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Publication numberUS20080026457 A1
Publication typeApplication
Application numberUS 11/789,961
Publication dateJan 31, 2008
Filing dateApr 26, 2007
Priority dateOct 22, 2004
Publication number11789961, 789961, US 2008/0026457 A1, US 2008/026457 A1, US 20080026457 A1, US 20080026457A1, US 2008026457 A1, US 2008026457A1, US-A1-20080026457, US-A1-2008026457, US2008/0026457A1, US2008/026457A1, US20080026457 A1, US20080026457A1, US2008026457 A1, US2008026457A1
InventorsKevin Wells, David Ayares
Original AssigneeKevin Wells, David Ayares
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Ungulates with genetically modified immune systems
US 20080026457 A1
Abstract
The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.
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Claims(1)
1. A targeting vector comprising: (a) a first nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31; (b) a selectable marker gene; and (c) a second nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31, which does not overlap with the first nucleotide sequence.
Description
    FIELD OF THE INVENTION
  • [0001]
    The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.
  • BACKGROUND OF THE INVENTION
  • [0002]
    An antigen is an agent or substance that can be recognized by the body as ‘foreign’. Often it is only one relatively small chemical group of a larger foreign substance which acts as the antigen, for example a component of the cell wall of a bacterium. Most antigens are proteins, though carbohydrates can act as weak antigens. Bacteria, viruses and other microorganisms commonly contain many antigens, as do pollens, dust mites, molds, foods, and other substances. The body reacts to antigens by making antibodies. Antibodies (also called immunoglobulins (Igs)) are proteins that are manufactured by cells of the immune system that bind to an antigen or foreign protein. Antibodies circulate in the serum of blood to detect foreign antigens and constitute the gamma globulin part of the blood proteins. These antibodies interact chemically with the antigen in a highly specific manner, like two pieces of a jigsaw puzzle, forming an antigen/antibody complex, or immune complex. This binding neutralizes or brings about the destruction of the antigen.
  • [0003]
    When a vertebrate first encounters an antigen, it exhibits a primary humoral immune response. If the animal encounters the same antigen after a few days the immune response is more rapid and has a greater magnitude. The initial encounter causes specific immune cell (B-cell) clones to proliferate and differentiate. The progeny lymphocytes include not only effector cells (antibody producing cells) but also clones of memory cells, which retain the capacity to produce both effector and memory cells upon subsequent stimulation by the original antigen. The effector cells live for only a few days. The memory cells live for a lifetime and can be reactivated by a second stimulation with the same antigen. Thus, when an antigen is encountered a second time, its memory cells quickly produce effector cells which rapidly produce massive quantities of antibodies.
  • [0004]
    By exploiting the unique ability of antibodies to interact with antigens in a highly specific manner, antibodies have been developed as molecules that can be manufactured and used for both diagnostic and therapeutic applications. Because of their unique ability to bind to antigenic epitopes, polyclonal and monoclonal antibodies can be used to identify molecules carrying that epitope or can be directed, by themselves or in conjunction with another moiety, to a specific site for diagnosis or therapy. Polyclonal and monoclonal antibodies can be generated against practically any pathogen or biological target. The term polyclonal antibody refers to immune sera that usually contain pathogen-specific antibodies of various isotypes and specificities. In contrast, monoclonal antibodies consist of a single immunoglobulin type, representing one isotype with one specificity.
  • [0005]
    In 1890, Shibasaburo Kitazato and Emil Behring conducted the fundamental experiment that demonstrated immunity can be transmitted from one animal to another by transferring the serum from an immune animal to a non-immune animal. This landmark experiment laid the foundation for the introduction of passive immunization into clinical practice. However, wide scale serum therapy was largely abandoned in the 1940s because of the toxicity associated with the administration of heterologous sera and the introduction of effective antimicrobial chemotherapy. Currently, such polyclonal antibody therapy is indicated to treat infectious diseases in relatively few situations, such as replacement therapy in immunoglobulin-deficient patients, post-exposure prophylaxis against several viruses (e.g., rabies, measles, hepatitis A and B, varicella), and toxin neutralization (diphtheria, tetanus, and botulism). Despite the limited use of serum therapy, in the United States, more than 16 metric tons of human antibodies are required each year for intravenous antibody therapy. Comparable levels of use exist in the economies of most highly industrialized countries, and the demand can be expected to grow rapidly in developing countries. Currently, human antibody for passive immunization is obtained from the pooled serum of donors. Thus, there is an inherent limitation in the amount of human antibody available for therapeutic and prophylactic therapies.
  • [0006]
    The use of antibodies for passive immunization against biological warfare agents represents a very promising defense strategy. The final line of defense against such agents is the immune system of the exposed individual. Current defense strategies against biological weapons include such measures as enhanced epidemiologic surveillance, vaccination, and use of antimicrobial agents. Since the potential threat of biological warfare and bioterrorism is inversely proportional to the number of immune persons in the targeted population, biological agents are potential weapons only against populations with a substantial proportion of susceptible persons.
  • [0007]
    Vaccination can reduce the susceptibility of a population against specific threats; provided that a safe vaccine exists that can induce a protective response. Unfortunately, inducing a protective response by vaccination may take longer than the time between exposure and onset of disease. Moreover, many vaccines require multiple doses to achieve a protective immune response, which would limit their usefulness in an emergency to provide rapid prophylaxis after an attack. In addition, not all vaccine recipients mount a protective response, even after receiving the recommended immunization schedule.
  • [0008]
    Drugs can provide protection when administered after exposure to certain agents, but none are available against many potential agents of biological warfare. Currently, no small-molecule drugs are available that prevent disease following exposure to preformed toxins. The only currently available intervention that could provide a state of immediate immunity is passive immunization with protective antibody (Arturo Casadevall “Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons” from Emerging Infectious Diseases, Posted Sep. 12, 2002).
  • [0009]
    In addition to providing protective immunity, modern antibody-based therapies constitute a potentially useful option against newly emergent pathogenic bacteria, fungi, virus and parasites (A. Casadevall and M. D. Scharff, Clinical Infectious Diseases 1995; 150). Therapies of patients with malignancies and cancer (C. Botti et al, Leukemia 1997; Suppl 2:S55-59; B. Bodey, S. E. Siegel, and H. E. Kaiser, Anticancer Res 1996; 16(2):661), therapy of steroid resistant rejection of transplanted organs as well as autoimmune diseases can also be achieved through the use of monoclonal or polyclonal antibody preparations (N. Bonnefoy-Berard and J. P. Revillard, J Heart Lung Transplant 1996; 15(5):435-442; C. Colby, et al Ann Pharmacother 1996; 30(10):1164-1174; M. J. Dugan, et al, Ann Hematol 1997; 75(1-2):41 2; W. Cendrowski, Boll Ist Sieroter Milan 1997; 58(4):339-343; L. K. Kastrukoff, et al Can J Neurol Sci 1978; 5(2):175178; J. E. Walker et al J Neurol Sci 1976; 29(2-4):303309).
  • [0010]
    Recent advances in the technology of antibody production provide the means to generate human antibody reagents, while avoiding the toxicities associated with human serum therapy. The advantages of antibody-based therapies include versatility, low toxicity, pathogen specificity, enhancement of immune function, and favorable pharmacokinetics.
  • [0011]
    The clinical use of monoclonal antibody therapeutics has just recently emerged. Monoclonal antibodies have now been approved as therapies in transplantation, cancer, infectious disease, cardiovascular disease and inflammation. In many more monoclonal antibodies are in late stage clinical trials to treat a broad range of disease indications. As a result, monoclonal antibodies represent one of the largest classes of drugs currently in development.
  • [0012]
    Despite the recent popularity of monoclonal antibodies as therapeutics, there are some obstacles for their use. For example, many therapeutic applications for monoclonal antibodies require repeated administrations, especially for chronic diseases such as autoimmunity or cancer. Because mice are convenient for immunization and recognize most human antigens as foreign, monoclonal antibodies against human targets with therapeutic potential have typically been of murine origin. However, murine monoclonal antibodies have inherent disadvantages as human therapeutics. For example, they require more frequent dosing to maintain a therapeutic level of monoclonal antibodies because of a shorter circulating half-life in humans than human antibodies. More critically, repeated administration of murine immunoglobulin creates the likelihood that the human immune system will recognize the mouse protein as foreign, generating a human anti-mouse antibody response, which can cause a severe allergic reaction. This possibility of reduced efficacy and safety has lead to the development of a number of technologies for reducing the immunogenicity of murine monoclonal antibodies.
  • [0013]
    Polyclonal antibodies are highly potent against multiple antigenic targets. They have the unique ability to target and kill a plurality of “evolving targets” linked with complex diseases. Also, of all drug classes, polyclonals have the highest probability of retaining activity in the event of antigen mutation. In addition, while monoclonals have limited therapeutic activity against infectious agents, polyclonals can both neutralize toxins and direct immune responses to eliminate pathogens, as well as biological warfare agents.
  • [0014]
    The development of polyclonal and monoclonal antibody production platforms to meet future demand for production capacity represents a promising area that is currently the subject of much research. One especially promising strategy is the introduction of human immunoglobulin genes into mice or large domestic animals. An extension of this technology would include inactivation of their endogenous immunoglobulin genes. Large animals, such as sheep, pigs and cattle, are all currently used in the production of plasma derived products, such as hyperimmune serum and clotting factors, for human use. This would support the use of human polyclonal antibodies from such species on the grounds of safety and ethics. Each of these species naturally produces considerable quantities of antibody in both serum and milk.
  • [0000]
    Arrangement of Genes Encoding Immunoglobulins
  • [0015]
    Antibody molecules are assembled from combinations of variable gene elements, and the possibilities resulting from combining the many variable gene elements in the germline enable the host to synthesize antibodies to an extraordinarily large number of antigens. Each antibody molecule consists of two classes of polypeptide chains, light (L) chains (that can be either kappa (κ) L-chain or lambda (λ) L-chain) and heavy (H) chains. The heavy and light chains join together to define a binding region for the epitope. A single antibody molecule has two identical copies of the L chain and two of the H chain. Each of the chains is comprised of a variable region (V) and a constant region (C). The variable region constitutes the antigen-binding site of the molecule. To achieve diverse antigen recognition, the DNA that encodes the variable region undergoes gene rearrangement. The constant region amino acid sequence is specific for a particular isotype of the antibody, as well as the host which produces the antibody, and thus does not undergo rearrangement.
  • [0016]
    The mechanism of DNA rearrangement is similar for the variable region of both the heavy- and light-chain loci, although only one joining event is needed to generate a light-chain gene whereas two are needed to generate a complete heavy-chain gene. The most common mode of rearrangement involves the looping-out and deletion of the DNA between two gene segments. This occurs when the coding sequences of the two gene segments are in the same orientation in the DNA. A second mode of recombination can occur between two gene segments that have opposite transcriptional orientations. This mode of recombination is less common, although such rearrangements can account for up to half of all Vκ to Jκ joins; the transcriptional orientation of half of the human Vκ gene segments is opposite to that of the Jκ gene segments.
  • [0017]
    The DNA sequence encoding a complete V region is generated by the somatic recombination of separate gene segments. The V region, or V domain, of an immunoglobulin heavy or light chain is encoded by more than one gene segment. For the light chain, the V domain is encoded by two separate DNA segments. The first segment encodes the first 95-101 amino acids of the light chain and is termed a V gene segment because it encodes most of the V domain. The second segment encodes the remainder of the V domain (up to 13 amino acids) and is termed a joining or J gene segment. The joining of a V and a J gene segment creates a continuous exon that encodes the whole of the light-chain V region. To make a complete immunoglobulin light-chain messenger RNA, the V-region exon is joined to the C-region sequence by RNA splicing after transcription.
  • [0018]
    A heavy-chain V region is encoded in three gene segments. In addition to the V and J gene segments (denoted VH and JH to distinguish them from the light-chain VL and JL), there is a third gene segment called the diversity or DH gene segment, which lies between the VH and JH gene segments. The process of recombination that generates a complete heavy-chain V region occurs in two separate stages. In the first, a DH gene segment is joined to a JH gene segment; then a VH gene segment rearranges to DJH to make a complete VH-region exon. As with the light-chain genes, RNA splicing joins the assembled V-region sequence to the neighboring C-region gene.
  • [0019]
    Diversification of the antibody repertoire occurs in two stages: primarily by rearrangement (“V(D)J recombination”) of Ig V, D and J gene segments in precursor B cells resident in the bone marrow, and then by somatic mutation and class switch recombination of these rearranged Ig genes when mature B cells are activated. Immunoglobulin somatic mutation and class switching are central to the maturation of the immune response and the generation of a “memory” response.
  • [0020]
    The genomic loci of antibodies are very large and they are located on different chromosomes. The immunoglobulin gene segments are organized into three clusters or genetic loci: the κ, λ, and heavy-chain loci. Each is organized slightly differently. For example, in humans, immunoglobulin genes are organized as follows. The λ light-chain locus is located on chromosome 22 and a cluster of Vλ gene segments is followed by four sets of Jλ gene segments each linked to a single Cλ gene. The κ light-chain locus is on chromosome 2 and the cluster of Vκ, gene segments is followed by a cluster of Jκ gene segments, and then by a single Cκ gene. The organization of the heavy-chain locus, on chromosome 14, resembles that of the κ locus, with separate clusters of VH, DH, and JH gene segments and of CH genes. The heavy-chain locus differs in one important way: instead of a single C-region, it contains a series of C regions arrayed one after the other, each of which corresponds to a different isotype. There are five immunoglobulin heavy chain isotypes: IgM, IgG, IgA, IgE and IgD. Generally, a cell expresses only one at a time, beginning with IgM. The expression of other isotypes, such as IgG, can occur through isotype switching.
  • [0021]
    The joining of various V, D and J genes is an entirely random event that results in approximately 50,000 different possible combinations for VDJ(H) and approximately 1,000 for VJ(L). Subsequent random pairing of H and L chains brings the total number of antibody specificities to about 107 possibilities. Diversity is further increased by the imprecise joining of different genetic segments. Rearrangements occur on both DNA strands, but only one strand is transcribed (due to allelic exclusion). Only one rearrangement occurs in the life of a B cell because of irreversible deletions in DNA. Consequently, each mature B cell maintains one immunologic specificity and is maintained in the progeny or clone. This constitutes the molecular basis of the clonal selection; i.e., each antigenic determinant triggers the response of the pre-existing clone of B lymphocytes bearing the specific receptor molecule. The primary repertoire of B cells, which is established by V(D)J recombination, is primarily controlled by two closely linked genes, recombination activating gene (RAG)-1 and RAG-2.
  • [0022]
    Over the last decade, considerable diversity among vertebrates in both Ig gene diversity and antibody repertoire development has been revealed. Rodents and humans have five heavy chain classes, IgM, IgD, IgG, IgE and IgA, and each have four subclasses of IgG and one or two subclasses of IgA, while rabbits have a single IgG heavy chain gene but 13 genes for different IgA subclasses (Burnett, R. C et al. EMBO J. 8:4047; Honjo, In Honjo, T, Alt. F. W. T. H. eds, Immunoglobulin Genes p. 123 Academic Press, New York). Swine have at least six IgG subclasses (Kacskovics, I et al. 1994 J Immunol 153:3565), but no IgD (Butler et al. 1996 Inter. Immunol 8:1897-1904). A gene encoding IgD has only been described in rodents and primates. Diversity in the mechanism of repertoire development is exemplified by contrasting the pattern seen in rodents and primates with that reported for chickens, rabbits, swine and the domesticated Bovidae. Whereas the former group have a large number of VH genes belonging to seven to 10 families (Rathbun, G. In Hongo, T. Alt. F. W. and Rabbitts, T. H., eds, Immunoglobulin Genes, p. 63, Academic press New York), the VH genes of each member of the latter group belong to a single VH gene family (Sun, J. et al. 1994 J. Immunol. 1553:56118; Dufour, V et al. 1996, J Immunol. 156:2163). With the exception of the rabbit, this family is composed of less than 25 genes. Whereas rodents and primates can utilize four to six JH segments, only a single JH is available for repertoire development in the chicken (Reynaud et al. 1989 Adv. Immunol. 57:353). Similarly, Butler et al. (1996 Inter. Immunol 8:1897-1904) hypothesized that swine may resemble the chicken in having only a single JH gene. These species generally have fewer V, D and J genes; in the pig and cow a single VH gene family exists, consisting of less than 20 gene segments (Butler et al, Advances in Swine in Biomedical Research, eds: Tumbleson and Schook, 1996; Sinclair et al, J. Immunol. 159: 3883, 1997). Together with lower numbers of J and D gene segments, this results in significantly less diversity being generated by gene rearrangement. However, there does appear to be greater numbers of light chain genes in these species. Similar to humans and mice, these species express a single κ light chain but multiple λ light chain genes. However, these do not seem to affect the restricted diversity that is achieved by rearrangement.
  • [0023]
    Since combinatorial joining of more than 100 VH, 20-30 DH and four to six JH gene segments is a major mechanism of generating the antibody repertoire in humans, species with fewer VH, DH or JH segments must either generate a smaller repertoire or use alternative mechanisms for repertoire development. Ruminants, pigs, rabbits and chickens, utilize several mechanisms to generate antibody diversity. In these species there appears to be an important secondary repertoire development, which occurs in highly specialized lymphoid tissue such as ileal Peyer's patches (Binns and Licence, Adv. Exp. Med. Biol. 186: 661, 1985). Secondary repertoire development occurs in these species by a process of somatic mutation which is a random and not fully understood process. The mechanism for this repertoire diversification appears to be templated mutation, or gene conversion (Sun et al, J. Immunol. 153: 5618, 1994) and somatic hypermutation.
  • [0024]
    Gene conversion is important for antibody diversification in some higher vertebrates, such as chickens, rabbits and cows. In mice, however, conversion events appear to be infrequent among endogenous antibody genes. Gene conversion is a distinct diversifying mechanism characterized by transfers of homologous sequences from a donor antibody V gene segment to an acceptor V gene segment. If donor and acceptor segments have numerous sequence differences then gene conversion can introduce a set of sequence changes into a V region by a single event. Depending on the species, gene conversion events can occur before and/or after antigen exposure during B cell differentiation (Tsai et al. International Immunology, Vol. 14, No. 1, 55-64, January 2002).
  • [0025]
    Somatic hypermutation achieves diversification of antibody genes in all higher vertebrate species. It is typified by the introduction of single point mutations into antibody V(D)J segments. Generally, hypermutation appears to be activated in B cells by antigenic stimulation.
  • [0000]
    Production of Animals with Humanized Immune Systems
  • [0026]
    In order to reduce the immunogenicity of antibodies generated in mice for human therapeutics, various attempts have been made to replace murine protein sequences with human protein sequences in a process now known as humanization. Transgenic mice have been constructed which have had their own immunoglobulin genes functionally replaced with human immunoglobulin genes so that they produce human antibodies upon immunization. Elimination of mouse antibody production was achieved by inactivation of mouse Ig genes in embryonic stem (ES) cells by using gene-targeting technology to delete crucial cis-acting sequences involved in the process of mouse Ig gene rearrangement and expression. B cell development in these mutant mice could be restored by the introduction of megabase-sized YACs containing a human germline-configuration H- and κ L-chain minilocus transgene. The expression of fully human antibody in these transgenic mice was predominant, at a level of several 100 μg/l of blood. This level of expression is several hundred-fold higher than that detected in wild-type mice expressing the human Ig gene, indicating the importance of inactivating the endogenous mouse Ig genes in order to enhance human antibody production by mice.
  • [0027]
    The first humanization attempts utilized molecular biology techniques to construct recombinant antibodies. For example, the complementarity determining regions (CDR) from a mouse antibody specific for a hapten were grafted onto a human antibody framework, effecting a CDR replacement. The new antibody retained the binding specificity conveyed by the CDR sequences (P. T. Jones et al. Nature 321: 522-525 (1986)). The next level of humanization involved combining an entire mouse VH region with a human constant region such as gamma1 (S. L. Morrison et al., Proc. Natl. Acad. Sci., 81, pp. 6851-6855 (1984)). However, these chimeric antibodies, which still contain greater than 30% xenogeneic sequences, are sometimes only marginally less immunogenic than totally xenogeneic antibodies (M. Bruggemann et al., J. Exp. Med., 170, pp. 2153-2157 (1989)).
  • [0028]
    Subsequently, attempts were carried out to introduce human immunoglobulin genes into the mouse, thus creating transgenic mice capable of responding to antigens with antibodies having human sequences (Bruggemann et al. Proc. Nat'l. Acad. Sci. USA 86:6709-6713 (1989)). Due to the large size of human immunoglobulin genomic loci, these attempts were thought to be limited by the amount of DNA, which could be stably maintained by available cloning vehicles. As a result, many investigators concentrated on producing mini-loci containing limited numbers of V region genes and having altered spatial distances between genes as compared to the natural or germline configuration (See, for example, U.S. Pat. No. 5,569,825). These studies indicated that producing human sequence antibodies in mice was possible, but serious obstacles remained regarding obtaining sufficient diversity of binding specificities and effector functions (isotypes) from these transgenic animals to meet the growing demand for antibody therapeutics.
  • [0029]
    In order to provide additional diversity, work has been conducted to add large germline fragments of the human Ig locus into transgenic mammals. For example, a majority of the human V, D, and J region genes arranged with the same spacing found in the unrearranged germline of the human genome and the human Cμ and Cδ constant regions was introduced into mice using yeast artificial chromosome (YAC) cloning vectors (See, for example, WO 94/02602). A 22 kb DNA fragment comprising sequences encoding a human gamma-2 constant region and the upstream sequences required for class-switch recombination was latter appended to the foregoing transgene. In addition, a portion of a human kappa locus comprising Vκ, Jκ and Cκ region genes, also arranged with substantially the same spacing found in the unrearranged germline of the human genome, was introduced into mice using YACS. Gene targeting was used to inactivate the murine IgH & kappa light chain immunoglobulin gene loci and such knockout strains were bred with the above transgenic strains to generate a line of mice having the human V, D, J, Cμ, Cδ and Cγ2 constant regions as well as the human Vκ, Jκ and Cκ region genes all on an inactivated murine immunoglobulin background (See, for example, PCT patent application WO 94/02602 to Kucherlapati et al.; see also Mendez et al., Nature Genetics 15:146-156 (1997)).
  • [0030]
    Yeast artificial chromosomes as cloning vectors in combination with gene targeting of endogenous loci and breeding of transgenic mouse strains provided one solution to the problem of antibody diversity. Several advantages were obtained by this approach. One advantage was that YACs can be used to transfer hundreds of kilobases of DNA into a host cell. Therefore, use of YAC cloning vehicles allows inclusion of substantial portions of the entire human Ig heavy and light chain regions into a transgenic mouse thus approaching the level of potential diversity available in the human. Another advantage of this approach is that the large number of V genes has been shown to restore full B cell development in mice deficient in murine immunoglobulin production. This ensures that these reconstituted mice are provided with the requisite cells for mounting a robust human antibody response to any given immunogen. (See, for example, WO 94/02602; L. Green and A. Jakobovits, J. Exp. Med. 188:483-495 (1998)). A further advantage is that sequences can be deleted or inserted onto the YAC by utilizing high frequency homologous recombination in yeast. This provides for facile engineering of the YAC transgenes.
  • [0031]
    In addition, Green et al. Nature Genetics 7:13-21 (1994) describe the generation of YACs containing 245 kb and 190 kb-sized germline configuration fragments of the human heavy chain locus and kappa light chain locus, respectively, which contained core variable and constant region sequences. The work of Green et al. was recently extended to the introduction of greater than approximately 80% of the human antibody repertoire through introduction of megabase sized, germline configuration YAC fragments of the human heavy chain loci and kappa light chain loci, respectively, to produce XenoMouse™ mice. See, for example, Mendez et al. Nature Genetics 15:146-156 (1997), Green and Jakobovits J. Exp. Med. 188:483-495 (1998), European Patent No. EP 0 463 151 B1, PCT Publication Nos. WO 94/02602, WO 96/34096 and WO 98/24893.
  • [0032]
    Several strategies exist for the generation of mammals that produce human antibodies. In particular, there is the “minilocus” approach that is typified by work of GenPharm International, Inc. and the Medical Research Council, YAC introduction of large and substantially germline fragments of the Ig loci that is typified by work of Abgenix, Inc. (formerly Cell Genesys). The introduction of entire or substantially entire loci through the use microcell fusion as typified by work of Kirin Beer Kabushiki Kaisha.
  • [0033]
    In the minilocus approach, an exogenous Ig locus is mimicked through the inclusion of pieces (individual genes) from the Ig locus. Thus, one or more VH genes, one or more DH genes, one or more JH genes, a mu constant region, and a second constant region (such as a gamma constant region) are formed into a construct for insertion into an animal. See, for example, U.S. Pat. Nos. 5,545,807, 5,545,806, 5,625,825, 5,625,126, 5,633,425, 5,661,016, 5,770,429, 5,789,650, 5,814,318, 5,591,669, 5,612,205, 5,721,367, 5,789,215, 5,643,763; European Patent No. 0 546 073; PCT Publication Nos. WO 92/03918, WO 92/22645, WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO 96/14436, WO 97/13852, and WO 98/24884; Taylor et al. Nucleic Acids Research 20:6287-6295 (1992), Chen et al. International Immunology 5:647-656 (1993), Tuaillon et al. J. Immunol. 154:6453-6465 (1995), Choi et al. Nature Genetics 4:117-123 (1993), Lonberg et al. Nature 368:856-859 (1994), Taylor et al. International Immunology 6:579-591 (1994), Tuaillon et al. J. Immunol. 154:6453-6465 (1995), and Fishwild et al. Nature Biotech. 14:845-851 (1996).
  • [0034]
    In the microcell fusion approach, portions or whole human chromosomes can be introduced into mice (see, for example, European Patent Application No. EP 0 843 961 A1). Mice generated using this approach and containing the human Ig heavy chain locus will generally possess more than one, and potentially all, of the human constant region genes. Such mice will produce, therefore, antibodies that bind to particular antigens having a number of different constant regions.
  • [0035]
    While mice remain the most developed animal for the expression of human immunoglobulins in humans, recent technological advances have allowed for progress to begin in applying these techniques to other animals, such as cows. The general approach in mice has been to genetically modify embryonic stem cells of mice to knock-out murine immunoglobulins and then insert YACs containing human immunoglobulins into the ES cells. However, ES cells are not available for cows or other large animals such as sheep and pigs. Thus, several fundamental developments had to occur before even the possibility existed to generate large animals with immunoglobulin genes knocked-out and that express human antibody. The alternative to ES cell manipulation to create genetically modified animals is cloning using somatic cells that have been genetically modified. Cloning using genetically modified somatic cells for nuclear transfer has only recently been accomplished.
  • [0036]
    Since the announcement of Dolly's (a cloned sheep) birth from an adult somatic cell in 1997 (Wilmut, I., et al (1997) Nature 385: 810-813), ungulates, including cattle (Cibelli, J et al 1998 Science 280: 1266-1258; Kubota, C. et al. 2000 Proc. Nat'l. Acad. Sci. 97: 990-995), goats (Baguisi, A. et al., (1999) Nat. Biotechnology 17: 456-461), and pigs (Polejaeva, I. A., et al. 2000 Nature 407: 86-90; Betthauser, J. et al. 2000 Nat. Biotechnology 18: 1055-1059) have been cloned.
  • [0037]
    The next technological advance was the development of the technique to genetically modify the cells prior to nuclear transfer to produce genetically modified animals. PCT publication No. WO 00/51424 to PPL Therapeutics describes the targeted genetic modification of somatic cells for nuclear transfer.
  • [0038]
    Subsequent to these fundamental developments, single and double allele knockouts of genes and the birth of live animals with these modifications have been reported. Between 2002 and 2004, three independent groups, Immerge Biotherapeutics, Inc. in collaboration with the University of Missouri (Lai et al. (Science (2002) 295: 1089-1092) & Kolber-Simonds et al. (PNAS. (2004) 101(19):7335-40)), Alexion Pharmaceuticals (Ramsoondar et al. (Biol Reprod (2003)69: 437-445) and Revivicor, Inc. (Dai et al. (Nature Biotechnology (2002) 20: 251-255) & Phelps et al. (Science (2003) January 17; 299(5605):411-4)) produced pigs that lacked one allele or both alleles of the alpha-1,3-GT gene via nuclear transfer from somatic cells with targeted genetic deletions. In 2003, Sedai et al. (Transplantation (2003) 76:900-902) reported the targeted disruption of one allele of the alpha-1,3-GT gene in cattle, followed by the successful nuclear transfer of the nucleus of the genetically modified cell and production of transgenic fetuses.
  • [0039]
    Thus, the feasibility of knocking-out immunoglobulin genes in large animals and inserting human immunoglobulin loci into their cells is just now beginning to be explored. However, due to the complexity and species differences of immunoglobulin genes, the genomic sequences and arrangement of Ig kappa, lambda and heavy chains remain poorly understood in most species. For example, in pigs, partial genomic sequence and organization has only been described for heavy chain constant alpha, heavy chain constant mu and heavy chain constant delta (Brown and Butler Mol Immunol. 1994 June; 31(8):633-42, Butler et al Vet Immunol Immunopathol. 1994 October; 43(1-3):5-12, and Zhao et al J Immunol. 2003 Aug. 1; 171(3):1312-8).
  • [0040]
    In cows, the immunoglobulin heavy chain locus has been mapped (Zhao et al. 2003 J. Biol. Chem. 278:35024-32) and the cDNA sequence for the bovine kappa gene is known (See, for example, U.S. Patent Publication No. 2003/0037347). Further, approximately 4.6 kb of the bovine mu heavy chain locus has been sequenced and transgenic calves with decreased expression of heavy chain immunoglobulins have been created by disrupting one or both alleles of the bovine mu heavy chain. In addition, a mammalian artificial chromosome (MAC) vector containing the entire unarranged sequences of the human Ig H-chain and κ L-chain has been introduced into cows (TC cows) with the technology of microcell-mediated chromosome transfer and nuclear transfer of bovine fetal fibroblast cells (see, for example, Kuroiwa et al. 2002 Nature Biotechnology 20:889, Kuroiwa et al. 2004 Nat Genet. June 6 Epub, U.S. Patent Publication Nos. 2003/0037347, 2003/0056237, 2004/0068760 and PCT Publication No. WO 02/07648).
  • [0041]
    While significant progress has been made in the production of bovine that express human immunoglobulin, little has been accomplished in other large animals, such as sheep, goats and pigs. Although cDNA sequence information for immunoglobulin genes of sheeps, goats and pigs is readily available in Genbank, the unique nature of immunoglobulin loci, which undergo massive rearrangements, creates the need to characterize beyond sequences known to be present in mRNAs (or cDNAs). Since immunoglobulin loci are modular and the coding regions are redundant, deletion of a known coding region does not ensure altered function of the locus. For example, if one were to delete the coding region of a heavy-chain variable region, the function of the locus would not be significantly altered because hundreds of other function variable genes remain in the locus. Therefore, one must first characterize the locus to identify a potential “Achilles heel”.
  • [0042]
    Despite some advancements in expressing human antibodies in cattle, greater challenges remain for inactivation of the endogenous bovine Ig genes, increasing expression levels of the human antibodies and creating human antibody expression in other large animals, such as porcine, for which the sequence and arrangement of immunoglobulin genes are largely unknown.
  • [0043]
    It is therefore an object of the present invention to provide the arrangement of ungulate immunoglobin germline gene sequence.
  • [0044]
    It is another object of the present invention to provide novel ungulate immunoglobulin genomic sequences.
  • [0045]
    It is a further object of the present invention to provide cells, tissues and animals lacking at least one allele of a heavy and/or light chain immunoglobulin gene.
  • [0046]
    It is another object of the present invention to provide ungulates that express human immunoglobulins.
  • [0047]
    It is a still further object of the present invention to provide methods to generate cells, tissues and animals lacking at least one allele of novel ungulate immunoglobulin gene sequences and/or express human immunoglobulins.
  • SUMMARY OF THE INVENTION
  • [0048]
    The present invention provides for the first time ungulate immunoglobin germline gene sequence arrangement as well as novel genomic sequences thereof. In addition, novel ungulate cells, tissues and animals that lack at least one allele of a heavy or light chain immunoglobulin gene are provided. Based on this discovery, ungulates can be produced that completely lack at least one allele of a heavy and/or light chain immunoglobulin gene. In addition, these ungulates can be further modified to express xenoogenous, such as human, immunoglobulin loci or fragments thereof.
  • [0049]
    In one aspect of the present invention, a transgenic ungulate that lacks any expression of functional endogenous immunoglobulins is provided. In one embodiment, the ungulate can lack any expression of endogenous heavy and/or light chain immunoglobulins. The light chain immunoglobulin can be a kappa and/or lambda immunoglobulin. In additional embodiments, transgenic ungulates are provided that lack expression of at least one allele of an endogenous immunoglobulin wherein the immunoglobulin is selected from the group consisting of heavy chain, kappa light chain and lambda light chain or any combination thereof. In one embodiment, the expression of functional endogenous immunoglobulins can be accomplished by genetic targeting of the endogenous immunoglobulin loci to prevent expression of the endogenous immunoglobulin. In one embodiment, the genetic targeting can be accomplished via homologous recombination. In another embodiment, the transgenic ungulate can be produced via nuclear transfer.
  • [0050]
    In other embodiments, the transgenic ungulate that lacks any expression of functional endogenous immunoglobulins can be further genetically modified to express an xenogenous immunoglobulin loci. In an alternative embodiment, porcine animals are provided that contain an xenogeous immunoglobulin locus. In one embodiment, the xenogeous immunoglobulin loci can be a heavy and/or light chain immunoglobulin or fragment thereof. In another embodiment, the xenogenous immunoglobulin loci can be a kappa chain locus or fragment thereof and/or a lambda chain locus or fragment thereof. In still further embodiments, an artificial chromosome (AC) can contain the xenogenous immunoglobulin. In one embodiment, the AC can be a yeast AC or a mammalian AC. In a further embodiment, the xenogenous locus can be a human immunoglobulin locus or fragment thereof. In one embodiment, the human immunoglobulin locus can be human chromosome 14, human chromosome 2, and human chromosome 22 or fragments thereof. In another embodiment, the human immunoglobulin locus can include any fragment of a human immunoglobulin that can undergo rearrangement. In a further embodiment, the human immunoglobulin loci can include any fragment of a human immunoglobulin heavy chain and a human immunoglobulin light chain that can undergo rearrangement. In still further embodiment, the human immunoglobulin loci can include any human immunoglobulin locus or fragment thereof that can produce an antibody upon exposure to an antigen. In a particular embodiment, the exogenous human immunoglobulin can be expressed in B cells to produce xenogenous immunoglobulin in response to exposure to one or more antigens.
  • [0051]
    In another aspect of the present invention, transgenic ungulates are provided that expresses a xenogenous immunoglobulin loci or fragment thereof, wherein the immunoglobulin can be expressed from an immunoglobulin locus that is integrated within an endogenous ungulate chromosome. In one embodiment, ungulate cells derived from the transgenic animals are provided. In one embodiment, the xenogenous immunoglobulin locus can be inherited by offspring. In another embodiment, the xenogenous immunoglobulin locus can be inherited through the male germ line by offspring. In still further embodiments, an artificial chromosome (AC) can contain the xenogenous immunoglobulin. In one embodiment, the AC can be a yeast AC or a mammalian AC. In a further embodiment, the xenogenous locus can be a human immunoglobulin locus or fragment thereof. In one embodiment, the human immunoglobulin locus can be human chromosome 14, human chromosome 2, and human chromosome 22 or fragments thereof. In another embodiment, the human immunoglobulin locus can include any fragment of a human immunoglobulin that can undergo rearrangement. In a further embodiment, the human immunoglobulin loci can include any fragment of a human immunoglobulin heavy chain and a human immunoglobulin light chain that can undergo rearrangement. In still further embodiment, the human immunoglobulin loci can include any human immunoglobulin locus or fragment thereof that can produce an antibody upon exposure to an antigen. In a particular embodiment, the exogenous human immunoglobulin can be expressed in B cells to produce xenogenous immunoglobulin in response to exposure to one or more antigens.
  • [0052]
    In another aspect of the present invention, novel genomic sequences encoding the heavy chain locus of ungulate immunoglobulin are provided. In one embodiment, an isolated nucleotide sequence encoding porcine heavy chain is provided that includes at least one variable region, two diversity regions, at least four joining regions and at least one constant region, such as the mu constant region, for example, as represented in Seq ID No. 29. In another embodiment, an isolated nucleotide sequence is provided that includes at least four joining regions and at least one constant region, such as the mu constant region, of the porcine heavy chain genomic sequence, for example, as represented in Seq ID No. 4. In a further embodiment, nucleotide sequence is provided that includes 5′ flanking sequence to the first joining region of the porcine heavy chain genomic sequence, for example, as represented in Seq ID No 1. Still further, nucleotide sequence is provided that includes 3′ flanking sequence to the first joining region of the porcine heavy chain genomic sequence, for example, as represented in the 3′ region of Seq ID No 4. In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 1, 4 or 29 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 1, 4 or 29 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 1, 4 or 29 are provided. In one embodiment, the nucleotide sequence contains at least 17, 20, 25 or 30 contiguous nucleotides of Seq ID No 4 or residues 1-9,070 of Seq ID No 29. In another embodiment, the nucleotide sequence contains residues 9,070-11039 of Seq ID No 29. Further provided are nucleotide sequences that hybridize, optionally under stringent conditions, to Seq ID Nos 1, 4 or 29, as well as, nucleotides homologous thereto.
  • [0053]
    In another embodiment, novel genomic sequences encoding the kappa light chain locus of ungulate immunoglobulin are provided. The present invention provides the first reported genomic sequence of ungulate kappa light chain regions. In one embodiment, nucleic acid sequence is provided that encodes the porcine kappa light chain locus. In another embodiment, the nucleic acid sequence can contain at least one joining region, one constant region and/or one enhancer region of kappa light chain. In a further embodiment, the nucleotide sequence can include at least five joining regions, one constant region and one enhancer region, for example, as represented in Seq ID No. 30. In a further embodiment, an isolated nucleotide sequence is provided that contains at least one, at least two, at least three, at least four or five joining regions and 3′ flanking sequence to the joining region of porcine genomic kappa light chain, for example, as represented in Seq ID No 12. In another embodiment, an isolated nucleotide sequence of porcine genomic kappa light chain is provided that contains 5′ flanking sequence to the first joining region, for example, as represented in Seq ID No 25. In a further embodiment, an isolated nucleotide sequence is provided that contains 3′ flanking sequence to the constant region and, optionally, the 5′ portion of the enhancer region, of porcine genomic kappa light chain, for example, as represented in Seq ID Nos. 15, 16 and/or 19.
  • [0054]
    In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 30, 12, 25, 15, 16 or 19 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 30, 12, 25, 15, 16 or 19 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 30, 12, 25, 15, 16 or 19 are provided. Further provided are nucleotide sequences that hybridizes, optionally under stringent conditions, to Seq ID Nos 30, 12, 25, 15, 16 or 19, as well as, nucleotides homologous thereto.
  • [0055]
    In another embodiment, novel genomic sequences encoding the lambda light chain locus of ungulate immunoglobulin are provided. The present invention provides the first reported genomic sequence of ungulate lambda light chain regions. In one embodiment, the porcine lambda light chain nucleotides include a concatamer of J to C units. In a specific embodiment, an isolated porcine lambda nucleotide sequence is provided, such as that depicted in Seq ID No. 28. In one embodiment, a nucleotide sequence is provided that includes 5′ flanking sequence to the first lambda J/C unit of the porcine lambda light chain genomic sequence, for example, as represented by Seq ID No 32. Still further, nucleotide sequence is provided that includes 3′ flanking sequence to the J/C cluster region of the porcine lambda light chain genomic sequence, for example, approximately 200 base pairs downstream of lambda J/C, such as that represented by Seq ID No 33. Alternatively, nucleotide sequence is provided that includes 3′ flanking sequence to the J/C cluster region of the porcine lambda light chain genomic sequence, for example, as represented by Seq ID No 34, 35, 36, 37, 38, and/or 39.
  • [0056]
    In a further embodiment, nucleic acid sequences are provided that encode bovine lambda light chain locus, which can include at least one joining region-constant region pair and/or at least one variable region, for example, as represented by Seq ID No. 31. In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are provided. Further provided are nucleotide sequences that hybridizes, optionally under stringent conditions, to Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39, as well as, nucleotides homologous thereto.
  • [0057]
    In another embodiment, nucleic acid targeting vector constructs are also provided. The targeting vectors can be designed to accomplish homologous recombination in cells. These targeting vectors can be transformed into mammalian cells to target the ungulate heavy chain, kappa light chain or lambda light chain genes via homologous recombination. In one embodiment, the targeting vectors can contain a 3′ recombination arm and a 5′ recombination arm (i.e. flanking sequence) that is homologous to the genomic sequence of ungulate heavy chain, kappa light chain or lambda light chain genomic sequence, for example, sequence represented by Seq ID Nos. 1, 4, 29, 30, 12, 25, 15, 16, 19, 28 or 31, as described above. 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 genomic sequence.
  • [0058]
    In one embodiment, the 5′ and 3′ recombination arms of the targeting vector can be designed such that they flank the 5′ and 3′ ends of at least one functional variable, joining, diversity, and/or constant region of the genomic sequence. The targeting of a functional region can render it inactive, which results in the inability of the cell to produce functional immunoglobulin molecules. In another embodiment, the homologous DNA sequence can include one or more intron and/or exon sequences. 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. The selectable marker can be located between the 5′ and 3′ recombination arm sequence.
  • [0059]
    In one particular embodiment, the targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 3′ and 5′ flanking sequence of the J6 region of the porcine immunoglobulin heavy chain locus. Since the J6 region is the only functional joining region of the porcine immunoglobulin heavy chain locus, this will prevent the expression of a functional porcine heavy chain immunoglobulin. In a specific embodiment, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the J6 region, including J1-4, and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the J6 region, including the mu constant region (a “J6 targeting construct”), see for example, FIG. 1. Further, this J6 targeting construct can also contain a selectable marker gene that is located between the 5′ and 3′ recombination arms, see for example, Seq ID No 5 and FIG. 1. In other embodiments, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the diversity region, and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the diversity region of the porcine heavy chain locus. In a further embodiment, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the mu constant region and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the mu constant region of the porcine heavy chain locus.
  • [0060]
    In another particular embodiment, the targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 3′ and 5′ flanking sequence of the constant region of the porcine immunoglobulin kappa light chain locus. Since the present invention discovered that there is only one constant region of the porcine immunoglobulin kappa light chain locus, this will prevent the expression of a functional porcine kappa light chain immunoglobulin. In a specific embodiment, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the constant region, optionally including the joining region, and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the constant region, optionally including at least part of the enhancer region (a “Kappa constant targeting construct”), see for example, FIG. 2. Further, this kappa constant targeting construct can also contain a selectable marker gene that is located between the 5′ and 3′ recombination arms, see for example, Seq ID No 20 and FIG. 2. In other embodiments, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the joining region, and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the joining region of the porcine kappa light chain locus.
  • [0061]
    In another particular embodiment, the targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 3′ and 5′ flanking sequence of the J/C region of the porcine lambda light chain. See FIG. 3. Disruption of the J/C region will prevent the expression of a functional porcine kappa light chain immunoglobulin. In one embodiment, the targeting vector can contain a 5′ recombination arm that contains sequence homologous to genomic sequence 5′ of the first J/C unit and a 3′ recombination arm that contains sequence homologous to genomic sequence 3′ of the last J/C unit. Further, this lambda light chain targeting construct can also contain a selectable marker gene that is located between the 5′ and 3′ recombination arms, see for example FIG. 4.
  • [0062]
    In a further embodiment, more than one targeting vector can be used to target the ungulate heavy chain, kappa light chain or lambda light chain genes via homologous recombination. For example, two targeting vectors can be used to target the gene of interest. A first targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 5′ flanking sequence of at least one functional variable, joining, diversity, and/or constant region of the genomic sequence. A second targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 3′ flanking sequence at least one functional variable, joining, diversity, and/or constant region of the genomic sequence.
  • [0063]
    In a particular embodiment, the first targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 5′ flanking sequence of the first J/C unit in the J/C cluster region. See FIG. 5. According to this embodiment, a second targeting vector can contain 5′ and 3′ recombination arms that contain homologous sequence to the 3′ flanking sequence of the last J/C unit in the J/C cluster region. See FIG. 6.
  • [0064]
    In another embodiment, primers are provided to generate 3′ and 5′ sequences of a targeting vector. The oligonucleotide primers can be capable of hybridizing to porcine immunoglobulin genomic sequence, such as Seq ID Nos. 1, 4, 29, 30, 12, 25, 15, 16, 19, 28 or 31, as described above. In a particular embodiment, the primers hybridize under stringent conditions to Seq ID Nos. 1, 4, 29, 30, 12, 25, 15, 16, 19, 28 or 31, as described above. Another embodiment provides oligonucleotide probes capable of hybridizing to porcine heavy chain, kappa light chain or lambda light chain nucleic acid sequences, such as Seq ID Nos. 1, 4, 29, 30, 12, 25, 15, 16, 19, 28 or 31, as described above. The polynucleotide primers or probes can have at least 14 bases, 20 bases, 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 particular embodiment, are at least 15, 20, 25, 28, or 30 nucleotides in length.
  • [0065]
    In one embodiment, primers are provided to amplify a fragment of porcine Ig heavy-chain that includes the functional joining region (the J6 region). In one non-limiting embodiment, the amplified fragment of heavy chain can be represented by Seq ID No 4 and the primers used to amplify this fragment can be complementary to a portion of the J-region, such as, but not limited to Seq ID No 2, to produce the 5′ recombination arm and complementary to a portion of Ig heavy-chain mu constant region, such as, but not limited to Seq ID No 3, to produce the 3′ recombination arm. In another embodiment, regions of the porcine Ig heavy chain (such as, but not limited to Seq ID No 4) can be subcloned and assembled into a targeting vector.
  • [0066]
    In other embodiments, primers are provided to amplify a fragment of porcine Ig kappa light-chain that includes the constant region. In another embodiment, primers are provided to amplify a fragment of porcine Ig kappa light-chain that includes the J region. In one non-limiting embodiment, the primers used to amplify this fragment can be complementary to a portion of the J-region, such as, but not limited to Seq ID No 21 or 10, to produce the 5′ recombination arm and complementary to genomic sequence 3′ of the constant region, such as, but not limited to Seq ID No 14, 24 or 18, to produce the 3′ recombination arm. In another embodiment, regions of the porcine Ig heavy chain (such as, but not limited to Seq ID No 20) can be subcloned and assembled into a targeting vector.
  • [0067]
    In another aspect of the present invention, ungulate cells lacking at least one allele of a functional region of an ungulate heavy chain, kappa light chain and/or lambda light chain locus 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 an ungulate heavy chain, kappa light chain or lambda light chain gene, cells can be produced which have reduced capability for expression of ungulate antibodies. In other embodiments, mammalian cells lacking both alleles of an ungulate heavy chain, kappa light chain and/or lambda light chain gene can be produced according to the process, sequences and/or constructs described herein. In a further embodiment, porcine animals are provided in which at least one allele of an ungulate heavy chain, kappa light chain and/or lambda light chain 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 an ungulate heavy chain, kappa light chain and/or lambda light chain gene are inactivated via a genetic targeting event. The gene can be targeted via homologous recombination.
  • [0068]
    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. To achieve multiple genetic modifications of ungulate immunoglobulin genes, in one embodiment, cells can be modified sequentially to contain multiple genetic modifications. In other embodiments, animals can be bred together to produce animals that contain multiple genetic modifications of immunoglobulin genes. As an illustrative example, animals that lack expression of at least one allele of an ungulate heavy chain gene can be further genetically modified or bred with animals lacking at least one allele of a kappa light chain gene.
  • [0069]
    In embodiments of the present invention, alleles of ungulate heavy chain, kappa light chain or lambda light chain gene are rendered inactive according to the process, sequences and/or constructs described herein, such that functional ungulate immunoglobulins can no longer be produced. In one embodiment, the targeted immunoglobulin gene can be transcribed into RNA, but not translated into protein. In another embodiment, the targeted immunoglobulin 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 targeted immunoglobulin gene can be inactivated in such a way that no transcription of the gene occurs. In a further embodiment, the targeted immunoglobulin gene can be transcribed and then translated into a nonfunctional protein.
  • [0070]
    In a further aspect of the present invention, ungulate, such as porcine or bovine, cells lacking one allele, optionally both alleles of an ungulate heavy chain, kappa light chain and/or lambda light chain gene can be used as donor cells for nuclear transfer into recipient cells to produce cloned, transgenic animals. Alternatively, ungulate heavy chain, kappa light chain and/or lambda light chain gene knockouts can be created in embryonic stem cells, which are then used to produce offspring. Offspring lacking a single allele of a functional ungulate heavy chain, kappa light chain and/or lambda light chain 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.
  • [0071]
    In one aspect of the present invention, a method is provided to disrupt the expression of an ungulate immunoglobulin gene by (i) analyzing the germline configuration of the ungulate heavy chain, kappa light chain or lambda light chain genomic locus; (ii) determining the location of nucleotide sequences that flank the 5′ end and the 3′ end of at least one functional region of the locus; and (iii) transfecting a targeting construct containing the flanking sequence into a cell wherein, upon successful homologous recombination, at least one functional region of the immunoglobulin locus is disrupted thereby reducing or preventing the expression of the immunoglobulin gene. In one embodiment, the germline configuration of the porcine heavy chain locus is provided. The porcine heavy chain locus contains at least four variable regions, two diversity regions, six joining regions and five constant regions, for example, as illustrated in FIG. 1. In a specific embodiment, only one of the six joining regions, J6, is functional. In another embodiment, the germline configuration of the porcine kappa light chain locus is provided. The porcine kappa light chain locus contains at least six variable regions, six joining regions, one constant region and one enhancer region, for example, as illustrated in FIG. 2. In a further embodiment, the germline configuration of the porcine lambda light chain locus is provided. The porcine lambda light chain locus contains a variable region and the J/C region. See FIG. 3.
  • [0072]
    In a further aspect of the present invention, a method is provided to disrupt the expression of an ungulate lambda light chain locus by (i) analyzing the germline configuration of the ungulate lambda light chain genomic locus; (ii) determining the location of nucleotide sequences that flank the 5′ end of at least one functional region of the locus; (ii) constructing a 5′ targeting construct; (iv) determining the location of nucleotide sequences that flank the 3′ end of at least one functional region of the locus; (v) constructing a 3′ targeting construct; (vi) transfecting both the 5′ and the 3′ targeting constructs into a cell wherein, upon successful homologous recombination of each targeting construct, at least one functional region of the immunoglobulin locus is disrupted thereby reducing or preventing the expression of the immunoglobulin gene. See FIGS. 5 and 6.
  • [0073]
    In one embodiment, the germline configuration of the porcine lambda light chain locus is provided. The porcine lambda light chain locus contains a variable region and a J/C region. See FIG. 3.
  • [0074]
    In further aspects of the present invention provides ungulates and ungulate cells that lack at least one allele of a functional region of an ungulate heavy chain, kappa light chain and/or lambda light chain locus produced according to the processes, sequences and/or constructs described herein, which are further modified to express at least part of a human antibody (i.e. immunoglobulin (Ig)) locus. In additional embodiments, porcine animals are provided that express xenogenous immunoglobulin. This human locus can undergo rearrangement and express a diverse population of human antibody molecules in the ungulate. These cloned, transgenic ungulates provide a replenishable, theoretically infinite supply of human antibodies (such as polyclonal antibodies), which can be used for therapeutic, diagnostic, purification, and other clinically relevant purposes. In one particular embodiment, artificial chromosomes (ACs), such as yeast or mammalian artificial chromosomes (YACS or MACS) can be used to allow expression of human immunoglobulin genes into ungulate cells and animals. All or part of human immunoglobulin genes, such as the Ig heavy chain gene (human chromosome 414), Ig kappa chain gene (human chromosome #2) and/or the Ig lambda chain gene (chromosome #22) can be inserted into the artificial chromosomes, which can then be inserted into ungulate cells. In further embodiments, ungulates and ungulate cells are provided that contain either part or all of at least one human antibody gene locus, which undergoes rearrangement and expresses a diverse population of human antibody molecules.
