGACAAAATTTGTTATTTACTGCGGATTATAA ACTCTAACAAATAGCGATCTCTTTGCTTCATA AAAACATAAACACTAGCTAGTAATAAAATGAG TTCTGCAG

TABLE-US-00003 TABLE 2 Full length Amino Acid Sequence M S S I E Q T T E I L L C L S P A E A A Seq ID No 2 N L K E G I N F V R N K S T G K D Y I L F K N K S R L K A C K N M C K H Q G G L F I K D I E D L N G R S V K C T K H N W K L D V S S M K Y I N P P G S F C Q D E L V V E K D E E N G V L L L E L N P P N P W D S E P R S P E D L A F G E V Q I T Y L T H A C M D L K L G D K R M V F D P W L I G P A F A R G W W L L H E P P S D W L E R L S R A D L I Y I S H M H S D H L S Y P T L K K L A E R R P D V P I Y V G N T E R P V F W N L N Q S G V Q L T N I N V V P F G I W Q Q V D K N L R F M I L M D G V H P E M D T C I I V E Y K G H K I L N T V D C T R P N G G R L P M K V A L M M S D F A G G A S G F P M T F S G G K F T E E W K A Q F I K T E R K K L L N Y K A R L V K D L Q P R I Y C P F P G Y F V E S H P A D K Y I K E T N I K N D P N E L N N L I K K N S E V V T W T P R P G A T L D L G R M L K D P T D S K G I V E P P E G T K I Y K D S W D F G P Y L N I L N A A I G D E I F R H S S W I K E Y F T W A G F K D Y N L V V R M I E T D E D F S P L P G G Y D Y L V D F L D L S F P K E R P S R E H P Y E E I R S R V D V I R H V V K N G L L W D D L Y I G F Q T R L Q R D P D I Y H H L F W N H F Q I K L P L T P P D W K S F L M C S G

Variants

[0078]Another aspect of the present invention provides novel nucleic acid cDNA sequences of three novel variants of CMP-Neu5Ac hydroxylase gene transcript (FIG. 2, Tables 3, 5, and 7, Seq ID Nos. 3, 5, and 7). Seq ID No 3 represents the cDNA of a variant of the gene, variant-1, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15a, 16, 17, and 18. Exon 15a is a cryptic Exon that normally appears in Intron 15, approximately 460 bp upstream of Exon 16. The start codon for variant-1 is located in Exon 4, while the stop codon is located in Exon 17. Seq ID No 5 represents the cDNA of a variant of the gene, variant-2, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 12a. Exon 12a is a cryptic Exon which is retained from a partial sequence of Intron 12 (see SEQ ID. No. 21). The start codon for variant-2 is located in Exon 4, while the stop codon is located in the terminal end of Exon 12a. Seq ID No 7 represents the cDNA of a variant of the gene, variant-3, that includes Exons 1, 4, 5, 6, 7, 8, 9, 10, 11 and 11a. Exon 11a is a cryptic Exon which is retained from a partial sequence of Intron 11 (see Seq ID No. 19). The start codon for variant-3 is located in Exon 4, while the stop codon is located in Exon 11a. Another aspect of the present invention provides predicted amino acid peptide sequences of three novel variants of the porcine CMP-Neu5Ac Hydroxylase gene transcript. Seq ID Nos 4, 6 and 8 represent the amino acid sequences of variant-1, variant-2 and variant-3, respectively. Nucleotide and amino acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 3-8 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 15, 17, 20, 25, 30, 50, 100, 150, 200, 300, 400, 500 or 1000 contiguous nucleotide or amino acid sequences of Seq ID Nos 3-8 are also provided. Further provided are fragments, derivatives and analogs of Seq ID Nos 3-8. Fragments of Seq ID Nos. 3-8 can include any contiguous nucleic acid or peptide sequence that includes at least about 10 bp, 15 bp, 17 bp, 20 bp, 50 bp, 100 bp, 500 bp, 1 kbp, 5 kbp or 10 kbp.

TABLE-US-00004 TABLE 3 Variant-1 cDNA CCCGACGTCCTGGCAGCGCCCAGGCACTGTT Exons 1, Seq ID No 3 ATTGGTGCCTCCTGTGTCCACGCGCTTCCCG 4-13, GCCAGGCAGCCCTGGCGGATCCTATTTTCTG 15a, 16, TTCCCCCGATTCTGGTACCTCTCCCTCCCGC 17, 18 CCTCGGTGCGCAGCCGTCCTCCTGCAGTGCC TGCTCCTCCAGGGGCGAAACCGATCAGGGAT CAGGCCACCCGCCTCCTGAACATCCCTCCTT AGTTCCCACAGTCTAATGCCTTGTGGAAGCA AATGAGCCACAGAAGCTGAAGGAAAAACCAC CATTTCTTTCTTAATACCTGGAGAGAGGCAA CGACAGACTATGAGCAGCATCGAACAAACGA CGGAGATCCTGTTGTGCCTCTCACCTGCCGA AGCTGCCAATCTCAAGGAAGGAATCAATTTT GTTCGAAATAAGAGCACTGGCAAGGATTACA TCTTATTTAAGAATAAGAGCCGCCTGAAGGC ATGTAAGAACATGTGCAAGCACCAAGGAGGC CTCTTCATTAAAGACATTGAGGATCTAAATG GAAGGTCTGTTAAATGCACAAAACACAACTG GAAGTTAGATGTAAGCAGCATGAAGTATATC AATCCTCCTGGAAGCTTCTGTCAAGACGAAC TGGTTGTAGAAAAGGATGAAGAAAATGGAGT TTTGCTTCTAGAACTAAATCCTCCTAACCCG TGGGATTCAGAACCCAGATCTCCTGAAGATT TGGCATTTGGGGAAGTGCAGATCACGTACCT TACTCACGCCTGCATGGACCTCAAGCTGGGG GACAAGAGAATGGTGTTCGACCCTTGGTTAA TCGGTCCTGCTTTTGCGCGAGGATGGTGGTT ACTACACGAGCCTCCATCTGATTGGCTGGAG AGGCTGAGCCGCGCAGACTTAATTTACATCA GTCACATGCACTCAGACCACCTGAGTTACCC AACACTGAAGAAGCTTGCTGAGAGAAGACCA GATGTTCCCATTTATGTTGGCAACACGGAAA GACCTGTATTTTGGAATCTGAATCAGAGTGG CGTCCAGTTGACTAATATCAATGTAGTGCCA TTTGGAATATGGCAGCAGGTAGACAAAAATC TTCGATTCATGATCTTGATGGATGGCGTTCA TCCTGAGATGGACACTTGCATTATTGTGGAA TACAAAGGTCATAAAATACTCAATACAGTGG ATTGCACCAGACCCAATGGAGGAAGGCTGCC TATGAAGGTTGCATTAATGATGAGTGATTTT GCTGGAGGAGCTTCAGGCTTTCCAATGACTT TCAGTGGTGGAAAATTTACTGAGGAATGGAA AGCCCAATTCATTAAAACAGAAAGGAAGAAA CTCCTGAACTACAAGGCTCGGCTGGTGAAGG ACCTACAACCCAGAATTTACTGCCCCTTTCC TGGGTATTTCGTGGAATCCCACCCAGCAGAC AAGTATATTAAGGAAACAAACATCAAAAATG ACCCAAATGAACTCAACAATCTTATCAAGAA GAATTCTGAGGTGGTAACCTGGACCCCAAGA CCTGGAGCCACTCTTGATCTGGGTAGGATGC TAAAGGACCCAACAGACAGATCCTGTGTCAG GAGTTGGGATTCTTTGAAGATTCGGAGCCGG GTTGATGTCATCAGACACGTGGTAAAGAATG GTCTGCTCTGGGATGACTTGTACATAGGATT CCAAACCCGGCTTCAGCGGGATCCTGATATA TACCATCATCTGTTTTGGAATCATTTTCAAA TAAAACTCCCCCTCACACCACCTGACTGGAA GTCCTTCCTGATGTGCTCTGGGTAGAGAGGA CCTGAGCTGTCCCAGGGGTGCCCAACAACAT GAAAAAATCAAGAATTTATTGCTGCTACGTC AAAGCTTATACCAGAGATTATGCCTTATAGA CATTAGCAATGGATAATTATATGTTGCACTT GTGAAATGTGCACATATCCTGTTTATGAATC ACCACATAGCCAGATTATCAATATTTTACTT ATTTCGTAAAAAATCCACAATTTTCCATAAC AGAATCAACGTGTGCAATAGGAACAAGATTG CTATGGAAAACGAGGGTAACAGGAGGAGATA TTAATCCAAGCATAGAAGAAATAGACAAATG AGGGGCCATAAGGGGAATATAGGGAAGAGAA AAAAATTAAGATGGAATTTTAAAAGGAGAAT GTAAAAAATAGATATTTGTTCCTTAATAGGT TGATTCCTCAAATAGAGCCCATGAATATAAT CAAATAGGAAGGGTTCATGACTGTTTTCAAT TTTTCAAAAAGCTTTGTTGAAATCATAGACT TGCAAAACAAGGCTGTAGAGGCCACCCTAAA ATGGAAAATTTCACTGGGACTGAAATTATTT TGATTCAATGACAAAATTTGTTATTTACTGC GGATTATAAACTCTAACAAATAGCGATCTCT TTGCTTCATAAAAACATAAACACTAGCTAGT AATAAAATGAGTTCTGCAG

TABLE-US-00005 TABLE 4 Variant-1 Amino Acid Sequence M S S I E Q T T E I L L C L S P A E A A Seq ID No 4 N L K E G I N F V R N K S T G K D Y I L F K N K S R L K A C K N M C K H Q G G L F I K D I E D L N G R S V K C T K H N W K L D V S S M K Y I N P P G S F C Q D E L V V E K D E E N G V L L L E L N P P N P W D S E P R S P E D L A F G E V Q I T Y L T H A C M D L K L G D K R M V F D P W L I G P A F A R G W W L L H E P P S D W L E R L S R A D L I Y I S H M H S D H L S Y P T L K K L A E R R P D V P I Y V G N T E R P V F W N L N Q S G V Q L T N I N V V P F G I W Q Q V D K N L R F M I L M D G V H P E M D T C I I V E Y K G H K I L N T V D C T R P N G G R L P M K V A L M M S D F A G G A S G F P M T F S G G K F T E E W K A Q F I K T E R K K L L N Y K A R L V K D L Q P R I Y C P F P G Y F V E S H P A D K Y I K E T N I K N D P N E L N N L I K K N S E V V T W T P R P G A T L D L G R M L K D P T D R S C V R S W D S L K I R S R V D V I R H V V K N G L L W D D L Y I G F Q T R L Q R D P D I Y H H L F W N H F Q I K L P L T P P D W K S F L M C S G

TABLE-US-00006 TABLE 5 Variant-2 cDNA CCCGACGTCCTGGCAGCGCCCAGGCACTG Exons 1, Seq ID No 5 TTATTGGTGCCTCCTGTGTCCACGCGCTT 4-12, 12a CCCGGCCAGGCAGCCCTGGCGGATCCTAT TTTCTGTTCCCCCGATTCTGGTACCTCTC CCTCCCGCCCTCGGTGCGCAGCCGTCCTC CTGCAGTGCCTGCTCCTCCAGGGGCGAAA CCGATCAGGGATCAGGCCACCCGCCTCCT GAACATCCCTCCTTAGTTCCCACAGTCTA ATGCCTTGTGGAAGCAAATGAGCCACAGA AGCTGAAGGAAAAACCACCATTCTTTCTT AATACCTGGAGAGAGGCAACGACAGACTA TGAGCAGCATCGAACAAACGACGGAGATC CTGTTGTGCCTCTCACCTGCCGAAGCTGC CAATCTCAAGGAAGGAATCAATTTTGTTC GAAATAAGAGCACTGGCAAGGATTACATC TTATTTAAGAATAAGAGCCGCCTGAAGGC ATGTAAGAACATGTGCAAGCACCAAGGAG GCCTCTTCATTAAAGACATTGAGGATCTA AATGGAAGGTCTGTTAAATGCACAAAACA CAACTGGAAGTTAGATGTAAGCAGCATGA AGTATATCAATCCTCCTGGAAGCTTCTGT CAAGACGAACTGGTTGTAGAAAAGGATGA AGAAAATGGAGTTTTGCTTCTAGAACTAA ATCCTCCTAACCCGTGGGATTCAGAACCC AGATCTCCTGAAGATTTGGCATTTGGGGA AGTGCAGATCACGTACCTTACTCACGCCT GCATGGACCTCAAGCTGGGGGACAAGAGA ATGGTGTTCGACCCTTGGTTAATCGGTCC TGCTTTTGCGCGAGGATGGTGGTTACTAC ACGAGCCTCCATCTGATTGGCTGGAGAGG CTGAGCCGCGCAGACTTAATTTACATCAG TCACATGCACTCAGACCACCTGAGTTACC CAACACTGAAGAAGCTTGCTGAGAGAAGA CCAGATGTTCCCATTTATGTTGGCAACAC GGAAAGACCTGTATTTTGGAATCTGAATC AGAGTGGCGTCCAGTTGACTAATATCAAT GTAGTGCCATTTGGAATATGGCAGCAGGT AGACAAAAATCTTCGATTCATGATCTTGA TGGATGGCGTTCATCCTGAGATGGACACT TGCATTATTGTGGAATACAAAGGTCATAA AATACTCAATACAGTGGATTGCACCAGAC CCAATGGAGGAAGGCTGCCTATGAAGGTT GCATTAATGATGAGTGATTTTGCTGGAGG AGCTTCAGGCTTTCCAATGACTTTCAGTG GTGGAAAATTTACTGAGGAATGGAAAGCC CAATTCATTAAAACAGAAAGGAAGAAACT CCTGAACTACAAGGCTCGGCTGGTGAAGG ACCTACAACCCAGAATTTACTGCCCCTTT CCTGGGTATTTCGTGGAATCCCACCCAGC AGACAAGTATGGCTGGATATTTTATATAA CGTGTTTACGCATAAGTTAATATATGCTG AATGAGTGATTTAGCTGTGAAACAACATG AAATGAGAAAGAATGATTAGTAGGGGTCT GGAGCTTATTTTAACAAGCAGCCTGAAAA CAGAAAGTATGAATAAAAAAAATTAAATG CAAAAAAAAAAAAAAAAAAAAAAAAAAAA

TABLE-US-00007 TABLE 6 Variant-2 Amino Acid Sequence M S S I E Q T T E I L L C L S P A E A A Seq ID No 6 N L K E G I N F V R N K S T G K D Y I L F K N K S R L K A C K N M C K H Q G G L F I K D I E D L N G R S V K C T K H N W K L D V S S M K Y I N P P G S F C Q D E L V V E K D E E N G V L L L E L N P P N P W D S E P R S P E D L A F G E V Q I T Y L T H A C M D L K L G D K R M V F D P W L I G P A F A R G W W L L H E P P S D W L E R L S R A D L I Y I S H M H S D H L S Y P T L K K L A E R R P D V P I Y V G N T E R P V F W N L N Q S G V Q L T N I N V V P F G I W Q Q V D K N L R F M I L M D G V H P E M D T C I I V E Y K G H K I L N T V D C T R P N G G R L P M K V A L M M S D F A G G A S G F P M T F S G G K F T E E W K A Q F I K T E R K K L L N Y K A R L V K D L Q P R I Y C P F P G Y F V E S H P A D K Y G W I F Y I T C L R I S

TABLE-US-00008 TABLE 7 Variant-3 cDNA CCCGACGTCCTGGCAGCGCCCAGGCACTG Exons 1, Seq ID No 7 TTATTGGTGCCTCCTGTGTCCACGCGCTT 4-11, 11a CCCGGCCAGGCAGCCCTGGCGGATCCTAT TTTCTGTTCCCCCGATTCTGGTACCTCTC CCTCCCGCCCTCGGTGCGCAGCCGTCCTC CTGCAGTGCCTGCTCCTCCAGGGGCGAAA CCGATCAGGGATCAGGCCACCCGCCTCCT GAACATCCCTCCTTAGTTCCCACAGTCTA ATGCCTTGTGGAAGCAAATGAGCCACAGA AGCTGAAGGAAAAACCACCATTCTTTCTT AATACCTGGAGAGAGGCAACGACAGACTA TGAGCAGCATCGAACAAACGACGGAGATC CTGTTGTGCCTCTCACCTGCCGAAGCTGC CAATCTCAAGGAAGGAATCAATTTTGTTC GAAATAAGAGCACTGGCAAGGATTACATC TTATTTAAGAATAAGAGCCGCCTGAAGGC ATGTAAGAACATGTGCAAGCACCAAGGAG GCCTCTTCATTAAAGACATTGAGGATCTA AATGGAAGGTCTGTTAAATGCACAAAACA CAACTGGAAGTTAGATGTAAGCAGCATGA AGTATATCAATCCTCCTGGAAGCTTCTGT CAAGACGAACTGGTTGTAGAAAAGGATGA AGAAAATGGAGTTTTGCTTCTAGAACTAA ATCCTCCTAACCCGTGGGATTCAGAACCC AGATCTCCTGAAGATTTGGCATTTGGGGA AGTGCAGATCACGTACCTTACTCACGCCT GCATGGACCTCAAGCTGGGGGACAAGAGA ATGGTGTTCGACCCTTGGTTAATCGGTCC TGCTTTTGCGCGAGGATGGTGGTTACTAC ACGAGCCTCCATCTGATTGGCTGGAGAGG CTGAGCCGCGCAGACTTAATTTACATCAG TCACATGCACTCAGACCACCTGAGTTACC CAACACTGAAGAAGCTTGCTGAGAGAAGA CCAGATGTTCCCATTTATGTTGGCAACAC GGAAAGACCTGTATTTTGGAATCTGAATC AGAGTGGCGTCCAGTTGACTAATATCAAT GTAGTGCCATTTGGAATATGGCAGCAGGT AGACAAAAATCTTCGATTCATGATCTTGA TGGATGGCGTTCATCCTGAGATGGACACT TGCATTATTGTGGAATACAAAGGTCATAA AATACTCAATACAGTGGATTGCACCAGAC CCAATGGAGGAAGGCTGCCTATGAAGGTT GCATTAATGATGAGTGATTTTGCTGGAGG AGCTTCAGGCTTTCCAATGACTTTCAGTG GTGGAAAATTTACTGGTAATTCTTTATAT CAAAATGATGCCAAGGAGTTGGCATGGCA CTTTGCTAAATGCTGTGTGAATCAATACA AAGATAATTAGGACATGGTTCTTCCTCAC AAGAGGTGTGCAATCTTATTGGGAAATCA TACTTGCAAGTCACAAATATAGACTAAAG TTTCCAGCTGAGAATATGCTGATGGAGCA TGAAACACTAAGGAGACAGGGAGAATCTC AGGAAAAATCAAGAATAATTTGGATCAAA TGGATTCCTGACATAGAACATAGAGCTGA TCAGAAAGAGTCTGACATTGGTAATCCAG GCTTAAGTGCTCTTTGTATGTGGTTCAGA ACAGAGTGTGGGCAGCCTGAGGGGGATAC ATACCCTTGACCTCGTGGAAAGCTCATAC GGGGGAGGGATGAGGCTAAGGAAGCCCCT CTAAAGTGTGGGATTACGAGAGGTTGGGG GGGTGGTAGGGAAAATAGTGGTCAAAGAG TATAAACTTCCAGTTACAAGATGAATAAA TTCTAGGGGTATAATAACAGCATGGCACT ATAGATAGCATATTGTACTATATACTGGA AGTGCTGAGAGTAGATCTTACATGTTCTA ACCACACACACACACACACACACACACAC ACCACACACACACACCACACACACACACG TGCACACAAACAGAAATGGTAATTATGTG AGGTGATGGCGGTGTTAACTAACTTTATT GTGGTCATCATTTAGCCATACATGCATGT CATGAAATCACCATGTTGTACACCTTAAA GTTATGTAATACTAGATGTCAGTTATATC TCAAAGCTAGAAAAAATGTGGGGACCAAG GCAGAAGCTCTTCTGCTCTGTGTCTAAGG GTGGTTCTGGGGCTGGGATGGGGAGGATG GTTAAGTGGTATATTTTTTTCATACCTTT GCTCAGTACTATCATTGTAAGTGTTCAAT ATATGTCTGCTTAATAAATTAATGTTTTT AGTAAAAAAAAAAAAAAAAAAAAAAAAAA AA

TABLE-US-00009 TABLE 8 Variant-3 Amino Acid Sequence M S S I E Q T T E I L L C L S P A E A A Seq ID No 8 N L K E G I N F V R N K S T G K D Y I L F K N K S R L K A C K N M C K H Q G G L F I K D I E D L N G R S V K C T K H N W K L D V S S M K Y I N P P G S F C Q D E L V V E K D E E N G V L L L E L N P P N P W D S E P R S P E D L A F G E V Q I T Y L T H A C M D L K L G D K R M V F D P W L I G P A F A R G W W L L H E P P S D W L E R L S R A D L I Y I S H M H S D H L S Y P T L K K L A E R R P D V P I Y V G N T E R P V F W N L N Q S G V Q L T N I N V V P F G I W Q Q V D K N L R F M I L M D G V H P E M D T C I I V E Y K G H K I L N T V D C T R P N G G R L P M K V A L M M S D F A G G A S G F P M T F S G G K F T G N S L Y Q N D A K E L A W H F A K C C V N Q Y K D N

[0079]In other aspects of the present invention, nucleic acid constructs are provided that contain cDNA or variants thereof encoding CMP-Neu5Ac hydroxylase. These cDNA sequences can be SEQ ID NO 1, 3, 5 or 7, or derived from SEQ ID Nos. 2, 4, 6, or 8 or any fragment thereof. Constructs can contain one, or more than one, internal ribosome entry site (IRES). The construct can also contain a promoter operably linked to the nucleic acid sequence encoding CMP-Neu5Ac hydroxylase, or, alternatively, the construct can be promoterless. In another embodiment, nucleic acid constructs are provided that contain nucleic acid sequences that permit random or targeted insertion into a host genome. In addition to the nucleic acid sequences the expression vector can contain selectable marker sequences, such as, for example, enhanced Green Fluorescent Protein (eGFP) gene sequences, initiation and/or enhancer sequences, poly A-tail sequences, and/or nucleic acid sequences that provide for the expression of the construct in prokaryotic and/or eukaryotic host cells. Suitable vectors and selectable markers are described below. The expression constructs can further contain sites for transcription initiation, termination, and/or ribosome binding sites. The constructs can be expressed in any prokaryotic or eukaryotic cell, including, but not limited to yeast cells, bacterial cells, such as E. Coli, mammalian cells, such as CHO cells, and/or plant cells.

[0080]Promoters for use in such constructs, include, but are not limited to, the phage lambda PL promoter, E. coli lac, E. coli trp, E. coli phoA, E. coli tac promoters, SV40 early, SV40 late, retroviral LTRs, PGKI, GALI, GALIO genes, CYCI, PH05, TRPI, ADHI, ADH2, forglymaldehyde phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, triose phosphate isomerase, phosphoglucose isomerase, glucokinase alpha-mating factor pheromone, PRBI, GUT2, GPDI promoter, metallothionein promoter, and/or mammalian viral promoters, such as those derived from adenovirus and vaccinia virus. Other promoters will be known to one skilled in the art.

II. Genomic Sequences of the CMP-Neu5Ac Hydroxylase Gene

[0081]Nucleic acid sequences representing the genomic DNA organization of the CMP-Neu5Ac hydroxylase gene (FIG. 1, Table 9) are also provided. Seq ID Nos 10-28 represent Exons 1, 4-11, 11a, 12, 12a, 13-15, 15a, and 16-18, respectively. Exons 11a, 12a, and 15a are cryptic Exons that are retained in certain variant transcripts of CMP-Neu5Ac hydroxylase. SEQ ID Nos 29-45 represent Intronic sequence between Exon 1 and Exon 4 (hereinafter Intron 1a and Intron 1b, respectively), 4-15, 15a, 16, and 17, respectively. Intron 15a is the 3' downstream portion of Intron 15 that follows the cryptic Exon 15a. Seq ID No. 9 represents the 5' untranslated region of the porcine CMP-Neu5Ac hydroxylase gene. Nucleic acid sequence representing the genomic DNA sequence of the porcine CMP-Neu5Ac hydroxylase gene (Table 10, SEQ ID No. 46) is also provided. In addition, contiguous genomic sequence representing the 5' contiguous genomic sequence containing 5' UTR, Exon 1 and a portion of intronic sequence located between Exon 1 and Exon 4 (Intron 1a) (SEQ ID No. 47, Table 11) is provided. Contiguous genomic sequence containing an intronic sequence located between Exon 1 and Exon 4 (Intron 1b) through Exon 18 (SEQ ID No. 48, Table 12) is also provided. Nucleotide and amino acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to SEQ ID Nos 9-45, 46, 47, 48, 49 and 50 are provided. In addition, nucleotide and peptide sequences that contain at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90. 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 550, 600, 700, 750, 800, 850, 900, 1000, 5000 or 10,000 contiguous nucleotide or amino acid sequences of SEQ ID Nos 9-45, 46, 47, 48, 49 and 50 are also provided, as well as any nucleotide sequence 80, 85, 90, 95, 98 or 99% homologous thereto. Further provided are fragments, derivatives and analogs of SEQ ID Nos 9-45, 46, 47, 48, 49, and 50. Fragments of Seq ID Nos. 9-45, 46, 47, 48, 49, and 50 can include any contiguous nucleic acid or peptide sequence or at least about 10 bp, 15 bp, 17 bp, 20 bp, 50 bp, 100 bp, 500 bp, 1 kbp, 5 kbp or 10 kbp.

[0082]In addition, regulatory regions in the form of putative transcription factor binding sites of the genomic sequence have been identified (see FIG. 4). These binding sites are located in the 5'UTR and Exon 1 of the porcine CMP-Neu5Ac hydroxylase genome, and include binding sites for transcription factors such as, for example, ETSF, MZF1, SF1, CMYB, MEF2, TATA, MEF2, NMP4, CAAT, AP1, BRN2, SATB1, ATF, GAT1, USF, WHN, NMP4, ZF5, NFKB, ZBP89, MOK2, ZF5, NFY, and MYCMAX.

TABLE-US-00010 TABLE 9 Genomic Organizational Sequences ctgccagcctaagccacagccacagc 5'UTR Seq ID No 9 aacgctgggtctgagccatgtctgca gcctatgccagagctccccgcagcgc cggatgcttaacccactgagcaaggc cagggattgaaccctcgtcctcatgg atagcagttgagttgtttccacggaa ctcttaggggaactcctgattatttt ttatttaaatttatatttctctgact ttttcgtgtgctcatcagccactgac tgtgtatctccattagtcatggtttg ttaactctgtcattcaaaccctcttc atccttgctacgcagataacatcatt ataataaaatcgtgcctgaagaccag tgacgcccccaagctaagttactgct tcccctggggggaaaaagaagcaccg cgcgggcgctgacacgaagtccgggc agaggaagacggggcagaggaagacg ggggagcagtgggagcagcgggcagg gcgcgggaagcactggggatgttccg cgttggcaggagggtgttgggcgagc tcccggtgatgcaggggggaggagcc ttttccgaagtagcgggacaagagcc acgggaaggaactgttctgagttccc agt CCCGACGTCCTGGCAGCGCCCAGGCA Exon 1 Seq ID No 10 CTGTTATTGGTGCCTCCTGTGTCCAC GCGCTTCCCGGCCAGGCAGCCCTGGC GGATCCTATTTTCTGTTCCCCCGATT CTGGTACCTCTCCCTCCCGCCCTCGG TGCGCAGCCGTCCTCCTGCAGTGCCT GCTCCTCCAGGGGCGAAACCGATCAG GGATCAGGCCACCCGCCTCCT gtgagaaggcttcgccgctgctgccg Intron 1a Seq ID No 29 ctggcgccggcagcgccctccacgca cttcgtagtgggcgcgcgccctcctg cattgtttctaaaagattttttttta tccgcttatgctatcagttactgagg aagtatttacaaatctactattattt tgaatttgcctttttctccttatagt ttatcagtatctcttgagactgttat tggtgcctgcaaatttaaaatgattg gggttttatgaggaagtgaacctttt atctttatgaaacgcctaactgaggc aatgttaattgcttaaaatactttct tattatcagtgtggccatgccagtgt cctcttggttagaatttgcctgat ctgccaaagctgggagatgggggaaa Intron 1b Seq ID No 30 gtagagtgggttattgaaactgaata tagagttcagcatctaaaagcgaggt agtagaggaggaagctgtgtcaacgg aaatactgagctgggttcacatcctc tttctccacacag TCTAATGCCTTGTGGAAGCAAATGAG Exon 4 Seq ID No 11 CCACAGAAGCTGAAGGAAAAACCACC ATTCTTTCTTAATACCTGGAGAGAGG CAACGACAGACTATGAGCAG gcaagtgagagggggctttagctgtc Intron 4 Seq ID No 31 agggaaggcggagataaacccttgat gggtaggatggccattgaaaggaggg gagaaatttgccccagcaggtagcca ccaagcttggggacttggagggaggg ctttcaaacgtattttcataaaaaag acctgtggagctgtcaatgctcaggg attctctcttaaaatctaacagtatt aatctgctaaaacatttgccttttca tag CATCGAACAAACGACGGAGATCCTGT Exon 5 Seq ID No 12 TGTGCCTCTCACCTGCCGAAGCTGCC AATCTCAAGGAAGGAATCAATTTTGT TCGAAATAAGAGCACTGGCAAGGATT ACATCTTATTTAAGAATAAGAGCCGC CTGAAGGCATGTAAGAACATGTGCAA GCACCAAGGAGGCCTCTTCATTAAAG ACATTGAGGATCTAAATGGAAG gtactgagaatcctttgctttctccc Intron 5 Seq ID No 32 tggcgatcctttctcccaattaggtt tggcaggaaatgtgctcattgagaaa ttttaaatgatccaatcaacatgcta tttcccccagcacatgcctaactttt tcttaagctcctttacggcagctctc tgattttgatttatgaccttgactta atttcccatcctctctgaagaactat tgtttaaaatgtattcctagttgata aacagtgaaacttctaaggcacatgt gtgtgtgtgtgtgtgtgtgtgtgtgt ttaccagcttttatattcaaagactc aagcctcttttggatttcctttcctg ctctctcagaagtgtgtgtgtgaggt gagtgcttgtccaaacactgccctag aacagagagactttccctgatgaaaa cccgaaaaatggcagagctctagctg cacctggcctcaacagcggctcttct gatcatttcttggaagaacgagtgct ggtaccccttttccccagccccttga ttaaacctgcatatcgcttgcctccc catctcaggagcaattctaggaggga gggtgggctttcttttcaggattgac aaagctacccagcttgcaaaccaggg ggatctggggggggggtttgcacctg atgctcccccactgataatgaatgag ggattgaccccatcttttcaagcttt gcttcagcctaacttgactctcgtag tgtttcagccgtttccatattaggct tgtcttccaccgtgtcgtgtcgtcaa tcttatttctcaggtcatctgtgggc agtttagtgcgaatggactcagaggt aactggtagctgtccaagagctccct gctctaactgtatagaagatcaccac ccaagtctggaatcttcttacactgg cccacagacttgcatcactgcatact tagcttcagggcccagctcccaggtt aagtgctgtcatacctgtagcttgct tggctctgcagatagggttgctagat taggcaaatagagggtgcccagtcaa atttgcatttcagataaacaacgaat atatttttagttagatatgtttcagg cactgcatgggacatacttttggtag gcagcctactctggaagaacctcttg gttgtttgctgacagactgcttttga gtcccttgcatcttctgggtggtttc aagttagggagacctcagccataggt tgttctgtcaccaagaagcttctgca agcacgtgcaggccttgaggtcttcc gacttgtggcccggggactctgcttt ttctctgtccttttttctccttagtg ggccatgtcctgtggtgttgtcttag ccagttgtttaagggagtgttgcagc tttatgattaagagcatggtctttcc ttgcaaactgcttggtttagaagcct ggctccaccacttagcggctctgtga cctcggacacatttcttagcctttct gggcctcgctcttcttcctcataaag tgaaaatgaaagtagacaaagccttc tctgtctggctactgagaggatggag tgatttcatacacataaagcacttaa aataatgtctggcatatgatacatgc tcaataaatgtcacttacatttgcta ttattattactctgccatgatcttgt gtagcttaagaacagaggtctttaca ggaattcaggctgttcttgaatctgg cttgctcagcttaatatggtaattgc tttgccacagactggtcttcctctcc ttcacccaaagccttagggggtgaac gatcccagtttcaacctattctgttg gcaggctaacatggagatggcaccat cttagctctgctgcaggtggggagcc agattcacccagctttgctcccagat acagctccccaagcatttatatgctg aaactccatcccaagagcagtctaca tggtacactcccccatccatctctcc aaatttggctgcttctacttaggctc tctgtgcagcaattcacctgaaatat ctcttccacgatacagtcaagggcag tgacctacctgttccaccttcccttc ctcagccatttttcttctttgtacat aatcaagatcaggaactctcataagc tgtggtcctcattttgtcaatctaat ttcacagcctcttggcacatgaagct gtcctctctctcctttctgcctactg cccatgagcagttgtgacactgccac atttctcctttaacgacccagcctgc tgaatagctgcatttggaatgttttc aatttttgttaatttatttatttcat cttttttttttttttttttttttttt ttttttagggccgcacccatgggata tggaggttcccaggctagggatccaa tgggagctgtagctgctggcctacac cacagccacagcaatgcacaattcga gccaatctttgacctacaccagagct cacggcaacactggattcttaaccca ctgattgaggccagggatcaaactct cgtcctcatagatacgagtcagattc gttaacctctgagccatgatagttgt tagttactcattgatgagaaaggaag tgtcacaaaatatcctccataagtcg aagtttgaatatgttttctgccttgt tactagaaaagagcattaaaaattct tgattggaatgaagcttggaaaaaat cagcatagtttactgatatataagtg aaaatagaccttgttagtttaaacca tctgatatttctggtggaagacatat ttgtctgtaaaaaaaaaaaatcttga acctgtttaaaaaaaaaacttgactg gaaacactaccaaaatatgggagttc ctactgggacacagcagaaatgaatc taactagtatccatgaggacacaggt ttgatgcctggcctcgctaagtgggt taaggatatggtgttgctgcagctcc aattcaacccctatcctgggaacccc catatgccaccctaaaaagcaaaaag aaaggtgctgccctaaaaagcaaaaa gaaagaaagaaagacagccagacaga ctaccaaatatggagaggaaatggaa cttttaggccctatctccaactatca catccctatcaccgtctggtaagaaa tggaaaaaatattactaagcctcctt tgttgctacaattaatctgattctca ttctgaagcagtgttgccagagttaa caaataaaaatgcaaagctgggtagt taaatttgaattacagataaacaaat tttcagtatatgttcaatatcgtgta agacgttttaaaataattttttattt atctgaaatttatatttttcctgtat tttatctggcaaccatgatcagaaat ctttaaacaatcaggaagtctttttt cttagacaaatgaaaatttgagttga tcttaggtttagtacactatactagg ggccaagggttatagtgtgactatta aatcacagataatctttattactaca ttatttccttatactggccccacttg gatcttacccagcttagcttttgtat gagagtcatccttaaagatgacttta ttctttaaaaaaaaaaacaaatttta agggctgcacccatagcatatagaag ttcctaggctagcggtcaaattagag ctgcagctgccagcctatgccacagc cacagcaatgccagatctgagctgca tctgtgacctacactgcagcttgcag caatgctggatccttaacccattgaa caatgccagggattgaacacacatcc tcatggatactgctcaggttcctaac ctgctgagccacagttggaactccaa agcagactttattctgatggctctgc tgatctctaacacgttattttgtgcc atggtgtttatcttcactttactcaa gtcagggaaacacgaagagtctcata caggataaacccaaggagaaatgtgc aaagtcacatacaaatcaaactgaca aaaatcaaatacaaggaaaaaatatc ttcactttcaaaatcacctactgatg atgagtttatatttccttggatattt gaatattagctatttttttcctttca tgagttttgtgttcaaccaactacag tcgtttactttgatcacagaataatg catttaagccttaaatagattaatat ttattttcaccatttcataaacctaa gtacaatttccatccag

GTCTGTTAAATGCACAAAACACAACT Exon 6 Seq ID No 13 GGAAGTTAGATGTAAGCAGCATGAAG TATATCAATCCTCCTGGAAGCTTCTG TCAAGACGAACTGG gtaaataccatcaatactgatcaatg Intron 6 Seq ID No 33 ttttctgctgttactgtcattggggt ccctcttgtcaacttgtttccaatct cattagaagccttggatgcattctga ttttaaactgaggtattttaaaagta accatcactgaaaattctaggcaagt tttctctaaaaaatcccttcattcat tcatttgttcagtaagtatttgatga gaccttaccatgtgtaaacattgcac taggtattaagaaatacaaagatgga taagatagagtcggcgtaaatgagat gatataatgagacgttataatgaaac tcacaattccagttgggaaataaagt ccttcaaattccatgactctttctgg cacacgttagaggctacagcttctgt gtgattctcatgctggctccacttcc actttttccttcttcctactcaagaa agcctatagaaatatgagtaagaagg gcttaatcataggaataaatttgtct ctgttctaagtgattaaaaatgtctt tatcagtataaaaagttacttgggaa gattcttaaaactgcttttacacact gttctagaatgactgttatataaata aaaaagtagatttgatctaacacaat taaatgacctttggaaatattgacta attctcaccttgcccctcaaagggat gcctgaaccatttccttcttttgcca gaaagcccccaccctttgtctgttga cctagcctaggaaatcttcagatcac gttgttagcacgaactggttacatgt gctgtacaaatactatttaattcatc tgattaaaaaaaaagagataagaagc aaaagtttgactatcttaaactgttt gcgtaggtgagaggacaattgaccat ctactttatgagtatgtaacccagaa acttaaagctccttaagggagctaag tcttttggataagacctatagtgaga ccttttagcaaaatggttaagactga atggagctcactagcgtgggttcata tcctgatgctcaaacacgcaattaaa tgactttaggtgggttagtctctgtt ccttagtttcctcaatgggagataat attggtagtagcgattttactgggtt gttgaaagaacatctgttaaatgttc agaacgtgttacgacagagtacagag taatgatttgcttgtatatgtatgac tcaaatagtctgccatatgccttgtg actgggtcctgtggagcaggaaggag ggatttcccacccagcagaaagttgg gtaaactggaaaatagactgaggcca ggaaatgatgcaaagcgttgatgttc actgccacggcaggtgaagggcaggg ccagagttgtcagtagggtcagggga ggactggaaataaccaagacccactg cacttttcagcctttgctccagtaag gtaatgttgtgagagtagaaaatttt gttaacagaacccacttttcagtaca gtgctaccaatactgtagtgatttca taccacatcccaagaaagaaaaagat ggctcaatcccatgtgagctgagatt atttggttttattgttaaataaatag cattgtgtggtcatcattaaaaaagg tagatgttaggaaagtagaaggaaga agactctcacctacattttcatcact gttttggtatctgccagttgtcacct tggtccccttccccgcctctcccctg cctcctcttcctccttctcctttttt tggaatacaattcaggtaccataaaa tttacccttttagagtgtttgactca atggtttttagtattttcacatgttg tgctattactatcactatataattcc aggtcattcacatcaccccccaaaga aaccttctaactattagcagtccatt cccttcttccctcagcccctggcaac cactaatctacttactgtctccatgg atgttcctatattgaatcaagctagc ataaaccccacttgctcatggtcata attcttttttatagtgctaaattaca tttgctaatattcaattaaggatttc tatgtccatattcataaggaatattg gtgtgtagttttctctttgtgtgata tctttgtctggttgggggatcagagt aataattactgctctcatagaatgaa ttgagaagtgttccctccttttctat ttattggaagagtttgtgaagtatat tggtattgattcttctttaaacattt ggtcagattcaccagtgaagccatct gggccatggctaatctttgtgaaaag ttttttgattactaattaaatctctt taatttgttatgggtctgctcctcag acgttctagttcttcttgagtcagtt ttgttcatttgtttcttcctaggact ttctccctttcatttggattatttag attgatagtaatatcccccttttaat tcctggctgtagtaatttgggtcttt tctcttttttcttggtcagtttagct aaaggtttgtaattgtattaatcttt tcaaataactaacttttttgttttgt ttgttttttgttttttgttttttgtt ttttgtttttttttgctttttaaggc tgcacctgaggcatatggaagttctc aggctagaggtctaatcggagctaca gctgctggcctataccacaaccatag caatgccagattcaagctgcatctgc gacctacaccacaactcggccaggga tcacacccgcaacctcatggttccta gtcggatttgttaaccactgtgccac gacgggaactcccgcccatttttttt aacacctcatactttaacataaagat gggcttcacatggactgatagctcaa atgaggaaggtaagactatgaaagta atggaagaaatgtagactatttttgt gacctagagattactgatacttcttg acttttcaaacaatacttcaaaagta cagcccaaagggaaaaaagaaagaaa aaagaaacacacatatacacaaacct agtgaataagatatcatcgatacact acagatttctatgaactggaagaccc catggacaaagttaaagaacatatga tagtttgagtgattattttgcaatat ttacaaccaatgagggaatattatcc agcttataggaggaagtaatgcaaat cgacaagaaaaagataggaaacccaa tataaaaattaagaaaatacaaaaat taagaaaggatatgaactagcatttt acaaaagaaaaatctccaaaagtcaa tcagcacatgaaaatatgctcaaacc taattattagaaaactacagactgaa gcaatgaggtgctttactttacatct ttttgactgataaaaagttagaaaca aaggtgatatcaaatgtcagggataa aaggatatagaaatcgtcatgcctgt ggtgggagtatggccggtgcagtcat gtgggaaggtaatctgacagtggtta ggcagagcaggtttatgaatacactg tggcccatcaatcccacgcctgttta tgtaccaaagaaatcctgttgtggca gaatctatgggtccacccctgggagc atgaattaataaaatgtggcaccagg gtgtgtgaaactccagctagagatga gatgtccacatggcaacatgaatgca tcttagaaacatagatttgagtgaaa aagagtaagaaacagccgggaaaccc aataccatttataaaaattaaagatg cacacatacaatgtagtaaatatttt gcatgaactttcaaatggttgcctac agggggggagagtaaagaagagtaga aaacaaagataaagggagtaagtaag tagctctgcctggactgaatataatg tgtcatgaactgagaaatatggttaa cataatcctcttaacttgaggtccta aatgaatgaatgagtccactattcat ttacccattctttaatgtgtattgca ttataatccatttttttagaaccaac gaattttgttcccataactactaatc agcctgccttttctccctcattccct tatcagctcaggggcattcctagttt ttcaaacgttcctcatttgaaccaaa aatagcatcattgtttaaattatact tgttttcaaatacgatgcttatatat tccaagtgtgtttgcccattttctta ggtggtagaaatttttcattctactt ttctatctactcagattttcccgttg gaattatttccattgctattaaactt agaagtcccccctgtgatatgccatt tttttcatactttttaagcacttggt tgcttttctttgtgtctttaagcacc tagaatacttataaccattgcacagc actgtgtatcaggcagcccttcctct tccactaatttatggtccttctctta gactatattaaactgttatttaatta ggatcctctcttcgtccttatgattt aattattatagttttctaatatgttt ttattataattcctcttcattattcc tccctattaaaaattttaatgaattc catttgtttgttcttctagttaaata ttaagtcataatccaaataacttaga tgtcattagtttatgtggtcaaagta aggataccacatctttatagatgcag gcagttggcagatgtcatgattttct tcagtgcataaatgcaatttatcttt gagcaaggggcataaaaacttttatg gtattggctttgaaataatagttaag aactgcagactcagtttttcctgctt ttcttgaaaaagaacacttctaaaga aggaaaatccttaagcatggatatcg atgtaattttctgaaagtctcctgta attccttgggatttttgttgttgttt gttggtcggtttttttgggtttttgt ttgtttgttttgttttgttttgtttt gcttttagggctgcacctgtggcata tggaagttcccaggctaggggtccaa ctggagctacagctgccagcctactc cacagccacagcaacatgggatccta gctgcatctgtgacctaaccacagct cttggtaatgccagattgttaaccca ctgagcaatgccagagatcgaatctg cctcctcatggacactagtcagatta gtttctgctgagccacaatgggaatt cccaattccttgtatttttgaactgg ttatgtgctagcatataattttgttt cttgaatctttgtgggtttttttttt tttttttttttgtctcttgtcttttt aaggctgcacccacagcatatggagg ttcccaggctagaggtcaaattggag ctacagctgccagcctacacaacaac tgcagcaaagtggggcccaacttata tgacagttcgtggcaatgccggattc ctaacccactgagcagggccagggat cgaacctgagtttccagtcagtttcg ttaaccactgagccatgatagtaact cctgtttgttcagtcttgaacctcct ttttaattctttattccttgagggtg aaataattgccataataatactatca tttattacatgccttctctgtgctag gcatagtgacactttaggatttatta tatcacttaatccctacaacaactct gcaaagtatgtatcataatcctattt gacagatcaggaaattgcagcccagg atgcagataatatgcatccatcacaa gtgactagatatagtccctctgctat tcagcagggtctcattgcctttccat tccaaatgcaatagtttgcatctatt gtatatgtgttttggggtttttttgt ctttttttttttttttgtcttttctg gggcctcacccttggcataggtaggt tcccaggctaggggtcaaattgaagc tgcagctgccagcctacaccacagcc acagcaactcgggatctgagcctcat ctgcaacctacaccaaagctcacggc aacaccggatccttaacccactgagt gaggccagagatcaaaccggcaacct catggttcctagtcggattcattaac cactgagccacgatgggaactcccta aatgcaatagtttgctctattaaccc caaactcccagtccatcccactccct cctcctccctcttggcaaccacaagt ctgttctccatgtccatgattttctt ttctggggaaagtttcatttgtgcca tttttcattttacgggtaatttttac ttcagtttcttccactagcagttgtc ttaaagtgagtataattaatattcat ttggaaaatgtaagcaaaacattttt taaagggccatgcccacagcatatga aagtttctgggccaggggttgaatcc aggctccaagttgcagctgtgcccta

cactgcagctgggcaatgctggatcc tttaacccactgtgcccggctaggga tcaaacctgcatttccacagctaccc gagccattgcagttggattcttaacc cactgcactacagtgggaactcccac aaaacattttttaatgtcctttgaat aaagtaggaaagtgctcgtctttgag ggcagggcggcaatgccatttccaca aggtttgctttggcttgggacctcat ctgctgtcatttagtaatgaataaaa ttgctgacagtaataggattaactgt gtgtggagatagccagggttagagat aaaaacactggagaagtcaaataagt tgctcgaggtcctctagctaataagc tattaagtgggagagtgagggctaga aacaggccatctgtctcccaagcaca tgtccattagtggtttgctgatagcc ttccagaacaacagagaggactctca aacatggtcttgcctccctccaattg atcccctccatgtgcctcacagcggg tctttctaaaattaagttctgatttt aattctcccttgctatagcacttagg tatggctttcagccgtgcaataaaaa gcaggcaagagtggctcaatcatata ggaggttgtttttcttagatcccaag caggtaatcctgggcattatggttgt tctgcgtttatcaaggagccaaattc tctatcacctcctgttctatcctcct cagtatctggctctattcttcagcat ctcaagatggcttgtgctcctccaag catggcagtcaaattccacacaagag ggggaaatatgaagggcagacagtgc tggtctcctgagctgtccctctttgt cggggaaataaatgtattccttcaag tcccgtgagacttctgaagtagacgt ctgcttacgtctcacccaccagaact atgtaaactgcacatagtgctaggtc tacatagccactcataactgccaggg ggtgggaaatctttaaataggtgtac caccacacaattaggatgctaatagt aagggagaaggagagaataggttttg cgcaagccaccagcatgcctgccaca attgcttaaaattcttcattgacccc tcattgccacaggatgaaatccaaac gccttcttagttgggaatctgaccta cctgtctctcccacctggttcagaca ccattctccttggtcataaaattcca gtcatttgtgaacatccagctccccc atgcctccatgcctttgcacatgctg ttcttttatcttttatgttgtccttt tatcttttatccaaaagagatatccc atcatcacatctcttttgtcagcccc caaatactttgtctttcaagttcagc tggaggattacctcctatttgaaatc agctttgtctcttacaaccaaacaag gttttccttccgagacactcccacag caccttgaactcatctctatcaatca ttcatttgataatgaagttgttggtg gtatgcctgtgtctctgacacatctg cgatctcatgagttccttaagtggaa tgtgaatagcgggatgaacagtattg gtcttcagccctcatctctgcagatg ttgcttgacccaaatgagcgttgcct tttattttgattttgctttgatttgt ctactccatgtacttgagccatgcat ttctgtcttagcgatgctttttaaaa gtcattttttggttgattatccagat ttgtccacctttgcttctag TTGTAGAAAAGGATGAAGAAAATGGA Exon 7 Seq ID No 14 GTTTTGCTTCTAGAACTAAATCCTCC TAACCCGTGGGATTCAGAACCCAGAT CTCCTGAAGATTTGGCATTTGGGGAA GTGCAG gtaaggaaatgttaaattgcaatatt Intron 7 Seq ID No 34 cttaaaaacacaaataaagctaacat atcaatttatatatatatatatatat atatttttttttttttttacatctta tattaccttgagtattcttggaagtg gctagttaggacatataataaagtta ttctgaagtctttttttttctttttc catggtgagcagtggcttgatgtgga tctcagctcccagacgaggcactgaa cctgagccgcagtggtgaaagcacca agttctagccactagaccaccaggga actccctattctaaattcttgagcac attatttaggaacctcaggaacttgg caggattacaggaaatatatctagat ttaaaaaaaaatcttttaacagaggt cccaaaggagagtcatgcacagctat gggaggaagttcagaaactgcccttg ctaccagatcactgtcagataaaatg gccagctacatgtttctgcacattgc cctaagatctttacaaacttttctgt gcatttttccacttttaaaagaaaat ttcggggttcctgttgttgctcagtg gttaacgaacccaactagtatccatg gggacaggggttcgagccctggcctc actcagtgggttaagaatctggcatt gctgtggctgtggcgtaggctggcgg ctacagctcagattggacccctagcc tgagaacctccatatgccgcaggtat ggccctaaaaaaaaaaaaaaagagag agagagaatttcctccagaaaaaaca ctttggtagtttgggagaagtaaaca accaaaaattaatttttctggagtat tcgggaagcttgtaaaaatgggctct tacttttttgaggagacaaatgggaa cctacccagaagaggcacaatcacct gcatttgatttcttgacctctcccta ccttctttgctggctttccacatttg gatttctgtgaccttatctctgctcc ttggtgttttcatttttcctgtggac gtgccagactatgggaagggagtaag gcgttgatttagaatcctgtagtctc tgcctgtctctagtcattgttttcac ccttctcaaaggaccttgacatcctg agtgagtccgcaagtaatttagggga gaagccttagaagccagtgcagccag gctacatgactgtgtccacccactgg aaccagtcatttttatacctattcac agcccccctaccatttaaatccccag aggtctgccataacatctgtaactcc ctttcctggtaaattgtgttctaaaa gactggtaacaaaagatattctgtgg tacagagcataattaaatacctggga gctgatttgagtggggtaaatcaact ggtttgacccctaaaacccaccatga gcatttctgttctaataaagtaatgc ccgtgctgggaagttctacggaaatg ctcctgctgtgtctttcttgagtcct gtgtcattgaacatgcttaggagcaa aggtcccccatgtggcttgtctgcta accagcccagttccttgttctggctg gtaatgatccgatcatctgaatctca ctgtcttccaacag ATCACGTACCTTACTCACGCCTGCAT Exon 8 Seq ID No 15 GGACCTCAAGCTGGGGGACAAGAGAA TGGTGTTCGACCCTTGGTTAATCGGT CCTGCTTTTGCGCGAGGATGGTGGTT ACTACACGAGCCTCCATCTGATTGGC TGGAGAGGCTGAGCCGCGCAGACTTA ATTTACATCAGTCACATGCACTCAGA CCACCTGAG gtaaggaagggtgagccctcaactcc Intron 8 Seq ID No 35 gaagaaaatgctgcaataaaagcact gttggttttcagctttttttgtaatc actgctcattctgaggtagattcgct tgggctgataaaaagagaactaattc agataaatgcttgcatttgcatagcc tctttttttaaaaacttttttttttt ttttttttttttggcttttcagggct gaacctgtggcatatggaggttccca ggctaggggtcgaatcagagctgtag ccccgggcctatgccactgccatagc aacatgcatagcctcctttttaaagt gccttcctgttttataccattgggat gtgagaagagctattgtggaaangag catggggtnataaccctggacctctc acgtcctaccctcaggntagtgggaa aactctgagtttaaggacatcaaagt gactcctttttagttacattatggng gaatcagcncatatttttacaagggg cggagngtaanctgttggagtttaca agacatatggtggcattgcaactact taaccctactattatagcacaaaagc agccatagtcggtcctgaaggagcct gatgccttcagctttataggcaatga cgtgtgaatatcacaaacagtttcct gtgtcaccaaacatgattgccttttg atttccctttcaaccctttaaaaaaa ggtaaaagcccttcttagcattcagc agcaggtcgctgtgttttgccaactc ctgatctgtagcatttcgacaacact gagctctcaacttttgaaccctgagt ccaccacatccttcagtgaaaccaga gccatgtgatactaaggatagaaacg gaaacttcctgaatccaggcgatcaa ataggagggagaaagaggaactttca ttgacaaaaccacaaatattgtgaat ggactgttacaaatattgtgaatgct cctattcccaaccccctggcttcatt acagggtcctatgtgttcatccttat tgagaaatttgtattgctactgccag gttgccaatacccagcggtgcccatg gtgttctaaaatgaagcaatttcaac tttatttttttttcctgtgactttac atgacaagttcacatgaaggatatac tttgatagtaatgtccatggttaggg aatatacattgtttgctggttgactg gcccctggatttttctattgaaagtc catgagatctcgaaggcacaggtgtg ttctctcgctttttaaggaaagggtt taaaaacttaagtaattaacagcttt agtaacaaattacctataacacactt aaaaaccgaataccacccactggagt attgtgctacgattaaaaatctactt gtctactacatgatatctttgtccca cagaaggttctggaaccaaacttgta atttcaggattatgagagccctgagt tcacgcattgtgtaataactatgttg tgtggtagtcaatttgtacagcttgc ttagagagaacaatgtcaagttaagg aggcgattgctttatagtgcctgtca caagatgccattgccattgtcctagc aagagatattctatgggagtatacta cattttagtgaggataagaacttttt atggcatttagtccggtcatttccca accactgtcctgaaaaccaatttcat tttgatttcaggggcttgtgtgggca aagttgccaggcattaaaaagccact tctcaactgtagtatcacaatgcttt agttgggtagtgtattgcagatagct tatggctgaaaagttaccaagccttg cagttttcactcctttgagtttattt ccttgacagaattgaccctgagtttt ttgactcttacctgctcaactaataa acaccagagtcatttatctccattgc tcttgtctgacctttatttaccgaat aatgccttatgggttcacaaaaacaa ggggggagggggccagcatgccttag aaactgtctttagtcaagaaatgnga ttttattatgtaaatatatgagtatt ataatagatagtgttattaatagaca ccagcaagaattgtcaataatttaaa aatcacaaattaaaatacatccatgt tagnatcatttatcctaactcccaaa gccctttaaagtggaagatttagatg ttaacccagagattaaagacatgttc aaagaatccttgatttttttttgaat cccttgtttttagagaagaaaaccta atgattttccccctctggattctaca tattaaatatagttttggaacttgaa tattagtatggttaataagtgctgat atgctgattttgtttatatttttctt atgagtaaatatcctatatcaccaga cattatagtctatgtacaaatatgat tcttaaacctgatagcacattcatta gagttggaattgcctttttttttttt ttttttacagttgcacctgcaacata tgaaagttcccaggctaggggttgaa tccaagctgcagctgccaccctacat tacagccgtagtaacagcagatccga gctgcatctgcaacctatgctgcagc tcagggcaatgccagatccactgagt gaagccagggatggaacttgcatcct catagagacaacgtcgtgtccttaac ccactgagccagaacaggaactccag

aatttcctttcaatagaagaagcacc aagtttaggatcagaaagcctgaatt tgaataccaatttactatttgttagt catatatttctgagtgtgtttcctca tttattaaaagcagactaaaagatga gagggtcttttgttgagaatcaaata caataacatgtgaaagtgtgtaacac tatgattgaaatatacctacacagcc atttatttgtttattgttcatgtttt gccacccacacagtagtatataatcc ttttatgtaataaatgctaataatga aagttggcaacttatgtaagtactca aaatgctggaggtcatgggatactga ctgggatactacagaggtaatgtcat ttcctctgcgctaaacttattgtctt gtagttagggactgactctctttagg acaaggagttcattctgtataccatg tgtggctatcacccttcgaagttgaa aaactgccccagggtgggcacccatc cgttctcttagatatatggccgagac ctttctctcactgggagggaaccaca ctgaggaatgagaaaaaaaaaaggaa aatcaagatgaaaccagaaacctctt tggcataacttctccactctgtactt tttgttagaactacccttgcacaaag cagcatcagtgtggaagacagaattt gcacacctggtttgatatacatgccg tggtatatgggatgttctaacaataa agaggactctcccaggaaatctcctc actgttatagtcagccttgaggaaag agctcttcttttggactctggggaga gtctagtttttcagttccttgcttct cggtcaacgtgttggtgtaaggatca cactctctcttatactagataattct attttttcacctttcaacctgtctat ccttctgaccctag TTACCCAACACTGAAGAAGCTTGCTG Exon 9 Seq ID No 16 AGAGAAGACCAGATGTTCCCATTTAT GTTGGCAACACGGAAAGACCTGTATT TTGGAATCTGAATCAGAGTGGCGTCC AGTTGACTAATATCAATGTAGTGCCA TTTGGAATATGGCAGCAG gtctgtgttctttccacatgtttggg Intron 9 Seq ID No 36 ttatcctttctgggataaatttgagg cgagatagaaactttaagactaaaga aacaatggcctactttttttgtacat ggtcctgtgtaaatctctatttgagc tgaaataagatggtcttcctctccaa ttatccatggtatgactctgatggat aacaaatccagttctgaaaaaagggg atttctttccagaagagaggacagtt tcttcaaatattgaattaaaagcaaa atagatgtaaaccgttgttggtttta ttgttgaattccag GTAGACAAAAATCTTCGATTCATGAT Exon 10 Seq ID No 17 CTTGATGGATGGCGTTCATCCTGAGA TGGACACTTGCATTATTGTGGAATAC AAAG gtattttcttgccctcatcagcatga Intron 10 Seq ID No 37 aattgctcttggtagaaaggataata atagttatccaaaacatcatcctatg ttcatctgtttcttccctcttcattt tccatagagtacagtatattctatct ctgtcttaggaaaatggactgtcatt catataatcttacagagaatcaatta gtaatgtactctatgccgtgacaggt gcgaaggttttttttgaaggcaacag ataaaaatatcctatatttcacctat tgtaatttccttaaaactgacattat tgaataaatgttttactttcatcttg aatattattatgttatggaatcatac actttaccccaataatcatcgaaaag aatttccaaaaggttgagagagttgt gttgatctgattactttcctctgcat cctttgagcttaacctttgaatatag tttgctaaggaaagtagtctgtttat gatcctggagtggaatcaggctaagt gtcctcattcagaacccactgaatca gacagaatgaatttatttccttgaaa gttcaaaatgtgtcactcagagtata aattttcaaatcttactctctctttt ccttggatgtgagcaattcttcgata attgaatgaggcagattatatagact tacatggaagactgttggcctgagaa ttcaaactatggtgttcaagacttca cngngagtccgatgccatttgtttcc cacag GTCATAAAATACTCAATACAGTGGAT Exon 11 Seq ID No 18 TGCACCAGACCCAATGGAGGAAGGCT GCCTATGAAGGTTGCATTAATGATGA GTGATTTTGCTGGAGGAGCTTCAGGC TTTCCAATGACTTTCAGTGGTGGAAA ATTTACTG GTAATTCTTTATATCAAAATGATGCC Exon 11a Seq ID No 19 AAGGAGTTGGCATGGCACTTTGCTAA ATGCTGTGTGAATCAATACAAAGATA ATTAGGACATGGTTCTTCCTCACAAG AGGTGTGCAATCTTATTGGGAAATCA TACTTGCAAGTCACAAATATAGACTA AAGTTTCCAGCTGAGAATATGCTGAT GGAGCATGAAACACTAAGGAGACAGG GAGAATCTCAGGAAAAATCAAGAATA ATTTGGATCAAATGGATTCCTGACAT AGAACATAGAGCTGATCAGAAAGAGT CTGACATTGGTAATCCAGGCTTAAGT GCTCTTTGTATGTGGTTCAGAACAGA GTGTGGGCAGCCTGAGGGGGATACAT ACCCTTGACCTCGTGGAAAGCTCATA CGGGGGAGGGATGAGGCTAAGGAAGC CCCTCTAAAGTGTGGGATTACGAGAG GTTGGGGGGGTGGTAGGGAAAATAGT GGTCAAAGAGTATAAACTTCCAGTTA CAAGATGAATAAATTCTAGGGGTATA ATAACAGCATGGCACTATAGATAGCA TATTGTACTATATACTGGAAGTGCTG AGAGTAGATCTTACATGTTCTAACCA CACACACACACACACACACACACACA CCACACACACACACCACACACACACA CGTGCACACAAACAGAAATGGTAATT ATGTGAGGTGATGGCGGTGTTAACTA ACTTTATTGTGGTCATCATTTAGCCA TACATGCATGTCATGAAATCACCATG TTGTACACCTTAAAGTTATGTAATAC TAGATGTCAGTTATATCTCAAAGCTA GAAAAAATGTGGGGACCAAGGCAGAA GCTCTTCTGCTCTGTGTCTAAGGGTG GTTCTGGGGCTGGGATGGGGAGGATG GTTAAGTGGTATATTTTTTTCATACC TTTGCTCAGTACTATCATTGTAAGTG TTCAATATATGTCTGCTTAATAAATT AATGTTTTTAGTAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAA gtaattctttatatcaaaatgatgcc Intron 11 Seq ID No 38 aaggagttggcatggcactttgctaa atgctgtgtgaatcaatacaaagata attaggacatggttcttcctcacaag aggtgtgcaatcttattgggaaatca tacttgcaagtcacaaatatagacta aagtttccagctgagaatatgctgat ggagcatgaaacactaaggagacagg gagaatctcaggaaaaatcaagaata atttggatcaaatggattcctgacat agaacatagagctgatcagaaagagt ctgacattggtaatccaggcttaagt gctctttgtatgtggttcagaacaga gtgtgggcagcctgagggggatacat acccttgacctcgtggaaagctcata cgggggagggatgaggctaaggaagc ccctctaaagtgtgggattacgagag gttgggggggtggtagggaaaatagt ggtcaaagagtataaacttccagtta caagatgaataaattctaggggtata ataacagcatggcactatagatagca tattgtactatatactggaagtgctg agagtagatcttacatgttctaacca cacacacacacacacacacacacaca ccacacacacacaccacacacacaca cgtgcacacaaacagaaatggtaatt atgtgaggtgatggcggtgttaacta actttattgtggtcatcatttagcca tacatgcatgtcatgaaatcaccatg ttgtacaccttaaagttatgtaatac tagatgtcagttatatctcaaagcta gaaaaaatgtggggaccaaggcagaa gctcttctgctctgtgtctaagggtg gttctggggctgggatggggaggatg gttaagtggtatatttttttcatacc tttgctcagtactatcattgtaagtg ttcaatatatgtctgcttaataaatt aatgtttttagtaagtaatctctgtt tagtaatgtgtcagaaatgccctact tgcaataggaagaaaacctgtccagt cccttccttttttctgtaagtctgat ttcattgcctcccagaatgcatcacc atgtgagagatagagggaaggtgctg tccttatggggttaacagtgtgacta gggaggcaaaatatacctactaaagg gtggtagcataattcagttcttatgt gagtatgtgtatgtgtgtgagtatgt gcacatgcacatacattttaaaaggt ctgtaatatactaacatgttcatagt ggttacacctagcttataggtaacat tttttcccctgtatccttgtttgtgt ttatcaaattttcataacagtaatgg tagaaggagtacctgacatggtacca tacatgctnggncctgcctaatttct cnatttcctttattgcccataccccc attgcttgacaagcataagtccatac tggcttgttttcgttcctcagactca gtacaccatgtagctccatgccctgg gtctttgtatgtgctatttctactgc ttagagtgctattgcccctgaccacc acgtggtcagcaacttctcttctgcg tctgtgtctatggtctatgattccag atgtcatcttcactaactacccttct aatatgcccttccatcccacccgtcc tcatccttaccccagccactctctat ttggtggctctgttttattttcttcc tagctcatcactctttgaaatgaact tatttacttattcaatatttgcttct ttcactagaatgaatgctccatgaga gcagggacctgctttatcttgctcgc cactgtattcacagtgcctagaacta cgtctggcacatagtaggtgctcaat aaatatcgatcaaatgaaagaatgag caaacgaacaaatgaacaacacgtga ggtaggcatcatgattccatcaacag aggagaaaaccagacttaaagnaatg aagtggnggagctgcatttgatcttg actgactccaacatccatgctcttga ccactgtgcatctccagagtgtaatg aacatactttacttttatattccacc aaaataacaaagccatgcccatgtta gtagagagttaatcgacagtgccctt aaaatatgcatgcacccagggtacaa ctatgcatgctgccctgtgttttcag ttggatccaaatgaattgccgtaaac aaagaggggattcaatgtctttgact agtttgggatattttcctagtaacca actttgcaaaataaagccactaatga caaggagctttgttctacttctgcat cactcaactgtcaatttttatctctt gcaagacttctaatctactagaactt ttgtttttctgtgatttctgaacaga gaagactaatccaaaccctgtcattc cag AGGAATGGAAAGCCCAATTCATTAAA Exon 12 Seq ID No 20 ACAGAAAGGAAGAAACTCCTGAACTA CAAGGCTCGGCTGGTGAAGGACCTAC AACCCAGAATTTACTGCCCCTTTCCT GGGTATTTCGTGGAATCCCACCCAGC AGACAA GTATGGCTGGATATTTTATATAACGT Exon 12a Seq ID No. 21 GTTTACGCATAAGTTAATATATGCTG AATGAGTGATTTAGCTGTGAAACAAC ATGAAATGAGAAAGAATGATTAGTAG GGGTCTGGAGCTTATTTTAACAAGCA GCCTGAAAACAGAGAGTATGAATAAA AAAAATTAAATAC gtatggctggatattttatataacgt Intron 12 Seq ID No 39 gtttacgcataagttaatatatgctg

aatgagtgatttagctgtgaaacaac atgaaatgagaaagaatgattagtag gggtctggagcttattttaacaagca gcctgaaaacagagagtatgaataaa aaaaattaaatacaagagtgtgctat taccaattatgtataatagtcttgta catctaacttcaattccaatcactat atgcttatactaaaaaacgaagtata gagtcaaccttctttgactaacagct cttccctagtcagggacattagctca agtatagtctttatttttcctggggt aagaaaagaaggattgggaagtagga atgcaaagaaataaaaaataattctg tcattgttcaaataagaatgtcatct gaaaataaactgccttacatgggaat gctcttatttgtcag GTATATTAAGGAAACAAACATCAAAA Exon 13 Seq ID No 22 ATGACCCAAATGAACTCAACAATCTT ATCAAGAAGAATTCTGAGGTGGTAAC CTGGACCCCAAGACCTGGAGCCACTC TTGATCTGGGTAGGATGCTAAAGGAC CCAACAGACAG gtttgacttgaatatttacagggaac Intron 13 Seq ID No 40 aaaaatgatttctgaattttttcatg tttatgagaaaataaagggcatacct atggcctcttggcaggtccctgtttg taggaatattaagtttttcttgacta gcatcctgagcttgtcatgcattaag atctacacaccaccctttaaagtggg agtcttactgtataaaataaactatt aaataagtatctttcaactctggggt ggggggggagactgagttttttcaca gtcctatataataattttcttatcct ataaaataattaggagttcccgtagt ggctcagcaatagcaaacccgactag tatcgatgaggatgcgggttcgattc ctggcccccctcagtgggttaaggat ctggcattgccgtgagctgtggtgta ggtggcagacacggctcagatcccac gttactgtggctgtggcataggccag cagctccagctctgattagaccctta gcctgggaacttccatatgctgtggg tgtggccttgaaaaaaaataaataaa taagataattactcaaatgttttcct tgtctcagaaccttacttcaggataa agagtgagaaagttttttttatgaag ggccattattacagctcaaaaataag ttgtcttcagcaagtagaaagcaata agcctgagagttagtgttcctatcag tgtaaatattacctcctcgccaatcc ccagacagtccatttgaacaattaac ggtgccctgggagtacagttcagaaa cattaatgtggatgttccagacctgt atttttataagtacttgtcttgagcc ggatggaaccatcattcctcaccatt atttagaagtggactgtgactctgtt ggagatcagggcacacggttaccaaa agcacacccttctcctggccttacct ttgcaaagctggggtctgggacacag tcagctgattatacccttttactaac ttcccacagctcaaatctggtcaatt ctccttcacaaatctcttaaaaatcc atcactcacctccagcctcttctgct gtggccttgattcagcctctcacaat ttttttttaaccagaattctggcagt ggcccctgacttgcctctgtgctccc agccccgctgtcctctgatccatcct ccatgccagcctttttcaatctgctg gtcacgattcattgatgggttaggaa atcaatggcatcacaactagcattta gaaaaaggaaataggcgttcccgccg tggcacagcagaaataaatccgacta ggaaccataaggttgcgggttcaacc cctggccttgttcagtgggttaagga tccggcattgccgtgggctgttttgt aagtcacagacatggctctgatccgg cattgctgtggctctggcgtaggcct gcagcatcagctccaattagacccct atcctgggagcctccatatgctgcaa gtgcagccctaaaaaaaataaaaaaa taaaaaaaaataaataaaagaagtag acaaattgtatagaacaaccctgagt atgttgcctgagcacatataacaagg gtaagtattatttcaggaaactctgg tttcacagatactcttggcatatgga cccctagagtcctgatgtaaaatata ttcttcctgggatcttaggcaagaag tttgaaagctccaactctgcactgct gccaaagaaatgatttttaagtgcaa aactcttcccgttcccttccctgtat aaaattccataggatctctccagtgc ctctaggataaaggcagttttcattc tctagttcaaggtgagagaagatttt aattatttcacgttttagtggggaat tcaagagtctggcacctgacatttgc tgaactctctccattatccctctcta gttccccagacgcatcctatggtaga aattcgcaaactagagtgagcgtcag agtaacccaaggaaactgggtaaatg cagctccctgggctctaccccctgag attctgattcagtagatctgaagcag agccctggaatatgcatatgcatcat tgtgtcacaccaagcattctgggtaa tgagagttgatgttaggttctcagta gtaagacaagtatagagattccgggg gactgagtgctcagctctgccttggg gaggagggagagggctaaagagaaca ggagatggggacagggaatgctcaac ctccaatcttaggcatttgagctatg tcttaggggtcaggaggaggttacca atatagtgattaagagattgaggttc cagtcagagggatatgctggagaagg ggggtgaaaataatgtcataggtttg gtgagtgcagatactttgagtttttt aatatttttattgaaatatagttgat ttacaatgctcttagtgagtacaatt actttgaataagtgcatagatgtatg ccattcttccagaaatgatttattga gctcctttgggcatcatgctaagtac aggggaaacagctgtgaagaggtcct tcccttatgaagtcattcatcccctt cagtaaatgaaggtaaaggaaaagga tgagacagggacgccgtgttggacca gggtcagaaaggccttataagacctt gcctggagggcaaggaacttgcctgt gagtaaggagagcttgagaaagcgat aaagcaaagaaggaacattactgcat tgtgttttagaaaaaccatgtcctgg ggaagaactcctagagtcaggggggc cagttgggagactgtgcttttttcca ggaggagataagtgaggctgctggct gagatggagcaaggatttagagaagc agatatgagattcatttagaagttag acattttaggatctgacacataattt atcaccaaaaccagtgcatctctggc tttgggccaccagttttggagaagtg gaatgtagggacctaccattacctgc caatctttactacacagatgcctatt tccctcctcatatttcctttctccag atcacgtcctattctattgccaggac tcaagattccaccttgcatgcagtga tccatcttcacactggatggacagct ctagggatgtcagagcacactcttgt ccatactgctgactgggtctcctgtc agcccatctgtctatcagctgtggta ttattagtataataagagggctgtat atgagagacacaaaattctaggtgta gctcaaagataggctagagttattcc tatgtacaacaaatatttatgggacc ccttctgtgtactgtcatggttgctg ctttcatcatacttgtagtctaatgg aggtgggggcagggcaggaataagcg gatgtccacaaatcagtaagaccact tatattcaacattttcataatttagt tatttgagcccaaagggtccacatcc gtggtattccaacttttttttccccg gacatggatctttatctttttttttt tttcttttttgcggccagacctgcgg catatggaagttcccaggccaggggt tgaatgggagttgcagctgcctggtc tacaccacagccacagcaaggtggga tctgagctgcatctgtgacatacacc gcagctgaggtaacaccagattctga acccactgaatgaggccagggatgga acccgtctccttatgaacactatgtc atgttcttcaccctctgagccacaac gggaactccagacttcgtctttaaat gtattctgacttggagagctatcaca ctaagcaattaacaggagctgacctg gtttaggctggggtggggccctactc ctcaatgttccctgaggcacatctgt gggacccctgggcatcatctatctga gcagccttagagctgctcatccagtt gactgttgatgtagaagtgcaaactt ctgccttccttatttgttgctttctt ttttcattgttctctcccctttgtgt ctttaag CAAGGGCATCGTAGAGCCTCCAGAAG Exon 14 Seq ID No 23 GGACTAAGATTTACAAGGATTCCTGG GATTTTGGCCCATATTTGAATATCTT GAATGCTGCTATAGGAGATGAAATAT TTCGTCACTCATCCTGGATAAAAGAA TACTTCACTTGGGCTGGATTTAAGGA TTATAACCTGGTGGTCAGG gtatgctatgaagttattatttgttt Intron 14 Seq ID No 41 ttgttttcttgtattacagagctata tgaaaacctcttagtattccagttgg tttctcaataagcattcattgagcct tactgactgtcagacggagggcgtat tggactatgtgctgaaacaatccttt gttgaaaatgtagggaatgttgaaaa tgtagggaatgaaatgtagatccagc tctgtttctcttttggaggattcttt ttcctccatcaccgtgtcttggttct tgtttgttttgggtttttgtgggtgt tgtattgtgttgtgttggttatggca gtgacagctatttaaactgtgaaacg ggggagttcccgtcgtggcgcagtgg ttaacgaatccgactgggaaccatga ggttgcgggttcggtccctgcccttg ctcagtgggttaacgatccggcgttg ccgtgagctgtggtgtaggttgcaga cacggctcggatcccgcgttgctgtg gctctagcgtaggccagcggctacag ctccgattggacccctagcctgggaa cctccatatgccgcaggagcggccca aagaaatagcaaaaagacaaaataaa taaataaataaataagtaagtaaaat aaactgtgaaacggggagttcccttc atggctcagcagttaacaaacccagc taggatccatgaggatgtaggttcga tccctggccttgctcagtgggttaag aatccagcgttgctgtgagctgtgat gtaggtcgcagatgcagcccagatcc tgcattgctgtggctgtggcgtaggc tggcagctgaagctccgattcaaccc ctagcctgggaacatccatatgctgc aggtgtggccttaagaggcaaaaaaa taaaaaaataaaaaataaataaattg tgggacagacaggtggctccactgca gagctggtgtcctgtagcagcctgga agcaggtaaggtaaggactgcagctg ggtaaggactgaattgcaccaactgg gaagtaagcctagatctagaacttaa gttagccctgacatagacacacagag ctcaccagctaagtggttcagcttat aagctggtcactgaaactgaggatgt ccacaaaagcaaaataagtagcaaca ggcagcgggatgcaagagaaagagga ggcctaaaatggtctgggaatccctg ccatacctatattttatcctacttat atttagtgcctgaatgtgtgcctgga gagcaaagtttagggaaagcatcggg aaatgcacagtattcatacccttagg aacaaagatcagttacctccagggta aagactatttccaagtttaaatttca acccctgaacattagtactgggtacc aggcaacacttgccatcctcaaaatc aatgaatcctaaaattcaacctgggg gtcagtgacagtctgtgacaaagttt ttgctggtcagtaacgaaataagtat gagcaccatctgagtatggtcaccaa gatgtcaactctctttcctttggacg aattgtcattattccaagattaggtc ctttctatttttgaggtgtgaaaaca tctttcctttcataaaataaaaggat agtaggtggaagaattttttttgttt

tttggtctttttgctatttctttggg ccgcttctgcagcatatggaggttcc caggccaggggtcgaatcggagcttt agccaccggcccacgccagagccaca gcaacacgggatccaagccgcatctg cagcctacaccacagctcacggcaat gccggatcgttaacccactgagcaag ggcagggaccgaacccgcaacctcat ggttcctagtcggattcgttaaccac tgcgccacgacgggaactcctaatga tactcttttatatttagctactatgt gatgatgagaaacagtccacatttta ttattttttagccaatttgatatctc attactaagataatgataattttctc tataaattttatttaagttagtgtta tgaagtggttttgctagtgtagaagg ctaggatttgaattcagttcaagaaa gaagagagggagggagggagagggat gggtagagggatggggcagtgggaga gagcaaagaggagagacagtttttgt attaattctgcttcattgctatcatt taagggcacttgggtcttgcacattc tagaatttctaaggaccttgaccgcc agattgatatgcttcttccctttacc atgttgtcatttgaacag ATGATTGAGACAGATGAGGACTTCAG Exon 15 Seq ID No 24 CCCTTTGCCTGGAGGATATGACTATT TGGTTGACTTTCTGGATTTATCCTTT CCAAAAGAAAGACCAAGCCGGGAACA TCCATATGAGGAA gtaagcaggaataccagtggaagtgc Intron 15 Seq ID No 42 ccctttcttccttccttcctaaataa acttttttattttggaacaactttag agttacagaaaagttgcaaagatatt atagacagtagtgtttatatatatat ataaatttttttttgctttttatgac cacacctgtggcatatggaggttccc agtctaggggttgaattggagctaca gctgccagtctgtgccataaccacag caatgcaggatctgggccacgtctgt gacctacaccaaagctcacagctgga ttcttaacccactgagcaaggccagg gattgaacctgcatcctcgtggttcc tagttggattcgtttccgctttgccg caatgggaactccaaattattgttaa tatcttactttactggggtacatttg ttacaaccaatactctgatactgaaa cattactgttaactccgtacttgctt ctttttgagtcatttgcaaagactgg cttcttgacctgcttccttccaaaca gctggcctgcctatgctgttctcaga cctgcaagcactgatctctgcccccc ttgccttctctccagtggtgtctcct tccccaaacaaacccagtgtggctct ggaaagggagttaagtcaacataaac caacacatattttgttgagctccaat tttgagcaaatccctcacctacggca gacaggcatgatgttaagaactaggg ctttggacacaaggtcaagaccaaga agggttcctcacccctactgattcag ataaccaataatgaggctttgaatcc ctgtccaaaggttgttttttttccct tctattgagcttcttgccaccttatc agttttttttatgacagtcaaatgac atgatatatgtgagcatacatggtaa tttttaattctatataaatgaatcac taaataaattaggaggatatatagtc cacctttaagcgtattacacgtgtca catgaatgtgtggcgacttaattgta gaggtttaaatgtagcttcctataat agatgtgttcctaaactacattttaa tcattggacttgtatttttatgttag cacttgctgttgaagaaaagcctatg ccaaaagttcagtgaaaccaataatc cactgccagctttctgagttaaaaaa aatccctgggttttcacacacaggaa caccctgtgtgaaacactcatttaga gcaaaatgcatctgataaggagttcc tgttgtgcctcaactggttaaggacc tgacattctccatgagaatgtgagtt tgatccccggccccactcgatgggtt aaggatctggtgttgccacaaactgc agctccgattcatctcctagcctaga aacttccacagcccagaatatgccac agaattcggctgtttaaaaaaaaaaa gaaaaaaaaaagaatcataaatgtgt tggtttgttcaccaaatacatgataa cttgctcttgccaagctcagcttcat aaatattaagtcatttaatacagcag ccaccttatgaacagatattactata cttcccatttacagataaggaaaatg ccatatttaaccaagagattaaataa ctttcccgaggtcttatagcaagtaa atcatggtgcaggggtttgaccacac gcagtctatcctccagagtctgtgta tttagccactgttttactttcaaatt taaatttataaaacttctaaattatc tgttaaccataatctttggaattttt aaaaccacgagttcctataaaatgtt tcattgaaagtaagtcacttttccat agcttttgataatacatctgtaggat aaagtaagccacagctctcttgcaga cttggtacaccctggggcaaagcatc atgcctgtcacgtacatggtggtcct tactttgactctcagtgcttttattg cccaggaattttgtgagatttctagt tgttgaggtttgtttaaagaggttat gccggtacttggaagagctcttttct tgctacctggagccttctcatatttc ctttttgaggagggacatgaattgcc tttcaaactcataaatatattttcta gtacacaagtctccatcttccttaga cgcatggctcctggagttctccatcc tcctgctccactttgggtgggctcct ctctgggtctgccaccaatctgccac ccagagacatccttgacccacttcca gaccccaccatggcttcactttcttc gctttcctcctttgtggaaccttctg cttaagaatctgaggaagaaaatttg cacgtgagctaaactggaggtacttt cctgcctggtcttgcacgatagcttg gctgagcccatgatgctgggtggctg ttactttccatggacacccgaaggcg ttgctcctttggcttctagttgcatg cagtgttgcttatcccaggctgatct ttcttccactgtaggtgacttttaag aattaagggattaatctatatctaca acaacaacaacaaagaccttttcaag ctgaggtagggctttctgtatatgtt tggagtggttatccagcagactttac ttgaaggcaggggtcatatcctcaag tgctcataaacggaccacagaaagat ctcataattgggtggagctgggtggg gaccgtgtcatgtggccaggaaatgc cagatgggaagggagtggcccttact gagctccagctgaactctgaattttc tagaaaactcagaaatctggattttt catgtgtaatacccagatttatagat gtggaaagctaattcttttttttttt aagggactataggcaatgaactaaga tctaggttgtatttggacaaggggtc atcagtttaagctgtgtagttgagcg ctcagctattgggctgagggacccct aaatactgagacggggaggtccttgc tctggggcatcacaagtacactccct ggtctcattcaaacacttttcctaca aaattgatcccatttcttcagtgcac tgtctgaatgcatttggcccagagcc gtgctgaggcatagggaaggggtcca cggtttcatggcatcgttttgtgctg tgtgtccctgctgtcgtccaggatac ctacctctcctcctcctgcatctgaa tgtccccccacagactctctgggatt ctacagcctctggcctgttcctcaga cacctcttacctgccagctttccaga ttcacattagttagtccaaatctact gccgtcagtgactcacttcatttctt cttctccgaggcagttcagcccggta cagttgttttgtcaacacttcagttg agtctggaagatgtgcatgggttatg cacgagagcggtccatcattttgagc tagaagtcctttctcagcccagagac aagtcctcatctcctttacttcctga ctcttcttcctctgcatccttccaag atatctctttctccagccaccaccta aatctcttcttttcccggggttccgt gctcaacccactcttcttcttaaatc tgtggctgggtgaacgcatctgctgg caccacttctctgctaaagactccaa aaatccataggtcctgcccggccttt gcccacctctctccaacactgtccag ctttagatgtagagctaatcccccca gagatatcattccctggatgtctaag tcctttggtatctcactttcagcgtg ttcaaaatcctcttacaactgttctt tctccttttccatcttgattattggc aacatgccagcctttcccctaccccc agcagtgagccaagctagaaacaagg gcttaatcttcaatctttccttctcc atccctaaacctaatgagtctccaag cccttcccagtttacaccctaaatgt tgctcaaaacatcccctagttcttcc acgtgctctcctctatattgaaaggt caagaaaggccatcttccctccactg tgaggaaatagatcttgatactgccc ctgagctgggcagtcctcgacctgac aaactgtgcagtgtttctaaatctct actggcaaaatgagagtgcctttgac ctgtgttgcgatctcagatcacagtg gatgtaattgttttataggaatggtg aacgaaaaagaagtaaatccctaatg ccaaactcctgatcattctatgtcat ttaatagcctgtcatttatgataaag tttcctctactggcattagcacaata cttctcaggaaaaaaaaatatgatgc cagatactgaaaagctcctgggtaaa catgaacatgggtaccgataaaatgg tgaagccagtccaatcttagagtgac ttcccttcatgctacttcatgctctt ttttttttttttttttaagaaaaacc ccttttttttttctcacaccagtcac agaggagaccgaggcttagcaaggtt aaggtcacatgattagtaagtgctgg gctgaaactcaaaaccatctctgctt gtctcctaaccctgtgcacctctgac tattcaacag ATCCTGTGTCAGGAGTTGGGATTCTT Exon 15a Seq ID No 25 TGAAG gtaagggccttgaccaccgaattaag Intron 15a Seq ID No 43 gtaatcttgctctgtggcaggccttg ttttcagtattttaagtacactggct caggtaatcctcacaacagccccagg aggaatgttctattacctccactgta tagatgaggaacttgaggcacagaat ggttgccaaggtcacacagctatatt gggggttcatacccagccatccaact ctgtctgtactctctgccactctgca cccccagctcctgatccacttcctgt ttccatccctcgatttctgctgcact caggggcccctctccccctcggcctg tgagatctgcttcagtaggcttttct ccctgactcctccatccctgtcctta caggcagctgcttctctccgggacac gaggggtccatacggacactctctac tggctgggttgcgcctaactcgtgat tcctcctctgtttcag ATTCGGAGCCGGGTTGATGTCATCAG Exon 16 Seq ID No 26 ACACGTGGTAAAGAATGGTCTGCTCT GGGATGACTTGTACATAGGATTCCAA ACCCGGCTTCAGCGGGATCCTGATAT ATACCATCATCT gtaagtccgaaaatgcctgtcgtgtg Intron 16 Seq ID No 44 tgccttaggctgctgcggaggaggcc agggctatataagcagagtcagtgac tgactgtgccctgcagtgttgatggc catggagattccaccgttagagcttt tttctttgttaaccttgaaggcaaat ctggttaggaagataactttcaaaga gtcaccatctggacattcatgcccat gtgcttcaatcctgtatacaagcagt ttagagtacagggaagggaaggacat tatgaaagggagagggtgtgtttgga tccagcagctccatcctcagaattta tctgaagacactgcaaaattactaag aatcactatgacaagaatgaggatgg

ggtgatatggcaaagttgtgatcctg gaagaccttcatctcccatgttgccc aactctgaacatgaatttggtgaact agttggttaaggggatgatcctccaa gtttctccctggttgagctccaaaaa ccatgtaagtttctcatagcaaaacc gtataggtccttagggctttagttgg aatatttgtgctgaaatgctggaaag ccccatttgccatttttgtatttgca aaataatcatcaagaggggagaatgc attctttcatgaccactgaccctctg aaaaggtcaggaatttagtctgaagt aggcaagcctcctaccccgcttctgc catgagcttgcacgcacaggcctgtc ttgacatttcttctttatagatttct ttttgaatatcttgaaattgctttaa aaatatttaaagaatgtagaattata taaaataaaaaggaaataaccccaca cctcccacaaaaccctgtttcctgcc tttctccacccactctccagggtaac acttggtaacagcatagttgtatcac cccaggcctatttttgagcatatcag catttcaagaaatgtattttttctca ataaaacatcccttatagttgaggag gggaggttatcattcctgggttttgt tttttttttttttttaatgtaatcct ggtacatcggtaatttgcatttttta ttcattaatatctttggtatttctag tgttgggacacacaggtcaacctcag tttttgggtttttttttttgtctttt tgtctttctagggccacacctgcagc atatggacgttcccaagctaggagtc taatcagagctgtagccaccagccta cgtcatagccatagcaacgtcagatc caagccgtgtctgtgacctacaagca cagctcatggcaacaccggatcctta accactgaacgaggccaggggatcga acacacatcctcatggatcctagtca tgttcattaaccactgagtcatgatg ggaactccaacttcaactattttaat gtctgtaaaacattccatttggaaac catttcatttgtaaagcaaaatgaaa acattttgttcattttcaacagagtt cgtagctgacttctgttctggaaaaa aggaaatggagcaaatttgagtgaga aagattcaaagataacttttctttta aaaaaaattatatcttggaaacttct gggctattgattctgaagactatttt tctatatactgttttgatagcaaagt tcataaatgtgaaaggatcctgcgat gaatcttgggaagcagtcatagccca atatatctttgttgcttttaaaatga gatttagtttactaaatatttttctg atcataaaaataacacagatctaccg cagaaaatttggaaaaaaaaaaactt ttaaattcaaaaaacagttaaaccac aaatgatcccaccatccagagagcaa tttgtactttggtgtctagttcatct ttctttttctgtttacaagcacatat accacaagcattttttcaaaaaatga aaatgggataatactatacatacgtc tgtacacctgcatagttactgaacag tctttgatctaccctgtaagtttcta acttttcattatttgaaatgatgttt tggcaaagaaatatgtaggtgtgtct cgcacactttcataatgatttcttag gataaatttcttaggataaattcata atgatttcttataataatccatactc tgccaactgatcttcagggaagccaa ctcgccttctcagaaataacatataa cccatttacttgccctctcaccaata ctaggtcctaatgtttttgtgtacag attctatatttttacatacaagaatt ccttaaagcaaggcatgtcacagaaa aatagaaggaagacacaattgtcatg tttaaggactgcattctgtaccaaaa atgctaagttaaatgaacatctgaaa cagtacagaaacgctatctttcaggg aaagctgagtaccaggtactgaacag attttggcaaatacagcaggcatgga tgtttccaaaacatgtttttctactt tatctcttacag GTTTTGGAATCATTTTCAAATAAAAC Exon 17 Seq ID No 27 TCCCCCTCACACCACCTGACTGGAAG TCCTTCCTGATGTGCTCTGGGTAGAG AGGACCTGAGCTGTCCCAG gtaaagcatcctgcaggtctgggaga Intron 17 Seq ID No 45 cactcttattctccagcccatcacac tgtgtttggcatcagaattaagcagg cactatgcctatcagaaaacctgact tttgggggaatgaaagaagctaacat tacaagaatgtctgtgtttaaaaata agtcaataagggagttcccatcgtgg ctcagtggtaacgaaccctactagta tccattgaggacacaggttcaatatc tggcctcactcagtcggctaaggatc cagtgatgccgtgagctgcagtgtag gccacagacgtggctcagatctggtg ctgctgtggctatggtgtaggccggc cccctgtaactccaattcgaccccta ggctgggaacctaaaaagaccccaaa aaagtcgctttaatgaatagtgaata catccagcccaaagtccacagactct ttggtctggttgtggcaaacatacag ccagttaacaaacaagacaaaaatta tcctaggtggtcagtgggggttcaga gctgaatcctgaacactggaaggaaa acagcaaccaaatccaaatactgtat ggttttgcttatatgtagaatctaaa ttcaaagcaaatgagcaaaccaattg aaacagttatggaagacaagcaggtg gttgtcaggggggagataaggggagg caggaaagacctgggcgagggagatt aagaggtaccaactttcagttgcaaa acaaatgagtcaccagtatgaaatgt gcaatgtgggaaatacaggccataac tttataatctcttttttttttttgtc ttttttgccttttctaaggctgctcc cgtggcatatggaggttcccaggcta ggagtccaaacagagctgtagctgcc agcctacaccagagccacagcaacac gggaaccttaacccgctgagcaaggc cagggatcgaacccgagtcctcacag atgccagtagggttcattaaccactg agccacgacaggaattccagggtctg ttgtgttcttaaaacacttccaggag agtgagtggtatgtcataagtaaaca ataaatgttaaccacaacaagcttat gaaataaacaggaaagccatatgacc tacaatcagtcattgggagaatccac aaaaggttgagcagaggatcaattcc agctcacactccagttttagattctc ccctgccttaaagcatcacagactac ataatctgagctgaagaataaaaatt aaaactcaccccagtgcaaaacagaa atgaaaaagtattaaaacgaggttca tactgttgttcattagcaatatcttt tattcacag GGGTGCCCAACAACATGAAAAAATCA Exon 18 Seq ID No 28 AGAATTTATTGCTGCTACGTCAAAGC TTATACCAGAGATTATGCCTTATAGA CATTAGCAATGGATAATTATATGTTG CACTTGTGAAATGTGCACATATCCTG TTTATGAATCACCACATAGCCAGATT ATCAATATTTTACTTATTTCGTAAAA AATCCACAATTTTCCATAACAGAATC AACGTGTGCAATAGGAACAAGATTGC TATGGAAAACGAGGGTAACAGGAGGA GATATTAATCCAAGCATAGAAGAAAT AGACAAATGAGGGGCCATAAGGGGAA TATAGGGAAGAGAAAAAAATTAAGAT GGAATTTTAAAAGGAGAATGTAAAAA ATAGATATTTGTTCCTTAATAGGTTG ATTCCTCAAATAGAGCCCATGAATAT AATCAAATAGGAAGGGTTCATGACTG TTTTCAATTTTTCAAAAAGCTTTGTT GAAATCATAGACTTGCAAAACAAGGC TGTAGAGGCCACCCTAAAATGGAAAA TTTCACTGGGACTGAAATTATTTTGA TTCAATGACAAAATTTGTTATTTACT GCGGATTATAAACTCTAACAAATAGC GATCTCTTTGCTTCATAAAAACATAA ACACTAGCTAGTAATAAAATGAGTTC TGCAG

