System for production of antibodies and their derivatives

Abstract

The present disclosure provides methods and compositions for the production of chimeric antibodies that specifically bind an antigen of interest.

Claims

1. A method for producing a chimeric immunoglobulin-G (IgG) antibody that specifically binds an antigen of interest comprising: a) isolating nucleic acid sequences encoding IgG heavy and light chain variable regions from a single immune cell producing an IgG that specifically binds the antigen of interest; b) cloning the light chain variable region nucleic acid sequences of part a) into the expression vector pVLentry-Hyg10, and cloning the heavy chain variable region nucleic acid sequences of part a) into an expression vector selected from the group consisting of pVHentry-Cm5, pVHentry-GFP1, pVHentry-MLuc7, pVHentry-Hisbio1, and pVHentry-CBD1; wherein the light chain variable region nucleic acid sequences are operably linked to nucleic acid sequences encoding a light chain constant region, and wherein the heavy chain variable region nucleic acid sequences are operably linked to nucleic acid sequences encoding a heavy chain constant region; c) combining the vectors used for part b) into a single vector comprising nucleic acid sequences encoding the IgG heavy and light chain variable regions; d) introducing the expression vector of part c) into a host cell; e) establishing one or more stable cell lines from the host cell of part d); and f) isolating the IgG produced by the one or more stable cell lines of part e).

2. The method of claim 1, wherein the antigen of interest is derived from a pathogen.

3. The method of claim 1, wherein the antigen of interest is a Clostridium botulinum neurotoxin.

4. The method of claim 1, wherein the one or more stable cell lines of part e) is established through expression of antibiotic resistance genes present in the expression vectors of part b) or part c).

5. The method of claim 4, wherein the level of expression of the antibiotic resistance genes by the one or more stable cell lines correlates to the level of IgG production by the cell lines.

6. The method of claim 1, wherein parts a) and b) comprise the steps of: i) reverse-transcription of mRNA released from the immune cell upon exposure to perfingolysin O; ii) simultaneous amplification of cDNAs produced in part i) encoding the IgG heavy chain variable region (VH) and the IgG light chain variable region (VL); iii) separate re-amplification of the VH and VL sequences of part ii), and iv) insertion of the re-amplified sequences of part iii) into the expression vectors of part b).

7. The method of claim 6, wherein the reverse transcription is performed using a primer selected from the group consisting of IgG-CHH, Cm1, and Clv-3.

8. The method of claim 6, wherein the simultaneous amplification is performed using primers selected from the group consisting of pVk-1, pVk-2, pVk-3, pVk-4, hIgGk-3, IgGH-1, IgGH-2, IgGH-3, IgGH-4, IgGH-5, IgG-CHH, M1, M2, M3, M4, Cm1, V11-5T7, V12-5T7, V13-5T7, V14-5T7, V15-5T7, and C1-3.

9. The method of claim 6, wherein the re-amplification is performed using primers selected from the group consisting of Vk-1/2-5T7, Vk-3-5T7, Vk-4-5T7, hIgGk-3, IgG-CH, Vh-1-3T7, Vh-1-3T75, Vh-1-5T7, Vh-2-5T7, Vh-3-5T7, Vh-4-5T7, Vh-5-5T7, Vh-6-5T7, Vh-7-5T7, Vh-8-5T7, Vh-1-3T75, Vm-1-5T7, Vm-2-5T7, Vm-3-5T7, Vh-1-3T75, V11-5T7, V12-5T7, V13-5T7, V14-5T7, V15-5T7, and hIgGl-3.

10. The method of claim 1, wherein the host cell is selected from the group consisting of a Chinese hamster ovary(CHO) cell, a human embryonic kidney (HEK), a mouse NS1/1-Ag 4-1 cell, a NSO/u cell, an X63/Ag 8.653 cell, an SP2/0 Ag14 cell, a rat Y3 (210.RCY3.Ag 1.2.3) cell, a YB213.0Ag3 (Y0) cell, and any other mammalian secondary cell line capable of producing immunoglobulins.

11. A method for producing a chimeric immunoglobulin-G (IgG) antibody that specifically binds an antigen of interest comprising: a) isolating nucleic acid sequences encoding IgG heavy and light chain variable regions from a single immune cell producing an IgG that specifically binds the antigen of interest; b) cloning the light chain variable region nucleic acid sequences of part a) into the expression vector pVLentry-Hyg10, and cloning the heavy chain variable region nucleic acid sequences of part a) into an expression vector selected from the group consisting of pVHentry-Cm5, pVHentry-GFP1, pVHentry-MLuc7, pVHentry-Hisbio1, and pVHentry-CBD1; wherein the light chain variable region nucleic acid sequences are operably linked to nucleic acid sequences encoding a light chain constant region, and wherein the heavy chain variable region nucleic acid sequences are operably linked to nucleic acid sequences encoding a heavy chain constant region; c) introducing the expression vectors of part b) into a host cell; d) establishing one or more stable cell lines from the host cell of part c); and e) isolating the IgG produced by the one or more stable cell lines of part d).

12. The method of claim 11, wherein the antigen of interest is derived from a pathogen.

13. The method of claim 11, wherein the antigen of interest is a Clostridium botulinum neurotoxin.

14. The method of claim 11, wherein the one or more stable cell lines of part d) is established through expression of antibiotic resistance genes present in the expression vectors of part b).

15. The method of claim 14, wherein the level of expression of the antibiotic resistance genes by the one or more stable cell lines correlates to the level of IgG production by the cell lines.

16. The method of claim 11, wherein parts a) and b) comprise the steps of: i) reverse-transcription of mRNA released from the immune cell upon exposure to perfingolysin O; ii) simultaneous amplification of cDNAs produced in part i) encoding the IgG heavy chain variable region (VH) and the IgG light chain variable region (VL); iii) separate re-amplification of the VH and VL sequences of part ii), and iv) insertion of the re-amplified sequences of part iii) into the expression vectors of part b).

17. The method of claim 16, wherein the reverse transcription is performed using a primer selected from the group consisting of IgG-CHH, Cm1, and Clv-3.

18. The method of claim 16, wherein the simultaneous amplification is performed using primers selected from the group consisting of pVk-1, pVk-2, pVk-3, pVk-4, hIgGk-3, IgGH-1, IgGH-2, IgGH-3, IgGH-4, IgGH-5, IgG-CHH, M1, M2, M3, M4, Cm1, V11-5T7, V12-5T7, V13-5T7, V14-5T7, V15-5T7, and C1-3.

19. The method of claim 16, wherein the re-amplification is performed using primers selected from the group consisting of Vk-1/2-5T7, Vk-3-5T7, Vk-4-5T7, hIgGk-3, IgG-CH, Vh-1-3T7, Vh-1-3T75, Vh-1-5T7, Vh-2-5T7, Vh-3-5T7, Vh-4-5T7, Vh-5-5T7, Vh-6-5T7, Vh-7-5T7, Vh-8-5T7, Vh-1-3T75, Vm-1-5T7, Vm-2-5T7, Vm-3-5T7, Vh-1-3T75, V11-5T7, V12-5T7, V13-5T7, V14-5T7, V15-5T7, and hIgGl-3.

20. The method of claim 11, wherein the host cell is selected from the group consisting of a Chinese hamster ovary(CHO) cell, a human embryonic kidney (HEK), a mouse NS1/1-Ag 4-1 cell, a NSO/u cell, an X63/Ag 8.653 cell, an SP2/0 Ag14 cell, a rat Y3 (210.RCY3.Ag 1.2.3) cell, a YB213.0Ag3 (Y0) cell, and any other mammalian secondary cell line capable of producing immunoglobulins.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows the structure of the pVLentry-Hyg10 and pVHentry-Cm5 vectors. Plac and Pampbacterial promoters; PCMV iethe immediate early promoter of CMV; IRESinternal ribosome entry site; SV40 poly A and HSV TK polyAtranscription terminators; fl ori and pUC oriphage and plasmid origins of replication; 10b, IGHG1, and lacZsequences encoding phage T7 protein 10b, constant part of human IgG and -peptide of -galactosidase, respectively; Ap(R), CM(R), Km(R) and Hygromycin-delEspsequences encoding resistance to antibiotics ampicillin, chloramphenicol, G418 and Hygromycin B (this sequence was modified to remove Esp3I site), respectively. Underlined are sequences of cohesive ends generated by Esp3I.

(2) FIG. 2 shows the assembly of IgG-encoding sequences using cohesive ends generated by DNA polymerase T4. DNApolT4 (dCTP)designates treatment with DNA polymerase T4 in the mixture containing only dCTP. Esp3I and ligasetwo additional types of treatments with endonuclease Esp3I and DNA ligase, respectively, that are required for assembly of IgG-encoding sequences. IG-V, IGHG1 and 10bsequences encoding variable and constant parts of IgG chain and protein 10b, respectively. FIG. 2 shows SEQ ID NOs: 92-95, 94, 96-97, in order of appearance.

(3) FIG. 3 shows the interaction of gfpBoNT/A-CH5 with its receptors on the surface of the neuroblastoma cell. gfpBONT/A-CH5 was added to SH-SY5Y cells and after 15 minutes cells were subject to microscopy.

(4) FIG. 4 shows the effect of antibiotic resistance selection on production of human IgG by CHO cells. Dilutions of media from the original IgG-producing culture and its derivative selected at higher concentrations of antibiotics were loaded into wells of a 96-well plate covered with BoNT/A-CH. Immobilized IgGs were visualized by treatment of wells with biotinylated anti-human antibodies followed by treatment with streptavidin-horse radish peroxidase and 1-STEP Slow TMB-ELISA (Pierce, Inc.).

(5) FIG. 5 shows the composition of proteins purified from cell culture media. Proteins were separated by SDS-PAGE and were either stained by Coomassie (right portion) or transferred onto a nitrocellulose membrane and treated with biotinylated anti-human IgG. Bound antibodies were visualized by treatment with streptavidin-horse radish peroxidase conjugate and 1-STEP Slow TMB-ELISA (Pierce, Inc.) and 1-STEP Ultra TMB (Pierce, Inc.). Line 1 contains pre-stained molecular weight markers from Fermentas, Inc.; 2protein purified from media of cells generated by transfection with plasmid encoding both chains of IgG; 3protein from cells transfected with plasmid encoding human IgG whose heavy chain is fused with GFP; 4protein from cells transfected with plasmid encoding human IgG whose heavy chain is fused with MLuc.

(6) FIG. 6 shows the interaction of purified human IgGs with receptor-recognizing domain of BoNT/A. Dilutions of IgGs purified from media of isolated cell cultures were loaded into wells of a 96-well plate covered with BoNT/A-CH5. Immobilized IgGs were visualized by treatment of wells with biotinylated anti-human antibodies followed by treatment with streptavidin-horse radish peroxidase and Metal Enhanced DAB Substrate Kit (Pierce, Inc.). The control line corresponds to the highest OD.sub.450 of wells that were treated the same way as others but did not contain BoNT/A-CH5.

DETAILED DESCRIPTION

(7) The present disclosure provides methods and compositions for robust generation of human monoclonal antibodies targeted at pathogens of interest.

(8) In addition to the set of products that address existing needs, this technology advances our understanding of structure-function relationships in the neurotoxin molecule and provides information about mechanisms of inactivation of this molecule by antibodies.

(9) In practicing the present disclosure, many conventional techniques in cell biology, molecular biology, protein biochemistry, immunology, and bacteriology are used. These techniques are well-known in the art and are provided in any number of available publications, including Current Protocols in Molecular Biology, Vols. I-III, Ausubel, Ed. (1997); Sambrook et al., Molecular Cloning: A Laboratory Manual, Second Ed. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989).

(10) Certain terms used herein are defined below. Unless defined otherwise, all technical and scientific terms used herein have the same general meaning as commonly understood by one skilled in the art.

(11) Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. As used in this specification and the appended claims, the singular forms a, an and the include plural referents unless the content clearly dictates otherwise. For example, reference to a cell includes a combination of two or more cells, and the like. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry, analytical chemistry and nucleic acid chemistry and hybridization described below are those well-known and commonly employed in the art. All references cited herein are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, or patent application were specifically and individually incorporated by reference in its entirety for all purposes.

(12) As used herein, about will be understood by persons of ordinary skill in the art and will vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used, about will mean up to plus or minus 10% of the particular term.

(13) As used herein, administration of a composition to a subject includes any route of delivering the compound to the subject to perform its intended function. Administration can be carried out by any suitable route including oral, intranasal, parenteral (intravenous, intramuscular, intraperitoneal, or subcutaneous), or topical. Administration includes self-administration and administration by another.

(14) As used herein, the terms antigen and antigenic refer to molecules with the capacity to be recognized by an antibody or otherwise act as a member of an antibody-ligand pair. Specific binding refers to the interaction of an antigen with the variable regions of immunoglobulin heavy and light chains. Antibody-antigen binding may occur in vivo or in vitro. The skilled artisan will understand that macromolecules, including proteins, nucleic acids, fatty acids, lipids, lipopolysaccharides and polysaccharides have the potential to act as an antigen. The skilled artisan will further understand that nucleic acids encoding a protein with the potential to act as an antibody ligand necessarily encodes an antigen. The artisan will further understand that antigens are not limited to full-length proteins, but can also include partial amino acid sequences. Moreover, sequences from different sources may be combined to generate mosaic antigens, depending on the specific intended use. In some embodiments, the mosaic antigen will include epitopes derived from different proteins. In some embodiments, the mosaic antigen will include epitopes derived from the same protein. The term antigenic is an adjectival reference to molecules having the properties of an antigen. In some embodiments, the antigen of interest is a bacterial toxin. In some embodiments the antigen of interest is a botulinum neurotoxin.

(15) As used herein, the term epitope refers to that portion of a molecule that forms a site specifically recognized by an antibody or immune cell. A protein epitope may comprise amino acid residues directly involved in antibody binding, as well as residues not directly involved in binding that are nonetheless included in the antibody-epitope footprint and excluded from the solvent surface. Epitopes may derive from a variety of physical characteristics of a protein, including primary, secondary, and tertiary amino acid structure, and amino acid/protein charge. Epitopes present within a molecule are referred to as real epitopes. Real epitopes encompass wild-type sequences and variants of wild-type sequences. Real epitopes may exist within a wild-type protein, a naturally occurring variant of a wild-type protein, or an engineered variant of a wild-type protein. The term mimetic epitope refers to a molecule whose primary structure is unrelated to the primary structure of a given real epitope that nonetheless specifically binds to antibodies that recognize the real epitope. Epitopes may be isolated, purified, or otherwise prepared by those skilled in the art. They may be obtained from natural sources including cells and tissues, or they may be isolated from host cells expressing a recombinant form of the epitope.

(16) As used herein, effective amount refers to a quantity sufficient to achieve a desired effect. In the context of therapeutic or prophylactic applications, the effective amount will depend on the type and severity of the condition at issue and on the characteristics of the individual subject, such as general health, age, sex, body weight, and tolerance to pharmaceutical compositions. In the context of an antigenic composition, in some embodiments, an effective amount is an amount sufficient to result in a protective response against a pathogen. In other embodiments, an effective amount of an antigenic composition is an amount sufficient to result in antibody generation against the antigen. With respect to antigenic compositions, in some embodiments, an effective amount will depend on the intended use, the degree of immunogenicity of a particular antigenic compound, and the health/responsiveness of the subject's immune system, in addition to the factors described above. The skilled artisan will be able to determine appropriate amounts depending on these and other factors. In the case of a biochemical application, in some embodiments, an effective amount will depend on the size and nature of the sample in question. It will also depend on the nature and sensitivity of the methods in use. The skilled artisan will be able to determine the effective amount based on these and other considerations.

(17) As used herein, the term polymer resin refers to resins, such as, but not limited to polysaccharide polymers such as agarose, cellulose, and Sepharose. The skilled artisan will understand that proteins may be covalently attached to the resin using methods well known in the art, including but not limited to cyanogen bromide activation, reductive animation of aldehydes, and the addition of iodoacetyl functional groups. The skilled artisan will further understand that functional equivalents of polysaccharide polymers may also be to immobilize proteins.

(18) As used herein, the term BoNT refers to any of the seven serologically distinct botulinum neurotoxins produced by Clostridium botulinum, Clostridium argentiensis, and Clostridium baratti. Individual serotypes are referred to as BoNT/A, BoNT/B, BoNT/C, BoNT/D, BoNT/E, BoNT/F, and BoNT/G. Exemplary, non-limiting nucleic acid sequences of BoNT/A, /B, /C, /D, /E, /F, and /G are found in GenBank Accession numbers DQ409059, FM865705, AB200364, NZ ACSJ01000015, AM695754, X81714, and X74162, respectively. Exemplary, non-limiting amino acid sequences of BoNT/A, /B, /C, /D, /E, /F, and /G are found in GenBank Accession numbers ABD65472, CAR97779, BAD90572, ZP 04863672, CAM91137, CAA57358, and CAA52275, respectively. Exemplary, non-limiting nucleic and amino acid sequences of C. tetani tetanus toxin are found in GenBank Accession numbers AF154828 and AAF73267, respectively. As used herein, the term BoNT/A-L refers to the full-length botulinum neurotoxin A light chain. As used herein, the term BoNT/B-L refers to the full-length botulinum neurotoxin B light chain.

(19) As used herein, the term anti-BoNT antibody refers to an antibody capable of specifically binding to BoNT. As used herein, an antibody includes a polyclonal antibody, a monoclonal antibody, and also refers to functional fragments (e.g., fragments which bind an antigen/epitope), such as Fv, Fab, Fc and CDRs.

(20) As used herein, the terms immunogen and immunogenic refer to molecules with the capacity to elicit an immune response. The response may involve antibody production or the activation of immune cells. The response may occur in vivo or in vitro. The skilled artisan will understand that a variety of macromolecule, including proteins, have the potential to be immunogenic. The skilled artisan will further understand that nucleic acids encoding a molecule capable of eliciting an immune response necessarily encodes an immunogen. The artisan will further understand that immunogens are not limited to full-length molecules, but may include partial amino acid sequences (e.g., epitopes). Moreover, sequences from different sources may be combined to generate mosaic immunogens, depending on the specific intended use.

(21) As used herein, the terms isolate and purify refer to processes of obtaining a biological substance that is substantially free of material and/or contaminants normally found in its natural environment (e.g., from the cells or tissues from which a protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized).

(22) As used herein, the term the terms polypeptide, peptide, and protein are used interchangeable to mean a polymer comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds (i.e., peptide isosteres). Polypeptides may include amino acids other than the naturally-occurring amino acids, as well as amino acid analogs and mimetics prepared by techniques that are well known in the art. The skilled artisan will understand that polypeptides, peptides, and proteins may be obtained in a variety of ways including isolation from cells and tissues expressing the protein endogenously, isolation from cell or tissues expressing a recombinant form of the molecule, or synthesized chemically.

(23) As used herein, the term subject refers to a member of any vertebrate species. In some embodiments, the subject is avian and includes domestic (e.g., chicken, turkey) and wild bird species. In some embodiments, subjects include mammals such as humans, as well as those mammals of importance due to being endangered, of economic importance (animals raised on farms for consumption by humans) and/or social importance (animals kept as pets or in zoos) to humans. In particular embodiments, the subject is a human. In other embodiments, the subject is not human.

(24) As used herein, the term pathogen refers to any entity that causes disease, including, for example, but not limited to, mycoplasma, fungi, bacteria, viruses, viroids, virus-like organisms, protozoa, and nematodes, toxins, and prions. In some embodiments, the pathogen is a Clostridium. In some embodiments, the pathogen is Clostridium botulinum.

(25) As used herein, the term chimera and chimeric refers to biological molecules comprising materials derived from two or more organisms of the same or different species. For example, the terms chimeric antibody, and chimeric IgG refer to antibodies comprising amino acid sequences derived from two or more organisms of the same or different species. In some embodiments, the organisms are both of the same species. In some embodiments, the organisms are both human. In some embodiments, the organisms are from different species. In some embodiments, the terms refer to nucleic acid sequences encoding chimeric polypeptide sequences.

(26) The present disclosure provides methods and compositions for high-throughput production of chimeric antibodies that specifically bind to an antigen of interest. The methods combine three procedures into one streamlined process: 1) isolation of lymphocytes producing antibodies of interest from the blood of immunized individuals, 2) amplification of sequences encoding variable domains of light and heavy chains of immunoglobulin from individual isolated cells, and 3) assembly of amplified sequences into specially designed vectors and construction of cells encoding human/human chimeras targeted at antigens of interest. The uniqueness of this process is its ability to generate multiple (up to 100) immunoglobulin-producing clones within a very short time (one-two months). Each such clone encodes an IgG whose variable domains of light and heavy chains originate from the same lymphocyte.

(27) Since the required antibody-producing blood cells could come from a patient recovered from the infection, this system does not depend on the availability of a developed vaccine. Consequently, this system could be used to develop protective entities against rare and even new natural and engineered pathogens at very early signs of appearance. Additionally, the system does not involve use of viruses and, consequently, is safe to use.

(28) The methods allow for rapid generation of IgGs whose heavy chains carry additional polypeptides at the C-termini. This grants the opportunity to produce derivatives of antibodies that can be used to monitor corresponding antigens (IgGs fused with reporter molecules) or to immobilize those pathogens (IgGs fused with polypeptides like Cellulose Binding Domain). Among other fusions, the system allows creation of fusions with Metridia longa luciferase, which allows fast and inexpensive examination of conditions to identify those for optimal production of antibodies. Also, the methods allow for the use of fluorescence activated cell sorting (FACS) for fast selection of clones producing increased levels of IgGs.

(29) The present disclosure provides methods and compositions for robust development of human antibodies targeted at specific antigens of interest. The chosen approach required the ability to 1) isolate individual human lymphocytes specific to the chosen antigen, 2) isolate immunoglobulin-encoding sequences from a single selected cell, and 3) assemble immunoglobulin-encoding constructs that can be introduced into chosen cell cultures for production of corresponding antibodies. Prior to this work, it was unknown whether the dynamics of antibody secretion and the limited number of antigen-specific lymphocytes in the peripheral blood would permit efficient separation of these specific cells from all others. It was unclear whether protocols for rtPCR at the single cell level would be robust enough to allow their application in a high throughput format. Finally, described procedures for assembling expression vectors carrying IgG-encoding sequences were suitable for manipulation with just a very small number of IgG-encoding sequences at a time. By contrast, suitable methods for high throughput production must be capable of simultaneous handling of tens and even hundreds of different sequences.

(30) In some embodiments, the compositions comprise expression vectors encoding constant regions of either light or heavy chains of human IgG. In some embodiments, the compositions comprise an expression vector encoding the constant regions of both the IgG heavy and light chains.

(31) In some embodiments, the methods comprise isolating sequences encoding variable domains of light and heavy chains of IgG from single cells and assembly of Ig-encoding vectors.

(32) In some embodiments, the methods comprise introducing designed IgG-encoding constructs into mammalian cells and evaluation of conditions for efficient IgG production. In some embodiments, the methods comprise producing and characterizing chimeric IgGs. In some embodiments, the chimeric IgGs are specific for botulinum neurotoxin serotype A (BoNT/A).

(33) Embodiments described herein are set forth in the following non-limiting examples.

EXAMPLES

Example 1

Development of Expression Vectors

(34) This Example demonstrates the construction of expression vectors for the cloning and production of chimeric IgG antibodies that specifically bind an antigen of interest.

(35) In order to create a system for generation of human antibodies that is capable of working in a high throughput format, vectors were necessary that would allow 1) a 100%-certain assembly of sequences encoding light and heavy chains of immunoglobulins, 2) simple assembly of such sequences into one plasmid, and 3) robust selection of cells carrying such plasmids and expressing both chains of immunoglobulins. Plasmids pVLentry-Hyg10 and pVHentry-Cm5 are designed for assembly of expression-competent sequences for light and heavy chains of IgG, respectively, meet all of these requirements (FIG. 1). Specifically, both of these plasmids possess two recognition sites for restriction endonuclease Esp3I per plasmid and these sites flank the sequence encoding protein 10b of bacteriophage T7. These two features ensure that practically 100% of colonies growing after cloning experiments utilizing vectors pVLentry-Hyg10 and pVHentry-Cm5 carry inserts of interest in a pre-determined orientation.

(36) Restriction endonuclease Esp3I cuts DNA outside of its recognition sequence and generates four nucleotide-long cohesive 5-overhanging ends. As depicted in FIG. 1, each Esp3I cleavage site in plasmids pVLentry-Hyg10 and pVHentry-Cm5 is unique. Therefore, fragments generated as a result of treatment of these plasmids with Esp3I and removal of the protein 10b-encoding sequence are not able to form a viable circular DNA unless the reaction is supplemented with a DNA fragment carrying appropriate sticky ends. As demonstrated in FIG. 2, the insertion of such a DNA fragment will occur only in one orientation, thus eliminating the need for following analysis of recombinant clones. The sequence encoding protein 10b of bacteriophage T7 functions as a safeguard, preventing re-assembly of the original vector.

(37) In our vectors, its expression is controlled by the lactose promoter. Expression of this sequence is lethal to F plasmid-containing E. coli (17). Therefore, while our vectors are maintained in F-negative cells, cloning experiments require strains carrying F factor and, after transformation, cells are grown in the presence of IPTG and the corresponding antibiotic (ampicillin in the case of plasmid pVLentry-Hyg10 and chloramphenicol in the case of plasmid pVHentry-Cm5). Under these conditions, only cells carrying plasmids in which the protein 10b-encoding fragment has been substituted with a new insert survive.

(38) Another important element of our vectors is a strong promoter that can direct transcription of the inserted sequence in mammalian cells. In vectors pVLentry-Hyg10 and pVHentry-Cm5, this role is served by the sequence from cytomegalovirus (CMV). However, we also designed plasmids in which a sequence from Rouse Sarcoma virus is used for this purpose. Plasmids pVLentry-Hyg10 and pVHentry-Cm5 are designed in such a way that transcripts initiated from the CMV promoter incorporate not only a sequence lying immediately downstream of the promoter, but also an Internal Ribosome Entry Site (IRES) and sequence for antibiotic resistance. In the case of plasmid pVLentry-Hyg10, this is resistance to Hygromycin B and, in the case of plasmid pVHentry-Cm5, this sequence confers resistance to G418. Presence of IRES makes synthesis of antibiotic-inactivating protein proportional to synthesis of protein encoded by the preceding portion of the transcript (immunoglobulin chain in the derivatives of these plasmids). This feature is not absolutely necessary for selection of stable transfectants (in some of our plasmids it is not present), however, it makes further maintenance of selected clones easier and opens opportunities for their further improvement.

(39) In addition, design of our vectors allows simple combination of sequences encoding light and heavy chains of IgG in the same plasmid, which, in turn, ensures equal amounts of IgG chain-encoding sequences to be introduced into the cell during transfection. I-SceI recognition sites are one of elements enabling such combination.

(40) I-SceI is a site-specific homing endonuclease that recognizes an 18 nucleotide-long sequence and generates DNAs with cohesive ends that can be used for cloning. Due to the length of the target sequence, its occurrence in the sequence encoding a variable domain of Ig is practically impossible. Therefore, using this enzyme enabled transfer of entire IgG-encoding sequences from one plasmid into another without destroying the integrity of these sequences. Nonsymmetrical cohesive ends generated by the I-SceI 1 ensure that, in all generated plasmids, relative orientation of IgG-encoding sequences is the same. This feature allows further improvement of the reproducibility of IgG production experiments. As shown in FIG. 1, plasmids pVLentry-Hyg10 and pVHentry-Cm5 possess two I-SceI sites each. However, in plasmid pVLentry-Hyg10, I-SceI sites flank the Ig-encoding cassette, while in plasmid pVHentry-Cm5, both I-SceI sites are located on one side of the Ig-encoding cassette and flank the gene of the alpha peptide of beta-galactosidase (lacZ).

(41) In addition to differences in location of I-SceI sites, both plasmids possess different antibiotic-resistance markers. Both of these plasmids use the same origin of replication for propagation in E. coli cells and therefore are not be able to coexist in the same cell. All of these features allow us to speed up the process of assembly and identification of the plasmid carrying both L- and H-chain encoding sequences. Indeed, a simple treatment of the mixture of L- and H-chain encoding plasmids with I-SceI and ligase generates the required hybrid plasmid. Similarly to one of its parents, this plasmid inherits the chloramphenicol-resistance gene, while, unlike this parent, it will not be able to produce the alpha-peptide of beta-galactosidase. As a result, only cells carrying the required plasmid and not the three others present in the mixture are able to form white colonies on the media supplemented with chloramphenicol, X-Gal and isopropyl--D-thiogalactopyranoside (IPTG).

(42) Also disclosed are four derivatives of plasmid pVHentry-Cm5. These derivatives have all elements described above. However, instead of the sequence encoding the constant part of IgG heavy chain alone, all these plasmids contain sequences that encode fusions of the same part of IgG heavy chain with different polypeptides. One of them encodes a fusion with green fluorescent protein (GFP), the seconda fusion with luciferase from Metridia longa (MLuc) (18, 19), the thirda fusion with His-tag and a peptide that can be biotinylated by biotin ligase, and the fourtha fusion with a polypeptide that specifically binds cellulose (20, 21).

Example 2

Isolation of Sequences Encoding Variable Domains of Light and Heavy Chains of IgG

(43) A single individual who was vaccinated with pentavalent botulinum toxoid vaccine six years prior received several boosts and served as a donor of blood cells. These cells were subject to fractionation on Ficoll gradient, enrichment on BD IMag Anti-human CD19 Particles-DM, and, finally, cell sorting. As a marker for cells producing anti-BoNT/A, we used a fusion between Green Fluorescent Protein and the receptor-recognizing domain of BoNT/A (gfpBoNT/A-CH5). This protein was constructed in our lab and, prior to use in cell sorting experiments, was tested for the ability to recognize specific receptors present in neuroblastoma cells (FIG. 3).

(44) Cells simultaneously binding APC-Mouse-anti-human CD19 and gfpBoNT/A-CH5 were sorted into wells of a 96-well plate, one cell per well.

(45) Isolated cells were used as a source of sequences encoding V.sub.H- and V.sub.L-regions. We have developed a procedure for rtPCR of these sequences that includes three steps: 1) reverse transcription of mRNA released from the cell by perfringolysin 0, 2) simultaneous amplification of cDNAs encoding V.sub.H- and V.sub.L-regions in the same tube by PCR and 3) re-amplification of sequences encoding each region in its own tube. Each step has its own set of primers. The whole procedure takes less than 8 hours. The number of cells that can be processed during this time is mostly limited by the capacity of the available thermo-cycler. Primers were designed based on the analysis of available human Ig-encoding sequences known in the art (8, 22). Primers used during each step are summarized in Table 1. Primers used in the re-amplification step were designed to introduce unique sequences, which can be converted into four-nucleotide-long cohesive ends compatible with ends generated by Esp3I restriction endonuclease in the corresponding vectors (see previous section), into the ends of amplified fragments. The conversion occurs as a result of treatment of purified DNA fragments by DNA polymerase T4 in the presence of dCTP as demonstrated in FIG. 2. The lack of restriction endonucleases at this stage guarantees that none of the sequences is lost due to the presence of sites for corresponding restriction endonucleases in some of them.

