# Patent

## Title
Inhibition of hairless protein mRNA

## Abstract

Methods for inhibition of hairless protein mRNA using RNA interference is described, in particular methods for hair removal. Also described are nucleic acid constructs for RNAi-mediated inhibition of hairless protein mRNA and compositions including such constructs.

## Background
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
This application is a continuation of U.S. application Ser. No. 11/113,423 filed Apr. 22, 2005, now abandoned which is based on U.S. Provisional Application Ser. No. 60/565,127 filed Apr. 23, 2004, the contents of each of which are incorporated by reference herein, and to each of which priority is claimed.


SEQUENCE LISTING
The specification further incorporates by reference a substitute Sequence Listing submitted via EFS on Jul. 2, 2007. Pursuant to 37 C.F.R. §1.52(e)(5), the substitute Sequence Listing text file, identified as 700503051.txt, is 2.0 Mb and was created on Jul. 2, 2007. The substitute Sequence Listing, electronically filed herewith, does not extend beyond the scope of the specification and thus does not contain new matter.
The sequence listing, submitted in duplicate on compact disk (CD), in lieu of a paper copy in compliance with 37 C.F.R. §§1.821(c) and 1.52(e), and in duplicate on CD (CRF copy), in compliance with 37 C.F.R. §1.821 (e) has been generated from the specification and figures and does not constitute new matter. The Sequence Listing has been prepared using FastSeq for Windows Version 4.0 software. Four identical CDs, labeled COPY 1, COPY 2, CRF of Sequence Listing submitted under 37 C.F.R. §1.821(e)—COPY 1 and CRF of Sequence Listing submitted under 37 C.F.R. §1.821(e)—COPY 2, (total four (4) CDs), created on Apr. 22, 2005 each contain file: “AP36462_SEQLIST.TXT”, of size 2.28 MB (2,398,842 bytes). The specification incorporates herein by reference, the CD copies of the Sequence Listing submitted under 37 C.F.R §§1.821(c) and 1.52(e). The sequence listing, submitted herein, does not extend beyond the scope of the specification, and thus, does not contain new matter.
BACKGROUND OF THE INVENTION
The following is a discussion of some relevant art relating to hairless protein, and to RNAi. This discussion is provided only to assist the understanding of the reader, and does not constitute an admission that any of the information provided or references cited constitutes prior art to the present invention.
As described in Christiano et al., PCT/US99/02128, WO 99/38965, The human hair follicle is a dynamic structure which generates hair through a complex and highly regulated cycle of growth and remodeling. Hardy, 1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev. Dynamics 205:379. Hair growth is typically described as having three distinct phases. In the first phase, knows as anagen, the follicle is generated and new hair grows.
During the second phase, known as catagen, the follicle enters the stage where elongation ceases and the follicle regresses because the matrix cells stop proliferating. At this stage, the lower, transient half of the follicle is eliminated due to terminal differentiation and keratinization, and programmed cell death. Rosenquist and Martin, 1996, Dev. Dynamics 205:379. Also during catagen, although the dermal papilla remains intact, it undergoes several remodeling events, including degradation of the extracellular matrix that is deposited during anagen. At the close of catagen, the hair is only loosely anchored in a matrix of keratin, with the dermal papilla located just below. The catagen stage occurs at a genetically predetermined time, which is specific for each hair type in a species.
The third phase, known as telogen, is characterized by the follicle entering a quiescent phase, during which the hair is usually shed. When a new hair cycle is initiated, it is thought that a signal from the dermal papilla stimulates the stem cells, which are thought to reside in the permanent portion of the follicle, to undergo a phase of downward proliferation and genesis of a new bulbous base containing matrix cells which then surround the dermal papilla. As the new anagen state progresses, these hair matrix cells produce a new hair, the cycle begins again. Each follicle appears to be under completely asynchronous control, resulting in a continuum of follicles in anagen, catagen, and telegen phases, leading to a relatively homogeneous hair distribution. Hardy, 1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev. Dynamics 205:379.
Christiano et al., PCT/US99/02128, WO 99/38965 describes isolated nucleic acid encoding human hairless protein, the isolated protein, and methods for identifying a compound that is capable of enhancing or inhibiting expression of a human hairless protein, and states that “A therapeutic approach using antisense to human hairless can be used to directly interfere with the translation of Human hairless protein messenger RNA into protein.” It further states that “antisense nucleic acid or ribozymes could be used to bind to the Human hairless protein mRNA or to cleave it.”
Thompson, U.S. Pat. No. 6,348,348, issued Feb. 19, 2002, describes human hairless gene and protein, and screening methods to identify agents that affect expression of the human hairless gene.
Christiano, U.S. patent application Ser. No. 10/122,013, publication 20030077614 (and corresponding Internation Application PCT/US02/11683, WO 02/083891), indicates that “The present invention provides DNAzymes and ribozymes that specifically cleave Hairless Protein mRNA.” The present invention also provides antisense oligonucleotides that specifically inhibit translation of Hairless Protein mRNA. (Abstract.) Also, it states that “This invention provides a nucleic acid molecule that specifically hybridizes to Hairless Protein mRNA so as to inhibit the translation thereof in a cell”; (Specification ¶ 0099) and that “Antisense oligodeoxynucleotides were synthesized as directed to the inhibition of Hairless expression based on the Hairless mRNA sequence.”
SUMMARY OF THE INVENTION
The present invention concerns the use of RNA interference (RNAi) to inhibit mRNA's involved in hair growth, resulting in inhibition of hair growth. For many applications, short interfering RNA (siRNA) are used. Thus, inhibition of hairless protein mRNA, particularly during catagen phase, can result in permanent or at least long term inhibition of hair growth, and thus provides a method for hair removal. Consequently, inhibition of hairless protein mRNA can be used for hair removal and/or hair growth inhibition in cosmetic, therapeutic, and industrial applications.
Thus, in a first aspect, the invention provides a method for hair removal from a mammal, e.g., a human. The method involves applying to a human in an area comprising hair follicles a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto.
In particular embodiments, the inhibition of hair growth in the treated area persists at least 1, 2, 4, 6, 8, 10, 12, or 24 months, or longer, or permanently.
In certain embodiments, the method also involves synchronizing hair growth cycles for hair follicles in the treated area, e.g., by extracting hairs such as by waxing. Such extraction causes follicles in anagen to transition into catagen thereby making those follicles susceptible to inhibition using this invention, and triggers new hair growth of follicles in telogen and thus makes those follicles suitable for transitioning into catagen. Thus, these methods synchronize hair follicles in the hair cycle.
As used in connection with this invention, the term “hair removal” refers to physical removal and continuing inhibition of hair growth from one or more hair follicles. Typically the hair removal applies to a plurality of hair follicles in a skin area on a subject. For example, the area can be up to 2, 5, 10, 20, 50, 100, 200, 400, or more cm2. For hair removal in an area, the hair removal may apply to all or a fraction of the hair follicles in the area.
The term “hair follicle” is used conventionally to refer to a biological hair producing structure.
As used in connection with the present methods, the term “applying” indicates that a substance is placed such that the substance is physically present on or in an area.
The term “nucleic acid molecule” refers to a polymer that includes a plurality of linked nucleotides or nucleotide analogs, and may include one or more modified internucleotidic linkages.
The term “hairless gene” refers to a mammalian gene that corresponds to reference human cDNA GenBank reference number NM—005144, FIG. 1 (SEQ ID NO: 11412) and version NM—005144.3, GI:62750351, FIG. 2 (SEQ ID NO:11413), recognizing that polymorphisms and potentially sequencing errors may be present, or a species homolog of that sequence, e.g., mouse homolog cDNA sequence NM—021877. Similarly the terms “hairless protein mRNA” and “hairless mRNA” refer to an mRNA encoding a hairless gene protein, and “human hairless mRNA” refers to a human homolog of such mRNA.
The phrase “inhibition of hair growth” is used to refer to a reduction or stoppage of hair growth caused at least in part by an agent not normally present in cells in a hair follicle.
As used herein, the phrase “synchronizing hair growth cycles” means that at least 10% of hair follicles in catagen or telogen phase in a particular area are caused to enter anagen phase essentially simultaneously (i.e., within 2 weeks). Such synchronizing can be accomplished, for example, with a physical action such as hair extraction or with one or more chemical or biomolecular agents.
As used herein, the term “hair extraction” refers to pulling of individual hair shafts out of their follicles.
A related aspect concerns a method for hair removal from an area of a mammal comprising hair follicles, where the method involves applying to the area a composition that includes at least one double stranded nucleic acid molecule able to inhibit hairless mRNA translation in vitro.
In certain embodiments, the method also includes synchronizing hair growth cycles for hair follicles in the treated area, such as by hair extraction, e.g., using waxing; the mammal is a human; the mammal is a mouse; the mammal is a rat; the mammal is a bovine.
In another aspect, the invention provides a method of inhibiting expression of hairless protein in a mammal. The method involves administering a double stranded nucleic acid molecule to the mammal, where the double stranded nucleic acid molecule includes a sequence selected from the group consisting of oligonucleotides 1-5664 and their respective antisense sequences, or the species homology of such sequences, and a sequence complementary thereto.
As used in the context of this invention, the term “inhibiting expression” indicates that the level of mRNA and/or corresponding protein or rate of production of the corresponding protein in a cell that would otherwise produce the mRNA and/or protein is reduced as compared to a non-inhibited but otherwise equivalent cell. Reduction in the rate of production can be at various levels, including stopping such production.
The term “species homolog” refers to a form of a gene, or corresponding nucleic acid molecule, or polypeptide from a particular species that is sufficiently similar in sequence to the gene, corresponding nucleic acid, or polypeptide from a reference species that one skilled in the art recognizes a common evolutionary origin.
Thus, as used in connection with a molecule or composition, the phrase “able to inhibit hairless mRNA translation” indicates that the molecule or composition has the property that when present in a cell that would translate hairless mRNA to produce protein in the absence of an inhibitor, the molecule or composition reduces the rate of biosynthesis of hairless protein (or even eliminate such biosynthesis). Such reduction can occur in various ways, for example, by reducing the amount of mRNA available for translation or by at least partially blocking translation of mRNA that is present.
Reference to Oligonucleotides by number utilizes the oligonucleotide numbering in Table 1, and therefore, specifies a nucleotide sequence.
In particular embodiments, the mammal is a human, a mouse, a rat, a bovine (such as a cow), an ovine (such as a sheep), a monkey, a porcine (such as domestic pig).
The term “bovine” is used conventionally to refer to cattle, oxen, and closely related ruminants.
Another aspect concerns a method for treating a human desirous of losing hair. The method involves administering to the human a composition that includes a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto.
As used herein, the phrase “desirous of losing hair” refers to an objective indication of consent or request for a process to remove hair from a body area in a manner reducing or eliminating future hair growth in that area for a period of time, e.g., at least 1 week, 2 weeks, 1 month, 2 months, or longer.
A further aspect concerns a method for marketing a composition for hair removal, which includes providing for sale to medical practitioners (e.g., doctors, nurse practitioners, doctor's assistants, and nurses) or to the public (e.g., spas and other body care businesses, and individuals) a packaged pharmaceutical composition that includes a double stranded nucleic acid molecule containing a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto; and a package label or insert indicating that the pharmaceutical composition can be used for hair removal.
In particular embodiments, the pharmaceutical composition is approved by the U.S. Food and Drug Administration, and/or by an equivalent regulatory agency in Europe or Japan, for hair removal in humans; the pharmaceutical composition is packaged with a hair removal wax or other component adapted for hair removal.
The term “pharmaceutical composition” refers to a substance that contains at least one biologically active component. The composition typically also contains at least one pharmaceutically acceptable carrier or excipient.
As used herein, the term “packaged” means that the referenced material or composition is enclosed in a container or containers in a manner suitable for storage or transportation. For example, a pharmaceutical composition may be sealed in a vial, bottle, tube, or the like, which may itself be inside a box. Typically, a label on the container identifies the contents and may also provide instructions for use and/or cautions to prevent misuse.
The term “hair removal wax” refers to refer to a substance that is adapted for removal of hair by embedding hair in the substance and then pulling the material away, thereby pulling embedded hairs out of the hair follicles. The substance may be used with a backing material such as paper or cloth. Both hot and cold waxes are commonly available. Unless clearly indicated, the term is not limited to substances that are chemically waxes; for example, the term will generally include substances such as caramel-based substances that are used for “sugaring”.
The term “other component adapted for hair removal” refers to a material or device that can be used for physically removing hairs and is either generally recognized as suitable for such use, of instructions are provided indicating that the component can be used for physical hair removal or providing instructions on performing such removal.
Another aspect concerns an isolated double stranded nucleic acid molecule that includes a nucleotide sequence corresponding to 19-25 contiguous nucleotides from human hairless mRNA, where the nucleotide sequence contains a nucleotide sequence selected from the group consisting of oligonucleotides 1-5664; and a nucleotide sequence complementary thereto, where the double stranded nucleic acid molecule induces RNA interference in a human cell in vitro.
Indication that a molecule or material of interest “induces RNA interference in a human cell in vitro” means that when present in cultured cells that are capable of RNA interference and under conditions such that a molecule or molecules that will normally induce RNA interference do induce RNAi in the cell, the molecule or material of interest will induce such RNA interference.
Likewise, in another aspect the invention provides a pharmaceutical composition that includes a double stranded nucleic acid molecule that contains a nucleotide sequence corresponding to 14-50, 17-40, 17-30, 17-25, 19-30, 19-29, 19-28, 19-26, 19-25, 19-24, 19-23, 20-23, 20-22, or 21-22 contiguous nucleotides from human hairless mRNA including a nucleotide sequence selected from the group consisting of oligonucleotides 1-5664, and a sequence complementary thereto, wherein said double stranded nucleic acid molecule induces RNA interference in a human cell in vitro.
In yet another aspect, the invention provides a kit that includes a pharmaceutical composition that contains a double stranded nucleic acid molecule that includes a sequence of at least a portion of human hairless protein mRNA and a sequence complementary thereto; and a package label or insert indicating that said pharmaceutical composition can be used for hair removal.
In certain embodiments, the kit is approved by the U.S. Food and Drug Administration or equivalent regulatory agency in Europe or Japan, for human hair removal.
In certain embodiments of the above aspects or other aspects described herein, the double stranded nucleic acid includes at least one (i.e., one or two) 3′-overhang, e.g., a 1, 2, or 3 nucleotide overhang. In certain embodiments, such overhang includes one or more non-ribonucleotides; includes 1, 2, or 3 deoxynucleotide; includes a modified linkage; each strand has a 1, 2, or 3 nucleotide overhang.
In certain embodiments of the above aspects, at least one strand of the double stranded nucleic acid includes at least one nucleotide analog or internucleotidic linkage different from unmodified RNA; each strand includes at least one nucleotide analog or internucleotidic linkage different from unmodified RNA; at least one strand includes at least one modified nucleotide; each strand includes at least one modified nucleotide.
In certain embodiments of the above aspects, the double stranded nucleic acid molecule induces RNA interference in a cell in vitro and includes the RNA sense sequence of Oligonucleotide 131, namely 5′-CUCUCCAGACAUUUGGCAA-3′ (SEQ ID NO: 11329), and its complementary RNA sequence 5′-TTGCCAAATGTCTGGAGAG-3′ (SEQ ID NO:262); includes the RNA sense sequence of Oligonucleotide 1194, namely 5′-GUGCGGCCGAUCCGCGCCG-3′ (SEQ ID NO: 11330), and its complementary RNA sequence 5′-CGGCGCGGAUCGGCCGCAC-3′ (SEQ ID NO:11331); includes the RNA sense sequence of Oligonucleotide 1521, namely 5′-TGGGAGAAGACGGCCCCAG-3′ (SEQ ID NO:3041) its complementary RNA sequence 5′-CTGGGGCCGTCTTCTCCCA-3′ (SEQ ID NO: 3042); includes an RNA sense sequence and a complementary RNA antisense sequence selected from the group consisting of oligonucleotides 1-5664; is targeted to hairless mRNA corresponding to a site in the coding sequence (CDS) covering nucleotides 1482 to 5051; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 5032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 4032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 3032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1482 to 2032; includes a nucleotide sequence corresponding to an oligonucleotide selected from Oligonucleotides 1582 to 1732.
In certain embodiments of the above aspects, in the double stranded nucleic acid molecule, the sense sequence and the antisense sequence each include 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.
In certain embodiments of the above aspects, chemically modified nucleic acids are used, e.g., chemically modified siRNAs (siNAs) as described in McSwiggen et al., PCT/US03/05346, WO 03/070918, which is incorporated herein by reference.
As used herein, the terms “siRNA” and “siNA” both refer to double stranded nucleic acid that induces RNAi, and includes unmodified RNA oligonucleotides and chemically modified oligonucleotides. When unmodified RNA is intended, the term “unmodified RNA” is expressly used.
The term “RNAi inducing oligonucleotide” or “RNA interference inducing oligonucleotide” refers to an oligonucleotide, generally a double stranded molecule (usually an siRNA molecule), that is able to induce RNA interference in a suitable cell.
In certain embodiments of the above aspects involving application of the present oligonucleotides to a mammal, the oligonucleotides are applied at 0.01 to 0.1 microgram/cm2, 0.1 to 0.2 microgram/cm2, 0.2 to 0.5 microgram/cm2, 0.5 to 1.0 microgram/cm2, 1.0 to 2.0 microgram/cm2, 2.0 to 5.0 microgram/cm2, or 5.0 to 10.0 microgram/cm2; a combination of different RNAi inducing oligonucleotides is applied, which application can be as a mixture or mixtures or separately, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more different oligonucleotides; one or more different RNAi inducing oligonucleotides (e.g., all targeted to hairless, e.g., siRNA) is applied in combination (as a mixture or separately) with one or more different agents that inhibit hairless translation or hairless activity; one or more different RNAi inducing oligonucleotides is applied in combination with one or more other hair removal agents, such as chemical depilatories and/or enzymatic hair removal agents. In accordance with the preceding description of embodiments, certain of the present pharmaceutical compositions also include at least one hairless inhibiting agent different from an RNAi inducing agent, at least one chemical depilatory; at least one enzymatic hair removal agent.
In certain embodiments, the present RNAi inducing oligonucleotides are applied once; applied daily for at least 7 days; applied daily for at least 14 days; applied on at least 4 days within a one month period; applied on at least 7 days within a one month period; applied at least 4 days per week for at least a four week period.
In particular embodiments, the RNAi inducing oligonucleotide does not include the sequence of a siRNA as shown in the Examples; the RNAi oligonucleotide includes the sequence of an siRNA shown in the Examples and the method of use includes synchronizing hair cycles, e.g., as described herein.
In particular embodiments involving mammalian mRNAs, the RNAi inducing oligonucleotide (e.g., siRNA) includes a sequence 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length (or at least one of those lengths) of one of the sequences shown in Table 3, or a sequence complementary thereto; the RNAi inducing oligonucleotide targets a mammalian hairless mRNA sequence corresponding to a sequence shown in Table 3.
In particular embodiments, the RNAi inducing oligonucleotide (e.g., siRNA) targets a human hairless mRNA sequence as identified in Table 4; the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or at least one of those lengths).
In particular embodiments, the RNAi inducing oligonucleotide (e.g., siRNA) targets a mouse hairless mRNA sequence as identified in Table 5; the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or at least one of those lengths).
Additional embodiments will be apparent from the Detailed Description and from the claims.



BRIEF DESCRIPTION OF THE FIGURES
FIG. 1. NM005144 (SEQ ID NO:11412)
FIG. 2. NM005144.3 (SEQ ID NO: 11413)



DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention concerns methods for inhibiting hair growth, by inhibiting particular mRNAs using RNAi, e.g., using siRNA. In particular non-limiting embodiments, the present invention provides for siRNA molecules, e.g., double stranded RNA oligonucleotides (which optionally may be chemically modified and/or comprise at least one 3′ overhang, as set forth below), comprising a nucleotide sequence that is complementary to a target nucleotide sequence which may be 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length, where the siRNA contains a sequence 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 base pairs in length. Preferably, the hairless in RNA target nucleotide sequence comprises a 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotide portion of the human hairless mRNA sequence set forth in FIG. 1 (SEQ ID NO: 11412) and/or FIG. 2 (SEQ ID NO: 11413). Non-limiting examples of target sequences may be identified as loops identified in secondary mRNA structure using software designed for such purpose (e.g. RnaDraw, RnaMotif, Rnaview-RnaMLView, RnaViz, Vienna RNA Package, etc.).
A. RNAi and siRNA
RNA interference (RNAi) refers to the process of sequence-specific post-transcriptional gene silencing in animals mediated by short interfering RNAs (siRNAs) (Fire et al., 1998, Nature, 391, 806). The corresponding process in plants is commonly referred to as post-transcriptional gene silencing or RNA silencing and is also referred to as quelling in fungi. The process of post-transcriptional gene silencing is thought to be an evolutionarily-conserved cellular defense mechanism used to prevent the expression of foreign genes and is commonly shared by diverse flora and phyla (Fire et al., 1999, Trends Genet., 15, 358). The presence of dsRNA in cells triggers the RNAi response though a mechanism that appears to be different from the interferon response that results from dsRNA-mediated activation of protein kinase PKR and 2′,5′-oligoadenylate synthetase resulting in non-specific cleavage of mRNA by ribonuclease L.
The presence of long dsRNAs in cells stimulates the activity of the enzyme, dicer, a ribonuclease III. Dicer is involved in the processing of the dsRNA into short pieces of dsRNA known as short interfering RNAs (siRNAs) (Berstein et al., 2001, Nature, 409, 363). The resulting RNAs are typically about 21 to about 23 nucleotides in length, with complementary sequences of about 19 base pairs. Dicer has also been implicated in the excision of 21- and 22-nucleotide small temporal RNAs (stRNAs) from precursor RNA of conserved structure that are implicated in translational control (Hutvagner et al., 2001, Science, 293, 834). The RNAi response also involves an endonuclease complex, commonly referred to as an RNA-induced silencing complex (RISC), which mediates cleavage of single-stranded RNA having sequence complementary to the antisense strand of the siRNA duplex. Cleavage of the target RNA takes place in the middle of the region complementary to the antisense strand of the siRNA duplex (Elbashir et al., 2001, Genes Dev., 15, 188).
RNAi has been studied in a variety of systems. Fire et al., 1998, Nature, 391, 806, described RNAi in C. elegans. Wianny and Goetz, 1999, Nature Cell Biol., 2, 70, describe RNAi mediated by dsRNA in mouse embryos. Hammond et al., 2000, Nature, 404, 293, describe RNAi in Drosophila cells transfected with dsRNA. Elbashir et al., 2001, Nature, 411, 494, describe RNAi induced by introduction of duplexes of synthetic 21-nucleotide RNAs in cultured mammalian cells including human embryonic kidney and HeLa cells.
Work in Drosophila embryonic lysates (Elbashir et al., 2001, EMBO J, 20, 6877) has revealed certain factors of siRNA length, structure, chemical composition, and sequence that are significantly affect efficient RNAi activity. These studies have shown that 21-nucleotide siRNA duplexes are most active when containing 3′-terminal nucleotide overhangs. Furthermore, complete substitution of one or both siRNA strands with 2′-deoxy (2′-H) or 2′-O-methyl nucleotides abolishes RNAi activity, whereas substitution of the 3′-terminal siRNA overhang nucleotides with 2′-deoxy nucleotides (2′-H) was shown to be tolerated. Single mismatch sequences in the center of the siRNA duplex were also shown to abolish RNAi activity. In addition, these studies also indicate that the position of the cleavage site in the target RNA is defined by the 5′-end of the siRNA guide sequence rather than the 3′-end of the guide sequence (Elbashir et al., 2001, EMBO J., 20, 6877). Other studies have suggested that a 5′-phosphate on the target-complementary strand of a siRNA duplex is important for siRNA activity and that ATP is utilized to maintain the 5′-phosphate moiety on the siRNA (Nykanen et al., 2001, Cell, 107, 309).
Studies have shown that replacing the 3′-terminal nucleotide overhanging segments of a 21-mer siRNA duplex having two 2-nucleotide 3′-overhangs with deoxyribonucleotides does not have an adverse effect on RNAi activity. Replacing up to 4 nucleotides on each end of the siRNA with deoxyribonucleotides has been reported to be well-tolerated whereas complete substitution with deoxyribonucleotides results in no RNAi activity, but that substitution of siRNA with 2′-O-methyl nucleotides completely abolishes RNAi activity. (Elbashir et al., 2001, EMBO J., 20, 6877.)
Li et al., International PCT Publication No. WO 00/44914, and Beach et al., International PCT Publication No. WO 01/68836 both suggest that siRNA “may include modifications to either the phosphate-sugar backbone or the nucleoside . . . to include at least one of a nitrogen or sulfur heteroatom.”
Kreutzer and Limmer, Canadian Patent Application No. 2,359,180, also describe certain chemical modifications for use in dsRNA constructs in order to counteract activation of double-stranded RNA-dependent protein kinase PKR, specifically 2′-amino or 2′-O-methyl nucleotides, and nucleotides containing a 2′-O or 4′-C methylene bridge
Parrish et al., 2000, Molecular Cell, 6, 1977-1087, tested certain chemical modifications targeting the unc-22 gene in C. elegans using long (>25 nt) siRNA transcripts. The authors describe the introduction of thiophosphate residues into these siRNA transcripts by incorporating thiophosphate nucleotide analogs with T7 and T3 RNA polymerase and observed that “RNAs with two [phosphorothioate] modified bases also had substantial decreases in effectiveness as RNAi triggers (data not shown); [phosphorothioate] modification of more than two residues greatly destabilized the RNAs in vitro and we were not able to assay interference activities.” Id. at 1081. The authors also tested certain modifications at the 2′-position of the nucleotide sugar in the long siRNA transcripts and observed that substituting deoxynucleotides for ribonucleotides “produced a substantial decrease in interference activity,” especially in the case of Uridine to Thymidine and/or Cytidine to deoxy-Cytidine substitutions. Id. In addition, the authors tested certain base modifications, including substituting, in sense and antisense strands of the siRNA, 4-thiouracil, 5-bromouracil, 5-iodouracil, and 3-(aminoallyl)uracil for uracil, and inosine for guanosine. They found that whereas 4-thiouracil and 5-bromouracil were all well-tolerated, inosine “produced a substantial decrease in interference activity” when incorporated in either strand. Incorporation of 5-iodouracil and 3-(aminoallyl)uracil in the antisense strand resulted in substantial decrease in RNAi activity as well.
Beach et al., International PCT Publication No. WO 01/68836, describes specific methods for attenuating gene expression using endogenously-derived dsRNA.
Tuschl et al., International PCT Publication No. WO 01/75164, describe a Drosophila in vitro RNAi system and the use of specific siRNA molecules for certain functional genomic and certain therapeutic applications; although Tuschl, 2001, Chem. Biochem., 2, 239-245, doubts that RNAi can be used to cure genetic diseases or viral infection due “to the danger of activating interferon response.”
Li et al., International PCT Publication No. WO 00/44914, describe the use of specific dsRNAs for use in attenuating the expression of certain target genes.
Zernicka-Goetz et al., International PCT Publication No. WO 01/36646, describe certain methods for inhibiting the expression of particular genes in mammalian cells using certain dsRNA molecules.
Fire et al., International PCT Publication No. WO 99/32619, describe particular methods for introducing certain dsRNA molecules into cells for use in inhibiting gene expression.
Plaetinck et al., International PCT Publication No. WO 00/01846, describe certain methods for identifying specific genes responsible for conferring a particular phenotype in a cell using specific dsRNA molecules.
Mello et al., International PCT Publication No. WO 01/29058, describe the identification of specific genes involved in dsRNA-mediated RNAi.
Deschamps Depaillette et al., International PCT Publication No. WO 99/07409, describe specific compositions consisting of particular dsRNA molecules combined with certain anti-viral agents.
Waterhouse et al., International PCT Publication No. 99/53050, describe certain methods for decreasing the phenotypic expression of a nucleic acid in plant cells.
Driscoll et al., International PCT Publication No. WO 01/49844, describe specific DNA constructs for use in facilitating gene silencing in targeted organisms.
Parrish et al., 2000, Molecular Cell, 6, 1977-1087, describe specific chemically-modified siRNA constructs targeting the unc-22 gene of C. elegans. 
Grossniklaus, International PCT Publication No. WO 01/38551, describes certain methods for regulating polycomb gene expression in plants.
Churikov et al., International PCT Publication No. WO 01/42443, describe certain methods for modifying genetic characteristics of an organism.
Cogoni et al., International PCT Publication No. WO 01/53475, describe certain methods for isolating a Neurospora silencing gene and uses thereof.
Reed et al., International PCT Publication No. WO 01/68836, describe certain methods for gene silencing in plants.
Honer et al., International PCT Publication No. WO 01/70944, describe certain methods of drug screening using transgenic nematodes as Parkinson's Disease models.
Deak et al., International PCT Publication No. WO 01/72774, describe certain Drosophila-derived gene products.
Arndt et al., International PCT Publication No. WO 01/92513, describe certain methods for mediating gene suppression by using factors that enhance RNAi.
Tuschl et al., International PCT Publication No. WO 02/44321, describe certain synthetic siRNA constructs.
Pachuk et al., International PCT Publication No. WO 00/63364, and Satishchandran et al., International PCT Publication No. WO 01/04313, describe certain methods and compositions for inhibiting the function of certain oligonucleotide sequences.
Echeverri et al., International PCT Publication No. WO 02/38805, describe certain C. elegans genes identified via RNAi.
Kreutzer et al., International PCT Publications Nos. WO 02/055692, WO 02/055693, and EP 1144623 B1 describes certain methods for inhibiting gene expression using RNAi.
Graham et al., International PCT Publications Nos. WO 99/49029 and WO 01/70949, and AU 4037501 describe certain vector expressed long double stranded RNA molecules.
McSwiggen et al., PCT/US03/05028, WO 03/074654 describes RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA), and provides a table listing thousands of mRNAs, which is believed to include hairless protein mRNA, as potential targets for such siNA.
McSwiggen et al., PCT/US03/05346, WO 03/070918 describes synthetic chemically modified small nucleic acid molecules capable of mediating RNA interference against target nucleic acid sequences. The reference reports that up to all of the nucleotides in the RNA strands can be replaced with moieties that are not ribonucleotides.
B. Hairless Protein mRNA
Applicant's have found that RNAi can be used to inhibit translation from hairless protein mRNA, resulting in hair removal. This hair removal is long term, or even permanent, thus providing cosmetic and therapeutic methods, as well as methods useful for laboratory experimental mammals, and for de-hairing in the leather industry.
The Hairless Protein gene is expressed during a narrow window during the hair cycle, just at the transition to catagen (the regression phase). (Panteleyev et al. 1998, Exp Dermatol. 7:249-67; Panteleyev et al. 2000, Am J Pathol. 157:1071-9). In both humans and mice with mutations in the hairless gene, the cardinal finding is a wave of hair shedding shortly after birth, and no subsequent hair growth throughout life. The phenotype results from permanent structural damage to the hair follicle, after which no further hair cycling can occur. In addition, humans and mice which are genetically deficient in hairless gene expression exhibit no other phenotypic manifestations or abnormalities that might be associated with a deleterious effect (Zlotogorski et al., 2002, J Invest Dermatol. 118:887-90), suggesting that hairless is specifically involved and indispensable in regulating the hair cycle, and that its functions elsewhere in the body (if any) are compensated by other factors.
As a result, hair removal using RNAi targeted to hairless mRNA provides an advantageous approach, as any inadvertent, non-localized inhibition of hairless mRNA will not adversely affect the subject.
C. Applications and Conditions to be Treated
As indicated above, the present invention concerns inhibition of hair growth, and consequent hair removal, and is applicable to a number of different therapeutic, cosmetic, and industrial applications. The methods can be readily adapted to any of the various mammals having hairless protein analogs, for example, human, mouse, rat, cattle (and other bovines), equines.
1. Long Term (Permanent) Hair Removal
Permanent, or at least long term, hair removal can involve inhibition of hairless protein. Such hair removal is useful for both cosmetic and therapeutic applications. Exemplary cosmetic applications can include, for example, back and chest hair for men and upper lip, eyebrow, leg, arm, underarm, and pubic hair for women.
In addition to cosmetic applications, permanent or long term hair removal is also useful in certain conditions, e.g., trachoma, the various forms of hypertrichosis, and hirsutism.
Hypertrichosis
Hypertrichosis describes all forms of hair growth that are excessive for the bodily location and age of an individual, and which do not result from androgen stimulation. The present invention can be used for the various forms and causes of hypertrichosis, e.g., those described herein.
Hypertrichosis is usually categorized on the basis of the age of onset (at birth or during later years), the extent of distribution (universal or localized), the site of involvement (elbows, anterior or posterior neck), and the cause (genetic or acquired).
Acquired hypertrichosis may result from the use of particular drugs, for example, oral minoxidil, phenyloin, and cyclosporin. Acquired hypertrichosis lanuginosa may also be a manifestation of an underlying malignancy. In the dermatological literature, this is known as “malignant down”. Additional causes of acquired hypertrichosis include hormonal imbalances, malnutrition, HIV and local inflammation.
In addition, some forms of hypertrichosis are clearly hereditary but the genes involved generally remain unknown. Genetic forms of hypertrichosis are very rare human disorders.
There are only a small number of human disorders that have generalized congenital hypertrichosis as the leading phenotypic feature. These include:
Hypertrichosis universalis (MIM145700)
Hypertrichosis universalis congenita, Ambras type (MIM145701)
Gingival fibromatosis with hypertrichosis (MIMI 35400)
Barber-Say syndrome (MIM209885)
Amaurosis congenita, cone-rod type, with hypertrichosis (MIM204110),
CAHMR syndrome (MIM21770)
Cantu syndrome (MIM239850)
Gingival fibromatosis with hypertrichosis and mental retardation MIM605400)
X-linked hypertrichosis (MIM307150)
Acromegaly and hypertrichosis (Irvine et al, 1996).
Of these, only Hypertrichosis universalis, Ambras type hypertrichosis, and X-linked hypertrichosis have excessive hair as the predominant feature. In all the other listed syndromes hypertrichosis is associated with additional more prominent abnormalities. The present invention can be used to treat hypertrichosis, e.g., in any of the conditions listed above, as well as in other conditions in which trichosis occurs.
Trachoma
Trachoma is the leading cause of blindness worldwide. The World Health Organization estimates that there are 146 million people with trachoma and that the disease has caused blindness in 5.9 million people, 15% of the world's blindness. Trachoma is caused by the gram-negative bacterium Chlamydia trachomatis, an intracellular parasite transmitted by fly infestation. In trachoma, the conjunctival lining of the eyelids becomes infected with the bacterium, which over the long term, causes an inflammatory response. The inflammation can lead to scarring, shortening of the lid and in-turning of the eyelashes. Trichiasis, the condition when eyelashes rub on the cornea, can lead to blindness. An estimated 10.6 million adults have inturned eyelashes that require surgery.
While it is advantageous of the Chlamydia infection is prevented, or treated before in-turning of the eyelashes, there is a need for non-surgical approaches to treatment that can at least reduce the corneal scarring. Thus, removal of the eyelash hairs (without leaving stubble) using the present invention can substantially slow, or even prevent such corneal damage, thereby preserving the individual's vision.
Trichiasis
In addition to trachoma, in-turned eyelashes (trichiasis) can have other causes, and are a common source of recurrent ocular irritation for some patients. The in-turned lash (or lashes) in contact with the conjunctiva and/or cornea may lead to a foreign body sensation, localized conjunctival injection, pain and photophobia.
Trichiasis is the term used for misdirection or aberrant placement of eyelashes along the eyelid margin resulting in lash growth toward the cornea. Trichiasis is an acquired condition that may be caused by the following inflammatory or traumatic processes involving the eyelids. The present invention can be used in all cases of trichiasis, including those in the following causal situations:
Chronic blepharitis with meibomianitis—chronic inflammatory changes within the tarsal plate and posterior eyelid margin may cause destruction and misdirection of lash follicles, resulting in chronic trichiasis.
Lid lacerations and thermal burns to the lid margin—may cause redirection of the lash roots with resultant trichiasis.
Previous surgery on eyelids—For example, lid adhesions (tarsorrhaphys) done to prevent exposure in some patients with seventh nerve palsies may cause misdirection of lashes. Similarly, in many reconstructive eyelid procedures, the new eyelid margin may contain fine skin hairs (lanugo-type) that rub on the cornea.
Mucocutaneous diseases—Stevens-Johnson syndrome and Ocular Cicatricial Pemphigoid result not only in the destruction of the eyelid margins and trichiasis but also in the formation of new lashes from the meibomian gland orifices (a condition referred to as distichiasis).
Other cicatricial conjunctival diseases—Herpes Simplex conjunctivitis and Herpes Zoster may cause a cicatrizing conjunctivitis with destruction of the lid margin and lash follicles. Trachoma may also cause a chronic tarsitis with cicatrizing conjunctivitis in the upper or lower eyelid and resultant trichiasis (as well as a cicatricial entropion).
Irradiation and chemical burns—Therapeutic irradiation for eyelid cancers or alkali burns may lead to a disruption of the normal eyelid margin anatomy and resultant misdirection of eyelashes. Both of these processes may also lead to metaplasia of squamous epithelium of the mucocutaneous margin of the eyelid with resultant keratinization, a source of ocular irritation. In addition, destruction of the goblet cells, accessory lacrimal glands, and lacrimal gland will disrupt the normal tear flow, compounding the above problems.
Other conditions in which eyelashes contact the cornea also exist, and the present invention can be used in those cases also. For example:
A condition similar to trichiasis is Eyelid entropion—True entropion (e.g. involutional type seen in the aging population) is characterized by a normal eyelid margin architecture: the eyelid inverts as a result of eyelid laxity, allowing the eyelashes to rub on the cornea. Several of the entities mentioned above (Ocular Pemphigoid, Stevens-Johnson Syndrome) may cause a cicatrization of the conjunctiva as well as the lid margin and create a cicatricial entropion with trichiasis (i.e. the eyelid is inverted due to a cicatricial process). In addition, eyelashes may be misdirected not only due to the lid position, but also due to the inflammatory process involving the actual lash follicles. Therefore, sometimes there may be two problems present (entropion and trichiasis) both of which may require treatment.
Epiblepharon—Epiblepharon is a congenital condition commonly seen in the lower Asian eyelid. A fold of skin and muscle roll upwards and presses the lashes toward the cornea. This does not represent true trichiasis.
Distichiasis—is an abnormality in which an aberrant second row of lashes, (usually from the meibomian gland orifices) grows behind the normal lash line. It may be congenital or acquired. Any process causing chronic inflammation of the lid margin and meibomian glands may transform the meibomian glands into pilosebaceous units capable of producing hair (e.g. chronic blepharitis).
Combined eyelid margin process—Several of the eyelid processes mentioned (Stevens-Johnson syndrome, Ocular Pemphigoid, irradiation, chemical burns) not only may cause entropion and trichiasis, but in addition may lead to squamous metaplasia and keratinization of the non-keratinizing squamous epithelium of the eyelid margin. Keratinized tissue is very irritating to the eye. Therefore, several factors may contribute to the ocular irritation, and as a result, several types of treatment could be required.
Marginal entropion—Is a subtle form of entropion that is seen only at the lid margin. Usually there is chronic inflammation at the eyelid margin with a mild cicatricial process that is starting to roll the lid margin inward. The eyelashes appear more vertical with some truly trichiatic lashes. The clinical clue is the meibomian gland orifices. Normally they should be vertical and not covered by conjunctival epithelium. If the openings are rolled inward and conjunctiva is growing over the opening, then marginal entropion is present in addition to trichiasis. It is important to distinguish this condition when considering treatment.
Hirsutism
Hirsutism is excessive hair growth on a female in a male growth pattern, typically excessive facial hair. Hirsutism is usually caused by an increased sensitivity of the skin to a group of hormones called androgens (testosterone and androstenedione) or increased production of these hormones. Androgen disorders (hyperandrogenism) affects between 5% to 10% of all women. Hair from this condition can be removed in full or part using the present invention.
Pseudofolliculitis barbae
Pseudofolliculitis barbae (razor bumps) is a common condition of the beard area occurring in African American men and other people with curly hair. The problem results when highly curved hairs grow back into the skin causing inflammation and a foreign body reaction. Over time, this can cause keloidal scarring which looks like hard bumps of the beard area and neck. Currently this is usually addressed by attempting to prevent the hair from curving back and growing into the skin with altered shaving practices and the like. The present invention can be used to eliminate hairs causing such difficulties.
Experimental Animals
Permanent hair removal as described herein can also be used with experimental animals to remove hair from all or a portion of the body of an experimental animal. Thus, for example, a hairless spot can be created on a mouse, rat, sheep, monkey, chimpanzee, rabbit or other animal for application over an extended period of time of topically applied pharmaceutical compounds or other materials. Thus, the present invention can be used for this purpose, either with or without shaving shaveing, waxing, or depilation, or other such treatment. In some cases, the hairless spot or area on the animal is initially created with shaving, waxing, or other hair removal method, and the present invention allows the bare area to be maintained (which may be after a sustained period of application of the present compositions, e.g., at least 2, 4, 7, or 10 days, or 2, 3, 4, 5, 6, 8, 10, 12, weeks or even longer).
Industrial Applications
In addition, permanent hair removal as described herein can also be useful to remove hair from mammals whose hides will be used for leather. Dehairing is one of the main initial steps in leather production. Five methods of dehairing are commonly used: i.e., (i) clipping process, (ii) scalding process, (iii) chemical process, (iv) sweating process, and (v) enzymatic process. Of these, the most commonly practiced method of dehairing of hides and skins is the chemical process using lime and sodium sulphide. However, the use of high concentrations of lime and sodium sulphide creates an extremely alkaline environment resulting in the pulping of hair and its subsequent removal, and presents substantial pollution problems. Thus, removal of hairs using the present invention allows hides to be prepared for leather production while eliminating or at least reducing the use of the pollution-causing methods.
D. Use of RNAi and Oligo Sequences
The use of RNAi to reduce or eliminate translation from a targeted mRNA has been described in a number of patents and published patent applications, e.g., as mentioned in the Background of the Invention. In the present invention, particular target sites in hairless protein mRNA can be identified experimentally and/or using software programs to identify accessible sites. For example, procedures such as those described below can be used to identify sites, and to select an optimal site and active oligonucleotide.
Identification of Potential RNAi (e.g., siRNA) Target Sites in any RNA Sequence
The sequence of an RNA target of interest, such as a viral or human mRNA transcript, is screened for target sites, for example by using a computer folding algorithm. In a non-limiting example, the sequence of a gene or RNA gene transcript derived from a database, such as Genbank, is used to generate siNA targets having complementarity to the target. Such sequences can be obtained from a database, or can be determined experimentally as known in the art. Target sites that are known, for example, those target sites determined to be effective target sites based on studies with other nucleic acid molecules, for example ribozymes or antisense, or those targets known to be associated with a disease or condition such as those sites containing mutations or deletions, can be used to design siNA molecules targeting those sites as well. Various parameters can be used to determine which sites are the most suitable target sites within the target RNA sequence. These parameters include but are not limited to secondary or tertiary RNA structure, the nucleotide base composition of the target sequence, the degree of homology between various regions of the target sequence, or the relative position of the target sequence within the RNA transcript. Based on these determinations, any number of target sites within the RNA transcript can be chosen to screen siNA molecules for efficacy, for example by using in vitro RNA cleavage assays, cell culture, or animal models. In a non-limiting example, anywhere from 1 to 1000 target sites are chosen within the transcript based on the size of the siNA construct to be used. High throughput screening assays can be developed for screening siNA molecules using methods known in the art, such as with multi-well or multi-plate assays or combinatorial/siNA library screening assays to determine efficient reduction in target gene expression.
Selection of siNA Molecule Target Sites in a RNA
The following non-limiting steps can be used to carry out the selection of siNAs targeting a given gene sequence or transcript.

    
    
        1 The target sequence is parsed in silico into a list of all fragments or subsequences of a particular length, for example 23 nucleotide fragments, contained within the target sequence. This step is typically carried out using a custom Perl script, but commercial sequence analysis programs such as Oligo, MacVector, or the GCG Wisconsin Package can be employed as well.
        2 In some instances the siNAs correspond to more than one target sequence; such would be the case for example in targeting different transcripts of the same gene, targeting different transcripts of more than one gene, or for targeting both the human gene and an animal homolog. In this case, a subsequence list of a particular length is generated for each of the targets, and then the lists are compared to find matching sequences in each list. The subsequences are then ranked according to the number of target sequences that contain the given subsequence; the goal is to find subsequences that are present in most or all of the target sequences. Alternately, the ranking can identify subsequences that are unique to a target sequence, such as a mutant target sequence. Such an approach would enable the use of siNA to target specifically the mutant sequence and not effect the expression of the normal sequence.
        3 In some instances the siNA subsequences are absent in one or more sequences while present in the desired target sequence; such would be the case if the siNA targets a gene with a paralogous family member that is to remain untargeted. As in case 2 above, a subsequence list of a particular length is generated for each of the targets, and then the lists are compared to find sequences that are present in the target gene but are absent in the untargeted paralog.
        4 The ranked siNA subsequences can be further analyzed and ranked according to GC content. A preference can be given to sites containing 30-70% GC, with a further preference to sites containing 40-60% GC.
        5 The ranked siNA subsequences can be further analyzed and ranked according to self-folding and internal hairpins. Weaker internal folds are preferred; strong hairpin structures are to be avoided.
        6 The ranked siNA subsequences can be further analyzed and ranked according to whether they have runs of GGG or CCC in the sequence. GGG (or even more Gs) in either strand can make oligonucleotide synthesis problematic and can potentially interfere with RNAi activity, so it is avoided whenever better sequences are available. CCC is searched in the target strand because that will place GGG in the antisense strand.
        7 The ranked siNA subsequences can be further analyzed and ranked according to whether they have the dinucleotide UU (uridine dinucleotide) on the 3′-end of the sequence, and/or AA on the 5′-end of the sequence (to yield 3′ UU on the antisense sequence). These sequences allow one to design siNA molecules with terminal TT thymidine dinucleotides.
        8 Four or five target sites are chosen from the ranked list of subsequences as described above. For example, in subsequences having 23 nucleotides, the right 21 nucleotides of each chosen 23-mer subsequence are then designed and synthesized for the upper (sense) strand of the siNA duplex, while the reverse complement of the left 21 nucleotides of each chosen 23-mer subsequence are then designed and synthesized for the lower (antisense) strand of the siNA duplex. If terminal TT residues are desired for the sequence (as described in paragraph 7), then the two 3′ terminal nucleotides of both the sense and antisense strands are replaced by TT prior to synthesizing the oligos.
        9 The siNA molecules are screened in an in vitro, cell culture or animal model system to identify the most active siNA molecule or the most preferred target site within the target RNA sequence.
    
    


In an alternate approach, a pool of siNA constructs specific to a target sequence is used to screen for target sites in cells expressing target RNA, such as human lung HeLa cells. A non-limiting example of such as pool is a pool comprising sequences having antisense sequences complementary to the target RNA sequence and sense sequences complementary to the antisense sequences. Cells (e.g., HeLa cells) expressing the target gene are transfected with the pool of siNA constructs and cells that demonstrate a phenotype associated with gene silencing are sorted. The pool of siNA constructs can be chemically modified as described herein and synthesized, for example, in a high throughput manner. The siNA from cells demonstrating a positive phenotypic change (e.g., decreased target mRNA levels or target protein expression), are identified, for example by positional analysis within the assay, and are used to determine the most suitable target site(s) within the target RNA sequence based upon the complementary sequence to the corresponding siNA antisense strand identified in the assay.
Exemplary siNA Design
siNA target sites are chosen by analyzing sequences of the target RNA target and optionally prioritizing the target sites on the basis of folding (structure of any given sequence analyzed to determine siNA accessibility to the target), by using a library of siNA molecules as described, or alternately by using an in vitro siNA system as described herein. siNA molecules were designed that could bind each target and are optionally individually analyzed by computer folding to assess whether the siNA molecule can interact with the target sequence. Varying the length of the siNA molecules can be chosen to optimize activity. Generally, a sufficient number of complementary nucleotide bases are chosen to bind to, or otherwise interact with, the target RNA, but the degree of complementarity can be modulated to accommodate siNA duplexes or varying length or base composition. By using such methodologies, siNA molecules can be designed to target sites within any known RNA sequence, for example those RNA sequences corresponding to the any gene transcript.
Chemically modified siNA constructs are designed to provide nuclease stability for systemic administration in vivo and/or improved pharmacokinetic, localization, and delivery properties while preserving the ability to mediate RNAi activity. Chemical modifications as described herein are introduced synthetically using synthetic methods described herein and those generally known in the art. The synthetic siNA constructs are then assayed for nuclease stability in serum and/or cellular/tissue extracts (e.g. liver extracts). The synthetic siNA constructs are also tested in parallel for RNAi activity using an appropriate assay, such as a luciferase reporter assay as described herein or another suitable assay that can quantity RNAi activity. Synthetic siNA constructs that possess both nuclease stability and RNAi activity can be further modified and re-evaluated in stability and activity assays. The chemical modifications of the stabilized active siNA constructs can then be applied to any siNA sequence targeting any chosen RNA and used, for example, in target screening assays to pick lead siNA compounds for therapeutic development.
RNAi In Vitro Assay to Assess siNA Activity
An in vitro assay that recapitulates RNAi in a cell free system is used to evaluate siNA constructs specific to target RNA. The assay comprises the system described by Tuschl et al., 1999, Genes and Development, 13, 3191-3197 and Zamore et al., 2000, Cell, 101, 25-33 adapted for use with a specific target RNA. A Drosophila extract derived from syncytial blastoderm is used to reconstitute RNAi activity in vitro. Target RNA is generated via in vitro transcription from an appropriate plasmid using T7 RNA polymerase or via chemical synthesis as described herein. Sense and antisense siNA strands (for example 20 uM each) are annealed by incubation in buffer (such as 100 mM potassium acetate, 30 mM HEPES-KOH, pH 7.4, 2 mM magnesium acetate) for 1 min. at 90° C. followed by 1 hour at 37° C., then diluted in lysis buffer (for example 100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate). Annealing can be monitored by gel electrophoresis on an agarose gel in TBE buffer and stained with ethidium bromide. The Drosophila lysate is prepared using zero to two hour old embryos from Oregon R flies collected on yeasted molasses agar that are dechorionated and lysed. The lysate is centrifuged and the supernatant isolated. The assay comprises a reaction mixture containing 50% lysate [vol/vol], RNA (10-50 pM final concentration), and 10% [vol/vol] lysis buffer containing siNA (10 nM final concentration). The reaction mixture also contains 10 mM creatine phosphate, 10 ug.ml creatine phosphokinase, 100 um GTP, 100 uM UTP, 100 uM CTP, 500 uM ATP, 5 mM DTT, 0.1 U/uL RNasin (Promega), and 100 uM of each amino acid. The final concentration of potassium acetate is adjusted to 100 mM. The reactions are pre-assembled on ice and preincubated at 25° C. for 10 minutes before adding RNA, then incubated at 25° C. for an additional 60 minutes. Reactions are quenched with 4 volumes of 1.25× Passive Lysis Buffer (Promega). Target RNA cleavage is assayed by RT-PCR analysis or other methods known in the art and are compared to control reactions in which siNA is omitted from the reaction.
Alternately, internally-labeled target RNA for the assay is prepared by in vitro transcription in the presence of [a-32P] CTP, passed over a G 50 Sephadex column by spin chromatography and used as target RNA without further purification. Optionally, target RNA is 5′-32P-end labeled using T4 oligonucleotide kinase enzyme. Assays are performed as described above and target RNA and the specific RNA cleavage products generated by RNAi are visualized on an autoradiograph of a gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing intact control RNA or RNA from control reactions without siNA and the cleavage products generated by the assay.
In one embodiment, this assay is used to determine target sites in the RNA target for siNA mediated RNAi cleavage, wherein a plurality of siNA constructs are screened for RNAi mediated cleavage of the RNA target, for example by analyzing the assay reaction by electrophoresis of labeled target RNA, or by northern blotting, as well as by other methodology well known in the art.
Specific hairless protein target sequences and the complementary sequences are provided as 19-mers in Table 1 following the Examples. In the table, the oligo number (first column on the left), e.g., 1, 2, 3, etc. matches the 1st (5′) nucleotide in the reference sense cDNA sequence. Thus, Oligonucleotide 1 begins at nucleotide 1 in the reference hairless cDNA sequence, Oligonucleotide 2, begins at nucleotide 2 in the reference sequence, and so on. Thus, one skilled in the art recognizes that the nucleotide position of each nucleotide in each oligonucleotide in Table 1 is specified as if each nucleotide were marked with the respective number.
The sequences shown in Table 1 are provided as DNA sequences, but one skilled in the art understands that Table 1 also describes the matching RNA sequence. One skilled in the art understands that the RNA sequence has a U replacing each T shown in the DNA sequence. For example, for Oligonucleotide 1 in Table 1, the DNA sequence is 5′-TCTCCCGGGAGCCACTCCC-3′ (SEQ ID NO: 1), and the matching RNA sequence is 5′-UCUCCCGGGAGCCACUCCC-3′ (SEQ ID NO: 11332).
While oligonucleotides are shown in Table 1 as 19-mers, this description expressly includes the additional 20-mer, 21-mer, 22-mer, 23-mer, 24-mer, 25-mer, 26-mer, 27-mer, 28-mer, and 29-mer oligonucleotides as if they were included in the table. The sequence descriptions of those 20-29-mers is provided by taking a starting 19-mer that has the same 5′-nucleotide as the respective 20-29-mer, and adding the next 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 3′-nucleotides from the subsequent 19-mer oligonucleotides from the table. Thus, for example, the 19-mer sense RNA Oligonucleotide 4 has the sequence:










5′-CCCGGGAGCCACUCCCAUG-3′
(SEQ ID NO: 11333)






and the complementary 19-mer RNA described has the sequence











5′-CAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11334)






Further, a 20-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next nucleotide 3′, i.e., the 3′-terminal G from Oligo 5. Thus, the 20-mer RNA described has the sequence










5′-CCCGGGAGCCACUCCCAUGG-3′
(SEQ ID NO: 11335)






and the complementary 20-mer RNA described has the sequence











5′-CCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11336)






Similarly, a 21-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next two nucleotides 3′, i.e., the 3′-terminal GG from Oligo 6. Thus, the 21-mer RNA described has the sequence










5′-CCCGGGAGCCACUCCCAUGGG-3′
(SEQ ID NO: 11337)






and the complementary 21-mer RNA described has the sequence









5′-CCCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11338)






As the next oligonucleotide described, a 22-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next three nucleotides 3′, i.e., the 3′-terminal GGC from Oligo 7. Thus, the 22-mer RNA described has the sequence








5′-CCCGGGAGCCACUCCCAUGGGC-3′
((SEQ ID NO: 11339)






and the complementary 22-mer RNA described has the sequence









5′-GCCCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11340)






A 23-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next four nucleotides 3′, i.e., the 3′-terminal GGCG from Oligo 8. Thus, the 23-mer RNA described has the sequence








5′-CCCGGGAGCCACUCCCAUGGGCG-3′
(SEQ ID NO: 11341)






and the complementary 23-mer RNA described has the sequence









5′-CGCCCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11342)






A 24-mer RNA that includes the Oligonucleotide 4 sequence is described by the Oligo 4 sequence with the next five nucleotides 3′, i.e., the 3′-terminal GGCGC from Oligo 9. Thus, the 24-mer RNA described has the sequence








5′-CCCGGGAGCCACUCCCAUGGGCGC-3′
(SEQ ID NO: 11343)






and the complementary 24-mer RNA described has the sequence









5′-GCGCCCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11344)






In similar fashion, a 25-mer that includes the Oligonucleotide 4 sequence is described as








5′-CCCGGGAGCCACUCCCAUGGGCGCC-3′
(SEQ ID NO: 11345)






and the complementary 25-mer RNA described has the sequence









5′-GGCGCCCAUGGGAGUGGCUCCCGGG-3′.
(SEQ ID NO: 11346)






A 26-mer that includes the Oligonucleotide 4 sequence is described as








5′-CCCGGGAGCCACUCCCAUGGGCGCCU-3′
(SEQ ID NO: 11347)






and the complementary 26-mer RNA described has the sequence








(SEQ ID NO: 11348)









5′-AGGCGCCCAUGGGAGUGGCUCCCGGG-3′.






A 27-mer that includes the Oligonucleotide 4 sequence is described as







(SEQ ID NO: 11349)









5′-CCCGGGAGCCACUCCCAUGGGCGCCUC-3′






and the complementary 27-mer RNA described has the sequence








(SEQ ID NO: 11350)









5′-GAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.






A 28-mer that includes the Oligonucleotide 4 sequence is described as







(SEQ ID NO: 11351)









5′-CCCGGGAGCCACUCCCAUGGGCGCCUCU-3′






and the complementary 28-mer RNA described has the sequence








(SEQ ID NO: 11352)









5′-AGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.






A 29-mer that includes the Oligonucleotide 4 sequence is described as







(SEQ ID NO: 11353)


5′-CCCGGGAGCCACUCCCAUGGGCGCCUCUC-3′






and the complementary 29-mer RNA described has the sequence








(SEQ ID NO: 11354)


5′-GAGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.






Thus, Table 1 describes each of the 19-mers shown in Table 1 as DNA and RNA, and the corresponding 20-mers and longer.
In addition, the Table describes double stranded oligonucleotides with the sense and antisense oligonucleotide strands hybridized, as well as such double stranded oligonucleotides with one or both strands having a 3′-overhang. Such an overhang consists of one or more 3′-terminal nucleotides of an oligonucleotide strand in a double stranded molecule that are not hybridized with the complementary strand. In the present case, such overhang nucleotides often match the corresponding nucleotides from the target mRNA sequence, but can be different.
Table 1 also describes oligonucleotides that contain known polymorphisms. Those polymorphic sites are described in Table 2 along with the replacement nucleotide. Thus, Table 1 with Table 2 describes the oligonucleotides with the alternate nucleotides at a polymorphic site.
Chemical Modifications
As indicated above, for many applications it is advantageous to use chemically modified oligonucleotides rather than unmodified RNA for RNAi (e.g., siRNA). Such modification can dramatically increase the cellular and/or serum lifetime of the modified oligonucleotide compared to the unmodified form.
Description of such chemical modification is provided in McSwiggen et al., PCT/US03/05346, WO 03/070918. Thus, the introduction of chemically modified nucleotides into nucleic acid molecules assists in overcoming potential limitations of in vivo stability and bioavailability inherent to native RNA molecules that are delivered exogenously. For example, the use of chemically modified nucleic acid molecules can enable a lower dose of a particular nucleic acid molecule for a given therapeutic effect since chemically modified nucleic acid molecules tend to have a longer half-life in serum. Furthermore, certain chemical modifications can improve the bioavailability of nucleic acid molecules by targeting particular cells or tissues and/or improving cellular uptake of the nucleic acid molecule. Therefore, even if the activity of a chemically modified nucleic acid molecule is reduced as compared to a native nucleic acid molecule, for example when compared to an all RNA nucleic acid molecule, the overall activity of the modified nucleic acid molecule can be greater than the native molecule due to improved stability and/or delivery of the molecule. Unlike native unmodified siRNA, chemically modified siNA can also minimize the possibility of activating interferon activity in humans.
Thus, in some embodiments of the present invention, the nucleic acid molecules that act as mediators of the RNA interference gene silencing response are chemically modified double stranded nucleic acid molecules, generally about 19-29 nucleotides in length. The most active siRNA molecules are thought to have such duplexes with overhanging ends of 1-3 nucleotides, for example 21 nucleotide duplexes with 19 base pairs and 2 nucleotide 3′-overhangs. These overhanging segments are readily hydrolyzed by endonucleases in vivo. Studies have shown that replacing the 3′-overhanging segments of a 21-mer siRNA duplex having 2 nucleotide 3′ overhangs with deoxyribonucleotides does not have an adverse effect on RNAi activity. Replacing up to 4 nucleotides on each end of the siRNA with deoxyribonucleotides has been reported to be well tolerated whereas complete substitution with deoxyribonucleotides results in no RNAi activity (Elbashir et al., 2001, EMBO J., 20, 6877). In addition, Elbashir et al. also report that full substitution of siRNA with 2′-O-methyl nucleotides completely abolishes RNAi activity.
In some embodiments, the chemically modified siNA constructs having specificity for target nucleic acid molecules in a cell. Non-limiting examples of such chemical modifications include without limitation phosphorothioate internucleotide linkages, 2′-O-methyl ribonucleotides, 2′-deoxy-2′-fluoro ribonucleotides, “universal base” nucleotides, 5-C-methyl nucleotides, and inverted deoxyabasic residue incorporation. These chemical modifications, when used in various siNA constructs, are shown to preserve RNAi activity in cells while at the same time, dramatically increasing the serum stability of these compounds. Furthermore, contrary to the data published by Parrish et al., supra, applicant demonstrates that multiple (greater than one) phosphorothioate substitutions are well-tolerated and confer substantial increases in serum stability for modified siNA constructs.
In one embodiment, a siNA molecule of the invention comprises modified nucleotides while maintaining the ability to mediate RNAi. The modified nucleotides can be used to improve in vitro or in vivo characteristics such as stability, activity, and/or bioavailability. For example, a siNA molecule of the invention can comprise modified nucleotides as a percentage of the total number of nucleotides present in the siNA molecule. As such, a siNA molecule of the invention can generally comprise modified nucleotides at between 5 and 100% of the nucleotide positions (e.g., 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotide positions). The actual percentage of modified nucleotides present in a given siNA molecule will depend on the total number of nucleotides present in the siNA. If the siNA molecule is single stranded, the percent modification can be based upon the total number of nucleotides present in the single stranded siNA molecules. Likewise, if the siNA molecule is double stranded, the percent modification can be based upon the total number of nucleotides present in the sense strand, antisense strand, or both the sense and antisense strands. In addition, the actual percentage of modified nucleotides present in a given siNA molecule can also depend on the total number of purine and pyrimidine nucleotides present in the siNA, for example wherein all pyrimidine nucleotides and/or all purine nucleotides present in the siNA molecule are modified.
In a non-limiting example, the introduction of chemically-modified nucleotides into nucleic acid molecules will provide a powerful tool in overcoming potential limitations of in vivo stability and bioavailability inherent to native RNA molecules that are delivered exogenously. For example, the use of chemically-modified nucleic acid molecules can enable a lower dose of a particular nucleic acid molecule for a given therapeutic effect since chemically-modified nucleic acid molecules tend to have a longer half-life in serum. Furthermore, certain chemical modifications can improve the bioavailability of nucleic acid molecules by targeting particular cells or tissues and/or improving cellular uptake of the nucleic acid molecule. Therefore, even if the activity of a chemically-modified nucleic acid molecule is reduced as compared to a native nucleic acid molecule, for example when compared to an all-RNA nucleic acid molecule, the overall activity of the modified nucleic acid molecule can be greater than that of the native molecule due to improved stability and/or delivery of the molecule. Unlike native unmodified siNA, chemically-modified siNA can also minimize the possibility of activating interferon activity in humans.
The antisense region of a siNA molecule of the invention can comprise a phosphorothioate internucleotide linkage at the 3′-end of said antisense region. The antisense region can comprise between about one and about five phosphorothioate internucleotide linkages at the 5′-end of said antisense region. The 3′-terminal nucleotide overhangs of a siNA molecule of the invention can comprise ribonucleotides or deoxyribonucleotides that are chemically-modified at a nucleic acid sugar, base, or backbone. The 3′-terminal nucleotide overhangs can comprise one or more universal base ribonucleotides. The 3′-terminal nucleotide overhangs can comprise one or more acyclic nucleotides.
In certain embodiments, the chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, includes one or more chemically modified nucleotides (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) comprising a backbone modified internucleotide linkage having Formula I:




wherein each R1 and R2 is independently any nucleotide, non-nucleotide, or oligonucleotide which can be naturally-occurring or chemically-modified, each X and Y is independently O, S, N, alkyl, or substituted alkyl, each Z and W is independently O, S, N, alkyl, substituted alkyl, O-alkyl, S-alkyl, alkaryl, or aralkyl, and wherein W, X, Y, and Z are optionally not all O.

The chemically-modified internucleotide linkages having Formula I, for example wherein any Z, W, X, and/or Y independently comprises a sulphur atom, can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) chemically-modified internucleotide linkages having Formula I at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified internucleotide linkages having Formula I at the 5′-end of the sense strand, the antisense strand, or both strands. In another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) pyrimidine nucleotides with chemically-modified internucleotide linkages having Formula I in the sense strand, the antisense strand, or both strands. In yet another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) purine nucleotides with chemically-modified internucleotide linkages having Formula I in the sense strand, the antisense strand, or both strands. In another embodiment, a siNA molecule of the invention having internucleotide linkage(s) of Formula I also comprises a chemically-modified nucleotide or non-nucleotide having any of Formulae I-VII.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotides having Formula II:




wherein each R3, R4, R5, R6, R7, R8, R10, R1 and R12 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine, guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine, 2,6-diaminopurine, or any other non-naturally occurring base that can be complementary or non-complementary to target RNA or a non-nucleosidic base such as phenyl, naphthyl, 3-nitropyrrole, 5-nitroindole, nebularine, pyridone, pyridinone, or any other non-naturally occurring universal base that can be complementary or non-complementary to target RNA.

The chemically-modified nucleotide or non-nucleotide of Formula II can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more chemically-modified nucleotide or non-nucleotide of Formula II at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotides or non-nucleotides of Formula II at the 5′-end of the sense strand, the antisense strand, or both strands. In anther non-limiting example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotides or non-nucleotides of Formula II at the 3′-end of the sense strand, the antisense strand, or both strands.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotides having Formula III:




wherein each R3, R4, R5, R6, R7, R8, R10, R11 and R12 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine, guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine, 2,6-diaminopurine, or any other non-naturally occurring base that can be employed to be complementary or non-complementary to target RNA or a non-nucleosidic base such as phenyl, naphthyl, 3-nitropyrrole, 5-nitroindole, nebularine, pyridone, pyridinone, or any other non-naturally occurring universal base that can be complementary or non-complementary to target RNA.

The chemically-modified nucleotide or non-nucleotide of Formula III can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more chemically-modified nucleotide or non-nucleotide of Formula III at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotide(s) or non-nucleotide(s) of Formula III at the 5′-end of the sense strand, the antisense strand, or both strands. In anther non-limiting example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) chemically-modified nucleotide or non-nucleotide of Formula III at the 3′-end of the sense strand, the antisense strand, or both strands.
In another embodiment, a siNA molecule of the invention comprises a nucleotide having Formula II or III, wherein the nucleotide having Formula II or III is in an inverted configuration. For example, the nucleotide having Formula II or III is connected to the siNA construct in a 3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises a 5′-terminal phosphate group having Formula IV:




wherein each X and Y is independently O, S, N, alkyl, substituted alkyl, or alkylhalo; wherein each Z and W is independently O, S, N, alkyl, substituted alkyl, O-alkyl, S-alkyl, alkaryl, aralkyl, or alkylhalo; and wherein W, X, Y and Z are not all O.

In one embodiment, the invention features a siNA molecule having a 5′-terminal phosphate group having Formula IV on the target-complementary strand, for example a strand complementary to a target RNA, wherein the siNA molecule comprises an all RNA siNA molecule. In another embodiment, the invention features a siNA molecule having a 5′-terminal phosphate group having Formula IV on the target-complementary strand wherein the siNA molecule also comprises about 1-3 (e.g., about 1, 2, or 3) nucleotide 3′-terminal nucleotide overhangs having between about 1 and about 4 (e.g., about 1, 2, 3, or 4) deoxyribonucleotides on the 3′-end of one or both strands. In another embodiment, a 5′-terminal phosphate group having Formula IV is present on the target-complementary strand of a siNA molecule of the invention, for example a siNA molecule having chemical modifications having any of Formulae I-VII.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more phosphorothioate internucleotide linkages. For example, in a non-limiting example, the invention features a chemically-modified short interfering nucleic acid (siNA) having about 1, 2, 3, 4, 5, 6, 7, 8 or more phosphorothioate internucleotide linkages in one siNA strand. In yet another embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) individually having about 1, 2, 3, 4, 5, 6, 7, 8 or more phosphorothioate internucleotide linkages in both siNA strands. The phosphorothioate internucleotide linkages can be present in one or both oligonucleotide strands of the siNA duplex, for example in the sense strand, the antisense strand, or both strands. The siNA molecules of the invention can comprise one or more phosphorothioate internucleotide linkages at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand, the antisense strand, or both strands. For example, an exemplary siNA molecule of the invention can comprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) consecutive phosphorothioate internucleotide linkages at the 5′-end of the sense strand, the antisense strand, or both strands. In another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) pyrimidine phosphorothioate internucleotide linkages in the sense strand, the antisense strand, or both strands. In yet another non-limiting example, an exemplary siNA molecule of the invention can comprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) purine phosphorothioate internucleotide linkages in the sense strand, the antisense strand, or both strands.
In one embodiment, the invention features a siNA molecule, wherein the sense strand comprises one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′ end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between 1 and 10 or more, specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.
In another embodiment, the invention features a siNA molecule, wherein the sense strand comprises between about 1 and about 5, specifically about 1, 2, 3, 4, or 5 phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5, or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without between about 1 and about 5 or more, for example about 1, 2, 3, 4, 5, or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.
In one embodiment, the invention features a siNA molecule, wherein the antisense strand comprises one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/or between one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 10, specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends, being present in the same or different strand.
In another embodiment, the invention features a siNA molecule, wherein the antisense strand comprises between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand; and wherein the antisense strand comprises any of between about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides, and optionally a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of the antisense strand. In another embodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more pyrimidine nucleotides of the sense and/or antisense siNA strand are chemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoro nucleotides, with or without between about 1 and about 5, for example about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages and/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends, being present in the same or different strand.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule having between about 1 and about 5, specifically about 1, 2, 3, 4, 5 or more phosphorothioate internucleotide linkages in each strand of the siNA molecule.
In another embodiment, the invention features a siNA molecule comprising 2′-5′ internucleotide linkages. The 2′-5′ internucleotide linkage(s) can be at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of one or both siNA sequence strands. In addition, the 2′-5′ internucleotide linkage(s) can be present at various other positions within one or both siNA sequence strands, for example, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including every internucleotide linkage of a pyrimidine nucleotide in one or both strands of the siNA molecule can comprise a 2′-5′ internucleotide linkage, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including every internucleotide linkage of a purine nucleotide in one or both strands of the siNA molecule can comprise a 2′-5′ internucleotide linkage.
In another embodiment, a chemically-modified siNA molecule of the invention comprises a duplex having two strands, one or both of which can be chemically-modified, wherein each strand is between about 18 and about 27 (e.g., about 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27) nucleotides in length, wherein the duplex has between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the chemical modification comprises a structure having any of Formulae I-VII. For example, an exemplary chemically-modified siNA molecule of the invention comprises a duplex having two strands, one or both of which can be chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein each strand consists of about 21 nucleotides, each having a 2-nucleotide 3′-terminal nucleotide overhang, and wherein the duplex has about 19 base pairs. In another embodiment, a siNA molecule of the invention comprises a single stranded hairpin structure, wherein the siNA is between about 36 and about 70 (e.g., about 36, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length having between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the siNA can include a chemical modification comprising a structure having any of Formulae I-VII or any combination thereof. For example, an exemplary chemically-modified siNA molecule of the invention comprises a linear oligonucleotide having between about 42 and about 50 (e.g., about 42, 43, 44, 45, 46, 47, 48, 49, or 50) nucleotides that is chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein the linear oligonucleotide forms a hairpin structure having about 19 base pairs and a 2-nucleotide 3′-terminal nucleotide overhang. In another embodiment, a linear hairpin siNA molecule of the invention contains a stem loop motif, wherein the loop portion of the siNA molecule is biodegradable. For example, a linear hairpin siNA molecule of the invention is designed such that degradation of the loop portion of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising about 2 nucleotides.
In another embodiment, a siNA molecule of the invention comprises a circular nucleic acid molecule, wherein the siNA is between about 38 and about 70 (e.g., about 38, 40, 45, 50, 55, 60, 65, or 70) nucleotides in length having between about 18 and about 23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein the siNA can include a chemical modification, which comprises a structure having any of Formulae I-VII or any combination thereof. For example, an exemplary chemically-modified siNA molecule of the invention comprises a circular oligonucleotide having between about 42 and about 50 (e.g., about 42, 43, 44, 45, 46, 47, 48, 49, or 50) nucleotides that is chemically-modified with a chemical modification having any of Formulae I-VII or any combination thereof, wherein the circular oligonucleotide forms a dumbbell shaped structure having about 19 base pairs and 2 loops.
In another embodiment, a circular siNA molecule of the invention contains two loop motifs, wherein one or both loop portions of the siNA molecule is biodegradable. For example, a circular siNA molecule of the invention is designed such that degradation of the loop portions of the siNA molecule in vivo can generate a double-stranded siNA molecule with 3′-terminal overhangs, such as 3′-terminal nucleotide overhangs comprising about 2 nucleotides.
In one embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) abasic moiety, for example a compound having Formula V:




wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2.

In one embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) inverted abasic moiety, for example a compound having Formula VI:




wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or group having Formula I; R9 is O, S, CH2, S═O, CHF, or CF2, and either R2, R3, R8 or R13 serve as points of attachment to the siNA molecule of the invention.

In another embodiment, a siNA molecule of the invention comprises at least one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) substituted polyalkyl moieties, for example a compound having Formula VII:




wherein each n is independently an integer from 1 to 12, each R1, R2 and R3 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-S-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalklylamino, substituted silyl, or a group having Formula I, and R1, R2 or R3 serves as points of attachment to the siNA molecule of the invention.