  • [0075]
    In additional embodiments, methods of producing xenogenous antibodies are provided, wherein the method can include: (a) administering one or more antigens of interest to an ungulate whose cells comprise one or more artificial chromosomes and lack any expression of functional endogenous immunoglobulin, each artificial chromosome comprising one or more xenogenous immunoglobulin loci that undergo rearrangement, resulting in production of xenogenous antibodies against the one or more antigens; and/or (b) recovering the xenogenous antibodies from the ungulate. In one embodiment, the immunoglobulin loci can undergo rearrangement in a B cell.
  • [0076]
    In one aspect of the present invention, an ungulate, such as a pig or a cow, can be prepared by a method in accordance with any aspect of the present invention. These cloned, transgenic ungulates (e.g., porcine and bovine animals) provide a replenishable, theoretically infinite supply of human polyclonal antibodies, which can be used as therapeutics, diagnostics and for purification purposes. For example, transgenic animals produced according to the process, sequences and/or constructs described herein that produce polyclonal human antibodies in the bloodstream can be used to produce an array of different antibodies which are specific to a desired antigen. The availability of large quantities of polyclonal antibodies can also be used for treatment and prophylaxis of infectious disease, vaccination against biological warfare agents, modulation of the immune system, removal of undesired human cells such as cancer cells, and modulation of specific human molecules.
  • [0077]
    In other embodiments, animals or cells lacking expression of functional immunoglobulin, produced according to the process, sequences and/or constructs described herein, can contain additional genetic modifications to eliminate the expression of xenoantigens. Such animals can be modified to eliminate the expression of at least one allele of the alpha-1,3-galactosyltransferase gene, the CMP-Neu5Ac hydroxylase gene (see, for example, U.S. Ser. No. 10/863,116), the iGb3 synthase gene (see, for example, U.S. Patent Application 60/517,524), and/or the Forssman synthase gene (see, for example, U.S. Patent Application 60/568,922). In additional embodiments, the animals discloses herein can also contain genetic modifications to express fucosyltransferase and/or sialyltransferase. To achieve these additional genetic modifications, in one embodiment, cells can be modified to contain multiple genetic modifications. In other embodiments, animals can be bred together to achieve multiple genetic modifications. In one specific embodiment, animals, such as pigs, lacking expression of functional immunoglobulin, produced according to the process, sequences and/or constructs described herein, can be bred with animals, such as pigs, lacking expression of alpha-1,3-galactosyl transferase (for example, as described in WO 04/028243).
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0078]
    FIG. 1 illustrates the design of a targeting vector that disrupts the expression of the joining region of the porcine heavy chain immunoglobulin gene.
  • [0079]
    FIG. 2 illustrates the design of a targeting vector that disrupts the expression of the constant region of the porcine kappa light chain immunoglobulin gene.
  • [0080]
    FIG. 3 illustrates the genomic organization of the porcine lambda immunoglobulin locus, including a concatamer of J-C sequences or units as well as flanking regions that include the variable region 5′ to the JC cluster region. Bacterial artificial chromosomes (BAC1 and BAC2) represent fragments of the porcine immunoglobulin genome that can be obtained from BAC libraries.
  • [0081]
    FIG. 4 represents the design of a targeting vector that disrupts the expression of the JC cluster region of the porcine lambda light chain immunoglobulin gene. “SM” stands for a selectable marker gene, which can be used in the targeting vector.
  • [0082]
    FIG. 5 illustrates a targeting strategy to insert a site specific recombinase target or recognition site into the region 5′ of the JC cluster region of the porcine lambda immunoglobulin locus. “SM” stands for a selectable marker gene, which can be used in the targeting vector. “SSRRS” stands for a specific recombinase target or recognition site.
  • [0083]
    FIG. 6 illustrates a targeting strategy to insert a site specific recombinase target or recognition site into the region 3′ of the JC cluster region of the porcine lambda immunoglobulin locus. “SM” stands for a selectable marker gene, which can be used in the targeting vector. “SSRRS” stands for a specific recombinase target or recognition site.
  • [0084]
    FIG. 7 illustrates the site specific recombinase mediated transfer of a YAC into a host genome. “SSRRS” stands for a specific recombinase target or recognition site.
  • DETAILED DESCRIPTION
  • [0085]
    The present invention provides for the first time ungulate immunoglobin germline gene sequence arrangement as well as novel genomic sequences thereof. In addition, novel ungulate cells, tissues and animals that lack at least one allele of a heavy or light chain immunoglobulin gene are provided. Based on this discovery, ungulates can be produced that completely lack at least one allele of a heavy and/or light chain immunoglobulin gene. In addition, these ungulates can be further modified to express xenoogenous, such as human, immunoglobulin loci or fragments thereof.
  • [0086]
    In one aspect of the present invention, a transgenic ungulate that lacks any expression of functional endogenous immunoglobulins is provided. In one embodiment, the ungulate can lack any expression of endogenous heavy and/or light chain immunoglobulins. The light chain immunoglobulin can be a kappa and/or lambda immunoglobulin. In additional embodiments, transgenic ungulates are provided that lack expression of at least one allele of an endogenous immunoglobulin wherein the immunoglobulin is selected from the group consisting of heavy chain, kappa light chain and lambda light chain or any combination thereof. In one embodiment, the expression of functional endogenous immunoglobulins can be accomplished by genetic targeting of the endogenous immunoglobulin loci to prevent expression of the endogenous immunoglobulin. In one embodiment, the genetic targeting can be accomplished via homologous recombination. In another embodiment, the transgenic ungulate can be produced via nuclear transfer.
  • [0087]
    In other embodiments, the transgenic ungulate that lacks any expression of functional endogenous immunoglobulins can be further genetically modified to express an xenogenous immunoglobulin loci. In an alternative embodiment, porcine animals are provided that contain an xenogeous immunoglobulin locus. In one embodiment, the xenogeous immunoglobulin loci can be a heavy and/or light chain immunoglobulin or fragment thereof. In another embodiment, the xenogenous immunoglobulin loci can be a kappa chain locus or fragment thereof and/or a lambda chain locus or fragment thereof. In still further embodiments, an artificial chromosome (AC) can contain the xenogenous immunoglobulin. In one embodiment, the AC can be a yeast AC or a mammalian AC. In a further embodiment, the xenogenous locus can be a human immunoglobulin locus or fragment thereof. In one embodiment, the human immunoglobulin locus can be human chromosome 14, human chromosome 2, and human chromosome 22 or fragments thereof. In another embodiment, the human immunoglobulin locus can include any fragment of a human immunoglobulin that can undergo rearrangement. In a further embodiment, the human immunoglobulin loci can include any fragment of a human immunoglobulin heavy chain and a human immunoglobulin light chain that can undergo rearrangement. In still further embodiment, the human immunoglobulin loci can include any human immunoglobulin locus or fragment thereof that can produce an antibody upon exposure to an antigen. In a particular embodiment, the exogenous human immunoglobulin can be expressed in B cells to produce xenogenous immunoglobulin in response to exposure to one or more antigens.
  • [0088]
    In another aspect of the present invention, transgenic ungulates are provided that expresses a xenogenous immunoglobulin loci or fragment thereof, wherein the immunoglobulin can be expressed from an immunoglobulin locus that is integrated within an endogenous ungulate chromosome. In one embodiment, ungulate cells derived from the transgenic animals are provided. In one embodiment, the xenogenous immunoglobulin locus can be inherited by offspring. In another embodiment, the xenogenous immunoglobulin locus can be inherited through the male germ line by offspring. In still further embodiments, an artificial chromosome (AC) can contain the xenogenous immunoglobulin. In one embodiment, the AC can be a yeast AC or a mammalian AC. In a further embodiment, the xenogenous locus can be a human immunoglobulin locus or fragment thereof. In one embodiment, the human immunoglobulin locus can be human chromosome 14, human chromosome 2, and human chromosome 22 or fragments thereof. In another embodiment, the human immunoglobulin locus can include any fragment of a human immunoglobulin that can undergo rearrangement. In a further embodiment, the human immunoglobulin loci can include any fragment of a human immunoglobulin heavy chain and a human immunoglobulin light chain that can undergo rearrangement. In still further embodiment, the human immunoglobulin loci can include any human immunoglobulin locus or fragment thereof that can produce an antibody upon exposure to an antigen. In a particular embodiment, the exogenous human immunoglobulin can be expressed in B cells to produce xenogenous immunoglobulin in response to exposure to one or more antigens.
  • [0089]
    Definitions
  • [0090]
    The terms “recombinant DNA technology,” “DNA cloning,” “molecular cloning,” or “gene cloning” refer to the process of transferring a DNA sequence into a cell or organism. The transfer of a DNA fragment can be from one organism to a self-replicating genetic element (e.g., bacterial plasmid) that permits a copy of any specific part of a DNA (or RNA) sequence to be selected among many others and produced in an unlimited amount. Plasmids and other types of cloning vectors such as artificial chromosomes can be used to copy genes and other pieces of chromosomes to generate enough identical material for further study. In addition to bacterial plasmids, which can carry up to 20 kb of foreign DNA, other cloning vectors include viruses, cosmids, and artificial chromosomes (e.g., bacteria artificial chromosomes (BACs) or yeast artificial chromosomes (YACs)). When the fragment of chromosomal DNA is ultimately joined with its cloning vector in the lab, it is called a “recombinant DNA molecule.” Shortly after the recombinant plasmid is introduced into suitable host cells, the newly inserted segment will be reproduced along with the host cell DNA.
  • [0091]
    “Cosmids” are artificially constructed cloning vectors that carry up to 45 kb of foreign DNA. They can be packaged in lambda phage particles for infection into E. coli cells.
  • [0092]
    As used herein, the term “mammal” (as in “genetically modified (or altered) mammal”) is meant to include any non-human mammal, including but not limited to pigs, sheep, goats, cattle (bovine), deer, mules, horses, monkeys, dogs, cats, rats, mice, birds, chickens, reptiles, fish, and insects. In one embodiment of the invention, genetically altered pigs and methods of production thereof are provided.
  • [0093]
    The term “ungulate” refers to hoofed mammals. Artiodactyls are even-toed (cloven-hooved) ungulates, including antelopes, camels, cows, deer, goats, pigs, and sheep. Perissodactyls are odd toes ungulates, which include horses, zebras, rhinoceroses, and tapirs. The term ungulate as used herein refers to an adult, embryonic or fetal ungulate animal.
  • [0094]
    As used herein, the terms “porcine”, “porcine animal”, “pig” and “swine” are generic terms referring to the same type of animal without regard to gender, size, or breed.
  • [0095]
    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, at least 95% or 98% identity between the sequences.
  • [0096]
    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, or at least about 99.5-99.9% identical with the reference DNA sequence, and in certain uses 100% identical with the reference DNA sequence.
  • [0097]
    “Homologous recombination” refers to the process of DNA recombination based on sequence homology.
  • [0098]
    “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.
  • [0099]
    “Non-homologous or random integration” refers to any process by which DNA is integrated into the genome that does not involve homologous recombination.
  • [0100]
    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.
  • [0101]
    The term “contiguous” is used herein in its standard meaning, i.e., without interruption, or uninterrupted.
  • [0102]
    “Stringent conditions” refers to conditions that (1) employ low ionic strength and high temperature for washing, for example, 0.015 M NaCl/0.0015 M sodium citrate/0.1% SDS at 50 C., or (2) employ during hybridization a denaturing agent such as, for example, formamide. One skilled in the art can determine and vary the stringency conditions appropriately to obtain a clear and detectable hybridization signal. For example, stringency can generally be reduced by increasing the salt content present during hybridization and washing, reducing the temperature, or a combination thereof. See, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y., (1989).
  • [0000]
    I. Immunoglobulin Genes
  • [0103]
    In one aspect of the present invention, a transgenic ungulate that lacks any expression of functional endogenous immunoglobulins is provided. In one embodiment, the ungulate can lack any expression of endogenous heavy and/or light chain immunoglobulins. The light chain immunoglobulin can be a kappa and/or lambda immunoglobulin. In additional embodiments, transgenic ungulates are provided that lack expression of at least one allele of an endogenous immunoglobulin wherein the immunoglobulin is selected from the group consisting of heavy chain, kappa light chain and lambda light chain or any combination thereof. In one embodiment, the expression of functional endogenous immunoglobulins can be accomplished by genetic targeting of the endogenous immunoglobulin loci to prevent expression of the endogenous immunoglobulin. In one embodiment, the genetic targeting can be accomplished via homologous recombination. In another embodiment, the transgenic ungulate can be produced via nuclear transfer.
  • [0104]
    In another aspect of the present invention, a method is provided to disrupt the expression of an ungulate immunoglobulin gene by (i) analyzing the germline configuration of the ungulate heavy chain, kappa light chain or lambda light chain genomic locus; (ii) determining the location of nucleotide sequences that flank the 5′ end and the 3′ end of at least one functional region of the locus; and (iii) transfecting a targeting construct containing the flanking sequence into a cell wherein, upon successful homologous recombination, at least one functional region of the immunoglobulin locus is disrupted thereby reducing or preventing the expression of the immunoglobulin gene.
  • [0105]
    In one embodiment, the germline configuration of the porcine heavy chain locus is provided. The porcine heavy chain locus contains at least four variable regions, two diversity regions, six joining regions and five constant regions, for example, as illustrated in FIG. 1. In a specific embodiment, only one of the six joining regions, J6, is functional.
  • [0106]
    In another embodiment, the germline configuration of the porcine kappa light chain locus is provided. The porcine kappa light chain locus contains at least six variable regions, six joining regions, one constant region and one enhancer region, for example, as illustrated in FIG. 2.
  • [0107]
    In a further embodiment, the germline configuration of the porcine lambda light chain locus is provided.
  • [0108]
    Isolated nucleotide sequences as depicted in Seq ID Nos 1-39 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to any one of Seq ID Nos 1-39 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of any one of Seq ID Nos 1-39 are provided. Further provided are nucleotide sequences that hybridize, optionally under stringent conditions, to Seq ID Nos 1-39, as well as, nucleotides homologous thereto.
  • [0109]
    Homology or identity at the nucleotide or amino acid sequence level can be determined by BLAST (Basic Local Alignment Search Tool) analysis using the algorithm employed by the programs blastp, blastn, blastx, tblastn and tblastx (see, for example, Altschul, S. F. et al (1997) Nucleic Acids Res 25:3389-3402 and Karlin et al, (1900) Proc. Natl. Acad. Sci. USA 87, 2264-2268) which are tailored for sequence similarity searching. The approach used by the BLAST program is to first consider similar segments, with and without gaps, between a query sequence and a database sequence, then to evaluate the statistical significance of all matches that are identified and finally to summarize only those matches which satisfy a preselected threshold of significance. See, for example, Altschul et al., (1994) (Nature Genetics 6, 119-129). The search parameters for histogram, descriptions, alignments, expect (i.e., the statistical significance threshold for reporting matches against database sequences), cutoff, matrix and filter (low co M'plexity) are at the default settings. The default scoring matrix used by blastp, blastx, tblastn, and tblastx is the BLOSUM62 matrix (Henikoff et al., (1992) Proc. Natl. Acad. Sci. USA 89, 10915-10919), which is recommended for query sequences over 85 in length (nucleotide bases or amino acids).
  • [0000]
    Porcine Heavy Chain
  • [0110]
    In another aspect of the present invention, novel genomic sequences encoding the heavy chain locus of ungulate immunoglobulin are provided. In one embodiment, an isolated nucleotide sequence encoding porcine heavy chain is provided that includes at least one variable region, two diversity regions, at least four joining regions and at least one constant region, such as the mu constant region, for example, as represented in Seq ID No. 29. In another embodiment, an isolated nucleotide sequence is provided that includes at least four joining regions and at least one constant region, such as the mu constant region, of the porcine heavy chain genomic sequence, for example, as represented in Seq ID No. 4. In a further embodiment, nucleotide sequence is provided that includes 5′ flanking sequence to the first joining region of the porcine heavy chain genomic sequence, for example, as represented in Seq ID No 1. Still further, nucleotide sequence is provided that includes 3′ flanking sequence to the first joining region of the porcine heavy chain genomic sequence, for example, as represented in the 3′ region of Seq ID No 4. In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 1, 4 or 29 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 1, 4 or 29 are also provided. Further provided are nucleotide sequences that hybridize, optionally under stringent conditions, to Seq ID Nos 1, 4 or 29, as well as, nucleotides homologous thereto.
  • [0111]
    In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 1, 4 or 29 are provided. In one embodiment, the nucleotide sequence contains at least 17, 20, 25 or 30 contiguous nucleotides of Seq ID No 4 or residues 1-9,070 of Seq ID No 29. In other embodiments, nucleotide sequences that contain at least 50, 100, 1,000, 2,500, 4,000, 4,500, 5,000, 7,000, 8,000, 8,500, 9,000, 10,000 or 15,000 contiguous nucleotides of Seq ID No. 29 are provided. In another embodiment, the nucleotide sequence contains residues 9,070-11039 of Seq ID No 29.
  • [0112]
    In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 1, 4 or 29 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 1, 4 or 29 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 1, 4 or 29 are provided. Further provided are nucleotide sequences that hybridize, optionally under stringent conditions, to Seq ID Nos 1, 4 or 29, as well as, nucleotides homologous thereto.
  • [0113]
    In one embodiment, an isolated nucleotide sequence encoding porcine heavy chain is provided that includes at least one variable region, two diversity regions, at least four joining regions and at least one constant region, such as the mu constant region, for example, as represented in Seq ID No. 29. In Seq ID No. 29, the Diversity region of heavy chain is represented, for example, by residues 1089-1099 (D(pseudo)), the Joining region of heavy chain is represented, for example, by residues 1887-3352 (for example: J(psuedo): 1887-1931, J(psuedo): 2364-2411, J(psuedo): 2756-2804, J (functional J): 3296-3352), the recombination signals are represented, for example, by residues 3001-3261 (Nonamer), 3292-3298 (Heptamer), the Constant Region is represented by the following residues: 3353-9070 (J to C mu intron), 5522-8700 (Switch region), 9071-9388 (Mu Exon 1), 9389-9469 (Mu Intron A), 9470-9802 (Mu Exon 2), 9830-10069 (Mu Intron B), 10070-10387 (Mu Exon 3), 10388-10517 (Mu Intron C), 10815-11052 (Mu Exon 4), 11034-11039 (Poly(A) signal).
    Seq ID No. 29
    tctagaagacgctggagagaggccagacttcctcggaacagctcaaagag
    ctctgtcaaagccagatcccatcacacgtgggcaccaataggccatgcca
    gcctccaagggccgaactgggttctccacggcgcacatgaagcctgcagc
    ctggcttatcctcttccgtggtgaagaggcaggcccgggactggacgagg
    ggctagcagggtgtggtaggcaccttgcgccccccaccccggcaggaacc
    agagaccctggggctgagagtgagcctccaaacaggatgccccacccttc
    aggccacctttcaatccagctacactccacctgccattctcctctgggca
    cagggcccagcccctggatcttggccttggctcgacttgcacccacgcgc
    acacacacacttcctaacgtgctgtccgctcacccctccccagcgtggtc
    catgggcagcacggcagtgcgcgtccggcggtagtgagtgcagaggtccc
    ttcccctcccccaggagccccaggggtgtgtgcagatctgggggctcctg
    tcccttacaccttcatgcccctcccctcatacccaccctccaggcgggag
    gcagcgagacctttgcccagggactcagccaacgggcacacgggaggcca
    gccctcagcagctggctcccaaagaggaggtgggaggtaggtccacagct
    gccacagagagaaaccctgacggaccccacaggggccacgccagccggaa
    ccagctccctcgtgggtgagcaatggccagggccccgccggccaccacgg
    ctggccttgcgccagctgagaactcacgtccagtgcagggagactcaaga
    cagcctgtgcacacagcctcggatctgctcccatttcaagcagaaaaagg
    aaaccgtgcaggcagccctcagcatttcaaggattgtagcagcggccaac
    tattcgtcggcagtggccgattagaatgaccgtggagaagggcggaaggg
    tctctcgtgggctctgcggccaacaggccctggctccacctgcccgctgc
    cagcccgaggggcttgggccgagccaggaaccacagtgctcaccgggacc
    acagtgactgaccaaactcccggccagagcagccccaggccagccgggct
    ctcgccctggaggactcaccatcagatgcacaagggggcgagtgtggaag
    agacgtgtcgcccgggccatttgggaaggcgaagggaccttccaggtgga
    caggaggtgggacgcactccaggcaagggactgggtccccaaggcctggg
    gaaggggtactggcttgggggttagcctggccagggaacggggagcgggg
    cggggggctgagcagggaggacctgacctcgtgggagcgaggcaagtcag
    gcttcaggcagcagccgcacatcccagaccaggaggctgaggcaggaggg
    gcttgcagcggggcgggggcctgcctggctccgggggctcctgggggacg
    ctggctcttgtttccgtgtcccgcagcacagggccagctcgctgggccta
    tgcttaccttgatgtctggggccggggcgtcagggtcgtcgtctcctcag
    gggagagtcccctgaggctacgctgggg*ggggactatggcagctccacc
    aggggcctggggaccaggggcctggaccaggctgcagcccggaggacggg
    cagggctctggctctccagcatctggccctcggaaatggcagaacccctg
    gcgggtgagcgagctgagagcgggtcagacagacaggggccggccggaaa
    ggagaagttgggggcagagcccgccaggggccaggcccaaggttctgtgt
    gccagggcctgggtgggcacattggtgtggccatggctacttagattcgt
    ggggccagggcatcctggtcaccgtctcctcaggtgagcctggtgtctga
    tgtccagctaggcgctggtgggccgcgggtgggcctgtctcaggctaggg
    caggggctgggatgtgtatttgtcaaggaggggcaacagggtgcagactg
    tgcccctggaaacttgaccactggggcaggggcgtcctggtcacgtctcc
    tcaggtaagacggccctgtgcccctctctcgcgggactggaaaaggaatt
    ttccaagattccttggtctgtgtggggccctctggggcccccgggggtgg
    ctcccctcctgcccagatggggcctcggcctgtggagcacgggctgggca
    cacagctcgagtctagggccacagaggcccgggctcagggctctgtgtgg
    cccggcgactggcagggggctcgggtttttggacaccccctaatgggggc
    cacagcactgtgaccatcttcacagctggggccgaggagtcgaggtcacc
    gtctcctcaggtgagtcctcgtcagccctctctcactctctggggggttt
    tgctgcattttgtgggggaaagaggatgcctgggtctcaggtctaaaggt
    ctagggccagcgccggggcccaggaaggggccgaggggccaggctcggct
    cggccaggagcagagcttccagacatctcgcctcctggcggctgcagtca
    ggcctttggccgggggggtctcagcaccaccaggcctcttggctcccgag
    gtccccggccccggctgcctcaccaggcaccgtgcgcggtgggcccgggc
    tcttggtcggccaccctttcttaactgggatccgggcttagttgtcgcaa
    tgtgacaacgggctcgaaagctggggccaggggaccctagtctacgacgc
    ctcgggtgggtgtcccgcacccctccccactttcacggcactcggcgaga
    cctggggagtcaggtgttggggacactttggaggtcaggaacgggagctg
    gggagagggctctgtcagcggggtccagagatgggccgccctccaaggac
    gccctgcgcggggacaagggcttcttggcctggcctggccgcttcacttg
    ggcgtcagggggggcttcccggggcaggcggtcagtcgaggcgggttgga
    attctgagtctgggttcggggttcggggttcggccttcatgaacagacag
    cccaggcgggccgttgtttggcccctgggggcctggttggaatgcgaggt
    ctcgggaagtcaggagggagcctggccagcagagggttcccagccctgcg
    gccgagggacctggagacgggcagggcattggccgtcgcagggccaggcc
    acaccccccaGGTTTTTGTggggcgagcctggagattgcacCACTGTGAT
    TACTATGCTATGGATCTCTGGGGCCCAGGCGTTGAAGTCGTCGTGTCCTC
    AGgtaagaacggccctccagggcctttaatttctgctctcgtctgtgggc
    ttttctgactctgatcctcgggaggcgtctgtgccccccccggggatgag
    gccggcttgccaggaggggtcagggaccaggagcctgtgggaagttctga
    cgggggctgcaggcgggaagggccccaccggggggcgagccccaggccgc
    tgggcggcaggagacccgtgagagtgcgccttgaggagggtgtctgcgga
    accacgaacgcccgccgggaagggcttgctgcaatgcggtcttcagacgg
    gaggcgtcttctgccctcaccgtctttcaagcccttgtgggtctgaaaga
    gccatgtcggagagagaagggacaggcctgtcccgacctggccgagagcg
    ggcagccccgggggagagcggggcgatcggcctgggctctgtgaggccag
    gtccaagggaggacgtgtggtcctcgtgacaggtgcacttgcgaaacctt
    agaagacggggtatgttggaagcggctcctgatgtttaagaaaagggaga
    ctgtaaagtgagcagagtcctcaagtgtgttaaggttttaaaggtcaaag
    tgttttaaacctttgtgactgcagttagcaagcgtgcggggagtgaatgg
    ggtgccagggtggccgagaggcagtacgagggccgtgccgtcctctaatt
    cagggcttagttttgcagaataaagtcggcctgttttctaaaagcattgg
    tggtgctgagctggtggaggaggccgcgggcagccctggccacctgcagc
    aggtggcaggaagcaggtcggccaagaggctattttaggaagccagaaaa
    cacggtcgatgaatttatagcttctggtttccaggaggtggttgggcatg
    gctttgcgcagcgccacagaaccgaaagtgcccactgagaaaaaacaact
    cctgcttaatttgcatttttctaaaagaagaaacagaggctgacggaaac
    tggaaagttcctgttttaactactcgaattgagttttcggtcttagctta
    tcaactgctcacttagattcattttcaaagtaaacgtttaagagccgagg
    cattcctatcctcttctaaggcgttattcctggaggctcattcaccgcca
    gcacctccgctgcctgcaggcattgctgtcaccgtcaccgtgacggcgcg
    cacgattttcagttggcccgcttcccctcgtgattaggacagacgcgggc
    actctggcccagccgtcttggctcagtatctgcaggcgtccgtctcggga
    cggagctcaggggaagagcgtgactccagttgaacgtgatagtcggtgcg
    ttgagaggagacccagtcgggtgtcgagtcagaaggggcccggggcccga
    ggccctgggcaggacggcccgtgccctgcatcacgggcccagcgtcctag
    aggcaggactctggtggagagtgtgagggtgcctggggcccctccggagc
    tggggccgtgcggtgcaggttgggctctcggcgcggtgttggctgtttct
    gcgggatttggaggaattcttccagtgatgggagtcgccagtgaccgggc
    accaggctggtaagagggaggccgccgtcgtggccagagcagctgggagg
    gttcggtaaaaggctcgcccgtttcctttaatgaggacttttcctggagg
    gcatttagtctagtcgggaccgttttcgactcgggaagagggatgcggag
    gagggcatgtgcccaggagccgaaggcgccgcggggagaagcccagggct
    ctcctgtccccacagaggcgacgccactgccgcagacagacagggccttt
    ccctctgatgacggcaaaggcgcctcggctcttgcggggtgctggggggg
    agtcgccccgaagccgctcacccagaggcctgaggggtgagactgaccga
    tgcctcttggccgggcctggggccggaccgagggggactccgtggaggca
    gggcgatggtggctgcgggagggaaccgaccctgggccgagcccggcttg
    gcgattcccgggcgagggccctcagccgaggcgagtgggtccggcggaac
    caccctttctggccagcgccacagggctctcgggactgtccggggcgacg
    ctgggctgcccgtggcaggccTGGGCTGACCTGGACTTCACCAGACAGAA
    CAGGGCTTTCAGGGCTGAGCTGAGCCAGGTTTAGCGAGGCCAAGTGGGGC
    TGAACCAGGCTCAACTGGCCTGAGCTGGGTTGAGCTGGGCTGACCTGGGC
    TGAGCTGAGCTGGGCTGGGCTGGGCTGGGCTGGGCTGGGCTGGGCTGGAC
    TGGCTGAGCTGAGCTGGGTTGAGCTGAGCTGAGCTGGCCTGGGTTGAGCT
    GGGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGTTGAGCTGGGTTGATCT
    GAGCTGAGCTGGGCTGAGCTGAGCTAGGCTGGGGTGAGCTGGGCTGAGCT
    GGTTTGAGTTGGGTTGAGCTGAGCTGAGCTGGGCTGTGCTGGCTGAGCTA
    GGCTGAGCTAGGCTAGGTTGAGCTGGGCTGGGCTGAGGTGAGCTAGGCTG
    GGCTGATTTGGGCTGAGCTGAGCTGAGCTAGGCTGCGTTGAGCTGGCTGG
    GCTGGATTGAGCTGGCTGAGCTGGCTGAGCTGGGCTGAGCTGGCCTGGGT
    TGAGCTGAGCTGGACTGGTTTGAGCTGGGTCGATCTGGGTTGAGCTGTCC
    TGGGTTGAGCTGGGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGCTCAGC
    AGAGCTGGGTTGGGCTGAGCTGGGTTGAGCTGAGCTGGGCTGAGCTGGCC
    TGGGTTGAGCTGGGCTGAGCTGAGCTGGGCTGAGCTGGCCTGTGTTGAGC
    TGGGCTGGGTTGAGCTGGGCTGAGCTGGATTGAGCTGGGTTGAGCTGAGC
    TGGGCTGGGCTGTGCTGACTGAGCTGGGCTGAGCTAGGCTGGGGTGAGCT
    GGGCTGAGCTGATCCGAGCTAGGCTGGGCTGGTTTGGGCTGAGCTGAGCT
    GAGCTAGGCTGGATTGATCTGGCTGAGCTGGGTTGAGCTGAGCTGGGCTG
    AGCTGGTCTGAGCTGGCCTGGGTCGAGCTGAGCTGGACTGGTTTGAGCTG
    GGTCGATCTGGGCTGAGCTGGCCTGGGTTGAGCTGGGCTGGGTTGAGCTG
    AGCTGGGTTGAGCTGGGCTGAGCTGAGGGCTGGGGTGAGCTGGGCTGAAC
    TAGCCTAGCTAGGTTGGGCTGAGCTGGGCTGGTTTGGGCTGAGCTGAGCT
    GAGCTAGGCTGCATTGAGCAGGCTGAGCTGGGCTGAGCAGGCCTGGGGTG
    AGCTGGGCTAGGTGGAGCTGAGCTGGGTCGAGCTGAGTTGGGCTGAGCTG
    GCCTGGGTTGAGGTAGGCTGAGCTGAGCTGAGCTAGGCTGGGTTGAGCTG
    GCTGGGCTGGTTTGCGCTGGGTCAAGCTGGGCCGAGCTGGCCTGGGTTGA
    GCTGGGCTCGGTTGAGCTGGGCTGAGCTGAGCCGACCTAGGCTGGGATGA
    GCTGGGCTGATTTGGGCTGAGCTGAGCTGAGCTAGGCTGCATTGAGCAGG
    CTGAGCTGGGCCTGGAGCCTGGCCTGGGGTGAGCTGGGCTGAGCTGCGCT
    GAGCTAGGCTGGGTTGAGCTGGCTGGGCTGGTTTGCGCTGGGTCAAGCTG
    GGCCGAGCTGGCCTGGGATGAGCTGGGCCGGTTTGGGCTGAGCTGAGCTG
    AGCTAGGCTGCATTGAGCAGGCTGAGCTGGGCTGAGCTGGCCTGGGGTGA
    GCTGGGCTGAGCTAAGCTGAGCTGGGCTGGTTTGGGCTGAGCTGGCTGAG
    CTGGGTCCTGCTGAGCTGGGCTGAGCTGACCAGGGGTGAGCTGGGCTGAG
    TTAGGCTGGGCTCAGCTAGGCTGGGTTGATCTGGCAGGGCTGGTTTGCGC
    TGGGTCAAGCTCCCGGGAGATGGCCTGGGATGAGCTGGGCTGGTTTGGGC
    TGAGCTGAGCTGAGCTGAGCTAGGCTGCATTGAGCAGGCTGAGCTGGGCT
    GAGCTGGCCTGGGGTGAGCTGGGCTGGGTGGAGCTGAGCTGGGCTGAACT
    GGGCTAAGCTGGCTGAGCTGGATCGAGCTGAGCTGGGCTGAGCTGGCCTG
    GGGTTAGCTGGGCTGAGCTGAGCTGAGCTAGGCTGGGTTGAGCTGGCTGG
    GCTGGTTTGCGCTGGGTCAAGCTGGGCCGAGCTGGCCTGGGTTGAGCTGG
    GCTGGGCTGAGCTGAGCTAGGCTGGGTTGAGCTGGGCTGGGCTGAGCTGA
    GCTAGGCTGCATTGAGCTGGCTGGGATGGATTGAGCTGGCTGAGCTGGCT
    GAGCTGGCTGAGCTGGGCTGAGCTGGCCTGGGTTGAGCTGGGCTGGGTTG
    AGCTGAGCTGGGCTGAGCTGGGCTCAGCAGAGCTGGGTTGAGCTGAGCTG
    GGTTGAGCTGGGGTGAGCTGGGCTGAGCAGAGCTGGGTTGAGCTGAGCTG
    GGTTGAGCTGGGCTCGAGCAGAGCTGGGTTGAGCTGAGCTGGGTTGAGCT
    GGGCTCAGCAGAGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGCTGAGCT
    AGCTGGGCTCAGCTAGGCTGGGTTGAGCTGAGCTGGGCTGAACTGGGCTG
    AGCTGGGCTGAACTGGGCTGAGCTGGGCTGAGCTGGGCTGAGCAGAGCTG
    GGCTGAGCAGAGCTGGGTTGGTCTGAGCTGGGTTGAGCTGGGCTGAGCTG
    GGCTGAGCAGAGTTGGGTTGAGCTGAGCTGGGTTCAGCTGGGCTGAGCTA
    GGCTGGGTTGAGCTGGGTTGAGTTGGGCTGAGCTGGGCTGGGTTGAGCGG
    AGCTGGGCTGAACTGGGCTGAGCTGGGCTGAGCGGAACTGGGTTGATCTG
    AATTGAGCTGGGCTGAGCCGGGCTGAGCCGGGCTGAGCTGGGCTAGGTTG
    AGCTTGGGTGAGCTTGCCTCAGCTGGTCTGAGCTAGGTTGGGTGGAGCTA
    GGCTGGATTGAGCTGGGCTGAGCTGAGCTGATCTGGCCTCAGCTGGGCTG
    AGGTAGGCTGAACTGGGCTGTGCTGGGCTGAGCTGAGCTGAGCCAGTTTG
    AGCTGGGTTGAGCTGGGCTGAGCTGGGCTGTGTTGATCTTTCCTGAACTG
    GGCTGAGCTGGGCTGAGCTGGCCTAGCTGGATTGAACGGGGGTAAGCTGG
    GCCAGGCTGGACTGGGCTGAGCTGAGCTAGGCTGAGCTGAGTTGAATTGG
    GTTAAGCTGGGCTGAGATGGGCTGAGCTGGGCTGAGCTGGGTTGAGCCAG
    GTCGGACTGGGTTACCCTGGGCCACACTGGGCTGAGCTGGGCGGAGCTCG
    attaacctggtcaggctgagtcgggtccagcagacatgcgctggccaggc
    tggcttgacctggacacgttcgatgagctgccttgggatggttcacctca
    gctgagccaggtggctccagctgggctgagctggtgaccctgggtgacct
    cggtgaccaggttgtcctgagtccgggccaagccgaggctgcatcagact
    cgccagacccaaggcctgggccccggctggcaagccaggggcggtgaagg
    ctgggctggcaggactgtcccggaaggaggtgcacgtggagccgcccgga
    ccccgaccggcaggacctggaaagacgcctctcactcccctttctcttct
    gtcccctctcgggtcctcagAGAGCCAGTCTGCCCCGAATCTCTACCCCC
    TCGTCTCCTGCGTCAGCCCCCCGTCCGATGAGAGCCTGGTGGCCCTGGGC
    TGCCTGGCCCGGGACTTCCTGCCCAGCTCCGTCACCTTCTCCTGGAACTA
    CAAGAACAGCAGCAAGGTCAGCAGCCAGAACATCCAGGACTTCCCGTCC
    GTCCTGAGAGGCGGCAAGTACTTGGCCTCCTCCCGGGTGCTCCTACCCTCT
    GTGAGCATCCCCCAGGACCCAGAGGCCTTCCTGGTGTGCGAGGTCCAGCA
    CCCCAGTGGCACCAAGTCCGTGTCCATCTCTGGGCCAGgtgagctgggct
    ccccctgtggctgtggcgggggcggggccgggtgccgccggcacagtgac
    gccccgttcctgcctgcagTCGTAGAGGAGCAGCCCCCCGTCTTGAACATC
    TTCGTCCCCACCCGGGAGTCCTTCTCCAGTACTCCCCAGCGCACGTCCAAG
    CTCATCTGCCAGGCCTCAGACTTCAGCCCCAAGCAGATCTCCATGGCCTGG
    TTCCGTGATGGGAAACGGGTGGTGTCTGGCGTCAGGACAGGCCCCGTGGAG
    ACCCTACAGTCCAGTGGGGTGACCTACAGGCTCCACAGCATGCTGACCGTCA
    CGGAGTCCGAGTGGGTCAGCCAGAGCGTCTTCACCTGCCAGGTGGAGCACAAA
    GGGCTGAACTACGAGAAGAACGCGTCCTCTCTGTGCACCTCCAgtgagtgcag
    cccctcgggccgggcggcggggcggcgggagccacacacacaccagctgctcc
    ctgagccttggcttccgggagtggccaaggcggggaggggctgtgcagggcagc
    tggagggcactgtcagctggggcccagcaccccctcaccccggcagggcccggg
    ctccgaggggccccgcagtcgcaggccctgctcttgggggaagccctacttggc
    cccttcagggcgctgacgctccccccacccacccccgcctagATCCCAACTCTC
    CCATCACCGTCTTCGCCATCGCCCCCTCCTTCGCTGGCATCTTCCTCACCAAGT
    CGGCGAAGCTTTCCTGCCTGGTCAGGGGCCTCGTCACCAGGGAGAGCGTCAACA
    TCTCCTGGACCCGCCAGGACGGCGAGGTTCTGAAGACCAGTATCGTCTTCTCTG
    AGATCTACGCCAACGGCACCTTCGGCGCCAGGGGCGAAGCCTCCGTCTGCGTGG
    AGGACTGGGAGTCGGGCGACAGGTTCACGTGCACGGTGACCCACACGGACCTGC
    CCTCGCCGCTGAAGCAGAGCGTCTCCAAGCCCAGAGgtaggccctgccctgccc
    ctgcctccgcccggcctgtgccttggccgccggggcgggagccgagcctggccg
    aggagcgccctcggccccccgcggtcccgacccacacccctcctgctctcctcc
    ccagGGATCGCCAGGCACATGCCGTCCGTGTACGTGCTGCCGCCGGCCCCGGAG
    GAGCTGAGCCTGCAGGAGTGGGCCTCGGTCACCTGCCTGGTGAAGGGCTTCTCC
    CCGGCGGACGTGTTCGTGCAGTGGCTGCAGAAGGGGGAGCCCGTGTCCGCCGAC
    AAGTACGTGACCAGCGGGCCGGTGCCCGAGCCCGAGCCCAAGGCCCCCGCCTCC
    TACTTCGTGCAGAGCGTCCTGACGGTGAGCGCCAAGGACTGGAGCGACGGGGAG
    ACCTACACCTGCGTCGTGGGCCACGAGGCCCTGCCCCACACGGTGACCGAGAGG
    ACCGTGGACAAGTCCACCGGTAAACCCACCCTGTACAACGTCTCCCTGGTCCTG
    TCCGACACGGCCAGCACCTGCTACTGACCCCCTGGCTGCCCGCCGCGGCCGGGG
    CCAGAGCCCCCGGGCGACCATCGCTCTGTGTGGGCCTGTGTGCAACCCGACCC
    TGTCGGGGTGAGCGGTCGCATTTCTGAAAATTAGAaataaaAGATCTCGTGC
    CG
    Seq ID No. 1
    TCTAgAAGACGCTGGAGAGAGGCCagACTTCCTGGGAACAGCTCAAAGAG
    CTCTGTCAAAGCCAGATCCCATCACACGTGGGCACCAATAGGCCATGCCA
    GCCTCCAAGGGCCGAACTGGGTTCTCCACGGCGCACATGAAGCCTGCAGC
    CTGGCTTATCCTCTTCCGTGGTGAAGAGGCAGGCCCGGGACTGGACGAGG
    GGCTAGCAGGGTGTGGTAGGCACCTTGCGCCCCCCACCCCGGCAGGAACC
    AGAGACCCTGGGGCTGAGAGTGAGCCTCCAAACAGGATGCCCCACCCTTC
    AGGCCACCTTTCAATCCAGCTACACTCCACCTGCCATTCTCCTCTGGGCA
    CAGGGCCCAGCCCCTGGATCTTGGCCTTGGCTCGACTTGCACCGACGCGC
    ACACACACACTTCCTAACGTGCTGTCCGCTCACCCCTCCCCAGCGTGGTC
    CATGGGCAGCACGGCAGTGCGCGTCCGGCGGTAGTGAGTGCAGAGGTCCC
    TTCCCCTCCCCCAGGAGCCCCAGGGGTGTGTGCAGATCTGGGGGCTCCTG
    TCCCTTACACCTTCATGCCCCTCCCCTCATACCCACCCTCCAGGCGGGAG
    GCAGCGAGACCTTTGCCCAGGGACTCAGCCAACGGGCACACGGGAGGCC
    A GCCCTCAGCAGCTGGG
    Seq ID No. 4
    GGCCAGACTTCCTCGGAACAGCTCAAAGAGCTCTGTCAAAGCCAGATCCC
    0
    ATCACACGTGGGCACCAATAGGCCATGCCAGCCTCCAAGGGCCGAACTGG
    GTTCTCCACGGCGCACATGAAGCCTGCAGCCTGGCTTATCCTCTTCCGTG
    GTGAAGAGGCAGGCCCGGGACTGGACGAGGGGCTAGCAGGGTGTGGTAG
    GCACCTTGCGCCCCCCACCCCGGCAGGAACCAGAGACCCTGGGGCTGAGA
    G
    TGAGCCTCCAAACAGGATGCCCCACCCTTCAGGCCACCTTTCAATCCAGC
    TACACTCCACCTGCCATTCTCCTCTGGGCACAGGGCCCAGCCCCTGGATC
    TTGGCCTTGGCTCGACTTGCACCCACGCGCACACACACACTTCCTAACGT
    GCTGTCCGCTCACCCCTCCCCAGCGTGGTCCATGGGCAGCACGGCAGTGC
    GCGTCCGGCGGTAGTGAGTGCAGAGGTCCCTTCCCCTCCCCCAGGAGCCC
    CAGGGGTGTGTGCAGATCTGGGGGCTCCTGTCCCTTACACCTTCATGCCC
    CTCCCCTCATACCCACCCTCCAGGCGGGAGGCAGCGAGACCTTTGCCCAG
    GGACTCAGCCAACGGGCACACGGGAGGCCAGCCCTCAGCAGCTGGCTCCC
    AAAGAGGAGGTGGGAGGTAGGTCCACAGCTGCCACAGAGAGAAACCCTG
    ACGGACCCCACAGGGGCCACGCCAGCCGGAACCAGCTCCCTCGTGGGTGA
    GCAATGGCCAGGGCCCCGCCGGCCACCACGGCTGGCCTTGCGCCAGCTGA
    G
    AACTCACGTCCAGTGCAGGGAGACTCAAGACAGCCTGTGCACACAGCCTC
    GGATCTGCTCCCATTTCAAGCAGAAAAAGGAAACCGTGCAGGCAGCCCTC
    AGCATTTCAAGGATTGTAGCAGCGGCCAACTATTCGTCGGCAGTGGCCGA
    TTAGAATGACCGTGGAGAAGGGCGGAAGGGTCTCTCGTGGGCTCTGCGGC
    CAACAGGCCCTGGCTCCACCTGCCCGCTGCCAGCCCGAGGGGCTTGGGCC
    GAGCCAGGAACCACAGTGCTCACCGGGACCACAGTGACTGACCAAACTCC
    CGGCCAGAGCAGCCCCAGGCCAGCCGGGCTCTCGCCCTGGAGGACTCACC
    ATCAGATGCACAAGGGGGCGAGTGTGGAAGAGACGTGTCGCCCGGGCCA
    T
    TTGGGAAGGCGAAGGGACCTTCCAGGTGGACAGGAGGTGGGACGCACTC
    C
    AGGCAAGGGACTGGGTCCCCAAGGCCTGGGGAAGGGGTACTGGCTTGGG
    G
    GTTAGCCTGGCCAGGGAACGGGGAGCGGGGCGGGGGGCTGAGCAGGGAG
    G
    ACCTGACCTCGTGGGAGCGAGGCAAGTCAGGCTTCAGGCAGCAGCCGCAC
    ATCCCAGACCAGGAGGCTGAGGCAGGAGGGGCTTGCAGCGGGGCGGGGG
    C
    CTGCCTGGCTCCGGGGGCTCCTGGGGGACGCTGGCTCTTGTTTCCGTGTC
    CCGCAGCACAGGGCCAGCTCGCTGGGCCTATGCTTACCTTGATGTCTGGG
    GCCGGGGCGTCAGGGTCGTCGTCTCCTCAGGGGAGAGTCCCCTGAGGCTA
    CGCTGGGG*GGGGACTATGGCAGCTCCACCAGGGGCCTGGGGACCAGGG
    G
    CCTGGACCAGGCTGCAGCCCGGAGGACGGGCAGGGCTCTGGCTCTCCAGC
    ATCTGGCCCTCGGAAATGGCAGAACCCCTGGCGGGTGAGCGAGCTGAGA
    G
    CGGGTCAGACAGACAGGGGCCGGCCGGAAAGGAGAAGTTGGGGGCAGAG
    C
    CCGCCAGGGGCCAGGCCCAAGGTTCTGTGTGCCAGGGCCTGGGTGGGCAC
    ATTGGTGTGGCCATGGCTACTTAGATTCGTGGGGCCAGGGCATCCTGGTC
    ACCGTCTCCTCAGGTGAGCCTGGTGTCTGATGTCCAGCTAGGCGCTGGTG
    GGCCGCGGGTGGGCCTGTCTCAGGCTAGGGCAGGGGCTGGGATGTGTATT
    TGTCAAGGAGGGGCAACAGGGTGCAGACTGTGCCCCTGGAAACTTGACCA
    CTGGGGCAGGGGCGTCCTGGTCACGTCTCCTCAGGTAAGACGGCCCTGTG
    CCCCTCTCTCGCGGGACTGGAAAAGGAATTTTCCAAGATTCCTTGGTCTG
    TGTGGGGCCCTCTGGGGCCCCCGGGGGTGGCTCCCCTCCTGCCCAGATGG
    GGCCTCGGCCTGTGGAGCACGGGCTGGGCACACAGCTCGAGTCTAGGGCC
    ACAGAGGCCCGGGCTCAGGGCTCTGTGTGGCCCGGCGACTGGCAGGGGG
    C
    TCGGGTTTTTGGACACCCCCTAATGGGGGCCACAGCACTGTGACCATCTT
    CACAGCTGGGGCCGAGGAGTCGAGGTCACCGTCTCCTCAGGTGAGTCCTC
    GTCAGCCCTCTCTCACTCTCTGGGGGGTTTTGCTGCATTTTGTGGGGGAA
    AGAGGATGCCTGGGTCTCAGGTCTAAAGGTCTAGGGCCAGCGCCGGGGCC
    CAGGAAGGGGCCGAGGGGCCAGGCTCGGCTCGGCCAGGAGCAGAGCTTC
    C
    AGACATCTCGCCTCCTGGCGGGTGCAGTCAGGCCTTTGGCCGGGGGGGTC
    TCAGCACCACGAGGCCTCTTGGCTCCCGAGGTGGCCGGCCCCGGCTGCCT
    CACCAGGCACCGTGCGCGGTGGGCCCGGGCTCTTGGTCGGCCACCCTTTC
    TTAACTGGGATCCGGGCTTAGTTGTCGCAATGTGACAACGGGCTCGAAAG
    CTGGGGCCAGGGGACCCTAGT*TAGGACGCCTCGGGTGGGTGTCCCGCAC
    CCCTCCCCACTTTCACGGCACTCGGCGAGACCTGGGGAGTCAGGTGTTGG
    GGACACTTTGGAGGTCAGGAACGGGAGCTGGGGAGAGGGCTCTGTCAGC
    G
    GGGTCCAGAGATGGGCCGCCCTCCAAGGACGCCCTGCGCGGGGACAAGG
    G
    CTTCTTGGCCTGGCCTGGCCGCTTCACTTGGGCGTCAGGGGGGGCTTCCC
    GGGGCAGGCGGTCAGTCGAGGCGGGTTGGAATTCTGAGTCTGGGTTCGGG
    GTTCGGGGTTCGGCCTTCATGAACAGACAGCCCAGGCGGGCCGTTGTTTG
    GCCCCTGGGGGCCTGGTTGGAATGCGAGGTCTCGGGAAGTCAGGAGGGA
    G
    CCTGGCCAGCAGAGGGTTCCCAGCCCTGCGGCCGAGGGACCTGGAGACG
    G
    GCAGGGCATTGGCCGTCGCAGGGCCAGGCCACACCCCCCAGGTTTTTGTG
    GGGCGAGCCTGGAGATTGCACCACTGTGATTACTATGCTATGGATCTCTG
    GGGCCCAGGCGTTGAAGTCGTCGTGTCCTCAGGTAAGAACGGCCCTCCAG
    GGCCTTTAATTTCTGCTCTCGTCTGTGGGCTTTTCTGACTCTGATCCTCG
    GGAGGCGTCTGTGCCCCCCCCGGGGATGAGGCCGGCTTGCCAGGAGGGGT
    CAGGGACCAGGAGCCTGTGGGAAGTTCTGACGGGGGCTGCAGGCGGGAA
    G
    GGCCCCACCGGGGGGCGAGCCCCAGGCCGCTGGGCGGCAGGAGACCCGT
    G
    AGAGTGCGCCTTGAGGAGGGTGTCTGCGGAACCACGAACGCCCGCCGGG
    A
    AGGGCTTGCTGCAATGCGGTCTTCAGACGGGAGGCGTCTTCTGCCCTCAC
    CGTCTTTCAAGCCCTTGTGGGTCTGAAAGAGCCATGTCGGAGAGAGAAGG
    GACAGGCCTGTCCCGACCTGGCCGAGAGCGGGCAGCCCCGGGGGAGAGC
    G
    GGGCGATCGGCCTGGGCTCTGTGAGGCCAGGTCCAAGGGAGGACGTGTG
    G
    TCCTCGTGACAGGTGCACTTGCGAAACCTTAGAAGACGGGGTATGTTGGA
    AGCGGCTCCTGATGTTTAAGAAAAGGGAGACTGTAAAGTGAGCAGAGTCC
    TCAAGTGTGTTAAGGTTTTAAAGGTCAAAGTGTTTTAAACCTTTGTGACT
    GCAGTTAGCAAGCGTGCGGGGAGTGAATGGGGTGCCAGGGTGGCCGAGA
    G
    GCAGTACGAGGGCCGTGCCGTCCTCTAATTCAGGGCTTAGTTTTGCAGAA
    TAAAGTCGGCCTGTTTTCTAAAAGCATTGGTGGTGCTGAGCTGGTGGAGG
    AGGCCGCGGGCAGCCCTGGCCACCTGCAGCAGGTGGCAGGAAGCAGGTC
    G
    GCCAAGAGGCTATTTTAGGAAGCCAGAAAACACGGTCGATGAATTTATAG
    CTTCTGGTTTCCAGGAGGTGGTTGGGCATGGCTTTGCGCAGCGCCACAGA
    ACCGAAAGTGCCCACTGAGAAAAAACAACTCCTGCTTAATTTGCATTTTT
    CTAAAAGAAGAAACAGAGGCTGACGGAAACTGGAAAGTTCCTGTTTTAAC
    TACTCGAATTGAGTTTTCGGTCTTAGCTTATCAACTGCTCACTTAGATTC
    ATTTTCAAAGTAAACGTTTAAGAGCCGAGGCATTCCTATCCTCTTCTAAG
    GCGTTATTCCTGGAGGCTCATTCACCGCCAGCACCTCCGCTGCCTGCAGG
    CATTGCTGTCACCGTCACCGTGACGGCGCGCACGATTTTCAGTTGGCCCG
    CTTCCCCTCGTGATTAGGACAGACGCGGGCACTCTGGCCCAGCCGTCTTG
    GCTCAGTATCTGCAGGCGTCCGTCTCGGGACGGAGCTCAGGGGAAGAGCG
    TGACTCCAGTTGAACGTGATAGTCGGTGCGTTGAGAGGAGACCCAGTCGG
    GTGTCGAGTCAGAAGGGGCCCGGGGCCCGAGGCCCTGGGCAGGACGGCC
    C
    GTGCCCTGCATCACGGGCCCAGCGTCCTAGAGGCAGGACTCTGGTGGAGA
    GTGTGAGGGTGCCTGGGGCCCCTCCGGAGCTGGGGCCGTGCGGTGCAGGT
    TGGGCTCTCGGCGCGGTGTTGGCTGTTTCTGCGGGATTTGGAGGAATTCT
    TCCAGTGATGGGAGTCGCCAGTGACCGGGCACCAGGGTGGTAAGAGGGA
    G
    GCGGCCGTCGTGGCCAGAGCAGCTGGGAGGGTTCGGTAAAAGGCTCGCCC
    GTTTCCTTTAATGAGGACTTTTCCTGGAGGGCATTTAGTCTAGTCGGGAC
    CGTTTTCGACTCGGGAAGAGGGATGCGGAGGAGGGCATGTGCCCAGGAG
    C
    CGAAGGCGCCGCGGGGAGAAGCCCAGGGCTCTCCTGTCCCCACAGAGGC
    G
    ACGCCACTGCCGCAGACAGACAGGGCCTTTCCCTCTGATGACGGCAAAGG
    CGCCTCGGCTCTTGCGGGGTGCTGGGGGGGAGTCGCCCCGAAGCCGCTCA
    CCCAGAGGCCTGAGGGGTGAGACTGACCGATGCCTCTTGGCCGGGCCTGG
    GGCCGGACCGAGGGGGACTCCGTGGAGGCAGGGCGATGGTGGCTGCGGG
    A
    GGGAACCGACCCTGGGCCGAGCCCGGCTTGGCGATTCCCGGGCGAGGGCC
    CTCAGCCGAGGCGAGTGGGTCCGGCGGAACCACCCTTTCTGGCCAGCGCC
    ACAGGGCTCTCGGGACTGTCCGGGGCGACGCTGGGCTGCCCGTGGCAGGC
    CTGGGCTGACCTGGACTTCACCAGACAGAACAGGGCTTTCAGGGCTGAGC
    TGAGCCAGGTTTAGCGAGGCCAAGTGGGGCTGAACCAGGCTCAACTGGCC
    TGAGCTGGGTTGAGCTGGGCTGACCTGGGCTGAGCTGAGCTGGGCTGGGC
    TGGGCTGGGGTGGGCTGGGCTGGGCTGGACTGGCTGAGCTGAGCTGGGTT
    GAGCTGAGCTGAGCTGGCCTGGGTTGAGCTGGGCTGGGTTGAGCTGAGCT
    GGGTTGAGCTGGGTTGAGCTGGGTTGATCTGAGCTGAGCTGGGCTGAGCT
    GAGCTAGGCTGGGGTGAGCTGGGCTGAGCTGGTTTGAGTTGGGTTGAGCT
    GAGCTGAGCTGGGCTGTGCTGGCTGAGCTAGGCTGAGCTAGGCTAGGTTG
    AGCTGGGCTGGGCTGAGCTGAGCTAGGCTGGGCTGATTTGGGCTGAGCTG
    AGCTGAGCTAGGCTGCGTTGAGCTGGGTGGGCTGGATTGAGCTGGCTGAG
    CTGGCTGAGCTGGGCTGAGCTGGCCTGGGTTGAGCTGAGCTGGACTGGTT
    TGAGCTGGGTCGATCTGGGTTGAGCTGTCCTGGGTTGAGCTGGGCTGGGT
    TGAGCTGAGCTGGGTTGAGCTGGGCTCAGCAGAGCTGGGTTGGGCTGAGC
    TGGGTTGAGCTGAGCTGGGCTGAGCTGGCCTGGGTTGAGCTGGGCTGAGC
    TGAGCTGGGCTGAGCTGGCCTGTGTTGAGCTGGGCTGGGTTGAGCTGGGC
    TGAGCTGGATTGAGCTGGGTTGAGCTGAGCTGGGCTGGGCTGTGCTGACT
    GAGCTGGGCTGAGCTAGGCTGGGGTGAGCTGGGCTGAGCTGATCCGAGCT
    AGGCTGGGCTGGTTTGGGCTGAGCTGAGCTGAGCTAGGCTGGATTGATCT
    GGCTGAGCTGGGTTGAGCTGAGCTGGGCTGAGCTGGTCTGAGCTGGGCTG
    GGTCGAGCTGAGCTGGACTGGTTTGAGCTGGGTCGATCTGGGCTGAGCTG
    GCCTGGGTTGAGCTGGGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGCTG
    AGCTGAGGGCTGGGGTGAGCTGGGCTGAACTAGCCTAGCTAGGTTGGGCT
    GAGCTGGGCTGGTTTGGGCTGAGCTGAGCTGAGCTAGGCTGCATTGAGCA
    GGCTGAGCTGGGCTGAGCAGGCCTGGGGTGAGCTGGGCTAGGTGGAGCT
    G
    AGCTGGGTCGAGCTGAGTTGGGCTGAGCTGGCCTGGGTTGAGGTAGGCTG
    AGCTGAGCTGAGCTAGGCTGGGTTGAGCTGGCTGGGCTGGTTTGCGCTGG
    GTCAAGCTGGGCCGAGCTGOCCTGGGTTGAGCTGGGCTCGGTTGAGCTGG
    GCTGAGCTGAGCCGACCTAGGCTGGGATGAGCTGGGCTGATTTGGGCTGA
    GCTGAGCTGAGCTAGGCTGCATTGAGCAGGCTGAGCTGGGCCTGGAGCCT
    GGCCTGGGGTGAGCTGGGCTGAGCTGCGCTGAGCTAGGCTGGGTTGAGCT
    GGCTGGGCTGGTTTGCGCTGGGTCAAGCTGGGCCGAGCTGGCCTGGGATG
    AGCTGGGCCGGTTTGGGCTGAGCTGAGCTGAGCTAGGCTGCATTGAGCAG
    GCTGAGCTGGGCTGAGCTGGCCTGGGGTGAGCTGGGCTGAGCTAAGCTGA
    GCTGGGCTGGTTTGGGCTGAGCTGGCTGAGCTGGGTCCTGCTGAGCTGGG
    CTGAGCTGACCAGGGGTGAGCTGGGCTGAGTTAGGCTGGGCTCAGCTAGG
    CTGGGTTGATCTGGCAGGGCTGGTTTGCGCTGGGTCAAGCTCCCGGGAGA
    TGGCCTGGGATGAGCTGGGCTGGTTTGGGCTGAGCTGAGCTGAGCTGAGC
    TAGGCTGCATTGAGCAGGCTGAGCTGGGCTGAGCTGGCCTGGGGTGAGCT
    GGGCTGGGTGGAGCTGAGCTGGGCTGAACTGGGCTAAGCTGGCTGAGCTG
    GATCGAGCTGAGCTGGGCTGAGCTGGCCTGGGGTTAGCTGGGCTGAGCTG
    AGCTGAGCTAGGCTGGGTTGAGCTGGCTGGGCTGGTTTGCGCTGGGTCAA
    GCTGGGCCGAGCTGGCCTGGGTTGAGCTGGGCTGGGCTGAGCTGAGCTAG
    GCTGGGTTGAGCTGGGCTGGGCTGAGCTGAGCTAGGCTGCATTGAGCTGG
    CTGGGATGGATTGAGCTGGCTGAGCTGGCTGAGCTGGCTGAGCTGGGCTG
    AGCTGGCCTGGGTTGAGCTGGGCTGGGTTGAGCTGAGCTGGGCTGAGCTG
    GGCTCAGCAGAGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGGTGAGCTG
    GGCTGAGCAGAGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGCTCGAGCA
    GAGCTGGGTTGAGCTGAGCTGGGTTGAGCTGGGCTCAGCAGAGCTGGGTT
    GAGCTGAGCTGGGTTGAGCTGGGCTGAGCTAGCTGGGCTCAGCTAGGCTG
    GGTTGAGCTGAGCTGGGCTGAACTGGGCTGAGCTGGGCTGAACTGGGCTG
    AGCTGGGGTGAGCTGGGCTGAGCAGAGCTGGGCTGAGCAGAGCTGGGTT
    G
    GTCTGAGCTGGGTTGAGCTGGGCTGAGCTGGGCTGAGCAGAGTTGGGTTG
    AGCTGAGCTGGGTTCAGCTGGGCTGAGCTAGGCTGGGTTGAGCTGGGTTG
    AGTTGGGCTGAGCTGGGCTGGGTTGAGCGGAGCTGGGCTGAACTGGGCTG
    AGCTGGGCTGAGCGGAACTGGGTTGATCTGAATTGAGCTGGGCTGAGCCG
    GGCTGAGCCGGGCTGAGCTGGGCTAGGTTGAGCTTGGGTGAGCTTGCCTC
    AGCTGGTCTGAGCTAGGTTGGGTGGAGCTAGGCTGGATTGAGCTGGGCTG
    AGCTGAGCTGATCTGGCCTCAGCTGGGCTGAGGTAGGCTGAACTGGGCTG
    TGCTGGGCTGAGCTGAGCTGAGCCAGTTTGAGCTGGGTTGAGCTGGGCTG
    AGCTGGGCTGTGTTGATCTTTCCTGAACTGGGCTGAGCTGGGCTGAGCTG
    GCCTAGCTGGATTGAACGGGGGTAAGCTGGGCCAGGCTGGACTGGGCTGA
    GCTGAGCTAGGCTGAGCTGAGTTGAATTGGGTTAAGCTGGGCTGAGATGG
    GCTGAGCTGGGCTGAGCTGGGTTGAGCCAGGTCGGACTGGGTTACCCTGG
    GCCACACTGGGCTGAGCTGGGCGGAGCTCGATTAACCTGGTCAGGCTGAG
    TCGGGTCCAGCAGACATGCGCTGGCCAGGCTGGCTTGACCTGGACACGTT
    CGATGAGCTGCCTTGGGATGGTTCACCTCAGCTGAGCCAGGTGGCTCCAG
    CTGGGCTGAGCTGGTGACCCTGGGTGACCTCGGTGACCAGGTTGTCCTGA
    GTCCGGGCCAAGCCGAGGCTGCATCAGACTCGCCAGACCCAAGGCCTGGG
    CCCCGGCTGGCAAGCCAGGGGCGGTGAAGGCTGGGCTGGCAGGACTGTC
    CCGGAAGGAGGTGCACGTGGAGCCGCCCGGACCCCGACCGGCAGGACCT
    GGAAAGACGCCTCTCACTCCCCTTTCTCTTCTGTCCCCTCTCGGGTCCTCA
    GAGAGCCAGTCTGCCCCGAATCTCTACCCCCTCGTCTCCTGCGTCAGCCCC
    CCGTCCGATGAGAGCCTGGTGGCCCTGGGCTGCCTGGCCCGGGACTTCCT
    GCCCAGCTCCGTCACCTTCTCCTGGAA

    Porcine Kappa Light Chain
  • [0114]
    In another embodiment, novel genomic sequences encoding the kappa light chain locus of ungulate immunoglobulin are provided. The present invention provides the first reported genomic sequence of ungulate kappa light chain regions. In one embodiment, nucleic acid sequence is provided that encodes the porcine kappa light chain locus. In another embodiment, the nucleic acid sequence can contain at least one joining region, one constant region and/or one enhancer region of kappa light chain. In a further embodiment, the nucleotide sequence can include at least five joining regions, one constant region and one enhancer region, for example, as represented in Seq ID No. 30. In a further embodiment, an isolated nucleotide sequence is provided that contains at least one, at least two, at least three, at least four or five joining regions and 3′ flanking sequence to the joining region of porcine genomic kappa light chain, for example, as represented in Seq ID No 12. In another embodiment, an isolated nucleotide sequence of porcine genomic kappa light chain is provided that contains 5′ flanking sequence to the first joining region, for example, as represented in Seq ID No. 25. In a further embodiment, an isolated nucleotide sequence is provided that contains 3′ flanking sequence to the constant region and, optionally, the 5′ portion of the enhancer region, of porcine genomic kappa light chain, for example, as represented in Seq ID Nos. 15, 16 and/or 19.