TABLE-US-00011 TABLE 10 Genomic Sequence of CMP-Neu5Ac Hydroxylase gene ctgccagcctaagccacagccacagcaacgctgggtc Seq ID No. 46 tgagccatgtctgcagcctatgccagagctccccgca gcgccggatgcttaacccactgagcaaggccagggat tgaaccctcgtcctcatggatagcagttgagttgttt ccacggaactcttaggggaactcctgattatttttta tttaaatttatatttctctgactttttcgtgtgctca tcagccactgactgtgtatctccattagtcatggttt gttaactctgtcattcaaaccctcttcatccttgcta cgcagataacatcattataataaaatcgtgcctgaag accagtgacgcccccaagctaagttactgcttcccct ggggggaaaaagaagcaccgcgcgggcgctgacacga agtccgggcagaggaagacggggcagaggaagacggg ggagcagtgggagcagcgggcagggcgcgggaagcac tggggatgttccgcgttggcaggagggtgttgggcga gctcccggtgatgcaggggggaggagccttttccgaa gtagcgggacaagagccacgggaaggaactgttctga gttcccagtCCCGACGTCCTGGCAGCGCCCAGGCACT GTTATTGGTGCCTCCTGTGTCCACGCGCTTCCCGGCC AGGCAGCCCTGGCGGATCCTATTTTCTGTTCCCCCGA TTCTGGTACCTCTCCCTCCCGCCCTCGGTGCGCAGCC GTCCTCCTGCAGTGCCTGCTCCTCCAGGGGCGAAACC GATCAGGGATCAGGCCACCCGCCTCCTGAACATCCCT CCTTAGTTCCCACAGgtgagaaggcttcgccgctgct gccgctggcgccggcagcgccctccacgcacttcgta gtgggcgcgcgccctcctgcattgtttctaaaagatt tttttttatccgcttatgctatcagttactgaggaag tatttacaaatctactattattttgaatttgcctttt tctccttatagtttatcagtatctcttgagactgtta ttggtgcctgcaaatttaaaatgattggggttttatg aggaagtgaaccttttatctttatgaaacgcctaact gaggcaatgttaattgcttaaaatactttctttatta tcagtgtggccatgccagtgtcctcttggttagaatt tgcctgat............................. ............ctgccaaagctgggagatgggggaa agtagagtgggttattgaaactgaatatagagttcag catctaaaagcgaggtagtagaggaggaagctgtgtc aacggaaatactgagctgggttcacatcctctttctc cacacagTCTAATGCCTTGTGGAAGCAAATGAGCCAC AGAAGCTGAAGGAAAAACCACCATTCTTTCTTAATAC CTGGAGAGAGGCAACGACAGACTATGAGCAGgcaagt gagagggggctttagctgtcagggaaggcggagataa acccttgatgggtaggatggccattgaaaggagggga gaaatttgccccagcaggtagccaccaagcttgggga cttggagggagggctttcaaacgtattttcataaaaa agacctgtggagctgtcaatgctcagggattctctct taaaatctaacagtattaatctgctaaaacatttgcc ttttcatagCATCGAACAAACGACGGAGATCCTGTTG TGCCTCTCACCTGCCGAAGCTGCCAATCTCAAGGAAG GAATCAATTTTGTTCGAAATAAGAGCACTGGCAAGGA TTACATCTTATTTAAGAATAAGAGCCGCCTGAAGGCA TGTAAGAACATGTGCAAGCACCAAGGAGGCCTCTTCA TTAAAGACATTGAGGATCTAAATGGAAGgtactgaga atcctttgctttctccctggcgatcctttctcccaat taggtttggcaggaaatgtgctcattgagaaatttta aatgatccaatcaacatgctatttcccccagcacatg cctaactttttcttaagctcctttacggcagctctct gattttgatttatgaccttgacttaatttcccatcct ctctgaagaactattgtttaaaatgtattcctagttg ataaacagtgaaacttctaaggcacatgtgtgtgtgt gtgtgtgtgtgtgtgtgtttaccagcttttatattca aagactcaagcctcttttggatttcctttcctgctct ctcagaagtgtgtgtgtgaggtgagtgcttgtccaaa cactgccctagaacagagagactttccctgatgaaaa cccgaaaaatggcagagctctagctgcacctggcctc aacagcggctcttctgatcatttcttggaagaacgag tgctggtaccccttttccccagccccttgattaaacc tgcatatcgcttgcctccccatctcaggagcaattct aggagggagggtgggctttcttttcaggattgacaaa gctacccagcttgcaaaccagggggatctgggggggg ggtttgcacctgatgctcccccactgataatgaatga gggattgaccccatcttttcaagctttgcttcagcct aacttgactctcgtagtgtttcagccgtttccatatt aggccttccaccgtgtcgtgtcgtcaatcttatttct caggtcatctgtgggcagtttagtgcgaatggactca gaggtaactggtagctgtccaagagctccctgctcta actgtatagaagatcaccacccaagtctggaatcttc ttacactggcccacagacttgcatcactgcatactta gcttcagggcccagctcccaggttaagtgctgtcata cctgtagcttgcttggctctgcagatagggttgctag attaggcaaatagagggtgcccagtcaaatttgcatt tcagataaacaacgaatatatttttagttagatatgt ttcaggcactgcatgggacatacttttggtaggcagc ctactctggaagaacctcttggttgtttgctgacaga ctgcttttgagtcccttgcatcttctgggtggtttca agttagggagacctcagccataggttgttctgtcacc aagaagcttctgcaagcacgtgcaggccttgaggtct tccgacttgtggcccggggactctgctttttctctgt ccttttttctccttagtgggccatgtcctgtggtgtg tcttagccagttgtttaagggagtgttgcagctttat gattaagagcatggtctttccttgcaaactgcttggt ttagaagcctggctccaccacttagcggctctgtgac ctcggacacatttcttagcctttctgggcctcgctct tcttcctcataaagtgaaaatgaaagtagacaaagcc ttctctgtctggctactgagaggatggagtgatttca tacacataaagcacttaaaataatgtctggcatatga tacatgctcaataaatgtcacttacatttgctattat tattactctgccatgatcttgtgtagcttaagaacag aggtctttacaggaattcaggctgttcttgaatctgg cttgctcagcttaatatggtaattgctttgccacaga ctggtcttcctctccttcacccaaagccttagggggt gaacgatcccagtttcaacctattctgttggcaggct aacatggagatggcaccatcttagctctgctgcaggt ggggagccagattcacccagctttgctcccagataca gctccccaagcatttatatgctgaaactccatcccag agcagtctacatggtacactcccccatccatctctcc aaatttggctgcttctacttaggctctctgtgcagca attcacctgaaatatctcttccacgatacagtcaagg gcagtgacctacctgttccaccttcccttcctcagcc atttttcttctttgtacataatcaagatcaggaactc tcataagctgtggtcctcattttgtcaatctaatttc acagcctcttggcacatgaagctgtcctctctctcct ttctgcctactgcccatgagcagttgtgacactgcca catttctcctttaacgacccagcctgctgaatagctg catttggaatgttttcaatttttgttaatttatttat ttcatcttttttttttttttttttttttttttttttt agggccgcacccatgggatatggaggttcccaggcta gggatccaatgggagctgtagctgctggcctacacca cagccacagcaatgcacaattcgagccaatctttgac ctacaccagagctcacggcaacactggattcttaacc cactgattgaggccagggatcaaactctcgtcctcat agatacgagtcagattcgttaacctctgagccatgat agttgttagttactcattgatgagaaaggaagtgtca caaaatatcctccataagtcgaagtttgaatatgttt

tctgccttgttactagaaaagagcattaaaaattctt gattggaatgaagcttggaaaaaatcagcatagttta ctgatatataagtgaaaatagaccttgttagtttaaa ccatctgatatttctggtggaagacatatttgtctgt aaaaaaaaaaaatcttgaacctgtttaaaaaaaaaac ttgactggaaacactaccaaaatatgggagttcctac tgggacacagcagaaatgaatctaactagtatccatg aggacacaggtttgatgcctggcctcgctaagtgggt taaggatatggtgttgctgcagctccaattcaacccc tatcctgggaacccccatatgccaccctaaaaagcaa aaagaaaggtgctgccctaaaaagcaaaaagaaagaa agaaagacagccagacagactaccaaatatggagagg aaatggaacttttaggccctatctccaactatcacat ccctatcaccgtctggtaagaaatggaaaaaatatta ctaagcctcctttgttgctacaattaatctgattctc attctgaagcagtgttgccagagttaacaaataaaaa tgcaaagctgggtagttaaatttgaattacagataaa caaattttcagtatatgttcaatatcgtgtaagacgt tttaaaataattttttatttatctgaaatttatattt ttcctgtattttatctggcaaccatgatcagaaatct ttaaacaatcaggaagtcttttttcttagacaaatga aaatttgagttgatcttaggtttagtacactatacta ggggccaagggttatagtgtgactattaaatcacaga taatctttattactacattatttccttatactggccc cacttggatcttacccagcttagcttttgtatgagag tcatccttaaagatgactttattctttaaaaaaaaaa acaaattttaagggctgcacccatagcatatagaagt tcctaggctagcggtcaaattagagctgcagctgcca gcctatgccacagccacagcaatgccagatctgagct gcatctgtgacctacactgcagcttgcagcaatgctg gatccttaacccattgaacaatgccagggattgaaca cacatcctcatggatactgctcaggttcctaacctgc tgagccacagttggaactccaaagcagactttattct gatggctctgctgatctctaacacgttattttgtgcc atggtgtttatcttcactttactcaagtcagggaaac acgaagagtctcatacaggataaacccaaggagaaat gtgcaaagtcacatacaaatcaaactgacaaaaatca aatacaaggaaaaaatatcttcactttcaaaatcacc tactgatgatgagtttatatttccttggatatttgaa tattagctatttttttcctttcatgagttttgtgttc aaccaactacagtcgtttactttgatcacagaataat gcatttaagccttaaatagattaatatttattttcac catttcataaacctaagtacaatttccatccagGTCT GTTAAATGCACAAAACACAACTGGAAGTTAGATGTAA GCAGCATGAAGTATATCAATCCTCCTGGAAGCTTCTG TCAAGACGAACTGGgtaaataccatcaatactgatca atgttttctgctgttactgtcattggggtccctcttg tcaacttgtttccaatctcattagaagccttggatgc attctgattttaaactgaggtattttaaaagtaacca tcactgaaaattctaggcaagttttctctaaaaaatc ccttcattcattcatttgttcagtaagtatttgatga gaccttaccatgtgtaaacattgcactaggtattaag aaatacaaagatggataagatagagtcggcgtaaatg agatgatataatgagacgttataatgaaactcacaat tccagttgggaaataaagtccttcaaattccatgact ctttctggcacacgttagaggctacagcttctgtgtg attctcatgctggctccacttccactttttccttctt cctactcaagaaagcctatagaaatatgagtaagaag ggcttaatcataggaataaatttgtctctgttctaag tgattaaaaatgtctttatcagtataaaaagttactt gggaagattcttaaaactgcttttacacactgttcta gaatgactgttatataaataaaaaagtagatttgatc taacacaattaaatgacctttggaaatattgactaat tctcaccttgcccctcaaagggatgcctgaaccattt ccttcttttgccagaaagcccccaccctttgtctgtt gacctagcctaggaaatcttcagatcacgttgttagc acgaactggttacatgtgctgtacaaatactatttaa ttcatctgattaaaaaaaaagagataagaagcaaaag tttgactatcttaaactgtttgcgtaggtgagaggac aattgaccatctactttatgagtatgtaacccagaaa cttaaagctccttaagggagctaagtcttttggataa gacctatagtgagaccttttagcaaaatggttaagac tgaatggagctcactagcgtgggttcatatcctgatg ctcaaacacgcaattaaatgactttaggtgggttagt ctctgttccttagtttcctcaatgggagataatattg gtagtagcgattttactgggttgttgaaagaacatct gttaaatgttcagaacgtgttacgacagagtacagag taatgatttgcttgtatatgtatgactcaaatagtct gccatatgccttgtgactgggtcctgtggagcaggaa ggagggatttcccacccagcagaaagttgggtaaact ggaaaatagactgaggccaggaaatgatgcaaagcgt tgatgttcactgccacggcaggtgaagggcagggcca gagttgtcagtagggtcaggggaggactggaaataac caagacccactgcacttttcagcctttgctccagtaa ggtaatgttgtgagagtagaaaattttgttaacagaa cccacttttcagtacagtgctaccaatactgtagtga tttcataccacatcccaagaaagaaaaagatggctca atcccatgtgagctgagattatttggttttattgtta aataaatagcattgtgtggtcatcattaaaaaaggta gatgttaggaaagtagaaggaagaagactctcaccta cattttcatcactgttttggtatctgccagttgtcac cttggtccccttccccgcctctcccctgcctcctctt cctccttctcctttttttggaatacaattcaggtacc ataaaatttacccttttagagtgtttgactcaatggt ttttagtattttcacatgttgtgctattactatcact atataattccaggtcattcacatcaccccccaaagaa accttctaactattagcagtccattcccttcttccct cagcccctggcaaccactaatctacttactgtctcca tggatgttcctatattgaatcaagctagcataaaccc cacttgctcatggtcataattcttttttatagtgcta aattacatttgctaatattcaattaaggatttctatg tccatattcataaggaatattggtgtgtagttttctc tttgtgtgatatctttgtctggttgggggatcagagt aataattactgctctcatagaatgaattgagaagtgt tccctccttttctatttattggaagagtttgtgaagt atattggtattgattcttctttaaacatttggtcaga ttcaccagtgaagccatctgggccatggctaatcttt gtgaaaagttttttgattactaattaaatctctttaa tttgttatgggtctgctcctcagacgttctagttctt cttgagtcagttttgttcatttgtttcttcctaggac tttctccctttcatttggattatttagattgatagta atatcccccttttaattcctggctgtagtaatttggg tcttttctcttttttcttggtcagtttagctaaaggt ttgtaattgtattaatcttttcaaataactaactttt ttgttttgtttgttttttgttttttgttttttgtttt ttgtttttttttgctttttaaggctgcacctgaggca tatggaagttctcaggctagaggtctaatcggagcta cagctgctggcctataccacaaccatagcaatgccag attcaagctgcatctgcgacctacaccacaactcggc cagggatcacacccgcaacctcatggttcctagtcgg atttgttaaccactgtgccacgacgggaactcccgcc cattttttttaacacctcatactttaacataaagatg ggcttcacatggactgatagctcaaatgaggaaggta agactatgaaagtaatggaagaaatgtagactatttt tgtgacctagagattactgatacttcttgacttttca aacaatacttcaaaagtacagcccaaagggaaaaaag

aaagaaaaaagaaacacacatatacacaaacctagtg aataagatatcatcgatacactacagatttctatgaa ctggaagaccccatggacaaagttaaagaacatatga tagtttgagtgattattttgcaatatttacaaccaat gagggaatattatccagcttataggaggaagtaatgc aaatcgacaagaaaaagataggaaacccaatataaaa attaagaaaatacaaaaattaagaaaggatatgaact agcattttacaaaagaaaaatctccaaaagtcaatca gcacatgaaaatatgctcaaacctattaattattaga aaactacagactgaagcaatgaggtgctttactttac atctttttgactgataaaaagttagaaacaaaggtga tatcaaatgtcagggataaaaggatatagaaatcgtc atgcctgtggtgggagtatggccggtgcagtcatgtg ggaaggtaatctgacagtggttaggcagagcaggttt atgaatacactgtggcccatcaatcccacgcctgttt atgtaccaaagaaatcctgttgtggcagaatctatgg gtccacccctgggagcatgaattaataaaatgtggca ccagggtgtgtgaaactccagctagagatgagatgtc cacatggcaacatgaatgcatcttagaaacatagatt tgagtgaaaaagagtaagaaacagccgggaaacccaa taccatttataaaaattaaagatgcacacatacaatg tagtaaatattttgcatgaactttcaaatggttgcct acagggggggagagtaaagaagagtagaaaacaaaga taaagggagtaagtaagtagctctgcctggactgaat ataatgtgtcatgaactgagaaatatggttaacataa tcctcttaacttgaggtcctaaatgaatgaatgagtc cactattcatttacccattctttaatgtgtattgcat tataatccatttttttagaaccaacgaattttgttcc cataactactaatcagcctgccttttctccctcattc ccttatcagctcaggggcattcctagtttttcaaacg ttcctcatttgaaccaaaaatagcatcattgtttaaa ttatacttgttttcaaatacgatgcttatatattcca agtgtgtttgcccattttcttaggtggtagaaatttt tcattctacttttctatctactcagattttcccgttg gaattatttccattgctattaaacttagaagtccccc ctgtgatatgccatttttttcatactttttaagcact tggttgcttttctttgtgtctttaagcacctagaata cttataaccattgcacagcactgtgtatcaggcagcc cttcctcttccactaatttatggtccttctcttagac tatattaaactgttatttaattaggatcctctcttcg tccttatgatttaattattatagttttctaatatgtt tttattataattcctcttcattattcctccctattaa aaattttaatgaattccatttgtttgttcttctagtt aaatattaagtcataatccaaataacttagatgtcat tagtttatgtggtcaaagtaaggataccacatcttta tagatgcaggcagttggcagatgtcatgattttcttc agtgcataaatgcaatttatctttgagcaaggggcat aaaaacttttatggtattggctttgaaataatagtta agaactgcagactcagtttttcctgcttttcttgaaa aagaacacttctaaagaaggaaaatccttaagcatgg atatcgatgtaattttctgaaagtctcctgtaattcc ttgggatttttgttgttgtttgttggtcggttttttt gggtttttgtttgtttgttttgttttgttttgttttg cttttagggctgcacctgtggcatatggaagttccca ggctaggggtccaactggagctacagctgccagccta ctccacagccacagcaacatgggatcctagctgcatc tgtgacctaaccacagctcttggtaatgccagattgt taacccactgagcaatgccagagatcgaatctgcctc ctcatggacactagtcagattagtttctgctgagcca caatgggaattcccaattccttgtatttttgaactgg ttatgtgctagcatataattttgtttcttgaatcttt gtgggtttttttttttttttttttttgtctcttgtct ttttaaggctgcacccacagcatatggaggttcccag gctagaggtcaaattggagctacagctgccagcctac acaacaactgcagcaaagtggggcccaacttatatga cagttcgtggcaatgccggattcctaacccactgagc agggccagggatcgaacctgagtttccagtcagtttc gttaaccactgagccatgatagtaactcctgtttgtt cagtcttgaacctcctttttaattctttattccttga gggtgaaataattgccataataatactatcatttatt acatgccttctctgtgctaggcatagtgacactttag gatttattatatcacttaatccctacaacaactctgc aaagtatgtatcataatcctatttgacagatcaggaa attgcagcccaggatgcagataatatgcatccatcac aagtgactagatatagtccctctgctattcagcaggg tctcattgcctttccattccaaatgcaatagtttgca tctattgtatatgtgttttggggtttttttgtctttt tttttttttttgtcttttctggggcctcacccttggc ataggtaggttcccaggctaggggtcaaattgaagct gcagctgccagcctacaccacagccacagcaactcgg gatctgagcctcatctgcaacctacaccaaagctcac ggcaacaccggatccttaacccactgagtgaggccag agatcaaaccggcaacctcatggttcctagtcggatt cattaaccactgagccacgatgggaactccctaaatg caatagtttgctctattaaccccaaactcccagtcca tcccactccctcctcctccctcttggcaaccacaagt ctgttctccatgtccatgattttcttttctggggaaa gtttcatttgtgccatttttcattttacgggtaattt ttacttcagtttcttccactagcagttgtcttaaagt gagtataattaatattcatttggaaaatgtaagcaaa acattttttaaagggccatgcccacagcatatgaaag tttctgggccaggggttgaatccaggctccaagttgc agctgtgccctacactgcagctgggcaatgctggatc ctttaacccactgtgcccggctagggatcaaacctgc atttccacagctacccgagccattgcagttggattct taacccactgcactacagtgggaactcccacaaaaca ttttttaatgtcctttgaataaagtaggaaagtgctc gtctttgagggcagggcggcaatgccatttccacaag gtttgctttggcttgggacctcatctgctgtcattta gtaatgaataaaattgctgacagtaataggattaact gtgtgtggagatagccagggttagagataaaaacact ggagaagtcaaataagttgctcgaggtcctctagcta ataagctattaagtgggagagtgagggctagaaacag gccatctgtctcccaagcacatgtccattagtggttt gctgatagccttccagaacaacagagaggactctcaa acatggtcttgcctccctccaattgatcccctccatg tgcctcacagcgggtctttctaaaattaagttctgat tttaattctcccttgctatagcacttaggtatggctt tcagccgtgcaataaaaagcaggcaagagtggctcaa tcatataggaggttgtttttcttagatcccaagcagg taatcctgggcattatggttgttctgcgtttatcaag gagccaaattctctatcacctcctgttctatcctcct cagtatctggctctattcttcagcatctcaagatggc ttgtgctcctccaagcatggcagtcaaattccacaca agagggggaaatatgaagggcagacagtgctggtctc ctgagctgtccctctttgtcggggaaataaatgtatt ccttcatgtcccgtgagacttctgaagtagacgtctg cttacgtctcacccaccagaactatgtaaactgcaca tagtgctaggtctacatagccactcataactgccagg gggtgggaaatctttaaataggtgtaccaccacacaa ttaggatgctaatagtaagggagaaggagagaatagg ttttgcgcaagccaccagcatgcctgccacaattgct taaaattcttcattgacccctcattgccacaggatga aatccaaacgccttcttagttgggaatctgacctacc tgtctctcccacctggttcagacaccattctccttgg

tcataaaattccagtcatttgtgaacatccagctccc ccatgcctccatgcctttgcacatgctgttcttttat cttttatgttgtccttttatcttttatccaaaagaga tatcccatcatcacatctcttttgtcagcccccaaat actttgtctttcaagttcagctggaggattacctcct atttgaaatcagctttgtctcttacaaccaaacaagg ttttccttccgagacactcccacagcaccttgaactc atctctatcaatcattcatttgattgtaatgaagttg ttggtggtatgcctgtgtctctgacacatctgcgatc tcatgagttccttaagtggaatgtgaatagcgggatg aacagtattggtcttcagccctcatctctgcagatgt tgcttgacccaaatgagcgttgccttttattttgatt ttgctttgatttgtctactccatgtacttgagccatg catttctgtcttagcgatgctttttaaaagtcatttt ttggttgattatccagatttgtccacctttgcttcta gTTGTAGAAAAGGATGAAGAAAATGGAGTTTTGCTTC TAGAACTAAATCCTCCTAACCCGTGGGATTCAGAACC CAGATCTCCTGAAGATTTGGCATTTGGGGAAGTGCAG gtaaggaaatgttaaattgcaatattcttaaaaacac aaataaagctaacatatcaatttatatatatatatat atatatatttttttttttttttacatcttatattacc ttgagtattcttggaagtggctagttaggacatataa taaagttattctgaagtctttttttttctttttccat ggtgagcagtggcttgatgtggatctcagctcccaga cgaggcactgaacctgagccgcagtggtgaaagcacc aagttctagccactagaccaccagggaactccctatt ctaaattcttgagcacattatttaggaacctcaggaa cttggcaggattacaggaaatatatctagatttaaaa aaaaatcttttaacagaggtcccaaaggagagtcatg cacagctatgggaggaagttcagaaactgcccttgct accagatcactgtcagataaaatggccagctacatgt ttctgcacattgccctaagatctttacaaacttttct gtgcatttttccacttttaaaagaaaatttcggggtt cctgttgttgctcagtggttaacgaacccaactagta tccatggggacaggggttcgagccctggcctcactca gtgggttaagaatctggcattgctgtggctgtggcgt aggctggcggctacagctcagattggacccctagcct gagaacctccatatgccgcaggtatggccctaaaaaa aaaaaaaaagagagagagagaatttcctccagaaaaa acactttggtagtttgggagaagtaaacaaccaaaaa ttaatttttctggagtattcgggaagcttgtaaaaat gggctcttacttttttgaggagacaaatgggaaccta cccagaagaggcacaatcacctgcatttgatttcttg acctctccctaccttctttgctggctttccacatttg gatttctgtgaccttatctctgctccttggtgttttc atttttcctgtggacgtgccagactatgggaagggag taaggcgttgatttagaatcctgtagtctctgcctgt ctctagtcattgttttcacccttctcaaaggaccttg acatcctgagtgagtccgcaagtaatttaggggagaa gccttagaagccagtgcagccaggctacatgactgtg tccacccactggaaccagtcatttttatacctattca cagcccccctaccatttaaatccccagaggtctgcca taacatctgtaactccctttcctggtaaattgtgttc taaaagactggtaacaaaagatattctgtggtacaga gcataattaaatacctgggagctgatttgagtggggt aaatcaactggtttgacccctaaaacccaccatgagc atttctgttctaataaagtaatgcccgtgctgggaat tgtgttctacggaaatgctcctgctgtgtctttcttg agtcctgtgtcattgaacatgcttaggagcaaaggtc ccccatgtggcttgtctgctaaccagcccagttcctt gttctggctggtaatgatccgatcatctgaatctcac tgtcttccaacagATCACGTACCTTACTCACGCCTGC ATGGACCTCAAGCTGGGGGACAAGAGAATGGTGTTCG ACCCTTGGTTAATCGGTCCTGCTTTTGCGCGAGGATG GTGGTTACTACACGAGCCTCCATCTGATTGGCTGGAG AGGCTGAGCCGCGCAGACTTAATTTACATCAGTCACA TGCACTCAGACCACCTGAGgtaaggaagggtgagccc tcaactccgaagaaaatgctgcaataaaagcactgtt ggttttcagctttttttgtaatcactgctcattctga ggtagattcgcttgggctgataaaaagagaactaatt cagataaatgcttgcatttgcatagcctcttttttta aaaactttttttttttttttttttttttggcttttca gggctgaacctgtggcatatggaggttcccaggctag gggtcgaatcagagctgtagccccgggcctatgccac tgccatagcaacatgcatagcctcctttttaaagtgc cttcctgttttataccattgggatgtgagaagagcta ttgtggaaangagcatggggtnataaccctggacctc tcacgtcctaccctcaggntagtgggaaaactctgag tttaaggacatcaaagtgactcctttttagttacatt atggnggaatcagcncatatttttacaaggggcggag ngtaanctgttggagtttacaagacatatggtggcat tgcaactacttaaccctactattatagcacaaaagca gccatagtcggtcctgaaggagcctgatgccttcagc tttataggcaatgacgtgtgaatatcacaaacagttt cctgtgtcaccaaacatgattgccttttgatttccct ttcaaccctttaaaaaaaggtaaaagcccttcttagc attcagcagcaggtcgctgtgttttgccaactcctga tctgtagcatttcgacaacactgagctctcaactttt gaaccctgagtccaccacatccttcagtgaaaccaga gccatgtgatactaaggatagaaacggaaacttcctg aatccaggcgatcaaataggagggagaaagaggaact ttcattgacaaaaccacaaatattgtgaatggactgt tacaaatattgtgaatgctcctattcccaaccccctg gcttcattacagggtcctatgtgttcatccttattga gaaatttgtattgctactgccaggttgccaataccca gcggtgcccatggtgttctaaaatgaagcaatttcaa ctttatttttttttcctgtgactttacatgacaagtt cacatgaaggatatactttgatagtaatgtccatggt tagggaatatacattgtttgctggttgactggcccct ggatttttctattgaaagtccatgagatctcgaaggc acaggtgtgttctctcgctttttaaggaaagggttta aaaacttaagtaattaacagctttagtaacaaattac ctataacacacttaaaaaccgaataccacccactgga gtattgtgctacgattaaaaatctacttgtctactac atgatatctttgtcccacagaaggttctggaaccaaa cttgtaatttcaggattatgagagccctgagttcacg cattgtgtaataactatgttgtgtggtagtcaatttg tacagcttgcttagagagaacaatgtcaagttaagga ggcgattgctttatagtgcctgtcacaagatgccatt gccattgtcctagcaagagatattctatgggagtata ctacattttagtgaggataagaactttttatggcatt tagtccggtcatttcccaaccactgtcctgaaaacca atttcattttgatttcaggggcttgtgtgggcaaagt tgccaggcattaaaaagccacttctcaactgtagtat cacaatgctttagttgggtagtgtattgcagatagct tatggctgaaaagttaccaagccttgcagttttcact cctttgagtttatttccttgacagaattgaccctgag ttttttgactcttacctgctcaactaataaacaccag agtcatttatctccattgctcttgtctgacctttatt taccgaataatgccttatgggttcacaaaaacaaggg gggagggggccagcatgccttagaaactgtctttagt caagaaatgngattttattatgtaaatatatgagtat tataatagatagtgttattaatagacaccagcaagaa ttgtcaataatttaaaaatcacaaattaaaatacatc catgttagnatcatttatcctaactcccaaagccctt taaagtggaagatttagatgttaacccagagattaaa

gacatgttcaaagaatccttgatttttttttgaatcc cttgtttttagagaagaaaacctaatgattttccccc tctggattctacatattaaatatagttttggaacttg aatattagtatggttaataagtgctgatatgctgatt ttgtttatatttttcttatgagtaaatatcctatatc accagacattatagtctatgtacaaatatgattctta aacctgatagcacattcattagagttggaattgcctt ttttttttttttttttacagttgcacctgcaacatat gaaagttcccaggctaggggttgaatccaagctgcag ctgccaccctacattacagccgtagtaacagcagatc cgagctgcatctgcaacctatgctgcagctcagggca atgccagatccactgagtgaagccagggatggaactt gcatcctcatagagacaacgtcgtgtccttaacccac tgagccagaacaggaactccagaatttcctttcaata gaagaagcaccaagtttaggatcagaaagcctgaatt tgaataccaatttactatttgttagtcatatatttct gagtgtgtttcctcatttattaaaagcagactaaaag atgagagggtcttttgttgagaatcaaatacaataac atgtgaaagtgtgtaacactatgattgaaatatacct acacagccatttatttgtttattgttcatgttttgcc acccacacagtagtatataatccttttatgtaataaa tgctaataatgaaagttggcaacttatgtaagtactc aaaatgctggaggtcatgggatactgactgggatact acagaggtaatgtcatttcctctgcgctaaacttatt gtctgtagttagggactgactctctttaggacaagga gttcattctgtataccatgtgtggctatcacccttcg aagttgaaaaactgccccagggtgggcacccatccgt tctcttagatatatggccgagacctttctctcactgg gagggaaccacactgaggaatgagaaaaaaaaaagga aaatcaagatgaaaccagaaacctctttggcataact tctccactctgtactttttgttagaactacccttgca caaagcagcatcagtgtggaagacagaatttgcacac ctggtttgatatacatgccgtggtatatgggatgttc taacaataaagaggactctcccaggaaatctcctcac tgttatagtcagccttgaggaaagagctcttcttttg gactctggggagagtctagtttttcagttccttgctt ctcggtcaacgtgttggtgtaaggatcacactctctc ttatactagataattctattttttcacctttcaacct gtctatccttctgaccctagTTACCCAACACTGAAGA AGCTTGCTGAGAGAAGACCAGATGTTCCCATTTATGT TGGCAACACGGAAAGACCTGTATTTTGGAATCTGAAT CAGAGTGGCGTCCAGTTGACTAATATCAATGTAGTGC CATTTGGAATATGGCAGCAGgtctgtgttctttccac atgtttgggttatcctttctgggataaatttgaggcg agatagaaactttaagactaaagaaacaatggcctac tttttttgtacatggtcctgtgtaaatctctatttga gctgaaataagatggtcttcctctccaattatccatg gtatgactctgatggataacaaatccagttctgaaaa aaggggatttctttccagaagagaggacagtttcttc aaatattgaattaaaagcaaaatagatgtaaaccgtt gttggttttattgttgaattccagGTAGACAAAAATC TTCGATTCATGATCTTGATGGATGGCGTTCATCCTGA GATGGACACTTGCATTATTGTGGAATACAAAGgtatt ttcttgccctcatcagcatgaaattgctcttggtaga aaggataataatagttatccaaaacatcatcctatgt tcatctgtttcttccctcttcattttccatagagtac agtatattctatctctgtcttaggaaaatggactgtc attcatataatcttacagagaatcaattagtaatgta ctctatgccgtgacaggtgcgaaggttttttttgaag gcaacagataaaaatatcctatatttcacctattgta atttccttaaaactgacattattgaataaatgtttta ctttcatcttgaatattattatgttatggaatcatac actttaccccaataatcatcgaaaagaatttccaaaa ggttgagagagttgtgttgatctgattactttcctct gcatcctttgagcttaacctttgaatatagtttgcta aggaaagtagtctgtttatgatcctggagtggaatca ggctaagtgtcctcattcagaacccactgaatcagac agaatgaatttatttccttgaaagttcaaaatgtgtc actcaagagtataaattttcaaatcttactctctctt ttccttggatgtgagcaattcttcgataattgaatga ggcagattatatagacttacatggaagactgttggcc tgagaattcaaactatggtgttcaagacttcacngng agtccgatgccatttgtttcccacagGTCATAAAATA CTCAATACAGTGGATTGCACCAGACCCAATGGAGGAA GGCTGCCTATGAAGGTTGCATTAATGATGAGTGATTT TGCTGGAGGAGCTTCAGGCTTTCCAATGACTTTCAGT GGTGGAAAATTTACTGgtaattctttatatcaaaatg atgccaaggagttggcatggcactttgctaaatgctg tgtgaatcaatacaaagataattaggacatggttctt cctcacaagaggtgtgcaatcttattgggaaatcata cttgcaagtcacaaatatagactaaagtttccagctg agaatatgctgatggagcatgaaacactaaggagaca gggagaatctcaggaaaaatcaagaataatttggatc aaatggattcctgacatagaacatagagctgatcaga aagagtctgacattggtaatccaggcttaagtgctct ttgtatgtggttcagaacagagtgtgggcagcctgag ggggatacatacccttgacctcgtggaaagctcatac gggggagggatgaggctaaggaagcccctctaaagtg tgggattacgagaggttgggggggtggtagggaaaat agtggtcaaagagtataaacttccagttacaagatga ataaattctaggggtataataacagcatggcactata gatagcatattgtactatatactggaagtgctgagag tagatcttacatgttctaaccacacacacacacacac acacacacacaccacacacacacaccacacacacaca cgtgcacacaaacagaaatggtaattatgtgaggtga tggcggtgttaactaactttattgtggtcatcattta gccatacatgcatgtcatgaaatcaccatgttgtaca ccttaaagttatgtaatactagatgtcagttatatct caaagctagaaaaaatgtggggaccaaggcagaagct cttctgctctgtgtctaagggtggttctggggctggg atggggaggatggttaagtggtatatttttttcatac ctttgctcagtactatcattgtaagtgttcaatatat gtctgcttaataaattaatgtttttagtaagtaatct ctgtttagtaatgtgtcagaaatgccctacttgcaat aggaagaaaacctgtccagtcccttccttttttctgt aagtctgatttcattgcctcccagaatgcatcaccat gtgagagatagagggaaggtgctgtccttatggggtt aacagtgtgactagggaggcaaaatatacctactaaa gggtggtagcataattcagttcttatgtgagtatgtg tatgtgtgtgagtatgtgcacatgcacatacatttta aaaggtctgtaatatactaacatgttcatagtggtta cacctagcttataggtaacattttttcccctgtatcc ttgtttgtgtttatcaaattttcataacagtaatggt agaaggagtacctgacatggtaccatacatgctnggn cctgcctaatttctcnatttcctttattgcccatacc cccattgcttgacaagcataagtccatactggcttgt tttcgttcctcagactcagtacaccatgtagctccat gccctgggtctttgtatgtgctatttctactgcttag agtgctattgcccctgaccaccacgtggtcagcaact tctcttctgcgtctgtgtctatggtctatgattccag atgtcatcttcactaactacccttctaatatgccctt ccatcccacccgtcctcatccttaccccagccactct ctatttggtggctctgttttattttcttcctagctca tcactctttgaaatgaacttatttacttattcaatat ttgcttctttcactagaatgaatgctccatgagagca

gggacctgctttatcttgctcgccactgtattcacag tgcctagaactacgtctggcacatagtaggtgctcaa taaatatcgatcaaatgaaagaatgagcaaacgaaca aatgaacaacacgtgaggtaggcatcatgattccatc aacagaggagaaaaccagacttaaagnaatgaagtgg nggagctgcatttgatcttgactgactccaacatcca tgctcttgaccactgtgcatctccagagtgtaatgaa catactttacttttatattccaccaaaataacaaagc catgcccatgttagtagagagttaatcgacagtgccc ttaaaatatgcatgcacccagggtacaactatgcatg ctgccctgtgttttcagttggatccaaatgaattgcc gtaaacaaagaggggattcaatgtctttgactagttt gggatattttcctagtaaccaactttgcaaaataaag ccactaatgacaaggagctttgttctacttctgcatc actcaactgtcaatttttatctcttgcaagacttcta atctactagaacttttgtttttctgtgatttctgaac agagaagactaatccaaaccctgtcattccagAGGAA TGGAAAGCCCAATTCATTAAAACAGAAAGGAAGAAAC TCCTGAACTACAAGGCTCGGCTGGTGAAGGACCTACA ACCCAGAATTTACTGCCCCTTTCCTGGGTATTTCGTG GAATCCCACCCAGCAGACAAgtatggctggatatttt atataacgtgtttacgcataagttaatatatgctgaa tgagtgatttagctgtgaaacaacatgaaatgagaaa gaatgattagtaggggtctggagcttattttaacaag cagcctgaaaacagagagtatgaataaaaaaaattaa atacaagagctattaccaattatgtataatagtcttg tacatctaacttcaattccaatcactatatgcttata ctaaaaaacgaagtatagagtcaaccttctttgacta acagctcttccctagtcagggacattagctcaagtat agtctttatttttcctggggtaagaaaagaaggattg ggaagtaggaatgcaaagaaataaaaaataattctgt cattgttcaaataagaatgtcatctgaaaataaactg ccttacatgggaatgctcttatttgtcagGTATATTA AGGAAACAAACATCAAAAATGACCCAAATGAACTCAA CAATCTTATCAAGAAGAATTCTGAGGTGGTAACCTGG ACCCCAAGACCTGGAGCCACTCTTGATCTGGGTAGGA TGCTAAAGGACCCAACAGACAGgtttgacttgaatat ttacagggaacaaaaatgatttctgaattttttcatg tttatgagaaaataaagggcatacctatggcctcttg gcaggtccctgtttgtaggaatattaagtttttcttg actagcatcctgagcttgtcatgcattaagatctaca caccaccctttaaagtgggagtcttactgtataaaat aaactattaaataagtatctttcaactctggggtggg gggggagactgagttttttcacagtcctatataataa ttttcttatcctataaaataattaggagttcccgtag tggctcagcaatagcaaacccgactagtatcgatgag gatgcgggttcgattcctggcccccctcagtgggtta aggatctggcattgccgtgagctgtggtgtaggtggc agacacggctcagatcccacgttactgtggctgtggc ataggccagcagctccagctctgattagacccttagc ctgggaacttccatatgctgtgggtgtggccttgaaa aaaaataaataaataagataattactcaaatgttttc cttgtctcagaaccttacttcaggataaagagtgaga aagttttttttatgaagggccattattacagctcaaa aataagttgtcttcagcaagtagaaagcaataagcct gagagttagtgttcctatcagtgtaaatattacctcc tcgccaatccccagacagtccatttgaacaattaacg gtgccctgggagtacagttcagaaacattaatgtgga tgttccagacctgtatttttataagtacttgtcttga gccggatggaaccatcattcctcaccattatttagaa gtggactgtgactctgttggagatcagggcacacggt taccaaaagcacacccttctcctggccttacctttgc aaagctggggtctgggacacagtcagctgattatacc cttttactaacttcccacagctcaaatctggtcaatt ctccttcacaaatctcttaaaaatccatcactcacct ccagcctcttctgctgtggccttgattcagcctctca caatttttttttaaccagaattctggcagtggcccct gacttgcctctgtgctcccagccccgctgtcctctga tccatcctccatgccagcctttttcaatctgctggtc acgattcattgatgggttaggaaatcaatggcatcac aactagcatttagaaaaaggaaataggcgttcccgcc gtggcacagcagaaataaatccgactaggaaccataa ggttgcgggttcaacccctggccttgttcagtgggtt aaggatccggcattgccgtgggctgttttgtaagtca cagacatggctctgatccggcattgctgtggctctgg cgtaggcctgcagcatcagctccaattagacccctat cctgggagcctccatatgctgcaagtgcagccctaaa aaaaataaaaaaataaaaaaaaataaataaaagaagt agacaaattgtatagaacaaccctgagtatgttgcct gagcacatataacaagggtaagtattatttcaggaaa ctctggtttcacagatactcttggcatatggacccct agagtcctgatgtaaaatatattcttcctgggatctt aggcaagaagtttgaaagctccaactctgcactgctg ccaaagaaatgatttttaagtgcaaaactcttcccgt tcccttccctgtataaaattccataggatctctccag tgcctctaggataaaggcagttttcattctctagttc aaggtgagagaagattttaattatttcacgttttagt ggggaattcaagagtctggcacctgacatttgctgaa ctctctccattatccctctctagttccccagacgcat cctatggtagaaattcgcaaactagagtgagcgtcag agtaacccaaggaaactgggtaaatgcagctccctgg gctctaccccctgagattctgattcagtagatctgaa gcagagccctggaatatgcatatgcatcattgtgtca caccaagcattctgggtaatgagagttgatgttaggt tctcagtagtaagacaagtatagagattccgggggac tgagtgctcagctctgccttggggaggagggagaggg ctaaagagaacaggagatggggacagggaatgctcaa cctccaatcttaggcatttgagctatgtcttaggggt caggaggaggttaccaatatagtgattaagagattga ggttccagtcagagggatatgctggagaaggggggtg aaaataatgtcataggtttggtgagtgcagatacttt gagttttttaatatttttattgaaatatagttgattt acaatgctcttagtgagtacaattactttgaataagt gcatagatgtatgccattcttccagaaatgatttatt gagctcctttgggcatcatgctaagtacaggggaaac agctgtgaagaggtccttcccttatgaagtcattcat ccccttcagtaaatgaaggtaaaggaaaaggatgaga cagggacgccgtgttggaccagggtcagaaaggcctt ataagaccttgcctggagggcaaggaacttgcctgtg agtaaggagagcttgagaaagcgataaagcaaagaag gaacattactgcattgtgttttagaaaaaccatgtcc tggggaagaactcctagagtcaggggggccagttggg agactgtgcttttttccaggaggagataagtgaggct gctggctgagatggagcaaggatttagagaagcagat atgagattcatttagaagttagacattttaggatctg acacataatttatcaccaaaaccagtgcatctctggc tttgggccaccagttttggagaagtggaatgtaggga cctaccattacctgccaatctttactacacagatgcc tatttccctcctcatatttcctttctccagatcacgt cctattctattgccaggactcaagattccaccttgca tgcagtgatccatcttcacactggatggacagctcta gggatgtcagagcacactcccatactgctgactgggt ctcctgtcagcccatctgtctatcagctgtggtatta ttagtataataagagggctgtatatgagagacacaaa attctaggtgtagctcaaagataggctagagttattc ctatgtacaacaaatatttatgggaccccttctgtgt

actgtcatggttgctgctttcatcatacttgtagtct aatggaggtgggggcagggcaggaataagcggatgtc cacaaaatcagtaagaccacttatattcaacattttc ataatttagttatttgagcccaaagggtccacatccg tggtattccaacttttttttccccggacatggatctt tatctttttttttttttcttttttgcggccagacctg cggcatatggaagttcccaggccaggggttgaatggg agttgcagctgcctggtctacaccacagccacagcaa ggtgggatctgagctgcatctgtgacatacaccgcag ctgaggtaacaccagattctgaacccactgaatgagg ccagggatggaacccgtctccttatgaacactatgtc atgttcttcaccctctgagccacaacgggaactccag acttcgtctttaaatgtattctgacttggagagctat cacactaagcaattaacaggagctgacctggtttagg ctggggtggggccctactcctcaatgttccctgaggc acatctgtgggacccctgggcatcatctatctgagca gccttagagctgctcatccagttgactgttgatgtag aagtgcaaacttctgccttccttatgcttlctttttt cattgttctctcccctttgtgtctttaagCAAGGGCA TCGTAGAGCCTCCAGAAGGGACTAAGATTTACAAGGA TTCCTGGGATTTTGGCCCATATTTGAATATCTTGAAT GCTGCTATAGGAGATGAAATATTTCGTCACTCATCCT GGATAAAAGAATACTTCACTTGGGCTGGATTTAAGGA TTATAACCTGGTGGTCAGGgtatgctatgaagttatt atttgtttttgttttcttgtattacagagctatatga aaacctcttagtattccagttggtttctcaataagca ttcattgagccttactgactgtcagacggagggcgta ttggactatgtgctgaaacaatcctttgttgaaaatg tagggaatgttgaaaatgtagggaatgaaatgtagat ccagctctgtttctcttttggaggattctttttcctc catcaccgtgtcttggttcttgtttgttttgggtttt tgtgggtgttgtattgtgttgtgttggttatggcagt gacagctatttaaactgtgaaacgggggagttcccgt cgtggcgcagtggttaacgaatccgactgggaaccat gaggttgcgggttcggtccctgcccttgctcagtggg ttaacgatccggcgttgccgtgagctgtggtgtaggt tgcagacacggctcggatcccgcgttgctgtggctct agcgtaggccagcggctacagctccgattggacccct agcctgggaacctccatatgccgcaggagcggcccaa agaaatagcaaaaagacaaaataaataaataaataaa taagtaagtaaaataaactgtgaaacggggagttccc ttcatggctcagcagttaacaaacccagctaggatcc atgaggatgtaggttcgatccctggccttgctcagtg ggttaagaatccagcgttgctgtgagctgtgatgtag gtcgcagatgcagcccagatcctgcattgctgtggct gtggcgtaggctggcagctgaagctccgattcaaccc ctagcctgggaacatccatatgctgcaggtgtggcct taagaggcaaaaaaataaaaaaataaaaaataaataa attgtgggacagacaggtggctccactgcagagctgg tgtcctgtagcagcctggaagcaggtaaggtaaggac tgcagctgggtaaggactgaattgcaccaactgggaa gtaagcctagatctagaacttaagttagccctgacat agacacacagagctcaccagctaagtggttcagctta taagctggtcactgaaactgaggatgtccacaaaagc aaaataagtagcaacaggcagcgggatgcaagagaaa gaggaggcctaaaatggtctgggaatccctgccatac ctatattttatcctacttatatttagtgcctgaatgt gtgcctggagagcaaagtttagggaaagcatcgggaa atgcacagtattcatacccttaggaacaaagatcagt tacctccagggtaaagactatttccaagtttaaattt caacccctgaacattagtactgggtaccaggcaacac ttgccatcctcaaaatcaatgaatcctaaaattcaac ctgggggtcagtgacagtctgtgacaaagtttttgct ggtcagtaacgaaataagtatgagcaccatctgagta tggtcaccaagatgtcaactctctttcctttggacga attgtcattattccaagattaggtcctttctattttt gaggtgtgaaaacatctttcctttcataaaataaaag gatagtaggtggaagaattttttttgttttttggtct ttttgctatttctttgggccgcttctgcagcatatgg aggttcccaggccaggggtcgaatcggagctttagcc accggcccacgccagagccacagcaacacgggatcca agccgcatctgcagcctacaccacagctcacggcaat gccggatcgttaacccactgagcaagggcagggaccg aacccgcaacctcatggttcctagtcggattcgttaa ccactgcgccacgacgggaactcctaatgatactctt ttatatttagctactatgtgatgatgagaaacagtcc acattttattattttttagccaatttgatatctcatt actaagataatgataattttctctataaattttattt aagttagtgttatgaagtggttttgctagtgtagaag gctaggatttgaattcagttcaagaaagaagagaggg agggagggagagggatgggtagagggatggggcagtg ggagagagcaaagaggagagacagtttttgtattaat tctgcttcattgctatcatttaagggcacttgggtct tgcacattctagaattttctaaggaccttgaccgcca gattgatatgcttcttccctttaccatgttgtcattt gaacagATGATTGAGACAGATGAGGACTTCAGCCCTT TGCCTGGAGGATATGACTATTTGGTTGACTTTCTGGA TTTATCCTTTCCAAAAGAAAGACCAAGCCGGGAACAT CCATATGAGGAAgtaagcaggaataccagtggaagtg cccctttcttccttccttcctaaataaacttttttat tttggaacaactttagagttacagaaaagttgcaaag atattatagacagtagtgtttatatatatatataaat ttttttttgctttttatgaccacacctgtggcatatg gaggttcccagtctaggggttgaattggagctacagc tgccagtctgtgccataaccacagcaatgcaggatct gggccacgtctgtgacctacaccaaagctcacagctg gattcttaacccactgagcaaggccagggattgaacc tgcatcctcgtggttcctagttggattcgtttccgct ttgccgcaatgggaactccaaattattgttaatatct tactttactggggtacatttgttacaaccaatactct gatactgaaacattactgttaactccgtacttgcttc tttttgagtcatttgcaaagactggcttcttgacctg cttccttccaaacagctggcctgcctatgctgttctc agacctgcaagcactgatctctgccccccttgccttc tctccagtggtgtctccttccccaaacaaacccagtg tggctctggaaagggagttaagtcaacataaaccaac acatattttgttgagctccaattttgagcaaatccct cacctacggcagacaggcatgatgttaagaactaggg ctttggacacaaggtcaagaccaagaagggttcctca cccctactgattcagataaccaataatgaggctttga atccctgtccaaaggttgttttttttcccttctattg agcttcttgccaccttatcagttttttttatgacagt caaatgacatgatatatgtgagcatacatggtaattt ttaattctatataaatgaatcactaaataaataggag gatatatagtccacctttaagcgtattacacgtgtca catgaatgtggcgacttaattgtagaggtttaaatgt agcttcctataatagatgtgttcctaaactacatttt aatcattggacttgtatttttatgttagcacttgctg ttgaagaaaagcctatgccaaaagttcagtgaaacca ataatccactgccagctttctgagttaaaaaaaatcc ctgggttttcacacacaggaacaccctgtgtgaaaca ctcatttagagcaaaatgcatctgataaggagttcct gttgtgcctcaactggttaaggacctgacattctcca tgagaatgtgagtttgatccccggccccactcgatgg gttaaggatctggtgttgccacaaactgcagctccga

ttcatctcctagcctagaaacttccacagcccagaat atgccacagaattcggctgtttaaaaaaaaaaagaaa aaaaaaagaatcataaatgtgttggtttgttcaccaa atacatgataacttgctcttgccaagctcagcttcat aaatattaagtcatttaatacagcagccaccttatga acagatattactatacttcccatttacagataaggaa aatgccatatttaaccaagagattaaataactttccc gaggtcttatagcaagtaaatcatggtgcaggggttt gaccacacgcagtctatctccagagtctgtgtattta gccactgttttactttcaaatttaaatttataaaact tctaaattatctgttaaccataatctttggaattttt aaaaccacgagttcctataaaatgtttcattgaaagt aagtcacttttccatagcttttgataatacatctgta ggataaagtaagccacagctctcttgcagacttggta caccctggggcaaagcatcatgcctgtcacgtacatg gtggtccttactttgactctcagtgcttttattgccc aggaattttgtgagatttctagttgttgaggtttgtt taaagaggttatgccggtacttggaagagctcttttc ttgctacctggagccttctcatatttcctttttgagg agggacatgaattgcctttcaaactcataaatatatt ttctagtacacaagtctccatcttccttagacgcatg gctcctggagttctccatcctcctgctccactttggg tgggctcctctctgggtctgccaccaatctgccaccc agagacatccttgacccacttccagaccccaccatgg cttcactttcttcgctttcctcctttgtggaaccttc tgcttaagaatctgaggaagaaaatttgcacgtgagc taaactggaggtactttcctgcctggtcttgcacgat agcttggctgagcccatgatgctgggtggctgttact ttccatggacacccgaaggcgttgctcctttggcttc tagttgcatgcagtgttgcttatcccaggctgatctt tcttccactgtaggtgacttttaagaattaagggatt aatctatatctacaacaacaacaacaaagaccttttc aagctgaggtagggctttctgtatatgtttggagtgg ttatccagcagactttacttgaaggcaggggtcatat cctcaagtgctcataaacggaccacagaaagatctca taattgggtggagctgggtggggaccgtgtcatgtgg ccaggaaatgccagatgggaagggagtggcccttact gagctccagctgaactctgaattttctagaaaactca gaaatctggatttttcatgtgtaatacccagatttat agatgtggaaagctaattctttttttttttaagggac tataggcaatgaactaagatctaggttgtatttggac aaggggtcatcagtttaagctgtgtagttgagcgctc agctattgggctgagggacccctaaatactgagacgg ggaggtccttgctctggggcatcacaagtacactccc tggtctcattcaaacacttttcctacaaaattgatcc catttcttcagtgcactgtctgaatgcatttggccca gagccgtgctgaggcatagggaaggggtccacggttt catggcatcgttttgtgctgtgtgtccctgctgtcgt ccaggatacctacctctcctcctcctgcatctgaatg tccccccacagactctctgggattctacagcctctgg cctgttcctcagacacctcttacctgccagctttcca gattcacattagttagtccaaatctactgccgtcagt gactcacttcatttcttcttctccgaggcagttcagc ccggtacagttgttttgtcaacacttcagttgagtct ggaagatgtgcatgggttatgcacgagagcggtccat cattttgagctagaagtcctttctcagcccagagaca agtcctcatctcctttacttcctgactcttcttcctc tgcatccttccaagatatctctttctccagccaccac ctaaatctcttcttttcccggggttccgtgctcaacc cactcttcttcttaaatctgtggctgggtgaacgcat ctgctggcaccacttctctgctaagactccaaaaatc cataggtcctgcccggcctttgcccacctctctccaa cactgtccagctttagatgtagagctaatccccccag agatatcattccctggatgtctaagtcctttggtatc tcactttcagcgtgttcaaaatcctcttacaactgtt ctttctccttttccatcttgattattggcaacatgcc agcctttcccctacccccagcagtgagccaagctaga aacaagggcttaatcttcaatctttccttctccatcc ctaaacctaatgagtctccaagcccttcccagtttac accctaaatgttgctcaaaacatcccctagttcttcc acgtgctctcctctatattgaaaggtcaagaaaggcc atcttccctccactgtgaggaaatagatcttgatact gcccctgagctgggcagtcctcgacctgacaaactgt gcagtgtttctaaatctctactggcaaaatgagagtg cctttgacctgtgttgcgatctcagatcacagtggat gtaattgttttataggaatggtgaacgaaaaagaagt aaatccctaatgccaaactcctgatcattctatgtca tttaatagcctgtcatttatgataaagtttcctctac tggcattagcacaatacttctcaggaaaaaaaaatat gatgccagatactgaaaagctcctgggtaaacatgaa catgggtaccgataaaatggtgaagccagtccaatct tagagtgacttcccttcatgctacttcatgctctttt ttttttttttttttaagaaaaaccccttttttttttc tcacaccagtcacagaggagaccgaggcttagcaagg ttaaggtcacatgattagtaagtgctgggctgaaact caaaaccatctctgcttgtctcctaaccctgtgcacc tctgactattcaacagATCCTGTGTCAGGAGTTGGGA TTCTTTGAAGgtaagggccttgaccaccgaattaagg taatcttgctctgtggcaggccttgttttcagtattt taagtacactggctcaggtaatcctcacaacagcccc aggaggaatgttctattacctccactgtatagatgag gaacttgaggcacagaatggttgccaaggtcacacag ctatattgggggttcatacccagccatccaactctgt ctgtactctctgccactctgcacccccagctcctgat ccacttcctgtttccatccctcgatttctgctgcact caggggcccctctccccctcggcctgtgagatctgct tcagtaggcttttctccctgactcctccatccctgtc cttacaggcagctgcttctctccgggacacgaggggt ccatacggacactctctactggctgggttgcgcctaa ctcgtgattcctcctctgtttcagATTCGGAGCCGGG TTGATGTCATCAGACACGTGGTAAAGAATGGTCTGCT CTGGGATGACTTGTACATAGGATTCCAAACCCGGCTT CAGCGGGATCCTGATATATACCATCATCTgtaagtcc gaaaatgcctgtcgtgtgtgccttaggctgctgcgga ggaggccagggctatataagcagagtcagtgactgac tgtgccctgcagtgttgatggccatggagattccacc gttagagcttttttctttgttaaccttgaaggcaaat ctggttaggaagataactttcaaagagtcaccatctg gacattcatgcccatgtgcttcaatcctgtatacaag cagtttagagtacagggaagggaaggacattatgaaa gggagagggtgtgtttggatccagcagctccatcctc agaatttatctgaagacactgcaaaattactaagaat cactatgacaagaatgaggatggggtgatatggcaaa gttgtgatcctggaagaccttcatctcccatgttgcc caactctgaacatgaatttggtgaactagttggttaa ggggatgatcctccaagtttctccctggttgagctcc aaaaaccatgtaagtttctcatagcaaaaccgtatag gtccttagggctttagttggaatatttgtgctgaaat gctggaaagccccatttgccatttttgtatttgcaaa ataatcatcaagaggggagaatgcattctttcatgac cactgaccctctgaaaaggtcaggaatttagtctgaa gtaggcaagcctcctaccccgcttctgccatgagctt gcacgcacaggcctgtcttgacatttcttctttatag atttctttttgaatatcttgaaattgctttaaaaata tttaaagaatgtagaattatataaaataaaaaggaaa taaccccacacctcccacaaaaccctgtttcctgcct

ttctccacccactctccagggtaacacttggtaacag catagttgtatcaccccaggcctatttttgagcatat cagcatttcaagaaatgtattttttctcaataaaaca tcccttatagttgaggaggggaggttatcattcctgg gttttgttttttttttttttttaatgtaatcctggta catcggtaatttgcattttttattcattaatatcttt ggtatttctagtgttgggacacacaggtcaacctcag tttttgggtttttttttttgtctttttgtctttctag ggccacacctgcagcatatggacgttcccaagctagg agtctaatcagagctgtagccaccagcctacgtcata gccatagcaacgtcagatccaagccgtgtctgtgacc tacaagcacagctcatggcaacaccggatccttaacc actgaacgaggccaggggatcgaacacacatcctcat ggatcctagtcatgttcattaaccactgagtcatgat gggaactccaacttcaactattttaatgtctgtaaaa cattccatttggaaaccatttcatttgtaaagcaaaa tgaaaacattttgttcattttcaacagagttcgtagc tgacttctgttctggaaaaaaggaaatggagcaaatt tgagtgagaaagattcaaagataacttttcttttaaa aaaaattatatcttggaaacttctgggctattgattc tgaagactatttttctatatactgttttgatagcaaa gttcataaatgtgaaaggatcctgcgatgaatcttgg gaagcagtcatagcccaatatatctttgttgctttta aaatgagatttagtttactaaatatttttctgatcat aaaaataacacagatctaccgcagaaaatttggaaaa aaaaaaacttttaaattcaaaaaacagttaaaccaca aatgatcccaccatccagagagcaatttgtactttgg tgtctagttcatctttctttttctgtttacaagcaca tataccacaagcattttttcaaaaaatgaaaatggga taatactatacatacgtctgtacacctgcatagttac tgaacagtctttgatctaccctgtaagtttctaactt ttcattatttgaaatgatgttttggcaaagaaatatg taggtgtgtctcgcacactttcataatgatttcttag gataaatttcttaggataaattcataatgatttctta taataatccatactctgccaactgatcttcagggaag ccaactcgccttctcagaaataacatataacccattt acttgccctctcaccaatactaggtcctaatgttttt gtgtacagattctatatttttacatacaagaattcct taaagcaaggcatgtcacagaaaaatagaaggaagac acaattgtcatgtttaaggactgcattctgtaccaaa aatgctaagttaaatgaacatctgaaacagtacagaa acgctatctttcagggaaagctgagtaccaggtactg aacagattttggcaaatacagcaggcatggatgtttc caaaacatgtttttctactttatctcttacagGTTTT GGAATCATTTTCAAATAAAACTCCCCCTCACACCACC TGACTGGAAGTCCTTCCTGATGTGCTCTGGGTAGAGA GGACCTGAGCTGTCCCAGgtaaagcatcctgcaggtc tgggagacactcttattctccagcccatcacactgtg tttggcatcagaattaagcaggcactatgcctatcag aaaacctgacttttgggggaatgaaagaagctaacat tacaagaatgtctgtgtttaaaaataagtcaataagg gagttcccatcgtggctcagtggtaacgaaccctact agtatccattgaggacacaggttcaatatctggcctc actcagtcggctaaggatccagtgatgccgtgagctg cagtgtaggccacagacgtggctcagatctggtgctg ctgtggctatggtgtaggccggccccctgtaactcca attcgacccctaggctgggaacctaaaaagaccccaa aaaagtcgctttaatgaatagtgaatacatccagccc aaagtccacagactctttggtctggttgtggcaaaca tacagccagacaaacaagacaaaaattatcctaggtg gtcagtgggggttcagagctgaatcctgaacactgga aggaaaacagcaaccaaatccaaatactgtatggttt tgcttatatgtagaatctaaattcaaagcaaatgagc aaaccaattgaaacagttatggaagacaagcaggtgg ttgtcaggggggagataaggggaggcaggaaagacct gggcgagggagattaagaggtaccaactttcagttgc aaaacaaatgagtcaccagtatgaaatgtgcaatgtg ggaaatacaggccataactttataatctctttttttt ttttgtcttttttgccttttctaaggctgctcccgtg gcatatggaggttcccaggctaggagtccaaacagag ctgtagctgccagcctacaccagagccacagcaacac gggaaccttaacccgctgagcaaggccagggatcgaa cccgagtcctcacagatgccagtagggttcattacca ctgagccacgacaggaattccagggtctgttgtgttc ttaaaacacttccaggagagtgagtggtatgtcataa gtaaacaataaatgttaaccacaacaagcttatgaaa taaacaggaaagccatatgacctacaatcagtcattg ggagaatccacaaaaggttgagcagaggatcaattcc agctcacactccagttttagattctcccctgccttaa agcatcacagactacataatctgagctgaagaataaa aattaaaactcaccccagtgcaaaacagaaatgaaaa agtattaaaacgaggttcatactgttgttcattagca atatcttttattcacagGGGTGCCCAACAACATGAAA AAATCAAGAATTTATTGCTGCTACGTCAAAGCTTATA CCAGAGATTATGCCTTATAGACATTAGCAATGGATAA TTATATGTTGCACTTGTGAAATGTGCACATATCCTGT TTATGAATCACCACATAGCCAGATTATCAATATTTTA CTTATTTCGTAAAAAATCCACAATTTTCCATAACAGA ATCAACGTGTGCAATAGGAACAAGATTGCTATGGAAA ACGAGGGTAACAGGAGGAGATATTAATCCAAGCATAG AAGAAATAGACAAATGAGGGGCCATAAGGGGAATATA GGG

TABLE-US-00012 TABLE 11 Contiguous 5' Genomic Sequence of CMP-Neu5Ac Hydroxylase gene ctgccagcctaagccacagccacagcaacgctgggtc Seq ID No. 47 tgagccatgtctgcagcctatgccagagctccccgca gcgccggatgcttaacccactgagcaaggccagggat tgaaccctcgtcctcatggatagcagttgagttgttt ccacggaactcttaggggaactcctgattatttttta tttaaatttatatttctctgactttttcgtgtgctca tcagccactgactgtgtatctccattagtcatggttt gttaactctgtcattcaaaccctcttcatccttgcta cgcagataacatcattataataaaatcgtgcctgaag accagtgacgcccccaagctaagttactgcttcccct ggggggaaaaagaagcaccgcgcgggcgctgacacga agtccgggcagaggaagacggggcagaggaagacggg ggagcagtgggagcagcgggcagggcgcgggaagcac tggggatgttccgcgttggcaggagggtgttgggcga gctcccggtgatgcaggggggaggagccttttccgaa gtagcgggacaagagccacgggaaggaactgttctga gttcccagtCCCGACGTCCTGGCAGCGCCCAGGCACT GTTATTGGTGCCTCCTGTGTCCACGCGCTTCCCGGCC AGGCAGCCCTGGCGGATCCTATTTTCTGTTCCCCCGA TTCTGGTACCTCTCCCTCCCGCCCTCGGTGCGCAGCC GTCCTCCTGCAGTGCCTGCTCCTCCAGGGGCGAAACC GATCAGGGATCAGGCCACCCGCCTCCTGAACATCCCT CCTTAGTTCCCACAGgtgagaaggcttcgccgctgct gccgctggcgccggcagcgccctccacgcacttcgta gtgggcgcgcgccctcctgcattgtttctaaaagatt tttttttatccgcttatgctatcagttactgaggaag tatttacaaatctactattattttgaatttgcctttt tctccttatagtttatcagtatctcttgagactgtta ttggtgcctgcaaatttaaaatgattggggttttatg aggaagtgaaccttttatctttatgaaacgcctaact gaggcaatgttaattgcttaaaatactttctttatta tcagtgtggccatgccagtgtcctcttggttagaatt tgcctgat