In another embodiment, the invention features a compound having Formula VII, wherein R1 and R2 are hydroxyl (OH) groups, n=1, and R3 comprises O and is the point of attachment to the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both strands of a double-stranded siNA molecule of the invention or to a single-stranded siNA molecule of the invention. This modification is referred to herein as “glyceryl”.
In another embodiment, a moiety having any of Formula V, VI or VII of the invention is at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of a siNA molecule of the invention. For example, a moiety having Formula V, VI or VII can be present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense strand, the sense strand, or both antisense and sense strands of the siNA molecule. In addition, a moiety having Formula VII can be present at the 3′-end or the 5′-end of a hairpin siNA molecule as described herein.
In another embodiment, a siNA molecule of the invention comprises an abasic residue having Formula V or VI, wherein the abasic residue having Formula VI or VI is connected to the siNA construct in a 3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.
In one embodiment, a siNA molecule of the invention comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) locked nucleic acid (LNA) nucleotides, for example at the 5′-end, the 3′-end, both of the 5′ and 3′-ends, or any combination thereof, of the siNA molecule.
In another embodiment, a siNA molecule of the invention comprises one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) acyclic nucleotides, for example at the 5′-end, the 3′-end, both of the 5′ and 3′-ends, or any combination thereof, of the siNA molecule.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises a sense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides).
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises a sense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), wherein any nucleotides comprising a 3′-terminal nucleotide overhang that are present in said sense region are 2′-deoxy nucleotides.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides).
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), wherein any nucleotides comprising a 3′-terminal nucleotide overhang that are present in said antisense region are 2′-deoxy nucleotides.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention, wherein the chemically-modified siNA comprises an antisense region, where any (e.g., one or more or all) pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where any (e.g., one or more or all) purine nucleotides present in the antisense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides).
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemically-modified siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where one or more purine nucleotides present in the sense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), and inverted deoxy abasic modifications that are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the chemically-modified short interfering nucleic acid molecule comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein one or more purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and where one or more purine nucleotides present in the sense region are purine ribonucleotides (e.g., wherein all purine nucleotides are purine ribonucleotides or alternately a plurality of purine nucleotides are purine ribonucleotides), and inverted deoxy abasic modifications that are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the siNA comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid (siNA) molecule of the invention capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemically-modified siNA comprises a sense region, where one or more pyrimidine nucleotides present in the sense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and for example where one or more purine nucleotides present in the sense region are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides (e.g., wherein all purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides or alternately a plurality of purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides), and wherein inverted deoxy abasic modifications are optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense region, the sense region optionally further comprising a 3′-terminal overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein the chemically-modified short interfering nucleic acid molecule comprises an antisense region, where one or more pyrimidine nucleotides present in the antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein one or more purine nucleotides present in the antisense region are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides (e.g., wherein all purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides or alternately a plurality of purine nucleotides are selected from the group consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides), and a terminal cap modification, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the antisense region optionally further comprising a 3′-terminal nucleotide overhang having between about 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhang nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages.
In another embodiment, any modified nucleotides present in the siNA molecules of the invention, preferably in the antisense strand of the siNA molecules of the invention, comprise modified nucleotides having properties or characteristics similar to naturally occurring ribonucleotides. For example, the invention features siNA molecules including modified nucleotides having a Northern conformation (e.g., Northern pseudorotation cycle, see for example Saenger, Principles of Nucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemically modified nucleotides present in the siNA molecules of the invention, preferably in the antisense strand of the siNA molecules of the invention, are preferably resistant to nuclease degradation while at the same time maintaining the capacity to mediate RNAi. Non-limiting examples of nucleotides having a northern configuration include locked nucleic acid (LNA) nucleotides (e.g., 2′-O,4′-C-methylene-(D-ribofuranosyl) nucleotides); 2′-methoxyethoxy (MOE) nucleotides; 2′-deoxy-2′-fluoro nucleotides, 2′-deoxy-2′-chloro nucleotides, 2′-azido nucleotides, and 2′-O-methyl nucleotides.
In one embodiment, the invention features a chemically-modified short interfering nucleic acid molecule (siNA) capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein the chemical modification comprises one or more conjugates covalently attached to the chemically-modified siNA molecule. In another embodiment, the conjugate is covalently attached to the chemically-modified siNA molecule via a biodegradable linker. In one embodiment, the conjugate molecule is attached at the 3′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule. In another embodiment, the conjugate molecule is attached at the 5′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule. In yet another embodiment, the conjugate molecule is attached both the 3′-end and 5′-end of either the sense strand, the antisense strand, or both strands of the chemically-modified siNA molecule, or any combination thereof. In one embodiment, a conjugate molecule of the invention comprises a molecule that facilitates delivery of a chemically-modified siNA molecule into a biological system such as a cell. In another embodiment, the conjugate molecule attached to the chemically-modified siNA molecule is a poly ethylene glycol, human serum albumin, or a ligand for a cellular receptor that can mediate cellular uptake. Examples of specific conjugate molecules contemplated by the instant invention that can be attached to chemically-modified siNA molecules are described in Vargeese et al., U.S. Ser. No. 60/311,865, incorporated by reference herein. The type of conjugates used and the extent of conjugation of siNA molecules of the invention can be evaluated for improved pharmacokinetic profiles, bioavailability, and/or stability of siNA constructs while at the same time maintaining the ability of the siNA to mediate RNAi activity. As such, one skilled in the art can screen siNA constructs that are modified with various conjugates to determine whether the siNA conjugate complex possesses improved properties while maintaining the ability to mediate RNAi, for example in animal models as are generally known in the art.
In one embodiment, the invention features a short interfering nucleic acid (siNA) molecule of the invention, wherein the siNA further comprises a nucleotide, non-nucleotide, or mixed nucleotide/non-nucleotide linker that joins the sense region of the siNA to the antisense region of the siNA. In another embodiment, a nucleotide linker of the invention can be a linker of ≧2 nucleotides in length, for example 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In yet another embodiment, the nucleotide linker can be a nucleic acid aptamer. By “aptamer” or “nucleic acid aptamer” as used herein is meant a nucleic acid molecule that binds specifically to a target molecule wherein the nucleic acid molecule has sequence that is comprises a sequence recognized by the target molecule in its natural setting. Alternately, an aptamer can be a nucleic acid molecule that binds to a target molecule where the target molecule does not naturally bind to a nucleic acid. The target molecule can be any molecule of interest. For example, the aptamer can be used to bind to a ligand-binding domain of a protein, thereby preventing interaction of the naturally occurring ligand with the protein. This is a non-limiting example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628.
In yet another embodiment, a non-nucleotide linker of the invention comprises abasic nucleotide, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, polyhydrocarbon, or other polymeric compounds (e.g. polyethylene glycols such as those having between 2 and 100 ethylene glycol units). Specific examples include those described by Seela and Kaiser, Nucleic Acids Res. 1990, 18:6353 and Nucleic Acids Res. 1987, 15:3113; Cload and Schepartz, J. Am. Chem. Soc. 1991, 113:6324; Richardson and Schepartz, J. Am. Chem. Soc. 1991, 113:5109; Ma et al., Nucleic Acids Res. 1993, 21:2585 and Biochemistry 1993, 32:1751; Durand et al., Nucleic Acids Res. 1990, 18:6353; McCurdy et al., Nucleosides & Nucleotides 1991, 10:287; Jschke et al., Tetrahedron Lett. 1993, 34:301; Ono et al., Biochemistry 1991, 30:9914; Arnold et al., International Publication No. WO 89/02439; Usman et al., International Publication No. WO 95/06731; Dudycz et al., International Publication No. WO 95/11910 and Ferentz and Verdine, J. Am. Chem. Soc. 1991, 113:4000, all hereby incorporated by reference herein. A “non-nucleotide” further means any group or compound that can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound can be abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine, for example at the C1 position of the sugar.
In one embodiment, the invention features a short interfering nucleic acid (siNA) molecule capable of mediating RNA interference (RNAi) inside a cell or reconstituted in vitro system, wherein one or both strands of the siNA molecule that are assembled from two separate oligonucleotides do not comprise any ribonucleotides. All positions within the siNA can include chemically modified nucleotides and/or non-nucleotides such as nucleotides and or non-nucleotides having Formula I, II, III, IV, V, VI, or VII or any combination thereof to the extent that the ability of the siNA molecule to support RNAi activity in a cell is maintained.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence. In another embodiment, the single stranded siNA molecule of the invention comprises a 5′-terminal phosphate group. In another embodiment, the single stranded siNA molecule of the invention comprises a 5′-terminal phosphate group and a 3′-terminal phosphate group (e.g., a 2′,3′-cyclic phosphate). In another embodiment, the single stranded siNA molecule of the invention comprises between 19 and 29 nucleotides. In yet another embodiment, the single stranded siNA molecule of the invention comprises one or more chemically modified nucleotides or non-nucleotides described herein. For example, all the positions within the siNA molecule can include chemically-modified nucleotides such as nucleotides having any of Formulae I-VII, or any combination thereof to the extent that the ability of the siNA molecule to support RNAi activity in a cell is maintained.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-O-methyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-deoxy purine nucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides or alternately a plurality of purine nucleotides are 2′-deoxy purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are locked nucleic acid (LNA) nucleotides (e.g., wherein all purine nucleotides are LNA nucleotides or alternately a plurality of purine nucleotides are LNA nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are 2′-methoxyethyl purine nucleotides (e.g., wherein all purine nucleotides are 2′-methoxyethyl purine nucleotides or alternately a plurality of purine nucleotides are 2′-methoxyethyl purine nucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.
In one embodiment, a siNA molecule of the invention is a single stranded siNA molecule that mediates RNAi activity in a cell or reconstituted in vitro system, wherein the siNA molecule comprises a single stranded oligonucleotide having complementarity to a target nucleic acid sequence, and wherein one or more pyrimidine nucleotides present in the siNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purine nucleotides present in the antisense region are purine ribonucleotides (e.g., wherein all purine nucleotides are purine ribonucleotides or alternately a plurality of purine nucleotides are purine ribonucleotides), and a terminal cap modification, such as any modification described herein, that is optionally present at the 3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisense sequence, the siNA optionally further comprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, wherein the terminal nucleotides can further comprise one or more (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages, and wherein the siNA optionally further comprises a terminal phosphate group, such as a 5′-terminal phosphate group.
In another embodiment, any modified nucleotides present in the single stranded siNA molecules of the invention comprise modified nucleotides having properties or characteristics similar to naturally occurring ribonucleotides. For example, the invention features siNA molecules including modified nucleotides having a Northern conformation (e.g., Northern pseudorotation cycle, see for example Saenger, Principles of Nucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemically modified nucleotides present in the single stranded siNA molecules of the invention are preferably resistant to nuclease degradation while at the same time maintaining the capacity to mediate RNAi.
E. Preparation of Oligonucleotides
The present oligonucleotides can be prepared by methods available to those skilled in the art. For example, unmodified RNA can be prepared by transcription, e.g., in vitro, using methods and constructs available in the art. The sequence for the particular target, and its complementary sequence can be inserted into a selected vector, and transcribed to produce the desired oligonucleotides by conventional methods.
In many cases, it will be desirable to chemically synthesize the oligonucleotides, e.g., for chemically modified oligonucleotides. Such syntheses are known in the art, and are described, for example, below.
Thus, siNA molecules can be designed to interact with various sites in the RNA message, for example target sequences within the RNA sequences described herein. The sequence of one strand of the siNA molecule(s) is complementary to the target site sequences described above. The siNA molecules can be chemically synthesized using methods described herein. Inactive siNA molecules that are used as control sequences can be synthesized by scrambling the sequence of the siNA molecules such that it is not complementary to the target sequence. Generally, siNA constructs can by synthesized using solid phase oligonucleotide synthesis methods as described herein (see for example Usman et al., U.S. Pat. Nos. 5,804,683; 5,831,071; 5,998,203; 6,117,657; 6,353,098; 6,362,323; 6,437,117; 6,469,158; Scaringe et al., U.S. Pat. Nos. 6,111,086; 6,008,400; 6,111,086). Modification of synthesis conditions can be used to optimize coupling efficiency, for example by using differing coupling times, differing reagent/phosphoramidite concentrations, differing contact times, differing solid supports and solid support linker chemistries depending on the particular chemical composition of the siNA to be synthesized. Deprotection and purification of the siNA can be performed as is generally described in Vargeese et al., U.S. Ser. No. 10/194,875, incorporated by reference herein in its entirety. Additionally, deprotection conditions can be modified to provide the best possible yield and purity of siNA constructs. For example, applicant has observed that oligonucleotides comprising 2′-deoxy-2′-fluoro nucleotides can degrade under inappropriate deprotection conditions. Such oligonucleotides are deprotected using aqueous methylamine at about 35° C. for 30 minutes. If the 2′-deoxy-2′-fluoro containing oligonucleotide also comprises ribonucleotides, after deprotection with aqueous methylamine at about 35° C. for 30 minutes, TEA-HF is added and the reaction maintained at about 65° C. for an additional 15 minutes.
Synthesis of Nucleic Acid Molecules
In greater detail, synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs, “small” refers to nucleic acid motifs no more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., individual siNA oligonucleotide sequences or siNA sequences synthesized in tandem) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of protein and/or RNA structure. Exemplary molecules of the instant invention are chemically synthesized, and others can similarly be synthesized.
Oligonucleotides (e.g., certain modified oligonucleotides or portions of oligonucleotides lacking ribonucleotides) are synthesized using protocols known in the art, for example as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, Thompson et al., International PCT Publication No. WO 99/54459, Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, U.S. Pat. No. 6,001,311. All of these references are incorporated herein by reference. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45 sec coupling step for 2′-deoxy nucleotides or 2′-deoxy-2′-fluoro nucleotides. Alternatively, syntheses at the 0.2 μmol scale can be performed on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 22-fold excess (40 μL of 0.11 M=4.4 μmol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tetrazole (40 μL of 0.25 M=10 μmol) can be used in each coupling cycle of deoxy residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVETM). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide, 0.05 M in acetonitrile) is used.
Deprotection of the DNA-based oligonucleotides is performed as follows: the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder.
The method of synthesis used for RNA including certain siNA molecules of the invention follows the procedure as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433; and Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684 Wincott et al., 1997, Methods Mol. Bio., 74, 59, and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5 min coupling step for alkylsilyl protected nucleotides and a 2.5 min coupling step for 2′-O-methylated nucleotides. Alternatively, syntheses at the 0.2 μmol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 66-fold excess (120 μL of 0.11 M=13.2 μmol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 μL of 0.25 M=30 μmol) can be used in each coupling cycle of ribo residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVETM). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide 0.05 M in acetonitrile) is used.
Deprotection of the RNA is performed using either a two-pot or one-pot protocol. For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The base deprotected oligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300 μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mL TEA•3HF to provide a 1.4 M HF concentration) and heated to 65° C. After 1.5 h, the oligomer is quenched with 1.5 M NH4HCO3.
Alternatively, for the one-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL) at 65° C. for 15 min. The vial is brought to r.t. TEA•3HF (0.1 mL) is added and the vial is heated at 65° C. for 15 min. The sample is cooled at −20° C. and then quenched with 1.5 M NH4HCO3.
For purification of the trityl-on oligomers, the quenched NH4HCO3 solution is loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA is detritylated with 0.5% TFA for 13 min. The cartridge is then washed again with water, salt exchanged with 1 M NaCl and washed with water again. The oligonucleotide is then eluted with 30% acetonitrile.
The average stepwise coupling yields are typically >98% (Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the example described above including but not limited to 96-well format.
Alternatively, the nucleic acid molecules of the present invention can be synthesized separately and joined together post-synthetically, for example, by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204), or by hybridization following synthesis and/or deprotection.
The siNA molecules of the invention can also be synthesized via a tandem synthesis methodology as described below, where both siNA strands are synthesized as a single contiguous oligonucleotide fragment or strand separated by a cleavable linker which is subsequently cleaved to provide separate siNA fragments or strands that hybridize and permit purification of the siNA duplex. The linker can be a oligonucleotide linker or a non-nucleotide linker. The tandem synthesis of siNA as described herein can be readily adapted to both multiwell/multiplate synthesis platforms such as 96 well or similarly larger multi-well platforms. The tandem synthesis of siNA as described herein can also be readily adapted to large scale synthesis platforms employing batch reactors, synthesis columns and the like.
A siNA molecule can also be assembled from two distinct nucleic acid strands or fragments wherein one fragment includes the sense region and the second fragment includes the antisense region of the RNA molecule.
The nucleic acid molecules of the present invention can be modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163). siNA constructs can be purified by gel electrophoresis using general methods or can be purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra, the totality of which is hereby incorporated herein by reference) and re-suspended in water.
In another aspect of the invention, siNA molecules of the invention are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors can be DNA plasmids or viral vectors. siNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. The recombinant vectors capable of expressing the siNA molecules can be delivered as described herein, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of siNA molecules.
Tandem Synthesis of siNA Constructs
Exemplary siNA molecules are synthesized in tandem using a cleavable linker, for example a succinyl-based linker. Tandem synthesis as described herein is followed by a one-step purification process that provides RNAi molecules in high yield. This approach is highly amenable to siNA synthesis in support of high throughput RNAi screening, and can be readily adapted to multi-column or multi-well synthesis platforms.
After completing a tandem synthesis of an siNA oligo and its complement in which the 5′-terminal dimethoxytrityl (5′-O-DMT) group remains intact (trityl on synthesis), the oligonucleotides are deprotected as described above. Following deprotection, the siNA sequence strands are allowed to spontaneously hybridize. This hybridization yields a duplex in which one strand has retained the 5′-O-DMT group while the complementary strand comprises a terminal 5′-hydroxyl. The newly formed duplex behaves as a single molecule during routine solid-phase extraction purification (Trityl-On purification) even though only one molecule has a dimethoxytrityl group. Because the strands form a stable duplex, this dimethoxytrityl group (or an equivalent group, such as other trityl groups or other hydrophobic moieties) is all that is required to purify the pair of oligos, for example by using a C18 cartridge.
Standard phosphoramidite synthesis chemistry is used up to point of introducing a tandem linker, such as an inverted deoxy abasic succinate or glyceryl succinate linker or an equivalent cleavable linker. A non-limiting example of linker coupling conditions that can be used includes a hindered base such as diisopropylethylamine (DIPA) and/or DMAP in the presence of an activator reagent such as Bromotripyrrolidinophosphoniumhexafluororophosphate (PyBrOP). After the linker is coupled, standard synthesis chemistry is utilized to complete synthesis of the second sequence leaving the terminal the 5′-O-DMT intact. Following synthesis, the resulting oligonucleotide is deprotected according to the procedures described herein and quenched with a suitable buffer, for example with 50 mM NaOAc or 1.5M NH4H2CO3.
Purification of the siNA duplex can be readily accomplished using solid phase extraction, for example using a Waters C18 SepPak 1 g cartridge conditioned with 1 column volume (CV) of acetonitrile, 2 CV H2O, and 2 CV 50 mM NaOAc: The sample is loaded and then washed with 1 CV H2O or 50 mM NaOAc. Failure sequences are eluted with 1 CV 14% ACN (Aqueous with 50 mM NaOAc and 50 mM NaCl). The column is then washed, for example with 1 CV H2O followed by on-column detritylation, for example by passing 1 CV of 1% aqueous trifluoroacetic acid (TFA) over the column, then adding a second CV of 1% aqueous TFA to the column and allowing to stand for approx. 10 minutes. The remaining TFA solution is removed and the column washed with H2O followed by 1 CV 1 M NaCl and additional H2O. The siNA duplex product is then eluted, for example using 1 CV 20% aqueous CAN.
Optimizing Activity of the Nucleic Acid Molecules.
Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) can prevent their degradation by serum ribonucleases, which can increase their potency (see e.g., Eckstein et al., International Publication No. WO 92/07065; Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman and Cedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; and Rossi et al., International Publication No. WO 91/03162; Sproat, U.S. Pat. No. 5,334,711; Gold et al., U.S. Pat. No. 6,300,074; and Burgin et al., supra; all of which are incorporated by reference herein). All of the above references describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of the nucleic acid molecules described herein. Modifications that enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired.
There are several examples in the art describing sugar, base and phosphate modifications that can be introduced into nucleic acid molecules with significant enhancement in their nuclease stability and efficacy. For example, oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-O-methyl, 2′-O-allyl, 2′-H, nucleotide base modifications (for a review see Usman and Cedergren, 1992, TIBS. 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996, Biochemistry, 35, 14090). Sugar modification of nucleic acid molecules have been extensively described in the art (see Eckstein et al., International Publication PCT No. WO 92/07065; Perrault et al. Nature, 1990, 344, 565-568; Pieken et al. Science, 1991, 253, 314-317; Usman and Cedergren, Trends in Biochem. Sci., 1992, 17, 334-339; Usman et al. International Publication PCT No. WO 93/15187; Sproat, U.S. Pat. No. 5,334,711 and Beigelman et al., 1995, J. Biol. Chem., 270, 25702; Beigelman et al., International PCT publication No. WO 97/26270; Beigelman et al., U.S. Pat. No. 5,716,824; Usman et al., U.S. Pat. No. 5,627,053; Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., U.S. Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Karpeisky et al., 1998, Tetrahedron Lett., 39, 1131; Earnshaw and Gait, 1998, Biopolymers (Nucleic Acid Sciences), 48, 39-55; Verma and Eckstein, 1998, Annu. Rev. Biochem., 67, 99-134; and Burlina et al., 1997, Bioorg. Med. Chem., 5, 1999-2010; all of the references are hereby incorporated in their totality by reference herein). Such publications describe general methods and strategies to determine the location of incorporation of sugar, base and/or phosphate modifications and the like into nucleic acid molecules without modulating catalysis, and are incorporated by reference herein. In view of such teachings, similar modifications can be used as described herein to modify the siNA nucleic acid molecules of the instant invention so long as the ability of siNA to promote RNAi is cells is not significantly inhibited.
While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorodithioate, and/or 5′-methylphosphonate linkages improves stability, excessive modifications can cause some toxicity or decreased activity. Therefore, when designing nucleic acid molecules, the amount of these internucleotide linkages should be minimized. The reduction in the concentration of these linkages should lower toxicity, resulting in increased efficacy and higher specificity of these molecules.
Short interfering nucleic acid (siNA) molecules having chemical modifications that maintain or enhance activity are provided. Such a nucleic acid is also generally more resistant to nucleases than an unmodified nucleic acid. Accordingly, the in vitro and/or in vivo activity should not be significantly lowered. In cases in which modulation is the goal, therapeutic nucleic acid molecules delivered exogenously should optimally be stable within cells until translation of the target RNA has been modulated long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Improvements in the chemical synthesis of RNA and DNA (Wincott et al., 1995, Nucleic Acids Res. 23, 2677; Caruthers et al., 1992, Methods in Enzymology 211, 3-19 (incorporated by reference herein)) have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability, as described above.
In one embodiment, nucleic acid molecules of the invention include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) G-clamp nucleotides. A G-clamp nucleotide is a modified cytosine analog wherein the modifications confer the ability to hydrogen bond both Watson-Crick and Hoogsteen faces of a complementary guanine within a duplex, see for example Lin and Matteucci, 1998, J. Am. Chem. Soc., 120, 8531-8532. A single G-clamp analog substitution within an oligonucleotide can result in substantially enhanced helical thermal stability and mismatch discrimination when hybridized to complementary oligonucleotides. The inclusion of such nucleotides in nucleic acid molecules of the invention results in both enhanced affinity and specificity to nucleic acid targets, complementary sequences, or template strands. In another embodiment, nucleic acid molecules of the invention include one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) LNA “locked nucleic acid” nucleotides such as a 2′,4′-C mythylene bicyclo nucleotide (see for example Wengel et al., International PCT Publication No. WO 00/66604 and WO 99/14226).
In another embodiment, the invention features conjugates and/or complexes of siNA molecules of the invention. Such conjugates and/or complexes can be used to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes. In general, the transporters described are designed to be used either individually or as part of a multi-component system, with or without degradable linkers. These compounds are expected to improve delivery and/or localization of nucleic acid molecules of the invention into a number of cell types originating from different tissues, in the presence or absence of serum (see Sullenger and Cech, U.S. Pat. No. 5,854,038). Conjugates of the molecules described herein can be attached to biologically active molecules via linkers that are biodegradable, such as biodegradable nucleic acid linker molecules.
The term “biodegradable linker” as used herein, refers to a nucleic acid or non-nucleic acid linker molecule that is designed as a biodegradable linker to connect one molecule to another molecule, for example, a biologically active molecule to a siNA molecule of the invention or the sense and antisense strands of a siNA molecule of the invention. The biodegradable linker is designed such that its stability can be modulated for a particular purpose, such as delivery to a particular tissue or cell type. The stability of a nucleic acid-based biodegradable linker molecule can be modulated by using various chemistries, for example combinations of ribonucleotides, deoxyribonucleotides, and chemically-modified nucleotides, such as 2′-O-methyl, 2′-fluoro, 2′-amino, 2′-O-amino, 2′-C-allyl, 2′-O-allyl, and other 2′-modified or base modified nucleotides. The biodegradable nucleic acid linker molecule can be a dimer, trimer, tetramer or longer nucleic acid molecule, for example, an oligonucleotide of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, or can comprise a single nucleotide with a phosphorus-based linkage, for example, a phosphoramidate or phosphodiester linkage. The biodegradable nucleic acid linker molecule can also comprise nucleic acid backbone, nucleic acid sugar, or nucleic acid base modifications.
The term “biodegradable” as used herein, refers to degradation in a biological system, for example enzymatic degradation or chemical degradation.
The term “biologically active molecule” as used herein, refers to compounds or molecules that are capable of eliciting or modifying a biological response in a system. Non-limiting examples of biologically active siNA molecules either alone or in combination with other molecules contemplated by the instant invention include therapeutically active molecules such as antibodies, hormones, antivirals, peptides, proteins, chemotherapeutics, small molecules, vitamins, co-factors, nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids, antisense nucleic acids, triplex forming oligonucleotides, 2,5-A chimeras, siNA, dsRNA, allozymes, aptamers, decoys and analogs thereof. Biologically active molecules of the invention also include molecules capable of modulating the pharmacokinetics and/or pharmacodynamics of other biologically active molecules, for example, lipids and polymers such as polyamines, polyamides, polyethylene glycol and other polyethers.
The term “phospholipid” as used herein, refers to a hydrophobic molecule comprising at least one phosphorus group. For example, a phospholipid can comprise a phosphorus-containing group and saturated or unsaturated alkyl group, optionally substituted with OH, COOH, oxo, amine, or substituted or unsubstituted aryl groups.
Therapeutic nucleic acid molecules (e.g., siNA molecules) delivered exogenously optimally are stable within cells until reverse transcription of the RNA has been modulated long enough to reduce the levels of the RNA transcript. The nucleic acid molecules are resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of nucleic acid molecules described in the instant invention and in the art have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.
In yet another embodiment, siNA molecules having chemical modifications that maintain or enhance enzymatic activity of proteins involved in RNAi are provided. Such nucleic acids are also generally more resistant to nucleases than unmodified nucleic acids. Thus, in vitro and/or in vivo the activity should not be significantly lowered.
Use of the nucleic acid-based molecules of the invention will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple siNA molecules targeted to different genes; nucleic acid molecules coupled with known small molecule modulators; or intermittent treatment with combinations of molecules, including different motifs and/or other chemical or biological molecules). The treatment of subjects with siNA molecules can also include combinations of different types of nucleic acid molecules, such as enzymatic nucleic acid molecules (ribozymes), allozymes, antisense, 2,5-A oligoadenylate, decoys, and aptamers.
In another aspect a siNA molecule of the invention comprises one or more 5′ and/or a 3′-cap structure, for example on only the sense siNA strand, the antisense siNA strand, or both siNA strands.
By “cap structure” is meant chemical modifications, which have been incorporated at either terminus of the oligonucleotide (see, for example, Adamic et al., U.S. Pat. No. 5,998,203, incorporated by reference herein). These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and may help in delivery and/or localization within a cell. The cap may be present at the 5′-terminus (5′-cap) or at the 3′-terminal (3′-cap) or may be present on both termini. In non-limiting examples: the 5′-cap is selected from the group comprising glyceryl, inverted deoxy abasic residue (moiety); 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide, 4′-thio nucleotide; carbocyclic nucleotide; 1,5-anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide, 3′-3′-inverted nucleotide moiety; 3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety; 3′-2′-inverted abasic moiety; 1,4-butanediol phosphate; 3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate; 3′-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety.
In yet another embodiment, the 3′-cap is selected from a group comprising glyceryl, inverted deoxy abasic residue (moiety), 4′,5′-methylene nucleotide; I-(beta-D-erythrofuranosyl) nucleotide; 4′-thio nucleotide, carbocyclic nucleotide; 5′-amino-alkyl phosphate; 1,3-diamino-2-propyl phosphate; 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety; 5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate; 1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging 5′-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5′-mercapto moieties (for more details see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).
By the term “non-nucleotide” is meant any group or compound which can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine and therefore lacks a base at the 1′-position.
An “alkyl” group refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain, and cyclic alkyl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably, it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group can be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino, or SH. The term also includes alkenyl groups that are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has 1 to 12 carbons. More preferably, it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkenyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2, halogen, N(CH3)2, amino, or SH. The term “alkyl” also includes alkynyl groups that have an unsaturated hydrocarbon group containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has 1 to 12 carbons. More preferably, it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkynyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino or SH.
Such alkyl groups can also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. An “aryl” group refers to an aromatic group that has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An “alkylaryl” group refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder of the ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen, and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. An “amide” refers to an —C(O)—NH—R, where R is either alkyl, aryl, alkylaryl or hydrogen. An “ester” refers to an —C(O)—OR′, where R is either alkyl, aryl, alkylaryl or hydrogen.
By “nucleotide” as used herein is as recognized in the art to include natural bases (standard), and modified bases well known in the art. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. Nucleotides generally comprise a base, sugar and a phosphate group. The nucleotides can be unmodified or modified at the sugar, phosphate and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, non-natural nucleotides, non-standard nucleotides and other; see, for example, Usman and McSwiggen, supra; Eckstein et al., International PCT Publication No. WO 92/07065; Usman et al., International PCT Publication No. WO 93/15187; Uhlman & Peyman, supra, all are hereby incorporated by reference herein). There are several examples of modified nucleic acid bases known in the art as summarized by Limbach et al., 1994, Nucleic Acids Res. 22, 2183. Some of the non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxy benzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By “modified bases” in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1′ position or their equivalents.
In one embodiment, the invention features modified siNA molecules, with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, phosphotriester, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications, see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al., 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39.
By “abasic” is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1′ position, see for example Adamic et al., U.S. Pat. No. 5,998,203.
By “unmodified nucleoside” is meant one of the bases adenine, cytosine, guanine, thymine, or uracil joined to the 1′ carbon of β-D-ribo-furanose.
By “modified nucleoside” is meant any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate. Non-limiting examples of modified nucleotides are shown by Formulae I-VII and/or other modifications described herein.
In connection with 2′-modified nucleotides as described for the present invention, by “amino” is meant 2′—NH2 or 2′-O—NH2, which may be modified or unmodified. Such modified groups are described, for example, in Eckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., U.S. Pat. No. 6,248,878, which are both incorporated by reference in their entireties.
Various modifications to nucleic acid siNA structure can be made to enhance the utility of these molecules. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.
F. Compositions for Administration
Suitable pharmaceutical compositions containing the present RNAi inducing oligonucleotides can be prepared in many different forms. In most cases, it is desirable to apply the active oligonucleotide topically to one or more hair producing skin areas on a subject. For these applications, a composition that flows, or is spreadable or sprayable is advantageous. Examples of such compositions include, for example, solutions, suspensions, emulsions, lotions, creams, gels, ointments, liposome preparations, and the like. Preparation of such pharmaceutical compositions is well-known in the art, and can be utilized for the present invention.
Thus, the oligonucleotide formulations useful in the present invention will generally include the oligonucleotide(s) and a pharmaceutically acceptable carrier, e.g., any liquid or nonliquid carrier, gel, cream, ointment, lotion, paste, emulsifier, solvent, liquid diluent, powder, or the like, which is stable with respect to all components of the topical pharmaceutical formulation and which is suitable for topical administration of oligonucleotides according to the method of the invention. Such carriers are well known in the art.
A topical carrier, as noted above, is one which is generally suited to topical drug administration and includes any such materials known in the art. The topical carrier is selected so as to provide the composition in the desired form, e.g., as a liquid, lotion, cream, paste, gel, or ointment, and may be comprised of a material of either naturally occurring or synthetic origin. It is essential, clearly, that the selected carrier not adversely affect the oligonucleotide or other components of the topical formulation. Examples of suitable topical carriers for use herein include water, alcohols and other nontoxic organic solvents, glycerin, mineral oil, silicone, petroleum jelly, lanolin, fatty acids, vegetable oils, waxes, and the like. Particularly preferred formulations herein are colorless, odorless ointments, lotions, creams and gels.
Ointments, which are semisolid preparations, are typically based on petrolatum or other petroleum derivatives. As will be appreciated by the ordinarily skilled artisan, the specific ointment base to be used is one that provides for optimum oligonucleotide delivery, and, preferably, provides for other desired characteristics as well, e.g., emolliency or the like. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.: Mack Publishing Co., 1995), at pages 1399-1404, ointment bases may be grouped in four classes: oleaginous bases; emulsifiable bases; emulsion bases; and water-soluble bases. Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semisolid hydrocarbons obtained from petroleum. Emulsifiable ointment bases, also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum. Emulsion ointment bases are either water-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid. Preferred water-soluble ointment bases are prepared from polyethylene glycols of varying molecular weight; again, reference may be had to Remington: The Science and Practice of Pharmacy for further information.
Lotions, which are preparations that are to be applied to the skin surface without friction, are typically liquid or semiliquid preparations in which solid particles, including the oligonucleotide, are present in a water or alcohol base. Lotions are usually suspensions of solids, and preferably, for the present purpose, comprise a liquid oily emulsion of the oil-in-water type. Lotions are preferred formulations for oligonucleotide delivery to large body areas, because of the ease of applying a more fluid composition. It is generally necessary that the insoluble matter in a lotion be finely divided. Lotions will typically contain suspending agents to produce better dispersions as well as compounds useful for localizing and holding the active agent in contact with the skin, e.g., methylcellulose, sodium carboxymethyl-cellulose, or the like.
Creams containing a oligonucleotide for delivery according to the method of the invention are viscous liquid or semisolid emulsions, either oil-in-water or water-in-oil. Cream bases are water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also sometimes called the “internal” phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation, as explained in Remington, supra, is generally a nonionic, anionic, cationic or amphoteric surfactant.
Gel formulations can also be used in connection with the present invention. As will be appreciated by those working in the field of topical drug formulation, gels are semisolid, suspension-type systems. Single-phase gels contain organic macromolecules distributed substantially uniformly throughout the carrier liquid, which is typically aqueous, but also, preferably, contain an alcohol and, optionally, an oil.
The oligonucleotide formulations useful in the invention also encompass sprays, that generally provide the oligonucleotide in an aqueous solution which can be misted onto the skin for delivery. Such sprays include those formulated to provide for concentration of the oligonucleotide solution at the site of administration following delivery, e.g., the spray solution can be primarily composed of alcohol or other like volatile liquid in which the oligonucleotide can be dissolved. Upon delivery to the skin, the alcohol carrier evaporates, leaving concentrated oligonucleotide at the site of administration.
The oligonucleotide formulations useful in the invention can also contain other optional such as opacifiers, anti-oxidants, gelling agents, thickening agents, stabilizers, and the like. Other agents may also be added, such as antimicrobial agents, antifungal agents, antibiotics and anti-inflammatory agents such as steroids.
The oligonucleotide formulations can include other components that, while not necessary for delivery of oligonucleotides to the skin, may enhance such delivery. For example, although it is not necessary to the practice of the invention, the oligonucleotide formulations may also contain a skin permeation enhancer. Suitable enhancers are well know in the art and include, for example, dimethylsulfoxide (DMSO), dimethyl formamide (DMF), N,N-dimethylacetamide (DMA), decylmethylsulfoxide (C.sub.10 MSO), C.sub.2-C.sub.6 alkanediols, and the 1-substituted azacycloheptan-2-ones, particularly 1-n-dodecylcyclazacycloheptan-2-one (available under the trademark Azone® from Whitby Research Incorporated, Richmond, Va.), alcohols, and the like. Preferably, the oligonucleotides delivered are substantially free of such permeation enhancers.
The additional components should not substantially interfere with the integrity or biological activity of the oligonucleotide or the formulation in which it is provided, i.e., the additional components do not adversely affect the uptake of the oligonucleotide by skin cells or chemically modify the oligonucleotide in an undesirable manner.
It will be recognized by those skilled in the art that the optimal quantity and spacing of individual dosages of oligonucleotides will be determined by the precise form and components of the oligonucleotide formulation to be delivered, the site of administration, the use to which the delivery device is applied (e.g., immunization, treatment of a condition, production of transgenic animals, etc.), and the particular subject to which the oligonucleotide formulation is to be delivered, and that such optimums can be determined by conventional techniques. It will also be appreciated by one skilled in the art that the optimal dosing regimen, i.e., the number of doses of oligonucleotides, can be ascertained using conventional methods, e.g., course of treatment determination tests. Generally, a dosing regimen will involve administration of the selected oligonucleotide formulation at least once daily, and may be one to four times daily or more.
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of drug formulation, particularly topical drug formulation, which are within the skill of the art. Such techniques are fully explained in the literature. See Remington: The Science and Practice of Pharmacy, cited supra, as well as Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed. (New York: McGraw-Hill, 1996).
Dosage Forms of the Oligonucleotide Formulations
The oligonucleotides can be prepared in unit dosage form (e.g., in ampules), or in multidose form. The oligonucleotides may be present in such forms as suspensions, solutions, gels, or creams, preferably in an aqueous vehicle (e.g., in a buffered solution). Alternatively, the oligonucleotide salt may be in lyophilized form for reconstitution, at the time of delivery, with a suitable vehicle, such as sterile pyrogen-free water or phosphate-buffered saline (PBS). Both liquid as well as lyophilized forms that are to be reconstituted preferably comprise agents, preferably buffers, in amounts necessary to suitably adjust the pH of the solution. Nonionic materials, such as sugars, are preferred for adjusting tonicity, and sucrose is particularly preferred. Any of these forms may further comprise suitable formulatory agents, such as starch or sugar, glycerol or saline. The compositions per unit dosage, whether liquid, gel, cream, or solid, may contain from 0.1% to 99% of oligonucleotide material.
Delivery Devices
The oligonucleotide formulation can administered using and be provided within, a delivery device (e.g., a patch, bandage, etc.) that provides for both maintenance of contact between the skin of the subject and the oligonucleotide formulation and substantially uninhibited movement of the oligonucleotide into the skin. The delivery device generally does not in and of itself facilitate movement of the oligonucleotide contained therein into the skin, but rather primarily acts to ensure that the oligonucleotide formulation is in contact with the skin for a time sufficient to allow genetic alteration of skin cells. The delivery device comprises a delivery means, or “reservoir,” which is saturated with a formulation that comprises an amount of oligonucleotide sufficient to genetic alteration of skin cells to which it is to be delivered and sufficient to elicit the desired biological effect. For example, where the delivery device is to be used to deliver a oligonucleotide for genetic immunization of a human, the delivery means of the device preferably contains an amount of oligonucleotide ranging from about 10 .mu.g to about 1,000 .mu.g, preferably from about 100 .mu.g to about 500 .mu.g.
Suitable delivery means of the delivery devices of the invention include, but are not limited to, sponges, hydrogels, and absorptive materials (e.g., gauze) that allow for retention of the oligonucleotide formulation at the site of oligonucleotide administration without substantially interfering with the delivery of oligonucleotide to the skin. It is important that, upon contact of the delivery means with the skin, the oligonucleotides contained in the delivery means diffuse or otherwise pass from the delivery means into the skin at a rate and in an amount suitable to accomplish the desired effect.
In general, the delivery means has at least two surfaces: a first surface that serves as a skin-contacting surface; and a second surface opposite the skin-contacting surface. Preferably, the second surface is in contact with a liquid-impermeable coating that substantially prevents movement of the oligonucleotide out of the delivery means through the second surface (e.g., in a direction away from the first skin-contacting surface). Preferably, the liquid-impermeable coating also decreases the rate of dehydration of the oligonucleotide formulation contained in the delivery means. In one embodiment, the first skin-contacting surface of the delivery means is associated with a liquid-impermeable, removable layer (e.g., release liner), which layer is removed just prior to placement of the first surface on the skin of a subject for administration of the oligonucleotide.
The delivery device preferably comprises an adhesive means, which can be a polymeric matrix of a pharmaceutically acceptable contact adhesive material, which serves to affix the system to the skin during drug delivery. The adhesive means facilitates retention of the delivery means on the skin at the desired site of administration. Preferably, the adhesive means comprises an adhesive substance that allows for retention of the delivery means at the desired site for a selected amount of time, but additionally allows for easy removal of the delivery means without substantially adversely affecting the skin with which the adhesive substance was in contact.
The adhesive substance used must be biocompatible with the skin of the subject, and should not substantially interfere with the delivery of oligonucleotide to the subject. Examples of suitable skin contact adhesive materials include, but are not limited to, polyethylenes, polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and the like. The particular polymeric adhesive selected will depend on the particular oligonucleotide formulation, vehicle, etc., i.e., the adhesive must be compatible with all components of the oligonucleotide formulation.
In one embodiment, the delivery means and skin contact adhesive are present as separate and distinct layers of the delivery device, with the adhesive underlying the delivery means which, in this case, may be either a polymeric matrix as described above, or it may be a liquid or hydrogel reservoir, or may take some other form. In another embodiment, the delivery means is an adhesive bandage. Exemplary delivery devices suitable for use in the invention include, but are not limited to, those devices described in U.S. Pat. No. 5,160,328; U.S. Pat. No. 5,254,346; U.S. Pat. No. 5,714,162; U.S. Pat. No. 5,667,798; U.S. Pat. No. 5,230,896; and U.S. Pat. No. 5,260,066. Methods for preparation of suitable delivery means and other elements associated with the delivery means, such as an adhesive means are well known in the art.
In another embodiment, the oligonucleotide formulation of the invention is provided as a patch, wherein the drug composition is contained within, for example, a laminated structure that serves as a drug delivery device to be affixed to the skin. In such a structure, the oligonucleotide composition is contained within a delivery means, or “reservoir,” which lies beneath an upper backing layer. The laminated structure may contain a single reservoir, or it may contain multiple reservoirs.
The backing layer in the laminates of the patch, which serves as the upper surface of the delivery device, functions as the primary structural element of the laminated structure and provides the device with much of its flexibility. The material selected for the backing material should be selected so that it is substantially impermeable to oligonucleotide and, preferably, to other components of the oligonucleotide formulation, thus preventing loss of any components through the upper surface of the device, and preferably substantially impeding dehydration of the composition in the reservoir. The backing layer may be either occlusive or nonocclusive, depending on whether it is desired that the skin become hydrated during drug delivery. The backing is preferably made of a sheet or film of a preferably flexible elastomeric material. Examples of polymers that are suitable for the backing layer include polyethylene, polypropylene, polyesters, and the like.
During storage and prior to use, the laminated structure includes a release liner. Immediately prior to use, this layer is removed from the device to expose the skin-contacting surface of the device, which as noted above may be either the reservoir itself or a separate contact adhesive layer, so that the system may be affixed to the skin. The release liner is preferably made of a material that is substantially impermeable to the oligonucleotide and other components in the oligonucleotide formulation.
Delivery devices suitable for use in the present invention may be fabricated using conventional techniques, known in the art, for example by casting a fluid admixture of adhesive, oligonucleotide, and carrier/vehicle onto the backing layer, followed by lamination of the release liner. Similarly, the adhesive mixture may be cast onto the release liner, followed by lamination of the backing layer. Alternatively, the oligonucleotide reservoir may be prepared in the absence of oligonucleotide formulation or excipient, and then loaded by “soaking” in a drug/vehicle mixture.
As with the topical formulations of the invention, the oligonucleotide formulation contained within the delivery means of the delivery devices may contain a number of components. Furthermore, such delivery devices can be used in connection with administration of any of the oligonucleotide formulations described herein, e.g., naked oligonucleotide formulations, or lipid- or liposome-comprising oligonucleotide formulations. Regardless of the specific basic components of the oligonucleotide formulation, the oligonucleotide formulation will generally dissolved, dispersed or suspended in a suitable pharmaceutically acceptable vehicle, typically an aqueous solution or gel. Other components that may be present include preservatives, stabilizers, and the like.
Packaging of the Oligonucleotide Formulations and Delivery Devices
The units dosage ampules, multidose containers, and/or delivery devices (e.g., patches) in which the oligonucleotides are packaged prior to use may comprise an hermetically sealed container enclosing an amount of oligonucleotide or oligonucleotide formulation containing a oligonucleotide suitable for a pharmaceutically effective dose thereof, or multiples of an effective dose. The oligonucleotide is preferably packaged as a sterile formulation, and the hermetically sealed container is designed to preserve sterility of the formulation until use. Where the oligonucleotides are provided in a patch-style delivery device, the patches may be contained in a strip of individually separable packaged patches for ease in dispensing.
The container in which the oligonucleotide formulation and/or delivery device is packaged is labeled, and the label bears a notice in the form prescribed by any appropriate governmental agency. For example, where the oligonucleotides are to be administered to humans, the package comprises a notice that reflects approval by the Food and Drug Administration under the applicable federal law, of the manufacture, use, or sale of the oligonucleotide material therein for human administration. Federal law requires that the use of pharmaceutical agents in the therapy of humans be approved by an agency of the Federal government. Responsibility for enforcement is the responsibility of the Food and Drug Administration, which issues appropriate regulations for securing such approval, detailed in 21 U.S.C. 301-392. Regulation for biologic material, comprising products made from the tissues of animals is provided under 42 U.S.C 262. Similar approval is required by most foreign countries. Regulations vary from country to country, but the individual procedures are well known to those in the art.
Introduction of Oligonucleotides into Skin Cells According to the Method of the Invention
Application of the Oligonucleotide to Skin
Administration of the oligonucleotide is accomplished by contacting a oligonucleotide-comprising formulation (e.g., a buffered salt solution comprising the oligonucleotide) with an area of skin for a time sufficient to allow genetic alteration of skin cells. Preferably, the oligonucleotide is applied to hirsute skin. The oligonucleotide can be applied to skin without substantial pretreatment or with pretreatment, preferably without pretreatment of the skin. “Pretreatment” can generally encompass removal of hair from the skin, increasing skin permeability by mechanical means (e.g, abrasion), increasing skin permeability by application of a chemical agent to the site either before or during oligonucleotide administration, and application of an irritant or other like chemical agent to elicit a non-specific immune response or an immune response toward the irritant (e.g., by application of a keratinolytic agent). Administration of the oligonucleotide can be accomplished according to the invention without the application of an electric field or electric pulse (e.g., as in iontophoresis), without breaking the skin (e.g., by abrasion or through use of a needle), and without application of pressure to the site of administration (e.g., via jet propulsion, pressurized air, etc.). Furthermore, oligonucleotide administration can be accomplished using a oligonucleotide formulation that is substantially free of permeabilizing agents, detergents, or other chemical agents that facilitate entry of the oligonucleotide into the skin.
Once the oligonucleotide-comprising formulation is brought into contact with skin, contact is maintained for a time sufficient to allow movement of the oligonucleotide from the formulation into skin and into skin cells. In general, the time of contact between the oligonucleotide and the skin will be at least about 1 min to about 1 hr or more, preferably at least about 30 min. Because there is substantially no toxicity associated with contacting the oligonucleotide with the skin, the time of contact maintained between the oligonucleotide and the skin to which the oligonucleotide is to be delivered is limited only by such factors as the ability to keep the oligonucleotide in a suitable delivery form (e.g., a time during which the oligonucleotide-comprising solution can be prevented from dehydrating) and the ability to physically maintain contact between the oligonucleotide and the site of delivery (e.g., maintenance of a patch comprising the oligonucleotide(s) on the skin). Therefore, the time of contact of a single dose can be as long as several hours to several days, and may be weeks or more. Furthermore, the time of delivery can be further extended by additional subsequent applications of the oligonucleotide to the same or different delivery site on the skin.
While an ethanolic/propylene glycol solution of anti-hairless oligonucleotide as found to deliver beneficial amounts of oligonucleotide to the hair follicle and result in inhibition of hairless, other formulations can also advantageously be used. In particular, liposome compositions can be advantageous. Liposomes were introduced first in about 1980 for topical drug delivery and have since attracted considerable interest due to their potential utility both as a drug carrier and a reservoir for controlled release of drugs within various layers of the skin and the hair follicle. In addition to reducing the undesirable high systemic absorption of topically applied drugs, the major advantage of liposomes compared to other formulations such as ointments or creams, is based on their ability to create a depot, from which the drug is slowly released. The delivery agents also provide advantages in that they protect oligonucleotides against degradation, increase cellular uptake, and may target the drug to specific cells or tissue compartment. Thus, a delivery system allowing the controlled and sustained release of oligonucleotides in vivo can greatly increase the efficacy of gene inhibition technology.
One of the most favored sites of liposome penetration is into the hair follicle, since the hair canal opens directly onto the surface of the skin. Liposomes applied to cultured hair follicles are easily detected in cells lining the inner root sheath. (Li et al., 1992b, In Vitro Cell Dev Biol 28A:679-681.) Liposomes also find their way into the pilosebaceous unit once traveling down the root sheath. (Lieb et al. 1992, J Invest Dermatol 99:108-113.) Liposomes have been shown to direct compounds into the sebaceous gland, when they would otherwise be trapped in the stratum corneum. (Bernard et al., 1997, J Pharm Sci 86:573-578.) Liposomes function both as a controlled release system and as a delivery system transporting encapsulated substances into cells. After topical application, and upon drying, the liposomes develop into a structured film that fills the follicular openings, intimately mixing with the follicular contents, and fostering drug diffusion to the depths of the follicles.
A number of different compositions of liposomes have been tested for in vivo oligonucleotide delivery. For example, three different lipids were compared: N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium chloride (DOTMA), 2,3-dioleyloxy-N-[2(sperminecarboxamido) ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA) and N-(1-(2,3-dimyristyloxypropyl)-N,N dimethyl-(2-hydroxyethyl) ammonium bromide (DMRIE). The macrophages incorporated tenfold more oligonucleotide when delivered in conjunction with DOSPA than with the other cationic lipids.
Liposome preparation and encapsulation of oligonucleotides are available from commercial manufacturer, e.g., BioZone Laboratories, Inc. Pittsburg, Calif., which manufactures a wide range of topically applied LipoCeutical products that include cationic lipids.
In addition to cationic lipid liposomes, other types of liposomes can also be used, e.g. pH-sensitive liposomes. The cellular uptake of liposomes passes mainly through an endocytic pathway, and occasionally, liposomes and their contents inadvertently arrive in the lysosomes where they are degraded. The quantity of oligonucleotides that can avoid degradation and reach their nuclear or cytoplasmic target is probably very low. To overcome lysosomal degradation and in order to increase the efficiency of delivery, pH sensitive fusogenic liposomes have been used. These consist of a non-bilayer-forming lipid such as dioleylphosphatidylethanolamine (DOPE) and a titratable acidic amphiphile such as oleic acid (OA) or cholesterylhemisuccinate (CHEMS). (DeOliveira et al., 1998, Biochim. Biophys. Acta Biomembr. 1372:301-310.) At pH 7, the amphiphile maintains the lipid mix in a bilayer (liposome) structure. However, as the complex moves through the endosomes, the pH drops and the amphiphile becomes protonated. This causes the liposome to collapse resulting in fusion with the endosomal membrane and release of the liposome contents into the cytoplasm. However, the anionic nature of pH-sensitive liposomes may lead to poor encapsulation of ODNs. (Hughes et al., 2000, Methods Enzymol 313:342-358.).
As one alternative to liposomes, other carriers/delivery agents can be used, such as cationic polymers. The most widely studied polymers are polylactides and co-polymers of lactic acid and glycolic acid P(LA-GA) and both of these have been evaluated for the use for delivery of oligonucleotides. (Lewis et al., 1998, J Drug Target 5:291-302; Hudson et al., 1999, Int J Pharm 182:49-58.)
In addition to the above, certain patents have described methods for delivery that can be used in the present invention. Examples include the following.
Li and Lishko, U.S. Pat. No. 5,914,126 (incorporated herein by reference in its entirety) describes methods to deliver macromolecules to hair follicles, where the method involves applying to the skin a formulation that includes a macromolecule, such as a nucleic acid, in a liposomal formulation, such that the liposomes target the macromolecule selectively into hair follicle cells by transfer into the follicle without entry into the circulation of the adjacent skin tissue.
Khavari et al., U.S. Pat. No. 6,087,341 (incorporated herein by reference in its entirety) describes methods and compositions for introduction of nucleic acid into skin cells by topical application.
Li and Baranov, U.S. Pat. No. 6,080,127 (incorporated herein by reference in its entirety) describes a skin vibration method for topical targeted delivery of beneficial agents into hair follicles. The vibration frequency can, for example, be about 1 Hz to 100 Hz.
In some applications, it may be useful to include transdermal penetration enhancers, for example, as described in Karande et al., 2004, Nature Biotech. 192-197. As described, two types of compositions were particularly effective. One included sodium laureth sulfate (SLA) with phenyl piperazine (PP). In a particular composition the SLA:PP was as 0.5% (w/v) with the weight ration of SLA=0.7 in the combination. The second included N-lauroyl sarcosine (NLS) with sorbitan monolaurate (S20). In a particular composition, the combination was at 1.0% (w/v) with the weight ration of NLS=0.6.
G. Administration
The present compositions can be administered in various ways, e.g., depending on the condition to be treated, and the type of composition to be used. In many cases, topical administration will be used. This mode of administration is particularly suitable for local hair removal.
In some applications, hair removal is desired in only a portion of the skin area of a subject. In those cases, the composition can be applied locally.
Exemplary Topical Application Methods
Spreading
In most cases, the composition containing the RNAi inducing oligonucleotides will be spread or wiped on the treatment area to form a thin film. Thus, for example, for any of the forms of liquid suspension or solution, cream, lotion, gel, or ointment, a quantity of the composition is spread on the treatment surface or surfaces of the subject, and left for a time to allow oligonucleotides (which may be in a carrier species such as in liposomes, to migrate to the hair follicles.
Spraying
For compositions that are sufficiently liquid, the composition can be sprayed on the treatment site, either with or without protection against overspray on surrounding areas. For spray applications, it may be desirable to protect against inhalation of sprayed material, e.g., by using masks that will filter out the relevant sized aerosol particles.
Injection
In some applications, it will be desirable to remove only specific hairs. Thus, rather than contacting a particular area, a composition will be delivered to one or more particular hair follicles. Such individual follicle delivery can be accomplished in various ways. For example, a drop of liquid containing the active oligonucleotide(s) can be deposited on the hair shaft, and allowed to migrate down the shaft to the follicle. In another approach, a needle can be inserted in the hair channel, and liquid or other composition deposited at or near the follicle.
Application Site Preparation and Hair Cycle Synchronization
In some cases, the present compositions can be applied without any special preparation of the application site. In other cases, however, it is advantageous to prepare the site, e.g., by preliminary removal of hair from the site and/or to combine the present invention with a supplementary method of hair removal. Such removal can be beneficial in several different ways. For example, such removal can reduce the amount of active agent required for the present invention because the material will not be lost by adhering to the hair, and instead will be available for absorption/migration to the hair follicles.
Such removal can also be beneficially be used to supplement the present invention by removing residual hairs. Depending on the manner and amount of RNAi inducing oligonucleotide delivered to the hair follicles, some of the follicles may not be sufficiently inhibited, such that some hairs may grow in the treated area and/or some hairs may be reduced in thickness or length but still present. In such cases, a supplementary method of hair removal can be used to produce a desired level of hair removal, e.g., shaving, chemical depilation, enzymatic hair removal; laser treatment; electrolysis. Certain embodiments of the present invention include such an supplemental method.
It can also be advantageous to synchronize hair cycles in the treatment area. Such synchronization can advantageously be done prior to application of the present compositions, or during an interval of treatment with the present compositions, or in an interval between two occasions or intervals of application of the present compositions.
Such synchronization can be accomplished, for example, by pulling hairs from the follicles (either individually or in larger numbers). Examples of methods for pulling the hairs include plucking and waxing. In some circumstances it will be necessary/desirable to induce follicle synchrony by molecular means. In these instances, skin is treated with a known follicle growth inducer such as cyclosporin A, TPA, Noggin, estrogen receptor agonist, and the like.
In general, if a hair is pulled from a follicle in anagen, that follicle goes into catagen; if a hair is pulled from a follicle in telogen, the follicle is stimulated to produce hair, and thus goes into anagen. Thus, for a more extensive effect using the present invention, a distribution of hairs in anagen, catagen, and telogen can be synchronized in catagen, with one pulling to push anagen follicles to catagen, and two pullings to stimulate telegen follicles to anagen, and then push the newly anagen follicles to catagen. Depending on the reaction of the follicles, such procedure can produce a single phase synchrony, or a two phase synchrony.
EXAMPLE 1
In Vitro siRNA Inhibition of Hairless mRNA
siRNAs were commercially obtained from Ambion, Inc. for human and mouse hairless genes. These are validated, chemically synthesized siRNAs, that are HPLC purified, annealed and ready to use, and guaranteed to reduce target gene expression by 70% or more. For both human and mouse transcripts, two different siRNAs were used. The sequence of the hairless siRNAs is given in the following table. In this and the subsequent tables in this example, upper case letter are used to refer to the human homologs, and lower case letter refer to the mouse homologs of the specified genes.
List of Pre-Designed siRNAs Used for Gene Silencing Experiments.












siRNA
Sense Sequence
Antisense Sequence







HR#1
5′-GGACAUGCUCCCACUUGUGtt-3′
5′-CACAAGUGGGAGCAUGUCCtt-3′



(SEQ ID NO: 11355)
(SEQ ID NO: 11356)


 


HR#2
5′-GGAGGCCAUGCUUACCCAUtt-3′
5′-AUGGGUAAGCAUGGCCUCCtt-3′



(SEQ ID NO: 11357)
(SEQ ID NO: 11358)


 


hr#1
5′-GGACACACUCUCACUGGUGtt-3′
5′-CACCAGUGAGAGUGUGUCCtt-3′



(SEQ ID NO: 11359)
(SEQ ID NO: 11360)


 


hr#2
5′-GGGCUUUUACCACAAGGAUtt-3′
5′-AUCCUUGUGGUAAAAGCCCtt-3′



(SEQ ID NO: 11361)
(SEQ ID NO: 11362)









We also used siRNAs for the mouse glyceraldehyde-3-phosphate dehydrogenase (gapdh) gene, SilencerTM GAPDH siRNA (Cat no. 4605, Ambion, Inc. Austin, Tex.) as controls to monitor and optimize siRNA experiments.
Human HaCaT, HeLa and mouse NIH 3T3 cells were used in siRNA transfection experiments. Cells were plated on 6-well tissue culture plates in Dulbecco's Modified Eagle Media (D-MEM, Cat no. 10569-010, Invitrogen Corp., Carlsbad, Calif.) with 10% Fetal Bovine Serum (Cat no. 16000-044, Invitrogen, Corp.) so that they were 30-50% confluent at the time of transfection. Immediately before the transfection, the cells were washed in Opti-MEM I Reduced Serum Medium (Cat no. 31985-070, Invitrogen, Inc.). We used 200 μmol of short interfering RNA (siRNA) for each well and the OligofectamineTM reagent. The transfections were performed according to the manufacturer's instructions (Cat no. 12252-011, Invitrogen, Inc).
Total RNA was isolated 24 and 48 hours post-transfection using the RNeasy Mini Kit (Cat no. 74104, QIAGEN, Inc., Valencia, Calif.) according to the manufacturer's instructions. cDNA synthesis was performed using the SuperScript First-Strand Synthesis System for RT-PCR kit (Cat no. 11904-018, Invitrogen, Corp.) and oligo (dT) primers. Gene activity was determined by the Real-Time quantitative RT-PCR (qRT-PCR) technique.
Real Time Quantitative RT-PCR (qRT-PCR)
Real-Time qRT-PCR was performed using MJ Research Opticon 2 continuous fluorescence detector. For qRT-PCR 40 ng of cDNA obtained from cultured HaCaT, HeLa, and NIH3T3 cells (siRNA treated and untreated), was amplified using the MJ Research DyNAmo Hot Start SYBR Green qPCR kit (Cat no. F-410L, MJ Research, Inc., Waltham, Mass. The DyNAmo Hot Start SYBR Green qPCR kit is a master mix of a modified hot start DNA polymerase with SYBR Green I and the appropriate buffers, all of which have been optimized for real-time quantitative analysis with the MJ Research Opticon 2. PCR amplification of cDNA samples was performed in 96 well optical plates under the following conditions:













1.
Incubate at 95.0 C. tor 00:10:00


2.
Incubate at 95.0 C. for 00:00:20


3.
Incubate at 55.0 C. for 00:00:30


4.
Incubate at 72.0 C. for 00:00:40


5.
Plate Read


6.
Incubate at 77.0 C. for 00:00:01


7.
Plate Read


8.
Go to line 3 for 39 more times


9.
Incubate at 72.0 C. for 00:05:00


10.
Melting Curve from 65.0 C. to 95.0 C.



read every 0.2 C. hold 00:00:01


11.
Incubate at 72.0 C. for 00:05:00







END









The list of PCR primers used for Real Time PCR amplifications is given in the following table.
PCR primers used for Real-Time RT-PCR amplifications of mouse and human hairless, mouse glyceraldehyde-3-phosphate dehydrogenase gene, and hypoxanthine guanine phosphoriboxyltransferase 1 (hprt). (HPRT was used as a normalizing internal control in mouse cells the same way GAPDH was used for the human cell lines.)












Gene
Forward primer
Reverse primer







Hr
5′-TTCTACCGCGGTCAAACTCT-3′
5′-TTGGTGTCAGGGATCCAAAG-3′



(SEQ ID NO: 11363)
(SEQ ID NO: 11364)


 


GAPDH
5′-AGCCACATCGCTCAGAACAC-3′
5′-GAGGCATTGCTGATGATCTTG-3′



(SEQ ID NO: 11365)
(SEQ ID NO: 11366)


 


hr
5′-ACATCAAAGAAGAGACCCCAG-3′
5′-TTCGCACTGGTGACAATGGAA-3′



(SEQ ID NO: 11367)
(SEQ ID NO: 11368)


 


gapdh
5′-GTGAACGGATTTGGCCGTATT-3′
5′-TTTTGGCTCCACCCTTCAAGT-3′



(SEQ ID NO: 11369)
(SEQ ID NO: 11370)


 


hplt
5′-CCCTGGTTAAGCAGTACAGC-3′
5′-CAGGACTAGAACACCTGCTAA-3′



(SEQ ID NO: 11371)
(SEQ ID NO: 11372)









Plate readings for fluorescence levels are taken at two steps, 5 and 7. These values indicate the relative amounts of amplicon per well at a particular cycle. The raw numbers obtained from these readings were used to determine the PCR amplification efficiency. This is the measurement of fold amplification per PCR cycle, and is expressed as a fraction or percentage relative to perfect doubling. A PCR resulting in perfect doubling would exhibit 100% amplification efficiency. All of the calculations are done using the LinRegPCR program by J. M. Ruijter and C. Ramakers. The crossing threshold for the experiment is determined manually and is defined at the cycle at which amplification for all samples becomes logarithmic. The relative fold for each amplicon is then determined using the amplification efficiency and crossing threshold for that particular amplicon and normalizing it against the relative starting amounts, which is determined by the GAPDH amplification efficiency and crossing threshold that corresponds to that sample. This is done using parameters and equations set by Lui and Saint (Analytical Biochemistry 302, 52-59 (2002)). The final values can then be used to compare the fold differences in gene expression of a particular gene across several different samples or conditions.
This technique and analysis can be applied to determine the levels of hairless expression, or more specifically, the efficiency of gene silencing using hairless siRNA through comparison of the treated and untreated cell populations.
The following table shows the percentage of gene silencing observed following siRNA treatment of human HeLa and HaCaT cells. Total RNA was collected 48 hours following transfection with siRNAs for hairless (Hr) gene. Gene activity was assayed by real-time quantitative RT-PCR (qRT-PCR) technique. Percent knockdown is calculated by obtaining the ratio of the normalized level of Hr expression in treated and untreated cell populations and subtracting this value from 1 (100% expression).















Gene






Expression
Cell
Percent
RNA isolation


siRNA
Tested
Type
Knockdown
time point







HR#1
Hr
HeLa
97.3%
48 hours


HR#2
Hr
HeLa
98.7%
48 hours


HR#2
Hr
HaCaT
95.8%
48 hours









The following table shows the percentage of gene silencing observed following siRNA treatment of mouse NIH3T3 cells. Total RNA was collected 48 hours following transfection with siRNAs for hairless (hr) and glyceraldehyde-3-phosphate dehydrogenase (gpdh) genes. Gene activity was assayed by real-time quantitative RT-PCR (qRT-PCR) technique. Percent knockdown is calculated by obtaining the ratio of the normalized level of hr and gapdh expression in treated and untreated cell populations and subtracting this value from 1 (100% expression).















Gene






Expression
Cell
Percent
RNA isolation


siRNA
Tested
Type
Knockdown
time point







hr#1
Hr
NIH3T3
99.3%
48 hours


hr#2
Hr
NIH3T3
99.17%
48 hours


Gapdh
Gapdh
NIH3T3
99.3%
48 hours









EXAMPLE 2
In Vivo Testing: A Phase 1 Clinical Trial of Anti-Hairless siRNA
The goal of this study is to establish the safety of topical application of anti-hairless siRNA (Trichozyme) in healthy human subjects at a dose of 10 μg daily, administered over a period of 3 months.
Inhibition of gene expression using or siRNA technology is a recently developing area of therapy. Several recent studies indicate the usefulness of such therapeutic strategies in a number of different conditions. Our preliminary in vivo studies demonstrated the inhibition of hairless mRNA can be used to permanently inhibit hair growth in experimental animals. Briefly, they inhibit translation from the mRNA transcript originating from the human hairless gene, the first known gene participating in the regulation of the human hair cycle as identified by our group earlier, preventing the synthesis of functional hairless protein. Presence of hairless protein is necessary for uninterrupted hair cycling, and lack of hairless gene expression due to a deleterious mutation or temporary inhibition leads to a permanent inhibition of hair growth and the involution of hair follicles as evidenced by our own in vivo trials in animal models. The successful translation of the result of animal studies to human application leads to a strategy to obtain permanent inhibition of hair growth by temporary topical treatment with Trichozyme.
Study Design
This will be an open label, uncontrolled, safety study. Monitoring for side effects, alterations in hematology, serum chemistries and urine analysis will continue during the 3 month treatment period as well as during the 6 month follow up period after the application is stopped. Subjects will be seen daily by Study personnel during the treatment period and monthly during the follow-up period. The Study will not offer treatment of any side effects that develop.
We will enlist 20 subjects, 10 of which will be treated with the siRNA in an isopropranol or liposomal based vehicle, the other 10 subject will receive treatment with vehicle only. Hair from the dorsal surface of the left forearm will be removed by waxing before applying treatment during the first 30 days of the study. Treatment will consist of topical application of an isopropranol based solution alone or containing anti-hairless siRNA over a 15 cm2 area of the dorsal surface of the left forearm using a glass rod. Ample time will be left for absorption.
Subjective side effects, alterations in serum chemistry, hematology and urine analysis will be monitored as well as serum and urine isopropranol level and presence of Trichozymes in serum and urine samples. Photography of the treatment area and hair count will be performed during the initial visit and weekly afterwards during the treatment period of the study then monthly during the follow-up period of the study.
Study Procedures
Before entering in the study subjects will sign an informed consent for disclosure of medical records. A screening questionnaire will be completed as well as a review of medical records to exclude any preexisting medical conditions affecting hair growth or other preexisting diseases listed as exclusion criteria.
Laboratory evaluation—Fasting blood and urine samples will be obtained for the following tests: (a) Hematology—hemoglobin and hematocrit, CBC with differential and platelet count, (b) Serum Chemistry—sodium, total bilirubin, potassium, glucose, chloride, alkaline phosphatase, calcium, AST, ALT, inorganic phosphorus, BUN, creatinine, bicarbonate; (c) urinalysis—protein, glucose, pH, Ketones, nitrates, blood (d.) pregnancy test.
Screening/Baseline Visit—Informed consent for study participation signed. Complete history (including record of systemic and topical medication, both prescription and non-prescription). Physical exam—Comprehensive skin exam and photography of the treatment area and hair count. (e) Review criteria for inclusion/exclusion and determine eligibility.
Daily Clinic Visits for treatment—waxing of the treatment area (for first 30 days only) followed by topical application of Treatment. Blood and urine samples for Hematology, Serum chemistry, Urine analysis, Isporopranol serum/urine level and siRNA detection in serum/urine will be obtained monthly. Photography of the treatment area and hair count will be performed weekly. Subjects will be interviewed for subjective side effects weekly.
Monthly Clinic Visits for follow-up—Blood and urine samples for Hematology, Serum chemistry, Urine analysis, Isporopranol serum/urine level and siRNA detection in serum/urine will be obtained. Photography of the treatment area and hair count. Subjects will be interviewed for subjective side effects.
Study Site—Subjects will be seen at the clinical facilities for the study.
Study Drugs
siRNAs for the study are are oligonucleotides with RNAi activity that is specific to mRNA sequences present in the human hairless mRNA. This study will utilize a mixture of 8-10 different siRNAs. To date there is no data available of topical cutaneous application of any deoxy-ribozymes. The siRNAs to be used in this study will be provided by a manufacturer offering custom synthesized human grade oligonucleotides.
Study Questionnaires
All subjects will complete study questionnaires at baseline.
Study Subjects
Criteria—Inclusion—(i) Study subjects must be 18 to 35 years of age, female of Hispanic ethnicity. (ii) Have no previous medical history of hair growth abnormalities or endocrine, renal, autoimmune, cardiac, pulmonary, hematological or psychiatric disorders. (iii) Other inclusion criteria: (iv) The subject has provided written informed consent prior to administration of any study-related procedures. (v) The subject has been using adequate contraception since her last menses and will use adequate contraception during the study, is not lactating, and has a documented negative serum pregnancy test within 14 days prior to the first dose of study medication. (vi) The subject is willing to abstain from any voluntary alteration of body hair of the treated area. (vii) The subject is willing to abstain from application of prescription and over the counter topical medications for the duration of the study, including moisturizers, emollients and sunscreens. (viii) The subject is willing to return for scheduled follow-up visits for the duration of the study. (ix) The subject must meet the following laboratory criteria during a time not to exceed 8 weeks prior to randomization: 1) hemoglobin level of greater than 12.0 (women) or 13.0 (men); 2) WBC count greater than 3000/mm3; 3) platelet count greater than 125,000; 4) BUN within normal limits; 5) electrolytes within normal limits; 6) creatinine≦1.5×ULN; 7) AST≦1.5×ULN; 8) ALT≦1.5×ULN; 9) total bilirubin within normal limits; and 10) creatinin clearance within normal limits.
Exclusion—(i) existence of any medical conditions listed above. (ii) any laboratory values that do not meet the criteria listed above. (iii) Pregnancy or lactation. (iv) Invasive cancer or anticipated hormonal, chemo-, or radiotherapy while participating in the study. (v) Any medical or psychosocial condition that, in the opinion of the investigator, could jeopardize subject's participation in this study.
Recruitment of Subjects
Potential subjects for this Study will be recruited from among residents in proximity to the study site because of the daily visit requirements. Subjects with Hispanic ethnicity will be recruited to avoid inter-ethnicity variations of hair density and follicle site as well as blonde hair that is less appropriate for complete hair count and photography.
EXAMPLE 3
Hair Removal Using In Vivo Knockdown of Hairless mRNA
It was demonstrated that inhibiting the expression of hairless mRNA in an animal model system created essentially a hairless condition. This exemplary test was conducted using ribozymes targeting the hairless mRNA, and is described in Cserhalmi-Friedman et al., Exp Dermatol., 2004 March; 13(3):155-62, which is incorporated herein by reference in its entirety.
Short Term Results in Newborn Mice
The mice, who were gender-matched littermates, were sacrificed after four weeks of treatment that started immediately after the animals were born. All treated mice demonstrated a variable degree of visible sparseness of hair at the treated area of the back, which was not observed in the control animals treated with nonspecific deoxyribozymes. The specimens taken from the control animal show the presence of large number of hair follicles in anagen V stage, corresponding to the clinical appearance. In contrast, the samples taken from the treated mice demonstrate the presence of smaller hair follicles with morphological features similar to those observed in anagen III stage (i.e.: hair shaft did not reach the level of the sebaceous gland). A large portion of the hair follicles in the treated region showed delayed anagen development as well as significant dilatation of the hair canal, reminiscent of utricles characteristic of the hairless phenotype. In these samples, we observed several large cysts filled with keratinous material and remnants of coiled and degraded hair follicles. These dermal cysts are believed to be the result of hair follicle disintegration and abnormal hair shaft formation. Importantly, dermal cysts are hallmark features of the hairless phenotype and usually contain either keratinous mass or a degraded hair shaft, as seen in the sample taken from the skin of a hairless mouse. The inhibition of hair growth, formation of the utriculi, and appearance of dermal cysts were present in all treated mice, but were not detected in any control animals.
b. Long Term Results in Newborn Mice
Another group of littermates of identical gender was sacrificed after seven weeks of treatment that started immediately after the animals were born. A noticeable decrease in the density of hair was present in the treated animals as compared to the control mice treated with on specific deoxyribozymes. The sample from the control animals showed the presence of regularly spaced telogen hair follicles. In the treated area, we observed a significantly decreased number of follicles with large areas of the skin devoid of any hair follicles at all. In the treated area, we detected the presence of large cysts filled with amorphous keratin material, corresponding to dermal cysts, which are characteristics of the hairless phenotype. Histopathology of the treated area showed the presence of small dense groups of cells with condensed nuclei in the deep dermis. These cell groups were reminiscent of detached dermal papillae, which are typically found in hairless mice. The lack of hair follicles, the presence of dermal cysts and the detached dermal papillae were present in every treated animal, while all the control animals showed the presence of evenly spaced telogen follicles.
c. Results in Depilated Animals
This group of eight week old female littermates was wax-depilated and subsequently sacrificed after four weeks of treatment that began immediately after the depilation. Clinically, the control animals showed active hair regrowth in the depilated area.
In contrast, the hair regrowth was of lesser magnitude in the treated mice, and the hair became sparse (not shown). Histopathology of the control mouse skin shows the presence of a large number of hair follicles in advanced anagen. In the samples taken from the treated animals, the treated regions could be easily identified by the lack of depilation-induced hair regrowth. These untreated hair follicles were identical to those observed in the control animals treated with nonspecific deoxyribozymes. On histology, the treated area with small telogen hair follicles could be easily distinguished from neighboring untreated area with hair follicles at advanced anagen stages, suggesting that in the treated portion of skin the hair follicles were not able to enter depilation-induced anagen at all, or exhibited much lower growth rates compare to control skin.
All patents and other references cited in the specification are indicative of the level of skill of those skilled in the art to which the invention pertains, and are incorporated by reference in their entireties, including any tables and figures, to the same extent as if each reference had been incorporated by reference in its entirety individually.
One skilled in the art would readily appreciate that the present invention is well adapted to obtain the ends and advantages mentioned, as well as those inherent therein. The methods, variances, and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. For example, variations can be made to the number, length, and chemical modifications in the dsRNA. Thus, such additional embodiments are within the scope of the present invention and the following claims.
The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.
In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group.
Also, unless indicated to the contrary, where various numerical values are provided for embodiments, additional embodiments are described by taking any 2 different values as the endpoints of a range. Such ranges are also within the scope of the described invention.
Thus, additional embodiments are within the scope of the invention and within the following claims.