  • [0115]
    In further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 30, 12, 25, 15, 16 or 19 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 30, 12, 25, 15, 16 or 19 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 30, 12, 25, 15, 16 or 19 are provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25 or 30 contiguous nucleotides of Seq ID Nos 1, 4 or 29 are provided. In other embodiments, nucleotide sequences that contain at least 50, 100, 1,000, 2,500, 5,000, 7,000, 8,000, 8,500, 9,000, 10,000 or 15,000 contiguous nucleotides of Seq ID No. 30 are provided. Further provided are nucleotide sequences that hybridizes, optionally under stringent conditions, to Seq ID Nos 30, 12, 25, 15, 16 or 19, as well as, nucleotides homologous thereto.
  • [0116]
    In one embodiment, an isolated nucleotide sequence encoding kappa light chain is provided that includes at least five joining regions, one constant region and one enhancer region, for example, as represented in Seq ID No. 30. In Seq ID No. 30, the coding region of kappa light chain is represented, for example by residues 1-549 and 10026-10549, whereas the intronic sequence is represented, for example, by residues 550-10025, the Joining region of kappa light chain is represented, for example, by residues 5822-7207 (for example, J1:5822-5859, J2:6180-6218, J3:6486-6523, J4:6826-6863, J5:7170-7207), the Constant Region is represented by the following residues: 10026-10549 (C exon) and 10026-10354 (C coding), 10524-10529 (Poly(A) signal) and 11160-11264 (SINE element).
    Seq ID No 30
    GCGTCCGAAGTCAAAAATATCTGCAGCCTTCATGTATTCATAGAAACAAG
    GAATGTCTACATTTTCCAAAGTGGGACCAGAATCTTGGGTGATGTCTAAG
    GCATGTGCATTTGCACATGGTAGGCAAAGGACTTTGCTTCTCCCAGCACA
    TCTTTCTGCAGAGATCCATGGAAACAAGACTCAACTCCAAAGCAGCAAAG
    AAGCAGCAAGTTCTCAAGTGATCTCCTCTGACTCCCTCCTCCCAGGCTAA
    TGAAGCCATGTTGCCCCTGGGGGATTAAGGGCAGGTGTCCATTGTGGCAC
    CCAGCCCGAAGACAAGCAATTTGATCAGGTTCTGAGCACTCCTGAATGTG
    GACTCTGGAATTTTCTCCTCACCTTGTGGCATATCAGCTTAAGTCAAGTA
    CAAGTGACAAACAACATAATCCTAAGAAGAGAGGAATCAAGCTGAAGTC
    A
    AAGGATCACTGCCTTGGATTCTACTGTGAATGATGACCTGGAAAATATCC
    TGAACAACAGCTTCAGGGTGATCATCAGAGACAAAAGTTCCAGAGCCAGg
    tagggaaaccctcaagccttgcaaagagcaaaatcatgccattgggttct
    taacctgctgagtgatttactatatgttactgtgggaggcaaagcgctca
    aatagcctgggtaagtatgtcaaataaaaagcaaaagtggtgtttcttga
    aatgttagacctgaggaaggaatattgataacttaccaataattttcaga
    atgatttatagatgtgcacttagtcagtgtctctccaccccgcacctgac
    aagcagtttagaatttattctaagaatctaggtttgctgggggctacatg
    ggaatcagcttcagtgaagagtttgttggaatgattcactaaattttcta
    tttccagcataaatccaagaacctctcagactagtttattgacactgctt
    ttcctccataatccatctcatctccgtccatcatggacactttgtagaat
    gacaggtcctggcagagactcacagatgcttctgaaacatcctttgcctt
    caaagaatgaacagcacacatactaaggatctcagtgatccacaaattag
    tttttgccacaatggttcttatgataaaagtctttcattaacagcaaatt
    gttttataatagttgttctgctttataataattgcatgcttcactttctt
    ttcttttctttttttttctttttttgctttttagtgccgcaggtgcagca
    tatgaaatttcccaggctaggggtcaaatcagaactacacctactggcct
    acgccacagccacagcaactcaggatctaagccatgtcggtgacctacac
    tacagctcatggcaatgccagatccttaacccaatgagcgaggccaggga
    tcgaacccatgtcctcatggatactagtcaggctcattatccgctgagcc
    ataacaggaactcccgagtttgctttttatcaaaattggtacagccttat
    tgtttctgaaaaccacaaaatgaatgtattcacataattttaaaaggtta
    aataatttatgatatacaagacaatagaaagagaaaacgtcattgcctct
    ttcttccacgacaacacgcctccttaattgatttgaagaaataactactg
    agcatggtttagtgtacttctttcagcaattagcctgtattcatagccat
    acatattcaattaaaatgagatcatgatatcacacaatacataccataca
    gcctatagggatttttacaatcatcttccacatgactacataaaaaccta
    cctaaaaaaaaaaaaaaccctacttcatcctcctattggctgctttgtgc
    tccattaaaaagctctatcataattaggttatgatgaggatttccatttt
    ctacctttcaagcaacatttcaatgcacagtcttatatacacatttgagc
    ctacttttctttttctttctttttttggtttttttttttttttttttttt
    ggtctttttgtcttttctaaggctgcatatggaggttcccaggctagctg
    tctaatcagaactatagctgctggcctacgccacatccacagcaatacaa
    gatctgagccatgtctgcaacttacaccacagctcacagcaacggtggat
    ccttaaaccactgagcaaggccagggatcaaacccataacttcatggctc
    ctagttggatttgttaaccactgagccatgatggcaactcctgagcctac
    ttttctaatcatttccaaccctaggacacttttttaagtttcatttttct
    ccccccaccccctgttttctgaagtgtgtttgcttccactgggtgacttc
    actcccaggatctcatctgcaggatactgcagctaagtgtatgagctctg
    aatttgaatcccaactctgccactcaaagggataggagtttccgatgtgg
    cccaatgggatcagtggcatctctgcagtgccaggacgcaggttccatcc
    ctggcccagcacagtgggttaagaatctggcattgctgcagctgaggcat
    agatttcaattgtgcctcagatctgatccttggcccaaggactgcatatg
    cctcagggcaaccaaaaaagagaaaaggggggtgatagcattagtttcta
    gatttgggggataattaaataaagtgatccatgtacaatgtatggcattt
    tgtaaatgctcaacaaatttcaactattatggagttcccatcatggctca
    gtggaagggaatctgattagcatccatgaggacacaggtccaaccccgac
    cttgctcagtgggcattgctgtgagctgtggcatgggttacagacgaagc
    tcggatctggcattgctgtggctgtggtgtaagccagcaactacagctct
    cattcagcccctagcctgggaacctccatatgcctaaaagacaaaaaata
    aaatttaaattaaaaataaagaaatgttaactattatgattggtactgct
    tgcattactgcaaagaaagtcactttctatactctttaatatcttagttg
    actgtgtgctcagtgaactattttggacacttaatttccactctcttcta
    tctccaacttgacaactctctttcctctcttctggtgagatccactgctg
    actttgctctttaaggcaactagaaaagtgctcagtgacaaaatcaaaga
    aagttaccttaatcttcagaattacaatcttaagttctcttgtaaagctt
    actatttcagtggttagtattattccttggtcccttacaacttatcagct
    ctgatctattgctgattttcaactatttattgttggagttttttcctttt
    ttccctgttcattctgcaaatgtttgctgagcatftgtcaagtgaagata
    ctggactgggccttccaaatataagacaatgaaacatcgggagttctcat
    tatggtgcagcagaaacgaatccaactaggaaatgtgaggttgcaggttc
    gatccctgcccttgctcagtgggttaaggatccagcattaccgtgagctg
    tggtgtaggttgcagacgtggctcagatcctgcgttgctgtggctgtggc
    ataggctggcagctctagctctgattcgaccgctagcctgggaacctcca
    tgcgccccgagtgcagcccttaaaaagcaaaaaaaaaagaaagaaagaaa
    aagacaatgaaacatcaaacagctaacaatccagtagggtagaaagaatc
    tggcaacagataagagcgattaaatgttctaggtccagtgaccttgcctc
    tgtgctctacacagtcgtgccacttgctgagggagaaggtctctcttgag
    ttgagtcctgaaagacattagttgttcacaaactaatgccagtgagtgaa
    ggtgtttccaagcagagggagagtttggtaaaaagctggaagtcacagaa
    agactctaaagagtttaggatggtgggagcaacatacgctgagatggggc
    tggaaggttaagagggaaacaactatagtaagtgaagctggactcacagc
    aaagtgaggacctcagcatccttgatggggttaccatggaaacaccaagg
    cacaccttgatttccaaaacagcaggcacctgattcagcccaatgtgaca
    tggtgggtacccctctagctctacctgttctgtgacaactgacaaccaac
    gaagttaagtctggattttctactctgctgatccttgtttttgtttcaca
    cgtcatctatagcttcatgccaaaatagagttcaaggtaagacgcgggcc
    ttggtttgatatacatgtagtctatcttgtttgagacaatatggtggcaa
    ggaagaggttcaaacaggaaaatactctctaattatgattaactgagaaa
    agctaaagagtcccataatgacactgaatgaagttcatcatttgcaaaag
    ccttcccccccccccaggagactataaaaaagtgcaattttttaaatgaa
    cttatttacaaaacagaaatagactcacagacataggaaacgaacagatg
    gttaccaagggtgaaagggagtaggagggataaataaggagtctggggtt
    agcagatacaccccagtgtacacaaaataaacaacagggacctactatat
    agcacagggaactatatgcagtagcttacaataacctataatggaaaaga
    atgtgaaaaagaatatatgtatgcgtgtgtgtgtaactgaatcactttgc
    tgtaacctgaatctaacataacattgtaaatcaactacagtttttttttt
    ttttaagtgcagggttttggtgttttttttttttcatttttgtttttgtt
    tttgttttttgctttttagggccacacccagacatatgggggttcccagg
    ctaggggtctaattagagctacagttgccggcttgcaccacagccacagc
    aacatcagatccgagccgcacttgcgacttacaccacagctcatggcaat
    accagatccttaacccactgagcaaggcccagggatcgtacccgcaacct
    catggttcctagtcagattcatttctgctgcgctacaatgggaactccaa
    gtgcagttttttgtaatgtgcttgtctttctttgtaattcatattcatcc
    tacttcccaataaataaataaatacataaataataaacataccattgtaa
    atcaactacaattttttttaaatgcagggtttttgttttttgttttttgt
    tttgtctttttgccttttctagggccgctcccatggcatatggaggttcc
    caggctaggggtcgaatcggagctgtagccaccggcctacgccagagcca
    cagcaacgcgggatccgagccgcgtctgcaacctacaccacagctcacgg
    caacgccggatcgttaacccactgagcaagggcagggatcgaacctgcaa
    cctcatggttcctagtcagattcgttaactactgagccacaacggaaact
    cctaaagtgcagtttttaaatgtgcttgtctttctttgtaatttacactc
    aacctacttcccaataaataaataaataaacaaataaatcatagacatgg
    ttgaattctaaaggaagggaccatcaggccttagacagaaatacgtcatc
    ttctagtattttaaaacacactaaagaagacaaacatgctctgccagaga
    agcccagggcctccacagctgcttgcaaagggagttaggcttcagtagct
    gacccaaggctctgttcctcttcagggaaaagggtttttgttcagtgaga
    cagcagacagctgtcactgtgGTGGACGTTCGGCCAAGGAACCAAGCTGG
    AACTCAAACgtaagtcaatccaaacgttccttccttggctgtctgtgtct
    tacggtctctgtggctctgaaatgattcatgtgctgactctctgaaacca
    gactgacattctccagggcaaaactaaagcctgtcatcaaactggaaaac
    tgagggcacattttctgggcagaactaagagtcaggcactgggtgaggaa
    aaacttgttagaatgatagtttcagaaacttactgggaagcaaagcccat
    gttctgaacagagctctgctcaagggtcaggaggggaaccagtttttgta
    caggagggaagttgagacgaacccctgtgTATATGGTTTCGGCGCGGGGA
    CCAAGCTGGAGCTCAAACgtaagtggctttttccgactgattctttgctg
    tttctaattgttggttggctttttgtccatttttcagtgttttcatcgaa
    ttagttgtcagggaccaaacaaattgccttcccagattaggtaccaggga
    ggggacattgctgcatgggagaccagagggtggctaatttttaacgtttc
    caagccaaaataactggggaagggggcttgctgtcctgtgagggtaggtt
    tttatagaagtggaagttaaggggaaatcgctatgGTTGACTTTTGGCTC
    GGGGACCAAAGTGGAGCCCAAAAttgagtacattttccatcaattatttg
    tgagatttttgtcctgttgtgtcatttgtgcaagtttttgacattttggt
    tgaatgagccattcccagggacccaaaaggatgagaccgaaaagtagaaa
    agagccaacttttaagctgagcagacagaccgaattgttgagtttgtgag
    gagagtagggtttgtagggagaaaggggaacagatcgctggctttttctc
    tgaattagcctttctcatgggactggcttcagagggggtttttgatgagg
    gaagtgttctagagccttaactgtgGGTTGTGTTCGGTAGCGGGACCAAG
    CTGGAAATCAAACgtaagtgcacttttctactcctttttctttcttatac
    gggtgtgaaattggggacttttcatgtttggagtatgagttgaggtcagt
    tctgaagagagtgggactcatccaaaaatctgaggagtaagggtcagaac
    agagttgtctcatggaagaacaaagacctagttagttgatgaggcagcta
    aatgagtcagttgacttgggatccaaatggccagacttcgtctgtaacca
    acaatctaatgagatgtagcagcaaaaagagatttccattgaggggaaag
    taaaattgttaatattgtgGATCACCTTTGGTGAAGGGACATCCGTGGAG
    ATTGAACgtaagtattttttctctactaccttctgaaatttgtctaaatg
    ccagtgttgacttttagaggcttaagtgtcagttttgtgaaaaatgggta
    aacaagagcatttcatatttattatcagtttcaaaagttaaactcagctc
    caaaaatgaatttgtagacaaaaagattaatttaagccaaattgaatgat
    tcaaaggaaaaaaaaattagtgtagatgaaaaaggaattcttacagctcc
    aaagagcaaaagcgaattaattttctttgaactttgccaaatcttgtaaa
    tgatttttgttctttacaatttaaaaaggttagagaaatgtatttcttag
    tctgttttctctcttctgtctgataaattattatatgagataaaaatgaa
    aattaataggatgtgctaaaaaatcagtaagaagttagaaaaatatatgt
    ttatgttaaagttgccacttaattgagaatcagaagcaatgttattttta
    aagtctaaaatgagagataaactgtcaatacttaaattctgcagagattc
    tatatcttgacagatatctcctttttcaaaaatccaatttctatggtaga
    ctaaatttgaaatgatcttcctcataatggagggaaaagatggactgacc
    ccaaaagctcagatttaaagaaatctgtttaagtgaaagaaaataaaaga
    actgcattttttaaaggcccatgaatttgtagaaaaataggaaatatttt
    aataagtgtattcttttattttcctgttattacttgatggtgtttttata
    ccgccaaggaggccgtggcaccgtcagtgtgatctgtagaccccatggcg
    gccttttttcgcgattgaatgaccttggcggtgggtccccagggctctgg
    tggcagcgcaccagccgctaaaagccgctaaaaactgccgctaaaggcca
    cagcaaccccgcgaccgcccgttcaactgtgctgacacagtgatacagat
    aatgtcgctaacagaggagaatagaaatatgacgggcacacgctaatgtg
    gggaaaagagggagaagcctgatttttattttttagagattctagagata
    aaattcccagtattatatccttttaataaaaaatttctattaggagatta
    taaagaatttaaagctatttttttaagtggggtgtaattctttcagtagt
    ctcttgtcaaatggatttaagtaatagaggcttaatccaaatgagagaaa
    tagacgcataaccctttcaaggcaaaagctacaagagcaaaaattgaaca
    cagcagccagccatctagccactcagattttgatcagttttactgagttt
    gaagtaaatatcatgaaggtataattgctgataaaaaaataagatacagg
    tgtgacacatctttaagtttcagaaatttaatggcttcagtaggattata
    tttcacgtatacaaagtatctaagcagataaaaatgccattaatggaaac
    ttaatagaaatatatttttaaattccttcattctgtgacagaaattttct
    aatctgggtcttttaatcacctaccctttgaaagagtttagtaatttgct
    atttgccatcgctgtttactccagctaatttcaaaagtgatacttgagaa
    agattatttttggtttgcaaccacctggcaggactattttagggccattt
    taaaactcttttcaaactaagtattftaaactgttctaaaccatttaggg
    ccttttaaaaatcttttcatgaatttcaaacttcgttaaaagttattaag
    gtgtctggcaagaacttccttatcaaatatgctaatagtttaatctgtta
    atgcaggatataaaattaaagtgatcaaggcttgacccaaacaggagtat
    cttcatagcatatttcccctcctttttttctagaattcatatgattttgc
    tgccaaggctattttatataatctctggaaaaaaaatagtaatgaaggtt
    aaaagagaagaaaatatcagaacattaagaattcggtattttactaactg
    cttggttaacatgaaggtttttattttattaaggtttctatctttataaa
    aatctgttcccttttctgctgatttctccaagcaaaagattcttgatttg
    ttttttaactcttactctcccacccaagggcctgaatgcccacaaagggg
    acttccaggaggccatctggcagctgctcaccgtcagaagtgaagccagc
    cagttcctcctgggcaggtggccaaaattacagttgacccctcctggtct
    ggctgaaccttgccccatatggtgacagccatctggccagggcccaggtc
    tccctctgaagcctttgggaggagagggagagtggctggcccgatcacag
    atgcggaaggggctgactcctcaaccggggtgcagactctgcagggtggg
    tctgggcccaacacacccaaagcacgcccaggaaggaaaggcagcttggt
    atcactgcccagagctaggagaggcaccgggaaaatgatctgtccaagac
    ccgttcttgcttctaaactccgagggggtcagatgaagtggttttgtttc
    ttggcctgaagcatcgtgttccctgcaagaagcggggaacacagaggaag
    gagagaaaagatgaactgaacaaagcatgcaaggcaaaaaaggccttagg
    atggctgcaggaagttagttcttctgcattggctccttactggctcgtcg
    atcgcccacaaacaacgcacccagtggagaacttccctgttacttaaaca
    ccattctctgtgcttgcttcctcagGGGCTGATGCCAAGCCATCCGTCTT
    CATCTTCCCGCCATCGAAGGAGCAGTTAGCGACCCCAACTGTCTCTGTGG
    TGTGCTTGATCAATAACTTCTTCCCCAGAGAAATCAGTGTCAAGTGGAAA
    GTGGATGGGGTGGTCCAAAGCAGTGGTCATCCGGATAGTGTCACAGAGCA
    GGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTCTCGCTGCCCA
    CGTCACAGTACCTAAGTCATAATTTATATTCCTGTGAGGTCACCCACAAG
    ACCCTGGCCTCCCCTCTGGTCACAAGCTTCAACAGGAACGAGTGTGAGGC
    TtagAGGCCCACAGGCCCCTGGCCTGCCCCCAGCCCCAGCCCCCCTCCCC
    ACCTGAAGCCTCAGGCCCTTGCCCCAGAGGATCCTTGGCAATCCCCCAGC
    CCCTCTTCCCTCCTCATCCCCTCCCCCTCTTTGGCTTTAACCGTGTTAAT
    ACTGGGGGGTGGGGGAATGAATAaataaaGTGAACCTTTGCACCTGTGAt
    ttctctctcctgtctgattttaaggttgttaaatgttgttttccccatta
    tagttaatcttttaaggaactacatactgagttgctaaaaactacaccat
    cacttataaaattcacgccttctcagttctcccctcccctcctgtcctcc
    gtaagacaggcctccgtgaaacccataagcacttctctttacaccctctc
    ctgggccggggtaggagactttttgatgtcccctcttcagcaagcctcag
    aaccattttgagggggacagttcttacagtcacat*tcctgtgatctaat
    gactttagttaccgaaaagccagtctctcaaaaagaagggaacggctaga
    aaccaagtcatagaaatatatatgtataaaatatatatatatccatatat
    gtaaaataacaaaataatgataacagcataggtcaacaggcaacagggaa
    tgttgaagtccattctggcacttcaatttaagggaataggatgccttcat
    tacattttaaatacaatacacatggagagcttcctatctgccaaagacca
    tcctgaatgccttccacactcactacaaggttaaaagcattcattacaat
    gttgatcgaggagttcccgttgtggctcagcaggttaagaacgtgactgg
    tatccaggaggatgcgggtttggtccccagcctcgctcagtggattaagg
    atccagtgttgctgcaagatcacgggctcagatcccgtgttctatggcta
    tggtgtaggctggtagctgcatgcagccctaatttgacccctagcctggg
    aactgccatatgccacatgtgaggcccttaaaacctaaaagaaaaaaaaa
    gaaaagaaatatcttacacccaatttatagataagagagaagctaaggtg
    gcaggcccaggatcaaagccctacctgcctatcttgacacctgatacaaa
    ttctgtcttctagggtttccaacactgcatagaacagagggtcaaacatg
    ctaccctcccagggactcctcccttcaaatgacataaattttgttgccca
    tctctgggggcaaaactcaacaatcaatggcatctctagtaccaagcaag
    gctcttctcatgaagcaaaactctgaagccagatccatcatgacccaagg
    aagtaaagacaggtgttactggttgaactgtatccttcaattcaatatgc
    tcaatttccaactcccagtccccgtaaatacaaccccctttgggaagaga
    gtccttgcagatgtagccacgttaaaaagagattatacagaaaggctagt
    gaggatgcagtgaaacgggatctttcatacattgctggtggaaatgtaaa
    atgctgcaggcactctagaaaataatttgccagttttttgaaaagctaaa
    caaaatagtttagttgcattctgggttatttatcccccagaaattaaaaa
    ttatgtccgcacaaaaacgtgtacataatcattcataacagccttgtac
    Seq ID No. 12
    caaggaaccaagctggaactcaaacgtaagtcaatccaaacgttccttcc
    ttggctgtctgtgtcttacggtctctgtggctctgaaatgattcatgtgc
    tgactctctgaaaccagactgacattctccagggcaaaactaaagcctgt
    catcaaactggaaaactgagggcacattttctgggcagaactaagagtca
    ggcactgggtgaggaaaaacttgttagaatgatagtttcagaaacttact
    gggaagcaaagcccatgttctgaacagagctctgctcaagggtcaggagg
    ggaaccagtttttgtacaggagggaagttgagacgaacccctgtgtatat
    ggtttcggcgcggggaccaagctggagctcaaacgtaagtggctttttcc
    gactgattctttgctgtttctaattgttggttggctttttgtccattttt
    cagtgttttcatcgaattagttgtcagggaccaaacaaattgccttccca
    gattaggtaccagggaggggacattgctgcatgggagaccagagggtggc
    taatttttaacgtttccaagccaaaataactggggaagggggcttgctgt
    cctgtgagggtaggtttttatagaagtggaagttaaggggaaatcgctat
    ggttcacttttggctcggggaccaaagtggagcccaaaattgagtacatt
    ttccatcaattatttgtgagatttttgtcctgttgtgtcatttgtgcaag
    tttttgacattttggttgaatgagccattcccagggacccaaaaggatga
    gaccgaaaagtagaaaagagccaacttttaagctgagcagacagaccgaa
    ttgttgagtttgtgaggagagtagggtttgtagggagaaaggggaacaga
    tcgctggctttttctctgaattagcctttctcatgggactggcttcagag
    ggggtttttgatgagggaagtgttctagagccttaactgtgggttgtgtt
    cggtagcgggaccaagctggaaatcaaacgtaagtgcacttttctactcc
    tttttctttcttatacgggtgtgaaattggggacttttcatgtttggagt
    atgagttgaggtcagttctgaagagagtgggactcatccaaaaatctgag
    gagtaagggtcagaacagagttgtctcatggaagaacaaagacctagtta
    gttgatgaggcagctaaatgagtcagttgacttgggatccaaatggccag
    acttcgtctgtaaccaacaatctaatgagatgtagcagcaaaaagagatt
    tccattgaggggaaagtaaaattgttaatattgtggatcacctttggtga
    agggacatccgtggagattgaacgtaagtattttttctctactaccttct
    gaaatttgtctaaatgccagtgttgacttttagaggcttaagtgtcagtt
    ttgtgaaaaatgggtaaacaagagcatttcatatttattatcagtttcaa
    aagttaaactcagctccaaaaatgaatttgtagacaaaaagattaattta
    agccaaattgaatgattcaaaggaaaaaaaaattagtgtagatgaaaaag
    gaattcttacagctccaaagagcaaaagcgaattaattttctttgaactt
    tgccaaatcttgtaaatgatttttgttctttacaatttaaaaaggttaga
    gaaatgtatttcttagtctgttttctctcttctgtctgataaattattat
    atgagataaaaatgaaaattaataggatgtgctaaaaaatcagtaagaag
    ttagaaaaatatatgtttatgttaaagttgccacttaattgagaatcaga
    agcaatgttatttttaaagtctaaaatgagagataaactgtcaatactta
    aattctgcagagattctatatcttgacagatatctcctttttcaaaaatc
    caatttctatggtagactaaatttgaaatgatcttcctcataatggaggg
    aaaagatggactgaccccaaaagctcagattt*aagaaaacctgtttaag
    *gaaagaaaataaaagaactgcattttttaaaggcccatgaatttgtaga
    aaaataggaaatattttaataagtgtattcttttattttcctgttattac
    ttgatggtgtttttataccgccaaggaggccgtggcaccgtcagtgtgat
    ctgtagaccccatggcggccttttttcgcgattgaatgaccttggcggtg
    ggtccccagggctctggtggcagcgcaccagccgctaaaagccgctaaaa
    actgccgctaaaggccacagcaaccccgcgaccgcccgttcaactgtgct
    gacacagtgatacagataatgtcgctaacagaggagaatagaaatatgac
    gggcacacgctaatgtggggaaaagagggagaagcctgatttttattttt
    tagagattctagagataaaattcccagtattatatccttttaataaaaaa
    tttctattaggagattataaagaatttaaagctatttttttaagtggggt
    gtaattctttcagtagtctcttgtcaaatggatttaagtaatagaggctt
    aatccaaatgagagaaatagacgcataaccctttcaaggcaaaagctaca
    agagcaaaaattgaacacagcagccagccatctagccactcagattttga
    tcagttttactgagtttgaagtaaatatcatgaaggtataattgctgata
    aaaaaataagatacaggtgtgacacatctttaagtttcagaaatttaatg
    gcttcagtaggattatatttcacgtatacaaagtatctaagcagataaaa
    atgccattaatggaaacttaatagaaatatatttttaaattccttcattc
    tgtgacagaaattttctaatctgggtcttttaatcacctaccctttgaaa
    gagtttagtaatttgctatttgccatcgctgtttactccagctaatttca
    aaagtgatacttgagaaagattatttttggtttgcaaccacctggcagga
    ctattttagggccattttaaaactcttttcaaactaagtattttaaactg
    ttctaaaccatttagggccttttaaaaatcttttcatgaatttcaaactt
    cgttaaaagttattaaggtgtctggcaagaacttccttatcaaatatgct
    aatagtttaatctgttaatgcaggatataaaattaaagtgatcaaggctt
    gacccaaacaggagtatcttcatagcatatttcccctcctttttttctag
    aattcatatgattttgctgccaaggctattttatataatctctggaaaaa
    aaatagtaatgaaggttaaaagagaagaaaatatcagaacattaagaatt
    cggtattttactaactgcttggttaacatgaaggtttttattttattaag
    gtttctatctttataaaaatctgttcccttttctgctgatttctccaagc
    aaaagattcttgatttgttttttaactcttactctcccacccaagggcct
    gaatgcccacaaaggggacttccaggaggccatctggcagctgctcaccg
    tcagaagtgaagccagccagttcctcctgggcaggtggccaaaattacag
    ttgacccctcctggtctggctgaaccttgccccatatggtgacagccatc
    tggccagggcccaggtctccctctgaagcctttgggaggagagggagagt
    ggctggcccgatcacagatgcggaaggggctgactcctcaaccggggtgc
    agactctgcagggtgggtctgggcccaacacacccaaagcacgcccagga
    aggaaaggcagcttggtatcactgcccagagctaggagaggcaccgggaa
    aatgatctgtccaagacccgttcttgcttctaaactccgagggggtcaga
    tgaagtggttttgtttcttggcctgaagcatcgtgttccctgcaagaagc
    ggggaacacagaggaaggagagaaaagatgaactgaacaaagcatgcaag
    gcaaaaaaggccttaggatggctgcaggaagttagttcttctgcattggc
    tccttactggctcgtcgatcgcccacaaacaacgcacccagtggagaact
    tccctgttacttaaacaccattctctgtgcttgcttcctcaggggctgat
    gccaagccatccgtcttcatcttcccgccatcgaaggagcagttagcgac
    cccaactgtctctgtggtgtgcttgatca
    Seq ID No. 15
    gatgccaagccatccgtcttcatcttcccgccatcgaaggagcagttagc
    gaccccaactgtctctgtggtgtgcttgatcaataacttcttccccagag
    aaatcagtgtcaagtggaaagtggatggggtggtccaaagcagtggtcat
    ccggatagtgtcacagagcaggacagcaaggacagcacctacagcctcag
    cagcaccctctcgctgcccacgtcacagtacctaagtcataatttatatt
    cctgtgaggtcacccacaagaccctggcctcccctctggtcacAAGCTTC
    AACAGGAACGAGTGTGAGGCTTAGAGGCCCACAGGCCCCTGGCCTGCCCC
    CAGCCCCAGCCCCGCTCCCCACCTCAAGCCTCAGGCCCTTGCCCCAGAGG
    ATCCTTGGCAATCCCCCAGCCCCTCTTCCCTCCTCATCCCCTCCCCCTCT
    TTGGCTTTAACCGTGTTAATACTGGGGGGTGGGGGAATGAATAAATAAAG
    TGAACCTTTGCACCTGTGATTTCTCTCTCCTGTCTGATTTTAAGGTTGTT
    AAATGTTGTTTTCCCCATTATAGTTAATCTTTTAAGGAACTACATACTGA
    GTTGCTAAAAACTACACCATCACTTATAAAATTCAcgCCTTCTCAGTTCT
    CCCCTCCCCTCCTGTCCTCCGTAAGACAGGCCTCCGTGAAACCCATAAGC
    ACTTCTCTTTACACCCTCTCCTGGGCCGGGGTAGGAGACTTTTTGATGTC
    CCCTcTTCAGCAAGCCTCAGAACCATTTTGAGGGGGACAGTTCTTACAGT
    CACAT*TCCtGtGATCTAATGACTTTAGTTaCCGAAAAGCCAGTGTCTCA
    AAAAGAAGGGAACGGCTAGAAACCAAGTCATAGAAATATATATGTATAAA
    ATATATATATATCCATATATGTAAAATAACAAAATAATGATAACAGCATA
    GGTCAACAGGCAACAGGGAATGTTGAAGTCCATTCTGGCACTTCAATTTA
    AGGGAATAGGATGCCTTCATTACATTTTAAATACAATACACATGGAGAGC
    TTCCTATCTGCCAAAGACCATCCTGAATGCCTTCCACACTCACTACAAGG
    TTAAAAGCATTCATTACAATGTTGATCGAGGAGTTCCCGTTGTGGCTCAG
    CAGGTTAAGAACGTGACTGGTATCCAGGAGGATGCGGGTTTGGTCCCCAG
    CCTCGCTCAGTGGATTAAGGATCCAGTGTTGCTGCAAGATCACGGGCTCA
    GATCCCGTGTTCTATGGCTATGGTGTAGGCTGGTAGCTGCATGCAGCCCT
    AATTTGACCCCTAGCCTGGGAACTGCCATAtGCCACATGTGAGGCCCTTA
    AAACCTAAAAGAAAAAaAAAGAAAAGAAATATCTTACACCCAATTTATAG
    ATAAGAGAGAAGCTAAGGTGGCAGGCCCAGGATCAAAGCCCTACCTGCCT
    ATCTTGACACCTGAtACAAATTCTGTCTTCTAGGGtTTCCAACACTGCAT
    AGAACAGAGGGTCAAACATGCTACCCTCCCAGGGACTCCTCCCTTCAAAT
    GACATAAATTTTGTTGCCCATCTCTGGGGGCAAAACTCAACAATCAATGG
    CATCTCTAGTACCAAGCAAGGCTCTTCTCATGAAGCAAAACTCTGAAGCC
    AGATCCATCATGACCCAAGGAAGTAAAGACAGGTGTTACTGGTTGAACTG
    TATCCTTCAATTCAATATGCTCAATTTCCAACTCCCAGTCCCCGTAAATA
    CAACCCCCTTTGGGAAGAGAGTCCTTGCAGATGTAGCCACGTTAAAAAGA
    GATTATACAGAAAGGCTAGTGAGGATGCAGTGAAACGGGATCTTTCATAC
    ATTGCTGGTGGAAATGTAAAATGCTGCAGGCACTCTAGAAAATAATTTGC
    CAGTTTTTTGAAAAGCTAAACAAAATAGTTTAGTTGCATTCTGGGTTATT
    TATCCCCCAGAAATTAAAAATTATGTCCGCACAAAAACGTGTACATAATC
    ATTCATAACAGCCTTGTACGAAAAGCTT
    Seq ID No. 16
    GGATCCTTAACCCACTAATCGAGGATCAAACACGCATCCTCATGGACAAT
    ATGTTGGGTTCTTAGCCTGCTGAGACACAACAGGAACTCCCCTGGCACCA
    CTTTAGAGGCCAGAGAAACAGCACAGATAAAATTCCCTGCCCTCATGAAG
    CTTATAGTCTAGCTGGGGAGATATCATAGGCAAGATAAACACATACAAAT
    ACATCATCTTAGGTAATAATATATACTAAGGAGAAAATTACAGGGGAGAA
    AGAGGACAGGAATTGCTAGGGTAGGATTATAAGTTCAGATAGTTCATCAG
    GAACACTGTfGCTGAGAAGATAACATTTAGGTAAAGACCGAAGTAGTAAG
    GAAATGGACCGTGTGCCTAAGTGGGTAAGACCATTCTAGGCAGCAGGAAC
    AGCGATGAAAGCACTGAGGTGGGTGTTCACTGCACAGAGTTGTTCACTGC
    ACAGAGTTGTGTGGGGAGGGGTAGGTCTTGCAGGGTCTTATGGTCACAGG
    AAGAATTGTTTTACTCCCACCGAGATGAAGGTTGGTGGATTTTGAGCAGA
    AGAATAATTCTGCCTGGTTTATATATAACAGGATTTCCCTGGGTGCTCTG
    ATGAGAATAATCTGTCAGGGGTGGGATAGGGAGAGATATGGCAATAGGAG
    CCTTGGCTAGGAGCCCACGACAATAATTCCAAGTGAGAGGTGGTGCTGCA
    TTGAAAGCAGGACTAACAAGACCTGCTGACAGTGTGGATGTAGAAAAAGA
    TAGAGGAGACGAAGGTGCATCTAGGGTTTTCTGCCTGAGGAATTAGAAAG
    ATAAAGCTAAAGCTTATAGAAGATGCAGCGCTCTGGGGAGAAAGACCAGC
    AGCTCAGTTTTGATCCATCTGGAATTAATTTTGGCATAAAGTATGAGGTA
    TGTGGGTTAACATTATTTGTTTTTTTTTTTTCCATGTAGCTATCCAACTG
    TCCCAGCATCATTTATTTTAAAAGACTTTCCTTTCCCCTATTGGATTGTT
    TTGGCACCTTCACTGAAGATCAACTGAGCATAAAATTGGGTCTATTTCTA
    AGCTCTTGATTCCATTCCATGACCTATTTGTTCATCTTTACCCCAGTAGA
    CACTGCCTTGATGATTAAAGCCCCTGTTACCATGTCTGTTTTGGACATGG
    TAAATCTGAGATGCCTATTAGCCAACCAAGCAAGCACGGCCCTTAGAGAG
    CTAGATATGAGAGCCTGGAATTCAGACGAGAAAGGTCAGTCCTAGAGACA
    TACATGTAGTGCCATCACCATGCGGATGGTGTTAAAAGCCATCAGACTGC
    AACAGACTGTGAGAGGGTACCAAGCTAGAGAGCATGGATAGAGAAACCCA
    AGCACTGAGCTGGGAGGTGCTCCTACATTAAGAGATTAGTGAGATGAAGG
    ACTGAGAAGATTGATCAGAGAAGAAGGAaAATCAGGAAAATGGTGCTGTC
    cTGAAAATCCAAGGGAAGAGATGTTCCAAAGAGGAGAaAACTGATCAGTT
    GTCAGCTAGCGTCAATTGGGATGAAAATGGACCATTGGACAGAGGGATGT
    AGTGGGTCATGGGTGAATAGATAAGAGCAGCTTCTATAGAATGGCAGGGG
    CAAAATTCTCATCTGATCGGCATGGGTTcTAAAGAAAACGGGAAGAAAAA
    ATTGAGTGCATGACCAGTCCCTTCAAGTAGAGAGGTgGAAAAGGGAAGGA
    GGAAAATGAGGCCACGACAACATGAGAGAAATGACAGCATTTTTAAAAAT
    TTTTTATTTTATTTtATTTATTTATTTTTGCTTTTTAGGGCTGCCCCTGC
    AAcatatggaggttcccaggttaggggtctaatcagagctatagctgcca
    gcctacaccacagccatagcaatgccagatctacatgacctacaccacag
    ctcacagcaacgccggatccttaacccactgagtgaggccagagatcaaa
    cccatatccttatggatactagtcaggttcattaccactgagccaaaatg
    ggaaATCCTGAGTAATGACAGCATTTTTTAATGTGCCAGGAAGCAAAACT
    TGCCACCCCGAAATGTCTCTCAGGCATGTGGATTATTTTGAGCTGAAAAC
    GATTAAGGCCCAAAAAACACAAGAAGAAATGTGGACCTTCCCCCAACAGC
    CTAAAAAATTTAGATTGAGGGCCTGTTCCCAGAATAGAGCTATTGCCAGA
    CTTGTCTACAGAGGCTAAGGGCTAGGTGTGGTGGGGAAACCCTCAGAGAT
    CAGAGGGACGTTTATGTACCAAGCATTGACATTTCCATCTCCATGCGAAT
    GGCCTTCTTCCCCTCTGTAGCCCCAAACCACCACCCCCAAAATCTTCTTC
    TGTCTTTAGCTGAAGATGGTGTTGAAGGTGATAGTTTCAGCCACTTTGGC
    GAGTTCCTCAGTTGTTCTGGGTCTTTCCTCCGGATCCACATTATTCGACT
    GTGTTTGATTTTCTCCTGTTTATCTGTCTCATTGGCACCCATTTCATTCT
    TAGACCAGCCCAAAGAACCTAGAAGAGTGAAGGAAAATTTCTTCCACCCT
    GACAAATGCTAAATGAGAATCACCgCAGTAGAGGAAAATGATCTGGTgCT
    GCGGGAGATAGAAGAGAAAATcGCTGGAGAGATGTCACTGAGTAGGTGAG
    ATGGGAAAGGGGGGGCACAGGTGGAGGTGTTGCCCTCAGCTAGGAAGACA
    GACAGTTcacagaagagaagcgggtgtccgtGGACATCTTGCCTCATGGA
    TGAGGAAACCGAGGCTAAGAAAGACTGCAAAAGAAAGGTAAGGATTGCAG
    AGAGGTCGATCCATGACTAAAATCACAGTAACCAACCCCAAACCACCATG
    TTTTCTCCTAGTCTGGCACGTGGCAGGTACTGTGTAGGTTTTCAATATTA
    TTGGTTTGTAACAGTACCTATTAGGCCTCCATCcCCTCCTCTAATACTAA
    CAAAAGTGTGAGACTGGTCAGTGAAAAATGGTCTTCTTTCTCTATGCAAT
    CTTTCTCAAGAAGATACATAACTTTTTATTTTATCATaGGCTTGAAGAGC
    AAATGAGAAACAgCCTCCAACCTATGACACCGTAACAAAGTGTTTATGAT
    CAGTGAAGGGCAAGAAACAAAACATACACaGTAAAGACCCTCCATAATAT
    TGtGGGCTGGCCCAaCACAGGCCAGGTTGTAAAAGCTTTTTATTCTTTGA
    TAGAGGAATGGATAGTAATGTTTCAACCTGGACAGAGAT*CATGTTCACT
    GAATCCTTCCAAAAATTCATGGGTAGTTTGAAtTATAAGGAAAATAAGAC
    TTAGGATAAATACTTTgTCCA*GATCCCAGAGTTAATgCCAAAATCAGTT
    TTCAGACTCCAGGCAGCCTGATCAAGAGCCTAAACTTTAAAGACACAGTC
    CCTTAATAACTACTATTCACAGTTGCACTTTCAgGGCGCAAAGACTCATT