TABLE-US-00013 TABLE 12 Contiguous 3' Genomic Sequence of the Porcine CMP-Neu5Ac Hydroxylase Gene ctgccaaagctgggagatgggggaaagtagagtgggt Seq ID No. 48 tattgaaactgaatatagagttcagcatctaaaagcg aggtagtagaggaggaagctgtgtcaacggaaatact gagctgggttcacatcctctttctccacacagTCTAA TGCCTTGTGGAAGCAAATGAGCCACAGAAGCTGAAGG AAAAACCACCATTCTTTCTTAATACCTGGAGAGAGGC AACGACAGACTATGAGCAGgcaagtgagagggggctt tagctgtcaGggaaggcggagataaacccttgatggg taggatggccattgaaaggaggggagaaatttgcccc agcaggtagccaccaagcttggggacttggagggagg gctttcaaacgtattttcataaaaaagacctgtggag ctgtcaatgctcagggattctctcttaaaatctaaca gtattaatctgctaaaacatttgccttttcatagCAT CGAACAAACGACGGAGATCCTGTTGTGCCTCTCACCT GCCGAAGCTGCCAATCTCAAGGAAGGAATCAATTTTG TTCGAAATAAGAGCACTGGCAAGGATTACATCTTATT TAAGAATAAGAGCCGCCTGAAGGCATGTAAGAACATG TGCAAGCACCAAGGAGGCCTCTTCATTAAAGACATTG AGGATCTAAATGGAAGgtactgagaatcctttgcttt ctccctggcgatcctttctcccaattaggtttggcag gaaatgtgctcattgagaaattttaaatgatccaatc aacatgctatttcccccagcacatgcctaactttttc ttaagctcctttacggcagctctctgattttgattta tgaccttgacttaatttcccatcctctctgaagaact attgtttaaaatgtattcctagttgataaacagtgaa acttctaaggcacatgtgtgtgtgtgtgtgtgtgtgt gtgtgtttaccagcttttatattcaaagactcaagcc tcttttggatttcctttcctgctctctcagaagtgtg tgtgtgaggtgagtgcttgtccaaacactgccctaga acagagagactttccctgatgaaaacccgaaaaatgg cagagctctagctgcacctggcctcaacagcggctct tctgatcatttcttggaagaacgagtgctggtacccc ttttccccagccccttgattaaacctgcatatcgctt gcctccccatctcaggagcaattctaggagggagggt gggctttcttttcaggattgacaaagctacccagctt gcaaaccagggggatctggggggggggtttgcacctg atgctcccccactgataatgaatgagggattgacccc atcttttcaagctttgcttcagcctaacttgactctc gtagtgtttcagccgtttccatattaggctcttccac cgtgtcgtgtcgtcaatcttatttctcaggtcatctg tgggcagtttagtgcgaatggactcagaggtaactgg tagctgtccaagagctccctgctctaactgtatagaa gatcaccacccaagtctggaatcttcttacactggcc cacagacttgcatcactgcatacttagcttcagggcc cagctcccaggttaagtgctgtcatacctgtagcttg cttggctctgcagatagggttgctagattaggcaaat agagggtgcccagtcaaatttgcatttcagataaaca acgaatatatttttagttagatatgtttcaggcactg catgggacatacttttggtaggcagcctactctggaa gaacctcttggttgtttgctgacagactgcttttgag tcccttgcatcttctgggtggtttcaagttagggaga cctcagccataggttgttctgtcaccaagaagcttct gcaagcacgtgcaggccttgaggtcttccgacttgtg gcccggggactctgctttttctctgtccttttttctc cttagtgggccatgtcctgtggtgttgtcttagccag ttgtttaagggagtgttgcagctttatgattaagagc atggtctttccttgcaaactgcttggtttagaagcct ggctccaccacttagcggctctgtgacctcggacaca tttcttagcctttctgggcctcgctcttcttcctcat aaagtgaaaatgaaagtagacaaagccttctctgtct ggctactgagaggatggagtgatttcatacacataaa gcacttaaaataatgtctggcatatgatacatgctca ataaatgtcacttacatttgctattattattactctg ccatgatcgtagcttaagaacagaggtctttacagga attcaggctgttcttgaatctggcttgctcagcttaa tatggtaattgctttgccacagactggtcttcctctc cttcacccaaagccttagggggtgaacgatcccagtt tcaacctattctgttggcaggctaacatggagatggc accatcttagctctgctgcaggtggggagccagattc acccagctttgctcccagatacagctccccaagcatt tatatgctgaaactccatcccaagagcagtctacatg gtacactcccccatccatctctccaaatttggctgct tctacttaggctctctgtgcagcaattcacctgaaat atctcttccacgatacagtcaagggcagtgacctacc tgttccaccttcccttcctcagccatttttcttcttt gtacataatcaagatcaggaactctcataagctgtgg tcctcattttgtcaatctaatttcacagcctcttggc acatgaagctgtcctctctctcctttctgcctactgc ccatgagcagttgtgacactgccacatttctccttta acgacccagcctgctgaatagctgcatttggaatgtt ttcaatttttgttaatttatttatttcatcttttttt tttttttttttttttttttttttagggccgcacccat gggatatggaggttcccaggctagggatccaatggga gctgtagctgctggcctacaccacagccacagcaatg cacaattcgagccaatctttgacctacaccagagctc acggcaacactggattcttaacccactgattgaggcc agggatcaaactctcgtcctcatagatacgagtcaga tcgttaacctctgagccatgatagttgttagttactc attgatgagaaaggaagtgtcacaaaatatcctccat aagtcgaagtttgaatatgttttctgccttgttacta gaaaagagcattaaaaattcttgattggaatgaagct tggaaaaaatcagcatagtttactgatatataagtga aaatagaccttgttagtttaaaccatctgatatttct ggtggaagacatatttgtctgtaaaaaaaaaaaatct tgaacctgtttaaaaaaaaaacttgactggaaacact accaaaatatgggagttcctactgggacacagcagaa atgaatctaactagtatccatgaggacacaggtttga tgcctggcctcgctaagtgggttaaggatatggtgtt gctgcagctccaattcaacccctatcctgggaacccc catatgccaccctaaaaagcaaaaagaaaggtgctgc cctaaaaagcaaaaagaaagaaagaaagacagccaga cagactaccaaatatggagaggaaatggaacttttag gccctatctccaactatcacatccctatcaccgtctg gtaagaaatggaaaaaatattactaagcctcctttgt tgctacaattaatctgattctcattctgaagcagtgt tgccagagttaacaaataaaaatgcaaagctgggtag ttaaatttgaattacagataaacaaattcagtatatg ttcaatatcgtgtaagacgttttaaaataatttttat ttatctgaaatttatatttttcctgtattttatctgg caaccatgatcagaaatctttaaacaatcaggaagtc ttttttcttagacaaatgaaaatttgagttgatctta ggtttagtacactatactaggggccaagggttatagt gtgactattaaatcacagataatctttattactacat tatttccttatactggccccacttggatcttacccag cttagcttttgtatgagagtcatccttaaagatgact ttattctttaaaaaaaaaaacaaattttaagggctgc acccatagcatatagaagttcctaggctagcggtcaa attagagctgcagctgccagcctatgccacagccaca gcaatgccagatctgagctgcatctgtgacctacact gcagcttgcagcaatgctggatccttaacccattgaa caatgccagggattgaacacacatcctcatggatact gctcaggttcctaacctgctgagccacagttggaact

ccaaagcagactttattctgatggctctgctgatctc taacacgttattttgtgccatggtgtttatcttcact ttactcaagtcagggaaacacgaagagtctcatacag gataaacccaaggagaaatgtgcaaagtcacatacaa atcaaactgacaaaaatcaaatacaaggaaaaaatat cttcactttcaaaatcacctactgatgatgagtttat atttccttggatatttgaatattagctatttttttcc tttcatgagttttgtgttcaaccaactacagtcgttt actttgatcacagaataatgcatttaagccttaaata gattaatatttattttcaccatttcataaacctaagt acaatttccatccagGTCTGTTAAATGCACAAAACAC AACTGGAAGTTAGATGTAAGCAGCATGAAGTATATCA ATCCTCCTGGAAGCTTCTGTCAAGACGAACTGGgtaa ataccatcaatactgatcaatgttttctgctgttact gtcattggggtccctcttgtcaacttgtttccaatct cattagaagccttggatgcattctgattttaaactga ggtattttaaaagtaaccatcactgaaaattctaggc aagttttctctaaaaaatcccttcattcattcatttg ttcagtaagtatttgatgagaccttaccatgtgtaaa cattgcactaggtattaagaaatacaaagatggataa gatagagtcggcgtaaatgagatgatataatgagacg ttataatgaaactcacaattccagttgggaaataaag tccttcaaattccatgactctttctggcacacgttag aggctacagcttctgtgtgattctcatgctggctcca cttccactttttccttcttcctactcaagaaagccta tagaaatatgagtaagaagggcttaatcataggaata aatttgtctctgttctaagtgattaaaaatgtcttta tcagtataaaaagttacttgggaagattcttaaaact gcttttacacactgttctagaatgactgttatataaa taaaaaagtagatttgatctaacacaattaaatgacc tttggaaatattgactaattctcaccttgcccctcaa agggatgcctgaaccatttccttcttttgccagaaag cccccaccctttgtctgttgacctagcctaggaaatc ttcagatcacgttgttagcacgaactggttacatgtg ctgtacaaatactatttaattcatctgattaaaaaaa aagagataagaagcaaaagtttgactatcttaaactg tttgcgtaggtgagaggacaattgaccatctacttta tgagtatgtaacccagaaacttaaagctccttaaggg agctaagtcttttggataagacctatagtgagacctt ttagcaaaatggttaagactgaatggagctcactagc gtgggttcatatcctgatgctcaaacacgcaattaaa tgactttaggtgggttagtctctgttccttagtttcc tcaatgggagataatattggtagtagcgattttactg ggttgttgaaagaacatctgttaaatgttcagaacgt gttacgacagagtacagagtaatgatttgcttgtata tgtatgactcaaatagtctgccatatgccttgtgact gggtcctgtggagcaggaaggagggatttcccaccca gcagaaagttgggtaaactggaaaatagactgaggcc aggaaatgatgcaaagcgttgatgttcactgccacgg caggtgaagggcagggccagagttgtcagtagggtca ggggaggactggaaataaccaagacccactgcacttt tcagcctttgctccagtaaggtaatgtgtgagagtag aaaattttgttaacagaacccacttttcagtacagtg ctaccaatactgtagtgatttcataccacatcccaag aaagaaaaagatggctcaatcccatgtgagctgagat tatttggttttattgttaaataaatagcattgtgtgg tcatcattaaaaaaggtagatgttaggaaagtagaag gaagaagactctcacctacattttcatcactgttttg gtatctgccagttgtcaccttggtccccttccccgcc tctcccctgcctcctcttcctccttctcctttttttg gaatacaattcaggtaccataaaatttacccttttag agtgtttgactcaatggtttttagtattttcacatgt tgtgctattactatcactatataattccaggtcattc acatcaccccccaaagaaaccttctaactattagcag tccattcccttcttccctcagcccctggcaaccacta atctacttactgtctccatggatgttcctatattgaa tcaagctagcataaaccccacttgctcatggtcataa ttcttttttatagtgctaaattacatttgctaatatt caattaaggatttctatgtccatattcataaggaata ttggtgtgtagttttctctttgtgatatcttgtctgg ttgggggatcagagtaataattactgctctcatagaa tgaattgagaagtgttccctccttttctatttattgg aagagtttgtgaagtatattggtattgattcttcttt aaacatttggtcagattcaccagtgaagccatctggg ccatggctaatctttgtgaaaagttttttgattacta attaaatctctttaatttgttatgggtctgctcctca gacgttctagttcttcttgagtcagttttgttcattt gtttcttcctaggactttctccctttcatttggatta tttagattgatagtaatatcccccttttaattcctgg ctgtagtaatttgggtcttttctcttttttcttggtc agtttagctaaaggtttgtaattgtattaatcttttc aaataactaacttttttgttttgtttgttttttgttt tttgttttttgttttttgtttttttttgctttttaag gctgcacctgaggcatatggaagttctcaggctagag gtctaatcggagctacagctgctggcctataccacaa ccatagcaatgccagattcaagctgcatctgcgacct acaccacaactcggccagggatcacacccgcaacctc atggttcctagtcggatttgttaaccactgtgccacg acgggaactcccgcccattttttttaacacctcatac tttaacataaagatgggcttcacatggactgatagct caaatgaggaaggtaagactatgaaagtaatggaaga aatgtagactatttttgtgacctagagattactgata cttcttgacttttcaaacaatacttcaaaagtacagc ccaaagggaaaaaagaaagaaaaaagaaacacacata tacacaaacctagtgaataagatatcatcgatacact acagatttctatgaactggaagaccccatggacaaag ttaaagaacatatgatagtttgagtgattattttgca atatttacaaccaatgagggaatattatccagcttat aggaggaagtaatgcaaatcgacaagaaaaagatagg aaacccaatataaaaattaagaaaatacaaaaattaa gaaaggatatgaactagcattttacaaaagaaaaatc tccaaaagtcaatcagcacatgaaaatatgctcaaac ctattaattattagaaaactacagactgaagcaatga ggtgctttactttacatctttttgactgataaaaagt tagaaacaaaggtgatatcaaatgtcagggataaaag gatatagaaatcgtcatgcctgtggtgggagtatggc cggtgcagtcatgtgggaaggtaatctgacagtggtt aggcagagcaggtttatgaatacactgtggcccatca atcccacgcctgtttatgtaccaaagaaatcctgttg tggcagaatctatgggtccacccctgggagcatgaat taataaaatgtggcaccagggtgtgtgaaactccagc tagagatgagatgtccacatggcaacatgaatgcatc ttagaacatagatttgagtgaaaaagagtaagaaaca gccgggaaacccaataccatttataaaaattaaagat gcacacatacaatgtagtaaatattttgcatgaactt tcaaatggttgcctacagggggggagagtaaagaaga gtagaaaacaaagataagggagtaagtaagtagctct gcctggactgaatataatgtgtcatgaactgagaaat atggttaacataatcctcttaacttgaggtcctaaat gaatgaatgagtccactattcatttacccattcttta atgtgtattgcattataatccatttttttagaaccaa cgaattttgttcccataactactaatcagcctgcctt ttctccctcattcccttatcagctcaggggcattcct agtttttcaaacgttcctcatttgaaccaaaaatagc atcattgtttaaattatacttgttttcaaatacgatg cttatatattccaagtgtgtttgcccattttcttagg

tggtagaaatttttcattctacttttctatctactca gattttcccgttggaattatttccattgctattaaac ttagaagtcccccctgtgatatgccatttttttcata ctttttaagcacttggttgcttttctttgtgtcttta agcacctagaatacttataaccattgcacagcactgt gtatcaggcagcccttcctcttccactaatttatggt ccttctcttagactatattaaactgttatttaattag gatcctctcttcgtccttatgatttaattattatagt tttctaatatgtttttattataattcctcttcattat tcctccctattaaaaattttaatgaattccatttgtt tgttcttctagttaaatattaagtcataatccaaata acttagatgtcattagtttatgtggtcaaagtaagga taccacatctttatagatgcaggcagttggcagatgt catgattttcttcagtgcataaatgcaatatctttga gcaaggggcataaaaacttttatggtattggctttga aataatagttaagaactgcagactcagtttttcctgc ttttcttgaaaaagaacacttctaaagaaggaaaatc cttaagcatggatatcgatgtaattttctgaaagtct cctgtaattccttgggatttttgttgttgtttgttgg tcggtttttttgggtttttgtttgtttgttttgtttt gttttgttttgcttttagggctgcacctgtggcatat ggaagttcccaggctaggggtccaactggagctacag ctgccagcctactccacagccacagcaacatgggatc ctagctgcatctgtgacctaaccacagctcttggtaa tgccagattgttaacccactgagcaatgccagagatc gaatctgcctcctcatggacactagtcagattagttt ctgctgagccacaatgggaattcccaattccttgtat ttttgaactggttatgtgctagcatataattttgttt cttgaatctttgtgggttttttttttttttttttttt gtctcttgtctttttaaggctgcacccacagcatatg gaggttcccaggctagaggtcaaattggagctacagc tgccagcctacacaacaactgcagcaaagtggggccc aacttatatgacagttcgtggcaatgccggattccta acccactgagcagggccagggatcgaacctgagtttc cagtcagtttcgttaaccactgagccatgatagtaac tcctgtttgttcagtcttgaacctcctttttaattct ttattccttgagggtgaaataattgccataataatac tatcatttattacatgccttctctgtgctaggcatag tgacactttaggatttattatatcacttaatccctac aacaactctgcaaagtatgtatcataatcctatttga cagatcaggaaattgcagcccaggatgcagataatat gcatccatcacaagtgactagatatagtccctctgct attcagcagggtctcattgcctttccattccaaatgc aatagtttgcatctattgtatatgtgttttggggttt ttttgtctttttttttttttttgtcttttctggggcc tcacccttggcataggtaggttcccaggctaggggtc aaattgaagctgcagctgccagcctacaccacagcca cagcaactcgggatctgagcctcatctgcaacctaca ccaaagctcacggcaacaccggatccttaacccactg agtgaggccagagatcaaaccggcaacctcatggttc ctagtcggattcattaaccactgagccacgatgggaa ctccctaaatgcaatagtttgctctattaaccccaaa ctcccagtccatcccactccctcctcctccctcttgg caaccacaagtctgttctccatgtccatgattttctt ttctggggaaagtttcatttgtgccatttttcatttt acgggtaatttttacttcagtttcttccactagcagt tgtcttaaagtgagtataattaatattcatttggaaa atgtaagcaaaacattttttaaagggccatgcccaca gcatatgaaagtttctgggccaggggttgaatccagg ctccaagttgcagctgtgccctacactgcagctgggc aatgctggatcctttaacccactgtgcccggctaggg atcaaacctgcatttccacagctacccgagccattgc agttggattcttaacccactgcactacagtgggaact cccacaaaacattttttaatgtcctttgaataaagta ggaaagtgctcgtctttgagggcagggcggcaatgcc atttccacaaggtttgctttggcttgggacctcatct gctgtcatttagtaatgaataaaattgctgacagtaa taggattaactgtgtgtggagatagccagggttagag ataaaaacactggagaagtcaaataagttgctcgagg tcctctagctaataagctattaagtgggagagtgagg gctagaaacaggccatctgtctcccaagcacatgtcc attagtggtttgctgatagccttccagaacaacagag aggactctcaaacatggtcttgcctccctccaattga tcccctccatgtgcctcacagcgggtctttctaaaat taagttctgattttaattctcccttgctatagcactt aggtatggctttcagccgtgcaataaaaagcaggcaa gagtggctcaatcatataggaggttgtttttcttaga tcccaagcaggtaatcctgggcattatggttgttctg cgtttatcaaggagccaaattctctatcacctcctgt tctatcctcctcagtatctggctctattcttcagcat ctcaagatggcttgtgctcctccaagcatggcagtca aattccacacaagagggggaaatatgaagggcagaca gtgctggtctcctgagctgtccctccggggaaataaa tgtattccttcaagtcccgtgagacttctgaagtaga cgtctgcttacgtctcacccaccagaactatgtaaac tgcacatagtgctaggtctacatagccactcataact gccagggggtgggaaatctttaaataggtgtaccacc acacaattaggatgctaatagtaagggagaaggagag aataggttttgcgcaagccaccagcatgcctgccaca attgcttaaaattcttcattgacccctcattgccaca ggatgaaatccaaacgccttcttagttgggaatctga cctacctgtctctcccacctggttcagacaccattct ccttggtcataaaattccagtcatttgtgaacatcca gctcccccatgcctccatgcctttgcacatgctgttc ttttatcttttatgttgtccttttatcttttatccaa aagagatatcccatcatcacatctcttttgtcagccc ccaaatactttgtctttcaagttcagctggaggatta cctcctatttgaaatcagctttgtctcttacaaccaa acaaggttttccttccgagacactcccacagcacctt gaactcatctctatcaatcattcatttgattgtaatg aagttgttggtggtatgcctgtgtctctgacacatct gcgatctcatgagttccttaagtggaatgtgaatagc gggatgaacagtattggtcttcagccctcatctctgc agatgttgcttgacccaaatgagcgttgccttttatt ttgattttgctttgatttgtctactccatgtacttga gccatgcatttctgtcttagcgatgctttttaaaagt cattttttggttgattatccagatttgtccacctttg cttctagTTGTAGAAAAGGATGAAGAAAATGGAGTTT TGCTTCTAGAACTAAATCCTCCTAACCCGTGGGATTC AGAACCCAGATCTCCTGAAGATTTGGCATTTGGGGAA GTGCAGgtaaggaaatgttaaattgcaatattcttaa aaacacaaataaagctaacatatcaatttatatatat atatatatatatatttttttttttttttacatcttat attaccttgagtattcttggaagtggctagttaggac atataataaagttattctgaagtctttttttttcttt ttccatggtgagcagtggcttgatgtggatctcagct cccagacgaggcactgaacctgagccgcagtggtgaa agcaccaagttctagccactagaccaccagggaactc cctattctaaattcttgagcacattatttaggaacct caggaacttggcaggattacaggaaatatatctagat ttaaaaaaaaatcttttaacagaggtcccaaaggaga gtcatgcacagctatgggaggaagttcagaaactgcc cttgctaccagatcactgtcagataaaatggccagct acatgtttctgcacattgccctaagatctttacaaac ttttctgtgcatttttccacttttaaaagaaaatttc

ggggttcctgttgttgctcagtggttaacgaacccaa ctagtatccatggggacaggggttcgagccctggcct cactcagtgggttaagaatctggcattgctgtggctg tggcgtaggctggcggctacagctcagattggacccc tagcctgagaacctccatatgccgcaggtatggccct aaaaaaaaaaaaaaagagagagagagaatttcctcca gaaaaaacactttggtagtttgggagaagtaaacaac caaaaattaatttttctggagtattcgggaagcttgt aaaaatgggctcttacttttttgaggagacaaatggg aacctacccagaagaggcacaatcacctgcatttgat ttcttgacctctccctaccttctttgctggctttcca catttggatttctgtgaccttatctctgctccttggt gttttcatttttcctgtggacgtgccagactatggga agggagtaaggcgttgatttagaatcctgtagtctct gcctgtctctagtcattgttttcacccttctcaaagg accttgacatcctgagtgagtccgcaagtaatttagg ggagaagccttagaagccagtgcagccaggctacatg actgtgtccacccactggaaccagtcatttttatacc tattcacagcccccctaccatttaaatccccagaggt ctgccataacatctgtaactccctttcctggtaaatt gtgttctaaaagactggtaacaaaagatattctgtgg tacagagcataattaaatacctgggagctgatttgag tggggtaaatcaactggtttgacccctaaaacccacc atgagcatttctgttcaataaagtaatgcccgtgctg ggaattgtgttctacggaaatgctcctgctgtgtctt tcttgagtcctgtgtcattgaacatgcttaggagcaa aggtcccccatgtggcttgtctgctaaccagcccagt tccttgttctggctggtaatgatccgatcatctgaat ctcactgtcttccaacagATCACGTACCTTACTCACG CCTGCATGGACCTCAAGCTGGGGGACAAGAGAATGGT GTTCGACCCTTGGTTATCGGTCCTGCTTTTGCGCGAG GATGGTGGTTACTACACGAGCCTCCATCTGATTGGCT GGAGAGGCTGAGCCGCGCAGACTTAATTTACATCAGT CACATGCACTCAGACCACCTGAGgtaaggaagggtga gccctcaactccgaagaaaatgctgcaataaaagcac tgttggttttcagctttttttgtaatcactgctcatt ctgaggtagattcgcttgggctgataaaaagagaact aattcagataaatgcttgcatttgcatagcctctttt tttaaaaactttttttttttttttttttttttggctt ttcagggctgaacctgtggcatatggaggttcccagg ctaggggtcgaatcagagctgtagccccgggcctatg ccactgccatagcaacatgcatagcctcctttttaaa gtgccttcctgttttataccattgggatgtgagaaga gctattgtggaaangagcatggggtnataaccctgga cctctcacgtcctaccctcaggntagtgggaaaactc tgagtttaaggacatcaaagtgactcctttttagtta cattatggnggaatcagcncatatttttacaaggggc ggagngtaanctgttggagtttacaagacatatggtg gcattgcaactacttaaccctactattatagcacaaa agcagccatagtcggtcctgaaggagcctgatgcctt cagctttataggcaatgacgtgtgaatatcacaaaca gtttcctgtgtcaccaaacatgattgccttttgattt ccctttcaaccctttaaaaaaaggtaaaagcccttct tagcattcagcagcaggtcgctgtgttttgccaactc ctgatctgtagcatttcgacaacactgagctctcaac ttttgaaccctgagtccaccacatccttcagtgaaac cagagccatgtgatactaaggatagaaacggaaactt cctgaatccaggcgatcaaataggagggagaaagagg aactttcattgacaaaaccacaaatattgtgaatgga ctgttacaaatattgtgaatgctcctattcccaaccc cctggcttcattacagggtcctatgtgttcatcctta ttgagaaatttgtattgctactgccaggttgccaata cccagcggtgcccatggtgttctaaaatgaagcaatt tcaactttatttttttttcctgtgactttacatgaca agttcacatgaaggatatactttgatagtaatgtcca tggttagggaatatacattgtttgctggttgactggc ccctggatttttctattgaaagtccatgagatctcga aggcacaggtgtgttctctcgctttttaaggaaaggg tttaaaaacttaagtaattaacagctttagtaacaaa ttacctataacacacttaaaaaccgaataccacccac tggagtattgtgctacgattaaaaatctacttgtcta ctacatgatatctttgtcccacagaaggttctggaac caaacttgtaatttcaggattatgagagccctgagtt cacgcattgtgtaataactatgttgtgtggtagtcaa tttgtacagcttgcttagagagaacaatgtcaagtta aggaggcgattgctttatagtgcctgtcacaagatgc cattgccattgtcctagcaagagatattctatgggag tatactacattttagtgaggataagaactttttatgg catttagtccggtcatttcccaaccactgtcctgaaa accaatttcattttgatttcaggggcttgtgtgggca aagttgccaggcattaaaaagccacttctcaactgta gtatcacaatgctttagttgggtagtgtattgcagat agcttatggctgaaaagttaccaagccttgcagtttt cactcctttgagtttatttccttgacagaattgaccc tgagttttttgactcttacctgctcaactaataaaca ccagagtcatttatctccattgctcttgtctgacctt tatttaccgaataatgccttatgggttcacaaaaaca aggggggagggggccagcatgccttagaaactgtctt tagtcaagaaatgngattttattatgtaaatatatga gtattataatagatagtgttattaatagacaccagca agaattgtcaataatttaaaaatcacaaattaaaata catccatgttagnatcatttatcctaactcccaaagc cctttaaagtggaagatttagatgttaacccagagat taaagacatgttcaaagaatccttgatttttttttga atcccttgtttttagagaagaaaacctaatgattttc cccctctggattctacatattaaatatagttttggaa cttgaatattagtatggttaataagtgctgatatgct gattttgtttatatttttcttatgagtaaatatccta tatcaccagacattatagtctatgtacaaatatgatt cttaaacctgatagcacattcattagagttggaattg ccttttttttttttttttttacagttgcacctgcaac atatgaaagttcccaggctaggggttgaatccaagct gcagctgccaccctacattacagccgtagtaacagca gatccgagctgcatctgcaacctatgctgcagctcag ggcaatgccagatccactgagtgaagccagggatgga acttgcatcctcatagagacaacgtcgtgtccttaac ccactgagccagaacaggaactccagaatttcctttc aatagaagaagcaccaagtttaggatcagaaagcctg aatttgaataccaatttactattttagtcatatattt ctgagtgtgntcctcatttattaaaagcagactaaaa gatgagagggtcttttgttgagaatcaaatacaataa catgtgaaagtgtgtaacactatgattgaaatatacc tacacagccatttatttgtttattgttcatgttttgc cacccacacagtagtatataatccttttatgtaataa atgctaataatgaaagttggcaacttatgtaagtact caaaatgctggaggtcatgggatactgactgggatac tacagaggtaatgtcatttcctctgcgctaaacttat tgtcttgtagttagggactgactctctttaggacaag gagttcattctgtataccatgtgtggctatcaccctt cgaagttgaaaaactgccccagggtgggcacccatcc gttctcttagatatatggccgagacctttctctcact gggagggaaccacactgaggaatgagaaaaaaaaaag gaaaatcaagatgaaaccagaaacctctttggcataa cttctccactctgtactttttgttagaactacccttg cacaaagcagcatcagtgtggaagacagaatttgcac acctggtttgatatacatgccgtggtatatgggatgt

tctaacaataaagaggactctcccaggaaatctcctc actgttatagtcagccttgaggaaagagctcttcttt tggactctggggagagtctagtttttcagttccttgc ttctcggtcaacgtgttggtgtaaggatcacactctc tcttatactagataattctattttttcaccTTTcaac ctgtctatccttctgaccctagTTACCCAACACTGAA GAAGCTTGCTGAGAGAAGACCAGATGTTCCCATTTAT GTTGGCAACACGGAAAGACCTGTATTTTGGAATCTGA ATCAGAGTGGCGTCCAGTTGACTAATATCAATGTAGT GCCATTTGGAATATGGCAGCAGgtctgtgttctttcc acatgtttgggttatcctttctgggataaatttgagg cgagatagaaactttaagactaaagaaacaatggcct actttttttgtacatggtcctgtgtaaatctctattt gagctgaaataagatggtcttcctctccaattatcca tggtatgactctgatggataacaaatccagttctgaa aaaaggggatttctttccagaagagaggacagtttct tcaaatattgaattaaaagcaaaatagatgtaaaccg ttgttggttttattgttgaattccagGTAGACAAAAA TCTTCGATTCATGATCTTGATGGATGGCGTTCATCCT GAGATGGACACTTGCATTATTGTGGAATACAAAGgta ttttcttgccctcatcagcatgaaattgctcttggta gaaaggataataatagttatccaaaacatcatcctat gttcatctgtttcttccctcttcattttccatagagt acagtatattctatctctgtcttaggaaaatggactg tcattcatataatcttacagagaatcaattagtaatg tactctatgccgtgacaggtgcgaaggttttttttga aggcaacagataaaaatatcctatatttcacctattg taatttccttaaaactgacattattgaataaatgttt tactttcatcttgaatattattatgttatggaatcat acactttaccccaataatcatcgaaaagaatttccaa aaggttgagagagttgtgttgatctgattactttcct ctgcatcctttgagcttaacctttgaatatagtttgc taaggaaagtagtctgtttatgatcctggagtggaat caggctaagtgtcctcattcagaacccactgaatcag acagaatgaatttatttccttgaaagttcaaaatgtg tcactcaagagtataaattttcaaatcttactctctc ttttccttggatgtgagcaattcttcgataattgaat gaggcagattatatagacttacatggaagactgttgg cctgagaattcaaactatggtgttcaagacttcacng ngagtccgatgccatttgtttcccacagGTCATAAAA TACTCAATACAGTGGATTGCACCAGACCCAATGGAGG AAGGCTGCCTATGAAGGTTGCATTAATGATGAGTGAT TTTGCTGGAGGAGCTTCAGGCTTTCCAATGACTTTCA GTGGTGGAAAATTTACTGgtaattctttatatcaaaa tgatgccaaggagttggcatggcactttgctaaatgc tgtgtgaatcaatacaaagataattaggacatggttc ttcctcacaagaggtgtgcaatcttattgggaaatca tacttgcaagtcacaaatatagactaaagtttccagc tgagaatatgctgatggagcatgaaacactaaggaga cagggagaatctcaggaaaaatcaagaataatttgga tcaaatggattcctgacatagaacatagagctgatca gaaagagtctgacattggtaatccaggcttaagtgct ctttgtatgtggttcagaacagagtgtgggcagcctg agggggatacatacccttgacctcgtggaaagctcat acgggggagggatgaggctaaggaagcccctctaaag tgtgggattacgagaggttgggggggtggtagggaaa atagtggtcaaagagtataaacttccagttacaagat gaataaattctaggggtataataacagcatggcacta tagatagcatattgtactatatactggaagtgctgag agtagatcttacatgttctaaccacacacacacacac acacacacacacaccacacacacacaccacacacaca cacgtgcacacaaacagaaatggtaattatgtgaggt gatggcggtgttaactaactttattgtggtcatcatt tagccatacatgcatgtcatgaaatcaccatgttgta caccttaaagttatgtaatactagatgtcagttatat ctcaaagctagaaaaaatgtggggaccaaggcagaag ctcttctgctctgtgtctaagggtggttctggggctg ggatggggaggatggttaagtggtatatttttttcat acctttgctcagtactatcattgtaagtgttcaatat atgtctgcttaataaattaatgtttttagtaagtaat ctctgtttagtaatgtgtcagaaatgccctacttgca ataggaagaaaacctgtccagtcccttccttttttct gtaagtctgatttcattgcctcccagaatgcatcacc atgtgagagatagagggaaggtgctgtccttatgggg ttaacagtgtgactagggaggcaaaatatacctacta aagggtggtagcataattcagttcttatgtgagtatg tgtatgtgtgtgagtatgtgcacatgcacatacattt taaaaggtctgtaatatactaacatgttcatagtggt tacacctagcttataggtaacattttttcccctgtat ccttgtttgtgtttatcaaattttcataacagtaatg gtagaaggagtacctgacatggtaccatacatgctng gncctgcctaatttctcnatttcctttattgcccata cccccattgcttgacaagcataagtccatactggctt gttttcgttcctcagactcagtacaccatgtagctcc atgccctgggtctttgtatgtgctatttctactgctt agagtgctattgcccctgaccaccacgtggtcagcaa cttctcttctgcgtctgtgtctatggtctatgattcc agatgtcatcttcactaactacccttctaatatgccc ttccatcccacccgtcctcatccttaccccagccact ctctatttggtggctctgttttattttcttcctagct catcactctttgaaatgaacttatttacttattcaat tgcttctttcactagaatgaatgctccatgagagcag ggacctgctttatcttgctcgccactgtattcacagt gcctagaactacgtctggcacatagtaggtgctcaat aaatatcgatcaaatgaaagaatgagcaaacgaacaa atgaacaacacgtgaggtaggcatcatgattccatca acagaggagaaaaccagacttaaagnaatgaagtggn ggagctgcatttgatcttgactgactccacatccatg ctcttgaccactgtgcatctccagagtgtaatgaaca tactttacttttatattccaccaaaataacaaagcca tgcccatgttagtagagagttaatcgacagtgccctt aaaatatgcatgcacccagggtacaactatgcatgct gccctgtgttttcagttggatccaaatgaattgccgt aaacaaagaggggattcaatgtctttgactagtttgg gatattttcctagtaaccaactttgcaaaataaagcc actaatgacaaggagctttgttctacttctgcatcac tcaactgtcaatttttatctcttgcaagacttctaat ctactagaacttttgtttttctgtgatttctgaacag agaagactaatccaaaccctgtcattccagAGGAATG GAAAGCCCAATTCATTAAAACAGAAAGGAAGAAACTC CTGAACTACAAGGCTCGGCTGGTGAAGGACCTACAAC CCAGAATTTACTGCCCCTTTCCTGGGTATTTCGTGGA ATCCCACCCAGCAGACAAgtatggctggatattttat ataacgtgtttacgcataagttaatatatgctgaatg agtgatttagctgtgaaacaacatgaaatgagaaaga atgattagtaggggtctggagcttattttaacaagca gcctgaaaacagagagtatgaataaaaaaaattaaat acaagagtgtgctattaccaattatgtataatagtct tgtacatctaacttcaattccaatcactatatgctta tactaaaaaacgaagtatagagtcaaccttctttgac taacagctcttccctagtcagggacattagctcaagt atagtctttatttttcctggggtaagaaaagaaggat tgggaagtaggaatgcaaagaaataaaaaataattct gtcattgttcaaataagaatgtcatctgaaaataaac tgccttacatgggaatgctcttatttgtcagGTATAT

TAAGGAAACAAACATCAAAAATGACCCAAATGAACTC AACAATCTTATCAAGAAGAATTCTGAGGTGGTAACCT GGACCCCAAGACCTGGAGCCACTCTTGATCTGGGTAG GATGCTAAAGGACCCAACAGACAGgtttgacttgaat atttacagggaacaaaaatgatttctgaattttttca tgtttatgagaaaataaagggcatacctatggcctct tggcaggtccctgtttgtaggaatattaagtttttct tgactagcatcctgagcttgtcatgcattaagatcta cacaccaccctttaaagtgggagtcttactgtataaa ataaactattaaataagtatctttcaactctggggtg gggggggagactgagttttttcacagtcctatataat aattttcttatcctataaaataattaggagttcccgt agtggctcagcaatagcaaacccgactagtatcgatg aggatgcgggttcgattcctggcccccctcagtgggt taaggatctggcattgccgtgagctgtggtgtaggtg gcagacacggctcagatcccacgttactgtggctgtg gcataggccagcagctccagctctgattagaccctta gcctgggaacttccatatgctgtgggtgtggccttga aaaaaaataaataaataagataattactcaaatgttt tccttgtctcagaaccttacttcaggataaagagtga gaaagttttttttatgaagggccattattacagctca aaaataagttgtcttcagcaagtagaaagcaataagc ctgagagttagtgttcctatcagtgtaaatattacct cctcgccaatccccagacagtccatttgaacaattaa cggtgccctgggagtacagttcagaaacattaatgtg gatgttccagacctgtatttttataagtacttgtctt gagccggatggaaccatcattcctcaccattatttag aagtggactgtgactctgttggagatcagggcacacg gttaccaaaagcacacccttctcctggccttaccttt gcaaagctggggtctgggacacagtcagctgattata cccttttactaacttcccacagctcaaatctggtcaa ttctccttcacaaatctcttaaaaatccatcactcac ctccagcctcttctgctgtggccttgattcagcctct cacaatttttttttaaccagaattctggcagtggccc ctgacttgcctctgtgctcccagccccgctgtcctct gatccatcctccatgccagccttcaatctgctggtca cgattcattgatgggttaggaaatcaatggcatcaca actagcatttagaaaaaggaaataggcgttcccgccg tggcacagcagaaataaatccgactaggaaccataag gttgcgggttcaacccctggccttgttcagtgggtta aggatccggcattgccgtgggctgttttgtaagtcac agacatggctctgatccggcattgctgtggctctggc gtaggcctgcagcatcagctccaattagacccctatc ctgggagcctccatatgctgcaagtgcagccctaaaa aaaataaaaaaataaaaaaaaataaataaaagaagta gacaaattgtatagaacaaccctgagtatgttgcctg agcacatataacaagggtaagtattatttcaggaaac tctggtttcacagatactcttggcatatggaccccta gagtcctgatgtaaaatatattcttcctgggatctta ggcaagaagtttgaaagctccaactctgcactgctgc caaagaaatgatttttaagtgcaaaactcttcccgtt cccttccctgtataaaattccataggatctctccagt gcctctaggataaaggcagttttcattctctagttca aggtgagagaagattttaattatttcacgttttagtg gggaattcaagagtctggcacctgacatttgctgaac tctctccattatccctctctagttccccagacgcatc ctatggtagaaattcgcaactagagtgagcgtcagag taacccaaggaaactgggtaaatgcagctccctgggc tctaccccctgagattctgattcagtagatctgaagc agagccctggaatatgcatatgcatcattgtgtcaca ccaagcattctgggtaatgagagttgatgttaggttc tcagtagtaagacaagtatagagattccgggggactg agtgctcagctctgccttggggaggagggagagggct aaagagaacaggagatggggacagggaatgctcaacc tccaatcttaggcatttgagctatgtcttaggggtca ggaggaggttaccaatatagtgattaagagattgagg ttccagtcagagggatatgctggagaaggggggtgaa aataatgtcataggtttggtgagtgcagatactttga gttttttaatatttttattgaaatatagttgatttac aatgctcttagtgagtacaattactttgaataagtgc atagatgtatgccattcttccagaaatgatttattga gctcctttgggcatcatgctaagtacaggggaaacag ctgtgaagaggtccttcccttatgaagtcattcatcc ccttcagtaaatgaaggtaaaggaaaaggatgagaca gggacgccgtgttggaccagggtcagaaaggccttat aagaccttgcctggagggcaaggaacttgcctgtgag taaggagagcttgagaaagcgataaagcaaagaagga acattactgcattgtgttttagaaaaaccatgtcctg gggaagaactcctagagtcaggggggccagttgggag actgtgcttttttccaggaggagataagtgaggctgc tggctgagatggagcaaggatttagagaagcagatat gagattcatttagaagttagacattttaggatctgac acataatttatcaccaaaaccagtgcatctctggctt tgggccaccagttttggagaagtggaatgtagggacc taccattacctgccaatctttactacacagatgccta tttccctcctcatatttcctttctccagatcacgtcc tattctattgccaggactcaagattccaccttgcatg cagtgatccatcttcacactggatggacagctctagg gatgtcagagcacactcttgtccatactgctgactgg gtctcctgtcagcccatctgtctatcagctgtggtat tattagtataataagagggctgtatatgagagacaca aaattctaggtgtagctcaaagataggctagagttat tcctatgtacaacaaatatttatgggaccccttctgt gtactgtcatggttgctgctttcatcatacttgtagt ctaatggaggtgggggcagggcaggaataagcggatg tccacaaaatcagtaagaccacttatattcaacattt tcataatttagttatttgagcccaaagggtccacatc cgtggtattccaacttttttttccccggacatggatc tttatctttttttttttttcttttttgcggccagacc tgcggcatatggaagttcccaggccaggggttgaatg ggagttgcagctgcctggtctacaccacagccacagc aaggtgggatctgagctgcatctgtgacatacaccgc agctgaggtaacaccagattctgaacccactgaatga ggccagggatggaacccgtctccttatgaacactatg tcatgttcttcaccctctgagccacaacgggaactcc agacttcgtctttaaatgtattctgacttggagagct atcacactaagcaattaacaggagctgacctggttta ggctggggtggggccctactcctcaatgttccctgag gcacatctgtgggacccctgggcatcatctatctgag cagccttagagctgctcatccagttgactgttgatgt agaagtgcaaacttctgccttccttatttgttgcttt cttttttcattgttctctcccctttgtgtctttaagC AAGGGCATCGTAGAGCCTCCAGAAGGGACTAAGATTT ACAAGGATTCCTGGGATTTTGGCCCATATTTGAATAT CTTGAATGCTGCTATAGGAGATGAAATATTTCGTCAC TCATCCTGGATAAAAGAATACTTCACTTGGGCTGGAT TTAAGGATTATAACCTGGTGGTCAGGgtatgctatga agttattatttgtttttgttttcttgtattacagagc tatatgaaaacctcttagtattccagttggtttctca ataagcattcattgagccttactgactgtcagacgga gggcgtattggactatgtgctgaaacaatcctttgtt gaaaatgtagggaatgttgaaaatgtagggaatgaaa tgtagatccagctctgtttctcttttggaggattctt tttcctccatcaccgtgtcttggttcttgtttgtttt gggtttttgtgggtgttgtattgtgttgtgttggtta tggcagtgacagctatttaaactgtgaaacgggggag

ttcccgtcgtggcgcagtggttaacgaatccgactgg gaaccatgaggttgcgggttcggtccctgcccttgct cagtgggttaacgatccggcgttgccgtgagctgtgg tgtaggttgcagacacggctcggatcccgcgttgctg tggctctagcgtaggccagcggctacagctccgattg gacccctagcctgggaacctccatatgccgcaggagc ggcccaaagaaatagcaaaaagacaaaataaataaat aaataaataagtaagtaaaataaactgtgaaacgggg agttcccttcatggctcagcagttaacaaacccagct aggatccatgaggatgtaggttcgatccctggccttg ctcagtgggttaagaatccagcgttgctgtgagctgt gatgtaggtcgcagatgcagcccagatcctgcattgc tgtggctgtggcgtaggctggcagctgaagctccgat tcaacccctagcctgggaacatccatatgctgcaggt gtggccttaagaggcaaaaaaataaaaaaataaaaaa taaataaattgtgggacagacaggtggctccactgca gagctggtgtcctgtagcagcctggaagcaggtaagg taaggactgcagctgggtaaggactgaattgcaccaa ctgggaagtaagcctagatctagaacttaagttagcc ctgacatagacacacagagctcaccagctaagtggtt cagcttataagctggtcactgaaactgaggatgtcca caaaagcaaaataagtagcaacaggcagcgggatgca agagaaagaggaggcctaaaatggtctgggaatccct gccatacctatattttatcctacttatatttagtgcc tgaatgtgtgcctggagagcaaagtttagggaaagca tcgggaaatgcacagtattcatacccttaggaacaaa gatcagttacctccagggtaaagactatttccaagtt taaatttcaacccctgaacattagtactgggtaccag gcaacacttgccatcctcaaaatcaatgaatcctaaa attcaacctgggggtcagtgacagtctgtgacaaagt ttttgctggtcagtaacgaaataagtatgagcaccat ctgagtatggtcaccaagatgtcaactctctttcctt tggacgaattgtcattattccaagattaggtcctttc tatttttgaggtgtgaaaacatctttcctttcataaa ataaaaggatagtaggtggaagaattttttttgtttt ttggtctttttgctatttctttgggccgcttctgcag catatggaggttcccaggccaggggtcgaatcggagc tttagccaccggcccacgccagagccacagcaacacg ggatccaagccgcatctgcagcctacaccacagctca cggcaatgccggatcgttaacccactgagcaagggca gggaccgaacccgcaacctcatggttcctagtcggat tcgttaaccactgcgccacgacgggaactcctaatga tactcttttatatttagctactatgtgatgatgagaa acagtccacattttattattttttagccaatttgata tctcattactaagataatgataattttctctataaat tttatttaagttagtgttatgaagtggttttgctagt gtagaaggctaggatttgaattcagttcaagaaagaa gagagggagggagggagagggatgggtagagggatgg ggcagtgggagagagcaaagaggagagacagtttttg tattaattctgcttcattgctatcatttaagggcact tgggtcttgcacattctagaattttctaaggaccttg accgccagattgatatgcttcttccctttaccatgtt gtcatttgaacagATGATTGAGACAGATGAGGACTTC AGCCCTTTGCCTGGAGGATATGACTATTTGGTTGACT TTCTGGATTTATCCTTTCCAAAAGAAAGACCAAGCCG GGAACATCCATATGAGGAAgtaagcaggaataccagt ggaagtgcccctttcttccttccttcctaaataaact tttttattttggaacaactttagagttacagaaaagt tgcaaagatattatagacagtagtgtttatatatata tataaatttttttttgctttttatgaccacacctgtg gcatatggaggttcccagtctaggggttgaattggag ctacagctgccagtctgtgccataaccacagcaatgc aggatctgggccacgtctgtgacctacaccaaagctc acagctggattcttaacccactgagcaaggccaggga ttgaacctgcatcctcgtggttcctagttggattcgt ttccgctttgccgcaatgggaactccaaattattgtt aatatcttactttactggggtacatttgttacaacca atactctgatactgaaacattactgttaactccgtac ttgcttctttttgagtcatttgcaaagactggcttct tgacctgcttccttccaaacagctggcctgcctatgc tgttctcagacctgcaagcactgatctctgcccccct tgccttctctccagtggtgtctccttccccaaacaaa cccagtgtggctctggaaagggagttaagtcaacata aaccaacacatattttgttgagctccaattttgagca aatccctcaccacggcagacaggcatgatgttaagaa ctagggctttggacacaaggtcaagaccaagaagggt tcctcacccctactgattcagataaccaataatgagg ctttgaatccctgtccaaaggttgttttttttccctt ctattgagcttcttgccaccttatcagttttttttat gacagtcaaatgacatgatatatgtgagcatacatgg taatttttaattctatataaatgaatcactaaataaa ttaggaggatatatagtccacctttaagcgtattaca cgtgtcacatgaatgtgtggcgacttaattgtagagg tttaaatgtagcttcctataatagatgtgttcctaaa ctacattttaatcattggacttgtatttttatgttag cacttgctgttgaagaaaagcctatgccaaaagttca gtgaaaccaataatccactgccagctttctgagttaa aaaaaatccctgggttttcacacacaggaacaccctg tgtgaaacactcatttagagcaaaatgcatctgataa ggagttcctgttgtgcctcaactggttaaggacctga cattctccatgagaatgtgagtttgatccccggcccc actcgatgggttaaggatctggtgttgccacaaactg cagctccgattcatctcctagcctagaaacttccaca gcccagaatatgccacagaattcggctgtttaaaaaa aaaaagaaaaaaaaaagaatcataaatgtgttggttt gttcaccaaatacatgataacttgctcttgccaagct cagcttcataaatattaagtcatttaatacagcagcc accttatgaacagatattactatacttcccatttaca gataaggaaaatgccatatttaaccaagagattaaat aactttcccgaggtcttatagcaagtaaatcatggtg caggggtttgaccacacgcagtctatctccagagtct gtgtatttagccactgttttactttcaaatttaaatt tataaaacttctaaattatctgttaaccataatcttt ggaatttttaaaaccacgagttcctataaaatgtttc attgaaagtaagtcacttttccatagcttttgataat acatctgtaggataaagtaagccacagctctcttgca gacttggtacaccctggggcaaagcatcatgcctgtc acgtacatggtggtccttactttgactctcagtgctt ttattgcccaggaattttgtgagatttctagttgttg aggtttgtttaaagaggttatgccggtacttggaaga gctcttttcttgctacctggagccttctcatatttcc tttttgaggagggacatgaattgcctttcaaactcat aaatatattttctagtacacaagtctccatcttcctt agacgcatggctcctggagttctccatcctcctgctc cactttgggtgggctcctctctgggtctgccaccaat ctgccacccagagacatccttgacccacttccagacc ccaccatggcttcactttcttcgctttcctcctttgt ggaaccttctgcttaagaatctgaggaagaaaatttg cacgtgagctaaactggaggtactttcctgcctggtc ttgcacgatagcttggctgagcccatgatgctgggtg gctgttactttccatggacacccgaaggcgttgctcc tttggcttctagttgcatgcagtgttgcttatcccag gctgatctttcttccactgtaggtgacttttaagaat taagggattaatctatatctacaacaacaacaacaaa gaccttttcaagctgaggtagggctttctgtatatgt

ttggagtggttatccagcagactttacttgaaggcag gggtcatatcctcaagtgctcataaacggaccacaga aagatctcataattgggtggagctgggtggggaccgt gtcatgtggccaggaaatgccagatgggaagggagtg gcccttactgagctccagctgaactctgaattttcta gaaaactcagaaatctggatttttcatgtgtaatacc cagatttatagatgtggaaagctaattcttttttttt ttaagggactataggcaatgaactaagatctaggttg tatttggacaaggggtcatcagtttaagctgtgtagt tgagcgctcagctattgggctgagggacccctaaata ctgagacggggaggtccttgctctggggcatcacaag tacactccctggtctcattcaaacacttttcctacaa aattgatcccatttcttcagtgcactgtctgaatgca tttggcccagagccgtgctgaggcatagggaaggggt ccacggtttcatggcatcgttttgtgctgtgtgtccc tgctgtcgtccaggatacctacctctcctcctcctgc atctgaatgtccccccacagactctctgggattctac agcctctggcctgttcctcagacacctcttacctgcc agctttccagattcacattagttagtccaaatctact gccgtcagtgactcacttcatttcttcttctccgagg cagttcagcccggtacagttgttttgtcaacacttca gttgagtctggaagatgtgcatgggttatgcacgaga gcggtccatcattttgagctagaagtcctttctcagc ccagagacaagtcctcatctcctttacttcctgactc ttcttcctctgcatccttccaagatatctctttctcc agccaccacctaaatctcttcttttcccggggttccg tgctcaacccactcttcttcttaaatctgtggctggg tgaacgcatctgctggcaccacttctctgctaaagac tccaaaaatccataggtcctgcccggcctttgcccac ctctctccaacactgtccagctttagatgtagagcta atccccccagagatatcattccctggatgtctaagtc ctttggtatctcactttcagcgtgttcaaaatcctct tacaactgttctttctccttttccatcttgattattg gcaacatgccagcctttcccctacccccagcagtgag ccaagctagaaacaagggcttaatcttcaatctttcc ttctccatccctaaacctaatgagtctccaagccctt cccagtttacaccctaaatgttgctcaaaacatcccc tagttcttccacgtgctctcctctatattgaaaggtc aagaaaggccatcttccctccactgtgaggaaataga tcttgatactgcccctgagctgggcagtcctcgacct gacaaactgtgcagtgtttctaaatctctactggcaa aatgagagtgcctttgacctgtgttgcgatctcagat cacagtggatgtaattgttttataggaatggtgaacg aaaaagaagtaaatccctaatgccaaactcctgatca ttctatgtcatttaatagcctgtcatttatgataaag tttcctctactggcattagcacaatacttctcaggaa aaaaaaatatgatgccagatactgaaaagctcctggg taaacatgaacatgggtaccgataaaatggtgaagcc agtccaatcttagagtgacttcccttcatgctacttc atgctcttttttttttttttttttaagaaaaacccct tttttttttctcacaccagtcacagaggagaccgagg cttagcaaggttaaggtcacatgattagtaagtgctg ggctgaaactcaaaaccatctctgcttgtctcctaac cctgtgcacctctgactattcaacagATCCTGTGTCA GGAGTTGGGATTCTTTGAAGgtaagggccttgaccac cgaattaaggtaatcttgctctgtggcaggccttgtt ttcagtattttaagtacactggctcaggtaatcctca caacagccccaggaggaatgttctattacctccactg tatagatgaggaacttgaggcacagaatggttgccaa ggtcacacagctatattgggggttcatacccagccat ccaactctgtctgtactctctgccactctgcaccccc agctcctgatccacttcctgtttccatccctcgattt ctgctgcactcaggggcccctctccccctcggcctgt gagatctgcttcagtaggcttttctccctgactcctc catccctgtccttacaggcagctgcttctctccggga cacgaggggtccatacggacactctctactggctggg ttgcgcctaactcgtgattcctcctctgtttcagATT CGGAGCCGGGTTGATGTCATCAGACACGTGGTAAAGA ATGGTCTGCTCTGGGATGACTTGTACATAGGATTCCA AACCCGGCTTCAGCGGGATCCTGATATATACCATCAT CTgtaagtccgaaaatgcctgtcgtgtgtgccttagg ctgctgcggaggaggccagggctatataagcagagtc agtgactgactgtgccctgcagtgttgatggccatgg agattccaccgttagagcttttttctttgttaacctt gaaggcaaatctggttaggaagataactttcaaagag tcaccatctggacattcatgcccatgtgcttcaatcc tgtatacaagcagtttagagtacagggaagggaagga cattatgaaagggagagggtgtgtttggatccagcag ctccatcctcagaatttatctgaagacactgcaaaat tactaagaatcactatgacaagaatgaggatggggtg atatggcaaagttgtgatcctggaagaccttcatctc ccatgttgcccaactctgaacatgaatttggtgaact agttggttaaggggatgatcctccaagtttctccctg gttgagctccaaaaaccatgtaagtttctcatagcaa aaccgtataggtccttagggctttagttggaatattt gtgctgaaatgctggaaagccccatttgccatttttg tatttgcaaaataatcatcaagaggggagaatgcatt ctttcatgaccactgaccctctgaaaaggtcaggaat ttagtctgaagtaggcaagcctcctaccccgcttctg ccatgagcttgcacgcacaggcctglcttgacatttc ttctttatagatttctttttgaatatcttgaaattgc tttaaaaatatttaaagaatgtagaattatataaaat aaaaaggaaataaccccacacctcccacaaaaccctg tttcctgcctttctccacccactctccagggtaacac ttggtaacagcatagttgtatcaccccaggcctattt ttgagcatatcagcatttcaagaaatgtattttttct caataaaacatcccttatagttgaggaggggaggtta tcattcctgggttttgttttttttttttttttaatgt aatcctggtacatcggtaatttgcattttttattcat taatatctttggtatttctagtgttgggacacacagg tcaacctcagtttttgggtttttttttttgtcttttt gtctttctagggccacacctgcagcatatggacgttc ccaagctaggagtctaatcagagctgtagccaccagc ctacgtcatagccatagcaacgtcagatccaagccgt gtctgtgacctacaagcacagctcatggcaacaccgg atccttaaccactgaacgaggccaggggatcgaacac acatcctcatggatcctagtcatgttcattaaccact gagtcatgatgggaactccaacttcaactattttaat gtctgtaaaacattccatttggaaaccatttcatttg taaagcaaaatgaaaacattttgttcattttcaacag agttcgtagctgacttctgttctggaaaaaaggaaat ggagcaaatttgagtgagaaagattcaaagataactt ttcttttaaaaaaaattatatcttggaaacttctggg ctattgattctgaagactatttttctatatactgttt tgatagcaaagttcataaatgtgaaaggatcctgcga tgaatcttgggaagcagtcatagcccaatatatcttt gttgcttttaaaatgagatttagtttactaaatattt ttctgatcataaaaataacacagatctaccgcagaaa atttggaaaaaaaaaaacttttaaattcaaaaaacag ttaaaccacaaatgatcccaccatccagagagcaatt tgtactttggtgtctagttcatctttctttttctgtt tacaagcacatataccacaagcattttttcaaaaaat gaaaatgggataatactatacatacgtctgtacacct gcatagttactgaacagtctttgatctaccctgtaag tttctaacttttcattatttgaaatgatgttttggca aagaaatatgtaggtgtgtctcgcacactttcataat

gatttcttaggataaatttcttaggataaattcataa tgatttcttataataatccatactctgccaactgatc ttcagggaagccaactcgccttctcagaaataacata taacccatttacttgccctctcaccaatactaggtcc taatgtttttgtgtacagattctatatttttacatac aagaattccttaaagcaaggcatgtcacagaaaaata gaaggaagacacaattgtcatgtttaaggactgcatt ctgtaccaaaaatgctaagttaaatgaacatctgaaa cagtacagaaacgctatctttcagggaaagctgagta ccaggtactgaacagattttggcaaatacagcaggca tggatgtttccaaaacatgtttttctactttatctct tacagGTTTTGGAATCATTTTCAAATAAAACTCCCCC TCACACCACCTGACTGGAAGTCCTTCCTGATGTGCTC TGGGTAGAGAGGACCTGAGCTGTCCCAGgtaaagcat cctgcaggtctgggagacactcttattctccagccca tcacactgtgtttggcatcagaattaagcaggcacta tgcctatcagaaaacctgacttttgggggaatgaaag aagctaacattacaagaatgtctgtgtttaaaaataa gtcaataagggagttcccatcgtggctcagtggtaac gaaccctactagtatccattgaggacacaggttcaat atctggcctcactcagtcggctaaggatccagtgatg ccgtgagctgcagtgtaggccacagacgtggctcaga tctggtgctgctgtggctatggtgtaggccggccccc tgtaactccaattcgacccctaggctgggaacctaaa aagaccccaaaaaagtcgctatgaatagtgaatacat ccagcccaaagtccacagactctttggtctggttgtg gcaaacatacagccagttaacaaacaagacaaaaatt atcctaggtggtcagtgggggttcagagctgaatcct gaacactggaaggaaaacagcaaccaaatccaaatac tgtatggttttgcttatatgtagaatctaaattcaaa gcaaatgagcaaaccaattgaaacagttatggaagac aagcaggtggttgtcaggggggagataaggggaggca ggaaagacctgggcgagggagattaagaggtaccaac tttcagttgcaaaacaaatgagtcaccagtatgaaat gtgcaatgtgggaaatacaggccataactttataatc tcttttttttttttgtcttttttgccttttctaaggc tgctcccgtggcatatggaggttcccaggctaggagt ccaaacagagctgtagctgccagcctacaccagagcc acagcaacacgggaaccttaacccgctgagcaaggcc agggatcgaacccgagtcctcacagatgccagtaggg ttcattaaccactgagccacgacaggaattccagggt ctgttgtgttcttaaaacacttccaggagagtgagtg gtatgtcataagtaaacaataaatgttaaccacaaca agcttatgaaataaacaggaaagccatatgacctaca atcagtcattgggagaatccacaaaaggttgagcaga ggatcaattccagctcacactccagttttagattctc ccctgccttaaagcatcacagactacataatctgagc tgaagaataaaaattaaaactcaccccagtgcaaaac agaaatgaaaaagtattaaaacgaggttcatactgtt gttcattagcaatatcttttattcacagGGGTGCCCA ACAACATGAAAAAATCAAGAATTTATTGCTGCTACGT CAAAGCTTATACCAGAGATTATGCCTTATAGACATTA GCAATGGATAATTATATGTTGCACTTGTGAAATGTGC ACATATCCTGTTTATGAATCACCACATAGCCAGATTA TCAATATTTTACTTATTTCGTAAAAAATCCACAATTT TCCATAACAGAATCAACGTGTGCAATAGGAACAAGAT TGCTATGGAAAACGAGGGTAACAGGAGGAGATATTAA TCCAAGCATAGAAGAAATAGACAAATGAGGGGCCATA AGGGGAATATAGGG

TABLE-US-00014 TABLE 13 SEQ ID NO. 49 TCTAATGCCTTGTGGAAGCAAATGAGCCACAGAAGCT SEQ ID NO 49 GAAGGAAAAACCACCATTCTTTCTTAATACCTGGAGA GAGGCAACGACAGACTATGAGCAG gcaagtgagagggggctttagctgtcagggaaggcgg agataaacccttgatgggtaggatggccattgaaagg aggggagaaatttgccccagcaggtagccaccaagct tggggacttggagggagggctttcaaacgtattttca taaaaaagacctgtggagctgtcaatgctcagggatt ctctcttaaaatctaacagtattaatctgctaaaaca tttgccttttcatag CATCGAACAAACGACGGAGATCCTGTGTGCCTCTCAC CTGCCGAAGCTGCCAATCTCAAGGAAGGAATCAATTT TGTTCGAAATAAGAGCACTGGCAAGGATTACATCTTA TTTAAGAATAAGAGCCGCCTGAAGGCATGTAAGAACA TGTGCAAGCACCAAGGAGGCCTCTTCATTAAAGACAT TGAGGATCTAAATGGAAG gtactgagaatcctttgctttctccctggcgatcctt tctcccaattaggtttggcaggaaatgtgctcattga gaaattttaaatgatccaatcaacatgctatttcccc cagcacatgcctaactttttcttaagctcctttacgg cagctctctgattttgatttatgaccttgacttaatt tcccatcctctctgaagaactattgtttaaaatgtat tcctagttgataaacagtgaaacttctaaggcacatg tgtgtgtgtgtgtgtgtgtgtgtgtgtttaccagctt ttatattcaaagactcaagcctcttttggatttcctt tcctgctctctcagaagtgtgtgtgtgaggtgagtgc ttgtccaaacactgccctagaacagagagactttccc tgatgaaaacccgaaaaatggcagagctctagctgca cctggcctcaacagcggctcttctgatcatttcttgg aagaacgagtgctggtaccccttttccccagcccctt gattaaacctgcatatcgcttgcctccccatctcagg agcaattctaggagggagggtgggctttcttttcagg attgacaaagctacccagcttgcaaaccagggggatc tggggggggggtttgcacctgatgctcccccactgat aatgaatgagggattgaccccatcttttcaagctttg cttcagcctaacttgactctcgtagtgtttcagccgt ttccatattaggcttgtcttccaccgtgtcgtgtcgt caatcttatttctcaggtcatctgtgggcagtttagt gcgaatggactcagaggtaactggtagctgtccaaga gctccctgctctaactgtatagaagatcaccacccaa gtctggaatcttcttacactggcccacagacttgcat cactgcatacttagcttcagggcccagctcccaggtt aagtgctgtcatacctgtagcttgcttggctctgcag atagggttgctagattaggcaaatagagggtgcccag tcaaatttgcatttcagataaacaacgaatatatttt tagttagatatgtttcaggcactgcatgggacatact tttggtaggcagcctactctggaagaacctcttggtt gtttgctgacagactgcttttgagtcccttgcatctt ctgggtggtttcaagttagggagacctcagccatagg ttgttctgtcaccaagaagcttctgcaagcacgtgca ggccttgaggtcttccgacttgtggcccggggactct gctttttctctgtccttttttctccttagtgggccat gtcctgtggtgttgtcttagccagttgtttaagggag tgttgcagctttatgattaagagcatggtctttcctt gcaaactgcttggtttagaagcctggctccaccactt agcggctctgtgacctcggacacatttcttagccttt ctgggcctcgctcttcttcctcataaagtgaaaatga aagtagacaaagccttctctgtctggctactgagagg atggagtgatttcatacacataaagcacttaaaataa tgtctggcatatgatacatgctcaataaatgtcactt acatttgctattattattactctgccatgatcttgtg tagcttaagaacagaggtctttacaggaattcaggct gttcttgaatctggcttgctcagcttaatatggtaat tgctttgccacagactggtcttcctctccttcaccca aagccttagggggtgaacgatcccagtttcaacctat tctgttggcaggctaacatggagatggcaccatctta gctctgctgcaggtggggagccagattcacccagctt tgctcccagatacagctccccaagcatttatatgctg aaactccatcccaagagcagtctacatggtacactcc cccatccatctctccaaatttggctgcttctacttag gctctctgtgcagcaattcacctgaaatatctcttcc acgatacagtcaagggcagtgacctacctgttccacc ttcccttcctcagccatttttcttctttgtacataat caagatcaggaactctcataagctgtggtcctcattt tgtcaatctaatttcacagcctcttggcacatgaagc tgtcctctctctcctttctgcctactgcccatgagca gttgtgacactgccacatttctcctttaacgacccag cctgctgaatagctgcatttggaatgttttcaatttt tgttaatttatttatttcatctttttttttttttttt tttttttttttttttagggccgcacccatgggatatg gaggttcccaggctagggatccaatgggagctgtagc tgctggcctacaccacagccacagcaatgcacaattc gagccaatctttgacctacaccagagctcacggcaac actggattcttaacccactgattgaggccagggatca aactctcgtcctcatagatacgagtcagattcgttaa cctctgagccatgatagttgttagttactcattgatg agaaaggaagtgtcacaaaatatcctccataagtcga agtttgaatatgttttctgccttgttactagaaaaga gcattaaaaattcttgattggaatgaagcttggaaaa aatcagcatagtttactgatatataagtgaaaataga ccttgttagtttaaaccatctgatatttctggtggaa gacatatttgtctgtaaaaaaaaaaaatcttgaacct gtttaaaaaaaaaacttgactggaaacactaccaaaa tatgggagttcctactgggacacagcagaaatgaatc taactagtatccatgaggacacaggtttgatgcctgg cctcgctaagtgggttaaggatatggtgttgctgcag ctccaattcaacccctatcctgggaacccccatatgc caccctaaaaagcaaaaagaaaggtgctgccctaaaa agcaaaaagaaagaaagaaagacagccagacagacta ccaaatatggagaggaaatggaacttttaggccctat ctccaactatcacatccctatcaccgtctggtaagaa atggaaaaaatattactaagcctcctttgttgctaca attaatctgattctcattctgaagcagtgttgccaga gttaacaaataaaaatgcaaagctgggtagttaaatt tgaattacagataaacaaattttcagtatatgttcaa tatcgtgtaagacgttttaaaataattttttatttat ctgaaatttatatttttcctgtattttatctggcaac catgatcagaaatctttaaacaatcaggaagtctttt ttcttagacaaatgaaaatttgagttgatcttaggtt tagtacactatactaggggccaagggttatagtgtga ctattaaatcacagataatctttattactacattatt tccttatactggccccacttggatcttacccagctta gctttgtatgagagtcatccttaaagatgactttatt ctttaaaaaaaaaaacaaattttaagggctgcaccca tagcatatagaagttcctaggctagcggtcaaattag agctgcagctgccagcctatgccacagccacagcaat gccagatctgagctgcatctgtgacctacactgcagc ttgcagcaatgctggatccttaacccattgaacaatg ccagggattgaacacacatcctcatggatactgctca ggttcctaacctgctgagccacagttggaactccaaa gcagactttattctgatggctctgctgatctctaaca cgttattttgtgccatggtgtttatcttcactttact caagtcagggaaacacgaagagtctcatacaggataa

acccaaggagaaatgtgcaaagtcacatacaaatcaa actgacaaaaatcaaatacaaggaaaaaatatcttca ctttcaaaatcacctactgatgatgagtttatatttc cttggatatttgaatattagctatttttttcctttca tgagttttgtgttcaaccaactacagtcgtttacttt gatcacagaataatgcatttaagccttaaatagatta atatttattttcaccatttcataaacctaagtacaat ttccatccag GTCTGTTAAATGCACAAAACACAACTGGAAGTTAGAT GTAAGCAGCATGAAGTATATCAATCCTCCTGGAAGCT TCTGTCAAGACGAACTGG gtaaataccatcaatactgatcaatgttttctgctgt tactgtcattggggtccctcttgtcaacttgtttcca atctcattagaagccttggatgcattctgattttaaa ctgaggtattttaaaagtaaccatcactgaaaattct aggcaagttttctctaaaaaatcccttcattcattca tttgttcagtaagtatttgatgagaccttaccatgtg taaacattgcactaggtattaagaaatacaaagatgg ataagatagagtcggcgtaaatgagatgatataatga gacgttataatgaaactcacaattccagttgggaaat aaagtccttcaaattccatgactctttctggcacacg ttagaggctacagcttctgtgtgattctcatgctggc tccacttccactttttccttcttcctactcaagaaag cctatagaaatatgagtaagaagggcttaatcatagg aataaatttgtctctgttctaagtgattaaaaatgtc tttatcagtataaaaagttacttgggaagattcttaa aactgcttttacacactgttctagaatgactgttata taaataaaaaagtagatttgatctaacacaattaaat gacctttggaaatattgactaattctcaccttgcccc tcaaagggatgcctgaaccatttccttcttttgccag aaagcccccaccctttgtctgttgacctagcctagga aatcttcagatcacgttgttagcacgaactggttaca tgtgctgtacaaatactatttaattcatctgattaaa aaaaaagagataagaagcaaaagtttgactatcttaa actgtttgcgtaggtgagaggacaattgaccatctac tttatgagtatgtaacccagaaacttaaagctcctta agggagctaagtcttttggataagacctatagtgaga ccttttagcaaaatggttaagactgaatggagctcac tagcgtgggttcatatcctgatgctcaaacacgcaat taaatgactttaggtgggttagtctctgttccttagt ttcctcaatgggagataatattggtagtagcgatttt actgggttgttgaaagaacatctgttaaatgttcaga acgtgttacgacagagtacagagtaatgatttgcttg tatatgtatgactcaaatagtctgccatatgccttgt gactgggtcctgtggagcaggaaggagggatttccca cccagcagaaagttgggtaaactggaaaatagactga ggccaggaaatgatgcaaagcgttgatgttcactgcc acggcaggtgaagggcagggccagagttgtcagtagg gtcaggggaggactggaaataaccaagacccactgca cttttcagcctttgctccagtaaggtaatgttgtgag agtagaaaattttgttaacagaacccacttttcagta cagtgctaccaaactgtagtgatttcataccacatcc caagaaagaaaaagatggctcaatcccatgtgagctg agattatttggttttattgttaaataaatagcattgt gtggtcatcattaaaaaaggtagatgttaggaaagta gaaggaagaagactctcacctacattttcatcactgt tttggtatctgccagttgtcaccttggtccccttccc cgcctctcccctgcctcctcttcctccttctcctttt tttggaatacaattcaggtaccataaaatttaccctt ttagagtgtttgactcaatggtttttagtattttcac atgttgtgctattactatcactatataattccaggtc attcacatcaccccccaaagaaaccttctaactatta gcagtccattcccttcttccctcagcccctggcaacc actaatctacttactgtctccatggatgttcctatat tgaatcaagctagcataaaccccacttgctcatggtc ataattcttttttatagtgctaaattacatttgctaa tattcaattaaggatttctatgtccatattcataagg aatattggtgtgtagttttctctttgtgtgatatctt tgtctggttgggggatcagagtaataattactgctct catagaatgaattgagaagtgttccctccttttctat ttattggaagagtttgtgaagtatattggtattgatt cttctttaaacatttggtcagattcaccagtgaagcc atctgggccatggctaatctttgtgaaaagttttttg attactaattaaatctctttaatttgttatgggtctg ctcctcagacgttctagttcttcttgagtcagttttg ttcatttgtttcttcctaggactttctccctttcatt tggattatttagattgatagtaatatcccccttttaa ttcctggctgtagtaatttgggtcttttctctttttt cttggtcagtttagctaaaggtttgtaattgtattaa tcttttcaaataactaacttttttgttttgtttgttt tttgttttttgttttttgttttttgtttttttttgct ttttaaggctgcacctgaggcatatggaagttctcag gctagaggtctaatcggagctacagctgctggcctat accacaaccatagcaatgccagattcaagctgcatct gcgacctacaccacaactcggccagggatcacacccg caacctcatggttcctagtcggatttgttaaccactg tgccacgacgggaactcccgcccattttttttaacac ctcatactttaacataaagatgggcttcacatggact gatagctcaaatgaggaaggtaagactatgaaagtaa tggaagaaatgtagactatttttgtgacctagagatt actgatacttcttgacttttcaaacaatacttcaaaa gtacagcccaaagggaaaaaagaaagaaaaaagaaac acacatatacacaaacctagtgaataagatatcatcg atacactacagatttctatgaactggaagaccccatg gacaaagttaaagaacatatgatagtttgagtgatta ttttgcaatatttacaaccaatgagggaatattatcc agcttataggaggaagtaatgcaaatcgacaagaaaa agataggaaacccaatataaaaattaagaaaatacaa aaattaagaaaggatatgaactagcattttacaaaag aaaaatctccaaaagtcaatcagcacatgaaaatatg ctcaaacctattaattattagaaaactacagactgaa gcaatgaggtgctttactttacatctttttgactgat aaaaagttagaaacaaaggtgatatcaaatgtcaggg ataaaaggatatagaaatcgtcatgcctgtggtggga gtatggccggtgcagtcatgtgggaaggtaatctgac agtggttaggcagagcaggtttatgaatacactgtgg cccatcaatcccacgcctgtttatgtaccaaagaaat cctgttgtggcagaatctatgggtccacccctgggag catgaattaataaaatgtggcaccagggtgtgtgaaa ctccagctagagatgagatgtccacatggcaacatga atgcatcttagaaacatagatttgagtgaaaaagagt aagaaacagccgggaaacccaataccatttataaaaa ttaaagatgcacacatacaatgtagtaaatattttgc atgaactttcaaatggttgcctacagggggggagagt aaagaagagtagaaaacaaagataaagggagtaagta agtagctctgcctggactgaatataatgtgtcatgaa ctgagaaatatggttaacataatcctctaacttgagg tcctaaatgaatgaatgagtccactattcatttaccc attctttaatgtgtattgcattataatccattttttt agaaccaacgaattttgttcccataactactaatcag cctgccttttctccctcattcccttatcagctcaggg gcattcctagtttttcaaacgttcctcatttgaacca aaaatagcatcattgtttaaattatacttgttttcaa atacgatgcttatatattccaagtgtgtttgcccatt ttcttaggtggtagaaatttttcattctacttttcta

tctactcagattttcccgttggaattatttccattgc tattaaacttagaagtcccccctgtgatatgccattt ttttcatactttttaagcacttggttgcttttctttg tgtctttaagcacctagaatacttataaccattgcac agcactgtgtatcaggcagcccttcctcttccactaa tttatggtccttctcttagactatattaaactgttat ttaattaggatcctctcttcgtccttatgatttaatt attatagttttctaatatgtttttattataattcctc ttcattattcctccctattaaaaattttaatgaattc catttgtttgttcttctagttaaatattaagtcataa tccaaataacttagatgtcattagtttatgtggtcaa agtaaggataccacatctttatagatgcaggcagttg gcagatgtcatgattttcttcagtgcataaatgcaat ttatctttgagcaaggggcataaaaacttttatggta ttggctttgaaataatagttaagaactgcagactcag tttttcctgcttttcttgaaaaagaacacttctaaag aaggaaaatccttaagcatggatatcgatgtaatttt ctgaaagtctcctgtaattccttgggatttttgttgt tgtttgttggtcggtttttttgggtttttgtttgttt gttttgttttgttttgttttgcttttagggctgcacc tgtggcatatggaagttcccaggctaggggtccaact ggagctacagctgccagcctactccacagccacagca acatgggatcctagctgcatctgtgacctaaccacag ctcttggtaatgccagattgttaacccactgagcaat gccagagatcgaatctgcctcctcatggacactagtc agattagtttctgctgagccacaatgggaattcccaa ttccttgtatttttgaactggttatgtgctagcatat aattttgtttcttgaatctttgtgggttttttttttt ttttttttttgtctcttgtctttttaaggctgcaccc acagcatatggaggttcccaggctagaggtcaaattg gagctacagctgccagcctacacaacaactgcagcaa agtggggcccaacttatatgacagttcgtggcaatgc cggattcctaacccactgagcagggccagggatcgaa cctgagtttccagtcagtttcgttaaccactgagcca tgatagtaactcctgtttgttcagtcttgaacctcct ttttaattctttattccttgagggtgaaataattgcc ataataatactatcatttattacatgccttctctgtg ctaggcatagtgacactttaggatttattatatcact taatccctacaacaactctgcaaagtatgtatcataa tcctatttgacagatcaggaaattgcagcccaggatg cagataatatgcatccatcacaagtgactagatatag tccctctgctattcagcagggtctcattgcctttcca ttccaaatgcaatagtttgcatctattgtatatgtgt tttggggtttttttgtctttttttttttttttgtctt ttctggggcctcacccttggcataggtaggttcccag gctaggggtcaaattgaagctgcagctgccagcctac accacagccacagcaactcgggatctgagcctcatct gcaacctacaccaaagctcacggcaacaccggatcct taacccactgagtgaggccagagatcaaaccggcaac ctcatggttcctagtcggattcattaaccactgagcc acgatgggaactccctaaatgcaatagtttgctctat taaccccaaactcccagtccatcccactccctcctcc tccctcttggcaaccacaagtctgttctccatgtcca tgattttcttttctggggaaagtttcatttgtgccat ttttcattttacgggtaatttttacttcagtttcttc cactagcagttgtcttaaagtgagtataattaatatt catttggaaaatgtaagcaaaacattttttaaagggc catgcccacagcatatgaaagtttctgggccaggggt tgaatccaggctccaagttgcagctgtgccctacact gcagctgggcaatgctggatcctttaacccactgtgc ccggctagggatcaaacctgcatttccacagctaccc gagccattgcagttggattcttaacccactgcactac agtgggaactcccacaaaacattttttaatgtccttt gaataaagtaggaaagtgctcgtctttgagggcaggg cggcaatgccatttccacaaggtgctttggcttggga cctcatctgctgtcatttagtaatgaataaaattgct gacagtaataggattaactgtgtgtggagatagccag ggttagagataaaaacactggagaagtcaaataagtt gctcgaggtcctctagctaataagctattaagtggga gagtgagggctagaaacaggccatctgtctcccaagc acatgtccattagtggtttgctgatagccttccagaa caacagagaggactctcaaacatggtcttgcctccct ccaattgatcccctccatgtgcctcacagcgggtctt tctaaaattaagttctgattttaattctcccttgcta tagcacttaggtatggctttcagccgtgcaataaaaa gcaggcaagagtggctcaatcatataggaggttgttt ttcttagatcccaagcaggtaatcctgggcattatgg ttgttctgcgtttatcaaggagccaaattctctatca cctcctgttctatcctcctcagtatctggctctattc ttcagcatctcaagatggcttgtgctcctccaagcat ggcagtcaaattccacacaagagggggaaaatgaagg gcagacagtgctggtctcctgagctgtccctctttgt cggggaaataaatgtattccttcaagtcccgtgagac ttctgaagtagacgtctgcttacgtctcacccaccag aactatgtaaactgcacatagtgctaggtctacatag ccactcataactgccagggggtgggaaatctttaaat aggtgtaccaccacacaattaggatgctaatagtaag ggagaaggagagaataggttttgcgcaagccaccagc atgcctgccacaattgcttaaaattcttcattgaccc ctcattgccacaggatgaaatccaaacgccttcttag ttgggaatctgacctacctgtctctcccacctggttc agacaccattctccttggtcataaaattccagtcatt tgtgaacatccagctcccccatgcctccatgcctttg cacatgctgttcttttatcttttatgttgtcctttta tcttttatccaaaagagatatcccatcatcacatctc ttcagcccccaaatactttgtctttcaagttcagctg gaggattacctcctatttgaaatcagctttgtctctt acaaccaaacaaggttttccttccgagacactcccac agcaccttgaactcatctctatcaatcattcatttga tgtaatgaagttgttggtggtatgcctgtgtctctga cacatctgcgatctcatgagttccttaagtggaatgt gaatagcgggatgaacagtattggtcttcagccctca tctctgcagatgttgcttgacccaaatgagcgttgcc ttttattttgattttgctttgatttgtctactccatg tacttgagccatgcatttctgtcttagcgatgctttt taaaagtcattttttggttgattatccagatttgtcc acctttgcttctag TTGTAGAAAAGGATGAAGAAAATGGAGTTTTGCTTCT AGAACTAAATCCTCCTAACCCGTGGGATTCAGAACCC AGATCTCCTGAAGATTTGGCATTTGGGGAAGTGCAG gtaaggaaatgttaaattgcaatattcttaaaaacac aaataaagctaacatatcaatttatatatatatatat atatatatttttttttttttttacatcttatattacc ttgagtattcttggaagtggctagttaggacatataa taaagttattctgaagtctttttttttctttttccat ggtgagcagtggcttgatgtggatctcagctcccaga cgaggcactgaacctgagccgcagtggtgaaagcacc aagttctagccactagaccaccagggaactccctatt ctaaattcttgagcacattatttaggaacctcaggaa cttggcaggattacaggaaatatatctagatttaaaa aaaaatcttttaacagaggtcccaaaggagagtcatg cacagctatgggaggaagttcagaaactgcccttgct accagatcactgtcagataaaatggccagctacatgt ttctgcacattgccctaagatctttacaaacttttct gtgcatttttccacttttaaaagaaaatttcggggtt cctgttgttgctcagtggttaacgaacccaactagta

tccatggggacaggggttcgagccctggcctcactca gtgggttaagaatctggcattgctgtggctgtggcgt aggctggcggctacagctcagattggacccctagcct gagaacctccatatgccgcaggtatggccctaaaaaa aaaaaaaaagagagagagagaatttcctccagaaaaa acactttggtagtttgggagaagtaaacaaccaaaaa ttaatttttctggagtattcgggaagcttgtaaaaat gggctcttacttttttgaggagacaaatgggaaccta cccagaagaggcacaatcacctgcatttgatttcttg acctctccctaccttctttgctggctttccacatttg gatttctgtgaccttatctctgctccttggtgttttc atttttcctgtggacgtgccagactatgggaagggag taaggcgttgatttagaatcctgtagtctctgcctgt ctctagtcattgttttcacccttctcaaaggaccttg acatcctgagtgagtccgcaagtaatttaggggagaa gccttagaagccagtgcagccaggctacatgactgtg tccacccactggaaccagtcatttttatacctattca cagcccccctaccatttaaatccccagaggtctgcca taacatctgtaactccctttcctggtaaattgtgttc taaaagactggtaacaaaagatattctgtggtacaga gcataattaaatacctgggagctgatttgagtggggt aaatcaactggtttgacccctaaaacccaccatgagc atttctgttctaataaagtaatgcccgtgctgggaat tgtgttctacggaaatgctcctgctgtgtctttcttg agtcctgtgtcattgaacatgcttaggagcaaaggtc ccccatgtggcttgtctgctaaccagcccagttcctt gttctggctggtaatgatccgatcatctgaatctcac tgtcttccaacag ATCACGTACCTTACTCACGCCTGCATGGACCTCAAGC TGGGGGACAAGAGAATGGTGTTCGACCCTTGGTTAAT CGGTCCTGCTTTTGCGCGAGGATGGTGGTTACTACAC GAGCCTCCATCTGATTGGCTGGAGAGGCTGAGCCGCG CAGACTTAATTTACATCAGTCACATGCACTCAGACCA CCTGAG

[0083]SEQ ID NO. 49 represents contiguous genomic sequences containing Intronic sequence 5' to Exon 4, Exon 4, Intron 4, Exon 5, Intron 5, Exon 6, Intron 6, Exon 7, Intron 7 and Exon 8 (Table 13). Further, nucleotide sequences that contain at least 1750, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400, 3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10000, 11000, 12000, 13000, 14000, 15000, 16000, 17000, 18000, 19000, or 20000 contiguous nucleotides of SEQ ID NO. 49 are provided, as well as nucleotide sequences at least 80, 85, 90, 95, 98, or 99% homologous to SEQ ID NO. 49.