(46) TABLE-US-00001 TABLE1 Primersusedforamplificationofsequences encodingvariabledomainsof humanimmunoglobulins. SEQID NO: Primersusedforreversetranscription IgG-CHH GGGGAAGAGGAAGACTGACGGTC 2 Cm1 CAGTACTGCGATGAGTGGCA 3 Clv-3 TGTGGCCTTGTTGGCTTG 4 OligodT PrimersusedatthePCRamplificationstage pVk-1 GAGTCAGDYYCDRYCAGGACACAGCATG 5 pVk-2 AGACCCTGTCAGGACACAGCATAGACATG 6 pVk-3 GGACTCCTCAGTTCACCTTCTCACAATG 7 pVk-4 TGCTCAGTTAGGACCCAGAGGAACCATG 8 hIgGk-3 TAATGGCCTAACACTCTCCCCTGTTG 9 AAGCTCTT IgGH-1 TGAGVDMMGYWCHTCACCATGGACTG 10 IgGH-2 ACTGAACACAGAGGACTCACCATGGA 11 IgGH-3 CAGTGACTCCTGTGCCCCACCATGGACA 12 IgGH-4 TTTCTGTCCTCCACCATCATGGGGTC 13 IgGH-5 GCACTGAACACAGACCACCAATCATGG 14 IgG-CHH GGGGAAGAGGAAGACTGACGGTC 15 M1 CCTGGGAGCACAGCTCATCACCATGGA 16 M2 CACTGAACACAGAGGACTCACCATGGA 17 M3 CATGGACCTCCTGCACAAGAACATGAA 18 M4 ACTGAACAGAGAGAACTCACCATGGA 19 Cm1 CAGTACTGCGATGAGTGGCA 20 Vl1-5T7 TTTAGGCCATGGCCTGGACCCCTCTCCTGCTC 21 Vl2-5T7 TTTAGGCCATGGCCTGGACCKTTCTCCTCCTC 22 Vl3-5T7 TTTAGGCCATGGCCTGGDCTCYKCTCCTYCTC 23 Vl4-5T7 TTTAGGCCATGGCATGGCCAGCTTCCCTCT 24 CCTCCTC Vl5-5T7 TTTAGGCCATGACCTGCTCCCCTCTCCTCCTC 25 Cl-3 CCTGCAGCTCTAGTCTCCCGTGG 26 Primersusedatthere-amplificationstage Vk-1/2-5T7 TTTAGGCATGGACATGAGGGTCCCCGCTCAG 27 CTCCTGG Vk-3-5T7 TTTAGGCATGGAAACCCCAGCGCAGCTTCT 28 Vk-4-5T7 TTTAGGCATGGTGTTGCAGACCCAGGTCTT 29 hIgGk-3 TAATGGCCTAACACTCTCCCCTGTTGAAGCTCTT 30 IgG-CH TATTGGCGAGCTGGCCTCTCACCAACTGTCTT 31 GTCCACCTTGGTGTTG Vh-1-3T7 CACTGGAGACGGTGACCAGBGTBCCYTGKCCCCA 32 Vh-1-3T75 TATTGGCactcacggaagagacggtgaccag 33 BgtBccYtg Vh-1-5T7 TATAGccatggactggacctgga 34 Vh-2-5T7 TATAGccatggacatactttgttccac 35 Vh-3-5T7 TATAGccatggagtttgggctgagc 36 Vh-4-5T7 TATAGccatgaaacacctgtggttctt 37 Vh-5-5T7 TATAGccatggggtcaaccgccatcct 38 Vh-6-5T7 TATAGccatgtctgtctccttcctcat 39 Vh-7-5T7 TATAGccatggaatttgggcttagct 40 Vh-8-5T7 TATAGccatggaattggggctgag 41 Vh-1-3T75 TATTGGCactcacggaagagacggtgaccag 42 BgtBccYtg Vm-1-5T7 TATAGaccatggactggacctggaggttcct 43 Vm-2-5T7 TATAGaccatggagtttgggctgagctgggt 44 Vm-3-5T7 TATAGaacatgaaacacctgtggttcttcct 45 Vh-1-3T75 TATTGGCactcacggaagagacggtgaccag 46 BgtBccYtg V11-5T7 TTTAGGccatggcctggacccctctcctgctc 47 V12-5T7 TTTAGGccatggcctggacckttctcctcctc 48 V13-5T7 TTTAGGccatggcctggdctcykctcctyctc 49 V14-5T7 TTTAGGccatggcatggccagcttccct 50 ctcctcctc V15-5T7 TTTAGGccatgacctgctcccctctcctcctc 51 hIgG1-3 taatggcCTATGAACATTCTGTAGGGGCCAC 52

(47) In the end, only 24% of originally sorted cells produced sequences for both V.sub.H- and V.sub.L-regions. This may sound like a relatively low success rate. However, given the potential of collecting hundreds of cells and the ability to process them in just few days, this allows the accumulation of tens of pairs of sequences for further antibody assembly. In the future, we expect to increase this rate by including anti-CD27 or anti-B220 monoclonal antibodies in the cell sorting protocol and thus increase the number of those among selected cells that produce antibodies versus those that may just absorb them.

(48) Sequencing of 11 pairs of isolated DNA fragments revealed that practically all pairs were unique. Even when two pairs had one identical chain, the second chains were different (Sequences of variable domains of light and heavy chains are listed in Appendix 2 and 3).

Example 3

Introduction of Designed IgG-Encoding Constructs into Mammalian Cells and Evaluation of Conditions for Efficient IgG Production

(49) Eight pairs of isolated sequences were incorporated into the previously-described vectors and the resulting plasmids were introduced into CHO and HEK cells. ELISA registered accumulation of human antibodies in media of both of these cultures. In isolated stable cell lines, the level of production varied but did not exceed 1-2 g/ml (the level of production was determined on the basis of the amount of anti-BoNT/A purified from 100 ml of culture mediawill be described below). In our experience, HEK cells proved to be more robust and capable of producing more antibodies from the same volume of media. Also, these cells were easier to adapt to grow and produce IgGs in the serum-free media. This is why, in most of our later analyses, we preferred to use HEK cells.

(50) To select clones with higher production, we decided to use correlation between translations of sequences encoding light and heavy chains of IgGs and those encoding antibiotic-inactivating proteins, built into our system and discussed earlier. Specifically, by gradually increasing amounts of antibiotics in the culture media, we were able to select cell lines whose resistance to antibiotics is 3-4 times higher than resistance of originally selected cultures. As demonstrated in FIG. 4, ELISA revealed that cells with increased resistance to antibiotics did not produce substantially more immunoglobulins than cells possessing a lower level of resistance to these antibiotics.

(51) This data suggest that the bottleneck of production lies somewhere at the post-translational level. The conventional way for identifying cells with increased production of IgGs is a limiting dilution cloning. The low throughput nature of this method significantly limits the number of clones that can feasibly be screened. We tested whether fluorescence activated cell sorting (FACS) can be used to increase throughput. As a marker for IgG-producing cells, we used previously mentioned gfpBoNT/A-CH5. Cells were released from the solid support via treatment with trypsin and washed two times with fresh RPMI media to remove trypsin. Then, cells were incubated in RPMI media for 1 hour, co-incubated with gfpBoNT/A-CH5 for 10 minutes and subject to FACS. Out of the 1% of cells with the highest fluorescence intensity, corresponding to the highest antibody production rates, single cells were sorted directly into 96-well plates at one cell per well. One plate was assembled per each IgG-producing cell line. Table 2 demonstrates that we were able to find clones with increased production of IgG-luciferase hybrids for five cell lines out of seven used in the experiment. These results clearly demonstrate the potential of FACS for further development of cell lines producing high quantities of IgGs.

(52) TABLE-US-00002 TABLE 2 Production of IgG-MLuc by original cultures and individual clones selected from these cultures Original culture Luminescence Clone Luminescence HEK-1HL-MLuc 657,148 1E7 1,641,522 HEK-7HL-MLuc 1,387,980 7B8 8,013,339 HEK-8HL-MLuc 981,702 8E8 3,783,486 HEK-9HL-MLuc 1,991,512 9F6 2,778,794 HEK-14HL-MLuc 951,132 14G11 721,576 HEK-15HL-MLuc 104,466 15F2 594,677 HEK-41HL-MLuc 3,274,119 41C9 3,163,750

(53) Production of the Chimera IgGs and their Characterization.

(54) As result of the reasons mentioned in the previous section, most of the IgG constructs were purified from culture media of HEK cells. Our analysis of accumulation of luciferase activity in the culture media of two cell lines encoding IgG-MLuc fusions revealed that the accumulation in both continued for seven days. Therefore, all HEK cultures were grown for seven days in the same media, which was then passed through a column containing the hybrid between staphylococcal protein A and streptococcal protein G. In the case of CHO cells, the media was collected after three days. Elution of absorbed IgGs was achieved by a buffer change to 0.1 M glycine HCl (pH 2.3). Immediately after elution, the pH of collected fractions was increased by addition of 1 M Tris-Base. Then, fractions were subjected to buffer exchange and concentrated by ultrafiltration.

(55) In addition to IgGs alone, we purified fusions of these IgGs with luciferase, GFP, and His-tag connected to the peptide that serves as a target for biotin ligase (BirA). Analysis confirmed the presence of polypeptides with expected molecular weights and recognized by anti-human antibodies in isolated fractions (FIG. 5).

(56) Fractions with IgG-MLuc fusions produced light in the presence of luciferase's substrate-coelenterazine. The IgG-GFP fusion emitted the green light characteristic of GFP upon illumination with UV light. Finally, the IgG fusion with His-tag and BirA substrate interacted with Ni-column and, after treatment with BirA in the presence of biotin and ATP, was recognized by streptavidin-alkaline phosphatase substrate (data not presented).

(57) ELISA revealed that out of eight different IgGs that we purified, all eight recognize the receptor-recognizing domain of BoNT/A (FIG. 6). This data suggests that practically all isolated cells from which we were able to recover IgG-encoding sequences produced BoNT/A-specific antibodies.

(58) IgGs were recognized by hybrid proteins composed of staphylococcal protein A, streptococcal protein G and Metridia longa luciferase (spAG-MLuc and spAG-N-MLuc) and developed in our lab (sequences of plasmids encoding these proteins are presented in Appendix 4). These hybrids allowed quantitative monitoring of IgG present in wells of 96-well plate. Hybrid spAG-MLuc possessed luciferase activity only when it was purified from culture media of mammalian cells. Hybrid spAG-N-MLuc possesses luciferase activity irrespective to where it was expressed, E. coli or mammalian cells.

(59) Examples 1-3 demonstrate 1) the number of peripheral blood cells encoding specific IgGs in blood and the efficiency of cell sorting protocols used are sufficient to produce hundreds of cells that can serve as a source of Ig-encoding sequences; 2) the methods disclosed herein permit reliable isolation of cDNA encoding variable domains of both Ig-chains from of all isolated individual lymphocytes; 3) practically all isolated cDNA pairs encode IgG specific to the antigen used in the cell sorting procedure; 4) the expression vectors described herein are suitable for high throughput assembly of plasmids encoding both full size human IgGs, as well as their derivatives carrying polypeptides that allow monitoring or/and specific binding of these IgGs to other molecules; 5) the vectors allow efficient selection of cells producing both IgG chains; and 6) FACS can be used as an efficient tool allowing selection of clones producing increased quantities of IgGs and their derivatives.

(60) Accordingly, the compositions and methods described herein are useful in methods comprising one or more of these aspects.

Example 4

Construction and Expression of Libraries of Anti-Botulinum Chimeras that Recognize Regions of BoNT/a

(61) This example demonstrates the construction and use of libraries of anti-botulinum chimeras that recognize regions of BoNT/A.

(62) First, we will use conventional methods of gene engineering to create fusions of corresponding domains with GFP. Similar to previously-mentioned gfpBoNT/A-CH5, these fusions will be used as markers for lymphocytes producing antibodies specific for catalytic and transport domains of BoNT/A. As a source of lymphocytes, we will use white blood cells from the blood of an immunized individual that were generated and tested previously, and preserved under liquid nitrogen. It has been demonstrated that such cells can be used as a source of immunoglobulin-encoding sequences (25). These cells will be subjected to enrichment on BD IMag Anti-human CD19 Particles-DM and then sorted into wells of a 96-well plate, one cell per well. Prior to FACS, cells will be labeled with APC Mouse Anti-Human CD19 (BD Biosciences) and the corresponding GFP-BoNT/A fusion. To increase the level of discrimination of IgG-producing cells from those that do not produce, but instead absorb them from serum, we will include an additional markermemory B cell marker. Bleesing and Fleisher reported that human B cells expose either B220 or CD27 on their surface [30]. Therefore, as the third component of the cell labeling mixture, we will use anti-CD27 (Ancell Co.) and/or anti-B220 (Beckman Coulter) monoclonal antibodies, each conjugated to R-Phycoerythrin.

(63) Isolated cells will be used as a source of sequences encoding V.sub.H- and V.sub.L-regions. Isolation and further handling of these sequences will be done according to protocols described above. At this stage, the goal will be to isolate 10-20 V.sub.H- and V.sub.L-encoding pairs that have unique sequences per each BoNT/A domain.

(64) Unique V.sub.H- and V.sub.L-encoding pairs will be used to assemble and produce human/human IgG chimeras as described above.

Example 5

Identification of IgGs and their Combinations that can Neutralize Toxic Activity of BoNT/A

(65) This Example demonstrates the identification of chimeric IgG antibodies with the capacity to neutralize toxicity of BoNT/A using phage display.

(66) Choosing V.sub.H- and V.sub.L-encoding pairs with unique sequences does not guarantee that they will recognize different epitopes. Therefore, prior to conducting expensive toxin neutralizing experiments, we will sort developed IgGs according to their epitope specificities. For this, we will use phage display known in the art. This technology involves a library of random peptides. Sequences of these peptides are incorporated in the region of the phage genome that encodes the capsid protein. As a result, each phage particle in the library encodes and exposes on its surface only one type of peptide. We previously demonstrated that incubation of such a library with immobilized polyclonal antibodies raised against BoNT/A allows isolation of phage particles that encode peptides mimicking BoNT/A epitopes (mimetics).

(67) We will use a similar approach to sort developed IgGs according to their epitope specificities. Specifically, each developed IgG will be purified and immobilized on a solid support. Then, each immobilized IgG will be co-incubated with the phage display library MD-12 (Alpha Universe, LLC). Phages that do not bind to IgG will be removed by washing and those bound to IgG will be released and grown on appropriate host cells. Following this amplification, phages will be subjected to two additional cycles of the above-described screening procedure. According to our previous experience, practically all phages released after the third cycle will possess affinity to the IgG used in selection. To ensure that selected phages carry mimetics of BoNT/A, we have to prevent isolation of phages that interact with IgG parts other than the antigen-binding region. In order to do this, phages will be subject to depletion with human nave serum every time prior to incubation with immobilized developed IgG. After mixing with phages, components of human nave serum, as well as phage particles bound to them, will be removed by addition of magnetic beads with immobilized staphylococcal protein A-streptococcal protein G hybrid to the mixture.

(68) Individual phages carrying BoNT/A mimetics will be used for characterization of developed IgGs. Specifically, each IgG will be immobilized on wells of a 96-well plate and each immobilized IgG will be incubated with all chosen mimetic-exposing phages. Wells with bound phages will be identified using M13 phage-specific antibodies conjugated with horse radish peroxidase (GE Healthcare) and 1-Step Slow TMB-ELISA (PIERCE). IgGs interacting with the same phage will be considered as recognizing the same epitope.

(69) In addition to classification of developed IgGs according to their epitope (actually, mimetic) specificity, we will characterize these IgGs according to the nature of recognized epitopes (linear or structural). In these experiments, we will compare interaction of developed IgGs with corresponding recombinant domains subjected or not subjected to denaturing treatment. For this, corresponding BoNT/A fragments will be subjected to native or SDS polyacrylamide gel electrophoresis, transferred onto a nitrocellulose membrane and probed with each chosen IgG separately. Then, filters will be treated with biotinylated anti-human IgGs, followed by treatment with streptavidin-horse radish conjugate and Metal Enhanced DAB Substrate Kit (Pierce, Inc.). IgGs recognizing both forms of BoNT/A fragment will be considered as recognizing linear epitopes. Those that recognize only BoNT/A fragments not subjected to denaturing conditions will be considered as recognizing structural epitopes.

(70) The information about the nature of the recognized epitope will not only be used to verify epitope-based grouping of IgGs, but also to gain information about locations of corresponding epitopes on the BoNT/A molecule. Specifically, our previous experience suggests that, in the case of mimetics of linear epitopes, some similarities between sequences of these mimetics and the BoNT/A sequence can be observed. Such similarities may be used as indicators of the location of the corresponding epitope in the structure of the molecule.

(71) After developed IgGs are classified and grouped, representatives from each group will be tested for the ability to neutralize BoNT/A.

(72) It has been demonstrated that even when individual monoclonal antibodies do not have substantial protective activity, their combination may have such activity (24). This is why the analysis will include testing of the BoNT/A-neutralization potential of each chosen IgG separately and, then, testing of such potential for selected groups of IgGs.

(73) The goal of this analysis will be to identify IgGs or their combinations that will be able to protect mice from at least 1000 minimal doses that are lethal to a fifty percentage of mouse (MLD.sub.50) of BoNT/A. In addition, the aim will be to determine which among three regions of the BoNT/A molecule (catalytic, transport, or receptor-recognizing) contains the highest number of protective epitopes. This information will be instrumental for development of antibodies capable of neutralizing other serotypes of BoNTs.

Example 6

Development of Human/Human IgG Chimeras Capable of Neutralizing BoNT/B

(74) This Example demonstrates the development of human/human IgG chimeras capable of neutralizing BoNT/B.

(75) Previously, we demonstrated that different serotypes of BoNTs have similar epitopes and information about locations of epitopes in one serotype can be used to predict locations of epitopes in other serotypes (26). We will use this phenomenon to speed up the process of development of IgGs capable of neutralizing BoNT serotype B. Specifically, instead of developing IgGs to the whole molecule of BoNT/B, we will focus on just one region. This region will be the same one as that revealed in BoNT/A as possessing the most potent protective epitopes. We will create a fusion between GFP and a fragment of BoNT/B after the targeted region of BoNT/B is determined. This fusion will be used to isolate corresponding lymphocytes from the same cryopreserved fractions of blood cells mentioned earlier. FACS and following isolation of cDNAs, their PCR, cloning, expression of assembled sequences, purification of IgGs, and analysis of their protective properties will be done the same way as described in the previous two sections.

(76) As in case with BoNT/A, our goal will be to identify IgGs or their combinations that will ensure protection of mice from at least 1000 MLD.sub.50.

(77) Optimization of Protocols for Production of Chosen Chimeras.

(78) The ability to efficiently produce developed protective IgGs is a key element for the system to become a commercially viable. Earlier analysis of different monoclonal antibody-producing cell lines conducted by O'Callaghan and coauthors revealed that each cell line had its own bottleneck, limiting production of antibodies (27). This research supports the approach for selection of high producers from population of cells already producing IgG. This approach has been successfully used by many groups including ourselves. However, such selection often requires multiple cycles and is very lengthy. Development of a strain with bottlenecks that are widened or even removed will substantially increase the potential for high throughput development of cells producing high quantities of IgGs. Recent reports of successful increase of antibody production via introduction of specific DNA sequences into the cells suggest the possibility of such an approach (28-30).

(79) To create a cell line originally capable of producing increased quantities of IgGs, we will produce IgG derivatives carrying different polypeptides on the C-termini of heavy chains. Specifically, we will engineer a plasmid encoding one of the anti-BoNT/A IgGs fused with the trans-membrane domain of platelet derived growth factor receptor (31). This plasmid will allow generation of transiently transfected cells expressing IgG anchored in the cell membrane. Such cells will be stained with gfpBoNT/A-CH5 and subjected to FACS. Individual cells carrying the highest levels of fluorescent label will be sorted into wells of a 96-well plate and allowed to grow. We anticipate that the majority of such cells will lose IgG-encoding plasmids. As a result, such cells will stop producing the corresponding IgG derivative and antibiotic-inactivating enzymes encoded by the plasmid. Cell lines grown from such cells will be transfected again. This time, we will use the plasmid encoding IgG-luciferase hybrid formed by different V.sub.H- and V.sub.L-pair that was used in the previous transfection. Parental cell lines for those transient transfectants whose culture media contains the highest amounts of luciferase will be tested further for the ability to produce high quantities of other types of IgG-luciferase fusions. Eventually, we expect to be able to isolate a cell line that will produce increased quantities if IgGs irrespective of sequences of their V.sub.H- and V.sub.L-regions.

(80) To increase the success rate of the above-described selection, we will use a cell line whose diversity will be increased by chemical mutagenesis. Further, to eliminate difficulties associated with sorting originally adherent cells, we will use FREESTYLE CHO-S cells (Invitrogen, Inc.). This cell line has been adapted to grow in suspension in serum-free media. The latter feature will beneficial for future production of antibodies.

(81) Even with a developed host cell line capable of increased production of IgGs, we do not exclude the need for additional selection of super-producers among created IgG-producing cells. Traditionally, such selection is done by Limiting dilution cloning, which is a very labor-intensive process. We will use FACS protocols for the isolation of cells that bind the highest amounts of the label after a very short exposure to it from the population, followed by isolation of cells that lose this label faster than others.

(82) As a result of these activities, we will not only generate cell lines producing high quantities of chosen IgGs, but will also determine the best way to efficiently develop new IgG-producing cell lines.