    GAATCCTACAATAGAATGAGTTTAGATATCAAATCTCTCAGTAATAGATG
    AGGAGACTAAATAGCGGGCATGACCTGGTCACTTAAAGACAGAATTGAGA
    TTCAAGGCTAGTGTTCTTTCTACCTGTTTTGTTTCTACAAGATGTAGCAA
    TGCGCTAATTACAGACCTCTCAGGGAAGGAATTCACAACCCTCAGCAAAA
    ACCAAAGACAAATCTAAGACAACTAAGAGTGTTGGTTTAATTTGGAAAAA
    TAACTCACTAACCAAACGCCCCTCTTAGCACCCCAATGTCTTCCACCATC
    ACAGTGCTCAGGCCTCAACCATGCCCCAATCACCCCAGCCCCAGACTGGT
    TATTACCAAGTTTCATGATGACTGGCCTGAGAAGATCAAAAAAGCAATGA
    CATCTTACAGGGGACTACCCCGAGGACCAAGATAGCAACTGTCATAGCAA
    CCGTCACACTGCTTTGGTCA
    Seq ID No. 19
    ggatcaaacacgcatcctcatggacaatatgttgggttcttagcctgctg
    agacacaacaggaactcccctggcaccactttagaggccagagaaacagc
    acagataaaattccctgccctcatgaagcttatagtctagctggggagat
    atcataggcaagataaacacatacaaatacatcatcttaggtaataatat
    atactaaggagaaaattacaggggagaaagaggacaggaattgctagggt
    aggattataagttcagatagttcatcaggaacactgttgctgagaagata
    acatttaggtaaagaccgaagtagtaaggaaatggaccgtgtgcctaagt
    gggtaagaccattctaggcagcaggaacagcgatgaaagcactgaggtgg
    gtgttcactgcacagagttgttcactgcacagagttgtgtggggaggggt
    aggtcttgcaggctcttatggtcacaggaagaattgttttactcccaccg
    agatgaaggttggtggattttgagcagaagaataattctgcctggtttat
    atataacaggatttccctgggtgctctgatgagaataatctgtcaggggt
    gggatagggagagatatggcaataggagccttggctaggagcccacgaca
    ataattccaagtgagaggtggtgctgcattgaaagcaggactaacaagac
    ctgctgacagtgtggatgtagaaaaagatagaggagacgaaggtgcatct
    agggttttctgcctgaggaattagaaagataaagctaaagcttatagaag
    atgcagcgctctggggagaaagaccagcagctcagttttgatccatctgg
    aattaattttggcataaagtatgaggtatgtgggttaacattatttgttt
    tttttttttccatgtagctatccaactgtcccagcatcatttattttaaa
    agactttcctttcccctattggattgttttggcaccttcactgaagatca
    actgagcataaaattgggtctatttctaagctcttgattccattccatga
    cctatttgttcatctttaccccagtagacactgccttgatgattaaagcc
    cctgttaccatgtctgttttggacatggtaaatctgagatgcctattagc
    caaccaagcaagcacggcccttagagagctagatatgagagcctggaatt
    cagacgagaaaggtcagtcctagagacatacatgtagtgccatcaccatg
    cggatggtgttaaaagccatcagactgcaacagactgtgagagggtacca
    agctagagagcatggatagagaaacccaagcactgagctgggaggtgctc
    ctacattaagagattagtgagatgaaggactgagaagattgatcagagaa
    gaaggaaaatcaggaaaatggtgctgtcctgaaaatccaagggaagagat
    gttccaaagaggagaaaactgatcagttgtcagctagcgtcaattgggat
    gaaaatggaccattggacagagggatgtagtgggtcatgggtgaatagat
    aagagcagcttctatagaatggcaggggcaaaattctcatctgatcggca
    tgggttctaaagaaaacgggaagaaaaaattgagtgcatgaccagtccct
    tcaagtagagaggtggaaaagggaaggaggaaaatgaggccacgacaaca
    tgagagaaatgacagcatttttaaaaattttttattttattttatttatt
    tatttttgctttttagggctgcccctgcaacatatggaggttcccaggtt
    aggggtctaatcagagctatagctgccagcctacaccacagccatagcaa
    tgccagatctacatgacctacaccacagctcacagcaacgccggatcctt
    aacccactgagtgaggccagagatcaaacccatatccttatggatactag
    tcaggttcattaccactgagccaaaatgggaaatcctgagtaatgacagc
    attttttaatgtgccaggaagcaaaacttgccaccccgaaatgtctctca
    ggcatgtggattattttgagctgaaaacgattaaggcccaaaaaacacaa
    gaagaaatgtggaccttcccccaacagcctaaaaaatttagattgagggc
    ctgttcccagaatagagctattgccagacttgtctacagaggctaagggc
    taggtgtggtggggaaaccctcagagatcagagggacgtttatgtaccaa
    gcattgacatttccatctccatgcgaatggccttcttcccctctgtagcc
    ccaaaccaccacccccaaaatcttcttctgtctttagctgaagatggtgt
    tgaaggtgatagtttcagccactttggcgagttcctcagttgttctgggt
    ctttcctccTgatccacattattcgactgtgtttgattttctcctgttta
    tctgtctcattggcacccatttcattcttagaccagcccaaagaacctag
    aagagtgaaggaaaatttcttccaccctgacaaatgctaaatgagaatca
    ccgcagtagaggaaaatgatctggtgctgcgggagatagaagagaaaatc
    gctggagagatgtcactgagtaggtgagatgggaaaggggtgacacaggt
    ggaggtgttgccctcagctaggaagacagacagttcacagaagagaagcg
    ggtgtccgtggacatcttgcctcatggatgaggaaaccgaggctaagaaa
    gactgcaaaagaaaggtaaggattgcagagaggtcgatccatgactaaaa
    tcacagtaaccaaccccaaaccaccatgttttctcctagtctggcacgtg
    gcaggtactgtgtaggttttcaatattattggtttgtaacagtacctatt
    aggcctccatcccctcctctaatactaacaaaagtgtgagactggtcagt
    gaaaaatggtcttctttctctatgaatctttctcaagaagatacataact
    ttttattttatcataggcttgaagagcaaatgagaaacagcctccaacct
    atgacaccgtaacaaaatgtttatgatcagtgaagggcaagaaacaaaac
    atacacagtaaagaccctccataatattgtgggtggcccaacacaggcca
    ggttgtaaaagctttttattctttgatagaggaatggatagtaatgtttc
    aacctggacagagatcatgttcactgaatccttccaaaaattcatgggta
    gtttgaattataaggaaaataagacttaggataaatactttgtccaagat
    cccagagttaatgccaaaatcagttttcagactccaggcagcctgatcaa
    gagcctaaactttaaagacacagtcccttaataactactattcacagttg
    cactttcagggcgcaaagactcattgaatcctacaatagaatgagtttag
    atatcaaatctctcagtaatagatgaggagactaaatagcgggcatgacc
    tggtcacttaaagacagaattgagattcaaggctagtgttctttctacct
    gttttgtttctacaagatgtagcaatgcgctaattacagacctctcaggg
    aaggaattcacaaccctcagcaaaaaccaaagacaaatctaagacaacta
    agagtgttggtttaatttggaaaaataactcactaaccaaacgcccctct
    tagcaccccaatgtcttccaccatcacagtgctcaggcctcaaccatgcc
    ccaatcacc
    Seq ID No. 25
    GCACATGGTAGGCAAAGGACTTTGCTTCTCCCAGCACATCTTTCTGCAGA
    GATCCATGGAAACAAGACTCAACTCCAAAGCAGCAAAGAAGCAGCAAGTT
    CTCAAGTGATCTCCTCTGACTCCCTCCTCCCAGGCTAATGAAGCCATGTT
    GCCCCTGGGGGATTAAGGGCAGGTGTCCATTGTGGGACCCAGCCCGAAGA
    CAAGCAATTTGATCAGGTTCTGAGCACTCCTGAATGTGGACTCTGGAATT
    TTCTCCTCACCTTGTGGCATATCAGCTTAAGTCAAGTACAAGTGACAAAC
    AACATAATCCTAAGAAGAGAGGAATCAAGCTGAAGTCAAAGGATCACTGC
    CTTGGATTCTACTGTGAATGATGACCTGGAAAATATCCTGAACAACAGCT
    TCAGGGTGATCATCAGAGACAAAAGTTCCAGAGCCAGGTAGGGAAACCCT
    CAAGCCTTGCAAAGAGCAAAATCATGCCATTGGGTTCTTAACCTGCTGAG
    TGATTTACTATATGTTACTGTGGGAGGCAAAGCGCTCAAATAGCCTGGGT
    AAGTATGTCAAATAAAAAGCAAAAGTGGTGTTTCTTGAAATGTTAGACCT
    GAGGAAGGAATATTGATAACTTACCAATAATTTTCAGAATGATTTATAGA
    TGTGCACTTAGTCAGTGTCTCTCCACCCCGCACCTGACAAGCAGTTTAGA
    ATTTATTCTAAGAATCTAGGTTTGCTGGGGGCTACATGGGAATCAGCTTC
    AGTGAAGAGTTTGTTGGAATGATTCACTAAATTTTCTATTTCCAGCATAA
    ATCCAAGAACCTCTCAGACTAGTTTATTGACACTGCTTTTCCTCCATAAT
    CCATCTCATCTCCGTCCATCATGGACACTTTGTAGAATGACAGGTCCTGG
    CAgAGACTCaCAGATGCTTCTGAAACATCCTTTGCCTTCAAAGAATGAAC
    AGCACACATACTAAGGATCTCAGTGATCCACAAATTAGTTTTTGCCACAA
    TGGTTCTTATGATAAAAGTCTTTCATTAACAGCAAATTGTTTTATAATAG
    TTGTTCTGCTTTATAATAATTGCATGCTrCACTTTCTTTTCTTTTCTTTT
    TTTTTCTTTTTTTGCTTTTTAGTGCCGCAGGTgcagcatatgaaatttcc
    caggctaggggtcaaatcagaactacacctactggcctacgccacagcca
    cagcaactcaggatctaagccatgtcggtgacctacactacagctcatgg
    caatgccagatccttaacccaatgagcgaggccagggatcgaacccatgt
    cctcatggatactagtcaggctcattatccgctgagccataacaggaact
    cccGAGTTTGCTTTTTATCAAAATTGGTACAGCCTTATTGTTTCTGAAAA
    CCACAAAATGAATGTATTCACATAATTTTAAAAGGTTAAATAATTTATGA
    TATACAAGACAATAGAAAGAGAAAACGTCATTGCCTCTTTCTTCCACGAC
    AACACGCCTCCTTAATTGATTTGAAGAAATAACTACTGAGCATGGTTTAG
    TGTACTTCTTTCAGCAATTAGCCTGTATTCATAGCCATACATATTCAATT
    AAAATGAGATCATGATATCACACAATACATACCATACAGCCTATAGGGAT
    TTTTACAATCATCTTCCACATGACTACATAAAAACCTACCTAAAAAAAAA
    AAAAACCCTACTTCATCCTCCTATTGGCTGCTTTGTGCACCATTAAAAAG
    CTCTATCATAATTAGGTTATGATGAGGATTTCCATTTTCTACCTTTCAAG
    CAACATTTCAATGCACAGTCTTATATACACATTTGAGCCTACTTTTCTTT
    TTCTTTCTTTTTTTGGTTTTTTTTTTTTTTTTTTTTTTGGTCTTTTTGTC
    TTTTCTAAGgctgcatatggaggttcccaggctagctgtctaatcagaac
    tatagctgctggcctacgccacatccacagcaatacaagatctgagccat
    gtctgcaacttacaccacagctcacagcaacggtggatccttaaaccact
    gagcaaggccagggatcaaacccatAACTTCATGGCTCCTAGTTGGATTT
    GTTAACCACTGAGCCATGATGGCAACTCCTGAGCCTACTTTTCTAATCAT
    TTCCAACCCTAGGACACTTTTTTAAGTTTCATTTTTCTCCCCCCACCCCC
    TGTTTTCTGAAGtGTGTTTGCTTCCACTGGGTGACTTCACtCCCAGGATC
    TCATCTGCAGGATACTGCAGCTAAGTGTATGAGCTCTGAATTTGAATCCC
    AACTCTGCCACTCAAAGGGATAGGAGTTTCCGATGTGGCCCAATGGGATC
    AGTGGCATCTCTGCAGTGCCAGGACGCaggttccatccctggcccagcac
    agtgggttaagaatctggCATTGCTGCAGCTGAGGCATAGATTTCAATTG
    TGCCTCAgATCTGATCCTTGGCCCAAGGACTGCATATGCCTCAGGGCAAC
    CAAAAAAGAGAAAAGGGGGGTGATAGCATTAGTTTCTAGATTTGGGGGAT
    AATTAAATAAAGTGATCCATGTACAATGTATGGCATTTTGTAAATGCTCA
    ACAAATTTCAACTATTATggagttcccatcatggctcagtggaagggaat
    ctgattagcatccatgaggacacaggtCCAACCCCGACCTTGCTCAGTGG
    GCATTGCTGTGAGCTGTGGCATGGGTTACAGACGAAGCTCGGATCTGGCA
    TTGCTGTGGCTGTGGTGTAAGCCAgCAActacagctctcattcagcccct
    agcctgggaacctccatatgccTAAAAGACAAAAAATAAAATTTAAATTA
    AAAATAAAGAAATGTTAACTATTATGATTGgTACTGCTTGCATTACTGCA
    AAGAAAGTCACTTTCTATACTCTTTAATATCTTAGTTGACTGTGTGCTCA
    GTGAACTATTTTGGACACTTAATTTCCACTCTCTTCTATCTCCAACTTGA
    CAACTCTCTTTCCTCTCTTCTGGTGAGATCCACTGCTGACTTTGCTCTTT
    AAGGCAACTAGAAAAGTGCTCAGTGACAAAATCAAAGAAAGTTACCTTAA
    TCTTCAGAATTACAATCTTAAGTTCTCTTGTAAAGCTTACTATTTCAGTG
    GTTAGTATTATTCCTTGGTCCCTTACAACTTATCAGCTCTGATCTATTGC
    TGATTTTCAACTATTTATTGTTGGAGTTTTTTCCTTTTTTCCCTGTTCAT
    TCTGCAAATGTTTGCTGAGCATTTGTCAAGTGAAGATACTGGACTGGGCC
    TTCCAAATATAAGACAATGAAACATCGGGAGTTCTCATTATGGTGCAGCA
    GAaacgaatccaactaggaaatgtgaggttgcaggttcgatccctgccct
    tgctcagtgggttaaggatccagcattaccgtgagctgtggtgtaggttg
    cagacgtggctcagatcctgcgttgctgtggctgtggcataggctggcag
    ctctagctctgattcgaccgctagcctgggaacctccatGCGCCCCGAGT
    GCAGCCCTTAAAAAGCAAAAAAAAAAGAAAGAAAGAAAAAGACAATGAAA
    CATCAAACAGCTAACAATCCAGTAGGGTAGAAAGAATCTGGGAACAGATA
    AGAGCGATTAAATGTTCTAGGTCCAGTGACCTTGCCTCTGTGCTCTACAC
    AGTCGTGCCACTTGCTGAGGGAGAAGGTCTCTCTTGAGTTGAGTCCTGAA
    AGACATTAGTTGTTCACAAACTAATGCCAGTGAGTGAAGGTGTTTCCAAG
    CAGAGGGAGAGTTTGGTAAAAAGCTGGAAGTCACAGAAAGACTCTAAAGA
    GTTTAGGATGGTGGGAGCAACATACGCTGAGATGGGGCTGGAAGGTTAAG
    AGGGAAACAACTATAGTAAGTGAAGCTGGACTCACAGCAAAGTGAGGACC
    TCAGCATCCTTGATGGGGTTACCATGGAAACACCAAGGCACACCTTGATT
    TCCAAAACAGCAGGCACCTGATTCAGCCCAATGTGACATGGTGGGTACCC
    CTCTAGCTCTACCTGTTCTGTGACAACTGACAACCAACGAAGTTAAGTCT
    GGATTTTCTACTCTGCTGATCCTTGTTTTTGTTTCACACGTCATCTATAG
    CTTCATGCCAAAATAGAGTTCAAGGTAAGACGCGGGCCTTGGTTTGATAT
    ACATGTAGTCTATCTTGTTTGAGACAATATGGTGGCAAGGAAGAGGTTCA
    AACAGGAAAATACTCTCTAATTATGATTAAGTGAGAAAAGCTAAAGAGTC
    CCATAATGACACTGAATGAAGTTCATCATTTGCAAAAGCCTTCCCCCCCC
    CCCAGGAGACTATAAAAAAGTGCAATTTTTTAAATGAACTTATTTACAAA
    ACAGAAATAGAGTCACAGACATAGGAAACGAACAGATGGTTACCAAGGGT
    GAAAGGGAGTAGGAGGGATAAATAAGGAGTCTGGGGTTAGCAGATACACC
    CCAGTGTACACAAAATAAACAACAGGGACCTACTATATAGCACAGGGAAC
    TATATGCAGTAGCTTACAATAACCTATAATGGAAAAGAATGTGAAAAAGA
    ATATATGTATGCGTGTGTGTGTAACTGAATCACTTTGCTGTAACCTGAAT
    CTAACATAACATTGTAAATCAACTACAGTTTTTTTTTTTTTTAAGTGCAG
    GGTTTTGGTGTTTTTTTTTTTTCATTTTTGTTTTTGTTTTTGTTTTTTGC
    TTTTTAGGGCCACACCCAGACATATGGGGGTTCCCAGGctAGGGGTcTAa
    TTAGAGcTACAGtTGCCGGCTTGCAccacagccacagcaacatcagatcc
    gagccgcacttgcgacttacaccacagctcatggcaataccagatcctta
    acccactgagcaaggcccagggatcgtacccgcaacctcatggttcctag
    tcagattcattTCTGCTGCGCTACAATGGGAACTCCAAGTGCAGTTTTTT
    GTAATGTGCTtGTCTTTCTTTGTAATTCATATTCATCCTACTTCCCAATA
    AATAAATAAATACATAAATAATAAACATACCATTGTAAATCAACTACAAT
    TTTTTTTAAATGCAGGGTTTTTGTTTTTTGTTTTTTGTTTTGTCTTTTTG
    CCTTTTGTAgggccgctcccatggcatatggaggttcccaggctaggggt
    cgaatcggagctgtagccaccggcctacgccagagccacagcaacgcggg
    atccgagccgcgtctgcaacctacaccacagctcacggcaacgccggatc
    gttaacccactgagcaagggcagggatcgaacctgcaacctcatggttcc
    tagtcagattcgttaactactgagccacaacggaaacTCCTAAAGTGCAG
    TTTTTAAATGTGCTTGTCTTTCTTTGTAATTTACACTCAACCTACTTCCC
    AATAAATAAATAAATAAACAAATAAATCATAGACATGGTTGAATTCTAAA
    GGAAGGGACCATCAGGCCTTAGACAGAAATACGTCATCTTCTAGTATTTT
    AAAACACACTAAAGAAGACAAACATGCTCTGCCAGAGAAGCCCAGGGCCT
    CCACAGCTGCTTGCAAAGGGAGTTAGGCTTCAGTAGCTGACCCAAGGCTC
    TGTTCCTCTTCAGGGAAAAGGGTTTTTGTTCAGTGAGACAGCAGACAGCT
    GTCACTGTGgtggacgttcggccaaggaaccaagctggaactcaaacGTA
    AGTCAATCCAAACGTTCCTTCCTTGGCTGTCTGTGTCTTACGGTCTCTGT
    GGCTCTGAAATGATTCATGTGCTGACTCTCTGAAACCAGACTGACATTCT
    CCAGGGCAAAACTAAAGCCTGTCATGAAACcGGAAAACTGAGGGCACATT
    TTCTGGGCAGAACTAAGAGTCAGGCACTGGGTGAGGAAAAACTTGTTAGA
    ATGATAGTTTCAGAAACTTACTGGGAAGCAAAGCCCATGTTCTGAACAGA
    GCTCTGCTCAAGGGTCAGGAGGGGAACCAGTTTTTGTACAGGAGGGAAGT
    TGAGACGAACCCCTGTGTAtatggtttcggcgcggggaccaagctggagc
    tcaaacGTAAGTGGCTTTTTCCGACTGATTCTTTGCTGTTTCTAATTGTT
    GGTTGGCTTTTTGTCCATTTTTCAGTGTTTTCATCGAATTAGTTGTCAGG
    GACCAAACAAATTGCCTTCCCAGATTAGGTACCAGGGAGGGGACATTGCT
    GCATGGGAGACCAGAGGGTGGCTAATTTTTAACGTTTCCAAGCCAAAATA
    ACTGGGGAAGGGGGCTTGCTGTCCTGTGAGGGTAGGTTTTTATAGAAGTG
    GAAGTTAAGGGGAAATCGCTATGGTtcacttttggctcggggaccaaagt
    ggagcccaaaattgaGTACATTTTCCATCAATTATTTGTGAGATTTTTGT
    CCTGTTGTGTCATTTGTGCAAGTTTTTGACATTTTGGTTGAATGAGCCAT
    TCCCAGGGACCCAAAAGGATGAGACCGAAAAGTAGAAAAGAGCCAACTTT
    TAAGCTGAGCAGACAGACCGAATTGTTGAGTTTGTGAGGAGAGTAGGGTT
    TGTAGGGAGAAAGGGGAACAGATCGCTGGCTTTTTCTCTGAATTAGCCTT
    TCTCATGGGACTGGCTTCAGAGGGGGTTTTTGATGAGGGAAGTGTTCTAG
    AGCCTTAACTGTGGgttgtgttcggtagcgggaccaagctggaaatcaaa
    CGTAAGTGCACTTTTCTACTCC

    Porcine Lambda Light Chain
  • [0117]
    In another embodiment, novel genomic sequences encoding the lambda light chain locus of ungulate immunoglobulin are provided. The present invention provides the first reported genomic sequence of ungulate lambda light chain regions. In one embodiment, the porcine lambda light chain nucleotides include a concatamer of J to C units. In a specific embodiment, an isolated porcine lambda nucleotide sequence is provided, such as that depicted in Seq ID No. 28. See FIG. 3 for a diagram of the organization of the porcine lamba immunoglobulin locus.
  • [0118]
    In one embodiment, nucleotide sequence is provided that includes 5′ flanking sequence to the first lambda J/C region of the porcine lambda light chain genomic sequence, for example, as represented by Seq ID No 32.
  • [0119]
    Still further, nucleotide sequence is provided that includes 3′ flanking sequence to the J/C cluster region of the porcine lambda light chain genomic sequence, for example, approximately 200 base pairs downstream of lambda J/C, such as that represented by Seq ID No 33. Alternatively, nucleotide sequence is provided that includes 3′ flanking sequence to the J/C cluster region of the porcine lambda light chain genomic sequence, for example, approximately 11.8 kb downstream of the J/C cluster, near the enhancer (such as that represented by Seq ID No. 34), approximately 12 Kb downstream of lambda, including the enhancer region (such as that represented by Seq ID No. 35), approximately 17.6 Kb downstream of lambda (such as that represented by Seq ID No. 36, approximately 19.1 Kb downstream of lambda (such as that represented by Seq ID No. 37), approximately 21.3 Kb downstream of lambda (such as that represented by Seq ID No. 38), and/or approximately 27 Kb downstream of lambda (such as that represented by Seq ID No. 39).
  • [0120]
    In still further embodiments, isolated nucleotide sequences as depicted in Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are provided. Nucleic acid sequences at least 80, 85, 90, 95, 98 or 99% homologous to Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are also provided. In addition, nucleotide sequences that contain at least 10, 15, 17, 20, 25, 30, 40, 50, 75, 100, 150, 200, 250, 500 or 1,000 contiguous nucleotides of Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39 are provided. Further provided are nucleotide sequences that hybridizes, optionally under stringent conditions, to Seq ID Nos 28, 31, 32, 33, 34, 35, 36, 37, 38, or 39, as well as, nucleotides homologous thereto.
    Seq ID No. 28
    CCTTCCTCCTGCACCTGTCAACTCCCAATAAACCGTCCTCCTTGTCATTC
    AGAAATCATGCTCTCCGCTCACTTGTGTCTACCCATTTTCGGGCTTGCAT
    GGGGTCATCCTCGAAGGTGGAGAGAGTCCCCCTTGGCCTTGGGGAAGTCG
    AGGGGGGCGGGGGGAGGCCTGAGGCATGTGCCAGCGAGGGGGGTCACCTC
    CACGCCCCTGAGGACCTTCTAGAACCAGGGGCGTGGGGCCACCGCCTGAG
    TGGAAGGCTGTCCACTTTTCCCCCGGGCCCCCAGGCTCCCTCCTCCGTGT
    GGACCTTGTCCACCTCTGACTGGCCCAGCCACTCATGCATTGTTTCCCCG
    AAACCCCAGGACGATAGCTCAGCACGCGACAGTGTCCCCCTCTGAGGGCC
    TCTGTCCATTTCAGGACGACCCGCATGTACAGCGTGACCACTCTGCTCAC
    GCCCACTCACCACGTCCTAGAGCCCCACCCCCAGCCCCATCCTTAGGGGC
    ACAGCCAGcTCCGACCGCCCCGGGGACACCACCCTCTGCCCCTTcCCCAG
    GCCCTCCCTGTCACACGCACCACAGGGCCCTCCGTCCCGAGACCCTGCTC
    CCTCATCCCTCGGTCCCCTCAGGTAGCCTTCCACCCGCGTGTGTCCCGAG
    GTCCCAGATGCAGCAAGGCCCCTGGGACAACGCCAGATCTCTGCTCTcCC
    CGACCCCTCAGAAGCCAGCCCACGCCTGGCCCCACCACCACTGCCTAACg
    TCCAAGTGTCCATAGGCCTCGGGACCTCCAAGTCCAGGTTCTGCCTCTGG
    GATTCCGCCATGGGTCTGCCTGGGAAATGATGCACTTGGAGGAGCTCAGC
    ATGGGATGCGGGACCTTGTCTCTAGGCGCTcCCTCAGGATCCCACAGCTG
    CCCTGTGAGACACACACACACACACACACACACACACACACACACACACA
    CACACAAACACGCATGCACGCACGCCGGCACACACGCTATTGCAGAGATG
    GCCACGGTAGCTGTGCCTCGAGGCCGAGTGGAGTGTCTAGAACTCTCGGG
    GGTCCCCTCTGCAGACGACACTGCTCCATCCCCCCCGTGCCCTGAAGGGC
    TCCTCACTCTCCCATCAGGATCTCTCCAAGCTGCTGACCTGGAGAGGAAG
    GGGCCTGGGACAGGCGGGGACACTCAGACCTCCCTGCTGCCCCTCCTCTG
    CCTGGGCTTGGACGGCTCCCCCCTTCCCACGGGTGAAGGTGCAGGTGGGG
    AGAGGGCACCCCCCTCAGCCTCCCAGACCCAGACCAGCCCCCGTGGCAGG
    GGCAGCCTGTGAGCCTCCAGCCAGATGCAGGTGGCCTGGGGTGGGGGGTG
    GAGGGGGCGGGAGGTTTATGTTTGAGGCTGTATCACTGTGTAATATTTTC
    GGCGGTGGGACCCATCTGACCGTCCTCGGTGAGTCTCCCCTTTTCTCTCC
    TCCTTGGGGATCCGAGTGAAATCTGGGTCGATCTTCTCTCCGTTCTCCTC
    CGACTGGGGCTGAGGTCTGAACCTCGGTGGGGTCCGAAGAGGAGGCCCCT
    AGGCCAGGCTCCTCAGCCCCTCCAGCCCGACcgGCCCTCTTGACACAGGG
    TCCAGCTAAGGGCAGACATGGAGGCTGCTAGTCCAGGGCCAGGCTCTGAG
    ACCCAAGGGCGCTGCCCAAGGAACCCTTGCCCCAGGGACCCTGGGAGCAA
    AGCTCCTCACTCAGAGCCTGCAGCCCTGGGGTCTGAGGACAAGGAGGGAC
    TGAGGACTGGGCGTGGGGAGTTCAGGCGGGGACACCAGGTCCAGGGAGGT
    GACAAAGGCGCTGGGAGGGGGCGGACGGTGCCGGGGACTCCTCCTGGGCC
    CTGTGGGCTCGGGGTCCTTGTGAGGACCCTGAGGGACTGAGGGGCCCCTG
    GGCCTAGGGACTTGCAgTgAGGGAGGCAGGGAGTGTCCCTTGAGAACGTG
    GCCTCCGCGGGCTGGGTCCCCCTGCTGCTCCCAGCC*GGGAGGACACCCC
    AGAGCAAGCGCCCCAGGTGGGCGGGGAGGGTCTCCTCACAGGGGCAGCTG
    ACAGATAGAGGCCCCCGCCAGGCAGATGCTTGATCCTGGCAgTTATACTG
    GGTTC**GCACAACTTTCCCTGAACAAGGGGCCCTCCGAACAGACACAGA
    CGCAACCCAGTCGACCcaggCTCAGCACAgAAAATGCACTGACACCCAAA
    ACCCTCATCTggggGCCTGGCCGGcAtCCCGCCCCAGGACCCAAGGCCCC
    TGCCCCCTGGCAGCCCTGGACACGGTCCTCTGTGGGCGGTGGGGTCgGGG
    CTGTGGTGACGGTGGCATCGGGGAGCCTGTGCCCCCTCCCTGAAAGGGCG
    GAGAGGCTCAAGAGGGGAGAGAAATGTCCTCCCCTAGGAAGACGTCGGAC
    GGGGGCGGGGGGGTGGTCTCCGACAGACAGATGCCCGGGACCGACAGACC
    TGCCGAGGGAAGAGGGCACCTCGGTCGGGTTAGGCTCCAGGCAGCACGAG
    GGAGCGAGGCTGGGAGGGTGAGGACATGGGAGCCTGAGGAGGAGCTGGAG
    ACTTCAGCAGGCCCCCAGCTCCGGGCTTCGGGCTCTGAGATGCTCGGACG
    CAAGGTGAGTGACCCCACCTGTGGCTGACCTGACCTCAgGGgGACAAGGC
    TCAGCCTGGGAGTCTGTGTCCCCATCGCCTGcACAGGGGATTCCCCTGAT
    GGACACTGAGCCAACGACCTCCCGTCTGTCCCCGACCCCCAGGTCAGCCC
    AAgGCCaCTCCCACGGTCAACCTCTTCCCGCCCTCCTCTGAGGAGCTCGG
    CACCAACAAGGCCACCCTGGTGTGTCTAATAAGTGACTTCTACCCGGGCG
    CCGTGACGGTGACCTGGAAGGCAGGCGGCACCACCGTCACCCAGGGCGTG
    GAGACCACCAAGCCCTCGAAACAGAGCAACAACAAGTACGCGGCCAGCAG
    CTACCTGGCCCTGTCCGCCAGTGACTGGAAATCTTCCAGCGGCTTCACCT
    GCCAGGTCACCCACGAGGGGACCATTGTGGAGAAGACAGTGACGCCCTCC
    GAGTGCGCCTAGGTCCCTGGGCCCCCACCCTCAGGGGCCTGGAGCCACAG
    GACCCCCGCGAGGGTCTCCCCGCGACCCTGGTCCAGCCCAGCCCTTCCTC
    CTGCACCTGTCAACTCCCAATAAACCGTCCTCCTTGTCATTCAGAAATCA
    TGCTCTCCGCTCACTTGTGTCTACCCATTTTCGGGCTTGCATGGGGTCAT
    CCTCGAAGGTGGAGAGAGTCCCCCTTGGCCTTGGGgAAATCGAGGGGGGC
    GGGGGGAGGCCTGAGGCATGTGCCAGCGAGGGGGGTCACCTCCACGCCCC
    TGAGGACCTTCTAGAACCAGGGGCGTGGGGCCACCGCCAGAGTGGAAGGC
    TGTCCACTTTTCCCCCGGGCCCCCAGGCTCCCTCCTCCGTGTGGACCTTG
    TCCACCTCTGACTGGCCCAGCCACTCATGCATTGTTTCCCCGAAACCCCA
    GGACGATAGCTCAGCACGCGACAGTGTCCCCCTCTGAGGGCCTCTGTCCA
    TTTCAGGACGACCCGCATGTACAGCGTGACCACTCTGCTCACGCCCACTC
    ACCACGTCCTAGAGCCCCACCCCCAGCCCCATCCTTAGGGGCACAGCCAG
    CTCCGACCGCCCCGGGGACACCACCCTCTGCCCCTTCCCCAGGCCCTCCC
    TGTCACACGCACCACAGGGCCCTCCGTCCCGAGACCCTGCTCCCTCATCC
    CTCGGTCCCCTCAGGTAGCCTTCCACCCGCGTGTGTCCCGAGGTCCCAGA
    TGCAGCAAGGCCCCTGGGACAACGCCAGATCTCTGCTCTCCCCGACCCTC
    AGAAGCCAGCCCACGCCTGGCCCACCACCACTGCCTAACGTCCAAGTGTC
    CATAGGCTCGGGAcCTCcAaGTCCAGGTTCTGCCTCTGGGATTCCGCCAT
    GGGTCTGCCTGGAATGATGCACTTGGAGgAgCTCAGcATGGGATGcGGAA
    CTTGTCTAGcGCTCCTCAGATCCAcAGcTGCCTGtGAgAcacacacacac
    acacacacacaccAAAcaCGcATGCACGCACGCCGGCACACACGCTATTA
    CAGAGATGGCCACGGTAGCTGTGCCTCGAGGCCGAGTGGAGTGTCTAGAA
    CTCTCGGGGGTCCCCTCTGCAGACGACACTGCTCCATCCCCCCCGTGCCC
    TGAAGGGCTCCTCACTCTCCCATCAGGATCTCTCCAAGCTGCTGACCTGG
    AGAGGAAGGGGCCTGGGACAGGCGGGGACACTCAGACCTCCCTGCTGCCC
    CTGCTCTGCCTGGGCTTGGACGGCTCCCCCCTTCCCACGGGTGAAGGTGC
    AGGTGGGGAGAGGGCACCCCCCTCACCCTCCCAGACCCAGACCAGCCCCC
    GTGGCAGGGGCAGCCTGTGAGCCTCCAGCCAGATGCAGGTGGCCTGGGGT
    GGGGGGTGGAGGGGGCGGGAGGTTTATGTTTGAGGCTGTATTCATCTGTG
    TAATATttTCGGCGGTGGGACCCATCTGACCGTCCTCGGTGAGTCTCCCC
    TtttctttcctccttggggatccgagtgaaATcTGGGTCGATCTTCTCTC
    CGTTCTCCTCCGACTGGGGCTGAGGTCTGAACCTCGGTgGGGTCCGAAGA
    GGAGGCCCCTAGGCC*GGCTCcTCAGCCCCTCCAGGCCGACCCGCCCTCT
    TGACACAGGGTCCAGCTAAGGGCAGACAT***GGCTGCTAGTCCAGGGCC
    AGGCTcTGAGACCCAAGGGCGCTGCCCAAGGAACCCTTGCCCCAGGGACC
    CTGGGAGCAAAGCTCCTCACTCAGAGCCTGCAGCCCTGGgGTCTGAGGAC
    AAGGAGGGACTGAGGACTGGGCGTGGGGAGTTCAGGCgGGGACACCGGGT
    CCAGGGAGGTGACAAAGGCGCTGGGAGGGGGCGGACGGTGCCGGAGACTC
    CTCCTGGGCCCTGTGGGCTCGTGGTCCTTGTGAGGACCCTGAGGG*CTGA
    GGGGCCCCTGGGCCTAGGGACTTGCAGTGAGGGAGGCAGGGAGTGTCCCT
    TGAGAACGTGGCCTCCGCGGGCTGGGTCCCCCTCGTGCTCCCAGCAGGGA
    GGACACCCCAGAGCAAGCGCCCCAGGTGGGCGGGGAGGGTCTCCTCACAG
    GGGCAGCTGACAGATAGAC*GgccCCCGCCAGACAGATGCTTGATCCTGG
    TCag***TACTGGGTTCGCcACTTCCCTGAACAGGGGCCCTCCGAACAGA
    CACAGACGCAGACCaggCTCAGCACAgAAAATGCACTGACACCCAAAACC
    CTCATCTGggGGCCTGGCCGGCATCCCGCCCCAGGACCCAAGGCCCCTGC
    CCCCTGGCAGCCCTGGACACGGTCCTCTGTGGGCGGTGGGGTCgGGGCTG
    TGGTGACGGTGGCATCGGGGAGCCTGTGCCCCCTCCCTGAAAGGGCGGAG
    AGGCTCAAGAGGGGACAGAAATGTCCTCCCCTAGGAAGACCTCGGACGGG
    GGCGGGGGGGTGGTCTCCGACAGACAGATGCCCGGGACCGACAGACCTGC
    CGAGGGAAGAGGGCACCTCGGTCGGGTTAGGCTCCAGGCAGCACGAGGGA
    GCGAGGCTGGGAGGGTGAGGACATGGGAGCCTGAGGAGGAGCTGGAGACT
    TCAGCAGGCCCCCAGCTCCGGGCTTCGGGCTCTGAGATGCTCGGACGCAA
    GGTGAGTGACCCCACCTGTGGCTGACCTGACCTGACCtCAGGGGGACAAG
    GCTGAGCCTGGGACTCTgTGTCCCCATCGCCTGCACAGGGGATTCCCCTG
    ATGGACACTGAGCCAACGACCTCCCGTCTCTCCCCGACCCCCAGGTCAGC
    CCAAGGCCACTCCCACGGTCAACCTGTTCCCGCCCTCCTCTGAGGAGCTC
    GGCACCAACAAGGCCACCCTGGTGTGTCTA
    Seq ID No. 32
    GCCACGCCCACTCCATCATGCGGGGAGGGGATGGGCAGACCCTCCAGAAA
    GAAGCTCCCTGGGGTGCAGGTTAACAGCTTTCCCAGACACAGCCAGTACT
    AGAGTGAGGTGAATAAGACATCCTCCTTGCTTGTGAAATTTAGGAAGTGC
    CCCCAAACATCAGTCATTAAGATAAATAATATTGAATGCACTTTTTTTTT
    TTTATTTTTTTTTTTTGCTTTTTAGGGCCTAATCTGCAGCatatggaagt
    tcccaggctacaagtcgaaccagagctgcagctgccagcctacatcacag
    ccacagcaacaccagatccgagccacatctgtgactaacactgcagttca
    cagcaacgccagatccttaacccattgagtgaggccagggatcaaaccca
    catcctcatggatactagtctggttcgtaaaccactgagccaCAAGGGGA
    ACTCCTGAATGCAATATTTTTGAAAATTGAAATTAAATCTGTCACTCTTT
    CACTTAAGAGTCCCCTTAGATTGGGGAAAATTTAAATATCTGTCATCTTA
    GTGCATCTTTGCTCATATGATGTGAATAAAATCCCAAAATCCATATGAAT
    GAAGCATCAAAATGTACATGAAGTCAGCCTGACCCTGCACTGCCCTCACT
    TGCCTCATGTACCCCCCACCTCAAAGGAAGATGCAGAAAGGAGTCCAGCC
    CCTACACCGCCACCTGCCCCCACCACTGGAGCCCCTCAGGTCTCCCACCT
    CCTTTTCTGAGCTTCAGTCTTCCTGTGGCATTGCCTACCTCTACAGCTGC
    CCCCTACTAGGCCCTCCCCCTGGGGCTGAGCTCCAGGCACTGGACTGGGA
    AAGTTAGAGGTTAAAGCATGGAAAATTCCCAAAGCCACCAGTTCCAGGCT
    GCCCCCCACCCCACCGCCACGTCCAAAAAGGGGCATCTTCCCAGATCTCT
    GGCTGGTATTGGTAGGACCCAGGACATAGTCTTTATACCAATTCTGCTGT
    GTGTCTTAGGAAAGAaactctccctctctgtgcttcagtttcctcatcaa
    taaaAGGAGCAGGCCAGGTTGGAGGGTCTGTGACGTCTGCTGAAGCAGCA
    GGATTCTCTCTCCTTTTGCTGGAGGAGAACTGATCCTTCACCCCCAGGAT
    CAACAGAGAAGCCAAGGTCTTCAGCCTTCCTGGGGACCCCTCAGAGGGAA
    CTCAGGGCCACAGAGCCAGACCCTGATGCCAGAACCTTTGTCATATGCCC
    AGACGGAGACTTCATCCCCCTCCTCCTCAGACCCTCCAGGCCCCAACAGT
    GAGATGCTGAAGATATTAAGAGAAGGGCAAGTCAGcTTAAGTTTGGGGGT
    AGAGGGGAACAGGGAGTGAGGAGATCTGGCCTGAGAGATAGGAGCCCTGG
    TGGCCACAGGAGGACTCTTTGGGTCCTGTCGGATGGACACAGGGCGGCCC
    GGGGGCATGTTGGAGCCCGGCTGGTTCTTACCAGAGGCAGGGGGCACCCT
    CTGACACGGGAGCAGGGCATGTTCCATACATGACACACCCCTCTGCTCCA
    GGGCAGGTGGGTGGCGGCACAGAGGAGCCAGGGACTCTGAGCAAGGGGTC
    CACCAGTGGGGCAGTTGGATCCAGACTTCTCTGGGCCAGCGAGAGTCTAG
    CCCTCAGCCGTTCTCTGTCCAGGAGGGGGGTGGGGCAGGCCTGGGCGGCC
    AGAGCTCATCCCTCAAGGGTTCCCAGGGTCCTGCCAGACCCAGATTTCCG
    ACCGCAGCCACCACAAGAGGATGTGGTCTGCTGTGGCAGCTGCCAAGACC
    TTGCAGCAGGTGCAGGGTGGGGGGGTGGGGGCACCTGGGGGCAGCTGGGG
    TCACTGAGTTCAGGGAAAACCCCTTTTTTCCCCTAAACCTGGGGCCATCC
    CTAGGGGAAACCACAACTTCTGAGCCCTGGGCAGTGGCTGCTGGGAGGGA
    AGAGCTTCATCCTGGACCCTGGGGGGGAACCCAGCTCCAAAGGTGCAAGG
    GGCCCAGGTCCAAGGCTAGAGTGGGCCAAGCACCGCAATGGCCAGGGAGT
    GGGGGAGGTGGAGCTGGACTGGATCAGGGCCTCCTTGGGACTCCCTACAC
    CCTGTGTGACATGTTAGGGTACCCACACCCCATCACCAGTCAGGGCCTGG
    CCCATCTCCAGGGCCAGGGATGTGCATGTAAGTGTGTGTGAGTGTGTGTG
    TGTGGTGTAGTACACCCCTTGGCATCCGGTTCCGAGGCCTTGGGTTCCTC
    CAAAGTTGCTCTCTGAATTAGGTCAAACTGTGAGGTCCTGATCGCCATCA
    TCAACTTCGTTCTCCCCACCTCCCATCATTATCAAGAGCTGGGGAGGGTC
    TGGGATTTCTTCCCACCCACAAGCCAAAAGATAAGCCTGCTGGTGATGGC
    AGAAGACACAGGATCCTGGGTCAGAGACAAAGGCCAGTGTGTCACAGCGA
    GAGAGGCAGCCGGACTATCAGCTGTCACAGAGAGGCCTTAGTCCGCTGAA
    CTCAGGCCCCAGTGACTCCTGTTCCACTGGGCACTGGCCCCCCTCCACAG
    CGCCCCCAGGCCCCAGGGAGAGGCGTCACAGCTTAGAGATGGCCCTGCTG
    AACAGGGAACAAGAACAGGTGTGCCCCATCCAGCGCCCCAGGGGTGGGAC
    AGGTGGGCTGGATTTGGTGTGAAGCCCTTGAGCCCTGgAACCCAAcCACA
    GCAgGGCAGTTGGTAGATGCCATTTGGGGAGAGGCCCCAGGAGTAAGGGC
    CATGGGCCCTTGAGGGGGCCAGGAGCTGAGGACAGGGACAGAGACGGCCC
    AGGCAGAGGACAGGGCCATGAGGGGTGCACTGAGATGGCCACTGCCAGCA
    GGGGCAGCTGCCAACCCGTCCAGGGAACTTATTCAGCAGTCAGCTGGAGG
    TGCCATTGACGCTGAGGGCAGATGAAGCCCAGGCCAGGCTAGGTGGGCTG
    TGAAGACCCCAGGGGACAGAGCTCTGTCCCTGGGCAGCACTGGCCTCTCA
    TTCTGCAGGGCTTGACGGGATCCCAAGGCCTGCTGCCCCTGATGGTAGTG
    GCAGTACCGCCCAGAGCAGGACCCCAGCATGGAAACCCCAACGGGACGCA
    GCCTGCGGAGCCCACAAAACCAGTAAGGAGCCGAAGCAGTCATGGCACGG
    GGAGTGTGGACTTCCCTTTGATGGGGCCCAGGCATGAAGGACAGAATGGG
    ACAGCGGCCATGAGCAGAAAATCAGCCGGAGGGGATGGGCCTAGGCAGAC
    GCTGGCTTTATTTGAAGTGTTGGCATTTTGTCTGGTGTGTATTGTTGGTA
    TTGATTTTATTTTAGTATGTCAGTGACATACTGACATATTATGTAACGAC
    ATATTATTATGTGTTTTAAGAAGCACTCCAAGGGAACAGGCTGTCTGTAA
    TGTGTCCAGAGAAGAGAGCAAGAGCTTGGCTCAGTCTCCCCCAAGGAGGT
    CAGTTCCTCAACAGGGGTCCTAAATGTTTCCTGGAGCCAGGCCTGAATCA
    AGGGGgTCATATCTACACGTGGGGCAGACCCATGGACCATTTTCGGAGCA
    ATAAGATGGCAGGGAGGATACCAAGCTGGTCTTACAGATCCAGGGCTTTG
    ACCTGTGACGCGGGCGCTCCTCCAGGCAAAGGGAGAAGCCAGCAGGAAGC
    TTTCAGAACTGGGGAGAACAGGGTGCAGACCTCCAGGGTCTTGTACAACG
    CACCCTTTATCCTGGGGTCCAGGAGGGGTCACTGAGGGATTTAAGTGGGG
    GACCATCAGAACCAGGTTTGTGTTTTGGAAAAATGGCTCCAAAGCAGAGA
    CCAGTGTGAGGCCAGATTAGATGATGAAGAAGAGGCAGTGGAAAGTCGAT
    GGGTGGCCAGGTAGCAAGAGGGCCTATGGAGTTGGCAAGTGAATTTAAAG
    TGGTGGCACCAGAGGGCAGATGGGGAGGAGCAGGCACTGTCATGGACTGT
    CTATAGAAATCTAAAATGTATACCCTTTTTAGCAATATGCAGTGAGTCAT