TABLE-US-00015 TABLE 14 SEQ ID NO. 50 AGGAATGGAAAGCCCAATTCATTAAAACAGAAAGGAA SEQ ID NO. 50 GAAACTCCTGAACTACAAGGCTCGGCTGGTGAAGGAC CTACAACCCAGAATTTACTGCCCCTTTCCTGGGTATT TCGTGGAATCCCACCCAGCAGACAAGTATGGCTGGAT ATTTTATATAACGTGTTTACGCATAAGTTAATATATG CTGAATGAGTGATTTAGCTGTGAAACAACATGAAATG AGAAAGAATGATTAGTAGGGGTCTGGAGCTTATTTTA ACAAGCAGCCTGAAAACAGAGAGTATGAATAAAAAAA ATTAAATAC gtatggctggatattttatataacgtgtttacgcata agttaatatatgctgaatgagtgatttagctgtgaaa caacatgaaatgagaaagaatgattagtaggggtctg gagcttattttaacaagcagcctgaaaacagagagta tgaataaaaaaaattaaatacaagagtgtgctattac caattatgtataatagtcttgtacatctaacttcaat tccaatcactatatgcttatactaaaaaacgaagtat agagtcaaccttctttgactaacagctcttccctagt cagggacattagctcaagtatagtctttatttttcct ggggtaagaaaagaaggattgggaagtaggaatgcaa agaaataaaaaataattctgtcattgttcaaataaga atgtcatctgaaaataaactgccttacatgggaatgc tcttatttgtcag GTATATTAAGGAAACAAACATCAAAAATGACCCAAAT GAACTCAACAATCTTATCAAGAAGAATTCTGAGGTGG TAACCTGGACCCCAAGACCTGGAGCCACTCTTGATCT GGGTAGGATGCTAAAGGACCCAACAGACAG gtttgacttgaatatttacagggaacaaaaatgattt ctgaattttttcatgtttatgagaaaataaagggcat acctatggcctcttggcaggtccctgtttgtaggaat attaagtttttcttgactagcatcctgagcttgtcat gcattaagatctacacaccaccctttaaagtgggagt cttactgtataaaataaactattaaataagtatcttt caactctggggtggggggggagactgagttttttcac agtcctatataataattttcttatcctataaaataat taggagttcccgtagtggctcagcaatagcaaacccg actagtatcgatgaggatgcgggttcgattcctggcc cccctcagtgggttaaggatctggcattgccgtgagc tgtggtgtaggtggcagacacggctcagatcccacgt tactgtggctgtggcataggccagcagctccagctct gattagacccttagcctgggaacttccatatgctgtg ggtgtggccttgaaaaaaaataaataaataagataat tactcaaatgttttccttgtctcagaaccttacttca ggataaagagtgagaaagttttttttatgaagggcca ttattacagctcaaaaataagttgtcttcagcaagta gaaagcaataagcctgagagttagtgttcctatcagt gtaaatattacctcctcgccaatccccagacagtcca tttgaacaattaacggtgccctgggagtacagttcag aaacattaatgtggatgttccagacctgtatttttat aagtaccttgagccggatggaaccatcattcctcacc attatttagaagtggactgtgactctgttggagatca gggcacacggttaccaaaagcacacccttctcctggc cttacctttgcaaagctggggtctgggacacagtcag ctgattatacccttttactaacttcccacagctcaaa tctggtcaattctccttcacaaatctcttaaaaatcc atcactcacctccagcctcttctgctgtggccttgat tcagcctctcacaatttttttttaaccagaattctgg cagtggcccctgacttgcctctgtgctcccagccccg ctgtcctctgatccatcctccatgccagcctttttca atctgctggtcacgattcattgatgggttaggaaatc aatggcatcacaactagcatttagaaaaaggaaatag gcgttcccgccgtggcacagcagaaataaatccgact aggaaccataaggttgcgggttcaacccctggccttg ttcagtgggttaaggatccggcattgccgtgggctgt tttgtaagtcacagacatggctctgatccggcattgc tgtggctctggcgtaggcctgcagcatcagctccaat tagacccctatcctgggagcctccatatgctgcaagt gcagccctaaaaaaaataaaaaaataaaaaaaaataa ataaaagaagtagacaaattgtatagaacaaccctga gtatgttgcctgagcacatataacaagggtaagtatt atttcaggaaactctggtttcacagatactcttggca tatggacccctagagtcctgatgtaaaatatattctt cctgggatcttaggcaagaagtttgaaagctccaact ctgcactgctgccaaagaaatgatttttaagtgcaaa actcttcccgttcccttccctgtataaaattccatag gatctctccagtgcctctaggataaaggcagttttca ttctctagttcaaggtgagagaagattttaattattt cacgttttagtggggaattcaagagtctggcacctga catttgctgaactctctccattatccctctctagttc cccagacgcatcctatggtagaaattcgcaaactaga gtgagcgtcagagtaacccaaggaaactgggtaaatg cagctccctgggctctaccccctgagattctgattca gtagatctgaagcagagccctggaatatgcatatgca tcattgtgtcacaccaagcattctgggtaatgagagt tgatgttaggttctcagtagtaagacaagtatagaga ttccgggggactgagtgctcagctctgccttggggag gagggagagggctaaagagaacaggagatggggacag ggaatgctcaacctccaatcttaggcatttgagctat gtcttaggggtcaggaggaggttaccaatatagtgat taagagattgaggttccagtcagagggatatgctgga gaaggggggtgaaaataatgtcataggtttggtgagt gcagatactttgagttttttaatatttttattgaaat atagttgatttacaatgctcttagtgagtacaattac tttgaataagtgcatagatgtatgccattcttccaga aatgatttattgagctcctttgggcatcatgctaagt acaggggaaacagctgtgaagaggtccttcccttatg aagtcattcatccccttcagtaaatgaaggtaaagga aaaggatgagacagggacgccgtgttggaccagggtc agaaaggccttataagaccttgcctggagggcaagga acttgcctgtgagtaaggagagcttgagaaagcgata aagcaaagaaggaacattactgcattgtgttttagaa aaaccatgtcctggggaagaactcctagagtcagggg ggccagttgggagactgtgcttttttccaggaggaga taagtgaggctgctggctgagatggagcaaggattta gagaagcagatatgagattcatttagaagttagacat tttaggatctgacacataatttatcaccaaaaccagt gcatctctggctttgggccaccagttttggagaagtg gaatgtagggacctaccattacctgccaatctttact acacagatgcctatttccctcctcatatttcctttct ccagatcacgtcctattctattgccaggactcaagat tccaccttgcatgcagtgatccatcttcacactggat ggacagctctagggatgtcagagcacactcttgtcca tactgctgactgggtctcctgtcagcccatctgtcta tcagctgtggtattattagtataataagagggctgta tatgagagacacaaaattctaggtgtagctcaaagat aggctagagttattcctatgtacaacaaatatttatg ggaccccttctgactgtcatggttgctgctttcatca tacttgtagtctaatggaggtgggggcagggcaggaa taagcggatgtccacaaaatcagtaagaccacttata ttcaacattttcataatttagttatttgagcccaaag ggtccacatccgtggtattccaacttttttttccccg gacatggatctttatctttttttttttttcttttttg cggccagacctgcggcatatggaagttcccaggccag gggttgaatgggagttgcagctgcctggtctacacca

cagccacagcaaggtgggatctgagctgcatctgtga catacaccgcagctgaggtaacaccagattctgaacc cactgaatgaggccagggatggaacccgtctccttat gaacactatgtcatgttcttcaccctctgagccacaa cgggaactccagacttcgtctttaaatgtattctgac ttggagagctatcacactaagcaattaacaggagctg acctggtttaggctggggtggggccctactcctcaat gttccctgaggcacatctgtgggacccctgggcatca tctatctgagcagccttagagctgctcatccagttga ctgttgatgtagaagtgcaaacttctgccttccttat ttgttgctttcttttttcattgttctctcccctttgt gtctttaag CAAGGGCATCGTAGAGCCTCCAGAAGGGACTAAGATT TACAAGGATTCCTGGGATTTTGGCCCATATTTGAATA TCTTGAATGCTGCTATAGGAGATGAAATATTTCGTCA CTCATCCTGGATAAAAGAATACTTCACTTGGGCTGGA TTTAAGGATTATAACCTGGTGGTCAGG gtatgctatgaagttattatttgtttttgttttcttg tattacagagctatatgaaaacctcttagtattccag ttggtttctcaaaagcattcattgagccttactgact gtcagacggagggcgtattggactatgtgctgaaaca atcctttgttgaaaatgtagggaatgttgaaaatgta gggaatgaaatgtagatccagctctgtttctcttttg gaggattctttttcctccatcaccgtgtcttggttct tgtttgttttgggtttttgtgggtgttgtattgtgtt gtgttggttatggcagtgacagctatttaaactgtga aacgggggagttcccgtcgtggcgcagtggttaacga atccgactgggaaccatgaggttgcgggttcggtccc tgcccttgctcagtgggttaacgatccggcgttgccg tgagctgtggtgtaggttgcagacacggctcggatcc cgcgttgctgtggctctagcgtaggccagcggctaca gctccgattggacccctagcctgggaacctccatatg ccgcaggagcggcccaaagaaatagcaaaaagacaaa ataaataaataaataaataagtaagtaaaataaactg tgaaacggggagttcccttcatggctcagcagttaac aaacccagctaggatccatgaggatgtaggttcgatc cctggccttgctcagtgggttaagaatccagcgttgc tgtgagctgtgatgtaggtcgcagatgcagcccagat cctgcattgctgtggctgtggcgtaggctggcagctg aagctccgattcaacccctagcctgggaacatccata tgctgcaggtgtggccttaagaggcaaaaaaataaaa aaataaaaaataaataaattgtgggacagacaggtgg ctccactgcagagctggtgtcctgtagcagcctggaa gcaggtaaggtaaggactgcagctgggtaaggactga attgcaccaactgggaagtaagcctagatctagaact taagttagccctgacatagacacacagagctcaccag ctaagtggttcagcttataagctggtcactgaaactg aggatgtccacaaaagcaaaataagtagcaacaggca gcgggatgcaagagaaagaggaggcctaaaatggtct gggaatccctgccatacctatattttatcctacttat atttagtgcctgaatgtgtgcctggagagcaaagttt agggaaagcatcgggaaatgcacagtattcataccct taggaacaaagatcagttacctccagggtaaagacta tttccaagtttaaatttcaacccctgaacattagtac tgggtaccaggcaacacttgccatcctcaaaatcaat gaatcctaaaattcaacctgggggtcagtgacagtct gtgacaaagtttttgctggtcagtaacgaaataagta tgagcaccatctgagtatggtcaccaagatgtcaact ctctttcctttggacgaattgtcaltattccaagatt aggtcctttctatttttgaggtgtgaaaacatctttc ctttcataaaataaaaggatagtaggtggaagaattt tttttgttttttggtctttttgctatttctttgggcc gcttctgcagcatatggaggttcccaggccaggggtc gaatcggagctttagccaccggcccacgccagagcca cagcaacacgggatccaagccgcatctgcagcctaca ccacagctcacggcaatgccggatcgttaacccactg agcaagggcagggaccgaacccgcaacctcatggttc ctagtcggattcgttaaccactgcgccacgacgggaa ctcctaatgatactcttttatatttagctactatgtg atgatgagaaacagtccacattttattattttttagc caatttgatatctcattactaagataatgataatttt ctctataaattttatttaagttagtgttatgaagtgg ttttgctagtgtagaaggctaggatttgaattcagtt caagaaagaagagagggagggagggagagggatgggt agagggatggggcagtgggagagagcaaagaggagag acagtttttgtattaattctgcttcattgctatcatt taagggcacttgggtcttgcacattctagaattttct aaggaccttgaccgccagattgatatgcttcttccct ttaccatgttgtcatttgaacag ATGATTGAGACAGATGAGGACTTCAGCCCTTTGCCTG GAGGATATGACTATTTGGTTGACTTTCTGGATTTATC CTTTCCAAAAGAAAGACCAAGCCGGGAACATCCATAT GAGGAA gtaagcaggaataccagtggaagtgcccctttcttcc ttccttcctaaataaacttttttattttggaacaact ttagagttacagaaaagttgcaaagatattatagaca gtagtgtttatatatatatataaatttttttttgctt tttatgaccacacctgtggcatatggaggttcccagt ctaggggttgaattggagctacagctgccagtctgtg ccataaccacagcaatgcaggatctgggccacgtctg tgacctacaccaaagctcacagctggattcttaaccc actgagcaaggccagggattgaacctgcatcctcgtg gttcctagttggattcgtttccgctttgccgcaatgg gaactccaaattattgttaatatcttactttactggg gtacatttgttacaaccaatactctgatactgaaaca ttactgttaactccgtacttgcttctttttgagtcat ttgcaaagactggcttcttgacctgcttccttccaaa cagctggcctgcctatgctgttctcagacctgcaagc actgatctctgccccccttgccttctctccagtggtg tctccttccccaaacaaacccagtgtggctctggaaa gggagttaagtcaacataaaccaacacatattttgtt gagctccaattttgagcaaatccctcaccacggcaga caggcatgatgttaagaactagggctttggacacaag gtcaagaccaagaagggttcctcacccctactgattc agataaccaataatgaggctttgaatccctgtccaaa ggttgttttttttcccttctattgagcttcttgccac cttatcagttttttttatgacagtcaaatgacatgat atatgtgagcatacatggtaatttttaattctatata aatgaatcactaaataaattaggaggatatatagtcc acctttaagcgtattacacgtgtcacatgaatgtgtg gcgacttaattgtagaggtttaaatgtagcttcctat aatagatgtgttcctaaactacattttaatcattgga cttgtatttttatgttagcacttgctgttgaagaaaa gcctatgccaaaagttcagtgaaaccaataatccact gccagctttctgagttaaaaaaaatccctgggttttc acacacaggaacaccctgtgtgaaacactcatttaga gcaaaatgcatctgataaggagttcctgttgtgcctc aactggttaaggacctgacattctccatgagaatgtg agtttgatccccggccccactcgatgggttaaggatc tggtgttgccacaaactgcagctccgattcatctcct agcctagaaacttccacagcccagaatatgccacaga attcggctgtttaaaaaaaaaaagaaaaaaaaaagaa tcataaatgtgttggtttgttcaccaaatacatgata acttgctcttgccaagctcagcttcataaatattaag tcatttaatacagcagccaccttatgaacagatatta

ctatacttcccatttacagataaggaaaatgccatat ttaaccaagagattaaataactttcccgaggtcttat agcaagtaaatcatggtgcaggggtttgaccacacgc agtctatctccagagtctgtgtatttagccactgttt tactttcaaatttaaatttataaaacttctaaattat ctgttaaccataatctttggaatttttaaaaccacga gttcctataaaatgtttcattgaaagtaagtcacttt tccatagcttttgataatacatctgtaggataaagta agccacagctctcttgcagacttggtacaccctgggg caaagcatcatgcctgtcacgtacatggtggtcctta ctttgactctcagtgcttttattgcccaggaattttg tgagatttctagttgttgaggtttgtttaaagaggtt atgccggtacttggaagagctcttttcttgctacctg gagccttctcatatttcctttttgaggagggacatga attgcctttcaaactcataaatatattttctagtaca caagtctccatcttccttagacgcatggctcctggag ttctccatcctcctgctccactttgggtgggctcctc tctgggtctgccaccaatctgccacccagagacatcc ttgacccacttccagaccccaccatggcttcactttc ttcgctttcctcctttgtggaaccttctgcttaagaa tctgaggaagaaaatttgcacgtgagctaaactggag gtactttcctgcctggtcttgcacgatagcttggctg agcccatgatgctgggtggctgttactttccatggac acccgaaggcgttgctcctttggcttctagttgcatg cagtgttgcttatcccaggctgatctttcttccactg taggtgacttttaagaattaagggattaatctatatc tacaacaacaacaacaaagaccttttcaagctgaggt agggctttctgtatatgtttggagtggttatccagca gactttacttgaaggcaggggtcatatcctcaagtgc tcataaacggaccacagaaagatctcataattgggtg gagctgggtggggaccgtgtcatgtggccaggaaatg ccagatgggaagggagtggcccttactgagctccagc tgaactctgaattttctagaaaactcagaaatctgga tttttcatgtgtaatacccagatttatagatgtggaa agctaattctttttttttttaagggactataggcaat gaactaagatctaggttgtatttggacaaggggtcat cagtttaagctgtgtagttgagcgctcagctattggg ctgagggacccctaaatactgagacggggaggtcctt gctctggggcatcacaagtacactccctggtctcatt caaacacttttcctacaaaattgatcccatttcttca gtgcactgtctgaatgcatttggcccagagccgtgct gaggcatagggaaggggtccacggtttcatggcatcg ttttgtgctgtgtgtccctgctgtcgtccaggatacc tacctctcctcctcctgcatctgaatgtccccccaca gactctctgggattctacagcctctggcctgttcctc agacacctcttacctgccagctttccagattcacatt agttagtccaaatctactgccgtcagtgactcacttc atttcttcttctccgaggcagttcagcccggtacagt tgttttgtcaacacttcagttgagtctggaagatgtg catgggttatgcacgagagcggtccatcattttgagc tagaagtcctttctcagcccagagacaagtcctcatc tcctttacttcctgactcttcttcctctgcatccttc caagatatctctttctccagccaccacctaaatctct tcttttcccggggttccgtgctcaacccactcttctt cttaaatctgtggctgggtgaacgcatctgctggcac cacttctctgctaaagactccaaaatccataggtcct gcccggcctttgcccacctctctccaacactgtccag ctttagatgtagagctaatccccccagagatatcatt ccctggatgtctaagtcctttggtatctcactttcag cgtgttcaaaatcctcttacaactgttctttctcctt ttccatcttgattattggcaacatgccagcctttccc ctacccccagcagtgagccaagctagaaacaagggct taatcttcaatctttccttctccatccctaaacctaa tgagtctccaagcccttcccagtttacaccctaaatg ttgctcaaaacatcccctagttcttccacgtgctctc ctctatattgaaaggtcaagaaaggccatcttccctc cactgtgaggaaatagatcttgatactgcccctgagc tgggcagtcctcgacctgacaaactgtgcagtgtttc taaatctctactggcaaaatgagagtgcctttgacct gtgttgcgatctcagatcacagtggatgtaattgttt tataggaatggtgaacgaaaaagaagtaaatccctaa tgccaaactcctgatcattctatgtcatttaatagcc tgtcatttatgataaagtttcctctactggcattagc acaatacttctcaggaaaaaaaaatatgatgccagat actgaaaagctcctgggtaaacatgaacatgggtacc gataaaatggtgaagccagtccaatcttagagtgact tcccttcatgctacttcatgctctttttttttttttt ttttaagaaaaaccccttttttttttctcacaccagt cacagaggagaccgaggcttagcaaggttaaggtcac atgattagtaagtgctgggctgaaactcaaaaccatc tctgcttgtctcctaaccctgtgcacctctgactatt caacag ATCCTGTGTCAGGAGTTGGGATTCTTTGAAG gtaagggccttgaccaccgaattaaggtaatcttgct ctgtggcaggccttgttttcagtattttaagtacact ggctcaggtaatcctcacaacagccccaggaggaatg ttctattacctccactgtatagatgaggaacttgagg cacagaatggttgccaaggtcacacagctatattggg ggttcatacccagccatccaactctgtctgtactctc tgccactctgcacccccagctcctgatccacttcctg tttccatccctcgatttctgctgcactcaggggcccc tctccccctcggcctgtgagatctgcttcagtaggct tttctccctgactcctccatccctgtccttacaggca gctgcttctctccgggacacgaggggtccatacggac actctctactggctgggttgcgcctaactcgtgattc ctcctctgtttcag ATTCGGAGCCGGGTTGATGTCATCAGACACGTGGTAA AGAATGGTCTGCTCTGGGATGACTTGTACATAGGATT CCAAACCCGGCTTCAGCGGGATCCTGATATATACCAT CATCT gtaagtccgaaaatgcctgtcgtgtgtgccttaggct gctgcggaggaggccagggctatataagcagagtcag tgactgactgtgccctgcagtgttgatggccatggag attccaccgttagagcttttttctttgttaaccttga aggcaaatctggttaggaagataactttcaaagagtc accatctggacattcatgcccatgtgcttcaatcctg tatacaagcagtttagagtacagggaagggaaggaca ttatgaaagggagagggtgtgtttggatccagcagct ccatcctcagaatttatctgaagacactgcaaaatta ctaagaatcactatgacaagaatgaggatggggtgat atggcaaagttgtgatcctggaagaccttcatctccc atgttgcccaactctgaacatgaatttggtgaactag ttggttaaggggatgatcctccaagtttctccctggt tgagctccaaaaaccatgtaagtttctcatagcaaaa ccgtataggtccttagggctttagttggaatatttgt gctgaaatgctggaaagccccatttgccatttttgta tttgcaaaataatcatcaagaggggagaatgcattct ttcatgaccactgaccctctgaaaaggtcaggaattt agtctgaagtaggcaagcctcctaccccgcttctgcc atgagcttgcacgcacaggcctgtcttgacatttctt ctttatagatttctttttgaatatcttgaaattgctt taaaaatatttaaagaatgtagaattatataaaataa aaaggaaataaccccacacctcccacaaaaccctgtt tcctgcctttctccaCccactctccagggtaacactt ggtaacagcatagttgtatcaccccaggcctattttt gagcatatcagcatttcaagaaatgtattttttctca

ataaaacatcccttatagttgaggaggggaggttatc attcctgggttttgttttttttttttttttaatgtaa tcctggtacatcggtaatttgcattttttattcatta atatctttggtatttctagtgttgggacacacaggtc aacctcagtttttgggtttttttttttgtctttttgt ctttctagggccacacctgcagcatatggacgttccc aagctaggagtctaatcagagctgtagccaccagcct acgtcatagccatagcaacgtcagatccaagccgtgt ctgtgacctacaagcacagctcatggcaacaccggat ccttaaccactgaacgaggccaggggatcgaacacac atcctcatggatcctagtcatgttcattaaccactga gtcatgatgggaactccaacttcaactattttaatgt ctgtaaaacattccatttggaaaccatttcatttgta aagcaaaatgaaaacattttgttcattttcaacagag ttcgtagctgacttctgttctggaaaaaaggaaatgg agcaaatttgagtgagaaagattcaaagataactttt cttttaaaaaaaattatatcttggaaacttctgggct attgattctgaagactatttttctatatactgttttg atagcaaagttcataaatgtgaaaggatcctgcgatg aatcttgggaagcagtcatagcccaatatatctttgt tgcttttaaaatgagatttagtttactaaatattttt ctgatcataaaaataacacagatctaccgcagaaaat ttggaaaaaaaaaaacttttaaattcaaaaaacagtt aaaccacaaatgatcccaccatccagagagcaatttg tactttggtgtctagttcatctttctttttctgttta caagcacatataccacaagcattttttcaaaaaatga aaatgggataatactatacatacgtctgtacacctgc atagttactgaacagtctttgatctaccctgtaagtt tctaacttttcattatttgaaatgatgttttggcaaa gaaatatgtaggtgtgtctcgcacactttcataatga tttcttaggataaatttcttaggataaattcataatg atttcttataataatccatactctgccaactgatctt cagggaagccaactcgccttctcagaaataacatata acccatttacttgccctctcaccaatactaggtccta atgtttttgtgtacagattctatatttttacatacaa gaattccttaaagcaaggcatgtcacagaaaaataga aggaagacacaattgtcatgtttaaggactgcattct gtaccaaaaatgctaagttaaatgaacatctgaaaca gtacagaaacgctatctttcagggaaagctgagtacc aggtactgaacagattttggcaaatacagcaggcatg gatgtttccaaaacatgtttttctactttatctctta cag GTTTTGGAATCATTTTCAAATAAAACTCCCCCTCACA CCACCTGACTGGAAGTCCTTCCTGATGTGCTCTGGGT AGAGAGGACCTGAGCTGTCCCAG gtaaagcatcctgcaggtctgggagacactcttattc tccagcccatcacactgtgtttggcatcagaattaag caggcactatgcctatcagaaaacctgacttttgggg gaatgaaagaagctaacattacaagaatgtctgtgtt taaaaataagtcaataagggagttcccatcgtggctc agtggtaacgaaccctactagtatccattgaggacac aggttcaatatctggcctcactcagtcggctaaggat ccagtgatgccgtgagctgcagtgtaggccacagacg tggctcagatctggtgctgctgtggctatggtgtagg ccggccccctgtaactccaattcgacccctaggctgg gaacctaaaaagaccccaaaaaagtcgctttaatgaa tagtgaatacatccagcccaaagtccacagactcttt ggtctggttgtggcaaacatacagccagttaacaaac aagacaaaaattatcctaggtggtcagtgggggttca gagctgaatcctgaacactggaaggaaaacagcaacc aaatccaaatactgtatggttttgcttatatgtagaa tctaaattcaaagcaaatgagcaaaccaattgaaaca gttatggaagacaagcaggtggttgtcaggggggaga taaggggaggcaggaaagacctgggcgagggagatta agaggtaccaactttcagttgcaaaacaaatgagtca ccagtatgaaatgtgcaatgtgggaaatacaggccat aactttataatctcttttttttttttgtcttttttgc cttttctaaggctgctcccgtggcatatggaggttcc caggctaggagtccaaacagagctgtagctgccagcc tacaccagagccacagcaacacgggaaccttaacccg ctgagcaaggccagggatcgaacccgagtcctcacag atgccagtagggttcattaaccactgagccacgacag gaattccagggtctgttgtgttcttaaaacacttcca ggagagtgagtggtatgtcataagtaaacaataaatg ttaaccacaacaagcttatgaaataaacaggaaagcc atatgacctacaatcagtcattgggagaatccacaaa aggttgagcagaggatcaattccagctcacactccag ttttagattctcccctgccttaaagcatcacagacta cataatctgagctgaagaataaaaattaaaactcacc ccagtgcaaaacagaaatgaaaaagtattaaaacgag gttcatactgttgttcattagcaatatcttttattca cag GGGTGCCCAACAACATGAAAAAATCAAGAATTTATTG CTGCTACGTCAAAGCTTATACCAGAGATTATGCCTTA TAGACATTAGCAATGGATAATTATATGTTGCACTTGT GAAATGTGCACATATCCTGTTTATGAATCACCACATA GCCAGATTATCAATATTTTACTTATTTCGTAAAAAAT CCACAATTTTCCATAACAGAATCAACGTGTGCAATAG GAACAAGATTGCTATGGAAAACGAGGGTAACAGGAGG AGATATTAATCCAAGCATAGAAGAAATAGACAAATGA GGGGCCATAAGGGGAATATAGGGAAGAGAAAAAAATT AAGATGGAATTTTAAAAGGAGAATGTAAAAAATAGAT ATTTGTTCCTTAATAGGTTGATTCCTCAAATAGAGCC CATGAATATAATCAAATAGGAAGGGTTCATGACTGTT TTCAATTTTTCAAAAAGCTTTGTTGAAATCATAGACT TGCAAAACAAGGCTGTAGAGGCCACCCTAAAATGGAA AATTTCACTGGGACTGAAATTATTTTGATTCAATGAC AAAATTTGTTATTACTGCGGATTATAAACTCTAACAA ATAGCGATCTCTTTGCTTCATAAAAACATAAACACTA GCTAGTAATAAAATGAGTTCTGCAG

[0084]SEQ ID NO. 50 represents contiguous genomic sequences containing Exon 12, Intron 12, Exon 13, Intron 13, Exon 14, Intron 14, Exon 15, Intron 15, Exon 16, Intron 16, Exon 17, Intron 17, and Exon 18. Nucleotide sequences that contain at least 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10000, 11000, 12000, 13000, 14000, 15000, 16000, 17000, 18000, 19000 or 20,000 contiguous nucleotides of SEQ ID NO. 50 are provided, as well as nucleotide sequences at least 80, 85, 90, 95, 98, or 99% homologous to SEQ ID NO. 50.

VIII. Oligonucleotide Probes and Primers

[0085]The present invention further provides oligonucleotide probes and primers which hybridize to the hereinabove-described sequences (SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 and 50). Oligonucleotides are provided that can be homologous to SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 and 50, and fragments thereof. Oligonucleotides that hybridize under stringent conditions to SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 and 50 and fragments thereof, are also provided. Stringent conditions describe conditions under which hybridization will occur only if there is at least about 85%, about 90%, about 95%, or at least about 98% homology between the sequences. Alternatively, the oligonucleotide can have at least 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 75 or 100 bases which hybridize to SEQ ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 and 50, and fragments thereof. Such oligonucleotides can be used as primers and probes to detect the sequences provided herein. The probe or primer can be at least 14 nucleotides in length, and in a preferred embodiment, are at least 15, 20, 25, 28, 30, or 35 nucleotides in length.

[0086]Given the above sequences, one of ordinary skill in the art using standard algorithms can construct oligonucleotide probes and primes that are complementary to sequences contained in Seq ID Nos. 1, 3, 5, 7, 9-45, 46, 47, 48, 49 and 50, and fragments thereof. The rules for complementary pairing are well known: cytosine ("C") always pairs with guanine ("G") and thymine ("T") or uracil ("U") always pairs with adenine ("A"). It is recognized that it is not necessary for the primer or probe to be 100% complementary to the target nucleic acid sequence, as long as the primer or probe sufficiently hybridizes and can recognize the corresponding complementary sequence. A certain degree of pair mismatch can generally be tolerated.

[0087]Oligonucleotide sequences used as the hybridizing region of a primer can also be used as the hybridizing region of a probe. Suitability of a primer sequence for use as a probe depends on the hybridization characteristics of the primer. Similarly, an oligonucleotide used as a probe can be used as a primer.

[0088]It will be apparent to those skilled in the art that, provided with these specific embodiments, specific primers and probes can be prepared by, for example, the addition of nucleotides to either the 5' or 3' ends, which nucleotides are complementary to the target sequence or are not complimentary to the target sequence. So long as primer compositions serve as a point of initiation for extension on the target sequences, and so long as the primers and probes comprise at least 14 consecutive nucleotides contained within the above mentioned SEQ ID Nos. such compositions are within the scope of the invention.

[0089]The probes and primers herein can be selected by the following criteria, which are factors to be considered, but are not exclusive or determinative. The probes and primers are selected from the region of the CMP-Neu5Ac hydroxylase nucleic acid sequence identified in SEQ ID Nos. 1, 3, 5, 7, 945, 46, 47, 48, 49, 50, and fragments thereof. The probes and primers lack homology with sequences of other genes that would be expected to compromise the test. The probes or primers lack secondary structure formation in the amplified nucleic acid which can interfere with extension by the amplification enzyme such as E. coli DNA polymerase, preferably that portion of the DNA polymerase referred to as the Klenow fragment. This can be accomplished by employing up to about 15% by weight, preferably 5-10% by weight, dimethyl sulfoxide (DMSO) in the amplification medium and/or increasing the amplification temperatures to 30°-40° C.

[0090]Preferably, the probes or primers should contain approximately 50% guanine and cytosine nucleotides, as measured by the formula adenine (A)+thymine (T)+cytosine (C)+guanine (G)/cytosine (C)+guanine (G). Preferably, the probe or primer does not contain multiple consecutive adenine and thymine residues at the 3' end of the primer which can result in less stable hybrids.

[0091]The probes and primers of the invention can be about 10 to 30 nucleotides long, preferably at least 10, 11, 12, 13, 14, 15, 20, 25, or 28 nucleotides in length, including specifically 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides. The nucleotides as used in the present invention can be ribonucleotides, deoxyribonucleotides and modified nucleotides such as inosine or nucleotides containing modified groups which do not essentially alter their hybridization characteristics. Probe and primer sequences are represented throughout the specification as single stranded DNA oligonucleotides from the 5' to the 3' end. Any of the probes can be used as such, or in their complementary form, or in their RNA form (wherein T is replaced by U).

[0092]The probes and primers according to the invention can be prepared by cloning of recombinant plasmids containing inserts including the corresponding nucleotide sequences, optionally by cleaving the latter out from the cloned plasmids upon using the adequate nucleases and recovering them, e.g. by fractionation according to molecular weight. The probes and primers according to the present invention can also be synthesized chemically, for instance by the conventional phosphotriester or phosphodiester methods or automated embodiments thereof. In one such automated embodiment diethylphosphoramidites are used as starting materials and can be synthesized as described by Beaucage, et al., Tetrahedron Letters 22:1859-1862 (1981). One method of synthesizing oligonucleotides on a modified solid support is described in U.S. Pat. No. 4,458,066. It is also possible to use a probe or primer which has been isolated from a biological source (such as a restriction endonuclease digest).

[0093]The oligonucleotides used as primers or probes can also comprise nucleotide analogues such as phosphorothioates (Matsukura S., Naibunpi Gakkai Zasshi. 43(6):527-32 (1967)), alkylphosphorothiates (Miller P., et al., Biochemistry 18(23):5134-43 (1979), peptide nucleic acids (Nielsen P., et al., Science 254(5037):1497-500 (1991); Nielsen P., et al., Nucleic-Acids-Res. 21(2):197-200 (1993)), morpholino nucleic acids, locked nucleic acids, pseudocyclic oligonucleobases, 2'-O,4'-C-ethylene bridged nucleic acids or can contain intercalating agents (Asseline J., et al., Proc. Natl. Acad. Sci. USA 81(11):3297-301 (1984)).

[0094]For designing probes and primers with desired characteristics, the following useful guidelines known to the person skilled in the art can be applied. Because the extent and specificity of hybridization reactions are affected by a number of factors, manipulation of one or more of those factors will determine the exact sensitivity and specificity of a particular probe, whether perfectly complementary to its target or not. The importance and effect of various assay conditions, explained further herein, are known to those skilled in the art.

[0095]The stability of the probe and primer to target nucleic acid hybrid should be chosen to be compatible with the assay conditions. This can be accomplished by avoiding long AT-rich sequences, by terminating the hybrids with GC base pairs, and/or by designing the probe with an appropriate Tm. The beginning and end points of the probe should be chosen so that the length and % GC result in a Tm about 2-10° C. higher than the temperature at which the final assay will be performed. The base composition of the probe is significant because G-C base pairs exhibit greater thermal stability compared to A-T base pairs due to additional hydrogen bonding. Thus, hybridization involving complementary nucleic acids of higher G-C content will be stable at higher temperatures. Conditions such as ionic strength and incubation temperature under which probe will be used should also be taken into account when designing a probe. It is known that hybridization will increase as the ionic strength of the reaction mixture increases, and that the thermal stability of the hybrids will increase with increasing ionic strength. Chemical reagents, such as formamide, urea, DIVISO and alcohols, which disrupt hydrogen bonds, will increase the stringency of hybridization. Destabilization of the hydrogen bonds by such reagents can greatly reduce the Tm. In general, optimal hybridization for synthetic oligonucleotide probes of about 10-50 bases in length occurs approximately 5° C. below the melting temperature for a given duplex. Incubation at temperatures below the optimum can allow mismatched base sequences to hybridize and can therefore result in reduced specificity. It is desirable to have probes which hybridize only under conditions of high stringency. Under high stringency conditions only highly complementary nucleic acid hybrids will form; hybrids without a sufficient degree of complementarity will not form. Accordingly, the stringency of the assay conditions determines the amount of complementarity needed between two nucleic acid strands forming a hybrid. The degree of stringency is chosen such as to maximize the difference in stability between the hybrid formed with the target and the non-target nucleic acid. In the present case, single base pair changes need to be detected, which requires conditions of very high stringency.

[0096]The length of the target nucleic acid sequence and, accordingly, the length of the probe sequence can also be important. In some cases, there can be several sequences from a particular region, varying in location and length, which will yield probes and primers with the desired hybridization characteristics. In other cases, one sequence can be significantly better than another which differs merely by a single base.

[0097]While it is possible for nucleic acids that are not perfectly complementary to hybridize, the longest stretch of perfectly complementary base sequence will normally primarily determine hybrid stability. While oligonucleotide probes and primers of different lengths and base composition can be used, preferred oligonucleotide probes and primers of this invention are between about 14 and 30 bases in length and have a sufficient stretch in the sequence which is perfectly complementary to the target nucleic acid sequence.

[0098]Regions in the target DNA or RNA which are known to form strong internal structures inhibitory to hybridization are less preferred. Likewise, probes with extensive self-complementarity should be avoided. As explained above, hybridization is the association of two single strands of complementary nucleic acids to form a hydrogen bonded double strand. It is implicit that if one of the two strands is wholly or partially involved in a hybrid, it will be less able to participate in formation of a new hybrid. There can be intramolecular and intermolecular hybrids formed within the molecules of one type of probe if there is sufficient self complementarity. Such structures can be avoided through careful probe design. By designing a probe so that a substantial portion of the sequence of interest is single stranded, the rate and extent of hybridization can be greatly increased. Computer programs are available to search for this type of interaction. However, in certain instances, it may not be possible to avoid this type of interaction.

[0099]Specific primers and sequence specific oligonucleotide probes can be used in a polymerase chain reaction that enables amplification and detection of CMP-Neu5Ac hydroxylase nucleic acid sequences.

IV. Genetic Targeting of the CMP-Neu5Ac Hydroxylase Gene

[0100]Gene targeting allows for the selective manipulation of animal cell genomes. Using this technique, a particular DNA sequence can be targeted and modified in a site-specific and precise manner. Different types of DNA sequences can be targeted for modification, including regulatory regions, coding regions and regions of DNA between genes. Examples of regulatory regions include: promoter regions, enhancer regions, terminator regions and introns. By modifying these regulatory regions, the timing and level of expression of a gene can be altered. Coding regions can be modified to alter, enhance or eliminate the protein within a cell. Introns and exons, as well as inter-genic regions, are suitable targets for modification.

[0101]Modifications of DNA sequences can be of several types, including insertions, deletions, substitutions, or any combination thereof. A specific example of a modification is the inactivation of a gene by site-specific integration of a nucleotide sequence that disrupts expression of the gene product, i.e. a "knock out". For example, one approach to disrupting the CMP-Neu5Ac hydroxylase gene is to insert a selectable marker into the targeting DNA such that homologous recombination between the targeting DNA and the target DNA can result in insertion of the selectable marker into the coding region of the target gene. For example, see FIGS. 3, 12, and 13. In this way, for example, the CMP-Neu5Ac hydroxylase gene sequence is disrupted, rendering the encoded enzyme nonfunctional.

Homologous Recombination

[0102]Homologous recombination permits site-specific modifications in endogenous genes and thus novel alterations can be engineered into the genome. A primary step in homologous recombination is DNA strand exchange, which involves a pairing of a DNA duplex with at least one DNA strand containing a complementary sequence to form an intermediate recombination structure containing heteroduplex DNA (see, for example Radding, C. M. (1982) Ann. Rev. Genet. 16: 405; U.S. Pat. No. 4,888,274). The heteroduplex DNA can take several forms, including a three DNA strand containing triplex form wherein a single complementary strand invades the DNA duplex (Hsieh, et al., Genes and Development 4: 1951 (1990); Rao, et al., (1991) PNAS 88:2984)) and, when two complementary DNA strands pair with a DNA duplex, a classical Holliday recombination joint or chi structure (Holliday, R., Genet. Res. 5: 282 (1964)) can form, or a double-D loop ("Diagnostic Applications of Double-D Loop Formation" U.S. Ser. No. 07/755,462, filed Sep. 4, 1991). Once formed, a heteroduplex structure can be resolved by strand breakage and exchange, so that all or a portion of an invading DNA strand is spliced into a recipient DNA duplex, adding or replacing a segment of the recipient DNA duplex. Alternatively, a heteroduplex structure can result in gene conversion, wherein a sequence of an invading strand is transferred to a recipient DNA duplex by repair of mismatched bases using the invading strand as a template (Genes, 3^rd Ed. (1987) Lewin, B., John Wiley, New York, N.Y.; Lopez, et al., Nucleic Acids Res. 15: 5643 (1987)). Whether by the mechanism of breakage and rejoining or by the mechanism(s) of gene conversion, formation of heteroduplex DNA at homologously paired joints can serve to transfer genetic sequence information from one DNA molecule to another.

[0103]The ability of homologous recombination (gene conversion and classical strand breakage/rejoining) to transfer, genetic sequence information between DNA molecules renders targeted homologous recombination a powerful method in genetic engineering and gene manipulation.

[0104]In homologous recombination, the incoming DNA interacts with and integrates into a site in the genome that contains a substantially homologous DNA sequence. In non-homologous ("random" or "illicit") integration, the incoming DNA is not found at a homologous sequence in the genome but integrates elsewhere, at one of a large number of potential locations. In general, studies with higher eukaryotic cells have revealed that the frequency of homologous recombination is far less than the frequency of random integration. The ratio of these frequencies has direct implications for "gene targeting" which depends on integration via homologous recombination (i.e. recombination between the exogenous "targeting DNA" and the corresponding "target DNA" in the genome).

[0105]A number of papers describe the use of homologous recombination in mammalian cells. Illustrative of these papers are Kucherlapati, et al., Proc. Natl. Acad. Sci. (USA) 81:3153-3157, 1984; Kucherlapati, et al., Mol. Cell. Bio. 5:714-720, 1985; Smithies, et al, Nature 317:230-234, 1985; Wake, et al., Mol. Cell. Bio. 8:2080-2089, 1985; Ayares, et al., Genetics 111:375-388, 1985; Ayares, et al., Mol. Cell. Bio. 7:1656-1662, 1986; Song, et al., Proc. Natl. Acad. Sci. USA 84:6820-6824, 1987; Thomas, et al. Cell 44:419-428, 1986; Thomas and Capecchi, Cell 51: 503-512, 1987; Nandi, et al., Proc. Natl. Acad. Sci. USA 85:3845-3849, 1988; and Mansour, et al., Nature 336:348-352, 1988; Evans and Kaufman, Nature 294:146-154, 1981; Doetschman, et al., Nature 330:576-578, 1987; Thoma and Capecchi, Cell 51:503-512, 4987; Thompson, et al., Cell 56:316-321, 1989.

[0106]The present invention uses homologous recombination to inactivate the porcine CMP-Neu5Ac hydroxylase gene in cells, such as fibroblasts. The DNA can comprise at least a portion of the gene(s) at the particular locus with introduction of an alteration into at least one, optionally both copies, of the native gene(s), so as to prevent expression of a functional enzyme and production of a Hanganutziu-Deicher antigen molecule. The alteration can be an insertion, deletion, replacement or combination thereof. When the alteration is introduce into only one copy of the gene being inactivated, the cells having a single unmutated copy of the target gene are amplified and can be subjected to a second targeting step, where the alteration can be the same or different from the first alteration, usually different, and where a deletion, or replacement is involved, can be overlapping at least a portion of the alteration originally introduced. In this second targeting step, a targeting vector with the same arms of homology, but containing a different mammalian selectable markers can be used. The resulting transformants are screened for the absence of a functional target antigen and the DNA of the cell can be further screened to ensure the absence of a wild-type target gene. Alternatively, homozygosity as to a phenotype can be achieved by breeding hosts heterozygous for the mutation.

[0107]Porcine cells that can be genetically modified can be obtained from a variety of different organs and tissues such as, but not limited to, brain, heart, lungs, glands, brain, eye, stomach, spleen, pancreas, kidneys, liver, intestines, uterus, bladder, skin, hair, nails, ears, nose, mouth, lips, gums, teeth, tongue, salivary glands, tonsils, pharynx, esophagus, large intestine, small intestine, rectum, anus, pylorus, thyroid gland, thymus gland, suprarenal capsule, bones, cartilage, tendons, ligaments, skeletal muscles, smooth muscles, blood vessels, blood, spinal cord, trachea, ureters, urethra, hypothalamus, pituitary, adrenal glands, ovaries, oviducts, uterus, vagina, mammary glands, testes, seminal vesicles, penis, lymph, lymph nodes and lymph vessels. In one embodiment of the invention, porcine cells can be selected from the group consisting of, but not limited to, epithelial cells, fibroblast cells, neural cells, keratinocytes, hematopoietic cells, melanocytes, chondrocytes, lymphocytes (B and T), macrophages, monocytes, mononuclear cells, cardiac muscle cells, other muscle cells, quadraturehosphate cells, cumulus cells, epidermal cells, endothelial cells, Islets of Langerhans cells, blood cells, blood precursor cells, bone cells, bone precursor cells, neuronal stem cells, primordial stem cells, hepatocytes, keratinocytes, umbilical vein endothelial cells, aortic endothelial cells, microvascular endothelial cells, fibroblasts, liver stellate cells, aortic smooth muscle cells, cardiac myocytes, neurons, Kupffer cells, smooth muscle cells, Schwann cells, and epithelial cells, erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, adipocytes, chondrocytes, pancreatic islet cells, thyroid cells, parathyroid cells, parotid cells, tumor cells, glial cells, astrocytes, red blood cells, white blood cells, macrophages, epithelial cells, somatic cells, pituitary cells, adrenal cells, hair cells, bladder cells, kidney cells, retinal cells, rod cells, cone cells, heart cells, pacemaker cells, spleen cells, antigen presenting cells, memory cells, T cells, B cells, plasma cells, muscle cells, ovarian cells, uterine cells, prostate cells, vaginal epithelial cells, sperm cells, testicular cells, germ cells, egg cells, leydig cells, peritubular cells, sertoli cells, lutein cells, cervical cells, endometrial cells, mammary cells, follicle cells, mucous cells, ciliated cells, nonkeratinized epithelial cells, keratinized epithelial cells, lung cells, goblet cells, columnar epithelial cells, squamous epithelial cells, osteocytes, osteoblasts, and osteoclasts.

[0108]In one alternative embodiment, embryonic stem cells can be used. An embryonic stem cell line can be employed or embryonic stem cells can be obtained freshly from a host, such as a porcine animal. The cells can be grown on an appropriate fibroblast-feeder layer or grown in the presence of leukemia inhibiting factor (LIF). In a preferred embodiment, the porcine cells can be fibroblasts; in one specific embodiment, the porcine cells can be fetal fibroblasts. Fibroblast cells are a preferred somatic cell type because they can be obtained from developing fetuses and adult animals in large quantities.

[0109]These cells can be easily propagated in vitro with a rapid doubling time and can be clonally propagated for use in gene targeting procedures.

Targeting Vectors

[0110]Cells homozygous at a targeted locus can be produced by introducing DNA into the cells, where the DNA has homology to the target locus and includes a marker gene, allowing for selection of cells comprising the integrated construct. The homologous DNA in the target vector will recombine with the chromosomal DNA at the target locus (see, for example, FIGS. 3, 12, and 13). The marker gene can be flanked on both sides by homologous DNA sequences, a 3' recombination arm and a 5' recombination arm (See, for example, FIG. 11). Methods for the construction of targeting vectors have been described in the art, see, for example, Dai et al., Nature Biotechnology 20: 251-255, 2002; WO 00/51424.

[0111]Various constructs can be prepared for homologous recombination at a target locus. Usually, the construct can include at least 50 bp, 100 bp, 500 bp, 1 kbp, 2 kbp, 4 kbp, 5 kbp, 10 kbp, 15 kbp, 20 kbp, or 50 kbp of sequence homologous with the target locus. The sequence can include any contiguous sequence of the porcine CMP-Neu5Ac hydroxylase gene, including at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90.95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 550, 600, 700, 750, 800, 850, 900, 1000, 5000 or 10, 000 contiguous nucleotides of Seq ID Nos 9-45, 46, 47, 48, 49, and 50, or any combination or fragment thereof. Fragments of Seq ID Nos. 9-45, 46, 47, 48, 49 and 50 can include any contiguous nucleic acid or peptide sequence that includes at least about 10 bp, 15 bp, 17 bp, 20 bp, 50 bp, 100 bp, 500 bp, 1 kbp, 5 kbp or 10 kbp.

[0112]Various considerations can be involved in determining the extent of homology of target DNA sequences, such as, for example, the size of the target locus, availability of sequences, relative efficiency of double cross-over events at the target locus and the similarity of the target sequence with other sequences.

[0113]The targeting DNA can include a sequence in which DNA substantially isogenic flanks the desired sequence modifications with a corresponding target sequence in the genome to be modified. The substantially isogenic sequence can be at least about 95%, 97-98%, 99.0-99.5%, 99.6-99.9%, or 100% identical to the corresponding target sequence (except for the desired sequence modifications). The targeting DNA and the target DNA preferably can share stretches of DNA at least about 75, 150 or 500 base pairs that are 100% identical. Accordingly, targeting DNA can be derived from cells closely related to the cell line being targeted; or the targeting DNA can be derived from cells of the same cell line or animal as the cells being targeted.

[0114]The DNA constructs can be designed to modify the endogenous, target CMP-Neu5Ac hydroxylase. The homologous sequence for targeting the construct can have one or more deletions, insertions, substitutions or combinations thereof designed to disrupt the function of the resultant gene product. In one embodiment, the alteration can be the insertion of a selectable marker gene fused in reading frame with the upstream sequence of the target gene.

[0115]Suitable selectable marker genes include, but are not limited to: genes conferring the ability to grow on certain media substrates, such as the tk gene (thymidine kinase) or the hprt gene (hypoxanthine phosphoribosyltransferase) which confer the ability to grow on HAT medium (hypoxanthine, aminopterin and thymidine); the bacterial gpt gene (guanine/xanthine phosphoribosyltransferase) which allows growth on MAX medium (mycophenolic acid, adenine, and xanthine). See, for example, Song, K-Y., et al. Proc. Nat'l Acad. Sci. U.S.A. 84:6820-6824 (1987); Sambrook, J., et al., Molecular Cloning--A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989), Chapter 16. Other examples of selectable markers include: genes conferring resistance to compounds such as antibiotics, genes conferring the ability to grow on selected substrates, genes encoding proteins that produce detectable signals such as luminescence, such as green fluorescent protein, enhanced green fluorescent protein (eGFP). A wide variety of such markers are known and available, including, for example, antibiotic resistance genes such as the neomycin resistance gene (neo) (Southern, P., and P. Berg, J. Mol. Appl. Genet. 1:327-341 (1982)); and the hygromycin resistance gene (hyg) (Nucleic Acids Research 11:6895-6911 (1983), and Te Riele, H., et al., Nature 348:649-651 (1990)). Other selectable marker genes include: acetohydroxy acid synthase (AHAS), alkaline phosphatase (AP), beta galactosidase (LacZ), beta glucoronidase (GUS), chloramphenicol acetyltransferase (CAT), green fluorescent protein (GFP), red fluorescent protein (RFP), yellow fluorescent protein (YFP), cyan fluorescent protein (CFP), horseradish peroxidase (HRP), luciferase (Luc), nopaline synthase (NOS), octopine synthase (OCS), and derivatives thereof. Multiple selectable markers are available that confer resistance to ampicillin, bleomycin, chloramphenicol, gentamycin, hygromycin, kanamycin, lincomycin, methotrexate, phosphinothricin, puromycin, and tetracycline.

[0116]Methods for the incorporation of antibiotic resistance genes and negative selection factors will be familiar to those of ordinary skill in the art (see, e.g., WO 99/15650; U.S. Pat. No. 6,080,576; U.S. Pat. No. 6,136,566; Niwa, et al., J. Biochem. 113:343-349 (1993); and Yoshida, et al., Transgenic Research, 4:277-287 (1995)).

[0117]Additional selectable marker genes useful in this invention, for example, are described in U.S. Pat. Nos. 6,319,669; 6,316,181; 6,303,373; 6,291,177; 6,284,519; 6,284,496; 6,280,934; 6,274,354; 6,270,958; 6,268,201; 6,265,548; 6,261,760; 6,255,558; 6,255,071; 6,251,677; 6,251,602; 6,251,582; 6,251,384; 6,248,558; 6,248,550; 6,248,543; 6,232,107; 6,228,639; 6,225,082; 6,221,612; 6,218,185; 6,214,567; 6,214,563; 6,210,922; 6,210,910; 6,203,986; 6,197,928; 6,180,343; 6,172,188; 6,153,409; 6,150,176; 6,146,826; 6,140,132; 6,136,539; 6,136,538; 6,133,429; 6,130,313; 6,124,128; 6,110,711; 6,096,865; 6,096,717; 6,093,808; 6,090,919; 6,083,690; 6,077,707; 6,066,476; 6,060,247; 6,054,321; 6,037,133; 6,027,881; 6,025,192; 6,020,192; 6,013,447; 6,001,557; 5,994,077; 5,994,071; 5,993,778; 5,989,808; 5,985,577; 5,968,773; 5,968,738; 5,958,713; 5,952,236; 5,948,889; 5,948,681; 5,942,387; 5,932,435; 5,922,576; 5,919,445; and 5,914,233.

[0118]Combinations of selectable markers can also be used. For example, to target CMP-Neu5Ac hydroxylase, a neo gene (with or without its own promoter, as discussed above) can be cloned into a DNA sequence which is homologous to the CMP-Neu5Ac hydroxylase gene. To use a combination of markers, the HSV-tk gene can be cloned such that it is outside of the targeting DNA (another selectable marker could be placed on the opposite flank, if desired). After introducing the DNA construct into the cells to be targeted, the cells can be selected on the appropriate antibiotics. In this particular example, those cells which are resistant to G418 and gancyclovir are most likely to have arisen by homologous recombination in which the neo gene has been recombined into the CMP-Neu5Ac hydroxylase gene but the tk gene has been lost because it was located outside the region of the double crossover.

[0119]Deletions can be at least about 50 bp, more usually at least about 100 bp, and generally not more than about 20 kbp, where the deletion can normally include at least a portion of the coding region including a portion of or one or more exons, a portion of or one or more introns, and can or can not include a portion of the flanking non-coding regions, particularly the 5'-non-coding region (transcriptional regulatory region). Thus, the homologous region can extend beyond the coding region into the 5'-non-coding region or alternatively into the 3'-non-coding region. Insertions can generally not exceed 10 kbp, usually not exceed 5 kbp, generally being at least 50 bp, more usually at least 200 bp.

[0120]The region(s) of homology can include mutations, where mutations can further inactivate the target gene, in providing for a frame shift, or changing a key amino acid, or the mutation can correct a dysfunctional allele, etc. Usually, the mutation can be a subtle change, not exceeding about 5% of the homologous flanking sequences.

[0121]The construct can be prepared in accordance with methods known in the art, various fragments can be brought together, introduced into appropriate vectors, cloned, analyzed and then manipulated further until the desired construct has been achieved (see, for example FIGS. 5-11). Various modifications can be made to the sequence, to allow for restriction analysis, excision, identification of probes, etc. Silent mutations can be introduced, as desired. At various stages, restriction analysis, sequencing, amplification with the polymerase chain reaction, primer repair, in vitro mutagenesis, etc. can be employed.

[0122]The construct can be prepared using a bacterial vector, including a prokaryotic replication system, e.g. an origin recognizable by E. coli, at each stage the construct can be cloned and analyzed. A marker, the same as or different from the marker to be used for insertion, can be employed, which can be removed prior to introduction into the target cell. Once the vector containing the construct has been completed, it can be further manipulated, such as by deletion of the bacterial sequences, linearization, introducing a short deletion in the homologous sequence. After final manipulation, the construct can be introduced into the cell.

[0123]Techniques which can be used to allow the DNA construct entry into the host cell include calcium phosphate/DNA co-precipitation, microinjection of DNA into the nucleus, electroporation, bacterial protoplast fusion with intact cells, transfection, or any other technique known by one skilled in the art. The DNA can be single or double stranded, linear or circular, relaxed or supercoiled DNA. For various techniques for transfecting mammalian cells, see, for example, Keown et al., Methods in Enzymology Vol. 185, pp. 527-537 (1990).

[0124]The present invention further includes recombinant constructs comprising one or more of the sequences as broadly described above (for example in Tables 9-12). The constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a forward or reverse orientation. The construct can also include regulatory sequences, including, for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available. The following vectors are provided by way of example: pBs, pQE-9 (Qiagen), phagescript, PsiX174, pBluescript SK, pBsKS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia). Eukaryotic: pWLneo, pSv2cat, pOG44, pXT1, pSG (Stratagene) pSVK3, pBPv, pMSG, pSVL (Pharmacia). Also, any other plasmids and vectors can be used as long as they are replicable and viable in the host. Vectors known in the art and those commercially available (and variants or derivatives thereof) can in accordance with the invention be engineered to include one or more recombination sites for use in the methods of the invention. Such vectors can be obtained from, for example, Vector Laboratories Inc., Invitrogen, Promega, Novagen, NEB, Clontech, Boehringer Mannheim, Pharmacia, EpiCenter, OriGenes Technologies Inc., Stratagene, PerkinElmer, Pharmingen, and Research Genetics. Other vectors of interest include eukaryotic expression vectors such as pFastBac, pFastBacHT, pFastBacDUAL, pSFV, and pTet-Splice (Invitrogen), pEUK-C1, pPUR, pMAM, pMAMneo, pBI101, pBI121, pDR2, pCMVEBNA, and pYACneo (Clontech), pSVK3, pSVL, pMSG, pCH110, and pKK232-8 (Pharmacia, Inc.), p3'SS, pXT1, pSG5, pPbac, pMbac, pMC1neo, and pOG44 (Stratagene, Inc.), and pYES2, pAC360, pBlueBacHis A, B, and C, pVL1392, pBlueBacIII, pCDM8, pcDNA1, pZeoSV, pcDNA3 pREP4, pCEP4, and pEBVHis (Invitrogen, Corp.) and variants or derivatives thereof.

[0125]Other vectors suitable for use in the invention include pUC18, pUC19, pBlueScript, pSPORT, cosmids, phagemids, YAC's (yeast artificial chromosomes), BAC's (bacterial artificial chromosomes), PI (Escherichia coli phage), pQE70, pQE60, pQE9 (quagan), pBS vectors, PhageScript vectors, BlueScript vectors, pNH8A, pNH16A, pNH18A, pNH46A (Stratagene), pcDNA3 (Invitrogen), pGEX, pTrsfus, pTrc99A, pET-5, pET-9, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia), pSPORT1, pSPORT2, pCMVSPORT2.0 and pSV-SPORT1 (Invitrogen) and variants or derivatives thereof. Viral vectors can also be used, such as lentiviral vectors (see, for example, WO 03/059923; Tiscomia et al. PNAS 100:1844-1848 (2003)).

[0126]Additional vectors of interest include pTrxFus, pThioHis, pLEX, pTrcHis, pTrcHis2, pRSET, pBlueBacHis2, pcDNA3.1/His, pcDNA3.1(-)/Myc-His, pSecTag, pEBVHis, pPIC9K, pPIC3.5K, pAO815, pPICZ, pPICZA, pPICZB, pPICZC, pGAPZA, pGAPZB, pGAPZC, pBlueBac4.5, pBlueBacHis2, pMelBac, pSinRep5, pSinHis, pIND, pIND(SP1), pVgRXR, pcDNA2.1, pYES2, pZErO1.1, pZErO-2.1, pCR-Blunt, pSE280, pSE380, pSE420, pVL1392, pVL1393, pCDM8, pcDNA1.1, pcDNA 1.1/Amp, pcDNA3.1, pcDNA3.1/Zeo, pSe, SV2, pRc/CMV2, pRc/RSV, pREP4, pREP7, pREP8, pREP9, pREP 10, pCEP4, pEBVHis, pCR3.1, pCR2.1, pCR3.1-Uni, and pCRBac from Invitrogen; λ ExCell, λ gt11, pTrc99A, pKK223-3, pGEX-1λ T, pGEX-2T, pGEX-2TK, pGEX-4T-1, pGEX-4T-2, pGEX-4T-3, pGEX-3X, pGEX-5X-1, pGEX-5X-2, pGEX-5X-3, pEZZ18, pRIT2T, pMC1871, pSVK3, pSVL, pMSG, pCH110, pKK232-8, pSL1180, pNEO, and pUC4K from Pharmacia; pSCREEN-1b(+), pT7Blue(R), pT7Blue-2, pCITE-4abc(+), pOCUS-2, pTAg, pET-32LIC, pET-30LIC, pBAC-2 cp LIC, pBACgus-2 cp LIC, pT7Blue-2 LIC, pT7Blue-2, λ SCREEN-1, λ BlueSTAR, pET-3abcd, pET-7abc, pET9abcd, pET11abcd, pET12abc, pET-14b, pET-15b, pET-16b, pET-17b-pET-17xb, pET-19b, pET-20b(+), pET-21 abcd(+), pET-22b(+), pET-23abcd(+), pET-24abcd(+), pET-25b(+), pET-26b(+), pET-27b(+), pET-28abc(+), pET-29abc(+), pET-30abc(+), pET-31b(+), pET-32abc(+), pET-33b(+), pBAC-1, pBACgus-1, pBAC4x-1, pBACgus4x-1, pBAC-3 cp, pBACgus-2 cp, pBACsurf-1, pig, Signal pig, pYX, Selecta Vecta-Neo, Selecta Vecta-Hyg, and Selecta Vecta-Gpt from Novagen; pLexA, pB42AD, pGBT9, pAS2-1, pGAD424, pACT2, pGAD GL, pGAD GH, pGAD10, pGilda, pEZM3, pEGFP, pEGFP-1, pEGFP-N, pEGFP-C, pEBFP, pGFPuv, pGFP, p6xHis-GFP, pSEAP2-Basic, pSEAP2-Contral, pSEAP2-Promoter, pSEAP2-Enhancer, pβgal-Basic, pβgal-Control, pβgal-Promoter, pβgal-Enhancer, pCMV, pTet-Off, pTet-On, pTK-Hyg, pRetro-Off, pRetro-On, pIRES1neo, pIRES1hyg, pLXSN, pLNCX, pLAPSN, pMAMneo, pMAMneo-CAT, pMAMneo-LUC, pPUR, pSV2neo, pYEX4T-1/2/3, pYEX-S1, pBacPAK-His, pBacPAK8/9, pAcUW31, BacPAK6, pTriplEx, λgt10, λgt11, pWE15, and λTriplEx from Clontech; Lambda ZAP II, pBK-CMV, pBK-RSV, pBluescript II KS +/-, pBluescript II SK +/-, pAD-GAL4, pBD-GAL4 Cam, pSurfscript, Lambda FIX II, Lambda DASH, Lambda EMBL3, Lambda EMBL4, SuperCos, pCR-Script Amp, pCR-Script Cam, pCR-Script Direct, pBS +/-, pBC KS +/-, pBC SK +/-, Phagescript, pCAL-n-EK, pCAL-n, pCAL-c, pCAL-kc, pET-3abcd, pET-11abcd, pSPUTK, pESP-1, pCMVLacI, pOPRSVI/MCS, pOPI3 CAT, pXT1, pSG5, pPbac, pMbac, pMC1neo, pMC1neo Poly A, pOG44, pOG45, pFRTβGAL, pNEOβGAL, pRS403, pRS404, pRS405, pRS406, pRS413, pRS414, pRS415, and pRS416 from Stratagene.

[0127]Additional vectors include, for example, pPC86, pDBLeu, pDBTrp, pPC97, p2.5, pGAD1-3, pGAD10, pACt, pACT2, pGADGL, pGADGH, pAS2-1, pGAD424, pGBT8, pGBT9, pGAD-GAL4, pLexA, pBD-GAL4, pHISi, pHISi-1, placZi, pB42AD, pDG202, pJK202, pJG4-5, pNLexA, pYESTrp and variants or derivatives thereof.

[0128]Also, any other plasmids and vectors known in the art can be used as long as they are replicable and viable in the host.

Selection of Homologously Recombined Cells

[0129]Cells that have been homologously recombined to knock-out expression of the porcine CMP-Neu5Ac hydroxylase gene can then be grown in appropriately-selected medium to identify cells providing the appropriate integration. Those cells which show the desired phenotype can then be further analyzed by restriction analysis, electrophoresis, Southern analysis, polymerase chain reaction, or another technique known in the art. By identifying fragments which show the appropriate insertion at the target gene site, cells can be identified in which homologous recombination has occurred to inactivate or otherwise modify the target gene.

[0130]The presence of the selectable marker gene inserted into the CMP-Neu5Ac hydroxylase gene establishes the integration of the target construct into the host genome. Those cells which show the desired phenotype can then be further analyzed by restriction analysis, electrophoresis, Southern analysis, polymerase chain reaction, monoclonal antibody assays, Fluorescent Activated Cell Sorter (FACS), or any other techniques or methods known in the art to analyze the DNA in order to establish whether homologous or non-homologous recombination occurred. This can be determined by employing probes for the insert and then sequencing the 5' and 3' regions flanking the insert for the presence of the CMP-Neu5Ac hydroxylase gene extending beyond the flanking regions of the construct or identifying the presence of a deletion, when such deletion is introduced. Primers can also be used which are complementary to a sequence within the construct and complementary to a sequence outside the construct and at the target locus. In this way, one can only obtain DNA duplexes having both of the primers present in the complementary chains if homologous recombination has occurred. By demonstrating the presence of the primer sequences or the expected size sequence, the occurrence of homologous recombination is supported.

[0131]The polymerase chain reaction used for screening homologous recombination events is described, for example, in Kim and Smithies, Nucleic Acids Res. 16:8887-8903, 1988; and Joyner, et al., Nature 338:153-156, 1989.

[0132]An alternative method for screening homologous recombination events includes utilizing monoclonal or polyclonal antibodies specific for porcine CMP-Neu5Ac Hydroxylase and/or Neu5Gc, as described in, for example, Malykh, et al., European Journal of Cell Biology 80, 48-58 (2001), Malykh, et al., Glycoconjugate J. 15, 885-893 (1998).

[0133]Further characterization of porcine cells lacking expression of functional CMP-Neu5Ac Hydroxylase due to homologous recombination events include, but are not limited to, Southern Blot analysis, Northern Blot analysis, specific lectin binding assays, and/or sequence analysis, or by using anti-Neu5Gc or anti-CMP-Neu5Ac hydroxylase antibody assays as described, for example, in Y. Malykh, et. al. Biochem J. 370: 601-607 (2003); Y. Malykh, et al. European Journal of Cell Biology 80: 48-58 (2001); Y. Malykh et al. Glycoconjugate J. 15: 885-893 (1998). See generally, for example, A. Sharma, et al. Transplantation 75(4): 430-436 (2003).

[0134]The cell lines obtained from the first round of targeting are likely to be heterozygous for the targeted allele. Homozygosity, in which both alleles are modified, can be achieved in a number of ways. One approach is to grow up a number of cells in which one copy has been modified and then to subject these cells to another round of targeting of the remaining porcine CMP-Neu5Ac hydroxylase allele using a different selectable marker. Alternatively, homozygotes can be obtained by breeding animals heterozygous for the modified allele, according to traditional Mendelian genetics. In some situations, it can be desirable to have two different modified alleles. This can be achieved by successive rounds of gene targeting or by breeding heterozygotes, each of which carries one of the desired modified alleles.

VIII. Genetic Manipulation of Additional Genes to Overcome Immunologic Barriers of Xenotransplantation

[0135]In one aspect of the invention, cells homozygous for the nonfunctional CMP-Neu5Ac hydroxylase gene can be subject to further genetic modification. For example, one can introduce additional genetic capability into the homozygotic hosts, where the endogenous CMP Neu5Ac hydroxylase alleles have been made nonfunctional, to substitute, replace or provide different genetic capability to the host. One can remove the marker gene after homogenization. By introducing a construct comprising substantially the same homologous DNA, possibly with extended sequences, having the marker gene portion of the original construct deleted, one can be able to obtain homologous recombination with the target locus. By using a combination of marker genes for integration, one providing positive selection and the other negative selection, in the removal step, one can select against the cells retaining the marker genes.

[0136]In one embodiment, porcine cells are provided that lack the CMP-Neu5Ac hydroxylase gene and the α(1,3)GT gene. Animals lacking functional CMP-Neu5Ac hydroxylase can be produced according to the present invention, and then cells from this animal can be used to knockout the α(1,3)GT gene. Homozygous α(1,3)GT negative porcine have recently been reported (Phelps et. al. Science 2003; WO 04/028243). Alternatively, cells from these a(1,3)GT knockout animals can be used and further modified to inactivate the CMP-Neu5Ac hydroxylase gene.

[0137]In another embodiment, porcine cells are also provided that lack the porcine CMP-Neu5Ac hydroxylase gene and produce human complement inhibiting proteins. Animals lacking functional porcine CMP-Neu5Ac hydroxylase gene can be produced according to the present invention, and then cells from this animal can be further modified to express human complement inhibiting proteins, such as, but not limited to, CD59 (cDNA reported by Philbrick, W. M., et al. (1990) Eur. J. Immunol. 20:87-92), human decay accelerating factor (DAF) (cDNA reported by Medof, et al. (1987) Proc. Natl. Acad. Sci. USA 84: 2007), and human membrane cofactor protein (MCP) (cDNA reported by Lublin, D., et al. (1988) J. Exp. Med. 168: 181-194).

[0138]In an alternative embodiment, cells from transgenic pigs producing human complement inhibiting proteins can be used and further modified to inactivate the porcine CMP-Neu5Ac hydroxylase gene. Transgenic pigs producing human complement inhibiting proteins are known in the art (see, for example, U.S. Pat. No. 6,166,288).

[0139]In a further embodiment, porcine cells are provided that lack the porcine CMP-Neu5Ac hydroxylase gene and the porcine Forssman synthetase (FSM) gene. Animals lacking functional porcine CMP-Neu5Ac hydroxylase gene can be produced according to the present invention, and then cells from this animal can be further modified to knockout the porcine FSM synthetase gene, which is involved in the production of gal-α-gal epitopes, and plays a role in xenotransplant rejection. The porcine FSM synthetase gene has recently been identified (see U.S. Application 60/568,922). Alternatively, cells from these FSM synthetase gene knockout animals can be used and further modified to inactivate the porcine CMP-Neu5Ac hydroxylase gene.

[0140]In a still further embodiment, porcine cells are provided that lack the porcine CMP-Neu5Ac hydroxylase gene and the porcine isogloboside 3 synthase gene. Animals lacking functional porcine CMP-Neu5Ac hydroxylase gene can be produced according to the present invention, and then cells from this animal can be used to knockout the porcine iGb3 synthase gene. The porcine iGb3 synthase gene has recently been reported (U.S. Application No. 60/517,524). Alternatively, cells from these porcine iGb3 synthase gene knockout animals can be used and further modified to inactivate the porcine CMP-Neu5Ac hydroxylase gene.

[0141]In another embodiment, porcine cells are provided that lack the porcine CMP-Neu5Ac hydroxylase gene, the α(1,3)GT gene, the FSM synthetase gene, and the porcine iGb3 synthase gene. Animals lacking functional CMP-Neu5Ac hydroxylase gene can be produced according to the present invention, and then cells from this animal can be used to knockout the α(1,3)GT gene, the FSM synthetase gene, and the porcine iGb3 synthase gene. Homozygous α(1,3)GT-negative porcine have recently been reported (Phelps et al. supra, Science 2003; WO 04/028243) Alternatively, cells from these a(1,3)GT knockout animals can be used and further modified to inactivate the porcine iGb3 synthase gene, the porcine FSM synthetase gene, and the CMP-Neu5Ac hydroxylase gene, and, in addition, express human complement inhibiting proteins, such as, but not limited to, CD59, human decay accelerating factor (DAF), and human membrane cofactor protein (MCP).

VIII. Production of Genetically Modified Animals

[0142]The present invention provides methods of producing a transgenic pig that lacks expression of CMP-Neu5Ac hydroxylase through the genetic modification of porcine totipotent embryonic cells. In one embodiment, the animals can be produced by: (a) identifying one or more target CMP-Neu5Ac hydroxylase nucleic acid genomic sequences in an animal; (b) preparing one or more homologous recombination vectors targeting the CMP-Neu5Ac hydroxylase nucleic acid genomic sequences; (c) inserting the one or more targeting vectors into the genomes of a plurality of totipotent cells of the animal, thereby producing a plurality of transgenic totipotent cells; (d) obtaining a tetraploid blastocyst of the animal; (e) inserting the plurality of totipotent cells into the tetraploid blastocyst, thereby producing a transgenic embryo; (f) transferring the embryo to a recipient female animal; and (g) allowing the embryo to develop to term in the female animal. The method of transgenic animal production described here by which to generate a transgenic pig is further generally described in U.S. Pat. No. 6,492,575.

[0143]In another embodiment, the totipotent cells can be embryonic stem (ES) cells. The isolation of ES cells from blastocysts, the establishing of ES cell lines and their subsequent cultivation are carried out by conventional methods as described, for example, by Doetchmann et al., J. Embryol. Exp. Morph. 87:27-45 (1985); Li et al., Cell 69:915-926 (1992); Robertson, E. J. "Tetracarcinomas and Embryonic Stem Cells: A Practical Approach," ed. E. J. Robertson, IRL Press, Oxford, England (1987); Wurst and Joyner, "Gene Targeting: A Practical Approach," ed. A. L. Joyner, IRL Press, Oxford, England (1993); Hogen et al., "Manipulating the Mouse Embryo: A Laboratory Manual," eds. Hogan, Beddington, Costantini and Lacy, Cold Spring Harbor Laboratory Press, New York (1994); and Wang, et al., Nature 336:741-744 (1992). For example, after transforming embryonic stem cells with the targeting vector to alter the CMP-Neu5Ac hydroxylase gene, the cells can be plated onto a feeder layer in an appropriate medium, for example, such as fetal bovine serum enhanced DMEM. Cells containing the construct can be detected by employing a selective medium, and after sufficient time for colonies to grow, colonies can be picked and analyzed for the occurrence of homologous recombination. Polymerase chain reaction can be used, with primers within and without the construct sequence but at the target locus. Those colonies which show homologous recombination can then be used for embryo manipulating and blastocyst injection. Blastocysts can be obtained from superovulated females. The embryonic stem cells can then be trypsinized and the modified cells added to a droplet containing the blastocysts. At least one of the modified embryonic stem cells can be injected into the blastocoel of the blastocyst. After injection, at least one of the blastocysts can be returned to each uterine horn of pseudopregnant females. Females are then allowed to go to term and the resulting litters screened for mutant cells having the construct. The blastocysts are selected for different parentage from the transformed ES cells. By providing for a different phenotype of the blastocyst and the ES cells, chimeric progeny can be readily detected, and then genotyping can be conducted to probe for the presence of the modified CMP-Neu5Ac hydroxylase gene.

[0144]In a further embodiment of the invention, the totipotent cells can be embryonic germ (EG) cells. Embryonic Germ cells are undifferentiated cells functionally equivalent to ES cells, that is they can be cultured and transfected in vitro, then contribute to somatic and germ cell lineages of a chimera (Stewart et al., Dev. Biol. 161:626-628 (1994)). EG cells are derived by culture of primordial germ cells, the progenitors of the gametes, with a combination of growth factors: leukemia inhibitory factor, steel factor and basic fibroblast growth factor (Matsui, et al., Cell 70:841-847 (1992); Resnick, et al., Nature 359:550-551 (1992)). The cultivation of EG cells can be carried out using methods known to one skilled in the art, such as described in Donovan et al., "Transgenic Animals, Generation and Use," Ed. L. M. Houdebine, Harwood Academic Publishers (1997).

[0145]Tetraploid blastocysts for use in the invention can be obtained by natural zygote production and development, or by known methods by electrofusion of two-cell embryos and subsequently cultured as described, for example, by James, et al., Genet. Res. Camb. 60:185-194 (1992); Nagy and Rossant, "Gene Targeting: A Practical Approach," ed. A. L. Joyner, IRL Press, Oxford, England (1993); or by Kubiak and Tarkowski, Exp. Cell Res. 157:561-566 (1985).

[0146]The introduction of the ES cells or EG cells into the blastocysts can be carried out by any method known in the art, for example, as described by Wang, et al., EMBO J. 10:2437-2450 (1991).

[0147]A "plurality" of totipotent cells can encompass any number of cells greater than one. For example, the number of totipotent cells for use in the present invention can be about 2 to about 30 cells, about 5 to about 20 cells, or about 5 to about 10 cells. In one embodiment, about 5-10 ES cells taken from a single cell suspension are injected into a blastocyst immobilized by a holding pipette in a micromanipulation apparatus. Then the embryos are incubated for at least 3 hours, possibly overnight, prior to introduction into a female recipient animal via methods known in the art (see for example Robertson, E. J. "Teratocarcinomas and Embryonic Stem Cells: A Practical Approach" IRL Press, Oxford, England (1987)). The embryo can then be allowed to develop to term in the female animal.

Somatic Cell Nuclear Transfer to Produce Cloned, Transgenic Offspring

[0148]The present invention provides a method for cloning a pig lacking a functional CMP-Neu5Ac hydroxylase gene via somatic cell nuclear transfer. In general, a wide variety of methods to accomplish mammalian cloning are currently being rapidly developed and reported, any method that accomplishes the desired result can be used in the present invention. Nonlimiting examples of such methods are described below. For example, the pig can be produced by a nuclear transfer process comprising the following steps: obtaining desired differentiated pig cells to be used as a source of donor nuclei; obtaining oocytes from a pig; enucleating the oocytes; transferring the desired differentiated cell or cell nucleus into the enucleated oocyte, e.g., by fusion or injection, to form NT units; activating the resultant NT unit; and transferring said cultured NT unit to a host pig such that the NT unit develops into a fetus.

[0149]Nuclear transfer techniques or nuclear transplantation techniques are known in the art (Campbell et al, Theriogenology, 43:181 (1995); Collas, et al, Mol. Report. Dev., 38:264-267 (1994); Keefer et al, Biol. Reprod., 50:935-939 (1994); Sims, et al, Proc. Natl. Acad. Sci., USA, 90:6143-6147 (1993); WO 94/26884; WO 94/24274, and WO 90/03432, U.S. Pat. Nos. 4,944,384 and 5,057,420). In one nonlimiting example, methods are provided such as those described in U.S. Patent Publication No. 2003/0046722 to Collas, et al., which describes methods for cloning mammals that allow the donor chromosomes or donor cells to be reprogrammed prior to insertion into an enucleated oocyte. The invention also describes methods of inserting or fusing chromosomes, nuclei or cells with oocytes.

[0150]A donor cell nucleus, which has been modified to alter the CMP-Neu5Ac hydroxylase gene, is transferred to a recipient porcine oocyte. The use of this method is not restricted to a particular donor cell type. The donor cell can be as described in Wilmut, et al., Nature 385 810 (1997); Campbell, et al., Nature 380 64-66 (1996); or Cibelli, et al., Science 280 1256-1258 (1998). All cells of normal karyotype, including embryonic, fetal and adult somatic cells which can be used successfully in nuclear transfer can in principle be employed. Fetal fibroblasts are a particularly useful class of donor cells. Generally suitable methods of nuclear transfer are described in Campbell, et al., Theriogenology 43 181 (1995), Collas, et al., Mol. Reprod. Dev. 38 264-267 (1994), Keefer, et al., Biol. Reprod. 50 935-939 (1994), Sims, et al., Proc. Nat'l. Acad. Sci. USA 90 6143-6147 (1993), WO-A-9426884, WO-A-9424274, WO-A-9807841, WO-A-9003432, U.S. Pat. No. 4,994,384 and U.S. Pat. No. 5,057,420. Differentiated or at least partially differentiated donor cells can also be used. Donor cells can also be, but do not have to be, in culture and can be quiescent. Nuclear donor cells which are quiescent are cells which can be induced to enter quiescence or exist in a quiescent state in vivo. Prior art methods have also used embryonic cell types in cloning procedures (Campbell, et al. (Nature, 380:64-68, 1996) and Stice, et al (Biol. Reprod., 20 54:100-110, 1996).

[0151]Somatic nuclear donor cells may be obtained from a variety of different organs and tissues such as, but not limited to, skin, mesenchyme, lung, pancreas, heart, intestine, stomach, bladder, blood vessels, kidney, urethra, reproductive organs, and a disaggregated preparation of a whole or part of an embryo, fetus or adult animal. In a suitable embodiment of the invention, nuclear donor cells are selected from the group consisting of epithelial cells, fibroblast cells, neural cells, keratinocytes, hematopoietic cells, melanocytes, chondrocytes, lymphocytes (B and T), macrophages, monocytes, mononuclear cells, cardiac muscle cells, other muscle cells, granulose cells, cumulus cells, epidermal cells or endothelial cells. In another embodiment, the nuclear cell is an embryonic stem cell. In a preferred embodiment, fibroblast cells can be used as donor cells.

[0152]In another embodiment of the invention, the nuclear donor cells of the invention are germ cells of an animal. Any germ cell of an animal species in the embryonic, fetal, or adult stage may be used as a nuclear donor cell. In a suitable embodiment, the nuclear donor cell is an embryonic germ cell.

[0153]Nuclear donor cells may be arrested in any phase of the cell cycle (GO, GI, G2, S, M) so as to ensure coordination with the acceptor cell. Any method known in the art may be used to manipulate the cell cycle phase. Methods to control the cell cycle phase include, but are not limited to, GO quiescence induced by contact inhibition of cultured cells, GO quiescence induced by removal of serum or other essential nutrient, GO quiescence induced by senescence, GO quiescence induced by addition of a specific growth factor; GO or GI quiescence induced by physical or chemical means such as heat shock, hyperbaric pressure or other treatment with a chemical, hormone, growth factor or other substance; S-phase control via treatment with a chemical agent which interferes with any. Point of the replication procedure; M-phase control via selection using fluorescence activated cell sorting, mitotic shake off, treatment with microtubule disrupting agents or any chemical which disrupts progression in mitosis (see also Freshney, R. I., "Culture of Animal Cells: A Manual of Basic Technique," Alan R. Liss, Inc, New York (1983).

[0154]Methods for isolation of oocytes are well known in the art. Essentially, this can comprise isolating oocytes from the ovaries or reproductive tract of a pig. A readily available source of pig oocytes is slaughterhouse materials. For the combination of techniques such as genetic engineering, nuclear transfer and cloning, oocytes must generally be matured in vitro before these cells can be used as recipient cells for nuclear transfer, and before they can be fertilized by the sperm cell to develop into an embryo. This process generally requires collecting immature (prophase I) oocytes from mammalian ovaries, e.g., bovine ovaries obtained at a slaughterhouse, and maturing the oocytes in a maturation medium prior to fertilization or enucleation until the oocyte attains the metaphase II stage, which in the case of bovine oocytes generally occurs about 18-24 hours post-aspiration. This period of time is known as the "maturation period".

[0155]A metaphase II stage oocyte can be the recipient oocyte, at this stage it is believed that the oocyte can be or is sufficiently "activated" to treat the introduced nucleus as it does a fertilizing sperm. Metaphase II stage oocytes, which have been matured in vivo have been successfully used in nuclear transfer techniques. Essentially, mature metaphase II oocytes can be collected surgically from either non-superovulated or superovulated porcine 35 to 48, or 39-41, hours past the onset of estrus or past the injection of human chorionic gonadotropin (hCG) or similar hormone.

[0156]After a fixed time maturation period, which ranges from about 10 to 40 hours, and preferably about 16-18 hours, the oocytes can be enucleated. Prior to enucleation the oocytes can be removed and placed in appropriate medium, such as HECM containing 1 milligram per milliliter of hyaluronidase prior to removal of cumulus cells. The stripped oocytes can then be screened for polar bodies, and the selected metaphase II oocytes, as determined by the presence of polar bodies, are then used for nuclear transfer. Enucleation follows.

[0157]Enucleation can be performed by known methods, such as described in U.S. Pat. No. 4,994,384. For example, metaphase II oocytes can be placed in either HECM, optionally containing 7.5 micrograms per milliliter cytochalasin B, for immediate enucleation, or can be placed in a suitable medium, for example an embryo culture medium such as CR1aa, plus 10% estrus cow serum, and then enucleated later, preferably not more than 24 hours later, and more preferably 16-18 hours later.

[0158]Enucleation can be accomplished microsurgically using a micropipette to remove the polar body and the adjacent cytoplasm. The oocytes can then be screened to identify those of which have been successfully enucleated. One way to screen the oocytes is to stain the oocytes with 1 microgram per milliliter 33342 Hoechst dye in HECM, and then view the oocytes under ultraviolet irradiation for less than 10 seconds. The oocytes that have been successfully enucleated can then be placed in a suitable culture medium, for example, CR1 aa plus 10% serum.

[0159]A single mammalian cell of the same species as the enucleated oocyte can then be transferred into the perivitelline space of the enucleated oocyte used to produce the NT unit. The mammalian cell and the enucleated oocyte can be used to produce NT units according to methods known in the art. For example, the cells can be fused by electrofusion. Electrofusion is accomplished by providing a pulse of electricity that is sufficient to cause a transient breakdown of the plasma membrane. This breakdown of the plasma membrane is very short because the membrane reforms rapidly. Thus, if two adjacent membranes are induced to breakdown and upon reformation the lipid bilayers intermingle, small channels can open between the two cells. Due to the thermodynamic instability of such a small opening, it enlarges until the two cells become one. See, for example, U.S. Pat. No. 4,997,384 by Prather et al. A variety of electrofusion media can be used including, for example, sucrose, mannitol, sorbitol and phosphate buffered solution. Fusion can also be accomplished using Sendai virus as a fusogenic agent (Graham, Wister Inot. Symp. Monogr., 9, 19, 1969). Also, the nucleus can be injected directly into the oocyte rather than using electroporation fusion. See, for example, Collas and Barnes, Mol. Reprod. Dev., 38:264-267 (1994). After fusion, the resultant fused NT units are then placed in a suitable medium until activation, for example, CR1aa medium. Typically activation can be effected shortly thereafter, for example less than 24 hours later, or about 4-9 hours later.

[0160]The NT unit can be activated by any method that accomplishes the desired result. Such methods include, for example, culturing the NT unit at sub-physiological temperature, in essence by applying a cold, or actually cool temperature shock to the NT unit. This can be most conveniently done by culturing the NT unit at room temperature, which is cold relative to the physiological temperature conditions to which embryos are normally exposed. Alternatively, activation can be achieved by application of known activation agents. For example, penetration of oocytes by sperm during fertilization has been shown to activate prefusion oocytes to yield greater numbers of viable pregnancies and multiple genetically identical pigs after nuclear transfer. Also, treatments such as electrical and chemical shock can be used to activate NT embryos after fusion. See, for example, U.S. Pat. No. 5,496,720, to Susko-Parrish, et al. Additionally, activation can be effected by simultaneously or sequentially by increasing levels of divalent cations in the oocyte, and reducing phosphorylation of cellular proteins in the oocyte. This can generally be effected by introducing divalent cations into the oocyte cytoplasm, e.g., magnesium, strontium, barium or calcium, e.g., in the form of an ionophore. Other methods of increasing divalent cation levels include the use of electric shock, treatment with ethanol and treatment with caged chelators. Phosphorylation can be reduced by known methods, for example, by the addition of kinase inhibitors, e.g., serine-threonine kinase inhibitors, such as 6-dimethyl-aminopurine, staurosporine, 2-aminopurine, and sphingosine. Alternatively, phosphorylation of cellular proteins can be inhibited by introduction of a phosphatase into the oocyte, e.g., phosphatase 2A and phosphatase 2B.

[0161]The activated NT units can then be cultured in a suitable in vitro culture medium until the generation of cell colonies. Culture media suitable for culturing and maturation of embryos are well known in the art. Examples of known media, which can be used for embryo culture and maintenance, include Ham's F-10+10% fetal calf serum (FCS), Tissue Culture Medium-199 (TCM-199)+10% fetal calf serum, Tyrodes-Albumin-Lactate-Pyruvate (TALP), Dulbecco's Phosphate Buffered Saline (PBS), Eagle's and Whitten's media.

[0162]Afterward, the cultured NT unit or units can be washed and then placed in a suitable media contained in well plates which preferably contain a suitable confluent feeder layer. Suitable feeder layers include, by way of example, fibroblasts and epithelial cells. The NT units are cultured on the feeder layer until the NT units reach a size suitable for transferring to a recipient female, or for obtaining cells which can be used to produce cell colonies. Preferably, these NT units can be cultured until at least about 2 to 400 cells, more preferably about 4 to 128 cells, and most preferably at least about 50 cells.

[0163]Activated NT units can then be transferred (embryo transfers) to the oviduct of an female pigs. In one embodiment, the female pigs can be an estrus-synchronized recipient gilt. Crossbred gilts (large white/Duroc/Landrace) (280-400 lbs) can be used. The gilts can be synchronized as recipient animals by oral administration of 18-20 mg ReguMate (Altrenogest, Hoechst, Warren, N.J.) mixed into the feed. Regu-Mate can be fed for 14 consecutive days. One thousand units of Human Chorionic Gonadotropin (hCG, Intervet America, Millsboro, Del.) can then be administered i.m. about 105 h after the last Regu-Mate treatment. Embryo transfers of the can then be performed about 22-26 h after the hCG injection. In one embodiment, the pregnancy can be brought to term and result in the birth of live offspring. In another embodiment, the pregnancy can be 5 terminated early and embryonic cells can be harvested.

[0164]The methods for embryo transfer and recipient animal management in the present invention are standard procedures used in the embryo transfer industry. Synchronous transfers are important for success of the present invention, i.e., the stage of the NT embryo is in synchrony with the estrus cycle of the recipient female. See, for example, Siedel, G. E., Jr. "Critical review of embryo transfer procedures with cattle" in Fertilization and Embryonic Development in Vitro (1981) L. Mastroianni, Jr. and J. D. Biggers, ed., Plenum Press, New York, N.Y., page 323.

VIII. Porcine Animals, Organs, Tissues, Cells and Cell Lines

[0165]The present invention provides viable porcine in which both alleles of the CMP-Neu5Ac hydroxylase gene have been inactivated. The invention also provides organs, tissues, and cells derived from such porcine, which are useful for xenotransplantation.

[0166]In one embodiment, the invention provides porcine organs, tissues and/or purified or substantially pure cells or cell lines obtained from pigs that lack any expression of functional CMP-Neu5Ac hydroxylase.

[0167]In one embodiment, the invention provides organs that are useful for xenotransplantation. Any porcine organ can be used, including, but not limited to: brain, heart, lungs, glands, brain, eye, stomach, spleen, pancreas, kidneys, liver, intestines, uterus, bladder, skin, hair, nails, ears, nose, mouth, lips, gums, teeth, tongue, salivary glands, tonsils, pharynx, esophagus, large intestine, small intestine, rectum, anus, pylorus, thyroid gland, thymus gland, suprarenal capsule, bones, cartilage, tendons, ligaments, skeletal muscles, smooth muscles, blood vessels, blood, spinal cord, trachea, ureters, urethra, hypothalamus, pituitary, adrenal glands, ovaries, oviducts, uterus, vagina, mammary glands, testes, seminal vesicles, penis, lymph, lymph nodes and lymph vessels.

[0168]In another embodiment, the invention provides tissues that are useful for xenotransplantation. Any porcine tissue can be used, including, but not limited to: epithelium, connective tissue, blood, bone, cartilage, muscle, nerve, adenoid, adipose, areolar, bone, brown adipose, cancellous, muscle, cartaginous, cavernous, chondroid, chromaffin, dartoic, elastic, epithelial, fatty, fibrohyaline, fibrous, Gaingee, gelatinous, granulation, gut-associated lymphoid, Haller's vascular, hard hemopoietic, indifferent, interstitial, investing, islet, lymphatic, lymphoid, mesenchymal, mesonephric, mucous connective, multilocular adipose, myeloid, nasion soft, nephrogenic, nodal, osseous, osteogenic, osteoid, periapical, reticular, retiform, rubber, skeletal muscle, smooth muscle, and subcutaneous tissue.