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(84) TABLE-US-00003 APPENDIX1 Nucleotidesequencesofconstructedplasmids(SEQIDNOs:53-58,inorderofappearance). pVLentry-Hyg10: 1 TGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAA ACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTACTGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTT 101 TGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCG ACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAGTATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGC 201 CCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCA GGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCATGTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGT 301 GTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG CATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAGGTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCC 401 GACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTGGTTTAGTGAACC CTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCATCCGCACATGCCACCCTCCAGATATATTCGTCTCGACCAAATCACTTGG Esp3I ~~~~~~~ 501 GTCAGATCCGCTAGACGTCTCATTTAACTTTAAGAAGGAGATATACATATGGCTAGCATGACTGGTGGACAGCAAATGGGTACTAACCAAGGTAAAGGTG CAGTCTAGGCGATCTGCAGAGTAAATTGAAATTCTTCCTCTATATGTATACCGATCGTACTGACCACCTGTCGTTTACCCATGATTGGTTCCATTTCCAC 601 TAGTTGCTGCTGGAGATAAACTGGCGTTGTTCTTGAAGGTATTTGGCGGTGAAGTCCTGACTGCGTTCGCTCGTACCTCCGTGACCACTTCTCGCCACAT ATCAACGACGACCTCTATTTGACCGCAACAAGAACTTCCATAAACCGCCACTTCAGGACTGACGCAAGCGAGCATGGAGGCACTGGTGAAGAGCGGTGTA 701 GGTACGTTCCATCTCCAGCGGTAAATCCGCTCAGTTCCCTGTTCTGGGTCGCACTCAGGCAGCGTATCTGGCTCCGGGCGAGAACCTCGACGATAAACGT CCATGCAAGGTAGAGGTCGCCATTTAGGCGAGTCAAGGGACAAGACCCAGCGTGAGTCCGTCGCATAGACCGAGGCCCGCTCTTGGAGCTGCTATTTGCA 801 AAGGACATCAAACACACCGAGAAGGTAATCACCATTGACGGTCTCCTGACGGCTGACGTTCTGATTTATGATATTGAGGACGCGATGAACCACTACGACG TTCCTGTAGTTTGTGTGGCTCTTCCATTAGTGGTAACTGCCAGAGGACTGCCGACTGCAAGACTAAATACTATAACTCCTGCGCTACTTGGTGATGCTGC 901 TTCGCTCTGAGTATACCTCTCAGTTGGGTGAATCTCTGGCGATGGCTGCGGATGGTGCGGTTCTGGCTGAGATTGCCGGTCTGTGTAACGTGGAAAGCAA AAGCGAGACTCATATGGAGAGTCAACCCACTTAGAGACCGCTACCGACGCCTACCACGCCAAGACCGACTCTAACGGCCAGACACATTGCACCTTTCGTT 1001 ATATAATGAGAACATCGAGGGCTTAGGTACTGCTACCGTAATTGAGACCACTCAGAACAAGGCCGCACTTACCGACCAAGTTGCGCTGGGTAAGGAGATT TATATTACTCTTGTAGCTCCCGAATCCATGACGATGGCATTAACTCTGGTGAGTCTTGTTCCGGCGTGAATGGCTGGTTCAACGCGACCCATTCCTCTAA 1101 ATTGCGGCTCTGACTAAGGCTCGTGCGGCTCTGACCAAGAACTATGTTCCGGCTGCTGACCGTGTGTTCTACTGTGACCCAGATAGCTACTCTGCGATTC TAACGCCGAGACTGATTCCGAGCACGCCGAGACTGGTTCTTGATACAAGGCCGACGACTGGCACACAAGATGACACTGGGTCTATCGATGAGACGCTAAG 1201 TGGCAGCACTGATGCCGAACGCAGCAAACTACGCTGCTCTGATTGACCCTGAGAAGGGTTCTATCCGCAACGTTATGGGCTTTGAGGTTGTAGAAGTTCC ACCGTCGTGACTACGGCTTGCGTCGTTTGATGCGACGAGACTAACTGGGACTCTTCCCAAGATAGGCGTTGCAATACCCGAAACTCCAACATCTTCAAGG 1301 GCACCTCACCGCTGGTGGTGCTGGTACCGCTCGTGAGGGCACTACTGGTCAGAAGCACGTCTTCCCTGCCAATAAAGGTGAGGGTAATGTCAAGGTTGCT CGTGGAGTGGCGACCACCACGACCATGGCGAGCACTCCCGTGATGACCAGTCTTCGTGCAGAAGGGACGGTTATTTCCACTCCCATTACAGTTCCAACGA 1401 AAGGACAACGTTATCGGCCTGTTCATGCACCGCTCTGCGGTAGGTACTGTTAAGCTGCGTGACTTGGCTCTGGAGCGCGCTCGCCGTGCTAACTTCCAAG TTCCTGTTGCAATAGCCGGACAAGTACGTGGCGAGACGCCATCCATGACAATTCGACGCACTGAACCGAGACCTCGCGCGAGCGGCACGATTGAAGGTTC Esp3I ~~~~~~ 1501 CGGACCAGATTATCGCTAAGTACGCAATGGGCCACGGTGGTCTTCGCCCAGAAGCTGCAGGAGCTGTCGTATTCCAGTCAGGTTAATTACGAGACGCTCG GCCTGGTCTAATAGCGATTCATGCGTTACCCGGTGCCACCAGAAGCGGGTCTTCGACGTCCTCGACAGCATAAGGTCAGTCCAATTAATGCTCTGCGAGC 1601 AGCCGATCCGCATCAAAGCATGCTGTTTTCTGTCTGTCCCTAACATGCCCTGTGATTATCCGCAAACAACACACCCAAGGGCAGAACTTTGTTACTTAAA TCGGCTAGGCGTAGTTTCGTACGACAAAAGACAGACAGGGATTGTACGGGACACTAATAGGCGTTTGTTGTGTGGGTTCCCGTCTTGAAACAATGAATTT 1701 CACCATCCTGTTTGCTTCTTTCCTCAGGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT GTGGTAGGACAAACGAAGAAAGGAGTCCTTGACACCGACGTGGTAGACAGAAGTAGAAGGGCGGTAGACTACTCGTCAACTTTAGACCTTGACGGAGACA 1801 TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAG ACACACGGACGACTTATTGAAGATAGGGTCTCTCCGGTTTCATGTCACCTTCCACCTATTGCGGGAGGTTAGCCCATTGAGGGTCCTCTCACAGTGTCTC 1901 CAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATC GTCCTGTCGTTCCTGTCGTGGATGTCGGAGTCGTCGTGGGACTGCGACTCGTTTCGTCTGATGCTCTTTGTGTTTCAGATGCGGACGCTTCAGTGGGTAG 2001 AGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAGCGGCCAATTGGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGC TCCCGGACTCGAGCGGGCAGTGTTTCTCGAAGTTGTCCCCTCTCACAATCGCCGGTTAACCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACG 2101 CGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTT GCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAA 2201 GAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGG CTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCC 2301 TGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAAT ACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTA 2401 GGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATG CCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTAC 2501 TGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAG ACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATC 2601 GCTTTTGCAAAGATCGATCAGATCCCGGGGGGCAATGAGATATGAAAAAGCCTGAACTCACCGCGACGTCTGTCGAGAAGTTTCTGATCGAAAAGTTCGA CGAAAACGTTTCTAGCTAGTCTAGGGCCCCCCGTTACTCTATACTTTTTCGGACTTGAGTGGCGCTGCAGACAGCTCTTCAAAGACTAGCTTTTCAAGCT 2701 CAGCGTATCCGACCTGATGCAGCTCTCGGAGGGCGAAGAATCTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGATATGTCCTGCGGGTAAATAGCTGC GTCGCATAGGCTGGACTACGTCGAGAGCCTCCCGCTTCTTAGAGCACGAAAGTCGAAGCTACATCCTCCCGCACCTATACAGGACGCCCATTTATCGACG 2801 GCCGATGGTTTCTACAAAGATCGTTATGTTTATCGGCACTTTGCATCGGCCGCGCTCCCGATTCCGGAAGTGCTTGACATTGGGGAATTCAGCGAGAGCC CGGCTACCAAAGATGTTTCTAGCAATACAAATAGCCGTGAAACGTAGCCGGCGCGAGGGCTAAGGCCTTCACGAACTGTAACCCCTTAAGTCGCTCTCGG 2901 TGACCTATTGCATCTCCCGCCGTGCACAGGGTGTCACGTTGCAAGACCTGCCTGAAACCGAACTGCCCGCTGTTCTGCAGCCGGTCGCGGAGGCCATGGA ACTGGATAACGTAGAGGGCGGCACGTGTCCCACAGTGCAACGTTCTGGACGGACTTTGGCTTGACGGGCGACAAGACGTCGGCCAGCGCCTCCGGTACCT 3001 TGCGATCGCTGCGGCCGATCTTAGCCAGACGAGCGGGTTCGGCCCATTCGGACCGCAAGGAATCGGTCAATACACTACATGGCGTGATTTCATATGCGCG ACGCTAGCGACGCCGGCTAGAATCGGTCTGCTCGCCCAAGCCGGGTAAGCCTGGCGTTCCTTAGCCAGTTATGTGATGTACCGCACTAAAGTATACGCGC 3101 ATTGCTGATCCCCATGTGTATCACTGGCAAACTGTGATGGACGACACCGTCAGTGCGTCCGTCGCGCAGGCTCTCGATGAGCTGATGCTTTGGGCCGAGG TAACGACTAGGGGTACACATAGTGACCGTTTGACACTACCTGCTGTGGCAGTCACGCAGGCAGCGCGTCCGAGAGCTACTCGACTACGAAACCCGGCTCC 3201 ACTGCCCCGAAGTCCGGCACCTCGTGCACGCGGATTTCGGCTCCAACAATGTCCTGACGGACAATGGCCGCATAACAGCGGTCATTGACTGGAGCGAGGC TGACGGGGCTTCAGGCCGTGGAGCACGTGCGCCTAAAGCCGAGGTTGTTACAGGACTGCCTGTTACCGGCGTATTGTCGCCAGTAACTGACCTCGCTCCG 3301 GATGTTCGGGGATTCCCAATACGAGGTCGCCAACATCTTCTTCTGGAGGCCGTGGTTGGCTTGTATGGAGCAGCAGACGCGCTACTTCGAGCGGAGGCAT CTACAAGCCCCTAAGGGTTATGCTCCAGCGGTTGTAGAAGAAGACCTCCGGCACCAACCGAACATACCTCGTCGTCTGCGCGATGAAGCTCGCCTCCGTA 3401 CCGGAGCTTGCAGGATCGCCGCGGCTCCGGGCGTATATGCTCCGCATTGGTCTTGACCAACTCTATCAGAGCTTGGTTGACGGCAATTTCGATGATGCAG GGCCTCGAACGTCCTAGCGGCGCCGAGGCCCGCATATACGAGGCGTAACCAGAACTGGTTGAGATAGTCTCGAACCAACTGCCGTTAAAGCTACTACGTC 3501 CTTGGGCGCAGGGTCGATGCGACGCAATCGTCCGATCCGGAGCCGGGACTGTCGGGCGTACACAAATCGCCCGCAGAAGCGCGGCCGTCTGGACCGATGG GAACCCGCGTCCCAGCTACGCTGCGTTAGCAGGCTAGGCCTCGGCCCTGACAGCCCGCATGTGTTTAGCGGGCGTCTTCGCGCCGGCAGACCTGGCTACC 3601 CTGTGTAGAAGTACTCGCCGATAGTGGAAACCGACGCCCCAGCACTCGTCCGGATCGGGAGATGGGGGAGGCTAACTGAAACACGGAAGGAGACAATACC GACACATCTTCATGAGCGGCTATCACCTTTGGCTGCGGGGTCGTGAGCAGGCCTAGCCCTCTACCCCCTCCGATTGACTTTGTGCCTTCCTCTGTTATGG I-SceI ~~~~~~~~~~ 3701 GGAAGGAACCTCGACGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTATTACCCTGT CCTTCCTTGGAGCTGCAATTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAATAATGGGACA I-SceI ~~~~~~~~ 3801 TATCCCTAGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCA ATAGGGATCTTAAGTGACCGGCAGCAAAATGTTGCAGCACTGACCCTTTTGGGACCGCAATGGGTTGAATTAGCGGAACGTCGTGTAGGGGGAAAGCGGT 3901 GCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCA CGACCGCATTATCGCTTCTCCGGGCGTGGCTAGCGGGAAGGGTTGTCAACGCGTCGGACTTACCGCTTACCGCGGACTACGCCATAAAAGAGGAATGCGT 4001 TCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGA AGACACGCCATAAAGTGTGGCGTATGCAGTTTCGTTGGTATCATGCGCGGGACATCGCCGCGTAATTCGCGCCGCCCACACCACCAATGCGCGTCGCACT 4101 CCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGG GGCGATGTGAACGGTCGCGGGATCGCGGGCGAGGAAAGCGAAAGAAGGGAAGGAAAGAGCGGTGCAAGCGGCCGAAAGGGGCAGTTCGAGATTTAGCCCC 4201 GCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACG CGAGGGAAATCCCAAGGCTAAATCACGAAATGCCGTGGAGCTGGGGTTTTTTGAACTAAACCCACTACCAAGTGCATCACCCGGTAGCGGGACTATCTGC 4301 GTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATT CAAAAAGCGGGAAACTGCAACCTCAGGTGCAAGAAATTATCACCTGAGAACAAGGTTTGACCTTGTTGTGAGTTGGGATAGAGCCCGATAAGAAAACTAA 4401 TATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTT ATATTCCCTAAAACGGCTAAAGCCGGATAACCAATTTTTTACTCGACTAAATTGTTTTTAAATTGCGCTTAAAATTGTTTTATAATTGCAAATGTTAAAA 4501 ATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTC TACCACGTGAGAGTCATGTTAGACGAGACTACGGCGTATCAATTCGGTCGGGGCTGTGGGCGGTTGTGGGCGACTGCGCGGGACTGCCCGAACAGACGAG 4601 CCGGCATCCGCTTACAGACAAGCTGTGACCGTCTAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG GGCCGTAGGCGAATGTCTGTTCGACACTGGCAGATCTGCTTTCCCGGAGCACTATGCGGATAAAAATATCCAATTACAGTACTATTATTACCAAAGAATC 4701 ACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCT TGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTACTCTGTTATTGGGA 4801 GATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTT CTATTTACGAAGTTATTATAACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGCCGTAAAACGGAAGGACAAAA 4901 TGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTT ACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTAGCTTGACCTAGAGTTGTCGCCATTCTAGGAA 5001 GAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAAC CTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCATAATAGGGCATAACTGCGGCCCGTTCTCGTTG 5101 TCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAG AGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCATGAGTGGTCAGTGTCTTTTCGTAGAATGCCTACCGTACTGTCATTCTCTTAATACGTC 5201 TGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGAT ACGACGGTATTGGTACTCACTATTGTGACGCCGGTTGAATGAAGACTGTTGCTAGCCTCCTGGCTTCCTCGATTGGCGAAAAAACGTGTTGTACCCCCTA 5301 CATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGC GTACATTGAGCGGAACTAGCAACCCTTGGCCTCGACTTACTTCGGTATGGTTTGCTGCTCGCACTGTGGTGCTACGGACATCGTTACCGTTGTTGCAACG 5401 GCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGC CGTTTGATAATTGACCGCTTGATGAATGAGATCGAAGGGCCGTTGTTAATTATCTGACCTACCTCCGCCTATTTCAACGTCCTGGTGAAGACGCGAGCCG 5501 CCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGT GGAAGGCCGACCGACCAAATAACGACTATTTAGACCTCGGCCACTCGCACCCAGAGCGCCATAGTAACGTCGTGACCCCGGTCTACCATTCGGGAGGGCA 5601 ATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGT TAGCATCAATAGATGTGCTGCCCCTCAGTCCGTTGATACCTACTTGCTTTATCTGTCTAGCGACTCTATCCACGGAGTGACTAATTCGTAACCATTGACA 5701 CAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAA GTCTGGTTCAAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTT 5801 AATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACG 5901 TTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGA AACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCT 6001 TACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGT ATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCA 6101 GGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGC CCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACG 6201 ACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACA TGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGT 6301 GGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCT CCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGA 6401 CTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGG GACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACC 6501 CCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGA GGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGAAACTCACTCGACTATGGCGAGCGGCGTCGGCTTGCT 6601 CCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGA GGCTCGCGTCGCTCAGTCACTCGCTCCTTCGCCTTCTCGCGGGTTATGCGTTTGGCGGAGAGGGGCGCGCAACCGGCTAAGTAATACGTCGACCGTGCT 6701 CAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCT GTCCAAAGGGCTGACCTTTCGCCCGTCACTCGCGTTGCGTTAATTACACTCAATCGAGTGAGTAATCCGTGGGGTCCGAAATGTGAAATACGAAGGCCGA I-SceI ~~~~~~~~~~~~~~~~~~~~ 6801 CGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTAGGGATAACAGGGTAATCGCCATG GCATACAACACACCTTAACACTCGCCTATTGTTAAAGTGTGTCCTTTGTCGATACTGGTACTAATGCGGTTCGAAATCCCTATTGTCCCATTAGCGGTAC 6901 CATTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAA GTAATCAATAATTATCATTAGTTAATGCCCCAGTAATCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTT pVHentry-Cm5: Esp3I ~~~~~~~ 1 GGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATATACCTGACTGGAATACGACAGCTCCTGCAGCTTCTGGGCGAAGACCACCGTGGCCCATTGCGT CCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTATATGGACTGACCTTATGCTGTCGAGGACGTCGAAGACCCGCTTCTGGTGGCACCGGGTAACGCA 101 ACTTAGCGATAATCTGGTCCGCTTGGAAGTTAGCACGGCGAGCGCGCTCCAGAGCCAAGTCACGCAGCTTAACAGTACCTACCGCAGAGCGGTGCATGAA TGAATCGCTATTAGACCAGGCGAACCTTCAATCGTGCCGCTCGCGCGAGGTCTCGGTTCAGTGCGTCGAATTGTCATGGATGGCGTCTCGCCACGTACTT 201 CAGGCCGATAACGTTGTCCTTAGCAACCTTGACATTACCCTCACCTTTATTGGCAGGGAAGACGTGCTTCTGACCAGTAGTGCCCTCACGAGCGGTACCA GTCCGGCTATTGCAACAGGAATCGTTGGAACTGTAATGGGAGTGGAAATAACCGTCCCTTCTGCACGAAGACTGGTCATCACGGGAGTGCTCGCCATGGT 301 GCACCACCAGCGGTGAGGTGCGGAACTTCTACAACCTCAAAGCCCATAACGTTGCGGATAGAACCCTTCTCAGGGTCAATCAGAGCAGCGTAGTTTGCTG CGTGGTGGTCGCCACTCCACGCCTTGAAGATGTTGGAGTTTCGGGTATTGCAACGCCTATCTTGGGAAGAGTCCCAGTTAGTCTCGTCGCATCAAACGAC 401 CGTTCGGCATCAGTGCTGCCAGAATCGCAGAGTAGCTATCTGGGTCACAGTAGAACACACGGTCAGCAGCCGGAACATAGTTCTTGGTCAGAGCCGCACG GCAAGCCGTAGTCACGACGGTCTTAGCGTCTCATCGATAGACCCAGTGTCATCTTGTGTGCCAGTCGTCGGCCTTGTATCAAGAACCAGTCTCGGCGTGC 501 AGCCTTAGTCAGAGCCGCAATAATCTCCTTACCCAGCGCAACTTGGTCGGTAAGTGCGGCCTTGTTCTGAGTGGTCTCAATTACGGTAGCAGTACCTAAG TCGGAATCAGTCTCGGCGTTATTAGAGGAATGGGTCGCGTTGAACCAGCCATTCACGCCGGAACAAGACTCACCAGAGTTAATGCCATCGTCATGGATTC 601 CCCTCGATGTTCTCATTATATTTGCTTTCCACGTTACACAGACCGGCAATCTCAGCCAGAACCGCACCATCCGCAGCCATCGCCAGAGATTCACCCAACT GGGAGCTACAAGAGTAATATAAACGAAAGGTGCAATGTGTCTGGCCGTTAGAGTCGGTCTTGGCGTGGTAGGCGTCGGTAGCGGTCTCTAAGTGGGTTGA 701 GAGAGGTATACTCAGAGCGAACGTCGTAGTGGTTCATCGCGTCCTCAATATCATAAATCAGAACGTCAGCCGTCAGGAGACCGTCAATGGTGATTACCTT CTCTCCATATGAGTCTCGCTTGCAGCATCACCAAGTAGCGCAGGAGTTATAGTATTTAGTCTTGCAGTCGGCAGTCCTCTGGCAGTTACCACTAATGGAA 801 CTCGGTGTGTTTGATGTCCTTACGTTTATCGTCGAGGTTCTCGCCCGGAGCCAGATACGCTGCCTGAGTGCGACCCAGAACAGGGAACTGAGCGGATTTA GAGCCACACAAACTACAGGAATGCAAATAGCAGCTCCAAGAGCGGGCCTCGGTCTATGCGACGGACTCACGCTGGGTCTTGTCCCTTGACTCGCCTAAAT 901 CCGCTGGAGATGGAACGTACCATGTGGCGAGAAGTGGTCACGGAGGTACGAGCGAACGCAGTCAGGACTTCACCGCCAAATACCTTCAAGAACAACGCCA GGCGACCTCTACCTTGCATGGTACACCGCTCTTCACCAGTGCCTCCATGCTCGCTTGCGTCAGTCCTGAAGTGGCGGTTTATGGAAGTTCTTGTTGCGGT Esp3I ~~~~~ 1001 GTTTATCTCCAGCAGCAACTACACCTTTACCTTGGTTAGTACCCATTTGCTGTCCACCAGTCATGCTAGCCATATGTATATCTCCTTCTTAAAGTCGTCT CAAATAGAGGTCGTCGTTGATGTGGAAATGGAACCAATCATGGGTAAACGACAGGTGGTCAGTACGATCGGTATACATATAGAGGAAGAATTTCAGCAGA Esp3I ~ 1101 CCAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA GGTCACGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGCGGGACGAGGTCCTCGTGGAGGCTCTCGTGTCGCCGGGACCCGACGGACCAGTTCCTGAT 1201 CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC GAAGGGGCTTGGCCACTGCCACAGCACCTTGAGTCCGCGAGACTGGTCGCCGCACGTGTGGAAGGGTCGACAGGATGTCAGGAGTCCTGAGATGAGGGAG 1301 AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG TCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAAC 1401 AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCMAAACCCAAGGA TCGGGTTTAGAACACTGTTTTGAGTGTGTACGGGTGGCACGGGTCGTGGACTTGAGGACCCCCCTGGCAGTCAGAAGGAGAAGGGGGGKTTTGGGTTCCT 1501 CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GTGGGAGTACTAGAGGGCCTGGGGACTCCAGTGTACGCACCACCACCTGCACTCGGTGCTTCTGGGACTCCAGTTCAAGTTGACCATGCACCTGCCGCAC 1601 GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG CTCCACGTATTACGGTTCTGTTTCGGCGCCCTCCTCGTCATGTTGTCGTGCATGGCACACCAGTCGCAGGAGTGGCAGGACGTGGTCCTGACCGACTTAC 1701 GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CGTTCCTCATGTTCACGTTCCAGAGGTTGTTTCGGGAGGGTCGGGGGTAGCTCTTTTGGTAGAGGTTTCGGTTTCCCGTCGGGGCTCTTGGTGTCCACAT 1801 CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG GTGGGACGGGGGTAGGGCCCTACTCGACTGGTTCTTGGTCCAGTCGGACTGGACGGACCAGTTTCCGAAGATAGGGTCGCTGTAGCGGCACCTCACCCTC 1901 AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCA TCGTTACCCGTCGGCCTCTTGTTGATGTTCTGGTGCGGAGGGCACGACCTGAGGCTGCCGAGGAAGAAGGAGATGTCGTTCGAGTGGCACCTGTTCTCGT 2001 GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGC CCACCGTCGTCCCCTTGCAGAAGAGTACGAGGCACTACGTACTCCGAGACGTGTTGGTGATGTGCGTCTTCTCGGAGAGGGACAGAGGCCCATTTACTCG 2101 GGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGG CCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAGGATCC 2201 GGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGA CCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCT 2301 CCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTG GGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCAC 2401 CCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATG GGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAACATAC 2501 GGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTG CCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAAC 2601 AAAAACACGATGATAATATGGCCACCACCCATACCTAGGCTTTTGCAAAGATCGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGG TTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTTCTCTGTCCTACTCCTAGCAAAGCGTACTAACTTGTTCTACC 2701 ATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTG TAACGTGCGTCCAAGAGGCCGGCGAACCCACCTCTCCGATAAGCCGATACTGACCCGTGTTGTCTGTTAGCCGACGAGACTACGGCGGCACAAGGCCGAC 2801 TCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGA AGTCGCGTCCCCGCGGGCCAAGAAAAACAGTTCTGGCTGGACAGGCCACGGGACTTACTTGACGTTCTGCTCCGTCGCGCCGATAGCACCGACCGGTGCT 2901 CGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCA GCCCGCAAGGAACGCGTCGACACGAGCTGCAACAGTGACTTCGCCCTTCCCTGACCGACGATAACCCGCTTCACGGCCCCGTCCTAGAGGACAGTAGAGT 3001 CCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACAT GGAACGAGGACGGCTCTTTCATAGGTAGTACCGACTACGTTACGCCGCCGACGTATGCGAACTAGGCCGATGGACGGGTAAGCTGGTGGTTCGCTTTGTA 3101 CGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCA GCGTAGCTCGCTCGTGCATGAGCCTACCTTCGGCCAGAACAGCTAGTCCTACTAGACCTGCTTCTCGTAGTCCCCGAGCGCGGTCGGCTTGACAAGCGGT 3201 GGCTCAAGGCGAGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATT CCGAGTTCCGCTCGTACGGGCTGCCGCTCCTAGAGCAGCACTGGGTACCGCTACGGACGAACGGCTTATAGTACCACCTTTTACCGGCGAAAAGACCTAA 3301 CATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGC GTAGCTGACACCGGCCGACCCACACCGCCTGGCGATAGTCCTGTATCGCAACCGATGGGCACTATAACGACTTCTCGAACCGCCGCTTACCCGACTGGCG 3401 TTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGGGCC AAGGAGCACGAAATGCCATAGCGGCGAGGGCTAAGCGTCGCGTAGCGGAAGATAGCGGAAGAACTGCTCAAGAAGACTCGCCCTGAGACCCCAAGCCCGG 3501 GCACTCGAGCATAAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCT CGTGAGCTCGTATTTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAAAAAAGTGACGTAAGA I-SceI ~~~~~~~~~~~~~~~~~~~~ 3601 AGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAAGTAGGGATAACAGGGTAATTTTGTTAAATCAGCTCATTTTTTAACCAATAGGAACGCCATCAAA TCAACACCAAACAGGTTTGAGTAGTTACATAGAATTCATCCCTATTGTCCCATTAAAACAATTTAGTCGAGTAAAAAATTGGTTATCCTTGCGGTAGTTT 3701 AATAATTCGCGTCTGGCCTTCCTGTAGCCAGCTTTCATCAACATTAAATGTGAGCGAGTAACAACCCGTCGGATTCTCCGTGGGAACAAACGGCGGATTG TTATTAAGCGCAGACCGGAAGGACATCGGTCGAAAGTAGTTGTAATTTACACTCGCTCATTGTTGGGCAGCCTAAGAGGCACCCTTGTTTGCCGCCTAAC 3801 ACCGTAATGGGATAGGTTACGTTGGTGTAGATGGGCGCATCGTAACCGTGCATCTGCCAGTTTGAGGGGACGACGACCGTATCGGCCTCAGGAAGATCGC TGGCATTACCCTATCCAATGCAACCACATCTACCCGCGTAGCATTGGCACGTAGACGGTCAAACTCCCCTGCTGCTGGCATAGCCGGAGTCCTTCTAGCG 3901 ACTCCAGCCAGCTTTCCGGCACCGCTTCTGGTGCCGGAAACCAGGCAAAGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCG TGAGGTCGGTCGAAAGGCCGTGGCGAAGACCACGGCCTTTGGTCCGTTTCGCGGTAAGCGGTAAGTCCGACGCGTTGACAACCCTTCCCGCTAGCCACGC 4001 GGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACG CCGGAGAAGCGATAATGCGGTCGACCGCTTTCCCCCTACACGACGTTCCGCTAATTCAACCCATTGCGGTCCCAAAAGGGTCAGTGCTGCAACATTTTGC 4101 ACGGCCAGTGAATTGCAATTCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATA TGCCGGTCACTTAACGTTAAGCATTAGTACCAGTATCGACAAAGGACACACTTTAACAATAGGCGAGTGTTAAGGTGTGTTGTATGCTCGGCCTTCGTAT I-SceI ~~~~~~~~~~~~~~~~~~~~ 4201 AAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCATTACCCTGTTATCCCTAGTGAACCATCACCCTAA TTCACATTTCGGACCCCACGGATTACTCACTCGATTGAGTGTAATTAACGCAACGCGAGTGACGGTAATGGGACAATAGGGATCACTTGGTAGTGGGATT 4301 TCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGA AGTTCAAAAAACCCCAGCTCCACGGCATTTCGTGATTTAGCCTTGGGATTTCCCTCGGGGGCTAAATCTCGAACTGCCCCTTTCGGCCGCTTGCACCGCT 4401 GAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCC CTTTCCTTCCCTTCTTTCGCTTTCCTCGCCCGCGATCCCGCGACCGTTCACATCGCCAGTGCGACGCGCATTGGTGGTGTGGGCGGCGCGAATTACGCGG 4501 GCTACAGGGCGCGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGA CGATGTCCCGCGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTACTCT 4601 CAATAACCCTGATAAATGCTTCAATAATAACGACCGGTAATGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCG GTTATTGGGACTATTTACGAAGTTATTATTGCTGGCCATTACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGC 4701 GCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATC CGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTAGCTTGACCTAG 4801 TCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTAT AGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCATAATAGGGCATA 4901 TGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTCTAGCGTTGATCGGCACGTAAGAGGTTCCAACTTTCAC ACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCAGATCGCAACTAGCCGTGCATTCTCCAAGGTTGAAAGTG 5001 CATAATGAAATAAGATCACTACCGGGCGTATTTTTTGAGTTATCGAGATTTTCAGGAGCTAAGGAAGCTAAAATGGAGAAAAAAATCACTGGATATACCA GTATTACTTTATTCTAGTGATGGCCCGCATAAAAAACTCAATAGCTCTAAAAGTCCTCGATTCCTTCGATTTTACCTCTTTTTTTAGTGACCTATATGGT 5101 