    AAAAGAACACATATATATTTAAATTGTGTAATTCCACTTCTAAGGATTCA
    TCCCAAGGGGGGAAAATAATCAAAGATGTAACCAAAGGTTTACAAACAAG
    AACTCATCATTAATCTTCCTTGTTGTTATTTCAACGATATTATTATTATT
    ACTATTATTATTATTATTATTttgtctttttgcattttctagggccactc
    ccacggcatagagaggttcccaggctaggggtcaaatcggagctacagct
    gccggcctacgccagagccacagcaacgcaggatctgagccacagcaatg
    caggatctacaccacagctcatggtaacgctggatccttaacccaatgag
    tgaggccagggatcgaacctgtaacttcatggttcctagtcggattcatt
    aaccactgagccacgacaggaactccAACATTATTAATGATGGGAGAAAA
    CTGGAAGTAACCTAAATATCCAGCAGAAAGGGTGTGGCCAAATACAGCAT
    GGAGTAGCCATCATAAGGAATCTTACACAAGCCTCCAAAATTGTGTTTCT
    GAAATTGGGTTTAAAGTACGTTTGCATTTTAAAAAGCCTGCCAGAAAATA
    CAGAAAAATGTCTGTGATATGTCTCTGGCTGATAGGATTTTGCTTAGTTT
    TAATTTTGGCTTTATAATTTTCTATAGTTATGAAAATGTTCACAAGAAGA
    TATATTTCATTTTAGCTTCTAAAATAATTATAACACAGAAGTAATTTGTG
    CTTTAAAAAAATATTCAACACAGAAGTATATAAAGTAAAAATTGaggagt
    tcccatcgtggctcagtgattaacaaacccaactagtatccatgaggata
    tggatttgatccctggccttgctcagtgggttgaggatccagtgttgctg
    tgagctgtggtgtaggttgcagacacagcactctggcgttgctgtgactc
    tggcgtaggccggcagctacagctccatttggacccttagcctgggaacc
    tccatatgcctgagatacggcccTAAAAAGTCAAAAGCCAAAAAAATAGT
    AAAAATTGAGTGTTTCTACTTACCACCCCTGCCCACATCTTATGCTAAAA
    CCCGTTCTCCAGAGACAAACATCGTCAGGTGGGTCTATATATTTCCAGCC
    CTCCTCCTGTGTGTGTATGTCCGTAAAACACACACACACACACACACACG
    CACACACACACACACGTATCTAATTAGCATTGGTATTAGTTTTTCAAAAG
    GGAGGTCATGCTCTACCTTTTAGGCGGCAAATAGATTATTTAAACAAATC
    TGTTGACATTTTCTATATCAACCCATAAGATCTCCCATGTTCTTGGAAAG
    GCTTTGTAAGACATCAACATCTGGGTAAACCAGCATGGTTTTTAGGGGGT
    TGTGTGGATTTTTTTCATATTTTTTAGGGCACACCTGCAgcatatggagg
    ttcccaggctaggggttgaatcagagctgtagctgccggcctacaccaca
    gccacagcaacgccagatccttaacccactgagaaaggccagggattgaa
    cctgcatcctcatggATGCTGGTCAGATTTATTTCTGCTGAGCCACAACA
    GGAACTCCCTGAACCAGAATGCTTTTAACCATTCCACTTTGCATGGACAT
    TTAGATTGTTTCCATTTAAAAATACAAATTACAaggagttcccgtcgtgg
    ctcagtggtaacgaattggactaggaaccatgaggtttcgggttcgatcc
    ctggccttgctcggtgggttaaggatccagcattgatgtgagatatggtg
    taggtcgcagacgtggctcggatcccacgttgctgtggctctggcgtagg
    ccggcaacaacagctccgattcgacccctagccTGggaacctccatgtgc
    cacaggagcagccctaGAAAAGGCAAAAAGACAAAAAAATAAAAAATTAA
    AATGAAAAAATAAAATAAAAATACAAATTACAAGAGACGGCTACAAGGAA
    ATCCCCAAGTGTGTGCAAATGCCATATATGTATAAAATGTACTAGTGTCT
    CCTCGCGGGAAAGTTGCCTAAAAGTGGGTTGGCTGGACAGAGAGGACAGG
    CTTTGACATTCTCATAGGTAGTAGCAATGGGCTTCTCAAAATGCTGTTCC
    AGTTTACACTCACCATAGCAAATGACAGTGCCTCTTCCTCTCCACCCTTG
    CCAATAATGTGACAGGTGGATCTTTTTCTATTTTGTGTATCTGACAAGCA
    AAAAATGAGAACAggagttcctgtcgtggtgcagtggagacaaatctgac
    taggaaccatgaaatttcgggttcaatccctggcctcactcagtaggtaa
    aggatccagggttgcagtgagctgtggggtaggtcgcagacacagtgcaa
    atttggccctgttgtggctgtggtgtaggccggcagctatagctccaatt
    ggacccctagcctgggaacctccttatgccgtgggtgaggccctAAAAAA
    AAGAGTGCAAAAAAAAAAAATAAGAACAAAAATGATCATCGTTTAATTCT
    TTATTTGATCATTGGTGAAACTTATTTTCCTTTTATATTTTTATTGACTG
    ATTTTATTTCTCCTATGAATTTACCGGTCATAGTTTTGCCTGGGTGTTTT
    TACTCCGGTTTTAGTTTTGGTTGGTTGTATTTTCTTAGAGAGCTATAGAA
    ACTCTTCATCTATTTGGAATAGTAATTCCTCATTAAGTATTTGTGCTGCA
    AAAAATTTTCCCTGATCTGTTTTATGCTTTTGTTTGTGGGGTCTTTCACG
    AGAAAGCCTTTTTAGTTTTTACACCTCAGCTTGGTTGTTTTTCTTGATTG
    TGTCTGTAATCTGCGGCCAACATAGGAAACACATTTTTACTTTAGTGTTT
    TTTTCCTATTTTCTTCAAGTACGTCCATTGTTTTGGTGTCTGATTTTACT
    TTGCCTGGGGTTTGTTTTTGTGTGGCAGGAATATAAACTTATGTATTTTC
    CAAATGGAGAGCCAATGGTTGTATATTTGTTGAATTCAAATGCAACTTTA
    TCAAACACCAAATCATCGATTTATCACAACTCTTCTCTGGTTTATTGATC
    TAATGATCAATTCCTGTTCCACGCTGTTTTAATTATTTTAGCTTTGTGGA
    TTTTGGTGCCTGGTAGAGAACAAAGCCTCCATTATTTTCATTCAAAATAG
    TCCCGTCTATTATCTGCCATTGTTGTAGTATTAGACTTTAAAATCAATTT
    ACTGATTTTCAAAAGTTATTCCTTTGGTGATGTGGAATACTTTATACTTC
    ATAAGGTACATGGATTCATTTGTGGGGAATTGATGTCTTTGCTATTGTGG
    CCATTTGTCAAGTTGTGTAATATTTTACCCATGCCAACTTTGCATATTGT
    ATGTGAGTTTATTCCCAGGGTTTTTAATAGGATGTTTATTGAAGTTGTCA
    GTGTTTCCACAATTTCATCGCCTCAGTGCTTACTGTTTGCATAAAAGGAA
    ACCTACTCACTTTTGCCTATTGCTCTTGTATTCAATCATTTTAGTTAACT
    CTTGTGTTAATTTTGAGAGTTTTTCAGCTGACTGTCTGGGGTTTTCTTTA
    ATAGACTAGCCCTTTGTCTGTAAAGAATAATTTTATCGAATTTTTCTTAA
    CACTCACACTCTCCCCACCCCCACCCCCGCTGATCTCCTTTCATTGGGTC
    AAATCTGTAGAATACAATAAAAGTAAGAGTGGGAACCTTAGCCTTTAAGT
    CGATTTTGCCTTTAAATGTGAATGTTGCTATGTTTCGGGACATTCTCTTT
    ATCAAGTTGCGGATGTTTCCTTAGATAATTAACTTAATAAAAGACTGGAT
    GTTTGCTTTCTTCAAATCAGAATTGTGTTGAATTTATATTGCTATTCTGT
    TTAATTTTGTTTCAAAAAATTTACATGCACACCTTAAAGATAACCATGAC
    CAAATAGTCCTCCTGCTGAGAGAAAATGTTGGCCCCAATGCCACAGGTTA
    CCTCCCGACTCAGATAAACTACAATGGGAGATAAAATCAGATTTGGCAAA
    GCCTGTGGATTCTTGCCATAACTCTCAGAGCATGACTTGGGTGTTTTTTC
    CTTTTCTAAGTATTTTAATGGTATTTTTGTGTTACAATAGGAAATCTAGG
    ACACAGAGAGTGATTCAATGAGGGGAACGCATTCTGGGATGACTCTAGGC
    CTCTGGTTTGGGGAGAGCTCTATTGAAGTAAAGACAATGAGAGGAAGCAA
    GTTTGCAGGGAACTGTGAGGAATTTAGATGGGGAATGTTGGGTTTGAGGT
    TTCTATAGGGCACGCAAGCAGAGATGCACTCAGGAGGAAGAAGGAGCATA
    AATCTAGAGGCAAAAAGAGAGGTCAGGACTGGAAATAGAGATGCGAGACA
    CCAGGGTGGCAGTCAGAGAGCACAGTGTGGGTCAGAAGACAGTGGAAGAA
    CACAAGGGACAGAGAGGGATCTCCAACTTCACTGGGATGAGGGCCTTGTT
    GGCCTTGACCTGAGAGATTTCCAGGAGTTGAGGGTGGGAAGGAGAGGGCT
    CCTGCACATGTCCTGACATGAAACGGTGCCCAGCATATGGGTGCTTGGAA
    GACATTGTTGGACAGATGGATGGATGATGGATGATGGATGAATGGATGGA
    TGGAAGATGATGGATAAATGGATGATGGATGGATGGACAGAAGGACAAAG
    AGATGGACAGAAAGACAGTGATCTGAGAGAGCAGAGAAGGCTTCATGAAA
    GGACAGGAACTGAACTGTCTCAGTGGGTGGAGACAATGGTGTAGGGGGTT
    TCCACATGGAGGCACCAGGGGTCAGGAATAATCTAGTGTCCACAGGCCCA
    GGAAGGAAGCTGTCTGCAGGAAATTGTGGGGAAGAACCTCAGAGTCCTTA
    AATGAGGTCAGGAGTGGTCAGGAGGGTCTGATCAGGTAAGGACTCATGTC
    CATCATCACATGGTCACCTAAGGGCATGTAGCTCTCAGCATCTCCATCAG
    GACAGTCTCAGAATGGGGGCGGGGTCACACACTGGGTGACTCAAGGCGTG
    GGTCATGCCTGCCTCGGACGTGGGCCTGGGCATGGGGACACCTCCAGACC
    ATGGGCCCGCCCAGGGCTGCACTGGcctctggtgggctagctacccgtcc
    aagcaacacaggacacagccctacctgctgcaaccctgtgcccgaaacgc
    ccatctggttcctgctccagcccggccccagggaacaggactcaggtgct
    agcccaatggggttttgttcgagcctcagtcagcgtggTATTTCTCCGGC
    AGCGAGACTCAGTTCACCGCCTTAGGttaagtggttctcatgaatttcct
    agcagtcctgcactctgctatgccgggaaagtcacttttgtcgctggggg
    ctgtttccccgtgcccttggagaatcaaggattgcccaactttctctgtg
    ggggaggtggctggtcttggggtgaccagcaggaagggccccaaaagcag
    gagcagctgcctccagAATACAACTGTCGGCTACAGCTCAAACAGGAGGC
    CTGGACTGGGGTTTAACCACCAGGGCGGCACGAAGGAGCGAGGCTGGGAG
    GGTGAGGACATGGGAGCCTGAGGAGGAGCTGGAGACTTCAGCAGGCCCCC
    AGCTCCGGGCTTCGGGCTCTGAGATGCTCGGACGCAAGGTGAGTGACCCC
    ACCTGTGGCTGACCTGACCTCAGGGGGACAAGGCTCAGCCTGAGACTCTG
    TGTCCCCATCGCCTGCACAGgggattcccctgatggacactgagccaacg
    acctcccgtctctccccgacccccaggtcagcccaaggccgcccccacgg
    tcaacctcttcccgccctcctctgaggagctcggcaccaacaaggccacc
    ctggtgtgtctaataagtgacttctacccgAAGGGCGAATTCCAGCACAC
    TGGCGGCCGTTACTAGTGGATCCGAGCTCGGTACCAAGCTTGATGCATAG
    CTTGAGTATCTA
    Seq ID No. 33
    agatctttaaaccaccgagcaaggccagggatcgaacccgcatcctcatg
    aatcctagttgggttcgttaaccgctgaaccacaatgggaactcctGTCT
    TTCACATTTAATTCACAACCTCTCCAGGATTCTGGGGGTGGGTGGGGAAT
    CCTAGGTACCCACTGGGAAAGTAATCCAAGGGGAGAGGCTCACGGACTcT
    AGGGATCGGCGGAGGAGGGAAGGTATCTCCCAGGAAACTGGCCAGGACAC
    ATTGGTCCTCCGCCCTCCCCTTCCTCCCACTCCTCCTCCAGACAGGACTG
    TGCCCACCCCCTGCCACCTTTCTGGCCAGAACTGTCCATGGCAGGTGACC
    TTCACATGAGCCCTTCCTCCCTGCCTGCCCTAGTGGGACCCTCCATACCT
    CCCCCTGGACCCCGTTGTCCTTTCTTTCCAGTGTGGCCCTGAGCATAACT
    GATGCCATCATGGGCTGCTGACCCACCCGGGACTGTGTTGTGCAGTGAGT
    CACTTCTCTGTCATCAGGGCTTTGTAATTGATAGATAGTGTTTCATCATC
    ATTAGGACCGGGTGGCCTCTATGCTCTGTTAGTCTCCAAACACTGATGAA
    AACCTTCGTTGGCATAGTCCCAGCTTCCTGTTGCCCATCCATAAATCTTG
    ACTTAGGGATGCACATCCTGTCTCCAAGCAACCACCCCTCCCCTAGGCTA
    ACTATAAAACTGTCCCAATGGCCCTTGTGTGGTGCAGAGTTCATGCTTCC
    AGATCATTTCTGTGCTAGATCCATATCTCACCTTGTAAGTCATCCTATAA
    TAAACTGATCCATTGATTATTTGCTTCTGTTTTTTCCATCTCAAAACAGC
    TTCTCAGTTCAGTTCGAATTTTTTATTCCCTCCATCCACCCATACTTTCC
    TCAGCCTGGGGAACCCTTGCCCCCAGTCCCATGCCCTTCCTCCCTCTCTG
    CCCAGCTCAGCACCTGCCCACCCTCACCCTTCCTGTGACTCCCTAGGACT
    GGACCATCCACTGGGGCCAGGACACTCCAGCAGCCTTGGCTTCATGGGCT
    CTGAAATCCATGGCCCATCTCTATTCCTCACTGGATGGCAGGTTCAGAGA
    TGTGAAAGGTCTAGGAGGAAGCCAGGAAGGAAACTGTTGCATGAAAGGCC
    GGCCTGATGGTTCAGTACTTAAATAATATGAGCTCTGAGCTCCCCAGGAA
    CCAAAGCATGGAGGGAGTATGTGCCTCAGAATCTCTCTGAGATTCAGCAA
    AGCCTTTGCTAGAGGGAAAATAGTGGCTCAACCTTGAGGGCCAGCATCTT
    GCACCACAGTTAAAAGTGGGTATTTGTTTTACCTGAGGCCTCAGCATTAT
    GGGAACCGGGCTCTGACACAAACACAGGTGCAGCCCGGCAGCCTCAGAAC
    ACAGCAACGACCACAAGCTGGGACAGCTGCCCCTGAACGGGGAGTCCACC
    ATGCTTCTGTCTCGGGTACCACCAGGTCACCATCCCTGGGGGAGGTAGTT
    CCATAGCAGTAGTCCCCTGATTTCGCCCCTCGGGCGTGTAGCCAGGCAAG
    CTCCTGCCTCTGGACCCAGGGTGGACCCTTGCTCCCCACTACCCTGCACA
    TGCCAGACAGTCAAGACCACTCCCACCTCTGTCTGAGGCCCCCTTGGGTG
    TCCCAGGGCCCCCGAGCTGTCCTCTACTCATGGTTCTTCCACCTGGGTAC
    AAAAGAGGCGAGGGACACTTTTCTCAGGTTTGCGGCTCAGAAAGGTACCT
    TCCTAGGGTTTGTCCACTGGGAGTCACCTCCCTTGCATCTCAATGTCAGT
    GGGGAAAACTGGGTCCCATGGGGGGATTAGTGCCACTGTGAGGCCCCTGA
    AGTCTGGGGCCTCTAGACACTATGATGATGAGGGATGTGGTGAAAAACCC
    CACCCCAGCCCTTCTTGCCGGGACCCTGGGCTGTGGCTCCCCCATTGCAC
    TTGGGGTCAGAGGGGTGGATGGTGGCTATGGTGAGGCATGTTTCCCATGA
    GCTGGGGGCACCCTGGGTGACTTTCTCCTGTGAATCCTGAATTAGCAGCT
    ATAACAAATTGCCCAAACTCTTAGGCTTAAAACAACACACATTTATTCCT
    CTGGGTCCCAGGGTCAGAAGTCCAAAATGAGTCCTATAGGCTAAATTTGA
    GGTGTCTCTGGGTTGAGCTCCTCCTGGAAGCCTTTTCCAGCCTCTAGAGT
    CCCAAGTCCTTGGCTCTGGGCCCCTCCCTCAAGCTTCAAAGCCACAGAAG
    CTTCTAATCTCTCTCCCTTCCCCTCTGACCTCTGCTCCCATCCTCATACC
    CTGTCCCCTCACTCTGACCCTCCTGCCTCCCTCTTTCCCTTATAAAGACC
    CTGCATGGGGCCACGGAGATAATCCAGGGTAATCGCCCCTCTTCCAGCCC
    TTAACTCCATCCCATCTGCAAAATCCCTGTCACCCCATAATGGACCTACT
    GATGGTCTGGGGGTTAGGACGTGGACAACTTGGGGCCTTATTCATCTGAT
    CACAACTCCAGTTCCCAGACCCCCAGACCCCCGGGCATTAGGGAAACTTC
    TCCCAGTTCCTCTCCCTCTGTGTCCTGCCCAGTCTCCAGGATGGGCCACT
    CCCGAGGGCCCTTCAGCTCAGGCTCCCCCTCCTTTCTCCCTGGCCTCTTG
    TGGCCCCATCTCCTCCTCCGCTCACAGGGAGAGAACTTTGATTTCAGCTT
    TGGCTCTGGGGCTTTGCTTCCTTCTGGCCATTGGCTGAAGGGCGGGTTTC
    TCCAGGTCTTACCTGTCAGTCATCAAACCGCCCTTGGAGGAAGACCCTAA
    TATGATCCTTACCCTACAGATGGAGACTCGAGGCCCAGAGATCCTGAGTG
    ACCTGCTCACATTCACAGCAGGGACTGAACCCCAGTCACCTACCCAACTC
    CAGGGCTCAGCGCTTTTTTTTTTTTTTTTCTTTTTgccttttcgagggcc
    gctcccgcaacatatggagatttccaggctaggggtctaattggagcagt
    cgacactggcctaagccaaagccacagcaacaagggcaagccgcttctgc
    agcctataccacagctcacggcaatgccggatccttaacccactgagcaa
    agccagggattgaacctgcaacctcatgtttcctagtcaaatttgttaac
    cactgacccatgacgggaactcccAGGGCTCAGCTCTTGACTCCAGGTTC
    GCAGCTGCCCTGAAAGCAATGCAACCCTGGCTGGCCCCGCCTCATGCATC
    CGGCCTCCTGCCCAAAGAGCTCTGAGCCCACCTGGGCCTAGGTCCTCCTC
    CCTGGGACTCATGGCCTAAGGGTACAGAGTTACTGGGGCTGATGAAGGGA
    CCAATGGGGACAGGGGCCTCAAATCAAAGTGGCTGTCTCTCTCATGTCCC
    TTCCTCTCCTCAGGGTCCAAAATCAGGGTCAGGGCCCCAGGGCAGGGGCT
    GAGAGGGCCTCTTTCTGAAGGCCCTGTCTCAGTGCAGGTTATGGGGGTCT
    GGGGGAGGGTCAATGCAGGGCTCACCCTTCAGTGCCCCAAAGCCTAGAGA
    GTGAGTGCCTGCCAGTGGCTTCCCAGGCCCAATCCCTTGACTGCCTGGGA
    ATGCTCAAATGCAGGAACTGTCACAACACCTTCAGTCAGGGGCTGCTCTG
    GGAGGAAAAACACTCAGAATTGGGGGTTCAGGGAAGGCCCAGTGCCAAGC
    ATAGCAGGAGCTCAGGTGGCTGCAGATGGTGTGAACCCCAGGAGCAGGAT
    GGCCGGCACTCCCCCCAGACCCTCCAGAGCCCCAGGTTGGCTGCCCTCTT
    CACTGCCGACACCCCTGGGTCCACTTCTGCCCTTTCCCACCTAAAACCTT
    TAGGGCTCCCACTTTCTCCCAAATGTGAGACATCACCACGGCTCCCAGGG
    AGTGTCCAGAAGGGCATCTGGCTGAGAGGTCCTGACATCTGGGAGCCTCA
    GGCCCCACAATGGACAGACGCCCTGCCAGGATGCTGCTGCAGGGCTGTTA
    GCTAGGCGGGGTGGAGATGGGGTACTTTGCCTCTCAGAGGCCCCGGCCCC
    ACCATGAAACCTCAGTGACACCCCATTTCCCTGAGTTCACATACCTGTAT
    CCTACTCCAGTCACCTTCCCCACGAACCCCTGGGAGCCCAGGATGATGCT
    GGGGCTGGAGCCACGACCAGCCCACGAGTGATCCAGCTCTGCCAATCAGC
    AGTCATTTCCCAAGTGTTCCAGCCCTGCCAGGTCCCACTACAGCAGTAAT
    GGAGGCCCCAGACACCAGTCCAGCAGTTAGAGGGCTGGACTAGCACCAGC
    TTTCAAGCCTCAGCATCTCAAGGTGAATGGCCAGTGCCCCTCCCCGTGGC
    CATCACAGGATCGCAGATATGACCCTAGGGGAAGAAATATCCTGGGAGTA
    AGGAAGTGCCCATACTCAAGGATGGCCCCTCTGTGACCTAACCTGTCCCT
    GAGGATTGTACTTCCAGGCGTTAAAACAGTAGAACGCCTGCCTGTGAACC
    CCCGCCAAGGGACTGCTTGGGGAGGCCCCCTAAACCAGAACACAGGCACT
    CCAGCAGGACCTCTGAACTCTGACCACCCTCAGCAAGTGGCACCCCCCGC
    AGCTTCCAAGGCAC
    Seq ID No. 34
    AACAAGATGCTACCCCACCAACAAAATTCACCGGAGAAGACAAGGACAGG
    GGGTTCCTGGGGTCCTGACAGGGTCACCAAAGAGGGTTCTGGGGCAGCAG
    CAACTCCAGCCGCCTCAGAACAGAGCCTGGAAGCTGTACCCTCAGAGCAG
    AGGCGGAGAGAGAAAGGGCCTCTTGGTGGGTCAGCAGGAGCAGAGGCTCA
    GAGGTGGGGGTTGCAGCCCCCCCTTCAACAGGCCAACACAGTGAAGCAGC
    TGACCCCTCCACCTTGGAGACCCCAGACTCCTGTCTCCCACGCCACCTTG
    GTTTTTAAGGTAATTTTTATTTTATATCAGAGTATGGTTGACTTACAATG
    TTGTGTTGGTTTCAGGTGTACAGCAGAGTGATTCACTTCTACATAGACTC
    ATATCTATTCTTTCTCAGATTCTTTTCCCATATAGGTTATTACAGAATAT
    TGAGTAGATCCCTGCTGATTACCCATTTTTATAATTGTATATGTTAATCC
    CAAACTCCTAATTTATCCCTCCCCAGACTATGATTCTTTATATCTCTATC
    TGTTTCCTAATCTGTCTCCTCTAAGTCACCCTAGGAGAGCAGAGGGGTCA
    CGTCTGTCCTGTCCTGGCCCAGCCACCTCTCTCCACCCAGGAATCCCTTG
    CATTTGGTGCCAAGGGCCCGGCCCCGCCCTAAAGAGAAAGGAGAACGGGA
    TGTGGACAGGACACCGGGCAGAGAGGGACAAGCAGAGGATGCCAGGGTAG
    GGAGGTCTCCAGGGTGGATGGTGGTCTGTCCGGAGGCAGGATGAGGCAGG
    AAGGGTGTGGATGTACTCGGTGAGGCTGGCGCATGGCCTGGAGTGTCCTG
    AGCCCTGGGAGGCCTCAGCCCTGGATCAGATCTGTGATTCCAAAGGGCCA
    CTGCATCCAGAGACCGTTGAGTGGCCCATTGTCCTGAACCATTTATAGAA
    CACAGGACAAGCGGTACCTGACTAAGCTGCTCACAGATTCCATGAGGCTG
    ATGCCAGGGTTGTCACCCCATCTCACAGGCAGGGAAACTGATGCATATAC
    TGCAGAGCCAGGCAGAGGCCCTCCCAGTGCCCCCTCCCAGCCTGTGGCCC
    CCCTCCAGTGGCTGGACACTGAGGCCACACTGGGGCACCCTGTGGAGATC
    t
    Seq ID No. 35
    AGATCTGGCCAGGCCAGAGAAGCCCATGTGGTGACCTCCCTCCATCACTC
    CACGCCCTGACCTGCCAGGGAGCAGAAAGTAGGCCCAGGGTGGACCCGGT
    GGCCACCTGCCACCCCATGGCTGGGAGAAGGGAGGGCCTGGGCAAAGGGC
    CTGGGAAGCCTGTGGTGGGACCCCAGACCCCAGGGTGGACAGGGAGGGTC
    CCACACCCACAGCCATTTGCTTCCCTCTGTGGGTTCAGTGTCCTCATCTC
    ATCTGTGGGGAGGGGGCTGATAATGAATCTCCCCCATTGGGGTGGGCTTG
    GGGATTAAAGGGCCAGTGTCTGTGATATGCCTGGACCATAGTGACCCTCA
    CCCTCCCCAGCCATTGCTGTCACCTTCCGGGCTCTTGCCCAGGCCTGCCT
    GACATGCTGTGTGACCCTGGGCAAGATGATCCCCCTTTCTGGGCCCCAGC
    CTTCCTCTCTGCTCCGGAAGTGCTTCCTGGGGAAACCTGTGGGCTGGATC
    CTATAGGAAACCTGTCCAATTCCTGGATGCACAGAGGGGCAGGGAGGCCC
    TGGGCCTGGAGGGGCAGGGAGGCTCGAGGTGGGAGCAGGGTAGGGGCCAG
    TCCAGGGCAAGGAGGTGGGTGGGTAGGGTG
    Seq ID No. 36:
    GATCTGTGTTCCATCTCAGAGCTATCTTAGCAGAGAGGTGCAGGGGCCTC
    CAGGGCCACCAAAGTCCAGGCTCAGCCAGAGGCAATGGGGTATCGATGAG
    CTACAGGACACAGGCGTCAGCCCAGTGTCAGGGAGAATCACCTTGTTTGT
    TTTCTGAGTTCCTCTTAAAATAGAGTTAATTGGTCTTGGCCTTACGGTTT
    ACAATAACAACTGCACCCTGTAAACAACGTGAAGAGTACAGAACAACAAA
    TGGGGGAAAACATATTTCACCTGAAAGAGCCACCGCTCATATTTTGATGG
    ATTTCCTTCTAGTTTAATCCTGTTTTAATTGTAAACTGTTAAAACAAACA
    TAAATAAAGAAAATGCATCTGTAAAGTTTAAAAGTCATATCTATGGTGAT
    GGTTGCAAAACACTGTGAATGTTCACTTTGAAATCGTGAACTCTACGTGA
    TATGCATGTCCCGTTAATTAACCTCACAGGCTCAGAATGTGGTTCATTAT
    TTCTTTAATTTTCCTTTAATTTTATGTCCTCTGTGTGTGCCCTTAAACCA
    ACTACTTTTCAGCTCTGCCTGTTTTTGACCTTCACATAGATGACATTTGT
    GAGTGTTTTCTTTCTCAACACTGGGTCTGATACCCACCCACGCTGTCTGC
    TGTCACTGCGGACGTGGAGGGCCACCACCCAGCTATGGCCCCAGCCAGGC
    CAACACTGGATGAATCTGCCCCCAGAGCAGGGCCACCAACACTGGAGGTG
    CAGAGAGGGTTTCTTCAGGGCCATCATTATCCAAGGCATTGTTTCTACTG
    TAAGCTTTCAAAATGCTTCCCCTGATTATTAAAAGAAATAATAAGATGGG
    GGGAAAGTACAAGAAGGGAAGTTTCCAGCCCAGCCTGAAGATCGTGCTGG
    TTGTATCTGGAGCCTGTCTTCCTGACAGGCCTCTATTCCCAGAGTTA
    Seq ID No. 37:
    GGATCCTAGGGAAGGGAGGGCGGGGGCCTGGACAAAGGGGGCCTAAAGGA
    CATTCTCACCTATCCCACTGGACCcctgctgtgctctgagggagggagca
    gagagggggtctgaggccttttcccagCTCCTCTGAGTCCCTCCTCCGAG
    CACCTGGACGGAAGCCCCTCCTCAGGGAGTCCTCAGACCCCTCCCCTCCA
    GCCAGGTTGGCCTGTGTGGAGTCCCCAGTAAGAATAGAATGCTCAGGGCT
    TCGAGCTGAGCCCTGGCTACTTGGGGGGGTGCTGGGGATTGGGGGTGCTG
    GGCGGGGAGCTGGGGTGTCACTAGATGCCAGTAGGCTGTGGGCTCGGGTC
    TGGGGGGTCTGCACATGTGCAGCTGTGGGAAGGCCCTATTGGTGGTACCC
    TCAGACACATATGGCCCCTCAATTTCTGAGACCAGAGAGCCCAGTCTGGC
    CTTCCCAGAACAGCTGCCCCTGGTGGGGGAGATGTAGGGGGGCCTTCAGC
    CCAGGACCCCCAACGGCAGGGCCTGAGGCCCCCATCCCCTTGTCCTGGGC
    CCAGAGCCTCAGCTATCAGGCCTATCAGAGATCCTGGCTGCCCAGCTCAG
    GTTCCCCAGGAGCCAGAGGGAGGCCAGGGGTTACTAGGAAATCCGGAAAG
    GGTCTTTGAGGCTGGGCCCCACCCTCTCAGCTTTCACAGGAGAAACAGAG
    GCCCACAGGGGGCAAAGGACTTGCCAGACTCACAATGAGCCCAGCAGCTG
    GACTCAAGGCCCAGTGTTCGGCCCCACAACAGCACTCACGTGCCCTTGAT
    CGTGAGGGGCCCCCTCTCAGCCAGGCATTCAGACCTGTGACCTGCATCTA
    AGATTCAGCATCAGCCATTCTGAGCTGAAGAGCCCTCAGGGTCTGCAGTC
    AAGGCCAGAGGGCCAGACCTCCAACGGCCAGACATCCCAGCCAGATTCCT
    TTCTGGTCAATGGGCCCCAGTCTGGCTTGGCTCCTGCAGGCCCAGTGCCG
    CCTTCTTCCCCTGGGCCTGTGGAGTCCAGCCTTTCAGTTTCCCACCCACA
    TCCTCAGCCACAATCCAGGCTCAGAGGCAATGTCCGTGGGCAGCCCCTGT
    GTGACCCCTCTGTGGGTGATCCTCAGTCCTACCCTTAGCAGACAGCGCAT
    GAGGGGCCCTCTTGAACCTGAGGGATACTCCATGTCGGAGGGGAGAAGCT
    GGCCTTCCCCACCCCCACTTCCAGGCCTTGGGGAGCAGAGAAAGACCCCA
    GACCTGGGTCCCTTCTAACAGGCCAGGCCCCAGCCCAGCTCTCCACCAGC
    CCCAGGGGCCTGGGGTCCACGCCTGGGGACTGGAGGGTGGGCCTGTCAGG
    CGCTGACCCAGAGGCAGGACAGCCAAGTTCAGGATCCCAGCCAGGTGGTC
    CCCGTGCACCATGCAGGGGTGTCACCCACACAGGGGTGTTGCCACCCTCA
    CCTGACTGTCCTCATGGGCCACATGGAGGTATCCTGGGTTCATTACTGGT
    CAACATACCCGTGTCCCTGCAGTGCCCCCTCTGGcgcacgcgtgcacgcg
    cacacgcacacactcatacaGAGGCTCCAGCCAAGAGTGCCCTGTAGTAG
    GCACTGCTGTCACTTCTCTAAAAGGTCGCAATCATACTTGTAAAGACCCA
    AGATTGTTCAGAAATCCCAGATGGAGAAGTCTGGAAAGATCtTTTTCTCC
    TTTCACGGGCTGGGGAAATGTGACCTGGCCAAGGTCACACAGCAAGTGGT
    GGAACCCTGGCCCCTGATTCCAGCTCATTCCAGTTCCCAAGGCCCTGCCA
    GAGCCCAGAGGCTGGGCCCTCTGGGGCAGAGGAGCTGGGGTCCTCCCCCC
    TACACAGAGCACACAGCCCCGCAAGAGAGAAGAGACACCTTGGGGAGAGG
    AATCTCCAGACCAGAGATCCCAGTATGGGTCTCCTCTATGCTGACGGGAT
    GGGATGTCAAGAGGGGAGGGGGCTGGGCTTTAGGGAAACACACAAAAATC
    GCTGAGAACACTGACAGGTGCGACACACCCACCCCTAATGCTAACCTGTG
    GCCCATTACTCAgatct
    Seq ID No. 38
    GATCTTCTCCTAAGACCAAGGAAAACTGGTCATACCAGGTCCACTTGTCC
    CCTGTGGCCATTGTCCCTCCTTCCCCAGAAGAAACAAGCACTTTCCACTC
    CACAAGTAGCTCCTGATCAGCTTGGAAGCCCGGTGCTGCTCTGGGCCCTG
    GGGACACGGCAGGGGCATCAGAGACCAAATCCTGGAACAAAGTTCCAGTG
    GGTGAGGCAGGCCGGACAAGCAACACGTTATACCATAATATGAGGCAAAA
    TATAATGTGAGTTCTTTATGAAAGGAAGGGGTTGCAGGTGCAACTGTTGG
    CTTAGGTGGATGGTCACCCCTGAATGGAGGAGGGGGTTCCCAGGGCATGT
    GCCTGGGGAGAAGGGCTCCTGGCAGGAGGGACAGCAAGTGCAAGGGCCCT
    GTGATCAAATGTGCCTGGCAAGTTGCAGGAACAGCTAGAAGGCCAGCAAG
    GTTGGAACCAAGGAAGGGGTGAGGGGAGGGGCAGGGCCCTCAGGGCCTTG
    CCCAGCAGCCTGAGCATCTGGAGATTTGTCCAAAGTTTCAAATGTACCTG
    GGCAACCTCATGCCCATATACCATTCCTAACTTCTGCACTTAACATCTCT
    AGGACTGGGACCCAGCCAGTCAAGCGGGGGGACCCAGAGAGCTCCGGTGT
    GAACACCGAGGTGCTGGTGGGTCTGCGTGTGTGGACATAGGGCAGTCCCG
    GTCCTTCCTTCACTAACACGGCCCGGGAAGCCCTGTGCCTCCCTGGTGCG
    CGGGTCGGCGCTTCCGGAGGGTACAGGCCCACCTGGAGCCCGGGCACAGT
    GCATGCAAGTCGGGTTCACGGCAACCTGAGCTGGCTCTGCAGGGCAGTGG
    GACTCACAGCCAGGGGTACAGGGCAGACCGGTCCTGCCTCTGCGCCCCTC
    CCTGGCCTGTGGCCCCTGGACGTGATCCCCAACAGTTAGCATGCCCCGCC
    GGTGCTGAGAACCTGGACGAGGTCCGCAGGCGTCACTGGGCGGTCACTGA
    GCCCGCCCCAGGCCCCCTCTGCCCCTTCCTGGGGTGACCGTGGACTCCTG
    GATGACCCTGGACCCTAGACTTCCCAGGGTGTCTCGCGGAGGTTCCTCAG
    CCAGGATCTCTGCGTCTCCTCCTTCCATAGAGGGGACGGCGCCCCCTTGT
    GGCCAAGGAGGGGACGGTGGGTCCCGGAGCTGGGGCGGAGAACACAGGGA
    GCCCCTCCCAGACCCCGCTCTGGGCAGAACCTGGGAAGGGATGTGGCCAT
    CGGGGGATCCCTCCAGGCCATCTCCTCAGATGGGGGCTGGTCGACTAGCT
    TCTGAGTCCTCCAAGGAACCGGGTCCTTCTAGTCATGACTCTGCCCAGAT
    GAAGAAGGAGAGCACTTCTCTCCATCAGGAGGATCTGAGCTTCTCTTAAT
    TAGAATCAGCTCCTTGGCTTCTACCCCTTAAAAAAAGGTACAGAAACTTT
    GCACCTTGATCCAGTATCAGGGGAATTTATCAATCAATGTGGGAGAAATT
    GGCATCTTTACCACACTGAATCTTTCAATCCATGAATATCCTCTCTCTCT
    TCCATGCATAGGTTTTAATAATTCTCAATGGAGTTTAATGTAAGTTTTCC
    TCATAGACAATTGCCTTTGGACATCTCTTTAGAGTCATCTCTAGTAAACT
    GATATTCTTAATGCAATTATAAAATGTATCCTGCTTAATGTTATTTTCTA
    TTCATTTGCTGTTATATAGAGATACAATGAGTTTCCACATTTGAAACTGG
    ATCTGGTAAATTGGCTACCCTTTTTTTATAGATTCTATTAATTTTTATAC
    ATTCTGTGGGACTTGCTACATACTTAATCATGTCACCTGTGAAGAATGAC
    AATTTGGTTGCTACCCTCCCAATTCTTATATGTCTCATTTCTTTCCCTCT
    GCTGGTACTCTGGCAGCAGCAGGGAAGATAATGGGCCTCCTTATCTTGTC
    ACAAAAGGATGTTTTTAAAGATTTCGTTATAAAACATAACGCTTTCTGGT
    TTTCTTTAAAGATTCTCTCACCAGCTTAAGAAAATTTTCTTATACTCTGT
    ATGATAAATGGGTTTTTGACAATCATTTGTTGCATTTTACCTAGTGTTTT
    CTCTGCATCTTTATATGCTTTTTCTCCTTTAATCCTGAAAATTGTTTCGA
    TTTTTCTAACATTGAACCAATCTTACATTCCTGGAATGGATGGACCAGAC
    TAGTCCACATGTTTATTCTGCCCAATGGCTAGATTTTGTGTTCaatattt
    tgttcagaatgtttgcatctatattcttGAGTGAGACAGAGCTGCCCTTG
    TTAGGTTTCACAACCGAGGTTGTGTTAGCTTCATAAAATGAGACGTTTAT
    TCTCTAAAAGAATTGTTTCGCTTCTCTGGATGAATTTGTGTAAGGTTAGA
    ATTGCTTACCAGTGAagatctCGGGgCCAGTTCTTCTTTAGGGGAAGATT
    TTCAACAATTAAGCTCAATGCCTTTAGAAGAACTGAGAGTTTCTATTATT
    TCTTGAGTTAAATATATGTATTTAATTAGACTTTCTAGGAATAGTCTCAT
    TTCATCTCAAATAATTGACATATGCTATTAAAGCAGATTCTCATGAACCA
    TTGTAGGTATTCCAGGTCTAGAAAAATGTTCCCCTTTGCATCCCTAATGT
    GTTTAATTTTCACCTTCTTTCTTTTGTTCTTGAGAAATTCACCAAATCAT
    TTTCAATTTCAGTCATATCCCAAAGCAACCAACTCTCTACCTTCTTGTTT
    TATCATCCCTGCTGGATTTTTGTTATCTACTTCTTCAGTATTTGTTCTTC
    CCTTTCTTCTATTCCTCATTCCATTTTTCCCTTGTTTTCTAACTTTCTGA
    GATATATGCTTAGTTCCTTCATTTGAAGCCTTTTTATTTTCTTTTTTTTT
    TTTTGGTCTTTTTGTCTTTtGTTGTTGTTGTTGTGCTATTtCTTGGGCCG
    CTCCCGCGGCATATGGAGGTTCCCAGGCTAGGAGTCGAATCGGAGCTGTA
    GCCACCGGCCTACGCCAGAGCCACAGCAATGCGGGATCCGAGCCGCGTCT
    GCAACCTACACCACAGCTCATGGCAACGCCGGATCGTTAACCCACTGAGC
    AAGGGCAGGAACCGAACCCGCAACCTCATGGTTCCTAGTCGGATTCGTAA
    CCACTGTGCCACAACAGGAACTCCGCCTTTTTATTTTCTATAAAAATTTC
    TATGTACATTTTAAGGTTATAGGTTTCCTTCTATGTACCCCATTGGCTGT
    ATCCTCAGGGTTCTGTGGAGTGATTTCATTATTGTTCAAGTTCAATATGT
    CTTCTGATTTTCCAATTTGAATACCTCTCTAAATCAGTAGGTGAATATTT
    CTTTTTCTTTTTCTTTTCTTTTCTTCTTTTTTTTTTTCTTTCAGCCAGGT
    CCATGGCATGCAGAAATTCCCAGGCCAGGAATCAAACTCTCACCATGGCA
    GTGACAATGTCGGATCCTTTACCCACTAGGCCACCAGGGAACTCTGGGAG
    CATATGTTTTTATTTCCCGACATCTGAGGATGCCTAGTATGTCTTCATTA
    TTGATTTCTAGTTTGCCACTGATTTCTAGTATTTTGCTCATAGAGTGTAT
    GCTCAATGGTTTTGGTCATTTGAAATGTATTTAGTCCTGCTTTATGACCC
    AGTATGTGGTCAGTTTTGTCAATGTTCCTTTTCTGCTTGAAGAGAACCTA
    CATGCTGTAACTCTGGGTGCATGTTCTGTATATAAGTCTATAGGCTGAGC
    CGGGGGAGCCTTCTAATCTGCCGTTATCTTCTTCGAGTTATTCTAGGTAC
    TATTTCTTAGCCATAAACCTTTAAATTCTGATATCAATATAATGACCCCA
    GCCCGCTTAGGGTCGGCACTTCATGTTATCTTTTTCCATCCATTTAATGC
    CTCCCCACTGTTTTGGCCACACCCGTGGGATATGGGAGTTCCTGGGCCAA
    GGATCaGATCTGAGCCGCAGCTGCCACCTATGCCACAGCAgcagcaatga
    tggatctttaacccactgcaccacactggggattgaacccaagcctcagc
    agcaacccaagctactgcagagacaacaccagatccttaacctgctgtgc
    catagcgggaaTTTCCATCCATTTACTTTCAAGCCAGCTGAATAACCTAG
    CCCACCATGGCTGGACATGGGTGCTCTGCTTCAAATGATTTTGTTCAGTC
    AGCATCCATCTCTGAAATGTGTGCCAAGCATTTATATGCATGCAAGAGTC
    ATGTTGGCACTTCTATCATTTCCAACAGTTCAGTAGCCTTTGTATCATGA
    CATTTCTTGGCCTTTTCTCTACAATATTTGAGGCTGAGCAGACTGGCCGT
    GCCCCTGTCCATGCTTCCAGAGCCTGTGTGCAGACTTCTGCTCTAGACAG
    AGACAGCTAACCATCCTGCAGTGCCCAGAAAACCCAACTCAAAGACCCTC
    AAGTAAGGAAGGATTTATTGGCTCACGTAATCTGGAATCCAGGCATGGGG
    TATTCAGGGCGACCTGAACCAGAGGCCCTGGCCCTGTTCTCTAAGCTTCT
    TCCTGCCCTGCCCTCGTTCTGGAAGTGACCCTGAAGGACAGCAATGAAGG
    GCAGCTCCCCCAGGGACAGATGACTGAGAGGTCCATTTCAAGTCCAACTT
    GGCCTAGATTGAGAGGCAGCAAGAAATATGGACCTACAGTGAGTCACAGG
    ATTTACCAGTGGTTTGGCTGGGTTGTCAGTGTTACAGGCTAAACATTTGG
    GTCCCTCCAAAATTAACATGTTGCCACTCTAACCACCAAAATCatggtat
    ttgggggtggggcccttggaggtaattaggtttagaaAGAATGAAGAGGG
    GGCCCTTGTGATGGGACTAGTGCCTTTATAGAGAGAGAAGAGAGAGGG
    Seq ID No. 39
    CACCTCATCCCCAACCACCTGGATGGTGGCAAGTGGCAGGCTGAGAGGCT
    GCATATGAGCTCATCAAGAGGGTCCCCACCCCACAGAGGCTGACCCAGCT
    GCCACTGCCACCTAGTGGCTGATCGGCCAAGAGCAGGAGCCCCAGGGGCA
    GCTCCATTCCCTGGGGCGGCCAGGGAACCACCTGGTGGTAGGACAATTCC
    ATTGCACCTCATCCATCAGGAAAAGGTTTGCCTTCCCTGGCAGTAATGCA
    TCTTCCCATAACATGGTCCCTGGCCTCTTGGAATGGCTTGGCCACCGTCA
    TGGCCTCACCCACAAAGCCTTGTGTCTCAGCAAGGAACTTATTCCACAGC
    AAAGGACTTGCAGCCTGGAATGAACTGGTCTGACTACATACCCCATTGCC
    CAGAAGTAGGTGGTCTATTGCAAAGTGGAGTGGCTTACCCAAGACTCAGT
    TGTGCCCAAGTTGAGAGATAGCATCCTAAAATATGGGCTTATGTCTCACT
    GGCTGAGGTTTATTCTTTGAATCAAAGACAATTATATGGTGTGGTCCCCC
    CAGAGATAGAATACATGAGTCTGGGAATCAAGGGATAGAAGTAAGAAGAG
    ATTTTGTCACCATTAATCCCAATAACTCGCCCAAAGAATATTTGCTTTCT
    GTCCTGGCAGCTCTGCTGCTTTGGCAATAACTTCCTAGAATATAATGTCT
    CCACCAGGGGACTCCACAACGGTTCCATTGATTTGAAGCCAATGGGCAGA
    GGAGGGGCTGCCTTACTGGTCGGACTGGTCAGCCCTGATTACTAAGGAGA
    AATCAGGCAACTTCAACAAAACTAAGGCAGGGGGGACTTTGTCTAGAACC
    CAAAGCACTAAGCATCTTAGTACTTTTTAGTTCTCAGAGCCTCCAAGAAC
    AAAGATTTAGCCCCTCAGCACCACCAGGTAAAGAACAGGTAAATCCAGCT
    GAGGACAAGAGAAATATTGAATGGATAGAGGAAGAAAGAAATTATAGATA
    TCAACTATGGCCTCATGACTAGAGTCTCCAGATTAAGCGGAATAAAAATA
    CAGATGATTaGATCTGAACATCAGGCCAAACAACGAACAACAGTTTAAGT
    GCGACCTAGGCAATATTTGGGACATACTTATACTAAAATTTTTTCGCTAT
    TTGAGCATCCTGTATTTTATCTGGCAACTTTATTCATCCCTAGCGAAAAA
    GGAACTGTGGTAACTTAGTGTATTTTTACTTTGCTCATTATTGTGTATAT
    ACCTACTTGTATTTATCAATCATATTTACTCTGTTCTCAGTATTACTTTA
    TATAGCAGTTGGTGGTGATGGTTAGCAACATATTCAGTGGAACTGTGACT
    GAATTTGAGGAGAAATTAACAGAGTTGGCTGTGGCTACAATAACCCTTCG
    GGACATGTGTCCCCTCATTTTGGGGAGATGGTTagatctCTGGGTAAATG
    TTAGGGCATCTGAGCCAGAAACCAAGATTTTGCCAGCTGGTGCAATGTCA
    GATTTTACCAGCAGAGGGTGCCAGAGGAATGCGGCAAAACCCGAGTGCCA
    GAAAGCACCTCCCTGTTTTCCAGCTTTTCTTCCTTTTTATTTATTTTATT
    TACGGCCCAGGAGTCCGTAATAGCGCTGAGGATGGCCCAGGCTCTTCTCA
    GCAGCCCTGACTGACTAGTTCAGCAATGCGCTCAGGCCCCATCTGGCCAC
    CGGGCAGCCTCTTCTGTGGTAGCTCCAGCCTCAGCCAGTGCAAAAGGCTA
    CCCTACACTGGCGCCACTTCTACAATCAGCACTGGCCACACCCTCCACGC
    CATCCGGCACGGAGCCAGGTGATCTGCCGGCCAGATTGCAGTTCGTGCTG
    CCTGAGTCCAGGTGATTACACTGGCTGCATCTTTTCTTTCTGGACCAtTC
    attccattttttt

    Bovine Lambda Light Chain
  • [0121]
    In a further embodiment, nucleic acid sequences are provided that encode bovine lambda light chain locus, which can include at least one joining region-constant region pair and/or at least one variable region, for example, as represented by Seq ID No. 31. In Seq ID No 31, bovine lambda C can be found at residues 993-1333, a J to C pair can be found at the complement of residues 33848-35628 where C is the complement of 33848-34328 and J is the complement of 35599-35628, V regions can be found at (or in the complement of) residues 10676-10728, 11092-11446, 15088-15381, 25239-25528, 29784-30228, and 51718-52357. Seq ID No. 31 can be found in Genbank ACCESSION No. AC117274. Further provided are vectors and/or targeting constructs that contain all or part of Seq ID No. 31, for example at least 100, 250, 500, 1000, 2000, 5000, 10000, 20000, 500000, 75000 or 100000 contiguous nucleotides of Seq ID No. 31, as well as cells and animals that contain a disrupted bovine lambda gene.