[0169]In a further embodiment, the invention provides cells and cell lines from porcine animals that lack expression of functional alpha1,3GT. In one embodiment, these cells or cell lines can be used for xenotransplantation. Cells from any porcine tissue or organ can be used, including, but not limited to: epithelial cells, fibroblast cells, neural cells, keratinocytes, hematopoietic cells, melanocytes, chondrocytes, lymphocytes (B and T), macrophages, monocytes, mononuclear cells, cardiac muscle cells, other muscle cells, quadraturehosphate cells, cumulus cells, epidermal cells, endothelial cells, Islets of Langerhans cells, pancreatic insulin secreting cells, pancreatic alpha-2 cells, pancreatic beta cells, pancreatic alpha-1 cells, blood cells, blood precursor cells, bone cells, bone precursor cells, neuronal stem cells, primordial stem cells, hepatocytes, keratinocytes, umbilical vein endothelial cells, aortic endothelial cells, microvascular endothelial cells, fibroblasts, liver stellate cells, aortic smooth muscle cells, cardiac myocytes, neurons, Kupffer cells, smooth muscle cells, Schwann cells, and epithelial cells, erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils, adipocytes, chondrocytes, pancreatic islet cells, thyroid cells, parathyroid cells, parotid cells, tumor cells, glial cells, astrocytes, red blood cells, white blood cells, macrophages, epithelial cells, somatic cells, pituitary cells, adrenal cells, hair cells, bladder cells, kidney cells, retinal cells, rod cells, cone cells, heart cells, pacemaker cells, spleen cells, antigen presenting cells, memory cells, T cells, B cells, plasma cells, muscle cells, ovarian cells, uterine cells, prostate cells, vaginal epithelial cells, sperm cells, testicular cells, germ cells, egg cells, leydig cells, peritubular cells, sertoli cells, lutein cells, cervical cells, endometrial cells, mammary cells, follicle cells, mucous cells, ciliated cells, nonkeratinized epithelial cells, keratinized epithelial cells, lung cells, goblet cells, columnar epithelial cells, dopaminergic cells, squamous epithelial cells, osteocytes, osteoblasts, osteoclasts, embryonic stem cells, fibroblasts and fetal fibroblasts. In a specific embodiment, pancreatic cells, including, but not limited to, Islets of Langerhans cells, insulin secreting cells, 48 alpha-2 cells, beta cells, alpha-1 cells from pigs that lack expression of functional alpha-1,3-GT are provided.

[0170]Nonviable derivatives include tissues stripped of viable cells by enzymatic or chemical treatment these tissue derivatives can be further processed via crosslinking or other chemical treatments prior to use in transplantation. In a preferred embodiment, the derivatives include extracellular matrix derived from a variety of tissues, including skin, urinary, bladder or organ submucosal tissues. Also, tendons, joints and bones stripped of viable tissue to include heart valves and other nonviable tissues as medical devices are provided.

Therapeutic Uses

[0171]The cells can be administered into a host in order in a wide variety of ways. Preferred modes of administration are parenteral, intraperitoneal, intravenous, intradermal, epidural, intraspinal, intrasternal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, intramuscular, intranasal, subcutaneous, intraorbital, intracapsular, topical, transdermal patch, via rectal, vaginal or urethral administration including via suppository, percutaneous, nasal spray, surgical implant, internal surgical paint, infusion pump, or via catheter. In one embodiment, the agent and carrier are administered in a slow release formulation such as a direct tissue injection or bolus, implant, microparticle, microsphere, nanoparticle or nanosphere.

[0172]Disorders that can be treated by infusion of the disclosed cells include, but are not limited to, diseases resulting from a failure of a dysfunction of normal blood cell production and maturation (i.e., aplastic anemia and hypoproliferative stem cell disorders); neoplastic, malignant diseases in the hematopoietic organs (e.g., leukemia and lymphomas); broad spectrum malignant solid tumors of non-hematopoietic origin; autoimmune conditions; and genetic disorders. Such disorders include, but are not limited to diseases resulting from a failure or dysfunction of normal blood cell production and maturation hyperproliferative stem cell disorders, including aplastic anemia, pancytopenia, agranulocytosis, thrombocytopenia, red cell aplasia, Blackfan Diamond syndrome, due to drugs, radiation, or infection, idiopathic; hematopoietic malignancies including acute lymphoblastic (lymphocytic) leukemia, chronic lymphocytic leukemia, acute myclogenous leukemia, chronic myelogenous, leukemia, acute malignant myelosclerosis, multiple myeloma, polycythemia vera, agnogenic myelometaplasia, Waldenstrom's macroglobulinemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma; immunosuppression in patients with malignant, solid tumors including malignant melanoma, carcinoma of the stomach, ovarian carcinoma, breast carcinoma, small cell lung carcinoma, retinoblastoma, testicular carcinoma, glioblastoma, rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, lymphoma; autoimmune diseases including rheumatoid arthritis, diabetes type 1, chronic hepatitis, multiple sclerosis, systemic lupus erythematosus; genetic (congenital) disorders including anemias, familial aplastic, Fanconi's syndrome, dihydrofolate reductase deficiencies, formamino transferase deficiency, Lesch-Nyhan syndrome, congenital dyserythropoietic syndrome IIV, Chwachmann-Diamond syndrome, dihydrofolate reductase deficiencies, forinamino transferase deficiency, Lesch-Nyhan syndrome, congenital spherocytosis, congenital elliptocytosis, congenital stomatocytosis, congenital Rh null disease, paroxysmal nocturnal hemoglobinuria, G6PD (glucose quadraturehosphate dehydrogenase) variants 1, 2, 3, pyruvate kinase deficiency, congenital erythropoietin sensitivity, deficiency, sickle cell disease and trait, thalassemia alpha, beta, gamma, met-hemoglobinemia, congenital disorders of immunity, severe combined immunodeficiency disease (SCID), bare lymphocyte syndrome, ionophore-responsive combined immunodeficiency, combined immunodeficiency with a capping abnormality, nucleoside phosphorylase deficiency, granulocyte actin deficiency, infantile agranulocytosis, Gaucher's disease, adenosine deaminase deficiency, Kostmann's syndrome, reticular dysgenesis, congenital Leukocyte dysfunction syndromes; and others such as osteoporosis, myelosclerosis, acquired hemolytic anemias, acquired immunodeficiencies, infectious disorders causing primary or secondary immunodeficiencies, bacterial infections (e.g., Brucellosis, Listerosis, tuberculosis, leprosy), parasitic infections (e.g., malaria, Leishmaniasis), fungal infections, disorders involving disproportionsin lymphoid cell sets and impaired immune functions due to aging, phagocyte disorders, Kostmann's agranulocytosis, chronic granulomatous disease, Chediak-Higachi syndrome, neutrophil actin deficiency, neutrophil membrane GP-180 deficiency, metabolic storage diseases, mucopolysaccharidoses, mucolipidoses, miscellaneous disorders involving immune mechanisms, Wiskott-Aldrich Syndrome, alpha lantirypsin deficiency, etc.

[0173]Diseases or pathologies include neurodegenerative diseases, hepatodegenerative diseases, nephrodegenerative disease, spinal cord injury, head trauma or surgery, viral infections that result in tissue, organ, or gland degeneration, and the like. Such neurodegenerative diseases include but are 10 not limited to, AIDS dementia complex; demyeliriating diseases, such as multiple sclerosis and acute transferase myelitis; extrapyramidal and cerebellar disorders, such as lesions of the ecorticospinal system; disorders of the basal ganglia or cerebellar disorders; hyperkinetic movement disorders, such as Huntington's Chorea and senile chorea; drug-induced movement disorders, such as those induced by drugs that block CNS dopamine receptors; hypokinetic movement disorders, such as Parkinson's disease; progressive supra-nucleo palsy; structural lesions of the cerebellum; spinocerebellar degenerations, such as spinal ataxia, Friedreich's ataxia, cerebellar cortical degenerations, multiple systems degenerations (Mencel, Dejerine Thomas, Shi-Drager, and Machado-Joseph), systermioc disorders, such as Rufsum's disease, abetalipoprotemia, ataxia, telangiectasia; and mitochondrial multisystem disorder; demyelinating core disorders, such as multiple sclerosis, acute transverse myelitis; and disorders of the motor unit, such as neurogenic muscular atrophies (anterior horn cell degeneration, such as amyotrophic lateral sclerosis, infantile spinal muscular atrophy and juvenile spinal muscular atrophy); Alzheimer's disease; Down's Syndrome in middle age; Diffuse Lewy body disease; Senile Dementia of Lewy body type; Parkinson's Disease, Wernicke-Korsakoff syndrome; chronic alcoholism; Creutzfeldt-Jakob disease; Subacute sclerosing panencephalitis hallefforden-Spatz disease; and Dementia pugilistica. See, e.g., Berkow et. al., (eds.) (1987), The Merck Manual, (15') ed.), Merck and Co., Rahway, N.J.

Industrial Farming Uses

[0174]The present invention provides viable porcine for purposes of farming applications in which one or both alleles of the CMP-Neu5Ac hydroxylase gene have been inactivated. Inactivation of one or both alleles of the CMP-Neu5Ac hydroxylase gene can reduce the susceptibility of porcine animals to zoonotic diseases and infections in pigs such as, for example, E. coli, pig rotavirus, and pig transmissible gastroenteritis coronavirus, and any other zoonotic or enterotoxigenic organism that utilizes Neu5Gc in a host animal. The reduction in disease susceptibility allows greater economic realization of farming operations due to the ability to harvest more healthy animals, and the reduction of animal death due to enterotoxigenic organisms.

[0175]The following examples are offered by way of illustration and not by way of limitation.

EXAMPLES

Isolation of Nucleic Acids

[0176]Combination strategy of PCR-based methods was employed to identify the porcine CMP-Neu5Ac hydroxylase gene. Such PCR methods are well known in the art and described, for example, in PCR Technology, H. A. Erlich, ed., Stockton Press, London, 1989; PCR Protocols: A Guide to Methods and Applications, M. A. Innis, D. H. Gelfand, J. J. Sninsky, and T. J. White, eds., Academic Press, Inc., New York, 1990.

[0177]Total RNA was extracted from an adult porcine (Great Yorkshire) spleen using Trizol reagent (Gibco, Grand Island, N.Y.). After treatment with Dnase I (Ambion, Inc., Austin, Tex.), poly A.sup.+ RNA was separated using the Dynabeads mRNA Purification Kit (Dynal, Oslo, Norway). To identify the 5'- or 3'-end of porcine CMP-Neu5Ac Hydroxylase gene, 5'- or 3'-RACE (rapid amplification of cDNA ends) procedures were performed using Marathon® cDNA Amplification kit (Clontech). To identify exon-intron boundaries, or 5'- or 3'-flanking region of the transcripts, porcine GenomeWalker® libraries were constructed using Universal GenomeWalker® Library kit (Clontech). Gene-specific and nested primer pairs were designed from the partial cDNA sequence provided by GenBank Accession #A59058.

Determination of cDNA and Genomic CMP-Neu5Ac Hydroxylase Sequence

[0178]5'- or 3'-RACE analysis: To identify the 5' and 3' ends of porcine CMP-Neu5Ac hydroxylase gene transcripts, 5'- and 3'-RACE procedures were performed using the Marathon cDNA Amplification Kit (Clontech) with poly A+ RNA isolated from adult porcine spleen as a template. First strand cDNA synthesis from 1 ug of poly A+ RNA was accomplished using 20 U of AMV-RT and 1 pmol of the supplied cDNA Synthesis Primer by incubating at 48° C. for 2 hours. Second strand cDNA synthesis involved incubating the entire first strand reaction with a supplied enzyme cocktail composed of Rnase H, E. coli DNA polymerase I, and E. coli DNA polymerase I, and E. coli DNA ligase at 16° C. for 1.5 hr. After blunting of the double stranded cDNA ends by T4 DNA polymerase, the supplied Marathon cDNA Adapters were ligated to an aliquot of purified, double-stranded cDNA. Dilution of the adapter-ligated product in 10 mM ticme-KOH/0.1 mM EDTA buffer provided with the kit readied the cDNA for PCR amplification.

[0179]To obtain the 5'- and 3'-most sequences of the porcine CMP-Neu5Ac hydroxylase gene transcripts, provided Marathon cDNA Amplification primer sets were paired with gene-specific and nested gene-specific primers based on the sequence provided by GenBank accession number A59058. These primer sets are provided for in Table 13. By this method, oligonucleotide primers based on the sequence contained in Genbank accession number A59058 are oriented in the 3' and 5' directions and are used to generate overlapping PCR fragments. These overlapping 3' and 5' products are combined to produce an intact full-length cDNA. This method is described, for example, in Innis, et al., supra; and Frohman et al., Proc. Natl. Acad. Sci., 85:8998, 1988, and further described, for example, in U.S. Pat. No. 4,683,195.

[0180]Genome Walking analysis: To identify exon-intron boundaries, or 5'- or 3'-flanking region of the porcine CMP-Neu5Ac hydroxylase transcripts, porcine GenomeWalker® libraries were constructed using the Universal GenomeWalker® Library Kit (Clontech, Palo Alto, Calif.).

[0181]Briefly, five aliquots of porcine genomic DNA were separately digested with a single blunt-cutting restriction endonuclease (DraI, EcoRV, PvuII, ScaI, or StuI). After phenol-chloroform extraction, ethanol precipitation, and resuspension of the restricted fragments, a portion of each digested aliquot was used in separate ligation reaction with the GenomeWalker adapters provided with the kit. This process created five libraries for use in the PCR based cloning strategy. Primer pairs identified in Table 13 were used in a genome walking strategy. Either eLON-Gase or TaKaRa LA Taq (Takara Shuzo Co., Ltd., Shiga, Japan) enzyme was used for PCR in all GenomeWalker experiments as well as for direct long PCR of genomic DNA. The thermal cycling conditions recommended by the manufacturer were employed in all GenomeWalker-PCR experiments on a Perkin Elmer Gene Amp System 9600 or 9700 thermocycler.

TABLE-US-00016 TABLE 13 Primers Used in PCR Strategies Primer PCR Set Strategy Sequence XA 3'-RACE/ 5'-CATGGACCTCAAGCTGGGGGACAAGA-3' Genome Walking XB 3'-RACE/ 5'-GTGTTCGACCCTTGGTTAATCGGTCCTG-3' Genome Walking XM 5'-RACE/ 5'-CAGGACCGATTAACCAAGGGTCGAACAC-3' Genome Walking XN 5'-RACE/ 5'-TCTTGTCCCCCAGCTTGAGGTCCATG-3' Genome Walking

[0182]Subcloning and sequencing of amplified products: PCR products amplified from genomic DNA, GeneWalker-PCR (Clontech), and 5'-3'-RACE wre gel-purified using the Qiagen Gel Extraction Kit (Qiagen, Valencia, Calif.), if necessary, then subcloned into the pCR11 vector provided with the Original TA Cloning Kit (Invitrogen, Carlsbad, Calif.). Plasmid DNA minipreps of pCR11-ligated inserts were prepared with the QIAprep Spin Miniprep Kit (Qiagen) as directed. Automated fluorescent sequencing of cloned inserts was performed using an ABI 377 Automated Sequence Analyzer (Applied Biosystems, Inc., Foster City, Calif.) with either the dRhodamine or BigDye Terminator Cycle Sequencing Kits (Applied Biosystems) primed with T7 and SP6 promoter primers or primers designed from internal insert sequences.

[0183]Primer Synthesis: All oligonucleotides used as primers in the various PCR-based methods were synthesized on an ABI 394 DNA Synthesizer (Applied Biosystems, Inc., Foster City Calif.) using solid phase synthesis and phosphoramidite nucleoside chemistry, unless otherwise stated.

Analysis of Transcription Factor Binding Sites

[0184]Analysis of possible transcription factors binding sites were performed using 228 bp of exon 1 sequence and 601 bp upstream of exon 1. The sequences were screened using "MatInspector" software available in www.genomatix.de. The sequences contain binding sites for the following transcription factors: MZF1, ETSF, SF1, CMYB, MEF2, NMP4, BRN2, AP1, GAT1, SATB1, ATF, USF, WHN, ZF5, NFκB, MOK2, NFY, MYCMAX, ZF5. See FIG. 4.

Construction of Porcine CMP-Neu5Ac Hydroxylase Homologous Recombination Targeting Vectors

[0185]CMP-Neu5Ac hydroxylase knock-out target vector: A vector targeting Exon 6 of the porcine CMP-Neu5Ac Hydroxylase gene for knockout can be constructed. In a first step, a portion of Intron 6 is amplified by PCR for use as a 3'-arm of the targeting vector utilizing primers such as pDH3 (5'-CTCCTGGAAGCTTCTGTCAAGACGAAC-3') and pDH4 (5'-GCCTGATACACAGTGCTGTGCAATGGT-3') (see FIG. 5). The amplified PCR product of approximately 3.7 kb can be inserted into the pCRII vector after restriction enzyme digestion utilizing EcoRI and ApaI. See FIG. 6.

[0186]Following the insertion of the 3'-arm, a portion of Intron 5 can be amplified by PCR for use as a 5'-arm in the targeting vector utilizing primers such as pDH1 (5'-ACCACCCAAGTCTGGAATCTTCTTACACT-3') and pDH2 (5'-GACTCTCATACAAAAGCTAAGCTGGGTAAG-3') (see FIG. 5). Following this initial amplification, successive PCR amplifications can be performed to introduce an EcoNI restriction site into the 3' portion of the 5'-arm utilizing primers such as pDH1 in conjunction with primers such as pDH2a (5'-GACTCTCATACAAAACCTAAGCTGGGTAAG-3'), pDH2b (5'-GACTCTCATACAAAACCTAGGCTGGGTAAG-3'), and pDH2c (5'-GACTCTCATACAAAACCTAGGCTAGGTAAG-3'), respectively (see FIG. 5). The amplified PCR product of approximately 2.6 kb containing the engineered EcoNI site can be restriction enzyme digested using ApaI and EcoNI, and inserted into the pCRII vector containing the previously inserted 3'-arm (See FIG. 7), generating a targeting vector (pDHΔex6) containing an approximate 6.3 kb porcine CMP-Neu5Ac hydroxylase targeting sequence (see FIG. 8).

EGFP knock-in target vector: pDHΔex6 can be further modified by an in-frame insertion of an enhanced green fluorescent protein sequence at the terminal 3' end of Exon 6 of the porcine CMP-Neu5Ac hydroxylase gene. In a first step, a portion of Intron 5 and a portion of Exon 6 of the porcine CMP-Neu5Ac hydroxylase gene can be amplified by PCR utilizing primers such as pDH5 (5'-CCTTATACTGGCCCCAATTGGATCTTAC-3') and pDH6 (5'-CCTTATACTGGCCCCAATTGGATCTTAC-3') (see FIG. 9), and inserted into a vector (pIRES-EGFP) containing the EGFP and a poly A tail following restriction enzyme digestion with MunI and EcoRv. Following insertion, PCR amplification can be performed on the pIRES-EGFP vector containing the insertion utilizing primer such as pDH7 (5'-CTTACCTAGCCTAGGTTTTGTATGAGAGTC-3') and pDH8 (5'-GACAAACCACAATTGGAATGCACTCGAG-3') (see FIG. 9). The PCR amplified product can be restriction enzyme digested using EcoNI and MunI and inserted into the previously constructed pDHΔex6 targeting vector (see FIG. 10). The resultant targeting vector (pDHΔex6-EGFP) is illustrated in FIG. 11.

Production of Porcine CMP-Neu5Ac Hydroxylase Deficient Fetal Fibroblast Cells

[0187]Fetal fibroblast cells are isolated from 10 fetuses of the same pregnancy at day 33 of gestation. After removing the head and viscera, fetuses are washed with Hanks' balanced salt solution (HBSS; Gibco-BRL, 1 5 Rockville, Md.), placed in 20 ml of HBSS, and diced with small surgical scissors. The tissue is pelleted and resuspended in 50-ml tubes with 40 ml of DMEM and 100 U/ml collagenase (Gibco-BRL) per fetus. Tubes are incubated for 40 min in a shaking water bath at 37 C. The digested tissue is allowed to settle for 3-4 min and the cell-rich supernatant is transferred to a new 50-ml tube and pelleted. The cells are then resuspended in 40 ml of DMEM containing 10% fetal calf serum (FCS), 1X nonessential amino acids, 1 mM sodium pyruvate and 2 ng/ml bFGF, and seeded into 10 cm. dishes. For transfections, 10 μg of linearized pDHΔex6EGFP vector is introduced into 2 million cells using lipofectamine 2000 (Carlsbad, Calif.) following manufacturer's guidelines. Forty-eight hours after transfection, the transfected cells are seeded into 48-well plates at a density of 2,000 cells per well and grown to confluence. Following confluence, cells are sorted via Fluorescent Activated Cell Sorting (FACS) (FACSCalibur, Becton Dickenson, San Jose, Calif.), wherein only cells having undergone homologous recombination and expressing the EGFP are selected (see, for example, FIG. 13).

[0188]Selected cells are then reseeded, and grown to confluency. Once confluency is reached, several small aliquots are frozen back for future use, and the remainder are utilized for PCR and Southern Blot verification of homologous recombination. The putative targeted clones can be screened by PCR across the Exon 6/EGFP insert utilizing a primer complimentary to the EGFP sequence and a primer complimentary to a sequence outside the vector as the antisense primer. The PCR products can be analyzed by Southern Blotting using an EGFP probe to identify the positive clones by the presence of the expected band from the targeted allele.

Generation of Cloned Pigs Using Heterologous CMP-Neu5Ac Hydroxylase Deficient Fetal Fibroblasts as Nuclear Donors

[0189]Preparation of cells for Nuclear Transfer: Donor cells are genetically manipulated to produce cells heterozygous for porcine CMP-Neu5Ac hydroxylase as described generally above. Nuclear transfer can be performed by methods that are well known in the art (see, e.g., Dai et al., Nature Biotechnology 20: 251255, 2002; and Polejaeva et al., Nature 407:86-90, 2000), using EGFP selected porcine fibroblasts as nuclear donors that are produced as described in detail hereinabove.

[0190]Oocytes can be isolated from synchronized super ovulated sexually mature Large-White X Landacre outcross gilts as described, for example, in 1. Polejaeva et al. Nature 407: 505 (2000). Donor cells are synchronized in presumptive G0/G1 by serum starvation (0.5%) between 24 to 120 hours. Oocytes enucleation, nuclear transfer, electrofusion, and electroactivation can be performed as essentially described in, for example, A. C. Boquest et al., Biol. Reproduction 68: 1283 (2002). Reconstructed embryos can be cultured overnight and can be transferred to the oviducts of asynchronous (-1 day) recipients. Pregnancies can be confirmed and monitored by real-time ultrasound.

[0191]Breeding of heterozygous CMP-Neu5Ac hydroxylase single knockout (SKO) male and female pigs can be performed to establish a miniherd of double knockout (DKO) pigs.

Verification of CMP-Neu5Ac Hydroxylase Deficient Pigs

[0192]Following breeding of the single knockout male and female pigs, verification of double knockout pigs is performed. Fibroblasts from the offspring are incubated with 1 μg of anti-N-glycolyl GM2 monoclonal antibody MK2-34 (Seikagaku Kogyo, JP) on ice for 30 minutes. FITC conjugated goat-anti-mouse IgG is added to the cells and antibody binding indicating the presence or absence of Neu5GC, and thus, an indication of the presence or absence of active CMP-Neu5Ac hydroxylase, is detected by flow cytometry (FACSCalibur, Becton Dickenson, San Jose, Calif.).