TABLE 1







cDNA Human Hairless 19-mer Target Sequences and


Complement Referenced to NM_005144-


Homo sapiens hairless homolog (mouse) (HR),


transcript variant 1, complete mRNA (1-5699 bp).


(SEQ ID NO: for Sense equals (2X − 1) SEQ ID


NO: for Antisense equals (2X), (e.g. where


X = 1 Sense has SEQ ID NO: 1 and Antisense


has SEQ ID NO: 2)









X
Sense (5′-3′)
Antisense (5′-3′)












1
TCTCCCGGGAGCCACTCCC
GGGAGTGGCTCCCGGGAGA


 


2
CTCCCGGGAGCCACTCCCA
TGGGAGTGGCTCCCGGGAG


 


3
TCCCGGGAGCCACTCCCAT
ATGGGAGTGGCTCCCGGGA


 


4
CCCGGGAGCCACTCCCATG
CATGGGAGTGGCTCCCGGG


 


5
CCGGGAGCCACTCCCATGG
CCATGGGAGTGGCTCCCGG


 


6
CGGGAGCCACTCCCATGGG
CCCATGGGAGTGGCTCCCG


 


7
GGGAGCCACTCCCATGGGC
GCCCATGGGAGTGGCTCCC


 


8
GGAGCCACTCCCATGGGCG
CGCCCATGGGAGTGGCTCC


 


9
GAGCCACTCCCATGGGCGC
GCGCCCATGGGAGTGGCTC


 


10
AGCCACTCCCATGGGCGCC
GGCGCCCATGGGAGTGGCT


 


11
GCCACTCCCATGGGCGCCT
AGGCGCCCATGGGAGTGGC


 


12
CCACTCCCATGGGCGCCTC
GAGGCGCCCATGGGAGTGG


 


13
CACTCCCATGGGCGCCTCT
AGAGGCGCCCATGGGAGTG


 


14
ACTCCCATGGGCGCCTCTC
GAGAGGCGCCCATGGGAGT


 


15
CTCCCATGGGCGCCTCTCC
GGAGAGGCGCCCATGGGAG


 


16
TCCCATGGGCGCCTCTCCA
TGGAGAGGCGCCCATGGGA


 


17
CCCATGGGCGCCTCTCCAG
CTGGAGAGGCGCCCATGGG


 


18
CCATGGGCGCCTCTCCAGC
GCTGGAGAGGCGCCCATGG


 


19
CATGGGCGCCTCTCCAGCC
GGCTGGAGAGGCGCCCATG


 


20
ATGGGCGCCTCTCCAGCCC
GGGCTGGAGAGGCGCCGAT


 


21
TGGGCGCCTCTCCAGCCCC
GGGGCTGGAGAGGCGCCCA


 


22
GGGCGCCTCTCCAGCCCCT
AGGGGCTGGAGAGGCGCCC


 


23
GGCGCCTCTCCAGCCCCTG
CAGGGGCTGGAGAGGCGCC


 


24
GCGCCTCTCCAGCCCCTGG
CCAGGGGCTGGAGAGGCGC


 


25
CGCCTCTCCAGCCCCTGGC
GCCAGGGGCTGGAGAGGCG


 


26
GCCTCTCCAGCCCCTGGCC
GGCCAGGGGCTGGAGAGGC


 


27
CCTCTCCAGCCCCTGGCCT
AGGCCAGGGGCTGGAGAGG


 


28
CTCTCCAGCCCCTGGCCTG
CAGGCCAGGGGCTGGAGAG


 


29
TCTCCAGCCCCTGGCCTGG
CCAGGCCAGGGGCTGGAGA


 


30
CTCCAGCCCCTGGCCTGGA
TCCAGGCCAGGGGCTGGAG


 


31
TCCAGCCCCTGGCCTGGAA
TTCCAGGCCAGGGGCTGGA


 


32
CCAGCCCCTGGCCTGGAAG
CTTCCAGGCCAGGGGCTGG


 


33
CAGCCCCTGGCCTGGAAGC
GCTTCCAGGCCAGGGGCTG


 


34
AGCCCCTGGCCTGGAAGCA
TGCTTCCAGGCCAGGGGCT


 


35
GCCCCTGGCCTGGAAGCAC
GTGCTTCCAGGCCAGGGGC


 


36
CCCCTGGCCTGGAAGCACC
GGTGCTTCCAGGCCAGGGG


 


37
CCCTGGCCTGGAAGCACCA
TGGTGCTTCCAGGCCAGGG


 


38
CCTGGCCTGGAAGCACCAG
CTGGTGCTTCCAGGCCAGG


 


39
CTGGCCTGGAAGCACCAGG
CCTGGTGCTTCCAGGCCAG


 


40
TGGCCTGGAAGCACCAGGA
TCCTGGTGCTTCCAGGCCA


 


41
GGCCTGGAAGCACCAGGAA
TTCCTGGTGCTTCCAGGCC


 


42
GCCTGGAAGCACCAGGAAC
GTTCCTGGTGCTTCCAGGC


 


43
CCTGGAAGCACCAGGAACC
GGTTCCTGGTGCTTCCAGG


 


44
CTGGAAGCACCAGGAACCC
GGGTTCCTGGTGCTTCCAG


 


45
TGGAAGCACCAGGAACCCT
AGGGTTCCTGGTGCTTCCA


 


46
GGAAGCACCAGGAACCCTG
CAGGGTTCCTGGTGCTTCC


 


47
GAAGCACCAGGAACCCTGG
CCAGGGTTCCTGGTGCTTC


 


48
AAGCACCAGGAACCCTGGG
CCCAGGGTTCCTGGTGCTT


 


49
AGCACCAGGAACCCTGGGG
CCCCAGGGTTCCTGGTGCT


 


50
GCACCAGGAACCCTGGGGA
TCCCCAGGGTTCCTGGTGC


 


51
CACCAGGAACCCTGGGGAT
ATCCCCAGGGTTCCTGGTG


 


52
ACCAGGAACCCTGGGGATG
CATCCCCAGGGTTCCTGGT


 


53
CCAGGAACCCTGGGGATGG
CCATCCCCAGGGTTCCTGG


 


54
CAGGAACCCTGGGGATGGG
CCCATCCCCAGGGTTCCTG


 


55
AGGAACCCTGGGGATGGGG
CCCCATCCCCAGGGTTCCT


 


56
GGAACCCTGGGGATGGGGC
GCCCCATCCCCAGGGTTCC


 


57
GAACCCTGGGGATGGGGCA
TGCCCCATCCCCAGGGTTC


 


58
AACCCTGGGGATGGGGCAG
CTGCCCCATCCCCAGGGTT


 


59
ACCCTGGGGATGGGGCAGA
TCTGCCCCATCCCCAGGGT


 


60
CCCTGGGGATGGGGCAGAC
GTCTGCCCCATCCCCAGGG


 


61
CCTGGGGATGGGGCAGACC
GGTCTGCCCCATCCCCAGG


 


62
CTGGGGATGGGGCAGACCC
GGGTCTGCCCCATCCCCAG


 


63
TGGGGATGGGGCAGACCCT
AGGGTCTGCCCCATCCCCA


 


64
GGGGATGGGGCAGACCCTC
GAGGGTCTGCCCCATCCCC


 


65
GGGATGGGGCAGACCCTCA
TGAGGGTCTGCCCCATCCC


 


66
GGATGGGGCAGACCCTCAC
GTGAGGGTCTGCCCCATCC


 


67
GATGGGGCAGACCCTCACA
TGTGAGGGTCTGCCCCATC


 


68
ATGGGGCAGACCCTCACAG
CTGTGAGGGTCTGCCCCAT


 


69
TGGGGCAGACCCTCACAGC
GCTGTGAGGGTCTGCCCCA


 


70
GGGGCAGACCCTCACAGCC
GGCTGTGAGGGTCTGCCCC


 


71
GGGCAGACCCTCACAGCCC
GGGCTGTGAGGGTCTGCCC


 


72
GGCAGACCCTCACAGCCCG
CGGGCTGTGAGGGTCTGCC


 


73
GCAGACCCTCACAGCCCGG
CCGGGCTGTGAGGGTCTGC


 


74
CAGACCCTCACAGCCCGGG
CCCGGGCTGTGAGGGTCTG


 


75
AGACCCTCACAGCCCGGGG
CCCCGGGCTGTGAGGGTCT


 


76
GACCCTCACAGCCCGGGGT
ACCCCGGGCTGTGAGGGTC


 


77
ACCCTCACAGCCCGGGGTC
GACCCCGGGCTGTGAGGGT


 


78
CCCTCACAGCCCGGGGTCT
AGACCCCGGGCTGTGAGGG


 


79
CCTCACAGCCCGGGGTCTG
CAGACCCCGGGCTGTGAGG


 


80
CTCACAGCCCGGGGTCTGG
CCAGACCCCGGGCTGTGAG


 


81
TCACAGCCCGGGGTCTGGA
TCCAGACCCCGGGCTGTGA


 


82
CACAGCCCGGGGTCTGGAG
CTCCAGACCCCGGGCTGTG


 


83
ACAGCCCGGGGTCTGGAGC
GCTCCAGACCCCGGGCTGT


 


84
CAGCCCGGGGTCTGGAGCC
GGCTCCAGACCCCGGGCTG


 


85
AGCCCGGGGTCTGGAGCCG
CGGCTCCAGACCCCGGGCT


 


86
GCCCGGGGTCTGGAGCCGG
CCGGCTCCAGACCCCGGGC


 


87
CCCGGGGTCTGGAGCCGGT
ACCGGCTCCAGACCCCGGG


 


88
CCGGGGTCTGGAGCCGGTG
CACCGGCTCCAGACCCCGG


 


89
CGGGGTCTGGAGCCGGTGT
ACACCGGCTCCAGACCCCG


 


90
GGGGTCTGGAGCCGGTGTC
GACACCGGCTCCAGACCCC


 


91
GGGTCTGGAGCCGGTGTCG
CGACACCGGCTCCAGACCC


 


92
GGTCTGGAGCCGGTGTCGG
CCGACACCGGCTCCAGACC


 


93
GTCTGGAGCCGGTGTCGGA
TCCGACACCGGCTCCAGAC


 


94
TCTGGAGCCGGTGTCGGAG
CTCCGACACCGGCTCCAGA


 


95
CTGGAGCCGGTGTCGGAGC
GCTCCGACACCGGCTCCAG


 


96
TGGAGCCGGTGTCGGAGCT
AGCTCCGACACCGGCTCCA


 


97
GGAGCCGGTGTCGGAGCTC
GAGCTCCGACACCGGCTCC


 


98
GAGCCGGTGTCGGAGCTCA
TGAGCTCCGACACCGGCTC


 


99
AGCCGGTGTCGGAGCTCAT
ATGAGCTCCGACACCGGCT


 


100
GCCGGTGTCGGAGCTCATC
GATGAGCTCCGACACCGGC


 


101
CCGGTGTCGGAGCTCATCT
AGATGAGCTCCGACACCGG


 


102
CGGTGTCGGAGCTCATCTG
CAGATGAGCTCCGACACCG


 


103
GGTGTCGGAGCTCATCTGG
CCAGATGAGCTCCGACACC


 


104
GTGTCGGAGCTCATCTGGG
CCCAGATGAGCTCCGACAC


 


105
TGTCGGAGCTCATCTGGGC
GCCCAGATGAGCTCCGACA


 


106
GTCGGAGCTCATCTGGGCC
GGCCCAGATGAGCTCCGAC


 


107
TCGGAGCTCATCTGGGCCC
GGGCCCAGATGAGCTCCGA


 


108
CGGAGCTCATCTGGGCCCA
TGGGCCCAGATGAGCTCCG


 


109
GGAGCTCATCTGGGCCCAT
ATGGGCCCAGATGAGCTCC


 


110
GAGCTCATCTGGGCCCATG
CATGGGCCCAGATGAGCTC


 


111
AGCTCATCTGGGCCCATGA
TCATGGGCCCAGATGAGCT


 


112
GCTCATCTGGGCCCATGAC
GTCATGGGCCCAGATGAGC


 


113
CTCATCTGGGCCCATGACC
GGTCATGGGCCCAGATGAG


 


114
TCATCTGGGCCCATGACCT
AGGTCATGGGCCCAGATGA


 


115
CATCTGGGCCCATGACCTC
GAGGTCATGGGCCCAGATG


 


116
ATCTGGGCCCATGACCTCT
AGAGGTCATGGGCCCAGAT


 


117
TCTGGGCCCATGACCTCTC
GAGAGGTCATGGGCCCAGA


 


118
CTGGGCCCATGACCTCTCC
GGAGAGGTCATGGGCCCAG


 


119
TGGGCCCATGACCTCTCCA
TGGAGAGGTCATGGGCCCA


 


120
GGGCCCATGACCTCTCCAG
CTGGAGAGGTCATGGGCCC


 


121
GGCCCATGACCTCTCCAGA
TCTGGAGAGGTCATGGGCC


 


122
GCCCATGACCTCTCCAGAC
GTCTGGAGAGGTCATGGGC


 


123
CCCATGACCTCTCCAGACA
TGTCTGGAGAGGTCATGGG


 


124
CCATGACCTCTCCAGACAT
ATGTCTGGAGAGGTCATGG


 


125
CATGACCTCTCCAGACATT
AATGTCTGGAGAGGTCATG


 


126
ATGACCTCTCCAGACATTT
AAATGTCTGGAGAGGTCAT


 


127
TGACCTCTCCAGACATTTG
CAAATGTCTGGAGAGGTCA


 


128
GACCTCTCCAGACATTTGG
CCAAATGTCTGGAGAGGTC


 


129
ACCTCTCCAGACATTTGGC
GCCAAATGTCTGGAGAGGT


 


130
CCTCTCCAGACATTTGGCA
TGCCAAATGTCTGGAGAGG


 


131
CTCTCCAGACATTTGGCAA
TTGCCAAATGTCTGGAGAG


 


132
TCTCCAGACATTTGGCAAA
TTTGCCAAATGTCTGGAGA


 


133
CTCCAGACATTTGGCAAAA
TTTTGCCAAATGTCTGGAG


 


134
TCCAGACATTTGGCAAAAT
ATTTTGCCAAATGTCTGGA


 


135
CCAGACATTTGGCAAAATC
GATTTTGCCAAATGTCTGG


 


136
CAGACATTTGGCAAAATCA
TGATTTTGCCAAATGTCTG


 


137
AGACATTTGGCAAAATCAA
TTGATTTTGCCAAATGTCT


 


138
GACATTTGGCAAAATCAAG
CTTGATTTTGCCAAATGTC


 


139
ACATTTGGCAAAATCAAGG
CCTTGATTTTGCCAAATGT


 


140
CATTTGGCAAAATCAAGGC
GCCTTGATTTTGCCAAATG


 


141
ATTTGGCAAAATCAAGGCC
GGCCTTGATTTTGCCAAAT


 


142
TTTGGCAAAATCAAGGCCC
GGGCCTTGATTTTGCCAAA


 


143
TTGGCAAAATCAAGGCCCT
AGGGCCTTGATTTTGCCAA


 


144
TGGCAAAATCAAGGCCCTT
AAGGGCCTTGATTTTGCCA


 


145
GGCAAAATCAAGGCCCTTA
TAAGGGCCTTGATTTTGCC


 


146
GCAAAATCAAGGCCCTTAG
CTAAGGGCCTTGATTTTGC


 


147
CAAAATCAAGGCCCTTAGA
TCTAAGGGCCTTGATTTTG


 


148
AAAATCAAGGCCCTTAGAC
GTCTAAGGGCCTTGATTTT


 


149
AAATCAAGGCCCTTAGACC
GGTCTAAGGGCCTTGATTT


 


150
AATCAAGGCCCTTAGACCA
TGGTCTAAGGGCCTTGATT


 


151
ATCAAGGCCCTTAGACCAG
CTGGTCTAAGGGCCTTGAT


 


152
TCAAGGCCCTTAGACCAGG
CCTGGTCTAAGGGCCTTGA


 


153
CAAGGCCCTTAGACCAGGG
CCCTGGTCTAAGGGCCTTG


 


154
AAGGCCCTTAGACCAGGGA
TCCCTGGTCTAAGGGCCTT


 


155
AGGCCCTTAGACCAGGGAC
GTCCCTGGTCTAAGGGCCT


 


156
GGCCCTTAGACCAGGGACA
TGTCCCTGGTCTAAGGGCC


 


157
GCCCTTAGACCAGGGACAG
CTGTCCCTGGTCTAAGGGC


 


158
CCCTTAGACCAGGGACAGA
TCTGTCCCTGGTCTAAGGG


 


159
CCTTAGACCAGGGACAGAC
GTCTGTCCCTGGTCTAAGG


 


160
CTTAGACCAGGGACAGACC
GGTCTGTCCCTGGTCTAAG


 


161
TTAGACCAGGGACAGACCC
GGGTCTGTCCCTGGTCTAA


 


162
TAGACCAGGGACAGACCCA
TGGGTCTGTCCCTGGTCTA


 


163
AGACCAGGGACAGACCCAA
TTGGGTCTGTCCCTGGTCT


 


164
GACCAGGGACAGACCCAAG
CTTGGGTCTGTCCCTGGTC


 


165
ACCAGGGACAGACCCAAGC
GCTTGGGTCTGTCCCTGGT


 


166
CCAGGGACAGACCCAAGCC
GGCTTGGGTCTGTCCCTGG


 


167
CAGGGACAGACCCAAGCCC
GGGCTTGGGTCTGTCCCTG


 


168
AGGGACAGACCCAAGCCCA
TGGGCTTGGGTCTGTCCCT


 


169
GGGACAGACCCAAGCCCAG
CTGGGCTTGGGTCTGTCCC


 


170
GGACAGACCCAAGCCCAGG
CCTGGGCTTGGGTCTGTCC


 


171
GACAGACCCAAGCCCAGGC
GCCTGGGCTTGGGTCTGTC


 


172
ACAGACCCAAGCCCAGGCC
GGCCTGGGCTTGGGTCTGT


 


173
CAGACCCAAGCCCAGGCCC
GGGCCTGGGCTTGGGTCTG


 


174
AGACCCAAGCCCAGGCCCT
AGGGCCTGGGCTTGGGTCT


 


175
GACCCAAGCCCAGGCCCTC
GAGGGCCTGGGCTTGGGTC


 


176
ACCCAAGCCCAGGCCCTCC
GGAGGGCCTGGGCTTGGGT


 


177
CCCAAGCCCAGGCCCTCCC
GGGAGGGCCTGGGCTTGGG


 


178
CCAAGCCCAGGCCCTCCCA
TGGGAGGGCCTGGGCTTGG


 


179
CAAGCCCAGGCCCTCCCAG
CTGGGAGGGCCTGGGCTTG


 


180
AAGCCCAGGCCCTCCCAGA
TCTGGGAGGGCCTGGGCTT


 


181
AGCCCAGGCCCTCCCAGAG
CTCTGGGAGGGCCTGGGCT


 


182
GCCCAGGCCCTCCCAGAGG
CCTCTGGGAGGGCCTGGGC


 


183
CCCAGGCCCTCCCAGAGGT
ACCTCTGGGAGGGCCTGGG


 


184
CCAGGCCCTCCCAGAGGTC
GACCTCTGGGAGGGCCTGG


 


185
CAGGCCCTCCCAGAGGTCC
GGACCTCTGGGAGGGCCTG


 


186
AGGCCCTCCCAGAGGTCCT
AGGACCTCTGGGAGGGCCT


 


187
GGCCCTCCCAGAGGTCCTA
TAGGACCTCTGGGAGGGCC


 


188
GCCCTCCCAGAGGTCCTAG
CTAGGACCTCTGGGAGGGC


 


189
CCCTCCCAGAGGTCCTAGG
CCTAGGACCTCTGGGAGGG


 


190
CCTCCCAGAGGTCCTAGGA
TCCTAGGACCTCTGGGAGG


 


191
CTCCCAGAGGTCCTAGGAC
GTCCTAGGACCTCTGGGAG


 


192
TCCCAGAGGTCCTAGGACG
CGTCCTAGGACCTCTGGGA


 


193
CCCAGAGGTCCTAGGACGC
GCGTCCTAGGACCTCTGGG


 


194
CCAGAGGTCCTAGGACGCA
TGCGTCCTAGGACCTCTGG


 


195
CAGAGGTCCTAGGACGCAA
TTGCGTCCTAGGACCTCTG


 


196
AGAGGTCCTAGGACGCAAC
GTTGCGTCCTAGGACCTCT


 


197
GAGGTCCTAGGACGCAACC
GGTTGCGTCCTAGGACCTC


 


198
AGGTCCTAGGACGCAACCC
GGGTTGCGTCCTAGGACCT


 


199
GGTCCTAGGACGCAACCCT
AGGGTTGCGTCCTAGGACC


 


200
GTCCTAGGACGCAACCCTT
AAGGGTTGCGTCCTAGGAC


 


201
TCCTAGGACGCAACCCTTT
AAAGGGTTGCGTCCTAGGA


 


202
CCTAGGACGCAACCCTTTG
CAAAGGGTTGCGTCCTAGG


 


203
CTAGGACGCAACCCTTTGT
ACAAAGGGTTGCGTCCTAG


 


204
TAGGACGCAACCCTTTGTG
CACAAAGGGTTGCGTCCTA


 


205
AGGACGCAACCCTTTGTGC
GCACAAAGGGTTGCGTCCT


 


206
GGACGCAACCCTTTGTGCC
GGCACAAAGGGTTGCGTCC


 


207
GACGCAACCCTTTGTGCCC
GGGCACAAAGGGTTGCGTC


 


208
ACGCAACCCTTTGTGCCCT
AGGGCACAAAGGGTTGCGT


 


209
CGCAACCCTTTGTGCCCTT
AAGGGCACAAAGGGTTGCG


 


210
GCAACCCTTTGTGCCCTTG
CAAGGGCACAAAGGGTTGC


 


211
CAACCCTTTGTGCCCTTGG
CCAAGGGCACAAAGGGTTG


 


212
AACCCTTTGTGCCCTTGGG
CCCAAGGGCACAAAGGGTT


 


213
ACCCTTTGTGCCCTTGGGC
GCCCAAGGGCACAAAGGGT


 


214
CCCTTTGTGCCCTTGGGCT
AGCCCAAGGGCACAAAGGG


 


215
CCTTTGTGCCCTTGGGCTC
GAGCCCAAGGGCACAAAGG


 


216
CTTTGTGCCCTTGGGCTCT
AGAGCCCAAGGGCACAAAG


 


217
TTTGTGCCCTTGGGCTCTG
CAGAGCCCAAGGGCACAAA


 


218
TTGTGCCCTTGGGCTCTGG
CCAGAGCCCAAGGGCACAA


 


219
TGTGCCCTTGGGCTCTGGA
TCCAGAGCCCAAGGGCACA


 


220
GTGCCCTTGGGCTCTGGAA
TTCCAGAGCCCAAGGGCAC


 


221
TGCCCTTGGGCTCTGGAAG
CTTCCAGAGCCCAAGGGCA


 


222
GCCCTTGGGCTCTGGAAGA
TCTTCCAGAGCCCAAGGGC


 


223
CCCTTGGGCTCTGGAAGAG
CTCTTCCAGAGCCCAAGGG


 


224
CCTTGGGCTCTGGAAGAGG
CCTCTTCCAGAGCCCAAGG


 


225
CTTGGGCTCTGGAAGAGGT
ACCTCTTCCAGAGCCCAAG


 


226
TTGGGCTCTGGAAGAGGTT
AACCTCTTCCAGAGCCCAA


 


227
TGGGCTCTGGAAGAGGTTT
AAACCTCTTCCAGAGCCCA


 


228
GGGCTCTGGAAGAGGTTTG
CAAACCTCTTCCAGAGCCC


 


229
GGCTCTGGAAGAGGTTTGG
CCAAACCTCTTCCAGAGCC


 


230
GCTCTGGAAGAGGTTTGGG
CCCAAACCTCTTCCAGAGC


 


231
CTCTGGAAGAGGTTTGGGA
TCCCAAACCTCTTCCAGAG


 


232
TCTGGAAGAGGTTTGGGAA
TTCCCAAACCTCTTCCAGA


 


233
CTGGAAGAGGTTTGGGAAG
CTTCCCAAACCTCTTCCAG


 


234
TGGAAGAGGTTTGGGAAGG
CCTTCCCAAACCTCTTCCA


 


235
GGAAGAGGTTTGGGAAGGG
CCCTTCCCAAACCTCTTCC


 


236
GAAGAGGTTTGGGAAGGGT
ACCCTTCCCAAACCTCTTC


 


237
AAGAGGTTTGGGAAGGGTT
AACCCTTCCCAAACCTCTT


 


238
AGAGGTTTGGGAAGGGTTT
AAACCCTTCCCAAACCTCT


 


239
GAGGTTTGGGAAGGGTTTG
CAAACCCTTCCCAAACCTC


 


240
AGGTTTGGGAAGGGTTTGG
CCAAACCCTTCCCAAACCT


 


241
GGTTTGGGAAGGGTTTGGG
CCCAAACCCTTCCCAAACC


 


242
GTTTGGGAAGGGTTTGGGG
CCCCAAACCCTTCCCAAAC


 


243
TTTGGGAAGGGTTTGGGGT
ACCCCAAACCCTTCCCAAA


 


244
TTGGGAAGGGTTTGGGGTG
CACCCCAAACCCTTCCCAA


 


245
TGGGAAGGGTTTGGGGTGG
CCACCCCAAACCCTTCCCA


 


246
GGGAAGGGTTTGGGGTGGA
TCCACCCCAAACCCTTCCC


 


247
GGAAGGGTTTGGGGTGGAA
TTCCACCCCAAACCCTTCC


 


248
GAAGGGTTTGGGGTGGAAG
CTTCCACCCCAAACCCTTC


 


249
AAGGGTTTGGGGTGGAAGA
TCTTCCACCCCAAACCCTT


 


250
AGGGTTTGGGGTGGAAGAT
ATCTTCCACCCCAAACCCT


 


251
GGGTTTGGGGTGGAAGATG
CATCTTCCACCCCAAACCC


 


252
GGTTTGGGGTGGAAGATGG
CCATCTTCCACCCCAAACC


 


253
GTTTGGGGTGGAAGATGGC
GCCATCTTCCACCCCAAAC


 


254
TTTGGGGTGGAAGATGGCA
TGCCATCTTCCACCCCAAA


 


255
TTGGGGTGGAAGATGGCAA
TTGCCATCTTCCACCCCAA


 


256
TGGGGTGGAAGATGGCAAA
TTTGCCATCTTCCACCCCA


 


257
GGGGTGGAAGATGGCAAAG
CTTTGCCATCTTCCACCCC


 


258
GGGTGGAAGATGGCAAAGA
TCTTTGCCATCTTCCACCC


 


259
GGTGGAAGATGGCAAAGAG
CCTCTTTGCCATCTTCCACC


 


260
GTGGAAGATGGCAAAGAGC
GCTCTTTGCCATCTTCCAC


 


261
TGGAAGATGGCAAAGAGCA
TGCTCTTTGCCATCTTCCA


 


262
GGAAGATGGCAAAGAGCAG
CTGCTCTTTGCCATCTTCC


 


263
GAAGATGGCAAAGAGCAGC
GCTGCTCTTTGCCATCTTC


 


264
AAGATGGCAAAGAGCAGCT
AGCTGCTCTTTGCCATCTT


 


265
AGATGGCAAAGAGCAGCTT
AAGCTGCTCTTTGCCATCT


 


266
GATGGCAAAGAGCAGCTTG
CAAGCTGCTCTTTGCCATC


 


267
ATGGCAAAGAGCAGCTTGG
CCAAGCTGCTCTTTGCCAT


 


268
TGGCAAAGAGCAGCTTGGC
GCCAAGCTGCTCTTTGCCA


 


269
GGCAAAGAGCAGCTTGGCC
GGCCAAGCTGCTCTTTGCC


 


270
GCAAAGAGCAGCTTGGCCA
TGGCCAAGCTGCTCTTTGC


 


271
CAAAGAGCAGCTTGGCCAG
CTGGCCAAGCTGCTCTTTG


 


272
AAAGAGCAGCTTGGCCAGG
CCTGGCCAAGCTGCTCTTT


 


273
AAGAGCAGCTTGGCCAGGT
ACCTGGCCAAGCTGCTCTT


 


274
AGAGCAGCTTGGCCAGGTG
CACCTGGCCAAGCTGCTCT


 


275
GAGCAGCTTGGCCAGGTGA
TCACCTGGCCAAGCTGCTC


 


276
AGCAGCTTGGCCAGGTGAG
CTCACCTGGCCAAGCTGCT


 


277
GCAGCTTGGCCAGGTGAGG
CCTCACCTGGCCAAGCTGC


 


278
CAGCTTGGCCAGGTGAGGA
TCCTCACCTGGCCAAGCTG


 


279
AGCTTGGCCAGGTGAGGAT
ATCCTCACCTGGCCAAGCT


 


280
GCTTGGCCAGGTGAGGATG
CATCCTCACCTGGCCAAGC


 


281
CTTGGCCAGGTGAGGATGA
TCATCCTCACCTGGCCAAG


 


282
TTGGCCAGGTGAGGATGAG
CTCATCCTCACCTGGCCAA


 


283
TGGCCAGGTGAGGATGAGG
CCTCATCCTCACCTGGCCA


 


284
GGCCAGGTGAGGATGAGGC
GCCTCATCCTCACCTGGCC


 


285
GCCAGGTGAGGATGAGGCA
TGCCTCATCCTCACCTGGC


 


286
CCAGGTGAGGATGAGGCAG
CTGCCTCATCCTCACCTGG


 


287
CAGGTGAGGATGAGGCAGG
CCTGCCTCATCCTCACCTG


 


288
AGGTGAGGATGAGGCAGGG
CCCTGCCTCATCCTCACCT


 


289
GGTGAGGATGAGGCAGGGC
GCCCTGCCTCATCCTCACC


 


290
GTGAGGATGAGGCAGGGCA
TGCCCTGCCTCATCCTCAC


 


291
TGAGGATGAGGCAGGGCAG
CTGCCCTGCCTCATCCTCA


 


292
GAGGATGAGGCAGGGCAGA
TCTGCCCTGCCTCATCCTC


 


293
AGGATGAGGCAGGGCAGAC
GTCTGCCCTGCCTCATCCT


 


294
GGATGAGGCAGGGCAGACA
TGTCTGCCCTGCCTCATCC


 


295
GATGAGGCAGGGCAGACAC
GTGTCTGCCCTGCCTCATC


 


296
ATGAGGCAGGGCAGACACA
TGTGTCTGCCCTGCCTCAT


 


297
TGAGGCAGGGCAGACACAG
CTGTGTCTGCCCTGCCTCA


 


298
GAGGCAGGGCAGACACAGG
CCTGTGTCTGCCCTGCCTC


 


299
AGGCAGGGCAGACACAGGC
GCCTGTGTCTGCCCTGCCT


 


300
GGCAGGGCAGACACAGGCC
GGCCTGTGTCTGCCCTGCC


 


301
GCAGGGCAGACACAGGCCA
TGGCCTGTGTCTGCCCTGC


 


302
CAGGGCAGACACAGGCCAG
CTGGCCTGTGTCTGCCCTG


 


303
AGGGCAGACACAGGCCAGT
ACTGGCCTGTGTCTGCCCT


 


304
GGGCAGACACAGGCCAGTG
CACTGGCCTGTGTCTGCCC


 


305
GGCAGACAGAGGCCAGTGG
CCACTGGCCTGTGTCTGCC


 


306
GCAGACACAGGCCAGTGGG
CCCACTGGCCTGTGTCTGC


 


307
CAGACACAGGCCAGTGGGG
CCCCACTGGCCTGTGTCTG


 


308
AGACACAGGCCAGTGGGGC
GCCCCACTGGCCTGTGTCT


 


309
GACACAGGCCAGTGGGGCG
CGCCCCACTGGCCTGTGTC


 


310
ACACAGGCCAGTGGGGCGT
ACGCCCCACTGGCCTGTGT


 


311
CACAGGCCAGTGGGGCGTG
CACGCCCCACTGGCCTGTG


 


312
ACAGGCCAGTGGGGCGTGC
GCACGCCCCACTGGCCTGT


 


313
CAGGCCAGTGGGGCGTGCC
GGCACGCCCCACTGGCCTG


 


314
AGGCCAGTGGGGCGTGCCA
TGGCACGCCCCACTGGCCT


 


315
GGCCAGTGGGGCGTGCCAT
ATGGCACGCCCCACTGGCC


 


316
GCCAGTGGGGCGTGCCATG
CATGGCACGCCCCACTGGC


 


317
CCAGTGGGGCGTGCCATGT
ACATGGCACGCCCCACTGG


 


318
CAGTGGGGCGTGCCATGTG
CACATGGCACGCCCCACTG


 


319
AGTGGGGCGTGCCATGTGC
GCACATGGCACGCCCCACT


 


320
GTGGGGCGTGCCATGTGCC
GGCACATGGCACGCCCCAC


 


321
TGGGGCGTGCCATGTGCCA
TGGCACATGGCACGCCCCA


 


322
GGGGCGTGCCATGTGCCAC
GTGGCACATGGCACGCCCC


 


323
GGGCGTGCCATGTGCCACA
TGTGGCACATGGCACGCCC


 


324
GGCGTGCCATGTGCCACAG
CTGTGGCACATGGCACGCC


 


325
GCGTGCCATGTGCCACAGA
TCTGTGGCACATGGCACGC


 


326
CGTGCCATGTGCCACAGAT
ATCTGTGGCACATGGCACG


 


327
GTGCCATGTGCCACAGATG
CATCTGTGGCACATGGCAC


 


328
TGCCATGTGCCACAGATGG
CCATCTGTGGCACATGGCA


 


329
GCCATGTGCCACAGATGGA
TCCATCTGTGGCACATGGC


 


330
CCATGTGCCACAGATGGAG
CTCCATCTGTGGCACATGG


 


331
CATGTGCCACAGATGGAGA
TCTCCATCTGTGGCACATG


 


332
ATGTGCCACAGATGGAGAG
CTCTCCATCTGTGGCACAT


 


333
TGTGCCACAGATGGAGAGG
CCTCTCCATCTGTGGCACA


 


334
GTGCCACAGATGGAGAGGA
TCCTCTCCATCTGTGGCAC


 


335
TGCCACAGATGGAGAGGAC
GTCCTCTCCATCTGTGGCA


 


336
GCCACAGATGGAGAGGACC
GGTCCTCTCCATCTGTGGC


 


337
CCACAGATGGAGAGGACCA
TGGTCCTCTCCATCTGTGG


 


338
CACAGATGGAGAGGACCAG
CTGGTCCTCTCCATCTGTG


 


339
ACAGATGGAGAGGACCAGG
CCTGGTCCTCTCCATCTGT


 


340
CAGATGGAGAGGACCAGGA
TCCTGGTCCTCTCCATCTG


 


341
AGATGGAGAGGACCAGGAG
CTCCTGGTCCTCTCCATCT


 


342
GATGGAGAGGACCAGGAGC
GCTCCTGGTCCTCTCCATC


 


343
ATGGAGAGGACCAGGAGCC
GGCTCCTGGTCCTCTCCAT


 


344
TGGAGAGGACCAGGAGCCA
TGGCTCCTGGTCCTCTCCA


 


345
GGAGAGGACCAGGAGCCAG
CTGGCTCCTGGTCCTCTCC


 


346
GAGAGGACCAGGAGCCAGT
ACTGGCTCCTGGTCCTCTC


 


347
AGAGGACCAGGAGCCAGTG
CACTGGCTCCTGGTCCTCT


 


348
GAGGACCAGGAGCCAGTGG
CCACTGGCTCCTGGTCCTC


 


349
AGGACCAGGAGCCAGTGGC
GCCACTGGCTCCTGGTCCT


 


350
GGACCAGGAGCCAGTGGCC
GGCCACTGGCTCCTGGTCC


 


351
GACCAGGAGCCAGTGGCCC
GGGCCACTGGCTCCTGGTC


 


352
ACCAGGAGCCAGTGGCCCG
CGGGCCACTGGCTCCTGGT


 


353
CCAGGAGCCAGTGGCCCGG
CCGGGCCACTGGCTCCTGG


 


354
CAGGAGCCAGTGGCCCGGC
GCCGGGCCACTGGCTCCTG


 


355
AGGAGCCAGTGGCCCGGCA
TGCCGGGCCACTGGCTCCT


 


356
GGAGCCAGTGGCCCGGCAG
CTGCCGGGCCACTGGCTCC


 


357
GAGCCAGTGGCCCGGCAGG
CCTGCCGGGCCACTGGCTC


 


358
AGCCAGTGGCCCGGCAGGC
GCCTGCCGGGCCACTGGCT


 


359
GCCAGTGGCCCGGCAGGCA
TGCCTGCCGGGCCACTGGC


 


360
CCAGTGGCCCGGCAGGCAC
GTGCCTGCCGGGCCACTGG


 


361
CAGTGGCCCGGCAGGCACA
TGTGCCTGCCGGGCCACTG


 


362
AGTGGCCCGGCAGGCACAG
CTGTGCCTGCCGGGCCACT


 


363
GTGGCCCGGCAGGCACAGC
GCTGTGCCTGCCGGGCCAC


 


364
TGGCCCGGCAGGCACAGCC
GGCTGTGCCTGCCGGGCCA


 


365
GGCCCGGCAGGCACAGCCC
GGGCTGTGCCTGCCGGGCC


 


366
GCCCGGCAGGCACAGCCCG
CGGGCTGTGCCTGCCGGGC


 


367
CCCGGCAGGCACAGCCCGG
CCGGGCTGTGCCTGCCGGG


 


368
CCGGCAGGCACAGCCCGGT
ACCGGGCTGTGCCTGCCGG


 


369
CGGCAGGCACAGCCCGGTT
AACCGGGCTGTGCCTGCCG


 


370
GGCAGGCACAGCCCGGTTG
CAACCGGGCTGTGCCTGCC


 


371
GCAGGCACAGCCCGGTTGG
CCAACCGGGCTGTGCCTGC


 


372
CAGGCACAGCCCGGTTGGC
GCCAACCGGGCTGTGCCTG


 


373
AGGCACAGCCCGGTTGGCG
CGCCAACCGGGCTGTGCCT


 


374
GGCACAGCCCGGTTGGCGT
ACGCCAACCGGGCTGTGCC


 


375
GCACAGCCCGGTTGGCGTG
CACGCCAACCGGGCTGTGC


 


376
CACAGCCCGGTTGGCGTGG
CCACGCCAACCGGGCTGTG


 


377
ACAGCCCGGTTGGCGTGGG
CCCACGCCAACCGGGCTGT


 


378
CAGCCCGGTTGGCGTGGGC
GCCCACGCCAACCGGGCTG


 


379
AGCCCGGTTGGCGTGGGCC
GGCCCACGCCAACCGGGCT


 


380
GCCCGGTTGGCGTGGGCCA
TGGCCCACGCCAACCGGGC


 


381
CCCGGTTGGCGTGGGCCAG
CTGGCCCACGCCAACCGGG


 


382
CCGGTTGGCGTGGGCCAGA
TCTGGCCCACGCCAACCGG


 


383
CGGTTGGCGTGGGCCAGAG
CTCTGGCCCACGCCAACCG


 


384
GGTTGGCGTGGGCCAGAGC
GCTCTGGCCCACGCCAACC


 


385
GTTGGCGTGGGCCAGAGCG
CGCTCTGGCCCACGCCAAC


 


386
TTGGCGTGGGCCAGAGCGC
GCGCTCTGGCCCACGCCAA


 


387
TGGCGTGGGCCAGAGCGCC
GGCGCTCTGGCCCACGCCA


 


388
GGCGTGGGCCAGAGCGCCC
GGGCGCTCTGGCCCACGCC


 


389
GCGTGGGCCAGAGCGCCCA
TGGGCGCTCTGGCCCACGC


 


390
CGTGGGCCAGAGCGCCCAT
ATGGGCGCTCTGGCCCACG


 


391
GTGGGCCAGAGCGCCCATC
GATGGGCGCTCTGGCCCAC


 


392
TGGGCCAGAGCGCCCATCA
TGATGGGCGCTCTGGCCCA


 


393
GGGCCAGAGCGCCCATCAC
GTGATGGGCGCTCTGGCCC


 


394
GGCCAGAGCGCCCATCACT
AGTGATGGGCGCTCTGGCC


 


395
GCCAGAGCGCCCATCACTG
CAGTGATGGGCGCTCTGGC


 


396
CCAGAGCGCCCATCACTGA
TCAGTGATGGGCGCTCTGG


 


397
CAGAGCGCCCATCACTGAC
GTCAGTGATGGGCGCTCTG


 


398
AGAGCGCCCATCACTGACC
GGTCAGTGATGGGCGCTCT


 


399
GAGCGCCCATCACTGACCC
GGGTCAGTGATGGGCGCTC


 


400
AGCGCCCATCACTGACCCG
CGGGTCAGTGATGGGCGCT


 


401
GCGCCCATCACTGACCCGT
ACGGGTCAGTGATGGGCGC


 


402
CGCCCATCACTGACCCGTG
CACGGGTCAGTGATGGGCG


 


403
GCCCATCACTGACCCGTGA
TCACGGGTCAGTGATGGGC


 


404
CCCATCACTGACCCGTGAG
CTCACGGGTCAGTGATGGG


 


405
CCATCACTGACCCGTGAGA
TCTCACGGGTCAGTGATGG


 


406
CATCACTGACCCGTGAGAA
TTCTCACGGGTCAGTGATG


 


407
ATCACTGACCCGTGAGAAC
GTTCTCACGGGTCAGTGAT


 


408
TCACTGACCCGTGAGAACT
AGTTCTCACGGGTCAGTGA


 


409
CACTGACCCGTGAGAACTC
GAGTTCTCACGGGTCAGTG


 


410
ACTGACCCGTGAGAACTCG
CGAGTTCTCACGGGTCAGT


 


411
CTGACCCGTGAGAACTCGA
TCGAGTTCTCACGGGTCAG


 


412
TGACCCGTGAGAACTCGAC
GTCGAGTTCTCACGGGTCA


 


413
GACCCGTGAGAACTCGACT
AGTCGAGTTCTCACGGGTC


 


414
ACCCGTGAGAACTCGACTG
CAGTCGAGTTCTCACGGGT


 


415
CCCGTGAGAACTCGACTGC
GCAGTCGAGTTCTCACGGG


 


416
CCGTGAGAACTCGACTGCC
GGCAGTCGAGTTCTCACGG


 


417
CGTGAGAACTCGACTGCCC
GGGCAGTCGAGTTCTCACG


 


418
GTGAGAACTCGACTGCCCC
GGGGCAGTCGAGTTCTCAC


 


419
TGAGAACTCGACTGCCCCT
AGGGGCAGTCGAGTTCTCA


 


420
GAGAACTCGACTGCCCCTG
CAGGGGCAGTCGAGTTCTC


 


421
AGAACTCGACTGCCCCTGC
GCAGGGGCAGTCGAGTTCT


 


422
GAACTCGACTGCCCCTGCC
GGCAGGGGCAGTCGAGTTC


 


423
AACTCGACTGCCCCTGCCA
TGGCAGGGGCAGTCGAGTT


 


424
ACTCGACTGCCCCTGCCAG
CTGGCAGGGGCAGTCGAGT


 


425
CTCGACTGCCCCTGCCAGC
GCTGGCAGGGGCAGTCGAG


 


426
TCGACTGCCCCTGCCAGCT
AGCTGGCAGGGGCAGTCGA


 


427
CGACTGCCCCTGCCAGCTC
GAGCTGGCAGGGGCAGTCG


 


428
GACTGCCCCTGCCAGCTCT
AGAGCTGGCAGGGGCAGTC


 


429
ACTGCCCCTGCCAGCTCTG
CAGAGCTGGCAGGGGCAGT


 


430
CTGCCCCTGCCAGCTCTGG
CCAGAGCTGGCAGGGGCAG


 


431
TGCCCCTGCCAGCTCTGGC
GCCAGAGCTGGCAGGGGCA


 


432
GCCCCTGCCAGCTCTGGCA
TGCCAGAGCTGGCAGGGGC


 


433
CCCCTGCCAGCTCTGGCAC
GTGCCAGAGCTGGCAGGGG


 


434
CCCTGCCAGCTCTGGCACT
AGTGCCAGAGCTGGCAGGG


 


435
CCTGCCAGCTCTGGCACTG
CAGTGCCAGAGCTGGCAGG


 


436
CTGCCAGCTCTGGCACTGC
GCAGTGCCAGAGCTGGCAG


 


437
TGCCAGCTCTGGCACTGCC
GGCAGTGCCAGAGCTGGCA


 


438
GCCAGCTCTGGCACTGCCC
GGGCAGTGCCAGAGCTGGC


 


439
CCAGCTCTGGCACTGCCCC
GGGGCAGTGCCAGAGCTGG


 


440
CAGCTCTGGCACTGCCCCC
GGGGGCAGTGCCAGAGCTG


 


441
AGCTCTGGCACTGCCCCCT
AGGGGGCAGTGCCAGAGCT


 


442
GCTCTGGCACTGCCCCCTC
GAGGGGGCAGTGCCAGAGC


 


443
CTCTGGCACTGCCCCCTCC
GGAGGGGGCAGTGCCAGAG


 


444
TCTGGCACTGCCCCCTCCC
GGGAGGGGGCAGTGCCAGA


 


445
CTGGCACTGCCCCCTCCCA
TGGGAGGGGGCAGTGCCAG


 


446
TGGCACTGCCCCCTCCCAG
CTGGGAGGGGGCAGTGCCA


 


447
GGCACTGCCCCCTCCCAGC
GCTGGGAGGGGGCAGTGCC


 


448
GCACTGCCCCCTCCCAGCC
GGCTGGGAGGGGGCAGTGC


 


449
CACTGCCCCCTCCCAGCCG
CGGCTGGGAGGGGGCAGTG


 


450
ACTGCCCCCTCCCAGCCGC
GCGGCTGGGAGGGGGCAGT


 


451
CTGCCCCCTCCCAGCCGCC
GGCGGCTGGGAGGGGGCAG


 


452
TGCCCCCTCCCAGCCGCCC
GGGCGGCTGGGAGGGGGCA


 


453
GCCCCCTCCCAGCCGCCCC
GGGGCGGCTGGGAGGGGGC


 


454
CCCCCTCCCAGCCGCCCCG
CGGGGCGGCTGGGAGGGGG


 


455
CCCCTCCCAGCCGCCCCGC
GCGGGGCGGCTGGGAGGGG


 


456
CCCTCCCAGCCGCCCCGCC
GGCGGGGCGGCTGGGAGGG


 


457
CCTCCCAGCCGCCCCGCCC
GGGCGGGGCGGCTGGGAGG


 


458
CTCCCAGCCGCCCCGCCCT
AGGGCGGGGCGGCTGGGAG


 


459
TCCCAGCCGCCCCGCCCTA
TAGGGCGGGGCGGCTGGGA


 


460
CCCAGCCGCCCCGCCCTAG
CTAGGGCGGGGCGGCTGGG


 


461
CCAGCCGCCCCGCCCTAGC
GCTAGGGCGGGGCGGCTGG


 


462
CAGCCGCCCCGCCCTAGCA
TGCTAGGGCGGGGCGGCTG


 


463
AGCCGCCCCGCCCTAGCAC
GTGCTAGGGCGGGGCGGCT


 


464
GCCGCCCCGCCCTAGCACC
GGTGCTAGGGCGGGGCGGC


 


465
CCGCCCCGCCCTAGCACCC
GGGTGCTAGGGCGGGGCGG


 


466
CGCCCCGCCCTAGCACCCT
AGGGTGCTAGGGCGGGGCG


 


467
GCCCCGCCCTAGCACCCTG
CAGGGTGCTAGGGCGGGGC


 


468
CCCCGCCCTAGCACCCTGG
CCAGGGTGCTAGGGCGGGG


 


469
CCCGCCCTAGCACCCTGGG
CCCAGGGTGCTAGGGCGGG


 


470
CCGCCCTAGCACCCTGGGG
CCCCAGGGTGCTAGGGCGG


 


471
CGCCCTAGCACCCTGGGGG
CCCCCAGGGTGCTAGGGCG


 


472
GCCCTAGCACCCTGGGGGG
CCCCCCAGGGTGCTAGGGC


 


473
CCCTAGCACCCTGGGGGGC
GCCCCCCAGGGTGCTAGGG


 


474
CCTAGCACCCTGGGGGGCA
TGCCCCCCAGGGTGCTAGG


 


475
CTAGCACCCTGGGGGGCAC
GTGCCCCCCAGGGTGCTAG


 


476
TAGCACCCTGGGGGGCACC
GGTGCCCCCCAGGGTGCTA


 


477
AGCACCCTGGGGGGCACCC
GGGTGCCCCCCAGGGTGCT


 


478
GCACCCTGGGGGGCACCCC
GGGGTGCCCCCCAGGGTGC


 


479
CACCCTGGGGGGCACCCCG
CGGGGTGCCCCCCAGGGTG


 


480
ACCCTGGGGGGCACCCCGC
GCGGGGTGCCCCCCAGGGT


 


481
CCCTGGGGGGCACCCCGCC
GGCGGGGTGCCCCCCAGGG


 


482
CCTGGGGGGCACCCCGCCC
GGGCGGGGTGCCCCCCAGG


 


483
CTGGGGGGCACCCCGCCCA
TGGGCGGGGTGCCCCCCAG


 


484
TGGGGGGCACCCCGCCCAA
TTGGGCGGGGTGCCCCCCA


 


485
GGGGGGCACCCCGCCCAAC
GTTGGGCGGGGTGCCCCCC


 


486
GGGGGCACCCCGCCCAACC
GGTTGGGCGGGGTGCCCCC


 


487
GGGGCACCCCGCCCAACCG
CGGTTGGGCGGGGTGCCCC


 


488
GGGCACCCCGCCCAACCGT
ACGGTTGGGCGGGGTGCCC


 


489
GGCACCCCGCCCAACCGTG
CACGGTTGGGCGGGGTGCC


 


490
GCACCCCGCCCAACCGTGG
CCACGGTTGGGCGGGGTGC


 


491
CACCCCGCCCAACCGTGGC
GCCACGGTTGGGCGGGGTG


 


492
ACCCCGCCCAACCGTGGCC
GGCCACGGTTGGGCGGGGT


 


493
CCCCGCCCAACCGTGGCCT
AGGCCACGGTTGGGCGGGG


 


494
CCCGCCCAACCGTGGCCTG
CAGGCCACGGTTGGGCGGG


 


495
CCGCCCAACCGTGGCCTGG
CCAGGCCACGGTTGGGCGG


 


496
CGCCCAACCGTGGCCTGGT
ACCAGGCCACGGTTGGGCG


 


497
GCCCAACCGTGGCCTGGTC
GACCAGGCCACGGTTGGGC


 


498
CCCAACCGTGGCCTGGTCC
GGACCAGGCCACGGTTGGG


 


499
CCAACCGTGGCCTGGTCCG
CGGACCAGGCCACGGTTGG


 


500
CAACCGTGGCCTGGTCCGG
CCGGACCAGGCCACGGTTG


 


501
AACCGTGGCCTGGTCCGGC
GCCGGACCAGGCCACGGTT


 


502
ACCGTGGCCTGGTCCGGCC
GGCCGGACCAGGCCACGGT


 


503
CCGTGGCCTGGTCCGGCCC
GGGCCGGACCAGGCCACGG


 


504
CGTGGCCTGGTCCGGCCCC
GGGGCCGGACCAGGCCACG


 


505
GTGGCCTGGTCCGGCCCCT
AGGGGCCGGACCAGGCCAC


 


506
TGGCCTGGTCCGGCCCCTC
GAGGGGCCGGACCAGGCCA


 


507
GGCCTGGTCCGGCCCCTCC
GGAGGGGCCGGACCAGGCC


 


508
GCCTGGTCCGGCCCCTCCC
GGGAGGGGCCGGACCAGGC


 


509
CCTGGTCCGGCCCCTCCCG
CGGGAGGGGCCGGACCAGG


 


510
CTGGTCCGGCCCCTCCCGC
GCGGGAGGGGCCGGACCAG


 


511
TGGTCCGGCCCCTCCCGCC
GGCGGGAGGGGCCGGACCA


 


512
GGTCCGGCCCCTCCCGCCC
GGGCGGGAGGGGCCGGACC


 


513
GTCCGGCCCCTCCCGCCCT
AGGGCGGGAGGGGCCGGAC


 


514
TCCGGCCCCTCCCGCCCTT
AAGGGCGGGAGGGGCCGGA


 


515
CCGGCCCCTCCCGCCCTTT
AAAGGGCGGGAGGGGCCGG


 


516
CGGCCCCTCCCGCCCTTTG
CAAAGGGCGGGAGGGGCCG


 


517
GGCCCCTCCCGCCCTTTGC
GCAAAGGGCGGGAGGGGCC


 


518
GCCCCTCCCGCCCTTTGCT
AGCAAAGGGCGGGAGGGGC


 


519
CCCCTCCCGCCCTTTGCTC
GAGCAAAGGGCGGGAGGGG


 


520
CCCTCCCGCCCTTTGCTCC
GGAGCAAAGGGCGGGAGGG


 


521
CCTCCCGCCCTTTGCTCCA
TGGAGCAAAGGGCGGGAGG


 


522
CTCCCGCCCTTTGCTCCAG
CTGGAGCAAAGGGCGGGAG


 


523
TCCCGCCCTTTGCTCCAGT
ACTGGAGCAAAGGGCGGGA


 


524
CCCGCCCTTTGCTCCAGTT
AACTGGAGCAAAGGGCGGG


 


525
CCGCCCTTTGCTCCAGTTC
GAACTGGAGCAAAGGGCGG


 


526
CGCCCTTTGCTCCAGTTCC
GGAACTGGAGCAAAGGGCG


 


527
GCCCTTTGCTCCAGTTCCC
GGGAACTGGAGCAAAGGGC


 


528
CCCTTTGCTCCAGTTCCCG
CGGGAACTGGAGCAAAGGG


 


529
CCTTTGCTCCAGTTCCCGG
CCGGGAACTGGAGCAAAGG


 


530
CTTTGCTCCAGTTCCCGGG
CCCGGGAACTGGAGCAAAG


 


531
TTTGCTCCAGTTCCCGGGC
GCCCGGGAACTGGAGCAAA


 


532
TTGCTCCAGTTCCCGGGCT
AGCCCGGGAACTGGAGCAA


 


533
TGCTCCAGTTCCCGGGCTT
AAGCCCGGGAACTGGAGCA


 


534
GCTCCAGTTCCCGGGCTTG
CAAGCCCGGGAACTGGAGC


 


535
CTCCAGTTCCCGGGCTTGG
CCAAGCCCGGGAACTGGAG


 


536
TCCAGTTCCCGGGCTTGGC
GCCAAGCCCGGGAACTGGA


 


537
CCAGTTCCCGGGCTTGGCA
TGCCAAGCCCGGGAACTGG


 


538
CAGTTCCCGGGCTTGGCAC
GTGCCAAGCCCGGGAACTG


 


539
AGTTCCCGGGCTTGGCACC
GGTGCCAAGCCCGGGAACT


 


540
GTTCCCGGGCTTGGCACCT
AGGTGCCAAGCCCGGGAAC


 


541
TTCCCGGGCTTGGCACCTA
TAGGTGCCAAGCCCGGGAA


 


542
TCCCGGGCTTGGCACCTAT
ATAGGTGCCAAGCCCGGGA


 


543
CCCGGGCTTGGCACCTATA
TATAGGTGCCAAGCCCGGG


 


544
CCGGGCTTGGCACCTATAG
CTATAGGTGCCAAGCCCGG


 


545
CGGGCTTGGCACCTATAGT
ACTATAGGTGCCAAGCCCG


 


546
GGGCTTGGCACCTATAGTG
CACTATAGGTGCCAAGCCC


 


547
GGCTTGGCACCTATAGTGG
CCACTATAGGTGCCAAGCC


 


548
GCTTGGCACCTATAGTGGG
CCCACTATAGGTGCCAAGC


 


549
CTTGGCACCTATAGTGGGG
CCCCACTATAGGTGCCAAG


 


550
TTGGCACCTATAGTGGGGG
CCCCCACTATAGGTGCCAA


 


551
TGGCACCTATAGTGGGGGT
ACCCCCACTATAGGTGCCA


 


552
GGCACCTATAGTGGGGGTG
CACCCCCACTATAGGTGCC


 


553
GCACCTATAGTGGGGGTGC
GCACCCCCACTATAGGTGC


 


554
CACCTATAGTGGGGGTGCC
GGCACCCCCACTATAGGTG


 


555
ACCTATAGTGGGGGTGCCG
CGGCACCCCCACTATAGGT


 


556
CCTATAGTGGGGGTGCCGC
GCGGCACCCCCACTATAGG


 


557
CTATAGTGGGGGTGCCGCC
GGCGGCACCCCCACTATAG


 


558
TATAGTGGGGGTGCCGCCC
GGGCGGCACCCCCACTATA


 


559
ATAGTGGGGGTGCCGCCCG
CGGGCGGCACCCCCACTAT


 


560
TAGTGGGGGTGCCGCCCGC
GCGGGCGGCACCCCCACTA


 


561
AGTGGGGGTGCCGCCCGCC
GGCGGGCGGCACCCCCACT


 


562
GTGGGGGTGCCGCCCGCCT
AGGCGGGCGGCACCCCCAC


 


563
TGGGGGTGCCGCCCGCCTG
CAGGCGGGCGGCACCCCCA


 


564
GGGGGTGCCGCCCGCCTGC
GCAGGCGGGCGGCACCCCC


 


565
GGGGTGCCGCCCGCCTGCC
GGCAGGCGGGCGGCACCCC


 


566
GGGTGCCGCCCGCCTGCCA
TGGCAGGCGGGCGGCACCC


 


567
GGTGCCGCCCGCCTGCCAG
CTGGCAGGCGGGCGGCACC


 


568
GTGCCGCCCGCCTGCCAGG
CCTGGCAGGCGGGCGGCAC


 


569
TGCCGCCCGCCTGCCAGGC
GCCTGGCAGGCGGGCGGCA


 


570
GCCGCCCGCCTGCCAGGCT
AGCCTGGCAGGCGGGCGGC


 


571
CCGCCCGCCTGCCAGGCTC
GAGCCTGGCAGGCGGGCGG


 


572
CGCCCGCCTGCCAGGCTCC
GGAGCCTGGCAGGCGGGCG


 


573
GCCCGCCTGCCAGGCTCCG
CGGAGCCTGGCAGGCGGGC


 


574
CCCGCCTGCCAGGCTCCGG
CCGGAGCCTGGCAGGCGGG


 


575
CCGCCTGCCAGGCTCCGGG
CCCGGAGCCTGGCAGGCGG


 


576
CGCCTGCCAGGCTCCGGGG
CCCCGGAGCCTGGCAGGCG


 


577
GCCTGCCAGGCTCCGGGGC
GCCCCGGAGCCTGGCAGGC


 


578
CCTGCCAGGCTCCGGGGCC
GGCCCCGGAGCCTGGCAGG


 


579
CTGCCAGGCTCCGGGGCCG
CGGCCCCGGAGCCTGGCAG


 


580
TGCCAGGCTCCGGGGCCGG
CCGGCCCCGGAGCCTGGCA


 


581
GCCAGGCTCCGGGGCCGGG
CCCGGCCCCGGAGCCTGGC


 


582
CCAGGCTCCGGGGCCGGGC
GCCCGGCCCCGGAGCCTGG


 


583
CAGGCTCCGGGGCCGGGCC
GGCCCGGCCCCGGAGCCTG


 


584
AGGCTCCGGGGCCGGGCCC
GGGCCCGGCCCCGGAGCCT


 


585
GGCTCCGGGGCCGGGCCCA
TGGGCCCGGCCCCGGAGCC


 


586
GCTCCGGGGCCGGGCCCAC
GTGGGCCCGGCCCCGGAGC


 


587
CTCCGGGGCCGGGCCCACG
CGTGGGCCCGGCCCCGGAG


 


588
TCCGGGGCCGGGCCCACGG
CCGTGGGCCCGGCCCCGGA


 


589
CCGGGGCCGGGCCCACGGG
CCCGTGGGCCCGGCCCCGG


 


590
CGGGGCCGGGCCCACGGGA
TCCCGTGGGCCCGGCCCCG


 


591
GGGGCCGGGCCCACGGGAG
CTCCCGTGGGCCCGGCCCC


 


592
GGGCCGGGCCCACGGGAGG
CCTCCCGTGGGCCCGGCCC


 


593
GGCCGGGCCCACGGGAGGG
CCCTCCCGTGGGCCCGGCC


 


594
GCCGGGCCCACGGGAGGGT
ACCCTCCCGTGGGCCCGGC


 


595
CCGGGCCCACGGGAGGGTG
CACCCTCCCGTGGGCCCGG


 


596
CGGGCCCACGGGAGGGTGG
CCACCCTCCCGTGGGCCCG


 


597
GGGCCCACGGGAGGGTGGG
CCCACCCTCCCGTGGGCCC


 


598
GGCCCACGGGAGGGTGGGG
CCCCACCCTCCCGTGGGCC


 


599
GCCCACGGGAGGGTGGGGC
GCCCCACCCTCCCGTGGGC


 


600
CCCACGGGAGGGTGGGGCG
CGCCCCACCCTCCCGTGGG


 


601
CCACGGGAGGGTGGGGCGG
CCGCCCCACCCTCCCGTGG


 


602
CACGGGAGGGTGGGGCGGC
GCCGCCCCACCCTCCCGTG


 


603
ACGGGAGGGTGGGGCGGCT
AGCCGCCCCACCCTCCCGT


 


604
CGGGAGGGTGGGGCGGCTG
CAGCCGCCCCACCCTCCCG


 


605
GGGAGGGTGGGGCGGCTGG
CCAGCCGCCCCACCCTCCC


 


606
GGAGGGTGGGGCGGCTGGG
CCCAGCCGCCCCACCCTCC


 


607
GAGGGTGGGGCGGCTGGGA
TCCCAGCCGCCCCACCCTC


 


608
AGGGTGGGGCGGCTGGGAA
TTCCCAGCCGCCCCACCCT


 


609
GGGTGGGGCGGCTGGGAAG
CTTCCCAGCCGCCCCACCC


 


610
GGTGGGGCGGCTGGGAAGC
GCTTCCCAGCCGCCCCACC


 


611
GTGGGGCGGCTGGGAAGCT
AGCTTCCCAGCCGCCCCAC


 


612
TGGGGCGGCTGGGAAGCTG
CAGCTTCCCAGCCGCCCCA


 


613
GGGGCGGCTGGGAAGCTGG
CCAGCTTCCCAGCCGCCCC


 


614
GGGCGGCTGGGAAGCTGGC
GCCAGCTTCCCAGCCGCCC


 


615
GGCGGCTGGGAAGCTGGCA
TGCCAGCTTCCCAGCCGCC


 


616
GCGGCTGGGAAGCTGGCAC
GTGCCAGCTTCCCAGCCGC


 


617
CGGCTGGGAAGCTGGCACG
CGTGCCAGCTTCCCAGCCG


 


618
GGCTGGGAAGCTGGCACGC
GCGTGCCAGCTTCCCAGCC


 


619
GCTGGGAAGCTGGCACGCT
AGCGTGCCAGCTTCCCAGC


 


620
CTGGGAAGCTGGCACGCTG
CAGCGTGCCAGCTTCCCAG


 


621
TGGGAAGCTGGCACGCTGC
GCAGCGTGCCAGCTTCCCA


 


622
GGGAAGCTGGCACGCTGCC
GGCAGCGTGCCAGCTTCCC


 


623
GGAAGCTGGCACGCTGCCC
GGGCAGCGTGCCAGCTTCC


 


624
GAAGCTGGCACGCTGCCCC
GGGGCAGCGTGCCAGCTTC


 


625
AAGCTGGCACGCTGCCCCG
CGGGGCAGCGTGCCAGCTT


 


626
AGCTGGCACGCTGCCCCGG
CCGGGGCAGCGTGCCAGCT


 


627
GCTGGCACGCTGCCCCGGG
CCCGGGGCAGCGTGCCAGC


 


628
CTGGCACGCTGCCCCGGGG
CCCCGGGGCAGCGTGCCAG


 


629
TGGCACGCTGCCCCGGGGG
CCCCCGGGGCAGCGTGCCA


 


630
GGCACGCTGCCCCGGGGGA
TCCCCCGGGGCAGCGTGCC


 


631
GCACGCTGCCCCGGGGGAG
CTCCCCCGGGGCAGCGTGC


 


632
CACGCTGCCCCGGGGGAGC
GCTCCCCCGGGGCAGCGTG


 


633
ACGCTGCCCCGGGGGAGCC
GGCTCCCCCGGGGCAGCGT


 


634
CGCTGCCCCGGGGGAGCCT
AGGCTCCCCCGGGGCAGCG


 


635
GCTGCCCCGGGGGAGCCTC
GAGGCTCCCCCGGGGCAGC


 


636
CTGCCCCGGGGGAGCCTCT
AGAGGCTCCCCCGGGGCAG


 


637
TGCCCCGGGGGAGCCTCTC
GAGAGGCTCCCCCGGGGCA


 


638
GCCCCGGGGGAGCCTCTCT
AGAGAGGCTCCCCCGGGGC


 


639
CCCCGGGGGAGCCTCTCTC
GAGAGAGGCTCCCCCGGGG


 


640
CCCGGGGGAGCCTCTCTCG
CGAGAGAGGCTCCCCCGGG


 


641
CCGGGGGAGCCTCTCTCGG
CCGAGAGAGGCTCCCCCGG


 


642
CGGGGGAGCCTCTCTCGGC
GCCGAGAGAGGCTCCCCCG


 


643
GGGGGAGCCTCTCTCGGCA
TGCCGAGAGAGGCTCCCCC


 


644
GGGGAGCCTCTCTCGGCAG
CTGCCGAGAGAGGCTCCCC


 


645
GGGAGCCTCTCTCGGCAGG
CCTGCCGAGAGAGGCTCCC


 


646
GGAGCCTCTCTCGGCAGGC
GCCTGCCGAGAGAGGCTCC


 


647
GAGCCTCTCTCGGCAGGCG
CGCCTGCCGAGAGAGGCTC


 


648
AGCCTCTCTCGGCAGGCGC
GCGCCTGCCGAGAGAGGCT


 


649
GCCTCTCTCGGCAGGCGCC
GGCGCCTGCCGAGAGAGGC


 


650
CCTCTCTCGGCAGGCGCCC
GGGCGCCTGCCGAGAGAGG


 


651
CTCTCTCGGCAGGCGCCCG
CGGGCGCCTGCCGAGAGAG


 


652
TCTCTCGGCAGGCGCCCGG
CCGGGCGCCTGCCGAGAGA


 


653
CTCTCGGCAGGCGCCCGGG
CCCGGGCGCCTGCCGAGAG


 


654
TCTCGGCAGGCGCCCGGGT
ACCCGGGCGCCTGCCGAGA


 


655
CTCGGCAGGCGCCCGGGTG
CACCCGGGCGCCTGCCGAG


 


656
TCGGCAGGCGCCCGGGTGC
GCACCCGGGCGCCTGCCGA


 


657
CGGCAGGCGCCCGGGTGCC
GGCACCCGGGCGCCTGCCG


 


658
GGCAGGCGCCCGGGTGCCG
CGGCACCCGGGCGCCTGCC


 


659
GCAGGCGCCCGGGTGCCGC
GCGGCACCCGGGCGCCTGC


 


660
CAGGCGCCCGGGTGCCGCG
CGCGGCACCCGGGCGCCTG


 


661
AGGCGCCCGGGTGCCGCGG
CCGCGGCACCCGGGCGCCT


 


662
GGCGCCCGGGTGCCGCGGG
CCCGCGGCACCCGGGCGCC


 


663
GCGCCCGGGTGCCGCGGGG
CCCCGCGGCACCCGGGCGC


 


664
CGCCCGGGTGCCGCGGGGG
CCCCCGCGGCACCCGGGCG


 


665
GCCCGGGTGCCGCGGGGGG
CCCCCCGCGGCACCCGGGC


 


666
CCCGGGTGCCGCGGGGGGG
CCCCCCCGCGGCACCCGGG


 


667
CCGGGTGCCGCGGGGGGGA
TCCCCCCCGCGGCACCCGG


 


668
CGGGTGCCGCGGGGGGGAG
CTCCCCCCCGCGGCACCCG


 


669
GGGTGCCGCGGGGGGGAGG
CCTCCCCCCCGCGGCACCC


 


670
GGTGCCGCGGGGGGGAGGG
CCCTCCCCCCCGCGGCACC


 


671
GTGCCGCGGGGGGGAGGGG
CCCCTCCCCCCCGCGGCAC


 


672
TGCCGCGGGGGGGAGGGGG
CCCCCTCCCCCCCGCGGCA


 


673
GCCGCGGGGGGGAGGGGGA
TCCCCCTCCCCCCCGCGGC


 


674
CCGCGGGGGGGAGGGGGAA
TTCCCCCTCCCCCCCGCGG


 


675
CGCGGGGGGGAGGGGGAAC
GTTCCCCCTCCCCCCCGCG


 


676
GCGGGGGGGAGGGGGAACA
TGTTCCCCCTCCCCCCCGC


 


677
CGGGGGGGAGGGGGAACAA
TTGTTCCCCCTCCCCCCCG


 


678
GGGGGGGAGGGGGAACAAA
TTTGTTCCCCCTCCCCCCC


 


679
GGGGGGAGGGGGAACAAAG
CTTTGTTCCCCCTCCCCCC


 


680
GGGGGAGGGGGAACAAAGG
CCTTTGTTCCCCCTCCCCC


 


681
GGGGAGGGGGAACAAAGGG
CCCTTTGTTCCCCCTCCCC


 


682
GGGAGGGGGAACAAAGGGC
GCCCTTTGTTCCCCCTCCC


 


683
GGAGGGGGAACAAAGGGCT
AGCCCTTTGTTCCCCCTCC


 


684
GAGGGGGAACAAAGGGCTC
GAGCCCTTTGTTCCCCCTC


 


685
AGGGGGAACAAAGGGCTCA
TGAGCCCTTTGTTCCCCCT


 


686
GGGGGAACAAAGGGCTCAT
ATGAGCCCTTTGTTCCCCC


 


687
GGGGAACAAAGGGCTCATT
AATGAGCCCTTTGTTCCCC


 


688
GGGAACAAAGGGCTCATTC
GAATGAGCCCTTTGTTCCC


 


689
GGAACAAAGGGCTCATTCT
AGAATGAGCCCTTTGTTCC


 


690
GAACAAAGGGCTCATTCTC
GAGAATGAGCCCTTTGTTC


 


691
AACAAAGGGCTCATTCTCC
GGAGAATGAGCCCTTTGTT


 


692
ACAAAGGGCTCATTCTCCC
GGGAGAATGAGCCCTTTGT


 


693
CAAAGGGCTCATTCTCCCC
GGGGAGAATGAGCCCTTTG


 


694
AAAGGGCTCATTCTCCCCG
CGGGGAGAATGAGCCCTTT


 


695
AAGGGCTCATTCTCCCCGT
ACGGGGAGAATGAGCCCTT


 


696
AGGGCTCATTCTCCCCGTG
CACGGGGAGAATGAGCCCT


 


697
GGGCTCATTCTCCCCGTGC
GCACGGGGAGAATGAGCCC


 


698
GGCTCATTCTCCCCGTGCG
CGCACGGGGAGAATGAGCC


 


699
GCTCATTCTCCCCGTGCGC
GCGCACGGGGAGAATGAGC


 


700
CTCATTCTCCCCGTGCGCA
TGCGCACGGGGAGAATGAG


 


701
TCATTCTCCCCGTGCGCAG
CTGCGCACGGGGAGAATGA


 


702
CATTCTCCCCGTGCGCAGC
GCTGCGCACGGGGAGAATG


 