    Seq ID No 1 tgggttctat gccacccagc ttggtctctg
    31 atggtcactt gaggccccca tctcatggca
    61 aagagggaac tggattgcag atgagggacc
    gtgggcagac atcagaggga cacagaaccc
    121 tcaaggctgg ggaccagagt cagagggcca
    ggaagggctg gggaccttgg gtctagggat
    181 ccgggtcagg gactcggcaa aggtggaggg
    ctccccaagg cctccatggg gcggacctgc
    241 agatcctggg ccggccaggg acccagggaa
    agtgcaaggg gaagacgggg gaggagaagg
    301 tgctgaactc agaactgggg aaagagatag
    gaggtcagga tgcaggggac acggactcct
    361 gagtctgcag gacacactcc tcagaagcag
    gagtccctga agaagcagag agacaggtac
    421 cagggcagga aacctccaga cccaagaaga
    ctcagagagg aacctgagct cagatctgcg
    481 gatgggggga ccgaggacag gcagacaggc
    tccccctcga ccagcacaga ggctccaagg
    541 gacacagact tggagaccaa cggacgcctt
    cgggcaaagg ctcgaacaca catgtcagct
    601 caaaatatac ctggactgac tcacaggagg
    ccagggaggc cacatcatcc actcagggga
    661 cagactgcca gccccaggca gaccccatca
    accgtcagac gggcaggcaa ggagagtgag
    721 ggtcagatgt ctgtgtggga aaccaagaac
    cagggagtct caggacagcg ctggcagggg
    781 tccaggctca ggctttccca ggaagatggg
    gaggtgcctg agaaaacccc acccaccttc
    841 cctggcacag gccctctggc tcacagtggt
    gcctggactc ggggtcctgc tgggctctca
    901 aaggatcctg tgtccccctg tgacacagac
    tcaggggctc ccatgacggg caccagacct
    961 ctgattgtgg tcttcttccc ctcgcccact
    ttgcaggtca gcccaagtcc acaccctcgg
    1021 tcaccctgtt cccgccctcc aaggaggagc
    tcagcaccaa caaggccacc ctggtgtgtc
    1081 tcatcagcga cttctacccg ggtagcgtga
    ccgtggtcta gaaggcagac ggcagcacca
    1141 tcacccgcaa cgtggagacc acccgggcct
    ccaaacagag caacagcaag tacgcggcca
    1201 gcagctacct gagcctgatg ggcagcgact
    ggaaatcgaa aggcagttac agctgcgagg
    1261 tcacgcacga ggggagcacc gtgacgaaga
    cagtgaagcc tcagagtgtt cttagggccc
    1321 tgggccccca ccccggaaag ttctaccctc
    ccaccctggt tccccctagc ccttcctcct
    1381 gcacacaatc agctcttaat aaaatgtcct
    cattgtcatt cagaaatgaa tgctctctgc
    1441 tcatttttgt tgatacattt ggtgccctga
    gctcagttat cttcaaagga aacaaatcct
    1501 cttagccttt gggaatcagg agagagggtg
    gaagcttggg ggtttgggga gggatgattt
    1561 cactgtcatc cagaatcccc cagagaacat
    tctggaacag gggatggggc cactgcagga
    1621 gtggaagtct gtccaccctc cccatcagcc
    gccatgcttc ctcctctgtg tggaccgtgt
    1681 ccagctctga tggtcacggc aacacactct
    ggttgccacg ggcccagggc agtatctcgg
    1741 ctccctccac tgggtgctca gcaatcacat
    ctggaagctg ctcctgctca agcggccctc
    1801 tgtccactta gatgatgacc cccctgaagt
    catgcgtgtt ttggctgaaa ccccaccctg
    1861 gtgattccca gtcgtcacag ccaagactcc
    ccccgactcg acctttccaa gggcactacc
    1921 ctctgcccct cccccagggc tccccctcac
    agtcttcagg ggaccggcaa gcccccaacc
    1981 ctggtcactc atctcacagt tcccccaggt
    cgccctcctc ccacttgcat ggcaggaggg
    2041 tcccagctga cttcgaggtc tctgaccagc
    ccagctctgc tctgcgaccc cttaaaactc
    2101 agcccaccac ggagcccagc accatctcag
    gtccaagtgg ccgttttggt tgatgggttc
    2161 cgtgagctca agcccagaat caggttaggg
    aggtcgtggc gtggtcatct ctgaccttgg
    2221 gtggtttctt aggagctcag aatgggagct
    gatacacgga taggctgtgc taggcactcc
    2281 cacgggacca cacgtgagca ccgttagaca
    cacacacaca cacacacaca cacacacaca
    2341 cacacacgag tcactacaaa cacggccatg
    ttggttggac gcatctctag gaccagaggc
    2401 gcttccagaa tccgccatgg cctcactctg
    cggagaccac agctccatcc cctccgggct
    2461 gaaaaccgtc tcctcaccct cccaccgggg
    tgacccccaa agctgctcac gaggagcccc
    2521 cacctcctcc aggagaagtt ccctgggacc
    cggtgtgaca cccagccgtc cctcctgccc
    2581 ctcccccgcc tggagatggc cggcgcccca
    tttcccaggg gtgaactcac aggacgggag
    2641 gggtcgctcc cctcacccgc ccggagggtc
    aaccagcccc tttgaccagg aggggggcgg
    2701 acctggggct ccgagtgcag ctgcaggcgg
    gcccccgggg gtggcggggc tggcggcagg
    2761 gtttatgctg gaggctgtgt cactgtgcgt
    gtttgctcgg tggagggacc cagctggcca
    2821 tccggggtga gtctcccctt tccagctttc
    cggagtcagg agtgacaaat gggtagattc
    2881 ttgtgttttt cttacccatc tggggctgag
    gtctccgtca ccctaggcct gtaaccctcc
    2941 cccttttagc ctgttccctc tgggcttctt
    cacgtttcct tgagggacag tttcactgtc
    3001 acccagcaaa gcccagagaa tatccagatg
    gggcaggcaa tatgggacgg caagctagtc
    3061 caccctctta ccttgggctc cccgcggcct
    ccggataatg tctgagctgc ctccctggat
    3121 gcttcacctt ctgagactgt gaggcaagaa
    accccctccc caaaagggag gagacccgac
    3181 cccagtgcag atgaacgtgc tgtgagggga
    ccctgggagt aagtggggtc tggcggggac
    3241 cgtgatcatt gcagactgat gccccaggca
    gggtgagagg tcatggccgc cgacaccagc
    3301 agctgcaggg agcacaggcc gggggcaagt
    catgcagaca ggacaggacg tgtgaccctg
    3361 aagagtcaga gtgacacgcg gggggggggc
    ccggagctcc cgagattagg gcttgggtcc
    3421 taacgggatc caggagggtc cacgggccca
    ccccagccct ctccctgcac ccaatcaact
    3481 tgcaataaaa cgtcctctat tgtcttacaa
    aaaccctgct ctctgctcat gtttttcctt
    3541 gccccgcatt taatcgtcaa cctctccagg
    attctggaac tggggtgggg nnnnnnnnnn
    3601 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnmnnnnnnn nnnnnnnnnn
    3661 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    agcttatgtg gtgggcaggg gggtagtaag
    3721 atcaaaagtg cttaaattaa taaagccggc
    atgatatacg agtttggata aaaaatagat
    3781 ggaaaagtaa gaaaggacag gaggggggtg
    aggcggaaga aagggggaag aaggaaaaaa
    3841 aaataagaga gaggaacaaa gaaagggagg
    ggggccggtg atgggggtgg gatagaatat
    3901 aataattgga gtaaagagta gcgggtggct
    gttaattccg ggggggaata gagaaaaaaa
    3961 aaaaaaaatg tgcgggtggg cggtaagtat
    ggagatttta taaatattat gtgtggaata
    4021 atgagcgggg gtggacgggc aaggcgagag
    taaaaagggg cgagagaaaa aaattaggat
    4081 ggaatatatg gggtaaattt taaatagagg
    gtgatatatg ttagattgag caagatataa
    4141 atatagatgg tgggggaaaa gagacaaggg
    tgagcgccaa aacgccctcc cgtatcattt
    4201 gccttccttc ctttaccacc tcgttcaaac
    tctttttcga gaaccctgaa gcggtcaggc
    4261 ccggggctgg gggtgggata cccggggagg
    ggctgcgcct cctcctttgc agagggggtc
    4321 gaggagtggg agctgaggca ggagactggc
    aggctggaga gatggctgtt gacttcctgc
    4381 ctgtttgaac tcacagtcac agtgccagac
    ccactgaatt gggctaaata ccatattttt
    4441 ctggggagag agtgtagagc gagcgactga
    ggcgagctca tgtcatctac agggccgcca
    4501 gctgcaggga ctttgtgtgt gtcgtgctcg
    ttgctcagtt gtgtccgact ctttatgact
    4561 tcatggactg taacctgcca ggctcctctg
    tccgtggaat tctccaggca agaatactgg
    4621 agtgggtagc cattctcatc tccgggggat
    cttcctgacc caagaatcaa acctgagtct
    4681 cccgcattgc aggcagcttc tttcttgtct
    gagccaccag ggaagcccct taagtggagg
    4741 atctaaatag agtgtttagg agtataagag
    aaaggaagga cgtctataca agatccttcg
    4801 gttcctgtaa ctacgactcg agttaacaag
    ccctgtgtga gtgagttgcc agtaattatt
    4861 gctaacctgt ttctttcact cactgagcca
    ggtatcctgt gagacggcat acttacctcc
    4921 tcttctgcat tcctcgggat ggagctgtgc
    ggtggcctct aggactacca catcgaccag
    4981 gtcagaccca gggacagagg attgctgaga
    tgcactgaga agtttgtcag cctaggtctt
    5041 cacccacaca gactgtgctg tcgtctacca
    cgtaattctt cctgtccaaa gaactggtta
    5101 aacgctcctg aagcgtattc tggtctgctt
    caaaaagtgc ctctttcctt tataagttcc
    5161 gccaatcctg gactttgtcc caggccagtc
    tactttattt gtgggaaagg tttttttggt
    5221 cttttttgtt ttaaactctg cagaaattgc
    ttacactttt ggtgtgcaat ggctcactct
    5281 tacggttcta gctgtattca aaggggttgc
    ttttctttgt ttttaaagct ttttgaacgt
    5341 ggaccatttt taaagtcttt attaaacgtc
    taacatcgtt tctggtttat tttctggtgg
    5401 tctggccatg aggcctacgg gtcttagctc
    ccctaccagg gtccaaccca catcccttgc
    5461 actggacggc aaggtcttaa cctttgaacc
    accagagagc ttctgaaagg ggctgctttt
    5521 ctccaatcct ctttgctccc tgcctgctgg
    tagggattca gcacccctgc aatagccctg
    5581 tctgttctta ggggctcagt agcctttctg
    cctgggtgtg gagctggggt tgtaagagag
    5641 cttcatggat ttggacacga cctacgactc
    agaggtaaga ctccatctta gcgctgtaat
    5701 gacctctttc caacaaccac ccccaccacc
    ctggaccact gatcaggaga gatgattctc
    5761 tctcttatca tcaacgtggt cagtcccaaa
    cttgcacccg gcctgtcata gatgtagcag
    5821 gtaagcaata aatatttgtt gaatgttaag
    tgaattgaaa taacataagt gaaaaagaaa
    5881 acacttaaaa acatgtgttt ttataattac
    acagtaaaca tataatcatt gtagaaaaaa
    5941 atcgaaagag tggcgggggc caagtgaaaa
    ccaccatccc tggtatgtcc acccgcccgg
    6001 gtagccccag gtaagaggtg cggacacgga
    tggccctgta gacacagaga cacacgctca
    6061 tatgctgggt cttgtcttgt gacctcttgg
    ggatgatgtt attttcacga tgccattcaa
    6121 accttctacc acaccatttt tagagggtcg
    ttcatcgtaa atcagttcac tgctttgttt
    6181 tctgattttg aaagtgtcac attcttcgag
    aaatgagaag gaacaggcgc gcataaggaa
    6241 gaaagtaaac acgtggcctt gcttccaggg
    ggcactcagc gtgttggtgt gcacgctggc
    6301 agtcttttct ctgtgacagt catggccttt
    tcccaaaggt gggctcagat aagaccgcct
    6361 cccatcccct gtccctgtcc ccgtccccta
    cggtggaacc cacccacggc acgtctccga
    6421 ggccctttgg ggctgtggac gttaggctgt
    gtggacatgc tgctggtggg gacccagggc
    6481 tgggcagcac gttgtccctg ggtcccgggc
    cagtgaggag ctcccaagga gcagggctgc
    6541 tgggccaaag ggcagtgcgt cccgaggcca
    tggacaaggg gatacatttc ctgctgaagg
    6601 gctggactgc gtctccctgg ggccccttgg
    agtcatgggc agtggggagg cctctgctca
    6661 ccccgttgcc cacccatggc tcagtctgca
    gccaggagcg cctggggctg ggacgccgag
    6721 gccggagccc ctccctgctg tgctgacggg
    ctcggtgacc ctgccgcccc ctccctgggg
    6781 ccctgctgac cgcgggggcc accccggcca
    gttctgagat tcccctgggg tccagccctc
    6841 caggatccca ggacccagga tggcaaggat
    gttgaggagg cagctagggg gcagcatcag
    6901 gcccagaccg gggctgggca ggggctgggc
    gcaggcgggt gggggggtct gcacnccccc
    6961 acctgcnagc tgdncnnncn tttgntnncg
    tcctccctgn tcctggtctg tcccgcccgg
    7021 ggggcccccc ctggtcttgt ttgttccccc
    tccccgtccc ttcccccctt tttccgtcct
    7081 cctcccttct tttattcgcc ccttgtggtc
    gttttttttc cgtccctctt ttgttttttt
    7141 gtctttttct ttttccccct cttctccctt
    gctctctttt tcattcgtcg gtttttctgc
    7201 tcccttccct ctcccccccg ctttttttcc
    ctgtctgctt tttgtgttct ccctctctac
    7261 cccccctgca gcctattttt tttatatatc
    catttccccc tagtatttgg cccccgctta
    7321 cttctcccta atttttattt tcctttcttt
    aactaaaatc accgtgtggt tataagtttt
    7381 aacctttttt gcaccgccca caatgcaatc
    ttcacgcacg ccccccccgt cagcctcctt
    7441 aaataccttt gcctactgcc cccctccttg
    tataataacg cgtcacgtgg tcaaccatta
    7501 tcacctctcc accaccttac cacattttcc
    ttcnnnnnnn nnnnnnnnnn nnnnnnnnnn
    7561 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    7621 nnnnnnnnnn nnntgaaaaa agaaaaggct
    gggcaggttt taatatgggg gggttggagt
    7681 ggaatgaaaa tgcattggag tggttgcaac
    aaatggaaag gtctcaggag cgctcctccc
    7741 ccatcaggag ctggaaagaa gtggaagcaa
    agcaaggaat tcgtgtgatg gccagaggtc
    7801 aggggcaggg agctgcaaag actgccggct
    gtttgtgact gnccgtctcc gggtgcattt
    7861 gttagcaggg aggcattaca ctcatgtctt
    ggtttgctaa ctaattctta ctattgttta
    7921 gttgcaaggt catgtctgac tctttgcaac
    ccagggactg cagcccgcca ggctcctctg
    7981 tccatgggat ttcgcaggca agaatactgg
    aggtggtagc cattttcttc accatgggat
    8041 cttcccgagc cagaaatgga acccgagtcg
    cctcctgtgc atggggtctg ctgcctaaca
    8101 ggcagatatt tgacgtctga gccaacaggg
    aggacagacg gtaattatac caaccattga
    8161 aagaggaatt acacactaat ctttatcaaa
    atctttcaaa cagtagagga gaaaggatac
    8221 tctctagttt attccataaa gttggaatta
    cgcttatcaa taaagacatt acaagaaaag
    8281 aaagtgaagc cccaaatgcc ttataaatat
    acaagaaaaa atcttttaag atattagcca
    8341 acttaatcaa caaaaaatgt atcaaaagtc
    caagtaacat tcaccccagg aatgcaagtg
    8401 tggttcagcc taagacaatc agtcatgagt
    ataccacgga aacaaattaa agagaaaaga
    8461 cattaaatct cacaaatggt gcagaaaaag
    atttggcaat atcgaacatc ttttcatgac
    8521 caaaggaaaa aaaagaaaca aaacaccaga
    aaattctgtg tagaaagaat atatctcaac
    8581 ccaatgaagg gcatttatga aaaacccaca
    gcatacatca cactccatga gaaagactga
    8641 aagctttccc cactgccatt gaactctgtc
    ctggaaattc tagtcacagc gacagaacaa
    8701 gagaaagaaa taacggccgt ctaaactggt
    aggaagaaat caaagcgtct ctattctctg
    8761 ggcgcataat acaatataga caaatttcta
    aagtccacaa aaattcctag agctcataat
    8821 gaatccagaa atgcgtcagg gctcaagatt
    cagatgcaaa aatcgtctgg gttttgatgc
    8881 accaacaaac aattccatta acaataatac
    caaggaatta atttaactta gaagagaaaa
    8941 gacctgttta cagagagtta taaaacattt
    ggtgatgaaa ttaaataaga gtaaatcata
    9001 tagaaacacc gttcgtgttt tggagaccta
    atgtcataaa cgtggcaaca cagagacgcc
    9061 tcacggggaa ccctgagcct ccttctccaa
    acaggcctgc tcatcatttc acaggtaacc
    9121 tgagacccta aagcttgact ctgaggcact
    ttgagggcat gaagagagca gtagctcctc
    9181 ccatgggacc gacagtcaag gcccagggaa
    tgaccacctg gacagatgac ttcccggcct
    9241 catcagcagt cggtgcagag tggccaccag
    ggggcagcag agagtcgctc aacactgcac
    9301 ctggagatga ggcaacctgg gcatcaggtg
    cccatgcagg ggctggatac ccacacctca
    9361 cacctgagga caggggccgg ctttctgtgg
    tgtcgccctc tcaggatgca cagactccac
    9421 cctcttcgct tgcattgaca gcctctgtcc
    ttcctggagg acaagctcca ccttccccat
    9481 ctctccccag ggggctgggg ccaacagtgt
    tctctcttgt ccactccagg aacacagagc
    9541 caagagattt atttgtctta attagaaaaa
    ctatttgtat tcctgcattt ccccagtaac
    9601 tgaaggcaac tttaaaaaat gtatttcctg
    gacttccctg gtgggccagt ggctagactc
    9661 tgagctccca gtgcatgggg cctgggttca
    atccctgctc aggaaactac atcccacagg
    9721 ctgcaaataa gatcctgcat gccacccgat
    gcaggcaaag aaacaagtgt tcggtatgca
    9781 tgtatttcac gtgaggtgtt tctataattt
    acagccagta ttctgtctta cacttagtca
    9841 ttcctttgag cacatgatcg gtcgatggcc
    cagaccacac acaggaatac tgaggcccag
    9901 cacccaccgg ctgcccagaa cctcatggcc
    aagggtggac acttacagga cctcagggga
    9961 cctttaagaa cgccccgtgc tcttggcagc
    ggagcagtgt taagcatggc tctgtccctc
    10021 gggagctgtg tctgggctgc gtgcatcacc
    tgtggtgtgg gcctggtgag ggtcaccgtc
    10081 caggggccct cgagggtcag aagaaccttc
    ccttaaaagt tctagaggtg gagctagaac
    10141 cagacccaca tgtgaactgc acccaaaaac
    agtgaaggat gagacacttc aaagtcctgg
    10201 gtgaaattaa gggccttccc ctgaaccagg
    atggagcaga ggaaggactt ggcttccagg
    10261 aaaccctgac gtctccaccg tgactctggc
    cggggtcatg gcagggccca ggatcctttg
    10321 gtgcaaagga ctcagggttc ctggaaaata
    cagtctccac ctctgagccc tcagtgagaa
    10381 gggcttctct cccaggagtg gggcaaggac
    ccagattggg gtggagctgt ccccccagac
    10441 cctgagacca gcaggtgcag gagcagcccc
    gggctgaggg gagtgtgagg gacgttcccc
    10501 ccgctctcaa ccgctgtagc cctgggctga
    gcctctccga ccacggctgc aggcagcccc
    10561 caccccaccc cccgaccctg gctcggactg
    atttgtatcc ccagcagcaa ggggataaga
    10621 caggcctggg aggagccctg cccagcctgg
    gtttggcgag cagactcagg gcgcctccac
    10681 catggcctgg accccctcct cctcggcctc
    ctggctcact gcacaggtga gccccagggt
    10741 ccacccaccc cagcccagaa ctcggggaca
    ggcctggccc tgactctgag ctcagtggga
    10801 tctgcccgtg agggcaggag gctcctgggg
    ctgctgcagg gtgggcagct ggaggggctg
    10861 aaatccccct ctgtgctcac tgctaggtca
    gccctgaggg ctgtgcctgc cagggaaagg
    10921 ggggtctcct ttactcagag actccatcca
    ccaggcacat gagccggggg tgctgagact
    10981 gacggggagg gtgtccctgg gggccagaga
    atctttggca cttaatctgc atcaggcagg
    11041 gggcttctgt tcctaggttc ttcacgtcca
    gctacctctc ctttcctctc ctgcaggcgc
    11101 tgtgtcctcc tacgagctga ctcagtcacc
    cccggcatcg atgtccccag gacagacggc
    11161 caggatcacg tgttgggggc ccagcgttgg
    aggtganaat gttgagtggc accagcagaa
    11221 gccaggccag gcctgtgcgc tggtctccta
    tggtgacgat aaccgaccca cgggggtccc
    11281 tgaccagttc tctggcgcca actcagggaa
    catggccacc ctgcccatca gcggggcccg
    11341 ggccaaggat gaggccgact attactgtca
    gctgtgggac agcagcagta acaatcctca
    11401 cagtgacaca ggcagacggg aagggagatg
    caaaccccct gcctggcccg cgcggcccag
    11461 cctcctcgga gcagctgcag gtcccgctga
    ggcccggtgc cctctgtgct cagggcctct
    11521 gttcatcttg ctgagcagcg gcaagtgggc
    attggttcca agtcctgggg gcatatcagc
    11581 acccttgagc cagagggtta ggggttaggg
    ttagggttag gctgtcctga gtcctaggac
    11641 agccgtgtcc cctgtccatg ctcagcttct
    ctcaggactg gtgggaagat tccagaacca
    11701 ggcaggaaac cgtcagtcgc ttgtggccgc
    tgagtcaggc agccattctg gtcagcctac
    11761 cggatcgtcc agcactgaga cccggggcct
    ccctggaggg caggaggtgg gactgcagcc
    11821 cggcccccac accgtcaccc caaaccctcg
    gagaaccgcg ctccccagga cgcctgcccc
    11881 tttgcaacct gacatccgaa cattttcatc
    agaacttctg caaaatattc acaccgctcc
    11941 tttatgcaca ttcctcagaa gctaaaagtt
    atcatggctt gctaaccact ctccttaaat
    12001 attcttctct aacgtccatc ttccctgctc
    cttagacgcg ttttcattcc acatgtctta
    12061 ctgcctttgg tctgctcgtg tattttcttt
    tttttttttt ttttattgga atatatttgc
    12121 gttacaatgt tgaatttgaa ttggtttctg
    ttgtacaaca atgtgaatta gttatacatg
    12181 tcctgaggag gggcggctgc gtgggtgcag
    gagggccgag aggagctact ccacgttcaa
    12241 ggtcaggagg ggcggccgtg aggagatacc
    cctcgtccaa ggtaagagaa acccaagtaa
    12301 gacggtaggt gttgcgagag ggcatcagag
    ggcagacaca ctgaaaccat aatcacagaa
    12361 actagccaat gtgatcacac ggaccacagc
    ctggtctaac tcagtgaaac taagccatgc
    12421 ccatggggcc aaccaagatg ggcgggtcat
    gtgcccatgg ggccaaccaa gatgggcggg
    12481 tcatggtgaa gaggtctgat ggaatgtggt
    ccactggaga agggaaaggc aaaccacttc
    12541 agtattcttg ccttgagagc cccatgaaca
    gtatgaaaag gcaaaatgat aggatactga
    12601 aagaggaact ccccaggtca gtaggtgccc
    aatatgctac tggagatcag tggagaaata
    12661 actccagaaa gaatgaaggg atggagccaa
    agcaaaaaca atacccagtt gtggatgtga
    12721 ctggtgatag aagcaagggc caatgatgta
    aagagcaata ttgcatagga acctggaatg
    12781 ttaagtccaa gannnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    12841 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnagaatttt
    12901 gagcattact ttactagcgt gtgagacgag
    tgcaattgtg cggtagtttg agcattcttt
    12961 ggcattgcct ttctttggga ttggaatgaa
    aactgacctg ttccaggcct gtggccactg
    13021 ctgagttttc caaatttgct ggcgtattga
    gtgcatcact ttaacagcat catcttttag
    13081 gatttgaaat agctcaactg gaattctatc
    actttagcta attccattca ttagctttgt
    13141 ttgtagtgat gcttcctaag gcccccctgg
    ctttatcttc ctggatgtct ggctctggtg
    13201 agtgatcaca ccgctgtgat tatctgggtc
    atgaaggtct ttttgtatag ttcttcttag
    13261 gaacagatat tatgatctcc atccttgcat
    ctcgttatat ctagagaagc actgactccc
    13321 ttcatggtga cgtcagatcc tcatgactaa
    caaatggcct tttgtaagat gagtgcctca
    13381 tggtattgag ctcccccgtc accaagacct
    tatgactgac ctcccccact gccccaggtg
    13441 cctctcgaag cgtctgagat gccgcctccc
    aggctgcact cctcattttg cccccaataa
    13501 aacttaactt gcagctctcc agctgtgcat
    ctgtgtttag ttgacagtac aaatataatg
    13561 gaaaatttaa attaaatata atctatgggg
    agaaatccaa acatcttatg agggagagag
    13621 agggagagaa aggaaagaag aagaagcagg
    aggaggagga gagtagagaa acagggggag
    13681 ggcggcaggg agacagaggg gaggacaccg
    aggggaaagg gaggaaggcg agtgcagtga
    13741 gagagaggcc agagttcatc agagtctgga
    ctcgcagccc aatcccacgg gtgtgtcccg
    13801 aagcagggga gagcctgagc caggcggaga
    cagagctgtg tctccagtcc tcgtggccgt
    13861 gacctggagc tgtgtggtca gcccccctga
    ccccagcctg gccctgctgg tggtcggagg
    13921 cagtgatcct ggacacagtg tctgagcgtc
    tgtctgaaat ccctgtggag gcgccactca
    13981 ggacggacct cgcctggccc cacctggatc
    tgcaggtcca ggcccgagtg gggcttcctg
    14041 cctggaactg agcagctgga ggggcgtctg
    caccccagca gtggagcggc cccaggggcg
    14101 ctcagagctg ccggggggac acagagcttg
    tctgagaccc agggctcgtc tccgaggggt
    14161 cccctaaggt gtcttctggc cagggtcaga
    gccgggatga gcacaggtct gagtcagact
    14221 ttcagagctg gtggctgcat ccctggggac
    agagggctgg gtcctaacct gggggtcaga
    14281 gggcaggacg ggagcccagc tgacccctgg
    ggactggcct cctctgtggt ctcccctggg
    14341 cagtcacagc ttccccggac gtggactctg
    aggaggacag ctggggcctg gctgtcagga
    14401 gggggttcga gaggccacac tcagaggagg
    agaccctggc ctgcttgggt tgtgactgag
    14461 tttttggggt cctctaggag actctggccc
    tgcaggccct gcaaggtcat ctctagtgga
    14521 gcaggactcc acaagattga tgaactgaat
    cctctaggag aggtgtggtt gtgagggggc
    14581 agcattctag aaccaacagc gtgtgcaggt
    agctggcacc gggtctagtg gcggcgggca
    14641 gggcactcag ggccgactag gggtctgggg
    gattcaatgg tgcccacagc actgggtctt
    14701 ccatcagaat cccagacttc acaaggcagt
    ttcggggatt aggtcaggac gtgagggcca
    14761 cagagaggtg gtgatggcct agacaagtcc
    ttcacagaga gagctccagg ggccatgata
    14821 agatggatgg gtctgtattg tcagtttccc
    cacatcaaca ccgtggtccc gccagcccat
    14881 aatgctctgt ggatgcccct gtgcagagcc
    tacctggagg cccgggaggc ggggccgcct
    14941 gggggctcag ctccggggta accgggccag
    gcctgtccct gctgtgtcca cagtcctccc
    15001 ggggttggag gagagtgtga gcaggacagg
    agggtttgtg tctcacttcc ctggctgtct
    15061 gtgtcactgg gaacattgta actgccactg
    gcccacgaca gacagtaata gtcggcttca
    15121 tcctcggcac ggaccccact gatggtcaag
    atggctgttt tgccggagct ggagccagag
    15181 aactggtcag ggatccctga gcgccgctta
    ctgtctttat aaatgaccag cttaggggcc
    15241 tggcccggct tctgctggta ccactgagta
    tattgttcat ccagcagctc ccccgagcag
    15301 gtgatcttgg ccgtctgtcc caaggccact
    gacactgaag tcaactgtgt cagttcatag
    15361 gagaccacgg agcctggaag agaggaggga
    gaggggatga gaaggaagga ctccttcccc
    15421 aagtgagaag ggcgcctccc ctgaggttgt
    gtctgggctg agctctgggt ttgaggcagg
    15481 ctcagtcctg agtgctgggg gaccagggcc
    ggggtgcagt gctggggggc cgcacctgtg
    15541 cagagagtga ggaggggcag caggagaggg
    gtccaggcca tggtggacgt gccccgagct
    15601 ctgcctctga gcccccagca gtgctgggct
    ctctgagacc ctttattccc tctcagagct
    15661 ttgcaggggc cagtgagggt ttgggtttat
    gcaaattcac cccccggggg cccctcactc
    15721 agaggcgggg tcaccacacc atcagccctg
    tctgtcccca gcttcctcct cggcttctca
    15781 cgtctgcaca tcagacttgt cctcagggac
    tgaggtcact gtcaccttcc ctgtgtctga
    15841 ccacatgacc actgtcccaa gcccccctgc
    ctgtggtcct gggctcccca gtggggcggt
    15901 cagcttggca gcgtcctggc cgtggactgc
    ggcatggtgt cctggggttc actgtgtatg
    15961 tgaccctcag aggtggtcac tagttctgag
    gggatggcct gtccagtcct gacttcctgc
    16021 caagcgctgc tccctggaca cctgtggacg
    cacagggctg gttcccctga agccccgctt
    16081 gggcagccca gcctctgacc tgctgctcct
    ggccgcgctc tgctgccccc tgctggctac
    16141 cccatgtgct gcctctagca gagctgtgat
    ttctcagcat aactgattac tgtctccagt
    16201 actttcatgt ccctgtgacg ggctgagtta
    gcatttctca cactagagaa ccacagtcct
    16261 cctgtgtaaa gtgatcacac tcctctctgt
    gggacttttg taaaagattc tgcagccagg
    16321 agtcatgggt ggtcttagct gagaaatgct
    ggatcagaga gacctgataa ccgatgtgaa
    16381 gaggggaacc tggaagatct tcagttcagt
    tcatttcagt cattcagttg tgtccgactg
    16441 tttgggatcc catggactgc cacacgccag
    tcctccctgt ccatcaccaa cttctgaagc
    16501 ttgttcaaac tcatgtccat caagttggag
    atgcctttca accatctcat cctctgtcat
    16561 ccccttctcc tcccgccttc aatcttccct
    agcattaggg tcttttccgt gagtcagttc
    16621 ttcgcatcag gtggccaagt tttggagttt
    cagtttcagc atcagtcctt tcaatgaata
    16681 gtaaggactg atttccttta ggatggactg
    gtttgatatc cttgcagttc aagggactct
    16741 caagagtctt ctccaacact gcagttaaaa
    gccatcaatt cttcggtgct cagctttctt
    16801 tttggtacaa ctctcacatt catacatgac
    taccgaaaat acattagtcg tgtagaacca
    16861 gtttggggct tcccacgtgg ctctagtggt
    aaagaatatg cctgccaact cagaagatgt
    16921 aagagatgcg gttcaatctc tgggtcggga
    agatcccctg gagaagggca tgacaaccca
    16981 ctccagtatt tttgcctgga gaatcccatg
    gacagagaag cctggtggac tgcagtccat
    17041 ggagtctcac agagtcagac acgactgaag
    caacttagct acttggaaaa gagcatgcac
    17101 gaagctgtct aaaaaacagg tcaagaagtc
    ttgtgttttg aaggtttact gagaaagttg
    17161 atgcactgct ccaacacttc ctctcagttg
    aaaagatcag aagcgttaga tcaaatggtg
    17221 gtcaatacct tggatgcgct ccaacaggtt
    atatctgcag atggaaatga aggcagttta
    17281 tggggtaact ggaggacaag atgagatcat
    acacttggaa cactgtctgg catcaaaggc
    17341 gtgtacagta aacattagct gttattagca
    aaataaattc agcttgaatc acccaaatca
    17401 gatggcattc ttaaagccac tgagtggtaa
    aatcaggggt gtgcagccaa aacgtccatt
    17461 ttgactcatt atgatttcca tgtcacaaga
    ctagaaagtc actttctcct cagcagaaga
    17521 gaaggtagaa cattttaacc tttttttgga
    gtgtcaaggg aattttgttt acactgtaaa
    17581 gtcagtgaaa atattgaagc ttttcatttg
    tggaaaatat taaatatgta aaattgaaat
    17641 tttaaaattt attcctgggt agttttgttt
    ttccagtagt catgcatgga tgtgagagtt
    17701 ggactataaa gaaagctgag cgctgaagaa
    ttaatgcttt tgaactgtgg cactggagaa
    17761 gactcttgag agtcccttgg tctgcaagga
    gatcaaacca gtccatccta aaggaaatca
    17821 gtcctgaata ttcactggaa ggactgatgc
    tgaagctgaa actccaatac tttggccacc
    17881 tgatgtgaag aactgactca tatgaaaaga
    ctcagatgct gggaaagatt gaaggtggga
    17941 ggagaagggg acgacagagg atgagatggc
    tgaatggcat caccgactcg atggacatga
    18001 gtctgaataa gctctgggag ttgttgatgg
    acagggaggc cctggagtgc tgcagtccat
    18061 gggattgcaa agagttggac atgactgagt
    gactgaactg aactgagttt ggtaacagat
    18121 atgagaatta tataatttaa atctaaactc
    ttggtatttc tttctttggc ggttccaaaa
    18181 gagctgtccc ttctgttaac tatataaatc
    ctttttgaga attactaaat tgataatgtt
    18241 cacaagttat ccaatttctc attactctta
    gttgtcagta taagaaatcc catttgattt
    18301 atcatgttat agtatctgca actctaatag
    ttcagttctg acaaattttt attttattta
    18361 aaaatattgg catacagtaa aatttcaaac
    aatatacaat tctccctttc agtttaaaaa
    18421 acaaaacaaa acaaaagtaa tattagttaa
    aaaaatccgg gaagaatcca agcatttaaa
    18481 attgcatcac atttctatgc tagacaagct
    gatataaagt tataattaat aaaggattgg
    18541 actattaaac tctttacata tgaggtaaca
    tggctctcta gcaaaacatt taaaaatatg
    18601 ttgtgggtaa attattgttg tccttaaaga
    aataaaaaga cataagcgta agcaattggn
    18661 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    18721 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnna aaatggataa ggggggagga
    18781 catgggtagg ggagcgcgat ggaggaagta
    aggtggtcga gggagttggg gggggaataa
    18841 gtgggtaaaa gggaagcggg cggaaggagg
    gggaagcagg agagaggggt gggcgtcaga
    18901 tcggggggag gggtatgagg gagagggaat
    ggtagacggg gggtgggaag cataaaggaa
    18961 aagatagggg ggggaaaagt tagaagaaga
    atgaggggat aggcggaaag ggaagagaaa
    19021 tgggagaaga acagaaaaat agggggaggg
    ggggcgtaaa gagggggggg gagggcaggt
    19081 gtggagatga cagatacggg gaatgccccg
    gtataaaaga gtatatggcg tggggcgaga
    19141 aggctgtcat cctgtgggag gggggacgcg
    gagaaccctt cgggctatag ggaggattcg
    19201 gggggatcgt tcgggaaggc agtcagcaca
    gcacccacca agggtgcagg gatggatctg
    19261 gggtcccaaa gaagaggccc aatcccgcgt
    cttggcagca aggagccctg gagactggga
    19321 agtgtccagg acactgaccc aggggttcga
    ggaacccaga agtgtgtctg tgaagatgtg
    19381 ttttgtgggg ggacaggtcc agagctttga
    gcagaaaagc ggccatggcc tgtggagggc
    19441 caaccacgct gatctttttt aaaaggtttt
    tgttttgatg tggaccattt ttaaagtctt
    19501 cattgaattt gctacaatat tgtttctggt
    ttatgctctg gtttcttcgg ctgcaaggtt
    19561 tgtgtgatcg tatctcctca accaggactg
    aacccacagc ccctgcactg gaaggcgaag
    19621 tcttaaccca gatcgccagg aacgtccctc
    ccctcactga tctaatccaa gaccctcatt
    19681 aaggaaaaac cgagattcaa agctccccca
    ggaggactcg gtggggagga gagagccaag
    19741 cactcagcac tcagtccagc acggcgccct
    ccctgtccag ggcgagggct cggccgaagg
    19801 accaccggag accctgtcgg attcaccagt
    aggattgtga ggaatttcaa cttacttttt
    19861 aaatctgtct ctcaaggctg ttacaagcgg
    actttaccag taacttaaaa gttgaaaggg
    19921 acttcccagg cggcacttgc ggtgaagaac
    ccgccggctg gttttaggag acataagaga
    19981 tgtgggttag atccctggtt caggaggatt
    cccctggaga aggaaatggc aacccactcc
    20041 agtattcttg cctggaaagc ctcacggaca
    gaggaggctg gcgggctaca gtccacgggg
    20101 tcgcacacga ctgaatcgac ttagcttcaa
    gttgagacag gaagaggcag tgactggtgg
    20161 caaaacaccg cacccatgct cccaggggac
    ctgcagcgct ctggttcatg agctgtgcta
    20221 acaaaaatca acccaacgag aggcccagac
    agagggaagc tgagttcatc aaacacgggc
    20281 atgatgtgga ggagataatc caggaaggga
    cctgccaagc ccatgacaga ccggtgtcct
    20341 gtctgagggc cgtcctggca gagcagtgca
    gggccctccg agaccgcccg agctccagac
    20401 ccggctgggg gctacagggt ggggctgagc
    tgcaaggact ctgctgtgag ccccacgtca
    20461 gggaggatca ccttgtttgt tttctgagtt
    tctcttaaaa tagcctttat gggtcctggt
    20521 ctttggtttt aaaataacaa ctgttctccg
    taaacaacgt gaaaaaaaac aaacaggagg
    20581 aaaacaacgc agcccgggca tttcacccgg
    aagagccgcc tctaacactt tgacgggttg
    20641 ccttctattt taaccctgtt ttcattgtaa
    actgtaaaaa ccacatcata aataaattaa
    20701 aggtctctgt gaagtttaaa aagtaagcat
    ggcggtggcg atggctgtgc cacaccgtga
    20761 acgctcgttt caaaacggta aattctaggg
    accccctggt ggtccagtgg gtgagatttt
    20821 gcttccattg caggagccgt gggtttgatc
    cctggttggg gaactaagat cccacatgct
    20881 gtatggagtg gccaaaaaga attttttgta
    aatggtgagt tttaggtgac gtgaatttcc
    20941 cattgatgca cttcacaggc tcagatgcag
    ccaggccctc aggaagcccg agtccaccgg
    21001 tcctttactt ttccttagag ttttatggct
    tctgtttctg cccttaaacc caccatgttt
    21061 caacctcatc tgattttgga ctttataata
    aagttaggct gtgtttcagg aaactttgct
    21121 cagtattctg taataatcta aatggaaaga
    atttgaaaaa agagcagaca cttgtacatg
    21181 cataactgaa tcactttggt gtacacctga
    aactcgagtg cagccgctca gtcgtgtccg
    21241 accctgcgac cccacggact gcagcacgcg
    ggcttccctg cccatcacca actcccggag
    21301 ttcactcaaa cacatgtccg tcgactcggt
    gatgccgtcc aaccgtctca tcctctgtcg
    21361 tccccttctc ctcccgcctt caatcttttc
    cagcatcagg gtcttttcaa atgagtcagt
    21421 tcttcacacc aggtggccag agtattggag
    tttcagcttc agcatcagcc cttccaacga
    21481 ccccccatac ctgaagctaa cacagtgcta
    atccactgtg ctgcaacatg aaagaaaaac
    21541 acatttttta agtttaggct gtgtgtgtct
    tccttctctc aacactgcgt ctgaccccac
    21601 ccacactgcc cagcactgca ttccccgtgg
    acaggaggcc ccctgcccca cagctgcgtg
    21661 ccggccggtc actgccgagc agacctgccc
    gcccagagtg gggcccctgg cactggggac
    21721 aaggcagggg cctctccagg gccggtcact
    gtccactgtt cctactggtt ttgttttcaa
    21781 aagtggaggc agcgtaatat ttccctgatt
    ataaaaagaa gtacacaggt tctccacaaa
    21841 taaaacaggg gaaaagtata aagaatggaa
    gttcccagca cagcctggag atcacgccgg
    21901 gtgcacctgg ggtgtccttc caggctggac
    ctcacatttc acgcagacat cagaaggctg
    21961 cgagatctac ccagaaggct gggtagatgg
    gggataggtc agtgacaaac agtagacaga
    22021 gagatataca gacagatgat ggatagacag
    acgctaagac accgagcgag gggacagacg
    22081 gatggaagac accatccttt gtcactgacc
    acacacccac atgggtgtgg tgagccggct
    22141 gtcatacttg tgaacctgct gctctcacaa
    caccagctgg gtccctccag ccccagcgtc
    22201 ccacacagca gactcccggc tccatcccca
    ggcaggaatc ccaccaccaa ctggggtgga
    22261 ccctccccgc aggaaggtcg tgctgtctaa
    ggccttgaga gcaagttaca gacctacttc
    22321 tgggaagaca gcgcacaacc gcctaccccg
    cagagcccag gaggacccct gagtcctagg
    22381 gaagggacca cgcggcctgg acggggagcg
    gccccaggac gctgccccca acctgtccca
    22441 cctcactcct gctctgctct gaggcggggc
    gcagagaggg gccctgaggc ctcttcccag
    22501 ttcttgggag cacccactgg gcctgaacca
    ggccagaagc cccctcctca aggtgtcccc
    22561 agaccactcc cctccacctc cggttgctct
    gtctcctggc agcagggagc cccagtgaga
    22621 agagacagct ccaggctgtg atcttggccc
    ctggctgctc tggcagtgtg gggggtgggg
    22681 gtcgctggga ggccatgagt gctgggggtc
    ggggctgtga aagcacctcg aggtcagtgg
    22741 gctgttggtc gggctctgcg aggtccgcac
    gggtagagct gtgccaggac acaggaggcc
    22801 tggtcagtgg tcccaagagt cagggccaaa
    ggaaggggtt cgggcccctc tggttcctca
    22861 gcttctgagg ccggggaccc cagtctggcc
    ttggtagggg ggcgattgga gggtacaacg
    22921 atccaaaaga aaacacacat ctacgaggga
    agagtcctga ggaggagaga gctacacaga
    22981 gggtctgcac actgcggaca ctgcttggag
    tctgagagct cgagtgcggg gcacagtgag
    23041 cgaagggagg acggaacctc caaggacacc
    ggacgccgat ggccagagac acacgcacgt
    23101 cccatgaggg ccggctgctc agacgcaggg
    gagctcctca ttaaggcctc tcgctgaata
    23161 gtgaggagaa ctggccccgt gtgtggggaa
    acttagccca gaagaaacgc tgccctggcc
    23221 ccaaggatca nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    23281 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn tgccctttgc
    23341 ctccagggag ggaggaagcg tggatcttgg
    gtttgccttg ggtttaaagg atccacccac
    23401 tcccttttta gccactccct gtgctggcaa
    tttcttaaga ctggaggtcg caaagagttg
    23461 gacacactga gcgagtgaac tgcactgagc
    ctaagaaaag tctttgaatt cctccaaaca
    23521 aaacacactt gtcttgggta ctttccttgg
    ttttgttaca aatgtctggt ccctctgttc
    23581 tcctggccag ctcctgggtg tcattttgac
    ctgacgaagt caaagggagc ctggaccctc
    23641 aaaatctgta ggacccagca cccctccatt
    acacctctgt tcccccgcga acgggcacgt
    23701 gtttcgccgt ctggcgtaat gtgtaagcga
    cggtgtgata ctcgggagtc ttactctgtt
    23761 tctttttctt ctggggtgac accaccatcc
    gcacgactct gtctgaatgt gaacatttgg
    23821 gtgatttgat gtggcccaga ctcccccaac
    gaatgtacct tcaggttggt tttcttcttt
    23881 tatattttgc ttttgtgaat agacacagga
    tcccatcagt tgtatgtagt gagaaagtaa
    23941 aaacccactc agccttagct ggatggagat
    ctagtagtaa gatagcacgt tagccggaaa
    24001 tggaaatttc agccagaatc tgaaaagcgt
    gtcctggaag gagaagaggg actcaggccc
    24061 gagcacactg ctccacgctg gagcctcagg
    ctctgacagc tgtacctgcc ggggtcttca
    24121 tgggacaggc catgcaggcc acgatcccgt
    tgagaagttt cttgcctttc catcacattg
    24181 gcaattgcac gctttgctct tgcttctaca
    tggagtttta cttttatccc agacagtttg
    24241 gtttcttctc tgattttcgc caattgtaca
    gatcgttaca gtatttctta accacataga
    24301 attcggcagg gggggtgggg ggacagggta
    gggtggggtg agagtgaggg gagggggctg
    24361 caccgagcag catctggggt cgtagctccc
    tgacggggat agacctcgtg cccctgcagt
    24421 gacagcacag agtcctcctc tctgaactgc
    cagggacgct cctgcaattg acttaatgaa
    24481 aggcatctaa ttaggaattt tggggtgaca
    ttttacattt aagtgtgtga gcagtgatta
    24541 tagttcatat cattttatag tttcgtgatt
    ttactagctt aaagggtttt tggggtttct
    24601 ttttgtttta aaagctaaaa tctgtttttt
    aattccatgg aatacaaaaa aaaaaagtct
    24661 gtagaatatt ttaaagagtg aaggctttgt
    tcggaatgtg agcgctttgc tccactgaac
    24721 cgaacggtaa taacatttgt agaagagacg
    cagagtgaaa ggtacctctt tttattgagt
    24781 gacatgacag cacccatcgc gtgagttatt
    ggctggagtt tagagacagg ccatgttggg
    24841 ctaaactcct tattgctgtt ctcagccttt
    gagtaataat cagaagcttt ctctgaagag
    24901 agtggggtca gctgtcagac tcctaggtgt
    ctacctgcag cagggctggg attaaatgca
    24961 gcagccagta gatacgggat ggggcaagag
    gtcaccttgt ccctttgttg ctgctgggag
    25021 agaggcttgt cctggtgcca gtggggccaa
    agctgtgact ttgtgaccac aggatgtctc
    25081 tgaccctgcc ttgggttccc tgagggtgga
    gggacagcag ggtctccccg gttccttggc
    25141 cggagaagga ccccccaccc cttgctctct
    gacatccccc caggacttgc cccggagtag
    25201 gttcttcagg atgggcatcc gggccccacc
    ctgactcctg gagctggccg gctagagctt
    25261 gctgcagaat gaggccttgg ccattgcggc
    cctgaaggag ctgcccgtca agctcttccc
    25321 gaggctgttt acggcggcct ttgccaggag
    gcacacccat gccgtgaagg cgatggtgca
    25381 ggcctggccc ttcccctacc tcccgatggg
    ggccctgatg aaggactacc agcctcatct
    25441 ggagaccttc caggctgtac ttgatggcct
    ggacctcctg cttgctgagg aggtccgccg
    25501 taggtaaggt cgacctggca gactggtggg
    gcctggggtg tgagcaagat gcagccaggc
    25561 caggaagatg aggggtcacc tgggaacagg
    cgttgggtgt acaggactgg ttgaggctca
    25621 gaggggacaa aaggcacgtg ggcctccccc
    ccagtgtccc ttaaagtggg aaccaagggg
    25681 gccccggaag ccggaggagc tgtggtgtgt
    ggagtgcaga gccctcgcgg ggtcctgatg
    25741 cccgtcggac tctgcacagc tcagcgtgtg
    ccccgcggcc cggtaggcgg tggaagctgc
    25801 aggtgctgga cttgcgccgg aacgcccacc
    agggacttct ggaccttgtg gtccggcatc
    25861 aaggccagcg tgtgctcact gctggagccc
    gagtcagccc agcccatgca gaagaggagc
    25921 agggtagagg gttccagggg tgggggctga
    agcctgtgcc gggccctttg gaggtgctgg
    25981 tcgacctgtg cctcaaggag gacacgctgg
    acgagaccct ctgctacctg ctgaagaagg
    26041 ccaagcagag gaggagcctg ctgcacctgc
    gctgccagaa gctgaggatc ttcgccatgc
    26101 ccatgcagag catcaggagg atcctgaggc
    tggtgcagct ggactccatc caggacctgg
    26161 aggtgaactg cacctggaag ctggctgggc
    cggatgggca acctgcgcgg ctgctgctgt
    26221 cgtgcatgcg cctgttgccg cgcaccgccc
    ccgaccggga ggagcactgc gttggccagc
    26281 tcaccgccca gttcctgagc ctgccccacc
    tgcaggagct ctacctggac tccatctcct
    26341 tcctcaaggg cccgctgcac caggtgctca
    ggtgaggcgt ggcgccagct ccaaagacca
    26401 gagcaggcct ctcttgtttc gtgcccgctg
    gggacattgc cagggtgccc ggccactcgg
    26461 aagtcctcac gatgccaccg ctctgaccct
    gggcatcttg tcaggtcact tccctggtta
    26521 gggtcagagg cgtggcctag gttaaatgct
    gtcaaagggg actcctttct gggagtccgc
    26581 atagtggggg cttggtgtga tgcccttggg
    aattctttcc gagagagtga tgtcttagct
    26641 gagataatga cagataacta agcgagaagg
    acggtccatc aggtgtgagg tttgaagtcc
    26701 aaagctctgt ctctccctcc cacctgcccc
    ttctgtcctg agctgtttta ggctccaggt
    26761 gagctgtggg aagtgggtga ttctggagat
    gacaagaagg gatcaggagg ggaaaattgt
    26821 ggctcctaag cagtccagag aagagaaaaa
    gtcaaataag cattattgtt aaagtggctc
    26881 cagtctcttt aagtccaaat tataattata
    attttcctct aagacttctg aatacatagg
    26941 aaatcctcag taacaggtta ttgctctgcc
    ttgaacacag tgataaaagc tgggaggatg
    27001 cagcctaatc tgtctgtgtg aatgagttgt
    attgattccc tttttggcag ctgcaaactc
    27061 caagcattag gaataaatat gttcactgag
    aaccccgaag aaagaaagaa agaaaaaaaa
    27121 aaagaattgt aggtgttgat ggacggtttg
    tggcccctga atatctgggg gatgttcacc
    27181 cagggatcac gtgtaactgc tgggaccccc
    agccccatgt ccactgcatc cagcctgctg
    27241 ttgaattccg cggatcnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    27301 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnncaat
    27361 tcgagctcgg taccccaaag gtccgtctag
    tcaaggctat ggtttttcca gtggtcatgt
    27421 atggatgtga gagttggact gtgaagaaag
    ctgagtgcca aagaattatt cttttgtact
    27481 gggtgttgga gaagactctt gagagtccct
    tgaactgcaa ggagatccaa ccagtccgtt
    27541 ctaaaggaga tcagtcctga atgttcattg
    gaaggactga tgctgaagct gaaactccaa
    27601 tactttggcc acctgacgtg aagagttgac
    tcattggaaa agaccatgat gctgagagga
    27661 attgggggca ggaggagaag gggacgacag
    aggatgagat ggctggatgg catcaccaac
    27721 tcgatgngac atgagtttgg ttaaactcca
    ggagttggtg atggacttgg aggcctggtg
    27781 tgctgggatt catggggtcg cagagtcgga
    catgactgag cgactgaact gaactgaact
    27841 gagctgaaga gctcacctgt accagagctc
    ctcaggtcct cctgcaggcc tggctgtaat
    27901 ggcccccagg tcaccgtcct gcctccttca
    tcccatcctt tcacgacagg ctgggagtgg
    27961 ggtgaggtga gttgtcttgt atctagaatt
    tctgcatgcg accctcagag tgcaatttag
    28021 ctccagagaa ctgagctcca agagttcatt
    ttttcctttt cttctttatg atactaccct
    28081 cttctgagca gagacctcat gtcagggaga
    aggggactct gccttcctca gccttttgtt
    28141 cctccaagac ccacacgggg agggtcgcct
    gcttcactga gccggaaggt tcaattgctc
    28201 atgtcctcca gaaacacccc cccccccaga
    gacccccaga aataagtgga acagcacctt
    28261 gtttcccaga caagtgggac acacgttatg
    aaccacctca gtgattaaaa tagtaacctc
    28321 tgtgtatgtg tatttactgg agaaggaaac
    ggcaacctac tccactattc ctgcctagaa
    28381 aattccatgg gagagaagcc aggcaggcta
    cagtccacgg ggtcacagag actgaacata
    28441 cacaagcaca tggaagtgta ttttgcagta
    tttttaaatt tgttcagttc aacatggagt
    28501 acaagaattc aaatcgtgaa gtcaattgac
    caagaaacca gaagaaatca ctgtgttgtg
    28561 atctctgtgg aggtaacatg ggtacctgtg