CCGTTGATATATCCCAATGGCATCGTAAAGAACATTTTGAGGCATTTCAGTCAGTTGCTCAATGTACCTATAACCAGACCGTTCAGCTGGATATTACGGC GGCAACTATATAGGGTTACCGTAGCATTTCTTGTAAAACTCCGTAAAGTCAGTCAACGAGTTACATGGATATTGGTCTGGCAAGTCGACCTATAATGCCG 5201 CTTTTTAAAGACCGTAAAGAAAAATAAGCACAAGTTTTATCCGGCCTTTATTCACATTCTTGCCCGCCTGATGAATGCTCATCCGGAATTCCGTATGGCA GAAAAATTTCTGGCATTTCTTTTTATTCGTGTTCAAAATAGGCCGGAAATAAGTGTAAGAACGGGCGGACTACTTACGAGTAGGCCTTAAGGCATACCGT 5301 ATGAAAGACGGTGAGCTGGTGATATGGGATAGTGTTCACCCTTGTTACACCGTTTTCCATGAGCAAACTGAAACGTTTTCATCGCTCTGGAGTGAATACC TACTTTCTGCCACTCGACCACTATACCCTATCACAAGTGGGAACAATGTGGCAAAAGGTACTCGTTTGACTTTGCAAAAGTAGCGAGACCTCACTTATGG 5401 ACGACGATTTCCGGCAGTTTCTACACATATATTCGCAAGATGTGGCGTGTTACGGTGAAAACCTGGCCTATTTCCCTAAAGGGTTTATTGAGAATATGTT TGCTGCTAAAGGCCGTCAAAGATGTGTATATAAGCGTTCTACACCGCACAATGCCACTTTTGGACCGGATAAAGGGATTTCCCAAATAACTCTTATACAA 5501 TTTCGTATCAGCCAATCCCTGGGTGAGTTTCACCAGTTTTGATTTAAACGTGGCCAATATGGACAACTTCTTCGCCCCCGTTTTCACCATGGGCAAATAT AAAGCATAGTCGGTTAGGGACCCACTCAAAGTGGTCAAAACTAAATTTGCACCGGTTATACCTGTTGAAGAAGCGGGGGCAAAAGTGGTACCCGTTTATA 5601 TATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTCAGGTTCATCATGCCGTCTGTGATGGCTTCCATGTCGGCAGAATGCTTAATGAATTACAAC ATATGCGTTCCGCTGTTCCACGACTACGGCGACCGCTAAGTCCAAGTAGTACGGCAGACACTACCGAAGGTACAGCCGTCTTACGAATTACTTAATGTTG 5701 AGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTAAGGCAGTTATTGGTGCCCTTAAACGCCTGGTGCTACGCCTGAATAAGTGATAATAAGCGG TCATGACGCTACTCACCGTCCCGCCCCGCATTAAAAAAATTCCGTCAATAACCACGGGAATTTGCGGACCACGATGCGGACTTATTCACTATTATTCGCC 5801 ATGAATGGCAGAAATTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGG TACTTACCGTCTTTAAGCTTTACTGGCTGGTTCGCTGCGGGTTGGACGGTAGTGCTCTAAAGCTAAGGTGGCGGCGGAAGATACTTTCCAACCCGAAGCC 5901 TTAGCAAAAGGCCCTGCGGCCGACCTACTAGGAGGTCGCGCCCCTAGAGTACGACCTCAAGAAGCGGGTGGGATCCCCCTCCGATTGACTTTGTGCCTTC GAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGTGTTGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCC 6001 CTCTGTTATGGCCTTCCTTGGGCGCGATACTGCCGTTATTTTTCTGTCTTATTTTGCGTGCCACAACCCAGCAAACAAGTATTTGCGCCCCAAGCCAGGG AGGGCTGGCACTCTGTCGATACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGTTCGGGTGAAGG 6101 TCCCGACCGTGAGACAGCTATGGGGTGGCTCTGGGGTAACCCCGGTTATGCGGGCGCAAAGAAGGAAAAGGGGTGGGGTGGGGGGTTCAAGCCCACTTCC CCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCCTCAGGTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAA 6201 GGGTCCCGAGCGTCGGTTGCAGCCCCGCCGTCCGGGACGGTATCGGAGTCCAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAATTT AGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAG 6301 TCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTC GATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACC 6401 CTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGG AACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTA 6501 TTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACAT GCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTAC 6601 CGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATG CGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCT 6701 GCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGA ATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGA 6801 TACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCT AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACG 6901 TTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGC CCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTAC 7001 GGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATG CGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCC 7101 GCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAATCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTTACCGGGCGG TGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG 7201 ACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTACTGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTTACCCACCTC TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATT 7301 ATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAGTATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGCGGACCGTAA ATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAA 7401 TACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCATGTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGTCATGTAGTT TGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCA 7501 ACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAGGTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGT AAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCT 7601 TTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCATCCGCACATGCCACCCTCCAGATATATTCGTCTCGA pVHentry-GFP1 Esp3I ~~~~~~~ 1 GGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATATACCTGACTGGAATACGACAGCTCCTGCAGCTTCTGGGCGAAGACCACCGTGGCCCATTGCGT CCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTATATGGACTGACCTTATGCTGTCGAGGACGTCGAAGACCCGCTTCTGGTGGCACCGGGTAACGCA 101 ACTTAGCGATAATCTGGTCCGCTTGGAAGTTAGCACGGCGAGCGCGCTCCAGAGCCAAGTCACGCAGCTTAACAGTACCTACCGCAGAGCGGTGCATGAA TGAATCGCTATTAGACCAGGCGAACCTTCAATCGTGCCGCTCGCGCGAGGTCTCGGTTCAGTGCGTCGAATTGTCATGGATGGCGTCTCGCCACGTACTT 201 CAGGCCGATAACGTTGTCCTTAGCAACCTTGACATTACCCTCACCTTTATTGGCAGGGAAGACGTGCTTCTGACCAGTAGTGCCCTCACGAGCGGTACCA GTCCGGCTATTGCAACAGGAATCGTTGGAACTGTAATGGGAGTGGAAATAACCGTCCCTTCTGCACGAAGACTGGTCATCACGGGAGTGCTCGCCATGGT 301 GCACCACCAGCGGTGAGGTGCGGAACTTCTACAACCTCAAAGCCCATAACGTTGCGGATAGAACCCTTCTCAGGGTCAATCAGAGCAGCGTAGTTTGCTG CGTGGTGGTCGCCACTCCACGCCTTGAAGATGTTGGAGTTTCGGGTATTGCAACGCCTATCTTGGGAAGAGTCCCAGTTAGTCTCGTCGCATCAAACGAC 401 CGTTCGGCATCAGTGCTGCCAGAATCGCAGAGTAGCTATCTGGGTCACAGTAGAACACACGGTCAGCAGCCGGAACATAGTTCTTGGTCAGAGCCGCACG GCAAGCCGTAGTCACGACGGTCTTAGCGTCTCATCGATAGACCCAGTGTCATCTTGTGTGCCAGTCGTCGGCCTTGTATCAAGAACCAGTCTCGGCGTGC 501 AGCCTTAGTCAGAGCCGCAATAATCTCCTTACCCAGCGCAACTTGGTCGGTAAGTGCGGCCTTGTTCTGAGTGGTCTCAATTACGGTAGCAGTACCTAAG TCGGAATCAGTCTCGGCGTTATTAGAGGAATGGGTCGCGTTGAACCAGCCATTCACGCCGGAACAAGACTCACCAGAGTTAATGCCATCGTCATGGATTC 601 CCCTCGATGTTCTCATTATATTTGCTTTCCACGTTACACAGACCGGCAATCTCAGCCAGAACCGCACCATCCGCAGCCATCGCCAGAGATTCACCCAACT GGGAGCTACAAGAGTAATATAAACGAAAGGTGCAATGTGTCTGGCCGTTAGAGTCGGTCTTGGCGTGGTAGGCGTCGGTAGCGGTCTCTAAGTGGGTTGA 701 GAGAGGTATACTCAGAGCGAACGTCGTAGTGGTTCATCGCGTCCTCAATATCATAAATCAGAACGTCAGCCGTCAGGAGACCGTCAATGGTGATTACCTT CTCTCCATATGAGTCTCGCTTGCAGCATCACCAAGTAGCGCAGGAGTTATAGTATTTAGTCTTGCAGTCGGCAGTCCTCTGGCAGTTACCACTAATGGAA 801 CTCGGTGTGTTTGATGTCCTTACGTTTATCGTCGAGGTTCTCGCCCGGAGCCAGATACGCTGCCTGAGTGCGACCCAGAACAGGGAACTGAGCGGATTTA GAGCCACACAAACTACAGGAATGCAAATAGCAGCTCCAAGAGCGGGCCTCGGTCTATGCGACGGACTCACGCTGGGTCTTGTCCCTTGACTCGCCTAAAT 901 CCGCTGGAGATGGAACGTACCATGTGGCGAGAAGTGGTCACGGAGGTACGAGCGAACGCAGTCAGGACTTCACCGCCAAATACCTTCAAGAACAACGCCA GGCGACCTCTACCTTGCATGGTACACCGCTCTTCACCAGTGCCTCCATGCTCGCTTGCGTCAGTCCTGAAGTGGCGGTTTATGGAAGTTCTTGTTGCGGT Esp3I ~~~~~ 1001 GTTTATCTCCAGCAGCAACTACACCTTTACCTTGGTTAGTACCCATTTGCTGTCCACCAGTCATGCTAGCCATATGTATATCTCCTTCTTAAAGTCGTCT CAAATAGAGGTCGTCGTTGATGTGGAAATGGAACCAATCATGGGTAAACGACAGGTGGTCAGTACGATCGGTATACATATAGAGGAAGAATTTCAGCAGA Esp3I ~ 1101 CCAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA GGTCACGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGCGGGACGAGGTCCTCGTGGAGGCTCTCGTGTCGCCGGGACCCGACGGACCAGTTCCTGAT 1201 CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC GAAGGGGCTTGGCCACTGCCACAGCACCTTGAGTCCGCGAGACTGGTCGCCGCACGTGTGGAAGGGTCGACAGGATGTCAGGAGTCCTGAGATGAGGGAG 1301 AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG TCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAAC 1401 AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCMAAACCCAAGGA TCGGGTTTAGAACACTGTTTTGAGTGTGTACGGGTGGCACGGGTCGTGGACTTGAGGACCCCCCTGGCAGTCAGAAGGAGAAGGGGGGKTTTGGGTTCCT 1501 CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GTGGGAGTACTAGAGGGCCTGGGGACTCCAGTGTACGCACCACCACCTGCACTCGGTGCTTCTGGGACTCCAGTTCAAGTTGACCATGCACCTGCCGCAC 1601 GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG CTCCACGTATTACGGTTCTGTTTCGGCGCCCTCCTCGTCATGTTGTCGTGCATGGCACACCAGTCGCAGGAGTGGCAGGACGTGGTCCTGACCGACTTAC 1701 GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CGTTCCTCATGTTCACGTTCCAGAGGTTGTTTCGGGAGGGTCGGGGGTAGCTCTTTTGGTAGAGGTTTCGGTTTCCCGTCGGGGCTCTTGGTGTCCACAT 1801 CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG GTGGGACGGGGGTAGGGCCCTACTCGACTGGTTCTTGGTCCAGTCGGACTGGACGGACCAGTTTCCGAAGATGGGGTCGCTGTAGCGGCACCTCACCCTC 1901 AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCA TCGTTACCCGTCGGCCTCTTGTTGATGTTCTGGTGCGGAGGGTACGACCTGAGGCTGCCGAGGAAGAAGGAGATGTCGTTCGAGTGGCACCTGTTCTCGT 2001 GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGGGAG CCACCGTCGTCCCCTTGCAGAAGAGTACGAGGCACTACGTACTCCGAGACGTGTTGGTGATGTGCGTCTTCTCGGAGAGGGACAGAGGCCCATTTCCCTC 2101 CTCGCCAGATAAGTGGTCAGATCCACCGGTCGCCACCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGC GAGCGGTCTATTCACCAGTCTAGGTGGCCAGCGGTGGTACCACTCGTTCCCGCTCCTCGACAAGTGGCCCCACCACGGGTAGGACCAGCTCGACCTGCCG 2201 GACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGC CTGCATTTGCCGGTGTTCAAGTCGCACAGGCCGCTCCCGCTCCCGCTACGGTGGATGCCGTTCGACTGGGACTTCAAGTAGACGTGGTGGCCGTTCGACG 2301 CCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGC GGCACGGGACCGGGTGGGAGCACTGGTGGGACTGGATGCCGCACGTCACGAAGTCGGCGATGGGGCTGGTGTACTTCGTCGTGCTGAAGAAGTTCAGGCG 2401 CATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTG GTACGGGCTTCCGATGCAGGTCCTCGCGTGGTAGAAGAAGTTCCTGCTGCCGTTGATGTTCTGGGCGCGGCTCCACTTCAAGCTCCCGCTGTGGGACCAC 2501 AACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGG TTGGCGTAGCTCGACTTCCCGTAGCTGAAGTTCCTCCTGCCGTTGTAGGACCCCGTGTTCGACCTCATGTTGATGTTGTCGGTGTTGCAGATATAGTACC 2601 CCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCC GGCTGTTCGTCTTCTTGCCGTAGTTCCACTTGAAGTTCTAGGCGGTGTTGTAGCTCCTGCCGTCGCACGTCGAGCGGCTGGTGATGGTCGTCTTGTGGGG 2701 CATCGGCGACGGCCCCGTGCTGCTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG GTAGCCGCTGCCGGGGCACGACGACGGGCTGTTGGTGATGGACTCGTGGGTCAGGCGGGACTCGTTTCTGGGGTTGCTCTTCGCGCTAGTGTACCAGGAC 2801 CTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTAAAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCG GACCTCAAGCACTGGCGGCGGCCCTAGTGAGAGCCGTACCTGCTCGACATGTTCATTTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGC 2901 TCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGA AGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACT 3001 ATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTG TACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCAC 3101 CCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGG GGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACC 3201 CTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTG GAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACAC 3301 TTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAGGC AAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCG 3401 TTTTGCAAAGATCGATCAAGAGACAGGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTA AAAACGTTTCTAGCTAGTTCTCTGTCCTACTCCTAGCAAAGCGTACTAACTTGTTCTACCTAACGTGCGTCCAAGAGGCCGGCGAACCCACCTCTCCGAT 3501 TTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACC AAGCCGATACTGACCCGTGTTGTCTGTTAGCCGACGAGACTACGGCGGCACAAGGCCGACAGTCGCGTCCCCGCGGGCCAAGAAAAACAGTTCTGGCTGG 3601 TGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGA ACAGGCCACGGGACTTACTTGACGTTCTGCTCCGTCGCGCCGATAGCACCGACCGGTGCTGCCCGCAAGGAACGCGTCGACACGAGCTGCAACAGTGACT 3701 AGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCA TCGCCCTTCCCTGACCGACGATAACCCGCTTCACGGCCCCGTCCTAGAGGACAGTAGAGTGGAACGAGGACGGCTCTTTCATAGGTAGTACCGACTACGT 3801 ATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTG TACGCCGCCGACGTATGCGAACTAGGCCGATGGACGGGTAAGCTGGTGGTTCGCTTTGTAGCGTAGCTCGCTCGTGCATGAGCCTACCTTCGGCCAGAAC 3901 TCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGATCTCGTCGT AGCTAGTCCTACTAGACCTGCTTCTCGTAGTCCCCGAGCGCGGTCGGCTTGACAAGCGGTCCGAGTTCCGCTCGTACGGGCTGCCGCTCCTAGAGCAGCA 4001 GACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAG CTGGGTACCGCTACGGACGAACGGCTTATAGTACCACCTTTTACCGGCGAAAAGACCTAAGTAGCTGACACCGGCCGACCCACACCGCCTGGCGATAGTC 4101 GACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGC CTGTATCGCAACCGATGGGCACTATAACGACTTCTCGAACCGCCGCTTACCCGACTGGCGAAGGAGCACGAAATGCCATAGCGGCGAGGGCTAAGCGTCG 4201 GCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTGGGGTTCGGGCCGCACTCGAGCATAAACTTGTTTATTGCAGCTTATAATGGT CGTAGCGGAAGATAGCGGAAGAACTGCTCAAGAAGACTCGCCCTGAGACCCCAAGCCCGGCGTGAGCTCGTATTTGAACAAATAACGTCGAATATTACCA I- SceI ~~~ 4301 TACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAAGTAG ATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAAAAAAGTGACGTAAGATCAACACCAAACAGGTTTGAGTAGTTACATAGAATTCATC I-SceI ~~~~~~~~~~~~~~~~ 4401 GGATAACAGGGTAATTTTGTTAAATCAGCTCATTTTTTAACCAATAGGAACGCCATCAAAAATAATTCGCGTCTGGCCTTCCTGTAGCCAGCTTTCATCA CCTATTGTCCCATTAAAACAATTTAGTCGAGTAAAAAATTGGTTATCCTTGCGGTAGTTTTTATTAAGCGCAGACCGGAAGGACATCGGTCGAAAGTAGT 4501 ACATTAAATGTGAGCGAGTAACAACCCGTCGGATTCTCCGTGGGAACAAACGGCGGATTGACCGTAATGGGATAGGTTACGTTGGTGTAGATGGGCGCAT TGTAATTTACACTCGCTCATTGTTGGGCAGCCTAAGAGGCACCCTTGTTTGCCGCCTAACTGGCATTACCCTATCCAATGCAACCACATCTACCCGCGTA 4601 CGTAACCGTGCATCTGCCAGTTTGAGGGGACGACGACCGTATCGGCCTCAGGAAGATCGCACTCCAGCCAGCTTTCCGGCACCGCTTCTGGTGCCGGAAA GCATTGGCACGTAGACGGTCAAACTCCCCTGCTGCTGGCATAGCCGGAGTCCTTCTAGCGTGAGGTCGGTCGAAAGGCCGTGGCGAAGACCACGGCCTTT 4701 CCAGGCAAAGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGT GGTCCGTTTCGCGGTAAGCGGTAAGTCCGACGCGTTGACAACCCTTCCCGCTAGCCACGCCCGGAGAAGCGATAATGCGGTCGACCGCTTTCCCCCTACA 4801 GCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTGCAATTCGTAATCATGGTCATAGCTG CGACGTTCCGCTAATTCAACCCATTGCGGTCCCAAAAGGGTCAGTGCTGCAACATTTTGCTGCCGGTCACTTAACGTTAAGCATTAGTACCAGTATCGAC 4901 TTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCA AAAGGACACACTTTAACAATAGGCGAGTGTTAAGGTGTGTTGTATGCTCGGCCTTCGTATTTCACATTTCGGACCCCACGGATTACTCACTCGATTGAGT I-SceI ~~~~~~~~~~~~~~~~~~~~ 5001 CATTAATTGCGTTGCGCTCACTGCCATTACCCTGTTATCCCTAGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATC GTAATTAACGCAACGCGAGTGACGGTAATGGGACAATAGGGATCACTTGGTAGTGGGATTAGTTCAAAAAACCCCAGCTCCACGGCATTTCGTGATTTAG 5101 GGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGC CCTTGGGATTTCCCTCGGGGGCTAAATCTCGAACTGCCCCTTTCGGCCGCTTGCACCGCTCTTTCCTTCCCTTCTTTCGCTTTCCTCGCCCGCGATCCCG 5201 GCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCAGGTGGCACTTTTCGGGGAAATGTG CGACCGTTCACATCGCCAGTGCGACGCGCATTGGTGGTGTGGGCGGCGCGAATTACGCGGCGATGTCCCGCGCAGTCCACCGTGAAAAGCCCCTTTACAC 5301 CGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAACGACCGGTAA GCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTACTCTGTTATTGGGACTATTTACGAAGTTATTATTGCTGGCCATT 5401 TGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGG ACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGCCGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACC 5501 TGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGA ACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTAGCTTGACCTAGAGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCT 5601 ACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTAT TGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCATAATAGGGCATAACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATA 5701 TCTCAGAATGACTTGGTTGAGTCTAGCGTTGATCGGCACGTAAGAGGTTCCAACTTTCACCATAATGAAATAAGATCACTACCGGGCGTATTTTTTGAGT AGAGTCTTACTGAACCAACTCAGATCGCAACTAGCCGTGCATTCTCCAAGGTTGAAAGTGGTATTACTTTATTCTAGTGATGGCCCGCATAAAAAACTCA 5801 TATCGAGATTTTCAGGAGCTAAGGAAGCTAAAATGGAGAAAAAAATCACTGGATATACCACCGTTGATATATCCCAATGGCATCGTAAAGAACATTTTGA ATAGCTCTAAAAGTCCTCGATTCCTTCGATTTTACCTCTTTTTTTAGTGACCTATATGGTGGCAACTATATAGGGTTACCGTAGCATTTCTTGTAAAACT 5901 GGCATTTCAGTCAGTTGCTCAATGTACCTATAACCAGACCGTTCAGCTGGATATTACGGCCTTTTTAAAGACCGTAAAGAAAAATAAGCACAAGTTTTAT CCGTAAAGTCAGTCAACGAGTTACATGGATATTGGTCTGGCAAGTCGACCTATAATGCCGGAAAAATTTCTGGCATTTCTTTTTATTCGTGTTCAAAATA 6001 CCGGCCTTTATTCACATTCTTGCCCGCCTGATGAATGCTCATCCGGAATTCCGTATGGCAATGAAAGACGGTGAGCTGGTGATATGGGATAGTGTTCACC GGCCGGAAATAAGTGTAAGAACGGGCGGACTACTTACGAGTAGGCCTTAAGGCATACCGTTACTTTCTGCCACTCGACCACTATACCCTATCACAAGTGG 6101 CTTGTTACACCGTTTTCCATGAGCAAACTGAAACGTTTTCATCGCTCTGGAGTGAATACCACGACGATTTCCGGCAGTTTCTACACATATATTCGCAAGA GAACAATGTGGCAAAAGGTACTCGTTTGACTTTGCAAAAGTAGCGAGACCTCACTTATGGTGCTGCTAAAGGCCGTCAAAGATGTGTATATAAGCGTTCT 6201 TGTGGCGTGTTACGGTGAAAACCTGGCCTATTTCCCTAAAGGGTTTATTGAGAATATGTTTTTCGTATCAGCCAATCCCTGGGTGAGTTTCACCAGTTTT ACACCGCACAATGCCACTTTTGGACCGGATAAAGGGATTTCCCAAATAACTCTTATACAAAAAGCATAGTCGGTTAGGGACCCACTCAAAGTGGTCAAAA 6301 GATTTAAACGTGGCCAATATGGACAACTTCTTCGCCCCCGTTTTCACCATGGGCAAATATTATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTC CTAAATTTGCACCGGTTATACCTGTTGAAGAAGCGGGGGCAAAAGTGGTACCCGTTTATAATATGCGTTCCGCTGTTCCACGACTACGGCGACCGCTAAG 6401 AGGTTCATCATGCCGTCTGTGATGGCTTCCATGTCGGCAGAATGCTTAATGAATTACAACAGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTA TCCAAGTAGTACGGCAGACACTACCGAAGGTACAGCCGTCTTACGAATTACTTAATGTTGTCATGACGCTACTCACCGTCCCGCCCCGCATTAAAAAAAT 6501 AGGCAGTTATTGGTGCCCTTAAACGCCTGGTGCTACGCCTGAATAAGTGATAATAAGCGGATGAATGGCAGAAATTCGAAATGACCGACCAAGCGACGCC TCCGTCAATAACCACGGGAATTTGCGGACCACGATGCGGACTTATTCACTATTATTCGCCTACTTACCGTCTTTAAGCTTTACTGGCTGGTTCGCTGCGG 6601 CAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGC GTTGGACGGTAGTGCTCTAAAGCTAAGGTGGCGGCGGAAGATACTTTCCAACCCGAAGCCTTAGCAAAAGGCCCTGCGGCCGACCTACTAGGAGGTCGCG 6701 GGGGATCTCATGCTGGAGTTCTTCGCCCACCCTAGGGGGAGGCTAACTGAAACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAA CCCCTAGAGTACGACCTCAAGAAGCGGGTGGGATCCCCCTCCGATTGACTTTGTGCCTTCCTCTGTTATGGCCTTCCTTGGGCGCGATACTGCCGTTATT 6801 AAAGACAGAATAAAACGCACGGTGTTGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCGAGACCCCATTG TTTCTGTCTTATTTTGCGTGCCACAACCCAGCAAACAAGTATTTGCGCCCCAAGCCAGGGTCCCGACCGTGAGACAGCTATGGGGTGGCTCTGGGGTAAC 6901 GGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCC CCCGGTTATGCGGGCGCAAAGAAGGAAAAGGGGTGGGGTGGGGGGTTCAAGCCCACTTCCGGGTCCCGAGCGTCGGTTGCAGCCCCGCCGTCCGGGACGG 7001 ATAGCCTCAGGTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCA TATCGGAGTCCAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGT 7101 AAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTG TTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGAC 7201 CTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAG GAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTC 7301 ATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAG TATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTC 7401 TGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG ACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCAC 7501 CACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGAC GTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTG 7601 AGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACC TCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGG 7701 TCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTG AGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGAC 7801 GCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTC CGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAG 7901 ATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATA TAATCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTAT 8001 ATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGT TACTGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACA 8101 ATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCA TAGTATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGT 8201 GTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGT CATGTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCA 8301 CTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCG GAGGTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGC 8401 GTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCT CATCCGCACATGCCACCCTCCAGATATATTCGTCTCGA pVHentry-MLuc7 Esp3I ~~~~~~~ 1 GGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATATACCTGACTGGAATACGACAGCTCCTGCAGCTTCTGGGCGAAGACCACCGTGGCCCATTGCGT CCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTATATGGACTGACCTTATGCTGTCGAGGACGTCGAAGACCCGCTTCTGGTGGCACCGGGTAACGCA 101 ACTTAGCGATAATCTGGTCCGCTTGGAAGTTAGCACGGCGAGCGCGCTCCAGAGCCAAGTCACGCAGCTTAACAGTACCTACCGCAGAGCGGTGCATGAA TGAATCGCTATTAGACCAGGCGAACCTTCAATCGTGCCGCTCGCGCGAGGTCTCGGTTCAGTGCGTCGAATTGTCATGGATGGCGTCTCGCCACGTACTT 201 CAGGCCGATAACGTTGTCCTTAGCAACCTTGACATTACCCTCACCTTTATTGGCAGGGAAGACGTGCTTCTGACCAGTAGTGCCCTCACGAGCGGTACCA GTCCGGCTATTGCAACAGGAATCGTTGGAACTGTAATGGGAGTGGAAATAACCGTCCCTTCTGCACGAAGACTGGTCATCACGGGAGTGCTCGCCATGGT 301 GCACCACCAGCGGTGAGGTGCGGAACTTCTACAACCTCAAAGCCCATAACGTTGCGGATAGAACCCTTCTCAGGGTCAATCAGAGCAGCGTAGTTTGCTG CGTGGTGGTCGCCACTCCACGCCTTGAAGATGTTGGAGTTTCGGGTATTGCAACGCCTATCTTGGGAAGAGTCCCAGTTAGTCTCGTCGCATCAAACGAC 401 CGTTCGGCATCAGTGCTGCCAGAATCGCAGAGTAGCTATCTGGGTCACAGTAGAACACACGGTCAGCAGCCGGAACATAGTTCTTGGTCAGAGCCGCACG GCAAGCCGTAGTCACGACGGTCTTAGCGTCTCATCGATAGACCCAGTGTCATCTTGTGTGCCAGTCGTCGGCCTTGTATCAAGAACCAGTCTCGGCGTGC 501 AGCCTTAGTCAGAGCCGCAATAATCTCCTTACCCAGCGCAACTTGGTCGGTAAGTGCGGCCTTGTTCTGAGTGGTCTCAATTACGGTAGCAGTACCTAAG TCGGAATCAGTCTCGGCGTTATTAGAGGAATGGGTCGCGTTGAACCAGCCATTCACGCCGGAACAAGACTCACCAGAGTTAATGCCATCGTCATGGATTC 601 CCCTCGATGTTCTCATTATATTTGCTTTCCACGTTACACAGACCGGCAATCTCAGCCAGAACCGCACCATCCGCAGCCATCGCCAGAGATTCACCCAACT GGGAGCTACAAGAGTAATATAAACGAAAGGTGCAATGTGTCTGGCCGTTAGAGTCGGTCTTGGCGTGGTAGGCGTCGGTAGCGGTCTCTAAGTGGGTTGA 701 GAGAGGTATACTCAGAGCGAACGTCGTAGTGGTTCATCGCGTCCTCAATATCATAAATCAGAACGTCAGCCGTCAGGAGACCGTCAATGGTGATTACCTT CTCTCCATATGAGTCTCGCTTGCAGCATCACCAAGTAGCGCAGGAGTTATAGTATTTAGTCTTGCAGTCGGCAGTCCTCTGGCAGTTACCACTAATGGAA 801 CTCGGTGTGTTTGATGTCCTTACGTTTATCGTCGAGGTTCTCGCCCGGAGCCAGATACGCTGCCTGAGTGCGACCCAGAACAGGGAACTGAGCGGATTTA GAGCCACACAAACTACAGGAATGCAAATAGCAGCTCCAAGAGCGGGCCTCGGTCTATGCGACGGACTCACGCTGGGTCTTGTCCCTTGACTCGCCTAAAT 901 CCGCTGGAGATGGAACGTACCATGTGGCGAGAAGTGGTCACGGAGGTACGAGCGAACGCAGTCAGGACTTCACCGCCAAATACCTTCAAGAACAACGCCA GGCGACCTCTACCTTGCATGGTACACCGCTCTTCACCAGTGCCTCCATGCTCGCTTGCGTCAGTCCTGAAGTGGCGGTTTATGGAAGTTCTTGTTGCGGT Esp3I ~~~~~ 1001 GTTTATCTCCAGCAGCAACTACACCTTTACCTTGGTTAGTACCCATTTGCTGTCCACCAGTCATGCTAGCCATATGTATATCTCCTTCTTAAAGTCGTCT