703
ATTCTCCCCGTGCGCAGCC
GGCTGCGCACGGGGAGAAT


 


704
TTCTCCCCGTGCGCAGCCG
CGGCTGCGCACGGGGAGAA


 


705
TCTCCCCGTGCGCAGCCGG
CCGGCTGCGCACGGGGAGA


 


706
CTCCCCGTGCGCAGCCGGT
ACCGGCTGCGCACGGGGAG


 


707
TCCCCGTGCGCAGCCGGTG
CACCGGCTGCGCACGGGGA


 


708
CCCCGTGCGCAGCCGGTGG
CCACCGGCTGCGCACGGGG


 


709
CCCGTGCGCAGCCGGTGGC
GCCACCGGCTGCGCACGGG


 


710
CCGTGCGCAGCCGGTGGCA
TGCCACCGGCTGCGCACGG


 


711
CGTGCGCAGCCGGTGGCAT
ATGCCACCGGCTGCGCACG


 


712
GTGCGCAGCCGGTGGCATC
GATGCCACCGGCTGCGCAC


 


713
TGCGCAGCCGGTGGCATCG
CGATGCCACCGGCTGCGCA


 


714
GCGCAGCCGGTGGCATCGC
GCGATGCCACCGGCTGCGC


 


715
CGCAGCCGGTGGCATCGCC
GGCGATGCCACCGGCTGCG


 


716
GCAGCCGGTGGCATCGCCG
CGGCGATGCCACCGGCTGC


 


717
CAGCCGGTGGCATCGCCGG
CCGGCGATGCCACCGGCTG


 


718
AGCCGGTGGCATCGCCGGG
CCCGGCGATGCCACCGGCT


 


719
GCCGGTGGCATCGCCGGGG
CCCCGGCGATGCCACCGGC


 


720
CCGGTGGCATCGCCGGGGC
GCCCCGGCGATGCCACCGG


 


721
CGGTGGCATCGCCGGGGCG
CGCCCCGGCGATGCCACCG


 


722
GGTGGCATCGCCGGGGCGT
ACGCCCCGGCGATGCCACC


 


723
GTGGCATCGCCGGGGCGTT
AACGCCCCGGCGATGCCAC


 


724
TGGCATCGCCGGGGCGTTG
CAACGCCCCGGCGATGCCA


 


725
GGCATCGCCGGGGCGTTGG
CCAACGCCCCGGCGATGCC


 


726
GCATCGCCGGGGCGTTGGC
GCCAACGCCCCGGCGATGC


 


727
CATCGCCGGGGCGTTGGCG
CGCCAACGCCCCGGCGATG


 


728
ATCGCCGGGGCGTTGGCGG
CCGCCAACGCCCCGGCGAT


 


729
TCGCCGGGGCGTTGGCGGA
TCCGCCAACGCCCCGGCGA


 


730
CGCCGGGGCGTTGGCGGAA
TTCCGCCAACGCCCCGGCG


 


731
GCCGGGGCGTTGGCGGAAG
CTTCCGCCAACGCCCCGGC


 


732
CCGGGGCGTTGGCGGAAGC
GCTTCCGCCAACGCCCCGG


 


733
CGGGGCGTTGGCGGAAGCC
GGCTTCCGCCAACGCCCCG


 


734
GGGGCGTTGGCGGAAGCCC
GGGCTTCCGCCAACGCCCC


 


735
GGGCGTTGGCGGAAGCCCC
GGGGCTTCCGCCAACGCCC


 


736
GGCGTTGGCGGAAGCCCCC
GGGGGCTTCCGCCAACGCC


 


737
GCGTTGGCGGAAGCCCCCG
CGGGGGCTTCCGCCAACGC


 


738
CGTTGGCGGAAGCCCCCGG
CCGGGGGCTTCCGCCAACG


 


739
GTTGGCGGAAGCCCCCGGG
CCCGGGGGCTTCCGCCAAC


 


740
TTGGCGGAAGCCCCCGGGG
CCCCGGGGGCTTCCGCCAA


 


741
TGGCGGAAGCCCCCGGGGC
GCCCCGGGGGCTTCCGCCA


 


742
GGCGGAAGCCCCCGGGGCC
GGCCCCGGGGGCTTCCGCC


 


743
GCGGAAGCCCCCGGGGCCC
GGGCCCCGGGGGCTTCCGC


 


744
CGGAAGCCCCCGGGGCCCG
CGGGCCCCGGGGGCTTCCG


 


745
GGAAGCCCCCGGGGCCCGG
CCGGGCCCCGGGGGCTTCC


 


746
GAAGCCCCCGGGGCCCGGG
CCCGGGCCCCGGGGGCTTC


 


747
AAGCCCCCGGGGCCCGGGA
TCCCGGGCCCCGGGGGCTT


 


748
AGCCCCCGGGGCCCGGGAG
CTCCCGGGCCCCGGGGGCT


 


749
GCCCCCGGGGCCCGGGAGG
CCTCCCGGGCCCCGGGGGC


 


750
CCCCCGGGGCCCGGGAGGG
CCCTCCCGGGCCCCGGGGG


 


751
CCCCGGGGCCCGGGAGGGG
CCCCTCCCGGGCCCCGGGG


 


752
CCCGGGGCCCGGGAGGGGG
CCCCCTCCCGGGCCCCGGG


 


753
CCGGGGCCCGGGAGGGGGC
GCCCCCTCCCGGGCCCCGG


 


754
CGGGGCCCGGGAGGGGGCA
TGCCCCCTCCCGGGCCCCG


 


755
GGGGCCCGGGAGGGGGCAG
CTGCCCCCTCCCGGGCCCC


 


756
GGGCCCGGGAGGGGGCAGG
CCTGCCCCCTCCCGGGCCC


 


757
GGCCCGGGAGGGGGCAGGC
GCCTGCCCCCTCCCGGGCC


 


758
GCCCGGGAGGGGGCAGGCC
GGCCTGCCCCCTCCCGGGC


 


759
CCCGGGAGGGGGCAGGCCC
GGGCCTGCCCCCTCCCGGG


 


760
CCGGGAGGGGGCAGGCCCA
TGGGCCTGCCCCCTCCCGG


 


761
CGGGAGGGGGCAGGCCCAG
CTGGGCCTGCCCCCTCCCG


 


762
GGGAGGGGGCAGGCCCAGG
CCTGGGCCTGCCCCCTCCC


 


763
GGAGGGGGCAGGCCCAGGC
GCCTGGGCCTGCCCCCTCC


 


764
GAGGGGGCAGGCCCAGGCG
CGCCTGGGCCTGCCCCCTC


 


765
AGGGGGCAGGCCCAGGCGC
GCGCCTGGGCCTGCCCCCT


 


766
GGGGGCAGGCCCAGGCGCG
CGCGCCTGGGCCTGCCCCC


 


767
GGGGCAGGCCCAGGCGCGG
CCGCGCCTGGGCCTGCCCC


 


768
GGGCAGGCCCAGGCGCGGC
GCCGCGCCTGGGCCTGCCC


 


769
GGCAGGCCCAGGCGCGGCC
GGCCGCGCCTGGGCCTGCC


 


770
GCAGGCCCAGGCGCGGCCG
CGGCCGCGCCTGGGCCTGC


 


771
CAGGCCCAGGCGCGGCCGC
GCGGCCGCGCCTGGGCCTG


 


772
AGGCCCAGGCGCGGCCGCC
GGCGGCCGCGCCTGGGCCT


 


773
GGCCCAGGCGCGGCCGCCG
CGGCGGCCGCGCCTGGGCC


 


774
GCCCAGGCGCGGCCGCCGA
TCGGCGGCCGCGCCTGGGC


 


775
CCCAGGCGCGGCCGCCGAA
TTCGGCGGCCGCGCCTGGG


 


776
CCAGGCGCGGCCGCCGAAT
ATTCGGCGGCCGCGCCTGG


 


777
CAGGCGCGGCCGCCGAATC
GATTCGGCGGCCGCGCCTG


 


778
AGGCGCGGCCGCCGAATCA
TGATTCGGCGGCCGCGCCT


 


779
GGCGCGGCCGCCGAATCAC
GTGATTCGGCGGCCGCGCC


 


780
GCGCGGCCGCCGAATCACG
CGTGATTCGGCGGCCGCGC


 


781
CGCGGCCGCCGAATCACGG
CCGTGATTCGGCGGCCGCG


 


782
GCGGCCGCCGAATCACGGG
CCCGTGATTCGGCGGCCGC


 


783
CGGCCGCCGAATCACGGGC
GCCCGTGATTCGGCGGCCG


 


784
GGCCGCCGAATCACGGGCT
AGCCCGTGATTCGGCGGCC


 


785
GCCGCCGAATCACGGGCTC
GAGCCCGTGATTCGGCGGC


 


786
CCGCCGAATCACGGGCTCC
GGAGCCCGTGATTCGGCGG


 


787
CGCCGAATCACGGGCTCCT
AGGAGCCCGTGATTCGGCG


 


788
GCCGAATCACGGGCTCCTG
CAGGAGCCCGTGATTCGGC


 


789
CCGAATCACGGGCTCCTGT
ACAGGAGCCCGTGATTCGG


 


790
CGAATCACGGGCTCCTGTT
AACAGGAGCCCGTGATTCG


 


791
GAATCACGGGCTCCTGTTT
AAACAGGAGCCCGTGATTC


 


792
AATCACGGGCTCCTGTTTC
GAAACAGGAGCCCGTGATT


 


793
ATCACGGGCTCCTGTTTCC
GGAAACAGGAGCCCGTGAT


 


794
TCACGGGCTCCTGTTTCCC
GGGAAACAGGAGCCCGTGA


 


795
CACGGGCTCCTGTTTCCCG
CGGGAAACAGGAGCCCGTG


 


796
ACGGGCTCCTGTTTCCCGC
GCGGGAAACAGGAGCCCGT


 


797
CGGGCTCCTGTTTCCCGCA
TGCGGGAAACAGGAGCCCG


 


798
GGGCTCCTGTTTCCCGCAG
CTGCGGGAAACAGGAGCCC


 


799
GGCTCCTGTTTCCCGCAGG
CCTGCGGGAAACAGGAGCC


 


800
GCTCCTGTTTCCCGCAGGG
CCCTGCGGGAAACAGGAGC


 


801
CTCCTGTTTCCCGCAGGGT
ACCCTGCGGGAAACAGGAG


 


802
TCCTGTTTCCCGCAGGGTG
CACCCTGCGGGAAACAGGA


 


803
CCTGTTTCCCGCAGGGTGC
GCACCCTGCGGGAAACAGG


 


804
CTGTTTCCCGCAGGGTGCT
AGCACCCTGCGGGAAACAG


 


805
TGTTTCCCGCAGGGTGCTG
CAGCACCCTGCGGGAAACA


 


806
GTTTCCCGCAGGGTGCTGG
CCAGCACCCTGCGGGAAAC


 


807
TTTCCCGCAGGGTGCTGGA
TCCAGCACCCTGCGGGAAA


 


808
TTCCCGCAGGGTGCTGGAG
CTCCAGCACCCTGCGGGAA


 


809
TCCCGCAGGGTGCTGGAGG
CCTCCAGCACCCTGCGGGA


 


810
CCCGCAGGGTGCTGGAGGA
TCCTCCAGCACCCTGCGGG


 


811
CCGCAGGGTGCTGGAGGAG
CTCCTCCAGCACCCTGCGG


 


812
CGCAGGGTGCTGGAGGAGG
CCTCCTCCAGCACCCTGCG


 


813
GCAGGGTGCTGGAGGAGGA
TCCTCCTCCAGCACCCTGC


 


814
CAGGGTGCTGGAGGAGGAA
TTCCTCCTCCAGCACCCTG


 


815
AGGGTGCTGGAGGAGGAAA
TTTCCTCCTCCAGCACCCT


 


816
GGGTGCTGGAGGAGGAAAC
GTTTCCTCCTCCAGCACCC


 


817
GGTGCTGGAGGAGGAAACC
GGTTTCCTCCTCCAGCACC


 


818
GTGCTGGAGGAGGAAACCG
CGGTTTCCTCCTCCAGCAC


 


819
TGCTGGAGGAGGAAACCGG
CCGGTTTCCTCCTCCAGCA


 


820
GCTGGAGGAGGAAACCGGC
GCCGGTTTCCTCCTCCAGC


 


821
CTGGAGGAGGAAACCGGCG
CGCCGGTTTCCTCCTCCAG


 


822
TGGAGGAGGAAACCGGCGG
CCGCCGGTTTCCTCCTCCA


 


823
GGAGGAGGAAACCGGCGGA
TCCGCCGGTTTCCTCCTCC


 


824
GAGGAGGAAACCGGCGGAG
CTCCGCCGGTTTCCTCCTC


 


825
AGGAGGAAACCGGCGGAGC
GCTCCGCCGGTTTCCTCCT


 


826
GGAGGAAACCGGCGGAGCA
TGCTCCGCCGGTTTCCTCC


 


827
GAGGAAACCGGCGGAGCAG
CTGCTCCGCCGGTTTCCTC


 


828
AGGAAACCGGCGGAGCAGC
GCTGCTCCGCCGGTTTCCT


 


829
GGAAACCGGCGGAGCAGCT
AGCTGCTCCGCCGGTTTCC


 


830
GAAACCGGCGGAGCAGCTT
AAGCTGCTCCGCCGGTTTC


 


831
AAACCGGCGGAGCAGCTTC
GAAGCTGCTCCGCCGGTTT


 


832
AACCGGCGGAGCAGCTTCC
GGAAGCTGCTCCGCCGGTT


 


833
ACCGGCGGAGCAGCTTCCC
GGGAAGCTGCTCCGCCGGT


 


834
CCGGCGGAGCAGCTTCCCC
GGGGAAGCTGCTCCGCCGG


 


835
CGGCGGAGCAGCTTCCCCA
TGGGGAAGCTGCTCCGCCG


 


836
GGCGGAGCAGCTTCCCCAC
GTGGGGAAGCTGCTCCGCC


 


837
GCGGAGCAGCTTCCCCACT
AGTGGGGAAGCTGCTCCGC


 


838
CGGAGCAGCTTCCCCACTC
GAGTGGGGAAGCTGCTCCG


 


839
GGAGCAGCTTCCCCACTCT
AGAGTGGGGAAGCTGCTCC


 


840
GAGCAGCTTCCCCACTCTC
GAGAGTGGGGAAGCTGCTC


 


841
AGCAGCTTCCCCACTCTCA
TGAGAGTGGGGAAGCTGCT


 


842
GCAGCTTCCCCACTCTCAG
CTGAGAGTGGGGAAGCTGC


 


843
CAGCTTCCCCACTCTCAGT
ACTGAGAGTGGGGAAGCTG


 


844
AGCTTCCCCACTCTCAGTT
AACTGAGAGTGGGGAAGCT


 


845
GCTTCCCCACTCTCAGTTG
CAACTGAGAGTGGGGAAGC


 


846
CTTCCCCACTCTCAGTTGC
GCAACTGAGAGTGGGGAAG


 


847
TTCCCCACTCTCAGTTGCG
CGCAACTGAGAGTGGGGAA


 


848
TCCCCACTCTCAGTTGCGC
GCGCAACTGAGAGTGGGGA


 


849
CCCCACTCTCAGTTGCGCT
AGCGCAACTGAGAGTGGGG


 


850
CCCACTCTCAGTTGCGCTT
AAGCGCAACTGAGAGTGGG


 


851
CCACTCTCAGTTGCGCTTC
GAAGCGCAACTGAGAGTGG


 


852
CACTCTCAGTTGCGCTTCT
AGAAGCGCAACTGAGAGTG


 


853
ACTCTCAGTTGCGCTTCTG
CAGAAGCGCAACTGAGAGT


 


854
CTCTCAGTTGCGCTTCTGG
CCAGAAGCGCAACTGAGAG


 


855
TCTCAGTTGCGCTTCTGGC
GCCAGAAGCGCAACTGAGA


 


856
CTCAGTTGCGCTTCTGGCG
CGCCAGAAGCGCAACTGAG


 


857
TCAGTTGCGCTTCTGGCGA
TCGCCAGAAGCGCAACTGA


 


858
CAGTTGCGCTTCTGGCGAT
ATCGCCAGAAGCGCAACTG


 


859
AGTTGCGCTTCTGGCGATG
CATCGCCAGAAGCGCAACT


 


860
GTTGCGCTTCTGGCGATGG
CCATCGCCAGAAGCGCAAC


 


861
TTGCGCTTCTGGCGATGGC
GCCATCGCCAGAAGCGCAA


 


862
TGCGCTTCTGGCGATGGCG
CGCCATCGCCAGAAGCGCA


 


863
GCGCTTCTGGCGATGGCGA
TCGCCATCGCCAGAAGCGC


 


864
CGCTTCTGGCGATGGCGAT
ATCGCCATCGCCAGAAGCG


 


865
GCTTCTGGCGATGGCGATC
GATCGCCATCGCCAGAAGC


 


866
CTTCTGGCGATGGCGATCA
TGATCGCCATCGCCAGAAG


 


867
TTCTGGCGATGGCGATCAG
CTGATCGCCATCGCCAGAA


 


868
TCTGGCGATGGCGATCAGA
TCTGATCGCCATCGCCAGA


 


869
CTGGCGATGGCGATCAGAG
CTCTGATCGCCATCGCCAG


 


870
TGGCGATGGCGATCAGAGG
CCTCTGATCGCCATCGCCA


 


871
GGCGATGGCGATCAGAGGT
ACCTCTGATCGCCATCGCC


 


872
GCGATGGCGATCAGAGGTC
GACCTCTGATCGCCATCGC


 


873
CGATGGCGATCAGAGGTCC
GGACCTCTGATCGCCATCG


 


874
GATGGCGATCAGAGGTCCT
AGGACCTCTGATCGCCATC


 


875
ATGGCGATCAGAGGTCCTG
CAGGACCTCTGATCGCCAT


 


876
TGGCGATCAGAGGTCCTGC
GCAGGACCTCTGATCGCCA


 


877
GGCGATCAGAGGTCCTGCT
AGCAGGACCTCTGATCGCC


 


878
GCGATCAGAGGTCCTGCTG
CAGCAGGACCTCTGATCGC


 


879
CGATCAGAGGTCCTGCTGC
GCAGCAGGACCTCTGATCG


 


880
GATCAGAGGTCCTGCTGCG
CGCAGCAGGACCTCTGATC


 


881
ATCAGAGGTCCTGCTGCGC
GCGCAGCAGGACCTCTGAT


 


882
TCAGAGGTCCTGCTGCGCT
AGCGCAGCAGGACCTCTGA


 


883
CAGAGGTCCTGCTGCGCTC
GAGCGCAGCAGGACCTCTG


 


884
AGAGGTCCTGCTGCGCTCT
AGAGCGCAGCAGGACCTCT


 


885
GAGGTCCTGCTGCGCTCTC
GAGAGCGCAGCAGGACCTC


 


886
AGGTCCTGCTGCGCTCTCC
GGAGAGCGCAGCAGGACCT


 


887
GGTCCTGCTGCGCTCTCCG
CGGAGAGCGCAGCAGGACC


 


888
GTCCTGCTGCGCTCTCCGC
GCGGAGAGCGCAGCAGGAC


 


889
TCCTGCTGCGCTCTCCGCC
GGCGGAGAGCGCAGCAGGA


 


890
CCTGCTGCGCTCTCCGCCG
CGGCGGAGAGCGCAGCAGG


 


891
CTGCTGCGCTCTCCGCCGC
GCGGCGGAGAGCGCAGCAG


 


892
TGCTGCGCTCTCCGCCGCG
CGCGGCGGAGAGCGCAGCA


 


893
GCTGCGCTCTCCGCCGCGC
GCGCGGCGGAGAGCGCAGC


 


894
CTGCGCTCTCCGCCGCGCT
AGCGCGGCGGAGAGCGCAG


 


895
TGCGCTCTCCGCCGCGCTC
GAGCGCGGCGGAGAGCGCA


 


896
GCGCTCTCCGCCGCGCTCT
AGAGCGCGGCGGAGAGCGC


 


897
CGCTCTCCGCCGCGCTCTA
TAGAGCGCGGCGGAGAGCG


 


898
GCTCTCCGCCGCGCTCTAC
GTAGAGCGCGGCGGAGAGC


 


899
CTCTCCGCCGCGCTCTACC
GGTAGAGCGCGGCGGAGAG


 


900
TCTCCGCCGCGCTCTACCT
AGGTAGAGCGCGGCGGAGA


 


901
CTCCGCCGCGCTCTACCTC
GAGGTAGAGCGCGGCGGAG


 


902
TCCGCCGCGCTCTACCTCC
GGAGGTAGAGCGCGGCGGA


 


903
CCGCCGCGCTCTACCTCCA
TGGAGGTAGAGCGCGGCGG


 


904
CGCCGCGCTCTACCTCCAT
ATGGAGGTAGAGCGCGGCG


 


905
GCCGCGCTCTACCTCCATT
AATGGAGGTAGAGCGCGGC


 


906
CCGCGCTCTACCTCCATTA
TAATGGAGGTAGAGCGCGG


 


907
CGCGCTCTACCTCCATTAG
CTAATGGAGGTAGAGCGCG


 


908
GCGCTCTACCTCCATTAGC
GCTAATGGAGGTAGAGCGC


 


909
CGCTCTACCTCCATTAGCC
GGCTAATGGAGGTAGAGCG


 


910
GCTCTACCTCCATTAGCCG
CGGCTAATGGAGGTAGAGC


 


911
CTCTACCTCCATTAGCCGC
GCGGCTAATGGAGGTAGAG


 


912
TCTACCTCCATTAGCCGCG
CGCGGCTAATGGAGGTAGA


 


913
CTACCTCCATTAGCCGCGC
GCGCGGCTAATGGAGGTAG


 


914
TACCTCCATTAGCCGCGCT
AGCGCGGCTAATGGAGGTA


 


915
ACCTCCATTAGCCGCGCTG
CAGCGCGGCTAATGGAGGT


 


916
CCTCCATTAGCCGCGCTGC
GCAGCGCGGCTAATGGAGG


 


917
CTCCATTAGCCGCGCTGCG
CGCAGCGCGGCTAATGGAG


 


918
TCCATTAGCCGCGCTGCGC
GCGCAGCGCGGCTAATGGA


 


919
CCATTAGCCGCGCTGCGCG
CGCGCAGCGCGGCTAATGG


 


920
CATTAGCCGCGCTGCGCGG
CCGCGCAGCGCGGCTAATG


 


921
ATTAGCCGCGCTGCGCGGT
ACCGCGCAGCGCGGCTAAT


 


922
TTAGCCGCGCTGCGCGGTG
CACCGCGCAGCGCGGCTAA


 


923
TAGCCGCGCTGCGCGGTGC
GCACCGCGCAGCGCGGCTA


 


924
AGCCGCGCTGCGCGGTGCT
AGCACCGCGCAGCGCGGCT


 


925
GCCGCGCTGCGCGGTGCTG
CAGCACCGCGCAGCGCGGC


 


926
CCGCGCTGCGCGGTGCTGC
GCAGCACCGCGCAGCGCGG


 


927
CGCGCTGCGCGGTGCTGCG
CGCAGCACCGCGCAGCGCG


 


928
GCGCTGCGCGGTGCTGCGC
GCGCAGCACCGCGCAGCGC


 


929
CGCTGCGCGGTGCTGCGCC
GGCGCAGCACCGCGCAGCG


 


930
GCTGCGCGGTGCTGCGCCC
GGGCGCAGCACCGCGCAGC


 


931
CTGCGCGGTGCTGCGCCCT
AGGGCGCAGCACCGCGCAG


 


932
TGCGCGGTGCTGCGCCCTC
GAGGGCGCAGCACCGCGCA


 


933
GCGCGGTGCTGCGCCCTCG
CGAGGGCGCAGCACCGCGC


 


934
CGCGGTGCTGCGCCCTCGC
GCGAGGGCGCAGCACCGCG


 


935
GCGGTGCTGCGCCCTCGCC
GGCGAGGGCGCAGCACCGC


 


936
CGGTGCTGCGCCCTCGCCG
CGGCGAGGGCGCAGCACCG


 


937
GGTGCTGCGCCCTCGCCGG
CCGGCGAGGGCGCAGCACC


 


938
GTGCTGCGCCCTCGCCGGT
ACCGGCGAGGGCGCAGCAC


 


939
TGCTGCGCCCTCGCCGGTG
CACCGGCGAGGGCGCAGCA


 


940
GCTGCGCCCTCGCCGGTGC
GCACCGGCGAGGGCGCAGC


 


941
CTGCGCCCTCGCCGGTGCC
GGCACCGGCGAGGGCGCAG


 


942
TGCGCCCTCGCCGGTGCCT
AGGCACCGGCGAGGGCGCA


 


943
GCGCCCTCGCCGGTGCCTC
GAGGCACCGGCGAGGGCGC


 


944
CGCCCTCGCCGGTGCCTCT
AGAGGCACCGGCGAGGGCG


 


945
GCCCTCGCCGGTGCCTCTC
GAGAGGCACCGGCGAGGGC


 


946
CCCTCGCCGGTGCCTCTCT
AGAGAGGCACCGGCGAGGG


 


947
CCTCGCCGGTGCCTCTCTC
GAGAGAGGCACCGGCGAGG


 


948
CTCGCCGGTGCCTCTCTCC
GGAGAGAGGCACCGGCGAG


 


949
TCGCCGGTGCCTCTCTCCT
AGGAGAGAGGCACCGGCGA


 


950
CGCCGGTGCCTCTCTCCTG
CAGGAGAGAGGCACCGGCG


 


951
GCCGGTGCCTCTCTCCTGG
CCAGGAGAGAGGCACCGGC


 


952
CCGGTGCCTCTCTCCTGGG
CCCAGGAGAGAGGCACCGG


 


953
CGGTGCCTCTCTCCTGGGT
ACCCAGGAGAGAGGCACCG


 


954
GGTGCCTCTCTCCTGGGTC
GACCCAGGAGAGAGGCACC


 


955
GTGCCTCTCTCCTGGGTCC
GGACCCAGGAGAGAGGCAC


 


956
TGCCTCTCTCCTGGGTCCC
GGGACCCAGGAGAGAGGCA


 


957
GCCTCTCTCCTGGGTCCCA
TGGGACCCAGGAGAGAGGC


 


958
CCTCTCTCCTGGGTCCCAG
CTGGGACCCAGGAGAGAGG


 


959
CTCTCTCCTGGGTCCCAGG
CCTGGGACCCAGGAGAGAG


 


960
TCTCTCCTGGGTCCCAGGA
TCCTGGGACCCAGGAGAGA


 


961
CTCTCCTGGGTCCCAGGAT
ATCCTGGGACCCAGGAGAG


 


962
TCTCCTGGGTCCCAGGATC
GATCCTGGGACCCAGGAGA


 


963
CTCCTGGGTCCCAGGATCG
CGATCCTGGGACCCAGGAG


 


964
TCCTGGGTCCCAGGATCGG
CCGATCCTGGGACCCAGGA


 


965
CCTGGGTCCCAGGATCGGC
GCCGATCCTGGGACCCAGG


 


966
CTGGGTCCCAGGATCGGCC
GGCCGATCCTGGGACCCAG


 


967
TGGGTCCCAGGATCGGCCC
GGGCCGATCCTGGGACCCA


 


968
GGGTCCCAGGATCGGCCCC
GGGGCCGATCCTGGGACCC


 


969
GGTCCCAGGATCGGCCCCC
GGGGGCCGATCCTGGGACC


 


970
GTCCCAGGATCGGCCCCCA
TGGGGGCCGATCCTGGGAC


 


971
TCCCAGGATCGGCCCCCAC
GTGGGGGCCGATCCTGGGA


 


972
CCCAGGATCGGCCCCCACC
GGTGGGGGCCGATCCTGGG


 


973
CCAGGATCGGCCCCCACCA
TGGTGGGGGCCGATCCTGG


 


974
CAGGATCGGCCCCCACCAT
ATGGTGGGGGCCGATCCTG


 


975
AGGATCGGCCCCCACCATC
GATGGTGGGGGCCGATCCT


 


976
GGATCGGCCCCCACCATCC
GGATGGTGGGGGCCGATCC


 


977
GATCGGCCCCCACCATCCA
TGGATGGTGGGGGCCGATC


 


978
ATCGGCCCCCACCATCCAG
CTGGATGGTGGGGGCCGAT


 


979
TCGGCCCCCACCATCCAGG
CCTGGATGGTGGGGGCCGA


 


980
CGGCCCCCACCATCCAGGC
GCCTGGATGGTGGGGGCCG


 


981
GGCCCCCACCATCCAGGCA
TGCCTGGATGGTGGGGGCC


 


982
GCCCCCACCATCCAGGCAC
GTGCCTGGATGGTGGGGGC


 


983
CCCCCACCATCCAGGCACG
CGTGCCTGGATGGTGGGGG


 


984
CCCCACCATCCAGGCACGA
TCGTGCCTGGATGGTGGGG


 


985
CCCACCATCCAGGCACGAC
GTCGTGCCTGGATGGTGGG


 


986
CCACCATCCAGGCACGACC
GGTCGTGCCTGGATGGTGG


 


987
CACCATCCAGGCACGACCC
GGGTCGTGCCTGGATGGTG


 


988
ACCATCCAGGCACGACCCC
GGGGTCGTGCCTGGATGGT


 


989
CCATCCAGGCACGACCCCC
GGGGGTCGTGCCTGGATGG


 


990
CATCCAGGCACGACCCCCT
AGGGGGTCGTGCCTGGATG


 


991
ATCCAGGCACGACCCCCTT
AAGGGGGTCGTGCCTGGAT


 


992
TCCAGGCACGACCCCCTTC
GAAGGGGGTCGTGCCTGGA


 


993
CCAGGCACGACCCCCTTCC
GGAAGGGGGTCGTGCCTGG


 


994
CAGGCACGACCCCCTTCCC
GGGAAGGGGGTCGTGCCTG


 


995
AGGCACGACCCCCTTCCCC
GGGGAAGGGGGTCGTGCCT


 


996
GGCACGACCCCCTTCCCCG
CGGGGAAGGGGGTCGTGCC


 


997
GCACGACCCCCTTCCCCGG
CCGGGGAAGGGGGTCGTGC


 


998
CACGACCCCCTTCCCCGGC
GCCGGGGAAGGGGGTCGTG


 


999
ACGACCCCCTTCCCCGGCC
GGCCGGGGAAGGGGGTCGT


 


1000
CGACCCCCTTCCCCGGCCC
GGGCCGGGGAAGGGGGTCG


 


1001
GACCCCCTTCCCCGGCCCC
GGGGCCGGGGAAGGGGGTC


 


1002
ACCCCCTTCCCCGGCCCCT
AGGGGCCGGGGAAGGGGGT


 


1003
CCCCCTTCCCCGGCCCCTC
GAGGGGCCGGGGAAGGGGG


 


1004
CCCCTTCCCCGGCCCCTCG
CGAGGGGCCGGGGAAGGGG


 


1005
CCCTTCCCCGGCCCCTCGG
CCGAGGGGCCGGGGAAGGG


 


1006
CCTTCCCCGGCCCCTCGGC
GCCGAGGGGCCGGGGAAGG


 


1007
CTTCCCCGGCCCCTCGGCC
GGCCGAGGGGCCGGGGAAG


 


1008
TTCCCCGGCCCCTCGGCCT
AGGCCGAGGGGCCGGGGAA


 


1009
TCCCCGGCCCCTCGGCCTT
AAGGCCGAGGGGCCGGGGA


 


1010
CCCCGGCCCCTCGGCCTTT
AAAGGCCGAGGGGCCGGGG


 


1011
CCCGGCCCCTCGGCCTTTC
GAAAGGCCGAGGGGCCGGG


 


1012
CCGGCCCCTCGGCCTTTCC
GGAAAGGCCGAGGGGCCGG


 


1013
CGGCCCCTCGGCCTTTCCC
GGGAAAGGCCGAGGGGCCG


 


1014
GGCCCCTCGGCCTTTCCCC
GGGGAAAGGCCGAGGGGCC


 


1015
GCCCCTCGGCCTTTCCCCC
GGGGGAAAGGCCGAGGGGC


 


1016
CCCCTCGGCCTTTCCCCCA
TGGGGGAAAGGCCGAGGGG


 


1017
CCCTCGGCCTTTCCCCCAA
TTGGGGGAAAGGCCGAGGG


 


1018
CCTCGGCCTTTCCCCCAAC
GTTGGGGGAAAGGCCGAGG


 


1019
CTCGGCCTTTCCCCCAACT
AGTTGGGGGAAAGGCCGAG


 


1020
TCGGCCTTTCCCCCAACTC
GAGTTGGGGGAAAGGCCGA


 


1021
CGGCCTTTCCCCCAACTCG
CGAGTTGGGGGAAAGGCCG


 


1022
GGCCTTTCCCCCAACTCGG
CCGAGTTGGGGGAAAGGCC


 


1023
GCCTTTCCCCCAACTCGGC
GCCGAGTTGGGGGAAAGGC


 


1024
CCTTTCCCCCAACTCGGCC
GGCCGAGTTGGGGGAAAGG


 


1025
CTTTCCCCCAACTCGGCCA
TGGCCGAGTTGGGGGAAAG


 


1026
TTTCCCCCAACTCGGCCAT
ATGGCCGAGTTGGGGGAAA


 


1027
TTCCCCCAACTCGGCCATC
GATGGCCGAGTTGGGGGAA


 


1028
TCCCCCAACTCGGCCATCT
AGATGGCCGAGTTGGGGGA


 


1029
CCCCCAACTCGGCCATCTC
GAGATGGCCGAGTTGGGGG


 


1030
CCCCAACTCGGCCATCTCC
GGAGATGGCCGAGTTGGGG


 


1031
CCCAACTCGGCCATCTCCG
CGGAGATGGCCGAGTTGGG


 


1032
CCAACTCGGCCATCTCCGA
TCGGAGATGGCCGAGTTGG


 


1033
CAACTCGGCCATCTCCGAC
GTCGGAGATGGCCGAGTTG


 


1034
AACTCGGCCATCTCCGACC
GGTCGGAGATGGCCGAGTT


 


1035
ACTCGGCCATCTCCGACCC
GGGTCGGAGATGGCCGAGT


 


1036
CTCGGCCATCTCCGACCCG
CGGGTCGGAGATGGCCGAG


 


1037
TCGGCCATCTCCGACCCGG
CCGGGTCGGAGATGGCCGA


 


1038
CGGCCATCTCCGACCCGGG
CCCGGGTCGGAGATGGCCG


 


1039
GGCCATCTCCGACCCGGGG
CCCCGGGTCGGAGATGGCC


 


1040
GCCATCTCCGACCCGGGGC
GCCCCGGGTCGGAGATGGC


 


1041
CCATCTCCGACCCGGGGCG
CGCCCCGGGTCGGAGATGG


 


1042
CATCTCCGACCCGGGGCGC
GCGCCCCGGGTCGGAGATG


 


1043
ATCTCCGACCCGGGGCGCG
CGCGCCCCGGGTCGGAGAT


 


1044
TCTCCGACCCGGGGCGCGT
ACGCGCCCCGGGTCGGAGA


 


1045
CTCCGACCCGGGGCGCGTG
CACGCGCCCCGGGTCGGAG


 


1046
TCCGACCCGGGGCGCGTGT
ACACGCGCCCCGGGTCGGA


 


1047
CCGACCCGGGGCGCGTGTT
AACACGCGCCCCGGGTCGG


 


1048
CGACCCGGGGCGCGTGTTC
GAACACGCGCCCCGGGTCG


 


1049
GACCCGGGGCGCGTGTTCC
GGAACACGCGCCCCGGGTC


 


1050
ACCCGGGGCGCGTGTTCCC
GGGAACACGCGCCCCGGGT


 


1051
CCCGGGGCGCGTGTTCCCC
GGGGAACACGCGCCCCGGG


 


1052
CCGGGGCGCGTGTTCCCCC
GGGGGAACACGCGCCCCGG


 


1053
CGGGGCGCGTGTTCCCCCC
GGGGGGAACACGCGCCCCG


 


1054
GGGGCGCGTGTTCCCCCCG
CGGGGGGAACACGCGCCCC


 


1055
GGGCGCGTGTTCCCCCCGG
CCGGGGGGAACACGCGCCC


 


1056
GGCGCGTGTTCCCCCCGGC
GCCGGGGGGAACACGCGCC


 


1057
GCGCGTGTTCCCCCCGGCC
GGCCGGGGGGAACACGCGC


 


1058
CGCGTGTTCCCCCCGGCCC
GGGCCGGGGGGAACACGCG


 


1059
GCGTGTTCCCCCCGGCCCG
CGGGCCGGGGGGAACACGC


 


1060
CGTGTTCCCCCCGGCCCGG
CCGGGCCGGGGGGAACACG


 


1061
GTGTTCCCCCCGGCCCGGC
GCCGGGCCGGGGGGAACAC


 


1062
TGTTCCCCCCGGCCCGGCG
CGCCGGGCCGGGGGGAACA


 


1063
GTTCCCCCCGGCCCGGCGC
GCGCCGGGCCGGGGGGAAC


 


1064
TTCCCCCCGGCCCGGCGCC
GGCGCCGGGCCGGGGGGAA


 


1065
TCCCCCCGGCCCGGCGCCT
AGGCGCCGGGCCGGGGGGA


 


1066
CCCCCCGGCCCGGCGCCTT
AAGGCGCCGGGCCGGGGGG


 


1067
CCCCCGGCCCGGCGCCTTC
GAAGGCGCCGGGCCGGGGG


 


1068
CCCCGGCCCGGCGCCTTCT
AGAAGGCGCCGGGCCGGGG


 


1069
CCCGGCCCGGCGCCTTCTC
GAGAAGGCGCCGGGCCGGG


 


1070
CCGGCCCGGCGCCTTCTCT
AGAGAAGGCGCCGGGCCGG


 


1071
CGGCCCGGCGCCTTCTCTC
GAGAGAAGGCGCCGGGCCG


 


1072
GGCCCGGCGCCTTCTCTCC
GGAGAGAAGGCGCCGGGCC


 


1073
GCCCGGCGCCTTCTCTCCC
GGGAGAGAAGGCGCCGGGC


 


1074
CCCGGCGCCTTCTCTCCCT
AGGGAGAGAAGGCGCCGGG


 


1075
CCGGCGCCTTCTCTCCCTC
GAGGGAGAGAAGGCGCCGG


 


1076
CGGCGCCTTCTCTCCCTCC
GGAGGGAGAGAAGGCGCCG


 


1077
GGCGCCTTCTCTCCCTCCG
CGGAGGGAGAGAAGGCGCC


 


1078
GCGCCTTCTCTCCCTCCGG
CCGGAGGGAGAGAAGGCGC


 


1079
CGCCTTCTCTCCCTCCGGG
CCCGGAGGGAGAGAAGGCG


 


1080
GCCTTCTCTCCCTCCGGGG
CCCCGGAGGGAGAGAAGGC


 


1081
CCTTCTCTCCCTCCGGGGG
CCCCCGGAGGGAGAGAAGG


 


1082
CTTCTCTCCCTCCGGGGGC
GCCCCCGGAGGGAGAGAAG


 


1083
TTCTCTCCCTCCGGGGGCA
TGCCCCCGGAGGGAGAGAA


 


1084
TCTCTCCCTCCGGGGGCAC
GTGCCCCCGGAGGGAGAGA


 


1085
CTCTCCCTCCGGGGGCACC
GGTGCCCCCGGAGGGAGAG


 


1086
TCTCCCTCCGGGGGCACCC
GGGTGCCCCCGGAGGGAGA


 


1087
CTCCCTCCGGGGGCACCCG
CGGGTGCCCCCGGAGGGAG


 


1088
TCCCTCCGGGGGCACCCGC
GCGGGTGCCCCCGGAGGGA


 


1089
CCCTCCGGGGGCACCCGCT
AGCGGGTGCCCCCGGAGGG


 


1090
CCTCCGGGGGCACCCGCTC
GAGCGGGTGCCCCCGGAGG


 


1091
CTCCGGGGGCACCCGCTCC
GGAGCGGGTGCCCCCGGAG


 


1092
TCCGGGGGCACCCGCTCCC
GGGAGCGGGTGCCCCCGGA


 


1093
CCGGGGGCACCCGCTCCCT
AGGGAGCGGGTGCCCCCGG


 


1094
CGGGGGCACCCGCTCCCTA
TAGGGAGCGGGTGCCCCCG


 


1095
GGGGGCACCCGCTCCCTAG
CTAGGGAGCGGGTGCCCCC


 


1096
GGGGCACCCGCTCCCTAGC
GCTAGGGAGCGGGTGCCCC


 


1097
GGGCACCCGCTCCCTAGCC
GGCTAGGGAGCGGGTGCCC


 


1098
GGCACCCGCTCCCTAGCCC
GGGCTAGGGAGCGGGTGCC


 


1099
GCACCCGCTCCCTAGCCCC
GGGGCTAGGGAGCGGGTGC


 


1100
CACCCGCTCCCTAGCCCCG
CGGGGCTAGGGAGCGGGTG


 


1101
ACCCGCTCCCTAGCCCCGG
CCGGGGCTAGGGAGCGGGT


 


1102
CCCGCTCCCTAGCCCCGGC
GCCGGGGCTAGGGAGCGGG


 


1103
CCGCTCCCTAGCCCCGGCC
GGCCGGGGCTAGGGAGCGG


 


1104
CGCTCCCTAGCCCCGGCCC
GGGCCGGGGCTAGGGAGCG


 


1105
GCTCCCTAGCCCCGGCCCG
CGGGCCGGGGCTAGGGAGC


 


1106
CTCCCTAGCCCCGGCCCGG
CCGGGCCGGGGCTAGGGAG


 


1107
TCCCTAGCCCCGGCCCGGC
GCCGGGCCGGGGCTAGGGA


 


1108
CCCTAGCCCCGGCCCGGCC
GGCCGGGCCGGGGCTAGGG


 


1109
CCTAGCCCCGGCCCGGCCC
GGGCCGGGCCGGGGCTAGG


 


1110
CTAGCCCCGGCCCGGCCCT
AGGGCCGGGCCGGGGCTAG


 


1111
TAGCCCCGGCCCGGCCCTC
GAGGGCCGGGCCGGGGCTA


 


1112
AGCCCCGGCCCGGCCCTCC
GGAGGGCCGGGCCGGGGCT


 


1113
GCCCCGGCCCGGCCCTCCC
GGGAGGGCCGGGCCGGGGC


 


1114
CCCCGGCCCGGCCCTCCCC
GGGGAGGGCCGGGCCGGGG


 


1115
CCCGGCCCGGCCCTCCCCG
CGGGGAGGGCCGGGCCGGG


 


1116
CCGGCCCGGCCCTCCCCGC
GCGGGGAGGGCCGGGCCGG


 


1117
CGGCCCGGCCCTCCCCGCG
CGCGGGGAGGGCCGGGCCG


 


1118
GGCCCGGCCCTCCCCGCGG
CCGCGGGGAGGGCCGGGCC


 


1119
GCCCGGCCCTCCCCGCGGC
GCCGCGGGGAGGGCCGGGC


 


1120
CCCGGCCCTCCCCGCGGCG
CGCCGCGGGGAGGGCCGGG


 


1121
CCGGCCCTCCCCGCGGCGC
GCGCCGCGGGGAGGGCCGG


 


1122
CGGCCCTCCCCGCGGCGCA
TGCGCCGCGGGGAGGGCCG


 


1123
GGCCCTCCCCGCGGCGCAG
CTGCGCCGCGGGGAGGGCC


 


1124
GCCCTCCCCGCGGCGCAGC
GCTGCGCCGCGGGGAGGGC


 


1125
CCCTCCCCGCGGCGCAGCA
TGCTGCGCCGCGGGGAGGG


 


1126
CCTCCCCGCGGCGCAGCAC
GTGCTGCGCCGCGGGGAGG


 


1127
CTCCCCGCGGCGCAGCACG
CGTGCTGCGCCGCGGGGAG


 


1128
TCCCCGCGGCGCAGCACGG
CCGTGCTGCGCCGCGGGGA


 


1129
CCCCGCGGCGCAGCACGGA
TCCGTGCTGCGCCGCGGGG


 


1130
CCCGCGGCGCAGCACGGAG
CTCCGTGCTGCGCCGCGGG


 


1131
CCGCGGCGCAGCACGGAGT
ACTCCGTGCTGCGCCGCGG


 


1132
CGCGGCGCAGCACGGAGTC
GACTCCGTGCTGCGCCGCG


 


1133
GCGGCGCAGCACGGAGTCT
AGACTCCGTGCTGCGCCGC


 


1134
CGGCGCAGCACGGAGTCTC
GAGACTCCGTGCTGCGCCG


 


1135
GGCGCAGCACGGAGTCTCG
CGAGACTCCGTGCTGCGCC


 


1136
GCGCAGCACGGAGTCTCGG
CCGAGACTCCGTGCTGCGC


 


1137
CGCAGCACGGAGTCTCGGC
GCCGAGACTCCGTGCTGCG


 


1138
GCAGCACGGAGTCTCGGCG
CGCCGAGACTCCGTGCTGC


 


1139
CAGCACGGAGTCTCGGCGT
ACGCCGAGACTCCGTGCTG


 


1140
AGCACGGAGTCTCGGCGTC
GACGCCGAGACTCCGTGCT


 


1141
GCACGGAGTCTCGGCGTCC
GGACGCCGAGACTCCGTGC


 


1142
CACGGAGTCTCGGCGTCCC
GGGACGCCGAGACTCCGTG


 


1143
ACGGAGTCTCGGCGTCCCA
TGGGACGCCGAGACTCCGT


 


1144
CGGAGTCTCGGCGTCCCAT
ATGGGACGCCGAGACTCCG


 


1145
GGAGTCTCGGCGTCCCATG
CATGGGACGCCGAGACTCC


 


1146
GAGTCTCGGCGTCCCATGG
CCATGGGACGCCGAGACTC


 


1147
AGTCTCGGCGTCCCATGGC
GCCATGGGACGCCGAGACT


 


1148
GTCTCGGCGTCCCATGGCG
CGCCATGGGACGCCGAGAC


 


1149
TCTCGGCGTCCCATGGCGC
GCGCCATGGGACGCCGAGA


 


1150
CTCGGCGTCCCATGGCGCA
TGCGCCATGGGACGCCGAG


 


1151
TCGGCGTCCCATGGCGCAA
TTGCGCCATGGGACGCCGA


 


1152
CGGCGTCCCATGGCGCAAC
GTTGCGCCATGGGACGCCG


 


1153
GGCGTCCCATGGCGCAACC
GGTTGCGCCATGGGACGCC


 


1154
GCGTCCCATGGCGCAACCT
AGGTTGCGCCATGGGACGC


 


1155
CGTCCCATGGCGCAACCTA
TAGGTTGCGCCATGGGACG


 


1156
GTCCCATGGCGCAACCTAC
GTAGGTTGCGCCATGGGAC


 


1157
TCCCATGGCGCAACCTACG
CGTAGGTTGCGCCATGGGA


 


1158
CCCATGGCGCAACCTACGG
CCGTAGGTTGCGCCATGGG


 


1159
CCATGGCGCAACCTACGGC
GCCGTAGGTTGCGCCATGG


 


1160
CATGGCGCAACCTACGGCC
GGCCGTAGGTTGCGCCATG


 


1161
ATGGCGCAACCTACGGCCT
AGGCCGTAGGTTGCGCCAT


 


1162
TGGCGCAACCTACGGCCTC
GAGGCCGTAGGTTGCGCCA


 


1163
GGCGCAACCTACGGCCTCG
CGAGGCCGTAGGTTGCGCC


 


1164
GCGCAACCTACGGCCTCGG
CCGAGGCCGTAGGTTGCGC


 


1165
CGCAACCTACGGCCTCGGC
GCCGAGGCCGTAGGTTGCG


 


1166
GCAACCTACGGCCTCGGCC
GGCCGAGGCCGTAGGTTGC


 


1167
CAACCTACGGCCTCGGCCC
GGGCCGAGGCCGTAGGTTG


 


1168
AACCTACGGCCTCGGCCCA
TGGGCCGAGGCCGTAGGTT


 


1169
ACCTACGGCCTCGGCCCAG
CTGGGCCGAGGCCGTAGGT


 


1170
CCTACGGCCTCGGCCCAGA
TCTGGGCCGAGGCCGTAGG


 


1171
CTACGGCCTCGGCCCAGAA
TTCTGGGCCGAGGCCGTAG


 


1172
TACGGCCTCGGCCCAGAAG
CTTCTGGGCCGAGGCCGTA


 


1173
ACGGCCTCGGCCCAGAAGC
GCTTCTGGGCCGAGGCCGT


 


1174
CGGCCTCGGCCCAGAAGCT
AGCTTCTGGGCCGAGGCCG


 


1175
GGCCTCGGCCCAGAAGCTG
CAGCTTCTGGGCCGAGGCC


 


1176
GCCTCGGCCCAGAAGCTGG
CCAGCTTCTGGGCCGAGGC


 


1177
CCTCGGCCCAGAAGCTGGT
ACCAGCTTCTGGGCCGAGG


 


1178
CTCGGCCCAGAAGCTGGTG
CACCAGCTTCTGGGCCGAG


 


1179
TCGGCCCAGAAGCTGGTGC
GCACCAGCTTCTGGGCCGA


 


1180
CGGCCCAGAAGCTGGTGCG
CGCACCAGCTTCTGGGCCG


 


1181
GGCCCAGAAGCTGGTGCGG
CCGCACCAGCTTCTGGGCC


 


1182
GCCCAGAAGCTGGTGCGGC
GCCGCACCAGCTTCTGGGC


 


1183
CCCAGAAGCTGGTGCGGCC
GGCCGCACCAGCTTCTGGG


 


1184
CCAGAAGCTGGTGCGGCCG
CGGCCGCACCAGCTTCTGG


 


1185
CAGAAGCTGGTGCGGCCGA
TCGGCCGCACCAGCTTCTG


 


1186
AGAAGCTGGTGCGGCCGAT
ATCGGCCGCACCAGCTTCT


 


1187
GAAGCTGGTGCGGCCGATC
GATCGGCCGCACCAGCTTC


 


1188
AAGCTGGTGCGGCCGATCC
GGATCGGCCGCACCAGCTT


 


1189
AGCTGGTGCGGCCGATCCG
CGGATCGGCCGCACCAGCT


 


1190
GCTGGTGCGGCCGATCCGC
GCGGATCGGCCGCACCAGC


 


1191
CTGGTGCGGCCGATCCGCG
CGCGGATCGGCCGCACCAG


 


1192
TGGTGCGGCCGATCCGCGC
GCGCGGATCGGCCGCACCA


 


1193
GGTGCGGCCGATCCGCGCC
GGCGCGGATCGGCCGCACC


 


1194
GTGCGGCCGATCCGCGCCG
CGGCGCGGATCGGCCGCAC


 


1195
TGCGGCCGATCCGCGCCGT
ACGGCGCGGATCGGCCGCA


 


1196
GCGGCCGATCCGCGCCGTG
CACGGCGCGGATCGGCCGC


 


1197
CGGCCGATCCGCGCCGTGT
ACACGGCGCGGATCGGCCG


 


1198
GGCCGATCCGCGCCGTGTG
CACACGGCGCGGATCGGCC


 


1199
GCCGATCCGCGCCGTGTGC
GCACACGGCGCGGATCGGC


 


1200
CCGATCCGCGCCGTGTGCC
GGCACACGGCGCGGATCGG


 


1201
CGATCCGCGCCGTGTGCCG
CGGCACACGGCGCGGATCG


 


1202
GATCCGCGCCGTGTGCCGC
GCGGCACACGGCGCGGATC


 


1203
ATCCGCGCCGTGTGCCGCA
TGCGGCACACGGCGCGGAT


 


1204
TCCGCGCCGTGTGCCGCAT
ATGCGGCACACGGCGCGGA


 


1205
CCGCGCCGTGTGCCGCATC
GATGCGGCACACGGCGCGG


 


1206
CGCGCCGTGTGCCGCATCC
GGATGCGGCACACGGCGCG


 


1207
GCGCCGTGTGCCGCATCCT
AGGATGCGGCACACGGCGC


 


1208
CGCCGTGTGCCGCATCCTG
CAGGATGCGGCACACGGCG


 


1209
GCCGTGTGCCGCATCCTGC
GCAGGATGCGGCACACGGC


 


1210
CCGTGTGCCGCATCCTGCA
TGCAGGATGCGGCACACGG


 


1211
CGTGTGCCGCATCCTGCAG
CTGCAGGATGCGGCACACG


 


1212
GTGTGCCGCATCCTGCAGA
TCTGCAGGATGCGGCACAC


 


1213
TGTGCCGCATCCTGCAGAT
ATCTGCAGGATGCGGCACA


 


1214
GTGCCGCATCCTGCAGATC
GATCTGCAGGATGCGGCAC


 


1215
TGCCGCATCCTGCAGATCC
GGATCTGCAGGATGCGGCA


 


1216
GCCGCATCCTGCAGATCCC
GGGATCTGCAGGATGCGGC


 


1217
CCGCATCCTGCAGATCCCG
CGGGATCTGCAGGATGCGG


 


1218
CGCATCCTGCAGATCCCGG
CCGGGATCTGCAGGATGCG


 


1219
GCATCCTGCAGATCCCGGA
TCCGGGATCTGCAGGATGC


 


1220
CATCCTGCAGATCCCGGAG
CTCCGGGATCTGCAGGATG


 


1221
ATCCTGCAGATCCCGGAGT
ACTCCGGGATCTGCAGGAT


 


1222
TCCTGCAGATCCCGGAGTC
GACTCCGGGATCTGCAGGA


 


1223
CCTGCAGATCCCGGAGTCC
GGACTCCGGGATCTGCAGG


 


1224
CTGCAGATCCCGGAGTCCG
CGGACTCCGGGATCTGCAG


 


1225
TGCAGATCCCGGAGTCCGA
TCGGACTCCGGGATCTGCA


 


1226
GCAGATCCCGGAGTCCGAC
GTCGGACTCCGGGATCTGC


 


1227
CAGATCCCGGAGTCCGACC
GGTCGGACTCCGGGATCTG


 


1228
AGATCCCGGAGTCCGACCC
GGGTCGGACTCCGGGATCT


 


1229
GATCCCGGAGTCCGACCCC
GGGGTCGGACTCCGGGATC


 


1230
ATCCCGGAGTCCGACCCCT
AGGGGTCGGACTCCGGGAT


 


1231
TCCCGGAGTCCGACCCCTC
GAGGGGTCGGACTCCGGGA


 


1232
CCCGGAGTCCGACCCCTCC
GGAGGGGTCGGACTCCGGG


 


1233
CCGGAGTCCGACCCCTCCA
TGGAGGGGTCGGACTCCGG


 


1234
CGGAGTCCGACCCCTCCAA
TTGGAGGGGTCGGACTCCG


 


1235
GGAGTCCGACCCCTCCAAC
GTTGGAGGGGTCGGACTCC


 


1236
GAGTCCGACCCCTCCAACC
GGTTGGAGGGGTCGGACTC


 


1237
AGTCCGACCCCTCCAACCT
AGGTTGGAGGGGTCGGACT


 


1238
GTCCGACCCCTCCAACCTG
CAGGTTGGAGGGGTCGGAC


 


1239
TCCGACCCCTCCAACCTGC
GCAGGTTGGAGGGGTCGGA


 


1240
CCGACCCCTCCAACCTGCG
CGCAGGTTGGAGGGGTCGG


 


1241
CGACCCCTCCAACCTGCGG
CCGCAGGTTGGAGGGGTCG


 


1242
GACCCCTCCAACCTGCGGC
GCCGCAGGTTGGAGGGGTC


 


1243
ACCCCTCCAACCTGCGGCC
GGCCGCAGGTTGGAGGGGT


 


1244
CCCCTCCAACCTGCGGCCC
GGGCCGCAGGTTGGAGGGG


 


1245
CCCTCCAACCTGCGGCCCT
AGGGCCGCAGGTTGGAGGG


 


1246
CCTCCAACCTGCGGCCCTA
TAGGGCCGCAGGTTGGAGG


 


1247
CTCCAACCTGCGGCCCTAG
CTAGGGCCGCAGGTTGGAG


 


1248
TCCAACCTGCGGCCCTAGA
TCTAGGGCCGCAGGTTGGA


 


1249
CCAACCTGCGGCCCTAGAG
CTCTAGGGCCGCAGGTTGG


 


1250
CAACCTGCGGCCCTAGAGC
GCTCTAGGGCCGCAGGTTG


 


1251
AACCTGCGGCCCTAGAGCG
CGCTCTAGGGCCGCAGGTT


 


1252
ACCTGCGGCCCTAGAGCGC
GCGCTCTAGGGCCGCAGGT


 


1253
CCTGCGGCCCTAGAGCGCC
GGCGCTCTAGGGCCGCAGG


 


1254
CTGCGGCCCTAGAGCGCCC
GGGCGCTCTAGGGCCGCAG


 


1255
TGCGGCCCTAGAGCGCCCC
GGGGCGCTCTAGGGCCGCA


 


1256
GCGGCCCTAGAGCGCCCCC
GGGGGCGCTCTAGGGCCGC


 


1257
CGGCCCTAGAGCGCCCCCG
CGGGGGCGCTCTAGGGCCG


 


1258
GGCCCTAGAGCGCCCCCGC
GCGGGGGCGCTCTAGGGCC


 


1259
GCCCTAGAGCGCCCCCGCC
GGCGGGGGCGCTCTAGGGC


 


1260
CCCTAGAGCGCCCCCGCCG
CGGCGGGGGCGCTCTAGGG


 


1261
CCTAGAGCGCCCCCGCCGC
GCGGCGGGGGCGCTCTAGG


 


1262
CTAGAGCGCCCCCGCCGCC
GGCGGCGGGGGCGCTCTAG


 


1263
TAGAGCGCCCCCGCCGCCC
GGGCGGCGGGGGCGCTCTA


 


1264
AGAGCGCCCCCGCCGCCCC
GGGGCGGCGGGGGCGCTCT


 


1265
GAGCGCCCCCGCCGCCCCG
CGGGGCGGCGGGGGCGCTC


 


1266
AGCGCCCCCGCCGCCCCGG
CCGGGGCGGCGGGGGCGCT


 


1267
GCGCCCCCGCCGCCCCGGG
CCCGGGGCGGCGGGGGCGC


 


1268
CGCCCCCGCCGCCCCGGGG
CCCCGGGGCGGCGGGGGCG


 


1269
GCCCCCGCCGCCCCGGGGG
CCCCCGGGGCGGCGGGGGC


 


1270
CCCCCGCCGCCCCGGGGGA
TCCCCCGGGGCGGCGGGGG


 


1271
CCCCGCCGCCCCGGGGGAA
TTCCCCCGGGGCGGCGGGG


 


1272
CCCGCCGCCCCGGGGGAAG
CTTCCCCCGGGGCGGCGGG


 


1273
CCGCCGCCCCGGGGGAAGG
CCTTCCCCCGGGGCGGCGG


 


1274
CGCCGCCCCGGGGGAAGGA
TCCTTCCCCCGGGGCGGCG


 


1275
GCCGCCCCGGGGGAAGGAG
CTCCTTCCCCCGGGGCGGC


 


1276
CCGCCCCGGGGGAAGGAGA
TCTCCTTCCCCCGGGGCGG


 


1277
CGCCCCGGGGGAAGGAGAG
CTCTCCTTCCCCCGGGGCG


 


1278
GCCCCGGGGGAAGGAGAGC
GCTCTCCTTCCCCCGGGGC


 


1279
CCCCGGGGGAAGGAGAGCG
CGCTCTCCTTCCCCCGGGG


 


1280
CCCGGGGGAAGGAGAGCGC
GCGCTCTCCTTCCCCCGGG


 


1281
CCGGGGGAAGGAGAGCGCG
CGCGCTCTCCTTCCCCCGG


 


1282
CGGGGGAAGGAGAGCGCGA
TCGCGCTCTCCTTCCCCCG


 


1283
GGGGGAAGGAGAGCGCGAG
CTCGCGCTCTCCTTCCCCC


 


1284
GGGGAAGGAGAGCGCGAGC
GCTCGCGCTCTCCTTCCCC


 


1285
GGGAAGGAGAGCGCGAGCG
CGCTCGCGCTCTCCTTCCC


 


1286
GGAAGGAGAGCGCGAGCGC
GCGCTCGCGCTCTCCTTCC


 


1287
GAAGGAGAGCGCGAGCGCG
CGCGCTCGCGCTCTCCTTC


 


1288
AAGGAGAGCGCGAGCGCGC
GCGCGCTCGCGCTCTCCTT


 


1289
AGGAGAGCGCGAGCGCGCT
AGCGCGCTCGCGCTCTCCT


 


1290
GGAGAGCGCGAGCGCGCTG
CAGCGCGCTCGCGCTCTCC


 


1291
GAGAGCGCGAGCGCGCTGA
TCAGCGCGCTCGCGCTCTC


 


1292
AGAGCGCGAGCGCGCTGAG
CTCAGCGCGCTCGCGCTCT


 


1293
GAGCGCGAGCGCGCTGAGC
GCTCAGCGCGCTCGCGCTC


 


1294
AGCGCGAGCGCGCTGAGCA
TGCTCAGCGCGCTCGCGCT


 


1295
GCGCGAGCGCGCTGAGCAG
CTGCTCAGCGCGCTCGCGC


 


1296
CGCGAGCGCGCTGAGCAGA
TCTGCTCAGCGCGCTCGCG


 


1297
GCGAGCGCGCTGAGCAGAC
GTCTGCTCAGCGCGCTCGC


 


1298
CGAGCGCGCTGAGCAGACA
TGTCTGCTCAGCGCGCTCG


 


1299
GAGCGCGCTGAGCAGACAG
CTGTCTGCTCAGCGCGCTC


 


1300
AGCGCGCTGAGCAGACAGA
TCTGTCTGCTCAGCGCGCT


 


1301
GCGCGCTGAGCAGACAGAG
CTCTGTCTGCTCAGCGCGC


 


1302
CGCGCTGAGCAGACAGAGC
GCTCTGTCTGCTCAGCGCG


 


1303
GCGCTGAGCAGACAGAGCG
CGCTCTGTCTGCTCAGCGC


 


1304
CGCTGAGCAGACAGAGCGG
CCGCTCTGTCTGCTCAGCG


 


1305
GCTGAGCAGACAGAGCGGG
CCCGCTCTGTCTGCTCAGC


 


1306
CTGAGCAGACAGAGCGGGA
TCCCGCTCTGTCTGCTCAG


 


1307
TGAGCAGACAGAGCGGGAG
CTCCCGCTCTGTCTGCTCA


 


1308
GAGCAGACAGAGCGGGAGA
TCTCCCGCTCTGTCTGCTC


 


1309
AGCAGACAGAGCGGGAGAA
TTCTCCCGCTCTGTCTGCT


 


1310
GCAGACAGAGCGGGAGAAC
GTTCTCCCGCTCTGTCTGC


 


1311
CAGACAGAGCGGGAGAACG
CGTTCTCCCGCTCTGTCTG


 


1312
AGACAGAGCGGGAGAACGC
GCGTTCTCCCGCTCTGTCT


 


1313
GACAGAGCGGGAGAACGCG
CGCGTTCTCCCGCTCTGTC


 


1314
ACAGAGCGGGAGAACGCGT
ACGCGTTCTCCCGCTCTGT


 


1315
CAGAGCGGGAGAACGCGTC
GACGCGTTCTCCCGCTCTG


 


1316
AGAGCGGGAGAACGCGTCC
GGACGCGTTCTCCCGCTCT


 


1317
GAGCGGGAGAACGCGTCCT
AGGACGCGTTCTCCCGCTC


 


1318
AGCGGGAGAACGCGTCCTC
GAGGACGCGTTCTCCCGCT


 


1319
GCGGGAGAACGCGTCCTCG
CGAGGACGCGTTCTCCCGC


 


1320
CGGGAGAACGCGTCCTCGC
GCGAGGACGCGTTCTCCCG


 


1321
GGGAGAACGCGTCCTCGCC
GGCGAGGACGCGTTCTCCC


 


1322
GGAGAACGCGTCCTCGCCC
GGGCGAGGACGCGTTCTCC


 


1323
GAGAACGCGTCCTCGCCCG
CGGGCGAGGACGCGTTCTC


 


1324
AGAACGCGTCCTCGCCCGC
GCGGGCGAGGACGCGTTCT


 


1325
GAACGCGTCCTCGCCCGCC
GGCGGGCGAGGACGCGTTC


 


1326
AACGCGTCCTCGCCCGCCG
CGGCGGGCGAGGACGCGTT


 


1327
ACGCGTCCTCGCCCGCCGG
CCGGCGGGCGAGGACGCGT


 


1328
CGCGTCCTCGCCCGCCGGC
GCCGGCGGGCGAGGACGCG


 


1329
GCGTCCTCGCCCGCCGGCC
GGCCGGCGGGCGAGGACGC


 


1330
CGTCCTCGCCCGCCGGCCG
CGGCCGGCGGGCGAGGACG


 


1331
GTCCTCGCCCGCCGGCCGG
CCGGCCGGCGGGCGAGGAC


 


1332
TCCTCGCCCGCCGGCCGGG
CCCGGCCGGCGGGCGAGGA


 


1333
CCTCGCCCGCCGGCCGGGA
TCCCGGCCGGCGGGCGAGG


 


1334
CTCGCCCGCCGGCCGGGAG
CTCCCGGCCGGCGGGCGAG


 


1335
TCGCCCGCCGGCCGGGAGG
CCTCCCGGCCGGCGGGCGA


 


1336
CGCCCGCCGGCCGGGAGGC
GCCTCCCGGCCGGCGGGCG


 


1337
GCCCGCCGGCCGGGAGGCC
GGCCTCCCGGCCGGCGGGC


 


1338
CCCGCCGGCCGGGAGGCCC
GGGCCTCCCGGCCGGCGGG


 


1339
CCGCCGGCCGGGAGGCCCC
GGGGCCTCCCGGCCGGCGG


 


1340
CGCCGGCCGGGAGGCCCCG
CGGGGCCTCCCGGCCGGCG


 


1341
GCCGGCCGGGAGGCCCCGG
CCGGGGCCTCCCGGCCGGC


 


1342
CCGGCCGGGAGGCCCCGGA
TCCGGGGCCTCCCGGCCGG


 


1343
CGGCCGGGAGGCCCCGGAG
CTCCGGGGCCTCCCGGCCG


 


1344
GGCCGGGAGGCCCCGGAGC
GCTCCGGGGCCTCCCGGCC


 


1345
GCCGGGAGGCCCCGGAGCT
AGCTCCGGGGCCTCCCGGC


 


1346
CCGGGAGGCCCCGGAGCTG
CAGCTCCGGGGCCTCCCGG


 


1347
CGGGAGGCCCCGGAGCTGG
CCAGCTCCGGGGCCTCCCG


 


1348
GGGAGGCCCCGGAGCTGGC
GCCAGCTCCGGGGCCTCCC


 


1349
GGAGGCCCCGGAGCTGGCC
GGCCAGCTCCGGGGCCTCC


 


1350
GAGGCCCCGGAGCTGGCCC
GGGCCAGCTCCGGGGCCTC


 


1351
AGGCCCCGGAGCTGGCCCA
TGGGCCAGCTCCGGGGCCT


 


1352
GGCCCCGGAGCTGGCCCAT
ATGGGCCAGCTCCGGGGCC


 


1353
GCCCCGGAGCTGGCCCATG
CATGGGCCAGCTCCGGGGC


 


1354
CCCCGGAGCTGGCCCATGG
CCATGGGCCAGCTCCGGGG


 


1355
CCCGGAGCTGGCCCATGGG
CCCATGGGCCAGCTCCGGG


 


1356
CCGGAGCTGGCCCATGGGG
CCCCATGGGCCAGCTCCGG


 


1357
CGGAGCTGGCCCATGGGGA
TCCCCATGGGCCAGCTCCG


 


1358
GGAGCTGGCCCATGGGGAG
CTCCCCATGGGCCAGCTCC


 


1359
GAGCTGGCCCATGGGGAGC
GCTCCCCATGGGCCAGCTC


 


1360
AGCTGGCCCATGGGGAGCA
TGCTCCCCATGGGCCAGCT


 


1361
GCTGGCCCATGGGGAGCAG
CTGCTCCCCATGGGCCAGC


 


1362
CTGGCCCATGGGGAGCAGG
CCTGCTCCCCATGGGCCAG


 


1363
TGGCCCATGGGGAGCAGGC
GCCTGCTCCCCATGGGCCA


 


1364
GGCCCATGGGGAGCAGGCG
CGCCTGCTCCCCATGGGCC


 


1365
GCCCATGGGGAGCAGGCGC
GCGCCTGCTCCCCATGGGC


 


1366
CCCATGGGGAGCAGGCGCC
GGCGCCTGCTCCCCATGGG


 


1367
CCATGGGGAGCAGGCGCCC
GGGCGCCTGCTCCCCATGG


 


1368
CATGGGGAGCAGGCGCCCG
CGGGCGCCTGCTCCCCATG


 


1369
ATGGGGAGCAGGCGCCCGG
CCGGGCGCCTGCTCCCCAT


 


1370
TGGGGAGCAGGCGCCCGGT
ACCGGGCGCCTGCTCCCCA


 


1371
GGGGAGCAGGCGCCCGGTG
CACCGGGCGCCTGCTCCCC


 


1372
GGGAGCAGGCGCCCGGTGC
GCACCGGGCGCCTGCTCCC


 


1373
GGAGCAGGCGCCCGGTGCC
GGCACCGGGCGCCTGCTCC


 


1374
GAGCAGGCGCCCGGTGCCG
CGGCACCGGGCGCCTGCTC


 


1375
AGCAGGCGCCCGGTGCCGG
CCGGCACCGGGCGCCTGCT


 


1376
GCAGGCGCCCGGTGCCGGC
GCCGGCACCGGGCGCCTGC


 


1377
CAGGCGCCCGGTGCCGGCC
GGCCGGCACCGGGCGCCTG


 


1378
AGGCGCCCGGTGCCGGCCA
TGGCCGGCACCGGGCGCCT


 


1379
GGCGCCCGGTGCCGGCCAC
GTGGCCGGCACCGGGCGCC


 


1380
GCGCCCGGTGCCGGCCACG
CGTGGCCGGCACCGGGCGC


 


1381
CGCCCGGTGCCGGCCACGA
TCGTGGCCGGCACCGGGCG


 


1382
GCCCGGTGCCGGCCACGAC
GTCGTGGCCGGCACCGGGC


 


1383
CCCGGTGCCGGCCACGACG
CGTCGTGGCCGGCACCGGG


 


1384
CCGGTGCCGGCCACGACGA
TCGTCGTGGCCGGCACCGG


 


1385
CGGTGCCGGCCACGACGAC
GTCGTCGTGGCCGGCACCG


 


1386
GGTGCCGGCCACGACGACC
GGTCGTCGTGGCCGGCACC


 


1387
GTGCCGGCCACGACGACCG
CGGTCGTCGTGGCCGGCAC


 


1388
TGCCGGCCACGACGACCGC
GCGGTCGTCGTGGCCGGCA


 


1389
GCCGGCCACGACGACCGCC
GGCGGTCGTCGTGGCCGGC


 


1390
CCGGCCACGACGACCGCCA
TGGCGGTCGTCGTGGCCGG


 


1391
CGGCCACGACGACCGCCAC
GTGGCGGTCGTCGTGGCCG


 


1392
GGCCACGACGACCGCCACC
GGTGGCGGTCGTCGTGGCC


 


1393
GCCACGACGACCGCCACCG
CGGTGGCGGTCGTCGTGGC


 


1394
CCACGACGACCGCCACCGC
GCGGTGGCGGTCGTCGTGG


 


1395
CACGACGACCGCCACCGCC
GGCGGTGGCGGTCGTCGTG


 


1396
ACGACGACCGCCACCGCCC
GGGCGGTGGCGGTCGTCGT


 


1397
CGACGACCGCCACCGCCCG
CGGGCGGTGGCGGTCGTCG


 


1398
GACGACCGCCACCGCCCGC
GCGGGCGGTGGCGGTCGTC


 


1399
ACGACCGCCACCGCCCGCG
CGCGGGCGGTGGCGGTCGT


 


1400
CGACCGCCACCGCCCGCGC
GCGCGGGCGGTGGCGGTCG


 


1401
GACCGCCACCGCCCGCGCC
GGCGCGGGCGGTGGCGGTC


 


1402
ACCGCCACCGCCCGCGCCG
CGGCGCGGGCGGTGGCGGT


 


1403
CCGCCACCGCCCGCGCCGC
GCGGCGCGGGCGGTGGCGG


 


1404
CGCCACCGCCCGCGCCGCG
CGCGGCGCGGGCGGTGGCG


 


1405
GCCACCGCCCGCGCCGCGA
TCGCGGCGCGGGCGGTGGC


 


1406
CCACCGCCCGCGCCGCGAC
GTCGCGGCGCGGGCGGTGG


 


1407
CACCGCCCGCGCCGCGACC
GGTCGCGGCGCGGGCGGTG


 


1408
ACCGCCCGCGCCGCGACCG
CGGTCGCGGCGCGGGCGGT


 


1409
CCGCCCGCGCCGCGACCGG
CCGGTCGCGGCGCGGGCGG


 


1410
CGCCCGCGCCGCGACCGGC
GCCGGTCGCGGCGCGGGCG


 


1411
GCCCGCGCCGCGACCGGCC
GGCCGGTCGCGGCGCGGGC


 


1412
CCCGCGCCGCGACCGGCCG
CGGCCGGTCGCGGCGCGGG


 


1413
CCGCGCCGCGACCGGCCGG
CCGGCCGGTCGCGGCGCGG


 