    ctctgaccct cacagcctct ggctctctct
    28621 ctacatgtac atacacatat atttccatgt
    atgtatgtat tcggaagatt tcacatacgt
    28681 ctcaccagtc cacagccccc gcgttccctg
    atgcccagaa catctgtgat agctgtgagt
    28741 attgtcacca gataagatct tccaggttcc
    tgcactcaca ttggttatca ggtctctctg
    28801 atccagcatt tctcagctaa gattccttgt
    gactcctggc tgcagaatct tctgcaaaag
    28861 tcccacagag aggagtgtga tcactgtaca
    caggagggcc gtggttctct agtgtgagaa
    28921 aagctaactc agcccgtcac agggacgtga
    atgtacctga gacagtaatc agttatgctg
    28981 agaaatcaca gctctgctag aggcagcaca
    tggggtagcc agcagggggc agcagagcac
    29041 ggccaggagc cgcaggtcag aggctgggct
    gcccaagcgg ggcttcaggg gaaccagccc
    29101 tgcgggtcca caggtgtcca gggagcagcg
    cttggcagga agtcaggacc ggacaggcca
    29161 tcccctcagg actagtgacc acctctgagg
    gtcacatcca cagtgaaccc cagagcacca
    29221 tgcctcagtc cacggccagg acgctgccag
    gctgaccgcc ccactgggga gtccagggga
    29281 gaccacaggc cggggggctt gggacagtga
    tcatgtggtc agacacagag aaggtgacag
    29341 tgacctcagt ccctgaggac aagtctgatg
    tgcagacgtg agaagccgag gaggaagctg
    29401 gggacagaca gggctgatgg tgtggtgacc
    ccgcctctca gtgaggggcc cccgggggtg
    29461 aatttgcata aacccaagcc ctcactgccc
    ccacaaagct ctgagaggga ataaaggggc
    29521 tcggagagcc cagcactgct gcgggctcag
    aggcagagct cggggcgcgt ccaccatggc
    29581 ctgggcccct ctcgtactgc ccctcctcac
    tctctgcgca ggtgcggccc cccagcctcg
    29641 gtccccaagt gaccaggcct caggctggcc
    tgtcagctca gcacaggggc tgctgcaggg
    29701 aatcggggcc gctgggagga gacgctcttc
    ccacactccc cttcctctcc tctcttctag
    29761 gtcacctggc ttcttctcag ctgactcagc
    cgcctgcggt gtccgtgtcc ttgggacaga
    29821 cggccagcat cacctgccag ggagacgact
    tagaaagcta ttatgctcac tggtaccagc
    29881 agaagccaag ccaggccccc tgtgctggtc
    atttatgagt ctagtgagag accctcaggg
    29941 atccctgacc ggttctctgg ctccagctca
    gggaacacgg ccaccctgac catcagcggg
    30001 gcccagactg aggacgaggc cgactattac
    tgtcagtcat atgacagcag cggtgatcct
    30061 cacagtgaca cagacagacg gggaagtgag
    acacaaacct tccagtcctg ctcacgctct
    30121 cctccagccc cgggaggact gtgggcacag
    cagggacagg cctggcccgg ttcccccgga
    30181 gctgagcccc caggcggccc cgcctcccgg
    ccctccaggc aggctctgca caggggcgtt
    30241 agcagtggac gatgggctgg caggccctgc
    tgtgtcgggg tctgggctgt ggagtgacct
    30301 ggagaacgga ggcctggatg aggactaaca
    gagggacaga gactcagtgc taatggcccc
    30361 tgggtgtcca tgtgatgctg gctggaccct
    cagcagccaa aatctcctgg attgacccca
    30421 gaacttccca gatccagatc cacgtggctt
    tagaaaggct taggaggtga acaagtgggg
    30481 tgagggctac catggtgacc tggaccagaa
    ctcctgagac ccatggcacc ccactccagt
    30541 actcttccct ggaaaatccc atggacggag
    gagcctggaa ggcttcagcc catggggtcg
    30601 ctaagagtca gacacgactg agcgacgtca
    ctttcccttt tcactttcat gcattggaga
    30661 aggaaatggc aacccagtcc agtgttcctg
    cctggaaaat cccagggaca ggggagcctg
    30721 gtgggctgcc atccatgggg ccacacagag
    tcagacacga ctgaagcaac ttagcagcag
    30781 cagcagcagc ccaataaaac tcagcttaag
    taatggcatc taaatggacc ctattgccaa
    30841 ataaggtcca ctcgcgtgca ctctgtttag
    gacttcagtt cctgattgtg gagggttccc
    30901 acaagacgtg tgtgtatatt ggtgttgccg
    gaaaacagtg tcaatgtgag catcccagac
    30961 tcatcaccct cctactccca ctattccatt
    gtctctgcag gtattaagca taaaggttaa
    31021 gggtcttatt agatggaaga ggagtgaata
    ctcgtctgtg cttaacacat accaagtacc
    31081 atcaaggtcc ttcctattta ttaacgtgtg
    ttttaatcag aaatatgcta tgtagaagca
    31141 tccggacgat agcccatgtt acagacgggg
    aagctgaggc atgaagttct cagcaccttg
    31201 tttcacgtca gacctgaaac ggggcagagc
    cggcagcaaa caaggttcct cttcccaagc
    31261 gcccgctctt cacccgcttc ctatggcttc
    tcactgtgct tcctaaacta agctctcccc
    31321 aaccctgtgg agacaggatt agagacttta
    ggagaaaaga ccaggaacat cccacacccg
    31381 acccgagtga gccactaaga caaggctttg
    taaggacaga accagcaggt gtcctcagcg
    31441 agccagggag agacctcgca ccaaaaacaa
    tattgtagca tcctgaccct ggacttctga
    31501 cctccagaaa tgtgaaaaag aaacgtgtgg
    ggtttaatca actcaccggt gttatttggt
    31561 tatgactgcc tgagttaaga aggagttggg
    aacacttgag tgtaggtgtt tatggaacat
    31621 aagtcttgtt tctctgaaat aaattcccaa
    gggtataatt cctaggttgt agggtaactg
    31681 ccacaaatct aggcagctta ttaaaaaaca
    aagatatcac tttgccagca aaggttcata
    31741 tagtcaaatt atggttttta tagtagtcat
    gtatggatgt aaaagttgga tcataaagaa
    31801 ggctgagcac cagagaattg atcccttcaa
    atcgtggtgc tggagaagac tcttgagagt
    31861 cccttggaca gcaaggagat ccaaccagtc
    aatcctaaag gaaatgaact gtgaatattc
    31921 actggaagga ctgatgctga agctgaagat
    ccaatacttt ggccacctga tgcgaagagt
    31981 tgactcattg gaaaagaccc tgatgctgga
    aagcttgagg gcaggaggag aagagggcgg
    32041 cagaggatga gacggttgga tggcatcact
    gactcaatgg acatgagttt gagccaactc
    32101 tgggagacag tgaaggatag ggaaggctgg
    cgtggtacag tgcatgcggt cacaaagagt
    32161 ctgacacatc ttagtgactc aacaacgaca
    gcaacacagg catcacacgc ttagtgtgat
    32221 aagcggcaga actgttttcc aggggtccgn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    32281 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    32341 nnnnnnnnng tacgattcga gctcggaccc
    tgacattgtg agtcacgtca tgagcagctg
    32401 ttttccggtc ttcagggatt gtggacgatt
    tctgtttggg tttgctcatg ataatttagt
    32461 tacagcttag gttctttctt tccaggccac
    gagcgacatg ttttcaggtg agatgacgtg
    32521 gtgggggatg ggcggccaag cccccactgg
    ggggggaggg attctgttgt gggcaggagt
    32581 tggcagcatc cctgaactga tgacctgcga
    tccaggtgac aagaaccggg ggatattatt
    32641 cctctgcctt ctcatgtcat gtcctcggtt
    cttcatgatg aaaacatatg acaatacagg
    32701 ggagttagat ttgggcgggc acaactctgg
    gtgggggacc cggtggcatt gtgcccagca
    32761 gggccatcaa gatgagggcg acctgggtgg
    tccccttctc ccctggggtc ttagttttcc
    32821 cctcatggaa atgggatcag gcagcagcca
    tggaacaccg cgaccgtggc ttctctcacc
    32881 tcctcgtctg tgattttggg tcgggatacc
    aggcatgaag acctggggcg gggggacatc
    32941 actcctctgc agcagggagg ccgcagagtc
    ctccgtccat gaggacttcg tccctgggct
    33001 gaccctgcgg actgctggag gctgaagctg
    gaggcacagg cgggctgcga ggccagggtc
    33061 ctgaggacga cagagccagt ggggctgcag
    ctctgagcag atggcccctc gccccgggcc
    33121 ctgagcttgt gtgtccagct gcaggttcgc
    tcaggtgagc cactacgtta tgggggaggc
    33181 gccctgggca gggatcgggg gtgctgactc
    ctccgagatt ccgaccttct gggagcactc
    33241 tggccacact ctaagcctgg caagagctgg
    gttcatcagt ctaactctcc tcctgaagtc
    33301 caatggactc tctccatgcg gcagtcactg
    gatggcctct ttatccccga tggtgtcctt
    33361 ttccgctgac ctggctctcc tgaccacctc
    ccagcccccc accatacagg aagatggcac
    33421 ctggtccctg cagagctaag tccacccctg
    gcctggcttc agatgcctac agtcctcctg
    33481 cgggaggccc cgctccccac taggccccaa
    gcctgccgtg tgagtctcag tctcacctgg
    33541 aaccctcctc atttctcccc agtcctcagc
    tcccaacccc agaggtatcc cctgcccctt
    33601 tcaaggccct tgtcccttcc tggggggatg
    gggtgtatgg gagggcaagc ctgatccccc
    33661 gagcctgtgc cgctgacaat gtccgtctct
    ggatcatcgc tcccctggct ctcagagctc
    33721 cctggtccct ggggatgggt tgcggtgatg
    acaagtggat ggactctcag gtcacacctg
    33781 tcccttccct aaggaactga cccttaaccc
    cgacactcgg ccagacccag aaagcacttc
    33841 agacatgtcg gctgataaat gagaaggtct
    ttattcagga gaaacaggaa cagggaggga
    33901 ggagaggccc ctggtgtgag gcgacctggg
    taggggctca ggggtccatg gagaggtggg
    33961 ggagggggtg tgggccagag ggcccccgag
    ggtgggggtc cagggcccta agaacacgct
    34021 gaggtcttca ctgtcttcgt cacggtgctc
    ccctcgtgcg tgacctcgca gctgtaactg
    34081 cctttcgatt tccagtcgct gcccgtcagg
    ctcagtagct gctggccgcg tatttgctgt
    34141 tgctctgttt ggaggcccgg gtggtctcca
    cgttgcgggt gatggtgctg ccgtctgcct
    34201 tccaggccac ggtcacgcta cccgggtaga
    agtcgctgat gagacacacc agggtggcct
    34261 tgttggcgct gagctcctcg gtggggggcg
    ggaacagggt gaccgagggt gcggacttgg
    34321 gctgacccgt gtggacagag gagagggtgt
    aagacgccgg ggaggttctg accttgtccc
    34381 cacggtagcc ctgtttgcct tctctgtgcc
    ctccgaccct tgccctcagc ccctgggcgg
    34441 cagacagccc ctcagaagcc attgcaatcc
    actctccaag tgaccagcca aacgtggcct
    34501 cagagtcccc ggctgcgacc agggctgctc
    tcctccgtcc tcctggcccc gggagtctgt
    34561 gtctgctctt ggcactgacc ccttgagccc
    tcagcccctg ccagacccct ccgtgacctt
    34621 ccgctcatgc agcccaggtg cctcctccgt
    gaacccgggt ccccccgccc acctgccagg
    34681 acggtcctga tgggagatgt ggggacaagc
    gtgctagggt catgtgcgga gccgggcccg
    34741 ggcctccctc tcctcgccca gcccagcctc
    agctctcctg gccaaagccc ggggctcctc
    34801 tgaggtcctg cctgtctacc gtccgccctg
    cctgagtgca gggcccctcg cctcacctgc
    34861 cttcagggga cggtgccccc acacagcacc
    tccaaagacc ccgattctgt gggagtcaga
    34921 gccctgttca tatctcctaa gtccaatgct
    cgcttcgagg ccagcggagg ccgaccctcg
    34981 gacaggtgtg acccctgggt cccaggggat
    caggtctccc agactgacga gtttctgccc
    35041 catgggaccc gctcctttct gaccgctgtc
    ctgagatcct ctggtcagct tgccccgtct
    35101 cagctgtgtc cacccggccc ctcagcccag
    agcgggcgag acccctctct ctctgccctc
    35161 cagggccttc cctcaggctg ccctctgtgt
    tcctggggcc tggtcatagc ccccgccgag
    35221 cccccaagct cctgtctggc ctcccggctg
    gggcatggag ctcacagcac agagcccggg
    35281 gcttggagat gcccctagtc agcaccagcc
    tctggcccgc accccagcgt ctgccctgca
    35341 agaggggaac aagtccctgc attcctggac
    caaacaccag ccccggcgcc ccgactggcc
    35401 ccattggacg gtcggccact ggatgctcct
    gctggttacc ccaagaccaa cccgcctccc
    35461 ctcccggccc cacggagaaa ggtggggatc
    ggcccttaag gccgggggga cagagaggaa
    35521 gctgccccca gagcaagaga agtgactttc
    ccgagagagc agagggtgag agaggctggg
    35581 gtagggtgag agccacttac ccaggacggt
    gacccaggtc ccgccgccta agacaaaata
    35641 cagagactaa gtctcggacc aaaacccgcc
    gggacagcgc ctggggcctg tcccccgggg
    35701 gggctgggcc gagcgggaac ctgctgggcg
    tgacgggcgc agggctgcag ccggtggggc
    35761 tgtgtcctcc gctgaggggt gttgtggagc
    cagccttcca gaggccaggg gaccttgtgt
    35821 cctggaggtg ccctgtgccc agccccctgg
    ccgaggcagc agccacacac gcccttgggg
    35881 tcacccagtg ccccctcact cggaggctgt
    cctggccacc actgacgcct tagcgctgag
    35941 ggagacgtgg agcgccgcgt ctgtgcgggg
    cggcagagga gtaccggcct ggcttggacc
    36001 tgcccagccg ctcctggcct cactgtaagg
    cctctgggtg ttccttcccc acagtcctca
    36061 cagtccagcc aggcagcttc cttcctgggg
    ctgtggacac cgggctattc ctcaggcccc
    36121 aagtggggaa ccctgccctt tttctccacc
    cacggagatg cagttcagtt tgttctcttc
    36181 aatgaacatt ctctgctgtc agatcactgt
    ctttctgtac atctgtttgt ccatccatcg
    36241 atccaacatc catccatcca tccatcaccc
    agccatccat ctgtcatcca acatccatcc
    36301 ttccatccat tgtccatcca tctgtccatc
    ttgcatctgt ctgtccaaca gtggccatca
    36361 agcacccgtc tgccaagccc tgtgtcacac
    gctgggactt ggtgggggga gccctcgccc
    36421 tcccaccctc ccatctctcc tgaaacttct
    ggggtcaagt ctaacaaggt cccatcccgt
    36481 ctagtctgag gtccccccgc agcctcctct
    tccactctct ctgcttctga cccacactgt
    36541 gcactcggac gaccacccag ggcccttgca
    tccctgtttc cttcctgacc tctttttttt
    36601 ggctctggat ttatacacat tctgcctcct
    ggaggcgtct cagcttgagt gtcccacaga
    36661 cgcctcagac tcagcatctt ccatcgaaac
    tgctcccagg tccttgcaga cctggtcccc
    36721 cacattgttc tcaattcggt agatttctcc
    acaagccaga ggcctggact catcccataa
    36781 tgcctgcccc tcattgagtc agcctctgtg
    tcctaccata accaaacatc cccttaaaaa
    36841 tctcagaaga acaaaaaaag cacccagatg
    gcactgtcag agtttatgat gacaagaatc
    36901 ctcagttcag ttcagtcact cagtcgtgtc
    cgactctttg cgaccccatg aatcgcagca
    36961 cgccaggcct ccctgtccat caccaactcc
    cggagttcac tcagactcac gtccattgag
    37021 tcagtgatgc catccagcca tctcatcctc
    tctcgtcccc ttctcctcct gcccccaatc
    37081 cctcccagca tcagagtttt ttccaatgag
    tcaactcttc gcgtgaggtg accaaagtac
    37141 tggagtttca gcttcagcat cattccttcc
    aaagaaatcc cagggctgat ctccttcaga
    37201 atggactggt tggatctcct tacagtccaa
    gggactctca agagtcttct ccaacaccac
    37261 agttcaaaag cctcaattct ttggcgctca
    gccttcttca cagtccaact ctcacatcca
    37321 tacatgacca caggaaaaac cataaccttg
    actagatgga cctttgttgg caaagtaatg
    37381 tctctgcttt ttaatatgct atctaggttg
    ctcataactt tccttccaag aagtaagtgt
    37441 cttttaattt catggctgca atcaacatct
    gcagtgattt tggagcccca aaaaataaag
    37501 tctgccactg tttccactgt ttccccatct
    atttcccatg aagtgatggg accagatgcc
    37561 atgatctttg ttttctgaat gttgagcttt
    aagccaactt ttcactctcc actttcactt
    37621 tcatcaagag gctttttagt tcctcttcac
    tttctgccat aagggtggtg tcatctgcat
    37681 atctgaggtt attgatattt ctcctggcaa
    tcttgattcc agtttgtgtt tcttccagtc
    37741 cagtgtttct catgatgtac tctgcatata
    agttaaataa gcagggtgat aatatacagc
    37801 cttgacgtac tccttttcct atttggaacc
    agtctgttgt tccatgtcca gttctaactg
    37861 ttgcttcctg acctgcatac agatttctca
    agaggcaggt caggtggtct ggtattccca
    37921 tctctttcag aattttccac agttgattgt
    gatccacaca gtcaaaggct ttggcatagt
    37981 caataaagca gaaatagatg tttttctgaa
    actctcttgc tttttccatg atccagcaga
    38041 tgttggcaat ttgatctctg gttcctctgc
    cttttctaaa accagcttga acatcaggaa
    38101 gttcacggtt catgtattgc tgaagcctgg
    cttggagaat tttgagcatt cctttgctag
    38161 cgtgtgagat gagtgcaatt gtgcggcagt
    ttgagcattc tttggcattg cctttctttg
    38221 ggattggaat gaaaactgac ctgttccagg
    cctgtggcca ctgttgagtt ttcccaattt
    38281 gctggcatat tgagtgcagc actttcacag
    catcatcttt caggatttga aatcgctcca
    38341 ctggaattcc atcacctcca ctagctttgt
    ttgtagtgat gctctctaag gcccacttga
    38401 cttcacattc caggatgtct ggctctagat
    gagtgatcac accatcgtga ttatctgggt
    38461 cgtgaagatc ttttttgtac agttcttctg
    tgtattcttg ccacctcttc ttaatatctt
    38521 ctgcttctgt taggcccata ccgtttctgt
    cctcgcctat cgagccctcg cctccctacg
    38581 tagagactct aagcaggaag gtgacccgtg
    ctgcactggg tccagcatgc ttttaattca
    38641 gcagtggaac ttctgggtca tgattgtgtt
    taagggatgc gcatacgatt tttgaagcaa
    38701 aatttaacag gacagcagtg taaagtcagt
    acttatttct gattaaagaa agcaaatatc
    38761 cagcctgtta ctaagttaat taactaaaga
    aacatcttca acttaataaa cagtatctcc
    38821 tgaaacttac agcatgcttc acatttaaag
    gcaaaaccat tttagaggcc agggttccca
    38881 cgcttacgtt tattatttaa tatatgctac
    agattcaagc ccatgacaca aaatgggggg
    38941 aagagtgtga gtgttaggaa aaatgagata
    aaattggttt ttgcaggtga tgggctagtt
    39001 tactttaaaa aaaaaaacaa aacaagctca
    agatgaactg aaggactatt agaactggta
    39061 caagagttaa cctgtgatcg aatacaagca
    ggctgggcaa aactcagcag gttttcttct
    39121 atacaggcag taatgattga gaatacgaaa
    cggcggaagc gcttacaacc tcgataacag
    39181 ttctattaaa agccctagga atgaacttaa
    cacggnnnnn nnnnnnnnnn nnnnnnnnnn
    39241 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    39301 nnnnnnnnnn nnnnngctcc ccccaccctc
    ccctcctccc cccccaccac cagtgcccca
    39361 ggtctcgtgc ccagagagct gaagatgcca
    gcaggcccgc tgcctgcctc gctcgcgtgg
    39421 cccgggctcg ctgccggtct gcctgcccag
    cacacagatg cagccccagc tctcgctgcc
    39481 acccgcctcc cccaggcagg actctcccac
    aacaccaagg gcgtctctgg gttcaggatg
    39541 gccctcgttg aggtgtaaag tgcttcccgg
    ggctgagacg aatgggccgg agatccaaac
    39601 gaggccaagg ccgccacggc gcctggcgca
    gggcacccat ggtgcagagc ggcccagctc
    39661 cctccctccc tccctccctc cctgcttctt
    tatgctcccg gctatgtcta tttttactct
    39721 gcaatttaga aatgataccg aaggacaaac
    accgttcccc ctgtgtgtct gctctaaacc
    39781 ctttatctac ttatctatta gcgtgtccaa
    gttttgctgc taagtgaatg aaggaacact
    39841 acccacaagc agcaacgtcc ccacgaccct
    cgcctgttca actgggaatg taaatgtgct
    39901 ttcaaaggac ctaagtttct atgttcaaaa
    ccgttgtgtg tttcttttgg gagtgaacct
    39961 aggccactcg ttgttctgcc tttcaaagca
    ttcttaacaa ctctccagaa cccagggctt
    40021 ggcttacgtt tccagaaatt ccaaagacag
    acacttggaa acctgatgaa gaaggcctgt
    40081 gagcacagca ggggccgggg tacctgaggt
    aggtgggggg ctcggtgctg atggacacgg
    40141 ccttgtactt ctcatcgttg ccgtccagga
    tctcctccac ctcggaggct ttcagcaggg
    40201 tcacgctggt ggccagggtc gtgtatccat
    gatctgcaac cagagacggg gctgcggtca
    40261 gcccgcgggc gggcagcagg caggagcagc
    caggagacgc agcacaccga ggtcctcaca
    40321 tgcaggaggt gggggaagcg gctgtggacc
    tcacgactgc ccgatgtggg cctcttccaa
    40381 agggccggcc tggaccctgg ctttctccag
    aggccctgct gggccgtccg cacaggctcc
    40441 agccacaggg cctcttggga caggagggct
    ccagagtgag ccggccggcg ggaagaggtc
    40501 tgacaccgct gcagtccaca acacgaagcg
    aggtggagat gggatgaggg atgagaaaca
    40561 cttttctttt aaaacaagag cccagagagt
    tggaaagagc tgctgcacac gcaacatgaa
    40621 ctcctggccc cggtgccagc ggcgctggga
    gcccgagttc tcggcaatcc gaccacagct
    40681 tgcctaggga gccgggtgga gacggagggt
    taggggaagg cggctcccca gggagcgcga
    40741 ggcccggggt cgccaaggct cgccaggggc
    aagcgcagct aggggcgcag ggttagtgac
    40801 cggcactgca cccggcgcag gagggccagg
    gaggggctga aaggtcacag cagtgtgtgg
    40861 acaagaggct ccggctcctg cgttaaaaga
    acgcggtgga cagaccacga cagcgccacg
    40921 gacacactca taccggacgg actgcggagt
    gcacgcgcgc gcacacacac acacacacca
    40981 cacacacaca cacacggccc gggacacact
    cataccggac ggactgcgga gtgcacgcgc
    41041 acacacacac ccaccacaca cacacccacc
    acacacacac ccaccacaca cacacacaca
    41101 cacacacacc cccacacaca cccacacaca
    cccacacaca cccacacaca cacacccaca
    41161 cacacacaca cacacacaca cacacacacg
    gcccggtggc cccaggcgca cacagcacgg
    41221 agcaaacatg cacagagcac agagcgagcg
    ctagcggacc ggctgccaga ccaggcgcca
    41281 cgcgatggat tgggggcggg gacggggagg
    ggcgggagca aacggnnnnn nnnnnnnnnn
    41341 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    41401 nnnnnnnnnn nnnnnnnnnn nnnnngtatt
    aaagaagccg ggagcgagaa tatgacggca
    41461 agaggatgta ggtgggggcg gggcaagagt
    aaagagagcg gacggtagag gggatgcgat
    41521 tgtgatgcgg aagcgagacg aggagtgatg
    ccgtattaga ttgatagcaa gaggaacagt
    41581 aggagggggg ggggagagga gggggaggtg
    gggggtggtg ggtgggaagg gaactttaaa
    41641 aaaaagaggg gagagttgga ggggggaata
    aacgggcggt aaaaaagaac aatttgaaat
    41701 taccagggtg gggcggccag gggggtgatt
    cattcttgga gggggcaaca tatggggggt
    41761 ggctgtcgcg gattaggaga aaataaatat
    caggggtgat taagtgtttg gcgttgggga
    41821 ataatgaagt aagaatcaaa tatgaatcgc
    gttggcatcg ttagccatcg ggggaaacat
    41881 ttcccatgca aggaacaagg atgtgagaat
    gcgtccgtct gaaccaccgt cccggggtcc
    41941 cagtaggact cgccgagctg atagttgccg
    gagcaacagt taagggagca gaagctgcta
    42001 caaaaccacc acctgccaaa gtagggtctc
    caattacgga gtgcgcctcc tgggtgtcgg
    42061 tccaaacctt tggaaaggac ctggaaataa
    gtgctaccca ccagatatta atataaaccc
    42121 acctggccag gagaggcagg cgctgctggc
    acaggaagtg tccccagact cagtcatcaa
    42181 ggtaaataat attttgggac ctccctggaa
    atccagtggt taggactctg cggttcaatc
    42241 cctggtcggg gaactaagat cccacaagtc
    acaagacatg gccaaattta aaaaagaaaa
    42301 aaagagagag aaatatttag tgcaataggt
    tttagaattg aaattaagct cctgcccacc
    42361 cccacccccc aatctggatg aataaagcat
    tgaaatagta agtgaagtca ggctctgaca
    42421 tgcactgatg tgactcacct taagcaaccc
    ccaccctagg actggtcggg gttccaggag
    42481 tttcaggggt gccaggaaga tggagtccag
    cccctgccct ctccccccac cacgtcctcc
    42541 actggagccg cctaccccac ctcccacccc
    tccgcaccct gctacccccc acccctgccc
    42601 ccaggtctcc cctgtcctgt gtctgagctc
    cacactttct gggcagtgtc tccctctaca
    42661 gctggtttct gctgcccgct accgggcccg
    tcccctctgt tcagttcagt tcagtcgctc
    42721 agtcatgtct gactctttgt gaccccatgg
    actgcagcac accaggcctc cctggccatc
    42781 accaaccccc agaacttact caaactcatg
    tccatcgagc cagtgatgcc atccaaccat
    42841 ctcatcctct gtcgacccct tctcctggcc
    tcaatctttc ccagcatcag ggtcttttcc
    42901 aatgagtcag ttctttgcat caggtagcca
    aagtattgga gtttcagctt cagcatcatt
    42961 tcttccaatg aatattcagg actcatttcc
    tttgggatga actggttgga tctccttgca
    43021 gtccaaggga ctctcaagag tcttctccaa
    caccacagtt caaaagcatc aattcttcag
    43081 tgctcagctc tctttatagt ccaactctca
    catccatacg tgaccactgg aaaaaccata
    43141 gcctcgacta gatggaactt tgtgggcaaa
    gtaatgtctc tgcttttgaa tatgctgtct
    43201 aggttggtca taacttttct tccaaggagc
    aagcgtcttt taatttcatg gctgcagtca
    43261 ccatctgcag tgatttttgg agcccaagaa
    aataaagtct gtcactgttt ccactgtttc
    43321 cccgtctatt taacggaggg aaatttccca
    gagcccccag gttccaggct gggccccacc
    43381 ccactcccat gtcccagaga gcctggtcct
    cccaggctcc cggctggcgc tggtaagtcc
    43441 caggatatag tctttacatc aagttgctgt
    gtgtcttagg aaagaaactc tccctctctg
    43501 tgcctctgtt ccctcatccg cagaagtgac
    tgccaggtcg gggagtctgt gacgtctcca
    43561 gaagccggag gattttctcc ccatttgctg
    aaagagagct cggggtgggg gaagcttctg
    43621 cacccctagg atcaccagag gagccagggt
    cttcagggtt cccggggacc cctcagtggg
    43681 ggctcaggaa ccacagagcc agaccctgat
    tccaaaaacc tggtcacacc tccagatgac
    43741 cctttgtccc ttggctccgc ctcaaatgct
    ccaagcccca acagtgaagc gcttaagaga
    43801 aggatccacc aggcttgagt ttggggagga
    gggaagtggg gagctggggg agggcctggg
    43861 cctgggagac aggaatccac catggcttca
    ggcagggtct ctggggcctg cggggtggag
    43921 agcgggcagg agcagacaga ggtgactgga
    cacgacacac ccctccactc caagggaggt
    43981 gggcaggggc ggggcacaga ggaacaagag
    accctgagaa ggggtccacc gagcagactg
    44041 ctggacccag acatctctga gccagctgga
    atccagctct aagccatgct cagcccaggc
    44101 agggtatagg gcaggactga gtggagtggc
    cagagctgca gctgcatggg ctgggaaggc
    44161 cctgcccgtc ccctgagggt cccccagggt
    ctagccagac tccaatttcc gaccgcagca
    44221 cacacaggag gaagtggtcg gggtggagtt
    ggcccagagg tctgggcagg tgcagggtgg
    44281 gggaaggggg gcagctggag tcacccgctg
    aattcaggga cagtcccttt ttctccctga
    44341 aacctggggc tgtcccgggg gccaccgcag
    cctccaggca gcggggggac ccagccccca
    44401 atatgtgaga agagcaggtc ccaggctgga
    gagagcgaag caccatggtg gggagaagtt
    44461 agactggatc ggggccccta ggggctcccc
    cggacctgca cggcagccgt cagggcaccc
    44521 gcaccccatt gctgttcagt gctggccagt
    gtccaaggcc agggatgtgt gtgtgtgtgt
    44581 gtgcgtgcgt gcgtgcgtgt gtgtgtgcgt
    gtgtgcgcgt gcgtgcgtgt gtgtgtgtgt
    44641 gcgtgcgtgt gcgtgcgtag acgtgtgcgt
    gcgtgcgtgc gtgcgtgcgt gtgtgtgcgc
    44701 acgcgcgcag cccagcctca gcactggacc
    aggcagcctg ggattcctcc aaaactgcct
    44761 tgtgagtttg gtcaaaccgt gaggctctga
    tcaccgccat ccattcgccc cctcctgccc
    44821 ccctcatcac cgtggttgtt gtcattatcg
    agagctgtgg agggtctggg aggtcatccc
    44881 acctgccagc taaaccgtga ggctgccgca
    atcgcactga tgcgggcaga cccgagacgc
    44941 tgtgccggag acgaaggcca gcttgtcacc
    ccgccagagc ggcagtcggg ccacaagcat
    45001 catccaagca gtggttctct gagcccgacg
    gggtgatgca aaggagccag gagacacctg
    45061 cgcgtccaag ctgggggacc ccaggtctgt
    tatgccggac agtaaacacg ttcagctccg
    45121 gagggagagg gttcccctac cttccagggt
    ttctcattcc acaaacatcc aaagacaatc
    45181 cataccgaag gcgatccgtg cctttgctcc
    tgagacgtgc ggaagcacag agatccacag
    45241 acactgtctc ccaggatcct atgtatgtaa
    aggaaccgaa gtcccaggct gtgtgtctgg
    45301 taccacatcc cacggaacag gctggactga
    ttttcaccaa atgtagcaga aacgttaagg
    45361 agtatcagct tcaaaatatg agggccagac
    atgtctgaga agtcccttcc agaaaagtcc
    45421 ctttggggtc cttccccaga gttgctgaaa
    cagagaaccg gaagggctgc agagctgaac
    45481 ttaaacaact ggatcgcaaa ggtccgtctc
    atcagagcga tggtttttcc agtggtcatg
    45541 tatggatgag agagttggac cataaagaaa
    gctgagcgcc gaagaatcga tgcttttgaa
    45601 ctctggtgtt ggagaagact cttgagagtc
    ccttggactg caaggagatc caaccagtca
    45661 atcctaaagg aaatcaatcc tgaatattca
    tgggaaggac tgatgctgaa gctgaaactc
    45721 caatactttg gccacttgat gcaaagaact
    gactcactgg aaaaaccctg atgctgggaa
    45781 aggttgaagg caggaggaga aggggtcgac
    agaggatgag atggttgggt ggcatcaccc
    45841 acccatggac tcaatggaca tgggtttgag
    taaactctgg gagttggtga tggacagaga
    45901 atcctggcat gctgcggtcc atggggtcat
    agagagtcag acacaactga gcgactgaca
    45961 gaactgaagc aactggcaag ccggagggta
    ggtgccggct gcgatgagcg ggaacgtgca
    46021 acctgccacg tggagctctt cctacaccca
    gagtcctgac ggcactggga ccctagccct
    46081 ccacggcctc tccagggcca cgagacaccc
    tcacagagca gagaagcgga acagagctgg
    46141 tgtgcagaac caggccccgg gggtggggcg
    gggctggtgg gcaggcttta gtgagaagcc
    46201 cttgagccct ggaaccagag cagagcagaa
    cagttggcag aggcccccct gggagaggcc
    46261 ccccgcccag agtaccggcc ctgggccctg
    ggggagaggg cggtgctggg ggcagggaca
    46321 gaaggcccag gcagaggatg ggccccgtgg
    gacggggcgc accaaaacag cccctgccag
    46381 caaggggaag ctggggcact ttcgaccccc
    tccaaggagg agcccacacc agcgcatctg
    46441 cccaaggtgc ccttggccct gggggcacat
    gaggcccagg ccaggccagg gggcccatga
    46501 ggcccccagg ggtcagtgca gtgtccccag
    gcagccctgg cctctcatcc tgctgggcct
    46561 ggcctcttat cccgtgggcg cccacggcct
    gctgcccccg acagcggcgc ctcagagcac
    46621 agccccccgc atggaagccc cgtcaggaaa
    gagcccttgg agcctgcagg acaggtaagg
    46681 gccgagggag tcatggtgca gggaagtggg
    gcttcccttc gatgggaccc aggggtgaat
    46741 gaccgcaggg gcggggaacg agaagggaaa
    ccagctggag agaaggagcc tgggcagacg
    46801 tggctgcacg cacagcgctg accctgggcc
    cagtgtgcct ttgtgttggg ttttattttt
    46861 aattttgtat tgagatgcta tttatctcgt
    ggagcttttg ccgccctgag attttgtacc
    46921 cgtggctggt gtccctcttg cctcaccccg
    gcctctgtag cagggcagac acggcgcaac
    46981 ggggcagggc gtgcccagga ggcactgtca
    ttttgggggc agcggcccca caaggcaggt
    47041 ctgccttcct cccctcttac aggcagcgac
    agaggtccag agaggtgagg caagctgccc
    47101 aatgtcacac agcacacggg cgcagtccca
    ggactgtaga aatcccggga ctagacaggc
    47161 accagagtgt cctgtgtttt taaaaaaacg
    gcccaagaga agaggcaagt ctgcaaggcg
    47221 tcccgggaag gcagcagggg cttggctcgg
    tctcccccaa ggaggccagc tcctcagcga
    47281 ggttcctaag tgtctaacgg agccaagcct
    gaaccaaggg ggtcacgtgc agctatggga
    47341 cactgacctg ggatggggga gctccaggca
    aagggagtag ggaggccaag gaggagagag
    47401 gggtgcacag gcctgcaggg agcttccaga
    gctggggaaa acggggttca gaccacgggg
    47461 tcatgtccac ccctccttta tcctgggatc
    cggggcaggt attgagggat ttatgtgcgg
    47521 ggctgtcagg gtccagttcg tgctgtggaa
    aaattgtttc agatcagaga ccagcgtgag
    47581 gtcaggttag aggatggaga agaagctgtg
    aaaaggtgat ggagagcggg gggacggtcc
    47641 tcggtgatca ggcaccgaga tcgcccatgg
    aatccgcagg cgaatttaca gtgacgtcgt
    47701 cagagggctg tcggggagga acaggcactg
    tcatgaactg gctacaaaaa tctaaaatgt
    47761 gcaccctttt cggcaatatg cagcaagtca
    taaaagaaaa cgcatttctt taaaattgcg
    47821 taattccgct tttaggaatt catctggggg
    cgggggaaca atcaaaaaga tgtgaccaaa
    47881 ggtttacaag ccaggaagtc aactcgttaa
    tgatgggaga aaaccggaaa taacctgaat
    47941 atccaacaga aagggtgtga tgaagcgcag
    catggcacat ccaccgcaag gaatcctaac
    48001 acaaacttcc aaaacaatat ttctgacgtt
    gggtttttaa agcatgcgtg cactttcaaa
    48061 agcttgtcag aaaacataga aatatgccaa
    taatgtgtct ctagccaaat tttttaattt
    48121 ttgctttata attttataaa gttataattg
    tatgaaatat aatgataaaa ttataaacta
    48181 taaaaaagtt atgaaaatgt tcacaagaag
    atatacatgt aattttatct tctacaatac
    48241 tttttaatac cagaataacg tgcttttaaa
    aaagattgag cacagaagcg tataaagtaa
    48301 aaattgagag tttctgctca ccaaccacac
    gtcttacctt aaaacccatt ctccagcgag
    48361 agacagtgtc atgtgggtct gtacacttct
    ggcctttctc ctaggcatgt atgtccctga
    48421 aaactcacac acacggctaa tggtgctggg
    attttagttt tcaaaacgga ctcatactct
    48481 gcctatgagc ctgcaactat ttattcagtc
    tgttgagatt ttctatatca gcccacatgg
    48541 atcccgcatg ttctctgaat ggctctgtat
    gaattcaaag tttggaagaa gcagcgtgtc
    48601 tttaatcatt cgcctattaa tggacgtttg
    gggtgtttcc actacaaaan nnnnnnnnnn
    48661 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    48721 nnnnnnnnnn nnnnnnnnnn nnnnnnnnng
    atacaattcg agctcggtac cctggcttga
    48781 actatatgaa cagagaacga tgagaacagt
    ttctcaaact tggaacagtt aacattttgg
    48841 gctaaatgat tcttttttgt gtggagttgg
    cctatgaata gaggatatta gcagcatcat
    48901 ttaaccttta ctcactacat acctgtagca
    actacatcct ctccatttgt gtcaatcaaa
    48961 actgtctccg gacatggaca agtgtgcccc
    tgggatgggt ggaatgacct tttgttaaga
    49021 accactgggt cagagattca tagatttttg
    tcttgttgac tttttaaaaa tacatcttgg
    49081 tttttatttt attggtttct gctcttatct
    ttatgattac cttcctttta cttggggctt
    49141 ccctgataga ttttcccttc tggctcagct
    ggtaaagaat ctgcctgcaa tgcaggagac
    49201 ctgggttcag tccctgggtt gggaggatcc
    cctggagagg agaagggcta cccaccccag
    49261 tattctggcc tggaggattc catggagtgt
    atagtccatg gggtcgcaga gtcggacatg
    49321 actgagtgac tttcacacac acatatgtcc
    ctggtagctc agctagtaaa gaatcccacc
    49381 cgcaatgcag gagaccccgg tccaattcct
    gggtccggaa gattcccttt tgtttactcc
    49441 ataagatctt atctggggac aaaactaaca
    gctatgccag accttctgga catcagggaa
    49501 cgtgaggggt gtggactgga cagatgtgtg
    tgttctccca aacacaaaca tacatctgta
    49561 tacatgtaca tggagagagg gggagggagg
    ctgtgagtct ccaggggacc gtgcaaccat
    49621 gtgacattca tggaggcgtt tgcgggtgat
    cactacacag tttcttcttc tggtttcttg
    49681 gtcaattgac ttcacaattc caattcctat
    acttcatttt agactgaggg aattttacac
    49741 tattgtaaga catatgtata catgagttat
    gttcagcgcc atgagggctc attttgtgtg
    49801 tccactttgc ctggaaacaa agttggactg
    atttacttct aggggtgcct gggggtgttt
    49861 ctggaggaca ggagcatttg aacccaaggg
    ctcggtgaag catgagcctc tctgcaggtg
    49921 gacccaggag gaacgcaagg ccgaggaagg
    cagactctcc tcctccctaa cccgaggtct
    49981 ctgctcagaa aagggacaat ataatgacta
    gaagaaaaga aagaacatca gctgtgggag
    50041 gtttgttctc tggagcagat tcacacgttg
    aggctcatgt gcaggaattc taggtgaaac
    50101 agagcagtca cccatgtgtg ttggaaaatt
    ttaaattaca tttgcagtta cgactttgtt
    50161 taagccagac agggtagcac agcaaagtca
    ccatgtggtc acctgtgttt tgtaaaggag
    50221 agagaacttg ctggcacatt caggaaaggc
    cgtgtctcag ctttggaggc acactgagag
    50281 gccacaagca gatggtgagg accagggtct
    cgggcagagg gatcaattca ctgctcttca
    50341 cttttgccac atctgtgtgc tgtccatcct
    ggccagagta gttcagtctt cagatgctgg
    50401 agttcccatt ggtagaaatc caatctgggt
    catttttaaa cctctcttgg ttctacttaa
    50461 tggttttaaa atctctttgg ctcaagaaaa
    aaaataaaca taattttaaa gggtggtttg
    50521 gggccttgac tataaagtac attatctggg
    ccatttcaga gcatggttga attaatacat
    50581 ttcgtgctta ctatagctcc tattttcttg
    attctttaca ggtaattttt gttaggaatc
    50641 gggtactgtg aatattttct tgttgaatac
    gggatctttg tattttttcc taattttttt
    50701 ttttttttca tttttggttt taccttcagg
    aaagtcacta ggactcagga aagtcctttg
    50761 tccgcctgtt atttcagtct cttacctggg
    gccagggcag cgtttcctct gggctaagtt
    50821 tccccacaac cggggccagt tctcctcact
    cttcaccctg aggccttaat gaggagctcc
    50881 cctgcgtctg agcagccggc cctcctgtga
    cgtgcgtgtg tctctggcca tcggcgtccg
    50941 gtgtccttgg aggttccgtc ctcccttcgc
    tcactgtgcc ccgcactcga gctctcaggc
    51001 tccaagcagt gtccgcagtg tgcagaccct
    ctgtgtagct ctctcctcct caggactctt
    51061 ccctctagat gtgtgttttc ttttggctcc
    ttggacctcc gctctgaacg caggcctggt
    51121 gctgagtgtg atctctggag ggaagcctgg
    gaggctggac gggtccgccc tgcggtgtgg
    51181 tgacaggtgt gggctcgggg cggggcctgc
    acgtcgtcct gacccgagcc gggactgggc
    51241 tccgggcctc aggcatcact gactgaatct
    ccctcacaga ggggtcaggg cctgggcggg
    51301 ggaaccgtct ctgcaatgac agcccctccc
    agggagggca cagcggggag ctgccgaggc
    51361 tccagcccta gtgggaggtc ggggagccca
    ggggagcggc ctgacggccc cacaccggcc
    51421 cagggctggt tcgttctgtt tctcgagctc
    aacagaagct ccgaggagct gggcagttct
    51481 ctgaattcgt cccggagttt tggctgctga
    gtgtcctgtc agcaccgtat ggacatccag
    51541 agtccattag cagtggtctc tgtccctctg
    tctgtccttc atcaggctct ttgtccaggt
    51601 caccacacgg ccaacaccag gacagtctgg
    tcccgccagc ccatcgtccc tgcggacgcc
    51661 cctgtgcagc ctgccgaagg gccgggaggc
    cgggggaacc gggccaggcc tgtccctgct
    51721 gtgtccacag tcctcccggg gctggaggag
    agcgtgagca ggacgggagg gtttgtgtct
    51781 cacttccccg tctgtctgtg tcactgtgag
    gattatcact gctgtcagct gactgacagt
    51841 aatagtcggc ctcgtcctcg gtctgggccc
    cgctgatggt cagcgtggct gttttgcctg
    51901 agctggagcc agagaaccgg tcagagatcc
    ctgagggccg ctcactatct ttataaatga
    51961 ccctcacagg gccctggccc ggcttctgct
    ggtaccactg agtatattgt tcatccagca
    52021 ggtcccccga gcaggtgatc ttggccgtct
    gtcccaaggc cactgacact gaagtcggct
    52081 gggtcagttc ataggagacc acggagccgg
    aagagaggag ggagagggga tgagaaagaa
    52141 ggaccccttc cccgggcatc ccaccctgag
    gcggtgcctg gagtgcactc tgggttcggg
    52201 gcaggcccca gcccagggtc ctgtgtggcc
    ggagcctgcg ggcagggccg gggggccgca
    52261 cctgtgcaga gagtgaggag gggcagcagg
    agaggggtcc aggccatggt ggatgcgccc
    52321 cgagctctgc ctctgagccc gcagcagcac
    tgggctctct gagacccttt attccctctc
    52381 agagctttgc aggggccagt gagggtttgg
    gtttatgcaa attcaccccc gggggcccct
    52441 cactgagagg cggggtcacc acaccatcag
    ccctgtctgt ccccagcttc ctcctcggct
    52501 tctcacgtct gcacatcaga cttgtcctca
    gggactgagg tcactgtcac cttccccgtc
    52561 tctgaccaca tgaccactgt cccaagcccc
    ccggcctgtg gtctcccctg gactccccag
    52621 tggggcggtc agcctggcag catcctggcc
    gtggactgag gcatggtgct ctggggttca
    52681 ctgtggatgt gaccctcaga ggtggtcact
    agtcctgagg ggatggcctg tccagtcctg
    52741 acttcctgcc aagcgctgct ccttggacag
    ctgtggaccc gcagggctgc ttcccctgaa
    52801 gctccccttg ggcagcccag cctctgacct
    gctgctcctg gccacgctct gctgccccct
    52861 gctggtggag gacgatcagg gcagcggctc
    ccctcccgca ggtcacccca aggcccctgt
    52921 cagcagagag ggtgtggacc tgggagtcca
    gccctgcctg gcccagcact agaggccgcc
    52981 tgcaccggga agttgctgtg ctgtgaccct
    gtctcagggc ggagatgacc gcgccgtccc
    53041 tttggtttgt tagtggagtg gagggtccgg
    gatgactcta gccgtaaact gccaggctcc
    53101 gtagcaacct gtgcgatgcc cccggggacc
    cagggctcct tgtgctggtg taccaaggtt
    53161 ggcactagtc ccaccccagg agggcacttc
    gctgatggtg ttcctggcag ttgagtgcat
    53221 ttgagaactt acatcatttt catcatcaca
    tcttcatcac cagtatcatc accaccatca
    53281 ccattccatc atctcttctc tctttttctt
    ttatgtcatc tcacaatctc acacccctca
    53341 agagtttgca ttggtagcat atttacttta
    gcacagtgtg cctcttttta ggaaactggg
    53401 ggtctcctgc tgatacccct gggaacccat
    ccagaaattg tactgatggc tgaacccctg
    53461 cgtttggatt cttgccgagg agaccctagg
    gcctcaaagt tctctgaatc actcccatag
    53521 ttaacaacac tcattgggcc tttttatact
    ttaatttgga aaaatatcct tgaagttagt
    53581 acctacctcc acattttaca gcaggtaaag
    ctgcttcgca tttgagagca agtccccaga
    53641 tcaataaaga gaatgggatg aacccaggat
    ggggcccagg ggtcctggat tcagactcca
    53701 gccgtttagg acagaacttg actaggtacg
    aagtgagcgg ggtggggggg caatctgggg
    53761 ggaactgtgg cacccccagg gctcggggcc
    atccccacca catcctggct ttcatcagta
    53821 gccccctcag cctgcgtgtg gaggaggcca
    gggaagctat ggtccaggtc atgctggaga
    53881 atatgtgggg ctggggtgct gctgggtcct
    aggggtctgg ccaggtcctg ctgcctctgc
    53941 tgggcagtga taattggtcc tcatcctcct
    gagaagtcac gagtgacagg tgtctcatgg
    54001 ccaagctatt ggaggaggca gtgagcactc
    ccacccctgc agacatctct ggaggcatca
    54061 gtggtcctgt aggtggtcct ggggcttggg
    ccgggggacc tgagattcag ccattgactc
    54121 tcagaggggc cagctgtggg tgcagcggca
    gggctgggcg gtggaggata cctcaccaga
    54181 gccaaaataa gagatcaccc aacggataga
    aattgactca caccctttgg tctggcacat
    54241 tctgtcttga aatttcttgt ggacaggaca
    cagtccctgg ataaagggat ttctatcttg
    54301 cgtgtgcaat agagctgtcg acacgcttgg
    ctgggacatg taatcctttg aacatggtat
    54361 taaattctgt tcactaacat ctgaaaggat
    ttttgcatca ataaacctaa ggtatattgc
    54421 cctgtcattt ccttgtcttg tagtgtctct
    gagtaggctg gaaggggtaa ccagcttcac
    54481 aaatcgagtt aggaaattcc cttattcttc
    cactgtctaa tagactttca taagattagt
    54541 gttaattcct ctttaaatcg ctgctataat
    catcactgtg gccaccggta ctgaattttt
    54601 tgttaggatg atttttaaac aagcatttta
    atgatttttc cttttatttt cggctgtgct
    54661 gggtctcgtt gctgtgtgcc ggcgttctct
    cgctgtggcc agtgggggcg ctgctctcgc
    54721 gttgcgaagc tcgggcttct gactgcagtg
    gcttctctcg ttgcagagcg cgggctccag
    54781 ggcgctcagg ctcgcgtggc tgcggcacgt
    gggctcagta gtcctggggc acaggtgcag
    54841 cagcctctca ggacgttttg ttcccagatg
    gtgggtcggt cgaaccggtg tcccctgcgt
    54901 tgcaaggtgg attcttcacc gctggaccac
    cagcgacgtt ccctggaggt ttttaattat
    54961 ggatttaagc tctcattaga tgtctcctca
    catttcctat ttctttttga gtcagtttga
    55021 tactttgttt gtgtctgtaa gtttgtccat
    tttatccaag tcatctaatg tgttgataga
    55081 caattattgg ttagtcatct aattgttggt
    ttacaatttt gagagcattg tcctgcaatt
    55141 ccttctatct gcaagattgg taataatatc
    tcccaagagg agtcacaaac tgaaatgaga
    55201 ttanatacag gctttttttt taaaagaatg
    aacttatgtt gttgcctttc tcatagatct
    55261 tacttcttag catgactgta cttactgact
    ggggcgtttt catgtctgtg tggagagcta
    55321 ccattagtac ttcttatcgc ccaaagacat
    cgggctcctg ggcacagtga aaacactcct
    55381 ttctgtggct attttgcaaa atatggccta
    gcctagcgtc ataagggatc acagctgaca
    55441 actgctggaa cagagggaca tgcgaagcaa
    cgtgagggct ggaacctgga gggtcctctc
    55501 tggggacagt ttaaccagct ataatggaca
    ttccagcatc tgggacatgg agctgtgaac
    55561 tggaccaatg actgtcattt ttggaagaga
    aatcccagga gagaagggtc caggggaatc
    55621 tgaggccgca tgcagtgcct caggacaggg
    gacaccttct ccagcagagc aggggggccc
    55681 gcccaggccg cctgcagtga ttccaccagg
    aggagatgca tccctgcaga cctctgacag
    55741 cacggccctc tcctgagaca cagggtcaca
    cccggggccc tggaaccctt tgagacccta
    55801 aacctttcct ttcctgacca ccctgacagc
    agtctagctc agaacagaca tcttcatttt
    55861 cagcaggaaa atccttttcc tcgtttgagg
    gagcgactgg caccggagga gctgagtctt
    55921 ttaaacacag gctgcctgaa cctcagggat
    gacctgcagc tgctcagagg aggctggagt
    55981 gtgatagctc actctaatgt tactaaaagg
    aacatattgg acaccccctc tctgaaaaat
    56041 ttccctcctg cctctcatct cttagtccac
    tttatcgccg ttttactgct tttctattta
    56101 ctactcttaa cgccaaccta tcttatttcc
    cctcccagtt taacacggtt ttccctccac
    56161 ccgctctctt taatctcaga agattctgcc
    tattcctcta ttatcacacg cccctacttt
    56221 ttattttttt tcttacccgc cttttattcc
    ctcccctcct cactctctat ttaattacat
    56281 cttaactaca ccgcctgcgc tatcttcgaa
    tgtatccaaa tatttttccc ttatataaca
    56341 ctccaggccg agcggctaac ttattataat
    ttctttatag cgcctaccta atttcccttt
    56401 atttctaatt atctatatat acccatgcaa
    tttcgnnnnn nnnnnnnnnn nnnnnnnnnn
    56461 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    56521 nnnnnnnnnn nnnnntgggt gtacgttata
    gagtaaacgc gcatgaagaa gtgggtcaat
    56581 ctatggctgt gagaggcaga aaataatatt
    atcatatata atttatgtta taacacactg
    56641 aggtggtggg ctcgtagaat agtgcggacg
    gggagaaagg tgggaaggag aagacacaag
    56701 agagagatgt tcgcctcgcg ggatggatgg
    gcggagggat agaagaataa aaagaggaga
    56761 ggtatagagg ggggcggggg gcataacgtg
    tggtggggta aatagtaggc ggtaattatg
    56821 aaaaaaagaa agacgggggg ggcggtaaca
    tagaatacgc aaaaaagtca tatactgaac
    56881 ggggattagg gagaagaggt ggggggcgtg
    gggtgcgggg gaaagaggtg tgtgtataat
    56941 tggtatggag tgttatttga atatatatta
    atgtaatagg gagtgtaatt agtgaaattg
    57001 tgggagtatt atattggggt gtgggggaca
    tggcaaagtg atgatcggga taaaaaaagt
    57061 aaagcaagag gggaggggaa aataaggggg