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 70 <210> SEQ ID NO 1 <211> LENGTH: 2728 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 1 cccgacgtcc tggcagcgcc caggcactgt tattggtgcc tcctgtgtcc acgcgcttcc 60 cggccaggca gccctggcgg atcctatttt ctgttccccc gattctggta cctctccctc 120 ccgccctcgg tgcgcagccg tcctcctgca gtgcctgctc ctccaggggc gaaaccgatc 180 agggatcagg ccacccgcct cctgaacatc cctccttagt tcccacagtc taatgccttg 240 tggaagcaaa tgagccacag aagctgaagg aaaaaccacc attctttctt aatacctgga 300 gagaggcaac gacagactat gagcagcatc gaacaaacga cggagatcct gttgtgcctc 360 tcacctgccg aagctgccaa tctcaaggaa ggaatcaatt ttgttcgaaa taagagcact 420 ggcaaggatt acatcttatt taagaataag agccgcctga aggcatgtaa gaacatgtgc 480 aagcaccaag gaggcctctt cattaaagac attgaggatc taaatggaag gtctgttaaa 540 tgcacaaaac acaactggaa gttagatgta agcagcatga agtatatcaa tcctcctgga 600 agcttctgtc aagacgaact ggttgtagaa aaggatgaag aaaatggagt tttgcttcta 660 gaactaaatc ctcctaaccc gtgggattca gaacccagat ctcctgaaga tttggcattt 720 ggggaagtgc agatcacgta ccttactcac gcctgcatgg acctcaagct gggggacaag 780 agaatggtgt tcgacccttg gttaatcggt cctgcttttg cgcgaggatg gtggttacta 840 cacgagcctc catctgattg gctggagagg ctgagccgcg cagacttaat ttacatcagt 900 cacatgcact cagaccacct gagttaccca acactgaaga agcttgctga gagaagacca 960 gatgttccca tttatgttgg caacacggaa agacctgtat tttggaatct gaatcagagt 1020 ggcgtccagt tgactaatat caatgtagtg ccatttggaa tatggcagca ggtagacaaa 1080 aatcttcgat tcatgatctt gatggatggc gttcatcctg agatggacac ttgcattatt 1140 gtggaataca aaggtcataa aatactcaat acagtggatt gcaccagacc caatggagga 1200 aggctgccta tgaaggttgc attaatgatg agtgattttg ctggaggagc ttcaggcttt 1260 ccaatgactt tcagtggtgg aaaatttact gaggaatgga aagcccaatt cattaaaaca 1320 gaaaggaaga aactcctgaa ctacaaggct cggctggtga aggacctaca acccagaatt 1380 tactgcccct ttcctgggta tttcgtggaa tcccacccag cagacaagta tattaaggaa 1440 acaaacatca aaaatgaccc aaatgaactc aacaatctta tcaagaagaa ttctgaggtg 1500 gtaacctgga ccccaagacc tggagccact cttgatctgg gtaggatgct aaaggaccca 1560 acagacagca agggcatcgt agagcctcca gaagggacta agatttacaa ggattcctgg 1620 gattttggcc catatttgaa tatcttgaat gctgctatag gagatgaaat atttcgtcac 1680 tcatcctgga taaaagaata cttcacttgg gctggattta aggattataa cctggtggtc 1740 aggatgattg agacagatga ggacttcagc cctttgcctg gaggatatga ctatttggtt 1800 gactttctgg atttatcctt tccaaaagaa agaccaagcc gggaacatcc atatgaggaa 1860 attcggagcc gggttgatgt catcagacac gtggtaaaga atggtctgct ctgggatgac 1920 ttgtacatag gattccaaac ccggcttcag cgggatcctg atatatacca tcatctgttt 1980 tggaatcatt ttcaaataaa actccccctc acaccacctg actggaagtc cttcctgatg 2040 tgctctgggt agagaggacc tgagctgtcc caggggtgcc caacaacatg aaaaaatcaa 2100 gaatttattg ctgctacgtc aaagcttata ccagagatta tgccttatag acattagcaa 2160 tggataatta tatgttgcac ttgtgaaatg tgcacatatc ctgtttatga atcaccacat 2220 agccagatta tcaatatttt acttatttcg taaaaaatcc acaattttcc ataacagaat 2280 caacgtgtgc aataggaaca agattgctat ggaaaacgag ggtaacagga ggagatatta 2340 atccaagcat agaagaaata gacaaatgag gggccataag gggaatatag ggaagagaaa 2400 aaaattaaga tggaatttta aaaggagaat gtaaaaaata gatatttgtt ccttaatagg 2460 ttgattcctc aaatagagcc catgaatata atcaaatagg aagggttcat gactgttttc 2520 aatttttcaa aaagctttgt tgaaatcata gacttgcaaa acaaggctgt agaggccacc 2580 ctaaaatgga aaatttcact gggactgaaa ttattttgat tcaatgacaa aatttgttat 2640 ttactgcgga ttataaactc taacaaatag cgatctcttt gcttcataaa aacataaaca 2700 ctagctagta ataaaatgag ttctgcag 2728 <210> SEQ ID NO 2 <211> LENGTH: 577 <212> TYPE: PRT <213> ORGANISM: Porcine <400> SEQUENCE: 2 Met Ser Ser Ile Glu Gln Thr Thr Glu Ile Leu Leu Cys Leu Ser Pro 1 5 10 15 Ala Glu Ala Ala Asn Leu Lys Glu Gly Ile Asn Phe Val Arg Asn Lys 20 25 30 Ser Thr Gly Lys Asp Tyr Ile Leu Phe Lys Asn Lys Ser Arg Leu Lys 35 40 45 Ala Cys Lys Asn Met Cys Lys His Gln Gly Gly Leu Phe Ile Lys Asp 50 55 60 Ile Glu Asp Leu Asn Gly Arg Ser Val Lys Cys Thr Lys His Asn Trp 65 70 75 80 Lys Leu Asp Val Ser Ser Met Lys Tyr Ile Asn Pro Pro Gly Ser Phe 85 90 95 Cys Gln Asp Glu Leu Val Val Glu Lys Asp Glu Glu Asn Gly Val Leu 100 105 110 Leu Leu Glu Leu Asn Pro Pro Asn Pro Trp Asp Ser Glu Pro Arg Ser 115 120 125 Pro Glu Asp Leu Ala Phe Gly Glu Val Gln Ile Thr Tyr Leu Thr His 130 135 140 Ala Cys Met Asp Leu Lys Leu Gly Asp Lys Arg Met Val Phe Asp Pro 145 150 155 160 Trp Leu Ile Gly Pro Ala Phe Ala Arg Gly Trp Trp Leu Leu His Glu 165 170 175 Pro Pro Ser Asp Trp Leu Glu Arg Leu Ser Arg Ala Asp Leu Ile Tyr 180 185 190 Ile Ser His Met His Ser Asp His Leu Ser Tyr Pro Thr Leu Lys Lys 195 200 205 Leu Ala Glu Arg Arg Pro Asp Val Pro Ile Tyr Val Gly Asn Thr Glu 210 215 220 Arg Pro Val Phe Trp Asn Leu Asn Gln Ser Gly Val Gln Leu Thr Asn 225 230 235 240 Ile Asn Val Val Pro Phe Gly Ile Trp Gln Gln Val Asp Lys Asn Leu 245 250 255 Arg Phe Met Ile Leu Met Asp Gly Val His Pro Glu Met Asp Thr Cys 260 265 270 Ile Ile Val Glu Tyr Lys Gly His Lys Ile Leu Asn Thr Val Asp Cys 275 280 285 Thr Arg Pro Asn Gly Gly Arg Leu Pro Met Lys Val Ala Leu Met Met 290 295 300 Ser Asp Phe Ala Gly Gly Ala Ser Gly Phe Pro Met Thr Phe Ser Gly 305 310 315 320 Gly Lys Phe Thr Glu Glu Trp Lys Ala Gln Phe Ile Lys Thr Glu Arg 325 330 335 Lys Lys Leu Leu Asn Tyr Lys Ala Arg Leu Val Lys Asp Leu Gln Pro 340 345 350 Arg Ile Tyr Cys Pro Phe Pro Gly Tyr Phe Val Glu Ser His Pro Ala 355 360 365 Asp Lys Tyr Ile Lys Glu Thr Asn Ile Lys Asn Asp Pro Asn Glu Leu 370 375 380 Asn Asn Leu Ile Lys Lys Asn Ser Glu Val Val Thr Trp Thr Pro Arg 385 390 395 400 Pro Gly Ala Thr Leu Asp Leu Gly Arg Met Leu Lys Asp Pro Thr Asp 405 410 415 Ser Lys Gly Ile Val Glu Pro Pro Glu Gly Thr Lys Ile Tyr Lys Asp 420 425 430 Ser Trp Asp Phe Gly Pro Tyr Leu Asn Ile Leu Asn Ala Ala Ile Gly 435 440 445 Asp Glu Ile Phe Arg His Ser Ser Trp Ile Lys Glu Tyr Phe Thr Trp 450 455 460 Ala Gly Phe Lys Asp Tyr Asn Leu Val Val Arg Met Ile Glu Thr Asp 465 470 475 480 Glu Asp Phe Ser Pro Leu Pro Gly Gly Tyr Asp Tyr Leu Val Asp Phe 485 490 495 Leu Asp Leu Ser Phe Pro Lys Glu Arg Pro Ser Arg Glu His Pro Tyr 500 505 510 Glu Glu Ile Arg Ser Arg Val Asp Val Ile Arg His Val Val Lys Asn 515 520 525 Gly Leu Leu Trp Asp Asp Leu Tyr Ile Gly Phe Gln Thr Arg Leu Gln 530 535 540 Arg Asp Pro Asp Ile Tyr His His Leu Phe Trp Asn His Phe Gln Ile 545 550 555 560 Lys Leu Pro Leu Thr Pro Pro Asp Trp Lys Ser Phe Leu Met Cys Ser 565 570 575 Gly <210> SEQ ID NO 3 <211> LENGTH: 2467 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 3 cccgacgtcc tggcagcgcc caggcactgt tattggtgcc tcctgtgtcc acgcgcttcc 60 cggccaggca gccctggcgg atcctatttt ctgttccccc gattctggta cctctccctc 120 ccgccctcgg tgcgcagccg tcctcctgca gtgcctgctc ctccaggggc gaaaccgatc 180 agggatcagg ccacccgcct cctgaacatc cctccttagt tcccacagtc taatgccttg 240 tggaagcaaa tgagccacag aagctgaagg aaaaaccacc attctttctt aatacctgga 300 gagaggcaac gacagactat gagcagcatc gaacaaacga cggagatcct gttgtgcctc 360 tcacctgccg aagctgccaa tctcaaggaa ggaatcaatt ttgttcgaaa taagagcact 420 ggcaaggatt acatcttatt taagaataag agccgcctga aggcatgtaa gaacatgtgc 480 aagcaccaag gaggcctctt cattaaagac attgaggatc taaatggaag gtctgttaaa 540 tgcacaaaac acaactggaa gttagatgta agcagcatga agtatatcaa tcctcctgga 600 agcttctgtc aagacgaact ggttgtagaa aaggatgaag aaaatggagt tttgcttcta 660 gaactaaatc ctcctaaccc gtgggattca gaacccagat ctcctgaaga tttggcattt 720 ggggaagtgc agatcacgta ccttactcac gcctgcatgg acctcaagct gggggacaag 780 agaatggtgt tcgacccttg gttaatcggt cctgcttttg cgcgaggatg gtggttacta 840 cacgagcctc catctgattg gctggagagg ctgagccgcg cagacttaat ttacatcagt 900 cacatgcact cagaccacct gagttaccca acactgaaga agcttgctga gagaagacca 960 gatgttccca tttatgttgg caacacggaa agacctgtat tttggaatct gaatcagagt 1020 ggcgtccagt tgactaatat caatgtagtg ccatttggaa tatggcagca ggtagacaaa 1080 aatcttcgat tcatgatctt gatggatggc gttcatcctg agatggacac ttgcattatt 1140 gtggaataca aaggtcataa aatactcaat acagtggatt gcaccagacc caatggagga 1200 aggctgccta tgaaggttgc attaatgatg agtgattttg ctggaggagc ttcaggcttt 1260 ccaatgactt tcagtggtgg aaaatttact gaggaatgga aagcccaatt cattaaaaca 1320 gaaaggaaga aactcctgaa ctacaaggct cggctggtga aggacctaca acccagaatt 1380 tactgcccct ttcctgggta tttcgtggaa tcccacccag cagacaagta tattaaggaa 1440 acaaacatca aaaatgaccc aaatgaactc aacaatctta tcaagaagaa ttctgaggtg 1500 gtaacctgga ccccaagacc tggagccact cttgatctgg gtaggatgct aaaggaccca 1560 acagacagat cctgtgtcag gagttgggat tctttgaaga ttcggagccg ggttgatgtc 1620 atcagacacg tggtaaagaa tggtctgctc tgggatgact tgtacatagg attccaaacc 1680 cggcttcagc gggatcctga tatataccat catctgtttt ggaatcattt tcaaataaaa 1740 ctccccctca caccacctga ctggaagtcc ttcctgatgt gctctgggta gagaggacct 1800 gagctgtccc aggggtgccc aacaacatga aaaaatcaag aatttattgc tgctacgtca 1860 aagcttatac cagagattat gccttataga cattagcaat ggataattat atgttgcact 1920 tgtgaaatgt gcacatatcc tgtttatgaa tcaccacata gccagattat caatatttta 1980 cttatttcgt aaaaaatcca caattttcca taacagaatc aacgtgtgca ataggaacaa 2040 gattgctatg gaaaacgagg gtaacaggag gagatattaa tccaagcata gaagaaatag 2100 acaaatgagg ggccataagg ggaatatagg gaagagaaaa aaattaagat ggaattttaa 2160 aaggagaatg taaaaaatag atatttgttc cttaataggt tgattcctca aatagagccc 2220 atgaatataa tcaaatagga agggttcatg actgttttca atttttcaaa aagctttgtt 2280 gaaatcatag acttgcaaaa caaggctgta gaggccaccc taaaatggaa aatttcactg 2340 ggactgaaat tattttgatt caatgacaaa atttgttatt tactgcggat tataaactct 2400 aacaaatagc gatctctttg cttcataaaa acataaacac tagctagtaa taaaatgagt 2460 tctgcag 2467 <210> SEQ ID NO 4 <211> LENGTH: 490 <212> TYPE: PRT <213> ORGANISM: Porcine <400> SEQUENCE: 4 Met Ser Ser Ile Glu Gln Thr Thr Glu Ile Leu Leu Cys Leu Ser Pro 1 5 10 15 Ala Glu Ala Ala Asn Leu Lys Glu Gly Ile Asn Phe Val Arg Asn Lys 20 25 30 Ser Thr Gly Lys Asp Tyr Ile Leu Phe Lys Asn Lys Ser Arg Leu Lys 35 40 45 Ala Cys Lys Asn Met Cys Lys His Gln Gly Gly Leu Phe Ile Lys Asp 50 55 60 Ile Glu Asp Leu Asn Gly Arg Ser Val Lys Cys Thr Lys His Asn Trp 65 70 75 80 Lys Leu Asp Val Ser Ser Met Lys Tyr Ile Asn Pro Pro Gly Ser Phe 85 90 95 Cys Gln Asp Glu Leu Val Val Glu Lys Asp Glu Glu Asn Gly Val Leu 100 105 110 Leu Leu Glu Leu Asn Pro Pro Asn Pro Trp Asp Ser Glu Pro Arg Ser 115 120 125 Pro Glu Asp Leu Ala Phe Gly Glu Val Gln Ile Thr Tyr Leu Thr His 130 135 140 Ala Cys Met Asp Leu Lys Leu Gly Asp Lys Arg Met Val Phe Asp Pro 145 150 155 160 Trp Leu Ile Gly Pro Ala Phe Ala Arg Gly Trp Trp Leu Leu His Glu 165 170 175 Pro Pro Ser Asp Trp Leu Glu Arg Leu Ser Arg Ala Asp Leu Ile Tyr 180 185 190 Ile Ser His Met His Ser Asp His Leu Ser Tyr Pro Thr Leu Lys Lys 195 200 205 Leu Ala Glu Arg Arg Pro Asp Val Pro Ile Tyr Val Gly Asn Thr Glu 210 215 220 Arg Pro Val Phe Trp Asn Leu Asn Gln Ser Gly Val Gln Leu Thr Asn 225 230 235 240 Ile Asn Val Val Pro Phe Gly Ile Trp Gln Gln Val Asp Lys Asn Leu 245 250 255 Arg Phe Met Ile Leu Met Asp Gly Val His Pro Glu Met Asp Thr Cys 260 265 270 Ile Ile Val Glu Tyr Lys Gly His Lys Ile Leu Asn Thr Val Asp Cys 275 280 285 Thr Arg Pro Asn Gly Gly Arg Leu Pro Met Lys Val Ala Leu Met Met 290 295 300 Ser Asp Phe Ala Gly Gly Ala Ser Gly Phe Pro Met Thr Phe Ser Gly 305 310 315 320 Gly Lys Phe Thr Glu Glu Trp Lys Ala Gln Phe Ile Lys Thr Glu Arg 325 330 335 Lys Lys Leu Leu Asn Tyr Lys Ala Arg Leu Val Lys Asp Leu Gln Pro 340 345 350 Arg Ile Tyr Cys Pro Phe Pro Gly Tyr Phe Val Glu Ser His Pro Ala 355 360 365 Asp Lys Tyr Ile Lys Glu Thr Asn Ile Lys Asn Asp Pro Asn Glu Leu 370 375 380 Asn Asn Leu Ile Lys Lys Asn Ser Glu Val Val Thr Trp Thr Pro Arg 385 390 395 400 Pro Gly Ala Thr Leu Asp Leu Gly Arg Met Leu Lys Asp Pro Thr Asp 405 410 415 Arg Ser Cys Val Arg Ser Trp Asp Ser Leu Lys Ile Arg Ser Arg Val 420 425 430 Asp Val Ile Arg His Val Val Lys Asn Gly Leu Leu Trp Asp Asp Leu 435 440 445 Tyr Ile Gly Phe Gln Thr Arg Leu Gln Arg Asp Pro Asp Ile Tyr His 450 455 460 His Leu Phe Trp Asn His Phe Gln Ile Lys Leu Pro Leu Thr Pro Pro 465 470 475 480 Asp Trp Lys Ser Phe Leu Met Cys Ser Gly 485 490 <210> SEQ ID NO 5 <211> LENGTH: 1624 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 5 cccgacgtcc tggcagcgcc caggcactgt tattggtgcc tcctgtgtcc acgcgcttcc 60 cggccaggca gccctggcgg atcctatttt ctgttccccc gattctggta cctctccctc 120 ccgccctcgg tgcgcagccg tcctcctgca gtgcctgctc ctccaggggc gaaaccgatc 180 agggatcagg ccacccgcct cctgaacatc cctccttagt tcccacagtc taatgccttg 240 tggaagcaaa tgagccacag aagctgaagg aaaaaccacc attctttctt aatacctgga 300 gagaggcaac gacagactat gagcagcatc gaacaaacga cggagatcct gttgtgcctc 360 tcacctgccg aagctgccaa tctcaaggaa ggaatcaatt ttgttcgaaa taagagcact 420 ggcaaggatt acatcttatt taagaataag agccgcctga aggcatgtaa gaacatgtgc 480 aagcaccaag gaggcctctt cattaaagac attgaggatc taaatggaag gtctgttaaa 540 tgcacaaaac acaactggaa gttagatgta agcagcatga agtatatcaa tcctcctgga 600 agcttctgtc aagacgaact ggttgtagaa aaggatgaag aaaatggagt tttgcttcta 660 gaactaaatc ctcctaaccc gtgggattca gaacccagat ctcctgaaga tttggcattt 720 ggggaagtgc agatcacgta ccttactcac gcctgcatgg acctcaagct gggggacaag 780 agaatggtgt tcgacccttg gttaatcggt cctgcttttg cgcgaggatg gtggttacta 840 cacgagcctc catctgattg gctggagagg ctgagccgcg cagacttaat ttacatcagt 900 cacatgcact cagaccacct gagttaccca acactgaaga agcttgctga gagaagacca 960 gatgttccca tttatgttgg caacacggaa agacctgtat tttggaatct gaatcagagt 1020 ggcgtccagt tgactaatat caatgtagtg ccatttggaa tatggcagca ggtagacaaa 1080 aatcttcgat tcatgatctt gatggatggc gttcatcctg agatggacac ttgcattatt 1140 gtggaataca aaggtcataa aatactcaat acagtggatt gcaccagacc caatggagga 1200 aggctgccta tgaaggttgc attaatgatg agtgattttg ctggaggagc ttcaggcttt 1260 ccaatgactt tcagtggtgg aaaatttact gaggaatgga aagcccaatt cattaaaaca 1320 gaaaggaaga aactcctgaa ctacaaggct cggctggtga aggacctaca acccagaatt 1380 tactgcccct ttcctgggta tttcgtggaa tcccacccag cagacaagta tggctggata 1440 ttttatataa cgtgtttacg cataagttaa tatatgctga atgagtgatt tagctgtgaa 1500 acaacatgaa atgagaaaga atgattagta ggggtctgga gcttatttta acaagcagcc 1560 tgaaaacaga aagtatgaat aaaaaaaatt aaatgcaaaa aaaaaaaaaa aaaaaaaaaa 1620 aaaa 1624 <210> SEQ ID NO 6 <211> LENGTH: 383 <212> TYPE: PRT <213> ORGANISM: Porcine <400> SEQUENCE: 6 Met Ser Ser Ile Glu Gln Thr Thr Glu Ile Leu Leu Cys Leu Ser Pro 1 5 10 15 Ala Glu Ala Ala Asn Leu Lys Glu Gly Ile Asn Phe Val Arg Asn Lys 20 25 30 Ser Thr Gly Lys Asp Tyr Ile Leu Phe Lys Asn Lys Ser Arg Leu Lys 35 40 45 Ala Cys Lys Asn Met Cys Lys His Gln Gly Gly Leu Phe Ile Lys Asp 50 55 60 Ile Glu Asp Leu Asn Gly Arg Ser Val Lys Cys Thr Lys His Asn Trp 65 70 75 80 Lys Leu Asp Val Ser Ser Met Lys Tyr Ile Asn Pro Pro Gly Ser Phe 85 90 95 Cys Gln Asp Glu Leu Val Val Glu Lys Asp Glu Glu Asn Gly Val Leu 100 105 110 Leu Leu Glu Leu Asn Pro Pro Asn Pro Trp Asp Ser Glu Pro Arg Ser 115 120 125 Pro Glu Asp Leu Ala Phe Gly Glu Val Gln Ile Thr Tyr Leu Thr His 130 135 140 Ala Cys Met Asp Leu Lys Leu Gly Asp Lys Arg Met Val Phe Asp Pro 145 150 155 160 Trp Leu Ile Gly Pro Ala Phe Ala Arg Gly Trp Trp Leu Leu His Glu 165 170 175 Pro Pro Ser Asp Trp Leu Glu Arg Leu Ser Arg Ala Asp Leu Ile Tyr 180 185 190 Ile Ser His Met His Ser Asp His Leu Ser Tyr Pro Thr Leu Lys Lys 195 200 205 Leu Ala Glu Arg Arg Pro Asp Val Pro Ile Tyr Val Gly Asn Thr Glu 210 215 220 Arg Pro Val Phe Trp Asn Leu Asn Gln Ser Gly Val Gln Leu Thr Asn 225 230 235 240 Ile Asn Val Val Pro Phe Gly Ile Trp Gln Gln Val Asp Lys Asn Leu 245 250 255 Arg Phe Met Ile Leu Met Asp Gly Val His Pro Glu Met Asp Thr Cys 260 265 270 Ile Ile Val Glu Tyr Lys Gly His Lys Ile Leu Asn Thr Val Asp Cys 275 280 285 Thr Arg Pro Asn Gly Gly Arg Leu Pro Met Lys Val Ala Leu Met Met 290 295 300 Ser Asp Phe Ala Gly Gly Ala Ser Gly Phe Pro Met Thr Phe Ser Gly 305 310 315 320 Gly Lys Phe Thr Glu Glu Trp Lys Ala Gln Phe Ile Lys Thr Glu Arg 325 330 335 Lys Lys Leu Leu Asn Tyr Lys Ala Arg Leu Val Lys Asp Leu Gln Pro 340 345 350 Arg Ile Tyr Cys Pro Phe Pro Gly Tyr Phe Val Glu Ser His Pro Ala 355 360 365 Asp Lys Tyr Gly Trp Ile Phe Tyr Ile Thr Cys Leu Arg Ile Ser 370 375 380 <210> SEQ ID NO 7 <211> LENGTH: 2293 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 7 cccgacgtcc tggcagcgcc caggcactgt tattggtgcc tcctgtgtcc acgcgcttcc 60 cggccaggca gccctggcgg atcctatttt ctgttccccc gattctggta cctctccctc 120 ccgccctcgg tgcgcagccg tcctcctgca gtgcctgctc ctccaggggc gaaaccgatc 180 agggatcagg ccacccgcct cctgaacatc cctccttagt tcccacagtc taatgccttg 240 tggaagcaaa tgagccacag aagctgaagg aaaaaccacc attctttctt aatacctgga 300 gagaggcaac gacagactat gagcagcatc gaacaaacga cggagatcct gttgtgcctc 360 tcacctgccg aagctgccaa tctcaaggaa ggaatcaatt ttgttcgaaa taagagcact 420 ggcaaggatt acatcttatt taagaataag agccgcctga aggcatgtaa gaacatgtgc 480 aagcaccaag gaggcctctt cattaaagac attgaggatc taaatggaag gtctgttaaa 540 tgcacaaaac acaactggaa gttagatgta agcagcatga agtatatcaa tcctcctgga 600 agcttctgtc aagacgaact ggttgtagaa aaggatgaag aaaatggagt tttgcttcta 660 gaactaaatc ctcctaaccc gtgggattca gaacccagat ctcctgaaga tttggcattt 720 ggggaagtgc agatcacgta ccttactcac gcctgcatgg acctcaagct gggggacaag 780 agaatggtgt tcgacccttg gttaatcggt cctgcttttg cgcgaggatg gtggttacta 840 cacgagcctc catctgattg gctggagagg ctgagccgcg cagacttaat ttacatcagt 900 cacatgcact cagaccacct gagttaccca acactgaaga agcttgctga gagaagacca 960 gatgttccca tttatgttgg caacacggaa agacctgtat tttggaatct gaatcagagt 1020 ggcgtccagt tgactaatat caatgtagtg ccatttggaa tatggcagca ggtagacaaa 1080 aatcttcgat tcatgatctt gatggatggc gttcatcctg agatggacac ttgcattatt 1140 gtggaataca aaggtcataa aatactcaat acagtggatt gcaccagacc caatggagga 1200 aggctgccta tgaaggttgc attaatgatg agtgattttg ctggaggagc ttcaggcttt 1260 ccaatgactt tcagtggtgg aaaatttact ggtaattctt tatatcaaaa tgatgccaag 1320 gagttggcat ggcactttgc taaatgctgt gtgaatcaat acaaagataa ttaggacatg 1380 gttcttcctc acaagaggtg tgcaatctta ttgggaaatc atacttgcaa gtcacaaata 1440 tagactaaag tttccagctg agaatatgct gatggagcat gaaacactaa ggagacaggg 1500 agaatctcag gaaaaatcaa gaataatttg gatcaaatgg attcctgaca tagaacatag 1560 agctgatcag aaagagtctg acattggtaa tccaggctta agtgctcttt gtatgtggtt 1620 cagaacagag tgtgggcagc ctgaggggga tacataccct tgacctcgtg gaaagctcat 1680 acgggggagg gatgaggcta aggaagcccc tctaaagtgt gggattacga gaggttgggg 1740 gggtggtagg gaaaatagtg gtcaaagagt ataaacttcc agttacaaga tgaataaatt 1800 ctaggggtat aataacagca tggcactata gatagcatat tgtactatat actggaagtg 1860 ctgagagtag atcttacatg ttctaaccac acacacacac acacacacac acacaccaca 1920 cacacacacc acacacacac acgtgcacac aaacagaaat ggtaattatg tgaggtgatg 1980 gcggtgttaa ctaactttat tgtggtcatc atttagccat acatgcatgt catgaaatca 2040 ccatgttgta caccttaaag ttatgtaata ctagatgtca gttatatctc aaagctagaa 2100 aaaatgtggg gaccaaggca gaagctcttc tgctctgtgt ctaagggtgg ttctggggct 2160 gggatgggga ggatggttaa gtggtatatt tttttcatac ctttgctcag tactatcatt 2220 gtaagtgttc aatatatgtc tgcttaataa attaatgttt ttagtaaaaa aaaaaaaaaa 2280 aaaaaaaaaa aaa 2293 <210> SEQ ID NO 8 <211> LENGTH: 351 <212> TYPE: PRT <213> ORGANISM: Porcine <400> SEQUENCE: 8 Met Ser Ser Ile Glu Gln Thr Thr Glu Ile Leu Leu Cys Leu Ser Pro 1 5 10 15 Ala Glu Ala Ala Asn Leu Lys Glu Gly Ile Asn Phe Val Arg Asn Lys 20 25 30 Ser Thr Gly Lys Asp Tyr Ile Leu Phe Lys Asn Lys Ser Arg Leu Lys 35 40 45 Ala Cys Lys Asn Met Cys Lys His Gln Gly Gly Leu Phe Ile Lys Asp 50 55 60 Ile Glu Asp Leu Asn Gly Arg Ser Val Lys Cys Thr Lys His Asn Trp 65 70 75 80 Lys Leu Asp Val Ser Ser Met Lys Tyr Ile Asn Pro Pro Gly Ser Phe 85 90 95 Cys Gln Asp Glu Leu Val Val Glu Lys Asp Glu Glu Asn Gly Val Leu 100 105 110 Leu Leu Glu Leu Asn Pro Pro Asn Pro Trp Asp Ser Glu Pro Arg Ser 115 120 125 Pro Glu Asp Leu Ala Phe Gly Glu Val Gln Ile Thr Tyr Leu Thr His 130 135 140 Ala Cys Met Asp Leu Lys Leu Gly Asp Lys Arg Met Val Phe Asp Pro 145 150 155 160 Trp Leu Ile Gly Pro Ala Phe Ala Arg Gly Trp Trp Leu Leu His Glu 165 170 175 Pro Pro Ser Asp Trp Leu Glu Arg Leu Ser Arg Ala Asp Leu Ile Tyr 180 185 190 Ile Ser His Met His Ser Asp His Leu Ser Tyr Pro Thr Leu Lys Lys 195 200 205 Leu Ala Glu Arg Arg Pro Asp Val Pro Ile Tyr Val Gly Asn Thr Glu 210 215 220 Arg Pro Val Phe Trp Asn Leu Asn Gln Ser Gly Val Gln Leu Thr Asn 225 230 235 240 Ile Asn Val Val Pro Phe Gly Ile Trp Gln Gln Val Asp Lys Asn Leu 245 250 255 Arg Phe Met Ile Leu Met Asp Gly Val His Pro Glu Met Asp Thr Cys 260 265 270 Ile Ile Val Glu Tyr Lys Gly His Lys Ile Leu Asn Thr Val Asp Cys 275 280 285 Thr Arg Pro Asn Gly Gly Arg Leu Pro Met Lys Val Ala Leu Met Met 290 295 300 Ser Asp Phe Ala Gly Gly Ala Ser Gly Phe Pro Met Thr Phe Ser Gly 305 310 315 320 Gly Lys Phe Thr Gly Asn Ser Leu Tyr Gln Asn Asp Ala Lys Glu Leu 325 330 335 Ala Trp His Phe Ala Lys Cys Cys Val Asn Gln Tyr Lys Asp Asn 340 345 350 <210> SEQ ID NO 9 <211> LENGTH: 601 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 9 ctgccagcct aagccacagc cacagcaacg ctgggtctga gccatgtctg cagcctatgc 60 cagagctccc cgcagcgccg gatgcttaac ccactgagca aggccaggga ttgaaccctc 120 gtcctcatgg atagcagttg agttgtttcc acggaactct taggggaact cctgattatt 180 ttttatttaa atttatattt ctctgacttt ttcgtgtgct catcagccac tgactgtgta 240 tctccattag tcatggtttg ttaactctgt cattcaaacc ctcttcatcc ttgctacgca 300 gataacatca ttataataaa atcgtgcctg aagaccagtg acgcccccaa gctaagttac 360 tgcttcccct ggggggaaaa agaagcaccg cgcgggcgct gacacgaagt ccgggcagag 420 gaagacgggg cagaggaaga cgggggagca gtgggagcag cgggcagggc gcgggaagca 480 ctggggatgt tccgcgttgg caggagggtg ttgggcgagc tcccggtgat gcagggggga 540 ggagcctttt ccgaagtagc gggacaagag ccacgggaag gaactgttct gagttcccag 600 t 601 <210> SEQ ID NO 10 <211> LENGTH: 228 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 10 cccgacgtcc tggcagcgcc caggcactgt tattggtgcc tcctgtgtcc acgcgcttcc 60 cggccaggca gccctggcgg atcctatttt ctgttccccc gattctggta cctctccctc 120 ccgccctcgg tgcgcagccg tcctcctgca gtgcctgctc ctccaggggc gaaaccgatc 180 agggatcagg ccacccgcct cctgaacatc cctccttagt tcccacag 228 <210> SEQ ID NO 11 <211> LENGTH: 98 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 11 tctaatgcct tgtggaagca aatgagccac agaagctgaa ggaaaaacca ccattctttc 60 ttaatacctg gagagaggca acgacagact atgagcag 98 <210> SEQ ID NO 12 <211> LENGTH: 204 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 12 catcgaacaa acgacggaga tcctgttgtg cctctcacct gccgaagctg ccaatctcaa 60 ggaaggaatc aattttgttc gaaataagag cactggcaag gattacatct tatttaagaa 120 taagagccgc ctgaaggcat gtaagaacat gtgcaagcac caaggaggcc tcttcattaa 180 agacattgag gatctaaatg gaag 204 <210> SEQ ID NO 13 <211> LENGTH: 92 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 13 gtctgttaaa tgcacaaaac acaactggaa gttagatgta agcagcatga agtatatcaa 60 tcctcctgga agcttctgtc aagacgaact gg 92 <210> SEQ ID NO 14 <211> LENGTH: 110 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 14 ttgtagaaaa ggatgaagaa aatggagttt tgcttctaga actaaatcct cctaacccgt 60 gggattcaga acccagatct cctgaagatt tggcatttgg ggaagtgcag 110 <210> SEQ ID NO 15 <211> LENGTH: 191 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 15 atcacgtacc ttactcacgc ctgcatggac ctcaagctgg gggacaagag aatggtgttc 60 gacccttggt taatcggtcc tgcttttgcg cgaggatggt ggttactaca cgagcctcca 120 tctgattggc tggagaggct gagccgcgca gacttaattt acatcagtca catgcactca 180 gaccacctga g 191 <210> SEQ ID NO 16 <211> LENGTH: 148 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 16 ttacccaaca ctgaagaagc ttgctgagag aagaccagat gttcccattt atgttggcaa 60 cacggaaaga cctgtatttt ggaatctgaa tcagagtggc gtccagttga ctaatatcaa 120 tgtagtgcca tttggaatat ggcagcag 148 <210> SEQ ID NO 17 <211> LENGTH: 82 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 17 gtagacaaaa atcttcgatt catgatcttg atggatggcg ttcatcctga gatggacact 60 tgcattattg tggaatacaa ag 82 <210> SEQ ID NO 18 <211> LENGTH: 138 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 18 gtcataaaat actcaataca gtggattgca ccagacccaa tggaggaagg ctgcctatga 60 aggttgcatt aatgatgagt gattttgctg gaggagcttc aggctttcca atgactttca 120 gtggtggaaa atttactg 138 <210> SEQ ID NO 19 <211> LENGTH: 1014 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 19 gtaattcttt atatcaaaat gatgccaagg agttggcatg gcactttgct aaatgctgtg 60 tgaatcaata caaagataat taggacatgg ttcttcctca caagaggtgt gcaatcttat 120 tgggaaatca tacttgcaag tcacaaatat agactaaagt ttccagctga gaatatgctg 180 atggagcatg aaacactaag gagacaggga gaatctcagg aaaaatcaag aataatttgg 240 atcaaatgga ttcctgacat agaacataga gctgatcaga aagagtctga cattggtaat 300 ccaggcttaa gtgctctttg tatgtggttc agaacagagt gtgggcagcc tgagggggat 360 acataccctt gacctcgtgg aaagctcata cgggggaggg atgaggctaa ggaagcccct 420 ctaaagtgtg ggattacgag aggttggggg ggtggtaggg aaaatagtgg tcaaagagta 480 taaacttcca gttacaagat gaataaattc taggggtata ataacagcat ggcactatag 540 atagcatatt gtactatata ctggaagtgc tgagagtaga tcttacatgt tctaaccaca 600 cacacacaca cacacacaca cacaccacac acacacacca cacacacaca cgtgcacaca 660 aacagaaatg gtaattatgt gaggtgatgg cggtgttaac taactttatt gtggtcatca 720 tttagccata catgcatgtc atgaaatcac catgttgtac accttaaagt tatgtaatac 780 tagatgtcag ttatatctca aagctagaaa aaatgtgggg accaaggcag aagctcttct 840 gctctgtgtc taagggtggt tctggggctg ggatggggag gatggttaag tggtatattt 900 ttttcatacc tttgctcagt actatcattg taagtgttca atatatgtct gcttaataaa 960 ttaatgtttt tagtaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 1014 <210> SEQ ID NO 20 <211> LENGTH: 136 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 20 aggaatggaa agcccaattc attaaaacag aaaggaagaa actcctgaac tacaaggctc 60 ggctggtgaa ggacctacaa cccagaattt actgcccctt tcctgggtat ttcgtggaat 120 cccacccagc agacaa 136 <210> SEQ ID NO 21 <211> LENGTH: 169 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 21 gtatggctgg atattttata taacgtgttt acgcataagt taatatatgc tgaatgagtg 60 atttagctgt gaaacaacat gaaatgagaa agaatgatta gtaggggtct ggagcttatt 120 ttaacaagca gcctgaaaac agagagtatg aataaaaaaa attaaatac 169 <210> SEQ ID NO 22 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 22 gtatattaag gaaacaaaca tcaaaaatga cccaaatgaa ctcaacaatc ttatcaagaa 60 gaattctgag gtggtaacct ggaccccaag acctggagcc actcttgatc tgggtaggat 120 gctaaaggac ccaacagaca g 141 <210> SEQ ID NO 23 <211> LENGTH: 175 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 23 caagggcatc gtagagcctc cagaagggac taagatttac aaggattcct gggattttgg 60 cccatatttg aatatcttga atgctgctat aggagatgaa atatttcgtc actcatcctg 120 gataaaagaa tacttcactt gggctggatt taaggattat aacctggtgg tcagg 175 <210> SEQ ID NO 24 <211> LENGTH: 117 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 24 atgattgaga cagatgagga cttcagccct ttgcctggag gatatgacta tttggttgac 60 tttctggatt tatcctttcc aaaagaaaga ccaagccggg aacatccata tgaggaa 117 <210> SEQ ID NO 25 <211> LENGTH: 31 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 25 atcctgtgtc aggagttggg attctttgaa g 31 <210> SEQ ID NO 26 <211> LENGTH: 116 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 26 attcggagcc gggttgatgt catcagacac gtggtaaaga atggtctgct ctgggatgac 60 ttgtacatag gattccaaac ccggcttcag cgggatcctg atatatacca tcatct 116 <210> SEQ ID NO 27 <211> LENGTH: 97 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 27 gttttggaat cattttcaaa taaaactccc cctcacacca cctgactgga agtccttcct 60 gatgtgctct gggtagagag gacctgagct gtcccag 97 <210> SEQ ID NO 28 <211> LENGTH: 655 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 28 gggtgcccaa caacatgaaa aaatcaagaa tttattgctg ctacgtcaaa gcttatacca 60 gagattatgc cttatagaca ttagcaatgg ataattatat gttgcacttg tgaaatgtgc 120 acatatcctg tttatgaatc accacatagc cagattatca atattttact tatttcgtaa 180 aaaatccaca attttccata acagaatcaa cgtgtgcaat aggaacaaga ttgctatgga 240 aaacgagggt aacaggagga gatattaatc caagcataga agaaatagac aaatgagggg 300 ccataagggg aatataggga agagaaaaaa attaagatgg aattttaaaa ggagaatgta 360 aaaaatagat atttgttcct taataggttg attcctcaaa tagagcccat gaatataatc 420 aaataggaag ggttcatgac tgttttcaat ttttcaaaaa gctttgttga aatcatagac 480 ttgcaaaaca aggctgtaga ggccacccta aaatggaaaa tttcactggg actgaaatta 540 ttttgattca atgacaaaat ttgttattta ctgcggatta taaactctaa caaatagcga 600 tctctttgct tcataaaaac ataaacacta gctagtaata aaatgagttc tgcag 655 <210> SEQ ID NO 29 <211> LENGTH: 363 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 29 gtgagaaggc ttcgccgctg ctgccgctgg cgccggcagc gccctccacg cacttcgtag 60 tgggcgcgcg ccctcctgca ttgtttctaa aagatttttt tttatccgct tatgctatca 120 gttactgagg aagtatttac aaatctacta ttattttgaa tttgcctttt tctccttata 180 gtttatcagt atctcttgag actgttattg gtgcctgcaa atttaaaatg attggggttt 240 tatgaggaag tgaacctttt atctttatga aacgcctaac tgaggcaatg ttaattgctt 300 aaaatacttt ctttattatc agtgtggcca tgccagtgtc ctcttggtta gaatttgcct 360 gat 363 <210> SEQ ID NO 30 <211> LENGTH: 143 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 30 ctgccaaagc tgggagatgg gggaaagtag agtgggttat tgaaactgaa tatagagttc 60 agcatctaaa agcgaggtag tagaggagga agctgtgtca acggaaatac tgagctgggt 120 tcacatcctc tttctccaca cag 143 <210> SEQ ID NO 31 <211> LENGTH: 237 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 31 gcaagtgaga gggggcttta gctgtcaggg aaggcggaga taaacccttg atgggtagga 60 tggccattga aaggagggga gaaatttgcc ccagcaggta gccaccaagc ttggggactt 120 ggagggaggg ctttcaaacg tattttcata aaaaagacct gtggagctgt caatgctcag 180 ggattctctc ttaaaatcta acagtattaa tctgctaaaa catttgcctt ttcatag 237 <210> SEQ ID NO 32 <211> LENGTH: 4229 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 32 gtactgagaa tcctttgctt tctccctggc gatcctttct cccaattagg tttggcagga 60 aatgtgctca ttgagaaatt ttaaatgatc caatcaacat gctatttccc ccagcacatg 120 cctaactttt tcttaagctc ctttacggca gctctctgat tttgatttat gaccttgact 180 taatttccca tcctctctga agaactattg tttaaaatgt attcctagtt gataaacagt 240 gaaacttcta aggcacatgt gtgtgtgtgt gtgtgtgtgt gtgtgtttac cagcttttat 300 attcaaagac tcaagcctct tttggatttc ctttcctgct ctctcagaag tgtgtgtgtg 360 aggtgagtgc ttgtccaaac actgccctag aacagagaga ctttccctga tgaaaacccg 420 aaaaatggca gagctctagc tgcacctggc ctcaacagcg gctcttctga tcatttcttg 480 gaagaacgag tgctggtacc ccttttcccc agccccttga ttaaacctgc atatcgcttg 540 cctccccatc tcaggagcaa ttctaggagg gagggtgggc tttcttttca ggattgacaa 600 agctacccag cttgcaaacc agggggatct gggggggggg tttgcacctg atgctccccc 660 actgataatg aatgagggat tgaccccatc ttttcaagct ttgcttcagc ctaacttgac 720 tctcgtagtg tttcagccgt ttccatatta ggcttgtctt ccaccgtgtc gtgtcgtcaa 780 tcttatttct caggtcatct gtgggcagtt tagtgcgaat ggactcagag gtaactggta 840 gctgtccaag agctccctgc tctaactgta tagaagatca ccacccaagt ctggaatctt 900 cttacactgg cccacagact tgcatcactg catacttagc ttcagggccc agctcccagg 960 ttaagtgctg tcatacctgt agcttgcttg gctctgcaga tagggttgct agattaggca 1020 aatagagggt gcccagtcaa atttgcattt cagataaaca acgaatatat ttttagttag 1080 atatgtttca ggcactgcat gggacatact tttggtaggc agcctactct ggaagaacct 1140 cttggttgtt tgctgacaga ctgcttttga gtcccttgca tcttctgggt ggtttcaagt 1200 tagggagacc tcagccatag gttgttctgt caccaagaag cttctgcaag cacgtgcagg 1260 ccttgaggtc ttccgacttg tggcccgggg actctgcttt ttctctgtcc ttttttctcc 1320 ttagtgggcc atgtcctgtg gtgttgtctt agccagttgt ttaagggagt gttgcagctt 1380 tatgattaag agcatggtct ttccttgcaa actgcttggt ttagaagcct ggctccacca 1440 cttagcggct ctgtgacctc ggacacattt cttagccttt ctgggcctcg ctcttcttcc 1500 tcataaagtg aaaatgaaag tagacaaagc cttctctgtc tggctactga gaggatggag 1560 tgatttcata cacataaagc acttaaaata atgtctggca tatgatacat gctcaataaa 1620 tgtcacttac atttgctatt attattactc tgccatgatc ttgtgtagct taagaacaga 1680 ggtctttaca ggaattcagg ctgttcttga atctggcttg ctcagcttaa tatggtaatt 1740 gctttgccac agactggtct tcctctcctt cacccaaagc cttagggggt gaacgatccc 1800 agtttcaacc tattctgttg gcaggctaac atggagatgg caccatctta gctctgctgc 1860 aggtggggag ccagattcac ccagctttgc tcccagatac agctccccaa gcatttatat 1920 gctgaaactc catcccaaga gcagtctaca tggtacactc ccccatccat ctctccaaat 1980 ttggctgctt ctacttaggc tctctgtgca gcaattcacc tgaaatatct cttccacgat 2040 acagtcaagg gcagtgacct acctgttcca ccttcccttc ctcagccatt tttcttcttt 2100 gtacataatc aagatcagga actctcataa gctgtggtcc tcattttgtc aatctaattt 2160 cacagcctct tggcacatga agctgtcctc tctctccttt ctgcctactg cccatgagca 2220 gttgtgacac tgccacattt ctcctttaac gacccagcct gctgaatagc tgcatttgga 2280 atgttttcaa tttttgttaa tttatttatt tcatcttttt tttttttttt tttttttttt 2340 ttttttaggg ccgcacccat gggatatgga ggttcccagg ctagggatcc aatgggagct 2400 gtagctgctg gcctacacca cagccacagc aatgcacaat tcgagccaat ctttgaccta 2460 caccagagct cacggcaaca ctggattctt aacccactga ttgaggccag ggatcaaact 2520 ctcgtcctca tagatacgag tcagattcgt taacctctga gccatgatag ttgttagtta 2580 ctcattgatg agaaaggaag tgtcacaaaa tatcctccat aagtcgaagt ttgaatatgt 2640 tttctgcctt gttactagaa aagagcatta aaaattcttg attggaatga agcttggaaa 2700 aaatcagcat agtttactga tatataagtg aaaatagacc ttgttagttt aaaccatctg 2760 atatttctgg tggaagacat atttgtctgt aaaaaaaaaa aatcttgaac ctgtttaaaa 2820 aaaaaacttg actggaaaca ctaccaaaat atgggagttc ctactgggac acagcagaaa 2880 tgaatctaac tagtatccat gaggacacag gtttgatgcc tggcctcgct aagtgggtta 2940 aggatatggt gttgctgcag ctccaattca acccctatcc tgggaacccc catatgccac 3000 cctaaaaagc aaaaagaaag gtgctgccct aaaaagcaaa aagaaagaaa gaaagacagc 3060 cagacagact accaaatatg gagaggaaat ggaactttta ggccctatct ccaactatca 3120 catccctatc accgtctggt aagaaatgga aaaaatatta ctaagcctcc tttgttgcta 3180 caattaatct gattctcatt ctgaagcagt gttgccagag ttaacaaata aaaatgcaaa 3240 gctgggtagt taaatttgaa ttacagataa acaaattttc agtatatgtt caatatcgtg 3300 taagacgttt taaaataatt ttttatttat ctgaaattta tatttttcct gtattttatc 3360 tggcaaccat gatcagaaat ctttaaacaa tcaggaagtc ttttttctta gacaaatgaa 3420 aatttgagtt gatcttaggt ttagtacact atactagggg ccaagggtta tagtgtgact 3480 attaaatcac agataatctt tattactaca ttatttcctt atactggccc cacttggatc 3540 ttacccagct tagcttttgt atgagagtca tccttaaaga tgactttatt ctttaaaaaa 3600 aaaaacaaat tttaagggct gcacccatag catatagaag ttcctaggct agcggtcaaa 3660 ttagagctgc agctgccagc ctatgccaca gccacagcaa tgccagatct gagctgcatc 3720 tgtgacctac actgcagctt gcagcaatgc tggatcctta acccattgaa caatgccagg 3780 gattgaacac acatcctcat ggatactgct caggttccta acctgctgag ccacagttgg 3840 aactccaaag cagactttat tctgatggct ctgctgatct ctaacacgtt attttgtgcc 3900 atggtgttta tcttcacttt actcaagtca gggaaacacg aagagtctca tacaggataa 3960 acccaaggag aaatgtgcaa agtcacatac aaatcaaact gacaaaaatc aaatacaagg 4020 aaaaaatatc ttcactttca aaatcaccta ctgatgatga gtttatattt ccttggatat 4080 ttgaatatta gctatttttt tcctttcatg agttttgtgt tcaaccaact acagtcgttt 4140 actttgatca cagaataatg catttaagcc ttaaatagat taatatttat tttcaccatt 4200 tcataaacct aagtacaatt tccatccag 4229 <210> SEQ ID NO 33 <211> LENGTH: 8164 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 33 gtaaatacca tcaatactga tcaatgtttt ctgctgttac tgtcattggg gtccctcttg 60 tcaacttgtt tccaatctca ttagaagcct tggatgcatt ctgattttaa actgaggtat 120 tttaaaagta accatcactg aaaattctag gcaagttttc tctaaaaaat cccttcattc 180 attcatttgt tcagtaagta tttgatgaga ccttaccatg tgtaaacatt gcactaggta 240 ttaagaaata caaagatgga taagatagag tcggcgtaaa tgagatgata taatgagacg 300 ttataatgaa actcacaatt ccagttggga aataaagtcc ttcaaattcc atgactcttt 360 ctggcacacg ttagaggcta cagcttctgt gtgattctca tgctggctcc acttccactt 420 tttccttctt cctactcaag aaagcctata gaaatatgag taagaagggc ttaatcatag 480 gaataaattt gtctctgttc taagtgatta aaaatgtctt tatcagtata aaaagttact 540 tgggaagatt cttaaaactg cttttacaca ctgttctaga atgactgtta tataaataaa 600 aaagtagatt tgatctaaca caattaaatg acctttggaa atattgacta attctcacct 660 tgcccctcaa agggatgcct gaaccatttc cttcttttgc cagaaagccc ccaccctttg 720 tctgttgacc tagcctagga aatcttcaga tcacgttgtt agcacgaact ggttacatgt 780 gctgtacaaa tactatttaa ttcatctgat taaaaaaaaa gagataagaa gcaaaagttt 840 gactatctta aactgtttgc gtaggtgaga ggacaattga ccatctactt tatgagtatg 900 taacccagaa acttaaagct ccttaaggga gctaagtctt ttggataaga cctatagtga 960 gaccttttag caaaatggtt aagactgaat ggagctcact agcgtgggtt catatcctga 1020 tgctcaaaca cgcaattaaa tgactttagg tgggttagtc tctgttcctt agtttcctca 1080 atgggagata atattggtag tagcgatttt actgggttgt tgaaagaaca tctgttaaat 1140 gttcagaacg tgttacgaca gagtacagag taatgatttg cttgtatatg tatgactcaa 1200 atagtctgcc atatgccttg tgactgggtc ctgtggagca ggaaggaggg atttcccacc 1260 cagcagaaag ttgggtaaac tggaaaatag actgaggcca ggaaatgatg caaagcgttg 1320 atgttcactg ccacggcagg tgaagggcag ggccagagtt gtcagtaggg tcaggggagg 1380 actggaaata accaagaccc actgcacttt tcagcctttg ctccagtaag gtaatgttgt 1440 gagagtagaa aattttgtta acagaaccca cttttcagta cagtgctacc aatactgtag 1500 tgatttcata ccacatccca agaaagaaaa agatggctca atcccatgtg agctgagatt 1560 atttggtttt attgttaaat aaatagcatt gtgtggtcat cattaaaaaa ggtagatgtt 1620 aggaaagtag aaggaagaag actctcacct acattttcat cactgttttg gtatctgcca 1680 gttgtcacct tggtcccctt ccccgcctct cccctgcctc ctcttcctcc ttctcctttt 1740 tttggaatac aattcaggta ccataaaatt taccctttta gagtgtttga ctcaatggtt 1800 tttagtattt tcacatgttg tgctattact atcactatat aattccaggt cattcacatc 1860 accccccaaa gaaaccttct aactattagc agtccattcc cttcttccct cagcccctgg 1920 caaccactaa tctacttact gtctccatgg atgttcctat attgaatcaa gctagcataa 1980 accccacttg ctcatggtca taattctttt ttatagtgct aaattacatt tgctaatatt 2040 caattaagga tttctatgtc catattcata aggaatattg gtgtgtagtt ttctctttgt 2100 gtgatatctt tgtctggttg ggggatcaga gtaataatta ctgctctcat agaatgaatt 2160 gagaagtgtt ccctcctttt ctatttattg gaagagtttg tgaagtatat tggtattgat 2220 tcttctttaa acatttggtc agattcacca gtgaagccat ctgggccatg gctaatcttt 2280 gtgaaaagtt ttttgattac taattaaatc tctttaattt gttatgggtc tgctcctcag 2340 acgttctagt tcttcttgag tcagttttgt tcatttgttt cttcctagga ctttctccct 2400 ttcatttgga ttatttagat tgatagtaat atcccccttt taattcctgg ctgtagtaat 2460 ttgggtcttt tctctttttt cttggtcagt ttagctaaag gtttgtaatt gtattaatct 2520 tttcaaataa ctaacttttt tgttttgttt gttttttgtt ttttgttttt tgttttttgt 2580 ttttttttgc tttttaaggc tgcacctgag gcatatggaa gttctcaggc tagaggtcta 2640 atcggagcta cagctgctgg cctataccac aaccatagca atgccagatt caagctgcat 2700 ctgcgaccta caccacaact cggccaggga tcacacccgc aacctcatgg ttcctagtcg 2760 gatttgttaa ccactgtgcc acgacgggaa ctcccgccca ttttttttaa cacctcatac 2820 tttaacataa agatgggctt cacatggact gatagctcaa atgaggaagg taagactatg 2880 aaagtaatgg aagaaatgta gactattttt gtgacctaga gattactgat acttcttgac 2940 ttttcaaaca atacttcaaa agtacagccc aaagggaaaa aagaaagaaa aaagaaacac 3000 acatatacac aaacctagtg aataagatat catcgataca ctacagattt ctatgaactg 3060 gaagacccca tggacaaagt taaagaacat atgatagttt gagtgattat tttgcaatat 3120 ttacaaccaa tgagggaata ttatccagct tataggagga agtaatgcaa atcgacaaga 3180 aaaagatagg aaacccaata taaaaattaa gaaaatacaa aaattaagaa aggatatgaa 3240 ctagcatttt acaaaagaaa aatctccaaa agtcaatcag cacatgaaaa tatgctcaaa 3300 cctattaatt attagaaaac tacagactga agcaatgagg tgctttactt tacatctttt 3360 tgactgataa aaagttagaa acaaaggtga tatcaaatgt cagggataaa aggatataga 3420 aatcgtcatg cctgtggtgg gagtatggcc ggtgcagtca tgtgggaagg taatctgaca 3480 gtggttaggc agagcaggtt tatgaataca ctgtggccca tcaatcccac gcctgtttat 3540 gtaccaaaga aatcctgttg tggcagaatc tatgggtcca cccctgggag catgaattaa 3600 taaaatgtgg caccagggtg tgtgaaactc cagctagaga tgagatgtcc acatggcaac 3660 atgaatgcat cttagaaaca tagatttgag tgaaaaagag taagaaacag ccgggaaacc 3720 caataccatt tataaaaatt aaagatgcac acatacaatg tagtaaatat tttgcatgaa 3780 ctttcaaatg gttgcctaca gggggggaga gtaaagaaga gtagaaaaca aagataaagg 3840 gagtaagtaa gtagctctgc ctggactgaa tataatgtgt catgaactga gaaatatggt 3900 taacataatc ctcttaactt gaggtcctaa atgaatgaat gagtccacta ttcatttacc 3960 cattctttaa tgtgtattgc attataatcc atttttttag aaccaacgaa ttttgttccc 4020 ataactacta atcagcctgc cttttctccc tcattccctt atcagctcag gggcattcct 4080 agtttttcaa acgttcctca tttgaaccaa aaatagcatc attgtttaaa ttatacttgt 4140 tttcaaatac gatgcttata tattccaagt gtgtttgccc attttcttag gtggtagaaa 4200 tttttcattc tacttttcta tctactcaga ttttcccgtt ggaattattt ccattgctat 4260 taaacttaga agtcccccct gtgatatgcc atttttttca tactttttaa gcacttggtt 4320 gcttttcttt gtgtctttaa gcacctagaa tacttataac cattgcacag cactgtgtat 4380 caggcagccc ttcctcttcc actaatttat ggtccttctc ttagactata ttaaactgtt 4440 atttaattag gatcctctct tcgtccttat gatttaatta ttatagtttt ctaatatgtt 4500 tttattataa ttcctcttca ttattcctcc ctattaaaaa ttttaatgaa ttccatttgt 4560 ttgttcttct agttaaatat taagtcataa tccaaataac ttagatgtca ttagtttatg 4620 tggtcaaagt aaggatacca catctttata gatgcaggca gttggcagat gtcatgattt 4680 tcttcagtgc ataaatgcaa tttatctttg agcaaggggc ataaaaactt ttatggtatt 4740 ggctttgaaa taatagttaa gaactgcaga ctcagttttt cctgcttttc ttgaaaaaga 4800 acacttctaa agaaggaaaa tccttaagca tggatatcga tgtaattttc tgaaagtctc 4860 ctgtaattcc ttgggatttt tgttgttgtt tgttggtcgg tttttttggg tttttgtttg 4920 tttgttttgt tttgttttgt tttgctttta gggctgcacc tgtggcatat ggaagttccc 4980 aggctagggg tccaactgga gctacagctg ccagcctact ccacagccac agcaacatgg 5040 gatcctagct gcatctgtga cctaaccaca gctcttggta atgccagatt gttaacccac 5100 tgagcaatgc cagagatcga atctgcctcc tcatggacac tagtcagatt agtttctgct 5160 gagccacaat gggaattccc aattccttgt atttttgaac tggttatgtg ctagcatata 5220 attttgtttc ttgaatcttt gtgggttttt tttttttttt ttttttgtct cttgtctttt 5280 taaggctgca cccacagcat atggaggttc ccaggctaga ggtcaaattg gagctacagc 5340 tgccagccta cacaacaact gcagcaaagt ggggcccaac ttatatgaca gttcgtggca 5400 atgccggatt cctaacccac tgagcagggc cagggatcga acctgagttt ccagtcagtt 5460 tcgttaacca ctgagccatg atagtaactc ctgtttgttc agtcttgaac ctccttttta 5520 attctttatt ccttgagggt gaaataattg ccataataat actatcattt attacatgcc 5580 ttctctgtgc taggcatagt gacactttag gatttattat atcacttaat ccctacaaca 5640 actctgcaaa gtatgtatca taatcctatt tgacagatca ggaaattgca gcccaggatg 5700 cagataatat gcatccatca caagtgacta gatatagtcc ctctgctatt cagcagggtc 5760 tcattgcctt tccattccaa atgcaatagt ttgcatctat tgtatatgtg ttttggggtt 5820 tttttgtctt tttttttttt tttgtctttt ctggggcctc acccttggca taggtaggtt 5880 cccaggctag gggtcaaatt gaagctgcag ctgccagcct acaccacagc cacagcaact 5940 cgggatctga gcctcatctg caacctacac caaagctcac ggcaacaccg gatccttaac 6000 ccactgagtg aggccagaga tcaaaccggc aacctcatgg ttcctagtcg gattcattaa 6060 ccactgagcc acgatgggaa ctccctaaat gcaatagttt gctctattaa ccccaaactc 6120 ccagtccatc ccactccctc ctcctccctc ttggcaacca caagtctgtt ctccatgtcc 6180 atgattttct tttctgggga aagtttcatt tgtgccattt ttcattttac gggtaatttt 6240 tacttcagtt tcttccacta gcagttgtct taaagtgagt ataattaata ttcatttgga 6300 aaatgtaagc aaaacatttt ttaaagggcc atgcccacag catatgaaag tttctgggcc 6360 aggggttgaa tccaggctcc aagttgcagc tgtgccctac actgcagctg ggcaatgctg 6420 gatcctttaa cccactgtgc ccggctaggg atcaaacctg catttccaca gctacccgag 6480 ccattgcagt tggattctta acccactgca ctacagtggg aactcccaca aaacattttt 6540 taatgtcctt tgaataaagt aggaaagtgc tcgtctttga gggcagggcg gcaatgccat 6600 ttccacaagg tttgctttgg cttgggacct catctgctgt catttagtaa tgaataaaat 6660 tgctgacagt aataggatta actgtgtgtg gagatagcca gggttagaga taaaaacact 6720 ggagaagtca aataagttgc tcgaggtcct ctagctaata agctattaag tgggagagtg 6780 agggctagaa acaggccatc tgtctcccaa gcacatgtcc attagtggtt tgctgatagc 6840 cttccagaac aacagagagg actctcaaac atggtcttgc ctccctccaa ttgatcccct 6900 ccatgtgcct cacagcgggt ctttctaaaa ttaagttctg attttaattc tcccttgcta 6960 tagcacttag gtatggcttt cagccgtgca ataaaaagca ggcaagagtg gctcaatcat 7020 ataggaggtt gtttttctta gatcccaagc aggtaatcct gggcattatg gttgttctgc 7080 gtttatcaag gagccaaatt ctctatcacc tcctgttcta tcctcctcag tatctggctc 7140 tattcttcag catctcaaga tggcttgtgc tcctccaagc atggcagtca aattccacac 7200 aagaggggga aatatgaagg gcagacagtg ctggtctcct gagctgtccc tctttgtcgg 7260 ggaaataaat gtattccttc aagtcccgtg agacttctga agtagacgtc tgcttacgtc 7320 tcacccacca gaactatgta aactgcacat agtgctaggt ctacatagcc actcataact 7380 gccagggggt gggaaatctt taaataggtg taccaccaca caattaggat gctaatagta 7440 agggagaagg agagaatagg ttttgcgcaa gccaccagca tgcctgccac aattgcttaa 7500 aattcttcat tgacccctca ttgccacagg atgaaatcca aacgccttct tagttgggaa 7560 tctgacctac ctgtctctcc cacctggttc agacaccatt ctccttggtc ataaaattcc 7620 agtcatttgt gaacatccag ctcccccatg cctccatgcc tttgcacatg ctgttctttt 7680 atcttttatg ttgtcctttt atcttttatc caaaagagat atcccatcat cacatctctt 7740 ttgtcagccc ccaaatactt tgtctttcaa gttcagctgg aggattacct cctatttgaa 7800 atcagctttg tctcttacaa ccaaacaagg ttttccttcc gagacactcc cacagcacct 7860 tgaactcatc tctatcaatc attcatttga ttgtaatgaa gttgttggtg gtatgcctgt 7920 gtctctgaca catctgcgat ctcatgagtt ccttaagtgg aatgtgaata gcgggatgaa 7980 cagtattggt cttcagccct catctctgca gatgttgctt gacccaaatg agcgttgcct 8040 tttattttga ttttgctttg atttgtctac tccatgtact tgagccatgc atttctgtct 8100 tagcgatgct ttttaaaagt cattttttgg ttgattatcc agatttgtcc acctttgctt 8160 ctag 8164 <210> SEQ ID NO 34 <211> LENGTH: 1604 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 34 gtaaggaaat gttaaattgc aatattctta aaaacacaaa taaagctaac atatcaattt 60 atatatatat atatatatat attttttttt ttttttacat cttatattac cttgagtatt 120 cttggaagtg gctagttagg acatataata aagttattct gaagtctttt tttttctttt 180 tccatggtga gcagtggctt gatgtggatc tcagctccca gacgaggcac tgaacctgag 240 ccgcagtggt gaaagcacca agttctagcc actagaccac cagggaactc cctattctaa 300 attcttgagc acattattta ggaacctcag gaacttggca ggattacagg aaatatatct 360 agatttaaaa aaaaatcttt taacagaggt cccaaaggag agtcatgcac agctatggga 420 ggaagttcag aaactgccct tgctaccaga tcactgtcag ataaaatggc cagctacatg 480 tttctgcaca ttgccctaag atctttacaa acttttctgt gcatttttcc acttttaaaa 540 gaaaatttcg gggttcctgt tgttgctcag tggttaacga acccaactag tatccatggg 600 gacaggggtt cgagccctgg cctcactcag tgggttaaga atctggcatt gctgtggctg 660 tggcgtaggc tggcggctac agctcagatt ggacccctag cctgagaacc tccatatgcc 720 gcaggtatgg ccctaaaaaa aaaaaaaaag agagagagag aatttcctcc agaaaaaaca 780 ctttggtagt ttgggagaag taaacaacca aaaattaatt tttctggagt attcgggaag 840 cttgtaaaaa tgggctctta cttttttgag gagacaaatg ggaacctacc cagaagaggc 900 acaatcacct gcatttgatt tcttgacctc tccctacctt ctttgctggc tttccacatt 960 tggatttctg tgaccttatc tctgctcctt ggtgttttca tttttcctgt ggacgtgcca 1020 gactatggga agggagtaag gcgttgattt agaatcctgt agtctctgcc tgtctctagt 1080 cattgttttc acccttctca aaggaccttg acatcctgag tgagtccgca agtaatttag 1140 gggagaagcc ttagaagcca gtgcagccag gctacatgac tgtgtccacc cactggaacc 1200 agtcattttt atacctattc acagcccccc taccatttaa atccccagag gtctgccata 1260 acatctgtaa ctccctttcc tggtaaattg tgttctaaaa gactggtaac aaaagatatt 1320 ctgtggtaca gagcataatt aaatacctgg gagctgattt gagtggggta aatcaactgg 1380 tttgacccct aaaacccacc atgagcattt ctgttctaat aaagtaatgc ccgtgctggg 1440 aattgtgttc tacggaaatg ctcctgctgt gtctttcttg agtcctgtgt cattgaacat 1500 gcttaggagc aaaggtcccc catgtggctt gtctgctaac cagcccagtt ccttgttctg 1560 gctggtaatg atccgatcat ctgaatctca ctgtcttcca acag 1604 <210> SEQ ID NO 35 <211> LENGTH: 3628 <212> TYPE: DNA <213> ORGANISM: Porcine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (361)..(361) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (373)..(373) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (407)..(407) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (467)..(467) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (477)..(477) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (500)..(500) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (505)..(505) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2026)..(2026) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (2136)..(2136) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 35 gtaaggaagg gtgagccctc aactccgaag aaaatgctgc aataaaagca ctgttggttt 60 tcagcttttt ttgtaatcac tgctcattct gaggtagatt cgcttgggct gataaaaaga 120 gaactaattc agataaatgc ttgcatttgc atagcctctt tttttaaaaa cttttttttt 180 tttttttttt ttttggcttt tcagggctga acctgtggca tatggaggtt cccaggctag 240 gggtcgaatc agagctgtag ccccgggcct atgccactgc catagcaaca tgcatagcct 300 cctttttaaa gtgccttcct gttttatacc attgggatgt gagaagagct attgtggaaa 360 ngagcatggg gtnataaccc tggacctctc acgtcctacc ctcaggntag tgggaaaact 420 ctgagtttaa ggacatcaaa gtgactcctt tttagttaca ttatggngga atcagcncat 480 atttttacaa ggggcggagn gtaanctgtt ggagtttaca agacatatgg tggcattgca 540 actacttaac cctactatta tagcacaaaa gcagccatag tcggtcctga aggagcctga 600 tgccttcagc tttataggca atgacgtgtg aatatcacaa acagtttcct gtgtcaccaa 660 acatgattgc cttttgattt ccctttcaac cctttaaaaa aaggtaaaag cccttcttag 720 cattcagcag caggtcgctg tgttttgcca actcctgatc tgtagcattt cgacaacact 780 gagctctcaa cttttgaacc ctgagtccac cacatccttc agtgaaacca gagccatgtg 840 atactaagga tagaaacgga aacttcctga atccaggcga tcaaatagga gggagaaaga 900 ggaactttca ttgacaaaac cacaaatatt gtgaatggac tgttacaaat attgtgaatg 960 ctcctattcc caaccccctg gcttcattac agggtcctat gtgttcatcc ttattgagaa 1020 atttgtattg ctactgccag gttgccaata cccagcggtg cccatggtgt tctaaaatga 1080 agcaatttca actttatttt tttttcctgt gactttacat gacaagttca catgaaggat 1140 atactttgat agtaatgtcc atggttaggg aatatacatt gtttgctggt tgactggccc 1200 ctggattttt ctattgaaag tccatgagat ctcgaaggca caggtgtgtt ctctcgcttt 1260 ttaaggaaag ggtttaaaaa cttaagtaat taacagcttt agtaacaaat tacctataac 1320 acacttaaaa accgaatacc acccactgga gtattgtgct acgattaaaa atctacttgt 1380 ctactacatg atatctttgt cccacagaag gttctggaac caaacttgta atttcaggat 1440 tatgagagcc ctgagttcac gcattgtgta ataactatgt tgtgtggtag tcaatttgta 1500 cagcttgctt agagagaaca atgtcaagtt aaggaggcga ttgctttata gtgcctgtca 1560 caagatgcca ttgccattgt cctagcaaga gatattctat gggagtatac tacattttag 1620 tgaggataag aactttttat ggcatttagt ccggtcattt cccaaccact gtcctgaaaa 1680 ccaatttcat tttgatttca ggggcttgtg tgggcaaagt tgccaggcat taaaaagcca 1740 cttctcaact gtagtatcac aatgctttag ttgggtagtg tattgcagat agcttatggc 1800 tgaaaagtta ccaagccttg cagttttcac tcctttgagt ttatttcctt gacagaattg 1860 accctgagtt ttttgactct tacctgctca actaataaac accagagtca tttatctcca 1920 ttgctcttgt ctgaccttta tttaccgaat aatgccttat gggttcacaa aaacaagggg 1980 ggagggggcc agcatgcctt agaaactgtc tttagtcaag aaatgngatt ttattatgta 2040 aatatatgag tattataata gatagtgtta ttaatagaca ccagcaagaa ttgtcaataa 2100 tttaaaaatc acaaattaaa atacatccat gttagnatca tttatcctaa ctcccaaagc 2160 cctttaaagt ggaagattta gatgttaacc cagagattaa agacatgttc aaagaatcct 2220 tgattttttt ttgaatccct tgtttttaga gaagaaaacc taatgatttt ccccctctgg 2280 attctacata ttaaatatag ttttggaact tgaatattag tatggttaat aagtgctgat 2340 atgctgattt tgtttatatt tttcttatga gtaaatatcc tatatcacca gacattatag 2400 tctatgtaca aatatgattc ttaaacctga tagcacattc attagagttg gaattgcctt 2460 tttttttttt ttttttacag ttgcacctgc aacatatgaa agttcccagg ctaggggttg 2520 aatccaagct gcagctgcca ccctacatta cagccgtagt aacagcagat ccgagctgca 2580 tctgcaacct atgctgcagc tcagggcaat gccagatcca ctgagtgaag ccagggatgg 2640 aacttgcatc ctcatagaga caacgtcgtg tccttaaccc actgagccag aacaggaact 2700 ccagaatttc ctttcaatag aagaagcacc aagtttagga tcagaaagcc tgaatttgaa 2760 taccaattta ctatttgtta gtcatatatt tctgagtgtg tttcctcatt tattaaaagc 2820 agactaaaag atgagagggt cttttgttga gaatcaaata caataacatg tgaaagtgtg 2880 taacactatg attgaaatat acctacacag ccatttattt gtttattgtt catgttttgc 2940 cacccacaca gtagtatata atccttttat gtaataaatg ctaataatga aagttggcaa 3000 cttatgtaag tactcaaaat gctggaggtc atgggatact gactgggata ctacagaggt 3060 aatgtcattt cctctgcgct aaacttattg tcttgtagtt agggactgac tctctttagg 3120 acaaggagtt cattctgtat accatgtgtg gctatcaccc ttcgaagttg aaaaactgcc 3180 ccagggtggg cacccatccg ttctcttaga tatatggccg agacctttct ctcactggga 3240 gggaaccaca ctgaggaatg agaaaaaaaa aaggaaaatc aagatgaaac cagaaacctc 3300 tttggcataa cttctccact ctgtactttt tgttagaact acccttgcac aaagcagcat 3360 cagtgtggaa gacagaattt gcacacctgg tttgatatac atgccgtggt atatgggatg 3420 ttctaacaat aaagaggact ctcccaggaa atctcctcac tgttatagtc agccttgagg 3480 aaagagctct tcttttggac tctggggaga gtctagtttt tcagttcctt gcttctcggt 3540 caacgtgttg gtgtaaggat cacactctct cttatactag ataattctat tttttcacct 3600 ttcaacctgt ctatccttct gaccctag 3628 <210> SEQ ID NO 36 <211> LENGTH: 300 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 36 gtctgtgttc tttccacatg tttgggttat cctttctggg ataaatttga ggcgagatag 60 aaactttaag actaaagaaa caatggccta ctttttttgt acatggtcct gtgtaaatct 120 ctatttgagc tgaaataaga tggtcttcct ctccaattat ccatggtatg actctgatgg 180 ataacaaatc cagttctgaa aaaaggggat ttctttccag aagagaggac agtttcttca 240 aatattgaat taaaagcaaa atagatgtaa accgttgttg gttttattgt tgaattccag 300 <210> SEQ ID NO 37 <211> LENGTH: 734 <212> TYPE: DNA <213> ORGANISM: Porcine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (705)..(705) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (707)..(707) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 37 gtattttctt gccctcatca gcatgaaatt gctcttggta gaaaggataa taatagttat 60 ccaaaacatc atcctatgtt catctgtttc ttccctcttc attttccata gagtacagta 120 tattctatct ctgtcttagg aaaatggact gtcattcata taatcttaca gagaatcaat 180 tagtaatgta ctctatgccg tgacaggtgc gaaggttttt tttgaaggca acagataaaa 240 atatcctata tttcacctat tgtaatttcc ttaaaactga cattattgaa taaatgtttt 300 actttcatct tgaatattat tatgttatgg aatcatacac tttaccccaa taatcatcga 360 aaagaatttc caaaaggttg agagagttgt gttgatctga ttactttcct ctgcatcctt 420 tgagcttaac ctttgaatat agtttgctaa ggaaagtagt ctgtttatga tcctggagtg 480 gaatcaggct aagtgtcctc attcagaacc cactgaatca gacagaatga atttatttcc 540 ttgaaagttc aaaatgtgtc actcaagagt ataaattttc aaatcttact ctctcttttc 600 cttggatgtg agcaattctt cgataattga atgaggcaga ttatatagac ttacatggaa 660 gactgttggc ctgagaattc aaactatggt gttcaagact tcacngngag tccgatgcca 720 tttgtttccc acag 734 <210> SEQ ID NO 38 <211> LENGTH: 2421 <212> TYPE: DNA <213> ORGANISM: Porcine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1387)..(1387) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1390)..(1390) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1406)..(1406) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1972)..(1972) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1983)..(1983) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 38 gtaattcttt atatcaaaat gatgccaagg agttggcatg gcactttgct aaatgctgtg 60 tgaatcaata caaagataat taggacatgg ttcttcctca caagaggtgt gcaatcttat 120 tgggaaatca tacttgcaag tcacaaatat agactaaagt ttccagctga gaatatgctg 180 atggagcatg aaacactaag gagacaggga gaatctcagg aaaaatcaag aataatttgg 240 atcaaatgga ttcctgacat agaacataga gctgatcaga aagagtctga cattggtaat 300 ccaggcttaa gtgctctttg tatgtggttc agaacagagt gtgggcagcc tgagggggat 360 acataccctt gacctcgtgg aaagctcata cgggggaggg atgaggctaa ggaagcccct 420 ctaaagtgtg ggattacgag aggttggggg ggtggtaggg aaaatagtgg tcaaagagta 480 taaacttcca gttacaagat gaataaattc taggggtata ataacagcat ggcactatag 540 atagcatatt gtactatata ctggaagtgc tgagagtaga tcttacatgt tctaaccaca 600 cacacacaca cacacacaca cacaccacac acacacacca cacacacaca cgtgcacaca 660 aacagaaatg gtaattatgt gaggtgatgg cggtgttaac taactttatt gtggtcatca 720 tttagccata catgcatgtc atgaaatcac catgttgtac accttaaagt tatgtaatac 780 tagatgtcag ttatatctca aagctagaaa aaatgtgggg accaaggcag aagctcttct 840 gctctgtgtc taagggtggt tctggggctg ggatggggag gatggttaag tggtatattt 900 ttttcatacc tttgctcagt actatcattg taagtgttca atatatgtct gcttaataaa 960 ttaatgtttt tagtaagtaa tctctgttta gtaatgtgtc agaaatgccc tacttgcaat 1020 aggaagaaaa cctgtccagt cccttccttt tttctgtaag tctgatttca ttgcctccca 1080 gaatgcatca ccatgtgaga gatagaggga aggtgctgtc cttatggggt taacagtgtg 1140 actagggagg caaaatatac ctactaaagg gtggtagcat aattcagttc ttatgtgagt 1200 atgtgtatgt gtgtgagtat gtgcacatgc acatacattt taaaaggtct gtaatatact 1260 aacatgttca tagtggttac acctagctta taggtaacat tttttcccct gtatccttgt 1320 ttgtgtttat caaattttca taacagtaat ggtagaagga gtacctgaca tggtaccata 1380 catgctnggn cctgcctaat ttctcnattt cctttattgc ccataccccc attgcttgac 1440 aagcataagt ccatactggc ttgttttcgt tcctcagact cagtacacca tgtagctcca 1500 tgccctgggt ctttgtatgt gctatttcta ctgcttagag tgctattgcc cctgaccacc 1560 acgtggtcag caacttctct tctgcgtctg tgtctatggt ctatgattcc agatgtcatc 1620 ttcactaact acccttctaa tatgcccttc catcccaccc gtcctcatcc ttaccccagc 1680 cactctctat ttggtggctc tgttttattt tcttcctagc tcatcactct ttgaaatgaa 1740 cttatttact tattcaatat ttgcttcttt cactagaatg aatgctccat gagagcaggg 1800 acctgcttta tcttgctcgc cactgtattc acagtgccta gaactacgtc tggcacatag 1860 taggtgctca ataaatatcg atcaaatgaa agaatgagca aacgaacaaa tgaacaacac 1920 gtgaggtagg catcatgatt ccatcaacag aggagaaaac cagacttaaa gnaatgaagt 1980 ggnggagctg catttgatct tgactgactc caacatccat gctcttgacc actgtgcatc 2040 tccagagtgt aatgaacata ctttactttt atattccacc aaaataacaa agccatgccc 2100 atgttagtag agagttaatc gacagtgccc ttaaaatatg catgcaccca gggtacaact 2160 atgcatgctg ccctgtgttt tcagttggat ccaaatgaat tgccgtaaac aaagagggga 2220 ttcaatgtct ttgactagtt tgggatattt tcctagtaac caactttgca aaataaagcc 2280 actaatgaca aggagctttg ttctacttct gcatcactca actgtcaatt tttatctctt 2340 gcaagacttc taatctacta gaacttttgt ttttctgtga tttctgaaca gagaagacta 2400 atccaaaccc tgtcattcca g 2421 <210> SEQ ID NO 39 <211> LENGTH: 457 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 39 gtatggctgg atattttata taacgtgttt acgcataagt taatatatgc tgaatgagtg 60 atttagctgt gaaacaacat gaaatgagaa agaatgatta gtaggggtct ggagcttatt 120 ttaacaagca gcctgaaaac agagagtatg aataaaaaaa attaaataca agagtgtgct 180 attaccaatt atgtataata gtcttgtaca tctaacttca attccaatca ctatatgctt 240 atactaaaaa acgaagtata gagtcaacct tctttgacta acagctcttc cctagtcagg 300 gacattagct caagtatagt ctttattttt cctggggtaa gaaaagaagg attgggaagt 360 aggaatgcaa agaaataaaa aataattctg tcattgttca aataagaatg tcatctgaaa 420 ataaactgcc ttacatggga atgctcttat ttgtcag 457 <210> SEQ ID NO 40 <211> LENGTH: 4012 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 40 gtttgacttg aatatttaca gggaacaaaa atgatttctg aattttttca tgtttatgag 60 aaaataaagg gcatacctat ggcctcttgg caggtccctg tttgtaggaa tattaagttt 120 ttcttgacta gcatcctgag cttgtcatgc attaagatct acacaccacc ctttaaagtg 180 ggagtcttac tgtataaaat aaactattaa ataagtatct ttcaactctg gggtgggggg 240 ggagactgag ttttttcaca gtcctatata ataattttct tatcctataa aataattagg 300 agttcccgta gtggctcagc aatagcaaac ccgactagta tcgatgagga tgcgggttcg 360 attcctggcc cccctcagtg ggttaaggat ctggcattgc cgtgagctgt ggtgtaggtg 420 gcagacacgg ctcagatccc acgttactgt ggctgtggca taggccagca gctccagctc 480 tgattagacc cttagcctgg gaacttccat atgctgtggg tgtggccttg aaaaaaaata 540 aataaataag ataattactc aaatgttttc cttgtctcag aaccttactt caggataaag 600 agtgagaaag ttttttttat gaagggccat tattacagct caaaaataag ttgtcttcag 660 caagtagaaa gcaataagcc tgagagttag tgttcctatc agtgtaaata ttacctcctc 720 gccaatcccc agacagtcca tttgaacaat taacggtgcc ctgggagtac agttcagaaa 780 cattaatgtg gatgttccag acctgtattt ttataagtac ttgtcttgag ccggatggaa 840 ccatcattcc tcaccattat ttagaagtgg actgtgactc tgttggagat cagggcacac 900 ggttaccaaa agcacaccct tctcctggcc ttacctttgc aaagctgggg tctgggacac 960 agtcagctga ttataccctt ttactaactt cccacagctc aaatctggtc aattctcctt 1020 cacaaatctc ttaaaaatcc atcactcacc tccagcctct tctgctgtgg ccttgattca 1080 gcctctcaca attttttttt aaccagaatt ctggcagtgg cccctgactt gcctctgtgc 1140 tcccagcccc gctgtcctct gatccatcct ccatgccagc ctttttcaat ctgctggtca 1200 cgattcattg atgggttagg aaatcaatgg catcacaact agcatttaga aaaaggaaat 1260 aggcgttccc gccgtggcac agcagaaata aatccgacta ggaaccataa ggttgcgggt 1320 tcaacccctg gccttgttca gtgggttaag gatccggcat tgccgtgggc tgttttgtaa 1380 gtcacagaca tggctctgat ccggcattgc tgtggctctg gcgtaggcct gcagcatcag 1440 ctccaattag acccctatcc tgggagcctc catatgctgc aagtgcagcc ctaaaaaaaa 1500 taaaaaaata aaaaaaaata aataaaagaa gtagacaaat tgtatagaac aaccctgagt 1560 atgttgcctg agcacatata acaagggtaa gtattatttc aggaaactct ggtttcacag 1620 atactcttgg catatggacc cctagagtcc tgatgtaaaa tatattcttc ctgggatctt 1680 aggcaagaag tttgaaagct ccaactctgc actgctgcca aagaaatgat ttttaagtgc 1740 aaaactcttc ccgttccctt ccctgtataa aattccatag gatctctcca gtgcctctag 1800 gataaaggca gttttcattc tctagttcaa ggtgagagaa gattttaatt atttcacgtt 1860 ttagtgggga attcaagagt ctggcacctg acatttgctg aactctctcc attatccctc 1920 tctagttccc cagacgcatc ctatggtaga aattcgcaaa ctagagtgag cgtcagagta 1980 acccaaggaa actgggtaaa tgcagctccc tgggctctac cccctgagat tctgattcag 2040 tagatctgaa gcagagccct ggaatatgca tatgcatcat tgtgtcacac caagcattct 2100 gggtaatgag agttgatgtt aggttctcag tagtaagaca agtatagaga ttccggggga 2160 ctgagtgctc agctctgcct tggggaggag ggagagggct aaagagaaca ggagatgggg 2220 acagggaatg ctcaacctcc aatcttaggc atttgagcta tgtcttaggg gtcaggagga 2280 ggttaccaat atagtgatta agagattgag gttccagtca gagggatatg ctggagaagg 2340 ggggtgaaaa taatgtcata ggtttggtga gtgcagatac tttgagtttt ttaatatttt 2400 tattgaaata tagttgattt acaatgctct tagtgagtac aattactttg aataagtgca 2460 tagatgtatg ccattcttcc agaaatgatt tattgagctc ctttgggcat catgctaagt 2520 acaggggaaa cagctgtgaa gaggtccttc ccttatgaag tcattcatcc ccttcagtaa 2580 atgaaggtaa aggaaaagga tgagacaggg acgccgtgtt ggaccagggt cagaaaggcc 2640 ttataagacc ttgcctggag ggcaaggaac ttgcctgtga gtaaggagag cttgagaaag 2700 cgataaagca aagaaggaac attactgcat tgtgttttag aaaaaccatg tcctggggaa 2760 gaactcctag agtcaggggg gccagttggg agactgtgct tttttccagg aggagataag 2820 tgaggctgct ggctgagatg gagcaaggat ttagagaagc agatatgaga ttcatttaga 2880 agttagacat tttaggatct gacacataat ttatcaccaa aaccagtgca tctctggctt 2940 tgggccacca gttttggaga agtggaatgt agggacctac cattacctgc caatctttac 3000 tacacagatg cctatttccc tcctcatatt tcctttctcc agatcacgtc ctattctatt 3060 gccaggactc aagattccac cttgcatgca gtgatccatc ttcacactgg atggacagct 3120 ctagggatgt cagagcacac tcttgtccat actgctgact gggtctcctg tcagcccatc 3180 tgtctatcag ctgtggtatt attagtataa taagagggct gtatatgaga gacacaaaat 3240 tctaggtgta gctcaaagat aggctagagt tattcctatg tacaacaaat atttatggga 3300 ccccttctgt gtactgtcat ggttgctgct ttcatcatac ttgtagtcta atggaggtgg 3360 gggcagggca ggaataagcg gatgtccaca aaatcagtaa gaccacttat attcaacatt 3420 ttcataattt agttatttga gcccaaaggg tccacatccg tggtattcca actttttttt 3480 ccccggacat ggatctttat cttttttttt ttttcttttt tgcggccaga cctgcggcat 3540 atggaagttc ccaggccagg ggttgaatgg gagttgcagc tgcctggtct acaccacagc 3600 cacagcaagg tgggatctga gctgcatctg tgacatacac cgcagctgag gtaacaccag 3660 attctgaacc cactgaatga ggccagggat ggaacccgtc tccttatgaa cactatgtca 3720 tgttcttcac cctctgagcc acaacgggaa ctccagactt cgtctttaaa tgtattctga 3780 cttggagagc tatcacacta agcaattaac aggagctgac ctggtttagg ctggggtggg 3840 gccctactcc tcaatgttcc ctgaggcaca tctgtgggac ccctgggcat catctatctg 3900 agcagcctta gagctgctca tccagttgac tgttgatgta gaagtgcaaa cttctgcctt 3960 ccttatttgt tgctttcttt tttcattgtt ctctcccctt tgtgtcttta ag 4012 <210> SEQ ID NO 41 <211> LENGTH: 2281 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 41 gtatgctatg aagttattat ttgtttttgt tttcttgtat tacagagcta tatgaaaacc 60 tcttagtatt ccagttggtt tctcaataag cattcattga gccttactga ctgtcagacg 120 gagggcgtat tggactatgt gctgaaacaa tcctttgttg aaaatgtagg gaatgttgaa 180 aatgtaggga atgaaatgta gatccagctc tgtttctctt ttggaggatt ctttttcctc 240 catcaccgtg tcttggttct tgtttgtttt gggtttttgt gggtgttgta ttgtgttgtg 300 ttggttatgg cagtgacagc tatttaaact gtgaaacggg ggagttcccg tcgtggcgca 360 gtggttaacg aatccgactg ggaaccatga ggttgcgggt tcggtccctg cccttgctca 420 gtgggttaac gatccggcgt tgccgtgagc tgtggtgtag gttgcagaca cggctcggat 480 cccgcgttgc tgtggctcta gcgtaggcca gcggctacag ctccgattgg acccctagcc 540 tgggaacctc catatgccgc aggagcggcc caaagaaata gcaaaaagac aaaataaata 600 aataaataaa taagtaagta aaataaactg tgaaacgggg agttcccttc atggctcagc 660 agttaacaaa cccagctagg atccatgagg atgtaggttc gatccctggc cttgctcagt 720 gggttaagaa tccagcgttg ctgtgagctg tgatgtaggt cgcagatgca gcccagatcc 780 tgcattgctg tggctgtggc gtaggctggc agctgaagct ccgattcaac ccctagcctg 840 ggaacatcca tatgctgcag gtgtggcctt aagaggcaaa aaaataaaaa aataaaaaat 900 aaataaattg tgggacagac aggtggctcc actgcagagc tggtgtcctg tagcagcctg 960 gaagcaggta aggtaaggac tgcagctggg taaggactga attgcaccaa ctgggaagta 1020 agcctagatc tagaacttaa gttagccctg acatagacac acagagctca ccagctaagt 1080 ggttcagctt ataagctggt cactgaaact gaggatgtcc acaaaagcaa aataagtagc 1140 aacaggcagc gggatgcaag agaaagagga ggcctaaaat ggtctgggaa tccctgccat 1200 acctatattt tatcctactt atatttagtg cctgaatgtg tgcctggaga gcaaagttta 1260 gggaaagcat cgggaaatgc acagtattca tacccttagg aacaaagatc agttacctcc 1320 agggtaaaga ctatttccaa gtttaaattt caacccctga acattagtac tgggtaccag 1380 gcaacacttg ccatcctcaa aatcaatgaa tcctaaaatt caacctgggg gtcagtgaca 1440 gtctgtgaca aagtttttgc tggtcagtaa cgaaataagt atgagcacca tctgagtatg 1500 gtcaccaaga tgtcaactct ctttcctttg gacgaattgt cattattcca agattaggtc 1560 ctttctattt ttgaggtgtg aaaacatctt tcctttcata aaataaaagg atagtaggtg 1620 gaagaatttt ttttgttttt tggtcttttt gctatttctt tgggccgctt ctgcagcata 1680 tggaggttcc caggccaggg gtcgaatcgg agctttagcc accggcccac gccagagcca 1740 cagcaacacg ggatccaagc cgcatctgca gcctacacca cagctcacgg caatgccgga 1800 tcgttaaccc actgagcaag ggcagggacc gaacccgcaa cctcatggtt cctagtcgga 1860 ttcgttaacc actgcgccac gacgggaact cctaatgata ctcttttata tttagctact 1920 atgtgatgat gagaaacagt ccacatttta ttatttttta gccaatttga tatctcatta 1980 ctaagataat gataattttc tctataaatt ttatttaagt tagtgttatg aagtggtttt 2040 gctagtgtag aaggctagga tttgaattca gttcaagaaa gaagagaggg agggagggag 2100 agggatgggt agagggatgg ggcagtggga gagagcaaag aggagagaca gtttttgtat 2160 taattctgct tcattgctat catttaaggg cacttgggtc ttgcacattc tagaattttc 2220 taaggacctt gaccgccaga ttgatatgct tcttcccttt accatgttgt catttgaaca 2280 g 2281 <210> SEQ ID NO 42 <211> LENGTH: 4559 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 42 gtaagcagga ataccagtgg aagtgcccct ttcttccttc cttcctaaat aaactttttt 60 attttggaac aactttagag ttacagaaaa gttgcaaaga tattatagac agtagtgttt 120 atatatatat ataaattttt ttttgctttt tatgaccaca cctgtggcat atggaggttc 180 ccagtctagg ggttgaattg gagctacagc tgccagtctg tgccataacc acagcaatgc 240 aggatctggg ccacgtctgt gacctacacc aaagctcaca gctggattct taacccactg 300 agcaaggcca gggattgaac ctgcatcctc gtggttccta gttggattcg tttccgcttt 360 gccgcaatgg gaactccaaa ttattgttaa tatcttactt tactggggta catttgttac 420 aaccaatact ctgatactga aacattactg ttaactccgt acttgcttct ttttgagtca 480 tttgcaaaga ctggcttctt gacctgcttc cttccaaaca gctggcctgc ctatgctgtt 540 ctcagacctg caagcactga tctctgcccc ccttgccttc tctccagtgg tgtctccttc 600 cccaaacaaa cccagtgtgg ctctggaaag ggagttaagt caacataaac caacacatat 660 tttgttgagc tccaattttg agcaaatccc tcacctacgg cagacaggca tgatgttaag 720 aactagggct ttggacacaa ggtcaagacc aagaagggtt cctcacccct actgattcag 780 ataaccaata atgaggcttt gaatccctgt ccaaaggttg ttttttttcc cttctattga 840 gcttcttgcc accttatcag ttttttttat gacagtcaaa tgacatgata tatgtgagca 900 tacatggtaa tttttaattc tatataaatg aatcactaaa taaattagga ggatatatag 960 tccaccttta agcgtattac acgtgtcaca tgaatgtgtg gcgacttaat tgtagaggtt 1020 taaatgtagc ttcctataat agatgtgttc ctaaactaca ttttaatcat tggacttgta 1080 tttttatgtt agcacttgct gttgaagaaa agcctatgcc aaaagttcag tgaaaccaat 1140 aatccactgc cagctttctg agttaaaaaa aatccctggg ttttcacaca caggaacacc 1200 ctgtgtgaaa cactcattta gagcaaaatg catctgataa ggagttcctg ttgtgcctca 1260 actggttaag gacctgacat tctccatgag aatgtgagtt tgatccccgg ccccactcga 1320 tgggttaagg atctggtgtt gccacaaact gcagctccga ttcatctcct agcctagaaa 1380 cttccacagc ccagaatatg ccacagaatt cggctgttta aaaaaaaaaa gaaaaaaaaa 1440 agaatcataa atgtgttggt ttgttcacca aatacatgat aacttgctct tgccaagctc 1500 agcttcataa atattaagtc atttaataca gcagccacct tatgaacaga tattactata 1560 cttcccattt acagataagg aaaatgccat atttaaccaa gagattaaat aactttcccg 1620 aggtcttata gcaagtaaat catggtgcag gggtttgacc acacgcagtc tatctccaga 1680 gtctgtgtat ttagccactg ttttactttc aaatttaaat ttataaaact tctaaattat 1740 ctgttaacca taatctttgg aatttttaaa accacgagtt cctataaaat gtttcattga 1800 aagtaagtca cttttccata gcttttgata atacatctgt aggataaagt aagccacagc 1860 tctcttgcag acttggtaca ccctggggca aagcatcatg cctgtcacgt acatggtggt 1920 ccttactttg actctcagtg cttttattgc ccaggaattt tgtgagattt ctagttgttg 1980 aggtttgttt aaagaggtta tgccggtact tggaagagct cttttcttgc tacctggagc 2040 cttctcatat ttcctttttg aggagggaca tgaattgcct ttcaaactca taaatatatt 2100 ttctagtaca caagtctcca tcttccttag acgcatggct cctggagttc tccatcctcc 2160 tgctccactt tgggtgggct cctctctggg tctgccacca atctgccacc cagagacatc 2220 cttgacccac ttccagaccc caccatggct tcactttctt cgctttcctc ctttgtggaa 2280 ccttctgctt aagaatctga ggaagaaaat ttgcacgtga gctaaactgg aggtactttc 2340 ctgcctggtc ttgcacgata gcttggctga gcccatgatg ctgggtggct gttactttcc 2400 atggacaccc gaaggcgttg ctcctttggc ttctagttgc atgcagtgtt gcttatccca 2460 ggctgatctt tcttccactg taggtgactt ttaagaatta agggattaat ctatatctac 2520 aacaacaaca acaaagacct tttcaagctg aggtagggct ttctgtatat gtttggagtg 2580 gttatccagc agactttact tgaaggcagg ggtcatatcc tcaagtgctc ataaacggac 2640 cacagaaaga tctcataatt gggtggagct gggtggggac cgtgtcatgt ggccaggaaa 2700 tgccagatgg gaagggagtg gcccttactg agctccagct gaactctgaa ttttctagaa 2760 aactcagaaa tctggatttt tcatgtgtaa tacccagatt tatagatgtg gaaagctaat 2820 tctttttttt tttaagggac tataggcaat gaactaagat ctaggttgta tttggacaag 2880 gggtcatcag tttaagctgt gtagttgagc gctcagctat tgggctgagg gacccctaaa 2940 tactgagacg gggaggtcct tgctctgggg catcacaagt acactccctg gtctcattca 3000 aacacttttc ctacaaaatt gatcccattt cttcagtgca ctgtctgaat gcatttggcc 3060 cagagccgtg ctgaggcata gggaaggggt ccacggtttc atggcatcgt tttgtgctgt 3120 gtgtccctgc tgtcgtccag gatacctacc tctcctcctc ctgcatctga atgtcccccc 3180 acagactctc tgggattcta cagcctctgg cctgttcctc agacacctct tacctgccag 3240 ctttccagat tcacattagt tagtccaaat ctactgccgt cagtgactca cttcatttct 3300 tcttctccga ggcagttcag cccggtacag ttgttttgtc aacacttcag ttgagtctgg 3360 aagatgtgca tgggttatgc acgagagcgg tccatcattt tgagctagaa gtcctttctc 3420 agcccagaga caagtcctca tctcctttac ttcctgactc ttcttcctct gcatccttcc 3480 aagatatctc tttctccagc caccacctaa atctcttctt ttcccggggt tccgtgctca 3540 acccactctt cttcttaaat ctgtggctgg gtgaacgcat ctgctggcac cacttctctg 3600 ctaaagactc caaaaatcca taggtcctgc ccggcctttg cccacctctc tccaacactg 3660 tccagcttta gatgtagagc taatcccccc agagatatca ttccctggat gtctaagtcc 3720 tttggtatct cactttcagc gtgttcaaaa tcctcttaca actgttcttt ctccttttcc 3780 atcttgatta ttggcaacat gccagccttt cccctacccc cagcagtgag ccaagctaga 3840 aacaagggct taatcttcaa tctttccttc tccatcccta aacctaatga gtctccaagc 3900 ccttcccagt ttacacccta aatgttgctc aaaacatccc ctagttcttc cacgtgctct 3960 cctctatatt gaaaggtcaa gaaaggccat cttccctcca ctgtgaggaa atagatcttg 4020 atactgcccc tgagctgggc agtcctcgac ctgacaaact gtgcagtgtt tctaaatctc 4080 tactggcaaa atgagagtgc ctttgacctg tgttgcgatc tcagatcaca gtggatgtaa 4140 ttgttttata ggaatggtga acgaaaaaga agtaaatccc taatgccaaa ctcctgatca 4200 ttctatgtca tttaatagcc tgtcatttat gataaagttt cctctactgg cattagcaca 4260 atacttctca ggaaaaaaaa atatgatgcc agatactgaa aagctcctgg gtaaacatga 4320 acatgggtac cgataaaatg gtgaagccag tccaatctta gagtgacttc ccttcatgct 4380 acttcatgct cttttttttt ttttttttta agaaaaaccc cttttttttt tctcacacca 4440 gtcacagagg agaccgaggc ttagcaaggt taaggtcaca tgattagtaa gtgctgggct 4500 gaaactcaaa accatctctg cttgtctcct aaccctgtgc acctctgact attcaacag 4559 <210> SEQ ID NO 43 <211> LENGTH: 458 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 43 gtaagggcct tgaccaccga attaaggtaa tcttgctctg tggcaggcct tgttttcagt 60 attttaagta cactggctca ggtaatcctc acaacagccc caggaggaat gttctattac 120 ctccactgta tagatgagga acttgaggca cagaatggtt gccaaggtca cacagctata 180 ttgggggttc atacccagcc atccaactct gtctgtactc tctgccactc tgcaccccca 240 gctcctgatc cacttcctgt ttccatccct cgatttctgc tgcactcagg ggcccctctc 300 cccctcggcc tgtgagatct gcttcagtag gcttttctcc ctgactcctc catccctgtc 360 cttacaggca gctgcttctc tccgggacac gaggggtcca tacggacact ctctactggc 420 tgggttgcgc ctaactcgtg attcctcctc tgtttcag 458 <210> SEQ ID NO 44 <211> LENGTH: 2482 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 44 gtaagtccga aaatgcctgt cgtgtgtgcc ttaggctgct gcggaggagg ccagggctat 60 ataagcagag tcagtgactg actgtgccct gcagtgttga tggccatgga gattccaccg 120 ttagagcttt tttctttgtt aaccttgaag gcaaatctgg ttaggaagat aactttcaaa 180 gagtcaccat ctggacattc atgcccatgt gcttcaatcc tgtatacaag cagtttagag 240 tacagggaag ggaaggacat tatgaaaggg agagggtgtg tttggatcca gcagctccat 300 cctcagaatt tatctgaaga cactgcaaaa ttactaagaa tcactatgac aagaatgagg 360 atggggtgat atggcaaagt tgtgatcctg gaagaccttc atctcccatg ttgcccaact 420 ctgaacatga atttggtgaa ctagttggtt aaggggatga tcctccaagt ttctccctgg 480 ttgagctcca aaaaccatgt aagtttctca tagcaaaacc gtataggtcc ttagggcttt 540 agttggaata tttgtgctga aatgctggaa agccccattt gccatttttg tatttgcaaa 600 ataatcatca agaggggaga atgcattctt tcatgaccac tgaccctctg aaaaggtcag 660 gaatttagtc tgaagtaggc aagcctccta ccccgcttct gccatgagct tgcacgcaca 720 ggcctgtctt gacatttctt ctttatagat ttctttttga atatcttgaa attgctttaa 780 aaatatttaa agaatgtaga attatataaa ataaaaagga aataacccca cacctcccac 840 aaaaccctgt ttcctgcctt tctccaccca ctctccaggg taacacttgg taacagcata 900 gttgtatcac cccaggccta tttttgagca tatcagcatt tcaagaaatg tattttttct 960 caataaaaca tcccttatag ttgaggaggg gaggttatca ttcctgggtt ttgttttttt 1020 ttttttttta atgtaatcct ggtacatcgg taatttgcat tttttattca ttaatatctt 1080 tggtatttct agtgttggga cacacaggtc aacctcagtt tttgggtttt tttttttgtc 1140 tttttgtctt tctagggcca cacctgcagc atatggacgt tcccaagcta ggagtctaat 1200 cagagctgta gccaccagcc tacgtcatag ccatagcaac gtcagatcca agccgtgtct 1260 gtgacctaca agcacagctc atggcaacac cggatcctta accactgaac gaggccaggg 1320 gatcgaacac acatcctcat ggatcctagt catgttcatt aaccactgag tcatgatggg 1380 aactccaact tcaactattt taatgtctgt aaaacattcc atttggaaac catttcattt 1440 gtaaagcaaa atgaaaacat tttgttcatt ttcaacagag ttcgtagctg acttctgttc 1500 tggaaaaaag gaaatggagc aaatttgagt gagaaagatt caaagataac ttttctttta 1560 aaaaaaatta tatcttggaa acttctgggc tattgattct gaagactatt tttctatata 1620 ctgttttgat agcaaagttc ataaatgtga aaggatcctg cgatgaatct tgggaagcag 1680 tcatagccca atatatcttt gttgctttta aaatgagatt tagtttacta aatatttttc 1740 tgatcataaa aataacacag atctaccgca gaaaatttgg aaaaaaaaaa acttttaaat 1800 tcaaaaaaca gttaaaccac aaatgatccc accatccaga gagcaatttg tactttggtg 1860 tctagttcat ctttcttttt ctgtttacaa gcacatatac cacaagcatt ttttcaaaaa 1920 atgaaaatgg gataatacta tacatacgtc tgtacacctg catagttact gaacagtctt 1980 tgatctaccc tgtaagtttc taacttttca ttatttgaaa tgatgttttg gcaaagaaat 2040 atgtaggtgt gtctcgcaca ctttcataat gatttcttag gataaatttc ttaggataaa 2100 ttcataatga tttcttataa taatccatac tctgccaact gatcttcagg gaagccaact 2160 cgccttctca gaaataacat ataacccatt tacttgccct ctcaccaata ctaggtccta 2220 atgtttttgt gtacagattc tatattttta catacaagaa ttccttaaag caaggcatgt 2280 cacagaaaaa tagaaggaag acacaattgt catgtttaag gactgcattc tgtaccaaaa 2340 atgctaagtt aaatgaacat ctgaaacagt acagaaacgc tatctttcag ggaaagctga 2400 gtaccaggta ctgaacagat tttggcaaat acagcaggca tggatgtttc caaaacatgt 2460 ttttctactt tatctcttac ag 2482 <210> SEQ ID NO 45 <211> LENGTH: 1335 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 45 gtaaagcatc ctgcaggtct gggagacact cttattctcc agcccatcac actgtgtttg 60 gcatcagaat taagcaggca ctatgcctat cagaaaacct gacttttggg ggaatgaaag 120 aagctaacat tacaagaatg tctgtgttta aaaataagtc aataagggag ttcccatcgt 180 ggctcagtgg taacgaaccc tactagtatc cattgaggac acaggttcaa tatctggcct 240 cactcagtcg gctaaggatc cagtgatgcc gtgagctgca gtgtaggcca cagacgtggc 300 tcagatctgg tgctgctgtg gctatggtgt aggccggccc cctgtaactc caattcgacc 360 cctaggctgg gaacctaaaa agaccccaaa aaagtcgctt taatgaatag tgaatacatc 420 cagcccaaag tccacagact ctttggtctg gttgtggcaa acatacagcc agttaacaaa 480 caagacaaaa attatcctag gtggtcagtg ggggttcaga gctgaatcct gaacactgga 540 aggaaaacag caaccaaatc caaatactgt atggttttgc ttatatgtag aatctaaatt 600 caaagcaaat gagcaaacca attgaaacag ttatggaaga caagcaggtg gttgtcaggg 660 gggagataag gggaggcagg aaagacctgg gcgagggaga ttaagaggta ccaactttca 720 gttgcaaaac aaatgagtca ccagtatgaa atgtgcaatg tgggaaatac aggccataac 780 tttataatct cttttttttt tttgtctttt ttgccttttc taaggctgct cccgtggcat 840 atggaggttc ccaggctagg agtccaaaca gagctgtagc tgccagccta caccagagcc 900 acagcaacac gggaacctta acccgctgag caaggccagg gatcgaaccc gagtcctcac 960 agatgccagt agggttcatt aaccactgag ccacgacagg aattccaggg tctgttgtgt 1020 tcttaaaaca cttccaggag agtgagtggt atgtcataag taaacaataa atgttaacca 1080 caacaagctt atgaaataaa caggaaagcc atatgaccta caatcagtca ttgggagaat 1140 ccacaaaagg ttgagcagag gatcaattcc agctcacact ccagttttag attctcccct 1200 gccttaaagc atcacagact acataatctg agctgaagaa taaaaattaa aactcacccc 1260 agtgcaaaac agaaatgaaa aagtattaaa acgaggttca tactgttgtt cattagcaat 1320 atcttttatt cacag 1335 <210> SEQ ID NO 46 <211> LENGTH: 40431 <212> TYPE: DNA <213> ORGANISM: Porcine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16625)..