1414
CGCGCCGCGACCGGCCGGT
ACCGGCCGGTCGCGGCGCG


 


1415
GCGCCGCGACCGGCCGGTG
CACCGGCCGGTCGCGGCGC


 


1416
CGCCGCGACCGGCCGGTGA
TCACCGGCCGGTCGCGGCG


 


1417
GCCGCGACCGGCCGGTGAA
TTCACCGGCCGGTCGCGGC


 


1418
CCGCGACCGGCCGGTGAAG
CTTCACCGGCCGGTCGCGG


 


1419
CGCGACCGGCCGGTGAAGC
GCTTCACCGGCCGGTCGCG


 


1420
GCGACCGGCCGGTGAAGCC
GGCTTCACCGGCCGGTCGC


 


1421
CGACCGGCCGGTGAAGCCC
GGGCTTCACCGGCCGGTCG


 


1422
GACCGGCCGGTGAAGCCCA
TGGGCTTCACCGGCCGGTC


 


1423
ACCGGCCGGTGAAGCCCAG
CTGGGCTTCACCGGCCGGT


 


1424
CCGGCCGGTGAAGCCCAGG
CCTGGGCTTCACCGGCCGG


 


1425
CGGCCGGTGAAGCCCAGGG
CCCTGGGCTTCACCGGCCG


 


1426
GGCCGGTGAAGCCCAGGGA
TCCCTGGGCTTCACCGGCC


 


1427
GCCGGTGAAGCCCAGGGAC
GTCCCTGGGCTTCACCGGC


 


1428
CCGGTGAAGCCCAGGGACC
GGTCCCTGGGCTTCACCGG


 


1429
CGGTGAAGCCCAGGGACCC
GGGTCCCTGGGCTTCACCG


 


1430
GGTGAAGCCCAGGGACCCC
GGGGTCCCTGGGCTTCACC


 


1431
GTGAAGCCCAGGGACCCCC
GGGGGTCCCTGGGCTTCAC


 


1432
TGAAGCCCAGGGACCCCCC
GGGGGGTCCCTGGGCTTCA


 


1433
GAAGCCCAGGGACCCCCCT
AGGGGGGTCCCTGGGCTTC


 


1434
AAGCCCAGGGACCCCCCTC
GAGGGGGGTCCCTGGGCTT


 


1435
AGCCCAGGGACCCCCCTCT
AGAGGGGGGTCCCTGGGCT


 


1436
GCCCAGGGACCCCCCTCTG
CAGAGGGGGGTCCCTGGGC


 


1437
CCCAGGGACCCCCCTCTGG
CCAGAGGGGGGTCCCTGGG


 


1438
CCAGGGACCCCCCTCTGGG
CCCAGAGGGGGGTCCCTGG


 


1439
CAGGGACCCCCCTCTGGGA
TCCCAGAGGGGGGTCCCTG


 


1440
AGGGACCCCCCTCTGGGAG
CTCCCAGAGGGGGGTCCCT


 


1441
GGGACCCCCCTCTGGGAGA
TCTCCCAGAGGGGGGTCCC


 


1442
GGACCCCCCTCTGGGAGAG
CTCTCCCAGAGGGGGGTCC


 


1443
GACCCCCCTCTGGGAGAGC
GCTCTCCCAGAGGGGGGTC


 


1444
ACCCCCCTCTGGGAGAGCC
GGCTCTCCCAGAGGGGGGT


 


1445
CCCCCCTCTGGGAGAGCCC
GGGCTCTCCCAGAGGGGGG


 


1446
CCCCCTCTGGGAGAGCCCC
GGGGCTCTCCCAGAGGGGG


 


1447
CCCCTCTGGGAGAGCCCCA
TGGGGCTCTCCCAGAGGGG


 


1448
CCCTCTGGGAGAGCCCCAT
ATGGGGCTCTCCCAGAGGG


 


1449
CCTCTGGGAGAGCCCCATG
CATGGGGCTCTCCCAGAGG


 


1450
CTCTGGGAGAGCCCCATGA
TCATGGGGCTCTCCCAGAG


 


1451
TCTGGGAGAGCCCCATGAG
CTCATGGGGCTCTCCCAGA


 


1452
CTGGGAGAGCCCCATGAGG
CCTCATGGGGCTCTCCCAG


 


1453
TGGGAGAGCCCCATGAGGG
CCCTCATGGGGCTCTCCCA


 


1454
GGGAGAGCCCCATGAGGGC
GCCCTCATGGGGCTCTCCC


 


1455
GGAGAGCCCCATGAGGGCA
TGCCCTCATGGGGCTCTCC


 


1456
GAGAGCCCCATGAGGGCAG
CTGCCCTCATGGGGCTCTC


 


1457
AGAGCCCCATGAGGGCAGG
CCTGCCCTCATGGGGCTCT


 


1458
GAGCCCCATGAGGGCAGGA
TCCTGCCCTCATGGGGCTC


 


1459
AGCCCCATGAGGGCAGGAG
CTCCTGCCCTCATGGGGCT


 


1460
GCCCCATGAGGGCAGGAGA
TCTCCTGCCCTCATGGGGC


 


1461
CCCCATGAGGGCAGGAGAG
CTCTCCTGCCCTCATGGGG


 


1462
CCCATGAGGGCAGGAGAGT
ACTCTCCTGCCCTCATGGG


 


1463
CCATGAGGGCAGGAGAGTG
CACTCTCCTGCCCTCATGG


 


1464
CATGAGGGCAGGAGAGTGA
TCACTCTCCTGCCCTCATG


 


1465
ATGAGGGCAGGAGAGTGAT
ATCACTCTCCTGCCCTCAT


 


1466
TGAGGGCAGGAGAGTGATG
CATCACTCTCCTGCCCTCA


 


1467
GAGGGCAGGAGAGTGATGG
CCATCACTCTCCTGCCCTC


 


1468
AGGGCAGGAGAGTGATGGA
TCCATCACTCTCCTGCCCT


 


1469
GGGCAGGAGAGTGATGGAG
CTCCATCACTCTCCTGCCC


 


1470
GGCAGGAGAGTGATGGAGA
TCTCCATCACTCTCCTGCC


 


1471
GCAGGAGAGTGATGGAGAG
CTCTCCATCACTCTCCTGC


 


1472
CAGGAGAGTGATGGAGAGT
ACTCTCCATCACTCTCCTG


 


1473
AGGAGAGTGATGGAGAGTA
TACTCTCCATCACTCTCCT


 


1474
GGAGAGTGATGGAGAGTAC
GTACTCTCCATCACTCTCC


 


1475
GAGAGTGATGGAGAGTACG
CGTACTCTCCATCACTCTC


 


1476
AGAGTGATGGAGAGTACGC
GCGTACTCTCCATCACTCT


 


1477
GAGTGATGGAGAGTACGCC
GGCGTACTCTCCATCACTC


 


1478
AGTGATGGAGAGTACGCCC
GGGCGTACTCTCCATCACT


 


1479
GTGATGGAGAGTACGCCCA
TGGGCGTACTCTCCATCAC


 


1480
TGATGGAGAGTACGCCCAG
CTGGGCGTACTCTCCATCA


 


1481
GATGGAGAGTACGCCCAGC
GCTGGGCGTACTCTCCATC


 


1482
ATGGAGAGTACGCCCAGCT
AGCTGGGCGTACTCTCCAT


 


1483
TGGAGAGTACGCCCAGCTT
AAGCTGGGCGTACTCTCCA


 


1484
GGAGAGTACGCCCAGCTTC
GAAGCTGGGCGTACTCTCC


 


1485
GAGAGTACGCCCAGCTTCC
GGAAGCTGGGCGTACTCTC


 


1486
AGAGTACGCCCAGCTTCCT
AGGAAGCTGGGCGTACTCT


 


1487
GAGTACGCCCAGCTTCCTG
CAGGAAGCTGGGCGTACTC


 


1488
AGTACGCCCAGCTTCCTGA
TCAGGAAGCTGGGCGTACT


 


1489
GTACGCCCAGCTTCCTGAA
TTCAGGAAGCTGGGCGTAC


 


1490
TACGCCCAGCTTCCTGAAG
CTTCAGGAAGCTGGGCGTA


 


1491
ACGCCCAGCTTCCTGAAGG
CCTTCAGGAAGCTGGGCGT


 


1492
CGCCCAGCTTCCTGAAGGG
CCCTTCAGGAAGCTGGGCG


 


1493
GCCCAGCTTCCTGAAGGGC
GCCCTTCAGGAAGCTGGGC


 


1494
CCCAGCTTCCTGAAGGGCA
TGCCCTTCAGGAAGCTGGG


 


1495
CCAGCTTCCTGAAGGGCAC
GTGCCCTTCAGGAAGCTGG


 


1496
CAGCTTCCTGAAGGGCACC
GGTGCCCTTCAGGAAGCTG


 


1497
AGCTTCCTGAAGGGCACCC
GGGTGCCCTTCAGGAAGCT


 


1498
GCTTCCTGAAGGGCACCCC
GGGGTGCCCTTCAGGAAGC


 


1499
CTTCCTGAAGGGCACCCCA
TGGGGTGCCCTTCAGGAAG


 


1500
TTCCTGAAGGGCACCCCAA
TTGGGGTGCCCTTCAGGAA


 


1501
TCCTGAAGGGCACCCCAAC
GTTGGGGTGCCCTTCAGGA


 


1502
CCTGAAGGGCACCCCAACC
GGTTGGGGTGCCCTTCAGG


 


1503
CTGAAGGGCACCCCAACCT
AGGTTGGGGTGCCCTTCAG


 


1504
TGAAGGGCACCCCAACCTG
CAGGTTGGGGTGCCCTTCA


 


1505
GAAGGGCACCCCAACCTGG
CCAGGTTGGGGTGCCCTTC


 


1506
AAGGGCACCCCAACCTGGG
CCCAGGTTGGGGTGCCCTT


 


1507
AGGGCACCCCAACCTGGGA
TCCCAGGTTGGGGTGCCCT


 


1508
GGGCACCCCAACCTGGGAG
CTCCCAGGTTGGGGTGCCC


 


1509
GGCACCCCAACCTGGGAGA
TCTCCCAGGTTGGGGTGCC


 


1510
GCACCCCAACCTGGGAGAA
TTCTCCCAGGTTGGGGTGC


 


1511
CACCCCAACCTGGGAGAAG
CTTCTCCCAGGTTGGGGTG


 


1512
ACCCCAACCTGGGAGAAGA
TCTTCTCCCAGGTTGGGGT


 


1513
CCCCAACCTGGGAGAAGAC
GTCTTCTCCCAGGTTGGGG


 


1514
CCCAACCTGGGAGAAGACG
CGTCTTCTCCCAGGTTGGG


 


1515
CCAACCTGGGAGAAGACGG
CCGTCTTCTCCCAGGTTGG


 


1516
CAACCTGGGAGAAGACGGC
GCCGTCTTCTCCCAGGTTG


 


1517
AACCTGGGAGAAGACGGCC
GGCCGTCTTCTCCCAGGTT


 


1518
ACCTGGGAGAAGACGGCCC
GGGCCGTCTTCTCCCAGGT


 


1519
CCTGGGAGAAGACGGCCCC
GGGGCCGTCTTCTCCCAGG


 


1520
CTGGGAGAAGACGGCCCCA
TGGGGCCGTCTTCTCCCAG


 


1521
TGGGAGAAGACGGCCCCAG
CTGGGGCCGTCTTCTCCCA


 


1522
GGGAGAAGACGGCCCCAGA
TCTGGGGCCGTCTTCTCCC


 


1523
GGAGAAGACGGCCCCAGAG
CTCTGGGGCCGTCTTCTCC


 


1524
GAGAAGACGGGGCCAGAGA
TCTCTGGGGCCGTCTTCTC


 


1525
AGAAGACGGCCCCAGAGAA
TTCTCTGGGGCCGTCTTCT


 


1526
GAAGACGGCCCCAGAGAAC
GTTCTCTGGGGCCGTCTTC


 


1527
AAGACGGCCCCAGAGAACG
CGTTCTCTGGGGCCGTCTT


 


1528
AGACGGCCCCAGAGAACGG
CCGTTCTCTGGGGCCGTCT


 


1529
GACGGCCCCAGAGAACGGC
GCCGTTCTCTGGGGCCGTC


 


1530
ACGGCCCCAGAGAACGGCA
TGCCGTTCTCTGGGGCCGT


 


1531
CGGCCCCAGAGAACGGCAT
ATGCCGTTCTCTGGGGCCG


 


1532
GGCCCCAGAGAACGGCATC
GATGCCGTTCTCTGGGGCC


 


1533
GCCCCAGAGAACGGCATCG
CGATGCCGTTCTCTGGGGC


 


1534
CCCCAGAGAACGGCATCGT
ACGATGCCGTTCTCTGGGG


 


1535
CCCAGAGAACGGCATCGTG
CACGATGCCGTTCTCTGGG


 


1536
CCAGAGAACGGCATCGTGA
TCACGATGCCGTTCTCTGG


 


1537
CAGAGAACGGCATCGTGAG
CTCACGATGCCGTTCTCTG


 


1538
AGAGAACGGCATCGTGAGA
TCTCACGATGCCGTTCTCT


 


1539
GAGAACGGCATCGTGAGAC
GTCTCACGATGCCGTTCTC


 


1540
AGAACGGCATCGTGAGACA
TGTCTCACGATGCCGTTCT


 


1541
GAACGGCATCGTGAGACAG
CTGTCTCACGATGCCGTTC


 


1542
AACGGCATCGTGAGACAGG
CCTGTCTCACGATGCCGTT


 


1543
ACGGCATCGTGAGACAGGA
TCCTGTCTCACGATGCCGT


 


1544
CGGCATCGTGAGACAGGAG
CTCCTGTCTCACGATGCCG


 


1545
GGCATCGTGAGACAGGAGC
GCTCCTGTCTCACGATGCC


 


1546
GCATCGTGAGACAGGAGCC
GGCTCCTGTCTCACGATGC


 


1547
CATCGTGAGACAGGAGCCC
GGGCTCCTGTCTCACGATG


 


1548
ATCGTGAGACAGGAGCCCG
CGGGCTCCTGTCTCACGAT


 


1549
TCGTGAGACAGGAGCCCGG
CCGGGCTCCTGTCTCACGA


 


1550
CGTGAGACAGGAGCCCGGC
GCCGGGCTCCTGTCTCACG


 


1551
GTGAGACAGGAGCCCGGCA
TGCCGGGCTCCTGTCTCAC


 


1552
TGAGACAGGAGCCCGGCAG
CTGCCGGGCTCCTGTCTCA


 


1553
GAGACAGGAGCCCGGCAGC
GCTGCCGGGCTCCTGTCTC


 


1554
AGACAGGAGCCCGGCAGCC
GGCTGCCGGGCTCCTGTCT


 


1555
GACAGGAGCCCGGCAGCCC
GGGCTGCCGGGCTCCTGTC


 


1556
ACAGGAGCCCGGCAGCCCG
CGGGCTGCCGGGCTCCTGT


 


1557
CAGGAGCCCGGCAGCCCGC
GCGGGCTGCCGGGCTCCTG


 


1558
AGGAGCCCGGCAGCCCGCC
GGCGGGCTGCCGGGCTCCT


 


1559
GGAGCCCGGCAGCCCGCCT
AGGCGGGCTGCCGGGCTCC


 


1560
GAGCCCGGCAGCCCGCCTC
GAGGCGGGCTGCCGGGCTC


 


1561
AGCCCGGCAGCCCGCCTCG
CGAGGCGGGCTGCCGGGCT


 


1562
GCCCGGCAGCCCGCCTCGA
TCGAGGCGGGCTGCCGGGC


 


1563
CCCGGCAGCCCGCCTCGAG
CTCGAGGCGGGCTGCCGGG


 


1564
CCGGCAGCCCGCCTCGAGA
TCTCGAGGCGGGCTGCCGG


 


1565
CGGCAGCCCGCCTCGAGAT
ATCTCGAGGCGGGCTGCCG


 


1566
GGCAGCCCGCCTCGAGATG
CATCTCGAGGCGGGCTGCC


 


1567
GCAGCCCGCCTCGAGATGG
CCATCTCGAGGCGGGCTGC


 


1568
CAGCCCGCCTCGAGATGGA
TCCATCTCGAGGCGGGCTG


 


1569
AGCCCGCCTCGAGATGGAC
GTCCATCTCGAGGCGGGCT


 


1570
GCCCGCCTCGAGATGGACT
AGTCCATCTCGAGGCGGGC


 


1571
CCCGCCTCGAGATGGACTG
CAGTCCATCTCGAGGCGGG


 


1572
CCGCCTCGAGATGGACTGC
GCAGTCCATCTCGAGGCGG


 


1573
CGCCTCGAGATGGACTGCA
TGCAGTCCATCTCGAGGCG


 


1574
GCCTCGAGATGGACTGCAC
GTGCAGTCCATCTCGAGGC


 


1575
CCTCGAGATGGACTGCACC
GGTGCAGTCCATCTCGAGG


 


1576
CTCGAGATGGACTGCACCA
TGGTGCAGTCCATCTCGAG


 


1577
TCGAGATGGACTGCACCAT
ATGGTGCAGTCCATCTCGA


 


1578
CGAGATGGACTGCACCATG
CATGGTGCAGTCCATCTCG


 


1579
GAGATGGACTGCACCATGG
CCATGGTGCAGTCCATCTC


 


1580
AGATGGACTGCACCATGGG
CCCATGGTGCAGTCCATCT


 


1581
GATGGACTGCACCATGGGC
GCCCATGGTGCAGTCCATC


 


1582
ATGGACTGCACCATGGGCC
GGCCCATGGTGCAGTCCAT


 


1583
TGGACTGCACCATGGGCCG
CGGCCCATGGTGCAGTCCA


 


1584
GGACTGCACCATGGGCCGC
GCGGCCCATGGTGCAGTCC


 


1585
GACTGCACCATGGGCCGCT
AGCGGCCCATGGTGCAGTC


 


1586
ACTGCACCATGGGCCGCTG
CAGCGGCCCATGGTGCAGT


 


1587
CTGCACCATGGGCCGCTGT
ACAGCGGCCCATGGTGCAG


 


1588
TGCACCATGGGCCGCTGTG
CACAGCGGCCCATGGTGCA


 


1589
GCACCATGGGCCGCTGTGC
GCACAGCGGCCCATGGTGC


 


1590
CACCATGGGCCGCTGTGCC
GGCACAGCGGCCCATGGTG


 


1591
ACCATGGGCCGCTGTGCCT
AGGCACAGCGGCCCATGGT


 


1592
CCATGGGCCGCTGTGCCTG
CAGGCACAGCGGCCCATGG


 


1593
CATGGGCCGCTGTGCCTGG
CCAGGCACAGCGGCCCATG


 


1594
ATGGGCCGCTGTGCCTGGG
CCCAGGCACAGCGGCCCAT


 


1595
TGGGCCGCTGTGCCTGGGA
TCCCAGGCACAGCGGCCCA


 


1596
GGGCCGCTGTGCCTGGGAG
CTCCCAGGCACAGCGGCCC


 


1597
GGCCGCTGTGCCTGGGAGA
TCTCCCAGGCACAGCGGCC


 


1598
GCCGCTGTGCCTGGGAGAG
CTCTCCCAGGCACAGCGGC


 


1599
CCGCTGTGCCTGGGAGAGC
GCTCTCCCAGGCACAGCGG


 


1600
CGCTGTGCCTGGGAGAGCC
GGCTCTCCCAGGCACAGCG


 


1601
GCTGTGCCTGGGAGAGCCT
AGGCTCTCCCAGGCACAGC


 


1602
CTGTGCCTGGGAGAGCCTG
CAGGCTCTCCCAGGCACAG


 


1603
TGTGCCTGGGAGAGCCTGC
GCAGGCTCTCCCAGGCACA


 


1604
GTGCCTGGGAGAGCCTGCT
AGCAGGCTCTCCCAGGCAC


 


1605
TGCCTGGGAGAGCCTGCTC
GAGCAGGCTCTCCCAGGCA


 


1606
GCCTGGGAGAGCCTGCTCC
GGAGCAGGCTCTCCCAGGC


 


1607
CCTGGGAGAGCCTGCTCCC
GGGAGCAGGCTCTCCCAGG


 


1608
CTGGGAGAGCCTGCTCCCT
AGGGAGCAGGCTCTCCCAG


 


1609
TGGGAGAGCCTGCTCCCTT
AAGGGAGCAGGCTCTCCCA


 


1610
GGGAGAGCCTGCTCCCTTT
AAAGGGAGCAGGCTCTCCC


 


1611
GGAGAGCCTGCTCCCTTTT
AAAAGGGAGCAGGCTCTCC


 


1612
GAGAGCCTGCTCCCTTTTG
CAAAAGGGAGCAGGCTCTC


 


1613
AGAGCCTGCTCCCTTTTGG
CCAAAAGGGAGCAGGCTCT


 


1614
GAGCCTGCTCCCTTTTGGA
TCCAAAAGGGAGCAGGCTC


 


1615
AGCCTGCTCCCTTTTGGAG
CTCCAAAAGGGAGCAGGCT


 


1616
GCCTGCTCCCTTTTGGAGG
CCTCCAAAAGGGAGCAGGC


 


1617
CCTGCTCCCTTTTGGAGGG
CCCTCCAAAAGGGAGCAGG


 


1618
CTGCTCCCTTTTGGAGGGG
CCCCTCCAAAAGGGAGCAG


 


1619
TGCTCCCTTTTGGAGGGGC
GCCCCTCCAAAAGGGAGCA


 


1620
GCTCCCTTTTGGAGGGGCG
CGCCCCTCCAAAAGGGAGC


 


1621
CTCCCTTTTGGAGGGGCGT
ACGCCCCTCCAAAAGGGAG


 


1622
TCCCTTTTGGAGGGGCGTC
GACGCCCCTCCAAAAGGGA


 


1623
CCCTTTTGGAGGGGCGTCC
GGACGCCCCTCCAAAAGGG


 


1624
CCTTTTGGAGGGGCGTCCT
AGGACGCCCCTCCAAAAGG


 


1625
CTTTTGGAGGGGCGTCCTG
CAGGACGCCCCTCCAAAAG


 


1626
TTTTGGAGGGGCGTCCTGA
TCAGGACGCCCCTCCAAAA


 


1627
TTTGGAGGGGCGTCCTGAG
CTCAGGACGCCCCTCCAAA


 


1628
TTGGAGGGGCGTCCTGAGC
GCTCAGGACGCCCCTCCAA


 


1629
TGGAGGGGCGTCCTGAGCA
TGCTCAGGACGCCCCTCCA


 


1630
GGAGGGGCGTCCTGAGCAC
GTGCTCAGGACGCCCCTCC


 


1631
GAGGGGCGTCCTGAGCACC
GGTGCTCAGGACGCCCCTC


 


1632
AGGGGCGTCCTGAGCACCC
GGGTGCTCAGGACGCCCCT


 


1633
GGGGCGTCCTGAGCACCCC
GGGGTGCTCAGGACGCCCC


 


1634
GGGCGTCCTGAGCACCCCA
TGGGGTGCTCAGGACGCCC


 


1635
GGCGTCCTGAGCACCCCAG
CTGGGGTGCTCAGGACGCC


 


1636
GCGTCCTGAGCACCCCAGA
TCTGGGGTGCTCAGGACGC


 


1637
CGTCCTGAGCACCCCAGAC
GTCTGGGGTGCTCAGGACG


 


1638
GTCCTGAGCACCCCAGACT
AGTCTGGGGTGCTCAGGAC


 


1639
TCCTGAGCACCCCAGACTC
GAGTCTGGGGTGCTCAGGA


 


1640
CCTGAGCACCCCAGACTCC
GGAGTCTGGGGTGCTCAGG


 


1641
CTGAGCACCCCAGACTCCT
AGGAGTCTGGGGTGCTCAG


 


1642
TGAGCACCCCAGACTCCTG
CAGGAGTCTGGGGTGCTCA


 


1643
GAGCACCCCAGACTCCTGG
CCAGGAGTCTGGGGTGCTC


 


1644
AGCACCCCAGACTCCTGGC
GCCAGGAGTCTGGGGTGCT


 


1645
GCACCCCAGACTCCTGGCT
AGCCAGGAGTCTGGGGTGC


 


1646
CACCCCAGACTCCTGGCTT
AAGCCAGGAGTCTGGGGTG


 


1647
ACCCCAGACTCCTGGCTTC
GAAGCCAGGAGTCTGGGGT


 


1648
CCCCAGACTCCTGGCTTCC
GGAAGCCAGGAGTCTGGGG


 


1649
CCCAGACTCCTGGCTTCCC
GGGAAGCCAGGAGTCTGGG


 


1650
CCAGACTCCTGGCTTCCCC
GGGGAAGCCAGGAGTCTGG


 


1651
CAGACTCCTGGCTTCCCCC
GGGGGAAGCCAGGAGTCTG


 


1652
AGACTCCTGGCTTCCCCCT
AGGGGGAAGCCAGGAGTCT


 


1653
GACTCCTGGCTTCCCCCTG
CAGGGGGAAGCCAGGAGTC


 


1654
ACTCCTGGCTTCCCCCTGG
CCAGGGGGAAGCCAGGAGT


 


1655
CTCCTGGCTTCCCCCTGGC
GCCAGGGGGAAGCCAGGAG


 


1656
TCCTGGCTTCCCCCTGGCT
AGCCAGGGGGAAGCCAGGA


 


1657
CCTGGCTTCCCCCTGGCTT
AAGCCAGGGGGAAGCCAGG


 


1658
CTGGCTTCCCCCTGGCTTC
GAAGCCAGGGGGAAGCCAG


 


1659
TGGCTTCCCCCTGGCTTCC
GGAAGCCAGGGGGAAGCCA


 


1660
GGCTTCCCCCTGGCTTCCC
GGGAAGCCAGGGGGAAGCC


 


1661
GCTTCCCCCTGGCTTCCCC
GGGGAAGCCAGGGGGAAGC


 


1662
CTTCCCCCTGGCTTCCCCC
GGGGGAAGCCAGGGGGAAG


 


1663
TTCCCCCTGGCTTCCCCCA
TGGGGGAAGCCAGGGGGAA


 


1664
TCCCCCTGGCTTCCCCCAG
CTGGGGGAAGCCAGGGGGA


 


1665
CCCCCTGGCTTCCCCCAGG
CCTGGGGGAAGCCAGGGGG


 


1666
CCCCTGGCTTCCCCCAGGG
CCCTGGGGGAAGCCAGGGG


 


1667
CCCTGGCTTCCCCCAGGGC
GCCCTGGGGGAAGCCAGGG


 


1668
CCTGGCTTCCCCCAGGGCC
GGCCCTGGGGGAAGCCAGG


 


1669
CTGGCTTCCCCCAGGGCCC
GGGCCCTGGGGGAAGCCAG


 


1670
TGGCTTCCCCCAGGGCCCC
GGGGCCCTGGGGGAAGCCA


 


1671
GGCTTCCCCCAGGGCCCCA
TGGGGCCCTGGGGGAAGCC


 


1672
GCTTCCCCCAGGGCCCCAA
TTGGGGCCCTGGGGGAAGC


 


1673
CTTCCCCCAGGGCCCCAAG
CTTGGGGCCCTGGGGGAAG


 


1674
TTCCCCCAGGGCCCCAAGG
CCTTGGGGCCCTGGGGGAA


 


1675
TCCCCCAGGGCCCCAAGGA
TCCTTGGGGCCCTGGGGGA


 


1676
CCCCCAGGGCCCCAAGGAC
GTCCTTGGGGCCCTGGGGG


 


1677
CCCCAGGGCCCCAAGGACA
TGTCCTTGGGGCCCTGGGG


 


1678
CCCAGGGCCCCAAGGACAT
ATGTCCTTGGGGCCCTGGG


 


1679
CCAGGGCCCCAAGGACATG
CATGTCCTTGGGGCCCTGG


 


1680
CAGGGCCCCAAGGACATGC
GCATGTCCTTGGGGCCCTG


 


1681
AGGGCCCCAAGGACATGCT
AGCATGTCCTTGGGGCCCT


 


1682
GGGCCCCAAGGACATGCTC
GAGCATGTCCTTGGGGCCC


 


1683
GGCCCCAAGGACATGCTCC
GGAGCATGTCCTTGGGGCC


 


1684
GCCCCAAGGACATGCTCCC
GGGAGCATGTCCTTGGGGC


 


1685
CCCCAAGGACATGCTCCCA
TGGGAGCATGTCCTTGGGG


 


1686
CCCAAGGACATGCTCCCAC
GTGGGAGCATGTCCTTGGG


 


1687
CCAAGGACATGCTCCCACT
AGTGGGAGCATGTCCTTGG


 


1688
CAAGGACATGCTCCCACTT
AAGTGGGAGCATGTCCTTG


 


1689
AAGGACATGCTCCCACTTG
CAAGTGGGAGCATGTCCTT


 


1690
AGGACATGCTCCCACTTGT
ACAAGTGGGAGCATGTCCT


 


1691
GGACATGCTCCCACTTGTG
CACAAGTGGGAGCATGTCC


 


1692
GACATGCTCCCACTTGTGG
CCACAAGTGGGAGCATGTC


 


1693
ACATGCTCCCACTTGTGGA
TCCACAAGTGGGAGCATGT


 


1694
CATGCTCCCACTTGTGGAG
CTCCACAAGTGGGAGCATG


 


1695
ATGCTCCCACTTGTGGAGG
CCTCCACAAGTGGGAGCAT


 


1696
TGCTCCCACTTGTGGAGGG
CCCTCCACAAGTGGGAGCA


 


1697
GCTCCCACTTGTGGAGGGC
GCCCTCCACAAGTGGGAGC


 


1698
CTCCCACTTGTGGAGGGCG
CGCCCTCCACAAGTGGGAG


 


1699
TCCCACTTGTGGAGGGCGA
TCGCCCTCCACAAGTGGGA


 


1700
CCCACTTGTGGAGGGCGAG
CTCGCCCTCCACAAGTGGG


 


1701
CCACTTGTGGAGGGCGAGG
CCTCGCCCTCCACAAGTGG


 


1702
CACTTGTGGAGGGCGAGGG
CCCTCGCCCTCCACAAGTG


 


1703
ACTTGTGGAGGGCGAGGGC
GCCCTCGCCCTCCACAAGT


 


1704
CTTGTGGAGGGCGAGGGCC
GGCCCTCGCCCTCCACAAG


 


1705
TTGTGGAGGGCGAGGGCCC
GGGCCCTCGCCCTCCACAA


 


1706
TGTGGAGGGCGAGGGCCCC
GGGGCCCTCGCCCTCCACA


 


1707
GTGGAGGGCGAGGGCCCCC
GGGGGCCCTCGCCCTCCAC


 


1708
TGGAGGGCGAGGGCCCCCA
TGGGGGCCCTCGCCCTCCA


 


1709
GGAGGGCGAGGGCCCCCAG
CTGGGGGCCCTCGCCCTCC


 


1710
GAGGGCGAGGGCCCCCAGA
TCTGGGGGCCCTCGCCCTC


 


1711
AGGGCGAGGGCCCCCAGAA
TTCTGGGGGCCCTCGCCCT


 


1712
GGGCGAGGGCCCCCAGAAT
ATTCTGGGGGCCCTCGCCC


 


1713
GGCGAGGGCCCCCAGAATG
CATTCTGGGGGCCCTCGCC


 


1714
GCGAGGGCCCCCAGAATGG
CCATTCTGGGGGCCCTCGC


 


1715
CGAGGGCCCCCAGAATGGG
CCCATTCTGGGGGCCCTCG


 


1716
GAGGGCCCCCAGAATGGGG
CCCCATTCTGGGGGCCCTC


 


1717
AGGGCCCCCAGAATGGGGA
TCCCCATTCTGGGGGCCCT


 


1718
GGGCCCCCAGAATGGGGAG
CTCCCCATTCTGGGGGCCC


 


1719
GGCCCCCAGAATGGGGAGA
TCTCCCCATTCTGGGGGCC


 


1720
GCCCCCAGAATGGGGAGAG
CTCTCCCCATTCTGGGGGC


 


1721
CCCCCAGAATGGGGAGAGG
CCTCTCCCCATTCTGGGGG


 


1722
CCCCAGAATGGGGAGAGGA
TCCTCTCCCCATTCTGGGG


 


1723
CCCAGAATGGGGAGAGGAA
TTCCTCTCCCCATTCTGGG


 


1724
CCAGAATGGGGAGAGGAAG
CTTCCTCTCCCCATTCTGG


 


1725
CAGAATGGGGAGAGGAAGG
CCTTCCTCTCCCCATTCTG


 


1726
AGAATGGGGAGAGGAAGGT
ACCTTCCTCTCCCCATTCT


 


1727
GAATGGGGAGAGGAAGGTC
GACCTTCCTCTCCCCATTC


 


1728
AATGGGGAGAGGAAGGTCA
TGACCTTCCTCTCCCCATT


 


1729
ATGGGGAGAGGAAGGTCAA
TTGACCTTCCTCTCCCCAT


 


1730
TGGGGAGAGGAAGGTCAAC
GTTGACCTTCCTCTCCCCA


 


1731
GGGGAGAGGAAGGTCAACT
AGTTGACCTTCCTCTCCCC


 


1732
GGGAGAGGAAGGTCAACTG
CAGTTGACCTTCCTCTCCC


 


1733
GGAGAGGAAGGTCAACTGG
CCAGTTGACCTTCCTCTCC


 


1734
GAGAGGAAGGTCAACTGGC
GCCAGTTGACCTTCCTCTC


 


1735
AGAGGAAGGTCAACTGGCT
AGCCAGTTGACCTTCCTCT


 


1736
GAGGAAGGTCAACTGGCTG
CAGCCAGTTGACCTTCCTC


 


1737
AGGAAGGTCAACTGGCTGG
CCAGCCAGTTGACCTTCCT


 


1738
GGAAGGTCAACTGGCTGGG
CCCAGCCAGTTGACCTTCC


 


1739
GAAGGTCAACTGGCTGGGC
GCCCAGCCAGTTGACCTTC


 


1740
AAGGTCAACTGGCTGGGCA
TGCCCAGCCAGTTGACCTT


 


1741
AGGTCAACTGGCTGGGCAG
CTGCCCAGCCAGTTGACCT


 


1742
GGTCAACTGGCTGGGCAGC
GCTGCCCAGCCAGTTGACC


 


1743
GTCAACTGGCTGGGCAGCA
TGCTGCCCAGCCAGTTGAC


 


1744
TCAACTGGCTGGGCAGCAA
TTGCTGCCCAGCCAGTTGA


 


1745
CAACTGGCTGGGCAGCAAA
TTTGCTGCCCAGCCAGTTG


 


1746
AACTGGCTGGGCAGCAAAG
CTTTGCTGCCCAGCCAGTT


 


1747
ACTGGCTGGGCAGCAAAGA
TCTTTGCTGCCCAGCCAGT


 


1748
CTGGCTGGGCAGCAAAGAG
CTCTTTGCTGCCCAGCCAG


 


1749
TGGCTGGGCAGCAAAGAGG
CCTCTTTGCTGCCCAGCCA


 


1750
GGCTGGGCAGCAAAGAGGG
CCCTCTTTGCTGCCCAGCC


 


1751
GCTGGGCAGCAAAGAGGGA
TCCCTCTTTGCTGCCCAGC


 


1752
CTGGGCAGCAAAGAGGGAC
GTCCCTCTTTGCTGCCCAG


 


1753
TGGGCAGCAAAGAGGGACT
AGTCCCTCTTTGCTGCCCA


 


1754
GGGCAGCAAAGAGGGACTG
CAGTCCCTCTTTGCTGCCC


 


1755
GGCAGCAAAGAGGGACTGC
GCAGTCCCTCTTTGCTGCC


 


1756
GCAGCAAAGAGGGACTGCG
CGCAGTCCCTCTTTGCTGC


 


1757
CAGCAAAGAGGGACTGCGC
GCGCAGTCCCTCTTTGCTG


 


1758
AGCAAAGAGGGACTGCGCT
AGCGCAGTCCCTCTTTGCT


 


1759
GCAAAGAGGGACTGCGCTG
CAGCGCAGTCCCTCTTTGC


 


1760
CAAAGAGGGACTGCGCTGG
CCAGCGCAGTCCCTCTTTG


 


1761
AAAGAGGGACTGCGCTGGA
TCCAGCGCAGTCCCTCTTT


 


1762
AAGAGGGACTGCGCTGGAA
TTCCAGCGCAGTCCCTCTT


 


1763
AGAGGGACTGCGCTGGAAG
CTTCCAGCGCAGTCCCTCT


 


1764
GAGGGACTGCGCTGGAAGG
CCTTCCAGCGCAGTCCCTC


 


1765
AGGGACTGCGCTGGAAGGA
TCCTTCCAGCGCAGTCCCT


 


1766
GGGACTGCGCTGGAAGGAG
CTCCTTCCAGCGCAGTCCC


 


1767
GGACTGCGCTGGAAGGAGG
CCTCCTTCCAGCGCAGTCC


 


1768
GACTGCGCTGGAAGGAGGC
GCCTCCTTCCAGCGCAGTC


 


1769
ACTGCGCTGGAAGGAGGCC
GGCCTCCTTCCAGCGCAGT


 


1770
CTGCGCTGGAAGGAGGCCA
TGGCCTCCTTCCAGCGCAG


 


1771
TGCGCTGGAAGGAGGCCAT
ATGGCCTCCTTCCAGCGCA


 


1772
GCGCTGGAAGGAGGCCATG
CATGGCCTCCTTCCAGCGC


 


1773
CGCTGGAAGGAGGCCATGC
GCATGGCCTCCTTCCAGCG


 


1774
GCTGGAAGGAGGCCATGCT
AGCATGGCCTCCTTCCAGC


 


1775
CTGGAAGGAGGCCATGCTT
AAGCATGGCCTCCTTCCAG


 


1776
TGGAAGGAGGCCATGCTTA
TAAGCATGGCCTCCTTCCA


 


1777
GGAAGGAGGCCATGCTTAC
GTAAGCATGGCCTCCTTCC


 


1778
GAAGGAGGCCATGCTTACC
GGTAAGCATGGCCTCCTTC


 


1779
AAGGAGGCCATGCTTACCC
GGGTAAGCATGGCCTCCTT


 


1780
AGGAGGCCATGCTTACCCA
TGGGTAAGCATGGCCTCCT


 


1781
GGAGGCCATGCTTACCCAT
ATGGGTAAGCATGGCCTCC


 


1782
GAGGCCATGCTTACCCATC
GATGGGTAAGCATGGCCTC


 


1783
AGGCCATGCTTACCCATCC
GGATGGGTAAGCATGGCCT


 


1784
GGCCATGCTTACCCATCCG
CGGATGGGTAAGCATGGCC


 


1785
GCCATGCTTACCCATCCGC
GCGGATGGGTAAGCATGGC


 


1786
CCATGCTTACCCATCCGCT
AGCGGATGGGTAAGCATGG


 


1787
CATGCTTACCCATCCGCTG
CAGCGGATGGGTAAGCATG


 


1788
ATGCTTACCCATCCGCTGG
CCAGCGGATGGGTAAGCAT


 


1789
TGCTTACCCATCCGCTGGC
GCCAGCGGATGGGTAAGCA


 


1790
GCTTACCCATCCGCTGGCA
TGCCAGCGGATGGGTAAGC


 


1791
CTTACCCATCCGCTGGCAT
ATGCCAGCGGATGGGTAAG


 


1792
TTACCCATCCGCTGGCATT
AATGCCAGCGGATGGGTAA


 


1793
TACCCATCCGCTGGCATTC
GAATGCCAGCGGATGGGTA


 


1794
ACCCATCCGCTGGCATTCT
AGAATGCCAGCGGATGGGT


 


1795
CCCATCCGCTGGCATTCTG
CAGAATGCCAGCGGATGGG


 


1796
CCATCCGCTGGCATTCTGC
GCAGAATGCCAGCGGATGG


 


1797
CATCCGCTGGCATTCTGCG
CGCAGAATGCCAGCGGATG


 


1798
ATCCGCTGGCATTCTGCGG
CCGCAGAATGCCAGCGGAT


 


1799
TCCGCTGGCATTCTGCGGG
CCCGCAGAATGCCAGCGGA


 


1800
CCGCTGGCATTCTGCGGGC
GCCCGCAGAATGCCAGCGG


 


1801
CGCTGGCATTCTGCGGGCC
GGCCCGCAGAATGCCAGCG


 


1802
GCTGGCATTCTGCGGGCCA
TGGCCCGCAGAATGCCAGC


 


1803
CTGGCATTCTGCGGGCCAG
CTGGCCCGCAGAATGCCAG


 


1804
TGGCATTCTGCGGGCCAGC
GCTGGCCCGCAGAATGCCA


 


1805
GGCATTCTGCGGGCCAGCG
CGCTGGCCCGCAGAATGCC


 


1806
GCATTCTGCGGGCCAGCGT
ACGCTGGCCCGCAGAATGC


 


1807
CATTCTGCGGGCCAGCGTG
CACGCTGGCCCGCAGAATG


 


1808
ATTCTGCGGGCCAGCGTGC
GCACGCTGGCCCGCAGAAT


 


1809
TTCTGCGGGCCAGCGTGCC
GGCACGCTGGCCCGCAGAA


 


1810
TCTGCGGGCCAGCGTGCCC
GGGCACGCTGGCCCGCAGA


 


1811
CTGCGGGCCAGCGTGCCCA
TGGGCACGCTGGCCCGCAG


 


1812
TGCGGGCCAGCGTGCCCAC
GTGGGCACGCTGGCCCGCA


 


1813
GCGGGCCAGCGTGCCCACC
GGTGGGCACGCTGGCCCGC


 


1814
CGGGCCAGCGTGCCCACCT
AGGTGGGCACGCTGGCCCG


 


1815
GGGCCAGCGTGCCCACCTC
GAGGTGGGCACGCTGGCCC


 


1816
GGCCAGCGTGCCCACCTCG
CGAGGTGGGCACGCTGGCC


 


1817
GCCAGCGTGCCCACCTCGC
GCGAGGTGGGCACGCTGGC


 


1818
CCAGCGTGCCCACCTCGCT
AGCGAGGTGGGCACGCTGG


 


1819
CAGCGTGCCCACCTCGCTG
CAGCGAGGTGGGCACGCTG


 


1820
AGCGTGCCCACCTCGCTGT
ACAGCGAGGTGGGCACGCT


 


1821
GCGTGCCCACCTCGCTGTG
CACAGCGAGGTGGGCACGC


 


1822
CGTGCCCACCTCGCTGTGG
CCACAGCGAGGTGGGCACG


 


1823
GTGCCCACCTCGCTGTGGC
GCCACAGCGAGGTGGGCAC


 


1824
TGCCCACCTCGCTGTGGCC
GGCCACAGCGAGGTGGGCA


 


1825
GCCCACCTCGCTGTGGCCC
GGGCCACAGCGAGGTGGGC


 


1826
CCCACCTCGCTGTGGCCCC
GGGGCCACAGCGAGGTGGG


 


1827
CCACCTCGCTGTGGCCCCC
GGGGGCCACAGCGAGGTGG


 


1828
CACCTCGCTGTGGCCCCCT
AGGGGGCCACAGCGAGGTG


 


1829
ACCTCGCTGTGGCCCCCTG
CAGGGGGCCACAGCGAGGT


 


1830
CCTCGCTGTGGCCCCCTGA
TCAGGGGGCCACAGCGAGG


 


1831
CTCGCTGTGGCCCCCTGAT
ATCAGGGGGCCACAGCGAG


 


1832
TCGCTGTGGCCCCCTGATG
CATCAGGGGGCCACAGCGA


 


1833
CGCTGTGGCCCCCTGATGC
GCATCAGGGGGCCACAGCG


 


1834
GCTGTGGCCCCCTGATGCC
GGCATCAGGGGGCCACAGC


 


1835
CTGTGGCCCCCTGATGCCT
AGGCATCAGGGGGCCACAG


 


1836
TGTGGCCCCCTGATGCCTG
CAGGCATCAGGGGGCCACA


 


1837
GTGGCCCCCTGATGCCTGA
TCAGGCATCAGGGGGCCAC


 


1838
TGGCCCCCTGATGCCTGAG
CTCAGGCATCAGGGGGCCA


 


1839
GGCCCCCTGATGCCTGAGC
GCTCAGGCATCAGGGGGCC


 


1840
GCCCCCTGATGCCTGAGCA
TGCTCAGGCATCAGGGGGC


 


1841
CCCCCTGATGCCTGAGCAT
ATGCTCAGGCATCAGGGGG


 


1842
CCCCTGATGCCTGAGCATA
TATGCTCAGGCATCAGGGG


 


1843
CCCTGATGCCTGAGCATAG
CTATGCTCAGGCATCAGGG


 


1844
CCTGATGCCTGAGCATAGT
ACTATGCTCAGGCATCAGG


 


1845
CTGATGCCTGAGCATAGTG
CACTATGCTCAGGCATCAG


 


1846
TGATGCCTGAGCATAGTGG
CCACTATGCTCAGGCATCA


 


1847
GATGCCTGAGCATAGTGGT
ACCACTATGCTCAGGCATC


 


1848
ATGCCTGAGCATAGTGGTG
CACCACTATGCTCAGGCAT


 


1849
TGCCTGAGCATAGTGGTGG
CCACCACTATGCTCAGGCA


 


1850
GCCTGAGCATAGTGGTGGC
GCCACCACTATGCTCAGGC


 


1851
CCTGAGCATAGTGGTGGCC
GGCCACCACTATGCTCAGG


 


1852
CTGAGCATAGTGGTGGCCA
TGGCCACCACTATGCTCAG


 


1853
TGAGCATAGTGGTGGCCAT
ATGGCCACCACTATGCTCA


 


1854
GAGCATAGTGGTGGCCATC
GATGGCCACCACTATGCTC


 


1855
AGCATAGTGGTGGCCATCT
AGATGGCCACCACTATGCT


 


1856
GCATAGTGGTGGCCATCTC
GAGATGGCCACCACTATGC


 


1857
CATAGTGGTGGCCATCTCA
TGAGATGGCCACCACTATG


 


1858
ATAGTGGTGGCCATCTCAA
TTGAGATGGCCACCACTAT


 


1859
TAGTGGTGGCCATCTCAAG
CTTGAGATGGCCACCACTA


 


1860
AGTGGTGGCCATCTCAAGA
TCTTGAGATGGCCACCACT


 


1861
GTGGTGGCCATCTCAAGAG
CTCTTGAGATGGCCACCAC


 


1862
TGGTGGCCATCTCAAGAGT
ACTCTTGAGATGGCCACCA


 


1863
GGTGGCCATCTCAAGAGTG
CACTCTTGAGATGGCCACC


 


1864
GTGGCCATCTCAAGAGTGA
TCACTCTTGAGATGGCCAC


 


1865
TGGCCATCTCAAGAGTGAC
GTCACTCTTGAGATGGCCA


 


1866
GGCCATCTCAAGAGTGACC
GGTCACTCTTGAGATGGCC


 


1867
GCCATCTCAAGAGTGACCC
GGGTCACTCTTGAGATGGC


 


1868
CCATCTCAAGAGTGACCCT
AGGGTCACTCTTGAGATGG


 


1869
CATCTCAAGAGTGACCCTG
CAGGGTCACTCTTGAGATG


 


1870
ATCTCAAGAGTGACCCTGT
ACAGGGTCACTCTTGAGAT


 


1871
TCTCAAGAGTGACCCTGTG
CACAGGGTCACTCTTGAGA


 


1872
CTCAAGAGTGACCCTGTGG
CCACAGGGTCACTCTTGAG


 


1873
TCAAGAGTGACCCTGTGGC
GCCACAGGGTCACTCTTGA


 


1874
CAAGAGTGACCCTGTGGCC
GGCCACAGGGTCACTCTTG


 


1875
AAGAGTGACCCTGTGGCCT
AGGCCACAGGGTCACTCTT


 


1876
AGAGTGACCCTGTGGCCTT
AAGGCCACAGGGTCACTCT


 


1877
GAGTGACCCTGTGGCCTTC
GAAGGCCACAGGGTCACTC


 


1878
AGTGACCCTGTGGCCTTCC
GGAAGGCCACAGGGTCACT


 


1879
GTGACCCTGTGGCCTTCCG
CGGAAGGCCACAGGGTCAC


 


1880
TGACCCTGTGGCCTTCCGG
CCGGAAGGCCACAGGGTCA


 


1881
GACCCTGTGGCCTTCCGGC
GCCGGAAGGCCACAGGGTC


 


1882
ACCCTGTGGCCTTCCGGCC
GGCCGGAAGGCCACAGGGT


 


1883
CCCTGTGGCCTTCCGGCCC
GGGCCGGAAGGCCACAGGG


 


1884
CCTGTGGCCTTCCGGCCCT
AGGGCCGGAAGGCCACAGG


 


1885
CTGTGGCCTTCCGGCCCTG
CAGGGCCGGAAGGCCACAG


 


1886
TGTGGCCTTCCGGCCCTGG
CCAGGGCCGGAAGGCCACA


 


1887
GTGGCCTTCCGGCCCTGGC
GCCAGGGCCGGAAGGCCAC


 


1888
TGGCCTTCCGGCCCTGGCA
TGCCAGGGCCGGAAGGCCA


 


1889
GGCCTTCCGGCCCTGGCAC
GTGCCAGGGCCGGAAGGCC


 


1890
GCCTTCCGGCCCTGGCACT
AGTGCCAGGGCCGGAAGGC


 


1891
CCTTCCGGCCCTGGCACTG
CAGTGCCAGGGCCGGAAGG


 


1892
CTTCCGGCCCTGGCACTGC
GCAGTGCCAGGGCCGGAAG


 


1893
TTCCGGCCCTGGCACTGCC
GGCAGTGCCAGGGCCGGAA


 


1894
TCCGGCCCTGGCACTGCCC
GGGCAGTGCCAGGGCCGGA


 


1895
CCGGCCCTGGCACTGCCCT
AGGGCAGTGCCAGGGCCGG


 


1896
CGGCCCTGGCACTGCCCTT
AAGGGCAGTGCCAGGGCCG


 


1897
GGCCCTGGCACTGCCCTTT
AAAGGGCAGTGCCAGGGCC


 


1898
GCCCTGGCACTGCCCTTTC
GAAAGGGCAGTGCCAGGGC


 


1899
CCCTGGCACTGCCCTTTCC
GGAAAGGGCAGTGCCAGGG


 


1900
CCTGGCACTGCCCTTTCCT
AGGAAAGGGCAGTGCCAGG


 


1901
CTGGCACTGCCCTTTCCTT
AAGGAAAGGGCAGTGCCAG


 


1902
TGGCACTGCCCTTTCCTTC
GAAGGAAAGGGCAGTGCCA


 


1903
GGCACTGCCCTTTCCTTCT
AGAAGGAAAGGGCAGTGCC


 


1904
GCACTGCCCTTTCCTTCTG
CAGAAGGAAAGGGCAGTGC


 


1905
CACTGCCCTTTCCTTCTGG
CCAGAAGGAAAGGGCAGTG


 


1906
ACTGCCCTTTCCTTCTGGA
TCCAGAAGGAAAGGGCAGT


 


1907
CTGCCCTTTCCTTCTGGAG
CTCCAGAAGGAAAGGGCAG


 


1908
TGCCCTTTCCTTCTGGAGA
TCTCCAGAAGGAAAGGGCA


 


1909
GCCCTTTCCTTCTGGAGAC
GTCTCCAGAAGGAAAGGGC


 


1910
CCCTTTCCTTCTGGAGACC
GGTCTCCAGAAGGAAAGGG


 


1911
CCTTTCCTTCTGGAGACCA
TGGTCTCCAGAAGGAAAGG


 


1912
CTTTCCTTCTGGAGACCAA
TTGGTCTCCAGAAGGAAAG


 


1913
TTTCCTTCTGGAGACCAAG
CTTGGTCTCCAGAAGGAAA


 


1914
TTCCTTCTGGAGACCAAGA
TCTTGGTCTCCAGAAGGAA


 


1915
TCCTTCTGGAGACCAAGAT
ATCTTGGTCTCCAGAAGGA


 


1916
CCTTCTGGAGACCAAGATC
GATCTTGGTCTCCAGAAGG


 


1917
CTTCTGGAGACCAAGATCC
GGATCTTGGTCTCCAGAAG


 


1918
TTCTGGAGACCAAGATCCT
AGGATCTTGGTCTCCAGAA


 


1919
TCTGGAGACCAAGATCCTG
CAGGATCTTGGTCTCCAGA


 


1920
CTGGAGACCAAGATCCTGG
CCAGGATCTTGGTCTCCAG


 


1921
TGGAGACCAAGATCCTGGA
TCCAGGATCTTGGTCTCCA


 


1922
GGAGACCAAGATCCTGGAG
CTCCAGGATCTTGGTCTCC


 


1923
GAGACCAAGATCCTGGAGC
GCTCCAGGATCTTGGTCTC


 


1924
AGACCAAGATCCTGGAGCG
CGCTCCAGGATCTTGGTCT


 


1925
GACCAAGATCCTGGAGCGA
TCGCTCCAGGATCTTGGTC


 


1926
ACCAAGATCCTGGAGCGAG
CTCGCTCCAGGATCTTGGT


 


1927
CCAAGATCCTGGAGCGAGC
GCTCGCTCCAGGATCTTGG


 


1928
CAAGATCCTGGAGCGAGCT
AGCTCGCTCCAGGATCTTG


 


1929
AAGATCCTGGAGCGAGCTC
GAGCTCGCTCCAGGATCTT


 


1930
AGATCCTGGAGCGAGCTCC
GGAGCTCGCTCCAGGATCT


 


1931
GATCCTGGAGCGAGCTCCC
GGGAGCTCGCTCCAGGATC


 


1932
ATCCTGGAGCGAGCTCCCT
AGGGAGCTCGCTCCAGGAT


 


1933
TCCTGGAGCGAGCTCCCTT
AAGGGAGCTCGCTCCAGGA


 


1934
CCTGGAGCGAGCTCCCTTC
GAAGGGAGCTCGCTCCAGG


 


1935
CTGGAGCGAGCTCCCTTCT
AGAAGGGAGCTCGCTCCAG


 


1936
TGGAGCGAGCTCCCTTCTG
CAGAAGGGAGCTCGCTCCA


 


1937
GGAGCGAGCTCCCTTCTGG
CCAGAAGGGAGCTCGCTCC


 


1938
GAGCGAGCTCCCTTCTGGG
CCCAGAAGGGAGCTCGCTC


 


1939
AGCGAGCTCCCTTCTGGGT
ACCCAGAAGGGAGCTCGCT


 


1940
GCGAGCTCCCTTCTGGGTG
CACCCAGAAGGGAGCTCGC


 


1941
CGAGCTCCCTTCTGGGTGC
GCACCCAGAAGGGAGCTCG


 


1942
GAGCTCCCTTCTGGGTGCC
GGCACCCAGAAGGGAGCTC


 


1943
AGCTCCCTTCTGGGTGCCC
GGGCACCCAGAAGGGAGCT


 


1944
GCTCCCTTCTGGGTGCCCA
TGGGCACCCAGAAGGGAGC


 


1945
CTCCCTTCTGGGTGCCCAC
GTGGGCACCCAGAAGGGAG


 


1946
TCCCTTCTGGGTGCCCACC
GGTGGGCACCCAGAAGGGA


 


1947
CCCTTCTGGGTGCCCACCT
AGGTGGGCACCCAGAAGGG


 


1948
CCTTCTGGGTGCCCACCTG
CAGGTGGGCACCCAGAAGG


 


1949
CTTCTGGGTGCCCACCTGC
GCAGGTGGGCACCCAGAAG


 


1950
TTCTGGGTGCCCACCTGCT
AGCAGGTGGGCACCCAGAA


 


1951
TCTGGGTGCCCACCTGCTT
AAGCAGGTGGGCACCCAGA


 


1952
CTGGGTGCCCACCTGCTTG
CAAGCAGGTGGGCACCCAG


 


1953
TGGGTGCCCACCTGCTTGC
GCAAGCAGGTGGGCACCCA


 


1954
GGGTGCCCACCTGCTTGCC
GGCAAGCAGGTGGGCACCC


 


1955
GGTGCCCACCTGCTTGCCA
TGGCAAGCAGGTGGGCACC


 


1956
GTGCCCACCTGCTTGCCAC
GTGGCAAGCAGGTGGGCAC


 


1957
TGCCCACCTGCTTGCCACC
GGTGGCAAGCAGGTGGGCA


 


1958
GCCCACCTGCTTGCCACCC
GGGTGGCAAGCAGGTGGGC


 


1959
CCCACCTGCTTGCCACCCT
AGGGTGGCAAGCAGGTGGG


 


1960
CCACCTGCTTGCCACCCTA
TAGGGTGGCAAGCAGGTGG


 


1961
CACCTGCTTGCCACCCTAC
GTAGGGTGGCAAGCAGGTG


 


1962
ACCTGCTTGCCACCCTACC
GGTAGGGTGGCAAGCAGGT


 


1963
CCTGCTTGCCACCCTACCT
AGGTAGGGTGGCAAGCAGG


 


1964
CTGCTTGCCACCCTACCTA
TAGGTAGGGTGGCAAGCAG


 


1965
TGCTTGCCACCCTACCTAG
CTAGGTAGGGTGGCAAGCA


 


1966
GCTTGCCACCCTACCTAGT
ACTAGGTAGGGTGGCAAGC


 


1967
CTTGCCACCCTACCTAGTG
CACTAGGTAGGGTGGCAAG


 


1968
TTGCCACCCTACCTAGTGT
ACACTAGGTAGGGTGGCAA


 


1969
TGCCACCCTACCTAGTGTC
GACACTAGGTAGGGTGGCA


 


1970
GCCACCCTACCTAGTGTCT
AGACACTAGGTAGGGTGGC


 


1971
CCACCCTACCTAGTGTCTG
CAGACACTAGGTAGGGTGG


 


1972
CACCCTACCTAGTGTCTGG
CCAGACACTAGGTAGGGTG


 


1973
ACCCTACCTAGTGTCTGGC
GCCAGACACTAGGTAGGGT


 


1974
CCCTACCTAGTGTCTGGCC
GGCCAGACACTAGGTAGGG


 


1975
CCTACCTAGTGTCTGGCCT
AGGCCAGACACTAGGTAGG


 


1976
CTACCTAGTGTCTGGCCTG
CAGGCCAGACACTAGGTAG


 


1977
TACCTAGTGTCTGGCCTGC
GCAGGCCAGACACTAGGTA


 


1978
ACCTAGTGTCTGGCCTGCC
GGCAGGCCAGACACTAGGT


 


1979
CCTAGTGTCTGGCCTGCCC
GGGCAGGCCAGACACTAGG


 


1980
CTAGTGTCTGGCCTGCCCC
GGGGCAGGCCAGACACTAG


 


1981
TAGTGTCTGGCCTGCCCCC
GGGGGCAGGCCAGACACTA


 


1982
AGTGTCTGGCCTGCCCCCA
TGGGGGCAGGCCAGACACT


 


1983
GTGTCTGGCCTGCCCCCAG
CTGGGGGCAGGCCAGACAC


 


1984
TGTCTGGCCTGCCCCCAGA
TCTGGGGGCAGGCCAGACA


 


1985
GTCTGGCCTGCCCCCAGAG
CTCTGGGGGCAGGCCAGAC


 


1986
TCTGGCCTGCCCCCAGAGC
GCTCTGGGGGCAGGCCAGA


 


1987
CTGGCCTGCCCCCAGAGCA
TGCTCTGGGGGCAGGCCAG


 


1988
TGGCCTGCCCCCAGAGCAT
ATGCTCTGGGGGCAGGCCA


 


1989
GGCCTGCCCCCAGAGCATC
GATGCTCTGGGGGCAGGCC


 


1990
GCCTGCCCCCAGAGCATCC
GGATGCTCTGGGGGCAGGC


 


1991
CCTGCCCCCAGAGCATCCA
TGGATGCTCTGGGGGCAGG


 


1992
CTGCCCCCAGAGCATCCAT
ATGGATGCTCTGGGGGCAG


 


1993
TGCCCCCAGAGCATCCATG
CATGGATGCTCTGGGGGCA


 


1994
GCCCCCAGAGCATCCATGT
ACATGGATGCTCTGGGGGC


 


1995
CCCCCAGAGCATCCATGTG
CACATGGATGCTCTGGGGG


 


1996
CCCCAGAGCATCCATGTGA
TCACATGGATGCTCTGGGG


 


1997
CCCAGAGCATCCATGTGAC
GTCACATGGATGCTCTGGG


 


1998
CCAGAGCATCCATGTGACT
AGTCACATGGATGCTCTGG


 


1999
CAGAGCATCCATGTGACTG
CAGTCACATGGATGCTCTG


 


2000
AGAGCATCCATGTGACTGG
CCAGTCACATGGATGCTCT


 


2001
GAGCATCCATGTGACTGGC
GCCAGTCACATGGATGCTC


 


2002
AGCATCCATGTGACTGGCC
GGCCAGTCACATGGATGCT


 


2003
GCATCCATGTGACTGGCCC
GGGCCAGTCACATGGATGC


 


2004
CATCCATGTGACTGGCCCC
GGGGCCAGTCACATGGATG


 


2005
ATCCATGTGACTGGCCCCT
AGGGGCCAGTCACATGGAT


 


2006
TCCATGTGACTGGCCCCTG
CAGGGGCCAGTCACATGGA


 


2007
CCATGTGACTGGCCCCTGA
TCAGGGGCCAGTCACATGG


 


2008
CATGTGACTGGCCCCTGAC
GTCAGGGGCCAGTCACATG


 


2009
ATGTGACTGGCCCCTGACC
GGTCAGGGGCCAGTCACAT


 


2010
TGTGACTGGCCCCTGACCC
GGGTCAGGGGCCAGTCACA


 


2011
GTGACTGGCCCCTGACCCC
GGGGTCAGGGGCCAGTCAC


 


2012
TGACTGGCCCCTGACCCCG
CGGGGTCAGGGGCCAGTCA


 


2013
GACTGGCCCCTGACCCCGC
GCGGGGTCAGGGGCCAGTC


 


2014
ACTGGCCCCTGACCCCGCA
TGCGGGGTCAGGGGCCAGT


 


2015
CTGGCCCCTGACCCCGCAC
GTGCGGGGTCAGGGGCCAG


 


2016
TGGCCCCTGACCCCGCACC
GGTGCGGGGTCAGGGGCCA


 


2017
GGCCCCTGACCCCGCACCC
GGGTGCGGGGTCAGGGGCC


 


2018
GCCCCTGACCCCGCACCCC
GGGGTGCGGGGTCAGGGGC


 


2019
CCCCTGACCCCGCACCCCT
AGGGGTGCGGGGTCAGGGG


 


2020
CCCTGACCCCGCACCCCTG
CAGGGGTGCGGGGTCAGGG


 


2021
CCTGACCCCGCACCCCTGG
CCAGGGGTGCGGGGTCAGG


 


2022
CTGACCCCGCACCCCTGGG
CCCAGGGGTGCGGGGTCAG


 


2023
TGACCCCGCACCCCTGGGT
ACCCAGGGGTGCGGGGTCA


 


2024
GACCCCGCACCCCTGGGTA
TACCCAGGGGTGCGGGGTC


 


2025
ACCCCGCACCCCTGGGTAT
ATACCCAGGGGTGCGGGGT


 


2026
CCCCGCACCCCTGGGTATA
TATACCCAGGGGTGCGGGG


 


2027
CCCGCACCCCTGGGTATAC
GTATACCCAGGGGTGCGGG


 


2028
CCGCACCCCTGGGTATACT
AGTATACCCAGGGGTGCGG


 


2029
CGCACCCCTGGGTATACTC
GAGTATACCCAGGGGTGCG


 


2030
GCACCCCTGGGTATACTCC
GGAGTATACCCAGGGGTGC


 


2031
CACCCCTGGGTATACTCCG
CGGAGTATACCCAGGGGTG


 


2032
ACCCCTGGGTATACTCCGG
CCGGAGTATACCCAGGGGT


 


2033
CCCCTGGGTATACTCCGGG
CCCGGAGTATACCCAGGGG


 


2034
CCCTGGGTATACTCCGGGG
CCCCGGAGTATACCCAGGG


 


2035
CCTGGGTATACTCCGGGGG
CCCCCGGAGTATACCCAGG


 


2036
CTGGGTATACTCCGGGGGC
GCCCCCGGAGTATACCCAG


 


2037
TGGGTATACTCCGGGGGCC
GGCCCCCGGAGTATACCCA


 


2038
GGGTATACTCCGGGGGCCA
TGGCCCCCGGAGTATACCC


 


2039
GGTATACTCCGGGGGCCAG
CTGGCCCCCGGAGTATACC


 


2040
GTATACTCCGGGGGCCAGC
GCTGGCCCCCGGAGTATAC


 


2041
TATACTCCGGGGGCCAGCC
GGCTGGCCCCCGGAGTATA


 


2042
ATACTCCGGGGGCCAGCCC
GGGCTGGCCCCCGGAGTAT


 


2043
TACTCCGGGGGCCAGCCCA
TGGGCTGGCCCCCGGAGTA


 


2044
ACTCCGGGGGCCAGCCCAA
TTGGGCTGGCCCCCGGAGT


 


2045
CTCCGGGGGCCAGCCCAAA
TTTGGGCTGGCCCCCGGAG


 


2046
TCCGGGGGCCAGCCCAAAG
CTTTGGGCTGGCCCCCGGA


 


2047
CCGGGGGCCAGCCCAAAGT
ACTTTGGGCTGGCCCCCGG


 


2048
CGGGGGCCAGCCCAAAGTG
CACTTTGGGCTGGCCCCCG


 


2049
GGGGGCCAGCCCAAAGTGC
GCACTTTGGGCTGGCCCCC


 


2050
GGGGCCAGCCCAAAGTGCC
GGCACTTTGGGCTGGCCCC


 


2051
GGGCCAGCCCAAAGTGCCC
GGGCACTTTGGGCTGGCCC


 


2052
GGCCAGCCCAAAGTGCCCT
AGGGCACTTTGGGCTGGCC


 


2053
GCCAGCCCAAAGTGCCCTC
GAGGGCACTTTGGGCTGGC


 


2054
CCAGCCCAAAGTGCCCTCT
AGAGGGCACTTTGGGCTGG


 


2055
CAGCCCAAAGTGCCCTCTG
CAGAGGGCACTTTGGGCTG


 


2056
AGCCCAAAGTGCCCTCTGC
GCAGAGGGCACTTTGGGCT


 


2057
GCCCAAAGTGCCCTCTGCC
GGCAGAGGGCACTTTGGGC


 


2058
CCCAAAGTGCCCTCTGCCT
AGGCAGAGGGCACTTTGGG


 


2059
CCAAAGTGCCCTCTGCCTT
AAGGCAGAGGGCACTTTGG


 


2060
CAAAGTGCCCTCTGCCTTC
GAAGGCAGAGGGCACTTTG


 


2061
AAAGTGCCCTCTGCCTTCA
TGAAGGCAGAGGGCACTTT


 


2062
AAGTGCCCTCTGCCTTCAG
CTGAAGGCAGAGGGCACTT


 


2063
AGTGCCCTCTGCCTTCAGC
GCTGAAGGCAGAGGGCACT


 


2064
GTGCCCTCTGCCTTCAGCT
AGCTGAAGGCAGAGGGCAC


 


2065
TGCCCTCTGCCTTCAGCTT
AAGCTGAAGGCAGAGGGCA


 


2066
GCCCTCTGCCTTCAGCTTA
TAAGCTGAAGGCAGAGGGC


 


2067
CCCTCTGCCTTCAGCTTAG
CTAAGCTGAAGGCAGAGGG


 


2068
CCTCTGCCTTCAGCTTAGG
CCTAAGCTGAAGGCAGAGG


 


2069
CTCTGCCTTCAGCTTAGGC
GCCTAAGCTGAAGGCAGAG


 


2070
TCTGCCTTCAGCTTAGGCA
TGCCTAAGCTGAAGGCAGA


 


2071
CTGCCTTCAGCTTAGGCAG
CTGCCTAAGCTGAAGGCAG


 


2072
TGCCTTCAGCTTAGGCAGC
GCTGCCTAAGCTGAAGGCA


 


2073
GCCTTCAGCTTAGGCAGCA
TGCTGCCTAAGCTGAAGGC


 


2074
CCTTCAGCTTAGGCAGCAA
TTGCTGCCTAAGCTGAAGG


 


2075
CTTCAGCTTAGGCAGCAAG
CTTGCTGCCTAAGCTGAAG


 


2076
TTCAGCTTAGGCAGCAAGG
CCTTGCTGCCTAAGCTGAA


 


2077
TCAGCTTAGGCAGCAAGGG
CCCTTGCTGCCTAAGCTGA


 


2078
CAGCTTAGGCAGCAAGGGC
GCCCTTGCTGCCTAAGCTG


 


2079
AGCTTAGGCAGCAAGGGCT
AGCCCTTGCTGCCTAAGCT


 


2080
GCTTAGGCAGCAAGGGCTT
AAGCCCTTGCTGCCTAAGC


 


2081
CTTAGGCAGCAAGGGCTTT
AAAGCCCTTGCTGCCTAAG


 


2082
TTAGGCAGCAAGGGCTTTT
AAAAGCCCTTGCTGCCTAA


 


2083
TAGGCAGCAAGGGCTTTTA
TAAAAGCCCTTGCTGCCTA


 


2084
AGGCAGCAAGGGCTTTTAC
GTAAAAGCCCTTGCTGCCT


 


2085
GGCAGCAAGGGCTTTTACT
AGTAAAAGCCCTTGCTGCC


 


2086
GCAGCAAGGGCTTTTACTA
TAGTAAAAGCCCTTGCTGC


 


2087
CAGCAAGGGCTTTTACTAC
GTAGTAAAAGCCCTTGCTG


 


2088
AGCAAGGGCTTTTACTACA
TGTAGTAAAAGCCCTTGCT


 


2089
GCAAGGGCTTTTACTACAA
TTGTAGTAAAAGCCCTTGC


 


2090
CAAGGGCTTTTACTACAAG
CTTGTAGTAAAAGCCCTTG


 


2091
AAGGGCTTTTACTACAAGG
CCTTGTAGTAAAAGCCCTT


 


2092
AGGGCTTTTACTACAAGGA
TCCTTGTAGTAAAAGCCCT


 


2093
GGGCTTTTACTACAAGGAT
ATCCTTGTAGTAAAAGCCC


 


2094
GGCTTTTACTACAAGGATC
GATCCTTGTAGTAAAAGCC


 


2095
GCTTTTACTACAAGGATCC
GGATCCTTGTAGTAAAAGC


 


2096
CTTTTACTACAAGGATCCG
CGGATCCTTGTAGTAAAAG


 


2097
TTTTACTACAAGGATCCGA
TCGGATCCTTGTAGTAAAA


 


2098
TTTACTACAAGGATCCGAG
CTCGGATCCTTGTAGTAAA


 


2099
TTACTACAAGGATCCGAGC
GCTCGGATCCTTGTAGTAA


 


2100
TACTACAAGGATCCGAGCA
TGCTCGGATCCTTGTAGTA


 


2101
ACTACAAGGATCCGAGCAT
ATGCTCGGATCCTTGTAGT


 


2102
CTACAAGGATCCGAGCATT
AATGCTCGGATCCTTGTAG


 


2103
TACAAGGATCCGAGCATTC
GAATGCTCGGATCCTTGTA


 


2104
ACAAGGATCCGAGCATTCC
GGAATGCTCGGATCCTTGT


 


2105
CAAGGATCCGAGCATTCCC
GGGAATGCTCGGATCCTTG


 


2106
AAGGATCCGAGCATTCCCA
TGGGAATGCTCGGATCCTT


 


2107
AGGATCCGAGCATTCCCAG
CTGGGAATGCTCGGATCCT


 


2108
GGATCCGAGCATTCCCAGG
CCTGGGAATGCTCGGATCC


 


2109
GATCCGAGCATTCCCAGGT
ACCTGGGAATGCTCGGATC


 


2110
ATCCGAGCATTCCCAGGTT
AACCTGGGAATGCTCGGAT


 


2111
TCCGAGCATTCCCAGGTTG
CAACCTGGGAATGCTCGGA


 


2112
CCGAGCATTCCCAGGTTGG
CCAACCTGGGAATGCTCGG


 


2113
CGAGCATTCCCAGGTTGGC
GCCAACCTGGGAATGCTCG


 


2114
GAGCATTCCCAGGTTGGCA
TGCCAACCTGGGAATGCTC


 


2115
AGCATTCCCAGGTTGGCAA
TTGCCAACCTGGGAATGCT


 


2116
GCATTCCCAGGTTGGCAAA
TTTGCCAACCTGGGAATGC


 


2117
CATTCCCAGGTTGGCAAAG
CTTTGCCAACCTGGGAATG


 


2118
ATTCCCAGGTTGGCAAAGG
CCTTTGCCAACCTGGGAAT


 


2119
TTCCCAGGTTGGCAAAGGA
TCCTTTGCCAACCTGGGAA


 


2120
TCCCAGGTTGGCAAAGGAG
CTCCTTTGCCAACCTGGGA


 


2121
CCCAGGTTGGCAAAGGAGC
GCTCCTTTGCCAACCTGGG


 


2122
CCAGGTTGGCAAAGGAGCC
GGCTCCTTTGCCAACCTGG


 


2123
CAGGTTGGCAAAGGAGCCC
GGGCTCCTTTGCCAACCTG


 


2124
AGGTTGGCAAAGGAGCCCT
AGGGCTCCTTTGCCAACCT


 


2125
GGTTGGCAAAGGAGCCCTT
AAGGGCTCCTTTGCCAACC


 