CAAATAGAGGTCGTCGTTGATGTGGAAATGGAACCAATCATGGGTAAACGACAGGTGGTCAGTACGATCGGTATACATATAGAGGAAGAATTTCAGCAGA Esp3I ~ 1101 CCAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA GGTCACGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGCGGGACGAGGTCCTCGTGGAGGCTCTCGTGTCGCCGGGACCCGACGGACCAGTTCCTGAT 1201 CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC GAAGGGGCTTGGCCACTGCCACAGCACCTTGAGTCCGCGAGACTGGTCGCCGCACGTGTGGAAGGGTCGACAGGATGTCAGGAGTCCTGAGATGAGGGAG 1301 AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG TCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAAC 1401 AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCMAAACCCAAGGA TCGGGTTTAGAACACTGTTTTGAGTGTGTACGGGTGGCACGGGTCGTGGACTTGAGGACCCCCCTGGCAGTCAGAAGGAGAAGGGGGGKTTTGGGTTCCT 1501 CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GTGGGAGTACTAGAGGGCCTGGGGACTCCAGTGTACGCACCACCACCTGCACTCGGTGCTTCTGGGACTCCAGTTCAAGTTGACCATGCACCTGCCGCAC 1601 GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG CTCCACGTATTACGGTTCTGTTTCGGCGCCCTCCTCGTCATGTTGTCGTGCATGGCACACCAGTCGCAGGAGTGGCAGGACGTGGTCCTGACCGACTTAC 1701 GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CGTTCCTCATGTTCACGTTCCAGAGGTTGTTTCGGGAGGGTCGGGGGTAGCTCTTTTGGTAGAGGTTTCGGTTTCCCGTCGGGGCTCTTGGTGTCCACAT 1801 CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG GTGGGACGGGGGTAGGGCCCTACTCGACTGGTTCTTGGTCCAGTCGGACTGGACGGACCAGTTTCCGAAGATGGGGTCGCTGTAGCGGCACCTCACCCTC 1901 AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCA TCGTTACCCGTCGGCCTCTTGTTGATGTTCTGGTGCGGAGGGTACGACCTGAGGCTGCCGAGGAAGAAGGAGATGTCGTTCGAGTGGCACCTGTTCTCGT 2001 GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGGGTA CCACCGTCGTCCCCTTGCAGAAGAGTACGAGGCACTACGTACTCCGAGACGTGTTGGTGATGTGCGTCTTCTCGGAGAGGGACAGAGGCCCATTTCCCAT 2101 CATGTCCCATATGCTCGACATGGCAAGCAGCCTGAGACAGATTCTGGACTCCCAGAAAATGGAGTGGAGGTCCAACGCCGGGGGCAGCGGTAGGGATAAG GTACAGGGTATACGAGCTGTACCGTTCGTCGGACTCTGTCTAAGACCTGAGGGTCTTTTACCTCACCTCCAGGTTGCGGCCCCCGTCGCCATCCCTATTC 2201 TGGTCAGATCTTCGCGACAATTCCAAATCAACTGAGTTCGATCCTAACATTGACATTGTTGGTTTAGAAGGAAAATTTGGTATTACAAACCTAGAAACGG ACCAGTCTAGAAGCGCTGTTAAGGTTTAGTTGACTCAAGCTAGGATTGTAACTGTAACAACCAAATCTTCCTTTTAAACCATAATGTTTGGATCTTTGCC 2301 ATTTATTCACAATCTGGGAGACAATGGAGGTCATGATCAAAGCAGATATTGCAGATACTGATAGAGCCAGCAACTTTGTTGCAACTGAAACCGATGCTAA TAAATAAGTGTTAGACCCTCTGTTACCTCCAGTACTAGTTTCGTCTATAACGTCTATGACTATCTCGGTCGTTGAAACAACGTTGACTTTGGCTACGATT 2401 CCGCGGAAAAATGCCTGGCAAAAAACTGCCACTGGCAGTTATCATGGAAATGGAAGCCAATGCTTTCAAAGCTGGCTGCACCAGGGGATGCCTTATCTGT GGCGCCTTTTTACGGACCGTTTTTTGACGGTGACCGTCAATAGTACCTTTACCTTCGGTTACGAAAGTTTCGACCGACGTGGTCCCCTACGGAATAGACA 2501 CTTTCAAAAATTAAGTGTACAGCCAAAATGAAGGTATACATTCCAGGAAGGTGTCACGATTATGGTGGTGACAAGAAAACTGGACAGGCAGGAATTGTTG GAAAGTTTTTAATTCACATGTCGGTTTTACTTCCATATGTAAGGTCCTTCCACAGTGCTAATACCACCACTGTTCTTTTGACCTGTCCGTCCTTAACAAC 2601 GTGCAATTGTTGACATTCCCGAAATCTCTGGATTTAAGGAGATGGCACCCATGGAACAGTTCATTGCTCAAGTTGATCGCTGCGCTTCCTCACTACTGG CACGTTAACAACTGTAAGGGCTTTAGAGACCTAAATTCCTCTACCGTGGGTACCTTGTCAAGTAACGAGTTCAACTAGCGACGCGAAGGACGTGATGACC 2701 ATGTCTCAAAGGTCTTGCCAATGTTAAGTGCTCTGAACTCCTGAAGAAATGGCTGCCTGACAGGTGTGCAAGTTTTGCTGACAAGATTCAAAAAGAAGTT TACAGAGTTTCCAGAACGGTTACAATTCACGAGACTTGAGGACTTCTTTACCGACGGACTGTCCACACGTTCAAAACGACTGTTCTAAGTTTTTCTTCAA 2801 CACAATATCAAAGGCATGGCCGGCGATCGATGAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGA GTGTTATAGTTTCCGTACCGGCCGCTAGCTACTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCT 2901 AACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCT TTGGACCGGGACAGAAGAACTGCTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGA 3001 GGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTA CCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACAT 3101 TAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGG ATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCC 3201 GGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTA CCGACTTCCTACGGGTCTTCCATGGGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGAT 3301 CGGCCCCCGAACCACGGGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAGGCTTTTGCAAAGATCGATCAAGAGACA CCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTTCTCTGT 3401 GGATGAGGATCGTTTCGCATGATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGA CCTACTCCTAGCAAAGCGTACTAACTTGTTCTACCTAACGTGCGTCCAAGAGGCCGGCGAACCCACCTCTCCGATAAGCCGATACTGACCCGTGTTGTCT 3501 CAATCGGCTGCTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCA GTTAGCCGACGAGACTACGGCGGCACAAGGCCGACAGTCGCGTCCCCGCGGGCCAAGAAAAACAGTTCTGGCTGGACAGGCCACGGGACTTACTTGACGT 3601 AGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTG TCTGCTCCGTCGCGCCGATAGCACCGACCGGTGCTGCCCGCAAGGAACGCGTCGACACGAGCTGCAACAGTGACTTCGCCCTTCCCTGACCGACGATAAC 3701 GGCGAAGTGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATC CCGCTTCACGGCCCCGTCCTAGAGGACAGTAGAGTGGAACGAGGACGGCTCTTTCATAGGTAGTACCGACTACGTTACGCCGCCGACGTATGCGAACTAG 3801 CGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGA GCCGATGGACGGGTAAGCTGGTGGTTCGCTTTGTAGCGTAGCTCGCTCGTGCATGAGCCTACCTTCGGCCAGAACAGCTAGTCCTACTAGACCTGCTTCT 3901 GCATCAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCG CGTAGTCCCCGAGCGCGGTCGGCTTGACAAGCGGTCCGAGTTCCGCTCGTACGGGCTGCCGCTCCTAGAGCAGCACTGGGTACCGCTACGGACGAACGGC 4001 AATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATA TTATAGTACCACCTTTTACCGGCGAAAAGACCTAAGTAGCTGACACCGGCCGACCCACACCGCCTGGCGATAGTCCTGTATCGCAACCGATGGGCACTAT 4101 TTGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGA AACGACTTCTCGAACCGCCGCTTACCCGACTGGCGAAGGAGCACGAAATGCCATAGCGGCGAGGGCTAAGCGTCGCGTAGCGGAAGATAGCGGAAGAACT 4201 CGAGTTCTTCTGAGCGGGACTCTGGGGTTCGGGCCGCACTCGAGCATAAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAA GCTCAAGAAGACTCGCCCTGAGACCCCAAGCCCGGCGTGAGCTCGTATTTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTT I-SceI ~~~~~~~~~~~~~~~~~~~~ 4301 ATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAAGTAGGGATAACAGGGTAATTTTGTTAAAT TAAAGTGTTTATTTCGTAAAAAAAGTGACGTAAGATCAACACCAAACAGGTTTGAGTAGTTACATAGAATTCATCCCTATTGTCCCATTAAAACAATTTA 4401 CAGCTCATTTTTTAACCAATAGGAACGCCATCAAAAATAATTCGCGTCTGGCCTTCCTGTAGCCAGCTTTCATCAACATTAAATGTGAGCGAGTAACAAC GTCGAGTAAAAAATTGGTTATCCTTGCGGTAGTTTTTATTAAGCGCAGACCGGAAGGACATCGGTCGAAAGTAGTTGTAATTTACACTCGCTCATTGTTG 4501 CCGTCGGATTCTCCGTGGGAACAAACGGCGGATTGACCGTAATGGGATAGGTTACGTTGGTGTAGATGGGCGCATCGTAACCGTGCATCTGCCAGTTTGA GGCAGCCTAAGAGGCACCCTTGTTTGCCGCCTAACTGGCATTACCCTATCCAATGCAACCACATCTACCCGCGTAGCATTGGCACGTAGACGGTCAAACT 4601 GGGGACGACGACCGTATCGGCCTCAGGAAGATCGCACTCCAGCCAGCTTTCCGGCACCGCTTCTGGTGCCGGAAACCAGGCAAAGCGCCATTCGCCATTC CCCCTGCTGCTGGCATAGCCGGAGTCCTTCTAGCGTGAGGTCGGTCGAAAGGCCGTGGCGAAGACCACGGCCTTTGGTCCGTTTCGCGGTAAGCGGTAAG 4701 AGGCTGCGCAACTGTTGGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAA TCCGACGCGTTGACAACCCTTCCCGCTAGCCACGCCCGGAGAAGCGATAATGCGGTCGACCGCTTTCCCCCTACACGACGTTCCGCTAATTCAACCCATT 4801 CGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGCCAGTGAATTGCAATTCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGC GCGGTCCCAAAAGGGTCAGTGCTGCAACATTTTGCTGCCGGTCACTTAACGTTAAGCATTAGTACCAGTATCGACAAAGGACACACTTTAACAATAGGCG 4901 TCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCC AGTGTTAAGGTGTGTTGTATGCTCGGCCTTCGTATTTCACATTTCGGACCCCACGGATTACTCACTCGATTGAGTGTAATTAACGCAACGCGAGTGACGG I-SceI ~~~~~~~~~~~~~~~~~~~ 5001 ATTACCCTGTTATCCCTAGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATT TAATGGGACAATAGGGATCACTTGGTAGTGGGATTAGTTCAAAAAACCCCAGCTCCACGGCATTTCGTGATTTAGCCTTGGGATTTCCCTCGGGGGCTAA 5101 TAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTG ATCTCGAACTGCCCCTTTCGGCCGCTTGCACCGCTCTTTCCTTCCCTTCTTTCGCTTTCCTCGCCCGCGATCCCGCGACCGTTCACATCGCCAGTGCGAC 5201 CGCGTAACCACCACACCCGCCGCGCTTAATGCGCCGCTACAGGGCGCGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTT GCGCATTGGTGGTGTGGGCGGCGCGAATTACGCGGCGATGTCCCGCGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAA 5301 TCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAACGACCGGTAATGAAAAAGGAAGAGTATGAGTATTC AGATTTATGTAAGTTTATACATAGGCGAGTACTCTGTTATTGGGACTATTTACGAAGTTATTATTGCTGGCCATTACTTTTTCCTTCTCATACTCATAAG 5401 AACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCA TTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGCCGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGT 5501 GTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTT CAACCCACGTGCTCACCCAATGTAGCTTGACCTAGAGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAA 5601 AAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTCTA TTTCAAGACGATACACCGCGCCATAATAGGGCATAACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCAGAT 5701 GCGTTGATCGGCACGTAAGAGGTTCCAACTTTCACCATAATGAAATAAGATCACTACCGGGCGTATTTTTTGAGTTATCGAGATTTTCAGGAGCTAAGGA CGCAACTAGCCGTGCATTCTCCAAGGTTGAAAGTGGTATTACTTTATTCTAGTGATGGCCCGCATAAAAAACTCAATAGCTCTAAAAGTCCTCGATTCCT 5801 AGCTAAAATGGAGAAAAAAATCACTGGATATACCACCGTTGATATATCCCAATGGCATCGTAAAGAACATTTTGAGGCATTTCAGTCAGTTGCTCAATGT TCGATTTTACCTCTTTTTTTAGTGACCTATATGGTGGCAACTATATAGGGTTACCGTAGCATTTCTTGTAAAACTCCGTAAAGTCAGTCAACGAGTTACA 5901 ACCTATAACCAGACCGTTCAGCTGGATATTACGGCCTTTTTAAAGACCGTAAAGAAAAATAAGCACAAGTTTTATCCGGCCTTTATTCACATTCTTGCCC TGGATATTGGTCTGGCAAGTCGACCTATAATGCCGGAAAAATTTCTGGCATTTCTTTTTATTCGTGTTCAAAATAGGCCGGAAATAAGTGTAAGAACGGG 6001 GCCTGATGAATGCTCATCCGGAATTCCGTATGGCAATGAAAGACGGTGAGCTGGTGATATGGGATAGTGTTCACCCTTGTTACACCGTTTTCCATGAGCA CGGACTACTTACGAGTAGGCCTTAAGGCATACCGTTACTTTCTGCCACTCGACCACTATACCCTATCACAAGTGGGAACAATGTGGCAAAAGGTACTCGT 6101 AACTGAAACGTTTTCATCGCTCTGGAGTGAATACCACGACGATTTCCGGCAGTTTCTACACATATATTCGCAAGATGTGGCGTGTTACGGTGAAAACCTG TTGACTTTGCAAAAGTAGCGAGACCTCACTTATGGTGCTGCTAAAGGCCGTCAAAGATGTGTATATAAGCGTTCTACACCGCACAATGCCACTTTTGGAC 6201 GCCTATTTCCCTAAAGGGTTTATTGAGAATATGTTTTTCGTATCAGCCAATCCCTGGGTGAGTTTCACCAGTTTTGATTTAAACGTGGCCAATATGGACA CGGATAAAGGGATTTCCCAAATAACTCTTATACAAAAAGCATAGTCGGTTAGGGACCCACTCAAAGTGGTCAAAACTAAATTTGCACCGGTTATACCTGT 6301 ACTTCTTCGCCCCCGTTTTCACCATGGGCAAATATTATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTCAGGTTCATCATGCCGTCTGTGATGG TGAAGAAGCGGGGGCAAAAGTGGTACCCGTTTATAATATGCGTTCCGCTGTTCCACGACTACGGCGACCGCTAAGTCCAAGTAGTACGGCAGACACTACC 6401 CTTCCATGTCGGCAGAATGCTTAATGAATTACAACAGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTAAGGCAGTTATTGGTGCCCTTAAACG GAAGGTACAGCCGTCTTACGAATTACTTAATGTTGTCATGACGCTACTCACCGTCCCGCCCCGCATTAAAAAAATTCCGTCAATAACCACGGGAATTTGC 6501 CCTGGTGCTACGCCTGAATAAGTGATAATAAGCGGATGAATGGCAGAAATTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGAT GGACCACGATGCGGACTTATTCACTATTATTCGCCTACTTACCGTCTTTAAGCTTTACTGGCTGGTTCGCTGCGGGTTGGACGGTAGTGCTCTAAAGCTA 6601 TCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCG AGGTGGCGGCGGAAGATACTTTCCAACCCGAAGCCTTAGCAAAAGGCCCTGCGGCCGACCTACTAGGAGGTCGCGCCCCTAGAGTACGACCTCAAGAAGC 6701 CCCACCCTAGGGGGAGGCTAACTGAAACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGTGT GGGTGGGATCCCCCTCCGATTGACTTTGTGCCTTCCTCTGTTATGGCCTTCCTTGGGCGCGATACTGCCGTTATTTTTCTGTCTTATTTTGCGTGCCACA 6801 TGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCC ACCCAGCAAACAAGTATTTGCGCCCCAAGCCAGGGTCCCGACCGTGAGACAGCTATGGGGTGGCTCTGGGGTAACCCCGGTTATGCGGGCGCAAAGAAGG 6901 TTTTCCCCACCCCACCCCCCAAGTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCCTCAGGTTACTCATATATAC AAAAGGGGTGGGGTGGGGGGTTCAAGCCCACTTCCGGGTCCCGAGCGTCGGTTGCAGCCCCGCCGTCCGGGACGGTATCGGAGTCCAATGAGTATATATG 7001 TTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTT AAATCTAACTAAATTTTGAAGTAAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAA 7101 CCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTA GGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGAT 7201 CCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGT GGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACA 7301 AGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTC TCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAG 7401 GTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACG CACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGC 7501 ACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCG TGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGC 7601 GAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTG CTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACAC 7701 ATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCT TACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGA 7801 GCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAG CGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAATCAAGTATCGGGTATATACCTC 7901 TTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGC AAGGCGCAATGTATTGAATGCCATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTACTGCATACAAGGGTATCATTGCG 8001 CAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTAT GTTATCCCTGAAAGGTAACTGCAGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAGTATACGGTTCATGCGGGGGATA 8101 TGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCT ACTGCAGTTACTGCCATTTACCGGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCATGTAGATGCATAATCAGTAGCGA 8201 ATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGA TAATGGTACCACTACGCCAAAACCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAGGTGGGGTAACTGCAGTTACCCT 8301 GTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTA CAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCATCCGCACATGCCACCCTCCAGAT 8401 TATAAGCAGAGCT ATATTCGTCTCGA pVHentry-Hisbio1 Esp3I ~~~~~~~ 1 GGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATATACCTGACTGGAATACGACAGCTCCTGCAGCTTCTGGGCGAAGACCACCGTGGCCCATTGCGT CCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTATATGGACTGACCTTATGCTGTCGAGGACGTCGAAGACCCGCTTCTGGTGGCACCGGGTAACGCA 101 ACTTAGCGATAATCTGGTCCGCTTGGAAGTTAGCACGGCGAGCGCGCTCCAGAGCCAAGTCACGCAGCTTAACAGTACCTACCGCAGAGCGGTGCATGAA TGAATCGCTATTAGACCAGGCGAACCTTCAATCGTGCCGCTCGCGCGAGGTCTCGGTTCAGTGCGTCGAATTGTCATGGATGGCGTCTCGCCACGTACTT 201 CAGGCCGATAACGTTGTCCTTAGCAACCTTGACATTACCCTCACCTTTATTGGCAGGGAAGACGTGCTTCTGACCAGTAGTGCCCTCACGAGCGGTACCA GTCCGGCTATTGCAACAGGAATCGTTGGAACTGTAATGGGAGTGGAAATAACCGTCCCTTCTGCACGAAGACTGGTCATCACGGGAGTGCTCGCCATGGT 301 GCACCACCAGCGGTGAGGTGCGGAACTTCTACAACCTCAAAGCCCATAACGTTGCGGATAGAACCCTTCTCAGGGTCAATCAGAGCAGCGTAGTTTGCTG CGTGGTGGTCGCCACTCCACGCCTTGAAGATGTTGGAGTTTCGGGTATTGCAACGCCTATCTTGGGAAGAGTCCCAGTTAGTCTCGTCGCATCAAACGAC 401 CGTTCGGCATCAGTGCTGCCAGAATCGCAGAGTAGCTATCTGGGTCACAGTAGAACACACGGTCAGCAGCCGGAACATAGTTCTTGGTCAGAGCCGCACG GCAAGCCGTAGTCACGACGGTCTTAGCGTCTCATCGATAGACCCAGTGTCATCTTGTGTGCCAGTCGTCGGCCTTGTATCAAGAACCAGTCTCGGCGTGC 501 AGCCTTAGTCAGAGCCGCAATAATCTCCTTACCCAGCGCAACTTGGTCGGTAAGTGCGGCCTTGTTCTGAGTGGTCTCAATTACGGTAGCAGTACCTAAG TCGGAATCAGTCTCGGCGTTATTAGAGGAATGGGTCGCGTTGAACCAGCCATTCACGCCGGAACAAGACTCACCAGAGTTAATGCCATCGTCATGGATTC 601 CCCTCGATGTTCTCATTATATTTGCTTTCCACGTTACACAGACCGGCAATCTCAGCCAGAACCGCACCATCCGCAGCCATCGCCAGAGATTCACCCAACT GGGAGCTACAAGAGTAATATAAACGAAAGGTGCAATGTGTCTGGCCGTTAGAGTCGGTCTTGGCGTGGTAGGCGTCGGTAGCGGTCTCTAAGTGGGTTGA 701 GAGAGGTATACTCAGAGCGAACGTCGTAGTGGTTCATCGCGTCCTCAATATCATAAATCAGAACGTCAGCCGTCAGGAGACCGTCAATGGTGATTACCTT CTCTCCATATGAGTCTCGCTTGCAGCATCACCAAGTAGCGCAGGAGTTATAGTATTTAGTCTTGCAGTCGGCAGTCCTCTGGCAGTTACCACTAATGGAA 801 CTCGGTGTGTTTGATGTCCTTACGTTTATCGTCGAGGTTCTCGCCCGGAGCCAGATACGCTGCCTGAGTGCGACCCAGAACAGGGAACTGAGCGGATTTA GAGCCACACAAACTACAGGAATGCAAATAGCAGCTCCAAGAGCGGGCCTCGGTCTATGCGACGGACTCACGCTGGGTCTTGTCCCTTGACTCGCCTAAAT 901 CCGCTGGAGATGGAACGTACCATGTGGCGAGAAGTGGTCACGGAGGTACGAGCGAACGCAGTCAGGACTTCACCGCCAAATACCTTCAAGAACAACGCCA GGCGACCTCTACCTTGCATGGTACACCGCTCTTCACCAGTGCCTCCATGCTCGCTTGCGTCAGTCCTGAAGTGGCGGTTTATGGAAGTTCTTGTTGCGGT Esp3I ~~~~~ 1001 GTTTATCTCCAGCAGCAACTACACCTTTACCTTGGTTAGTACCCATTTGCTGTCCACCAGTCATGCTAGCCATATGTATATCTCCTTCTTAAAGTCGTCT CAAATAGAGGTCGTCGTTGATGTGGAAATGGAACCAATCATGGGTAAACGACAGGTGGTCAGTACGATCGGTATACATATAGAGGAAGAATTTCAGCAGA Esp3I ~ 1101 CCAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA GGTCACGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGCGGGACGAGGTCCTCGTGGAGGCTCTCGTGTCGCCGGGACCCGACGGACCAGTTCCTGAT 1201 CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC GAAGGGGCTTGGCCACTGCCACAGCACCTTGAGTCCGCGAGACTGGTCGCCGCACGTGTGGAAGGGTCGACAGGATGTCAGGAGTCCTGAGATGAGGGAG 1301 AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG TCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAAC 1401 AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCMAAACCCAAGGA 1501 TCGGGTTTAGAACACTGTTTTGAGTGTGTACGGGTGGCACGGGTCGTGGACTTGAGGACCCCCCTGGCAGTCAGAAGGAGAAGGGGGGKTTTGGGTTCCT CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG 1601 GTGGGAGTACTAGAGGGCCTGGGGACTCCAGTGTACGCACCACCACCTGCACTCGGTGCTTCTGGGACTCCAGTTCAAGTTGACCATGCACCTGCCGCAC GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG 1701 CTCCACGTATTACGGTTCTGTTTCGGCGCCCTCCTCGTCATGTTGTCGTGCATGGCACACCAGTCGCAGGAGTGGCAGGACGTGGTCCTGACCGACTTAC GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA 1801 CGTTCCTCATGTTCACGTTCCAGAGGTTGTTTCGGGAGGGTCGGGGGTAGCTCTTTTGGTAGAGGTTTCGGTTTCCCGTCGGGGCTCTTGGTGTCCACAT CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG 1901 GTGGGACGGGGGTAGGGCCCTACTCGACTGGTTCTTGGTCCAGTCGGACTGGACGGACCAGTTTCCGAAGATGGGGTCGCTGTAGCGGCACCTCACCCTC AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCA 2001 TCGTTACCCGTCGGCCTCTTGTTGATGTTCTGGTGCGGAGGGTACGACCTGAGGCTGCCGAGGAAGAAGGAGATGTCGTTCGAGTGGCACCTGTTCTCGT GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGGGTA 2101 CCACCGTCGTCCCCTTGCAGAAGAGTACGAGGCACTACGTACTCCGAGACGTGTTGGTGATGTGCGTCTTCTCGGAGAGGGACAGAGGCCCATTTCCCAT CATGTCCCATATGCTCGACATGGCAAGCAGCCTGAGACAGATTCTGGACTCCCAGAAAATGGAGTGGAGGTCCAACGCCGGGGGCAGCGGTAGGGATAAG 2201 GTACAGGGTATACGAGCTGTACCGTTCGTCGGACTCTGTCTAAGACCTGAGGGTCTTTTACCTCACCTCCAGGTTGCGGCCCCCGTCGCCATCCCTATTC TGGTCAGATCTTCGCATGGGCAGCAGCCATCATCATCATCATCACAGCAGCGGCATGGCAAGCAGCCTGAGACAGATTCTGGACTCCCAGAAAATGGAGT ACCAGTCTAGAAGCGTACCCGTCGTCGGTAGTAGTAGTAGTAGTGTCGTCGCCGTACCGTTCGTCGGACTCTGTCTAAGACCTGAGGGTCTTTTACCTCA I-SceI ~~~~~~~~~~~~~~~~~~~~ 2301 GGAGGTCCAACGCCGGGGGCAGCGGTAGGGATAACAGGGTAATCCATATGCTCGAGGGGGCCAAGGCCGCGCCGGCCTGCAGGCATGCAAGCTTGGCGTA CCTCCAGGTTGCGGCCCCCGTCGCCATCCCTATTGTCCCATTAGGTATACGAGCTCCCCCGGTTCCGGCGCGGCCGGACGTCCGTACGTTCGAACCGCAT 2401 ATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAA TAGTACCAGTATCGACAAAGGACACACTTTAACAATAGGCGAGTGTTAAGGTGTGTTGTATGCTCGGCCTTCGTATTTCACATTTCGGACCCCACGGATT 2501 TGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCGAGCTCGAATTGTTGACATTCCCGAAA ACTCACTCGATTGAGTGTAATTAACGCAACGCGAGTGACGGGCGAAAGGTCAGCCCTTTGGACAGCACGGTCGCTCGAGCTTAACAACTGTAAGGGCTTT 2601 TCTCTGGATTTAAGGAGATGGCACCCATGGAACAGTTCATTGCTCAAGTTGATCGCTGCGCTTCCTGCACTACTGGATGTCTCAAAGGTCTTGCCAATGT AGAGACCTAAATTCCTCTACCGTGGGTACCTTGTCAAGTAACGAGTTCAACTAGCGACGCGAAGGACGTGATGACCTACAGAGTTTCCAGAACGGTTACA 2701 TAAGTGCTCTGAACTCCTGAAGAAATGGCTGCCTGACAGGTGTGCAAGTTTTGCTGACAAGATTCAAAAAGAAGTTCACAATATCAAAGGCATGGCCGGC ATTCACGAGACTTGAGGACTTCTTTACCGACGGACTGTCCACACGTTCAAAACGACTGTTCTAAGTTTTTCTTCAAGTGTTATAGTTTCCGTACCGGCCG 2801 GATCGATGAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGA CTAGCTACTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCT 2901 GCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAAC CGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTG 3001 GTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCA CAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGT 3101 CAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTAC GTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATG 3201 CCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTG GGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCAC 3301 GTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAGGCTTTTGCAAAGATCGATCAAGAGACAGGATGAGGATCGTTTCGCATGATT CAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTTCTCTGTCCTACTCCTAGCAAAGCGTACTAA 3401 GAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCCG CTTGTTCTACCTAACGTGCGTCCAAGAGGCCGGCGAACCCACCTCTCCGATAAGCCGATACTGACCCGTGTTGTCTGTTAGCCGACGAGACTACGGCGGC 3501 TGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATCGTG ACAAGGCCGACAGTCGCGTCCCCGCGGGCCAAGAAAAACAGTTCTGGCTGGACAGGCCACGGGACTTACTTGACGTTCTGCTCCGTCGCGCCGATAGCAC 3601 GCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATCTC CGACCGGTGCTGCCCGCAAGGAACGCGTCGACACGAGCTGCAACAGTGACTTCGCCCTTCCCTGACCGACGATAACCCGCTTCACGGCCCCGTCCTAGAG 3701 CTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACC GACAGTAGAGTGGAACGAGGACGGCTCTTTCATAGGTAGTACCGACTACGTTACGCCGCCGACGTATGCGAACTAGGCCGATGGACGGGTAAGCTGGTGG 3801 AAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCCGA TTCGCTTTGTAGCGTAGCTCGCTCGTGCATGAGCCTACCTTCGGCCAGAACAGCTAGTCCTACTAGACCTGCTTCTCGTAGTCCCCGAGCGCGGTCGGCT 3901 ACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGC TGACAAGCGGTCCGAGTTCCGCTCGTACGGGCTGCCGCTCCTAGAGCAGCACTGGGTACCGCTACGGACGAACGGCTTATAGTACCACCTTTTACCGGCG 4001 TTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGAAT AAAAGACCTAAGTAGCTGACACCGGCCGACCCACACCGCCTGGCGATAGTCCTGTATCGCAACCGATGGGCACTATAACGACTTCTCGAACCGCCGCTTA 4101 GGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTCTG CCCGACTGGCGAAGGAGCACGAAATGCCATAGCGGCGAGGGCTAAGCGTCGCGTAGCGGAAGATAGCGGAAGAACTGCTCAAGAAGACTCGCCCTGAGAC 4201 GGGTTCGGGCCGCACTCGAGCATAAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTT CCCAAGCCCGGCGTGAGCTCGTATTTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAAAAAA I-SceI ~~~~~~~~~~~~~~~~~~~~ 4301 CACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAAGTAGGGATAACAGGGTAATTTTGTTAAATCAGCTCATTTTTTAACCAATAGGA GTGACGTAAGATCAACACCAAACAGGTTTGAGTAGTTACATAGAATTCATCCCTATTGTCCCATTAAAACAATTTAGTCGAGTAAAAAATTGGTTATCCT 4401 ACGCCATCAAAAATAATTCGCGTCTGGCCTTCCTGTAGCCAGCTTTCATCAACATTAAATGTGAGCGAGTAACAACCCGTCGGATTCTCCGTGGGAACAA TGCGGTAGTTTTTATTAAGCGCAGACCGGAAGGACATCGGTCGAAAGTAGTTGTAATTTACACTCGCTCATTGTTGGGCAGCCTAAGAGGCACCCTTGTT 4501 ACGGCGGATTGACCGTAATGGGATAGGTTACGTTGGTGTAGATGGGCGCATCGTAACCGTGCATCTGCCAGTTTGAGGGGACGACGACCGTATCGGCCTC TGCCGCCTAACTGGCATTACCCTATCCAATGCAACCACATCTACCCGCGTAGCATTGGCACGTAGACGGTCAAACTCCCCTGCTGCTGGCATAGCCGGAG 4601 AGGAAGATCGCACTCCAGCCAGCTTTCCGGCACCGCTTCTGGTGCCGGAAACCAGGCAAAGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGG TCCTTCTAGCGTGAGGTCGGTCGAAAGGCCGTGGCGAAGACCACGGCCTTTGGTCCGTTTCGCGGTAAGCGGTAAGTCCGACGCGTTGACAACCCTTCCC 