    gggagaaggt cgaagaaaat aagaggaaga
    57121 agaaagaacg ggggtggcgg gcgggggggg
    cgccgctctt gtatctggct tttttgttgt
    57181 gtcggtggtt gttcgcgtct tgttgggtcc
    ggggcgggtg tgcggaaaaa aaaaaaggcg
    57241 ggaggcccgg ggcccggtca cgcggcaccc
    ccgcgggtcc ctggcttctc cttcggcagc
    57301 tccgggggtc ggtgagcctg cgccctccgg
    gccgccggcc cgagctgtgt gcgccctgga
    57361 gaatcggagc cgctgtggca gcacgcggag
    ggcgcgcgca agggccacgg gacggacctt
    57421 caaaggccgc ggcggagcgc ggcaagccga
    accgagggcg gtctggcgat cggccgagcc
    57481 ctgctccccc ctcccgcgtg gccccagggt
    cgcgggtgga ctggggcggg tacaaagcac
    57541 tcacccccgt cccgccccca gaaagcctcc
    caggactctc acagagcacc cgccaggagg
    57601 catccggttc ccccctcggc tcagttcagt
    tgctcagtcg tgtccaactc tttgcgaccc
    57661 catggactgc agcaccccaa gcttccctgt
    ccatcaccaa ctcccggagt ttactcaaac
    57721 tcatctattg agtcagtgat gccatccaac
    cgtctcatcc tctgttgtcc ccttctcctc
    57781 ccactttcaa tctttcccag catcagggtc
    ttttcttatg agccagttct tcacatcagg
    57841 tggtcagagt attggagttt cagcttcagc
    atcagtcctt ccaatgaaca ctcaggactg
    57901 atttccttta ggatggactg gctggatgca
    gcgccagaca ccgaccgcgt ttaccccgtg
    57961 tgtcctttcc aatggctgtc ccctgcgggc
    ctaggggcat tggtgcgggt ttgaatcctg
    58021 tggccttgaa ttttacgcct tagttccagg
    tccagggcag ggccatccgg attcaggatg
    58081 cttcccagcc cttcaggaat ggcaggtttt
    catggtcctt tctgagtgag ttctgagtgg
    58141 tcatattggt gcccttggca gggagggctc
    ctgactttcc tatcttcaca tcactgtccc
    58201 caacccccaa gagaggcctc ttggcccagg
    gactgcaggg aggatgaagt caggagcaga
    58261 agcatggggt agggggctca ggtgggcaga
    ggaggcccct ctgtgaggag gaacggcaag
    58321 cgaggaggga acaggggcac cggcagtgcc
    tggcaagctg ggtgatgtca cgactacgtc
    58381 ccgaccacac agtcctctca gccagcccga
    gaagcagggc cctcccctga cccccatctg
    58441 ggcctgggct tcagttttct cctccctgca
    atggggtgac tgtttgcctc caggagaggg
    58501 gagcatgtaa aggtggccac tctcttctgg
    cagacatgcc aggcctgggc cagcctccac
    58561 ccctttgctc ctgcagcccc tgctgacctg
    ctcctgtttg ccacaccggc ccctcctggg
    58621 ctgatcaggg cccccctcct gcaggaagcc
    ctctgggaca agcccagctt gctgtaactg
    58681 tggctttcca ctgtgacctg caacgtggga
    ggctgttact taaaactccc atgactggtg
    58741 gattgccggt ccccagaaca aggccacgca
    tccctggagg ccctcgagac catttaaggt
    58801 agttaaacat ttttacttta tgcattttca
    tgtgtatcag aaagaaaaaa aatgtatcat
    58861 cagttcatca aatccatgat ttcttgacca
    atattgctaa gatgaggctg aaataggcat
    58921 ttccattttt aaaaaactga atcactctga
    agaaacagat ggcaggcttc cctggtggtc
    58981 cggtggttaa cagtccatgc ttccagtgct
    gggggcatgg gttcgatccc tgaaaatttt
    59041 aaaaaggaag aaaaagatgg ctcccccgtc
    cctgggattc tccaggcaag aacactggag
    59101 tgggttgcca tttccttctc cagtgcatga
    aagggaaaag ggaaagtgaa gtcgctcagt
    59161 cgtgtgcgac tcttagcaac cccatggact
    gcagcctacc agactcctcc gtccatggga
    59221 ttttccaggc aagagtactg gagtggggtg
    ccattgcctt ctccaggcaa acggcctgct
    59281 actgctactg ctgctaaatc gcttcagtcg
    tgtccaactc tgtgcgaccc catagacggc
    59341 agcccaccag gctcccccgt ccctgggatt
    ctccaggcaa gaacactgga gtggggtgcc
    59401 attgccttca gcctgctgct gctgctgcta
    agtcgcttca gtcgtgtccg actctgtgtg
    59461 accgcataga cggcagccca ccaggctccc
    ccgtccctgg gattctccag gcaagaacac
    59521 tggagtgggt tgccatttcc ttctccaatg
    catgaaagtg aaaagttaaa gtgaaattgc
    59581 tcagtcgtgt ccgactctta gtgacccaat
    ggactgcagc ctaccagggt cctccatcca
    59641 tgggattttc caggcaagag tactggagtg
    gggtgccatt cggcctaggg agtgagaaat
    59701 cacggctgtc ttccctcttc tcgccctcta
    ggggtctctg tggagcctcc ctggagaggc
    59761 cgcggcggct ccggggactg gagggggagg
    gggggttgag tcagccggtg gccctcccct
    59821 cgctgcccgt ctcctccctt tttaggcaca
    agctgggcgc cctttttagg cgcagcctca
    59881 ccctgcgggc cactgcccgt gtttcggctc
    cccggagata aaacagattg cctgcacccc
    59941 gggtcatcac aaggattgta tgaccgtttc
    ccagtgtgct caccaccctc cctctgattc
    60001 tcagagacgc gccctcgcct caggaggctg
    ctcatcccag gccaaggggc ggcgtggggt
    60061 ccccagcgcc ccgcacagac actgccttct
    gaccacctcc tcccaacagc ttacctgcca
    60121 agaaggcctc ctgacccctc atcctgcccg
    gtggtttgga gaaagcctca tctggcccct
    60181 ccttctcggg gcctcagttt ccccctctgt
    gaactggcgg attctgccaa gctgacgtcc
    60241 tggccagccg cctccccgtg gccagtgtcc
    cccgggacac agctgaatgt ccctgctcgg
    60301 gatgcacctt cccaagttgg cctgtcagga
    ggcgggggcg agcagggaaa cccgactcct
    60361 ctcagacggc ccatcgcatt ggggacgctg
    aggcccggag cagcggcacc ctcctggcca
    60421 gggtcattct cccgccccgc cccgtccctc
    cgggcctccg agaccgcagc ccggcccgcc
    60481 ccgggaagga ccggatccgc gggccgggcc
    accccccttc cctggccgcg ggcgcggggc
    60541 gagtgcagaa caaaagcggg gggcggggcc
    ggggcggggg cggggcggag gatataaggg
    60601 gcggcggccg gcggcacccc agcaggccct
    gcacccccgg gggggatggc tcgggccgcc
    60661 ggcctccgcg gggcggcctc gcgcgccttt
    ttgtttttgg tgagggtgat gggggcggtc
    60721 gcggggtact attttttcat ttataattgg
    gtattagcta gcgagtggaa ccacaccctt
    60781 attccactat agccaatttt tgcgggggca
    tcttacatta cagactcgcc cgcctcttat
    60841 ttcggtacag catatcagat cgtctcttta
    ctcagacact agtgattatt gtctatagta
    60901 cacaaaaaga acggttgtgt cggcgtaatg
    gttgcatttt ccctcctcgt ttctcctgac
    60961 cacctcaatt acaccaacac tctactattt
    aaatcacgta ttgtacgcca ccctccgccc
    61021 gcgaactaaa agaatgtgca gatattctga
    agataaaatc gttcattgtt acgccccgcg
    61081 cgcttcgcgt atattactct tagaacttct
    tattcgcccg agcagttatt caccccccgc
    61141 aactagatgt cgccttaata tttgttctaa
    ccgttttgga ttctaacgat aggcgggaaa
    61201 ggtagacatt cgaccgctac gacaactaaa
    atcgacgagc acaggctatt tatatcgcga
    61261 ccacacgcgc gcggtataca naccgtaaaa
    ttatctaaca tcgagagtaa gggcacagag
    61321 cgaaatacaa gcggcgtggt gggaggtgtg
    tctgtagtga attcgcacct cgcgccgccg
    61381 cctctgtgcg tcgnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    61441 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnngatataa
    61501 tattaataaa cagcggatag atgtgtgtaa
    gggaggaggt gcataagaga ttaaagagag
    61561 gcgggcggag agaaatagag tagaggagga
    tgagagaaaa aagaaagcaa gcgtaggtac
    61621 aacggcgggt gggtagtatg ataaagtgag
    tgtatatatt tgagtaaagg aagggtagat
    61681 ggagtataaa gaagtaagga gaggagaggg
    cggcggagag agagagtgca aagaaaataa
    61741 gtgggcaaag gcggggtggg tgagaagcag
    tagaagagaa gatagagaag ggggaaaaag
    61801 aggaaaatga ggattagaac aagtaggaca
    ggatagatgt gaaaaatgag atcaggtcaa
    61861 ggtggagaaa aagtagaaac tggggcgtga
    ttgtaaaaaa gggaggccgc gatggggcag
    61921 caccataagc gaagagatga attaatgaaa
    gcaaggcagg gagaatcaaa tgagttgggt
    61981 ggaggaagga ggctgtgact tccttcgctg
    ccggaaagag aactagaata gcctcgggct
    62041 gtggggggag gtaaagataa agtgacttct
    gggccctggg ggaggcccag gagtttctac
    62101 cgagctgagc tgggtgcctc tcccaaatgc
    ccaaccccct gagagtcgac gggagagcac
    62161 agcctggcca aacctgggca gggcacacgt
    gtccttcacc ccacagtggt cacgagccca
    62221 gcgtggtccc tgcgtctggc gggaaacaca
    gaccctcaca ccccacacaa gggtccggcc
    62281 gctttcaaat aacagcagcc gtgccctctg
    ggccggtgac ccggacacag agagatgaag
    62341 tccgcatctc tcagagtgcg ctgtcctccg
    cccggtcagg cccgggtccc ctgcttctct
    62401 gaggtcacca ggagggattg catgtgggtc
    tcagggacac aggttcagtg atgtgacaga
    62461 gggtagtggg tcccagcagg gccggtcttt
    ggacccgttt ttctgaaaag ccagttggcg
    62521 acctggggtc acagcaaagc tgatcctgtt
    tggccaggag tctcccagtg acggcctccc
    62581 ccagaacatc gggcccagtg ggggctccag
    ggggtagact tgcctcccag ctcacgcccg
    62641 tgtcttgaca agtccatgat ttggtaaaat
    taatttgtgt tggatggagt tgatttagtg
    62701 gtgtgtgagt ttctgtggcg cagcaaagtc
    aatcagttac gcatacacat gtatccagct
    62761 cttcctacga ttctgttccc atataggtca
    ttatggggtg tcaggtagag cttcctgtgc
    62821 tacgcagtac ggccttattc agttcagctc
    agtcgtgtcc gactccttgt gaccccatgg
    62881 actgcagcac gccaggctcc cctgtccatc
    accaactcct ggagcttatt caaactcatg
    62941 tccatcgagc cggtgatgcc atccaaccat
    ctcatcctct gtcgttccct ctcctcctgc
    63001 cttcagtctt tcccagcacc ccctagagaa
    gggaatggca aaccacttcg gtattcttgc
    63061 cctgagaacc ccatgaacag tacggaaagt
    ccttattagt tttctatttt atatatagca
    63121 gtgcacacgt gtcagcccca atctcgcaat
    ttatcacccc cctccgccgc cgattggtag
    63181 tcatgtttgt tttctacatc tgcgactcta
    tttctgtttt gtaaacaagt tcatttacac
    63241 cactttttta gattctgcac atacgtggca
    agcccacagc aaacatgctc aatggtgaaa
    63301 gactgaaagc atttcctcta agatcaaaaa
    caagacgagg atgtccactc actccgtttt
    63361 tactcaacac agccctgaac gtcctagcca
    tggcaatcag agaagagaaa gaaattaagg
    63421 aatccaaatt ggaaaagaag aagtaaaact
    cactctttgc aaatgacatg acacttatac
    63481 ccagaaaatc ctagagatgc taccagataa
    ctattagagc tcatcagtga atttgttgca
    63541 ggatacaaaa ttaatacaca gaaatctcct
    gcattcctat agactgacaa caaaagatct
    63601 gagagagaaa ttaaggaaac catcccacgg
    catgaaaaag agtaaaatac ctaggaataa
    63661 agctacctaa agaggcaaaa gacctgtact
    cagaaaacta taaaatactg acaaaggaaa
    63721 tcagacgaca cagagagaga gagataccac
    gctcttggat gagaagaatc gatagtgtga
    63781 caatgactat actacccaga gaaacataca
    gattcagtac aacccctatc aaattcccaa
    63841 tggcattttt cacagaatca gaattagaac
    aaaaagtttt acaagtttca gggaaacaag
    63901 aaagatccta aagagccaga gcaatcttga
    gaaagaaaaa tggagctgga agagtcaggc
    63961 tccctgagtt ctgactgtgt atacaaagct
    ggcatgattt ttaacagcag gggtgtaaat
    64021 gaacttgttc acaaaacaga tggtggggtg
    ggcttccctg gtggctcagc tggtaaagaa
    64081 tcctcctgca acgcaggaga cctgggttcg
    atccctaggc tgggaagatc ccctggagaa
    64141 gggaaaggct acccactcca gtattctggc
    ctggaaaatt ccaaggacca tatagtccat
    64201 gggtttgcaa agagtcggac acgactgagc
    gacttccaat cctggaaacg tcccattgtg
    64261 gacggtgaac tggggttgtc caagctcagg
    gtaaccgttt gctgagtgac tgacactcct
    64321 tctcatgggt taaaatgtgg ggcccaaggc
    caggaccaga ccccgcagtc agccaggcag
    64381 accctgtgca gccccagcga gtgtgtggcc
    gccgtggagt tcctggcccc catgggcctc
    64441 gactggagcc cctggagtga gcccattccc
    tcccagcccg tgagaggctg ggtgcagccc
    64501 taaccatttc ccacccagtg acagatccgc
    ctgtgtggaa acctgctctt gtccccaggg
    64561 aacctggcag gactcaggga gaatgtctca
    gggcggccac agatcagggg ctgggggggc
    64621 agggctgggt ccagcagagg ccctgtgccc
    actccccgga aagagcagct gatggtcagc
    64681 atgacccacc agggcaccga cgcgtgcttg
    cacacaggcc gccccctcat ggtgacactc
    64741 ttttcctgtg gccacatctc gccccctcag
    gtccctcctg ctccccagct cctggcctgg
    64801 gaacctcttc cccgccccgg ggacgtcagg
    gctggtgtcc actgagcatc ccatgcccgg
    64861 gactgtgctg atcaccagca cctgcacccc
    ctctcgggtc tcaccaggat gggcaactcc
    64921 tgcccatcca gcacccagcc tcctgggtac
    acatcggggg aggagggaga agcctgggcc
    64981 agacccccag tgggctccct aaggaggaca
    gaaaggctgc cgtgggccag ccgagagcag
    65041 ctctctgaga gacgtgggac cccagaccac
    ctgtgagcca cccgcagtgt ctctgctcac
    65101 acgggccacc agcccagcac tagtgtggac
    gagggtgagt gggtgaggcc caggtgcacc
    65161 agggcaagtg ggtgaggccc gagtggacag
    ggtgagtggg tgaggcccag gtagaccagg
    65221 gcccatgtgg gtgaggcccg ggtggaccag
    agtgagcggg tgaggcccag gtggacaggg
    65281 cgagcgggtg aggcccaggt ggacagggcg
    agcgggtgag gcccgggtgg acagggcgag
    65341 cgggtgaggc ccgggtggac agggcgagcg
    ggtgaggccc gggtggacag ggcgagtggg
    65401 tgaggcccgg gtggaccagg gcgagtgggt
    gaggcccggg tggacagggc gagtgggtga
    65461 ggcccgggtg gaccagggcg agtgggtgag
    gcccaggtgg acagggtgag tgggtgaggc
    65521 ccaggtagac cagggcccag agcaaagccc
    cggctcagca gtgatttcct gagcgcccac
    65581 tgcttgcagg gacctcagcg atggtaaggc
    agccctgttg ggggctcccg actggggaca
    65641 gcatgcagag agcgagtggt cccctggaga
    aacagccagg gcatggccgg gcgccctgcc
    65701 aggctgcccc aggggccaca gctgagcccc
    gaggcggcca ggggccggga cagccctgat
    65761 tctgggttgg gggctggggg ccagagtgcc
    ctctgtgcag ctgggccggt gacagtggcg
    65821 cctcgctccc tgggggcccg ggagggacgg
    tcaggtggaa aatggacgtt tgcgggtctc
    65881 tggggttgac agttgtcgcc attggcactg
    ggctgttggg gcccagcagc ctcaggccag
    65941 cacccccggg gctccccacg ggccccgcac
    cctcacccca cgcagctggc ctggcgaaac
    66001 caagaggccc tgacgcccga aatagccagg
    aaaccccgac cgaccgccca gccctggcag
    66061 caggtgcctc cctctccccg gggtgggggg
    aggggttgct ccagttctgg aagcttccac
    66121 cagcccagct ggagaaaggc ccacatccca
    gcacccaggc cgcccaggcc cctgtgtcca
    66181 ggcctggccg cctgagacca cgtccgtcag
    aagcggcatc tcttatccca cgatcctgtg
    66241 tctgggatcc tggaggtcat ggcccctctc
    ggggccccag gagcccatct aagtgccagg
    66301 ctcagagctg aggctgccgc gggacacaga
    ggagctgggg ctggcctagg gcaccgcggt
    66361 cacacttccc ctgccgcccc tcacttggga
    ctctttgcgg ggagggactg agccaagtat
    66421 ggggatgggg agaaaaatgg ggaccctcac
    gatcactgcc ctgggagccc tggtgcgtct
    66481 ggagtaacaa tgcggtgact cgaagcacag
    ctgttcccca cgaggcctca cagggtcctt
    66541 ctccagggga cgggacctca gatggccagt
    cactcatcca ttccccacga ggcctcacag
    66601 ggtccttctc caggggacgg gacctcagat
    ggccagtcac tcatccattc cccatgaggt
    66661 ctcacagggt ccttctccag gggacgggac
    ctcagatggc cagtcactca tccattcccc
    66721 acgaggcctc acagggtcct tctccagggg
    acgggacccc agatgggcca gtcactcatc
    66781 catccgtctg tgcacccatc cgtccaacca
    tcacccttcc ctccatccat ctgaaagctt
    66841 ccctgaggcc tccccgggga cccagcctgc
    atgcggccct cagctgctca tcccaggcca
    66901 gtcaggcccg gcacagtcaa ggccaaagtc
    agacctggaa ggtgcctgct tcaccacggg
    66961 aggagggggg ctgtggacac agggcgcccc
    atgccctgcc cagcctgccc cccgtgctcg
    67021 gccgagatgc tgagggcaac gggggggcag
    gaggtgggac agacaggcca gcgtgggggg
    67081 ccagctgccg cctggctgcg ggtgagcaga
    ctgcccccct caccccaggt acaggtctcc
    67141 ctgatgtccc ctgccctccc tgcctccctg
    tccggctcca atcagagagg tcccggcatt
    67201 ccagggctcc gtggtcctca tgggaataaa
    aggtggggaa caagtacccg gcacgctctc
    67261 ctgagcccac ccccaaacac acacaaaaaa
    atccctccac cggtgggact tcaccagctc
    67321 gttctcaggg gagctgccag ggggtccccc
    agccccagga agccaggggc caggcctgca
    67381 agtccacagc cataacacca tgtcagctga
    cacagagaga cagtgtctgg tggacaggtg
    67441 cccccacctg cgagcctgga gagtgtggcc
    ctcgcctgcc ccagccgcgg tcagtcggct
    67501 cagcaaccgc tgtccactcc cagcgccctg
    gcctcccctg tgggcccagg tcaagtcctg
    67561 ggggtgaagc taagtcaggg agcctcatcc
    atgcccagcc cggagcccac agcgccatca
    67621 agaaatgctt cttccctcca tcaggaaaca
    ttagtgggaa agacaagagc tggggggttc
    67681 tggggtcctg ggggatcaga tgaaggggtc
    tgggagcagc agcagcctca ggcaccccaa
    67741 aacaaggccc aggagctgga ctcccagggc
    tgaggggcag agggaaggaa ggcctcctgg
    67801 ggggttggca tgagcaaagg cacccaggtg
    ggggctgagc acccctcggc tggcacacac
    67861 aggcccccac tgcagtacct tccccctcgg
    agaccctggg ctcccgtctc ccgcctggcc
    67921 tgccatcctg ctcaccaccc agaaatccct
    gagtgcggtg ccatgtgact gggccctgcc
    67981 ctggggagga aggagattca gacagacagg
    atgccagggc agagaggggc gagcagagga
    68041 tgctgggagg gggcccgggg aggcctgggg
    ggcagggggg caggagttct ccagggtgga
    68101 cggcgctgtg ctatgctcgg tgagcacaga
    ggccccgggt gtcccaggcc tgggaaccca
    68161 gcagaggggc agggacgggg ctcaaaggac
    ccaaaggccg agccctgacc agacctgtgg
    68221 gtccagaagg cagctgcgcc ctgaggccac
    tgagtggccc cgtgtcccga accaccgctg
    68281 aaacatggga cacacgttcc caggcggagc
    cactcctgcc ttccgggagg ctcccagcgg
    68341 gctcatcgct ccatcccaca gggagggaaa
    ccgaggccca gatgacgaac atcccggcga
    68401 gcaggtcaaa gccagcccct ggggtcccct
    ctcccggcct ggggcctccc ctctgcaggg
    68461 tgggaaaccg aggccacaca ggggctccat
    ggggctgccc tctgccaggc cctggacacc
    68521 ccgcgggtga cccccgcctc tatcatccca
    gccctgccag gccctggaca ccccgtggat
    68581 gacccccgcc tctatcatcc cagccctggg
    ggacagatgg gaggcccaag cgtggacccc
    68641 ctggccaccc cctaccccac agccgggagg
    agccgggagc tggtggccaa gggcctagag
    68701 gagccagann nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    68761 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnca atatagaggg
    68821 ggtgggataa agggtaatat gatgtttagg
    tagttagagt taaattagaa gggtttggat
    68881 aaagattaat aaaattacaa gcgtacatat
    cgtgtgagtg tgggtgataa tatttgtgta
    68941 tgtggggaat agaagtgagt gtgagtagta
    ttcaagatgt aagtgtgcga atacaggtct
    69001 gagcgatttg aatggaagtg aaaaaaagcg
    tgtgtgtgga ggaggcggga gaggaagata
    69061 gtgtggggga agaaaagaag gctagtgggt
    aaagaaatat cagtaggcgg ttgacgaaag
    69121 aagaactagg aagaattaat ataaaaataa
    agggaggatt aaaaaataaa gagggaggag
    69181 gtaacggaaa tagttagtta agaaaagaat
    ggagagtgga ggtaagataa ataagggagt
    69241 aatgggagtg aggaggaata aataaaaaaa
    tggtgaggga aaatagagta gaatgagaac
    69301 aagaatgaaa aagggagtga agggggtgaa
    aaaaagtgaa gttgaaaaaa gaggaaaaaa
    69361 aaggagaaga taaaaaaata aaataaaaaa
    aggaaaaaaa agaaaaaaag aaagaagggt
    69421 taaaggacga aaagaaggga agagaaaaaa
    aatagtttaa gtgggggagg gtaaaaaaga
    69481 attaataaag taaatatggt tgtggtcgaa
    aaaaaaaaaa aaattgttgt gttgatgaga
    69541 agaaaagaaa aaagaagaaa gggaaaagca
    aaaagaaagg agagaaaaag acaaccccac
    69601 cgcccgggcg catggagggt gaggatggcg
    cacgcccgcg gatggcacag catcacagca
    69661 atcctaaaac gttttcagac cggtgcatct
    tcaccgcgcg cgcgccccgc ccggccctcc
    69721 tcccgccctg accgcggacc cccacccgca
    ccggggagcc tacccccacc ccggggacgc
    69781 tccgccacgc taaggtcagg actgccgtga
    agacgcgccg gggtgaaaac gttttatctt
    69841 catgacataa gcgagtggtt ttgaaacagg
    tttacaaacc ctcgtgaaga cgcaccctta
    69901 gcgttaggtt ttgttttttt accatgtgac
    gatgcaacta ttttcttcct ctcttccaca
    69961 gtggctagtc gcctccagag cgaggggtat
    ctcttgtaca gagaccctcg gaacatccgg
    70021 aggtagtttc ccacctaggg gtaaagcgag
    aaggctcatt acgagggccg gggctcctcg
    70081 gggaagggca gggccctggc gcagaggctc
    tgccacctca gtgacacgca gaccacgcgc
    70141 ggcctgcagg cgccgggctc tgaaagcagg
    caaagcccga tctgctgaca tcaggggttc
    70201 cgcagcagcg aaggtctggc ccgcacctgg
    cccactggca gggggtaagc tctgcctccc
    70261 gacgacagca ccaagttcag gaagggccac
    gcagacactg gtgagacacg gcccccccgg
    70321 agctgcccga gaagctctga ctttgcacta
    aagatctctg gcgcggtcca aaaatgtaag
    70381 gcctctcttc cttttatctt aagactttga
    tatttttacg atgtaataaa taccaagaag
    70441 ggcttttaat ttcagacaga tgtaggataa
    tttcccccgt agcccttgct gctttgttta
    70501 gtaacgaaac tcaaaccaga aataccaaag
    gaattttcca aagagtttca aaagcgctta
    70561 tcagcaatca ctagactgct gcatacatca
    tcactgcccc aaacaatagc ctgcctgtgc
    70621 cagttactca aagtactact tacttgacga
    aaacaaatct agtcctaacg tttttacaaa
    70681 gaaactccac tcttccgcca acttttcaga
    aacaaccact cgatcacgtg gcaggggacc
    70741 gtggctggac tgggtgctgg ctccttctgt
    gaccaggcaa cactgccccc ttctcggcct
    70801 ccctacgcct cttgacaaat gttcatcagc
    tgtaaagttc accccacgag ggacccactt
    70861 ctgctatttc ccacgtacct accccattat
    aggagttttc tttgtgacag tttctgcatt
    70921 tttcatggat ttagaggttt acataatcag
    ggctgctgaa cagcatgaga gacgtggcca
    70981 caaggtccct cctgcacctt gccgcagggg
    cagggcgagt tatctggctt gagcgtggtt
    71041 accatcaggg ggtaaacaca gtttccagga
    cgtttttgac aagacactga cccggatgcc
    71101 cccactacca ccgtgcaggt cctgcaggcc
    tcccagcctc ccaggccctt cccgaggtcc
    71161 cttcggaact taggggactc ggtctgcccc
    cctgggtttt ccctgcacca gcttttgccc
    71221 cctctggacc caggtttccc aaatggaaaa
    cgaaggtgtg ggtatggaag ctccctgggc
    71281 tcctctcagc tgtgcctctg catggtgatg
    acggctgccc atcggggggg gcaggactgg
    71341 ggcagctgcg gacaccctcc caaggctgct
    acccccgagt ggtgtggggc gctgtgggca
    71401 cgctctgctc agcgcacctc ctggaaacca
    gcgcctgccg tctgcccggg gcaaccggcc
    71461 cgggagccaa gcaccactgc cgtcagagga
    gctgctggct gtgagtggac gccagtctag
    71521 ctctgaaccc tgcccaggcc tcctgaggtc
    tgaacattgt aaaatcaggc cccggacggc
    71581 aactgcctct ccctcctgcc gtctggtctc
    cataaactgc atctcaggac aaatcttctc
    71641 actcaccagg gctgaaacag aagactgcag
    ctatctttct caaatctaag gtgtgctaca
    71701 gggcaagtcg cagaaactgt ctggcctaag
    catctcatca gatgcctgag acaagagctg
    71761 tggacgccaa gctggagcca gagctcctcg
    cgttctgccc acctggcacc gcgttccacc
    71821 cagtaaacgc aggcttgatt ttcaaaagta
    ccaccgactc agagccaatg ctaaaccgac
    71881 cacttttcct gcccattaga ttgggtgaag
    gtttctttaa tcaatctgcc agtcaccaca
    71941 tgccgcctct gtgcccacag gctggcgaag
    acctttctga gctacggcat gtggcaggca
    72001 gcggcacctc tcttcagtac ggccagctgt
    caaggggagc gtttctgtga tgatgtgaaa
    72061 atacattgca tccggccccg tgtttcatga
    acacgggtga ggaaaggaaa cacacaaagt
    72121 tctgatgcga ctgacagcac gggtctcata
    actcaataca agtcagacaa accacaggga
    72181 gtcacaggga atcccaatag cctcatctag
    tgtgaccatc atgaggctta atttattcag
    72241 tgtattcaat cataaagagg gggaaaaatt
    gtaaaaaaaa aaaaaaagaa agagtgaaat
    72301 gtgtaatact gaaaactgtt gctaggagaa
    gcaagcattg gcgtttgtaa ctgctttgac
    72361 tccccaagac ccacactcgc ctcgctacaa
    aagggaggca ctgctgctca gtacttgcac
    72421 acccgaactg cggatttgta atttaaaaat
    gtgtgtgtgg acacagcaca agccagagac
    72481 tgccaaaggt tgagggacac tggaagaact
    taatatactt ggtgcatgct gccagtgaca
    72541 gtcagtcacc agctgattca atagagtgcc
    gaaaggtcac cttttaggta aggatgaagg
    72601 ggttctgggc tcgtttactt gcactaactc
    agagttagtc cgagatatcc gaagtgccag
    72661 gtgcctccca tttgctgatg gatctagctc
    agggacggct gggccctagc catccaaaaa
    72721 tcaagcattg ttctcccaac ctgtcttctc
    gctgataatg gaaggtcaga acgcccaccc
    72781 gcccacctca aagtcaaaga acaccaagcg
    ggtgagtccc cactaagctc ggtgtttcca
    72841 atcagcggtt tcaggattcc agctggggca
    atgagggagg gagcgtgcga gggatccaac
    72901 acctcgcccc gtgcgcagca agggataacc
    caacaccccg tttctgtacg tccggctgga
    72961 gttgtggaac tcagcgcgga cccggggcca
    ccgcgacccc cgggaccctg gccgcgcggc
    73021 gcatccccgc tgccgggaca cgggtaagcg
    tccccaaact gccggacgcg gggcggggcc
    73081 ttctccgcca cgccccgata ggccacgccc
    aaggacaagg atggtcgtgc ccagacggcc
    73141 ggggcgggnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    73201 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnncg gagggggggg
    73261 ggcggggcgg gggctgccgc cgcgcgtata
    ggacggtggt cgcccggcct ggggtccggc
    73321 cgggaatgac cccgcctctc cccgcatccc
    gcagccgccc cgccgcgccc tctgccgcgc
    73381 acccgcctgc gcacccgccg ccctcggccg
    cggccccggc ccccgccccg tcgggccagc
    73441 ccggcctgat ggcgcagatg gcgaccaccg
    ccgccggagt ggccgtgggc tcggctgtgg
    73501 gccacgtcgt gggcagcgct ctgaccggag
    ccttcagtgg ggggagctca gagcccgccc
    73561 agcctgcggc ccagcaggtg agcaagggct
    caggggaaac tgaggcccga cacagagccg
    73621 cagcaagaag gatcctactg gtcactcggc
    tgttggcctg gggtcatcac aggcgggctc
    73681 tcccaaccca tcccctgagg ccaaggtccc
    tagaaccccg tgggcagaca ccaaccagcc
    73741 ctttaaatat ggggaaacca aggtgcttag
    gggtcagaga tagccctagg tcgcccaacc
    73801 ctagtagaag ggagggctgt tggagttcct
    gagtgcccgc tctcccaccc cccgggaggc
    73861 cccttcctga gcccaagggt gactggtagt
    cagtgacttt gggcctgccg acctgtaccc
    73921 cactgggcac cccaccagtc ctgagccaca
    tttgggctta gtgacggggt cagggatcat
    73981 gaggatcaat gtggctgagc caggaaggtg
    ttagaacctg tcggcctgga gttcatacca
    74041 gcactgccct gggcttttct agacccatgt
    cccgcctcct gccccacctg cccctgttcc
    74101 cgcaccccac cagcagcggc aggggcttcg
    agagggctgt gggctcaccc tatttcaggg
    74161 atggagccgc taagacctgg ggcacactgc
    ccgctaggga cccctgaggc accagggccg
    74221 ggggctctgc ggaggggcag ccgccacccc
    cagctttgga gtcctctccc gggtgcccag
    74281 cccgagctga tccggctgcc tcccacgctg
    tgccccaggg cccggagcgc gccgccccgc
    74341 agcccctgca gatggggccc tgtgcctatg
    agatcaggca gttcctggac tgctccacca
    74401 cccagagcga cctgaccctg tgtgagggct
    tcagcgaggc cctgaagcag tgcaagtaca
    74461 accacggtga gcggctgctg cccgactggc
    gccagggtgg gaagggcggt ccacggctcc
    74521 cactccttcg gggtgctccc gctattccca
    ggtgctcctg cacttcccat gtgctcccga
    74581 ttctccctgg tgctccctct cctcctggct
    gctcctttgc ctcccaggtg ctcccacttc
    74641 tccctggtgc tcctgctcct cccggcggct
    cctgtacctt cggcctgacc tcctccctct
    74701 acaggtctga gctccctgcc ctaagagacc
    agagcagatt gggtggccag ccctgcaccc
    74761 acctgcaccc ccctcccacc gacagccgga
    ccatgacgtc agattgtacc caccgagctg
    74821 ggacccagag tgaggagggg gtccctcacc
    ccacagatga cctgagatga aaacgtgcaa
    74881 ttaaaagcct ttattttagc cgaacctgct
    gtgtctcctc ttgttggact gtctgcgggg
    74941 ggcggggggg agggagatgg aagtcccact
    gcggggtggg gtgccacccc ttcagctgct
    75001 gccccctgtg gggagggtga ccttgtcatc
    ctgcgtaatc cgacgggcag cgcagaccgg
    75061 atggtgaggc actaactgct gacctcaagc
    ctcaagggcg tccgactccg gccagctgga
    75121 gaccctggag gagcgtgccg cctccttctc
    gtctctgggg gcccctcggt ggcctcacgc
    75181 tctgtcggtc accttgcccc tcttgctgat
    gcaatttccc cgtaattgca gattcagcag
    75241 gaggaatgct tcgggccttt gcacctgacc
    gcatgagcag aggtcacggc cagccccctt
    75301 ggatctcagt ccagctcggc cgcttggccg
    tgacgttcca ggtcacaggg cctgccggca
    75361 cagaggagca ggcccttcag tgccgtcgag
    cactcggagc tgctgcctcc gctgagttca
    75421 ctcagtgtct acgcacagag cgcccactgt
    gtaccaggcc ctattccacg ttccccagtc
    75481 accgagcccc cagggctggt ggggacctgc
    cctcgggtac actgtgtccc gtcacgtggc
    75541 tttacgtgtg tctctgaggg aggctggcat
    tgcggtccac ctctcagcac aaacatctgt
    75601 cccctgggaa gggggtccca tttctgggtg
    cgagcagccc cctggggtcc gtgtctcctc
    75661 cttacctggc tcaaggcccc ggctcctggg
    tcctggacag cagggagccc acccctcggg
    75721 gctgtggagg gggaccttgc ttctggaggc
    cacgccgagg gcccaggcgc cgcctccggc
    75781 cgtcgccctg agggagcagg cccgacgcca
    gcgcggctcc tctgtgaggc ccgggaaacc
    75841 ctgcctgagg gtgcgggtgg gcaggtgccc
    ctgcccccag gctctcctgt gtgagtgaca
    75901 ctcaccagcc agctctggat gccacccatc
    cgggttctcc aggaggcact catagcgggt
    75961 ggggtcccct ccctcccccc tctgtggagg
    gagggagtct gatcactggg aggctggtgg
    76021 tccgtacccg cccccccgac tctggacgtg
    tttactaccc ccgcctgggc tcaggacagg
    76081 gcattggatg ggaaggacag ggctgggtcc
    tggccaggct gggggctctg cagggcatgg
    76141 gtgcccctgt ctcttcttat attccaacgt
    cactgcaggg gggcgcaaat cttggacccc
    76201 acttactgat gatctgcatc aggacatagg
    tcccccctcc tgcagcgggg ggctggccac
    76261 ggagggcgct ggggaaggcc cctcctccag
    cccctcggcg aggctcacca ggtgcccatc
    76321 ctcagccagc agggcgacgc tcgctgggag
    ggcggagagg gaggcagggc agggctggta
    76381 cgacccccgc tggggcgggg gggccctcag
    ccggtcctcc agcacccttg ctgccccccc
    76441 tcaccgtcag ggggcacctg gccgctctgc
    ctcaggtggg cggtgagggt cccaaggcca
    76501 caccaggtgt tcaccagctc ccagcagctg
    gctgtgggag aggggcagag gtgggcgcat
    76561 ggcacccgcc ttccccccag accaggatgc
    tctgccttcc tcccgcccat ctccccagac
    76621 atctgaagga ctcttgcctc caccatgcag
    ccccgcctcc accagaagct caggttcccc
    76681 gccccccctc cccgaagctg caggacccct
    gaccagcgaa gagatgggac agttggaaca
    76741 cacgctcccc cagcagcggc acagcagctg
    tgtggcccag aagagcccgc ctgtttccct
    76801 caagcaactc cccatggatg tcatcccatg
    gacaccccct tccccacacc gcctcctcgt
    76861 tctccccctc caaggcagag ggaacgcacc
    cccacctgtc tgctaggaca ggggacccca
    76921 cttacctccg aacatcacct tgataaacat
    ggccgtggtg gggacagatc cctccgaccc
    76981 ccaacttccg acctggggaa ggagctgggg
    tggagctcga ctgcagggtg gggccctgtg
    77041 ggaggtgtac gggtggagag ggtgatgggt
    gggtgggctc aagcggagct ccttgctcag
    77101 tccaggcggt ccctgcagct agtccaggat
    cctcagcctt ctccccctca ctggatcagg
    77161 gaagactgag gttccctccc ctgccccccc
    acccagcttc caagctggtc tctgtggcag
    77221 tgggagctgc caagaggtct gagcggccag
    tatccgggta acggggtttg tggagggtcc
    77281 gggcattccc ggtgcagggc tctagtgggg
    gctggagcct cgggcccaga gctgtccaga
    77341 gaccagtgcc ctcccaccgc cgccgcccgc
    aaggagagac agagctccca ggcggggagt
    77401 cggaggttcc tggaggggga gcatcctcaa
    ctctgcaggc ccccttccca ggcgcactcc
    77461 cggcctcccc gtcttctgtc ccctgctctt
    gttgaagtat gattggcata cagttcacag
    77521 ccactcttcg gagtgttctc cacactaagg
    atacagaaca tgtccctcgt ccccccaaac
    77581 tcccagccag gctgtcacga agagggaggc
    ggccgacggg gcagggcctt gcactcctgc
    77641 gtgtggggtc cacaggggtc gtccccgtgt
    cggtggcccc ttcctctcac gccaggaggg
    77701 tccccttgcc tggaggtgcc gtggatccgc
    tcgctgcctg ctctttgggt tgtttcccgc
    77761 atggggtgat gatgaagagg ccagtacaga
    cactcgccag caggtctctg ggtgaacagg
    77821 catttatttc tctttcctga gggcagatcc
    tgggagtggg gtgccggacc gtccggggag
    77881 agtatgcttc tgtttctaag aagctgccgt
    gttctccagt gtgctgcacc atgtcacggc
    77941 ccctctgtgc gtctggactc aggagacctc
    cttctcagcg gccctccccc ccaggtggtc
    78001 aggccatctg tgcccttctg ggggcagagc
    tcagcgccgg aggcgggagg aggcccagat
    78061 cccagcgcag cccaccagcg ttgctctgct
    tccctcggca ttcatagctg gagaaagggc
    78121 aaggagcacc ggctgaagcc ccacctggag
    gacgcacttc gatggcagca ggtgctcaga
    78181 ggtggccccg ggcagcattc cccagacgca
    caggccagtg ctttcttccc aggacaccac
    78241 tgtgtctggg gacccgagtc ctgcagcacg
    gtcgggagcg gctgtgccca gattccggcc
    78301 tgcacccttg gctccagcca ccacccctgt
    ttgtcaaggg gtttttgtct ttcgagccgc
    78361 cgaggaggga gtcttttgtc tgcagtgtca
    cagaagtgcc ataaagaggg gcccacagtg
    78421 ggagctttat aacattggtg cggagggctg
    taacaggtca gggaggcact tgagggagcc
    78481 ttctagggcg atggagatgt tctaaaattt
    ggtctgggta caggctacag agatgtgtgg
    78541 gtgtgtgtgt gtgtgtgtgt aaaaccctcg
    agccacacgt gtgaggtctg tgcatgtgac
    78601 cgtacacagg agacctcggt ggaaagcagc
    cacctgctct gactgcacct gtggatttcc
    78661 agctcctgcc ctcaggcggc cctgcggggc
    ccactggctg acggggagac ggcaccgccc
    78721 tcccccgctg tcagggtggg ggggctgacg
    atttgcatgt cgtgtcaggg tccagcggcc
    78781 tcccttgcgt ggaggtcccg aagcacctgg
    agcgccgccc gcagaacagc ggactcctgc
    78841 ctgcctccct gcctctggcc atggcctgcc
    cgcctctggc cctctttctg ctcggggccc
    78901 tcctggcagg tgagccctcc caaggcctgg
    ctcacctagg ggtgtgtaag acagcacggg
    78961 gctctagaag taaatcgcgg ggaagtaaat
    cgtagtgggc aggggggatg gtttccgaag
    79021 gggccctgag ggggacagga gacctggcct
    cagtttcccc actggtgagt gaccagatag
    79081 ccagggtacc tttggactct gactctgggg
    ggctctcaga gactggtctc ctactcagtt
    79141 tttcagaggg gaagctggtg tggccttgtc
    actgccctgc agggcctcag ggacaagcta
    79201 tccctgagga ggtctccagc agtcagtggc
    cggaggctga gccgatggat atagtaacag
    79261 cccaggcggc ctcttggggg tggtcagcct
    gtagccaggt tttggacgag ccgaagtgac
    79321 ctaagtgatg ggggtctgca gagcaaggga
    tgagggtggg cagcaggagg acccagagcc
    79381 caccagccca ccctctgaat tctggaccct
    tagctgcatg tggctccttg ggaagacggg
    79441 gcttaagggt tgcccgctct gtggcccaca
    cagtgctgat tccacagcac tggctgtgag
    79501 cttttgggag cagattctcc cggggagtct
    gacccaggct ttgtggggca ggggctggag
    79561 ggaaggggcc caggccagac ctgagtgtgt
    gtctctcagc ctcccagcca gccctgacca
    79621 agccagaagc actgctggtc ttcccaggac
    aagtggccca actgtcctgc acgatcagcc
    79681 cccattacgc catcgtcggg gacctcggcg
    tgtcctggta tcagcagcga gcaggcagcg
    79741 ccccccgcct gctcctctac taccgctcag
    aggagcacca acaccgggcc cccggcattc
    79801 cggaccgctt ctctgcagct gcggatgcag
    cccacaacac ctgcatcctg accatcagcc
    79861 ccgtgcagcc cgaagatgac gccgattatt
    actgctttgt gggtgactta ttctaggggt
    79921 gtgggatgag tgtcttccgt ctgcctgcca
    cttctactcc tgaccttggg accctctctc
    79981 tgagcctcag ttttcctcct ctgtgaaatg
    ggttaataac actcaccatg tcaacaataa
    80041 ctgctctgag ggttatgaga tccctgtggc
    tcggggtgtg ggggtaggga tggtcctggg
    80101 gattactgca gaagaggaag cacctgagac
    ccttggcgtg gggcccagcc tccccaccag
    80161 cccccagggg cccagactgg tggctcttgc
    cttcctgtga cgggaggagc tggagtgaga
    80221 gaaaaaggaa ccagcctttg ctggtcccgg
    ctctgcatgg ctggttgggt tccaacactc
    80281 aacgagggga ctggaccggg tcttcgggag
    cccctgccta ctcctgggtg gggcaagggg
    80341 gcaggtgtga gtgtgtgtgt ggggtgcaga
    cactcagagg cacctgaagg caggtgggca
    80401 gagggcaggg gaggcatggg cagcagccct
    cctggggtag agaggcaggc ttgccaccag
    80461 aagcagaact tagccctggg aggggggtgg
    gggggttgaa gaacacagct ctcttctctc
    80521 ccggttcctc taagaggcgc cacatgaaca
    gggggactac ccatcagatg nnnnnnnnnn
    80581 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    80641 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn
    agagggtggg tgggtggaat ttaatatagt
    80701 ggtgcgcgtg gagcgtgggc ggcgcattta
    aggcggtcat ctaaaatagt ggataggggg
    80761 tggtgtgaca ataacgggtg gtggatgtgg
    tttacggggg gtgcaatagt tctgagtftg
    80821 ttagtgtctt cttgatgggg ttgcggcgtg
    tggacctacg ccttgagtat gtgggggggg
    80881 aaaagcagtg agggtagtag ggatgggaaa
    tattggtgga ggttctttgt tggtgtattt
    80941 tttggtatta tgttgggtgg tggagtggtg
    ggttgggtgt aatttcgctt gcgttatgtg
    81001 ttttttttct ttttcgtgtc gtgggttggg
    ttggttggtg ctttgtggtg gtggtgggtt
    81061 gtggtataaa aaaaaatgtg tggttgtgct
    cagcttagcc ctataacggt cggctttgtt
    81121 tcttgtttgt tctgtgggcg tgagcggatg
    gctcgggcct ccgtgctccg cggcgcggcc
    81181 tcgcgcgccc tcctgctccc gctgctgctg
    ctgctgctgc tcccgccgcc gccgctgctg
    81241 ctggcccggg ccccgcggcc gccggtgagt
    gcccgccgtc ctccagcccc cccgccccgc
    81301 cccgccctcc acgccgaggg gcgccggctc
    gcagagctgg atccaagggg gtgcccggga
    81361 gtggcccggc gcggcccgtt accccgaaac
    gctgtctggg tgccccgggg gtgtggtgga
    81421 tagtgagctt cccgtccctg gaagtatgca
    agtgaagccg gcgccgggat cgctcgggct
    81481 ggctggtgag cgggcgggac tcggtcgggc
    gctagacgca cgccgccagc cccccagctc
    81541 ccagacctgc ccactccgcg cccgcccggc
    cgcgatcccg ggtgtgtgtg tgtgttgcag
    81601 gggagggaca gcgggagtgg ctacagggct
    cccgactcac cgcagggaca aagacccgcg
    81661 ggtccccagc tggcgtcagc cgccaggtgt
    gtggcctcgg tgagcacacc tccaggcggg
    81721 agggttgagg gaagcgctgt ggggagggca
    tgcggggtct gagcctggaa gagacggatg
    81781 ctaccgcctg ggacctgtga gtggcgggat
    tgggaggcta tggaatcagg aggcagccta
    81841 agcgtgagag ctccggtgtg gcctggcggg
    ggtggtaggg gggggacgcc cctgtgtgtg
    81901 ccagcctgcg tgtgccctaa aggctgcgcc
    ctcccccact gctggggctt cgggggacca
    81961 gtcacagcct aggctactgc aggcgcacag
    ctccccggga gcccggccca cgcgggtgtg
    82021 ccgctgagcc tccagcctgt cggggcaggg
    gtggggggca gggatggggt cgttagcggg
    82081 gttgggggca gacgcccagg cagactctct
    gggcacagct ccggtgacaa gggaggtctg
    82141 gcaagcctgg gccccttctg tccagccacg
    ccagctctgc cctggccagt cttgccccct
    82201 ggcagtgctg gggatggaag ggggagcggg
    tacctcagtc tgggggccct gcctcctccc
    82261 cagccccgcc cggcccccta ggcctagggg
    cagagtctag gggtcaccct ggggagctgc
    82321 tgaatccgcg ggtttaggaa ccggagggac
    ctgggctttt gaaccacgtg gccctaggtg
    82381 agccctccgg cgcctcggta gccctcaccc
    ccagccttgt ccaggtgggc gggtgggagg
    82441 cgacagtgcc cactgctggg ctgaacagcg
    tctgcaggga ggccaggaga gctgggcaca
    82501 cggacacgtt ccatcacctg gagctgccac
    tgtgccactt gtgcggggtc aggcggggtc
    82561 tgagccgggc tgtcatctgt cacgccacag
    atatgcaggg ggcactcggg gtcgcctcgg
    82621 acatgcttat ccctggacgg ctgttggcag
    ggccgggaag gctctgtaaa tatttatcca
    82681 tcccagctca cagctttcag ggttgatgaa
    agccccgccg cccgcccact gtgggggacc
    82741 ccgccttccc ttctggagcc agcggggtga
    gggggtgggg gagatggacc tgcctgccca
    82801 ggagcaggcg gtgtgactct ggcaggtcac
    ttgacctctc tgagcctcag ggagggcccg
    82861 ggatggtgtg cggatgctct ctgccttcct
    cccagcctga ccagtgtcct cccctcgggg
    82921 tcgcctcctg cccaccgcag agggggtggc
    tatggggacc tgggccgatg gcaggcaggc
    82981 cggagagggc atgcccggct cagccgtgcc
    cagcacttcc cagtccaggg gcccccgcca
    83041 ctcccagccg ctggctgcct cccattttcc
    cgattgcagg ttggccccga ggctgaccgg
    83101 agcctctggc tcagctggga gactgaattc
    cccaagcaat tcctcaagga tgtgtgaggc
    83161 tgtggtgtgg tgcctatccg ggagaggtgg
    ggtgagcgga ctgggcacct ccgcccaggg
    83221 caggcccagg gagacgctgg ctgacgagca
    ggcaggcctg caaggaggac gagcagccat
    83281 ctcaggaatg tgggttttgg agacaagcca
    cagctggggg ggtggggggg ccatgggtgg
    83341 ggaggcctga tccccaggtc taggtccagc
    tctgggctcc ctcgccgtgt gaccctgggc
    83401 caagacctgg acctctctgg gccccgtctc
    ttcccctggg aggtggggcg atgcctgctc
    83461 cccaatcccc cagggctgtg gatgaggcag
    acgaggtgtg tgctcatccc cacctcactg
    83521 ccttccagca gccccgggcg gggggggtgg
    tggggactgg cgcacccagg tgaggatcag
    83581 gccttggagc tagggagggc cccccagccc
    caggccagaa aggacacggg gagacagaat
    83641 gcaggagggc ggcagagcag gggccagcgg
    tggggaaact gaggccaaga gcctgtggac
    83701 gatgtgctcc aggaaaggac ctcgctgcct
    ggggcctgga tcctagagcc tccaggagcg
    83761 gtgaccatga cgtgggcagg gaaccggagg
    ccccggcttg caggtggacc cggcgcgagt
    83821 cactcttcct ctctggccct gagagcttcc
    ttccagctgc cgctcctgtg ttctaatgtc
    83881 aagtctggag gcctgggggg caggtggggg
    ctgactgcca ggtgggggag ggcaggaatt
    83941 tggcagagca gcgtcccaga gtgggagaag
    ccagcccatg gaggggactc tctccatgcc
    84001 tgctgcccca aagggcgtta tagagagagg
    tcggttaccc cttcgccatg gccccgttcc
    84061 cattgaacag atgggaaagt ggaggctgag
    agaaggctgt gacttgccca gggtctccgt
    84121 ggcatggaac tgggcctgct gagtctcagg
    ccggggatct cgctgctgca ctgagcacgc
    84181 caggatgcag gggtctgggc ctggacctag
    cgcctcgtgg gggcaagaga ggaaggcacg
    84241 ctgggcctgc ctgtcaccct ccaccccacc
    gtggcttgtt gctcaggcct tcctgggggc
    84301 agaggagagg ggagatttca ctcgctggca
    ggctaggccc tgggctctct ggggctccgg
    84361 gggaacaatg cagccctggt ctttctgagg
    agggtccttg gacctccacc agggttgagg
    84421 aaaggatttc tgttcctcct ggaggtcacg
    gagccgacat ggggaggagc aggggcaggc
    84481 ccggggccca catcctcagt gtgagacctg
    gacgtgtgtc ctcccacctg acgctggggg
    84541 tggggggtgg gggccggggg ggatccagtg
    aaccctgccc ccaaattgtc tggaagacag
    84601 cgggtacttg gtcatttccc cttcctcctc
    ttcgtttgcc ctggtgggga cagtccctcc
    84661 cctggggaag ggggacccca gcctgaagaa
    cagagcagag ctggggtcag gggtgtgctg
    84721 ggagcgcaga gagcctcctg ctctgcctgc
    tggtcattcc tggtggctct ggagtcggca
    84781 gctggtgggg agcggctggg gtgctcgtct
    gagctctggg gtgcccaggg cctgggagag
    84841 ttgccagagg ctgaggccga gggtggggcc
    ctggcggccc ggctcctgcc ccaaatatgg
    84901 ctcgggaagg ccacagcggc actgagcaga
    caggccgggc cagacgggcg ctgaggctcc
    84961 cggcctctcc cccagctccg ctgtgaccct
    cacctgcggc ccggggtgcc agggcccccg
    85021 cttggttctg ccgtgtcttt gcaggctgat
    cccacgggct ctccctgcct ctctgagctt
    85081 ccgccttttc caggcagggg aaccgcgacc
    tccaggctgg gacgcgggga gggtgtatgc
    85141 gccaggtcag aatcacccct ccaccgggag
    agcgtggtcc aggggccctg gcagggtggg
    85201 gaccgagcat ctgggaactg ccagccaccc
    ccacccatgc agaggggaca tacagaccac
    85261 acggaggctg tgcctccgct gcagcaactg
    gagaacaccc agccgcggcc aaacataaat
    85321 aactaaataa taaaagtttt aaagatcgtt
    acttaaaaaa acaagtgtgc cccagtgatc
    85381 ggaccccagt tcccggtgcc ctgagtggtg
    ccggccctgt gctgagcatg gcctggttgg
    85441 ttcaccccca gatccacact aaagggtggg
    atcaccccta ctagtcaggt gagcagatgc
    85501 agggggggag ggcggcagcc cctccatgct
    ggtgggtggc cgtg