(16625) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16637)..(16637) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16671)..(16671) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16731)..(16731) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16741)..(16741) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16764)..(16764) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (16769)..(16769) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18290)..(18290) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (18400)..(18400) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (21127)..(21127) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (21129)..(21129) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22681)..(22681) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22684)..(22684) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22700)..(22700) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (23266)..(23266) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (23277)..(23277) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 46 ctgccagcct aagccacagc cacagcaacg ctgggtctga gccatgtctg cagcctatgc 60 cagagctccc cgcagcgccg gatgcttaac ccactgagca aggccaggga ttgaaccctc 120 gtcctcatgg atagcagttg agttgtttcc acggaactct taggggaact cctgattatt 180 ttttatttaa atttatattt ctctgacttt ttcgtgtgct catcagccac tgactgtgta 240 tctccattag tcatggtttg ttaactctgt cattcaaacc ctcttcatcc ttgctacgca 300 gataacatca ttataataaa atcgtgcctg aagaccagtg acgcccccaa gctaagttac 360 tgcttcccct ggggggaaaa agaagcaccg cgcgggcgct gacacgaagt ccgggcagag 420 gaagacgggg cagaggaaga cgggggagca gtgggagcag cgggcagggc gcgggaagca 480 ctggggatgt tccgcgttgg caggagggtg ttgggcgagc tcccggtgat gcagggggga 540 ggagcctttt ccgaagtagc gggacaagag ccacgggaag gaactgttct gagttcccag 600 tcccgacgtc ctggcagcgc ccaggcactg ttattggtgc ctcctgtgtc cacgcgcttc 660 ccggccaggc agccctggcg gatcctattt tctgttcccc cgattctggt acctctccct 720 cccgccctcg gtgcgcagcc gtcctcctgc agtgcctgct cctccagggg cgaaaccgat 780 cagggatcag gccacccgcc tcctgaacat ccctccttag ttcccacagg tgagaaggct 840 tcgccgctgc tgccgctggc gccggcagcg ccctccacgc acttcgtagt gggcgcgcgc 900 cctcctgcat tgtttctaaa agattttttt ttatccgctt atgctatcag ttactgagga 960 agtatttaca aatctactat tattttgaat ttgccttttt ctccttatag tttatcagta 1020 tctcttgaga ctgttattgg tgcctgcaaa tttaaaatga ttggggtttt atgaggaagt 1080 gaacctttta tctttatgaa acgcctaact gaggcaatgt taattgctta aaatactttc 1140 tttattatca gtgtggccat gccagtgtcc tcttggttag aatttgcctg atctgccaaa 1200 gctgggagat gggggaaagt agagtgggtt attgaaactg aatatagagt tcagcatcta 1260 aaagcgaggt agtagaggag gaagctgtgt caacggaaat actgagctgg gttcacatcc 1320 tctttctcca cacagtctaa tgccttgtgg aagcaaatga gccacagaag ctgaaggaaa 1380 aaccaccatt ctttcttaat acctggagag aggcaacgac agactatgag caggcaagtg 1440 agagggggct ttagctgtca gggaaggcgg agataaaccc ttgatgggta ggatggccat 1500 tgaaaggagg ggagaaattt gccccagcag gtagccacca agcttgggga cttggaggga 1560 gggctttcaa acgtattttc ataaaaaaga cctgtggagc tgtcaatgct cagggattct 1620 ctcttaaaat ctaacagtat taatctgcta aaacatttgc cttttcatag catcgaacaa 1680 acgacggaga tcctgttgtg cctctcacct gccgaagctg ccaatctcaa ggaaggaatc 1740 aattttgttc gaaataagag cactggcaag gattacatct tatttaagaa taagagccgc 1800 ctgaaggcat gtaagaacat gtgcaagcac caaggaggcc tcttcattaa agacattgag 1860 gatctaaatg gaaggtactg agaatccttt gctttctccc tggcgatcct ttctcccaat 1920 taggtttggc aggaaatgtg ctcattgaga aattttaaat gatccaatca acatgctatt 1980 tcccccagca catgcctaac tttttcttaa gctcctttac ggcagctctc tgattttgat 2040 ttatgacctt gacttaattt cccatcctct ctgaagaact attgtttaaa atgtattcct 2100 agttgataaa cagtgaaact tctaaggcac atgtgtgtgt gtgtgtgtgt gtgtgtgtgt 2160 ttaccagctt ttatattcaa agactcaagc ctcttttgga tttcctttcc tgctctctca 2220 gaagtgtgtg tgtgaggtga gtgcttgtcc aaacactgcc ctagaacaga gagactttcc 2280 ctgatgaaaa cccgaaaaat ggcagagctc tagctgcacc tggcctcaac agcggctctt 2340 ctgatcattt cttggaagaa cgagtgctgg tacccctttt ccccagcccc ttgattaaac 2400 ctgcatatcg cttgcctccc catctcagga gcaattctag gagggagggt gggctttctt 2460 ttcaggattg acaaagctac ccagcttgca aaccaggggg atctgggggg ggggtttgca 2520 cctgatgctc ccccactgat aatgaatgag ggattgaccc catcttttca agctttgctt 2580 cagcctaact tgactctcgt agtgtttcag ccgtttccat attaggcttg tcttccaccg 2640 tgtcgtgtcg tcaatcttat ttctcaggtc atctgtgggc agtttagtgc gaatggactc 2700 agaggtaact ggtagctgtc caagagctcc ctgctctaac tgtatagaag atcaccaccc 2760 aagtctggaa tcttcttaca ctggcccaca gacttgcatc actgcatact tagcttcagg 2820 gcccagctcc caggttaagt gctgtcatac ctgtagcttg cttggctctg cagatagggt 2880 tgctagatta ggcaaataga gggtgcccag tcaaatttgc atttcagata aacaacgaat 2940 atatttttag ttagatatgt ttcaggcact gcatgggaca tacttttggt aggcagccta 3000 ctctggaaga acctcttggt tgtttgctga cagactgctt ttgagtccct tgcatcttct 3060 gggtggtttc aagttaggga gacctcagcc ataggttgtt ctgtcaccaa gaagcttctg 3120 caagcacgtg caggccttga ggtcttccga cttgtggccc ggggactctg ctttttctct 3180 gtcctttttt ctccttagtg ggccatgtcc tgtggtgttg tcttagccag ttgtttaagg 3240 gagtgttgca gctttatgat taagagcatg gtctttcctt gcaaactgct tggtttagaa 3300 gcctggctcc accacttagc ggctctgtga cctcggacac atttcttagc ctttctgggc 3360 ctcgctcttc ttcctcataa agtgaaaatg aaagtagaca aagccttctc tgtctggcta 3420 ctgagaggat ggagtgattt catacacata aagcacttaa aataatgtct ggcatatgat 3480 acatgctcaa taaatgtcac ttacatttgc tattattatt actctgccat gatcttgtgt 3540 agcttaagaa cagaggtctt tacaggaatt caggctgttc ttgaatctgg cttgctcagc 3600 ttaatatggt aattgctttg ccacagactg gtcttcctct ccttcaccca aagccttagg 3660 gggtgaacga tcccagtttc aacctattct gttggcaggc taacatggag atggcaccat 3720 cttagctctg ctgcaggtgg ggagccagat tcacccagct ttgctcccag atacagctcc 3780 ccaagcattt atatgctgaa actccatccc aagagcagtc tacatggtac actcccccat 3840 ccatctctcc aaatttggct gcttctactt aggctctctg tgcagcaatt cacctgaaat 3900 atctcttcca cgatacagtc aagggcagtg acctacctgt tccaccttcc cttcctcagc 3960 catttttctt ctttgtacat aatcaagatc aggaactctc ataagctgtg gtcctcattt 4020 tgtcaatcta atttcacagc ctcttggcac atgaagctgt cctctctctc ctttctgcct 4080 actgcccatg agcagttgtg acactgccac atttctcctt taacgaccca gcctgctgaa 4140 tagctgcatt tggaatgttt tcaatttttg ttaatttatt tatttcatct tttttttttt 4200 tttttttttt tttttttttt agggccgcac ccatgggata tggaggttcc caggctaggg 4260 atccaatggg agctgtagct gctggcctac accacagcca cagcaatgca caattcgagc 4320 caatctttga cctacaccag agctcacggc aacactggat tcttaaccca ctgattgagg 4380 ccagggatca aactctcgtc ctcatagata cgagtcagat tcgttaacct ctgagccatg 4440 atagttgtta gttactcatt gatgagaaag gaagtgtcac aaaatatcct ccataagtcg 4500 aagtttgaat atgttttctg ccttgttact agaaaagagc attaaaaatt cttgattgga 4560 atgaagcttg gaaaaaatca gcatagttta ctgatatata agtgaaaata gaccttgtta 4620 gtttaaacca tctgatattt ctggtggaag acatatttgt ctgtaaaaaa aaaaaatctt 4680 gaacctgttt aaaaaaaaaa cttgactgga aacactacca aaatatggga gttcctactg 4740 ggacacagca gaaatgaatc taactagtat ccatgaggac acaggtttga tgcctggcct 4800 cgctaagtgg gttaaggata tggtgttgct gcagctccaa ttcaacccct atcctgggaa 4860 cccccatatg ccaccctaaa aagcaaaaag aaaggtgctg ccctaaaaag caaaaagaaa 4920 gaaagaaaga cagccagaca gactaccaaa tatggagagg aaatggaact tttaggccct 4980 atctccaact atcacatccc tatcaccgtc tggtaagaaa tggaaaaaat attactaagc 5040 ctcctttgtt gctacaatta atctgattct cattctgaag cagtgttgcc agagttaaca 5100 aataaaaatg caaagctggg tagttaaatt tgaattacag ataaacaaat tttcagtata 5160 tgttcaatat cgtgtaagac gttttaaaat aattttttat ttatctgaaa tttatatttt 5220 tcctgtattt tatctggcaa ccatgatcag aaatctttaa acaatcagga agtctttttt 5280 cttagacaaa tgaaaatttg agttgatctt aggtttagta cactatacta ggggccaagg 5340 gttatagtgt gactattaaa tcacagataa tctttattac tacattattt ccttatactg 5400 gccccacttg gatcttaccc agcttagctt ttgtatgaga gtcatcctta aagatgactt 5460 tattctttaa aaaaaaaaac aaattttaag ggctgcaccc atagcatata gaagttccta 5520 ggctagcggt caaattagag ctgcagctgc cagcctatgc cacagccaca gcaatgccag 5580 atctgagctg catctgtgac ctacactgca gcttgcagca atgctggatc cttaacccat 5640 tgaacaatgc cagggattga acacacatcc tcatggatac tgctcaggtt cctaacctgc 5700 tgagccacag ttggaactcc aaagcagact ttattctgat ggctctgctg atctctaaca 5760 cgttattttg tgccatggtg tttatcttca ctttactcaa gtcagggaaa cacgaagagt 5820 ctcatacagg ataaacccaa ggagaaatgt gcaaagtcac atacaaatca aactgacaaa 5880 aatcaaatac aaggaaaaaa tatcttcact ttcaaaatca cctactgatg atgagtttat 5940 atttccttgg atatttgaat attagctatt tttttccttt catgagtttt gtgttcaacc 6000 aactacagtc gtttactttg atcacagaat aatgcattta agccttaaat agattaatat 6060 ttattttcac catttcataa acctaagtac aatttccatc caggtctgtt aaatgcacaa 6120 aacacaactg gaagttagat gtaagcagca tgaagtatat caatcctcct ggaagcttct 6180 gtcaagacga actgggtaaa taccatcaat actgatcaat gttttctgct gttactgtca 6240 ttggggtccc tcttgtcaac ttgtttccaa tctcattaga agccttggat gcattctgat 6300 tttaaactga ggtattttaa aagtaaccat cactgaaaat tctaggcaag ttttctctaa 6360 aaaatccctt cattcattca tttgttcagt aagtatttga tgagacctta ccatgtgtaa 6420 acattgcact aggtattaag aaatacaaag atggataaga tagagtcggc gtaaatgaga 6480 tgatataatg agacgttata atgaaactca caattccagt tgggaaataa agtccttcaa 6540 attccatgac tctttctggc acacgttaga ggctacagct tctgtgtgat tctcatgctg 6600 gctccacttc cactttttcc ttcttcctac tcaagaaagc ctatagaaat atgagtaaga 6660 agggcttaat cataggaata aatttgtctc tgttctaagt gattaaaaat gtctttatca 6720 gtataaaaag ttacttggga agattcttaa aactgctttt acacactgtt ctagaatgac 6780 tgttatataa ataaaaaagt agatttgatc taacacaatt aaatgacctt tggaaatatt 6840 gactaattct caccttgccc ctcaaaggga tgcctgaacc atttccttct tttgccagaa 6900 agcccccacc ctttgtctgt tgacctagcc taggaaatct tcagatcacg ttgttagcac 6960 gaactggtta catgtgctgt acaaatacta tttaattcat ctgattaaaa aaaaagagat 7020 aagaagcaaa agtttgacta tcttaaactg tttgcgtagg tgagaggaca attgaccatc 7080 tactttatga gtatgtaacc cagaaactta aagctcctta agggagctaa gtcttttgga 7140 taagacctat agtgagacct tttagcaaaa tggttaagac tgaatggagc tcactagcgt 7200 gggttcatat cctgatgctc aaacacgcaa ttaaatgact ttaggtgggt tagtctctgt 7260 tccttagttt cctcaatggg agataatatt ggtagtagcg attttactgg gttgttgaaa 7320 gaacatctgt taaatgttca gaacgtgtta cgacagagta cagagtaatg atttgcttgt 7380 atatgtatga ctcaaatagt ctgccatatg ccttgtgact gggtcctgtg gagcaggaag 7440 gagggatttc ccacccagca gaaagttggg taaactggaa aatagactga ggccaggaaa 7500 tgatgcaaag cgttgatgtt cactgccacg gcaggtgaag ggcagggcca gagttgtcag 7560 tagggtcagg ggaggactgg aaataaccaa gacccactgc acttttcagc ctttgctcca 7620 gtaaggtaat gttgtgagag tagaaaattt tgttaacaga acccactttt cagtacagtg 7680 ctaccaatac tgtagtgatt tcataccaca tcccaagaaa gaaaaagatg gctcaatccc 7740 atgtgagctg agattatttg gttttattgt taaataaata gcattgtgtg gtcatcatta 7800 aaaaaggtag atgttaggaa agtagaagga agaagactct cacctacatt ttcatcactg 7860 ttttggtatc tgccagttgt caccttggtc cccttccccg cctctcccct gcctcctctt 7920 cctccttctc ctttttttgg aatacaattc aggtaccata aaatttaccc ttttagagtg 7980 tttgactcaa tggtttttag tattttcaca tgttgtgcta ttactatcac tatataattc 8040 caggtcattc acatcacccc ccaaagaaac cttctaacta ttagcagtcc attcccttct 8100 tccctcagcc cctggcaacc actaatctac ttactgtctc catggatgtt cctatattga 8160 atcaagctag cataaacccc acttgctcat ggtcataatt cttttttata gtgctaaatt 8220 acatttgcta atattcaatt aaggatttct atgtccatat tcataaggaa tattggtgtg 8280 tagttttctc tttgtgtgat atctttgtct ggttggggga tcagagtaat aattactgct 8340 ctcatagaat gaattgagaa gtgttccctc cttttctatt tattggaaga gtttgtgaag 8400 tatattggta ttgattcttc tttaaacatt tggtcagatt caccagtgaa gccatctggg 8460 ccatggctaa tctttgtgaa aagttttttg attactaatt aaatctcttt aatttgttat 8520 gggtctgctc ctcagacgtt ctagttcttc ttgagtcagt tttgttcatt tgtttcttcc 8580 taggactttc tccctttcat ttggattatt tagattgata gtaatatccc ccttttaatt 8640 cctggctgta gtaatttggg tcttttctct tttttcttgg tcagtttagc taaaggtttg 8700 taattgtatt aatcttttca aataactaac ttttttgttt tgtttgtttt ttgttttttg 8760 ttttttgttt tttgtttttt tttgcttttt aaggctgcac ctgaggcata tggaagttct 8820 caggctagag gtctaatcgg agctacagct gctggcctat accacaacca tagcaatgcc 8880 agattcaagc tgcatctgcg acctacacca caactcggcc agggatcaca cccgcaacct 8940 catggttcct agtcggattt gttaaccact gtgccacgac gggaactccc gcccattttt 9000 tttaacacct catactttaa cataaagatg ggcttcacat ggactgatag ctcaaatgag 9060 gaaggtaaga ctatgaaagt aatggaagaa atgtagacta tttttgtgac ctagagatta 9120 ctgatacttc ttgacttttc aaacaatact tcaaaagtac agcccaaagg gaaaaaagaa 9180 agaaaaaaga aacacacata tacacaaacc tagtgaataa gatatcatcg atacactaca 9240 gatttctatg aactggaaga ccccatggac aaagttaaag aacatatgat agtttgagtg 9300 attattttgc aatatttaca accaatgagg gaatattatc cagcttatag gaggaagtaa 9360 tgcaaatcga caagaaaaag ataggaaacc caatataaaa attaagaaaa tacaaaaatt 9420 aagaaaggat atgaactagc attttacaaa agaaaaatct ccaaaagtca atcagcacat 9480 gaaaatatgc tcaaacctat taattattag aaaactacag actgaagcaa tgaggtgctt 9540 tactttacat ctttttgact gataaaaagt tagaaacaaa ggtgatatca aatgtcaggg 9600 ataaaaggat atagaaatcg tcatgcctgt ggtgggagta tggccggtgc agtcatgtgg 9660 gaaggtaatc tgacagtggt taggcagagc aggtttatga atacactgtg gcccatcaat 9720 cccacgcctg tttatgtacc aaagaaatcc tgttgtggca gaatctatgg gtccacccct 9780 gggagcatga attaataaaa tgtggcacca gggtgtgtga aactccagct agagatgaga 9840 tgtccacatg gcaacatgaa tgcatcttag aaacatagat ttgagtgaaa aagagtaaga 9900 aacagccggg aaacccaata ccatttataa aaattaaaga tgcacacata caatgtagta 9960 aatattttgc atgaactttc aaatggttgc ctacaggggg ggagagtaaa gaagagtaga 10020 aaacaaagat aaagggagta agtaagtagc tctgcctgga ctgaatataa tgtgtcatga 10080 actgagaaat atggttaaca taatcctctt aacttgaggt cctaaatgaa tgaatgagtc 10140 cactattcat ttacccattc tttaatgtgt attgcattat aatccatttt tttagaacca 10200 acgaattttg ttcccataac tactaatcag cctgcctttt ctccctcatt cccttatcag 10260 ctcaggggca ttcctagttt ttcaaacgtt cctcatttga accaaaaata gcatcattgt 10320 ttaaattata cttgttttca aatacgatgc ttatatattc caagtgtgtt tgcccatttt 10380 cttaggtggt agaaattttt cattctactt ttctatctac tcagattttc ccgttggaat 10440 tatttccatt gctattaaac ttagaagtcc cccctgtgat atgccatttt tttcatactt 10500 tttaagcact tggttgcttt tctttgtgtc tttaagcacc tagaatactt ataaccattg 10560 cacagcactg tgtatcaggc agcccttcct cttccactaa tttatggtcc ttctcttaga 10620 ctatattaaa ctgttattta attaggatcc tctcttcgtc cttatgattt aattattata 10680 gttttctaat atgtttttat tataattcct cttcattatt cctccctatt aaaaatttta 10740 atgaattcca tttgtttgtt cttctagtta aatattaagt cataatccaa ataacttaga 10800 tgtcattagt ttatgtggtc aaagtaagga taccacatct ttatagatgc aggcagttgg 10860 cagatgtcat gattttcttc agtgcataaa tgcaatttat ctttgagcaa ggggcataaa 10920 aacttttatg gtattggctt tgaaataata gttaagaact gcagactcag tttttcctgc 10980 ttttcttgaa aaagaacact tctaaagaag gaaaatcctt aagcatggat atcgatgtaa 11040 ttttctgaaa gtctcctgta attccttggg atttttgttg ttgtttgttg gtcggttttt 11100 ttgggttttt gtttgtttgt tttgttttgt tttgttttgc ttttagggct gcacctgtgg 11160 catatggaag ttcccaggct aggggtccaa ctggagctac agctgccagc ctactccaca 11220 gccacagcaa catgggatcc tagctgcatc tgtgacctaa ccacagctct tggtaatgcc 11280 agattgttaa cccactgagc aatgccagag atcgaatctg cctcctcatg gacactagtc 11340 agattagttt ctgctgagcc acaatgggaa ttcccaattc cttgtatttt tgaactggtt 11400 atgtgctagc atataatttt gtttcttgaa tctttgtggg tttttttttt tttttttttt 11460 tgtctcttgt ctttttaagg ctgcacccac agcatatgga ggttcccagg ctagaggtca 11520 aattggagct acagctgcca gcctacacaa caactgcagc aaagtggggc ccaacttata 11580 tgacagttcg tggcaatgcc ggattcctaa cccactgagc agggccaggg atcgaacctg 11640 agtttccagt cagtttcgtt aaccactgag ccatgatagt aactcctgtt tgttcagtct 11700 tgaacctcct ttttaattct ttattccttg agggtgaaat aattgccata ataatactat 11760 catttattac atgccttctc tgtgctaggc atagtgacac tttaggattt attatatcac 11820 ttaatcccta caacaactct gcaaagtatg tatcataatc ctatttgaca gatcaggaaa 11880 ttgcagccca ggatgcagat aatatgcatc catcacaagt gactagatat agtccctctg 11940 ctattcagca gggtctcatt gcctttccat tccaaatgca atagtttgca tctattgtat 12000 atgtgttttg gggttttttt gtcttttttt ttttttttgt cttttctggg gcctcaccct 12060 tggcataggt aggttcccag gctaggggtc aaattgaagc tgcagctgcc agcctacacc 12120 acagccacag caactcggga tctgagcctc atctgcaacc tacaccaaag ctcacggcaa 12180 caccggatcc ttaacccact gagtgaggcc agagatcaaa ccggcaacct catggttcct 12240 agtcggattc attaaccact gagccacgat gggaactccc taaatgcaat agtttgctct 12300 attaacccca aactcccagt ccatcccact ccctcctcct ccctcttggc aaccacaagt 12360 ctgttctcca tgtccatgat tttcttttct ggggaaagtt tcatttgtgc catttttcat 12420 tttacgggta atttttactt cagtttcttc cactagcagt tgtcttaaag tgagtataat 12480 taatattcat ttggaaaatg taagcaaaac attttttaaa gggccatgcc cacagcatat 12540 gaaagtttct gggccagggg ttgaatccag gctccaagtt gcagctgtgc cctacactgc 12600 agctgggcaa tgctggatcc tttaacccac tgtgcccggc tagggatcaa acctgcattt 12660 ccacagctac ccgagccatt gcagttggat tcttaaccca ctgcactaca gtgggaactc 12720 ccacaaaaca ttttttaatg tcctttgaat aaagtaggaa agtgctcgtc tttgagggca 12780 gggcggcaat gccatttcca caaggtttgc tttggcttgg gacctcatct gctgtcattt 12840 agtaatgaat aaaattgctg acagtaatag gattaactgt gtgtggagat agccagggtt 12900 agagataaaa acactggaga agtcaaataa gttgctcgag gtcctctagc taataagcta 12960 ttaagtggga gagtgagggc tagaaacagg ccatctgtct cccaagcaca tgtccattag 13020 tggtttgctg atagccttcc agaacaacag agaggactct caaacatggt cttgcctccc 13080 tccaattgat cccctccatg tgcctcacag cgggtctttc taaaattaag ttctgatttt 13140 aattctccct tgctatagca cttaggtatg gctttcagcc gtgcaataaa aagcaggcaa 13200 gagtggctca atcatatagg aggttgtttt tcttagatcc caagcaggta atcctgggca 13260 ttatggttgt tctgcgttta tcaaggagcc aaattctcta tcacctcctg ttctatcctc 13320 ctcagtatct ggctctattc ttcagcatct caagatggct tgtgctcctc caagcatggc 13380 agtcaaattc cacacaagag ggggaaatat gaagggcaga cagtgctggt ctcctgagct 13440 gtccctcttt gtcggggaaa taaatgtatt ccttcaagtc ccgtgagact tctgaagtag 13500 acgtctgctt acgtctcacc caccagaact atgtaaactg cacatagtgc taggtctaca 13560 tagccactca taactgccag ggggtgggaa atctttaaat aggtgtacca ccacacaatt 13620 aggatgctaa tagtaaggga gaaggagaga ataggttttg cgcaagccac cagcatgcct 13680 gccacaattg cttaaaattc ttcattgacc cctcattgcc acaggatgaa atccaaacgc 13740 cttcttagtt gggaatctga cctacctgtc tctcccacct ggttcagaca ccattctcct 13800 tggtcataaa attccagtca tttgtgaaca tccagctccc ccatgcctcc atgcctttgc 13860 acatgctgtt cttttatctt ttatgttgtc cttttatctt ttatccaaaa gagatatccc 13920 atcatcacat ctcttttgtc agcccccaaa tactttgtct ttcaagttca gctggaggat 13980 tacctcctat ttgaaatcag ctttgtctct tacaaccaaa caaggttttc cttccgagac 14040 actcccacag caccttgaac tcatctctat caatcattca tttgattgta atgaagttgt 14100 tggtggtatg cctgtgtctc tgacacatct gcgatctcat gagttcctta agtggaatgt 14160 gaatagcggg atgaacagta ttggtcttca gccctcatct ctgcagatgt tgcttgaccc 14220 aaatgagcgt tgccttttat tttgattttg ctttgatttg tctactccat gtacttgagc 14280 catgcatttc tgtcttagcg atgcttttta aaagtcattt tttggttgat tatccagatt 14340 tgtccacctt tgcttctagt tgtagaaaag gatgaagaaa atggagtttt gcttctagaa 14400 ctaaatcctc ctaacccgtg ggattcagaa cccagatctc ctgaagattt ggcatttggg 14460 gaagtgcagg taaggaaatg ttaaattgca atattcttaa aaacacaaat aaagctaaca 14520 tatcaattta tatatatata tatatatata tttttttttt tttttacatc ttatattacc 14580 ttgagtattc ttggaagtgg ctagttagga catataataa agttattctg aagtcttttt 14640 ttttcttttt ccatggtgag cagtggcttg atgtggatct cagctcccag acgaggcact 14700 gaacctgagc cgcagtggtg aaagcaccaa gttctagcca ctagaccacc agggaactcc 14760 ctattctaaa ttcttgagca cattatttag gaacctcagg aacttggcag gattacagga 14820 aatatatcta gatttaaaaa aaaatctttt aacagaggtc ccaaaggaga gtcatgcaca 14880 gctatgggag gaagttcaga aactgccctt gctaccagat cactgtcaga taaaatggcc 14940 agctacatgt ttctgcacat tgccctaaga tctttacaaa cttttctgtg catttttcca 15000 cttttaaaag aaaatttcgg ggttcctgtt gttgctcagt ggttaacgaa cccaactagt 15060 atccatgggg acaggggttc gagccctggc ctcactcagt gggttaagaa tctggcattg 15120 ctgtggctgt ggcgtaggct ggcggctaca gctcagattg gacccctagc ctgagaacct 15180 ccatatgccg caggtatggc cctaaaaaaa aaaaaaaaga gagagagaga atttcctcca 15240 gaaaaaacac tttggtagtt tgggagaagt aaacaaccaa aaattaattt ttctggagta 15300 ttcgggaagc ttgtaaaaat gggctcttac ttttttgagg agacaaatgg gaacctaccc 15360 agaagaggca caatcacctg catttgattt cttgacctct ccctaccttc tttgctggct 15420 ttccacattt ggatttctgt gaccttatct ctgctccttg gtgttttcat ttttcctgtg 15480 gacgtgccag actatgggaa gggagtaagg cgttgattta gaatcctgta gtctctgcct 15540 gtctctagtc attgttttca cccttctcaa aggaccttga catcctgagt gagtccgcaa 15600 gtaatttagg ggagaagcct tagaagccag tgcagccagg ctacatgact gtgtccaccc 15660 actggaacca gtcattttta tacctattca cagcccccct accatttaaa tccccagagg 15720 tctgccataa catctgtaac tccctttcct ggtaaattgt gttctaaaag actggtaaca 15780 aaagatattc tgtggtacag agcataatta aatacctggg agctgatttg agtggggtaa 15840 atcaactggt ttgaccccta aaacccacca tgagcatttc tgttctaata aagtaatgcc 15900 cgtgctggga attgtgttct acggaaatgc tcctgctgtg tctttcttga gtcctgtgtc 15960 attgaacatg cttaggagca aaggtccccc atgtggcttg tctgctaacc agcccagttc 16020 cttgttctgg ctggtaatga tccgatcatc tgaatctcac tgtcttccaa cagatcacgt 16080 accttactca cgcctgcatg gacctcaagc tgggggacaa gagaatggtg ttcgaccctt 16140 ggttaatcgg tcctgctttt gcgcgaggat ggtggttact acacgagcct ccatctgatt 16200 ggctggagag gctgagccgc gcagacttaa tttacatcag tcacatgcac tcagaccacc 16260 tgaggtaagg aagggtgagc cctcaactcc gaagaaaatg ctgcaataaa agcactgttg 16320 gttttcagct ttttttgtaa tcactgctca ttctgaggta gattcgcttg ggctgataaa 16380 aagagaacta attcagataa atgcttgcat ttgcatagcc tcttttttta aaaacttttt 16440 tttttttttt ttttttttgg cttttcaggg ctgaacctgt ggcatatgga ggttcccagg 16500 ctaggggtcg aatcagagct gtagccccgg gcctatgcca ctgccatagc aacatgcata 16560 gcctcctttt taaagtgcct tcctgtttta taccattggg atgtgagaag agctattgtg 16620 gaaangagca tggggtnata accctggacc tctcacgtcc taccctcagg ntagtgggaa 16680 aactctgagt ttaaggacat caaagtgact cctttttagt tacattatgg nggaatcagc 16740 ncatattttt acaaggggcg gagngtaanc tgttggagtt tacaagacat atggtggcat 16800 tgcaactact taaccctact attatagcac aaaagcagcc atagtcggtc ctgaaggagc 16860 ctgatgcctt cagctttata ggcaatgacg tgtgaatatc acaaacagtt tcctgtgtca 16920 ccaaacatga ttgccttttg atttcccttt caacccttta aaaaaaggta aaagcccttc 16980 ttagcattca gcagcaggtc gctgtgtttt gccaactcct gatctgtagc atttcgacaa 17040 cactgagctc tcaacttttg aaccctgagt ccaccacatc cttcagtgaa accagagcca 17100 tgtgatacta aggatagaaa cggaaacttc ctgaatccag gcgatcaaat aggagggaga 17160 aagaggaact ttcattgaca aaaccacaaa tattgtgaat ggactgttac aaatattgtg 17220 aatgctccta ttcccaaccc cctggcttca ttacagggtc ctatgtgttc atccttattg 17280 agaaatttgt attgctactg ccaggttgcc aatacccagc ggtgcccatg gtgttctaaa 17340 atgaagcaat ttcaacttta tttttttttc ctgtgacttt acatgacaag ttcacatgaa 17400 ggatatactt tgatagtaat gtccatggtt agggaatata cattgtttgc tggttgactg 17460 gcccctggat ttttctattg aaagtccatg agatctcgaa ggcacaggtg tgttctctcg 17520 ctttttaagg aaagggttta aaaacttaag taattaacag ctttagtaac aaattaccta 17580 taacacactt aaaaaccgaa taccacccac tggagtattg tgctacgatt aaaaatctac 17640 ttgtctacta catgatatct ttgtcccaca gaaggttctg gaaccaaact tgtaatttca 17700 ggattatgag agccctgagt tcacgcattg tgtaataact atgttgtgtg gtagtcaatt 17760 tgtacagctt gcttagagag aacaatgtca agttaaggag gcgattgctt tatagtgcct 17820 gtcacaagat gccattgcca ttgtcctagc aagagatatt ctatgggagt atactacatt 17880 ttagtgagga taagaacttt ttatggcatt tagtccggtc atttcccaac cactgtcctg 17940 aaaaccaatt tcattttgat ttcaggggct tgtgtgggca aagttgccag gcattaaaaa 18000 gccacttctc aactgtagta tcacaatgct ttagttgggt agtgtattgc agatagctta 18060 tggctgaaaa gttaccaagc cttgcagttt tcactccttt gagtttattt ccttgacaga 18120 attgaccctg agttttttga ctcttacctg ctcaactaat aaacaccaga gtcatttatc 18180 tccattgctc ttgtctgacc tttatttacc gaataatgcc ttatgggttc acaaaaacaa 18240 ggggggaggg ggccagcatg ccttagaaac tgtctttagt caagaaatgn gattttatta 18300 tgtaaatata tgagtattat aatagatagt gttattaata gacaccagca agaattgtca 18360 ataatttaaa aatcacaaat taaaatacat ccatgttagn atcatttatc ctaactccca 18420 aagcccttta aagtggaaga tttagatgtt aacccagaga ttaaagacat gttcaaagaa 18480 tccttgattt ttttttgaat cccttgtttt tagagaagaa aacctaatga ttttccccct 18540 ctggattcta catattaaat atagttttgg aacttgaata ttagtatggt taataagtgc 18600 tgatatgctg attttgttta tatttttctt atgagtaaat atcctatatc accagacatt 18660 atagtctatg tacaaatatg attcttaaac ctgatagcac attcattaga gttggaattg 18720 cctttttttt tttttttttt acagttgcac ctgcaacata tgaaagttcc caggctaggg 18780 gttgaatcca agctgcagct gccaccctac attacagccg tagtaacagc agatccgagc 18840 tgcatctgca acctatgctg cagctcaggg caatgccaga tccactgagt gaagccaggg 18900 atggaacttg catcctcata gagacaacgt cgtgtcctta acccactgag ccagaacagg 18960 aactccagaa tttcctttca atagaagaag caccaagttt aggatcagaa agcctgaatt 19020 tgaataccaa tttactattt gttagtcata tatttctgag tgtgtttcct catttattaa 19080 aagcagacta aaagatgaga gggtcttttg ttgagaatca aatacaataa catgtgaaag 19140 tgtgtaacac tatgattgaa atatacctac acagccattt atttgtttat tgttcatgtt 19200 ttgccaccca cacagtagta tataatcctt ttatgtaata aatgctaata atgaaagttg 19260 gcaacttatg taagtactca aaatgctgga ggtcatggga tactgactgg gatactacag 19320 aggtaatgtc atttcctctg cgctaaactt attgtcttgt agttagggac tgactctctt 19380 taggacaagg agttcattct gtataccatg tgtggctatc acccttcgaa gttgaaaaac 19440 tgccccaggg tgggcaccca tccgttctct tagatatatg gccgagacct ttctctcact 19500 gggagggaac cacactgagg aatgagaaaa aaaaaaggaa aatcaagatg aaaccagaaa 19560 cctctttggc ataacttctc cactctgtac tttttgttag aactaccctt gcacaaagca 19620 gcatcagtgt ggaagacaga atttgcacac ctggtttgat atacatgccg tggtatatgg 19680 gatgttctaa caataaagag gactctccca ggaaatctcc tcactgttat agtcagcctt 19740 gaggaaagag ctcttctttt ggactctggg gagagtctag tttttcagtt ccttgcttct 19800 cggtcaacgt gttggtgtaa ggatcacact ctctcttata ctagataatt ctattttttc 19860 acctttcaac ctgtctatcc ttctgaccct agttacccaa cactgaagaa gcttgctgag 19920 agaagaccag atgttcccat ttatgttggc aacacggaaa gacctgtatt ttggaatctg 19980 aatcagagtg gcgtccagtt gactaatatc aatgtagtgc catttggaat atggcagcag 20040 gtctgtgttc tttccacatg tttgggttat cctttctggg ataaatttga ggcgagatag 20100 aaactttaag actaaagaaa caatggccta ctttttttgt acatggtcct gtgtaaatct 20160 ctatttgagc tgaaataaga tggtcttcct ctccaattat ccatggtatg actctgatgg 20220 ataacaaatc cagttctgaa aaaaggggat ttctttccag aagagaggac agtttcttca 20280 aatattgaat taaaagcaaa atagatgtaa accgttgttg gttttattgt tgaattccag 20340 gtagacaaaa atcttcgatt catgatcttg atggatggcg ttcatcctga gatggacact 20400 tgcattattg tggaatacaa aggtattttc ttgccctcat cagcatgaaa ttgctcttgg 20460 tagaaaggat aataatagtt atccaaaaca tcatcctatg ttcatctgtt tcttccctct 20520 tcattttcca tagagtacag tatattctat ctctgtctta ggaaaatgga ctgtcattca 20580 tataatctta cagagaatca attagtaatg tactctatgc cgtgacaggt gcgaaggttt 20640 tttttgaagg caacagataa aaatatccta tatttcacct attgtaattt ccttaaaact 20700 gacattattg aataaatgtt ttactttcat cttgaatatt attatgttat ggaatcatac 20760 actttacccc aataatcatc gaaaagaatt tccaaaaggt tgagagagtt gtgttgatct 20820 gattactttc ctctgcatcc tttgagctta acctttgaat atagtttgct aaggaaagta 20880 gtctgtttat gatcctggag tggaatcagg ctaagtgtcc tcattcagaa cccactgaat 20940 cagacagaat gaatttattt ccttgaaagt tcaaaatgtg tcactcaaga gtataaattt 21000 tcaaatctta ctctctcttt tccttggatg tgagcaattc ttcgataatt gaatgaggca 21060 gattatatag acttacatgg aagactgttg gcctgagaat tcaaactatg gtgttcaaga 21120 cttcacngng agtccgatgc catttgtttc ccacaggtca taaaatactc aatacagtgg 21180 attgcaccag acccaatgga ggaaggctgc ctatgaaggt tgcattaatg atgagtgatt 21240 ttgctggagg agcttcaggc tttccaatga ctttcagtgg tggaaaattt actggtaatt 21300 ctttatatca aaatgatgcc aaggagttgg catggcactt tgctaaatgc tgtgtgaatc 21360 aatacaaaga taattaggac atggttcttc ctcacaagag gtgtgcaatc ttattgggaa 21420 atcatacttg caagtcacaa atatagacta aagtttccag ctgagaatat gctgatggag 21480 catgaaacac taaggagaca gggagaatct caggaaaaat caagaataat ttggatcaaa 21540 tggattcctg acatagaaca tagagctgat cagaaagagt ctgacattgg taatccaggc 21600 ttaagtgctc tttgtatgtg gttcagaaca gagtgtgggc agcctgaggg ggatacatac 21660 ccttgacctc gtggaaagct catacggggg agggatgagg ctaaggaagc ccctctaaag 21720 tgtgggatta cgagaggttg ggggggtggt agggaaaata gtggtcaaag agtataaact 21780 tccagttaca agatgaataa attctagggg tataataaca gcatggcact atagatagca 21840 tattgtacta tatactggaa gtgctgagag tagatcttac atgttctaac cacacacaca 21900 cacacacaca cacacacacc acacacacac accacacaca cacacgtgca cacaaacaga 21960 aatggtaatt atgtgaggtg atggcggtgt taactaactt tattgtggtc atcatttagc 22020 catacatgca tgtcatgaaa tcaccatgtt gtacacctta aagttatgta atactagatg 22080 tcagttatat ctcaaagcta gaaaaaatgt ggggaccaag gcagaagctc ttctgctctg 22140 tgtctaaggg tggttctggg gctgggatgg ggaggatggt taagtggtat atttttttca 22200 tacctttgct cagtactatc attgtaagtg ttcaatatat gtctgcttaa taaattaatg 22260 tttttagtaa gtaatctctg tttagtaatg tgtcagaaat gccctacttg caataggaag 22320 aaaacctgtc cagtcccttc cttttttctg taagtctgat ttcattgcct cccagaatgc 22380 atcaccatgt gagagataga gggaaggtgc tgtccttatg gggttaacag tgtgactagg 22440 gaggcaaaat atacctacta aagggtggta gcataattca gttcttatgt gagtatgtgt 22500 atgtgtgtga gtatgtgcac atgcacatac attttaaaag gtctgtaata tactaacatg 22560 ttcatagtgg ttacacctag cttataggta acattttttc ccctgtatcc ttgtttgtgt 22620 ttatcaaatt ttcataacag taatggtaga aggagtacct gacatggtac catacatgct 22680 nggncctgcc taatttctcn atttccttta ttgcccatac ccccattgct tgacaagcat 22740 aagtccatac tggcttgttt tcgttcctca gactcagtac accatgtagc tccatgccct 22800 gggtctttgt atgtgctatt tctactgctt agagtgctat tgcccctgac caccacgtgg 22860 tcagcaactt ctcttctgcg tctgtgtcta tggtctatga ttccagatgt catcttcact 22920 aactaccctt ctaatatgcc cttccatccc acccgtcctc atccttaccc cagccactct 22980 ctatttggtg gctctgtttt attttcttcc tagctcatca ctctttgaaa tgaacttatt 23040 tacttattca atatttgctt ctttcactag aatgaatgct ccatgagagc agggacctgc 23100 tttatcttgc tcgccactgt attcacagtg cctagaacta cgtctggcac atagtaggtg 23160 ctcaataaat atcgatcaaa tgaaagaatg agcaaacgaa caaatgaaca acacgtgagg 23220 taggcatcat gattccatca acagaggaga aaaccagact taaagnaatg aagtggngga 23280 gctgcatttg atcttgactg actccaacat ccatgctctt gaccactgtg catctccaga 23340 gtgtaatgaa catactttac ttttatattc caccaaaata acaaagccat gcccatgtta 23400 gtagagagtt aatcgacagt gcccttaaaa tatgcatgca cccagggtac aactatgcat 23460 gctgccctgt gttttcagtt ggatccaaat gaattgccgt aaacaaagag gggattcaat 23520 gtctttgact agtttgggat attttcctag taaccaactt tgcaaaataa agccactaat 23580 gacaaggagc tttgttctac ttctgcatca ctcaactgtc aatttttatc tcttgcaaga 23640 cttctaatct actagaactt ttgtttttct gtgatttctg aacagagaag actaatccaa 23700 accctgtcat tccagaggaa tggaaagccc aattcattaa aacagaaagg aagaaactcc 23760 tgaactacaa ggctcggctg gtgaaggacc tacaacccag aatttactgc ccctttcctg 23820 ggtatttcgt ggaatcccac ccagcagaca agtatggctg gatattttat ataacgtgtt 23880 tacgcataag ttaatatatg ctgaatgagt gatttagctg tgaaacaaca tgaaatgaga 23940 aagaatgatt agtaggggtc tggagcttat tttaacaagc agcctgaaaa cagagagtat 24000 gaataaaaaa aattaaatac aagagtgtgc tattaccaat tatgtataat agtcttgtac 24060 atctaacttc aattccaatc actatatgct tatactaaaa aacgaagtat agagtcaacc 24120 ttctttgact aacagctctt ccctagtcag ggacattagc tcaagtatag tctttatttt 24180 tcctggggta agaaaagaag gattgggaag taggaatgca aagaaataaa aaataattct 24240 gtcattgttc aaataagaat gtcatctgaa aataaactgc cttacatggg aatgctctta 24300 tttgtcaggt atattaagga aacaaacatc aaaaatgacc caaatgaact caacaatctt 24360 atcaagaaga attctgaggt ggtaacctgg accccaagac ctggagccac tcttgatctg 24420 ggtaggatgc taaaggaccc aacagacagg tttgacttga atatttacag ggaacaaaaa 24480 tgatttctga attttttcat gtttatgaga aaataaaggg catacctatg gcctcttggc 24540 aggtccctgt ttgtaggaat attaagtttt tcttgactag catcctgagc ttgtcatgca 24600 ttaagatcta cacaccaccc tttaaagtgg gagtcttact gtataaaata aactattaaa 24660 taagtatctt tcaactctgg ggtggggggg gagactgagt tttttcacag tcctatataa 24720 taattttctt atcctataaa ataattagga gttcccgtag tggctcagca atagcaaacc 24780 cgactagtat cgatgaggat gcgggttcga ttcctggccc ccctcagtgg gttaaggatc 24840 tggcattgcc gtgagctgtg gtgtaggtgg cagacacggc tcagatccca cgttactgtg 24900 gctgtggcat aggccagcag ctccagctct gattagaccc ttagcctggg aacttccata 24960 tgctgtgggt gtggccttga aaaaaaataa ataaataaga taattactca aatgttttcc 25020 ttgtctcaga accttacttc aggataaaga gtgagaaagt tttttttatg aagggccatt 25080 attacagctc aaaaataagt tgtcttcagc aagtagaaag caataagcct gagagttagt 25140 gttcctatca gtgtaaatat tacctcctcg ccaatcccca gacagtccat ttgaacaatt 25200 aacggtgccc tgggagtaca gttcagaaac attaatgtgg atgttccaga cctgtatttt 25260 tataagtact tgtcttgagc cggatggaac catcattcct caccattatt tagaagtgga 25320 ctgtgactct gttggagatc agggcacacg gttaccaaaa gcacaccctt ctcctggcct 25380 tacctttgca aagctggggt ctgggacaca gtcagctgat tatacccttt tactaacttc 25440 ccacagctca aatctggtca attctccttc acaaatctct taaaaatcca tcactcacct 25500 ccagcctctt ctgctgtggc cttgattcag cctctcacaa ttttttttta accagaattc 25560 tggcagtggc ccctgacttg cctctgtgct cccagccccg ctgtcctctg atccatcctc 25620 catgccagcc tttttcaatc tgctggtcac gattcattga tgggttagga aatcaatggc 25680 atcacaacta gcatttagaa aaaggaaata ggcgttcccg ccgtggcaca gcagaaataa 25740 atccgactag gaaccataag gttgcgggtt caacccctgg ccttgttcag tgggttaagg 25800 atccggcatt gccgtgggct gttttgtaag tcacagacat ggctctgatc cggcattgct 25860 gtggctctgg cgtaggcctg cagcatcagc tccaattaga cccctatcct gggagcctcc 25920 atatgctgca agtgcagccc taaaaaaaat aaaaaaataa aaaaaaataa ataaaagaag 25980 tagacaaatt gtatagaaca accctgagta tgttgcctga gcacatataa caagggtaag 26040 tattatttca ggaaactctg gtttcacaga tactcttggc atatggaccc ctagagtcct 26100 gatgtaaaat atattcttcc tgggatctta ggcaagaagt ttgaaagctc caactctgca 26160 ctgctgccaa agaaatgatt tttaagtgca aaactcttcc cgttcccttc cctgtataaa 26220 attccatagg atctctccag tgcctctagg ataaaggcag ttttcattct ctagttcaag 26280 gtgagagaag attttaatta tttcacgttt tagtggggaa ttcaagagtc tggcacctga 26340 catttgctga actctctcca ttatccctct ctagttcccc agacgcatcc tatggtagaa 26400 attcgcaaac tagagtgagc gtcagagtaa cccaaggaaa ctgggtaaat gcagctccct 26460 gggctctacc ccctgagatt ctgattcagt agatctgaag cagagccctg gaatatgcat 26520 atgcatcatt gtgtcacacc aagcattctg ggtaatgaga gttgatgtta ggttctcagt 26580 agtaagacaa gtatagagat tccgggggac tgagtgctca gctctgcctt ggggaggagg 26640 gagagggcta aagagaacag gagatgggga cagggaatgc tcaacctcca atcttaggca 26700 tttgagctat gtcttagggg tcaggaggag gttaccaata tagtgattaa gagattgagg 26760 ttccagtcag agggatatgc tggagaaggg gggtgaaaat aatgtcatag gtttggtgag 26820 tgcagatact ttgagttttt taatattttt attgaaatat agttgattta caatgctctt 26880 agtgagtaca attactttga ataagtgcat agatgtatgc cattcttcca gaaatgattt 26940 attgagctcc tttgggcatc atgctaagta caggggaaac agctgtgaag aggtccttcc 27000 cttatgaagt cattcatccc cttcagtaaa tgaaggtaaa ggaaaaggat gagacaggga 27060 cgccgtgttg gaccagggtc agaaaggcct tataagacct tgcctggagg gcaaggaact 27120 tgcctgtgag taaggagagc ttgagaaagc gataaagcaa agaaggaaca ttactgcatt 27180 gtgttttaga aaaaccatgt cctggggaag aactcctaga gtcagggggg ccagttggga 27240 gactgtgctt ttttccagga ggagataagt gaggctgctg gctgagatgg agcaaggatt 27300 tagagaagca gatatgagat tcatttagaa gttagacatt ttaggatctg acacataatt 27360 tatcaccaaa accagtgcat ctctggcttt gggccaccag ttttggagaa gtggaatgta 27420 gggacctacc attacctgcc aatctttact acacagatgc ctatttccct cctcatattt 27480 cctttctcca gatcacgtcc tattctattg ccaggactca agattccacc ttgcatgcag 27540 tgatccatct tcacactgga tggacagctc tagggatgtc agagcacact cttgtccata 27600 ctgctgactg ggtctcctgt cagcccatct gtctatcagc tgtggtatta ttagtataat 27660 aagagggctg tatatgagag acacaaaatt ctaggtgtag ctcaaagata ggctagagtt 27720 attcctatgt acaacaaata tttatgggac cccttctgtg tactgtcatg gttgctgctt 27780 tcatcatact tgtagtctaa tggaggtggg ggcagggcag gaataagcgg atgtccacaa 27840 aatcagtaag accacttata ttcaacattt tcataattta gttatttgag cccaaagggt 27900 ccacatccgt ggtattccaa cttttttttc cccggacatg gatctttatc tttttttttt 27960 tttctttttt gcggccagac ctgcggcata tggaagttcc caggccaggg gttgaatggg 28020 agttgcagct gcctggtcta caccacagcc acagcaaggt gggatctgag ctgcatctgt 28080 gacatacacc gcagctgagg taacaccaga ttctgaaccc actgaatgag gccagggatg 28140 gaacccgtct ccttatgaac actatgtcat gttcttcacc ctctgagcca caacgggaac 28200 tccagacttc gtctttaaat gtattctgac ttggagagct atcacactaa gcaattaaca 28260 ggagctgacc tggtttaggc tggggtgggg ccctactcct caatgttccc tgaggcacat 28320 ctgtgggacc cctgggcatc atctatctga gcagccttag agctgctcat ccagttgact 28380 gttgatgtag aagtgcaaac ttctgccttc cttatttgtt gctttctttt ttcattgttc 28440 tctccccttt gtgtctttaa gcaagggcat cgtagagcct ccagaaggga ctaagattta 28500 caaggattcc tgggattttg gcccatattt gaatatcttg aatgctgcta taggagatga 28560 aatatttcgt cactcatcct ggataaaaga atacttcact tgggctggat ttaaggatta 28620 taacctggtg gtcagggtat gctatgaagt tattatttgt ttttgttttc ttgtattaca 28680 gagctatatg aaaacctctt agtattccag ttggtttctc aataagcatt cattgagcct 28740 tactgactgt cagacggagg gcgtattgga ctatgtgctg aaacaatcct ttgttgaaaa 28800 tgtagggaat gttgaaaatg tagggaatga aatgtagatc cagctctgtt tctcttttgg 28860 aggattcttt ttcctccatc accgtgtctt ggttcttgtt tgttttgggt ttttgtgggt 28920 gttgtattgt gttgtgttgg ttatggcagt gacagctatt taaactgtga aacgggggag 28980 ttcccgtcgt ggcgcagtgg ttaacgaatc cgactgggaa ccatgaggtt gcgggttcgg 29040 tccctgccct tgctcagtgg gttaacgatc cggcgttgcc gtgagctgtg gtgtaggttg 29100 cagacacggc tcggatcccg cgttgctgtg gctctagcgt aggccagcgg ctacagctcc 29160 gattggaccc ctagcctggg aacctccata tgccgcagga gcggcccaaa gaaatagcaa 29220 aaagacaaaa taaataaata aataaataag taagtaaaat aaactgtgaa acggggagtt 29280 cccttcatgg ctcagcagtt aacaaaccca gctaggatcc atgaggatgt aggttcgatc 29340 cctggccttg ctcagtgggt taagaatcca gcgttgctgt gagctgtgat gtaggtcgca 29400 gatgcagccc agatcctgca ttgctgtggc tgtggcgtag gctggcagct gaagctccga 29460 ttcaacccct agcctgggaa catccatatg ctgcaggtgt ggccttaaga ggcaaaaaaa 29520 taaaaaaata aaaaataaat aaattgtggg acagacaggt ggctccactg cagagctggt 29580 gtcctgtagc agcctggaag caggtaaggt aaggactgca gctgggtaag gactgaattg 29640 caccaactgg gaagtaagcc tagatctaga acttaagtta gccctgacat agacacacag 29700 agctcaccag ctaagtggtt cagcttataa gctggtcact gaaactgagg atgtccacaa 29760 aagcaaaata agtagcaaca ggcagcggga tgcaagagaa agaggaggcc taaaatggtc 29820 tgggaatccc tgccatacct atattttatc ctacttatat ttagtgcctg aatgtgtgcc 29880 tggagagcaa agtttaggga aagcatcggg aaatgcacag tattcatacc cttaggaaca 29940 aagatcagtt acctccaggg taaagactat ttccaagttt aaatttcaac ccctgaacat 30000 tagtactggg taccaggcaa cacttgccat cctcaaaatc aatgaatcct aaaattcaac 30060 ctgggggtca gtgacagtct gtgacaaagt ttttgctggt cagtaacgaa ataagtatga 30120 gcaccatctg agtatggtca ccaagatgtc aactctcttt cctttggacg aattgtcatt 30180 attccaagat taggtccttt ctatttttga ggtgtgaaaa catctttcct ttcataaaat 30240 aaaaggatag taggtggaag aatttttttt gttttttggt ctttttgcta tttctttggg 30300 ccgcttctgc agcatatgga ggttcccagg ccaggggtcg aatcggagct ttagccaccg 30360 gcccacgcca gagccacagc aacacgggat ccaagccgca tctgcagcct acaccacagc 30420 tcacggcaat gccggatcgt taacccactg agcaagggca gggaccgaac ccgcaacctc 30480 atggttccta gtcggattcg ttaaccactg cgccacgacg ggaactccta atgatactct 30540 tttatattta gctactatgt gatgatgaga aacagtccac attttattat tttttagcca 30600 atttgatatc tcattactaa gataatgata attttctcta taaattttat ttaagttagt 30660 gttatgaagt ggttttgcta gtgtagaagg ctaggatttg aattcagttc aagaaagaag 30720 agagggaggg agggagaggg atgggtagag ggatggggca gtgggagaga gcaaagagga 30780 gagacagttt ttgtattaat tctgcttcat tgctatcatt taagggcact tgggtcttgc 30840 acattctaga attttctaag gaccttgacc gccagattga tatgcttctt ccctttacca 30900 tgttgtcatt tgaacagatg attgagacag atgaggactt cagccctttg cctggaggat 30960 atgactattt ggttgacttt ctggatttat cctttccaaa agaaagacca agccgggaac 31020 atccatatga ggaagtaagc aggaatacca gtggaagtgc ccctttcttc cttccttcct 31080 aaataaactt ttttattttg gaacaacttt agagttacag aaaagttgca aagatattat 31140 agacagtagt gtttatatat atatataaat ttttttttgc tttttatgac cacacctgtg 31200 gcatatggag gttcccagtc taggggttga attggagcta cagctgccag tctgtgccat 31260 aaccacagca atgcaggatc tgggccacgt ctgtgaccta caccaaagct cacagctgga 31320 ttcttaaccc actgagcaag gccagggatt gaacctgcat cctcgtggtt cctagttgga 31380 ttcgtttccg ctttgccgca atgggaactc caaattattg ttaatatctt actttactgg 31440 ggtacatttg ttacaaccaa tactctgata ctgaaacatt actgttaact ccgtacttgc 31500 ttctttttga gtcatttgca aagactggct tcttgacctg cttccttcca aacagctggc 31560 ctgcctatgc tgttctcaga cctgcaagca ctgatctctg ccccccttgc cttctctcca 31620 gtggtgtctc cttccccaaa caaacccagt gtggctctgg aaagggagtt aagtcaacat 31680 aaaccaacac atattttgtt gagctccaat tttgagcaaa tccctcacct acggcagaca 31740 ggcatgatgt taagaactag ggctttggac acaaggtcaa gaccaagaag ggttcctcac 31800 ccctactgat tcagataacc aataatgagg ctttgaatcc ctgtccaaag gttgtttttt 31860 ttcccttcta ttgagcttct tgccacctta tcagtttttt ttatgacagt caaatgacat 31920 gatatatgtg agcatacatg gtaattttta attctatata aatgaatcac taaataaatt 31980 aggaggatat atagtccacc tttaagcgta ttacacgtgt cacatgaatg tgtggcgact 32040 taattgtaga ggtttaaatg tagcttccta taatagatgt gttcctaaac tacattttaa 32100 tcattggact tgtattttta tgttagcact tgctgttgaa gaaaagccta tgccaaaagt 32160 tcagtgaaac caataatcca ctgccagctt tctgagttaa aaaaaatccc tgggttttca 32220 cacacaggaa caccctgtgt gaaacactca tttagagcaa aatgcatctg ataaggagtt 32280 cctgttgtgc ctcaactggt taaggacctg acattctcca tgagaatgtg agtttgatcc 32340 ccggccccac tcgatgggtt aaggatctgg tgttgccaca aactgcagct ccgattcatc 32400 tcctagccta gaaacttcca cagcccagaa tatgccacag aattcggctg tttaaaaaaa 32460 aaaagaaaaa aaaaagaatc ataaatgtgt tggtttgttc accaaataca tgataacttg 32520 ctcttgccaa gctcagcttc ataaatatta agtcatttaa tacagcagcc accttatgaa 32580 cagatattac tatacttccc atttacagat aaggaaaatg ccatatttaa ccaagagatt 32640 aaataacttt cccgaggtct tatagcaagt aaatcatggt gcaggggttt gaccacacgc 32700 agtctatctc cagagtctgt gtatttagcc actgttttac tttcaaattt aaatttataa 32760 aacttctaaa ttatctgtta accataatct ttggaatttt taaaaccacg agttcctata 32820 aaatgtttca ttgaaagtaa gtcacttttc catagctttt gataatacat ctgtaggata 32880 aagtaagcca cagctctctt gcagacttgg tacaccctgg ggcaaagcat catgcctgtc 32940 acgtacatgg tggtccttac tttgactctc agtgctttta ttgcccagga attttgtgag 33000 atttctagtt gttgaggttt gtttaaagag gttatgccgg tacttggaag agctcttttc 33060 ttgctacctg gagccttctc atatttcctt tttgaggagg gacatgaatt gcctttcaaa 33120 ctcataaata tattttctag tacacaagtc tccatcttcc ttagacgcat ggctcctgga 33180 gttctccatc ctcctgctcc actttgggtg ggctcctctc tgggtctgcc accaatctgc 33240 cacccagaga catccttgac ccacttccag accccaccat ggcttcactt tcttcgcttt 33300 cctcctttgt ggaaccttct gcttaagaat ctgaggaaga aaatttgcac gtgagctaaa 33360 ctggaggtac tttcctgcct ggtcttgcac gatagcttgg ctgagcccat gatgctgggt 33420 ggctgttact ttccatggac acccgaaggc gttgctcctt tggcttctag ttgcatgcag 33480 tgttgcttat cccaggctga tctttcttcc actgtaggtg acttttaaga attaagggat 33540 taatctatat ctacaacaac aacaacaaag accttttcaa gctgaggtag ggctttctgt 33600 atatgtttgg agtggttatc cagcagactt tacttgaagg caggggtcat atcctcaagt 33660 gctcataaac ggaccacaga aagatctcat aattgggtgg agctgggtgg ggaccgtgtc 33720 atgtggccag gaaatgccag atgggaaggg agtggccctt actgagctcc agctgaactc 33780 tgaattttct agaaaactca gaaatctgga tttttcatgt gtaataccca gatttataga 33840 tgtggaaagc taattctttt tttttttaag ggactatagg caatgaacta agatctaggt 33900 tgtatttgga caaggggtca tcagtttaag ctgtgtagtt gagcgctcag ctattgggct 33960 gagggacccc taaatactga gacggggagg tccttgctct ggggcatcac aagtacactc 34020 cctggtctca ttcaaacact tttcctacaa aattgatccc atttcttcag tgcactgtct 34080 gaatgcattt ggcccagagc cgtgctgagg catagggaag gggtccacgg tttcatggca 34140 tcgttttgtg ctgtgtgtcc ctgctgtcgt ccaggatacc tacctctcct cctcctgcat 34200 ctgaatgtcc ccccacagac tctctgggat tctacagcct ctggcctgtt cctcagacac 34260 ctcttacctg ccagctttcc agattcacat tagttagtcc aaatctactg ccgtcagtga 34320 ctcacttcat ttcttcttct ccgaggcagt tcagcccggt acagttgttt tgtcaacact 34380 tcagttgagt ctggaagatg tgcatgggtt atgcacgaga gcggtccatc attttgagct 34440 agaagtcctt tctcagccca gagacaagtc ctcatctcct ttacttcctg actcttcttc 34500 ctctgcatcc ttccaagata tctctttctc cagccaccac ctaaatctct tcttttcccg 34560 gggttccgtg ctcaacccac tcttcttctt aaatctgtgg ctgggtgaac gcatctgctg 34620 gcaccacttc tctgctaaag actccaaaaa tccataggtc ctgcccggcc tttgcccacc 34680 tctctccaac actgtccagc tttagatgta gagctaatcc ccccagagat atcattccct 34740 ggatgtctaa gtcctttggt atctcacttt cagcgtgttc aaaatcctct tacaactgtt 34800 ctttctcctt ttccatcttg attattggca acatgccagc ctttccccta cccccagcag 34860 tgagccaagc tagaaacaag ggcttaatct tcaatctttc cttctccatc cctaaaccta 34920 atgagtctcc aagcccttcc cagtttacac cctaaatgtt gctcaaaaca tcccctagtt 34980 cttccacgtg ctctcctcta tattgaaagg tcaagaaagg ccatcttccc tccactgtga 35040 ggaaatagat cttgatactg cccctgagct gggcagtcct cgacctgaca aactgtgcag 35100 tgtttctaaa tctctactgg caaaatgaga gtgcctttga cctgtgttgc gatctcagat 35160 cacagtggat gtaattgttt tataggaatg gtgaacgaaa aagaagtaaa tccctaatgc 35220 caaactcctg atcattctat gtcatttaat agcctgtcat ttatgataaa gtttcctcta 35280 ctggcattag cacaatactt ctcaggaaaa aaaaatatga tgccagatac tgaaaagctc 35340 ctgggtaaac atgaacatgg gtaccgataa aatggtgaag ccagtccaat cttagagtga 35400 cttcccttca tgctacttca tgctcttttt tttttttttt tttaagaaaa accccttttt 35460 tttttctcac accagtcaca gaggagaccg aggcttagca aggttaaggt cacatgatta 35520 gtaagtgctg ggctgaaact caaaaccatc tctgcttgtc tcctaaccct gtgcacctct 35580 gactattcaa cagatcctgt gtcaggagtt gggattcttt gaaggtaagg gccttgacca 35640 ccgaattaag gtaatcttgc tctgtggcag gccttgtttt cagtatttta agtacactgg 35700 ctcaggtaat cctcacaaca gccccaggag gaatgttcta ttacctccac tgtatagatg 35760 aggaacttga ggcacagaat ggttgccaag gtcacacagc tatattgggg gttcataccc 35820 agccatccaa ctctgtctgt actctctgcc actctgcacc cccagctcct gatccacttc 35880 ctgtttccat ccctcgattt ctgctgcact caggggcccc tctccccctc ggcctgtgag 35940 atctgcttca gtaggctttt ctccctgact cctccatccc tgtccttaca ggcagctgct 36000 tctctccggg acacgagggg tccatacgga cactctctac tggctgggtt gcgcctaact 36060 cgtgattcct cctctgtttc agattcggag ccgggttgat gtcatcagac acgtggtaaa 36120 gaatggtctg ctctgggatg acttgtacat aggattccaa acccggcttc agcgggatcc 36180 tgatatatac catcatctgt aagtccgaaa atgcctgtcg tgtgtgcctt aggctgctgc 36240 ggaggaggcc agggctatat aagcagagtc agtgactgac tgtgccctgc agtgttgatg 36300 gccatggaga ttccaccgtt agagcttttt tctttgttaa ccttgaaggc aaatctggtt 36360 aggaagataa ctttcaaaga gtcaccatct ggacattcat gcccatgtgc ttcaatcctg 36420 tatacaagca gtttagagta cagggaaggg aaggacatta tgaaagggag agggtgtgtt 36480 tggatccagc agctccatcc tcagaattta tctgaagaca ctgcaaaatt actaagaatc 36540 actatgacaa gaatgaggat ggggtgatat ggcaaagttg tgatcctgga agaccttcat 36600 ctcccatgtt gcccaactct gaacatgaat ttggtgaact agttggttaa ggggatgatc 36660 ctccaagttt ctccctggtt gagctccaaa aaccatgtaa gtttctcata gcaaaaccgt 36720 ataggtcctt agggctttag ttggaatatt tgtgctgaaa tgctggaaag ccccatttgc 36780 catttttgta tttgcaaaat aatcatcaag aggggagaat gcattctttc atgaccactg 36840 accctctgaa aaggtcagga atttagtctg aagtaggcaa gcctcctacc ccgcttctgc 36900 catgagcttg cacgcacagg cctgtcttga catttcttct ttatagattt ctttttgaat 36960 atcttgaaat tgctttaaaa atatttaaag aatgtagaat tatataaaat aaaaaggaaa 37020 taaccccaca cctcccacaa aaccctgttt cctgcctttc tccacccact ctccagggta 37080 acacttggta acagcatagt tgtatcaccc caggcctatt tttgagcata tcagcatttc 37140 aagaaatgta ttttttctca ataaaacatc ccttatagtt gaggagggga ggttatcatt 37200 cctgggtttt gttttttttt tttttttaat gtaatcctgg tacatcggta atttgcattt 37260 tttattcatt aatatctttg gtatttctag tgttgggaca cacaggtcaa cctcagtttt 37320 tgggtttttt tttttgtctt tttgtctttc tagggccaca cctgcagcat atggacgttc 37380 ccaagctagg agtctaatca gagctgtagc caccagccta cgtcatagcc atagcaacgt 37440 cagatccaag ccgtgtctgt gacctacaag cacagctcat ggcaacaccg gatccttaac 37500 cactgaacga ggccagggga tcgaacacac atcctcatgg atcctagtca tgttcattaa 37560 ccactgagtc atgatgggaa ctccaacttc aactatttta atgtctgtaa aacattccat 37620 ttggaaacca tttcatttgt aaagcaaaat gaaaacattt tgttcatttt caacagagtt 37680 cgtagctgac ttctgttctg gaaaaaagga aatggagcaa atttgagtga gaaagattca 37740 aagataactt ttcttttaaa aaaaattata tcttggaaac ttctgggcta ttgattctga 37800 agactatttt tctatatact gttttgatag caaagttcat aaatgtgaaa ggatcctgcg 37860 atgaatcttg ggaagcagtc atagcccaat atatctttgt tgcttttaaa atgagattta 37920 gtttactaaa tatttttctg atcataaaaa taacacagat ctaccgcaga aaatttggaa 37980 aaaaaaaaac ttttaaattc aaaaaacagt taaaccacaa atgatcccac catccagaga 38040 gcaatttgta ctttggtgtc tagttcatct ttctttttct gtttacaagc acatatacca 38100 caagcatttt ttcaaaaaat gaaaatggga taatactata catacgtctg tacacctgca 38160 tagttactga acagtctttg atctaccctg taagtttcta acttttcatt atttgaaatg 38220 atgttttggc aaagaaatat gtaggtgtgt ctcgcacact ttcataatga tttcttagga 38280 taaatttctt aggataaatt cataatgatt tcttataata atccatactc tgccaactga 38340 tcttcaggga agccaactcg ccttctcaga aataacatat aacccattta cttgccctct 38400 caccaatact aggtcctaat gtttttgtgt acagattcta tatttttaca tacaagaatt 38460 ccttaaagca aggcatgtca cagaaaaata gaaggaagac acaattgtca tgtttaagga 38520 ctgcattctg taccaaaaat gctaagttaa atgaacatct gaaacagtac agaaacgcta 38580 tctttcaggg aaagctgagt accaggtact gaacagattt tggcaaatac agcaggcatg 38640 gatgtttcca aaacatgttt ttctacttta tctcttacag gttttggaat cattttcaaa 38700 taaaactccc cctcacacca cctgactgga agtccttcct gatgtgctct gggtagagag 38760 gacctgagct gtcccaggta aagcatcctg caggtctggg agacactctt attctccagc 38820 ccatcacact gtgtttggca tcagaattaa gcaggcacta tgcctatcag aaaacctgac 38880 ttttggggga atgaaagaag ctaacattac aagaatgtct gtgtttaaaa ataagtcaat 38940 aagggagttc ccatcgtggc tcagtggtaa cgaaccctac tagtatccat tgaggacaca 39000 ggttcaatat ctggcctcac tcagtcggct aaggatccag tgatgccgtg agctgcagtg 39060 taggccacag acgtggctca gatctggtgc tgctgtggct atggtgtagg ccggccccct 39120 gtaactccaa ttcgacccct aggctgggaa cctaaaaaga ccccaaaaaa gtcgctttaa 39180 tgaatagtga atacatccag cccaaagtcc acagactctt tggtctggtt gtggcaaaca 39240 tacagccagt taacaaacaa gacaaaaatt atcctaggtg gtcagtgggg gttcagagct 39300 gaatcctgaa cactggaagg aaaacagcaa ccaaatccaa atactgtatg gttttgctta 39360 tatgtagaat ctaaattcaa agcaaatgag caaaccaatt gaaacagtta tggaagacaa 39420 gcaggtggtt gtcagggggg agataagggg aggcaggaaa gacctgggcg agggagatta 39480 agaggtacca actttcagtt gcaaaacaaa tgagtcacca gtatgaaatg tgcaatgtgg 39540 gaaatacagg ccataacttt ataatctctt tttttttttt gtcttttttg ccttttctaa 39600 ggctgctccc gtggcatatg gaggttccca ggctaggagt ccaaacagag ctgtagctgc 39660 cagcctacac cagagccaca gcaacacggg aaccttaacc cgctgagcaa ggccagggat 39720 cgaacccgag tcctcacaga tgccagtagg gttcattaac cactgagcca cgacaggaat 39780 tccagggtct gttgtgttct taaaacactt ccaggagagt gagtggtatg tcataagtaa 39840 acaataaatg ttaaccacaa caagcttatg aaataaacag gaaagccata tgacctacaa 39900 tcagtcattg ggagaatcca caaaaggttg agcagaggat caattccagc tcacactcca 39960 gttttagatt ctcccctgcc ttaaagcatc acagactaca taatctgagc tgaagaataa 40020 aaattaaaac tcaccccagt gcaaaacaga aatgaaaaag tattaaaacg aggttcatac 40080 tgttgttcat tagcaatatc ttttattcac aggggtgccc aacaacatga aaaaatcaag 40140 aatttattgc tgctacgtca aagcttatac cagagattat gccttataga cattagcaat 40200 ggataattat atgttgcact tgtgaaatgt gcacatatcc tgtttatgaa tcaccacata 40260 gccagattat caatatttta cttatttcgt aaaaaatcca caattttcca taacagaatc 40320 aacgtgtgca ataggaacaa gattgctatg gaaaacgagg gtaacaggag gagatattaa 40380 tccaagcata gaagaaatag acaaatgagg ggccataagg ggaatatagg g 40431 <210> SEQ ID NO 47 <211> LENGTH: 1192 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 47 ctgccagcct aagccacagc cacagcaacg ctgggtctga gccatgtctg cagcctatgc 60 cagagctccc cgcagcgccg gatgcttaac ccactgagca aggccaggga ttgaaccctc 120 gtcctcatgg atagcagttg agttgtttcc acggaactct taggggaact cctgattatt 180 ttttatttaa atttatattt ctctgacttt ttcgtgtgct catcagccac tgactgtgta 240 tctccattag tcatggtttg ttaactctgt cattcaaacc ctcttcatcc ttgctacgca 300 gataacatca ttataataaa atcgtgcctg aagaccagtg acgcccccaa gctaagttac 360 tgcttcccct ggggggaaaa agaagcaccg cgcgggcgct gacacgaagt ccgggcagag 420 gaagacgggg cagaggaaga cgggggagca gtgggagcag cgggcagggc gcgggaagca 480 ctggggatgt tccgcgttgg caggagggtg ttgggcgagc tcccggtgat gcagggggga 540 ggagcctttt ccgaagtagc gggacaagag ccacgggaag gaactgttct gagttcccag 600 tcccgacgtc ctggcagcgc ccaggcactg ttattggtgc ctcctgtgtc cacgcgcttc 660 ccggccaggc agccctggcg gatcctattt tctgttcccc cgattctggt acctctccct 720 cccgccctcg gtgcgcagcc gtcctcctgc agtgcctgct cctccagggg cgaaaccgat 780 cagggatcag gccacccgcc tcctgaacat ccctccttag ttcccacagg tgagaaggct 840 tcgccgctgc tgccgctggc gccggcagcg ccctccacgc acttcgtagt gggcgcgcgc 900 cctcctgcat tgtttctaaa agattttttt ttatccgctt atgctatcag ttactgagga 960 agtatttaca aatctactat tattttgaat ttgccttttt ctccttatag tttatcagta 1020 tctcttgaga ctgttattgg tgcctgcaaa tttaaaatga ttggggtttt atgaggaagt 1080 gaacctttta tctttatgaa acgcctaact gaggcaatgt taattgctta aaatactttc 1140 tttattatca gtgtggccat gccagtgtcc tcttggttag aatttgcctg at 1192 <210> SEQ ID NO 48 <211> LENGTH: 39239 <212> TYPE: DNA <213> ORGANISM: Porcine <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15433)..(15433) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15445)..(15445) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15479)..(15479) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15539)..(15539) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15549)..(15549) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15572)..(15572) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15577)..(15577) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (17098)..(17098) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (17208)..(17208) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19935)..(19935) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (19937)..(19937) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (21489)..(21489) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (21492)..(21492) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (21508)..(21508) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22074)..(22074) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (22085)..(22085) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 48 ctgccaaagc tgggagatgg gggaaagtag agtgggttat tgaaactgaa tatagagttc 60 agcatctaaa agcgaggtag tagaggagga agctgtgtca acggaaatac tgagctgggt 120 tcacatcctc tttctccaca cagtctaatg ccttgtggaa gcaaatgagc cacagaagct 180 gaaggaaaaa ccaccattct ttcttaatac ctggagagag gcaacgacag actatgagca 240 ggcaagtgag agggggcttt agctgtcagg gaaggcggag ataaaccctt gatgggtagg 300 atggccattg aaaggagggg agaaatttgc cccagcaggt agccaccaag cttggggact 360 tggagggagg gctttcaaac gtattttcat aaaaaagacc tgtggagctg tcaatgctca 420 gggattctct cttaaaatct aacagtatta atctgctaaa acatttgcct tttcatagca 480 tcgaacaaac gacggagatc ctgttgtgcc tctcacctgc cgaagctgcc aatctcaagg 540 aaggaatcaa ttttgttcga aataagagca ctggcaagga ttacatctta tttaagaata 600 agagccgcct gaaggcatgt aagaacatgt gcaagcacca aggaggcctc ttcattaaag 660 acattgagga tctaaatgga aggtactgag aatcctttgc tttctccctg gcgatccttt 720 ctcccaatta ggtttggcag gaaatgtgct cattgagaaa ttttaaatga tccaatcaac 780 atgctatttc ccccagcaca tgcctaactt tttcttaagc tcctttacgg cagctctctg 840 attttgattt atgaccttga cttaatttcc catcctctct gaagaactat tgtttaaaat 900 gtattcctag ttgataaaca gtgaaacttc taaggcacat gtgtgtgtgt gtgtgtgtgt 960 gtgtgtgttt accagctttt atattcaaag actcaagcct cttttggatt tcctttcctg 1020 ctctctcaga agtgtgtgtg tgaggtgagt gcttgtccaa acactgccct agaacagaga 1080 gactttccct gatgaaaacc cgaaaaatgg cagagctcta gctgcacctg gcctcaacag 1140 cggctcttct gatcatttct tggaagaacg agtgctggta ccccttttcc ccagcccctt 1200 gattaaacct gcatatcgct tgcctcccca tctcaggagc aattctagga gggagggtgg 1260 gctttctttt caggattgac aaagctaccc agcttgcaaa ccagggggat ctgggggggg 1320 ggtttgcacc tgatgctccc ccactgataa tgaatgaggg attgacccca tcttttcaag 1380 ctttgcttca gcctaacttg actctcgtag tgtttcagcc gtttccatat taggcttgtc 1440 ttccaccgtg tcgtgtcgtc aatcttattt ctcaggtcat ctgtgggcag tttagtgcga 1500 atggactcag aggtaactgg tagctgtcca agagctccct gctctaactg tatagaagat 1560 caccacccaa gtctggaatc ttcttacact ggcccacaga cttgcatcac tgcatactta 1620 gcttcagggc ccagctccca ggttaagtgc tgtcatacct gtagcttgct tggctctgca 1680 gatagggttg ctagattagg caaatagagg gtgcccagtc aaatttgcat ttcagataaa 1740 caacgaatat atttttagtt agatatgttt caggcactgc atgggacata cttttggtag 1800 gcagcctact ctggaagaac ctcttggttg tttgctgaca gactgctttt gagtcccttg 1860 catcttctgg gtggtttcaa gttagggaga cctcagccat aggttgttct gtcaccaaga 1920 agcttctgca agcacgtgca ggccttgagg tcttccgact tgtggcccgg ggactctgct 1980 ttttctctgt ccttttttct ccttagtggg ccatgtcctg tggtgttgtc ttagccagtt 2040 gtttaaggga gtgttgcagc tttatgatta agagcatggt ctttccttgc aaactgcttg 2100 gtttagaagc ctggctccac cacttagcgg ctctgtgacc tcggacacat ttcttagcct 2160 ttctgggcct cgctcttctt cctcataaag tgaaaatgaa agtagacaaa gccttctctg 2220 tctggctact gagaggatgg agtgatttca tacacataaa gcacttaaaa taatgtctgg 2280 catatgatac atgctcaata aatgtcactt acatttgcta ttattattac tctgccatga 2340 tcttgtgtag cttaagaaca gaggtcttta caggaattca ggctgttctt gaatctggct 2400 tgctcagctt aatatggtaa ttgctttgcc acagactggt cttcctctcc ttcacccaaa 2460 gccttagggg gtgaacgatc ccagtttcaa cctattctgt tggcaggcta acatggagat 2520 ggcaccatct tagctctgct gcaggtgggg agccagattc acccagcttt gctcccagat 2580 acagctcccc aagcatttat atgctgaaac tccatcccaa gagcagtcta catggtacac 2640 tcccccatcc atctctccaa atttggctgc ttctacttag gctctctgtg cagcaattca 2700 cctgaaatat ctcttccacg atacagtcaa gggcagtgac ctacctgttc caccttccct 2760 tcctcagcca tttttcttct ttgtacataa tcaagatcag gaactctcat aagctgtggt 2820 cctcattttg tcaatctaat ttcacagcct cttggcacat gaagctgtcc tctctctcct 2880 ttctgcctac tgcccatgag cagttgtgac actgccacat ttctccttta acgacccagc 2940 ctgctgaata gctgcatttg gaatgttttc aatttttgtt aatttattta tttcatcttt 3000 tttttttttt tttttttttt ttttttttag ggccgcaccc atgggatatg gaggttccca 3060 ggctagggat ccaatgggag ctgtagctgc tggcctacac cacagccaca gcaatgcaca 3120 attcgagcca atctttgacc tacaccagag ctcacggcaa cactggattc ttaacccact 3180 gattgaggcc agggatcaaa ctctcgtcct catagatacg agtcagattc gttaacctct 3240 gagccatgat agttgttagt tactcattga tgagaaagga agtgtcacaa aatatcctcc 3300 ataagtcgaa gtttgaatat gttttctgcc ttgttactag aaaagagcat taaaaattct 3360 tgattggaat gaagcttgga aaaaatcagc atagtttact gatatataag tgaaaataga 3420 ccttgttagt ttaaaccatc tgatatttct ggtggaagac atatttgtct gtaaaaaaaa 3480 aaaatcttga acctgtttaa aaaaaaaact tgactggaaa cactaccaaa atatgggagt 3540 tcctactggg acacagcaga aatgaatcta actagtatcc atgaggacac aggtttgatg 3600 cctggcctcg ctaagtgggt taaggatatg gtgttgctgc agctccaatt caacccctat 3660 cctgggaacc cccatatgcc accctaaaaa gcaaaaagaa aggtgctgcc ctaaaaagca 3720 aaaagaaaga aagaaagaca gccagacaga ctaccaaata tggagaggaa atggaacttt 3780 taggccctat ctccaactat cacatcccta tcaccgtctg gtaagaaatg gaaaaaatat 3840 tactaagcct cctttgttgc tacaattaat ctgattctca ttctgaagca gtgttgccag 3900 agttaacaaa taaaaatgca aagctgggta gttaaatttg aattacagat aaacaaattt 3960 tcagtatatg ttcaatatcg tgtaagacgt tttaaaataa ttttttattt atctgaaatt 4020 tatatttttc ctgtatttta tctggcaacc atgatcagaa atctttaaac aatcaggaag 4080 tcttttttct tagacaaatg aaaatttgag ttgatcttag gtttagtaca ctatactagg 4140 ggccaagggt tatagtgtga ctattaaatc acagataatc tttattacta cattatttcc 4200 ttatactggc cccacttgga tcttacccag cttagctttt gtatgagagt catccttaaa 4260 gatgacttta ttctttaaaa aaaaaaacaa attttaaggg ctgcacccat agcatataga 4320 agttcctagg ctagcggtca aattagagct gcagctgcca gcctatgcca cagccacagc 4380 aatgccagat ctgagctgca tctgtgacct acactgcagc ttgcagcaat gctggatcct 4440 taacccattg aacaatgcca gggattgaac acacatcctc atggatactg ctcaggttcc 4500 taacctgctg agccacagtt ggaactccaa agcagacttt attctgatgg ctctgctgat 4560 ctctaacacg ttattttgtg ccatggtgtt tatcttcact ttactcaagt cagggaaaca 4620 cgaagagtct catacaggat aaacccaagg agaaatgtgc aaagtcacat acaaatcaaa 4680 ctgacaaaaa tcaaatacaa ggaaaaaata tcttcacttt caaaatcacc tactgatgat 4740 gagtttatat ttccttggat atttgaatat tagctatttt tttcctttca tgagttttgt 4800 gttcaaccaa ctacagtcgt ttactttgat cacagaataa tgcatttaag ccttaaatag 4860 attaatattt attttcacca tttcataaac ctaagtacaa tttccatcca ggtctgttaa 4920 atgcacaaaa cacaactgga agttagatgt aagcagcatg aagtatatca atcctcctgg 4980 aagcttctgt caagacgaac tgggtaaata ccatcaatac tgatcaatgt tttctgctgt 5040 tactgtcatt ggggtccctc ttgtcaactt gtttccaatc tcattagaag ccttggatgc 5100 attctgattt taaactgagg tattttaaaa gtaaccatca ctgaaaattc taggcaagtt 5160 ttctctaaaa aatcccttca ttcattcatt tgttcagtaa gtatttgatg agaccttacc 5220 atgtgtaaac attgcactag gtattaagaa atacaaagat ggataagata gagtcggcgt 5280 aaatgagatg atataatgag acgttataat gaaactcaca attccagttg ggaaataaag 5340 tccttcaaat tccatgactc tttctggcac acgttagagg ctacagcttc tgtgtgattc 5400 tcatgctggc tccacttcca ctttttcctt cttcctactc aagaaagcct atagaaatat 5460 gagtaagaag ggcttaatca taggaataaa tttgtctctg ttctaagtga ttaaaaatgt 5520 ctttatcagt ataaaaagtt acttgggaag attcttaaaa ctgcttttac acactgttct 5580 agaatgactg ttatataaat aaaaaagtag atttgatcta acacaattaa atgacctttg 5640 gaaatattga ctaattctca ccttgcccct caaagggatg cctgaaccat ttccttcttt 5700 tgccagaaag cccccaccct ttgtctgttg acctagccta ggaaatcttc agatcacgtt 5760 gttagcacga actggttaca tgtgctgtac aaatactatt taattcatct gattaaaaaa 5820 aaagagataa gaagcaaaag tttgactatc ttaaactgtt tgcgtaggtg agaggacaat 5880 tgaccatcta ctttatgagt atgtaaccca gaaacttaaa gctccttaag ggagctaagt 5940 cttttggata agacctatag tgagaccttt tagcaaaatg gttaagactg aatggagctc 6000 actagcgtgg gttcatatcc tgatgctcaa acacgcaatt aaatgacttt aggtgggtta 6060 gtctctgttc cttagtttcc tcaatgggag ataatattgg tagtagcgat tttactgggt 6120 tgttgaaaga acatctgtta aatgttcaga acgtgttacg acagagtaca gagtaatgat 6180 ttgcttgtat atgtatgact caaatagtct gccatatgcc ttgtgactgg gtcctgtgga 6240 gcaggaagga gggatttccc acccagcaga aagttgggta aactggaaaa tagactgagg 6300 ccaggaaatg atgcaaagcg ttgatgttca ctgccacggc aggtgaaggg cagggccaga 6360 gttgtcagta gggtcagggg aggactggaa ataaccaaga cccactgcac ttttcagcct 6420 ttgctccagt aaggtaatgt tgtgagagta gaaaattttg ttaacagaac ccacttttca 6480 gtacagtgct accaatactg tagtgatttc ataccacatc ccaagaaaga aaaagatggc 6540 tcaatcccat gtgagctgag attatttggt tttattgtta aataaatagc attgtgtggt 6600 catcattaaa aaaggtagat gttaggaaag tagaaggaag aagactctca cctacatttt 6660 catcactgtt ttggtatctg ccagttgtca ccttggtccc cttccccgcc tctcccctgc 6720 ctcctcttcc tccttctcct ttttttggaa tacaattcag gtaccataaa atttaccctt 6780 ttagagtgtt tgactcaatg gtttttagta ttttcacatg ttgtgctatt actatcacta 6840 tataattcca ggtcattcac atcacccccc aaagaaacct tctaactatt agcagtccat 6900 tcccttcttc cctcagcccc tggcaaccac taatctactt actgtctcca tggatgttcc 6960 tatattgaat caagctagca taaaccccac ttgctcatgg tcataattct tttttatagt 7020 gctaaattac atttgctaat attcaattaa ggatttctat gtccatattc ataaggaata 7080 ttggtgtgta gttttctctt tgtgtgatat ctttgtctgg ttgggggatc agagtaataa 7140 ttactgctct catagaatga attgagaagt gttccctcct tttctattta ttggaagagt 7200 ttgtgaagta tattggtatt gattcttctt taaacatttg gtcagattca ccagtgaagc 7260 catctgggcc atggctaatc tttgtgaaaa gttttttgat tactaattaa atctctttaa 7320 tttgttatgg gtctgctcct cagacgttct agttcttctt gagtcagttt tgttcatttg 7380 tttcttccta ggactttctc cctttcattt ggattattta gattgatagt aatatccccc 7440 ttttaattcc tggctgtagt aatttgggtc ttttctcttt tttcttggtc agtttagcta 7500 aaggtttgta attgtattaa tcttttcaaa taactaactt ttttgttttg tttgtttttt 7560 gttttttgtt ttttgttttt tgtttttttt tgctttttaa ggctgcacct gaggcatatg 7620 gaagttctca ggctagaggt ctaatcggag ctacagctgc tggcctatac cacaaccata 7680 gcaatgccag attcaagctg catctgcgac ctacaccaca actcggccag ggatcacacc 7740 cgcaacctca tggttcctag tcggatttgt taaccactgt gccacgacgg gaactcccgc 7800 ccattttttt taacacctca tactttaaca taaagatggg cttcacatgg actgatagct 7860 caaatgagga aggtaagact atgaaagtaa tggaagaaat gtagactatt tttgtgacct 7920 agagattact gatacttctt gacttttcaa acaatacttc aaaagtacag cccaaaggga 7980 aaaaagaaag aaaaaagaaa cacacatata cacaaaccta gtgaataaga tatcatcgat 8040 acactacaga tttctatgaa ctggaagacc ccatggacaa agttaaagaa catatgatag 8100 tttgagtgat tattttgcaa tatttacaac caatgaggga atattatcca gcttatagga 8160 ggaagtaatg caaatcgaca agaaaaagat aggaaaccca atataaaaat taagaaaata 8220 caaaaattaa gaaaggatat gaactagcat tttacaaaag aaaaatctcc aaaagtcaat 8280 cagcacatga aaatatgctc aaacctatta attattagaa aactacagac tgaagcaatg 8340 aggtgcttta ctttacatct ttttgactga taaaaagtta gaaacaaagg tgatatcaaa 8400 tgtcagggat aaaaggatat agaaatcgtc atgcctgtgg tgggagtatg gccggtgcag 8460 tcatgtggga aggtaatctg acagtggtta ggcagagcag gtttatgaat acactgtggc 8520 ccatcaatcc cacgcctgtt tatgtaccaa agaaatcctg ttgtggcaga atctatgggt 8580 ccacccctgg gagcatgaat taataaaatg tggcaccagg gtgtgtgaaa ctccagctag 8640 agatgagatg tccacatggc aacatgaatg catcttagaa acatagattt gagtgaaaaa 8700 gagtaagaaa cagccgggaa acccaatacc atttataaaa attaaagatg cacacataca 8760 atgtagtaaa tattttgcat gaactttcaa atggttgcct acaggggggg agagtaaaga 8820 agagtagaaa acaaagataa agggagtaag taagtagctc tgcctggact gaatataatg 8880 tgtcatgaac tgagaaatat ggttaacata atcctcttaa cttgaggtcc taaatgaatg 8940 aatgagtcca ctattcattt acccattctt taatgtgtat tgcattataa tccatttttt 9000 tagaaccaac gaattttgtt cccataacta ctaatcagcc tgccttttct ccctcattcc 9060 cttatcagct caggggcatt cctagttttt caaacgttcc tcatttgaac caaaaatagc 9120 atcattgttt aaattatact tgttttcaaa tacgatgctt atatattcca agtgtgtttg 9180 cccattttct taggtggtag aaatttttca ttctactttt ctatctactc agattttccc 9240 gttggaatta tttccattgc tattaaactt agaagtcccc cctgtgatat gccatttttt 9300 tcatactttt taagcacttg gttgcttttc tttgtgtctt taagcaccta gaatacttat 9360 aaccattgca cagcactgtg tatcaggcag cccttcctct tccactaatt tatggtcctt 9420 ctcttagact atattaaact gttatttaat taggatcctc tcttcgtcct tatgatttaa 9480 ttattatagt tttctaatat gtttttatta taattcctct tcattattcc tccctattaa 9540 aaattttaat gaattccatt tgtttgttct tctagttaaa tattaagtca taatccaaat 9600 aacttagatg tcattagttt atgtggtcaa agtaaggata ccacatcttt atagatgcag 9660 gcagttggca gatgtcatga ttttcttcag tgcataaatg caatttatct ttgagcaagg 9720 ggcataaaaa cttttatggt attggctttg aaataatagt taagaactgc agactcagtt 9780 tttcctgctt ttcttgaaaa agaacacttc taaagaagga aaatccttaa gcatggatat 9840 cgatgtaatt ttctgaaagt ctcctgtaat tccttgggat ttttgttgtt gtttgttggt 9900 cggttttttt gggtttttgt ttgtttgttt tgttttgttt tgttttgctt ttagggctgc 9960 acctgtggca tatggaagtt cccaggctag gggtccaact ggagctacag ctgccagcct 10020 actccacagc cacagcaaca tgggatccta gctgcatctg tgacctaacc acagctcttg 10080 gtaatgccag attgttaacc cactgagcaa tgccagagat cgaatctgcc tcctcatgga 10140 cactagtcag attagtttct gctgagccac aatgggaatt cccaattcct tgtatttttg 10200 aactggttat gtgctagcat ataattttgt ttcttgaatc tttgtgggtt tttttttttt 10260 tttttttttg tctcttgtct ttttaaggct gcacccacag catatggagg ttcccaggct 10320 agaggtcaaa ttggagctac agctgccagc ctacacaaca actgcagcaa agtggggccc 10380 aacttatatg acagttcgtg gcaatgccgg attcctaacc cactgagcag ggccagggat 10440 cgaacctgag tttccagtca gtttcgttaa ccactgagcc atgatagtaa ctcctgtttg 10500 ttcagtcttg aacctccttt ttaattcttt attccttgag ggtgaaataa ttgccataat 10560 aatactatca tttattacat gccttctctg tgctaggcat agtgacactt taggatttat 10620 tatatcactt aatccctaca acaactctgc aaagtatgta tcataatcct atttgacaga 10680 tcaggaaatt gcagcccagg atgcagataa tatgcatcca tcacaagtga ctagatatag 10740 tccctctgct attcagcagg gtctcattgc ctttccattc caaatgcaat agtttgcatc 10800 tattgtatat gtgttttggg gtttttttgt cttttttttt ttttttgtct tttctggggc 10860 ctcacccttg gcataggtag gttcccaggc taggggtcaa attgaagctg cagctgccag 10920 cctacaccac agccacagca actcgggatc tgagcctcat ctgcaaccta caccaaagct 10980 cacggcaaca ccggatcctt aacccactga gtgaggccag agatcaaacc ggcaacctca 11040 tggttcctag tcggattcat taaccactga gccacgatgg gaactcccta aatgcaatag 11100 tttgctctat taaccccaaa ctcccagtcc atcccactcc ctcctcctcc ctcttggcaa 11160 ccacaagtct gttctccatg tccatgattt tcttttctgg ggaaagtttc atttgtgcca 11220 tttttcattt tacgggtaat ttttacttca gtttcttcca ctagcagttg tcttaaagtg 11280 agtataatta atattcattt ggaaaatgta agcaaaacat tttttaaagg gccatgccca 11340 cagcatatga aagtttctgg gccaggggtt gaatccaggc tccaagttgc agctgtgccc 11400 tacactgcag ctgggcaatg ctggatcctt taacccactg tgcccggcta gggatcaaac 11460 ctgcatttcc acagctaccc gagccattgc agttggattc ttaacccact gcactacagt 11520 gggaactccc acaaaacatt ttttaatgtc ctttgaataa agtaggaaag tgctcgtctt 11580 tgagggcagg gcggcaatgc catttccaca aggtttgctt tggcttggga cctcatctgc 11640 tgtcatttag taatgaataa aattgctgac agtaatagga ttaactgtgt gtggagatag 11700 ccagggttag agataaaaac actggagaag tcaaataagt tgctcgaggt cctctagcta 11760 ataagctatt aagtgggaga gtgagggcta gaaacaggcc atctgtctcc caagcacatg 11820 tccattagtg gtttgctgat agccttccag aacaacagag aggactctca aacatggtct 11880 tgcctccctc caattgatcc cctccatgtg cctcacagcg ggtctttcta aaattaagtt 11940 ctgattttaa ttctcccttg ctatagcact taggtatggc tttcagccgt gcaataaaaa 12000 gcaggcaaga gtggctcaat catataggag gttgtttttc ttagatccca agcaggtaat 12060 cctgggcatt atggttgttc tgcgtttatc aaggagccaa attctctatc acctcctgtt 12120 ctatcctcct cagtatctgg ctctattctt cagcatctca agatggcttg tgctcctcca 12180 agcatggcag tcaaattcca cacaagaggg ggaaatatga agggcagaca gtgctggtct 12240 cctgagctgt ccctctttgt cggggaaata aatgtattcc ttcaagtccc gtgagacttc 12300 tgaagtagac gtctgcttac gtctcaccca ccagaactat gtaaactgca catagtgcta 12360 ggtctacata gccactcata actgccaggg ggtgggaaat ctttaaatag gtgtaccacc 12420 acacaattag gatgctaata gtaagggaga aggagagaat aggttttgcg caagccacca 12480 gcatgcctgc cacaattgct taaaattctt cattgacccc tcattgccac aggatgaaat 12540 ccaaacgcct tcttagttgg gaatctgacc tacctgtctc tcccacctgg ttcagacacc 12600 attctccttg gtcataaaat tccagtcatt tgtgaacatc cagctccccc atgcctccat 12660 gcctttgcac atgctgttct tttatctttt atgttgtcct tttatctttt atccaaaaga 12720 gatatcccat catcacatct cttttgtcag cccccaaata ctttgtcttt caagttcagc 12780 tggaggatta cctcctattt gaaatcagct ttgtctctta caaccaaaca aggttttcct 12840 tccgagacac tcccacagca ccttgaactc atctctatca atcattcatt tgattgtaat 12900 gaagttgttg gtggtatgcc tgtgtctctg acacatctgc gatctcatga gttccttaag 12960 tggaatgtga atagcgggat gaacagtatt ggtcttcagc cctcatctct gcagatgttg 13020 cttgacccaa atgagcgttg ccttttattt tgattttgct ttgatttgtc tactccatgt 13080 acttgagcca tgcatttctg tcttagcgat gctttttaaa agtcattttt tggttgatta 13140 tccagatttg tccacctttg cttctagttg tagaaaagga tgaagaaaat ggagttttgc 13200 ttctagaact aaatcctcct aacccgtggg attcagaacc cagatctcct gaagatttgg 13260 catttgggga agtgcaggta aggaaatgtt aaattgcaat attcttaaaa acacaaataa 13320 agctaacata tcaatttata tatatatata tatatatatt tttttttttt tttacatctt 13380 atattacctt gagtattctt ggaagtggct agttaggaca tataataaag ttattctgaa 13440 gtcttttttt ttctttttcc atggtgagca gtggcttgat gtggatctca gctcccagac 13500 gaggcactga acctgagccg cagtggtgaa agcaccaagt tctagccact agaccaccag 13560 ggaactccct attctaaatt cttgagcaca ttatttagga acctcaggaa cttggcagga 13620 ttacaggaaa tatatctaga tttaaaaaaa aatcttttaa cagaggtccc aaaggagagt 13680 catgcacagc tatgggagga agttcagaaa ctgcccttgc taccagatca ctgtcagata 13740 aaatggccag ctacatgttt ctgcacattg ccctaagatc tttacaaact tttctgtgca 13800 tttttccact tttaaaagaa aatttcgggg ttcctgttgt tgctcagtgg ttaacgaacc 13860 caactagtat ccatggggac aggggttcga gccctggcct cactcagtgg gttaagaatc 13920 tggcattgct gtggctgtgg cgtaggctgg cggctacagc tcagattgga cccctagcct 13980 gagaacctcc atatgccgca ggtatggccc taaaaaaaaa aaaaaagaga gagagagaat 14040 ttcctccaga aaaaacactt tggtagtttg ggagaagtaa acaaccaaaa attaattttt 14100 ctggagtatt cgggaagctt gtaaaaatgg gctcttactt ttttgaggag acaaatggga 14160 acctacccag aagaggcaca atcacctgca tttgatttct tgacctctcc ctaccttctt 14220 tgctggcttt ccacatttgg atttctgtga ccttatctct gctccttggt gttttcattt 14280 ttcctgtgga cgtgccagac tatgggaagg gagtaaggcg ttgatttaga atcctgtagt 14340 ctctgcctgt ctctagtcat tgttttcacc cttctcaaag gaccttgaca tcctgagtga 14400 gtccgcaagt aatttagggg agaagcctta gaagccagtg cagccaggct acatgactgt 14460 gtccacccac tggaaccagt catttttata cctattcaca gcccccctac catttaaatc 14520 cccagaggtc tgccataaca tctgtaactc cctttcctgg taaattgtgt tctaaaagac 14580 tggtaacaaa agatattctg tggtacagag cataattaaa tacctgggag ctgatttgag 14640 tggggtaaat caactggttt gacccctaaa acccaccatg agcatttctg ttctaataaa 14700 gtaatgcccg tgctgggaat tgtgttctac ggaaatgctc ctgctgtgtc tttcttgagt 14760 cctgtgtcat tgaacatgct taggagcaaa ggtcccccat