4701 CGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGAC GCTAGCCACGCCCGGAGAAGCGATAATGCGGTCGACCGCTTTCCCCCTACACGACGTTCCGCTAATTCAACCCATTGCGGTCCCAAAAGGGTCAGTGCTG 4801 GTTGTAAAACGACGGCCAGTGAATTGCAATTCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAG CAACATTTTGCTGCCGGTCACTTAACGTTAAGCATTAGTACCAGTATCGACAAAGGACACACTTTAACAATAGGCGAGTGTTAAGGTGTGTTGTATGCTC 4901 CCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCATTACCCTGTTATCCCTAGTGAAC GGCCTTCGTATTTCACATTTCGGACCCCACGGATTACTCACTCGATTGAGTGTAATTAACGCAACGCGAGTGACGGTAATGGGACAATAGGGATCACTTG 5001 CATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCGGC GTAGTGGGATTAGTTCAAAAAACCCCAGCTCCACGGCATTTCGTGATTTAGCCTTGGGATTTCCCTCGGGGGCTAAATCTCGAACTGCCCCTTTCGGCCG 5101 GAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCG CTTGCACCGCTCTTTCCTTCCCTTCTTTCGCTTTCCTCGCCCGCGATCCCGCGACCGTTCACATCGCCAGTGCGACGCGCATTGGTGGTGTGGGCGGCGC 5201 CTTAATGCGCCGCTACAGGGCGCGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATC GAATTACGCGGCGATGTCCCGCGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAG 5301 CGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAACGACCGGTAATGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTC GCGAGTACTCTGTTATTGGGACTATTTACGAAGTTATTATTGCTGGCCATTACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAG 5401 CCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACAT GGAAAAAACGCCGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTA 5501 CGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTA GCTTGACCTAGAGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCAT 5601 TTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTCTAGCGTTGATCGGCACGTAAGAGGTT AATAGGGCATAACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCAGATCGCAACTAGCCGTGCATTCTCCAA 5701 CCAACTTTCACCATAATGAAATAAGATCACTACCGGGCGTATTTTTTGAGTTATCGAGATTTTCAGGAGCTAAGGAAGCTAAAATGGAGAAAAAAATCAC GGTTGAAAGTGGTATTACTTTATTCTAGTGATGGCCCGCATAAAAAACTCAATAGCTCTAAAAGTCCTCGATTCCTTCGATTTTACCTCTTTTTTTAGTG 5801 TGGATATACCACCGTTGATATATCCCAATGGCATCGTAAAGAACATTTTGAGGCATTTCAGTCAGTTGCTCAATGTACCTATAACCAGACCGTTCAGCTG ACCTATATGGTGGCAACTATATAGGGTTACCGTAGCATTTCTTGTAAAACTCCGTAAAGTCAGTCAACGAGTTACATGGATATTGGTCTGGCAAGTCGAC 5901 GATATTACGGCCTTTTTAAAGACCGTAAAGAAAAATAAGCACAAGTTTTATCCGGCCTTTATTCACATTCTTGCCCGCCTGATGAATGCTCATCCGGAAT CTATAATGCCGGAAAAATTTCTGGCATTTCTTTTTATTCGTGTTCAAAATAGGCCGGAAATAAGTGTAAGAACGGGCGGACTACTTACGAGTAGGCCTTA 6001 TCCGTATGGCAATGAAAGACGGTGAGCTGGTGATATGGGATAGTGTTCACCCTTGTTACACCGTTTTCCATGAGCAAACTGAAACGTTTTCATCGCTCTG AGGCATACCGTTACTTTCTGCCACTCGACCACTATACCCTATCACAAGTGGGAACAATGTGGCAAAAGGTACTCGTTTGACTTTGCAAAAGTAGCGAGAC 6101 GAGTGAATACCACGACGATTTCCGGCAGTTTCTACACATATATTCGCAAGATGTGGCGTGTTACGGTGAAAACCTGGCCTATTTCCCTAAAGGGTTTATT CTCACTTATGGTGCTGCTAAAGGCCGTCAAAGATGTGTATATAAGCGTTCTACACCGCACAATGCCACTTTTGGACCGGATAAAGGGATTTCCCAAATAA 6201 GAGAATATGTTTTTCGTATCAGCCAATCCCTGGGTGAGTTTCACCAGTTTTGATTTAAACGTGGCCAATATGGACAACTTCTTCGCCCCCGTTTTCACCA CTCTTATACAAAAAGCATAGTCGGTTAGGGACCCACTCAAAGTGGTCAAAACTAAATTTGCACCGGTTATACCTGTTGAAGAAGCGGGGGCAAAAGTGGT 6301 TGGGCAAATATTATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTCAGGTTCATCATGCCGTCTGTGATGGCTTCCATGTCGGCAGAATGCTTAA ACCCGTTTATAATATGCGTTCCGCTGTTCCACGACTACGGCGACCGCTAAGTCCAAGTAGTACGGCAGACACTACCGAAGGTACAGCCGTCTTACGAATT 6401 TGAATTACAACAGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTAAGGCAGTTATTGGTGCCCTTAAACGCCTGGTGCTACGCCTGAATAAGTG ACTTAATGTTGTCATGACGCTACTCACCGTCCCGCCCCGCATTAAAAAAATTCCGTCAATAACCACGGGAATTTGCGGACCACGATGCGGACTTATTCAC 6501 ATAATAAGCGGATGAATGGCAGAAATTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGG TATTATTCGCCTACTTACCGTCTTTAAGCTTTACTGGCTGGTTCGCTGCGGGTTGGACGGTAGTGCTCTAAAGCTAAGGTGGCGGCGGAAGATACTTTCC 6601 TTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCTAGGGGGAGGCTAACTG AACCCGAAGCCTTAGCAAAAGGCCCTGCGGCCGACCTACTAGGAGGTCGCGCCCCTAGAGTACGACCTCAAGAAGCGGGTGGGATCCCCCTCCGATTGAC 6701 AAACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGTGTTGGGTCGTTTGTTCATAAACGCGG TTTGTGCCTTCCTCTGTTATGGCCTTCCTTGGGCGCGATACTGCCGTTATTTTTCTGTCTTATTTTGCGTGCCACAACCCAGCAAACAAGTATTTGCGCC 6801 GGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGT CCAAGCCAGGGTCCCGACCGTGAGACAGCTATGGGGTGGCTCTGGGGTAACCCCGGTTATGCGGGCGCAAAGAAGGAAAAGGGGTGGGGTGGGGGGTTCA 6901 TCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCCTCAGGTTACTCATATATACTTTAGATTGATTTAAAACTTCATT AGCCCACTTCCGGGTCCCGAGCGTCGGTTGCAGCCCCGCCGTCCGGGACGGTATCGGAGTCCAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAA 7001 TTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGA AAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCT 7101 AAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGAT TTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTA 7201 CAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCA GTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGT 7301 AGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAG TCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTC 7401 ACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTA TGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGAT 7501 CAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC GTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCG 7601 TTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCT AAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGA 7701 ATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGAT TACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTA 7801 AACCGTATTACCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTA TTGGCATAATGGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAATCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCAT 7901 AATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTC TTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTACTGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAG 8001 AATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCC TTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAGTATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGG 8101 CGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGG GCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCATGTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACC 8201 CAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAAC GTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAGGTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTG 8301 GGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCT CCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCATCCGCACATGCCACCCTCCAGATATATTCGTCTCGA pVHentry-CBD1 Esp3I ~~~~~~~ 1 GGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATATACCTGACTGGAATACGACAGCTCCTGCAGCTTCTGGGCGAAGACCACCGTGGCCCATTGCGT CCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTATATGGACTGACCTTATGCTGTCGAGGACGTCGAAGACCCGCTTCTGGTGGCACCGGGTAACGCA 101 ACTTAGCGATAATCTGGTCCGCTTGGAAGTTAGCACGGCGAGCGCGCTCCAGAGCCAAGTCACGCAGCTTAACAGTACCTACCGCAGAGCGGTGCATGAA TGAATCGCTATTAGACCAGGCGAACCTTCAATCGTGCCGCTCGCGCGAGGTCTCGGTTCAGTGCGTCGAATTGTCATGGATGGCGTCTCGCCACGTACTT 201 CAGGCCGATAACGTTGTCCTTAGCAACCTTGACATTACCCTCACCTTTATTGGCAGGGAAGACGTGCTTCTGACCAGTAGTGCCCTCACGAGCGGTACCA GTCCGGCTATTGCAACAGGAATCGTTGGAACTGTAATGGGAGTGGAAATAACCGTCCCTTCTGCACGAAGACTGGTCATCACGGGAGTGCTCGCCATGGT 301 GCACCACCAGCGGTGAGGTGCGGAACTTCTACAACCTCAAAGCCCATAACGTTGCGGATAGAACCCTTCTCAGGGTCAATCAGAGCAGCGTAGTTTGCTG CGTGGTGGTCGCCACTCCACGCCTTGAAGATGTTGGAGTTTCGGGTATTGCAACGCCTATCTTGGGAAGAGTCCCAGTTAGTCTCGTCGCATCAAACGAC 401 CGTTCGGCATCAGTGCTGCCAGAATCGCAGAGTAGCTATCTGGGTCACAGTAGAACACACGGTCAGCAGCCGGAACATAGTTCTTGGTCAGAGCCGCACG GCAAGCCGTAGTCACGACGGTCTTAGCGTCTCATCGATAGACCCAGTGTCATCTTGTGTGCCAGTCGTCGGCCTTGTATCAAGAACCAGTCTCGGCGTGC 501 AGCCTTAGTCAGAGCCGCAATAATCTCCTTACCCAGCGCAACTTGGTCGGTAAGTGCGGCCTTGTTCTGAGTGGTCTCAATTACGGTAGCAGTACCTAAG TCGGAATCAGTCTCGGCGTTATTAGAGGAATGGGTCGCGTTGAACCAGCCATTCACGCCGGAACAAGACTCACCAGAGTTAATGCCATCGTCATGGATTC 601 CCCTCGATGTTCTCATTATATTTGCTTTCCACGTTACACAGACCGGCAATCTCAGCCAGAACCGCACCATCCGCAGCCATCGCCAGAGATTCACCCAACT GGGAGCTACAAGAGTAATATAAACGAAAGGTGCAATGTGTCTGGCCGTTAGAGTCGGTCTTGGCGTGGTAGGCGTCGGTAGCGGTCTCTAAGTGGGTTGA 701 GAGAGGTATACTCAGAGCGAACGTCGTAGTGGTTCATCGCGTCCTCAATATCATAAATCAGAACGTCAGCCGTCAGGAGACCGTCAATGGTGATTACCTT CTCTCCATATGAGTCTCGCTTGCAGCATCACCAAGTAGCGCAGGAGTTATAGTATTTAGTCTTGCAGTCGGCAGTCCTCTGGCAGTTACCACTAATGGAA 801 CTCGGTGTGTTTGATGTCCTTACGTTTATCGTCGAGGTTCTCGCCCGGAGCCAGATACGCTGCCTGAGTGCGACCCAGAACAGGGAACTGAGCGGATTTA GAGCCACACAAACTACAGGAATGCAAATAGCAGCTCCAAGAGCGGGCCTCGGTCTATGCGACGGACTCACGCTGGGTCTTGTCCCTTGACTCGCCTAAAT 901 CCGCTGGAGATGGAACGTACCATGTGGCGAGAAGTGGTCACGGAGGTACGAGCGAACGCAGTCAGGACTTCACCGCCAAATACCTTCAAGAACAACGCCA GGCGACCTCTACCTTGCATGGTACACCGCTCTTCACCAGTGCCTCCATGCTCGCTTGCGTCAGTCCTGAAGTGGCGGTTTATGGAAGTTCTTGTTGCGGT Esp3I ~~~~~ 1001 GTTTATCTCCAGCAGCAACTACACCTTTACCTTGGTTAGTACCCATTTGCTGTCCACCAGTCATGCTAGCCATATGTATATCTCCTTCTTAAAGTCGTCT CAAATAGAGGTCGTCGTTGATGTGGAAATGGAACCAATCATGGGTAAACGACAGGTGGTCAGTACGATCGGTATACATATAGAGGAAGAATTTCAGCAGA Esp3I ~ 1101 CCAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA GGTCACGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGCGGGACGAGGTCCTCGTGGAGGCTCTCGTGTCGCCGGGACCCGACGGACCAGTTCCTGAT 1201 CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC GAAGGGGCTTGGCCACTGCCACAGCACCTTGAGTCCGCGAGACTGGTCGCCGCACGTGTGGAAGGGTCGACAGGATGTCAGGAGTCCTGAGATGAGGGAG 1301 AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTG TCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAAC 1401 AGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCMAAACCCAAGGA TCGGGTTTAGAACACTGTTTTGAGTGTGTACGGGTGGCACGGGTCGTGGACTTGAGGACCCCCCTGGCAGTCAGAAGGAGAAGGGGGGKTTTGGGTTCCT 1501 CACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GTGGGAGTACTAGAGGGCCTGGGGACTCCAGTGTACGCACCACCACCTGCACTCGGTGCTTCTGGGACTCCAGTTCAAGTTGACCATGCACCTGCCGCAC 1601 GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATG CTCCACGTATTACGGTTCTGTTTCGGCGCCCTCCTCGTCATGTTGTCGTGCATGGCACACCAGTCGCAGGAGTGGCAGGACGTGGTCCTGACCGACTTAC 1701 GCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CGTTCCTCATGTTCACGTTCCAGAGGTTGTTTCGGGAGGGTCGGGGGTAGCTCTTTTGGTAGAGGTTTCGGTTTCCCGTCGGGGCTCTTGGTGTCCACAT 1801 CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAG GTGGGACGGGGGTAGGGCCCTACTCGACTGGTTCTTGGTCCAGTCGGACTGGACGGACCAGTTTCCGAAGATGGGGTCGCTGTAGCGGCACCTCACCCTC 1901 AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCA TCGTTACCCGTCGGCCTCTTGTTGATGTTCTGGTGCGGAGGGTACGACCTGAGGCTGCCGAGGAAGAAGGAGATGTCGTTCGAGTGGCACCTGTTCTCGT 2001 GGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGGGTA CCACCGTCGTCCCCTTGCAGAAGAGTACGAGGCACTACGTACTCCGAGACGTGTTGGTGATGTGCGTCTTCTCGGAGAGGGACAGAGGCCCATTTCCCAT 2101 CATGTCCCATATGCTCGACATGGCAAGCAGCCTGAGACAGATTCTGGACTCCCAGAAAATGGAGTGGAGGTCCAACGCCGGGGGCAGCGGTAGGGATAAG GTACAGGGTATACGAGCTGTACCGTTCGTCGGACTCTGTCTAAGACCTGAGGGTCTTTTACCTCACCTCCAGGTTGCGGCCCCCGTCGCCATCCCTATTC 2201 TGGTCAGATCTGGTACCGCGGGCGGCGACCAGCAGCATGAGCGTGGAATTTTATAACAGCAACAAAAGCGCGCAGACCAACAGCATTACCCCGATTATTA ACCAGTCTAGACCATGGCGCCCGCCGCTGGTCGTCGTACTCGCACCTTAAAATATTGTCGTTGTTTTCGCGCGTCTGGTTGTCGTAATGGGGCTAATAAT 2301 AAATTACCAACACCAGCGATAGCGATCTGAACCTGAACGATGTGAAAGTGCGCTATTATTATACCAGCGATGGCACCCAGGGCCAGACCTTTTGGTGCGA TTTAATGGTTGTGGTCGCTATCGCTAGACTTGGACTTGCTACACTTTCACGCGATAATAATATGGTCGCTACCGTGGGTCCCGGTCTGGAAAACCACGCT 2401 TCATGCGGGCGCGCTGCTGGGCAACAGCTATGTGGATAACACCAGCAAAGTGACCGCGAACTTTGTGAAAGAAACCGCGAGCCCGACCAGCACCTATGAT AGTACGCCCGCGCGACGACCCGTTGTCGATACACCTATTGTGGTCGTTTCACTGGCGCTTGAAACACTTTCTTTGGCGCTCGGGCTGGTCGTGGATACTA 2501 ACCTATGTGGAATTTGGCTTTGCGAGTGGCCGCGCGACCCTGAAAAAAGGCCAGTTTATTACCATTCAGGGCCGCATTACCAAAAGCGATTGGAGCAACT TGGATACACCTTAAACCGAAACGCTCACCGGCGCGCTGGGACTTTTTTCCGGTCAAATAATGGTAAGTCCCGGCGTAATGGTTTTCGCTAACCTCGTTGA 2601 ATACCCAGACCAACGATTATAGCTTTGATGCGAGCAGCAGCACCCCGGTGGTGAACCCGAAAGTGACCGGCTATATTGGCGGCGCGAAAGTGCTGGGCAC TATGGGTCTGGTTGCTAATATCGAAACTACGCTCGTCGTCGTGGGGCCACCACTTGGGCTTTCACTGGCCGATATAACCGCCGCGCTTTCACGACCCGTG 2701 CGCGCCGTAAAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGAC GCGCGGCATTTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTG 2801 GAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACA CTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGT 2901 ACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGG TGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCC 3001 CACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGT GTGTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCA 3101 ACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACG TGGGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGC 3201 TGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAGGCTTTTGCAAAGATCGATCAAGAGACAGGATGAGGATCGTTTCGCATGA ACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTTCTCTGTCCTACTCCTAGCAAAGCGTACT 3301 TTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGC AACTTGTTCTACCTAACGTGCGTCCAAGAGGCCGGCGAACCCACCTCTCCGATAAGCCGATACTGACCCGTGTTGTCTGTTAGCCGACGAGACTACGGCG 3401 CGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTGAATGAACTGCAAGACGAGGCAGCGCGGCTATCG GCACAAGGCCGACAGTCGCGTCCCCGCGGGCCAAGAAAAACAGTTCTGGCTGGACAGGCCACGGGACTTACTTGACGTTCTGCTCCGTCGCGCCGATAGC 3501 TGGCTGGCCACGACGGGCGTTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGATC ACCGACCGGTGCTGCCCGCAAGGAACGCGTCGACACGAGCTGCAACAGTGACTTCGCCCTTCCCTGACCGACGATAACCCGCTTCACGGCCCCGTCCTAG 3601 TCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCA AGGACAGTAGAGTGGAACGAGGACGGCTCTTTCATAGGTAGTACCGACTACGTTACGCCGCCGACGTATGCGAACTAGGCCGATGGACGGGTAAGCTGGT 3701 CCAAGCGAAACATCGCATCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCGCCAGCC GGTTCGCTTTGTAGCGTAGCTCGCTCGTGCATGAGCCTACCTTCGGCCAGAACAGCTAGTCCTACTAGACCTGCTTCTCGTAGTCCCCGAGCGCGGTCGG 3801 GAACTGTTCGCCAGGCTCAAGGCGAGCATGCCCGACGGCGAGGATCTCGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCC CTTGACAAGCGGTCCGAGTTCCGCTCGTACGGGCTGCCGCTCCTAGAGCAGCACTGGGTACCGCTACGGACGAACGGCTTATAGTACCACCTTTTACCGG 3901 GCTTTTCTGGATTCATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCTTGGCGGCGA CGAAAAGACCTAAGTAGCTGACACCGGCCGACCCACACCGCCTGGCGATAGTCCTGTATCGCAACCGATGGGCACTATAACGACTTCTCGAACCGCCGCT 4001 ATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGCGGGACTC TACCCGACTGGCGAAGGAGCACGAAATGCCATAGCGGCGAGGGCTAAGCGTCGCGTAGCGGAAGATAGCGGAAGAACTGCTCAAGAAGACTCGCCCTGAG 4101 TGGGGTTCGGGCCGCACTCGAGCATAAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTT ACCCCAAGCCCGGCGTGAGCTCGTATTTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAAAA I-SceI ~~~~~~~~~~~~~~~~~~~ 4201 TTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAAGTAGGGATAACAGGGTAATTTTGTTAAATCAGCTCATTTTTTAACCAATAG AAGTGACGTAAGATCAACACCAAACAGGTTTGAGTAGTTACATAGAATTCATCCCTATTGTCCCATTAAAACAATTTAGTCGAGTAAAAAATTGGTTATC 4301 GAACGCCATCAAAAATAATTCGCGTCTGGCCTTCCTGTAGCCAGCTTTCATCAACATTAAATGTGAGCGAGTAACAACCCGTCGGATTCTCCGTGGGAAC CTTGCGGTAGTTTTTATTAAGCGCAGACCGGAAGGACATCGGTCGAAAGTAGTTGTAATTTACACTCGCTCATTGTTGGGCAGCCTAAGAGGCACCCTTG 4401 AAACGGCGGATTGACCGTAATGGGATAGGTTACGTTGGTGTAGATGGGCGCATCGTAACCGTGCATCTGCCAGTTTGAGGGGACGACGACCGTATCGGCC TTTGCCGCCTAACTGGCATTACCCTATCCAATGCAACCACATCTACCCGCGTAGCATTGGCACGTAGACGGTCAAACTCCCCTGCTGCTGGCATAGCCGG 4501 TCAGGAAGATCGCACTCCAGCCAGCTTTCCGGCACCGCTTCTGGTGCCGGAAACCAGGCAAAGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAG AGTCCTTCTAGCGTGAGGTCGGTCGAAAGGCCGTGGCGAAGACCACGGCCTTTGGTCCGTTTCGCGGTAAGCGGTAAGTCCGACGCGTTGACAACCCTTC 4601 GGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACG CCGCTAGCCACGCCCGGAGAAGCGATAATGCGGTCGACCGCTTTCCCCCTACACGACGTTCCGCTAATTCAACCCATTGCGGTCCCAAAAGGGTCAGTGC 4701 ACGTTGTAAAACGACGGCCAGTGAATTGCAATTCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACG TGCAACATTTTGCTGCCGGTCACTTAACGTTAAGCATTAGTACCAGTATCGACAAAGGACACACTTTAACAATAGGCGAGTGTTAAGGTGTGTTGTATGC I-SceI ~~~~~~~~~~~~~~~~~~~~ 4801 AGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCATTACCCTGTTATCCCTAGTGA TCGGCCTTCGTATTTCACATTTCGGACCCCACGGATTACTCACTCGATTGAGTGTAATTAACGCAACGCGAGTGACGGTAATGGGACAATAGGGATCACT 4901 ACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCCG TGGTAGTGGGATTAGTTCAAAAAACCCCAGCTCCACGGCATTTCGTGATTTAGCCTTGGGATTTCCCTCGGGGGCTAAATCTCGAACTGCCCCTTTCGGC 5001 GCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCG CGCTTGCACCGCTCTTTCCTTCCCTTCTTTCGCTTTCCTCGCCCGCGATCCCGCGACCGTTCACATCGCCAGTGCGACGCGCATTGGTGGTGTGGGCGGC 5101 CGCTTAATGCGCCGCTACAGGGCGCGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA GCGAATTACGCGGCGATGTCCCGCGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACAT 5201 TCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAACGACCGGTAATGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTAT AGGCGAGTACTCTGTTATTGGGACTATTTACGAAGTTATTATTGCTGGCCATTACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATA 5301 TCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTAC AGGGAAAAAACGCCGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATG 5401 ATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGG TAGCTTGACCTAGAGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCC 5501 TATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTCTAGCGTTGATCGGCACGTAAGAGG ATAATAGGGCATAACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCAGATCGCAACTAGCCGTGCATTCTCC 5601 TTCCAACTTTCACCATAATGAAATAAGATCACTACCGGGCGTATTTTTTGAGTTATCGAGATTTTCAGGAGCTAAGGAAGCTAAAATGGAGAAAAAAATC AAGGTTGAAAGTGGTATTACTTTATTCTAGTGATGGCCCGCATAAAAAACTCAATAGCTCTAAAAGTCCTCGATTCCTTCGATTTTACCTCTTTTTTTAG 5701 ACTGGATATACCACCGTTGATATATCCCAATGGCATCGTAAAGAACATTTTGAGGCATTTCAGTCAGTTGCTCAATGTACCTATAACCAGACCGTTCAGC TGACCTATATGGTGGCAACTATATAGGGTTACCGTAGCATTTCTTGTAAAACTCCGTAAAGTCAGTCAACGAGTTACATGGATATTGGTCTGGCAAGTCG 5801 TGGATATTACGGCCTTTTTAAAGACCGTAAAGAAAAATAAGCACAAGTTTTATCCGGCCTTTATTCACATTCTTGCCCGCCTGATGAATGCTCATCCGGA ACCTATAATGCCGGAAAAATTTCTGGCATTTCTTTTTATTCGTGTTCAAAATAGGCCGGAAATAAGTGTAAGAACGGGCGGACTACTTACGAGTAGGCCT 5901 ATTCCGTATGGCAATGAAAGACGGTGAGCTGGTGATATGGGATAGTGTTCACCCTTGTTACACCGTTTTCCATGAGCAAACTGAAACGTTTTCATCGCTC TAAGGCATACCGTTACTTTCTGCCACTCGACCACTATACCCTATCACAAGTGGGAACAATGTGGCAAAAGGTACTCGTTTGACTTTGCAAAAGTAGCGAG 6001 TGGAGTGAATACCACGACGATTTCCGGCAGTTTCTACACATATATTCGCAAGATGTGGCGTGTTACGGTGAAAACCTGGCCTATTTCCCTAAAGGGTTTA ACCTCACTTATGGTGCTGCTAAAGGCCGTCAAAGATGTGTATATAAGCGTTCTACACCGCACAATGCCACTTTTGGACCGGATAAAGGGATTTCCCAAAT 6101 TTGAGAATATGTTTTTCGTATCAGCCAATCCCTGGGTGAGTTTCACCAGTTTTGATTTAAACGTGGCCAATATGGACAACTTCTTCGCCCCCGTTTTCAC AACTCTTATACAAAAAGCATAGTCGGTTAGGGACCCACTCAAAGTGGTCAAAACTAAATTTGCACCGGTTATACCTGTTGAAGAAGCGGGGGCAAAAGTG 6201 CATGGGCAAATATTATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTCAGGTTCATCATGCCGTCTGTGATGGCTTCCATGTCGGCAGAATGCTT GTACCCGTTTATAATATGCGTTCCGCTGTTCCACGACTACGGCGACCGCTAAGTCCAAGTAGTACGGCAGACACTACCGAAGGTACAGCCGTCTTACGAA 6301 AATGAATTACAACAGTACTGCGATGAGTGGCAGGGCGGGGCGTAATTTTTTTAAGGCAGTTATTGGTGCCCTTAAACGCCTGGTGCTACGCCTGAATAAG TTACTTAATGTTGTCATGACGCTACTCACCGTCCCGCCCCGCATTAAAAAAATTCCGTCAATAACCACGGGAATTTGCGGACCACGATGCGGACTTATTC 6401 TGATAATAAGCGGATGAATGGCAGAAATTCGAAATGACCGACCAAGCGACGCCCAACCTGCCATCACGAGATTTCGATTCCACCGCCGCCTTCTATGAAA ACTATTATTCGCCTACTTACCGTCTTTAAGCTTTACTGGCTGGTTCGCTGCGGGTTGGACGGTAGTGCTCTAAAGCTAAGGTGGCGGCGGAAGATACTTT 6501 GGTTGGGCTTCGGAATCGTTTTCCGGGACGCCGGCTGGATGATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCTAGGGGGAGGCTAAC CCAACCCGAAGCCTTAGCAAAAGGCCCTGCGGCCGACCTACTAGGAGGTCGCGCCCCTAGAGTACGACCTCAAGAAGCGGGTGGGATCCCCCTCCGATTG 6601 TGAAACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGTGTTGGGTCGTTTGTTCATAAACGC ACTTTGTGCCTTCCTCTGTTATGGCCTTCCTTGGGCGCGATACTGCCGTTATTTTTCTGTCTTATTTTGCGTGCCACAACCCAGCAAACAAGTATTTGCG 6701 GGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAA CCCCAAGCCAGGGTCCCGACCGTGAGACAGCTATGGGGTGGCTCTGGGGTAACCCCGGTTATGCGGGCGCAAAGAAGGAAAAGGGGTGGGGTGGGGGGTT 6801 GTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCCTCAGGTTACTCATATATACTTTAGATTGATTTAAAACTTCA CAAGCCCACTTCCGGGTCCCGAGCGTCGGTTGCAGCCCCGCCGTCCGGGACGGTATCGGAGTCCAATGAGTATATATGAAATCTAACTAAATTTTGAAGT 6901 TTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTA AAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCAT 7001 GAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGG CTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCC 7201 ATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTT TAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAA 7301 CAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCA GTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGT 7401 AGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACC TCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGG 7501 TACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGA ATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCT 7601 GCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGC CGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCG 7801 CTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGG GATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACC 7901 ATAACCGTATTACCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGG TATTGGCATAATGGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAATCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCC 8001 TAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACG ATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTACTGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGC 8101 TCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGG AGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAGTATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACC 8201 CCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTT GGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCATGTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAA 8301 GGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCA CCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAGGTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGT 8401 ACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCT TGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCATCCGCACATGCCACCCTCCAGATATATTCGTCTCGA