2126
GTTGGCAAAGGAGCCCTTG
CAAGGGCTCCTTTGCCAAC


 


2127
TTGGCAAAGGAGCCCTTGG
CCAAGGGCTCCTTTGCCAA


 


2128
TGGCAAAGGAGCCCTTGGC
GCCAAGGGCTCCTTTGCCA


 


2129
GGCAAAGGAGCCCTTGGCA
TGCCAAGGGCTCCTTTGCC


 


2130
GCAAAGGAGCCCTTGGCAG
CTGCCAAGGGCTCCTTTGC


 


2131
CAAAGGAGCCCTTGGCAGC
GCTGCCAAGGGCTCCTTTG


 


2132
AAAGGAGCCCTTGGCAGCT
AGCTGCCAAGGGCTCCTTT


 


2133
AAGGAGCCCTTGGCAGCTG
CAGCTGCCAAGGGCTCCTT


 


2134
AGGAGCCCTTGGCAGCTGC
GCAGCTGCCAAGGGCTCCT


 


2135
GGAGCCCTTGGCAGCTGCG
CGCAGCTGCCAAGGGCTCC


 


2136
GAGCCCTTGGCAGCTGCGG
CCGCAGCTGCCAAGGGCTC


 


2137
AGCCCTTGGCAGCTGCGGA
TCCGCAGCTGCCAAGGGCT


 


2138
GCCCTTGGCAGCTGCGGAA
TTCCGCAGCTGCCAAGGGC


 


2139
CCCTTGGCAGCTGCGGAAC
GTTCCGCAGCTGCCAAGGG


 


2140
CCTTGGCAGCTGCGGAACC
GGTTCCGCAGCTGCCAAGG


 


2141
CTTGGCAGCTGCGGAACCT
AGGTTCCGCAGCTGCCAAG


 


2142
TTGGCAGCTGCGGAACCTG
CAGGTTCCGCAGCTGCCAA


 


2143
TGGCAGCTGCGGAACCTGG
CCAGGTTCCGCAGCTGCCA


 


2144
GGCAGCTGCGGAACCTGGG
CCCAGGTTCCGCAGCTGCC


 


2145
GCAGCTGCGGAACCTGGGT
ACCCAGGTTCCGCAGCTGC


 


2146
CAGCTGCGGAACCTGGGTT
AACCCAGGTTCCGCAGCTG


 


2147
AGCTGCGGAACCTGGGTTG
CAACCCAGGTTCCGCAGCT


 


2148
GCTGCGGAACCTGGGTTGT
ACAACCCAGGTTCCGCAGC


 


2149
CTGCGGAACCTGGGTTGTT
AACAACCCAGGTTCCGCAG


 


2150
TGCGGAACCTGGGTTGTTT
AAACAACCCAGGTTCCGCA


 


2151
GCGGAACCTGGGTTGTTTG
CAAACAACCCAGGTTCCGC


 


2152
CGGAACCTGGGTTGTTTGG
CCAAACAACCCAGGTTCCG


 


2153
GGAACCTGGGTTGTTTGGC
GCCAAACAACCCAGGTTCC


 


2154
GAACCTGGGTTGTTTGGCT
AGCCAAACAACCCAGGTTC


 


2155
AACCTGGGTTGTTTGGCTT
AAGCCAAACAACCCAGGTT


 


2156
ACCTGGGTTGTTTGGCTTA
TAAGCCAAACAACCCAGGT


 


2157
CCTGGGTTGTTTGGCTTAA
TTAAGCCAAACAACCCAGG


 


2158
CTGGGTTGTTTGGCTTAAA
TTTAAGCCAAACAACCCAG


 


2159
TGGGTTGTTTGGCTTAAAC
GTTTAAGCCAAACAACCCA


 


2160
GGGTTGTTTGGCTTAAACT
AGTTTAAGCCAAACAACCC


 


2161
GGTTGTTTGGCTTAAACTC
GAGTTTAAGCCAAACAACC


 


2162
GTTGTTTGGCTTAAACTCT
AGAGTTTAAGCCAAACAAC


 


2163
TTGTTTGGCTTAAACTCTG
CAGAGTTTAAGCCAAACAA


 


2164
TGTTTGGCTTAAACTCTGG
CCAGAGTTTAAGCCAAACA


 


2165
GTTTGGCTTAAACTCTGGT
ACCAGAGTTTAAGCCAAAC


 


2166
TTTGGCTTAAACTCTGGTG
CACCAGAGTTTAAGCCAAA


 


2167
TTGGCTTAAACTCTGGTGG
CCACCAGAGTTTAAGCCAA


 


2168
TGGCTTAAACTCTGGTGGG
CCCACCAGAGTTTAAGCCA


 


2169
GGCTTAAACTCTGGTGGGC
GCCCACCAGAGTTTAAGCC


 


2170
GCTTAAACTCTGGTGGGCA
TGCCCACCAGAGTTTAAGC


 


2171
CTTAAACTCTGGTGGGCAC
GTGCCCACCAGAGTTTAAG


 


2172
TTAAACTCTGGTGGGCACC
GGTGCCCACCAGAGTTTAA


 


2173
TAAACTCTGGTGGGCACCT
AGGTGCCCACCAGAGTTTA


 


2174
AAACTCTGGTGGGCACCTG
CAGGTGCCCACCAGAGTTT


 


2175
AACTCTGGTGGGCACCTGC
GCAGGTGCCCACCAGAGTT


 


2176
ACTCTGGTGGGCACCTGCA
TGCAGGTGCCCACCAGAGT


 


2177
CTCTGGTGGGCACCTGCAG
CTGCAGGTGCCCACCAGAG


 


2178
TCTGGTGGGCACCTGCAGA
TCTGCAGGTGCCCACCAGA


 


2179
CTGGTGGGCACCTGCAGAG
CTCTGCAGGTGCCCACCAG


 


2180
TGGTGGGCACCTGCAGAGA
TCTCTGCAGGTGCCCACCA


 


2181
GGTGGGCACCTGCAGAGAG
CTCTCTGCAGGTGCCCACC


 


2182
GTGGGCACCTGCAGAGAGC
GCTCTCTGCAGGTGCCCAC


 


2183
TGGGCACCTGCAGAGAGCC
GGCTCTCTGCAGGTGCCCA


 


2184
GGGCACCTGCAGAGAGCCG
CGGCTCTCTGCAGGTGCCC


 


2185
GGCACCTGCAGAGAGCCGG
CCGGCTCTCTGCAGGTGCC


 


2186
GCACCTGCAGAGAGCCGGG
CCCGGCTCTCTGCAGGTGC


 


2187
CACCTGCAGAGAGCCGGGG
CCCCGGCTCTCTGCAGGTG


 


2188
ACCTGCAGAGAGCCGGGGA
TCCCCGGCTCTCTGCAGGT


 


2189
CCTGCAGAGAGCCGGGGAG
CTCCCCGGCTCTCTGCAGG


 


2190
CTGCAGAGAGCCGGGGAGG
CCTCCCCGGCTCTCTGCAG


 


2191
TGCAGAGAGCCGGGGAGGC
GCCTCCCCGGCTCTCTGCA


 


2192
GCAGAGAGCCGGGGAGGCC
GGCCTCCCCGGCTCTCTGC


 


2193
CAGAGAGCCGGGGAGGCCG
CGGCCTCCCCGGCTCTCTG


 


2194
AGAGAGCCGGGGAGGCCGA
TCGGCCTCCCCGGCTCTCT


 


2195
GAGAGCCGGGGAGGCCGAA
TTCGGCCTCCCCGGCTCTC


 


2196
AGAGCCGGGGAGGCCGAAC
GTTCGGCCTCCCCGGCTCT


 


2197
GAGCCGGGGAGGCCGAACG
CGTTCGGCCTCCCCGGCTC


 


2198
AGCCGGGGAGGCCGAACGC
GCGTTCGGCCTCCCCGGCT


 


2199
GCCGGGGAGGCCGAACGCC
GGCGTTCGGCCTCCCCGGC


 


2200
CCGGGGAGGCCGAACGCCC
GGGCGTTCGGCCTCCCCGG


 


2201
CGGGGAGGCCGAACGCCCT
AGGGCGTTCGGCCTCCCCG


 


2202
GGGGAGGCCGAACGCCCTT
AAGGGCGTTCGGCCTCCCC


 


2203
GGGAGGCCGAACGCCCTTC
GAAGGGCGTTCGGCCTCCC


 


2204
GGAGGCCGAACGCCCTTCA
TGAAGGGCGTTCGGCCTCC


 


2205
GAGGCCGAACGCCCTTCAC
GTGAAGGGCGTTCGGCCTC


 


2206
AGGCCGAACGCCCTTCACT
AGTGAAGGGCGTTCGGCCT


 


2207
GGCCGAACGCCCTTCACTG
CAGTGAAGGGCGTTCGGCC


 


2208
GCCGAACGCCCTTCACTGC
GCAGTGAAGGGCGTTCGGC


 


2209
CCGAACGCCCTTCACTGCA
TGCAGTGAAGGGCGTTCGG


 


2210
CGAACGCCCTTCACTGCAC
GTGCAGTGAAGGGCGTTCG


 


2211
GAACGCCCTTCACTGCACC
GGTGCAGTGAAGGGCGTTC


 


2212
AACGCCCTTCACTGCACCA
TGGTGCAGTGAAGGGCGTT


 


2213
ACGCCCTTCACTGCACCAG
CTGGTGCAGTGAAGGGCGT


 


2214
CGCCCTTCACTGCACCAGA
TCTGGTGCAGTGAAGGGCG


 


2215
GCCCTTCACTGCACCAGAG
CTCTGGTGCAGTGAAGGGC


 


2216
CCCTTCACTGCACCAGAGG
CCTCTGGTGCAGTGAAGGG


 


2217
CCTTCACTGCACCAGAGGG
CCCTCTGGTGCAGTGAAGG


 


2218
CTTCACTGCACCAGAGGGA
TCCCTCTGGTGCAGTGAAG


 


2219
TTCACTGCACCAGAGGGAT
ATCCCTCTGGTGCAGTGAA


 


2220
TCACTGCACCAGAGGGATG
CATCCCTCTGGTGCAGTGA


 


2221
CACTGCACCAGAGGGATGG
CCATCCCTCTGGTGCAGTG


 


2222
ACTGCACCAGAGGGATGGA
TCCATCCCTCTGGTGCAGT


 


2223
CTGCACCAGAGGGATGGAG
CTCCATCCCTCTGGTGCAG


 


2224
TGCACCAGAGGGATGGAGA
TCTCCATCCCTCTGGTGCA


 


2225
GCACCAGAGGGATGGAGAG
CTCTCCATCCCTCTGGTGC


 


2226
CACCAGAGGGATGGAGAGA
TCTCTCCATCCCTCTGGTG


 


2227
ACCAGAGGGATGGAGAGAT
ATCTCTCCATCCCTCTGGT


 


2228
CCAGAGGGATGGAGAGATG
CATCTCTCCATCCCTCTGG


 


2229
CAGAGGGATGGAGAGATGG
CCATCTCTCCATCCCTCTG


 


2230
AGAGGGATGGAGAGATGGG
CCCATCTCTCCATCCCTCT


 


2231
GAGGGATGGAGAGATGGGA
TCCCATCTCTCCATCCCTC


 


2232
AGGGATGGAGAGATGGGAG
CTCCCATCTCTCCATCCCT


 


2233
GGGATGGAGAGATGGGAGC
GCTCCCATCTCTCCATCCC


 


2234
GGATGGAGAGATGGGAGCT
AGCTCCCATCTCTCCATCC


 


2235
GATGGAGAGATGGGAGCTG
CAGCTCCCATCTCTCCATC


 


2236
ATGGAGAGATGGGAGCTGG
CCAGCTCCCATCTCTCCAT


 


2237
TGGAGAGATGGGAGCTGGC
GCCAGCTCCCATCTCTCCA


 


2238
GGAGAGATGGGAGCTGGCC
GGCCAGCTCCCATCTCTCC


 


2239
GAGAGATGGGAGCTGGCCG
CGGCCAGCTCCCATCTCTC


 


2240
AGAGATGGGAGCTGGCCGG
CCGGCCAGCTCCCATCTCT


 


2241
GAGATGGGAGCTGGCCGGC
GCCGGCCAGCTCCCATCTC


 


2242
AGATGGGAGCTGGCCGGCA
TGCCGGCCAGCTCCCATCT


 


2243
GATGGGAGCTGGCCGGCAG
CTGCCGGCCAGCTCCCATC


 


2244
ATGGGAGCTGGCCGGCAGC
GCTGCCGGCCAGCTCCCAT


 


2245
TGGGAGCTGGCCGGCAGCA
TGCTGCCGGCCAGCTCCCA


 


2246
GGGAGCTGGCCGGCAGCAG
CTGCTGCCGGCCAGCTCCC


 


2247
GGAGCTGGCCGGCAGCAGA
TCTGCTGCCGGCCAGCTCC


 


2248
GAGCTGGCCGGCAGCAGAA
TTCTGCTGCCGGCCAGCTC


 


2249
AGCTGGCCGGCAGCAGAAT
ATTCTGCTGCCGGCCAGCT


 


2250
GCTGGCCGGCAGCAGAATC
GATTCTGCTGCCGGCCAGC


 


2251
CTGGCCGGCAGCAGAATCC
GGATTCTGCTGCCGGCCAG


 


2252
TGGCCGGCAGCAGAATCCT
AGGATTCTGCTGCCGGCCA


 


2253
GGCCGGCAGCAGAATCCTT
AAGGATTCTGCTGCCGGCC


 


2254
GCCGGCAGCAGAATCCTTG
CAAGGATTCTGCTGCCGGC


 


2255
CCGGCAGCAGAATCCTTGC
GCAAGGATTCTGCTGCCGG


 


2256
CGGCAGCAGAATCCTTGCC
GGCAAGGATTCTGCTGCCG


 


2257
GGCAGCAGAATCCTTGCCC
GGGCAAGGATTCTGCTGCC


 


2258
GCAGCAGAATCCTTGCCCG
CGGGCAAGGATTCTGCTGC


 


2259
CAGCAGAATCCTTGCCCGC
GCGGGCAAGGATTCTGCTG


 


2260
AGCAGAATCCTTGCCCGCT
AGCGGGCAAGGATTCTGCT


 


2261
GCAGAATCCTTGCCCGCTC
GAGCGGGCAAGGATTCTGC


 


2262
CAGAATCCTTGCCCGCTCT
AGAGCGGGCAAGGATTCTG


 


2263
AGAATCCTTGCCCGCTCTT
AAGAGCGGGCAAGGATTCT


 


2264
GAATCCTTGCCCGCTCTTC
GAAGAGCGGGCAAGGATTC


 


2265
AATCCTTGCCCGCTCTTCC
GGAAGAGCGGGCAAGGATT


 


2266
ATCCTTGCCCGCTCTTCCT
AGGAAGAGCGGGCAAGGAT


 


2267
TCCTTGCCCGCTCTTCCTG
CAGGAAGAGCGGGCAAGGA


 


2268
CCTTGCCCGCTCTTCCTGG
CCAGGAAGAGCGGGCAAGG


 


2269
CTTGCCCGCTCTTCCTGGG
CCCAGGAAGAGCGGGCAAG


 


2270
TTGCCCGCTCTTCCTGGGG
CCCCAGGAAGAGCGGGCAA


 


2271
TGCCCGCTCTTCCTGGGGC
GCCCCAGGAAGAGCGGGCA


 


2272
GCCCGCTCTTCCTGGGGCA
TGCCCCAGGAAGAGCGGGC


 


2273
CCCGCTCTTCCTGGGGCAG
CTGCCCCAGGAAGAGCGGG


 


2274
CCGCTCTTCCTGGGGCAGC
GCTGCCCCAGGAAGAGCGG


 


2275
CGCTCTTCCTGGGGCAGCC
GGCTGCCCCAGGAAGAGCG


 


2276
GCTCTTCCTGGGGCAGCCA
TGGCTGCCCCAGGAAGAGC


 


2277
CTCTTCCTGGGGCAGCCAG
CTGGCTGCCCCAGGAAGAG


 


2278
TCTTCCTGGGGCAGCCAGA
TCTGGCTGCCCCAGGAAGA


 


2279
CTTCCTGGGGCAGCCAGAC
GTCTGGCTGCCCCAGGAAG


 


2280
TTCCTGGGGCAGCCAGACA
TGTCTGGCTGCCCCAGGAA


 


2281
TCCTGGGGCAGCCAGACAC
GTGTCTGGCTGCCCCAGGA


 


2282
CCTGGGGCAGCCAGACACT
AGTGTCTGGCTGCCCCAGG


 


2283
CTGGGGCAGCCAGACACTG
CAGTGTCTGGCTGCCCCAG


 


2284
TGGGGCAGCCAGACACTGT
ACAGTGTCTGGCTGCCCCA


 


2285
GGGGCAGCCAGACACTGTG
CACAGTGTCTGGCTGCCCC


 


2286
GGGCAGCCAGACACTGTGC
GCACAGTGTCTGGCTGCCC


 


2287
GGCAGCCAGACACTGTGCC
GGCACAGTGTCTGGCTGCC


 


2288
GCAGCCAGACACTGTGCCC
GGGCACAGTGTCTGGCTGC


 


2289
CAGCCAGACACTGTGCCCT
AGGGCACAGTGTCTGGCTG


 


2290
AGCCAGACACTGTGCCCTG
CAGGGCACAGTGTCTGGCT


 


2291
GCCAGACACTGTGCCCTGG
CCAGGGCACAGTGTCTGGC


 


2292
CCAGACACTGTGCCCTGGA
TCCAGGGCACAGTGTCTGG


 


2293
CAGACACTGTGCCCTGGAC
GTCCAGGGCACAGTGTCTG


 


2294
AGACACTGTGCCCTGGACC
GGTCCAGGGCACAGTGTCT


 


2295
GACACTGTGCCCTGGACCT
AGGTCCAGGGCACAGTGTC


 


2296
ACACTGTGCCCTGGACCTC
GAGGTCCAGGGCACAGTGT


 


2297
CACTGTGCCCTGGACCTCC
GGAGGTCCAGGGCACAGTG


 


2298
ACTGTGCCCTGGACCTCCT
AGGAGGTCCAGGGCACAGT


 


2299
CTGTGCCCTGGACCTCCTG
CAGGAGGTCCAGGGCACAG


 


2300
TGTGCCCTGGACCTCCTGG
CCAGGAGGTCCAGGGCACA


 


2301
GTGCCCTGGACCTCCTGGC
GCCAGGAGGTCCAGGGCAC


 


2302
TGCCCTGGACCTCCTGGCC
GGCCAGGAGGTCCAGGGCA


 


2303
GCCCTGGACCTCCTGGCCC
GGGCCAGGAGGTCCAGGGC


 


2304
CCCTGGACCTCCTGGCCCG
CGGGCCAGGAGGTCCAGGG


 


2305
CCTGGACCTCCTGGCCCGC
GCGGGCCAGGAGGTCCAGG


 


2306
CTGGACCTCCTGGCCCGCT
AGCGGGCCAGGAGGTCCAG


 


2307
TGGACCTCCTGGCCCGCTT
AAGCGGGCCAGGAGGTCCA


 


2308
GGACCTCCTGGCCCGCTTG
CAAGCGGGCCAGGAGGTCC


 


2309
GACCTCCTGGCCCGCTTGT
ACAAGCGGGCCAGGAGGTC


 


2310
ACCTCCTGGCCCGCTTGTC
GACAAGCGGGCCAGGAGGT


 


2311
CCTCCTGGCCCGCTTGTCC
GGACAAGCGGGCCAGGAGG


 


2312
CTCCTGGCCCGCTTGTCCC
GGGACAAGCGGGCCAGGAG


 


2313
TCCTGGCCCGCTTGTCCCC
GGGGACAAGCGGGCCAGGA


 


2314
CCTGGCCCGCTTGTCCCCC
GGGGGACAAGCGGGCCAGG


 


2315
CTGGCCCGCTTGTCCCCCA
TGGGGGACAAGCGGGCCAG


 


2316
TGGCCCGCTTGTCCCCCAG
CTGGGGGACAAGCGGGCCA


 


2317
GGCCCGCTTGTCCCCCAGG
CCTGGGGGACAAGCGGGCC


 


2318
GCCCGCTTGTCCCCCAGGC
GCCTGGGGGACAAGCGGGC


 


2319
CCCGCTTGTCCCCCAGGCC
GGCCTGGGGGACAAGCGGG


 


2320
CCGCTTGTCCCCCAGGCCT
AGGCCTGGGGGACAAGCGG


 


2321
CGCTTGTCCCCCAGGCCTT
AAGGCCTGGGGGACAAGCG


 


2322
GCTTGTCCCCCAGGCCTTG
CAAGGCCTGGGGGACAAGC


 


2323
CTTGTCCCCCAGGCCTTGT
ACAAGGCCTGGGGGACAAG


 


2324
TTGTCCCCCAGGCCTTGTT
AACAAGGCCTGGGGGACAA


 


2325
TGTCCCCCAGGCCTTGTTC
GAACAAGGCCTGGGGGACA


 


2326
GTCCCCCAGGCCTTGTTCA
TGAACAAGGCCTGGGGGAC


 


2327
TCCCCCAGGCCTTGTTCAT
ATGAACAAGGCCTGGGGGA


 


2328
CCCCCAGGCCTTGTTCATA
TATGAACAAGGCCTGGGGG


 


2329
CCCCAGGCCTTGTTCATAC
GTATGAACAAGGCCTGGGG


 


2330
CCCAGGCCTTGTTCATACT
AGTATGAACAAGGCCTGGG


 


2331
CCAGGCCTTGTTCATACTC
GAGTATGAACAAGGCCTGG


 


2332
CAGGCCTTGTTCATACTCT
AGAGTATGAACAAGGCCTG


 


2333
AGGCCTTGTTCATACTCTT
AAGAGTATGAACAAGGCCT


 


2334
GGCCTTGTTCATACTCTTG
CAAGAGTATGAACAAGGCC


 


2335
GCCTTGTTCATACTCTTGG
CCAAGAGTATGAACAAGGC


 


2336
CCTTGTTCATACTCTTGGC
GCCAAGAGTATGAACAAGG


 


2337
CTTGTTCATACTCTTGGCA
TGCCAAGAGTATGAACAAG


 


2338
TTGTTCATACTCTTGGCAA
TTGCCAAGAGTATGAACAA


 


2339
TGTTCATACTCTTGGCAAC
GTTGCCAAGAGTATGAACA


 


2340
GTTCATACTCTTGGCAACG
CGTTGCCAAGAGTATGAAC


 


2341
TTCATACTCTTGGCAACGT
ACGTTGCCAAGAGTATGAA


 


2342
TCATACTCTTGGCAACGTC
GACGTTGCCAAGAGTATGA


 


2343
CATACTCTTGGCAACGTCT
AGACGTTGCCAAGAGTATG


 


2344
ATACTCTTGGCAACGTCTG
CAGACGTTGCCAAGAGTAT


 


2345
TACTCTTGGCAACGTCTGG
CCAGACGTTGCCAAGAGTA


 


2346
ACTCTTGGCAACGTCTGGG
CCCAGACGTTGCCAAGAGT


 


2347
CTCTTGGCAACGTCTGGGC
GCCCAGACGTTGCCAAGAG


 


2348
TCTTGGCAACGTCTGGGCT
AGCCCAGACGTTGCCAAGA


 


2349
CTTGGCAACGTCTGGGCTG
CAGCCCAGACGTTGCCAAG


 


2350
TTGGCAACGTCTGGGCTGG
CCAGCCCAGACGTTGCCAA


 


2351
TGGCAACGTCTGGGCTGGG
CCCAGCCCAGACGTTGCCA


 


2352
GGCAACGTCTGGGCTGGGC
GCCCAGCCCAGACGTTGCC


 


2353
GCAACGTCTGGGCTGGGCC
GGCCCAGCCCAGACGTTGC


 


2354
CAACGTCTGGGCTGGGCCA
TGGCCCAGCCCAGACGTTG


 


2355
AACGTCTGGGCTGGGCCAG
CTGGCCCAGCCCAGACGTT


 


2356
ACGTCTGGGCTGGGCCAGG
CCTGGCCCAGCCCAGACGT


 


2357
CGTCTGGGCTGGGCCAGGC
GCCTGGCCCAGCCCAGACG


 


2358
GTCTGGGCTGGGCCAGGCG
CGCCTGGCCCAGCCCAGAC


 


2359
TCTGGGCTGGGCCAGGCGA
TCGCCTGGCCCAGCCCAGA


 


2360
CTGGGCTGGGCCAGGCGAT
ATCGCCTGGCCCAGCCCAG


 


2361
TGGGCTGGGCCAGGCGATG
CATCGCCTGGCCCAGCCCA


 


2362
GGGCTGGGCCAGGCGATGG
CCATCGCCTGGCCCAGCCC


 


2363
GGCTGGGCCAGGCGATGGG
CCCATCGCCTGGCCCAGCC


 


2364
GCTGGGCCAGGCGATGGGA
TCCCATCGCCTGGCCCAGC


 


2365
CTGGGCCAGGCGATGGGAA
TTCCCATCGCCTGGCCCAG


 


2366
TGGGCCAGGCGATGGGAAC
GTTCCCATCGCCTGGCCCA


 


2367
GGGCCAGGCGATGGGAACC
GGTTCCCATCGCCTGGCCC


 


2368
GGCCAGGCGATGGGAACCT
AGGTTCCCATCGCCTGGCC


 


2369
GCCAGGCGATGGGAACCTT
AAGGTTCCCATCGCCTGGC


 


2370
CCAGGCGATGGGAACCTTG
CAAGGTTCCCATCGCCTGG


 


2371
CAGGCGATGGGAACCTTGG
CCAAGGTTCCCATCGCCTG


 


2372
AGGCGATGGGAACCTTGGG
CCCAAGGTTCCCATCGCCT


 


2373
GGCGATGGGAACCTTGGGT
ACCCAAGGTTCCCATCGCC


 


2374
GCGATGGGAACCTTGGGTA
TACCCAAGGTTCCCATCGC


 


2375
CGATGGGAACCTTGGGTAC
GTACCCAAGGTTCCCATCG


 


2376
GATGGGAACCTTGGGTACC
GGTACCCAAGGTTCCCATC


 


2377
ATGGGAACCTTGGGTACCA
TGGTACCCAAGGTTCCCAT


 


2378
TGGGAACCTTGGGTACCAG
CTGGTACCCAAGGTTCCCA


 


2379
GGGAACCTTGGGTACCAGC
GCTGGTACCCAAGGTTCCC


 


2380
GGAACCTTGGGTACCAGCT
AGCTGGTACCCAAGGTTCC


 


2381
GAACCTTGGGTACCAGCTG
CAGCTGGTACCCAAGGTTC


 


2382
AACCTTGGGTACCAGCTGG
CCAGCTGGTACCCAAGGTT


 


2383
ACCTTGGGTACCAGCTGGG
CCCAGCTGGTACCCAAGGT


 


2384
CCTTGGGTACCAGCTGGGG
CCCCAGCTGGTACCCAAGG


 


2385
CTTGGGTACCAGCTGGGGC
GCCCCAGCTGGTACCCAAG


 


2386
TTGGGTACCAGCTGGGGCC
GGCCCCAGCTGGTACCCAA


 


2387
TGGGTACCAGCTGGGGCCA
TGGCCCCAGCTGGTACCCA


 


2388
GGGTACCAGCTGGGGCCAC
GTGGCCCCAGCTGGTACCC


 


2389
GGTACCAGCTGGGGCCACC
GGTGGCCCCAGCTGGTACC


 


2390
GTACCAGCTGGGGCCACCA
TGGTGGCCCCAGCTGGTAC


 


2391
TACCAGCTGGGGCCACCAG
CTGGTGGCCCCAGCTGGTA


 


2392
ACCAGCTGGGGCCACCAGC
GCTGGTGGCCCCAGCTGGT


 


2393
CCAGCTGGGGCCACCAGCA
TGCTGGTGGCCCCAGCTGG


 


2394
CAGCTGGGGCCACCAGCAA
TTGCTGGTGGCCCCAGCTG


 


2395
AGCTGGGGCCACCAGCAAC
GTTGCTGGTGGCCCCAGCT


 


2396
GCTGGGGCCACCAGCAACA
TGTTGCTGGTGGCCCCAGC


 


2397
CTGGGGCCACCAGCAACAC
GTGTTGCTGGTGGCCCCAG


 


2398
TGGGGCCACCAGCAACACC
GGTGTTGCTGGTGGCCCCA


 


2399
GGGGCCACCAGCAACACCA
TGGTGTTGCTGGTGGCCCC


 


2400
GGGCCACCAGCAACACCAA
TTGGTGTTGCTGGTGGCCC


 


2401
GGCCACCAGCAACACCAAG
CTTGGTGTTGCTGGTGGCC


 


2402
GCCACCAGCAACACCAAGG
CCTTGGTGTTGCTGGTGGC


 


2403
CCACCAGCAACACCAAGGT
ACCTTGGTGTTGCTGGTGG


 


2404
CACCAGCAACACCAAGGTG
CACCTTGGTGTTGCTGGTG


 


2405
ACCAGCAACACCAAGGTGC
GCACCTTGGTGTTGCTGGT


 


2406
CCAGCAACACCAAGGTGCC
GGCACCTTGGTGTTGCTGG


 


2407
CAGCAACACCAAGGTGCCC
GGGCACCTTGGTGTTGCTG


 


2408
AGCAACACCAAGGTGCCCC
GGGGCACCTTGGTGTTGCT


 


2409
GCAACACCAAGGTGCCCCT
AGGGGCACCTTGGTGTTGC


 


2410
CAACACCAAGGTGCCCCTC
GAGGGGCACCTTGGTGTTG


 


2411
AACACCAAGGTGCCCCTCT
AGAGGGGCACCTTGGTGTT


 


2412
ACACCAAGGTGCCCCTCTC
GAGAGGGGCACCTTGGTGT


 


2413
CACCAAGGTGCCCCTCTCC
GGAGAGGGGCACCTTGGTG


 


2414
ACCAAGGTGCCCCTCTCCT
AGGAGAGGGGCACCTTGGT


 


2415
CCAAGGTGCCCCTCTCCTG
CAGGAGAGGGGCACCTTGG


 


2416
CAAGGTGCCCCTCTCCTGA
TCAGGAGAGGGGCACCTTG


 


2417
AAGGTGCCCCTCTCCTGAG
CTCAGGAGAGGGGCACCTT


 


2418
AGGTGCCCCTCTCCTGAGC
GCTCAGGAGAGGGGCACCT


 


2419
GGTGCCCCTCTCCTGAGCC
GGCTCAGGAGAGGGGCACC


 


2420
GTGCCCCTCTCCTGAGCCG
CGGCTCAGGAGAGGGGCAC


 


2421
TGCCCCTCTCCTGAGCCGC
GCGGCTCAGGAGAGGGGCA


 


2422
GCCCCTCTCCTGAGCCGCC
GGCGGCTCAGGAGAGGGGC


 


2423
CCCCTCTCCTGAGCCGCCT
AGGCGGCTCAGGAGAGGGG


 


2424
CCCTCTCCTGAGCCGCCTG
CAGGCGGCTCAGGAGAGGG


 


2425
CCTCTCCTGAGCCGCCTGT
ACAGGCGGCTCAGGAGAGG


 


2426
CTCTCCTGAGCCGCCTGTC
GACAGGCGGCTCAGGAGAG


 


2427
TCTCCTGAGCCGCCTGTCA
TGACAGGCGGCTCAGGAGA


 


2428
CTCCTGAGCCGCCTGTCAC
GTGACAGGCGGCTCAGGAG


 


2429
TCCTGAGCCGCCTGTCACC
GGTGACAGGCGGCTCAGGA


 


2430
CCTGAGCCGCCTGTCACCC
GGGTGACAGGCGGCTCAGG


 


2431
CTGAGCCGCCTGTCACCCA
TGGGTGACAGGCGGCTCAG


 


2432
TGAGCCGCCTGTCACCCAG
CTGGGTGACAGGCGGCTCA


 


2433
GAGCCGCCTGTCACCCAGC
GCTGGGTGACAGGCGGCTC


 


2434
AGCCGCCTGTCACCCAGCG
CGCTGGGTGACAGGCGGCT


 


2435
GCCGCCTGTCACCCAGCGG
CCGCTGGGTGACAGGCGGC


 


2436
CCGCCTGTCACCCAGCGGG
CCCGCTGGGTGACAGGCGG


 


2437
CGCCTGTCACCCAGCGGGG
CCCCGCTGGGTGACAGGCG


 


2438
GCCTGTCACCCAGCGGGGC
GCCCCGCTGGGTGACAGGC


 


2439
CCTGTCACCCAGCGGGGCT
AGCCCCGCTGGGTGACAGG


 


2440
CTGTCACCCAGCGGGGCTG
CAGCCCCGCTGGGTGACAG


 


2441
TGTCACCCAGCGGGGCTGC
GCAGCCCCGCTGGGTGACA


 


2442
GTCACCCAGCGGGGCTGCT
AGCAGCCCCGCTGGGTGAC


 


2443
TCACCCAGCGGGGCTGCTG
CAGCAGCCCCGCTGGGTGA


 


2444
CACCCAGCGGGGCTGCTGT
ACAGCAGCCCCGCTGGGTG


 


2445
ACCCAGCGGGGCTGCTGTT
AACAGCAGCCCCGCTGGGT


 


2446
CCCAGCGGGGCTGCTGTTC
GAACAGCAGCCCCGCTGGG


 


2447
CCAGCGGGGCTGCTGTTCA
TGAACAGCAGCCCCGCTGG


 


2448
CAGCGGGGCTGCTGTTCAT
ATGAACAGCAGCCCCGCTG


 


2449
AGCGGGGCTGCTGTTCATC
GATGAACAGCAGCCCCGCT


 


2450
GCGGGGCTGCTGTTCATCC
GGATGAACAGCAGCCCCGC


 


2451
CGGGGCTGCTGTTCATCCT
AGGATGAACAGCAGCCCCG


 


2452
GGGGCTGCTGTTCATCCTA
TAGGATGAACAGCAGCCCC


 


2453
GGGCTGCTGTTCATCCTAC
GTAGGATGAACAGCAGCCC


 


2454
GGCTGCTGTTCATCCTACC
GGTAGGATGAACAGCAGCC


 


2455
GCTGCTGTTCATCCTACCC
GGGTAGGATGAACAGCAGC


 


2456
CTGCTGTTCATCCTACCCA
TGGGTAGGATGAACAGCAG


 


2457
TGCTGTTCATCCTACCCAC
GTGGGTAGGATGAACAGCA


 


2458
GCTGTTCATCCTACCCACC
GGTGGGTAGGATGAACAGC


 


2459
CTGTTCATCCTACCCACCC
GGGTCGGTAGGATGAACAG


 


2460
TGTTCATCCTACCCACCCA
TGGGTGGGTAGGATGAACA


 


2461
GTTCATCCTACCCACCCAC
GTGGGTGGGTAGGATGAAC


 


2462
TTCATCCTACCCACCCACT
AGTGGGTGGGTAGGATGAA


 


2463
TCATCCTACCCACCCACTA
TAGTGGGTGGGTAGGATGA


 


2464
CATCCTACCCACCCACTAA
TTAGTGGGTGGGTAGGATG


 


2465
ATCCTACCCACCCACTAAA
TTTAGTGGGTGGGTAGGAT


 


2466
TCCTACCCACCCACTAAAG
CTTTAGTGGGTGGGTAGGA


 


2467
CCTACCCACCCACTAAAGG
CCTTTAGTGGGTGGGTAGG


 


2468
CTACCCACCCACTAAAGGT
ACCTTTAGTGGGTGGGTAG


 


2469
TACCCACCCACTAAAGGTG
CACCTTTAGTGGGTGGGTA


 


2470
ACCCACCCACTAAAGGTGG
CCACCTTTAGTGGGTGGGT


 


2471
CCCACCCACTAAAGGTGGG
CCCACCTTTAGTGGGTGGG


 


2472
CCACCCACTAAAGGTGGGG
CCCCACCTTTAGTGGGTGG


 


2473
CACCCACTAAAGGTGGGGG
CCCCCACCTTTAGTGGGTG


 


2474
ACCCACTAAAGGTGGGGGT
ACCCCCACCTTTAGTGGGT


 


2475
CCCACTAAAGGTGGGGGTC
GACCCCCACCTTTAGTGGG


 


2476
CCACTAAAGGTGGGGGTCT
AGACCCCCACCTTTAGTGG


 


2477
CACTAAAGGTGGGGGTCTT
AAGACCCCCACCTTTAGTG


 


2478
ACTAAAGGTGGGGGTCTTG
CAAGACCCCCACCTTTAGT


 


2479
CTAAAGGTGGGGGTCTTGG
CCAAGACCCCCACCTTTAG


 


2480
TAAAGGTGGGGGTCTTGGC
GCCAAGACCCCCACCTTTA


 


2481
AAAGGTGGGGGTCTTGGCC
GGCCAAGACCCCCACCTTT


 


2482
AAGGTGGGGGTCTTGGCCC
GGGCCAAGACCCCCACCTT


 


2483
AGGTGGGGGTCTTGGCCCT
AGGGCCAAGACCCCCACCT


 


2484
GGTGGGGGTCTTGGCCCTT
AAGGGCCAAGACCCCCACC


 


2485
GTGGGGGTCTTGGCCCTTG
CAAGGGCCAAGACCCCCAC


 


2486
TGGGGGTCTTGGCCCTTGT
ACAAGGGCCAAGACCCCCA


 


2487
GGGGGTCTTGGCCCTTGTG
CACAAGGGCCAAGACCCCC


 


2488
GGGGTCTTGGCCCTTGTGG
CCACAAGGGCCAAGACCCC


 


2489
GGGTCTTGGCCCTTGTGGG
CCCACAAGGGCCAAGACCC


 


2490
GGTCTTGGCCCTTGTGGGA
TCCCACAAGGGCCAAGACC


 


2491
GTCTTGGCCCTTGTGGGAA
TTCCCACAAGGGCCAAGAC


 


2492
TCTTGGCCCTTGTGGGAAG
CTTCCCACAAGGGCCAAGA


 


2493
CTTGGCCCTTGTGGGAAGT
ACTTCCCACAAGGGCCAAG


 


2494
TTGGCCCTTGTGGGAAGTG
CACTTCCCACAAGGGCCAA


 


2495
TGGCCCTTGTGGGAAGTGC
GCACTTCCCACAAGGGCCA


 


2496
GGCCCTTGTGGGAAGTGCC
GGCACTTCCCACAAGGGCC


 


2497
GCCCTTGTGGGAAGTGCCA
TGGCACTTCCCACAAGGGC


 


2498
CCCTTGTGGGAAGTGCCAG
CTGGCACTTCCCACAAGGG


 


2499
CCTTGTGGGAAGTGCCAGG
CCTGGCACTTCCCACAAGG


 


2500
CTTGTGGGAAGTGCCAGGA
TCCTGGCACTTCCCACAAG


 


2501
TTGTGGGAAGTGCCAGGAG
CTCCTGGCACTTCCCACAA


 


2502
TGTGGGAAGTGCCAGGAGG
CCTCCTGGCACTTCCCACA


 


2503
GTGGGAAGTGCCAGGAGGG
CCCTCCTGGCACTTCCCAC


 


2504
TGGGAAGTGCCAGGAGGGC
GCCCTCCTGGCACTTCCCA


 


2505
GGGAAGTGCCAGGAGGGCC
GGCCCTCCTGGCACTTCCC


 


2506
GGAAGTGCCAGGAGGGCCT
AGGCCCTCCTGGCACTTCC


 


2507
GAAGTGCCAGGAGGGCCTG
CAGGCCCTCCTGGCACTTC


 


2508
AAGTGCCAGGAGGGCCTGG
CCAGGCCCTCCTGGCACTT


 


2509
AGTGCCAGGAGGGCCTGGA
TCCAGGCCCTCCTGGCACT


 


2510
GTGCCAGGAGGGCCTGGAG
CTCCAGGCCCTCCTGGCAC


 


2511
TGCCAGGAGGGCCTGGAGG
CCTCCAGGCCCTCCTGGCA


 


2512
GCCAGGAGGGCCTGGAGGG
CCCTCCAGGCCCTCCTGGC


 


2513
CCAGGAGGGCCTGGAGGGG
CCCCTCCAGGCCCTCCTGG


 


2514
CAGGAGGGCCTGGAGGGGG
CCCCCTCCAGGCCCTCCTG


 


2515
AGGAGGGCCTGGAGGGGGG
CCCCCCTCCAGGCCCTCCT


 


2516
GGAGGGCCTGGAGGGGGGT
ACCCCCCTCCAGGCCCTCC


 


2517
GAGGGCCTGGAGGGGGGTG
CACCCCCCTCCAGGCCCTC


 


2518
AGGGCCTGGAGGGGGGTGC
GCACCCCCCTCCAGGCCCT


 


2519
GGGCCTGGAGGGGGGTGCC
GGCACCCCCCTCCAGGCCC


 


2520
GGCCTGGAGGGGGGTGCCA
TGGCACCCCCCTCCAGGCC


 


2521
GCCTGGAGGGGGGTGCCAG
CTGGCACCCCCCTCCAGGC


 


2522
CCTGGAGGGGGGTGCCAGT
ACTGGCACCCCCCTCCAGG


 


2523
CTGGAGGGGGGTGCCAGTG
CACTGGCACCCCCCTCCAG


 


2524
TGGAGGGGGGTGCCAGTGG
CCACTGGCACCCCCCTCCA


 


2525
GGAGGGGGGTGCCAGTGGA
TCCACTGGCACCCCCCTCC


 


2526
GAGGGGGGTGCCAGTGGAG
CTCCACTGGCACCCCCCTC


 


2527
AGGGGGGTGCCAGTGGAGC
GCTCCACTGGCACCCCCCT


 


2528
GGGGGGTGCCAGTGGAGCC
GGCTCCACTGGCACCCCCC


 


2529
GGGGGTGCCAGTGGAGCCA
TGGCTCCACTGGCACCCCC


 


2530
GGGGTGCCAGTGGAGCCAG
CTGGCTCCACTGGCACCCC


 


2531
GGGTGCCAGTGGAGCCAGC
GCTGGCTCCACTGGCACCC


 


2532
GGTGCCAGTGGAGCCAGCG
CGCTGGCTCCACTGGCACC


 


2533
GTGCCAGTGGAGCCAGCGA
TCGCTGGCTCCACTGGCAC


 


2534
TGCCAGTGGAGCCAGCGAA
TTCGCTGGCTCCACTGGCA


 


2535
GCCAGTGGAGCCAGCGAAC
GTTCGCTGGCTCCACTGGC


 


2536
CCAGTGGAGCCAGCGAACC
GGTTCGCTGGCTCCACTGG


 


2537
CAGTGGAGCCAGCGAACCC
GGGTTCGCTGGCTCCACTG


 


2538
AGTGGAGCCAGCGAACCCA
TGGGTTCGCTGGCTCCACT


 


2539
GTGGAGCCAGCGAACCCAG
CTGGGTTCGCTGGCTCCAC


 


2540
TGGAGCCAGCGAACCCAGC
GCTGGGTTCGCTGGCTCCA


 


2541
GGAGCCAGCGAACCCAGCG
CGCTGGGTTCGCTGGCTCC


 


2542
GAGCCAGCGAACCCAGCGA
TCGCTGGGTTCGCTGGCTC


 


2543
AGCCAGCGAACCCAGCGAG
CTCGCTGGGTTCGCTGGCT


 


2544
GCCAGCGAACCCAGCGAGG
CCTCGCTGGGTTCGCTGGC


 


2545
CCAGCGAACCCAGCGAGGA
TCCTCGCTGGGTTCGCTGG


 


2546
CAGCGAACCCAGCGAGGAA
TTCCTCGCTGGGTTCGCTG


 


2547
AGCGAACCCAGCGAGGAAG
CTTCCTCGCTGGGTTCGCT


 


2548
GCGAACCCAGCGAGGAAGT
ACTTCCTCGCTGGGTTCGC


 


2549
CGAACCCAGCGAGGAAGTG
CACTTCCTCGCTGGGTTCG


 


2550
GAACCCAGCGAGGAAGTGA
TCACTTCCTCGCTGGGTTC


 


2551
AACCCAGCGAGGAAGTGAA
TTCACTTCCTCGCTGGGTT


 


2552
ACCCAGCGAGGAAGTGAAC
GTTCACTTCCTCGCTGGGT


 


2553
CCCAGCGAGGAAGTGAACA
TGTTCACTTCCTCGCTGGG


 


2554
CCAGCGAGGAAGTGAACAA
TTGTTCACTTCCTCGCTGG


 


2555
CAGCGAGGAAGTGAACAAG
CTTGTTCACTTCCTCGCTG


 


2556
AGCGAGGAAGTGAACAAGG
CCTTGTTCACTTCCTCGCT


 


2557
GCGAGGAAGTGAACAAGGC
GCCTTGTTCACTTCCTCGC


 


2558
CGAGGAAGTGAACAAGGCC
GGCCTTGTTCACTTCCTCG


 


2559
GAGGAAGTGAACAAGGCCT
AGGCCTTGTTCACTTCCTC


 


2560
AGGAAGTGAACAAGGCCTC
GAGGCCTTGTTCACTTCCT


 


2561
GGAAGTGAACAAGGCCTCT
AGAGGCCTTGTTCACTTCC


 


2562
GAAGTGAACAAGGCCTCTG
CAGAGGCCTTGTTCACTTC


 


2563
AAGTGAACAAGGCCTCTGG
CCAGAGGCCTTGTTCACTT


 


2564
AGTGAACAAGGCCTCTGGC
GCCAGAGGCCTTGTTCACT


 


2565
GTGAACAAGGCCTCTGGCC
GGCCAGAGGCCTTGTTCAC


 


2566
TGAACAAGGCCTCTGGCCC
GGGCCAGAGGCCTTGTTCA


 


2567
GAACAAGGCCTCTGGCCCC
GGGGCCAGAGGCCTTGTTC


 


2568
AACAAGGCCTCTGGCCCCA
TGGGGCCAGAGGCCTTGTT


 


2569
ACAAGGCCTCTGGCCCCAG
CTGGGGCCAGAGGCCTTGT


 


2570
CAAGGCCTCTGGCCCCAGG
CCTGGGGCCAGAGGCCTTG


 


2571
AAGGCCTCTGGCCCCAGGG
CCCTGGGGCCAGAGGCCTT


 


2572
AGGCCTCTGGCCCCAGGGC
GCCCTGGGGCCAGAGGCCT


 


2573
GGCCTCTGGCCCCAGGGCC
GGCCCTGGGGCCAGAGGCC


 


2574
GCCTCTGGCCCCAGGGCCT
AGGCCCTGGGGCCAGAGGC


 


2575
CCTCTGGCCCCAGGGCCTG
CAGGCCCTGGGGCCAGAGG


 


2576
CTCTGGCCCCAGGGCCTGT
ACAGGCCCTGGGGCCAGAG


 


2577
TCTGGCCCCAGGGCCTGTC
GACAGGCCCTGGGGCCAGA


 


2578
CTGGCCCCAGGGCCTGTCC
GGACAGGCCCTGGGGCCAG


 


2579
TGGCCCCAGGGCCTGTCCC
GGGACAGGCCCTGGGGCCA


 


2580
GGCCCCAGGGCCTGTCCCC
GGGGACAGGCCCTGGGGCC


 


2581
GCCCCAGGGCCTGTCCCCC
GGGGGACAGGCCCTGGGGC


 


2582
CCCCAGGGCCTGTCCCCCC
GGGGGGACAGGCCCTGGGG


 


2583
CCCAGGGCCTGTCCCCCCA
TGGGGGGACAGGCCCTGGG


 


2584
CCAGGGCCTGTCCCCCCAG
CTGGGGGGACAGGCCCTGG


 


2585
CAGGGCCTGTCCCCCCAGC
GCTGGGGGGACAGGCCCTG


 


2586
AGGGCCTGTCGCCCCAGCC
GGCTGGGGGGACAGGCCCT


 


2587
GGGCCTGTCCGCCCAGCCA
TGGCTGGGGGGACAGGCCC


 


2588
GGCCTGTCCCCCCAGCCAC
GTGGCTGGGGGGACAGGCC


 


2589
GCCTGTCCCCCCAGCCACC
GGTGGCTGGGGGGACAGGC


 


2590
CCTGTCCCCCCAGCCACCA
TGGTGGCTGGGGGGACAGG


 


2591
CTGTCCCCCCAGCGACCAC
GTGGTGGCTGGGGGGACAG


 


2592
TGTCCCCCCAGCCACCACA
TGTGGTGGCTGGGGGGACA


 


2593
GTCCCCCCAGCCACCACAC
GTGTGGTGGCTGGGGGGAC


 


2594
TCCCCCCAGCCACCACACC
GGTGTGGTGGCTGGGGGGA


 


2595
CCCCCCAGCCACCACACCA
TGGTGTGGTGGCTGGGGGG


 


2596
CCCCCAGCCACCACACCAA
TTGGTGTGGTGGCTGGGGG


 


2597
CCCCAGCCACCACACCAAG
CTTGGTGTGGTGGCTGGGG


 


2598
CCCAGCCACCACACCAAGC
GCTTGGTGTGGTGGCTGGG


 


2599
CCAGCCACCACACCAAGCT
AGCTTGGTGTGGTGGCTGG


 


2600
CAGCCACCACACCAAGCTG
CAGCTTGGTGTGGTGGCTG


 


2601
AGCCACCACACCAAGCTGA
TCAGCTTGGTGTGGTGGCT


 


2602
GCCACCACACCAAGCTGAA
TTCAGCTTGGTGTGGTGGC


 


2603
CCACCACACCAAGCTGAAG
CTTCAGCTTGGTGTGGTGG


 


2604
CACCACACCAAGCTGAAGA
TCTTCAGCTTGGTGTGGTG


 


2605
ACCACACCAAGCTGAAGAA
TTCTTCAGCTTGGTGTGGT


 


2606
CCACACCAAGCTGAAGAAG
CTTCTTCAGCTTGGTGTGG


 


2607
CACACCAAGCTGAAGAAGA
TCTTCTTCAGCTTGGTGTG


 


2608
ACACCAAGCTGAAGAAGAC
GTCTTCTTCAGCTTGGTGT


 


2609
CACCAAGCTGAAGAAGACA
TGTCTTCTTCAGCTTGGTG


 


2610
ACCAAGCTGAAGAAGACAT
ATGTCTTCTTCAGCTTGGT


 


2611
CCAAGCTGAAGAAGACATG
CATGTCTTCTTCAGCTTGG


 


2612
CAAGCTGAAGAAGACATGG
CCATGTCTTCTTCAGCTTG


 


2613
AAGCTGAAGAAGACATGGC
GCCATGTCTTCTTCAGCTT


 


2614
AGCTGAAGAAGACATGGCT
AGCCATGTCTTCTTCAGCT


 


2615
GCTGAAGAAGACATGGCTC
GAGCCATGTCTTCTTCAGC


 


2616
CTGAAGAAGACATGGCTCA
TGAGCCATGTCTTCTTCAG


 


2617
TGAAGAAGACATGGCTCAC
GTGAGCCATGTCTTCTTCA


 


2618
GAAGAAGACATGGCTCACA
TGTGAGCCATGTCTTCTTC


 


2619
AAGAAGACATGGCTCACAC
GTGTGAGCCATGTCTTCTT


 


2620
AGAAGACATGGCTCACACG
CGTGTGAGCCATGTCTTCT


 


2621
GAAGACATGGCTCACACGG
CCGTGTGAGCCATGTCTTC


 


2622
AAGACATGGCTCACACGGC
GCCGTGTGAGCCATGTCTT


 


2623
AGACATGGCTCACACGGCA
TGCCGTGTGAGCCATGTCT


 


2624
GACATGGCTCACACGGCAC
GTGCCGTGTGAGCCATGTC


 


2625
ACATGGCTCACACGGCACT
AGTGCCGTGTGAGCCATGT


 


2626
CATGGCTCACACGGCACTC
GAGTGCCGTGTGAGCCATG


 


2627
ATGGCTCACACGGCACTCG
CGAGTGCCGTGTGAGCCAT


 


2628
TGGCTCACACGGCACTCGG
CCGAGTGCCGTGTGAGCCA


 


2629
GGCTCACACGGCACTCGGA
TCCGAGTGCCGTGTGAGCC


 


2630
GCTCACACGGCACTCGGAG
CTCCGAGTGCCGTGTGAGC


 


2631
CTCACACGGCACTCGGAGC
GCTCCGAGTGCCGTGTGAG


 


2632
TCACACGGCACTCGGAGCA
TGCTCCGAGTGCCGTGTGA


 


2633
CACACGGCACTCGGAGCAG
CTGCTCCGAGTGCCGTGTG


 


2634
ACACGGCACTCGGAGCAGT
ACTGCTCCGAGTGCCGTGT


 


2635
CACGGCACTCGGAGCAGTT
AACTGCTCCGAGTGCCGTG


 


2636
ACGGCACTCGGAGCAGTTT
AAACTGCTCCGAGTGCCGT


 


2637
CGGCACTCGGAGCAGTTTG
CAAACTGCTCCGAGTGCCG


 


2638
GGCACTCGGAGCAGTTTGA
TCAAACTGCTCCGAGTGCC


 


2639
GCACTCGGAGCAGTTTGAA
TTCAAACTGCTCCGAGTGC


 


2640
CACTCGGAGCAGTTTGAAT
ATTCAAACTGCTCCGAGTG


 


2641
ACTCGGAGCAGTTTGAATG
CATTCAAACTGCTCCGAGT


 


2642
CTCGGAGCAGTTTGAATGT
ACATTCAAACTGCTCCGAG


 


2643
TCGGAGCAGTTTGAATGTC
GACATTCAAACTGCTCCGA


 


2644
CGGAGCAGTTTGAATGTCC
GGACATTCAAACTGCTCCG


 


2645
GGAGCAGTTTGAATGTCCA
TGGACATTCAAACTGCTCC


 


2646
GAGCAGTTTGAATGTCCAC
GTGGACATTCAAACTGCTC


 


2647
AGCAGTTTGAATGTCCACG
CGTGGACATTCAAACTGCT


 


2648
GCAGTTTGAATGTCCACGC
GCGTGGACATTCAAACTGC


 


2649
CAGTTTGAATGTCCACGCG
CGCGTGGACATTCAAACTG


 


2650
AGTTTGAATGTCCACGCGG
CCGCGTGGACATTCAAACT


 


2651
GTTTGAATGTCCACGCGGC
GCCGCGTGGACATTCAAAC


 


2652
TTTGAATGTCCACGCGGCT
AGCCGCGTGGACATTCAAA


 


2653
TTGAATGTCCACGCGGCTG
CAGCCGCGTGGACATTCAA


 


2654
TGAATGTCCACGCGGCTGC
GCAGCCGCGTGGACATTCA


 


2655
GAATGTCCACGCGGCTGCC
GGCAGCCGCGTGGACATTC


 


2656
AATGTCCACGCGGCTGCCC
GGGCAGCCGCGTGGACATT


 


2657
ATGTCCACGCGGCTGCCCT
AGGGCAGCCGCGTGGACAT


 


2658
TGTCCACGCGGCTGCCCTG
CAGGGCAGCCGCGTGGACA


 


2659
GTCCACGCGGCTGCCCTGA
TCAGGGCAGCCGCGTGGAC


 


2660
TCCACGCGGCTGCCCTGAG
CTCAGGGCAGCCGCGTGGA


 


2661
CCACGCGGCTGCCCTGAGG
CCTCAGGGCAGCCGCGTGG


 


2662
CACGCGGCTGCCCTGAGGT
ACCTCAGGGCAGCCGCGTG


 


2663
ACGCGGCTGCCCTGAGGTC
GACCTCAGGGCAGCCGCGT


 


2664
CGCGGCTGCCCTGAGGTCG
CGACCTCAGGGCAGCCGCG


 


2665
GCGGCTGCCCTGAGGTCGA
TCGACCTCAGGGCAGCCGC


 


2666
CGGCTGCCCTGAGGTCGAG
CTCGACCTCAGGGCAGCCG


 


2667
GGCTGCCCTGAGGTCGAGG
CCTCGACCTCAGGGCAGCC


 


2668
GCTGCCCTGAGGTCGAGGA
TCCTCGACCTCAGGGCAGC


 


2669
CTGCCCTGAGGTCGAGGAG
CTCCTCGACCTCAGGGCAG


 


2670
TGCCCTGAGGTCGAGGAGA
TCTCCTCGACCTCAGGGCA


 


2671
GCCCTGAGGTCGAGGAGAG
CTCTCCTCGACCTCAGGGC


 


2672
CCCTGAGGTCGAGGAGAGG
CCTCTCCTCGACCTCAGGG


 


2673
CCTGAGGTCGAGGAGAGGC
GCCTCTCCTCGACCTCAGG


 


2674
CTGAGGTCGAGGAGAGGCC
GGCCTCTCCTCGACCTCAG


 


2675
TGAGGTCGAGGAGAGGCCG
CGGCCTCTCCTCGACCTCA


 


2676
GAGGTCGAGGAGAGGCCGG
CCGGCCTCTCCTCGACCTC


 


2677
AGGTCGAGGAGAGGCCGGT
ACCGGCCTCTCCTCGACCT


 


2678
GGTCGAGGAGAGGCCGGTT
AACCGGCCTCTCCTCGACC


 


2679
GTCGAGGAGAGGCCGGTTG
CAACCGGCCTCTCCTCGAC


 


2680
TCGAGGAGAGGCCGGTTGC
GCAACCGGCCTCTCCTCGA


 


2681
CGAGGAGAGGCCGGTTGCT
AGCAACCGGCCTCTCCTCG


 


2682
GAGGAGAGGCCGGTTGCTC
GAGCAACCGGCCTCTCCTC


 


2683
AGGAGAGGCCGGTTGCTCG
CGAGCAACCGGCCTCTCCT


 


2684
GGAGAGGCCGGTTGCTCGG
CCGAGCAACCGGCCTCTCC


 


2685
GAGAGGCCGGTTGCTCGGC
GCCGAGCAACCGGCCTCTC


 


2686
AGAGGCCGGTTGCTCGGCT
AGCCGAGCAACCGGCCTCT


 


2687
GAGGCCGGTTGCTCGGCTC
GAGCCGAGCAACCGGCCTC


 


2688
AGGCCGGTTGCTCGGCTCC
GGAGCCGAGCAACCGGCCT


 


2689
GGCCGGTTGCTCGGCTCCG
CGGAGCCGAGCAACCGGCC


 


2690
GCCGGTTGCTCGGCTCCGG
CCGGAGCCGAGCAACCGGC


 


2691
CCGGTTGCTCGGCTCCGGG
CCCGGAGCCGAGCAACCGG


 


2692
CGGTTGCTCGGCTCCGGGC
GCCCGGAGCCGAGCAACCG


 


2693
GGTTGCTCGGCTCCGGGCC
GGCCCGGAGCCGAGCAACC


 


2694
GTTGCTCGGCTCCGGGCCC
GGGCCCGGAGCCGAGCAAC


 


2695
TTGCTCGGCTCCGGGCCCT
AGGGCCCGGAGCCGAGCAA


 


2696
TGCTCGGCTCCGGGCCCTC
GAGGGCCCGGAGCCGAGCA


 


2697
GCTCGGCTCCGGGCCCTCA
TGAGGGCCCGGAGCCGAGC


 


2698
CTCGGCTCCGGGCCCTCAA
TTGAGGGCCCGGAGCCGAG


 


2699
TCGGCTCCGGGCCCTCAAA
TTTGAGGGCCCGGAGCCGA


 


2700
CGGCTCCGGGCCCTCAAAA
TTTTGAGGGCCCGGAGCCG


 


2701
GGCTCCGGGCCCTCAAAAG
CTTTTGAGGGCCCGGAGCC


 


2702
GCTCCGGGCCCTCAAAAGG
CCTTTTGAGGGCCCGGAGC


 


2703
CTCCGGGCCCTCAAAAGGG
CCCTTTTGAGGGCCCGGAG


 


2704
TCCGGGCCCTCAAAAGGGC
GCCCTTTTGAGGGCCCGGA


 


2705
CCGGGCCCTCAAAAGGGCA
TGCCCTTTTGAGGGCCCGG


 


2706
CGGGCCCTCAAAAGGGCAG
CTGCCCTTTTGAGGGCCCG


 


2707
GGGCCCTCAAAAGGGCAGG
CCTGCCCTTTTGAGGGCCC


 


2708
GGCCCTCAAAAGGGCAGGC
GCCTGCCCTTTTGAGGGCC


 


2709
GCCCTCAAAAGGGCAGGCA
TGCCTGCCCTTTTGAGGGC


 


2710
CCCTCAAAAGGGCAGGCAG
CTGCCTGCCCTTTTGAGGG


 


2711
CCTCAAAAGGGCAGGCAGC
GCTGCCTGCCCTTTTGAGG


 


2712
CTCAAAAGGGCAGGCAGCC
GGCTGCCTGCCCTTTTGAG


 


2713
TCAAAAGGGCAGGCAGCCC
GGGCTGCCTGCCCTTTTGA


 


2714
CAAAAGGGCAGGCAGCCCC
GGGGCTGCCTGCCCTTTTG


 


2715
AAAAGGGCAGGCAGCCCCG
CGGGGCTGCCTGCCCTTTT


 


2716
AAAGGGCAGGCAGCCCCGA
TCGGGGCTGCCTGCCCTTT


 


2717
AAGGGCAGGCAGCCCCGAG
CTCGGGGCTGCCTGCCCTT


 


2718
AGGGCAGGCAGCCCCGAGG
CCTCGGGGCTGCCTGCCCT


 


2719
GGGCAGGCAGCCCCGAGGT
ACCTCGGGGCTGCCTGCCC


 


2720
GGCAGGCAGCCCCGAGGTC
GACCTCGGGGCTGCCTGCC


 


2721
GCAGGCAGCCCCGAGGTCC
GGACCTCGGGGCTGCCTGC


 


2722
CAGGCAGCCCCGAGGTCCA
TGGACCTCGGGGCTGCCTG


 


2723
AGGCAGCCCCGAGGTCCAG
CTGGACCTCGGGGCTGCCT


 


2724
GGCAGCCCCGAGGTCCAGG
CCTGGACCTCGGGGCTGCC


 


2725
GCAGCCCCGAGGTCCAGGG
CCCTGGACCTCGGGGCTGC


 


2726
CAGCCCCGAGGTCCAGGGA
TCCCTGGACCTCGGGGCTG


 


2727
AGCCCCGAGGTCCAGGGAG
CTCCCTGGACCTCGGGGCT


 


2728
GCCCCGAGGTCCAGGGAGC
GCTCCCTGGACCTCGGGGC


 


2729
CCCCGAGGTCCAGGGAGCA
TGCTCCCTGGACCTCGGGG


 


2730
CCCGAGGTCCAGGGAGCAA
TTGCTCCCTGGACCTCGGG


 


2731
CCGAGGTCCAGGGAGCAAT
ATTGCTCCCTGGACCTCGG


 


2732
CGAGGTCCAGGGAGCAATG
CATTGCTCCCTGGACCTCG


 


2733
GAGGTCCAGGGAGCAATGG
CCATTGCTCCCTGGACCTC


 


2734
AGGTCCAGGGAGCAATGGG
CCCATTGCTCCCTGGACCT


 


2735
GGTCCAGGGAGCAATGGGC
GCCCATTGCTCCCTGGACC


 


2736
GTCCAGGGAGCAATGGGCA
TGCCCATTGCTCCCTGGAC


 


2737
TCCAGGGAGCAATGGGCAG
CTGCCCATTGCTCCCTGGA


 


2738
CCAGGGAGCAATGGGCAGT
ACTGCCCATTGCTCCCTGG


 


2739
CAGGGAGCAATGGGCAGTC
GACTGCCCATTGCTCCCTG


 


2740
AGGGAGCAATGGGCAGTCC
GGACTGCCCATTGCTCCCT


 


2741
GGGAGCAATGGGCAGTCCA
TGGACTGCCCATTGCTCCC


 


2742
GGAGCAATGGGCAGTCCAG
CTGGACTGCCCATTGCTCC


 


2743
GAGCAATGGGCAGTCCAGC
GCTGGACTGCCCATTGCTC


 


2744
AGCAATGGGCAGTCCAGCC
GGCTGGACTGCCCATTGCT


 


2745
GCAATGGGCAGTCCAGCCC
GGGCTGGACTGCCCATTGC


 


2746
CAATGGGCAGTCCAGCCCC
GGGGCTGGACTGCCCATTG


 


2747
AATGGGCAGTCCAGCCCCC
GGGGGCTGGACTGCCCATT


 


2748
ATGGGCAGTCCAGCCCCCA
TGGGGGCTGGACTGCCCAT


 


2749
TGGGCAGTCCAGCCCCCAA
TTGGGGGCTGGACTGCCCA


 


2750
GGGCAGTCCAGCCCCCAAG
CTTGGGGGCTGGACTGCCC


 


2751
GGCAGTCCAGCCCCCAAGC
GCTTGGGGGCTGGACTGCC


 


2752
GCAGTCCAGCCCCCAAGCG
CGCTTGGGGGCTGGACTGC


 


2753
CAGTCCAGCCCCCAAGCGG
CCGCTTGGGGGCTGGACTG


 


2754
AGTCCAGCCCCCAAGCGGC
GCCGCTTGGGGGCTGGACT


 


2755
GTCCAGCCCCCAAGCGGCC
GGCCGCTTGGGGGCTGGAC


 


2756
TCCAGCCCCCAAGCGGCCA
TGGCCGCTTGGGGGCTGGA


 


2757
CCAGCCCCCAAGCGGCCAC
GTGGCCGCTTGGGGGCTGG


 


2758
CAGCCCCCAAGCGGCCACC
GGTGGCCGCTTGGGGGCTG


 


2759
AGCCCCCAAGCGGCCACCG
CGGTGGCCGCTTGGGGGCT


 


2760
GCCCCCAAGCGGCCACCGG
CCGGTGGCCGCTTGGGGGC


 


2761
CCCCCAAGCGGCCACCGGA
TCCGGTGGCCGCTTGGGGG


 


2762
CCCCAAGCGGCCACCGGAC
GTCCGGTGGCCGCTTGGGG


 


2763
CCCAAGCGGCCACCGGACC
GGTCCGGTGGCCGCTTGGG


 


2764
CCAAGCGGCCACCGGACCC
GGGTCCGGTGGCCGCTTGG


 


2765
CAAGCGGCCACCGGACCCT
AGGGTCCGGTGGCCGCTTG


 


2766
AAGCGGCCACCGGACCCTT
AAGGGTCCGGTGGCCGCTT


 


2767
AGCGGCCACCGGACCCTTT
AAAGGGTCCGGTGGCCGCT


 


2768
GCGGCCACCGGACCCTTTT
AAAAGGGTCCGGTGGCCGC


 


2769
CGGCCACCGGACCCTTTTC
GAAAAGGGTCCGGTGGCCG


 


2770
GGCCACCGGACCCTTTTCC
GGAAAAGGGTCCGGTGGCC


 


2771
GCCACCGGACCCTTTTCCA
TGGAAAAGGGTCCGGTGGC


 


2772
CCACCGGACCCTTTTCCAG
CTGGAAAAGGGTCCGGTGG


 


2773
CACCGGACCCTTTTCCAGG
CCTGGAAAAGGGTCCGGTG


 


2774
ACCGGACCCTTTTCCAGGC
GCCTGGAAAAGGGTCCGGT


 


2775
CCGGACCCTTTTCCAGGCA
TGCCTGGAAAAGGGTCCGG


 


2776
CGGACCCTTTTCCAGGCAC
GTGCCTGGAAAAGGGTCCG


 


2777
GGACCCTTTTCCAGGCACT
AGTGCCTGGAAAAGGGTCC


 


2778
GACCCTTTTCCAGGCACTG
CAGTGCCTGGAAAAGGGTC


 


2779
ACCCTTTTCCAGGCACTGC
GCAGTGCCTGGAAAAGGGT


 


2780
CCCTTTTCCAGGCACTGCA
TGCAGTGCCTGGAAAAGGG


 


2781
CCTTTTCCAGGCACTGCAG
CTGCAGTGCCTGGAAAAGG


 


2782
CTTTTCCAGGCACTGCAGA
TCTGCAGTGCCTGGAAAAG


 


2783
TTTTCCAGGCACTGCAGAA
TTCTGCAGTGCCTGGAAAA


 


2784
TTTCCAGGCACTGCAGAAC
GTTCTGCAGTGCCTGGAAA


 


2785
TTCCAGGCACTGCAGAACA
TGTTCTGCAGTGCCTGGAA


 


2786
TCCAGGCACTGCAGAACAG
CTGTTCTGCAGTGCCTGGA


 


2787
CCAGGCACTGCAGAACAGG
CCTGTTCTGCAGTGCCTGG


 


2788
CAGGCACTGCAGAACAGGG
CCCTGTTCTGCAGTGCCTG


 


2789
AGGCACTGCAGAACAGGGG
CCCCTGTTCTGCAGTGCCT


 


2790
GGCACTGCAGAACAGGGGG
CCCCCTGTTCTGCAGTGCC


 


2791
GCACTGCAGAACAGGGGGC
GCCCCCTGTTCTGCAGTGC


 


2792
CACTGCAGAACAGGGGGCT
AGCCCCCTGTTCTGCAGTG


 


2793
ACTGCAGAACAGGGGGCTG
CAGCCCCCTGTTCTGCAGT


 


2794
CTGCAGAACAGGGGGCTGG
CCAGCCCCCTGTTCTGCAG


 


2795
TGCAGAACAGGGGGCTGGG
CCCAGCCCCCTGTTCTGCA


 


2796
GCAGAACAGGGGGCTGGGG
CCCCAGCCCCCTGTTCTGC


 


2797
CAGAACAGGGGGCTGGGGG
CCCCCAGCCCCCTGTTCTG


 


2798
AGAACAGGGGGCTGGGGGT
ACCCCCAGCCCCCTGTTCT


 


2799
GAACAGGGGGCTGGGGGTT
AACCCCCAGCCCCCTGTTC


 


2800
AACAGGGGGCTGGGGGTTG
CAACCCCCAGCCCCCTGTT


 


2801
ACAGGGGGCTGGGGGTTGG
CCAACCCCCAGCCCCCTGT


 


2802
CAGGGGGCTGGGGGTTGGC
GCCAACCCCCAGCCCCCTG


 


2803
AGGGGGCTGGGGGTTGGCA
TGCCAACCCCCAGCCCCCT


 


2804
GGGGGCTGGGGGTTGGCAG
CTGCCAACCCCCAGCCCCC


 


2805
GGGGCTGGGGGTTGGCAGG
CCTGCCAACCCCCAGCCCC


 


2806
GGGCTGGGGGTTGGCAGGA
TCCTGCCAACCCCCAGCCC


 


2807
GGCTGGGGGTTGGCAGGAG
CTCCTGCCAACCCCCAGCC


 


2808
GCTGGGGGTTGGCAGGAGG
CCTCCTGCCAACCCCCAGC


 


2809
CTGGGGGTTGGCAGGAGGT
ACCTCCTGCCAACCCCCAG


 


2810
TGGGGGTTGGCAGGAGGTG
CACCTCCTGCCAACCCCCA


 


2811
GGGGGTTGGCAGGAGGTGC
GCACCTCCTGCCAACCCCC


 


2812
GGGGTTGGCAGGAGGTGCG
CGCACCTCCTGCCAACCCC


 


2813
GGGTTGGCAGGAGGTGCGG
CCGCACCTCCTGCCAACCC


 


2814
GGTTGGCAGGAGGTGCGGG
CCCGCACCTCCTGCCAACC


 


2815
GTTGGCAGGAGGTGCGGGA
TCCCGCACCTCCTGCCAAC


 


2816
TTGGCAGGAGGTGCGGGAC
GTCCCGCACCTCCTGCCAA


 


2817
TGGCAGGAGGTGCGGGACA
TGTCCCGCACCTCCTGCCA


 


2818
GGCAGGAGGTGCGGGACAC
GTGTCCCGCACCTCCTGCC


 


2819
GCAGGAGGTGCGGGACACA
TGTGTCCCGCACCTCCTGC


 


2820
CAGGAGGTGCGGGACACAT
ATGTGTCCCGCACCTCCTG


 


2821
AGGAGGTGCGGGACACATC
GATGTGTCCCGCACCTCCT


 


2822
GGAGGTGCGGGACACATCG
CGATGTGTCCCGCACCTCC


 


2823
GAGGTGCGGGACACATCGA
TCGATGTGTCCCGCACCTC


 


2824
AGGTGCGGGACACATCGAT
ATCGATGTGTCCCGCACCT


 


2825
GGTGCGGGACACATCGATA
TATCGATGTGTCCCGCACC


 


2826
GTGCGGGACACATCGATAG
CTATCGATGTGTCCCGCAC


 


2827
TGCGGGACACATCGATAGG
CCTATCGATGTGTCCCGCA


 


2828
GCGGGACACATCGATAGGG
CCCTATCGATGTGTCCCGC


 


2829
CGGGACACATCGATAGGGA
TCCCTATCGATGTGTCCCG


 


2830
GGGACACATCGATAGGGAA
TTCCCTATCGATGTGTCCC


 


2831
GGACACATCGATAGGGAAC
GTTCCCTATCGATGTGTCC


 


2832
GACACATCGATAGGGAACA
TGTTCCCTATCGATGTGTC


 


2833
ACACATCGATAGGGAACAA
TTGTTCCCTATCGATGTGT


 


2834
CACATCGATAGGGAACAAG
CTTGTTCCCTATCGATGTG


 


2835
ACATCGATAGGGAACAAGG
CCTTGTTCCCTATCGATGT


 


2836
CATCGATAGGGAACAAGGA
TCCTTGTTCCCTATCGATG


 