gtggcttgtc tgctaaccag 14820 cccagttcct tgttctggct ggtaatgatc cgatcatctg aatctcactg tcttccaaca 14880 gatcacgtac cttactcacg cctgcatgga cctcaagctg ggggacaaga gaatggtgtt 14940 cgacccttgg ttaatcggtc ctgcttttgc gcgaggatgg tggttactac acgagcctcc 15000 atctgattgg ctggagaggc tgagccgcgc agacttaatt tacatcagtc acatgcactc 15060 agaccacctg aggtaaggaa gggtgagccc tcaactccga agaaaatgct gcaataaaag 15120 cactgttggt tttcagcttt ttttgtaatc actgctcatt ctgaggtaga ttcgcttggg 15180 ctgataaaaa gagaactaat tcagataaat gcttgcattt gcatagcctc tttttttaaa 15240 aacttttttt tttttttttt ttttttggct tttcagggct gaacctgtgg catatggagg 15300 ttcccaggct aggggtcgaa tcagagctgt agccccgggc ctatgccact gccatagcaa 15360 catgcatagc ctccttttta aagtgccttc ctgttttata ccattgggat gtgagaagag 15420 ctattgtgga aangagcatg gggtnataac cctggacctc tcacgtccta ccctcaggnt 15480 agtgggaaaa ctctgagttt aaggacatca aagtgactcc tttttagtta cattatggng 15540 gaatcagcnc atatttttac aaggggcgga gngtaanctg ttggagttta caagacatat 15600 ggtggcattg caactactta accctactat tatagcacaa aagcagccat agtcggtcct 15660 gaaggagcct gatgccttca gctttatagg caatgacgtg tgaatatcac aaacagtttc 15720 ctgtgtcacc aaacatgatt gccttttgat ttccctttca accctttaaa aaaaggtaaa 15780 agcccttctt agcattcagc agcaggtcgc tgtgttttgc caactcctga tctgtagcat 15840 ttcgacaaca ctgagctctc aacttttgaa ccctgagtcc accacatcct tcagtgaaac 15900 cagagccatg tgatactaag gatagaaacg gaaacttcct gaatccaggc gatcaaatag 15960 gagggagaaa gaggaacttt cattgacaaa accacaaata ttgtgaatgg actgttacaa 16020 atattgtgaa tgctcctatt cccaaccccc tggcttcatt acagggtcct atgtgttcat 16080 ccttattgag aaatttgtat tgctactgcc aggttgccaa tacccagcgg tgcccatggt 16140 gttctaaaat gaagcaattt caactttatt tttttttcct gtgactttac atgacaagtt 16200 cacatgaagg atatactttg atagtaatgt ccatggttag ggaatataca ttgtttgctg 16260 gttgactggc ccctggattt ttctattgaa agtccatgag atctcgaagg cacaggtgtg 16320 ttctctcgct ttttaaggaa agggtttaaa aacttaagta attaacagct ttagtaacaa 16380 attacctata acacacttaa aaaccgaata ccacccactg gagtattgtg ctacgattaa 16440 aaatctactt gtctactaca tgatatcttt gtcccacaga aggttctgga accaaacttg 16500 taatttcagg attatgagag ccctgagttc acgcattgtg taataactat gttgtgtggt 16560 agtcaatttg tacagcttgc ttagagagaa caatgtcaag ttaaggaggc gattgcttta 16620 tagtgcctgt cacaagatgc cattgccatt gtcctagcaa gagatattct atgggagtat 16680 actacatttt agtgaggata agaacttttt atggcattta gtccggtcat ttcccaacca 16740 ctgtcctgaa aaccaatttc attttgattt caggggcttg tgtgggcaaa gttgccaggc 16800 attaaaaagc cacttctcaa ctgtagtatc acaatgcttt agttgggtag tgtattgcag 16860 atagcttatg gctgaaaagt taccaagcct tgcagttttc actcctttga gtttatttcc 16920 ttgacagaat tgaccctgag ttttttgact cttacctgct caactaataa acaccagagt 16980 catttatctc cattgctctt gtctgacctt tatttaccga ataatgcctt atgggttcac 17040 aaaaacaagg ggggaggggg ccagcatgcc ttagaaactg tctttagtca agaaatgnga 17100 ttttattatg taaatatatg agtattataa tagatagtgt tattaataga caccagcaag 17160 aattgtcaat aatttaaaaa tcacaaatta aaatacatcc atgttagnat catttatcct 17220 aactcccaaa gccctttaaa gtggaagatt tagatgttaa cccagagatt aaagacatgt 17280 tcaaagaatc cttgattttt ttttgaatcc cttgttttta gagaagaaaa cctaatgatt 17340 ttccccctct ggattctaca tattaaatat agttttggaa cttgaatatt agtatggtta 17400 ataagtgctg atatgctgat tttgtttata tttttcttat gagtaaatat cctatatcac 17460 cagacattat agtctatgta caaatatgat tcttaaacct gatagcacat tcattagagt 17520 tggaattgcc tttttttttt ttttttttac agttgcacct gcaacatatg aaagttccca 17580 ggctaggggt tgaatccaag ctgcagctgc caccctacat tacagccgta gtaacagcag 17640 atccgagctg catctgcaac ctatgctgca gctcagggca atgccagatc cactgagtga 17700 agccagggat ggaacttgca tcctcataga gacaacgtcg tgtccttaac ccactgagcc 17760 agaacaggaa ctccagaatt tcctttcaat agaagaagca ccaagtttag gatcagaaag 17820 cctgaatttg aataccaatt tactatttgt tagtcatata tttctgagtg tgtttcctca 17880 tttattaaaa gcagactaaa agatgagagg gtcttttgtt gagaatcaaa tacaataaca 17940 tgtgaaagtg tgtaacacta tgattgaaat atacctacac agccatttat ttgtttattg 18000 ttcatgtttt gccacccaca cagtagtata taatcctttt atgtaataaa tgctaataat 18060 gaaagttggc aacttatgta agtactcaaa atgctggagg tcatgggata ctgactggga 18120 tactacagag gtaatgtcat ttcctctgcg ctaaacttat tgtcttgtag ttagggactg 18180 actctcttta ggacaaggag ttcattctgt ataccatgtg tggctatcac ccttcgaagt 18240 tgaaaaactg ccccagggtg ggcacccatc cgttctctta gatatatggc cgagaccttt 18300 ctctcactgg gagggaacca cactgaggaa tgagaaaaaa aaaaggaaaa tcaagatgaa 18360 accagaaacc tctttggcat aacttctcca ctctgtactt tttgttagaa ctacccttgc 18420 acaaagcagc atcagtgtgg aagacagaat ttgcacacct ggtttgatat acatgccgtg 18480 gtatatggga tgttctaaca ataaagagga ctctcccagg aaatctcctc actgttatag 18540 tcagccttga ggaaagagct cttcttttgg actctgggga gagtctagtt tttcagttcc 18600 ttgcttctcg gtcaacgtgt tggtgtaagg atcacactct ctcttatact agataattct 18660 attttttcac ctttcaacct gtctatcctt ctgaccctag ttacccaaca ctgaagaagc 18720 ttgctgagag aagaccagat gttcccattt atgttggcaa cacggaaaga cctgtatttt 18780 ggaatctgaa tcagagtggc gtccagttga ctaatatcaa tgtagtgcca tttggaatat 18840 ggcagcaggt ctgtgttctt tccacatgtt tgggttatcc tttctgggat aaatttgagg 18900 cgagatagaa actttaagac taaagaaaca atggcctact ttttttgtac atggtcctgt 18960 gtaaatctct atttgagctg aaataagatg gtcttcctct ccaattatcc atggtatgac 19020 tctgatggat aacaaatcca gttctgaaaa aaggggattt ctttccagaa gagaggacag 19080 tttcttcaaa tattgaatta aaagcaaaat agatgtaaac cgttgttggt tttattgttg 19140 aattccaggt agacaaaaat cttcgattca tgatcttgat ggatggcgtt catcctgaga 19200 tggacacttg cattattgtg gaatacaaag gtattttctt gccctcatca gcatgaaatt 19260 gctcttggta gaaaggataa taatagttat ccaaaacatc atcctatgtt catctgtttc 19320 ttccctcttc attttccata gagtacagta tattctatct ctgtcttagg aaaatggact 19380 gtcattcata taatcttaca gagaatcaat tagtaatgta ctctatgccg tgacaggtgc 19440 gaaggttttt tttgaaggca acagataaaa atatcctata tttcacctat tgtaatttcc 19500 ttaaaactga cattattgaa taaatgtttt actttcatct tgaatattat tatgttatgg 19560 aatcatacac tttaccccaa taatcatcga aaagaatttc caaaaggttg agagagttgt 19620 gttgatctga ttactttcct ctgcatcctt tgagcttaac ctttgaatat agtttgctaa 19680 ggaaagtagt ctgtttatga tcctggagtg gaatcaggct aagtgtcctc attcagaacc 19740 cactgaatca gacagaatga atttatttcc ttgaaagttc aaaatgtgtc actcaagagt 19800 ataaattttc aaatcttact ctctcttttc cttggatgtg agcaattctt cgataattga 19860 atgaggcaga ttatatagac ttacatggaa gactgttggc ctgagaattc aaactatggt 19920 gttcaagact tcacngngag tccgatgcca tttgtttccc acaggtcata aaatactcaa 19980 tacagtggat tgcaccagac ccaatggagg aaggctgcct atgaaggttg cattaatgat 20040 gagtgatttt gctggaggag cttcaggctt tccaatgact ttcagtggtg gaaaatttac 20100 tggtaattct ttatatcaaa atgatgccaa ggagttggca tggcactttg ctaaatgctg 20160 tgtgaatcaa tacaaagata attaggacat ggttcttcct cacaagaggt gtgcaatctt 20220 attgggaaat catacttgca agtcacaaat atagactaaa gtttccagct gagaatatgc 20280 tgatggagca tgaaacacta aggagacagg gagaatctca ggaaaaatca agaataattt 20340 ggatcaaatg gattcctgac atagaacata gagctgatca gaaagagtct gacattggta 20400 atccaggctt aagtgctctt tgtatgtggt tcagaacaga gtgtgggcag cctgaggggg 20460 atacataccc ttgacctcgt ggaaagctca tacgggggag ggatgaggct aaggaagccc 20520 ctctaaagtg tgggattacg agaggttggg ggggtggtag ggaaaatagt ggtcaaagag 20580 tataaacttc cagttacaag atgaataaat tctaggggta taataacagc atggcactat 20640 agatagcata ttgtactata tactggaagt gctgagagta gatcttacat gttctaacca 20700 cacacacaca cacacacaca cacacaccac acacacacac cacacacaca cacgtgcaca 20760 caaacagaaa tggtaattat gtgaggtgat ggcggtgtta actaacttta ttgtggtcat 20820 catttagcca tacatgcatg tcatgaaatc accatgttgt acaccttaaa gttatgtaat 20880 actagatgtc agttatatct caaagctaga aaaaatgtgg ggaccaaggc agaagctctt 20940 ctgctctgtg tctaagggtg gttctggggc tgggatgggg aggatggtta agtggtatat 21000 ttttttcata cctttgctca gtactatcat tgtaagtgtt caatatatgt ctgcttaata 21060 aattaatgtt tttagtaagt aatctctgtt tagtaatgtg tcagaaatgc cctacttgca 21120 ataggaagaa aacctgtcca gtcccttcct tttttctgta agtctgattt cattgcctcc 21180 cagaatgcat caccatgtga gagatagagg gaaggtgctg tccttatggg gttaacagtg 21240 tgactaggga ggcaaaatat acctactaaa gggtggtagc ataattcagt tcttatgtga 21300 gtatgtgtat gtgtgtgagt atgtgcacat gcacatacat tttaaaaggt ctgtaatata 21360 ctaacatgtt catagtggtt acacctagct tataggtaac attttttccc ctgtatcctt 21420 gtttgtgttt atcaaatttt cataacagta atggtagaag gagtacctga catggtacca 21480 tacatgctng gncctgccta atttctcnat ttcctttatt gcccataccc ccattgcttg 21540 acaagcataa gtccatactg gcttgttttc gttcctcaga ctcagtacac catgtagctc 21600 catgccctgg gtctttgtat gtgctatttc tactgcttag agtgctattg cccctgacca 21660 ccacgtggtc agcaacttct cttctgcgtc tgtgtctatg gtctatgatt ccagatgtca 21720 tcttcactaa ctacccttct aatatgccct tccatcccac ccgtcctcat ccttacccca 21780 gccactctct atttggtggc tctgttttat tttcttccta gctcatcact ctttgaaatg 21840 aacttattta cttattcaat atttgcttct ttcactagaa tgaatgctcc atgagagcag 21900 ggacctgctt tatcttgctc gccactgtat tcacagtgcc tagaactacg tctggcacat 21960 agtaggtgct caataaatat cgatcaaatg aaagaatgag caaacgaaca aatgaacaac 22020 acgtgaggta ggcatcatga ttccatcaac agaggagaaa accagactta aagnaatgaa 22080 gtggnggagc tgcatttgat cttgactgac tccaacatcc atgctcttga ccactgtgca 22140 tctccagagt gtaatgaaca tactttactt ttatattcca ccaaaataac aaagccatgc 22200 ccatgttagt agagagttaa tcgacagtgc ccttaaaata tgcatgcacc cagggtacaa 22260 ctatgcatgc tgccctgtgt tttcagttgg atccaaatga attgccgtaa acaaagaggg 22320 gattcaatgt ctttgactag tttgggatat tttcctagta accaactttg caaaataaag 22380 ccactaatga caaggagctt tgttctactt ctgcatcact caactgtcaa tttttatctc 22440 ttgcaagact tctaatctac tagaactttt gtttttctgt gatttctgaa cagagaagac 22500 taatccaaac cctgtcattc cagaggaatg gaaagcccaa ttcattaaaa cagaaaggaa 22560 gaaactcctg aactacaagg ctcggctggt gaaggaccta caacccagaa tttactgccc 22620 ctttcctggg tatttcgtgg aatcccaccc agcagacaag tatggctgga tattttatat 22680 aacgtgttta cgcataagtt aatatatgct gaatgagtga tttagctgtg aaacaacatg 22740 aaatgagaaa gaatgattag taggggtctg gagcttattt taacaagcag cctgaaaaca 22800 gagagtatga ataaaaaaaa ttaaatacaa gagtgtgcta ttaccaatta tgtataatag 22860 tcttgtacat ctaacttcaa ttccaatcac tatatgctta tactaaaaaa cgaagtatag 22920 agtcaacctt ctttgactaa cagctcttcc ctagtcaggg acattagctc aagtatagtc 22980 tttatttttc ctggggtaag aaaagaagga ttgggaagta ggaatgcaaa gaaataaaaa 23040 ataattctgt cattgttcaa ataagaatgt catctgaaaa taaactgcct tacatgggaa 23100 tgctcttatt tgtcaggtat attaaggaaa caaacatcaa aaatgaccca aatgaactca 23160 acaatcttat caagaagaat tctgaggtgg taacctggac cccaagacct ggagccactc 23220 ttgatctggg taggatgcta aaggacccaa cagacaggtt tgacttgaat atttacaggg 23280 aacaaaaatg atttctgaat tttttcatgt ttatgagaaa ataaagggca tacctatggc 23340 ctcttggcag gtccctgttt gtaggaatat taagtttttc ttgactagca tcctgagctt 23400 gtcatgcatt aagatctaca caccaccctt taaagtggga gtcttactgt ataaaataaa 23460 ctattaaata agtatctttc aactctgggg tgggggggga gactgagttt tttcacagtc 23520 ctatataata attttcttat cctataaaat aattaggagt tcccgtagtg gctcagcaat 23580 agcaaacccg actagtatcg atgaggatgc gggttcgatt cctggccccc ctcagtgggt 23640 taaggatctg gcattgccgt gagctgtggt gtaggtggca gacacggctc agatcccacg 23700 ttactgtggc tgtggcatag gccagcagct ccagctctga ttagaccctt agcctgggaa 23760 cttccatatg ctgtgggtgt ggccttgaaa aaaaataaat aaataagata attactcaaa 23820 tgttttcctt gtctcagaac cttacttcag gataaagagt gagaaagttt tttttatgaa 23880 gggccattat tacagctcaa aaataagttg tcttcagcaa gtagaaagca ataagcctga 23940 gagttagtgt tcctatcagt gtaaatatta cctcctcgcc aatccccaga cagtccattt 24000 gaacaattaa cggtgccctg ggagtacagt tcagaaacat taatgtggat gttccagacc 24060 tgtattttta taagtacttg tcttgagccg gatggaacca tcattcctca ccattattta 24120 gaagtggact gtgactctgt tggagatcag ggcacacggt taccaaaagc acacccttct 24180 cctggcctta cctttgcaaa gctggggtct gggacacagt cagctgatta taccctttta 24240 ctaacttccc acagctcaaa tctggtcaat tctccttcac aaatctctta aaaatccatc 24300 actcacctcc agcctcttct gctgtggcct tgattcagcc tctcacaatt tttttttaac 24360 cagaattctg gcagtggccc ctgacttgcc tctgtgctcc cagccccgct gtcctctgat 24420 ccatcctcca tgccagcctt tttcaatctg ctggtcacga ttcattgatg ggttaggaaa 24480 tcaatggcat cacaactagc atttagaaaa aggaaatagg cgttcccgcc gtggcacagc 24540 agaaataaat ccgactagga accataaggt tgcgggttca acccctggcc ttgttcagtg 24600 ggttaaggat ccggcattgc cgtgggctgt tttgtaagtc acagacatgg ctctgatccg 24660 gcattgctgt ggctctggcg taggcctgca gcatcagctc caattagacc cctatcctgg 24720 gagcctccat atgctgcaag tgcagcccta aaaaaaataa aaaaataaaa aaaaataaat 24780 aaaagaagta gacaaattgt atagaacaac cctgagtatg ttgcctgagc acatataaca 24840 agggtaagta ttatttcagg aaactctggt ttcacagata ctcttggcat atggacccct 24900 agagtcctga tgtaaaatat attcttcctg ggatcttagg caagaagttt gaaagctcca 24960 actctgcact gctgccaaag aaatgatttt taagtgcaaa actcttcccg ttcccttccc 25020 tgtataaaat tccataggat ctctccagtg cctctaggat aaaggcagtt ttcattctct 25080 agttcaaggt gagagaagat tttaattatt tcacgtttta gtggggaatt caagagtctg 25140 gcacctgaca tttgctgaac tctctccatt atccctctct agttccccag acgcatccta 25200 tggtagaaat tcgcaaacta gagtgagcgt cagagtaacc caaggaaact gggtaaatgc 25260 agctccctgg gctctacccc ctgagattct gattcagtag atctgaagca gagccctgga 25320 atatgcatat gcatcattgt gtcacaccaa gcattctggg taatgagagt tgatgttagg 25380 ttctcagtag taagacaagt atagagattc cgggggactg agtgctcagc tctgccttgg 25440 ggaggaggga gagggctaaa gagaacagga gatggggaca gggaatgctc aacctccaat 25500 cttaggcatt tgagctatgt cttaggggtc aggaggaggt taccaatata gtgattaaga 25560 gattgaggtt ccagtcagag ggatatgctg gagaaggggg gtgaaaataa tgtcataggt 25620 ttggtgagtg cagatacttt gagtttttta atatttttat tgaaatatag ttgatttaca 25680 atgctcttag tgagtacaat tactttgaat aagtgcatag atgtatgcca ttcttccaga 25740 aatgatttat tgagctcctt tgggcatcat gctaagtaca ggggaaacag ctgtgaagag 25800 gtccttccct tatgaagtca ttcatcccct tcagtaaatg aaggtaaagg aaaaggatga 25860 gacagggacg ccgtgttgga ccagggtcag aaaggcctta taagaccttg cctggagggc 25920 aaggaacttg cctgtgagta aggagagctt gagaaagcga taaagcaaag aaggaacatt 25980 actgcattgt gttttagaaa aaccatgtcc tggggaagaa ctcctagagt caggggggcc 26040 agttgggaga ctgtgctttt ttccaggagg agataagtga ggctgctggc tgagatggag 26100 caaggattta gagaagcaga tatgagattc atttagaagt tagacatttt aggatctgac 26160 acataattta tcaccaaaac cagtgcatct ctggctttgg gccaccagtt ttggagaagt 26220 ggaatgtagg gacctaccat tacctgccaa tctttactac acagatgcct atttccctcc 26280 tcatatttcc tttctccaga tcacgtccta ttctattgcc aggactcaag attccacctt 26340 gcatgcagtg atccatcttc acactggatg gacagctcta gggatgtcag agcacactct 26400 tgtccatact gctgactggg tctcctgtca gcccatctgt ctatcagctg tggtattatt 26460 agtataataa gagggctgta tatgagagac acaaaattct aggtgtagct caaagatagg 26520 ctagagttat tcctatgtac aacaaatatt tatgggaccc cttctgtgta ctgtcatggt 26580 tgctgctttc atcatacttg tagtctaatg gaggtggggg cagggcagga ataagcggat 26640 gtccacaaaa tcagtaagac cacttatatt caacattttc ataatttagt tatttgagcc 26700 caaagggtcc acatccgtgg tattccaact tttttttccc cggacatgga tctttatctt 26760 tttttttttt tcttttttgc ggccagacct gcggcatatg gaagttccca ggccaggggt 26820 tgaatgggag ttgcagctgc ctggtctaca ccacagccac agcaaggtgg gatctgagct 26880 gcatctgtga catacaccgc agctgaggta acaccagatt ctgaacccac tgaatgaggc 26940 cagggatgga acccgtctcc ttatgaacac tatgtcatgt tcttcaccct ctgagccaca 27000 acgggaactc cagacttcgt ctttaaatgt attctgactt ggagagctat cacactaagc 27060 aattaacagg agctgacctg gtttaggctg gggtggggcc ctactcctca atgttccctg 27120 aggcacatct gtgggacccc tgggcatcat ctatctgagc agccttagag ctgctcatcc 27180 agttgactgt tgatgtagaa gtgcaaactt ctgccttcct tatttgttgc tttctttttt 27240 cattgttctc tcccctttgt gtctttaagc aagggcatcg tagagcctcc agaagggact 27300 aagatttaca aggattcctg ggattttggc ccatatttga atatcttgaa tgctgctata 27360 ggagatgaaa tatttcgtca ctcatcctgg ataaaagaat acttcacttg ggctggattt 27420 aaggattata acctggtggt cagggtatgc tatgaagtta ttatttgttt ttgttttctt 27480 gtattacaga gctatatgaa aacctcttag tattccagtt ggtttctcaa taagcattca 27540 ttgagcctta ctgactgtca gacggagggc gtattggact atgtgctgaa acaatccttt 27600 gttgaaaatg tagggaatgt tgaaaatgta gggaatgaaa tgtagatcca gctctgtttc 27660 tcttttggag gattcttttt cctccatcac cgtgtcttgg ttcttgtttg ttttgggttt 27720 ttgtgggtgt tgtattgtgt tgtgttggtt atggcagtga cagctattta aactgtgaaa 27780 cgggggagtt cccgtcgtgg cgcagtggtt aacgaatccg actgggaacc atgaggttgc 27840 gggttcggtc cctgcccttg ctcagtgggt taacgatccg gcgttgccgt gagctgtggt 27900 gtaggttgca gacacggctc ggatcccgcg ttgctgtggc tctagcgtag gccagcggct 27960 acagctccga ttggacccct agcctgggaa cctccatatg ccgcaggagc ggcccaaaga 28020 aatagcaaaa agacaaaata aataaataaa taaataagta agtaaaataa actgtgaaac 28080 ggggagttcc cttcatggct cagcagttaa caaacccagc taggatccat gaggatgtag 28140 gttcgatccc tggccttgct cagtgggtta agaatccagc gttgctgtga gctgtgatgt 28200 aggtcgcaga tgcagcccag atcctgcatt gctgtggctg tggcgtaggc tggcagctga 28260 agctccgatt caacccctag cctgggaaca tccatatgct gcaggtgtgg ccttaagagg 28320 caaaaaaata aaaaaataaa aaataaataa attgtgggac agacaggtgg ctccactgca 28380 gagctggtgt cctgtagcag cctggaagca ggtaaggtaa ggactgcagc tgggtaagga 28440 ctgaattgca ccaactggga agtaagccta gatctagaac ttaagttagc cctgacatag 28500 acacacagag ctcaccagct aagtggttca gcttataagc tggtcactga aactgaggat 28560 gtccacaaaa gcaaaataag tagcaacagg cagcgggatg caagagaaag aggaggccta 28620 aaatggtctg ggaatccctg ccatacctat attttatcct acttatattt agtgcctgaa 28680 tgtgtgcctg gagagcaaag tttagggaaa gcatcgggaa atgcacagta ttcataccct 28740 taggaacaaa gatcagttac ctccagggta aagactattt ccaagtttaa atttcaaccc 28800 ctgaacatta gtactgggta ccaggcaaca cttgccatcc tcaaaatcaa tgaatcctaa 28860 aattcaacct gggggtcagt gacagtctgt gacaaagttt ttgctggtca gtaacgaaat 28920 aagtatgagc accatctgag tatggtcacc aagatgtcaa ctctctttcc tttggacgaa 28980 ttgtcattat tccaagatta ggtcctttct atttttgagg tgtgaaaaca tctttccttt 29040 cataaaataa aaggatagta ggtggaagaa ttttttttgt tttttggtct ttttgctatt 29100 tctttgggcc gcttctgcag catatggagg ttcccaggcc aggggtcgaa tcggagcttt 29160 agccaccggc ccacgccaga gccacagcaa cacgggatcc aagccgcatc tgcagcctac 29220 accacagctc acggcaatgc cggatcgtta acccactgag caagggcagg gaccgaaccc 29280 gcaacctcat ggttcctagt cggattcgtt aaccactgcg ccacgacggg aactcctaat 29340 gatactcttt tatatttagc tactatgtga tgatgagaaa cagtccacat tttattattt 29400 tttagccaat ttgatatctc attactaaga taatgataat tttctctata aattttattt 29460 aagttagtgt tatgaagtgg ttttgctagt gtagaaggct aggatttgaa ttcagttcaa 29520 gaaagaagag agggagggag ggagagggat gggtagaggg atggggcagt gggagagagc 29580 aaagaggaga gacagttttt gtattaattc tgcttcattg ctatcattta agggcacttg 29640 ggtcttgcac attctagaat tttctaagga ccttgaccgc cagattgata tgcttcttcc 29700 ctttaccatg ttgtcatttg aacagatgat tgagacagat gaggacttca gccctttgcc 29760 tggaggatat gactatttgg ttgactttct ggatttatcc tttccaaaag aaagaccaag 29820 ccgggaacat ccatatgagg aagtaagcag gaataccagt ggaagtgccc ctttcttcct 29880 tccttcctaa ataaactttt ttattttgga acaactttag agttacagaa aagttgcaaa 29940 gatattatag acagtagtgt ttatatatat atataaattt ttttttgctt tttatgacca 30000 cacctgtggc atatggaggt tcccagtcta ggggttgaat tggagctaca gctgccagtc 30060 tgtgccataa ccacagcaat gcaggatctg ggccacgtct gtgacctaca ccaaagctca 30120 cagctggatt cttaacccac tgagcaaggc cagggattga acctgcatcc tcgtggttcc 30180 tagttggatt cgtttccgct ttgccgcaat gggaactcca aattattgtt aatatcttac 30240 tttactgggg tacatttgtt acaaccaata ctctgatact gaaacattac tgttaactcc 30300 gtacttgctt ctttttgagt catttgcaaa gactggcttc ttgacctgct tccttccaaa 30360 cagctggcct gcctatgctg ttctcagacc tgcaagcact gatctctgcc ccccttgcct 30420 tctctccagt ggtgtctcct tccccaaaca aacccagtgt ggctctggaa agggagttaa 30480 gtcaacataa accaacacat attttgttga gctccaattt tgagcaaatc cctcacctac 30540 ggcagacagg catgatgtta agaactaggg ctttggacac aaggtcaaga ccaagaaggg 30600 ttcctcaccc ctactgattc agataaccaa taatgaggct ttgaatccct gtccaaaggt 30660 tgtttttttt cccttctatt gagcttcttg ccaccttatc agtttttttt atgacagtca 30720 aatgacatga tatatgtgag catacatggt aatttttaat tctatataaa tgaatcacta 30780 aataaattag gaggatatat agtccacctt taagcgtatt acacgtgtca catgaatgtg 30840 tggcgactta attgtagagg tttaaatgta gcttcctata atagatgtgt tcctaaacta 30900 cattttaatc attggacttg tatttttatg ttagcacttg ctgttgaaga aaagcctatg 30960 ccaaaagttc agtgaaacca ataatccact gccagctttc tgagttaaaa aaaatccctg 31020 ggttttcaca cacaggaaca ccctgtgtga aacactcatt tagagcaaaa tgcatctgat 31080 aaggagttcc tgttgtgcct caactggtta aggacctgac attctccatg agaatgtgag 31140 tttgatcccc ggccccactc gatgggttaa ggatctggtg ttgccacaaa ctgcagctcc 31200 gattcatctc ctagcctaga aacttccaca gcccagaata tgccacagaa ttcggctgtt 31260 taaaaaaaaa aagaaaaaaa aaagaatcat aaatgtgttg gtttgttcac caaatacatg 31320 ataacttgct cttgccaagc tcagcttcat aaatattaag tcatttaata cagcagccac 31380 cttatgaaca gatattacta tacttcccat ttacagataa ggaaaatgcc atatttaacc 31440 aagagattaa ataactttcc cgaggtctta tagcaagtaa atcatggtgc aggggtttga 31500 ccacacgcag tctatctcca gagtctgtgt atttagccac tgttttactt tcaaatttaa 31560 atttataaaa cttctaaatt atctgttaac cataatcttt ggaattttta aaaccacgag 31620 ttcctataaa atgtttcatt gaaagtaagt cacttttcca tagcttttga taatacatct 31680 gtaggataaa gtaagccaca gctctcttgc agacttggta caccctgggg caaagcatca 31740 tgcctgtcac gtacatggtg gtccttactt tgactctcag tgcttttatt gcccaggaat 31800 tttgtgagat ttctagttgt tgaggtttgt ttaaagaggt tatgccggta cttggaagag 31860 ctcttttctt gctacctgga gccttctcat atttcctttt tgaggaggga catgaattgc 31920 ctttcaaact cataaatata ttttctagta cacaagtctc catcttcctt agacgcatgg 31980 ctcctggagt tctccatcct cctgctccac tttgggtggg ctcctctctg ggtctgccac 32040 caatctgcca cccagagaca tccttgaccc acttccagac cccaccatgg cttcactttc 32100 ttcgctttcc tcctttgtgg aaccttctgc ttaagaatct gaggaagaaa atttgcacgt 32160 gagctaaact ggaggtactt tcctgcctgg tcttgcacga tagcttggct gagcccatga 32220 tgctgggtgg ctgttacttt ccatggacac ccgaaggcgt tgctcctttg gcttctagtt 32280 gcatgcagtg ttgcttatcc caggctgatc tttcttccac tgtaggtgac ttttaagaat 32340 taagggatta atctatatct acaacaacaa caacaaagac cttttcaagc tgaggtaggg 32400 ctttctgtat atgtttggag tggttatcca gcagacttta cttgaaggca ggggtcatat 32460 cctcaagtgc tcataaacgg accacagaaa gatctcataa ttgggtggag ctgggtgggg 32520 accgtgtcat gtggccagga aatgccagat gggaagggag tggcccttac tgagctccag 32580 ctgaactctg aattttctag aaaactcaga aatctggatt tttcatgtgt aatacccaga 32640 tttatagatg tggaaagcta attctttttt tttttaaggg actataggca atgaactaag 32700 atctaggttg tatttggaca aggggtcatc agtttaagct gtgtagttga gcgctcagct 32760 attgggctga gggaccccta aatactgaga cggggaggtc cttgctctgg ggcatcacaa 32820 gtacactccc tggtctcatt caaacacttt tcctacaaaa ttgatcccat ttcttcagtg 32880 cactgtctga atgcatttgg cccagagccg tgctgaggca tagggaaggg gtccacggtt 32940 tcatggcatc gttttgtgct gtgtgtccct gctgtcgtcc aggataccta cctctcctcc 33000 tcctgcatct gaatgtcccc ccacagactc tctgggattc tacagcctct ggcctgttcc 33060 tcagacacct cttacctgcc agctttccag attcacatta gttagtccaa atctactgcc 33120 gtcagtgact cacttcattt cttcttctcc gaggcagttc agcccggtac agttgttttg 33180 tcaacacttc agttgagtct ggaagatgtg catgggttat gcacgagagc ggtccatcat 33240 tttgagctag aagtcctttc tcagcccaga gacaagtcct catctccttt acttcctgac 33300 tcttcttcct ctgcatcctt ccaagatatc tctttctcca gccaccacct aaatctcttc 33360 ttttcccggg gttccgtgct caacccactc ttcttcttaa atctgtggct gggtgaacgc 33420 atctgctggc accacttctc tgctaaagac tccaaaaatc cataggtcct gcccggcctt 33480 tgcccacctc tctccaacac tgtccagctt tagatgtaga gctaatcccc ccagagatat 33540 cattccctgg atgtctaagt cctttggtat ctcactttca gcgtgttcaa aatcctctta 33600 caactgttct ttctcctttt ccatcttgat tattggcaac atgccagcct ttcccctacc 33660 cccagcagtg agccaagcta gaaacaaggg cttaatcttc aatctttcct tctccatccc 33720 taaacctaat gagtctccaa gcccttccca gtttacaccc taaatgttgc tcaaaacatc 33780 ccctagttct tccacgtgct ctcctctata ttgaaaggtc aagaaaggcc atcttccctc 33840 cactgtgagg aaatagatct tgatactgcc cctgagctgg gcagtcctcg acctgacaaa 33900 ctgtgcagtg tttctaaatc tctactggca aaatgagagt gcctttgacc tgtgttgcga 33960 tctcagatca cagtggatgt aattgtttta taggaatggt gaacgaaaaa gaagtaaatc 34020 cctaatgcca aactcctgat cattctatgt catttaatag cctgtcattt atgataaagt 34080 ttcctctact ggcattagca caatacttct caggaaaaaa aaatatgatg ccagatactg 34140 aaaagctcct gggtaaacat gaacatgggt accgataaaa tggtgaagcc agtccaatct 34200 tagagtgact tcccttcatg ctacttcatg ctcttttttt tttttttttt taagaaaaac 34260 cccttttttt tttctcacac cagtcacaga ggagaccgag gcttagcaag gttaaggtca 34320 catgattagt aagtgctggg ctgaaactca aaaccatctc tgcttgtctc ctaaccctgt 34380 gcacctctga ctattcaaca gatcctgtgt caggagttgg gattctttga aggtaagggc 34440 cttgaccacc gaattaaggt aatcttgctc tgtggcaggc cttgttttca gtattttaag 34500 tacactggct caggtaatcc tcacaacagc cccaggagga atgttctatt acctccactg 34560 tatagatgag gaacttgagg cacagaatgg ttgccaaggt cacacagcta tattgggggt 34620 tcatacccag ccatccaact ctgtctgtac tctctgccac tctgcacccc cagctcctga 34680 tccacttcct gtttccatcc ctcgatttct gctgcactca ggggcccctc tccccctcgg 34740 cctgtgagat ctgcttcagt aggcttttct ccctgactcc tccatccctg tccttacagg 34800 cagctgcttc tctccgggac acgaggggtc catacggaca ctctctactg gctgggttgc 34860 gcctaactcg tgattcctcc tctgtttcag attcggagcc gggttgatgt catcagacac 34920 gtggtaaaga atggtctgct ctgggatgac ttgtacatag gattccaaac ccggcttcag 34980 cgggatcctg atatatacca tcatctgtaa gtccgaaaat gcctgtcgtg tgtgccttag 35040 gctgctgcgg aggaggccag ggctatataa gcagagtcag tgactgactg tgccctgcag 35100 tgttgatggc catggagatt ccaccgttag agcttttttc tttgttaacc ttgaaggcaa 35160 atctggttag gaagataact ttcaaagagt caccatctgg acattcatgc ccatgtgctt 35220 caatcctgta tacaagcagt ttagagtaca gggaagggaa ggacattatg aaagggagag 35280 ggtgtgtttg gatccagcag ctccatcctc agaatttatc tgaagacact gcaaaattac 35340 taagaatcac tatgacaaga atgaggatgg ggtgatatgg caaagttgtg atcctggaag 35400 accttcatct cccatgttgc ccaactctga acatgaattt ggtgaactag ttggttaagg 35460 ggatgatcct ccaagtttct ccctggttga gctccaaaaa ccatgtaagt ttctcatagc 35520 aaaaccgtat aggtccttag ggctttagtt ggaatatttg tgctgaaatg ctggaaagcc 35580 ccatttgcca tttttgtatt tgcaaaataa tcatcaagag gggagaatgc attctttcat 35640 gaccactgac cctctgaaaa ggtcaggaat ttagtctgaa gtaggcaagc ctcctacccc 35700 gcttctgcca tgagcttgca cgcacaggcc tgtcttgaca tttcttcttt atagatttct 35760 ttttgaatat cttgaaattg ctttaaaaat atttaaagaa tgtagaatta tataaaataa 35820 aaaggaaata accccacacc tcccacaaaa ccctgtttcc tgcctttctc cacccactct 35880 ccagggtaac acttggtaac agcatagttg tatcacccca ggcctatttt tgagcatatc 35940 agcatttcaa gaaatgtatt ttttctcaat aaaacatccc ttatagttga ggaggggagg 36000 ttatcattcc tgggttttgt tttttttttt tttttaatgt aatcctggta catcggtaat 36060 ttgcattttt tattcattaa tatctttggt atttctagtg ttgggacaca caggtcaacc 36120 tcagtttttg ggtttttttt tttgtctttt tgtctttcta gggccacacc tgcagcatat 36180 ggacgttccc aagctaggag tctaatcaga gctgtagcca ccagcctacg tcatagccat 36240 agcaacgtca gatccaagcc gtgtctgtga cctacaagca cagctcatgg caacaccgga 36300 tccttaacca ctgaacgagg ccaggggatc gaacacacat cctcatggat cctagtcatg 36360 ttcattaacc actgagtcat gatgggaact ccaacttcaa ctattttaat gtctgtaaaa 36420 cattccattt ggaaaccatt tcatttgtaa agcaaaatga aaacattttg ttcattttca 36480 acagagttcg tagctgactt ctgttctgga aaaaaggaaa tggagcaaat ttgagtgaga 36540 aagattcaaa gataactttt cttttaaaaa aaattatatc ttggaaactt ctgggctatt 36600 gattctgaag actatttttc tatatactgt tttgatagca aagttcataa atgtgaaagg 36660 atcctgcgat gaatcttggg aagcagtcat agcccaatat atctttgttg cttttaaaat 36720 gagatttagt ttactaaata tttttctgat cataaaaata acacagatct accgcagaaa 36780 atttggaaaa aaaaaaactt ttaaattcaa aaaacagtta aaccacaaat gatcccacca 36840 tccagagagc aatttgtact ttggtgtcta gttcatcttt ctttttctgt ttacaagcac 36900 atataccaca agcatttttt caaaaaatga aaatgggata atactataca tacgtctgta 36960 cacctgcata gttactgaac agtctttgat ctaccctgta agtttctaac ttttcattat 37020 ttgaaatgat gttttggcaa agaaatatgt aggtgtgtct cgcacacttt cataatgatt 37080 tcttaggata aatttcttag gataaattca taatgatttc ttataataat ccatactctg 37140 ccaactgatc ttcagggaag ccaactcgcc ttctcagaaa taacatataa cccatttact 37200 tgccctctca ccaatactag gtcctaatgt ttttgtgtac agattctata tttttacata 37260 caagaattcc ttaaagcaag gcatgtcaca gaaaaataga aggaagacac aattgtcatg 37320 tttaaggact gcattctgta ccaaaaatgc taagttaaat gaacatctga aacagtacag 37380 aaacgctatc tttcagggaa agctgagtac caggtactga acagattttg gcaaatacag 37440 caggcatgga tgtttccaaa acatgttttt ctactttatc tcttacaggt tttggaatca 37500 ttttcaaata aaactccccc tcacaccacc tgactggaag tccttcctga tgtgctctgg 37560 gtagagagga cctgagctgt cccaggtaaa gcatcctgca ggtctgggag acactcttat 37620 tctccagccc atcacactgt gtttggcatc agaattaagc aggcactatg cctatcagaa 37680 aacctgactt ttgggggaat gaaagaagct aacattacaa gaatgtctgt gtttaaaaat 37740 aagtcaataa gggagttccc atcgtggctc agtggtaacg aaccctacta gtatccattg 37800 aggacacagg ttcaatatct ggcctcactc agtcggctaa ggatccagtg atgccgtgag 37860 ctgcagtgta ggccacagac gtggctcaga tctggtgctg ctgtggctat ggtgtaggcc 37920 ggccccctgt aactccaatt cgacccctag gctgggaacc taaaaagacc ccaaaaaagt 37980 cgctttaatg aatagtgaat acatccagcc caaagtccac agactctttg gtctggttgt 38040 ggcaaacata cagccagtta acaaacaaga caaaaattat cctaggtggt cagtgggggt 38100 tcagagctga atcctgaaca ctggaaggaa aacagcaacc aaatccaaat actgtatggt 38160 tttgcttata tgtagaatct aaattcaaag caaatgagca aaccaattga aacagttatg 38220 gaagacaagc aggtggttgt caggggggag ataaggggag gcaggaaaga cctgggcgag 38280 ggagattaag aggtaccaac tttcagttgc aaaacaaatg agtcaccagt atgaaatgtg 38340 caatgtggga aatacaggcc ataactttat aatctctttt ttttttttgt cttttttgcc 38400 ttttctaagg ctgctcccgt ggcatatgga ggttcccagg ctaggagtcc aaacagagct 38460 gtagctgcca gcctacacca gagccacagc aacacgggaa ccttaacccg ctgagcaagg 38520 ccagggatcg aacccgagtc ctcacagatg ccagtagggt tcattaacca ctgagccacg 38580 acaggaattc cagggtctgt tgtgttctta aaacacttcc aggagagtga gtggtatgtc 38640 ataagtaaac aataaatgtt aaccacaaca agcttatgaa ataaacagga aagccatatg 38700 acctacaatc agtcattggg agaatccaca aaaggttgag cagaggatca attccagctc 38760 acactccagt tttagattct cccctgcctt aaagcatcac agactacata atctgagctg 38820 aagaataaaa attaaaactc accccagtgc aaaacagaaa tgaaaaagta ttaaaacgag 38880 gttcatactg ttgttcatta gcaatatctt ttattcacag gggtgcccaa caacatgaaa 38940 aaatcaagaa tttattgctg ctacgtcaaa gcttatacca gagattatgc cttatagaca 39000 ttagcaatgg ataattatat gttgcacttg tgaaatgtgc acatatcctg tttatgaatc 39060 accacatagc cagattatca atattttact tatttcgtaa aaaatccaca attttccata 39120 acagaatcaa cgtgtgcaat aggaacaaga ttgctatgga aaacgagggt aacaggagga 39180 gatattaatc caagcataga agaaatagac aaatgagggg ccataagggg aatataggg 39239 <210> SEQ ID NO 49 <211> LENGTH: 14929 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 49 tctaatgcct tgtggaagca aatgagccac agaagctgaa ggaaaaacca ccattctttc 60 ttaatacctg gagagaggca acgacagact atgagcaggc aagtgagagg gggctttagc 120 tgtcagggaa ggcggagata aacccttgat gggtaggatg gccattgaaa ggaggggaga 180 aatttgcccc agcaggtagc caccaagctt ggggacttgg agggagggct ttcaaacgta 240 ttttcataaa aaagacctgt ggagctgtca atgctcaggg attctctctt aaaatctaac 300 agtattaatc tgctaaaaca tttgcctttt catagcatcg aacaaacgac ggagatcctg 360 ttgtgcctct cacctgccga agctgccaat ctcaaggaag gaatcaattt tgttcgaaat 420 aagagcactg gcaaggatta catcttattt aagaataaga gccgcctgaa ggcatgtaag 480 aacatgtgca agcaccaagg aggcctcttc attaaagaca ttgaggatct aaatggaagg 540 tactgagaat cctttgcttt ctccctggcg atcctttctc ccaattaggt ttggcaggaa 600 atgtgctcat tgagaaattt taaatgatcc aatcaacatg ctatttcccc cagcacatgc 660 ctaacttttt cttaagctcc tttacggcag ctctctgatt ttgatttatg accttgactt 720 aatttcccat cctctctgaa gaactattgt ttaaaatgta ttcctagttg ataaacagtg 780 aaacttctaa ggcacatgtg tgtgtgtgtg tgtgtgtgtg tgtgtttacc agcttttata 840 ttcaaagact caagcctctt ttggatttcc tttcctgctc tctcagaagt gtgtgtgtga 900 ggtgagtgct tgtccaaaca ctgccctaga acagagagac tttccctgat gaaaacccga 960 aaaatggcag agctctagct gcacctggcc tcaacagcgg ctcttctgat catttcttgg 1020 aagaacgagt gctggtaccc cttttcccca gccccttgat taaacctgca tatcgcttgc 1080 ctccccatct caggagcaat tctaggaggg agggtgggct ttcttttcag gattgacaaa 1140 gctacccagc ttgcaaacca gggggatctg gggggggggt ttgcacctga tgctccccca 1200 ctgataatga atgagggatt gaccccatct tttcaagctt tgcttcagcc taacttgact 1260 ctcgtagtgt ttcagccgtt tccatattag gcttgtcttc caccgtgtcg tgtcgtcaat 1320 cttatttctc aggtcatctg tgggcagttt agtgcgaatg gactcagagg taactggtag 1380 ctgtccaaga gctccctgct ctaactgtat agaagatcac cacccaagtc tggaatcttc 1440 ttacactggc ccacagactt gcatcactgc atacttagct tcagggccca gctcccaggt 1500 taagtgctgt catacctgta gcttgcttgg ctctgcagat agggttgcta gattaggcaa 1560 atagagggtg cccagtcaaa tttgcatttc agataaacaa cgaatatatt tttagttaga 1620 tatgtttcag gcactgcatg ggacatactt ttggtaggca gcctactctg gaagaacctc 1680 ttggttgttt gctgacagac tgcttttgag tcccttgcat cttctgggtg gtttcaagtt 1740 agggagacct cagccatagg ttgttctgtc accaagaagc ttctgcaagc acgtgcaggc 1800 cttgaggtct tccgacttgt ggcccgggga ctctgctttt tctctgtcct tttttctcct 1860 tagtgggcca tgtcctgtgg tgttgtctta gccagttgtt taagggagtg ttgcagcttt 1920 atgattaaga gcatggtctt tccttgcaaa ctgcttggtt tagaagcctg gctccaccac 1980 ttagcggctc tgtgacctcg gacacatttc ttagcctttc tgggcctcgc tcttcttcct 2040 cataaagtga aaatgaaagt agacaaagcc ttctctgtct ggctactgag aggatggagt 2100 gatttcatac acataaagca cttaaaataa tgtctggcat atgatacatg ctcaataaat 2160 gtcacttaca tttgctatta ttattactct gccatgatct tgtgtagctt aagaacagag 2220 gtctttacag gaattcaggc tgttcttgaa tctggcttgc tcagcttaat atggtaattg 2280 ctttgccaca gactggtctt cctctccttc acccaaagcc ttagggggtg aacgatccca 2340 gtttcaacct attctgttgg caggctaaca tggagatggc accatcttag ctctgctgca 2400 ggtggggagc cagattcacc cagctttgct cccagataca gctccccaag catttatatg 2460 ctgaaactcc atcccaagag cagtctacat ggtacactcc cccatccatc tctccaaatt 2520 tggctgcttc tacttaggct ctctgtgcag caattcacct gaaatatctc ttccacgata 2580 cagtcaaggg cagtgaccta cctgttccac cttcccttcc tcagccattt ttcttctttg 2640 tacataatca agatcaggaa ctctcataag ctgtggtcct cattttgtca atctaatttc 2700 acagcctctt ggcacatgaa gctgtcctct ctctcctttc tgcctactgc ccatgagcag 2760 ttgtgacact gccacatttc tcctttaacg acccagcctg ctgaatagct gcatttggaa 2820 tgttttcaat ttttgttaat ttatttattt catctttttt tttttttttt tttttttttt 2880 tttttagggc cgcacccatg ggatatggag gttcccaggc tagggatcca atgggagctg 2940 tagctgctgg cctacaccac agccacagca atgcacaatt cgagccaatc tttgacctac 3000 accagagctc acggcaacac tggattctta acccactgat tgaggccagg gatcaaactc 3060 tcgtcctcat agatacgagt cagattcgtt aacctctgag ccatgatagt tgttagttac 3120 tcattgatga gaaaggaagt gtcacaaaat atcctccata agtcgaagtt tgaatatgtt 3180 ttctgccttg ttactagaaa agagcattaa aaattcttga ttggaatgaa gcttggaaaa 3240 aatcagcata gtttactgat atataagtga aaatagacct tgttagttta aaccatctga 3300 tatttctggt ggaagacata tttgtctgta aaaaaaaaaa atcttgaacc tgtttaaaaa 3360 aaaaacttga ctggaaacac taccaaaata tgggagttcc tactgggaca cagcagaaat 3420 gaatctaact agtatccatg aggacacagg tttgatgcct ggcctcgcta agtgggttaa 3480 ggatatggtg ttgctgcagc tccaattcaa cccctatcct gggaaccccc atatgccacc 3540 ctaaaaagca aaaagaaagg tgctgcccta aaaagcaaaa agaaagaaag aaagacagcc 3600 agacagacta ccaaatatgg agaggaaatg gaacttttag gccctatctc caactatcac 3660 atccctatca ccgtctggta agaaatggaa aaaatattac taagcctcct ttgttgctac 3720 aattaatctg attctcattc tgaagcagtg ttgccagagt taacaaataa aaatgcaaag 3780 ctgggtagtt aaatttgaat tacagataaa caaattttca gtatatgttc aatatcgtgt 3840 aagacgtttt aaaataattt tttatttatc tgaaatttat atttttcctg tattttatct 3900 ggcaaccatg atcagaaatc tttaaacaat caggaagtct tttttcttag acaaatgaaa 3960 atttgagttg atcttaggtt tagtacacta tactaggggc caagggttat agtgtgacta 4020 ttaaatcaca gataatcttt attactacat tatttcctta tactggcccc acttggatct 4080 tacccagctt agcttttgta tgagagtcat ccttaaagat gactttattc tttaaaaaaa 4140 aaaacaaatt ttaagggctg cacccatagc atatagaagt tcctaggcta gcggtcaaat 4200 tagagctgca gctgccagcc tatgccacag ccacagcaat gccagatctg agctgcatct 4260 gtgacctaca ctgcagcttg cagcaatgct ggatccttaa cccattgaac aatgccaggg 4320 attgaacaca catcctcatg gatactgctc aggttcctaa cctgctgagc cacagttgga 4380 actccaaagc agactttatt ctgatggctc tgctgatctc taacacgtta ttttgtgcca 4440 tggtgtttat cttcacttta ctcaagtcag ggaaacacga agagtctcat acaggataaa 4500 cccaaggaga aatgtgcaaa gtcacataca aatcaaactg acaaaaatca aatacaagga 4560 aaaaatatct tcactttcaa aatcacctac tgatgatgag tttatatttc cttggatatt 4620 tgaatattag ctattttttt cctttcatga gttttgtgtt caaccaacta cagtcgttta 4680 ctttgatcac agaataatgc atttaagcct taaatagatt aatatttatt ttcaccattt 4740 cataaaccta agtacaattt ccatccaggt ctgttaaatg cacaaaacac aactggaagt 4800 tagatgtaag cagcatgaag tatatcaatc ctcctggaag cttctgtcaa gacgaactgg 4860 gtaaatacca tcaatactga tcaatgtttt ctgctgttac tgtcattggg gtccctcttg 4920 tcaacttgtt tccaatctca ttagaagcct tggatgcatt ctgattttaa actgaggtat 4980 tttaaaagta accatcactg aaaattctag gcaagttttc tctaaaaaat cccttcattc 5040 attcatttgt tcagtaagta tttgatgaga ccttaccatg tgtaaacatt gcactaggta 5100 ttaagaaata caaagatgga taagatagag tcggcgtaaa tgagatgata taatgagacg 5160 ttataatgaa actcacaatt ccagttggga aataaagtcc ttcaaattcc atgactcttt 5220 ctggcacacg ttagaggcta cagcttctgt gtgattctca tgctggctcc acttccactt 5280 tttccttctt cctactcaag aaagcctata gaaatatgag taagaagggc ttaatcatag 5340 gaataaattt gtctctgttc taagtgatta aaaatgtctt tatcagtata aaaagttact 5400 tgggaagatt cttaaaactg cttttacaca ctgttctaga atgactgtta tataaataaa 5460 aaagtagatt tgatctaaca caattaaatg acctttggaa atattgacta attctcacct 5520 tgcccctcaa agggatgcct gaaccatttc cttcttttgc cagaaagccc ccaccctttg 5580 tctgttgacc tagcctagga aatcttcaga tcacgttgtt agcacgaact ggttacatgt 5640 gctgtacaaa tactatttaa ttcatctgat taaaaaaaaa gagataagaa gcaaaagttt 5700 gactatctta aactgtttgc gtaggtgaga ggacaattga ccatctactt tatgagtatg 5760 taacccagaa acttaaagct ccttaaggga gctaagtctt ttggataaga cctatagtga 5820 gaccttttag caaaatggtt aagactgaat ggagctcact agcgtgggtt catatcctga 5880 tgctcaaaca cgcaattaaa tgactttagg tgggttagtc tctgttcctt agtttcctca 5940 atgggagata atattggtag tagcgatttt actgggttgt tgaaagaaca tctgttaaat 6000 gttcagaacg tgttacgaca gagtacagag taatgatttg cttgtatatg tatgactcaa 6060 atagtctgcc atatgccttg tgactgggtc ctgtggagca ggaaggaggg atttcccacc 6120 cagcagaaag ttgggtaaac tggaaaatag actgaggcca ggaaatgatg caaagcgttg 6180 atgttcactg ccacggcagg tgaagggcag ggccagagtt gtcagtaggg tcaggggagg 6240 actggaaata accaagaccc actgcacttt tcagcctttg ctccagtaag gtaatgttgt 6300 gagagtagaa aattttgtta acagaaccca cttttcagta cagtgctacc aatactgtag 6360 tgatttcata ccacatccca agaaagaaaa agatggctca atcccatgtg agctgagatt 6420 atttggtttt attgttaaat aaatagcatt gtgtggtcat cattaaaaaa ggtagatgtt 6480 aggaaagtag aaggaagaag actctcacct acattttcat cactgttttg gtatctgcca 6540 gttgtcacct tggtcccctt ccccgcctct cccctgcctc ctcttcctcc ttctcctttt 6600 tttggaatac aattcaggta ccataaaatt taccctttta gagtgtttga ctcaatggtt 6660 tttagtattt tcacatgttg tgctattact atcactatat aattccaggt cattcacatc 6720 accccccaaa gaaaccttct aactattagc agtccattcc cttcttccct cagcccctgg 6780 caaccactaa tctacttact gtctccatgg atgttcctat attgaatcaa gctagcataa 6840 accccacttg ctcatggtca taattctttt ttatagtgct aaattacatt tgctaatatt 6900 caattaagga tttctatgtc catattcata aggaatattg gtgtgtagtt ttctctttgt 6960 gtgatatctt tgtctggttg ggggatcaga gtaataatta ctgctctcat agaatgaatt 7020 gagaagtgtt ccctcctttt ctatttattg gaagagtttg tgaagtatat tggtattgat 7080 tcttctttaa acatttggtc agattcacca gtgaagccat ctgggccatg gctaatcttt 7140 gtgaaaagtt ttttgattac taattaaatc tctttaattt gttatgggtc tgctcctcag 7200 acgttctagt tcttcttgag tcagttttgt tcatttgttt cttcctagga ctttctccct 7260 ttcatttgga ttatttagat tgatagtaat atcccccttt taattcctgg ctgtagtaat 7320 ttgggtcttt tctctttttt cttggtcagt ttagctaaag gtttgtaatt gtattaatct 7380 tttcaaataa ctaacttttt tgttttgttt gttttttgtt ttttgttttt tgttttttgt 7440 ttttttttgc tttttaaggc tgcacctgag gcatatggaa gttctcaggc tagaggtcta 7500 atcggagcta cagctgctgg cctataccac aaccatagca atgccagatt caagctgcat 7560 ctgcgaccta caccacaact cggccaggga tcacacccgc aacctcatgg ttcctagtcg 7620 gatttgttaa ccactgtgcc acgacgggaa ctcccgccca ttttttttaa cacctcatac 7680 tttaacataa agatgggctt cacatggact gatagctcaa atgaggaagg taagactatg 7740 aaagtaatgg aagaaatgta gactattttt gtgacctaga gattactgat acttcttgac 7800 ttttcaaaca atacttcaaa agtacagccc aaagggaaaa aagaaagaaa aaagaaacac 7860 acatatacac aaacctagtg aataagatat catcgataca ctacagattt ctatgaactg 7920 gaagacccca tggacaaagt taaagaacat atgatagttt gagtgattat tttgcaatat 7980 ttacaaccaa tgagggaata ttatccagct tataggagga agtaatgcaa atcgacaaga 8040 aaaagatagg aaacccaata taaaaattaa gaaaatacaa aaattaagaa aggatatgaa 8100 ctagcatttt acaaaagaaa aatctccaaa agtcaatcag cacatgaaaa tatgctcaaa 8160 cctattaatt attagaaaac tacagactga agcaatgagg tgctttactt tacatctttt 8220 tgactgataa aaagttagaa acaaaggtga tatcaaatgt cagggataaa aggatataga 8280 aatcgtcatg cctgtggtgg gagtatggcc ggtgcagtca tgtgggaagg taatctgaca 8340 gtggttaggc agagcaggtt tatgaataca ctgtggccca tcaatcccac gcctgtttat 8400 gtaccaaaga aatcctgttg tggcagaatc tatgggtcca cccctgggag catgaattaa 8460 taaaatgtgg caccagggtg tgtgaaactc cagctagaga tgagatgtcc acatggcaac 8520 atgaatgcat cttagaaaca tagatttgag tgaaaaagag taagaaacag ccgggaaacc 8580 caataccatt tataaaaatt aaagatgcac acatacaatg tagtaaatat tttgcatgaa 8640 ctttcaaatg gttgcctaca gggggggaga gtaaagaaga gtagaaaaca aagataaagg 8700 gagtaagtaa gtagctctgc ctggactgaa tataatgtgt catgaactga gaaatatggt 8760 taacataatc ctcttaactt gaggtcctaa atgaatgaat gagtccacta ttcatttacc 8820 cattctttaa tgtgtattgc attataatcc atttttttag aaccaacgaa ttttgttccc 8880 ataactacta atcagcctgc cttttctccc tcattccctt atcagctcag gggcattcct 8940 agtttttcaa acgttcctca tttgaaccaa aaatagcatc attgtttaaa ttatacttgt 9000 tttcaaatac gatgcttata tattccaagt gtgtttgccc attttcttag gtggtagaaa 9060 tttttcattc tacttttcta tctactcaga ttttcccgtt ggaattattt ccattgctat 9120 taaacttaga agtcccccct gtgatatgcc atttttttca tactttttaa gcacttggtt 9180 gcttttcttt gtgtctttaa gcacctagaa tacttataac cattgcacag cactgtgtat 9240 caggcagccc ttcctcttcc actaatttat ggtccttctc ttagactata ttaaactgtt 9300 atttaattag gatcctctct tcgtccttat gatttaatta ttatagtttt ctaatatgtt 9360 tttattataa ttcctcttca ttattcctcc ctattaaaaa ttttaatgaa ttccatttgt 9420 ttgttcttct agttaaatat taagtcataa tccaaataac ttagatgtca ttagtttatg 9480 tggtcaaagt aaggatacca catctttata gatgcaggca gttggcagat gtcatgattt 9540 tcttcagtgc ataaatgcaa tttatctttg agcaaggggc ataaaaactt ttatggtatt 9600 ggctttgaaa taatagttaa gaactgcaga ctcagttttt cctgcttttc ttgaaaaaga 9660 acacttctaa agaaggaaaa tccttaagca tggatatcga tgtaattttc tgaaagtctc 9720 ctgtaattcc ttgggatttt tgttgttgtt tgttggtcgg tttttttggg tttttgtttg 9780 tttgttttgt tttgttttgt tttgctttta gggctgcacc tgtggcatat ggaagttccc 9840 aggctagggg tccaactgga gctacagctg ccagcctact ccacagccac agcaacatgg 9900 gatcctagct gcatctgtga cctaaccaca gctcttggta atgccagatt gttaacccac 9960 tgagcaatgc cagagatcga atctgcctcc tcatggacac tagtcagatt agtttctgct 10020 gagccacaat gggaattccc aattccttgt atttttgaac tggttatgtg ctagcatata 10080 attttgtttc ttgaatcttt gtgggttttt tttttttttt ttttttgtct cttgtctttt 10140 taaggctgca cccacagcat atggaggttc ccaggctaga ggtcaaattg gagctacagc 10200 tgccagccta cacaacaact gcagcaaagt ggggcccaac ttatatgaca gttcgtggca 10260 atgccggatt cctaacccac tgagcagggc cagggatcga acctgagttt ccagtcagtt 10320 tcgttaacca ctgagccatg atagtaactc ctgtttgttc agtcttgaac ctccttttta 10380 attctttatt ccttgagggt gaaataattg ccataataat actatcattt attacatgcc 10440 ttctctgtgc taggcatagt gacactttag gatttattat atcacttaat ccctacaaca 10500 actctgcaaa gtatgtatca taatcctatt tgacagatca ggaaattgca gcccaggatg 10560 cagataatat gcatccatca caagtgacta gatatagtcc ctctgctatt cagcagggtc 10620 tcattgcctt tccattccaa atgcaatagt ttgcatctat tgtatatgtg ttttggggtt 10680 tttttgtctt tttttttttt tttgtctttt ctggggcctc acccttggca taggtaggtt 10740 cccaggctag gggtcaaatt gaagctgcag ctgccagcct acaccacagc cacagcaact 10800 cgggatctga gcctcatctg caacctacac caaagctcac ggcaacaccg gatccttaac 10860 ccactgagtg aggccagaga tcaaaccggc aacctcatgg ttcctagtcg gattcattaa 10920 ccactgagcc acgatgggaa ctccctaaat gcaatagttt gctctattaa ccccaaactc 10980 ccagtccatc ccactccctc ctcctccctc ttggcaacca caagtctgtt ctccatgtcc 11040 atgattttct tttctgggga aagtttcatt tgtgccattt ttcattttac gggtaatttt 11100 tacttcagtt tcttccacta gcagttgtct taaagtgagt ataattaata ttcatttgga 11160 aaatgtaagc aaaacatttt ttaaagggcc atgcccacag catatgaaag tttctgggcc 11220 aggggttgaa tccaggctcc aagttgcagc tgtgccctac actgcagctg ggcaatgctg 11280 gatcctttaa cccactgtgc ccggctaggg atcaaacctg catttccaca gctacccgag 11340 ccattgcagt tggattctta acccactgca ctacagtggg aactcccaca aaacattttt 11400 taatgtcctt tgaataaagt aggaaagtgc tcgtctttga gggcagggcg gcaatgccat 11460 ttccacaagg tttgctttgg cttgggacct catctgctgt catttagtaa tgaataaaat 11520 tgctgacagt aataggatta actgtgtgtg gagatagcca gggttagaga taaaaacact 11580 ggagaagtca aataagttgc tcgaggtcct ctagctaata agctattaag tgggagagtg 11640 agggctagaa acaggccatc tgtctcccaa gcacatgtcc attagtggtt tgctgatagc 11700 cttccagaac aacagagagg actctcaaac atggtcttgc ctccctccaa ttgatcccct 11760 ccatgtgcct cacagcgggt ctttctaaaa ttaagttctg attttaattc tcccttgcta 11820 tagcacttag gtatggcttt cagccgtgca ataaaaagca ggcaagagtg gctcaatcat 11880 ataggaggtt gtttttctta gatcccaagc aggtaatcct gggcattatg gttgttctgc 11940 gtttatcaag gagccaaatt ctctatcacc tcctgttcta tcctcctcag tatctggctc 12000 tattcttcag catctcaaga tggcttgtgc tcctccaagc atggcagtca aattccacac 12060 aagaggggga aatatgaagg gcagacagtg ctggtctcct gagctgtccc tctttgtcgg 12120 ggaaataaat gtattccttc aagtcccgtg agacttctga agtagacgtc tgcttacgtc 12180 tcacccacca gaactatgta aactgcacat agtgctaggt ctacatagcc actcataact 12240 gccagggggt gggaaatctt taaataggtg taccaccaca caattaggat gctaatagta 12300 agggagaagg agagaatagg ttttgcgcaa gccaccagca tgcctgccac aattgcttaa 12360 aattcttcat tgacccctca ttgccacagg atgaaatcca aacgccttct tagttgggaa 12420 tctgacctac ctgtctctcc cacctggttc agacaccatt ctccttggtc ataaaattcc 12480 agtcatttgt gaacatccag ctcccccatg cctccatgcc tttgcacatg ctgttctttt 12540 atcttttatg ttgtcctttt atcttttatc caaaagagat atcccatcat cacatctctt 12600 ttgtcagccc ccaaatactt tgtctttcaa gttcagctgg aggattacct cctatttgaa 12660 atcagctttg tctcttacaa ccaaacaagg ttttccttcc gagacactcc cacagcacct 12720 tgaactcatc tctatcaatc attcatttga ttgtaatgaa gttgttggtg gtatgcctgt 12780 gtctctgaca catctgcgat ctcatgagtt ccttaagtgg aatgtgaata gcgggatgaa 12840 cagtattggt cttcagccct catctctgca gatgttgctt gacccaaatg agcgttgcct 12900 tttattttga ttttgctttg atttgtctac tccatgtact tgagccatgc atttctgtct 12960 tagcgatgct ttttaaaagt cattttttgg ttgattatcc agatttgtcc acctttgctt 13020 ctagttgtag aaaaggatga agaaaatgga gttttgcttc tagaactaaa tcctcctaac 13080 ccgtgggatt cagaacccag atctcctgaa gatttggcat ttggggaagt gcaggtaagg 13140 aaatgttaaa ttgcaatatt cttaaaaaca caaataaagc taacatatca atttatatat 13200 atatatatat atatattttt tttttttttt acatcttata ttaccttgag tattcttgga 13260 agtggctagt taggacatat aataaagtta ttctgaagtc tttttttttc tttttccatg 13320 gtgagcagtg gcttgatgtg gatctcagct cccagacgag gcactgaacc tgagccgcag 13380 tggtgaaagc accaagttct agccactaga ccaccaggga actccctatt ctaaattctt 13440 gagcacatta tttaggaacc tcaggaactt ggcaggatta caggaaatat atctagattt 13500 aaaaaaaaat cttttaacag aggtcccaaa ggagagtcat gcacagctat gggaggaagt 13560 tcagaaactg cccttgctac cagatcactg tcagataaaa tggccagcta catgtttctg 13620 cacattgccc taagatcttt acaaactttt ctgtgcattt ttccactttt aaaagaaaat 13680 ttcggggttc ctgttgttgc tcagtggtta acgaacccaa ctagtatcca tggggacagg 13740 ggttcgagcc ctggcctcac tcagtgggtt aagaatctgg cattgctgtg gctgtggcgt 13800 aggctggcgg ctacagctca gattggaccc ctagcctgag aacctccata tgccgcaggt 13860 atggccctaa aaaaaaaaaa aaagagagag agagaatttc ctccagaaaa aacactttgg 13920 tagtttggga gaagtaaaca accaaaaatt aatttttctg gagtattcgg gaagcttgta 13980 aaaatgggct cttacttttt tgaggagaca aatgggaacc tacccagaag aggcacaatc 14040 acctgcattt gatttcttga cctctcccta ccttctttgc tggctttcca catttggatt 14100 tctgtgacct tatctctgct ccttggtgtt ttcatttttc ctgtggacgt gccagactat 14160 gggaagggag taaggcgttg atttagaatc ctgtagtctc tgcctgtctc tagtcattgt 14220 tttcaccctt ctcaaaggac cttgacatcc tgagtgagtc cgcaagtaat ttaggggaga 14280 agccttagaa gccagtgcag ccaggctaca tgactgtgtc cacccactgg aaccagtcat 14340 ttttatacct attcacagcc cccctaccat ttaaatcccc agaggtctgc cataacatct 14400 gtaactccct ttcctggtaa attgtgttct aaaagactgg taacaaaaga tattctgtgg 14460 tacagagcat aattaaatac ctgggagctg atttgagtgg ggtaaatcaa ctggtttgac 14520 ccctaaaacc caccatgagc atttctgttc taataaagta atgcccgtgc tgggaattgt 14580 gttctacgga aatgctcctg ctgtgtcttt cttgagtcct gtgtcattga acatgcttag 14640 gagcaaaggt cccccatgtg gcttgtctgc taaccagccc agttccttgt tctggctggt 14700 aatgatccga tcatctgaat ctcactgtct tccaacagat cacgtacctt actcacgcct 14760 gcatggacct caagctgggg gacaagagaa tggtgttcga cccttggtta atcggtcctg 14820 cttttgcgcg aggatggtgg ttactacacg agcctccatc tgattggctg gagaggctga 14880 gccgcgcaga cttaatttac atcagtcaca tgcactcaga ccacctgag 14929 <210> SEQ ID NO 50 <211> LENGTH: 17221 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 50 aggaatggaa agcccaattc attaaaacag aaaggaagaa actcctgaac tacaaggctc 60 ggctggtgaa ggacctacaa cccagaattt actgcccctt tcctgggtat ttcgtggaat 120 cccacccagc agacaagtat ggctggatat tttatataac gtgtttacgc ataagttaat 180 atatgctgaa tgagtgattt agctgtgaaa caacatgaaa tgagaaagaa tgattagtag 240 gggtctggag cttattttaa caagcagcct gaaaacagag agtatgaata aaaaaaatta 300 aatacgtatg gctggatatt ttatataacg tgtttacgca taagttaata tatgctgaat 360 gagtgattta gctgtgaaac aacatgaaat gagaaagaat gattagtagg ggtctggagc 420 ttattttaac aagcagcctg aaaacagaga gtatgaataa aaaaaattaa atacaagagt 480 gtgctattac caattatgta taatagtctt gtacatctaa cttcaattcc aatcactata 540 tgcttatact aaaaaacgaa gtatagagtc aaccttcttt gactaacagc tcttccctag 600 tcagggacat tagctcaagt atagtcttta tttttcctgg ggtaagaaaa gaaggattgg 660 gaagtaggaa tgcaaagaaa taaaaaataa ttctgtcatt gttcaaataa gaatgtcatc 720 tgaaaataaa ctgccttaca tgggaatgct cttatttgtc aggtatatta aggaaacaaa 780 catcaaaaat gacccaaatg aactcaacaa tcttatcaag aagaattctg aggtggtaac 840 ctggacccca agacctggag ccactcttga tctgggtagg atgctaaagg acccaacaga 900 caggtttgac ttgaatattt acagggaaca aaaatgattt ctgaattttt tcatgtttat 960 gagaaaataa agggcatacc tatggcctct tggcaggtcc ctgtttgtag gaatattaag 1020 tttttcttga ctagcatcct gagcttgtca tgcattaaga tctacacacc accctttaaa 1080 gtgggagtct tactgtataa aataaactat taaataagta tctttcaact ctggggtggg 1140 gggggagact gagttttttc acagtcctat ataataattt tcttatccta taaaataatt 1200 aggagttccc gtagtggctc agcaatagca aacccgacta gtatcgatga ggatgcgggt 1260 tcgattcctg gcccccctca gtgggttaag gatctggcat tgccgtgagc tgtggtgtag 1320 gtggcagaca cggctcagat cccacgttac tgtggctgtg gcataggcca gcagctccag 1380 ctctgattag acccttagcc tgggaacttc catatgctgt gggtgtggcc ttgaaaaaaa 1440 ataaataaat aagataatta ctcaaatgtt ttccttgtct cagaacctta cttcaggata 1500 aagagtgaga aagttttttt tatgaagggc cattattaca gctcaaaaat aagttgtctt 1560 cagcaagtag aaagcaataa gcctgagagt tagtgttcct atcagtgtaa atattacctc 1620 ctcgccaatc cccagacagt ccatttgaac aattaacggt gccctgggag tacagttcag 1680 aaacattaat gtggatgttc cagacctgta tttttataag tacttgtctt gagccggatg 1740 gaaccatcat tcctcaccat tatttagaag tggactgtga ctctgttgga gatcagggca 1800 cacggttacc aaaagcacac ccttctcctg gccttacctt tgcaaagctg gggtctggga 1860 cacagtcagc tgattatacc cttttactaa cttcccacag ctcaaatctg gtcaattctc 1920 cttcacaaat ctcttaaaaa tccatcactc acctccagcc tcttctgctg tggccttgat 1980 tcagcctctc acaatttttt tttaaccaga attctggcag tggcccctga cttgcctctg 2040 tgctcccagc cccgctgtcc tctgatccat cctccatgcc agcctttttc aatctgctgg 2100 tcacgattca ttgatgggtt aggaaatcaa tggcatcaca actagcattt agaaaaagga 2160 aataggcgtt cccgccgtgg cacagcagaa ataaatccga ctaggaacca taaggttgcg 2220 ggttcaaccc ctggccttgt tcagtgggtt aaggatccgg cattgccgtg ggctgttttg 2280 taagtcacag acatggctct gatccggcat tgctgtggct ctggcgtagg cctgcagcat 2340 cagctccaat tagaccccta tcctgggagc ctccatatgc tgcaagtgca gccctaaaaa 2400 aaataaaaaa ataaaaaaaa ataaataaaa gaagtagaca aattgtatag aacaaccctg 2460 agtatgttgc ctgagcacat ataacaaggg taagtattat ttcaggaaac tctggtttca 2520 cagatactct tggcatatgg acccctagag tcctgatgta aaatatattc ttcctgggat 2580 cttaggcaag aagtttgaaa gctccaactc tgcactgctg ccaaagaaat gatttttaag 2640 tgcaaaactc ttcccgttcc cttccctgta taaaattcca taggatctct ccagtgcctc 2700 taggataaag gcagttttca ttctctagtt caaggtgaga gaagatttta attatttcac 2760 gttttagtgg ggaattcaag agtctggcac ctgacatttg ctgaactctc tccattatcc 2820 ctctctagtt ccccagacgc atcctatggt agaaattcgc aaactagagt gagcgtcaga 2880 gtaacccaag gaaactgggt aaatgcagct ccctgggctc taccccctga gattctgatt 2940 cagtagatct gaagcagagc cctggaatat gcatatgcat cattgtgtca caccaagcat 3000 tctgggtaat gagagttgat gttaggttct cagtagtaag acaagtatag agattccggg 3060 ggactgagtg ctcagctctg ccttggggag gagggagagg gctaaagaga acaggagatg 3120 gggacaggga atgctcaacc tccaatctta ggcatttgag ctatgtctta ggggtcagga 3180 ggaggttacc aatatagtga ttaagagatt gaggttccag tcagagggat atgctggaga 3240 aggggggtga aaataatgtc ataggtttgg tgagtgcaga tactttgagt tttttaatat 3300 ttttattgaa atatagttga tttacaatgc tcttagtgag tacaattact ttgaataagt 3360 gcatagatgt atgccattct tccagaaatg atttattgag ctcctttggg catcatgcta 3420 agtacagggg aaacagctgt gaagaggtcc ttcccttatg aagtcattca tccccttcag 3480 taaatgaagg taaaggaaaa ggatgagaca gggacgccgt gttggaccag ggtcagaaag 3540 gccttataag accttgcctg gagggcaagg aacttgcctg tgagtaagga gagcttgaga 3600 aagcgataaa gcaaagaagg aacattactg cattgtgttt tagaaaaacc atgtcctggg 3660 gaagaactcc tagagtcagg ggggccagtt gggagactgt gcttttttcc aggaggagat 3720 aagtgaggct gctggctgag atggagcaag gatttagaga agcagatatg agattcattt 3780 agaagttaga cattttagga tctgacacat aatttatcac caaaaccagt gcatctctgg 3840 ctttgggcca ccagttttgg agaagtggaa tgtagggacc taccattacc tgccaatctt 3900 tactacacag atgcctattt ccctcctcat atttcctttc tccagatcac gtcctattct 3960 attgccagga ctcaagattc caccttgcat gcagtgatcc atcttcacac tggatggaca 4020 gctctaggga tgtcagagca cactcttgtc catactgctg actgggtctc ctgtcagccc 4080 atctgtctat cagctgtggt attattagta taataagagg gctgtatatg agagacacaa 4140 aattctaggt gtagctcaaa gataggctag agttattcct atgtacaaca aatatttatg 4200 ggaccccttc tgtgtactgt catggttgct gctttcatca tacttgtagt ctaatggagg 4260 tgggggcagg gcaggaataa gcggatgtcc acaaaatcag taagaccact tatattcaac 4320 attttcataa tttagttatt tgagcccaaa gggtccacat ccgtggtatt ccaacttttt 4380 tttccccgga catggatctt tatctttttt tttttttctt ttttgcggcc agacctgcgg 4440 catatggaag ttcccaggcc aggggttgaa tgggagttgc agctgcctgg tctacaccac 4500 agccacagca aggtgggatc tgagctgcat ctgtgacata caccgcagct gaggtaacac 4560 cagattctga acccactgaa tgaggccagg gatggaaccc gtctccttat gaacactatg 4620 tcatgttctt caccctctga gccacaacgg gaactccaga cttcgtcttt aaatgtattc 4680 tgacttggag agctatcaca ctaagcaatt aacaggagct gacctggttt aggctggggt 4740 ggggccctac tcctcaatgt tccctgaggc acatctgtgg gacccctggg catcatctat 4800 ctgagcagcc ttagagctgc tcatccagtt gactgttgat gtagaagtgc aaacttctgc 4860 cttccttatt tgttgctttc ttttttcatt gttctctccc ctttgtgtct ttaagcaagg 4920 gcatcgtaga gcctccagaa gggactaaga tttacaagga ttcctgggat tttggcccat 4980 atttgaatat cttgaatgct gctataggag atgaaatatt tcgtcactca tcctggataa 5040 aagaatactt cacttgggct ggatttaagg attataacct ggtggtcagg gtatgctatg 5100 aagttattat ttgtttttgt tttcttgtat tacagagcta tatgaaaacc tcttagtatt 5160 ccagttggtt tctcaataag cattcattga gccttactga ctgtcagacg gagggcgtat 5220 tggactatgt gctgaaacaa tcctttgttg aaaatgtagg gaatgttgaa aatgtaggga 5280 atgaaatgta gatccagctc tgtttctctt ttggaggatt ctttttcctc catcaccgtg 5340 tcttggttct tgtttgtttt gggtttttgt gggtgttgta ttgtgttgtg ttggttatgg 5400 cagtgacagc tatttaaact gtgaaacggg ggagttcccg tcgtggcgca gtggttaacg 5460 aatccgactg ggaaccatga ggttgcgggt tcggtccctg cccttgctca gtgggttaac 5520 gatccggcgt tgccgtgagc tgtggtgtag gttgcagaca cggctcggat cccgcgttgc 5580 tgtggctcta gcgtaggcca gcggctacag ctccgattgg acccctagcc tgggaacctc 5640 catatgccgc aggagcggcc caaagaaata gcaaaaagac aaaataaata aataaataaa 5700 taagtaagta aaataaactg tgaaacgggg agttcccttc atggctcagc agttaacaaa 5760 cccagctagg atccatgagg atgtaggttc gatccctggc cttgctcagt gggttaagaa 5820 tccagcgttg ctgtgagctg tgatgtaggt cgcagatgca gcccagatcc tgcattgctg 5880 tggctgtggc gtaggctggc agctgaagct ccgattcaac ccctagcctg ggaacatcca 5940 tatgctgcag gtgtggcctt aagaggcaaa aaaataaaaa aataaaaaat aaataaattg 6000 tgggacagac aggtggctcc actgcagagc tggtgtcctg tagcagcctg gaagcaggta 6060 aggtaaggac tgcagctggg taaggactga attgcaccaa ctgggaagta agcctagatc 6120 tagaacttaa gttagccctg acatagacac acagagctca ccagctaagt ggttcagctt 6180 ataagctggt cactgaaact gaggatgtcc acaaaagcaa aataagtagc aacaggcagc 6240 gggatgcaag agaaagagga ggcctaaaat ggtctgggaa tccctgccat acctatattt 6300 tatcctactt atatttagtg cctgaatgtg tgcctggaga gcaaagttta gggaaagcat 6360 cgggaaatgc acagtattca tacccttagg aacaaagatc agttacctcc agggtaaaga 6420 ctatttccaa gtttaaattt caacccctga acattagtac tgggtaccag gcaacacttg 6480 ccatcctcaa aatcaatgaa tcctaaaatt caacctgggg gtcagtgaca gtctgtgaca 6540 aagtttttgc tggtcagtaa cgaaataagt atgagcacca tctgagtatg gtcaccaaga 6600 tgtcaactct ctttcctttg gacgaattgt cattattcca agattaggtc ctttctattt 6660 ttgaggtgtg aaaacatctt tcctttcata aaataaaagg atagtaggtg gaagaatttt 6720 ttttgttttt tggtcttttt gctatttctt tgggccgctt ctgcagcata tggaggttcc 6780 caggccaggg gtcgaatcgg agctttagcc accggcccac gccagagcca cagcaacacg 6840 ggatccaagc cgcatctgca gcctacacca cagctcacgg caatgccgga tcgttaaccc 6900 actgagcaag ggcagggacc gaacccgcaa cctcatggtt cctagtcgga ttcgttaacc 6960 actgcgccac gacgggaact cctaatgata ctcttttata tttagctact atgtgatgat 7020 gagaaacagt ccacatttta ttatttttta gccaatttga tatctcatta ctaagataat 7080 gataattttc tctataaatt ttatttaagt tagtgttatg aagtggtttt gctagtgtag 7140 aaggctagga tttgaattca gttcaagaaa gaagagaggg agggagggag agggatgggt 7200 agagggatgg ggcagtggga gagagcaaag aggagagaca gtttttgtat taattctgct 7260 tcattgctat catttaaggg cacttgggtc ttgcacattc tagaattttc taaggacctt 7320 gaccgccaga ttgatatgct tcttcccttt accatgttgt catttgaaca gatgattgag 7380 acagatgagg acttcagccc tttgcctgga ggatatgact atttggttga ctttctggat 7440 ttatcctttc caaaagaaag accaagccgg gaacatccat atgaggaagt aagcaggaat 7500 accagtggaa gtgccccttt cttccttcct tcctaaataa acttttttat tttggaacaa 7560 ctttagagtt acagaaaagt tgcaaagata ttatagacag tagtgtttat atatatatat 7620 aaattttttt ttgcttttta tgaccacacc tgtggcatat ggaggttccc agtctagggg 7680 ttgaattgga gctacagctg ccagtctgtg ccataaccac agcaatgcag gatctgggcc 7740 acgtctgtga cctacaccaa agctcacagc tggattctta acccactgag caaggccagg 7800 gattgaacct gcatcctcgt ggttcctagt tggattcgtt tccgctttgc cgcaatggga 7860 actccaaatt attgttaata tcttacttta ctggggtaca tttgttacaa ccaatactct 7920 gatactgaaa cattactgtt aactccgtac ttgcttcttt ttgagtcatt tgcaaagact 7980 ggcttcttga cctgcttcct tccaaacagc tggcctgcct atgctgttct cagacctgca 8040 agcactgatc tctgcccccc ttgccttctc tccagtggtg tctccttccc caaacaaacc 8100 cagtgtggct ctggaaaggg agttaagtca acataaacca acacatattt tgttgagctc 8160 caattttgag caaatccctc acctacggca gacaggcatg atgttaagaa ctagggcttt 8220 ggacacaagg tcaagaccaa gaagggttcc tcacccctac tgattcagat aaccaataat 8280 gaggctttga atccctgtcc aaaggttgtt ttttttccct tctattgagc ttcttgccac 8340 cttatcagtt ttttttatga cagtcaaatg acatgatata tgtgagcata catggtaatt 8400 tttaattcta tataaatgaa tcactaaata aattaggagg atatatagtc cacctttaag 8460 cgtattacac gtgtcacatg aatgtgtggc gacttaattg tagaggttta aatgtagctt 8520 cctataatag atgtgttcct aaactacatt ttaatcattg gacttgtatt tttatgttag 8580 cacttgctgt tgaagaaaag cctatgccaa aagttcagtg aaaccaataa tccactgcca 8640 gctttctgag ttaaaaaaaa tccctgggtt ttcacacaca ggaacaccct gtgtgaaaca 8700 ctcatttaga gcaaaatgca tctgataagg agttcctgtt gtgcctcaac tggttaagga 8760 cctgacattc tccatgagaa tgtgagtttg atccccggcc ccactcgatg ggttaaggat 8820 ctggtgttgc cacaaactgc agctccgatt catctcctag cctagaaact tccacagccc 8880 agaatatgcc acagaattcg gctgtttaaa aaaaaaaaga aaaaaaaaag aatcataaat 8940 gtgttggttt gttcaccaaa tacatgataa cttgctcttg ccaagctcag cttcataaat 9000 attaagtcat ttaatacagc agccacctta tgaacagata ttactatact tcccatttac 9060 agataaggaa aatgccatat ttaaccaaga gattaaataa ctttcccgag gtcttatagc 9120 aagtaaatca tggtgcaggg gtttgaccac acgcagtcta tctccagagt ctgtgtattt 9180 agccactgtt ttactttcaa atttaaattt ataaaacttc taaattatct gttaaccata 9240 atctttggaa tttttaaaac cacgagttcc tataaaatgt ttcattgaaa gtaagtcact 9300 tttccatagc ttttgataat acatctgtag gataaagtaa gccacagctc tcttgcagac 9360 ttggtacacc ctggggcaaa gcatcatgcc tgtcacgtac atggtggtcc ttactttgac 9420 tctcagtgct tttattgccc aggaattttg tgagatttct agttgttgag gtttgtttaa 9480 agaggttatg ccggtacttg gaagagctct tttcttgcta cctggagcct tctcatattt 9540 cctttttgag gagggacatg aattgccttt caaactcata aatatatttt ctagtacaca 9600 agtctccatc ttccttagac gcatggctcc tggagttctc catcctcctg ctccactttg 9660 ggtgggctcc tctctgggtc tgccaccaat ctgccaccca gagacatcct tgacccactt 9720 ccagacccca ccatggcttc actttcttcg ctttcctcct ttgtggaacc ttctgcttaa 9780 gaatctgagg aagaaaattt gcacgtgagc taaactggag gtactttcct gcctggtctt 9840 gcacgatagc ttggctgagc ccatgatgct gggtggctgt tactttccat ggacacccga 9900 aggcgttgct cctttggctt ctagttgcat gcagtgttgc ttatcccagg ctgatctttc 9960 ttccactgta ggtgactttt aagaattaag ggattaatct atatctacaa caacaacaac 10020 aaagaccttt tcaagctgag gtagggcttt ctgtatatgt ttggagtggt tatccagcag 10080 actttacttg aaggcagggg tcatatcctc aagtgctcat aaacggacca cagaaagatc 10140 tcataattgg gtggagctgg gtggggaccg tgtcatgtgg ccaggaaatg ccagatggga 10200 agggagtggc ccttactgag ctccagctga actctgaatt ttctagaaaa ctcagaaatc 10260 tggatttttc atgtgtaata cccagattta tagatgtgga aagctaattc tttttttttt 10320 taagggacta taggcaatga actaagatct aggttgtatt tggacaaggg gtcatcagtt 10380 taagctgtgt agttgagcgc tcagctattg ggctgaggga cccctaaata ctgagacggg 10440 gaggtccttg ctctggggca tcacaagtac actccctggt ctcattcaaa cacttttcct 10500 acaaaattga tcccatttct tcagtgcact gtctgaatgc atttggccca gagccgtgct 10560 gaggcatagg gaaggggtcc acggtttcat ggcatcgttt tgtgctgtgt gtccctgctg 10620 tcgtccagga tacctacctc tcctcctcct gcatctgaat gtccccccac agactctctg 10680 ggattctaca gcctctggcc tgttcctcag acacctctta cctgccagct ttccagattc 10740 acattagtta gtccaaatct actgccgtca gtgactcact tcatttcttc ttctccgagg 10800 cagttcagcc cggtacagtt gttttgtcaa cacttcagtt gagtctggaa gatgtgcatg 10860 ggttatgcac gagagcggtc catcattttg agctagaagt cctttctcag cccagagaca 10920 agtcctcatc tcctttactt cctgactctt cttcctctgc atccttccaa gatatctctt 10980 tctccagcca ccacctaaat ctcttctttt cccggggttc cgtgctcaac ccactcttct 11040 tcttaaatct gtggctgggt gaacgcatct gctggcacca cttctctgct aaagactcca 11100 aaaatccata ggtcctgccc ggcctttgcc cacctctctc caacactgtc cagctttaga 11160 tgtagagcta atccccccag agatatcatt ccctggatgt ctaagtcctt tggtatctca 11220 ctttcagcgt gttcaaaatc ctcttacaac tgttctttct ccttttccat cttgattatt 11280 ggcaacatgc cagcctttcc cctaccccca gcagtgagcc aagctagaaa caagggctta 11340 atcttcaatc tttccttctc catccctaaa cctaatgagt ctccaagccc ttcccagttt 11400 acaccctaaa tgttgctcaa aacatcccct agttcttcca cgtgctctcc tctatattga 11460 aaggtcaaga aaggccatct tccctccact gtgaggaaat agatcttgat actgcccctg 11520 agctgggcag tcctcgacct gacaaactgt gcagtgtttc taaatctcta ctggcaaaat 11580 gagagtgcct ttgacctgtg ttgcgatctc agatcacagt ggatgtaatt gttttatagg 11640 aatggtgaac gaaaaagaag taaatcccta atgccaaact cctgatcatt ctatgtcatt 11700 taatagcctg tcatttatga taaagtttcc tctactggca ttagcacaat acttctcagg 11760 aaaaaaaaat atgatgccag atactgaaaa gctcctgggt aaacatgaac atgggtaccg 11820 ataaaatggt gaagccagtc caatcttaga gtgacttccc ttcatgctac ttcatgctct 11880 tttttttttt tttttttaag aaaaacccct tttttttttc tcacaccagt cacagaggag 11940 accgaggctt agcaaggtta aggtcacatg attagtaagt gctgggctga aactcaaaac 12000 catctctgct tgtctcctaa ccctgtgcac ctctgactat tcaacagatc ctgtgtcagg 12060 agttgggatt ctttgaaggt aagggccttg accaccgaat taaggtaatc ttgctctgtg 12120 gcaggccttg ttttcagtat tttaagtaca ctggctcagg taatcctcac aacagcccca 12180 ggaggaatgt tctattacct ccactgtata gatgaggaac ttgaggcaca gaatggttgc 12240 caaggtcaca cagctatatt gggggttcat acccagccat ccaactctgt ctgtactctc 12300 tgccactctg cacccccagc tcctgatcca cttcctgttt ccatccctcg atttctgctg 12360 cactcagggg cccctctccc cctcggcctg tgagatctgc ttcagtaggc ttttctccct 12420 gactcctcca tccctgtcct tacaggcagc tgcttctctc cgggacacga ggggtccata 12480 cggacactct ctactggctg ggttgcgcct aactcgtgat tcctcctctg tttcagattc 12540 ggagccgggt tgatgtcatc agacacgtgg taaagaatgg tctgctctgg gatgacttgt 12600 acataggatt ccaaacccgg cttcagcggg atcctgatat ataccatcat ctgtaagtcc 12660 gaaaatgcct gtcgtgtgtg ccttaggctg ctgcggagga ggccagggct atataagcag 12720 agtcagtgac tgactgtgcc ctgcagtgtt gatggccatg gagattccac cgttagagct 12780 tttttctttg ttaaccttga aggcaaatct ggttaggaag ataactttca aagagtcacc 12840 atctggacat tcatgcccat gtgcttcaat cctgtataca agcagtttag agtacaggga 12900 agggaaggac attatgaaag ggagagggtg tgtttggatc cagcagctcc atcctcagaa 12960 tttatctgaa gacactgcaa aattactaag aatcactatg acaagaatga ggatggggtg 13020 atatggcaaa gttgtgatcc tggaagacct tcatctccca tgttgcccaa ctctgaacat 13080 gaatttggtg aactagttgg ttaaggggat gatcctccaa gtttctccct ggttgagctc 13140 caaaaaccat gtaagtttct catagcaaaa ccgtataggt ccttagggct ttagttggaa 13200 tatttgtgct gaaatgctgg aaagccccat ttgccatttt tgtatttgca aaataatcat 13260 caagagggga gaatgcattc tttcatgacc actgaccctc tgaaaaggtc aggaatttag 13320 tctgaagtag gcaagcctcc taccccgctt ctgccatgag cttgcacgca caggcctgtc 13380 ttgacatttc ttctttatag atttcttttt gaatatcttg aaattgcttt aaaaatattt 13440 aaagaatgta gaattatata aaataaaaag gaaataaccc cacacctccc acaaaaccct 13500 gtttcctgcc tttctccacc cactctccag ggtaacactt ggtaacagca tagttgtatc 13560 accccaggcc tatttttgag catatcagca tttcaagaaa tgtatttttt ctcaataaaa 13620 catcccttat agttgaggag gggaggttat cattcctggg ttttgttttt tttttttttt 13680 taatgtaatc ctggtacatc ggtaatttgc attttttatt cattaatatc tttggtattt 13740 ctagtgttgg gacacacagg tcaacctcag tttttgggtt tttttttttg tctttttgtc 13800 tttctagggc cacacctgca gcatatggac gttcccaagc taggagtcta atcagagctg 13860 tagccaccag cctacgtcat agccatagca acgtcagatc caagccgtgt ctgtgaccta 13920 caagcacagc tcatggcaac accggatcct taaccactga acgaggccag gggatcgaac 13980 acacatcctc atggatccta gtcatgttca ttaaccactg agtcatgatg ggaactccaa 14040 cttcaactat tttaatgtct gtaaaacatt ccatttggaa accatttcat ttgtaaagca 14100 aaatgaaaac attttgttca ttttcaacag agttcgtagc tgacttctgt tctggaaaaa 14160 aggaaatgga gcaaatttga gtgagaaaga ttcaaagata acttttcttt taaaaaaaat 14220 tatatcttgg aaacttctgg gctattgatt ctgaagacta tttttctata tactgttttg 14280 atagcaaagt tcataaatgt gaaaggatcc tgcgatgaat cttgggaagc agtcatagcc 14340 caatatatct ttgttgcttt taaaatgaga tttagtttac taaatatttt tctgatcata 14400 aaaataacac agatctaccg cagaaaattt ggaaaaaaaa aaacttttaa attcaaaaaa 14460 cagttaaacc acaaatgatc ccaccatcca gagagcaatt tgtactttgg tgtctagttc 14520 atctttcttt ttctgtttac aagcacatat accacaagca ttttttcaaa aaatgaaaat 14580 gggataatac tatacatacg tctgtacacc tgcatagtta ctgaacagtc tttgatctac 14640 cctgtaagtt tctaactttt cattatttga aatgatgttt tggcaaagaa atatgtaggt 14700 gtgtctcgca cactttcata atgatttctt aggataaatt tcttaggata aattcataat 14760 gatttcttat aataatccat actctgccaa ctgatcttca gggaagccaa ctcgccttct 14820 cagaaataac atataaccca tttacttgcc ctctcaccaa tactaggtcc taatgttttt 14880 gtgtacagat tctatatttt tacatacaag aattccttaa agcaaggcat gtcacagaaa 14940 aatagaagga agacacaatt gtcatgttta aggactgcat tctgtaccaa aaatgctaag 15000 ttaaatgaac atctgaaaca gtacagaaac gctatctttc agggaaagct gagtaccagg 15060 tactgaacag attttggcaa atacagcagg catggatgtt tccaaaacat gtttttctac 15120 tttatctctt acaggttttg gaatcatttt caaataaaac tccccctcac accacctgac 15180 tggaagtcct tcctgatgtg ctctgggtag agaggacctg agctgtccca ggtaaagcat 15240 cctgcaggtc tgggagacac tcttattctc cagcccatca cactgtgttt ggcatcagaa 15300 ttaagcaggc actatgccta tcagaaaacc tgacttttgg gggaatgaaa gaagctaaca 15360 ttacaagaat gtctgtgttt aaaaataagt caataaggga gttcccatcg tggctcagtg 15420 gtaacgaacc ctactagtat ccattgagga cacaggttca atatctggcc tcactcagtc 15480 ggctaaggat ccagtgatgc cgtgagctgc agtgtaggcc acagacgtgg ctcagatctg 15540 gtgctgctgt ggctatggtg taggccggcc ccctgtaact ccaattcgac ccctaggctg 15600 ggaacctaaa aagaccccaa aaaagtcgct ttaatgaata gtgaatacat ccagcccaaa 15660 gtccacagac tctttggtct ggttgtggca aacatacagc cagttaacaa acaagacaaa 15720 aattatccta ggtggtcagt gggggttcag agctgaatcc tgaacactgg aaggaaaaca 15780 gcaaccaaat ccaaatactg tatggttttg cttatatgta gaatctaaat tcaaagcaaa 15840 tgagcaaacc aattgaaaca gttatggaag acaagcaggt ggttgtcagg ggggagataa 15900 ggggaggcag gaaagacctg ggcgagggag attaagaggt accaactttc agttgcaaaa 15960 caaatgagtc accagtatga aatgtgcaat gtgggaaata caggccataa ctttataatc 16020 tctttttttt ttttgtcttt tttgcctttt ctaaggctgc tcccgtggca tatggaggtt 16080 cccaggctag gagtccaaac agagctgtag ctgccagcct acaccagagc cacagcaaca 16140 cgggaacctt aacccgctga gcaaggccag ggatcgaacc cgagtcctca cagatgccag 16200 tagggttcat taaccactga gccacgacag gaattccagg gtctgttgtg ttcttaaaac 16260 acttccagga gagtgagtgg tatgtcataa gtaaacaata aatgttaacc acaacaagct 16320 tatgaaataa acaggaaagc catatgacct acaatcagtc attgggagaa tccacaaaag 16380 gttgagcaga ggatcaattc cagctcacac tccagtttta gattctcccc tgccttaaag 16440 catcacagac tacataatct gagctgaaga ataaaaatta aaactcaccc cagtgcaaaa 16500 cagaaatgaa aaagtattaa aacgaggttc atactgttgt tcattagcaa tatcttttat 16560 tcacaggggt gcccaacaac atgaaaaaat caagaattta ttgctgctac gtcaaagctt 16620 ataccagaga ttatgcctta tagacattag caatggataa ttatatgttg cacttgtgaa 16680 atgtgcacat atcctgttta tgaatcacca catagccaga ttatcaatat tttacttatt 16740 tcgtaaaaaa tccacaattt tccataacag aatcaacgtg tgcaatagga acaagattgc 16800 tatggaaaac gagggtaaca ggaggagata ttaatccaag catagaagaa atagacaaat 16860 gaggggccat aaggggaata tagggaagag aaaaaaatta agatggaatt ttaaaaggag 16920 aatgtaaaaa atagatattt gttccttaat aggttgattc ctcaaataga gcccatgaat 16980 ataatcaaat aggaagggtt catgactgtt ttcaattttt caaaaagctt tgttgaaatc 17040 atagacttgc aaaacaaggc tgtagaggcc accctaaaat ggaaaatttc actgggactg 17100 aaattatttt gattcaatga caaaatttgt tatttactgc ggattataaa ctctaacaaa 17160 tagcgatctc tttgcttcat aaaaacataa acactagcta gtaataaaat gagttctgca 17220 g 17221 <210> SEQ ID NO 51 <211> LENGTH: 26 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 51 catggacctc aagctggggg acaaga 26 <210> SEQ ID NO 52 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 52 gtgttcgacc cttggttaat cggtcctg 28 <210> SEQ ID NO 53 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 53 caggaccgat taaccaaggg tcgaacac 28 <210> SEQ ID NO 54 <211> LENGTH: 26 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 54 tcttgtcccc cagcttgagg tccatg 26 <210> SEQ ID NO 55 <211> LENGTH: 27 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 55 ctcctggaag cttctgtcaa gacgaac 27 <210> SEQ ID NO 56 <211> LENGTH: 27 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 56 gcctgataca cagtgctgtg caatggt 27 <210> SEQ ID NO 57 <211> LENGTH: 29 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 57 accacccaag tctggaatct tcttacact 29 <210> SEQ ID NO 58 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 58 gactctcata caaaagctaa gctgggtaag 30 <210> SEQ ID NO 59 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 59 gactctcata caaaacctaa gctgggtaag 30 <210> SEQ ID NO 60 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 60 gactctcata caaaacctag gctgggtaag 30 <210> SEQ ID NO 61 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 61 gactctcata caaaacctag gctaggtaag 30 <210> SEQ ID NO 62 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 62 ccttatactg gccccaattg gatcttac 28 <210> SEQ ID NO 63 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 63 ccttatactg gccccaattg gatcttac 28 <210> SEQ ID NO 64 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 64 cttacctagc ctaggttttg tatgagagtc 30 <210> SEQ ID NO 65 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: primer <400> SEQUENCE: 65 gacaaaccac aattggaatg cactcgag 28 <210> SEQ ID NO 66 <400> SEQUENCE: 66 000 <210> SEQ ID NO 67 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic probe - pDH6 <400> SEQUENCE: 67 caggaggatt gatatccttc atgctgct 28 <210> SEQ ID NO 68 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic probe - pDH7 <400> SEQUENCE: 68 cttacctagc ctaggttttg tatgagagtc 30 <210> SEQ ID NO 69 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic probe - pDH8 <400> SEQUENCE: 69 gacaaaccac aattggaatg cactcgag 28 <210> SEQ ID NO 70 <211> LENGTH: 829 <212> TYPE: DNA <213> ORGANISM: Porcine <400> SEQUENCE: 70 ctgccagcct aagccacagc cacagcaacg ctgggtctga gccatgtctg cagcctatgc 60 cagagctccc cgcagcgccg gatgcttaac ccactgagca aggccaggga ttgaaccctc 120 gtcctcatgg atagcagttg agttgtttcc acggaactct taggggaact cctgattatt 180 ttttatttaa atttatattt ctctgacttt ttcgtgtgct catcagccac tgactgtgta 240 tctccattag tcatggtttg ttaactctgt cattcaaacc ctcttcatcc ttgctacgca 300 gataacatca ttataataaa atcgtgcctg aagaccagtg acgcccccaa gctaagttac 360 tgcttcccct ggggggaaaa agaagcaccg cgcgggcgct gacacgaagt ccgggcagag 420 gaagacgggg cagaggaaga cgggggagca gtgggagcag cgggcagggc gcgggaagca 480 ctggggatgt tccgcgttgg caggagggtg ttgggcgagc tcccggtgat gcagggggga 540 ggagcctttt ccgaagtagc gggacaagag ccacgggaag gaactgttct gagttcccag 600 tcccgacgtc ctggcagcgc ccaggcactg ttattggtgc ctcctgtgtc cacgcgcttc 660 ccggccaggc agccctggcg gatcctattt tctgttcccc cgattctggt acctctccct 720 cccgccctcg gtgcgcagcc gtcctcctgc agtgcctgct cctccagggg cgaaaccgat 780 cagggatcag gccacccgcc tcctgaacat ccctccttag ttcccacag 829

Patent applications by Chihiro Koike, Pittsburgh, PA US

Patent applications in class Swine

Patent applications in all subclasses Swine

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Patent application title: PORCINE CMP-N-ACETYLNEURAMINIC ACID HYDROXYLASE GENE

Inventors: Chihiro Koike (Pittsburgh, PA, US)
IPC8 Class: AA01K67027FI
USPC Class: 800 17
Class name: Swine
Publication date: 02/19/2009
Patent application number: 20090049562

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Patent application title: PORCINE CMP-N-ACETYLNEURAMINIC ACID HYDROXYLASE GENE

Inventors: Chihiro Koike (Pittsburgh, PA, US) IPC8 Class: AA01K67027FI USPC Class: 800 17 Class name: Swine Publication date: 02/19/2009 Patent application number: 20090049562

Abstract:

Claims:

Description:

Inventors: Chihiro Koike (Pittsburgh, PA, US)
IPC8 Class: AA01K67027FI
USPC Class: 800 17
Class name: Swine
Publication date: 02/19/2009
Patent application number: 20090049562