(85) TABLE-US-00004 APPENDIX2 Sequencesofclonedlightchains(SEQIDNOs:59-75,inorderofappearance).

(86) TABLE-US-00005 APPENDIX3 Alignmentofsequencesofclonedvariabledomainsofheavychains(SEQIDNOs:76-87, inorderofappearance).

(87) TABLE-US-00006 APPENDIX4 SequencesofplasmidsencodingspAG-MLucandspAG-N-MLuchybrids(SEQIDNOs:88-90,inorderofappearance). pETspAG-N-MLucl 1 GGAAAAATGCCTGGCAAAAAACTGCCACTGGCAGTTATCATGGAAATGGAAGCCAATGCTTTCAAAGCTGGCTGCACCAGGGGATGCCTTATCTGTCTTT CCTTTTTACGGACCGTTTTTTGACGGTGACCGTCAATAGTACCTTTACCTTCGGTTACGAAAGTTTCGACCGACGTGGTCCCCTACGGAATAGACAGAAA 101 CAAAAATTAAGTGTACAGCCAAAATGAAGGTATACATTCCAGGAAGGTGTCACGATTATGGTGGTGACAAGAAAACTGGACAGGCAGGAATTGTTGGTGC GTTTTTAATTCACATGTCGGTTTTACTTCCATATGTAAGGTCCTTCCACAGTGCTAATACCACCACTGTTCTTTTGACCTGTCCGTCCTTAACAACCACG 201 AATTGTTGACATTCCCGAAATCTCTGGATTTAAGGAGATGGCACCCATGGAACAGTTCATTGCTCAAGTTGATCGCTGCGCTTCCTGCACTACTGGATGT TTAACAACTGTAAGGGCTTTAGAGACCTAAATTCCTCTACCGTGGGTACCTTGTCAAGTAACGAGTTCAACTAGCGACGCGAAGGACGTGATGACCTACA 301 CTCAAAGGTCTTGCCAATGTTAAGTGCTCTGAACTCCTGAAGAAATGGCTGCCTGACAGGTGTGCAAGTTTTGCTGACAAGATTCAAAAAGAAGTTCACA GAGTTTCCAGAACGGTTACAATTCACGAGACTTGAGGACTTCTTTACCGACGGACTGTCCACACGTTCAAAACGACTGTTCTAAGTTTTTCTTCAAGTGT 401 ATATCAAAGGCATGGCCGTACAGCTGCAGGTCGAGCACCACCACCACCACCACTGAGATCCGGCTGCTAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGC TATAGTTTCCGTACCGGCATGTCGACGTCCAGCTCGTGGTGGTGGTGGTGGTGACTCTAGGCCGACGATTGTTTCGGGCTTTCCTTCGACTCAACCGACG 501 TGCCACCGCTGAGCAATAACTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGAAAGGAGGAACTATATCCGGATTGGCGAAT ACGGTGGCGACTCGTTATTGATCGTATTGGGGAACCCCGGAGATTTGCCCAGAACTCCCCAAAAAACGACTTTCCTCCTTGATATAGGCCTAACCGCTTA 601 GGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGC CCCTGCGCGGGACATCGCCGCGTAATTCGCGCCGCCCACACCACCAATGCGCGTCGCACTGGCGATGTGAACGGTCGCGGGATCGCGGGCGAGGAAAGCG 701 TTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTC AAAGAAGGGAAGGAAAGAGCGGTGCAAGCGGCCGAAAGGGGCAGTTCGAGATTTAGCCCCCGAGGGAAATCCCAAGGCTAAATCACGAAATGCCGTGGAG 801 GACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATA CTGGGGTTTTTTGAACTAATCCCACTACCAAGTGCATCACCCGGTAGCGGGACTATCTGCCAAAAAGCGGGAAACTGCAACCTCAGGTGCAAGAAATTAT 901 GTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAA CACCTGAGAACAAGGTTTGACCTTGTTGTGAGTTGGGATAGAGCCAGATAAGAAAACTAAATATTCCCTAAAACGGCTAAAGCCGGATAACCAATTTTTT 1001 TGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATT ACTCGACTAAATTGTTTTTAAATTGCGCTTAAAATTGTTTTATAATTGCAAATGTTAAAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAA 1101 TGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAATTAATTCTTAGAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCA ACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTACTTAATTAAGAATCTTTTTGAGTAGCTCGTAGTTTACTTTGACGTTAAATAAGTATAGT 1201 GGATTATCAATACCATATTTTTGAAAAAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAAGATCCTGGTATCGGTCTG CCTAATAGTTATGGTATAAAAACTTTTTCGGCAAAGACATTACTTCCTCTTTTGAGTGGCTCCGTCAAGGTATCCTACCGTTCTAGGACCATAGCCAGAC 1301 CGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAAAATAAGGTTATCAAGTGAGAAATCACCATGAGTGACGACTGAATCCGG GCTAAGGCTGAGCAGGTTGTAGTTATGTTGGATAATTAAAGGGGAGCAGTTTTTATTCCAATAGTTCACTCTTTAGTGGTACTCACTGCTGACTTAGGCC 1401 TGAGAATGGCAAAAGTTTATGCATTTCTTTCCAGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAACCGTTATTC ACTCTTACCGTTTTCAAATACGTAAAGAAAGGTCTGAACAAGTTGTCCGGTCGGTAATGCGAGCAGTAGTTTTAGTGAGCGTAGTTGGTTTGGCAATAAG 1501 ATTCGTGATTGCGCCTGAGCGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTACAAACAGGAATCGAATGCAACCGGCGCAGGAACACTGCCAGCG TAAGCACTAACGCGGACTCGCTCTGCTTTATGCGCTAGCGACAATTTTCCTGTTAATGTTTGTCCTTAGCTTACGTTGGCCGCGTCCTTGTGACGGTCGC 1601 CATCAACAATATTTTCACCTGAATCAGGATATTCTTCTAATACCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGT GTAGTTGTTATAAAAGTGGACTTAGTCCTATAAGAAGATTATGGACCTTACGACAAAAGGGCCCCTAGCGTCACCACTCATTGGTACGTAGTAGTCCTCA 1701 ACGGATAAAATGCTTGATGGTCGGAAGAGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGTAACATCATTGGCAACGCTACCTTTGCCA TGCCTATTTTACGAACTACCAGCCTTCTCCGTATTTAAGGCAGTCGGTCAAATCAGACTGGTAGAGTAGACATTGTAGTAACCGTTGCGATGGAAACGGT 1801 TGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAATCGATAGATTGTCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATATA ACAAAGTCTTTGTTGAGACCGCGTAGCCCGAAGGGTATGTTAGCTATCTAACAGCGTGGACTAACGGGCTGTAATAGCGCTCGGGTAAATATGGGTATAT 1901 AATCAGCATCCATGTTGGAATTTAATCGCGGCCTAGAGCAAGACGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTATTACTGTTTATGTAAGCAGA TTAGTCGTAGGTACAACCTTAAATTAGCGCCGGATCTCGTTCTGCAAAGGGCAACTTATACCGAGTATTGTGGGGAACATAATGACAAATACATTCGTCT 2001 CAGTTTTATTGTTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTT GTCAAAATAACAAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAA 2101 TTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTA AAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCAT 2201 ACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCG TGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGC 2301 CTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTC GAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAG 2401 GGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTT CCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAA 2501 CCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATA GGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATAT 2601 GTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTT CAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAA 2701 ACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGAT TGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGAAACTCACTCGACTA 2801 ACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTA TGGCGAGCGGCGTCGGCTTGCTGGCTCGCGTCGCTCAGTCACTCGCTCCTTCGCCTTCTCGCGGACTACGCCATAAAAGAGGAATGCGTAGACACGCCAT 2901 TTTCACACCGCATATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATACACTCCGCTATCGCTACGTGACTGGGTCATGG AAAGTGTGGCGTATATACCACGTGAGAGTCATGTTAGACGAGACTACGGCGTATCAATTCGGTCATATGTGAGGCGATAGCGATGCACTGACCCAGTACC 3001 CTGCGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTG GACGCGGGGCTGTGGGCGGTTGTGGGCGACTGCGCGGGACTGCCCGAACAGACGAGGGCCGTAGGCGAATGTCTGTTCGACACTGGCAGAGGCCCTCGAC 3101 CATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGAGGCAGCTGCGGTAAAGCTCATCAGCGTGGTCGTGAAGCGATTCACAGATGTCTGCCTGT GTACACAGTCTCCAAAAGTGGCAGTAGTGGCTTTGCGCGCTCCGTCGACGCCATTTCGAGTAGTCGCACCAGCACTTCGCTAAGTGTCTACAGACGGACA 3201 TCATCCGCGTCCAGCTCGTTGAGTTTCTCCAGAAGCGTTAATGTCTGGCTTCTGATAAAGCGGGCCATGTTAAGGGCGGTTTTTTCCTGTTTGGTCACTG AGTAGGCGCAGGTCGAGCAACTCAAAGAGGTCTTCGCAATTACAGACCGAAGACTATTTCGCCCGGTACAATTCCCGCCAAAAAAGGACAAACCAGTGAC 3301 ATGCCTCCGTGTAAGGGGGATTTCTGTTCATGGGGGTAATGATACCGATGAAACGAGAGAGGATGCTCACGATACGGGTTACTGATGATGAACATGCCCG TACGGAGGCACATTCCCCCTAAAGACAAGTACCCCCATTACTATGGCTACTTTGCTCTCTCCTACGAGTGCTATGCCCAATGACTACTACTTGTACGGGC 3401 GTTACTGGAACGTTGTGAGGGTAAACAACTGGCGGTATGGATGCGGCGGGACCAGAGAAAAATCACTCAGGGTCAATGCCAGCGCTTCGTTAATACAGAT CAATGACCTTGCAACACTCCCATTTGTTGACCGCCATACCTACGCCGCCCTGGTCTCTTTTTAGTGAGTCCCAGTTACGGTCGCGAAGCAATTATGTCTA 3501 GTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCGATGCAGATCCGGAACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACAC CATCCACAAGGTGTCCCATCGGTCGTCGTAGGACGCTACGTCTAGGCCTTGTATTACCACGTCCCGCGACTGAAGGCGCAAAGGTCTGAAATGCTTTGTG 3601 GGAAACCGAAGACCATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTTCACGTTCGCTCGCGTATCGGTGATTCATTCTGCTAACC CCTTTGGCTTCTGGTAAGTACAACAACGAGTCCAGCGTCTGCAAAACGTCGTCGTCAGCGAAGTGCAAGCGAGCGCATAGCCACTAAGTAAGACGATTGG 3701 AGTAAGGCAACCCCGCCAGCCTAGCCGGGTCCTCAACGACAGGAGCACGATCATGCGCACCCGTGGGGCCGCCATGCCGGCGATAATGGCCTGCTTCTCG TCATTCCGTTGGGGCGGTCGGATCGGCCCAGGAGTTGCTGTCCTCGTGCTAGTACGCGTGGGCACCCCGGCGGTACGGCCGCTATTACCGGACGAAGAGC 3801 CCGAAACGTTTGGTGGCGGGACCAGTGACGAAGGCTTGAGCGAGGGCGTGCAAGATTCCGAATACCGCAAGCGACAGGCCGATCATCGTCGCGCTCCAGC GGCTTTGCAAACCACCGCCCTGGTCACTGCTTCCGAACTCGCTCCCGCACGTTCTAAGGCTTATGGCGTTCGCTGTCCGGCTAGTAGCAGCGCGAGGTCG 3901 GAAAGCGGTCCTCGCCGAAAATGACCCAGAGCGCTGCCGGCACCTGTCCTACGAGTTGCATGATAAAGAAGACAGTCATAAGTGCGGCGACGATAGTCAT CTTTCGCCAGGAGCGGCTTTTACTGGGTCTCGCGACGGCCGTGGACAGGATGCTCAACGTACTATTTCTTCTGTCAGTATTCACGCCGCTGCTATCAGTA 4001 GCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGAAGGCTCTCAAGGGCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCG CGGGGCGCGGGTGGCCTTCCTCGACTGACCCAACTTCCGAGAGTTCCCGTAGCCAGCTCTAGGGCCACGGATTACTCACTCGATTGAATGTAATTAACGC 4101 TTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCC AACGCGAGTGACGGGCGAAAGGTCAGCCCTTTGGACAGCACGGTCGACGTAATTACTTAGCCGGTTGCGCGCCCCTCTCCGCCAAACGCATAACCCGCGG 4201 AGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCAACAGCTGATTGCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCC TCCCACCAAAAAGAAAAGTGGTCACTCTGCCCGTTGTCGACTAACGGGAAGTGGCGGACCGGGACTCTCTCAACGTCGTTCGCCAGGTGCGACCAAACGG 4301 CCAGCAGGCGAAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGTATCGTCGTATCCCACTACCGAGATATCCGCACCAAC GGTCGTCCGCTTTTAGGACAAACTACCACCAATTGCCGCCCTATATTGTACTCGACAGAAGCCATAGCAGCATAGGGTGATGGCTCTATAGGCGTGGTTG 4401 GCGCAGCCCGGACTCGGTAATGGCGCGCATTGCGCCCAGCGCCATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGC CGCGTCGGGCCTGAGCCATTACCGCGCGTAACGCGGGTCGCGGTAGACTAGCAACCGTTGGTCGTAGCGTCACCCTTGCTACGGGAGTAAGTCGTAAACG 4501 ATGGTTTGTTGAAAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGCGAGTGAGATATTTATGCCAGCCAGCCAGAC TACCAAACAACTTTTGGCCTGTACCGTGAGGTCAGCGGAAGGGCAAGGCGATAGCCGACTTAAACTAACGCTCACTCTATAAATACGGTCGGTCGGTCTG 4601 GCAGACGCGCCGAGACAGAACTTAATGGGCCCGCTAACAGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTACCGTCTTC CGTCTGCGCGGCTCTGTCTTGAATTACCCGGGCGATTGTCGCGCTAAACGACCACTGGGTTACGCTGGTCTACGAGGTGCGGGTCAGCGCATGGCAGAAG 4701 ATGGGAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCGGAACATTAGTGCAGGCAGCTTCCACAGCAATGGCATCCTGG TACCCTCTTTTATTATGACAACTACCCACAGACCAGTCTCTGTAGTTCTTTATTGCGGCCTTGTAATCACGTCCGTCGAAGGTGTCGTTACCGTAGGACC 4801 TCATCCAGCGGATAGTTAATGATCAGCCCACTGACGCGTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGTTCTACCATCG AGTAGGTCGCCTATCAATTACTAGTCGGGTGACTGCGCAACGCGCTCTTCTAACACGTGGCGGCGAAATGTCCGAAGCTGCGGCGAAGCAAGATGGTAGC 4901 ACACCACCACGCTGGCACCCAGTTGATCGGCGCGAGATTTAATCGCCGCGACAATTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCAACGCCAAT TGTGGTGGTGCGACCGTGGGTCAACTAGCCGCGCTCTAAATTAGCGGCGCTGTTAAACGCTGCCGCGCACGTCCCGGTCTGACCTCCACCGTTGCGGTTA 5001 CAGCAACGACTGTTTGCCCGCCAGTTGTTGTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCACTTTTTCCCGCGTTTTCGCAGAA GTCGTTGCTGACAAACGGGCGGTCAACAACACGGTGCGCCAACCCTTACATTAAGTCGAGGCGGTAGCGGCGAAGGTGAAAAAGGGCGCAAAAGCGTCTT 5101 ACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGACACCGGCATACTCTGCGACATCGTATAACGTTACTGGTTTCACATTCACCACCC TGCACCGACCGGACCAAGTGGTGCGCCCTTTGCCAGACTATTCTCTGTGGCCGTATGAGACGCTGTAGCATATTGCAATGACCAAAGTGTAAGTGGTGGG 5201 TGAATTGACTCTCTTCCGGGCGCTATCATGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATCTCGACGCTCTCCCTTATGCGACTCCT ACTTAACTGAGAGAAGGCCCGCGATAGTACGGTATGGCGCTTTCCAAAACGCGGTAAGCTACCACAGGCCCTAGAGCTGCGAGAGGGAATACGCTGAGGA 5301 GCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTGAGCACCGCCGCCGCAAGGAATGGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCAC CGTAATCCTTCGTCGGGTCATCATCCAACTCCGGCAACTCGTGGCGGCGGCGTTCCTTACCACGTACGTTCCTCTACCGCGGGTTGTCAGGGGGCCGGTG 5401 GGGGCCTGCCACCATACCCACGCCGAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTCCCCATCGGTGATGTCGGCGATATAGGCGCCAGCA CCCCGGACGGTGGTATGGGTGCGGCTTTGTTCGCGAGTACTCGGGCTTCACCGCTCGGGCTAGAAGGGGTAGCCACTACAGCCGCTATATCCGCGGTCGT 5501 ACCGCACCTGTGGCGCCGGTGATGCCGGCCACGATGCGTCCGGCGTAGAGGATCGAGATCTCGATCCCGCGAAATTAATACGACTCACTATAGGGGAATT TGGCGTGGACACCGCGGCCACTACGGCCGGTGCTACGCAGGCCGCATCTCCTAGCTCTAGAGCTAGGGCGCTTTAATTATGCTGAGTGATATCCCCTTAA 5601 GTGAGCGGATAACAATTCCCCTCTAGAAATAATTTTGTTTAACTTTAAGAAGGAGATATACCATGGGCAGCAGCCATCATCATCATCATCACAGCAGCGG CACTCGCCTATTGTTAAGGGGAGATCTTTATTAAAACAAATTGAAATTCTTCCTCTATATGGTACCCGTCGTCGGTAGTAGTAGTAGTAGTGTCGTCGCC 5701 CCTGGTGCCGCGCGGCAGCCATAGGTCGACTCTAGAGGATCCAAGCCAAAGCACTAACGTTTTAGGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCG GGACCACGGCGCGCCGTCGGTATCCAGCTGAGATCTCCTAGGTTCGGTTTCGTGATTGCAAAATCCACTTCGATTTTTTAATTTGCTTAGAGTTCGTGGC 5801 AAAGCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAACTTGAACGAAGAACAACGCAATGGTTTCATCCAAA TTTCGACTGTTGTTAAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAGAACTTGTACGGATTGAACTTGCTTCTTGTTGCGTTACCAAAGTAGGTTT 5901 GCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTTTTAGCAGAAGCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCTGATAACAAATTCAACAAAGA CGAATTTTCTACTGGGTTCAGTTTCACGATTGGAAAATCGTCTTCGATTTTTCAATTTACTTAGAGTTCGTGGCTTTCGACTATTGTTTAAGTTGTTTCT 6001 ACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAATGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGC TGTTGTTTTACGAAAGATACTTTAGAATGTAAATGGATTGAATTTACTTCTTGTTGCGTTACCAAAGTAGGTTTCGAATTTTCTACTGGGTTCGGTTTCG 6101 GCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATTT CGATTGGAAAATCGTCTTCGATTTTTCGATTTACTACGTGTTCGTGGTTTTCGACTGTTGTTTAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAAA 6201 TACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCCCGGTCGACTCTAGCGGCAGCTTCCGGTGCTAGCAC ATGTAAATGGATTGAATTGACTTCTTGTTGCATTGCCGAAGTAGGTTTCGGAATTTCTGCTAGGGGCCAGCTGAGATCGCCGTCGAAGGCCACGATCGTG 6301 TGACACTTACAAATTAATCCTTAATGGTAAAACATTGAAAGGCGAAACAACTACTGAAGCTGTTGATGCTGCTACTGCAGAAAAAGTCTTCAAACAATAC ACTGTGAATGTTTAATTAGGAATTACCATTTTGTAACTTTCCGCTTTGTTGATGACTTCGACAACTACGACGATGACGTCTTTTTCAGAAGTTTGTTATG 6401 GCTAACGACAACGGTGTTGACGGTGAATGGACTTACGACGATGCGACTAAGACCTTTACAGTTACTGAAAAACCAGAAGTGATCGATGCGTCTGAATTAA CGATTGCTGTTGCCACAACTGCCACTTACCTGAATGCTGCTACGCTGATTCTGGAAATGTCAATGACTTTTTGGTCTTCACTAGCTACGCAGACTTAATT 6501 CACCAGCCGTGACAACTTACAAACTTGTTATTAATGGTAAAACATTGAAAGGCGAAACAACTACTAAAGCAGTAGACGCAGAAACTGCAGAAAAAGCCTT GTGGTCGGCACTGTTGAATGTTTGAACAATAATTACCATTTTGTAACTTTCCGCTTTGTTGATGATTTCGTCATCTGCGTCTTTGACGTCTTTTTCGGAA 6601 CAAACAATACGCTAACGACAACGGTGTTGATGGTGTTTGGACTTATGATGATGCGACTAAGACCTTTACGGTAACTGAAATGGTTACAGAGGTACCAGAT GTTTGTTATGCGATTGCTGTTGCCACAACTACCACAAACCTGAATACTACTACGCTGATTCTGGAAATGCCATTGACTTTACCAATGTCTCCATGGTCTA 6701 CTTAGCAACTTTGTTGCAACTGAAACCGATGCTAACCGC GAATCGTTGAAACAACGTTGACTTTGGCTACGATTGGCG pS14L-spAG-MLuc16 1 AGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAA TCGCGGGTTATGCGTTTGGCGGAGAGGGGCGCGCAACCGGCTAAGTAATTACGTCGACCGTGCTGTCCAAAGGGCTGACCTTTCGCCCGTCACTCGCGTT 101 CGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTT GCGTTAATTACACTCAATCGAGTGAGTAATCCGTGGGGTCCGAAATGTGAAATACGAAGGCCGAGCATACAACACACCTTAACACTCGCCTATTGTTAAA 201 CACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTAGGGATAACAGGGTAATCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATT GTGTGTCCTTTGTCGATACTGGTACTAATGCGGTTCGAAATCCCTATTGTCCCATTAGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAA 301 AGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATG TCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTAC 401 ACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATC TGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAG 501 ATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTA TATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCAT 601 CATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC GTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAG 701 CACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTA GTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCAT 801 GGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTGGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATTTAGGCATGGAAACCCCAGCGCAGCTTCT CCGCACATGCCACCCTCCAGATATATTCGTCTCGACCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTAAATCCGTACCTTTGGGGTCGCGTCGAAGA 901 CTTCCTCCTGCTACTCTGGATCCCAGACACCATTGAAGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGTCACCCTC GAAGGAGGACGATGAGACCTAGGGTCTGTGGTAACTTCTTTATCACTACTGCGTCAGAGGTCGGTGGGACAGACACAGAGGTCCCCTTTCTCAGTGGGAG 1001 TCCAGCAGCCATCATCATCATCATCACAGCAGCGGCCTGGTGCCGCGCGGCAGCCATAGGTCGACTCTAGAGGATCCAAGCCAAAGCACTAACGTTTTAG AGGTCGTCGGTAGTAGTAGTAGTAGTGTCGTCGCCGGACCACGGCGCGCCGTCGGTATCCAGCTGAGATCTCCTAGGTTCGGTTTCGTGATTGCAAAATC 1101 GTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAA CACTTCGATTTTTTAATTTGCTTAGAGTTCGTGGCTTTCGACTGTTGTTAAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAGAACTTGTACGGATT 1201 CTTGAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTTTTAGCAGAAGCTAAAAAGTTAAATGAATCT GAACTTGCTTCTTGTTGCGTTACCAAAGTAGGTTTCGAATTTTCTACTGGGTTCAGTTTCACGATTGGAAAATCGTCTTCGATTTTTCAATTTACTTAGA 1301 CAAGCACCGAAAGCTGATAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAATGAAGAACAACGCAATGGTT GTTCGTGGCTTTCGACTATTGTTTAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAGAATGTAAATGGATTGAATTTACTTCTTGTTGCGTTACCAA 1401 TCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATT AGTAGGTTTCGAATTTTCTACTGGGTTCGGTTATGCGATTGGAAAATCGTCTTCGATTTTTCGATTTACTACGTGTTCGTGGTTTTCGACTGTTGTTTAA 1501 CAACAAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCC GTTGTTTCTTGTTGTTTTACGAAAGATACTTTAAAATGTAAATGGATTGAATTGACTTCTTGTTGCATTGCCGAAGTAGGTTTCGGAATTTCTGCTAGGG 1601 CGGTCGACTCTAGCGGCAGCTTCCGGTGCTAGCACTGACACTTACAAATTAATCCTTAATGGTAAAACATTGAAAGGCGAAACAACTACTGAAGCTGTTG GCCAGCTGAGATCGCCGTCGAAGGCCACGATCGTGACTGTGAATGTTTAATTAGGAATTACCATTTTGTAACTTTCCGCTTTGTTGATGACTTCGACAAC 1701 ATGCTGCTACTGCAGAAAAAGTCTTCAAACAATACGCTAACGACAACGGTGTTGACGGTGAATGGACTTACGACGATGCGACTAAGACCTTTACAGTTAC TACGACGATGACGTCTTTTTCAGAAGTTTGTTATGCGATTGCTGTTGCCACAACTGCCACTTACCTGAATGCTGCTACGCTGATTCTGGAAATGTCAATG 1801 TGAAAAACCAGAAGTGATCGATGCGTCTGAATTAACACCAGCCGTGACAACTTACAAACTTGTTATTAATGGTAAAACATTGAAAGGCGAAACAACTACT ACTTTTTGGTCTTCACTAGCTACGCAGACTTAATTGTGGTCGGCACTGTTGAATGTTTGAACAATAATTACCATTTTGTAACTTTCCGCTTTGTTGATGA 1901 AAAGCAGTAGACGCAGAAACTGCAGAAAAAGCCTTCAAACAATACGCTAACGACAACGGTGTTGATGGTGTTTGGACTTATGATGATGCGACTAAGACCT TTTCGTCATCTGCGTCTTTGACGTCTTTTTCGGAAGTTTGTTATGCGATTGCTGTTGCCACAACTACCACAAACCTGAATACTACTACGCTGATTCTGGA 2001 TTACGGTAACTGAAATGGTTACAGAGGTACCGCGGGCCCGGGATCCACCGGCTAGCGGGAATTCCAAATCAACTGAGTTCGATCCTAACATTGACATTGT AATGCCATTGACTTTACCAATGTCTCCATGGCGCCCGGGCCCTAGGTGGCCGATCGCCCTTAAGGTTTAGTTGACTCAAGCTAGGATTGTAACTGTAACA 2101 TGGTTTAGAAGGAAAATTTGGTATTACAAACCTAGAGACGGATTTATTCACAATCTGGGAGACAATGGAGGTCATGATCAAAGCAGATATTGCAGATACT ACCAAATCTTCCTTTTAAACCATAATGTTTGGATCTCTGCCTAAATAAGTGTTAGACCCTCTGTTACCTCCAGTACTAGTTTCGTCTATAACGTCTATGA 2201 GATAGAGCCAGCAACTTTGTTGCAACTGAAACCGATGCTAACCGCGGAAAAATGCCTGGCAAAAAACTGCCACTGGCAGTTATCATGGAAATGGAAGCCA CTATCTCGGTCGTTGAAACAACGTTGACTTTGGCTACGATTGGCGCCTTTTTACGGACCGTTTTTTGACGGTGACCGTCAATAGTACCTTTACCTTCGGT 2301 ATGCTTTCAAAGCTGGCTGCACCAGGGGATGCCTTATCTGTCTTTCAAAAATTAAGTGTACAGCCAAAATGAAGGTATACATTCCAGGAAGGTGTCACGA TACGAAAGTTTCGACCGACGTGGTCCCCTACGGAATAGACAGAAAGTTTTTAATTCACATGTCGGTTTTACTTCCATATGTAAGGTCCTTCCACAGTGCT 2401 TTATGGTGGTGACAAGAAAACTGGACAGGCAGGAATTGTTGGTGCAATTGTTGACATTCCCGAAATCTCTGGATTTAAGGAGATGGCACCCATGGAACAG AATACCACCACTGTTCTTTTGACCTGTCCGTCCTTAACAACCACGTTAACAACTGTAAGGGCTTTAGAGACCTAAATTCCTCTACCGTGGGTACCTTGTC 2501 TTCATTGCTCAAGTTGATCGCTGCGCTTCCTGCACTACTGGATGTCTCAAAGGTCTTGCCAATGTTAAGTGCTCTGAACTCCTGAAGAAATGGCTGCCTG AAGTAACGAGTTCAACTAGCGACGCGAAGGACGTGATGACCTACAGAGTTTCCAGAACGGTTACAATTCACGAGACTTGAGGACTTCTTTACCGACGGAC 2601 ACAGGTGTGCAAGTTTTGCTGACAAGATTCAAAAAGAAGTTCACAATATCAAAGGCATGGCCGGCGATCGATGAGCGGCCGCAATTTAATTCCGGTTATT TGTCCACACGTTCAAAACGACTGTTCTAAGTTTTTCTTCAAGTGTTATAGTTTCCGTACCGGCCGCTAGCTACTCGCCGGCGTTAAATTAAGGCCAATAA 2701 TTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGA AAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCT 2801 ATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCC TACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGG 2901 CACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGT GTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCACGGTGCAACACTCAACCTATCAACA 3001 GGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGC CCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAACATACCCTAGACTAGACCCCGGAGCCACG 3101 ACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCA TGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGT 3201 CCACCCATACCTAGGCTTTTGCAAAGATCGATCAGATCCCGGGGGGCAATGAGATATGAAAAAGCCTGAACTCACCGCGACGTCTGTCGAGAAGTTTCTG GGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTCTAGGGCCCCCCGTTACTCTATACTTTTTCGGACTTGAGTGGCGCTGCAGACAGCTCTTCAAAGAC 3301 ATCGAAAAGTTCGACAGCGTCTCCGACCTGATGCAGCTCTCGGAGGGCGAAGAATCTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGATATGTCCTGC TAGCTTTTCAAGCTGTCGCAGAGGCTGGACTACGTCGAGAGCCTCCCGCTTCTTAGAGCACGAAAGTCGAAGCTACATCCTCCCGCACCTATACAGGACG 3401 GGGTAAATAGCTGCGCCGATGGTTTCTACAAAGATCGTTATGTTTATCGGCACTTTGCATCGGCCGCGCTCCCGATTCCGGAAGTGCTTGACATTGGGGA CCCATTTATCGACGCGGCTACCAAAGATGTTTCTAGCAATACAAATAGCCGTGAAACGTAGCCGGCGCGAGGGCTAAGGCCTTCACGAACTGTAACCCCT 3501 ATTCAGCGAGAGCCTGACCTATTGCATCTCCCGCCGTGCACAGGGTGTCACGTTGCAAGACCTGCCTGAAACCGAACTGCCCGCTGTTCTGCAGCCGGTC TAAGTCGCTCTCGGACTGGATAACGTAGAGGGCGGCACGTGTCCCACAGTGCAACGTTCTGGACGGACTTTGGCTTGACGGGCGACAAGACGTCGGCCAG 3601 GCGGAGGCCATGGATGCGATCGCTGCGGCCGATCTTAGCCAGACGAGCGGGTTCGGCCCATTCGGACCGCAAGGAATCGGTCAATACACTACATGGCGTG CGCCTCCGGTACCTACGCTAGCGACGCCGGCTAGAATCGGTCTGCTCGCCCAAGCCGGGTAAGCCTGGCGTTCCTTAGCCAGTTATGTGATGTACCGCAC 3701 ATTTCATATGCGCGATTGCTGATCCCCATGTGTATCACTGGCAAACTGTGATGGACGACACCGTCAGTGCGTCCGTCGCGCAGGCTCTCGATGAGCTGAT TAAAGTATACGCGCTAACGACTAGGGGTACACATAGTGACCGTTTGACACTACCTGCTGTGGCAGTCACGCAGGCAGCGCGTCCGAGAGCTACTCGACTA 3801 GCTTTGGGCCGAGGACTGCCCCGAAGTCCGGCACCTCGTGCACGCGGATTTCGGCTCCAACAATGTCCTGACGGACAATGGCCGCATAACAGCGGTCATT CGAAACCCGGCTCCTGACGGGGCTTCAGGCCGTGGAGCACGTGCGCCTAAAGCCGAGGTTGTTACAGGACTGCCTGTTACCGGCGTATTGTCGCCAGTAA 3901 GACTGGAGCGAGGCGATGTTCGGGGATTCCCAATACGAGGTCGCCAACATCTTCTTCTGGAGGCCGTGGTTGGCTTGTATGGAGCAGCAGACGCGCTACT CTGACCTCGCTCCGCTACAAGCCCCTAAGGGTTATGCTCCAGCGGTTGTAGAAGAAGACCTCCGGCACCAACCGAACATACCTCGTCGTCTGCGCGATGA 4001 TCGAGCGGAGGCATCCGGAGCTTGCAGGATCGCCGCGGCTCCGGGCGTATATGCTCCGCATTGGTCTTGACCAACTCTATCAGAGCTTGGTTGACGGCAA AGCTCGCCTCCGTAGGCCTCGAACGTCCTAGCGGCGCCGAGGCCCGCATATACGAGGCGTAACCAGAACTGGTTGAGATAGTCTCGAACCAACTGCCGTT 4101 TTTCGATGATGCAGCTTGGGCGCAGGGTCGATGCGACGCAATCGTCCGATCCGGAGCCGGGACTGTCGGGCGTACACAAATCGCCCGCAGAAGCGCGGCC AAAGCTACTACGTCGAACCCGCGTCCCAGCTACGCTGCGTTAGCAGGCTAGGCCTCGGCCCTGACAGCCCGCATGTGTTTAGCGGGCGTCTTCGCGCCGG 4201 GTCTGGACCGATGGCTGTGTAGAAGTACTCGCCGATAGTGGAAACCGACGCCCCAGCACTCGTCCGGATCGGGAGATGGGGGAGGCTAACTGAAACACGG CAGACCTGGCTACCGACACATCTTCATGAGCGGCTATCACCTTTGGCTGCGGGGTCGTGAGCAGGCCTAGCCCTCTACCCCCTCCGATTGACTTTGTGCC 4301 AAGGAGACAATACCGGAAGGAACCTCGACGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGC TTCCTCTGTTATGGCCTTCCTTGGAGCTGCAATTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCG 4401 ATTTATTACCCTGTTATCCCTAGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACA TAAATAATGGGACAATAGGGATCTTAAGTGACCGGCAGCAAAATGTTGCAGCACTGACCCTTTTGGGACCGCAATGGGTTGAATTAGCGGAACGTCGTGT 4501 TCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTAT AGGGGGAAAGCGGTCGACCGCATTATCGCTTCTCCGGGCGTGGCTAGCGGGAAGGGTTGTCAACGCGTCGGACTTACCGCTTACCGCGGACTACGCCATA 4601 TTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGT AAAGAGGAATGCGTAGACACGCCATAAAGTGTGGCGTATGCAGTTTCGTTGGTATCATGCGCGGGACATCGCCGCGTAATTCGCGCCGCCCACACCACCA 4701 TACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAA ATGCGCGTCGCACTGGCGATGTGAACGGTCGCGGGATCGCGGGCGAGGAAAGCGAAAGAAGGGAAGGAAAGAGCGGTGCAAGCGGCCGAAAGGGGCAGTT 4801 GCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCAT CGAGATTTAGCCCCCGAGGGAAATCCCAAGGCTAAATCACGAAATGCCGTGGAGCTGGGGTTTTTTGAACTAAACCCACTACCAAGTGCATCACCCGGTA 4901 CGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGG GCGGGACTATCTGCCAAAAAGCGGGAAACTGCAACCTCAGGTGCAAGAAATTATCACCTGAGAACAAGGTTTGACCTTGTTGTGAGTTGGGATAGAGCCC 5001 CTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTA GATAAGAAAACTAAATATTCCCTAAAACGGCTAAAGCCGGATAACCAATTTTTTACTCGACTAAATTGTTTTTAAATTGCGCTTAAAATTGTTTTATAAT 5101 ACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGAC TGCAAATGTTAAAATACCACGTGAGAGTCATGTTAGACGAGACTACGGCGTATCAATTCGGTCGGGGCTGTGGGCGGTTGTGGGCGACTGCGCGGGACTG 5201 GGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAA CCCGAACAGACGAGGGCCGTAGGCGAATGTCTGTTCGACACTGGCAGATCTGCTTTCCCGGAGCACTATGCGGATAAAAATATCCAATTACAGTACTATT 5301 TAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCAT ATTACCAAAGAATCTGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTA 5401 GAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTT CTCTGTTATTGGGACTATTTACGAAGTTATTATAACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGCCGTAAA 5501 TGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACA ACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTAGCTTGACCTAGAGTTGT 5601 GCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGC CGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCATAATAGGGCATAACTGCG 5701 CGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTA GCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCATGAGTGGTCAGTGTCTTTTCGTAGAATGCCTACCGTACTGTCAT 5801 AGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGC TCTCTTAATACGTCACGACGGTATTGGTACTCACTATTGTGACGCCGGTTGAATGAAGACTGTTGCTAGCCTCCTGGCTTCCTCGATTGGCGAAAAAACG 5901 ACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAAT TGTTGTACCCCCTAGTACATTGAGCGGAACTAGCAACCCTTGGCCTCGACTTACTTCGGTATGGTTTGCTGCTCGCACTGTGGTGCTACGGACATCGTTA 6001 GGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCA CCGTTGTTGCAACGCGTTTGATAATTGACCGCTTGATGAATGAGATCGAAGGGCCGTTGTTAATTATCTGACCTACCTCCGCCTATTTCAACGTCCTGGT 6101 CTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATG GAAGACGCGAGCCGGGAAGGCCGACCGACCAAATAACGACTATTTAGACCTCGGCCACTCGCACCCAGAGCGCCATAGTAACGTCGTGACCCCGGTCTAC 6201 GTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAA CATTCGGGAGGGCATAGCATCAATAGATGTGCTGCCCCTCAGTCCGTTGATACCTACTTGCTTTATCTGTCTAGCGACTCTATCCACGGAGTGACTAATT 6301 GCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGAT CGTAACCATTGACAGTCTGGTTCAAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTA 6401 AATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGC TTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACG 6501 GCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTT CGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAA 6601 CAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTA GTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGAT 6701 ATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAA TAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTT 6801 CGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGG GCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCC 6901 GAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTC CTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAG 7001 GGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCC CCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGG 7101 TGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCG ACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGAAACTCACTCGACTATGGCGAGC 7201 CCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAG GGCGTCGGCTTGCTGGCTCGCGTCGCTCAGTCACTCGCTCCTTCGCCTTC pS14L-spAG-N-MLuc15 1 AGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAA TCGCGGGTTATGCGTTTGGCGGAGAGGGGCGCGCAACCGGCTAAGTAATTACGTCGACCGTGCTGTCCAAAGGGCTGACCTTTCGCCCGTCACTCGCGTT 101 CGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTT GCGTTAATTACACTCAATCGAGTGAGTAATCCGTGGGGTCCGAAATGTGAAATACGAAGGCCGAGCATACAACACACCTTAACACTCGCCTATTGTTAAA 201 CACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTAGGGATAACAGGGTAATCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATT GTGTGTCCTTTGTCGATACTGGTACTAATGCGGTTCGAAATCCCTATTGTCCCATTAGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAA 301 AGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATG TCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTAC 401 ACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATC TGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAG 501 ATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTA TATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCAT 601 CATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC GTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAG 701 CACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTA GTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCAT 801 GGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTGGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATTTAGGCATGGAAACCCCAGCGCAGCTTCT CCGCACATGCCACCCTCCAGATATATTCGTCTCGACCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTAAATCCGTACCTTTGGGGTCGCGTCGAAGA 901 CTTCCTCCTGCTACTCTGGATCCCAGACACCATTGAAGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGTCACCCTC GAAGGAGGACGATGAGACCTAGGGTCTGTGGTAACTTCTTTATCACTACTGCGTCAGAGGTCGGTGGGACAGACACAGAGGTCCCCTTTCTCAGTGGGAG 1001 TCCAGCAGCCATCATCATCATCATCACAGCAGCGGCCTGGTGCCGCGCGGCAGCCATAGGTCGACTCTAGAGGATCCAAGCCAAAGCACTAACGTTTTAG AGGTCGTCGGTAGTAGTAGTAGTAGTGTCGTCGCCGGACCACGGCGCGCCGTCGGTATCCAGCTGAGATCTCCTAGGTTCGGTTTCGTGATTGCAAAATC 1101 GTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAA CACTTCGATTTTTTAATTTGCTTAGAGTTCGTGGCTTTCGACTGTTGTTAAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAGAACTTGTACGGATT 1201 CTTGAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTTTTAGCAGAAGCTAAAAAGTTAAATGAATCT GAACTTGCTTCTTGTTGCGTTACCAAAGTAGGTTTCGAATTTTCTACTGGGTTCAGTTTCACGATTGGAAAATCGTCTTCGATTTTTCAATTTACTTAGA 1301 CAAGCACCGAAAGCTGATAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAATGAAGAACAACGCAATGGTT GTTCGTGGCTTTCGACTATTGTTTAAGTTGTTTCTTGTTGTTTTACGAAAGATACTTTAGAATGTAAATGGATTGAATTTACTTCTTGTTGCGTTACCAA 1401 TCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATT AGTAGGTTTCGAATTTTCTACTGGGTTCGGTTTCGCGATTGGAAAATCGTCTTCGATTTTTCGATTTACTACGTGTTCGTGGTTTTCGACTGTTGTTTAA 1501 CAACAAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCC GTTGTTTCTTGTTGTTTTACGAAAGATACTTTAAAATGTAAATGGATTGAATTGACTTCTTGTTGCATTGCCGAAGTAGGTTTCGGAATTTCTGCTAGGG 1601 CGGTCGACTCTAGCGGCAGCTTCCGGTGCTAGCACTGACACTTACAAATTAATCCTTAATGGTAAAACATTGAAAGGCGAAACAACTACTGAAGCTGTTG GCCAGCTGAGATCGCCGTCGAAGGCCACGATCGTGACTGTGAATGTTTAATTAGGAATTACCATTTTGTAACTTTCCGCTTTGTTGATGACTTCGACAAC 1701 ATGCTGCTACTGCAGAAAAAGTCTTCAAACAATACGCTAACGACAACGGTGTTGACGGTGAATGGACTTACGACGATGCGACTAAGACCTTTACAGTTAC TACGACGATGACGTCTTTTTCAGAAGTTTGTTATGCGATTGCTGTTGCCACAACTGCCACTTACCTGAATGCTGCTACGCTGATTCTGGAAATGTCAATG 1801 TGAAAAACCAGAAGTGATCGATGCGTCTGAATTAACACCAGCCGTGACAACTTACAAACTTGTTATTAATGGTAAAACATTGAAAGGCGAAACAACTACT ACTTTTTGGTCTTCACTAGCTACGCAGACTTAATTGTGGTCGGCACTGTTGAATGTTTGAACAATAATTACCATTTTGTAACTTTCCGCTTTGTTGATGA 1901 AAAGCAGTAGACGCAGAAACTGCAGAAAAAGCCTTCAAACAATACGCTAACGACAACGGTGTTGATGGTGTTTGGACTTATGATGATGCGACTAAGACCT TTTCGTCATCTGCGTCTTTGACGTCTTTTTCGGAAGTTTGTTATGCGATTGCTGTTGCCACAACTACCACAAACCTGAATACTACTACGCTGATTCTGGA 2001 TTACGGTAACTGAAATGGTTACAGAGGTACCAGATCTTAGCAACTTTGTTGCAACTGAAACCGATGCTAACCGCGGAAAAATGCCTGGCAAAAAACTGCC AATGCCATTGACTTTACCAATGTCTCCATGGTCTAGAATCGTTGAAACAACGTTGACTTTGGCTACGATTGGCGCCTTTTTACGGACCGTTTTTTGACGG 2101 ACTGGCAGTTATCATGGAAATGGAAGCCAATGCTTTCAAAGCTGGCTGCACCAGGGGATGCCTTATCTGTCTTTCAAAAATTAAGTGTACAGCCAAAATG TGACCGTCAATAGTACCTTTACCTTCGGTTACGAAAGTTTCGACCGACGTGGTCCCCTACGGAATAGACAGAAAGTTTTTAATTCACATGTCGGTTTTAC 2201 AAGGTATACATTCCAGGAAGGTGTCACGATTATGGTGGTGACAAGAAAACTGGACAGGCAGGAATTGTTGGTGCAATTGTTGACATTCCCGAAATCTCTG TTCCATATGTAAGGTCCTTCCACAGTGCTAATACCACCACTGTTCTTTTGACCTGTCCGTCCTTAACAACCACGTTAACAACTGTAAGGGCTTTAGAGAC 2301 GATTTAAGGAGATGGCACCCATGGAACAGTTCATTGCTCAAGTTGATCGCTGCGCTTCCTGCACTACTGGATGTCTCAAAGGTCTTGCCAATGTTAAGTG CTAAATTCCTCTACCGTGGGTACCTTGTCAAGTAACGAGTTCAACTAGCGACGCGAAGGACGTGATGACCTACAGAGTTTCCAGAACGGTTACAATTCAC 2401 CTCTGAACTCCTGAAGAAATGGCTGCCTGACAGGTGTGCAAGTTTTGCTGACAAGATTCAAAAAGAAGTTCACAATATCAAAGGCATGGCCGGCGATCGA GAGACTTGAGGACTTCTTTACCGACGGACTGTCCACACGTTCAAAACGACTGTTCTAAGTTTTTCTTCAAGTGTTATAGTTTCCGTACCGGCCGCTAGCT 2501 TGAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTC ACTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTATAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAG 2601 CTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGT GATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCAGACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACA 201 AGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCC TCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGCTGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGG 2801 CAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGTCAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATT GTCACGGTGCAACACTCAACCTATCAACACCTTTCTCAGTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAA 2901 GTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTC CATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAATGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAG 3001 CTTTGAAAAACACGATGATAATATGGCCACCACCCATACCTAGGCTTTTGCAAAGATCGATCAGATCCCGGGGGGCAATGAGATATGAAAAAGCCTGAAC GAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTATGGATCCGAAAACGTTTCTAGCTAGTCTAGGGCCCCCCGTTACTCTATACTTTTTCGGACTTG 3101 TCACCGCGACGTCTGTCGAGAAGTTTCTGATCGAAAAGTTCGACAGCGTCTCCGACCTGATGCAGCTCTCGGAGGGCGAAGAATCTCGTGCTTTCAGCTT AGTGGCGCTGCAGACAGCTCTTCAAAGACTAGCTTTTCAAGCTGTCGCAGAGGCTGGACTACGTCGAGAGCCTCCCGCTTCTTAGAGCACGAAAGTCGAA 3201 CGATGTAGGAGGGCGTGGATATGTCCTGCGGGTAAATAGCTGCGCCGATGGTTTCTACAAAGATCGTTATGTTTATCGGCACTTTGCATCGGCCGCGCTC GCTACATCCTCCCGCACCTATACAGGACGCCCATTTATCGACGCGGCTACCAAAGATGTTTCTAGCAATACAAATAGCCGTGAAACGTAGCCGGCGCGAG 3301 CCGATTCCGGAAGTGCTTGACATTGGGGAATTCAGCGAGAGCCTGACCTATTGCATCTCCCGCCGTGCACAGGGTGTCACGTTGCAAGACCTGCCTGAAA GGCTAAGGCCTTCACGAACTGTAACCCCTTAAGTCGCTCTCGGACTGGATAACGTAGAGGGCGGCACGTGTCCCACAGTGCAACGTTCTGGACGGACTTT 3401 CCGAACTGCCCGCTGTTCTGCAGCCGGTCGCGGAGGCCATGGATGCGATCGCTGCGGCCGATCTTAGCCAGACGAGCGGGTTCGGCCCATTCGGACCGCA GGCTTGACGGGCGACAAGACGTCGGCCAGCGCCTCCGGTACCTACGCTAGCGACGCCGGCTAGAATCGGTCTGCTCGCCCAAGCCGGGTAAGCCTGGCGT 3501 AGGAATCGGTCAATACACTACATGGCGTGATTTCATATGCGCGATTGCTGATCCCCATGTGTATCACTGGCAAACTGTGATGGACGACACCGTCAGTGCG TCCTTAGCCAGTTATGTGATGTACCGCACTAAAGTATACGCGCTAACGACTAGGGGTACACATAGTGACCGTTTGACACTACCTGCTGTGGCAGTCACGC 3601 TCCGTCGCGCAGGCTCTCGATGAGCTGATGCTTTGGGCCGAGGACTGCCCCGAAGTCCGGCACCTCGTGCACGCGGATTTCGGCTCCAACAATGTCCTGA AGGCAGCGCGTCCGAGAGCTACTCGACTACGAAACCCGGCTCCTGACGGGGCTTCAGGCCGTGGAGCACGTGCGCCTAAAGCCGAGGTTGTTACAGGACT 3701 CGGACAATGGCCGCATAACAGCGGTCATTGACTGGAGCGAGGCGATGTTCGGGGATTCCCAATACGAGGTCGCCAACATCTGATTCTGGAGGCCGTGGTT GCCTGTTACCGGCGTATTGTCGCCAGTAACTGACCTCGCTCCGCTACAAGCCCCTAAGGGTTATGCTCCAGCGGTTGTAGAAGAAGACCTCCGGCACCAA 3801 GGCTTGTATGGAGCAGCAGACGCGCTACTTCGAGCGGAGGCATCCGGAGCTTGCAGGATCGCCGCGGCTCCGGGCGTATATGCTCCGCATTGGTCTTGAC CCGAACATACCTCGTCGTCTGCGCGATGAAGCTCGCCTCCGTAGGCCTCGAACGTCCTAGCGGCGCCGAGGCCCGCATATACGAGGCGTAACCAGAACTG 3901 CAACTCTATCAGAGCTTGGTTGACGGCAATTTCGATGATGCAGCTTGGGCGCAGGGTCGATGCGACGCAATCGTCCGATCCGGAGCCGGGACTGTCGGGC GTTGAGATAGTCTCGAACCAACTGCCGTTAAAGCTACTACGTCGAACCCGCGTCCCAGCTACGCTGCGTTAGCAGGCTAGGCCTCGGCCCTGACAGCCCG 4001 GTACACAAATCGCCCGCAGAAGCGCGGCCGTCTGGACCGATGGCTGTGTAGAAGTACTCGCCGATAGTGGAAACCGACGCCCCAGCACTCGTCCGGATCG CATGTGTTTAGCGGGCGTCTTCGCGCCGGCAGACCTGGCTACCGACACATCTTCATGAGCGGCTATCACCTTTGGCTGCGGGGTCGTGAGCAGGCCTAGC 4101 GGAGATGGGGGAGGCTAACTGAAACACGGAAGGAGACAATACCGGAAGGAACCTCGACGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGC CCTCTACCCCCTCCGATTGACTTTGTGCCTTCCTCTGTTATGGCCTTCCTTGGAGCTGCAATTGAACAAATAACGTCGAATATTACCAATGTTTATTTCG 4201 AATAGCATCACAAATTTCACAAATAAAGCATTTATTACCCTGTTATCCCTAGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGC TTATCGTAGTGTTTAAAGTGTTTATTTCGTAAATAATGGGACAATAGGGATCTTAAGTGACCGGCAGCAAAATGTTGCAGCACTGACCCTTTTGGGACCG 4301 GTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCC CAATGGGTTGAATTAGCGGAACGTCGTGTAGGGGGAAAGCGGTCGACCGCATTATCGCTTCTCCGGGCGTGGCTAGCGGGAAGGGTTGTCAACGCGTCGG 4401 TGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGC ACTTACCGCTTACCGCGGACTACGCCATAAAAGAGGAATGCGTAGACACGCCATAAAGTGTGGCGTATGCAGTTTCGTTGGTATCATGCGCGGGACATCG 4501 GGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTC CCGCGTAATTCGCGCCGCCCACACCACCAATGCGCGTCGCACTGGCGATGTGAACGGTCGCGGGATCGCGGGCGAGGAAAGCGAAAGAAGGGAAGGAAAG 4601 TCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGA AGCGGTGCAAGCGGCCGAAAGGGGCAGTTCGAGATTTAGCCCCCGAGGGAAATCCCAAGGCTAAATCACGAAATGCCGTGGAGCTGGGGTTTTTTGAACT 4701 TTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAA AAACCCACTACCAAGTGCATCACCCGGTAGCGGGACTATCTGCCAAAAAGCGGGAAACTGCAACCTCAGGTGCAAGAAATTATCACCTGAGAACAAGGTT 4801 ACTGGAACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAA TGACCTTGTTGTGAGTTGGGATAGAGCCCGATAAGAAAACTAAATATTCCCTAAAACGGCTAAAGCCGGATAACCAATTTTTTACTCGACTAAATTGTTT 4901 AATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACA TTAAATTGCGCTTAAAATTGTTTTATAATTGCAAATGTTAAAATACCACGTGAGAGTCATGTTAGACGAGACTACGGCGTATCAATTCGGTCGGGGCTGT 5001 CCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTAGACGAAAGGGCCTCGTGATACG GGGCGGTTGTGGGCGACTGCGCGGGACTGCCCGAACAGACGAGGGCCGTAGGCGAATGTCTGTTCGACACTGGCAGATCTGCTTTCCCGGAGCACTATGC 5101 CCATTTTGTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTC GGATAAAAATATCCAATTACAGTACTATTATTACCAAAGAATCTGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAG 5201 TAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTG ATTTATGTAAGTTTATACATAGGCGAGTACTCTGTTATTGGGACTATTTACGAAGTTATTATAACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCAC 5301 TCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACG AGCGGGAATAAGGGAAAAAACGCCGTAAAACGGAAGGACAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGC 5401 AGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTA TCACCCAATGTAGCTTGACCTAGAGTTGTCGCCATTCTAGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGAT 5501 TGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAG ACACCGCGCCATAATAGGGCATAACTGCGGCCCGTTCTCGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCATGAGTGGTCAGTGTC 5601 AAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGG TTTTCGTAGAATGCCTACCGTACTGTCATTCTCTTAATACGTCACGACGGTATTGGTACTCACTATTGTGACGCCGGTTGAATGAAGACTGTTGCTAGCC 5701 AGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGAC TCCTGGCTTCCTCGATTGGCGAAAAAACGTGTTGTACCCCCTAGTACATTGAGCGGAACTAGCAACCCTTGGCCTCGACTTACTTCGGTATGGTTTGCTG 5801 GAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACT CTCGCACTGTGGTGCTACGGACATCGTTACCGTTGTTGCAACGCGTTTGATAATTGACCGCTTGATGAATGAGATCGAAGGGCCGTTGTTAATTATCTGA 5901 GGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCG CCTACCTCCGCCTATTTCAACGTCCTGGTGAAGACGCGAGCCGGGAAGGCCGACCGACCAAATAACGACTATTTAGACCTCGGCCACTCGCACCCAGAGC 6001 CGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAG GCCATAGTAACGTCGTGACCCCGGTCTACCATTCGGGAGGGCATAGCATCAATAGATGTGCTGCCCCTCAGTCCGTTGATACCTACTTGCTTTATCTGTC 6101 ATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTA TAGCGACTCTATCCACGGAGTGACTAATTCGTAACCATTGACAGTCTGGTTCAAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAAT 6201 AAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAA TTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTACTGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTT 6301 AGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTA TCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGACGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGAT 6401 CCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTG GGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCGCGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGAC 6501 TAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTT ATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAATGGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAA 6601 ACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAG TGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAAGCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTC 6701 CTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGG GATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCGCCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCC 6801 GAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAA CTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCGGTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTT 6901 CGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATT GCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAACGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAA 7001 ACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAG TGGCGGAAACTCACTCGACTATGGCGAGCGGCGTCGGCTTGCTGGCTCGCGTCGCTCAGTCACTCGCTCCTTCGCCTTC