2837
ATCGATAGGGAACAAGGAT
ATCCTTGTTCCCTATCGAT


 


2838
TCGATAGGGAACAAGGATG
CATCCTTGTTCCCTATCGA


 


2839
CGATAGGGAACAAGGATGT
ACATCCTTGTTCCCTATCG


 


2840
GATAGGGAACAAGGATGTG
CACATCCTTGTTCCCTATC


 


2841
ATAGGGAACAAGGATGTGG
CCACATCCTTGTTCCCTAT


 


2842
TAGGGAACAAGGATGTGGA
TCCACATCCTTGTTCCCTA


 


2843
AGGGAACAAGGATGTGGAC
GTCCACATCCTTGTTCCCT


 


2844
GGGAACAAGGATGTGGACT
AGTCCACATCCTTGTTCCC


 


2845
GGAACAAGGATGTGGACTC
GAGTCCACATCCTTGTTCC


 


2846
GAACAAGGATGTGGACTCG
CGAGTCCACATCCTTGTTC


 


2847
AACAAGGATGTGGACTCGG
CCGAGTCCACATCCTTGTT


 


2848
ACAAGGATGTGGACTCGGG
CCCGAGTCCACATCCTTGT


 


2849
CAAGGATGTGGACTCGGGA
TCCCGAGTCCACATCCTTG


 


2850
AAGGATGTGGACTCGGGAC
GTCCCGAGTCCACATCCTT


 


2851
AGGATGTGGACTCGGGACA
TGTCCCGAGTCCACATCCT


 


2852
GGATGTGGACTCGGGACAG
CTGTCCCGAGTCCACATCC


 


2853
GATGTGGACTCGGGACAGC
GCTGTCCCGAGTCCACATC


 


2854
ATGTGGACTCGGGACAGCA
TGCTGTCCCGAGTCCACAT


 


2855
TGTGGACTCGGGACAGCAT
ATGCTGTCCCGAGTCCACA


 


2856
GTGGACTCGGGACAGCATG
CATGCTGTCCCGAGTCCAC


 


2857
TGGACTCGGGACAGCATGA
TCATGCTGTCCCGAGTCCA


 


2858
GGACTCGGGACAGCATGAT
ATCATGCTGTCCCGAGTCC


 


2859
GACTCGGGACAGCATGATG
CATCATGCTGTCCCGAGTC


 


2860
ACTCGGGACAGCATGATGA
TCATCATGCTGTCCCGAGT


 


2861
CTCGGGACAGCATGATGAG
CTCATCATGCTGTCCCGAG


 


2862
TCGGGACAGCATGATGAGC
GCTCATCATGCTGTCCCGA


 


2863
CGGGACAGCATGATGAGCA
TGCTCATCATGCTGTCCCG


 


2864
GGGACAGCATGATGAGCAG
CTGCTCATCATGCTGTCCC


 


2865
GGACAGCATGATGAGCAGA
TCTGCTCATCATGCTGTCC


 


2866
GACAGCATGATGAGCAGAA
TTCTGCTCATCATGCTGTC


 


2867
ACAGCATGATGAGCAGAAA
TTTCTGCTCATCATGCTGT


 


2868
CAGCATGATGAGCAGAAAG
CTTTCTGCTCATCATGCTG


 


2869
AGCATGATGAGCAGAAAGG
CCTTTCTGCTCATCATGCT


 


2870
GCATGATGAGCAGAAAGGA
TCCTTTCTGCTCATCATGC


 


2871
CATGATGAGCAGAAAGGAC
GTCCTTTCTGCTCATCATG


 


2872
ATGATGAGCAGAAAGGACC
GGTCCTTTCTGCTCATCAT


 


2873
TGATGAGCAGAAAGGACCC
GGGTCCTTTCTGCTCATCA


 


2874
GATGAGCAGAAAGGACCCC
GGGGTCCTTTCTGCTCATC


 


2875
ATGAGCAGAAAGGACCCCA
TGGGGTCCTTTCTGCTCAT


 


2876
TGAGCAGAAAGGACCCCAA
TTGGGGTCCTTTCTGCTCA


 


2877
GAGCAGAAAGGACCCCAAG
CTTGGGGTCCTTTCTGCTC


 


2878
AGCAGAAAGGACCCCAAGA
TCTTGGGGTCCTTTCTGCT


 


2879
GCAGAAAGGACCCCAAGAT
ATCTTGGGGTCCTTTCTGC


 


2880
CAGAAAGGACCCCAAGATG
CATCTTGGGGTCCTTTCTG


 


2881
AGAAAGGACCCCAAGATGG
CCATCTTGGGGTCCTTTCT


 


2882
GAAAGGACCCCAAGATGGC
GCCATCTTGGGGTCCTTTC


 


2883
AAAGGACCCCAAGATGGCC
GGCCATCTTGGGGTCCTTT


 


2884
AAGGACCCCAAGATGGCCA
TGGCCATCTTGGGGTCCTT


 


2885
AGGACCCCAAGATGGCCAG
CTGGCCATCTTGGGGTCCT


 


2886
GGACCCCAAGATGGCCAGG
CCTGGCCATCTTGGGGTCC


 


2887
GACCCCAAGATGGCCAGGC
GCCTGGCCATCTTGGGGTC


 


2888
ACCCCAAGATGGCCAGGCC
GGCCTGGCCATCTTGGGGT


 


2889
CCCCAAGATGGCCAGGCCA
TGGCCTGGCCATCTTGGGG


 


2890
CCCAAGATGGCCAGGCCAG
CTGGCCTGGCCATCTTGGG


 


2891
CCAAGATGGCCAGGCCAGT
ACTGGCCTGGCCATCTTGG


 


2892
CAAGATGGCCAGGCCAGTC
GACTGGCCTGGCCATCTTG


 


2893
AAGATGGCCAGGCCAGTCT
AGACTGGCCTGGCCATCTT


 


2894
AGATGGCCAGGCCAGTCTC
GAGACTGGCCTGGCCATCT


 


2895
GATGGCCAGGCCAGTCTCC
GGAGACTGGCCTGGCCATC


 


2896
ATGGCCAGGCCAGTCTCCA
TGGAGACTGGCCTGGCCAT


 


2897
TGGCCAGGCCAGTCTCCAG
CTGGAGACTGGCCTGGCCA


 


2898
GGCCAGGCCAGTCTCCAGG
CCTGGAGACTGGCCTGGCC


 


2899
GCCAGGCCAGTCTCCAGGA
TCCTGGAGACTGGCCTGGC


 


2900
CCAGGCCAGTCTCCAGGAC
GTCCTGGAGACTGGCCTGG


 


2901
CAGGCCAGTCTCCAGGACC
GGTCCTGGAGACTGGCCTG


 


2902
AGGCCAGTCTCCAGGACCC
GGGTCCTGGAGACTGGCCT


 


2903
GGCCAGTCTCCAGGACCCG
CGGGTCCTGGAGACTGGCC


 


2904
GCCAGTCTCCAGGACCCGG
CCGGGTCCTGGAGACTGGC


 


2905
CCAGTCTCCAGGACCCGGG
CCCGGGTCCTGGAGACTGG


 


2906
CAGTCTCCAGGACCCGGGA
TCCCGGGTCCTGGAGACTG


 


2907
AGTCTCCAGGACCCGGGAC
GTCCCGGGTCCTGGAGACT


 


2908
GTCTCCAGGACCCGGGACT
AGTCCCGGGTCCTGGAGAC


 


2909
TCTCCAGGACCCGGGACTT
AAGTCCCGGGTCCTGGAGA


 


2910
CTCCAGGACCCGGGACTTC
GAAGTCCCGGGTCCTGGAG


 


2911
TCCAGGACCCGGGACTTCA
TGAAGTCCCGGGTCCTGGA


 


2912
CCAGGACCCGGGACTTCAG
CTGAAGTCCCGGGTCCTGG


 


2913
CAGGACCCGGGACTTCAGG
CCTGAAGTCCCGGGTCCTG


 


2914
AGGACCCGGGACTTCAGGA
TCCTGAAGTCCCGGGTCCT


 


2915
GGACCCGGGACTTCAGGAC
GTCCTGAAGTCCCGGGTCC


 


2916
GACCCGGGACTTCAGGACA
TGTCCTGAAGTCCCGGGTC


 


2917
ACCCGGGACTTCAGGACAT
ATGTCCTGAAGTCCCGGGT


 


2918
CCCGGGACTTCAGGACATA
TATGTCCTGAAGTCCCGGG


 


2919
CCGGGACTTCAGGACATAC
GTATGTCCTGAAGTCCCGG


 


2920
CGGGACTTCAGGACATACC
GGTATGTCCTGAAGTCCCG


 


2921
GGGACTTCAGGACATACCA
TGGTATGTCCTGAAGTCCC


 


2922
GGACTTCAGGACATACCAT
ATGGTATGTCCTGAAGTCC


 


2923
GACTTCAGGACATACCATG
CATGGTATGTCCTGAAGTC


 


2924
ACTTCAGGACATACCATGC
GCATGGTATGTCCTGAAGT


 


2925
CTTCAGGACATACCATGCC
GGCATGGTATGTCCTGAAG


 


2926
TTCAGGACATACCATGCCT
AGGCATGGTATGTCCTGAA


 


2927
TCAGGACATACCATGCCTG
CAGGCATGGTATGTCCTGA


 


2928
CAGGACATACCATGCCTGG
CCAGGCATGGTATGTCCTG


 


2929
AGGACATACCATGCCTGGC
GCCAGGCATGGTATGTCCT


 


2930
GGACATACCATGCCTGGCT
AGCCAGGCATGGTATGTCC


 


2931
GACATACCATGCCTGGCTC
GAGCCAGGCATGGTATGTC


 


2932
ACATACCATGCCTGGCTCT
AGAGCCAGGCATGGTATGT


 


2933
CATACCATGCCTGGCTCTC
GAGAGCCAGGCATGGTATG


 


2934
ATACCATGCCTGGCTCTCC
GGAGAGCCAGGCATGGTAT


 


2935
TACCATGCCTGGCTCTCCC
GGGAGAGCCAGGCATGGTA


 


2936
ACCATGCCTGGCTCTCCCT
AGGGAGAGCCAGGCATGGT


 


2937
CCATGCCTGGCTCTCCCTG
CAGGGAGAGCCAGGCATGG


 


2938
CATGCCTGGCTCTCCCTGC
GCAGGGAGAGCCAGGCATG


 


2939
ATGCCTGGCTCTCCCTGCA
TGCAGGGAGAGCCAGGCAT


 


2940
TGCCTGGCTCTCCCTGCAA
TTGCAGGGAGAGCCAGGCA


 


2941
GCCTGGCTCTCCCTGCAAA
TTTGCAGGGAGAGCCAGGC


 


2942
CCTGGCTCTCCCTGCAAAA
TTTTGCAGGGAGAGCCAGG


 


2943
CTGGCTCTCCCTGCAAAAC
GTTTTGCAGGGAGAGCCAG


 


2944
TGGCTCTCCCTGCAAAACT
AGTTTTGCAGGGAGAGCCA


 


2945
GGCTCTCCCTGCAAAACTG
CAGTTTTGCAGGGAGAGCC


 


2946
GCTCTCCCTGCAAAACTGG
CCAGTTTTGCAGGGAGAGC


 


2947
CTCTCCCTGCAAAACTGGC
GCCAGTTTTGCAGGGAGAG


 


2948
TCTCCCTGCAAAACTGGCT
AGCCAGTTTTGCAGGGAGA


 


2949
CTCCCTGCAAAACTGGCTC
GAGCCAGTTTTGCAGGGAG


 


2950
TCCCTGCAAAACTGGCTCA
TGAGCCAGTTTTGCAGGGA


 


2951
CCCTGCAAAACTGGCTCAA
TTGAGCCAGTTTTGCAGGG


 


2952
CCTGCAAAACTGGCTCAAT
ATTGAGCCAGTTTTGCAGG


 


2953
CTGCAAAACTGGCTCAATG
CATTGAGCCAGTTTTGCAG


 


2954
TGCAAAACTGGCTCAATGC
GCATTGAGCCAGTTTTGCA


 


2955
GCAAAACTGGCTCAATGCC
GGCATTGAGCCAGTTTTGC


 


2956
CAAAACTGGCTCAATGCCA
TGGCATTGAGCCAGTTTTG


 


2957
AAAACTGGCTCAATGCCAA
TTGGCATTGAGCCAGTTTT


 


2958
AAACTGGCTCAATGCCAAA
TTTGGCATTGAGCCAGTTT


 


2959
AACTGGCTCAATGCCAAAG
CTTTGGCATTGAGCCAGTT


 


2960
ACTGGCTCAATGCCAAAGT
ACTTTGGCATTGAGCCAGT


 


2961
CTGGCTCAATGCCAAAGTT
AACTTTGGCATTGAGCCAG


 


2962
TGGCTCAATGCCAAAGTTG
CAACTTTGGCATTGAGCCA


 


2963
GGCTCAATGCCAAAGTTGT
ACAACTTTGGCATTGAGCC


 


2964
GCTCAATGCCAAAGTTGTG
CACAACTTTGGCATTGAGC


 


2965
CTCAATGCCAAAGTTGTGC
GCACAACTTTGGCATTGAG


 


2966
TCAATGCCAAAGTTGTGCC
GGCACAACTTTGGCATTGA


 


2967
CAATGCCAAAGTTGTGCCC
GGGCACAACTTTGGCATTG


 


2968
AATGCCAAAGTTGTGCCCA
TGGGCACAACTTTGGCATT


 


2969
ATGCCAAAGTTGTGCCCAG
CTGGGCACAACTTTGGCAT


 


2970
TGCCAAAGTTGTGCCCAGG
CCTGGGCACAACTTTGGCA


 


2971
GCCAAAGTTGTGCCCAGGC
GCCTGGGCACAACTTTGGC


 


2972
CCAAAGTTGTGCCCAGGCA
TGCCTGGGCACAACTTTGG


 


2973
CAAAGTTGTGCCCAGGCAG
CTGCCTGGGCACAACTTTG


 


2974
AAAGTTGTGCCCAGGCAGC
GCTGCCTGGGCACAACTTT


 


2975
AAGTTGTGCCCAGGCAGCT
AGCTGCCTGGGCACAACTT


 


2976
AGTTGTGCCCAGGCAGCTG
CAGCTGCCTGGGCACAACT


 


2977
GTTGTGCCCAGGCAGCTGG
CCAGCTGCCTGGGCACAAC


 


2978
TTGTGCCCAGGCAGCTGGA
TCCAGCTGCCTGGGCACAA


 


2979
TGTGCCCAGGCAGCTGGAG
CTCCAGCTGCCTGGGCACA


 


2980
GTGCCCAGGCAGCTGGAGA
TCTCCAGCTGCCTGGGCAC


 


2981
TGCCCAGGCAGCTGGAGAG
CTCTCCAGCTGCCTGGGCA


 


2982
GCCCAGGCAGCTGGAGAGG
CCTCTCCAGCTGCCTGGGC


 


2983
CCCAGGCAGCTGGAGAGGG
CCCTCTCCAGCTGCCTGGG


 


2984
CCAGGCAGCTGGAGAGGGA
TCCCTCTCCAGCTGCCTGG


 


2985
CAGGCAGCTGGAGAGGGAG
CTCCCTCTCCAGCTGCCTG


 


2986
AGGCAGCTGGAGAGGGAGG
CCTCCCTCTCCAGCTGCCT


 


2987
GGCAGCTGGAGAGGGAGGA
TCCTCCCTCTCCAGCTGCC


 


2988
GCAGCTGGAGAGGGAGGAG
CTCCTCCCTCTCCAGCTGC


 


2989
CAGCTGGAGAGGGAGGAGG
CCTCCTCCCTCTCCAGCTG


 


2990
AGCTGGAGAGGGAGGAGGG
CCCTCCTCCCTCTCCAGCT


 


2991
GCTGGAGAGGGAGGAGGGC
GCCCTCCTCCCTCTCCAGC


 


2992
CTGGAGAGGGAGGAGGGCA
TGCCCTCCTCCCTCTCCAG


 


2993
TGGAGAGGGAGGAGGGCAC
GTGCCCTCCTCCCTCTCCA


 


2994
GGAGAGGGAGGAGGGCACG
CGTGCCCTCCTCCCTCTCC


 


2995
GAGAGGGAGGAGGGCACGC
GCGTGCCCTCCTCCCTCTC


 


2996
AGAGGGAGGAGGGCACGCC
GGCGTGCCCTCCTCCCTCT


 


2997
GAGGGAGGAGGGCACGCCT
AGGCGTGCCCTCCTCCCTC


 


2998
AGGGAGGAGGGCACGCCTG
CAGGCGTGCCCTCCTCCCT


 


2999
GGGAGGAGGGCACGCCTGC
GCAGGCGTGCCCTCCTCCC


 


3000
GGAGGAGGGCACGCCTGCC
GGCAGGCGTGCCCTCCTCC


 


3001
GAGGAGGGCACGCCTGCCA
TGGCAGGCGTGCCCTCCTC


 


3002
AGGAGGGCACGCCTGCCAC
GTGGCAGGCGTGCCCTCCT


 


3003
GGAGGGCACGCCTGCCACT
AGTGGCAGGCGTGCCCTCC


 


3004
GAGGGCACGCCTGCCACTC
GAGTGGCAGGCGTGCCCTC


 


3005
AGGGCACGCCTGCCACTCT
AGAGTGGCAGGCGTGCCCT


 


3006
GGGCACGCCTGCCACTCTC
GAGAGTGGCAGGCGTGCCC


 


3007
GGCACGCCTGCCACTCTCA
TGAGAGTGGCAGGCGTGCC


 


3008
GCACGCCTGCCACTCTCAG
CTGAGAGTGGCAGGCGTGC


 


3009
CACGCCTGCCACTCTCAGC
GCTGAGAGTGGCAGGCGTG


 


3010
ACGCCTGCCACTCTCAGCA
TGCTGAGAGTGGCAGGCGT


 


3011
CGCCTGCCACTCTCAGCAA
TTGCTGAGAGTGGCAGGCG


 


3012
GCCTGCCACTCTCAGCAAG
CTTGCTGAGAGTGGCAGGC


 


3013
CCTGCCACTCTCAGCAAGT
ACTTGCTGAGAGTGGCAGG


 


3014
CTGCCACTCTCAGCAAGTG
CACTTGCTGAGAGTGGCAG


 


3015
TGCCACTCTCAGCAAGTGC
GCACTTGCTGAGAGTGGCA


 


3016
GCCACTCTCAGCAAGTGCG
CGCACTTGCTGAGAGTGGC


 


3017
CCACTCTCAGCAAGTGCGG
CCGCACTTGCTGAGAGTGG


 


3018
CACTCTCAGCAAGTGCGGA
TCCGCACTTGCTGAGAGTG


 


3019
ACTCTCAGCAAGTGCGGAG
CTCCGCACTTGCTGAGAGT


 


3020
CTCTCAGCAAGTGCGGAGA
TCTCCGCACTTGCTGAGAG


 


3021
TCTCAGCAAGTGCGGAGAT
ATCTCCGCACTTGCTGAGA


 


3022
CTCAGCAAGTGCGGAGATC
GATCTCCGCACTTGCTGAG


 


3023
TCAGCAAGTGCGGAGATCG
CGATCTCCGCACTTGCTGA


 


3024
CAGCAAGTGCGGAGATCGC
GCGATCTCCGCACTTGCTG


 


3025
AGCAAGTGCGGAGATCGCC
GGCGATCTCCGCACTTGCT


 


3026
GCAAGTGCGGAGATCGCCT
AGGCGATCTCCGCACTTGC


 


3027
CAAGTGCGGAGATCGCCTC
GAGGCGATCTCCGCACTTG


 


3028
AAGTGCGGAGATCGCCTCT
AGAGGCGATCTCCGCACTT


 


3029
AGTGCGGAGATCGCCTCTG
CAGAGGCGATCTCCGCACT


 


3030
GTGCGGAGATCGCCTCTGG
CCAGAGGCGATCTCCGCAC


 


3031
TGCGGAGATCGCCTCTGGG
CCCAGAGGCGATCTCCGCA


 


3032
GCGGAGATCGCCTCTGGGA
TCCCAGAGGCGATCTCCGC


 


3033
CGGAGATCGCCTCTGGGAG
CTCCCAGAGGCGATCTCCG


 


3034
GGAGATCGCCTCTGGGAGG
CCTCCCAGAGGCGATCTCC


 


3035
GAGATCGCCTCTGGGAGGG
CCCTCCCAGAGGCGATCTC


 


3036
AGATCGCCTCTGGGAGGGG
CCCCTCCCAGAGGCGATCT


 


3037
GATCGCCTCTGGGAGGGGA
TCCCCTCCCAGAGGCGATC


 


3038
ATCGCCTCTGGGAGGGGAG
CTCCCCTCCCAGAGGCGAT


 


3039
TCGCCTCTGGGAGGGGAGC
GCTCCCCTCCCAGAGGCGA


 


3040
CGCCTCTGGGAGGGGAGCT
AGCTCCCCTCCCAGAGGCG


 


3041
GCCTCTGGGAGGGGAGCTG
CAGCTCCCCTCCCAGAGGC


 


3042
CCTCTGGGAGGGGAGCTGC
GCAGCTCCCCTCCCAGAGG


 


3043
CTCTGGGAGGGGAGCTGCA
TGCAGCTCCCCTCCCAGAG


 


3044
TCTGGGAGGGGAGCTGCAG
CTGCAGCTCCCCTCCCAGA


 


3045
CTGGGAGGGGAGCTGCAGC
GCTGCAGCTCCCCTCCCAG


 


3046
TGGGAGGGGAGCTGCAGCA
TGCTGCAGCTCCCCTCCCA


 


3047
GGGAGGGGAGCTGCAGCAG
CTGCTGCAGCTCCCCTCCC


 


3048
GGAGGGGAGCTGCAGCAGG
CCTGCTGCAGCTCCCCTCC


 


3049
GAGGGGAGCTGCAGCAGGA
TCCTGCTGCAGCTCCCCTC


 


3050
AGGGGAGCTGCAGCAGGAG
CTCCTGCTGCAGCTCCCCT


 


3051
GGGGAGCTGCAGCAGGAGG
CCTCCTGCTGCAGCTCCCC


 


3052
GGGAGCTGCAGCAGGAGGA
TCCTCCTGCTGCAGCTCCC


 


3053
GGAGCTGCAGCAGGAGGAA
TTCCTCCTGCTGCAGCTCC


 


3054
GAGCTGCAGCAGGAGGAAG
CTTCCTCCTGCTGCAGCTC


 


3055
AGCTGCAGCAGGAGGAAGA
TCTTCCTCCTGCTGCAGCT


 


3056
GCTGCAGCAGGAGGAAGAC
GTCTTCCTCCTGCTGCAGC


 


3057
CTGCAGCAGGAGGAAGACA
TGTCTTCCTCCTGCTGCAG


 


3058
TGCAGCAGGAGGAAGACAC
GTGTCTTCCTCCTGCTGCA


 


3059
GCAGCAGGAGGAAGACACA
TGTGTCTTCCTCCTGCTGC


 


3060
CAGCAGGAGGAAGACACAG
CTGTGTCTTCCTCCTGCTG


 


3061
AGCAGGAGGAAGACACAGC
GCTGTGTCTTCCTCCTGCT


 


3062
GCAGGAGGAAGACACAGCC
GGCTGTGTCTTCCTCCTGC


 


3063
CAGGAGGAAGACACAGCCA
TGGCTGTGTCTTCCTCCTG


 


3064
AGGAGGAAGACACAGCCAC
GTGGCTGTGTCTTCCTCCT


 


3065
GGAGGAAGACACAGCCACC
GGTGGCTGTGTCTTCCTCC


 


3066
GAGGAAGAGACAGCCACCA
TGGTGGCTGTGTCTTCCTC


 


3067
AGGAAGACACAGCCACCAA
TTGGTGGCTGTGTCTTCCT


 


3068
GGAAGACACAGCCACCAAC
GTTGGTGGCTGTGTCTTCC


 


3069
GAAGACACAGCCACCAACT
AGTTGGTGGCTGTGTCTTC


 


3070
AAGACACAGCCACCAACTC
GAGTTGGTGGCTGTGTCTT


 


3071
AGACACAGCCACCAACTCC
GGAGTTGGTGGCTGTGTCT


 


3072
GACACAGCCACCAACTCCA
TGGAGTTGGTGGCTGTGTC


 


3073
ACACAGCCACCAACTCCAG
CTGGAGTTGGTGGCTGTGT


 


3074
CACAGCCACCAACTCCAGC
GCTGGAGTTGGTGGCTGTG


 


3075
ACAGCCACCAACTCCAGCT
AGCTGGAGTTGGTGGCTGT


 


3076
CAGCCACCAACTCCAGCTC
GAGCTGGAGTTGGTGGCTG


 


3077
AGCCACCAACTCCAGCTCT
AGAGCTGGAGTTGGTGGCT


 


3078
GCCACCAACTCCAGCTCTG
CAGAGCTGGAGTTGGTGGC


 


3079
CCACCAACTCCAGCTCTGA
TCAGAGCTGGAGTTGGTGG


 


3080
CACCAACTCCAGCTCTGAG
CTCAGAGCTGGAGTTGGTG


 


3081
ACCAACTCCAGCTCTGAGG
CCTCAGAGCTGGAGTTGGT


 


3082
CCAACTCCAGCTCTGAGGA
TCCTCAGAGCTGGAGTTGG


 


3083
CAACTCCAGCTCTGAGGAA
TTCCTCAGAGCTGGAGTTG


 


3084
AACTCCAGCTCTGAGGAAG
CTTCCTCAGAGCTGGAGTT


 


3085
ACTCCAGCTCTGAGGAAGG
CCTTCCTCAGAGCTGGAGT


 


3086
CTCCAGCTCTGAGGAAGGC
GCCTTCCTCAGAGCTGGAG


 


3087
TCCAGCTCTGAGGAAGGCC
GGCCTTCCTCAGAGCTGGA


 


3088
CCAGCTCTGAGGAAGGCCC
GGGCCTTCCTCAGAGCTGG


 


3089
CAGCTCTGAGGAAGGCCCA
TGGGCCTTCCTCAGAGCTG


 


3090
AGCTCTGAGGAAGGCCCAG
CTGGGCCTTCCTCAGAGCT


 


3091
GCTCTGAGGAAGGCCCAGG
CCTGGGCCTTCCTCAGAGC


 


3092
CTCTGAGGAAGGCCCAGGG
CCCTGGGCCTTCCTCAGAG


 


3093
TCTGAGGAAGGCCCAGGGT
ACCCTGGGCCTTCCTCAGA


 


3094
CTGAGGAAGGCCCAGGGTC
GACCCTGGGCCTTCCTCAG


 


3095
TGAGGAAGGCCCAGGGTCC
GGACCCTGGGCCTTCCTCA


 


3096
GAGGAAGGCCCAGGGTCCG
CCGACCCTGGGCCTTCCTC


 


3097
AGGAAGGCCCAGGGTCCGG
CCGGACCCTGGGCCTTCCT


 


3098
GGAAGGCCCAGGGTCCGGC
GCCGGACCCTGGGCCTTCC


 


3099
GAAGGCCCAGGGTCCGGCC
GGCCGGACCCTGGGCCTTC


 


3100
AAGGCCCAGGGTCCGGCCC
GGGCCGGACCCTGGGCCTT


 


3101
AGGCCCAGGGTCCGGCCCT
AGGGCCGGACCCTGGGCCT


 


3102
GGCCCAGGGTCCGGCCCTG
CAGGGCCGGACCCTGGGCC


 


3103
GCCCAGGGTCCGGCCCTGA
TCAGGGCCGGACCCTGGGC


 


3104
CCCAGGGTCCGGCCCTGAC
GTCAGGGCCGGACCCTGGG


 


3105
CCAGGGTCCGGCCCTGACA
TGTCAGGGCCGGACCCTGG


 


3106
CAGGGTCCGGCCCTGACAG
CTGTCAGGGCCGGACCCTG


 


3107
AGGGTCCGGCCCTGACAGC
GCTGTCAGGGCCGGACCCT


 


3108
GGGTCCGGCCCTGACAGCG
GGCTGTCAGGGCCGGACCC


 


3109
GGTCCGGCCCTGACAGCCG
CGGCTGTCAGGGCCGGACC


 


3110
GTCCGGCCCTGACAGCCGG
CCGGCTGTCAGGGCCGGAC


 


3111
TCCGGCCCTGACAGCCGGC
GCCGGCTGTCAGGGCCGGA


 


3112
CCGGCCCTGACAGCCGGCT
AGCCGGCTGTCAGGGCCGG


 


3113
CGGCCCTGACAGCCGGCTC
GAGCCGGCTGTCAGGGCCG


 


3114
GGCCCTGACAGCCGGCTCA
TGAGCCGGCTGTCAGGGCC


 


3115
GCCCTGACAGCCGGCTCAG
CTGAGCCGGCTGTCAGGGC


 


3116
CCCTGACAGCCGGCTCAGC
GCTGAGCCGGCTGTCAGGG


 


3117
CCTGACAGCCGGCTCAGCA
TGCTGAGCCGGCTGTCAGG


 


3118
CTGACAGCCGGCTCAGCAC
GTGCTGAGCCGGCTGTCAG


 


3119
TGACAGCCGGCTCAGCACA
TGTGCTGAGCCGGCTGTCA


 


3120
GACAGCCGGCTCAGCACAG
CTGTGCTGAGCCGGCTGTC


 


3121
ACAGCCGGCTCAGCACAGG
CCTGTGCTGAGCCGGCTGT


 


3122
CAGCCGGCTCAGCACAGGC
GCCTGTGCTGAGCCGGCTG


 


3123
AGCCGGCTCAGCACAGGCC
GGCCTGTGCTGAGCCGGCT


 


3124
GCCGGCTCAGCACAGGCCT
AGGCCTGTGCTGAGCCGGC


 


3125
CCGGCTCAGCACAGGCCTC
GAGGCCTGTGCTGAGCCGG


 


3126
CGGCTCAGCACAGGCCTCG
CGAGGCCTGTGCTGAGCCG


 


3127
GGCTCAGCACAGGCCTCGC
GCGAGGCCTGTGCTGAGCC


 


3128
GCTCAGCACAGGCCTCGCC
GGCGAGGCCTGTGCTGAGC


 


3129
CTCAGCACAGGCCTCGCCA
TGGCGAGGCCTGTGCTGAG


 


3130
TCAGCACAGGCCTCGCCAA
TTGGCGAGGCCTGTGCTGA


 


3131
CAGCACAGGCCTCGCCAAG
CTTGGCGAGGCCTGTGCTG


 


3132
AGCACAGGCCTCGCCAAGC
GCTTGGCGAGGCCTGTGCT


 


3133
GCACAGGCCTCGCCAAGCA
TGCTTGGCGAGGCCTGTGC


 


3134
CACAGGCCTCGCCAAGCAC
GTGCTTGGCGAGGCCTGTG


 


3135
ACAGGCCTCGCCAAGCACC
GGTGCTTGGCGAGGCCTGT


 


3136
CAGGCCTCGCCAAGCACCT
AGGTGCTTGGCGAGGCCTG


 


3137
AGGCCTCGCCAAGCACCTG
CAGGTGCTTGGCGAGGCCT


 


3138
GGCCTCGCCAAGCACCTGC
GCAGGTGCTTGGCGAGGCC


 


3139
GCCTCGCCAAGCACCTGCT
AGCAGGTGCTTGGCGAGGC


 


3140
CCTCGCCAAGCACCTGCTC
GAGCAGGTGCTTGGCGAGG


 


3141
CTCGCCAAGCACCTGCTCA
TGAGCAGGTGCTTGGCGAG


 


3142
TCGCCAAGCACCTGCTCAG
CTGAGCAGGTGCTTGGCGA


 


3143
CGCCAAGCACCTGCTCAGT
ACTGAGCAGGTGCTTGGCG


 


3144
GCCAAGCACCTGCTCAGTG
CACTGAGCAGGTGCTTGGC


 


3145
CCAAGCACCTGCTCAGTGG
CCACTGAGCAGGTGCTTGG


 


3146
CAAGCACCTGCTCAGTGGT
ACCACTGAGCAGGTGCTTG


 


3147
AAGCACCTGCTCAGTGGTT
AACCACTGAGCAGGTCCTT


 


3148
AGCACCTGCTCAGTGGTTT
AAACCACTGAGCAGGTGCT


 


3149
GCACCTGCTCAGTGGTTTG
CAAACCACTGAGCAGGTGC


 


3150
CACCTGCTCAGTGGTTTGG
CCAAACCACTGAGCAGGTG


 


3151
ACCTGCTCAGTGGTTTGGG
CCCAAACCACTGAGCAGGT


 


3152
CCTGCTCAGTGGTTTGGGG
CCCCAAACCACTGAGCAGG


 


3153
CTGCTCAGTGGTTTGGGGG
CCCCCAAACCACTGAGCAG


 


3154
TGCTCAGTGGTTTGGGGGA
TCCCCCAAACCACTGAGCA


 


3155
GCTCAGTGGTTTGGGGGAC
GTCCCCCAAACCACTGAGC


 


3156
CTCAGTGGTTTGGGGGACC
GGTCCCCCAAACCACTGAG


 


3157
TCAGTGGTTTGGGGGACCG
CGGTCCCCCAAACCACTGA


 


3158
CAGTGGTTTGGGGGACCGA
TCGGTCCCCCAAACCACTG


 


3159
AGTGGTTTGGGGGACCGAC
GTCGGTCCCCCAAACCACT


 


3160
GTGGTTTGGGGGACCGACT
AGTCGGTCCCCCAAACCAC


 


3161
TGGTTTGGGGGACCGACTG
CAGTCGGTCCCCCAAACCA


 


3162
GGTTTGGGGGACCGACTGT
ACAGTCGGTCCCCCAAACC


 


3163
GTTTGGGGGACCGACTGTG
CACAGTCGGTCCCCCAAAC


 


3164
TTTGGGGGACCGACTGTGC
GCACAGTCGGTCCCCCAAA


 


3165
TTGGGGGACCGACTGTGCC
GGCACAGTCGGTCCCCCAA


 


3166
TGGGGGACCGACTGTGCCG
CGGCACAGTCGGTCCCCCA


 


3167
GGGGGACCGACTGTGCCGC
GCGGCACAGTCGGTCCCCC


 


3168
GGGGACCGACTGTGCCGCC
GGCGGCACAGTCGGTCCCC


 


3169
GGGACCGACTGTGCCGCCT
AGGCGGCACAGTCGGTCCC


 


3170
GGACCGACTGTGCCGCCTG
CAGGCGGCACAGTCGGTCC


 


3171
GACCGACTGTGCCGCCTGC
GCAGGCGGCACAGTCGGTC


 


3172
ACCGACTGTGCCGCCTGCT
AGCAGGCGGCACAGTCGGT


 


3173
CCGACTGTGCCGCCTGCTG
CAGCAGGCGGCACAGTCGG


 


3174
CGACTGTGCCGCCTGCTGC
GCAGCAGGCGGCACAGTCG


 


3175
GACTGTGCCGCCTGCTGCG
CGCAGCAGGCGGCACAGTC


 


3176
ACTGTGCCGCCTGCTGCGG
CCGCAGCAGGCGGCACAGT


 


3177
CTGTGCCGCCTGCTGCGGA
TCCGCAGCAGGCGGCACAG


 


3178
TGTGCCGCCTGCTGCGGAG
CTCCGCAGCAGGCGGCACA


 


3179
GTGCCGCCTGCTGCGGAGG
CCTCCGCAGCAGGCGGCAC


 


3180
TGCCGCCTGCTGCGGAGGG
CCCTCCGCAGCAGGCGGCA


 


3181
GCCGCCTGCTGCGGAGGGA
TCCCTCCGCAGCAGGCGGC


 


3182
CCGCCTGCTGCGGAGGGAG
CTCCCTCCGCAGCAGGCGG


 


3183
CGCCTGCTGCGGAGGGAGC
GCTCCCTCCGCAGCAGGCG


 


3184
GCCTGCTGCGGAGGGAGCG
CGCTCCCTCCGCAGCAGGC


 


3185
CCTGCTGCGGAGGGAGCGG
CCGCTCCCTCCGCAGCAGG


 


3186
CTGCTGCGGAGGGAGCGGG
CCCGCTCCGTCCGCAGCAG


 


3187
TGCTGCGGAGGGAGCGGGA
TCCCGCTCCCTCCGCAGCA


 


3188
GCTGCGGAGGGAGCGGGAG
CTCCCGCTCCCTCCGCAGC


 


3189
CTGCGGAGGGAGCGGGAGG
CCTCCCGCTCCCTCCGCAG


 


3190
TGCGGAGGGAGCGGGAGGC
GCCTCCCGCTCCCTCCGCA


 


3191
GCGGAGGGAGCGGGAGGCC
GGCCTCCCGCTCCCTCCGC


 


3192
CGGAGGGAGCGGGAGGCCC
GGGCCTCCCGCTCCCTCCG


 


3193
GGAGGGAGCGGGAGGCCCT
AGGGCCTCCCGCTCCCTCC


 


3194
GAGGGAGCGGGAGGCCCTG
CAGGGCCTCCCGCTCCCTC


 


3195
AGGGAGCGGGAGGCCCTGG
CCAGGGCCTCCCGCTCCCT


 


3196
GGGAGCGGGAGGCCCTGGC
GCCAGGGCCTCCCGCTCCC


 


3197
GGAGCGGGAGGCCCTGGCT
AGCCAGGGCCTCCCGCTCC


 


3198
GAGCGGGAGGCCCTGGCTT
AAGCCAGGGCCTCCCGCTC


 


3199
AGCGGGAGGCCCTGGCTTG
CAAGCCAGGGCCTCCCGCT


 


3200
GCGGGAGGCCCTGGCTTGG
CCAAGCCAGGGCCTCCCGC


 


3201
CGGGAGGCCCTGGCTTGGG
CCCAAGCCAGGGCCTCCCG


 


3202
GGGAGGCCCTGGCTTGGGC
GCCCAAGCCAGGGCCTCCC


 


3203
GGAGGCCCTGGCTTGGGCC
GGCCCAAGCCAGGGCCTCC


 


3204
GAGGCCCTGGCTTGGGCCC
GGGCCCAAGCCAGGGCCTC


 


3205
AGGCCCTGGCTTGGGCCCA
TGGGCCCAAGCCAGGGCCT


 


3206
GGCCCTGGCTTGGGCCCAG
CTGGGCCCAAGCCAGGGCC


 


3207
GCCCTGGCTTGGGCCCAGC
GCTGGGCCCAAGCCAGGGC


 


3208
CCCTGGCTTGGGCCCAGCG
CGCTGGGCCCAAGCCAGGG


 


3209
CCTGGCTTGGGCCCAGCGG
CCGCTGGGCCCAAGCCAGG


 


3210
CTGGCTTGGGCCCAGCGGG
CCCGCTGGGCCCAAGCCAG


 


3211
TGGCTTGGGCCCAGCGGGA
TCCCGCTGGGCCCAAGCCA


 


3212
GGCTTGGGCCCAGCGGGAA
TTCCCGCTGGGCCCAAGCC


 


3213
GCTTGGGCCCAGCGGGAAG
CTTCCCGCTGGGCCCAAGC


 


3214
CTTGGGCCCAGCGGGAAGG
CCTTCCCGCTGGGCCCAAG


 


3215
TTGGGCCCAGCGGGAAGGC
GCCTTCCCGCTGGGCCCAA


 


3216
TGGGCCCAGCGGGAAGGCC
GGCCTTCCCGCTGGGCCCA


 


3217
GGGCCCAGCGGGAAGGCCA
TGGCCTTCCCGCTGGGCCC


 


3218
GGCCCAGCGGGAAGGCCAA
TTGGCCTTCCCGCTGGGCC


 


3219
GCCCAGCGGGAAGGCCAAG
CTTGGCCTTCCCGCTGGGC


 


3220
CCCAGCGGGAAGGCCAAGG
CCTTGGCCTTCCCGCTGGG


 


3221
CCAGCGGGAAGGCCAAGGG
CCCTTGGCCTTCCCGCTGG


 


3222
CAGCGGGAAGGCCAAGGGC
GCCCTTGGCCTTCCCGCTG


 


3223
AGCGGGAAGGCCAAGGGCC
GGCCCTTGGCCTTCCCGCT


 


3224
GCGGGAAGGCCAAGGGCCA
TGGCCCTTGGCCTTCCCGC


 


3225
CGGGAAGGCCAAGGGCCAG
CTGGCCCTTGGCCTTCCCG


 


3226
GGGAAGGCCAAGGGCCAGC
GCTGGCCCTTGGCCTTCCC


 


3227
GGAAGGCCAAGGGCCAGCC
GGCTGGCCCTTGGCCTTCC


 


3228
GAAGGCCAAGGGCCAGCCG
CGGCTGGCCCTTGGCCTTC


 


3229
AAGGCCAAGGGCCAGCCGT
ACGGCTGGCCCTTGGCCTT


 


3230
AGGCCAAGGGCCAGCCGTG
CACGGCTGGCCCTTGGCCT


 


3231
GGCCAAGGGCCAGCCGTGA
TCACGGCTGGCCCTTGGCC


 


3232
GCCAAGGGCCAGCCGTGAC
GTCACGGCTGGCCCTTGGC


 


3233
CCAAGGGCCAGCCGTGACA
TGTCACGGCTGGCCCTTGG


 


3234
CAAGGGCCAGCCGTGACAG
CTGTCACGGCTGGCCCTTG


 


3235
AAGGGCCAGCCGTGACAGA
TCTGTCACGGCTGGCCCTT


 


3236
AGGGCCAGCCGTGACAGAG
CTCTGTCACGGCTGGCCCT


 


3237
GGGCCAGCCGTGACAGAGG
CCTCTGTCACGGCTGGCCC


 


3238
GGCCAGCCGTGACAGAGGA
TCCTCTGTCACGGCTGGCC


 


3239
GCCAGCCGTGACAGAGGAC
GTCCTCTGTCACGGCTGGC


 


3240
CCAGCCGTGACAGAGGACA
TGTCCTCTGTCACGGCTGG


 


3241
CAGCCGTGACAGAGGACAG
CTGTCCTCTGTCACGGCTG


 


3242
AGCCGTGACAGAGGACAGC
GCTGTCCTCTGTCACGGCT


 


3243
GCCGTGACAGAGGACAGCC
GGCTGTCCTCTGTCACGGC


 


3244
CCGTGACACAGGACAGCCC
GGGCTGTCCTCTGTCACGG


 


3245
CGTGACAGAGGACAGCCCA
TGGGCTGTCCTCTGTCACG


 


3246
GTGACAGAGGACAGCCCAG
CTGGGCTGTCCTCTGTCAC


 


3247
TGACAGAGGACAGCCCAGG
CCTGGGCTGTCCTCTGTCA


 


3248
GACAGAGGACAGCCCAGGC
GCCTGGGCTGTCCTCTGTC


 


3249
ACAGAGGACAGCCCAGGCA
TGCCTGGGCTGTCCTCTGT


 


3250
CAGAGGACAGCCCAGGCAT
ATGCCTGGGCTGTCCTCTG


 


3251
AGAGGACAGCCCAGGCATT
AATGCCTGGGCTGTCCTCT


 


3252
GAGGACAGCCCAGGCATTC
GAATGCCTGGGCTGTCCTC


 


3253
AGGACAGCCCAGGCATTCC
GGAATGCCTGGGCTGTCCT


 


3254
GGACAGCCCAGGCATTCCA
TGGAATGCCTGGGCTGTCC


 


3255
GACAGCCCAGGCATTCCAC
GTGGAATGCCTGGGCTGTC


 


3256
ACAGCCCAGGCATTCCACG
CGTGGAATGCCTGGGCTGT


 


3257
CAGCCCAGGCATTCCACGC
GCGTGGAATGCCTGGGCTG


 


3258
AGCCCAGGCATTCCACGCT
AGCGTGGAATGCCTGGGCT


 


3259
GCCCAGGCATTCCACGCTG
CAGCGTGGAATGCCTGGGC


 


3260
CCCAGGCATTCCACGCTGC
GCAGCGTGGAATGCCTGGG


 


3261
CCAGGCATTCCACGCTGCT
AGCAGCGTGGAATGCCTGG


 


3262
CAGGCATTCCACGCTGCTG
CAGCAGCGTGGAATGCCTG


 


3263
AGGCATTCCACGCTGCTGC
GCAGCAGCGTGGAATGCCT


 


3264
GGCATTCCACGCTGCTGCA
TGCAGCAGCGTGGAATGCC


 


3265
GCATTCCACGCTGCTGCAG
CTGCAGCAGCGTGGAATGC


 


3266
CATTCCACGCTGCTGCAGC
GCTGCAGCAGCGTGGAATG


 


3267
ATTCCACGCTGCTGCAGCC
GGCTGCAGCAGCGTGGAAT


 


3268
TTCCACGCTGCTGCAGCCG
CGGCTGCAGCAGCGTGGAA


 


3269
TCCACGCTGCTGCAGCCGT
ACGGCTGCAGCAGCGTGGA


 


3270
CCACGCTGCTGCAGCCGTT
AACGGCTGCAGCAGCGTGG


 


3271
CACGCTGCTGCAGCCGTTG
CAACGGCTGCAGCAGCGTG


 


3272
ACGCTGCTGCAGCCGTTGC
GCAACGGCTGCAGCAGCGT


 


3273
CGCTGCTGCAGCCGTTGCC
GGCAACGGCTGCAGCAGCG


 


3274
GCTGCTGCAGCCGTTGCCA
TGGCAACGGCTGCAGCAGC


 


3275
CTGCTGCAGCCGTTGCCAC
GTGGCAACGGCTGCAGCAG


 


3276
TGCTGCAGCCGTTGCCACC
GGTGGCAACGGCTGCAGCA


 


3277
GCTGCAGCCGTTGCCACCA
TGGTGGCAACGGCTGCAGC


 


3278
CTGCAGCCGTTGCCACCAT
ATGGTGGCAACGGCTGCAG


 


3279
TGCAGCCGTTGCCACCATG
CATGGTGGCAACGGCTGCA


 


3280
GCAGCCGTTGCCACCATGG
CCATGGTGGCAACGGCTGC


 


3281
CAGCCGTTGCCACCATGGA
TCCATGGTGGCAACGGCTG


 


3282
AGCCGTTGCCACCATGGAC
GTCCATGGTGGCAACGGCT


 


3283
GCCGTTGCCACCATGGACT
AGTCCATGGTGGCAAGGGC


 


3284
CCGTTGCCACCATGGACTC
GAGTCCATGGTGGCAACGG


 


3285
CGTTGCCACCATGGACTCT
AGAGTCCATGGTGGCAACG


 


3286
GTTGCCACCATGGACTCTT
AAGAGTCCATGGTGGCAAC


 


3287
TTGCCACCATGGACTCTTC
GAAGAGTCCATGGTGGCAA


 


3288
TGCCACCATGGACTCTTCA
TGAAGAGTCCATGGTGGCA


 


3289
GCCACCATGGACTCTTCAA
TTGAAGAGTCCATGGTGGC


 


3290
CCACCATGGACTCTTCAAC
GTTGAAGAGTCCATGGTGG


 


3291
CACCATGGACTCTTCAACA
TGTTGAAGAGTCCATGGTG


 


3292
ACCATGGACTCTTCAACAC
GTGTTGAAGAGTCCATGGT


 


3293
CCATGGACTCTTCAACACC
GGTGTTGAAGAGTCCATGG


 


3294
CATGGACTCTTCAACACCC
GGGTGTTGAAGAGTCCATG


 


3295
ATGGACTCTTCAACACCCA
TGGGTGTTGAAGAGTCCAT


 


3296
TGGACTCTTCAACACCCAC
GTGGGTGTTGAAGAGTCCA


 


3297
GGACTCTTCAACACCCACT
AGTGGGTGTTGAAGAGTCC


 


3298
GACTCTTCAACACCCACTG
CAGTGGGTGTTGAAGAGTC


 


3299
ACTCTTCAACACCCACTGG
CCAGTGGGTGTTGAAGAGT


 


3300
CTCTTCAACACCCACTGGC
GCCAGTGGGTGTTGAAGAG


 


3301
TCTTCAACACCCACTGGCG
CGCCAGTGGGTGTTGAAGA


 


3302
CTTCAACACCCACTGGCGA
TCGCCAGTGGGTGTTGAAG


 


3303
TTCAACACCCACTGGCGAT
ATCGCCAGTGGGTGTTGAA


 


3304
TCAACACCCACTGGCGATG
CATCGCCAGTGGGTGTTGA


 


3305
CAACACCCACTGGCGATGT
ACATCGCCAGTGGGTGTTG


 


3306
AACACCCACTGGCGATGTC
GACATCGCCAGTGGGTGTT


 


3307
ACACCCACTGGCGATGTCC
GGACATCGCCAGTGGGTGT


 


3308
CACCCACTGGCGATGTCCC
GGGACATCGCCAGTGGGTG


 


3309
ACCCACTGGCGATGTCCCC
GGGGACATCGCCAGTGGGT


 


3310
CCCACTGGCGATGTCCCCG
CGGGGACATCGCCAGTGGG


 


3311
CCACTGGCGATGTCCCCGC
GCGGGGACATCGCCAGTGG


 


3312
CACTGGCGATGTCCCCGCT
AGCGGGGACATCGCCAGTG


 


3313
ACTGGCGATGTCCCCGCTG
CAGCGGGGACATCGCCAGT


 


3314
CTGGCGATGTCCCCGCTGC
GCAGCGGGGACATCGCCAG


 


3315
TGGCGATGTCCCCGCTGCA
TGCAGCGGGGACATCGCCA


 


3316
GGCGATGTCCCCGCTGCAG
CTGCAGCGGGGACATCGCC


 


3317
GCGATGTCCCCGCTGCAGC
GCTGCAGCGGGGACATCGC


 


3318
CGATGTCCCCGCTGCAGCC
GGCTGCAGCGGGGACATCG


 


3319
GATGTCCCCGCTGCAGCCA
TGGCTGCAGCGGGGACATC


 


3320
ATGTCCCCGCTGCAGCCAC
GTGGCTGCAGCGGGGACAT


 


3321
TGTCCCCGCTGCAGCCACC
GGTGGCTGCAGCGGGGACA


 


3322
GTCCCCGCTGCAGCCACCG
CGGTGGCTGCAGCGGGGAC


 


3323
TCCCCGCTGCAGCCACCGG
CCGGTGGCTGCAGCGGGGA


 


3324
CCCCGCTGCAGCCACCGGC
GCCGGTGGCTGCAGCGGGG


 


3325
CCCGCTGCAGCCACCGGCT
AGCCGGTGGCTGCAGCGGG


 


3326
CCGCTGCAGCCACCGGCTG
CAGCCGGTGGCTGCAGCGG


 


3327
CGCTGCAGCCACCGGCTGT
ACAGCCGGTGGCTGCAGCG


 


3328
GCTGCAGCCACCGGCTGTG
CACAGCCGGTGGCTGCAGC


 


3329
CTGCAGCCACCGGCTGTGT
ACACAGCCGGTGGCTGCAG


 


3330
TGCAGCCACCGGCTGTGTG
CACACAGCCGGTGGCTGCA


 


3331
GCAGCCACCGGCTGTGTGT
ACACACAGCCGGTGGCTGC


 


3332
CAGCCACCGGCTGTGTGTG
CACACACAGCCGGTGGCTG


 


3333
AGCCACCGGCTGTGTGTGG
CCACACACAGCCGGTGGCT


 


3334
GCCACCGGCTGTGTGTGGC
GCCACACACAGCCGGTGGC


 


3335
CCACCGGCTGTGTGTGGCC
GGCCACACACAGCCGGTGG


 


3336
CACCGGCTGTGTGTGGCCT
AGGCCACACACAGCCGGTG


 


3337
ACCGGCTGTGTGTGGCCTG
CAGGCCACACACAGCCGGT


 


3338
CCGGCTGTGTGTGGCCTGT
ACAGGCCACACACAGCCGG


 


3339
CGGCTGTGTGTGGCCTGTG
CACAGGCCACACACAGCCG


 


3340
GGCTGTGTGTGGCCTGTGG
CCACAGGCCACACACAGCC


 


3341
GCTGTGTGTGGCCTGTGGT
ACCACAGGCCACACACAGC


 


3342
CTGTGTGTGGCCTGTGGTC
GACCACAGGCCACACACAG


 


3343
TGTGTGTGGCCTGTGGTCG
CGACCACAGGCCACACACA


 


3344
GTGTGTGGCCTGTGGTCGT
ACGACCACAGGCCACACAC


 


3345
TGTGTGGCCTGTGGTCGTG
CACGACCACAGGCCACACA


 


3346
GTGTGGCCTGTGGTCGTGT
ACACGACCACAGGCCACAC


 


3347
TGTGGCCTGTGGTCGTGTG
CACACGACCACAGGCCACA


 


3348
GTGGCCTGTGGTCGTGTGG
CCACACGACCACAGGCCAC


 


3349
TGGCCTGTGGTCGTGTGGC
GCCACACGACCACAGGCCA


 


3350
GGCCTGTGGTCGTGTGGCA
TGCCACACGACCACAGGCC


 


3351
GCCTGTGGTCGTGTGGCAG
CTGCCACACGACCACAGGC


 


3352
CCTGTGGTCGTGTGGCAGG
CCTGCCACACGACCACAGG


 


3353
CTGTGGTCGTGTGGCAGGC
GCCTGCCACACGACCACAG


 


3354
TGTGGTCGTGTGGCAGGCA
TGCCTGCCACACGACCACA


 


3355
GTGGTCGTGTGGCAGGCAC
GTGCCTGCCACACGACCAC


 


3356
TGGTCGTGTGGCAGGCACT
AGTGCCTGCCACACGACCA


 


3357
GGTCGTGTGGCAGGCACTG
CAGTGCCTGCCACACGACC


 


3358
GTCGTGTGGCAGGCACTGG
CCAGTGCCTGCCACACGAC


 


3359
TCGTGTGGCAGGCACTGGG
CCCAGTGCCTGCCACACGA


 


3360
CGTGTGGCAGGCACTGGGC
GCCCAGTGCCTGCCACACG


 


3361
GTGTGGCAGGCACTGGGCG
CGCCCAGTGCCTGCCACAC


 


3362
TGTGGCAGGCACTGGGCGG
CCGCCCAGTGCCTGCCACA


 


3363
GTGGCAGGCACTGGGCGGG
CCCGCCCAGTGCCTGCCAC


 


3364
TGGCAGGCACTGGGCGGGC
GCCCGCCCAGTGCCTGCCA


 


3365
GGCAGGCACTGGGCGGGCC
GGCCCGCCCAGTGCCTGCC


 


3366
GCAGGCACTGGGCGGGCCA
TGGCCCGCCCAGTGCCTGC


 


3367
CAGGCACTGGGCGGGCCAG
CTGGCCCGCCCAGTGCCTG


 


3368
AGGCACTGGGCGGGCCAGG
CCTGGCCCGCCCAGTGCCT


 


3369
GGCACTGGGCGGGCCAGGG
CCCTGGCCCGCCCAGTGCC


 


3370
GCACTGGGCGGGCCAGGGA
TCCCTGGCCCGCCCAGTGC


 


3371
CACTGGGCGGGCCAGGGAG
CTCCCTGGCCCGCCCAGTG


 


3372
ACTGGGCGGGCCAGGGAGA
TCTCCCTGGCCCGCCCAGT


 


3373
CTGGGCGGGCCAGGGAGAA
TTCTCCCTGGCCCGCCCAG


 


3374
TGGGCGGGCCAGGGAGAAA
TTTCTCCCTGGCCCGCCCA


 


3375
GGGCGGGCCAGGGAGAAAG
CTTTCTCCCTGGCCCGCCC


 


3376
GGCGGGCCAGGGAGAAAGC
GCTTTCTCCCTGGCCCGCC


 


3377
GCGGGCCAGGGAGAAAGCA
TGCTTTCTCCCTGGCCCGC


 


3378
CGGGCCAGGGAGAAAGCAG
CTGCTTTCTCCCTGGCCCG


 


3379
GGGCCAGGGAGAAAGCAGG
CCTGCTTTCTCCCTGGCCC


 


3380
GGCCAGGGAGAAAGCAGGC
GCCTGCTTTCTCCCTGGCC


 


3381
GCCAGGGAGAAAGCAGGCT
AGCCTGCTTTCTCCCTGGC


 


3382
CCAGGGAGAAAGCAGGCTT
AAGCCTGCTTTCTCCCTGG


 


3383
CAGGGAGAAAGCAGGCTTT
AAAGCCTGCTTTCTCCCTG


 


3384
AGGGAGAAAGCAGGCTTTC
GAAAGCCTGCTTTCTCCCT


 


3385
GGGAGAAAGCAGGCTTTCA
TGAAAGCCTGCTTTCTCCC


 


3386
GGAGAAAGCAGGCTTTCAG
CTGAAAGCCTGCTTTCTCC


 


3387
GAGAAAGCAGGCTTTCAGG
CCTGAAAGCCTGCTTTCTC


 


3388
AGAAAGCAGGCTTTCAGGA
TCCTGAAAGCCTGCTTTCT


 


3389
GAAAGCAGGCTTTCAGGAG
CTCCTGAAAGCCTGCTTTC


 


3390
AAAGCAGGCTTTCAGGAGC
GCTCCTGAAAGCCTGCTTT


 


3391
AAGCAGGCTTTCAGGAGCA
TGCTCCTGAAAGCCTGCTT


 


3392
AGCAGGCTTTCAGGAGCAG
CTGCTCCTGAAAGCCTGCT


 


3393
GCAGGCTTTCAGGAGCAGT
ACTGCTCCTGAAAGCCTGC


 


3394
CAGGCTTTCAGGAGCAGTC
GACTGCTCCTGAAAGCCTG


 


3395
AGGCTTTCAGGAGCAGTCC
GGACTGCTCCTGAAAGCCT


 


3396
GGCTTTCAGGAGCAGTCCG
CGGACTGCTCCTGAAAGCC


 


3397
GCTTTCAGGAGCAGTCCGC
GCGGACTGCTCCTGAAAGC


 


3398
CTTTCAGGAGCAGTCCGCG
CGCGGACTGCTCCTGAAAG


 


3399
TTTCAGGAGCAGTCCGCGG
CCGCGGACTGCTCCTGAAA


 


3400
TTCAGGAGCAGTCCGCGGA
TCCGCGGACTGCTCCTGAA


 


3401
TCAGGAGCAGTCCGCGGAG
CTCCGCGGACTGCTCCTGA


 


3402
CAGGAGCAGTCCGCGGAGG
CCTCCGCGGACTGCTCCTG


 


3403
AGGAGCAGTCCGCGGAGGA
TCCTCCGCGGACTGCTCCT


 


3404
GGAGCAGTCCGCGGAGGAG
CTCCTCCGCGGACTGCTCC


 


3405
GAGCAGTCCGCGGAGGAGT
ACTCCTCCGCGGACTGCTC


 


3406
AGCAGTCCGCGGAGGAGTG
CACTCCTCCGCGGACTGCT


 


3407
GCAGTCCGCGGAGGAGTGC
GCACTCCTCCGCGGACTGC


 


3408
CAGTCCGCGGAGGAGTGCA
TGCACTCCTCCGCGGACTG


 


3409
AGTCCGCGGAGGAGTGCAC
GTGCACTCCTCCGCGGACT


 


3410
GTCCGCGGAGGAGTGCACG
CGTGCACTCCTCCGCGGAC


 


3411
TCCGCGGAGGAGTGCACGC
GCGTGCACTCCTCCGCGGA


 


3412
CCGCGGAGGAGTGCACGCA
TGCGTGCACTCCTCCGCGG


 


3413
CGCGGAGGAGTGCACGCAG
CTGCGTGCACTCCTCCGCG


 


3414
GCGGAGGAGTGCACGCAGG
CCTGCGTGCACTCCTCCGC


 


3415
CGGAGGAGTGCACGCAGGA
TCCTGCGTGCACTCCTCCG


 


3416
GGAGGAGTGCACGCAGGAG
CTCCTGCGTGCACTCCTCC


 


3417
GAGGAGTGCACGCAGGAGG
CCTCCTGCGTGCACTCCTC


 


3418
AGGAGTGCACGCAGGAGGC
GCCTCCTGCGTGCACTCCT


 


3419
GGAGTGCACGCAGGAGGCC
GGCCTCCTGCGTGCACTCC


 


3420
GAGTGCACGCAGGAGGCCG
CGGCCTCCTGCGTGCACTC


 


3421
AGTGCACGCAGGAGGCCGG
CCGGCCTCCTGCGTGCACT


 


3422
GTGCACGCAGGAGGCCGGG
CCCGGCCTCCTGCGTGCAC


 


3423
TGCACGCAGGAGGCCGGGC
GCCCGGCCTCCTGCGTGCA


 


3424
GCACGCAGGAGGCCGGGCA
TGCCCGGCCTCCTGCGTGC


 


3425
CACGCAGGAGGCCGGGCAC
GTGCCCGGCCTCCTGCGTG


 


3426
ACGCAGGAGGCCGGGCACG
CGTGCCCGGCCTCCTGCGT


 


3427
CGCAGGAGGCCGGGCACGC
GCGTGCCCGGCCTCCTGCG


 


3428
GCAGGAGGCCGGGCACGCT
AGCGTGCCCGGCCTCCTGC


 


3429
CAGGAGGCCGGGCACGCTG
CAGCGTGCCCGGCCTCCTG


 


3430
AGGAGGCCGGGCACGCTGC
GCAGCGTGCCCGGCCTCCT


 


3431
GGAGGCCGGGCACGCTGCC
GGCAGCGTGCCCGGCCTCC


 


3432
GAGGCCGGGCACGCTGCCT
AGGCAGCGTGCCCGGCCTC


 


3433
AGGCCGGGCACGCTGCCTG
CAGGCAGCGTGCCCGGCCT


 


3434
GGCCGGGCACGCTGCCTGT
ACAGGCAGCGTGCCCGGCC


 


3435
GCCGGGCACGCTGCCTGTT
AACAGGCAGCGTGCCCGGC


 


3436
CCGGGCACGCTGCCTGTTC
GAACAGGCAGCGTGCCCGG


 


3437
CGGGCACGCTGCCTGTTCC
GGAACAGGCAGCGTGCCCG


 


3438
GGGCACGCTGCCTGTTCCC
GGGAACAGGCAGCGTGCCC


 


3439
GGCACGCTGCCTGTTCCCT
AGGGAACAGGCAGCGTGCC


 


3440
GCACGCTGCCTGTTCCCTG
CAGGGAACAGGCAGCGTGC


 


3441
CACGCTGCCTGTTCCCTGA
TCAGGGAACAGGCAGCGTG


 


3442
ACGCTGCCTGTTCCCTGAT
ATCAGGGAACAGGCAGCGT


 


3443
CGCTGCCTGTTCCCTGATG
CATCAGGGAACAGGCAGCG


 


3444
GCTGCCTGTTCCCTGATGC
GCATCAGGGAACAGGCAGC


 


3445
CTGCCTGTTCCCTGATGCT
AGCATCAGGGAACAGGCAG


 


3446
TGCCTGTTCCCTGATGCTG
CAGCATCAGGGAACAGGCA


 


3447
GCCTGTTCCCTGATGCTGA
TCAGCATCAGGGAACAGGC


 


3448
CCTGTTCCCTGATGCTGAC
GTCAGCATCAGGGAACAGG


 


3449
CTGTTCCCTGATGCTGACC
GGTCAGCATCAGGGAACAG


 


3450
TGTTCCCTGATGCTGACCC
GGGTCAGCATCAGGGAACA


 


3451
GTTCCCTGATGCTGACCCA
TGGGTCAGCATCAGGGAAC


 


3452
TTCCCTGATGCTGACCCAG
CTGGGTCAGCATCAGGGAA


 


3453
TCCCTGATGCTGACCCAGT
ACTGGGTCAGCATCAGGGA


 


3454
CCCTGATGCTGACCCAGTT
AACTGGGTCAGCATCAGGG


 


3455
CCTGATGCTGACCCAGTTT
AAACTGGGTCAGCATCAGG


 


3456
CTGATGCTGACCCAGTTTG
CAAACTGGGTCAGCATCAG


 


3457
TGATGCTGACCCAGTTTGT
ACAAACTGGGTCAGCATCA


 


3458
GATGCTGACCCAGTTTGTC
GACAAACTGGGTCAGCATC


 


3459
ATGCTGACCCAGTTTGTCT
AGACAAACTGGGTCAGCAT


 


3460
TGCTGACCCAGTTTGTCTC
GAGACAAACTGGGTCAGCA


 


3461
GCTGACCCAGTTTGTCTCC
GGAGACAAACTGGGTCAGC


 


3462
CTGACCCAGTTTGTCTCCA
TGGAGACAAACTGGGTCAG


 


3463
TGACCCAGTTTGTCTCCAG
CTGGAGACAAACTGGGTCA


 


3464
GACCCAGTTTGTCTCCAGC
GCTGGAGACAAACTGGGTC


 


3465
ACCCAGTTTGTCTCCAGCC
GGCTGGAGACAAACTGGGT


 


3466
CCCAGTTTGTCTCCAGCCA
TGGCTGGAGACAAACTGGG


 


3467
CCAGTTTGTCTCCAGCCAG
CTGGCTGGAGACAAACTGG


 


3468
CAGTTTGTCTCCAGCCAGG
CCTGGCTGGAGACAAACTG


 


3469
AGTTTGTCTCCAGCCAGGC
GCCTGGCTGGAGACAAACT


 


3470
GTTTGTCTCCAGCCAGGCT
AGCCTGGCTGGAGACAAAC


 


3471
TTTGTCTCCAGCCAGGCTT
AAGCCTGGCTGGAGACAAA


 


3472
TTGTCTCCAGCCAGGCTTT
AAAGCCTGGCTGGAGACAA


 


3473
TGTCTCCAGCCAGGCTTTG
CAAAGCCTGGCTGGAGACA


 


3474
GTCTCCAGCCAGGCTTTGG
CCAAAGCCTGGCTGGAGAC


 


3475
TCTCCAGCCAGGCTTTGGC
GCCAAAGCCTGGCTGGAGA


 


3476
CTCCAGCCAGGCTTTGGCA
TGCCAAAGCCTGGCTGGAG


 


3477
TCCAGCCAGGCTTTGGCAG
CTGCCAAAGCCTGGCTGGA


 


3478
CCAGCCAGGCTTTGGCAGA
TCTGCCAAAGCCTGGCTGG


 


3479
CAGCCAGGCTTTGGCAGAG
CTCTGCCAAAGCCTGGCTG


 


3480
AGCCAGGCTTTGGCAGAGC
GCTCTGCCAAAGCCTGGCT


 


3481
GCCAGGCTTTGGCAGAGCT
AGCTCTGCCAAAGCCTGGC


 


3482
CCAGGCTTTGGCAGAGCTG
CAGCTCTGCCAAAGCCTGG


 


3483
CAGGCTTTGGCAGAGCTGA
TCAGCTCTGCCAAAGCCTG


 


3484
AGGCTTTGGCAGAGCTGAG
CTCAGCTCTGCCAAAGCCT


 


3485
GGCTTTGGCAGAGCTGAGC
GCTCAGCTCTGCCAAAGCC


 


3486
GCTTTGGCAGAGCTGAGCA
TGCTCAGCTCTGCCAAAGC


 


3487
CTTTGGCAGAGCTGAGCAC
GTGCTCAGCTCTGCCAAAG


 


3488
TTTGGCAGAGCTGAGCACT
AGTGCTCAGCTCTGCCAAA


 


3489
TTGGCAGAGCTGAGCACTG
CAGTGCTCAGCTCTGCCAA


 


3490
TGGCAGAGCTGAGCACTGC
GCAGTGCTCAGCTCTGCCA


 


3491
GGCAGAGCTGAGCACTGCA
TGCAGTGCTCAGCTCTGCC


 


3492
GCAGAGCTGAGCACTGCAA
TTGCAGTGCTCAGCTCTGC


 


3493
CAGAGCTGAGCACTGCAAT
ATTGCAGTGCTCAGCTCTG


 


3494
AGAGCTGAGCACTGCAATG
CATTGCAGTGCTCAGCTCT


 


3495
GAGCTGAGCACTGCAATGC
GCATTGCAGTGCTCAGCTC


 


3496
AGCTGAGCACTGCAATGCA
TGCATTGCAGTGCTCAGCT


 


3497
GCTGAGCACTGCAATGCAC
GTGCATTGCAGTGCTCAGC


 


3498
CTGAGCACTGCAATGCACC
GGTGCATTGCAGTGCTCAG


 


3499
TGAGCACTGCAATGCACCA
TGGTGCATTGCAGTGCTCA


 


3500
GAGCACTGCAATGCACCAG
CTGGTGCATTGCAGTGCTC


 


3501
AGCACTGCAATGCACCAGG
CCTGGTGCATTGCAGTGCT


 


3502
GCACTGCAATGCACCAGGT
ACCTGGTGCATTGCAGTGC


 


3503
CACTGCAATGCACCAGGTC
GACCTGGTGCATTGCAGTG


 


3504
ACTGCAATGCACCAGGTCT
AGACCTGGTGCATTGCAGT


 


3505
CTGCAATGCACCAGGTCTG
CAGACCTGGTGCATTGCAG


 


3506
TGCAATGCACCAGGTCTGG
CCAGACCTGGTGCATTGCA


 


3507
GCAATGCACCAGGTCTGGG
CCCAGACCTGGTGCATTGC


 


3508
CAATGCACCAGGTCTGGGT
ACCCAGACCTGGTGCATTG


 


3509
AATGCACCAGGTCTGGGTC
GACCCAGACCTGGTGCATT


 


3510
ATGCACCAGGTCTGGGTCA
TGACCCAGACCTGGTGCAT


 


3511
TGCACCAGGTCTGGGTCAA
TTGACCCAGACCTGGTGCA


 


3512
GCACCAGGTCTGGGTCAAG
CTTGACCCAGACCTGGTGC


 


3513
CACCAGGTCTGGGTCAAGT
ACTTGACCCAGACCTGGTG


 


3514
ACCAGGTCTGGGTCAAGTT
AACTTGACCCAGACCTGGT


 


3515
CCAGGTCTGGGTCAAGTTT
AAACTTGACCCAGACCTGG


 


3516
CAGGTCTGGGTCAAGTTTG
CAAACTTGACCCAGACCTG


 


3517
AGGTCTGGGTCAAGTTTGA
TCAAACTTGACCCAGACCT


 


3518
GGTCTGGGTCAAGTTTGAT
ATCAAACTTGACCCAGACC


 


3519
GTCTGGGTCAAGTTTGATA
TATCAAACTTGACCCAGAC


 


3520
TCTGGGTCAAGTTTGATAT
ATATCAAACTTGACCCAGA


 


3521
CTGGGTCAAGTTTGATATC
GATATCAAACTTGACCCAG


 


3522
TGGGTCAAGTTTGATATCC
GGATATCAAACTTGACCCA


 


3523
GGGTCAAGTTTGATATCCG
CGGATATCAAACTTGACCC


 


3524
GGTCAAGTTTGATATCCGG
CCGGATATCAAACTTGACC


 


3525
GTCAAGTTTGATATCCGGG
CCCGGATATCAAACTTGAC


 


3526
TCAAGTTTGATATCCGGGG
CCCCGGATATCAAACTTGA


 


3527
CAAGTTTGATATCCGGGGG
CCCCCGGATATCAAACTTG


 


3528
AAGTTTGATATCCGGGGGC
GCCCCCGGATATCAAACTT


 


3529
AGTTTGATATCCGGGGGCA
TGCCCCCGGATATCAAACT


 


3530
GTTTGATATCCGGGGGCAC
GTGCCCCCGGATATCAAAC


 


3531
TTTGATATCCGGGGGCACT
AGTGCCCCCGGATATCAAA


 


3532
TTGATATCCGGGGGCACTG
CAGTGCCCCCGGATATCAA


 


3533
TGATATCCGGGGGCACTGC
GCAGTGCCCCCGGATATCA


 


3534
GATATCCGGGGGCACTGCC
GGCAGTGCCCCCGGATATC


 


3535
ATATCCGGGGGCACTGCCC
GGGCAGTGCCCCCGGATAT


 


3536
TATCCGGGGGCACTGCCCC
GGGGCAGTGCCCCCGGATA


 


3537
ATCCGGGGGCACTGCCCCT
AGGGGCAGTGCCCCCGGAT


 


3538
TCCGGGGGCACTGCCCCTG
CAGGGGCAGTGCCCCCGGA


 


3539
CCGGGGGCACTGCCCCTGC
GCAGGGGCAGTGCCCCCGG


 


3540
CGGGGGCACTGCCCCTGCC
GGCAGGGGCAGTGCCCCCG


 


3541
GGGGGCACTGCCCCTGCCA
TGGCAGGGGCAGTGCCCCC


 


3542
GGGGCACTGCCCCTGCCAA
TTGGCAGGGGCAGTGCCCC


 


3543
GGGCACTGCCCCTGCCAAG
CTTGGCAGGGGCAGTGCCC


 


3544
GGCACTGCCCCTGCCAAGC
GCTTGGCAGGGGCAGTGCC


 


3545
GCACTGCCCCTGCCAAGCT
AGCTTGGCAGGGGCAGTGC


 


3546
CACTGCCCCTGCCAAGCTG
CAGCTTGGCAGGGGCAGTG


 


3547
ACTGCCCCTGCCAAGCTGA
TCAGCTTGGCAGGGGCAGT


 


3548
CTGCCCCTGCCAAGCTGAT
ATCAGCTTGGCAGGGGCAG


 


3549
TGCCCCTGCCAAGCTGATG
CATCAGCTTGGCAGGGGCA


 


3550
GCCCCTGCCAAGCTGATGC
GCATCAGCTTGGCAGGGGC


 