(88) TABLE-US-00007 APPENDIX5 SequenceoftheplasmidencodingbioSNAP25-AN-MLuchybrid(SEQIDNO:91). pS14LbioSNAP25-N-MLuc-CITE-Hyg1 1 AGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAA TCGCGGGTTATGCGTTTGGCGGAGAGGGGCGCGCAACCGGCTAAGTAATTACGTCGACCGTGCTGTCCAAAGGGCTGACCTTTCGCCCGTCACTCGCGTT 101 CCCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTT GCGTTAATTACACTCAATCGAGTGAGTAATCCGTGGGGTCCGAAATGTGAAATACGAAGGCCGAGCATACAACACACCTTAACACTCGCCTATTGTTAAA 201 CACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTAGGGATAACAGGGTAATCGCCATGCATTAGTTATTAATAGTAATCAATTACGGGGTCATT GTGTGTCCTTTGTCGATACTGGTACTAATGCGGTTCGAAATCCCTATTGTCCCATTAGCGGTACGTAATCAATAATTATCATTAGTTAATGCCCCAGTAA 301 AGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATG TCAAGTATCGGGTATATACCTCAAGGCGCAATGTATTGAATGCCATTTACCGGGCGGACCGACTGGCGGGTTGCTGGGGGCGGGTAACTGCAGTTATTAC 401 ACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATC TGCATACAAGGGTATCATTGCGGTTATCCCTGAAAGGTAACTGCAGTTACCCACCTCATAAATGCCATTTGACGGGTGAACCGTCATGTAGTTCACATAG 501 ATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTA TATACGGTTCATGCGGGGGATAACTGCAGTTACTGCCATTTACCGGGCGGACCGTAATACGGGTCATGTACTGGAATACCCTGAAAGGATGAACCGTCAT 601 CATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC GTAGATGCATAATCAGTAGCGATAATGGTACCACTACGCCAAAACCGTCATGTAGTTACCCGCACCTATCGCCAAACTGAGTGCCCCTAAAGGTTCAGAG 701 CACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTA GTGGGGTAACTGCAGTTACCCTCAAACAAAACCGTGGTTTTAGTTGCCCTGAAAGGTTTTACAGCATTGTTGAGGCGGGGTAACTGCGTTTACCCGCCAT 801 GGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTGGTTTAGTGAACCGTCAGATCCGCTAGACGTCTCATTTAGGCATGGAAACCCCAGCGCAGCTTCT CCGCACATGCCACCCTCCAGATATATTCGTCTCGACCAAATCACTTGGCAGTCTAGGCGATCTGCAGAGTAAATCCGTACCTTTGGGGTCGCGTCGAAGA 901 CTTCCTCCTGCTACTCTGGATCCCAGACACCATTGAAGAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGTCACCCTC GAAGGAGGACGATGAGACCTAGGGTCTGTGGTAACTTCTTTATCACTACTGCGTCAGAGGTCGGTGGGACAGACACAGAGGTCCCCTTTCTCAGTGGGAG 1001 TCCTCAGGCGGCGCAAGCAGCCTGAGACAGATTCTGGACTCCCAGAAAATGGAGTGGAGGTCCAACGCCGGGGGCAGCGGTAGGGATAACAGGGTAATCG AGGAGTCCGCCGCGTTCGTCGGACTCTGTCTAAGACCTGAGGGTCTTTTACCTCACCTCCAGGTTGCGGCCCCCGTCGCCATCCCTATTGTCCCATTAGC 1101 CCGAGGACGCAGACATGCGTAATGAACTGGAGGAGATGCAGAGGAGGGCTGACCAGCTGGCTGATGAGTCCCTGGAAAGCACCCGTCGCATGCTGCAGCT GGCTCCTGCGTCTGTACGCATTACTTGACCTCCTCTACGTCTCCTCCCGACTGGTCGACCGACTACTCAGGGACCTTTCGTGGGCAGCGTACGACGTCGA 1201 GGTCGAAGAGAGTAAAGATGCTGGCATCAGGACTTTGGTTATGTTGGATGAGCAAGGCGAACAACTGGAACGCATTGAGGAAGGGATGGACCAAATCAAT CCAGCTTCTCTCATTTCTACGACCGTAGTCCTGAAACCAATACAACCTACTCGTTCCGCTTGTTGACCTTGCGTAACTCCTTCCCTACCTGGTTTAGTTA 1301 AAGGATATGAAAGAAGCAGAAAAGAATTTGACGGACCTAGGAAAATTCTGCGGGCTTTGTGTGTGTCCCTGTAACAAGCTTAAATCCAGTGATGCTTACA TTCCTATACTTTCTTCGTCTTTTCTTAAACTGCCTGGATCCTTTTAAGACGCCCGAAACACACACAGGGACATTGTTCGAATTTAGGTCACTACGAATGT 1401 AAAAAGCCTGGGGCAATAATCAGGATGGAGTAGTGGCCAGCCAGCCTGCCCGTGTGGTGGATGAACGGGAGCAGATGGCCATCAGTGGTGGCTTCATCCG TTTTTCGGACCCCGTTATTAGTCCTACCTCATCACCGGTCGGTCGGACGGGCACACCACCTACTTGCCCTCGTCTACCGGTAGTCACCACCGAAGTAGGC 1501 CAGGGTAACAAACGATGCCCGGGAAAATGAAATGGATGAAAACCTAGAGCAGGTGAGCGGCATCATCGGAAACCTCCGTCATATGGCCCTAGACATGGGC GTCCCATTGTTTGCTACGGGCCCTTTTACTTTACCTACTTTTGGATCTCGTCCACTCGCCGTAGTAGCCTTTGGAGGCAGTATACCGGGATCTGTACCCG 1601 AATGAGATTGACACCCAGAATCGCCAGATTGACAGGATCATGGAGAAGGCTGACTCCAACAAAACCAGAATTGATGAAGCCAACCAACGTGCAACAAAGA TTACTCTAACTGTGGGTCTTAGCGGTCTAACTGTCCTAGTACCTCTTCCGACTGAGGTTGTTTTGGTCTTAACTACTTCGGTTGGTTGCACGTTGTTTCT 1701 TGCTGGGAAGTGGGGAGATCTCCGCGGCCCGGGATCCACCGGCTAGCGGGAATTCCAAATCAACTGAGTTCGATCCTAACATTGACATTGTTGGTTTAGA ACGACCCTTCACCCCTCTAGAGGCGCCGGGCCCTAGGTGGCCGATCGCCCTTAAGGTTTAGTTGACTCAAGCTAGGATTGTAACTGTAACAACCAAATCT 1801 AGGAAAATTTGGTATTACAAACCTAGAGACGGATTTATTCACAATCTGGGAGACAATGGAGGTCATGATCAAAGCAGATATTGCAGATACTGATAGAGCC TCCTTTTAAACCATAATGTTTGGATCTCTGCCTAAATAAGTGTTAGACCCTCTGTTACCTCCAGTACTAGTTTCGTCTATAACGTCTATGACTATCTCGG 1901 AGCAACTTTGTTGCAACTGAAACCGATGCTAACCGCGGAAAAATGCCTGGCAAAAAACTGCCACTGGCAGTTATCATGGAAATGGAAGCCAATGCTTTCA TCGTTGAAACAACGTTGACTTTGGCTACGATTGGCGCCTTTTTACGGACCGTTTTTTGACGGTGACCGTCAATAGTACCTTTACCTTCGGTTACGAAAGT 2001 AAGCTGGCTGCACCAGGGGATGCCTTATCTGTCTTTCAAAAATTAAGTGTACAGCCAAAATGAAGGTATACATTCCAGGAAGGTGTCACGATTATGGTGG TTCGACCGACGTGGTCCCCTACGGAATAGACAGAAAGTTTTTAATTCACATGTCGGTTTTACTTCCATATGTAAGGTCCTTCCACAGTGCTAATACCACC 2101 TGACAAGAAAACTGGACAGGCAGGAATTGTTGGTGCAATTGTTGACATTCCCGAAATCTCTGGATTTAAGGAGATGGCACCCATGGAACAGTTCATTGCT ACTGTTCTTTTGACCTGTCCGTCCTTAACAACCACGTTAACAACTGTAAGGGCTTTAGAGACCTAAATTCCTCTACCGTGGGTACCTTGTCAAGTAACGA 2201 CAAGTTGATCGCTGCGCTTCCTGCACTACTGGATGTCTCAAAGGTCTTGCCAATGTTAAGTGCTCTGAACTCCTGAAGAAATGGCTGCCTGACAGGTGTG GTTCAACTAGCGACGCGAAGGACGTGATGACCTACAGAGTTTCCAGAACGGTTACAATTCACGAGACTTGAGGACTTCTTTACCGACGGACTGTCCACAC 2301 CAAGTTTTGCTGACAAGATTCAAAAAGAAGTTCACAATATCAAAGGCATGGCCGGCGATCGATGAGCGGCCGCAATTTAATTCCGGTTATTTTCCACCAT GTTCAAAACGACTGTTCTAAGTTTTTCTTCAAGTGTTATAGTTTCCGTACCGGCCGCTAGCTACTCGCCGGCGTTAAATTAAGGCCAATAAAAGGTGGTA 2401 ATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGGCCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCGCCAAAGGAATGCAAGGT TAACGGCAGAAAACCGTTACACTCCCGGGCCTTTGGACCGGGACAGAAGAACTGCTCGTAAGGATCCCCAGAAAGGGGAGAGCGGTTTCCTTACGTTCCA 2501 CTGTTGAATGTCGTGAAGGAAGCAGTTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGACCCTTTGCAGGCAGCGGAACCCCCCACCTGGCG GACAACTTACAGCACTTCCTTCGTCAAGGAGACCTTCGAAGAACTTCTGTTTGTTGCAGACATCGCTGGGAAACGTCCGTCGCCTTGGGGGGTGGACCGC 2601 ACAGGTGCCTCTGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCGGCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAAGAGT TGTCCACGGAGACGCCGGTTTTCGGTGCACATATTCTATGTGGACGTTTCCGCCGTGTTGGGGTCACGGTGCAACACTCAACCTATCAACACCTTTCTCA 2701 CAAATGGCTCACCTCAAGCGTATTCAACAAGGGGCTGAAGGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGGCCTCGGTGCACATGCTTT GTTTACCGAGTGGAGTTCGCATAAGTTGTTCCCCGACTTCCTACGGGTCTTCCATGGGGTAACATACCCTAGACTAGACCCCGGAGCCACGTGTACGAAA 2801 ACATGTGTTTAGTCGAGGTTAAAAAACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTGAAAAACACGATGATAATATGGCCACCACCCATA TGTACACAAATCAGCTCCAATTTTTTGCAGATCCGGGGGGCTTGGTGCCCCTGCACCAAAAGGAAACTTTTTGTGCTACTATTATACCGGTGGTGGGTAT 2901 CCTAGGCTTTTGCAAAGATCGATCAGATCCCGGGGGGCAATGAGATATGAAAAAGCCTGAACTCACCGCGACGTCTGTCGAGAAGTTTCTGATCGAAAAG GGATCCGAAAACGTTTCTAGCTAGTCTAGGGCCCCCCGTTACTCTATACTTTTTCGGACTTGAGTGGCGCTGCAGACAGCTCTTCAAAGACTAGCTTTTC 3001 TTCGACAGCGTCTCCGACCTGATGCAGCTCTCGGAGGGCGAAGAATCTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGATATGTCCTGCGGGTAAATA AAGCTGTCGCAGAGGCTGGACTACGTCGAGAGCCTCCCGCTTCTTAGAGCACGAAAGTCGAAGCTACATCCTCCCGCACCTATACAGGACGCCCATTTAT 3101 GCTGCGCCGATGGTTTCTACAAAGATCGTTATGTTTATCGGCACTTTGCATCGGCCGCGCTCCCGATTCCGGAAGTGCTTGACATTGGGGAATTCAGCGA CGACGCGGCTACCAAAGATGTTTCTAGCAATACAAATAGCCGTGAAACGTAGCCGGCGCGAGGGCTAAGGCCTTCACGAACTGTAACCCCTTAAGTCGCT 3201 GAGCCTGACCTATTGCATCTCCCGCCGTGCACAGGGTGTCACGTTGCAAGACCTGCCTGAAACCGAACTGCCCGCTGTTCTGCAGCCGGTCGCGGAGGCC CTCGGACTGGATAACGTAGAGGGCGGCACGTGTCCCACAGTGCAACGTTCTGGACGGACTTTGGCTTGACGGGCGACAAGACGTCGGCCAGCGCCTCCGG 3301 ATGGATGCGATCGCTGCGGCCGATCTTAGCCAGACGAGCGGGTTCGGCCCATTCGGACCGCAAGGAATCGGTCAATACACTACATGGCGTGATTTCATAT TACCTACGCTAGCGACGCCGGCTAGAATCGGTCTGCTCGCCCAAGCCGGGTAAGCCTGGCGTTCCTTAGCCAGTTATGTGATGTACCGCACTAAAGTATA 3401 GCGCGATTGCTGATCCCCATGTGTATCACTGGCAAACTGTGATGGACGACACCGTCAGTGCGTCCGTCGCGCAGGCTCTCGATGAGCTGATGCTTTGGGC CGCGCTAACGACTAGGGGTACACATAGTGACCGTTTGACACTACCTGCTGTGGCAGTCACGCAGGCAGCGCGTCCGAGAGCTACTCGACTACGAAACCCG 3501 CGAGGACTGCCCCGAAGTCCGGCACCTCGTGCACGCGGATTTCGGCTCCAACAATGTCCTGACGGACAATGGCCGCATAACAGCGGTCATTGACTGGAGC GCTCCTGACGGGGCTTCAGGCCGTGGAGCACGTGCGCCTAAAGCCGAGGTTGTTACAGGACTGCCTGTTACCGGCGTATTGTCGCCAGTAACTGACCTCG 3601 GAGGCGATGTTCGGGGATTCCCAATACGAGGTCGCCAACATCTTCTTCTGGAGGCCGTGGTTGGCTTGTATGGAGCAGCAGACGCGCTACTTCGAGCGGA CTCCGCTACAAGCCCCTAAGGGTTATGCTCCAGCGGTTGTAGAAGAAGACCTCCGGCACCAACCGAACATACCTCGTCGTCTGCGCGATGAAGCTCGCCT 3701 GGCATCCGGAGCTTGCAGGATCGCCGCGGCTCCGGGCGTATATGCTCCGCATTGGTCTTGACCAACTCTATCAGAGCTTGGTTGACGGCAATTTCGATGA CCGTAGGCCTCGAACGTCCTAGCGGCGCCGAGGCCCGCATATACGAGGCGTAACCAGAACTGGTTGAGATAGTCTCGAACCAACTGCCGTTAAAGCTACT 3801 TGCAGCTTGGGCGCAGGGTCGATGCGACGCAATCGTCCGATCCGGAGCCGGGACTGTCGGGCGTACACAAATCGCCCGCAGAAGCGCGGCCGTCTGGACC ACGTCGAACCCGCGTCCCAGCTACGCTGCGTTAGCAGGCTAGGCCTCGGCCCTGACAGCCCGCATGTGTTTAGCGGGCGTCTTCGCGCCGGCAGACCTGG 3901 GATGGCTGTGTAGAAGTACTCGCCGATAGTGGAAACCGACGCCCCAGCACTCGTCCGGATCGGGAGATGGGGGAGGCTAACTGAAACACGGAAGGAGACA CTACCGACACATCTTCATGAGCGGCTATCACCTTTGGCTGCGGGGTCGTGAGCAGGCCTAGCCCTCTACCCCCTCCGATTGACTTTGTGCCTTCCTCTGT 4001 ATACCGGAAGGAACCTCGACGTTAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTATTAC TATGGCCTTCCTTGGAGCTGCAATTGAACAAATAACGTCGAATATTACCAATGTTTATTTCGTTATCGTAGTGTTTAAAGTGTTTATTTCGTAAATAATG 4101 CCTGTTATCCCTAGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTT GGACAATAGGGATCTTAAGTGACCGGCAGCAAAATGTTGCAGCACTGACCCTTTTGGGACCGCAATGGGTTGAATTAGCGGAACGTCGTGTAGGGGGAAA 4201 CGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTT GCGGTCGACCGCATTATCGCTTCTCCGGGCGTGGCTAGCGGGAAGGGTTGTCAACGCGTCGGACTTACCGCTTACCGCGGACTACGCCATAAAAGAGGAA 4301 ACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAG TGCGTAGACACGCCATAAAGTGTGGCGTATGCAGTTTCGTTGGTATCATGCGCGGGACATCGCCGCGTAATTGCGCCGCCCACACCACCAATGCGCGTC 4401 CGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAAT GCACTGGCGATGTGAACGGTCGCGGGATCGCGGGCGAGGAAAGCGAAAGAAGGGAAGGAAAGAGCGGTGCAAGCGGCCGAAAGGGGCAGTTCGAGATTTA 4501 CGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGAT GCCCCCGAGGGAAATCCCAAGGCTAAATCACGAAATGCCGTGGAGCTGGGGTTTTTTGAACTAAACCCACTACCAAGTGCATCACCCGGTAGCGGGACTA 4601 AGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGGCTATTCTTT TCTGCCAAAAAGCGGGAAACTGCAACCTCAGGTGCAAGAAATTATCACCTGAGAACAAGGTTTGACCTTGTTGTGAGTTGGGATAGAGCCCGATAAGAAA 4701 TGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACA ACTAAATATTCCCTAAAACGGCTAAAGCCGGATAACCAATTTTTTACTCGACTAAATTGTTTTTAAATTGCGCTTAAAATTGTTTTATAATTGCAAATGT 4801 ATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTC TAAAATACCACGTGAGAGTCATGTTAGACGAGACTACGGCGTATCAATTCGGTCGGGGCTGTGGGCGGTTGTGGGCGACTGCGCGGGACTGCCCGAACAG 4901 TGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTT ACGAGGGCCGTAGGCGAATGTCTGTTCGACACTGGCAGATCTGCTTTCCCGGAGCACTATGCGGATAAAAATATCCAATTACAGTACTATTATTACCAAA 5001 CTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATA GAATCTGCAGTCCACCGTGAAAAGCCCCTTTACACGCGCCTTGGGGATAAACAAATAAAAAGATTTATGTAAGTTTATACATAGGCGAGTACTCTGTTAT 5101 ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCT TGGGACTATTTACGAAGTTATTATAACTTTTTCCTTCTCATACTCATAAGTTGTAAAGGCACAGCGGGAATAAGGGAAAAAACGCCGTAAAACGGAAGGA 5201 GTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGA CAAAAACGAGTGGGTCTTTGCGACCACTTTCATTTTCTACGACTTCTAGTCAACCCACGTGCTCACCCAATGTAGCTTGACCTAGAGTTGTCGCCATTCT 5301 TCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGA AGGAACTCTCAAAAGCGGGGCTTCTTGCAAAAGGTTACTACTCGTGAAAATTTCAAGACGATACACCGCGCCATAATAGGGCATAACTGCGGCCCGTTCT 5401 GCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTA CGTTGAGCCAGCGGCGTATGTGATAAGAGTCTTACTGAACCAACTCATGAGTGGTCAGTGTCTTTTCGTAGAATGCCTACCGTACTGTCATTCTCTTAAT 5501 TGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGG ACGTCACGACGGTATTGGTACTCACTATTGTGACGCCGGTTGAATGAAGACTGTTGCTAGCCTCCTGGCTTCCTCGATTGGCGAAAAAACGTGTTGTACC 5601 GGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAAC CCCTAGTACATTGAGCGGAACTAGCAACCCTTGGCCTCGACTTACTTCGGTATGGTTTGCTGCTCGCACTGTGGTGCTACGGACATCGTTACCGTTGTTG 5701 GTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGC CAACGCGTTTGATAATTGACCGCTTGATGAATGAGATCGAAGGGCCGTTGTTAATTATCTGACCTACCTCCGCCTATTTCAACGTCCTGGTGAAGACGCG 5801 TCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCT AGCCGGGAAGGCCGACCGACCAAATAACGACTATTTAGACCTCGGCCACTCGCACCCAGAGCGCCATAGTAACGTCGTGACCCCGGTCTACCATTCGGGA 5901 CCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTA GGGCATAGCATCAATAGATGTGCTGCCCCTCAGTCCGTTGATACCTACTTGCTTTATCTGTCTAGCGACTCTATCCACGGAGTGACTAATTCGTAACCAT 6001 ACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATG TGACAGTCTGGTTCAAATGAGTATATATGAAATCTAACTAAATTTTGAAGTAAAAATTAAATTTTCCTAGATCCACTTCTAGGAAAAACTATTAGAGTAC 6101 ACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCT TGGTTTTAGGGAATTGCACTCAAAAGCAAGGTGACTCGCAGTCTGGGGCATCTTTTCTAGTTTCCTAGAAGAACTCTAGGAAAAAAAGACGCGCATTAGA 6201 GCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGC CGACGAACGTTTGTTTTTTTGGTGGCGATGGTCGCCACCAAACAAACGGCCTAGTTCTCGATGGTTGAGAAAAAGGCTTCCATTGACCGAAGTCGTCTCG 6301 GCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTA CGTCTATGGTTTATGACAGGAAGATCACATCGGCATCAATCCGGTGGTGAAGTTCTTGAGACATCGTGGCGGATGTATGGAGCGAGACGATTAGGACAAT 6401 CCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTT GGTCACCGACGACGGTCACCGCTATTCAGCACAGAATGGCCCAACCTGAGTTCTGCTATCAATGGCCTATTCCGCGTCGCCAGCCCGACTTGCCCCCCAA 6501 CGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGC GCACGTGTGTCGGGTCGAACCTCGCTTGCTGGATGTGGCTTGACTCTATGGATGTCGCACTCGATACTCTTTCGCGGTGCGAAGGGCTTCCCTCTTTCCG 6601 GGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGC CCTGTCCATAGGCCATTCGCCGTCCCAGCCTTGTCCTCTCGCGTGCTCCCTCGAAGGTCCCCCTTTGCGGACCATAGAAATATCAGGACAGCCCAAAGCG 6701 CACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTT GTGGAGACTGAACTCGCAGCTAAAAACACTACGAGCAGTCCCCCCGCCTCGGATACCTTTTTGCGGTCGTTGCGCCGGAAAAATGCCAAGGACCGGAAAA 6801 GCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCG CGACCGGAAAACGAGTGTACAAGAAAGGACGCAATAGGGGACTAAGACACCTATTGGCATAATGGCGGAAACTCACTCGACTATGGCGAGCGGCGTCGGC 6901 AACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAG TTGCTGGCTCGCGTCGCTCAGTCACTCGCTCCTTCGCCTTC