3551
CCCCTGCCAAGCTGATGCC
GGCATCAGCTTGGCAGGGG


 


3552
CCCTGCCAAGCTGATGCCC
GGGCATCAGCTTGGCAGGG


 


3553
CCTGCCAAGCTGATGCCCG
CGGGCATCAGCTTGGCAGG


 


3554
CTGCCAAGCTGATGCCCGG
CCGGGCATCAGCTTGGCAG


 


3555
TGCCAAGCTGATGCCCGGG
CCCGGGCATCAGCTTGGCA


 


3556
GCCAAGCTGATGCCCGGGT
ACCCGGGCATCAGCTTGGC


 


3557
CCAAGCTGATGCCCGGGTA
TACCCGGGCATCAGCTTGG


 


3558
CAAGCTGATGCCCGGGTAT
ATACCCGGGCATCAGCTTG


 


3559
AAGCTGATGCCCGGGTATG
CATACCCGGGCATCAGCTT


 


3560
AGCTGATGCCCGGGTATGG
CCATACCCGGGCATCAGCT


 


3561
GCTGATGCCCGGGTATGGG
CCCATACCCGGGCATCAGC


 


3562
CTGATGCCCGGGTATGGGC
GCCCATACCCGGGCATCAG


 


3563
TGATGCCCGGGTATGGGCC
GGCCCATACCCGGGCATCA


 


3564
GATGCCCGGGTATGGGCCC
GGGCCCATACCCGGGCATC


 


3565
ATGCCCGGGTATGGGCCCC
GGGGCCCATACCCGGGCAT


 


3566
TGCCCGGGTATGGGCCCCC
GGGGGCCCATACCCGGGCA


 


3567
GCCCGGGTATGGGCCCCCG
CGGGGGCCCATACCCGGGC


 


3568
CCCGGGTATGGGCCCCCGG
CCGGGGGCCCATACCCGGG


 


3569
CCGGGTATGGGCCCCCGGG
CCCGGGGGCCCATACCCGG


 


3570
CGGGTATGGGCCCCCGGGG
CCCCGGGGGCCCATACCCG


 


3571
GGGTATGGGCCCCCGGGGA
TCCCCGGGGGCCCATACCC


 


3572
GGTATGGGCCCCCGGGGAT
ATCCCCGGGGGCCCATACC


 


3573
GTATGGGCCCCCGGGGATG
CATCCCCGGGGGCCCATAC


 


3574
TATGGGCCCCCGGGGATGC
GCATCCCCGGGGGCCCATA


 


3575
ATGGGCCCCCGGGGATGCA
TGCATCCCCGGGGGCCCAT


 


3576
TGGGCCCCCGGGGATGCAG
CTGCATCCCCGGGGGCCCA


 


3577
GGGCCCCCGGGGATGCAGG
CCTGCATCCCCGGGGGCCC


 


3578
GGCCCCCGGGGATGCAGGC
GCCTGCATCCCCGGGGGCC


 


3579
GCCCCCGGGGATGCAGGCC
GGCCTGCATCCCCGGGGGC


 


3580
CCCCCGGGGATGCAGGCCA
TGGCCTGCATCCCCGGGGG


 


3581
CCCCGGGGATGCAGGCCAG
CTGGCCTGCATCCCCGGGG


 


3582
CCCGGGGATGCAGGCCAGC
GCTGGCCTGCATCCCCGGG


 


3583
CCGGGGATGCAGGCCAGCA
TGCTGGCCTGCATCCCCGG


 


3584
CGGGGATGCAGGCCAGCAG
CTGCTGGCCTGCATCCCCG


 


3585
GGGGATGCAGGCCAGCAGA
TCTGCTGGCCTGCATCCCC


 


3586
GGGATGCAGGCCAGCAGAA
TTCTGCTGGCCTGCATCCC


 


3587
GGATGCAGGCCAGCAGAAG
CTTCTGCTGGCCTGCATCC


 


3588
GATGCAGGCCAGCAGAAGG
CCTTCTGCTGGCCTGCATC


 


3589
ATGCAGGCCAGCAGAAGGA
TCCTTCTGCTGGCCTGCAT


 


3590
TGCAGGCCAGCAGAAGGAA
TTCCTTCTGCTGGCCTGCA


 


3591
GCAGGCCAGCAGAAGGAAT
ATTCCTTCTGCTGGCCTGC


 


3592
CAGGCCAGCAGAAGGAATC
GATTCCTTCTGCTGGCCTG


 


3593
AGGCCAGCAGAAGGAATCA
TGATTCCTTCTGCTGGCCT


 


3594
GGCCAGCAGAAGGAATCAA
TTGATTCCTTCTGCTGGCC


 


3595
GCCAGCAGAAGGAATCAAC
GTTGATTCCTTCTGCTGGC


 


3596
CCAGCAGAAGGAATCAACA
TGTTGATTCCTTCTGCTGG


 


3597
CAGCAGAAGGAATCAACAC
GTGTTGATTCCTTCTGCTG


 


3598
AGCAGAAGGAATCAACACA
TGTGTTGATTCCTTCTGCT


 


3599
GCAGAAGGAATCAACACAG
CTGTGTTGATTCCTTCTGC


 


3600
CAGAAGGAATCAACACAGA
TCTGTGTTGATTCCTTCTG


 


3601
AGAAGGAATCAACACAGAA
TTCTGTGTTGATTCCTTCT


 


3602
GAAGGAATCAACACAGAAA
TTTCTGTGTTGATTCCTTC


 


3603
AAGGAATCAACACAGAAAA
TTTTCTGTGTTGATTCCTT


 


3604
AGGAATCAACACAGAAAAC
GTTTTCTGTGTTGATTCCT


 


3605
GGAATCAACACAGAAAACG
CGTTTTCTGTGTTGATTCC


 


3606
GAATCAACACAGAAAACGC
GCGTTTTCTGTGTTGATTC


 


3607
AATCAACACAGAAAACGCC
GGCGTTTTCTGTGTTGATT


 


3608
ATCAACACAGAAAACGCCC
GGGCGTTTTCTGTGTTGAT


 


3609
TCAACACAGAAAACGCCCC
GGGGCGTTTTCTGTGTTGA


 


3610
CAACACAGAAAACGCCCCC
GGGGGCGTTTTCTGTGTTG


 


3611
AACACAGAAAACGCCCCCA
TGGGGGCGTTTTCTGTGTT


 


3612
ACACAGAAAACGCCCCCAA
TTGGGGGCGTTTTCTGTGT


 


3613
CACAGAAAACGCCCCCAAC
GTTGGGGGCGTTTTCTGTG


 


3614
ACAGAAAACGCCCCCAACT
AGTTGGGGGCGTTTTCTGT


 


3615
CAGAAAACGCCCCCAACTC
GAGTTGGGGGCGTTTTCTG


 


3616
AGAAAACGCCCCCAACTCC
GGAGTTGGGGGCGTTTTCT


 


3617
GAAAACGCCCCCAACTCCA
TGGAGTTGGGGGCGTTTTC


 


3618
AAAACGCCCCCAACTCCAC
GTGGAGTTGGGGGCGTTTT


 


3619
AAACGCCCCCAACTCCACA
TGTGGAGTTGGGGGCGTTT


 


3620
AACGCCCCCAACTCCACAA
TTGTGGAGTTGGGGGCGTT


 


3621
ACGCCCCCAACTCCACAAC
GTTGTGGAGTTGGGGGCGT


 


3622
CGCCCCCAACTCCACAACC
GGTTGTGGAGTTGGGGGCG


 


3623
GCCCCCAACTCCACAACCT
AGGTTGTGGAGTTGGGGGC


 


3624
CCCCCAACTCCACAACCTT
AAGGTTGTGGAGTTGGGGG


 


3625
CCCCAACTCCACAACCTTC
GAAGGTTGTGGAGTTGGGG


 


3626
CCCAACTCCACAACCTTCC
GGAAGGTTGTGGAGTTGGG


 


3627
CCAACTCCACAACCTTCCT
AGGAAGGTTGTGGAGTTGG


 


3628
CAACTCCACAACCTTCCTG
CAGGAAGGTTGTGGAGTTG


 


3629
AACTCCACAACCTTCCTGC
GCAGGAAGGTTGTGGAGTT


 


3630
ACTCCACAACCTTCCTGCA
TGCAGGAAGGTTGTGGAGT


 


3631
CTCCACAACCTTCCTGCAA
TTGCAGGAAGGTTGTGGAG


 


3632
TCCACAACCTTCCTGCAAT
ATTGCAGGAAGGTTGTGGA


 


3633
CCACAACCTTCCTGCAATG
CATTGCAGGAAGGTTGTGG


 


3634
CACAACCTTCCTGCAATGG
CCATTGCAGGAAGGTTGTG


 


3635
ACAACCTTCCTGCAATGGC
GCCATTGCAGGAAGGTTGT


 


3636
CAACCTTCCTGCAATGGCG
CGCCATTGCAGGAAGGTTG


 


3637
AACCTTCCTGCAATGGCGA
TCGCCATTGCAGGAAGGTT


 


3638
ACCTTCCTGCAATGGCGAC
GTCGCCATTGCAGGAAGGT


 


3639
CCTTCCTGCAATGGCGACA
TGTCGCCATTGCAGGAAGG


 


3640
CTTCCTGCAATGGCGACAC
GTGTCGCCATTGCAGGAAG


 


3641
TTCCTGCAATGGCGACACC
GGTGTCGCCATTGCAGGAA


 


3642
TCCTGCAATGGCGACACCC
GGGTGTCGCCATTGCAGGA


 


3643
CCTGCAATGGCGACACCCA
TGGGTGTCGCCATTGCAGG


 


3644
CTGCAATGGCGACACCCAC
GTGGGTGTCGCCATTGCAG


 


3645
TGCAATGGCGACACCCACA
TGTGGGTGTCGCCATTGCA


 


3646
GCAATGGCGACACCCACAG
CTGTGGGTGTCGCCATTGC


 


3647
CAATGGCGACACCCACAGG
CCTGTGGGTGTCGCCATTG


 


3648
AATGGCGACACCCACAGGA
TCCTGTGGGTGTCGCCATT


 


3649
ATGGCGACACCCACAGGAC
GTCCTGTGGGTGTCGCCAT


 


3650
TGGCGACACCCACAGGACC
GGTCCTGTGGGTGTCGCCA


 


3651
GGCGACACCCACAGGACCA
TGGTCCTGTGGGTGTCGCC


 


3652
GCGACACCCACAGGACCAA
TTGGTCCTGTGGGTGTCGC


 


3653
CGACACCCACAGGACCAAG
CTTGGTCCTGTGGGTGTCG


 


3654
GACACCCACAGGACCAAGA
TCTTGGTCCTGTGGGTGTC


 


3655
ACACCCACAGGACCAAGAG
CTCTTGGTCCTGTGGGTGT


 


3656
CACCCACAGGACCAAGAGC
GCTCTTGGTCCTGTGGGTG


 


3657
ACCCACAGGACCAAGAGCA
TGCTCTTGGTCCTGTGGGT


 


3658
CCCACAGGACCAAGAGCAT
ATGCTCTTGGTCCTGTGGG


 


3659
CCACAGGACCAAGAGCATC
GATGCTCTTGGTCCTGTGG


 


3660
CACAGGACCAAGAGCATCA
TGATGCTCTTGGTCCTGTG


 


3661
ACAGGACCAAGAGCATCAA
TTGATGCTCTTGGTCCTGT


 


3662
CAGGACCAAGAGCATCAAA
TTTGATGCTCTTGGTCCTG


 


3663
AGGACCAAGAGCATCAAAG
CTTTGATGCTCTTGGTCCT


 


3664
GGACCAAGAGCATCAAAGA
TCTTTGATGCTCTTGGTCC


 


3665
GACCAAGAGCATCAAAGAG
CTCTTTGATGCTCTTGGTC


 


3666
ACCAAGAGCATCAAAGAGG
CCTCTTTGATGCTCTTGGT


 


3667
CCAAGAGCATCAAAGAGGA
TCCTCTTTGATGCTCTTGG


 


3668
CAAGAGCATCAAAGAGGAG
CTCCTCTTTGATGCTCTTG


 


3669
AAGAGCATCAAAGAGGAGA
TCTCCTCTTTGATGCTCTT


 


3670
AGAGCATCAAAGAGGAGAC
GTCTCCTCTTTGATGCTCT


 


3671
GAGCATCAAAGAGGAGACC
GGTCTCCTCTTTGATGCTC


 


3672
AGCATCAAAGAGGAGACCC
GGGTCTCCTCTTTGATGCT


 


3673
GCATCAAAGAGGAGACCCC
GGGGTCTCCTCTTTGATGC


 


3674
CATCAAAGAGGAGACCCCC
GGGGGTCTCCTCTTTGATG


 


3675
ATCAAAGAGGAGACCCCCG
CGGGGGTCTCCTCTTTGAT


 


3676
TCAAAGAGGAGACCCCCGA
TCGGGGGTCTCCTCTTTGA


 


3677
CAAAGAGGAGACCCCCGAT
ATCGGGGGTCTCCTCTTTG


 


3678
AAAGAGGAGACCCCCGATT
AATCGGGGGTCTCCTCTTT


 


3679
AAGAGGAGACCCCCGATTC
GAATCGGGGGTCTCCTCTT


 


3680
AGAGGAGACCCCCGATTCC
GGAATCGGGGGTCTCCTCT


 


3681
GAGGAGACCCCCGATTCCG
CGGAATCGGGGGTCTCCTC


 


3682
AGGAGACCCCCGATTCCGC
GCGGAATCGGGGGTCTCCT


 


3683
GGAGACCCCCGATTCCGCT
AGCGGAATCGGGGGTCTCC


 


3684
GAGACCCCCGATTCCGCTG
CAGCGGAATCGGGGGTCTC


 


3685
AGACCCCCGATTCCGCTGA
TCAGCGGAATCGGGGGTCT


 


3686
GACCCCCGATTCCGCTGAG
CTCAGCGGAATCGGGGGTC


 


3687
ACCCCCGATTCCGCTGAGA
TCTCAGCGGAATCGGGGGT


 


3688
CCCCCGATTCCGCTGAGAC
GTCTCAGCGGAATCGGGGG


 


3689
CCCCGATTCCGCTGAGACC
GGTCTCAGCGGAATCGGGG


 


3690
CCCGATTCCGCTGAGACCC
GGGTCTCAGCGGAATCGGG


 


3691
CCGATTCCGCTGAGACCCC
GGGGTCTCAGCGGAATCGG


 


3692
CGATTCCGCTGAGACCCCA
TGGGGTCTCAGCGGAATCG


 


3693
GATTCCGCTGAGACCCCAG
CTGGGGTCTCAGCGGAATC


 


3694
ATTCCGCTGAGACCCCAGC
GCTGGGGTCTCAGCGGAAT


 


3695
TTCCGCTGAGACCCCAGCA
TGCTGGGGTCTCAGCGGAA


 


3696
TCCGCTGAGACCCCAGCAG
CTGCTGGGGTCTCAGCGGA


 


3697
CCGCTGAGACCCCAGCAGA
TCTGCTGGGGTCTCAGCGG


 


3698
CGCTGAGACCCCAGCAGAG
CTCTGCTGGGGTCTCAGCG


 


3699
GCTGAGACCCCAGCAGAGG
CCTCTGCTGGGGTCTCAGC


 


3700
CTGAGACCCCAGCAGAGGA
TCCTCTGCTGGGGTCTCAG


 


3701
TGAGACCCCAGCAGAGGAC
GTCCTCTGCTGGGGTCTCA


 


3702
GAGACCCCAGCAGAGGACC
GGTCCTCTGCTGGGGTCTC


 


3703
AGACCCCAGCAGAGGACCG
CGGTCCTCTGCTGGGGTCT


 


3704
GACCCCAGCAGAGGACCGT
ACGGTCCTCTGCTGGGGTC


 


3705
ACCCCAGCAGAGGACCGTG
CACGGTCCTCTGCTGGGGT


 


3706
CCCCAGCAGAGGACCGTGC
GCACGGTCCTCTGCTGGGG


 


3707
CCCAGCAGAGGACCGTGCT
AGCACGGTCCTCTGCTGGG


 


3708
CCAGCAGAGGACCGTGCTG
CAGCACGGTCCTCTGCTGG


 


3709
CAGCAGAGGACCGTGCTGG
CCAGCACGGTCCTCTGCTG


 


3710
AGCAGAGGACCGTGCTGGC
GCCAGCACGGTCCTCTGCT


 


3711
GCAGAGGACCGTGCTGGCC
GGCCAGCACGGTCCTCTGC


 


3712
CAGAGGACCGTGCTGGCCG
CGGCCAGCACGGTCCTCTG


 


3713
AGAGGACCGTGCTGGCCGA
TCGGCCAGCACGGTCCTCT


 


3714
GAGGACCGTGCTGGCCGAG
CTCGGCCAGCACGGTCCTC


 


3715
AGGACCGTGCTGGCCGAGG
CCTCGGCCAGCACGGTCCT


 


3716
GGACCGTGCTGGCCGAGGG
CCCTCGGCCAGCACGGTCC


 


3717
GACCGTGCTGGCCGAGGGC
GCCCTCGGCCAGCACGGTC


 


3718
ACCGTGCTGGCCGAGGGCC
GGCCCTCGGCCAGCACGGT


 


3719
CCGTGCTGGCCGAGGGCCC
GGGCCCTCGGCCAGCACGG


 


3720
CGTGCTGGCCGAGGGCCCC
GGGGCCCTCGGCCAGCACG


 


3721
GTGCTGGCCGAGGGCCCCT
AGGGGCCCTCGGCCAGCAC


 


3722
TGCTGGCCGAGGGCCCCTG
CAGGGGCCCTCGGCCAGCA


 


3723
GCTGGCCGAGGGCCCCTGC
GCAGGGGCCCTCGGCCAGC


 


3724
CTGGCCGAGGGCCCCTGCC
GGCAGGGGCCCTCGGCCAG


 


3725
TGGCCGAGGGCCCCTGCCT
AGGCAGGGGCCCTCGGCCA


 


3726
GGCCGAGGGCCCCTGCCTT
AAGGCAGGGGCCCTCGGCC


 


3727
GCCGAGGGCCCCTGCCTTG
CAAGGCAGGGGCCCTCGGC


 


3728
CCGAGGGCCCCTGCCTTGT
ACAAGGCAGGGGCCCTCGG


 


3729
CGAGGGCCCCTGCCTTGTC
GACAAGGCAGGGGCCCTCG


 


3730
GAGGGCCCCTGCCTTGTCC
GGACAAGGCAGGGGCCCTC


 


3731
AGGGCCCCTGCCTTGTCCT
AGGACAAGGCAGGGGCCCT


 


3732
GGGCCCCTGCCTTGTCCTT
AAGGACAAGGCAGGGGCCC


 


3733
GGCCCCTGCCTTGTCCTTC
GAAGGACAAGGCAGGGGCC


 


3734
GCCCCTGCCTTGTCCTTCT
AGAAGGACAAGGCAGGGGC


 


3735
CCCCTGCCTTGTCCTTCTC
GAGAAGGACAAGGCAGGGG


 


3736
CCCTGCCTTGTCCTTCTCT
AGAGAAGGACAAGGCAGGG


 


3737
CCTGCCTTGTCCTTCTCTC
GAGAGAAGGACAAGGCAGG


 


3738
CTGCCTTGTCCTTCTCTCT
AGAGAGAAGGACAAGGCAG


 


3739
TGCCTTGTCCTTCTCTCTG
CAGAGAGAAGGACAAGGCA


 


3740
GCCTTGTCCTTCTCTCTGC
GCAGAGAGAAGGACAAGGC


 


3741
CCTTGTCCTTCTCTCTGCG
CGCAGAGAGAAGGACAAGG


 


3742
CTTGTCCTTCTCTCTGCGA
TCGCAGAGAGAAGGACAAG


 


3743
TTGTCCTTCTCTCTGCGAA
TTCGCAGAGAGAAGGACAA


 


3744
TGTCCTTCTCTCTGCGAAC
GTTCGCAGAGAGAAGGACA


 


3745
GTCCTTCTCTCTGCGAACT
AGTTCGCAGAGAGAAGGAC


 


3746
TCCTTCTCTCTGCGAACTG
CAGTTCGCAGAGAGAAGGA


 


3747
CCTTCTCTCTGCGAACTGC
GCAGTTCGCAGAGAGAAGG


 


3748
CTTCTCTCTGCGAACTGCT
AGCAGTTCGCAGAGAGAAG


 


3749
TTCTCTCTGCGAACTGCTG
CAGCAGTTCGCAGAGAGAA


 


3750
TCTCTCTGCGAACTGCTGG
CCAGCAGTTCGCAGAGAGA


 


3751
CTCTCTGCGAACTGCTGGC
GCCAGCAGTTCGCAGAGAG


 


3752
TCTCTGCGAACTGCTGGCT
AGCCAGCAGTTCGCAGAGA


 


3753
CTCTGCGAACTGCTGGCTT
AAGCCAGCAGTTCGCAGAG


 


3754
TCTGCGAACTGCTGGCTTC
GAAGCCAGCAGTTCGCAGA


 


3755
CTGCGAACTGCTGGCTTCT
AGAAGCCAGCAGTTCGCAG


 


3756
TGCGAACTGCTGGCTTCTA
TAGAAGCCAGCAGTTCGCA


 


3757
GCGAACTGCTGGCTTCTAC
GTAGAAGCCAGCAGTTCGC


 


3758
CGAACTGCTGGCTTCTACC
GGTAGAAGCCAGCAGTTCG


 


3759
GAACTGCTGGCTTCTACCG
CGGTAGAAGCCAGCAGTTC


 


3760
AACTGCTGGCTTCTACCGC
GCGGTAGAAGCCAGCAGTT


 


3761
ACTGCTGGCTTCTACCGCG
CGCGGTAGAAGCCAGCAGT


 


3762
CTGCTGGCTTCTACCGCGG
CCGCGGTAGAAGCCAGCAG


 


3763
TGCTGGCTTCTACCGCGGT
ACCGCGGTAGAAGCCAGCA


 


3764
GCTGGCTTCTACCGCGGTC
GACCGCGGTAGAAGCCAGC


 


3765
CTGGCTTCTACCGCGGTCA
TGACCGCGGTAGAAGCCAG


 


3766
TGGCTTCTACCGCGGTCAA
TTGACCGCGGTAGAAGCCA


 


3767
GGCTTCTACCGCGGTCAAA
TTTGACCGCGGTAGAAGCC


 


3768
GCTTCTACCGCGGTCAAAC
GTTTGACCGCGGTAGAAGC


 


3769
CTTCTACCGCGGTCAAACT
AGTTTGACCGCGGTAGAAG


 


3770
TTCTACCGCGGTCAAACTC
GAGTTTGACCGCGGTAGAA


 


3771
TCTACCGCGGTCAAACTCT
AGAGTTTGACCGCGGTAGA


 


3772
CTACCGCGGTCAAACTCTG
CAGAGTTTGACCGCGGTAG


 


3773
TACCGCGGTCAAACTCTGC
GCAGAGTTTGACCGCGGTA


 


3774
ACCGCGGTCAAACTCTGCT
AGCAGAGTTTGACCGCGGT


 


3775
CCGCGGTCAAACTCTGCTT
AAGCAGAGTTTGACCGCGG


 


3776
CGCGGTCAAACTCTGCTTG
CAAGCAGAGTTTGACCGCG


 


3777
GCGGTCAAACTCTGCTTGG
CCAAGCAGAGTTTGACCGC


 


3778
CGGTCAAACTCTGCTTGGG
CCCAAGCAGAGTTTGACCG


 


3779
GGTCAAACTCTGCTTGGGC
GCCCAAGCAGAGTTTGACC


 


3780
GTCAAACTCTGCTTGGGCC
GGCCCAAGCAGAGTTTGAC


 


3781
TCAAACTCTGCTTGGGCCA
TGGCCCAAGCAGAGTTTGA


 


3782
CAAACTCTGCTTGGGCCAT
ATGGCCCAAGCAGAGTTTG


 


3783
AAACTCTGCTTGGGCCATG
CATGGCCCAAGCAGAGTTT


 


3784
AACTCTGCTTGGGCCATGA
TCATGGCCCAAGCAGAGTT


 


3785
ACTCTGCTTGGGCCATGAG
CTCATGGCCCAAGCAGAGT


 


3786
CTCTGCTTGGGCCATGAGC
GCTCATGGCCCAAGCAGAG


 


3787
TCTGCTTGGGCCATGAGCG
CGCTCATGGCCCAAGCAGA


 


3788
CTGCTTGGGCCATGAGCGA
TCGCTCATGGCCCAAGCAG


 


3789
TGCTTGGGCCATGAGCGAA
TTCGCTCATGGCCCAAGCA


 


3790
GCTTGGGCCATGAGCGAAT
ATTCGCTCATGGCCCAAGC


 


3791
CTTGGGCCATGAGCGAATA
TATTCGCTCATGGCCCAAG


 


3792
TTGGGCCATGAGCGAATAC
GTATTCGCTCATGGCCCAA


 


3793
TGGGCCATGAGCGAATACA
TGTATTCGCTCATGGCCCA


 


3794
GGGCCATGAGCGAATACAC
GTGTATTCGCTCATGGCCC


 


3795
GGCCATGAGCGAATACACA
TGTGTATTCGCTCATGGCC


 


3796
GCCATGAGCGAATACACAT
ATGTGTATTCGCTCATGGC


 


3797
CCATGAGCGAATACACATG
CATGTGTATTCGCTCATGG


 


3798
CATGAGCGAATACACATGG
CCATGTGTATTCGCTCATG


 


3799
ATGAGCGAATACACATGGC
GCCATGTGTATTCGCTCAT


 


3800
TGAGCGAATACACATGGCC
GGCCATGTGTATTCGCTCA


 


3801
GAGCGAATACACATGGCCT
AGGCCATGTGTATTCGCTC


 


3802
AGCGAATACACATGGCCTT
AAGGCCATGTGTATTCGCT


 


3803
GCGAATACACATGGCCTTC
GAAGGCCATGTGTATTCGC


 


3804
CGAATACACATGGCCTTCG
CGAAGGCCATGTGTATTCG


 


3805
GAATACACATGGCCTTCGC
GCGAAGGCCATGTGTATTC


 


3806
AATACACATGGCCTTCGCC
GGCGAAGGCCATGTGTATT


 


3807
ATACACATGGCCTTCGCCC
GGGCGAAGGCCATGTGTAT


 


3808
TACACATGGCCTTCGCCCC
GGGGCGAAGGCCATGTGTA


 


3809
ACACATGGCCTTCGCCCCC
GGGGGCGAAGGCCATGTGT


 


3810
CACATGGCCTTCGCCCCCG
CGGGGGCGAAGGCCATGTG


 


3811
ACATGGCCTTCGCCCCCGT
ACGGGGGCGAAGGCCATGT


 


3812
CATGGCCTTCGCCCCCGTC
GACGGGGGCGAAGGCCATG


 


3813
ATGGCCTTCGCCCCCGTCA
TGACGGGGGCGAAGGCCAT


 


3814
TGGCCTTCGCCCCCGTCAC
GTGACGGGGGCGAAGGCCA


 


3815
GGCCTTCGCCCCCGTCACT
AGTGACGGGGGCGAAGGCC


 


3816
GCCTTCGCCCCCGTCACTC
GAGTGACGGGGGCGAAGGC


 


3817
CCTTCGCCCCCGTCACTCC
GGAGTGACGGGGGCGAAGG


 


3818
CTTCGCCCCCGTCACTCCG
CGGAGTGACGGGGGCGAAG


 


3819
TTCGCCCCCGTCACTCCGG
CCGGAGTGACGGGGGCGAA


 


3820
TCGCCCCCGTCACTCCGGC
GCCGGAGTGACGGGGGCGA


 


3821
CGCCCCCGTCACTCCGGCC
GGCCGGAGTGACGGGGGCG


 


3822
GCCCCCGTCACTCCGGCCC
GGGCCGGAGTGACGGGGGC


 


3823
CCCCCGTCACTCCGGCCCT
AGGGCCGGAGTGACGGGGG


 


3824
CCCCGTCACTCCGGCCCTG
CAGGGCCGGAGTGACGGGG


 


3825
CCCGTCACTCCGGCCCTGC
GCAGGGCCGGAGTGACGGG


 


3826
CCGTCACTCCGGCCCTGCC
GGCAGGGCCGGAGTGACGG


 


3827
CGTCACTCCGGCCCTGCCC
GGGCAGGGCCGGAGTGACG


 


3828
GTCACTCCGGCCCTGCCCA
TGGGCAGGGCCGGAGTGAC


 


3829
TCACTCCGGCCCTGCCCAG
CTGGGCAGGGCCGGAGTGA


 


3830
CACTCCGGCCCTGCCCAGT
ACTGGGCAGGGCCGGAGTG


 


3831
ACTCCGGCCCTGCCCAGTG
CACTGGGCAGGGCCGGAGT


 


3832
CTCCGGCCCTGCCCAGTGA
TCACTGGGCAGGGCCGGAG


 


3833
TCCGGCCCTGCCCAGTGAT
ATCACTGGGCAGGGCCGGA


 


3834
CCGGCCCTGCCCAGTGATG
CATCACTGGGCAGGGCCGG


 


3835
CGGCCCTGCCCAGTGATGA
TCATCACTGGGCAGGGCCG


 


3836
GGCCCTGCCCAGTGATGAC
GTCATCACTGGGCAGGGCC


 


3837
GCCCTGCCCAGTGATGACC
GGTCATCACTGGGCAGGGC


 


3838
CCCTGCCCAGTGATGACCG
CGGTCATCACTGGGCAGGG


 


3839
CCTGCCCAGTGATGACCGC
GCGGTCATCACTGGGCAGG


 


3840
CTGCCCAGTGATGACCGCA
TGCGGTCATCACTGGGCAG


 


3841
TGCCCAGTGATGACCGCAT
ATGCGGTCATCACTGGGCA


 


3842
GCCCAGTGATGACCGCATC
GATGCGGTCATCACTGGGC


 


3843
CCCAGTGATGACCGCATCA
TGATGCGGTCATCACTGGG


 


3844
CCAGTGATGACCGCATCAC
GTGATGCGGTCATCACTGG


 


3845
CAGTGATGACCGCATCACC
GGTGATGCGGTCATCACTG


 


3846
AGTGATGACCGCATCACCA
TGGTGATGCGGTCATCACT


 


3847
GTGATGACCGCATCACCAA
TTGGTGATGCGGTCATCAC


 


3848
TGATGACCGCATCACCAAC
GTTGGTGATGCGGTCATCA


 


3849
GATGACCGCATCACCAACA
TGTTGGTGATGCGGTCATC


 


3850
ATGACCGCATCACCAACAT
ATGTTGGTGATGCGGTCAT


 


3851
TGACCGCATCACCAACATC
GATGTTGGTGATGCGGTCA


 


3852
GACCGCATCACCAACATCC
GGATGTTGGTGATGCGGTC


 


3853
ACCGCATCACCAACATCCT
AGGATGTTGGTGATGCGGT


 


3854
CCGCATCACCAACATCCTG
CAGGATGTTGGTGATGCGG


 


3855
CGCATCACCAACATCCTGG
CCAGGATGTTGGTGATGCG


 


3856
GCATCACCAACATCCTGGA
TCCAGGATGTTGGTGATGC


 


3857
CATCACCAACATCCTGGAC
GTCCAGGATGTTGGTGATG


 


3858
ATCACCAACATCCTGGACA
TGTCCAGGATGTTGGTGAT


 


3859
TCACCAACATCCTGGACAG
CTGTCCAGGATGTTGGTGA


 


3860
CACCAACATCCTGGACAGC
GCTGTCCAGGATGTTGGTG


 


3861
ACCAACATCCTGGACAGCA
TGCTGTCCAGGATGTTGGT


 


3862
CCAACATCCTGGACAGCAT
ATGCTGTCCAGGATGTTGG


 


3863
CAACATCCTGGACAGCATT
AATGCTGTCCAGGATGTTG


 


3864
AACATCCTGGACAGCATTA
TAATGCTGTCCAGGATGTT


 


3865
ACATCCTGGACAGCATTAT
ATAATGCTGTCCAGGATGT


 


3866
CATCCTGGACAGCATTATC
GATAATGCTGTCCAGGATG


 


3867
ATCCTGGACAGCATTATCG
CGATAATGCTGTCCAGGAT


 


3868
TCCTGGACAGCATTATCGC
GCGATAATGCTGTCCAGGA


 


3869
CCTGGACAGCATTATCGCA
TGCGATAATGCTGTCCAGG


 


3870
CTGGACAGCATTATCGCAC
GTGCGATAATGCTGTCCAG


 


3871
TGGACAGCATTATCGCACA
TGTGCGATAATGCTGTCCA


 


3872
GGACAGCATTATCGCACAG
CTGTGCGATAATGCTGTCC


 


3873
GACAGCATTATCGCACAGG
CCTGTGCGATAATGCTGTC


 


3874
ACAGCATTATCGCACAGGT
ACCTGTGCGATAATGCTGT


 


3875
CAGCATTATCGCACAGGTG
CACCTGTGCGATAATGCTG


 


3876
AGCATTATCGCACAGGTGG
CCACCTGTGCGATAATGCT


 


3877
GCATTATCGCACAGGTGGT
ACCACCTGTGCGATAATGC


 


3878
CATTATCGCACAGGTGGTG
CACCACCTGTGCGATAATG


 


3879
ATTATCGCACAGGTGGTGG
CCACCACCTGTGCGATAAT


 


3880
TTATCGCACAGGTGGTGGA
TCCACCACCTGTGCGATAA


 


3881
TATCGCACAGGTGGTGGAA
TTCCACCACCTGTGCGATA


 


3882
ATCGCACAGGTGGTGGAAC
GTTCCACCACCTGTGCGAT


 


3883
TCGCACAGGTGGTGGAACG
CGTTCCACCACCTGTGCGA


 


3884
CGCACAGGTGGTGGAACGG
CCGTTCCACCACCTGTGCG


 


3885
GCACAGGTGGTGGAACGGA
TCCGTTCCACCACCTGTGC


 


3886
CACAGGTGGTGGAACGGAA
TTCCGTTCCACCACCTGTG


 


3887
ACAGGTGGTGGAACGGAAG
CTTCCGTTCCACCACCTGT


 


3888
CAGGTGGTGGAACGGAAGA
TCTTCCGTTCCACCACCTG


 


3889
AGGTGGTGGAACGGAAGAT
ATCTTCCGTTCCACCACCT


 


3890
GGTGGTGGAACGGAAGATC
GATCTTCCGTTCCACCACC


 


3891
GTGGTGGAACGGAAGATCC
GGATCTTCCGTTCCACCAC


 


3892
TGGTGGAACGGAAGATCCA
TGGATCTTCCGTTCCACCA


 


3893
GGTGGAACGGAAGATCCAG
CTGGATCTTCCGTTCCACC


 


3894
GTGGAACGGAAGATCCAGG
CCTGGATCTTCCGTTCCAC


 


3895
TGGAACGGAAGATCCAGGA
TCCTGGATCTTCCGTTCCA


 


3896
GGAACGGAAGATCCAGGAG
CTCCTGGATCTTCCGTTCC


 


3897
GAACGGAAGATCCAGGAGA
TCTCCTGGATCTTCCGTTC


 


3898
AACGGAAGATCCAGGAGAA
TTCTCCTGGATCTTCCGTT


 


3899
ACGGAAGATCCAGGAGAAA
TTTCTCCTGGATCTTCCGT


 


3900
CGGAAGATCCAGGAGAAAG
CTTTCTCCTGGATCTTCCG


 


3901
GGAAGATCCAGGAGAAAGC
GCTTTCTCCTGGATCTTCC


 


3902
GAAGATCCAGGAGAAAGCC
GGCTTTCTCCTGGATCTTC


 


3903
AAGATCCAGGAGAAAGCCC
GGGCTTTCTCCTGGATCTT


 


3904
AGATCCAGGAGAAAGCCCT
AGGGCTTTCTCCTGGATCT


 


3905
GATCCAGGAGAAAGCCCTG
CAGGGCTTTCTCCTGGATC


 


3906
ATCCAGGAGAAAGCCCTGG
CCAGGGCTTTCTCCTGGAT


 


3907
TCCAGGAGAAAGCCCTGGG
CCCAGGGCTTTCTCCTGGA


 


3908
CCAGGAGAAAGCCCTGGGG
CCCCAGGGCTTTCTCCTGG


 


3909
CAGGAGAAAGCCCTGGGGC
GCCCCAGGGCTTTCTCCTG


 


3910
AGGAGAAAGCCCTGGGGCC
GGCCCCAGGGCTTTCTCCT


 


3911
GGAGAAAGCCCTGGGGCCG
CGGCCCCAGGGCTTTCTCC


 


3912
GAGAAAGCCCTGGGGCCGG
CCGGCCCCAGGGCTTTCTC


 


3913
AGAAAGCCCTGGGGCCGGG
CCCGGCCCCAGGGCTTTCT


 


3914
GAAAGCCCTGGGGCCGGGG
CCCCGGCCCCAGGGCTTTC


 


3915
AAAGCCCTGGGGCCGGGGC
GCCCCGGCCCCAGGGCTTT


 


3916
AAGCCCTGGGGCCGGGGCT
AGCCCCGGCCCCAGGGCTT


 


3917
AGCCCTGGGGCCGGGGCTT
AAGCCCCGGCCCCAGGGCT


 


3918
GCCCTGGGGCCGGGGCTTC
GAAGCCCCGGCCCCAGGGC


 


3919
CCCTGGGGCCGGGGCTTCG
CGAAGCCCCGGCCCCAGGG


 


3920
CCTGGGGCCGGGGCTTCGA
TCGAAGCCCCGGCCCCAGG


 


3921
CTGGGGCCGGGGCTTCGAG
CTCGAAGCCCCGGCCCCAG


 


3922
TGGGGCCGGGGCTTCGAGC
GCTCGAAGCCCCGGCCCCA


 


3923
GGGGCCGGGGCTTCGAGCT
AGCTCGAAGCCCCGGCCCC


 


3924
GGGCCGGGGCTTCGAGCTG
CAGCTCGAAGCCCCGGCCC


 


3925
GGCCGGGGCTTCGAGCTGG
CCAGCTCGAAGCCCCGGCC


 


3926
GCCGGGGCTTCGAGCTGGC
GCCAGCTCGAAGCCCCGGC


 


3927
CCGGGGCTTCGAGCTGGCC
GGCCAGCTCGAAGCCCCGG


 


3928
CGGGGCTTCGAGCTGGCCC
GGGCCAGCTCGAAGCCCCG


 


3929
GGGGCTTCGAGCTGGCCCG
CGGGCCAGCTCGAAGCCCC


 


3930
GGGCTTCGAGCTGGCCCGG
CCGGGCCAGCTCGAAGCCC


 


3931
GGCTTCGAGCTGGCCCGGG
CCCGGGCCAGCTCGAAGCC


 


3932
GCTTCGAGCTGGCCCGGGT
ACCCGGGCCAGCTCGAAGC


 


3933
CTTCGAGCTGGCCCGGGTC
GACCCGGGCCAGCTCGAAG


 


3934
TTCGAGCTGGCCCGGGTCT
AGACCCGGGCCAGCTCGAA


 


3935
TCGAGCTGGCCCGGGTCTG
CAGACCCGGGCCAGCTCGA


 


3936
CGAGCTGGCCCGGGTCTGC
GCAGACCCGGGCCAGCTCG


 


3937
GAGCTGGCCCGGGTCTGCG
CGCAGACCCGGGCCAGCTC


 


3938
AGCTGGCCCGGGTCTGCGC
GCGCAGACCCGGGCCAGCT


 


3939
GCTGGCCCGGGTCTGCGCA
TGCGCAGACCCGGGCCAGC


 


3940
CTGGCCCGGGTCTGCGCAA
TTGCGCAGACCCGGGCCAG


 


3941
TGGCCCGGGTCTGCGCAAG
CTTGCGCAGACCCGGGCCA


 


3942
GGCCCGGGTCTGCGCAAGG
CCTTGCGCAGACCCGGGCC


 


3943
GCCCGGGTCTGCGCAAGGG
CCCTTGCGCAGACCCGGGC


 


3944
CCCGGGTCTGCGCAAGGGC
GCCCTTGCGCAGACCCGGG


 


3945
CCGGGTCTGCGCAAGGGCC
GGCCCTTGCGCAGACCCGG


 


3946
CGGGTCTGCGCAAGGGCCT
AGGCCCTTGCGCAGACCCG


 


3947
GGGTCTGCGCAAGGGCCTG
CAGGCCCTTGCGCAGACCC


 


3948
GGTCTGCGCAAGGGCCTGG
CCAGGCCCTTGCGCAGACC


 


3949
GTCTGCGCAAGGGCCTGGG
CCCAGGCCCTTGCGCAGAC


 


3950
TCTGCGCAAGGGCCTGGGC
GCCCAGGCCCTTGCGCAGA


 


3951
CTGCGCAAGGGCCTGGGCC
GGCCCAGGCCCTTGCGCAG


 


3952
TGCGCAAGGGCCTGGGCCT
AGGCCCAGGCCCTTGCGCA


 


3953
GCGCAAGGGCCTGGGCCTG
CAGGCCCAGGCCCTTGCGC


 


3954
CGCAAGGGCCTGGGCCTGC
GCAGGCCCAGGCCCTTGCG


 


3955
GCAAGGGCCTGGGCCTGCC
GGCAGGCCCAGGCCCTTGC


 


3956
CAAGGGCCTGGGCCTGCCC
GGGCAGGCCCAGGCCCTTG


 


3957
AAGGGCCTGGGCCTGCCCC
GGGGCAGGCCCAGGCCCTT


 


3958
AGGGCCTGGGCCTGCCCCT
AGGGGCAGGCCCAGGCCCT


 


3959
GGGCCTGGGCCTGCCCCTC
GAGGGGCAGGCCCAGGCCC


 


3960
GGCCTGGGCCTGCCCCTCT
AGAGGGGCAGGCCCAGGCC


 


3961
GCCTGGGCCTGCCCCTCTC
GAGAGGGGCAGGCCCAGGC


 


3962
CCTGGGCCTGCCCCTCTCT
AGAGAGGGGCAGGCCCAGG


 


3963
CTGGGCCTGCCCCTCTCTC
GAGAGAGGGGCAGGCCCAG


 


3964
TGGGCCTGCCCCTCTCTCC
GGAGAGAGGGGCAGGCCCA


 


3965
GGGCCTGCCCCTCTCTCCA
TGGAGAGAGGGGCAGGCCC


 


3966
GGCCTGCCCCTCTCTCCAG
CTGGAGAGAGGGGCAGGCC


 


3967
GCCTGCCCCTCTCTCCAGT
ACTGGAGAGAGGGGCAGGC


 


3968
CCTGCCCCTCTCTCCAGTG
CACTGGAGAGAGGGGCAGG


 


3969
CTGCCCCTCTCTCCAGTGC
GCACTGGAGAGAGGGGCAG


 


3970
TGCCCCTCTCTCCAGTGCG
CGCACTGGAGAGAGGGGCA


 


3971
GCCCCTCTCTCCAGTGCGG
CCGCACTGGAGAGAGGGGC


 


3972
CCCCTCTCTCCAGTGCGGC
GCCGCACTGGAGAGAGGGG


 


3973
CCCTCTCTCCAGTGCGGCC
GGCCGCACTGGAGAGAGGG


 


3974
CCTCTCTCCAGTGCGGCCC
GGGCCGCACTGGAGAGAGG


 


3975
CTCTCTCCAGTGCGGCCCC
GGGGCCGCACTGGAGAGAG


 


3976
TCTCTCCAGTGCGGCCCCG
CGGGGCCGCACTGGAGAGA


 


3977
CTCTCCAGTGCGGCCCCGG
CCGGGGCCGCACTGGAGAG


 


3978
TCTCCAGTGCGGCCCCGGC
GCCGGGGCCGCACTGGAGA


 


3979
CTCCAGTGCGGCCCCGGCT
AGCCGGGGCCGCACTGGAG


 


3980
TCCAGTGCGGCCCCGGCTG
CAGCCGGGGCCGCACTGGA


 


3981
CCAGTGCGGCCCCGGCTGC
GCAGCCGGGGCCGCACTGG


 


3982
CAGTGCGGCCCCGGCTGCC
GGCAGCCGGGGCCGCACTG


 


3983
AGTGCGGCCCCGGCTGCCT
AGGCAGCCGGGGCCGCACT


 


3984
GTGCGGCCCCGGCTGCCTC
GAGGCAGCCGGGGCCGCAC


 


3985
TGCGGCCCCGGCTGCCTCC
GGAGGCAGCCGGGGCCGCA


 


3986
GCGGCCCCGGCTGCCTCCC
GGGAGGCAGCCGGGGCCGC


 


3987
CGGCCCCGGCTGCCTCCCC
GGGGAGGCAGCCGGGGCCG


 


3988
GGCCCCGGCTGCCTCCCCC
GGGGGAGGCAGCCGGGGCC


 


3989
GCCCCGGCTGCCTCCCCCA
TGGGGGAGGCAGCCGGGGC


 


3990
CCCCGGCTGCCTCCCCCAG
CTGGGGGAGGCAGCCGGGG


 


3991
CCCGGCTGCCTCCCCCAGG
CCTGGGGGAGGCAGCCGGG


 


3992
CCGGCTGCCTCCCCCAGGG
CCCTGGGGGAGGCAGCCGG


 


3993
CGGCTGCCTCCCCCAGGGG
CCCCTGGGGGAGGCAGCCG


 


3994
GGCTGCCTCCCCCAGGGGC
GCCCCTGGGGGAGGCAGCC


 


3995
GCTGCCTCCCCCAGGGGCT
AGCCCCTGGGGGAGGCAGC


 


3996
CTGCCTCCCCCAGGGGCTT
AAGCCCCTGGGGGAGGCAG


 


3997
TGCCTCCCCCAGGGGCTTT
AAAGCCCCTGGGGGAGGCA


 


3998
GCCTCCCCCAGGGGCTTTG
CAAAGCCCCTGGGGGAGGC


 


3999
CCTCCCCCAGGGGCTTTGC
GCAAAGCCCCTGGGGGAGG


 


4000
CTCCCCCAGGGGCTTTGCT
AGCAAAGCCCCTGGGGGAG


 


4001
TCCCCCAGGGGCTTTGCTG
CAGCAAAGCCCCTGGGGGA


 


4002
CCCCCAGGGGCTTTGCTGT
ACAGCAAAGCCCCTGGGGG


 


4003
CCCCAGGGGCTTTGCTGTG
CACAGCAAAGCCCCTGGGG


 


4004
CCCAGGGGCTTTGCTGTGG
CCACAGCAAAGCCCCTGGG


 


4005
CCAGGGGCTTTGCTGTGGC
GCCACAGCAAAGCCCCTGG


 


4006
CAGGGGCTTTGCTGTGGCT
AGCCACAGCAAAGCCCCTG


 


4007
AGGGGCTTTGCTGTGGCTG
CAGCCACAGCAAAGCCCCT


 


4008
GGGGCTTTGCTGTGGCTGC
GCAGCCACAGCAAAGCCCC


 


4009
GGGCTTTGCTGTGGCTGCA
TGCAGCCACAGCAAAGCCC


 


4010
GGCTTTGCTGTGGCTGCAG
CTGCAGCCACAGCAAAGCC


 


4011
GCTTTGCTGTGGCTGCAGG
CCTGCAGCCACAGCAAAGC


 


4012
CTTTGCTGTGGCTGCAGGA
TCCTGCAGCCACAGCAAAG


 


4013
TTTGCTGTGGCTGCAGGAG
CTCCTGCAGCCACAGCAAA


 


4014
TTGCTGTGGCTGCAGGAGC
GCTCCTGCAGCCACAGCAA


 


4015
TGCTGTGGCTGCAGGAGCC
GGCTCCTGCAGCCACAGCA


 


4016
GCTGTGGCTGCAGGAGCCC
GGGCTCCTGCAGCCACAGC


 


4017
CTGTGGCTGCAGGAGCCCC
GGGGCTCCTGCAGCCACAG


 


4018
TGTGGCTGCAGGAGCCCCA
TGGGGCTCCTGCAGCCACA


 


4019
GTGGCTGCAGGAGCCCCAG
CTGGGGCTCCTGCAGCCAC


 


4020
TGGCTGCAGGAGCCCCAGC
GCTGGGGCTCCTGCAGCCA


 


4021
GGCTGCAGGAGCCCCAGCC
GGCTGGGGCTCCTGCAGCC


 


4022
GCTGCAGGAGCCCCAGCCT
AGGCTGGGGCTCCTGCAGC


 


4023
CTGCAGGAGCCCCAGCCTT
AAGGCTGGGGCTCCTGCAG


 


4024
TGCAGGAGCCCCAGCCTTG
CAAGGCTGGGGCTCCTGCA


 


4025
GCAGGAGCCCCAGCCTTGC
GCAAGGCTGGGGCTCCTGC


 


4026
CAGGAGCCCCAGCCTTGCC
GGCAAGGCTGGGGCTCCTG


 


4027
AGGAGCCCCAGCCTTGCCC
GGGCAAGGCTGGGGCTCCT


 


4028
GGAGCCCCAGCCTTGCCCT
AGGGCAAGGCTGGGGCTCC


 


4029
GAGCCCCAGCCTTGCCCTC
GAGGGCAAGGCTGGGGCTC


 


4030
AGCCCCAGCCTTGCCCTCG
CGAGGGCAAGGCTGGGGCT


 


4031
GCCCCAGCCTTGCCCTCGG
CCGAGGGCAAGGCTGGGGC


 


4032
CCCCAGCCTTGCCCTCGGC
GCCGAGGGCAAGGCTGGGG


 


4033
CCCAGCCTTGCCCTCGGCG
CGCCGAGGGCAAGGCTGGG


 


4034
CCAGCCTTGCCCTCGGCGT
ACGCCGAGGGCAAGGCTGG


 


4035
CAGCCTTGCCCTCGGCGTG
CACGCCGAGGGCAAGGCTG


 


4036
AGCCTTGCCCTCGGCGTGG
CCACGCCGAGGGCAAGGCT


 


4037
GCCTTGCCCTCGGCGTGGC
GCCACGCCGAGGGCAAGGC


 


4038
CCTTGCCCTCGGCGTGGCT
AGCCACGCCGAGGGCAAGG


 


4039
CTTGCCCTCGGCGTGGCTT
AAGCCACGCCGAGGGCAAG


 


4040
TTGCCCTCGGCGTGGCTTC
GAAGCCACGCCGAGGGCAA


 


4041
TGCCCTCGGCGTGGCTTCC
GGAAGCCACGCCGAGGGCA


 


4042
GCCCTCGGCGTGGCTTCCA
TGGAAGCCACGCCGAGGGC


 


4043
CCCTCGGCGTGGCTTCCAC
GTGGAAGCCACGCCGAGGG


 


4044
CCTCGGCGTGGCTTCCACC
GGTGGAAGCCACGCCGAGG


 


4045
CTCGGCGTGGCTTCCACCT
AGGTGGAAGCCACGCCGAG


 


4046
TCGGCGTGGCTTCCACCTC
GAGGTGGAAGCCACGCCGA


 


4047
CGGCGTGGCTTCCACCTCT
AGAGGTGGAAGCCACGCCG


 


4048
GGCGTGGCTTCCACCTCTT
AAGAGGTGGAAGCCACGCC


 


4049
GCGTGGCTTCCACCTCTTC
GAAGAGGTGGAAGCCACGC


 


4050
CGTGGCTTCCACCTCTTCC
GGAAGAGGTGGAAGCCACG


 


4051
GTGGCTTCCACCTCTTCCA
TGGAAGAGGTGGAAGCCAC


 


4052
TGGCTTCCACCTCTTCCAG
CTGGAAGAGGTGGAAGCCA


 


4053
GGCTTCCACCTCTTCCAGG
CCTGGAAGAGGTGGAAGCC


 


4054
GCTTCCACCTCTTCCAGGA
TCCTGGAAGAGGTGGAAGC


 


4055
CTTCCACCTCTTCCAGGAG
CTCCTGGAAGAGGTGGAAG


 


4056
TTCCACCTCTTCCAGGAGC
GCTCCTGGAAGAGGTGGAA


 


4057
TCCACCTCTTCCAGGAGCA
TGCTCCTGGAAGAGGTGGA


 


4058
CCACCTCTTCCAGGAGCAC
GTGCTCCTGGAAGAGGTGG


 


4059
CACCTCTTCCAGGAGCACT
AGTGCTCCTGGAAGAGGTG


 


4060
ACCTCTTCCAGGAGCACTG
CAGTGCTCCTGGAAGAGGT


 


4061
CCTCTTCCAGGAGCACTGG
CCAGTGCTCCTGGAAGAGG


 


4062
CTCTTCCAGGAGCACTGGA
TCCAGTGCTCCTGGAAGAG


 


4063
TCTTCCAGGAGCACTGGAG
CTCCAGTGCTCCTGGAAGA


 


4064
CTTCCAGGAGCACTGGAGG
CCTCCAGTGCTCCTGGAAG


 


4065
TTCCAGGAGCACTGGAGGC
GCCTCCAGTGCTCCTGGAA


 


4066
TCCAGGAGCACTGGAGGCA
TGCCTCCAGTGCTCCTGGA


 


4067
CCAGGAGCACTGGAGGCAG
CTGCCTCCAGTGCTCCTGG


 


4068
CAGGAGCACTGGAGGCAGG
CCTGCCTCCAGTGCTCCTG


 


4069
AGGAGCACTGGAGGCAGGG
CCCTGCCTCCAGTGCTCCT


 


4070
GGAGCACTGGAGGCAGGGC
GCCCTGCCTCCAGTGCTCC


 


4071
GAGCACTGGAGGCAGGGCC
GGCCCTGCCTCCAGTGCTC


 


4072
AGCACTGGAGGCAGGGCCA
TGGCCCTGCCTCCAGTGCT


 


4073
GCACTGGAGGCAGGGCCAG
CTGGCCCTGCCTCCAGTGC


 


4074
CACTGGAGGCAGGGCCAGC
GCTGGCCCTGCCTCCAGTG


 


4075
ACTGGAGGCAGGGCCAGCC
GGCTGGCCCTGCCTCCAGT


 


4076
CTGGAGGCAGGGCCAGCCT
AGGCTGGCCCTGCCTCCAG


 


4077
TGGAGGCAGGGCCAGCCTG
CAGGCTGGCCCTGCCTCCA


 


4078
GGAGGCAGGGCCAGCCTGT
ACAGGCTGGCCCTGCCTCC


 


4079
GAGGCAGGGCCAGCCTGTG
CACAGGCTGGCCCTGCCTC


 


4080
AGGCAGGGCCAGCCTGTGT
ACACAGGCTGGCCCTGCCT


 


4081
GGCAGGGCCAGCCTGTGTT
AACACAGGCTGGCCCTGCC


 


4082
GCAGGGCCAGCCTGTGTTG
CAACACAGGCTGGCCCTGC


 


4083
CAGGGCCAGCCTGTGTTGG
CCAACACAGGCTGGCCCTG


 


4084
AGGGCCAGCCTGTGTTGGT
ACCAACACAGGCTGGCCCT


 


4085
GGGCCAGCCTGTGTTGGTG
CACCAACACAGGCTGGCCC


 


4086
GGCCAGCCTGTGTTGGTGT
ACACCAACACAGGCTGGCC


 


4087
GCCAGCCTGTGTTGGTGTC
GACACCAACACAGGCTGGC


 


4088
CCAGCCTGTGTTGGTGTCA
TGACACCAACACAGGCTGG


 


4089
CAGCCTGTGTTGGTGTCAG
CTGACACCAACACAGGCTG


 


4090
AGCCTGTGTTGGTGTCAGG
CCTGACACCAACACAGGCT


 


4091
GCCTGTGTTGGTGTCAGGG
CCCTGACACCAACACAGGC


 


4092
CCTGTGTTGGTGTCAGGGA
TCCCTGACACCAACACAGG


 


4093
CTGTGTTGGTGTCAGGGAT
ATCCCTGACACCAACACAG


 


4094
TGTGTTGGTGTCAGGGATC
GATCCCTGACACCAACACA


 


4095
GTGTTGGTGTCAGGGATCC
GGATCCCTGACACCAACAC


 


4096
TGTTGGTGTCAGGGATCCA
TGGATCCCTGACACCAACA


 


4097
GTTGGTGTCAGGGATCCAA
TTGGATCCCTGACACCAAC


 


4098
TTGGTGTCAGGGATCCAAA
TTTGGATCCCTGACACCAA


 


4099
TGGTGTCAGGGATCCAAAG
CTTTGGATCCCTGACACCA


 


4100
GGTGTCAGGGATCCAAAGG
CCTTTGGATCCCTGACACC


 


4101
GTGTCAGGGATCCAAAGGA
TCCTTTGGATCCCTGACAC


 


4102
TGTCAGGGATCCAAAGGAC
GTCCTTTGGATCCCTGACA


 


4103
GTCAGGGATCCAAAGGACA
TGTCCTTTGGATCCCTGAC


 


4104
TCAGGGATCCAAAGGACAT
ATGTCCTTTGGATCCCTGA


 


4105
CAGGGATCCAAAGGACATT
AATGTCCTTTGGATCCCTG


 


4106
AGGGATCCAAAGGACATTG
CAATGTCCTTTGGATCCCT


 


4107
GGGATCCAAAGGACATTGC
GCAATGTCCTTTGGATCCC


 


4108
GGATCCAAAGGACATTGCA
TGCAATGTCCTTTGGATCC


 


4109
GATCCAAAGGACATTGCAG
CTGCAATGTCCTTTGGATC


 


4110
ATCCAAAGGACATTGCAGG
CCTGCAATGTCCTTTGGAT


 


4111
TCCAAAGGACATTGCAGGG
CCCTGCAATGTCCTTTGGA


 


4112
CCAAAGGACATTGCAGGGC
GCCCTGCAATGTCCTTTGG


 


4113
CAAAGGACATTGCAGGGCA
TGCCCTGCAATGTCCTTTG


 


4114
AAAGGACATTGCAGGGCAA
TTGCCCTGCAATGTCCTTT


 


4115
AAGGACATTGCAGGGCAAC
GTTGCCCTGCAATGTCCTT


 


4116
AGGACATTGCAGGGCAACC
GGTTGCCCTGCAATGTCCT


 


4117
GGACATTGCAGGGCAACCT
AGGTTGCCCTGCAATGTCC


 


4118
GACATTGCAGGGCAACCTG
CAGGTTGCCCTGCAATGTC


 


4119
ACATTGCAGGGCAACCTGT
ACAGGTTGCCCTGCAATGT


 


4120
CATTGCAGGGCAACCTGTG
CACAGGTTGCCCTGCAATG


 


4121
ATTGCAGGGCAACCTGTGG
CCACAGGTTGCCCTGCAAT


 


4122
TTGCAGGGCAACCTGTGGG
CCCACAGGTTGCCCTGCAA


 


4123
TGCAGGGCAACCTGTGGGG
CCCCACAGGTTGCCCTGCA


 


4124
GCAGGGCAACCTGTGGGGG
CCCCCACAGGTTGCCCTGC


 


4125
CAGGGCAACCTGTGGGGGA
TCCCCCACAGGTTGCCCTG


 


4126
AGGGCAACCTGTGGGGGAC
GTCCCCCACAGGTTGCCCT


 


4127
GGGCAACCTGTGGGGGACA
TGTCCCCCACAGGTTGCCC


 


4128
GGCAACCTGTGGGGGACAG
CTGTCCCCCACAGGTTGCC


 


4129
GCAACCTGTGGGGGACAGA
TCTGTCCCCCACAGGTTGC


 


4130
CAACCTGTGGGGGACAGAA
TTCTGTCCCCCACAGGTTG


 


4131
AACCTGTGGGGGACAGAAG
CTTCTGTCCCCCACAGGTT


 


4132
ACCTGTGGGGGACAGAAGC
GCTTCTGTCCCCCACAGGT


 


4133
CCTGTGGGGGACAGAAGCT
AGCTTCTGTCCCCCACAGG


 


4134
CTGTGGGGGACAGAAGCTC
GAGCTTCTGTCCCCCACAG


 


4135
TGTGGGGGACAGAAGCTCT
AGAGCTTCTGTCCCCCACA


 


4136
GTGGGGGACAGAAGCTCTT
AAGAGCTTCTGTCCCCCAC


 


4137
TGGGGGACAGAAGCTCTTG
CAAGAGCTTCTGTCCCCCA


 


4138
GGGGGACAGAAGCTCTTGG
CCAAGAGCTTCTGTCCCCC


 


4139
GGGGACAGAAGCTCTTGGG
CCCAAGAGCTTCTGTCCCC


 


4140
GGGACAGAAGCTCTTGGGG
CCCCAAGAGCTTCTGTCCC


 


4141
GGACAGAAGCTCTTGGGGC
GCCCCAAGAGCTTCTGTCC


 


4142
GACAGAAGCTCTTGGGGCA
TGCCCCAAGAGCTTCTGTC


 


4143
ACAGAAGCTCTTGGGGCAC
GTGCCCCAAGAGCTTCTGT


 


4144
CAGAAGCTCTTGGGGCACT
AGTGCCCCAAGAGCTTCTG


 


4145
AGAAGCTGTTGGGGCACTT
AAGTGCCCCAAGAGCTTCT


 


4146
GAAGCTCTTGGGGCACTTG
CAAGTGCCCCAAGAGCTTC


 


4147
AAGCTCTTGGGGCACTTGG
CCAAGTGCCCCAAGAGCTT


 


4148
AGCTCTTGGGGCACTTGGA
TCCAAGTGCCCCAAGAGCT


 


4149
GCTCTTGGGGCACTTGGAG
CTCCAAGTGCCCCAAGAGC


 


4150
CTCTTGGGGCACTTGGAGG
CCTCCAAGTGCCCCAAGAG


 


4151
TCTTGGGGCACTTGGAGGC
GCCTCCAAGTGCCCCAAGA


 


4152
CTTGGGGCACTTGGAGGCC
GGCCTCCAAGTGCCCCAAG


 


4153
TTGGGGCACTTGGAGGCCA
TGGCCTCCAAGTGCCCCAA


 


4154
TGGGGCACTTGGAGGCCAG
CTGGCCTCCAAGTGCCCCA


 


4155
GGGGCACTTGGAGGCCAGG
CCTGGCCTCCAAGTGCCCC


 


4156
GGGCACTTGGAGGCCAGGT
ACCTGGCCTCCAAGTGCCC


 


4157
GGCACTTGGAGGCCAGGTG
CACCTGGCCTCCAAGTGCC


 


4158
GCACTTGGAGGCCAGGTGC
GCACCTGGCCTCCAAGTGC


 


4159
CACTTGGAGGCCAGGTGCA
TGCACCTGGCCTCCAAGTG


 


4160
ACTTGGAGGCCAGGTGCAG
CTGCACCTGGCCTCCAAGT


 


4161
CTTGGAGGCCAGGTGCAGG
CCTGCACCTGGCCTCCAAG


 


4162
TTGGAGGCCAGGTGCAGGC
GCCTGCACCTGGCCTCCAA


 


4163
TGGAGGCCAGGTGCAGGCG
CGCCTGCACCTGGCCTCCA


 


4164
GGAGGCCAGGTGCAGGCGC
GCGCCTGCACCTGGCCTCC


 


4165
GAGGCCAGGTGCAGGCGCT
AGCGCCTGCACCTGGCCTC


 


4166
AGGCCAGGTGCAGGCGCTG
CAGCGCCTGCACCTGGCCT


 


4167
GGCCAGGTGCAGGCGCTGA
TCAGCGCCTGCACCTGGCC


 


4168
GCCAGGTGCAGGCGCTGAG
CTCAGCGCCTGCACCTGGC


 


4169
CCAGGTGCAGGCGCTGAGC
GCTCAGCGCCTGCACCTGG


 


4170
CAGGTGCAGGCGCTGAGCC
GGCTCAGCGCCTGCACCTG


 


4171
AGGTGCAGGCGCTGAGCCC
GGGCTCAGCGCCTGCACCT


 


4172
GGTGCAGGCGCTGAGCCCC
GGGGCTCAGCGCCTGCACC


 


4173
GTGCAGGCGCTGAGCCCCC
GGGGGCTCAGCGCCTGCAC


 


4174
TGCAGGCGCTGAGCCCCCT
AGGGGGCTCAGCGCCTGCA


 


4175
GCAGGCGCTGAGCCCCCTC
GAGGGGGCTCAGCGCCTGC


 


4176
CAGGCGCTGAGCCCCCTCG
CGAGGGGGCTCAGCGCCTG


 


4177
AGGCGCTGAGCCCCCTCGG
CCGAGGGGGCTCAGCGCCT


 


4178
GGCGCTGAGCCCCCTCGGA
TCCGAGGGGGCTCAGCGCC


 


4179
GCGCTGAGCCCCCTCGGAC
GTCCGAGGGGGCTCAGCGC


 


4180
CGCTGAGCCCCCTCGGACC
GGTCCGAGGGGGCTCAGCG


 


4181
GCTGAGCCCCCTCGGACCT
AGGTCCGAGGGGGCTCAGC


 


4182
CTGAGCCCCCTCGGACCTC
GAGGTCCGAGGGGGCTCAG


 


4183
TGAGCCCCCTCGGACCTCC
GGAGGTCCGAGGGGGCTCA


 


4184
GAGCCCCCTCGGACCTCCC
GGGAGGTCCGAGGGGGCTC


 


4185
AGCCCCCTCGGACCTCCCC
GGGGAGGTCCGAGGGGGCT


 


4186
GCCCCCTCGGACCTCCCCA
TGGGGAGGTCCGAGGGGGC


 


4187
CCCCCTCGGACCTCCCCAG
CTGGGGAGGTCCGAGGGGG


 


4188
CCCCTCGGACCTCCCCAGC
GCTGGGGAGGTCCGAGGGG


 


4189
CCCTCGGACCTCCCCAGCC
GGCTGGGGAGGTCCGAGGG


 


4190
CCTCGGACCTCCCCAGCCC
GGGCTGGGGAGGTCCGAGG


 


4191
CTCGGACCTCCCCAGCCCA
TGGGCTGGGGAGGTCCGAG


 


4192
TCGGACCTCCCCAGCCCAG
CTGGGCTGGGGAGGTCCGA


 


4193
CGGACCTCCCCAGCCCAGC
GCTGGGCTGGGGAGGTCCG


 


4194
GGACCTCCCCAGCCCAGCA
TGCTGGGCTGGGGAGGTCC


 


4195
GACCTCCCCAGCCCAGCAG
CTGCTGGGCTGGGGAGGTC


 


4196
ACCTCCCCAGCCCAGCAGC
GCTGCTGGGCTGGGGAGGT


 


4197
CCTCCCCAGCCCAGCAGCC
GGCTGCTGGGCTGGGGAGG


 


4198
CTCCCCAGCCCAGCAGCCT
AGGCTGCTGGGCTGGGGAG


 


4199
TCCCCAGCCCAGCAGCCTG
CAGGCTGCTGGGCTGGGGA


 


4200
CCCCAGCCCAGCAGCCTGG
CCAGGCTGCTGGGCTGGGG


 


4201
CCCAGCCCAGCAGCCTGGG
CCCAGGCTGCTGGGCTGGG


 


4202
CCAGCCCAGCAGCCTGGGC
GCCCAGGCTGCTGGGCTGG


 


4203
CAGCCCAGCAGCCTGGGCA
TGCCCAGGCTGCTGGGCTG


 


4204
AGCCCAGCAGCCTGGGCAG
CTGCCCAGGCTGCTGGGCT


 


4205
GCCCAGCAGCCTGGGCAGC
GCTGCCCAGGCTGCTGGGC


 


4206
CCCAGCAGCCTGGGCAGCA
TGCTGCCCAGGCTGCTGGG


 


4207
CCAGCAGCCTGGGCAGCAC
GTGCTGCCCAGGCTGCTGG


 


4208
CAGCAGCCTGGGCAGCACA
TGTGCTGCCCAGGCTGCTG


 


4209
AGCAGCCTGGGCAGCACAA
TTGTGCTGCCCAGGCTGCT


 


4210
GCAGCCTGGGCAGCACAAC
GTTGTGCTGCCCAGGCTGC


 


4211
CAGCCTGGGCAGCACAACA
TGTTGTGCTGCCCAGGCTG


 


4212
AGCCTGGGCAGCACAACAT
ATGTTGTGCTGCCCAGGCT


 


4213
GCCTGGGCAGCACAACATT
AATGTTGTGCTGCCCAGGC


 


4214
CCTGGGCAGCACAACATTC
GAATGTTGTGCTGCCCAGG


 


4215
CTGGGCAGCACAACATTCT
AGAATGTTGTGCTGCCCAG


 


4216
TGGGCAGCACAACATTCTG
CAGAATGTTGTGCTGCCCA


 


4217
GGGCAGCACAACATTCTGG
CCAGAATGTTGTGCTGCCC


 


4218
GGCAGCACAACATTCTGGG
CCCAGAATGTTGTGCTGCC


 


4219
GCAGCACAACATTCTGGGA
TCCCAGAATGTTGTGCTGC


 


4220
CAGCACAACATTCTGGGAG
CTCCCAGAATGTTGTGCTG


 


4221
AGCACAACATTCTGGGAGG
CCTCCCAGAATGTTGTGCT


 


4222
GCACAACATTCTGGGAGGG
CCCTCCCAGAATGTTGTGC


 


4223
CACAACATTCTGGGAGGGC
GCCCTCCCAGAATGTTGTG


 


4224
ACAACATTCTGGGAGGGCT
AGCCCTCCCAGAATGTTGT


 


4225
CAACATTCTGGGAGGGCTT
AAGCCCTCCCAGAATGTTG


 


4226
AACATTCTGGGAGGGCTTC
GAAGCCCTCCCAGAATGTT


 


4227
ACATTCTGGGAGGGCTTCT
AGAAGCCCTCCCAGAATGT


 


4228
CATTCTGGGAGGGCTTCTC
GAGAAGCCCTCCCAGAATG


 


4229
ATTCTGGGAGGGCTTCTCC
GGAGAAGCCCTCCCAGAAT


 


4230
TTCTGGGAGGGCTTCTCCT
AGGAGAAGCCCTCCCAGAA


 


4231
TCTGGGAGGGCTTCTCCTG
CAGGAGAAGCCCTCCCAGA


 


4232
CTGGGAGGGCTTCTCCTGG
CCAGGAGAAGCCCTCCCAG


 


4233
TGGGAGGGCTTCTCCTGGC
GCCAGGAGAAGCCCTCCCA


 


4234
GGGAGGGCTTCTCCTGGCC
GGCCAGGAGAAGCCCTCCC


 


4235
GGAGGGCTTCTCCTGGCCT
AGGCCAGGAGAAGCCCTCC


 


4236
GAGGGCTTCTCCTGGCCTG
CAGGCCAGGAGAAGCCCTC


 


4237
AGGGCTTCTCCTGGCCTGA
TCAGGCCAGGAGAAGCCCT


 


4238
GGGCTTCTCCTGGCCTGAG
CTCAGGCCAGGAGAAGCCC


 


4239
GGCTTCTCCTGGCCTGAGC
GCTCAGGCCAGGAGAAGCC


 


4240
GCTTCTCCTGGCCTGAGCT
AGCTCAGGCCAGGAGAAGC


 


4241
CTTCTCCTGGCCTGAGCTT
AAGCTCAGGCCAGGAGAAG


 


4242
TTCTCCTGGCCTGAGCTTC
GAAGCTCAGGCCAGGAGAA


 


4243
TCTCCTGGCCTGAGCTTCG
CGAAGCTCAGGCCAGGAGA


 


4244
CTCCTGGCCTGAGCTTCGC
GCGAAGCTCAGGCCAGGAG


 


4245
TCCTGGCCTGAGCTTCGCC
GGCGAAGCTCAGGCCAGGA


 


4246
CCTGGCCTGAGCTTCGCCC
GGGCGAAGCTCAGGCCAGG


 


4247
CTGGCCTGAGCTTCGCCCA
TGGGCGAAGCTCAGGCCAG


 


4248
TGGCCTGAGCTTCGCCCAA
TTGGGCGAAGCTCAGGCCA


 


4249
GGCCTGAGCTTCGCCCAAA
TTTGGGCGAAGCTCAGGCC


 


4250
GCCTGAGCTTCGCCCAAAG
CTTTGGGCGAAGCTCAGGC


 


4251
CCTGAGCTTCGCCCAAAGT
ACTTTGGGCGAAGCTCAGG


 


4252
CTGAGCTTCGCCCAAAGTC
GACTTTGGGCGAAGCTCAG


 


4253
TGAGCTTCGCCCAAAGTCA
TGACTTTGGGCGAAGCTCA


 


4254
GAGCTTCGCCCAAAGTCAG
CTGACTTTGGGCGAAGCTC


 


4255
AGCTTCGCCCAAAGTCAGA
TCTGACTTTGGGCGAAGCT


 


4256
GCTTCGCCCAAAGTCAGAC
GTCTGACTTTGGGCGAAGC


 


4257
CTTCGCCCAAAGTCAGACG
CGTCTGACTTTGGGCGAAG


 


4258
TTCGCCCAAAGTCAGACGA
TCGTCTGACTTTGGGCGAA


 


4259
TCGCCCAAAGTCAGACGAG
CTCGTCTGACTTTGGGCGA


 


4260
CGCCCAAAGTCAGACGAGG
CCTCGTCTGACTTTGGGCG


 


4261
GCCCAAAGTCAGACGAGGG
CCCTCGTCTGACTTTGGGC


 


4262
CCCAAAGTCAGACGAGGGC
GCCCTCGTCTGACTTTGGG


 


4263
CCAAAGTCAGACGAGGGCT
AGCCCTCGTCTGACTTTGG


 


4264
CAAAGTCAGACGAGGGCTC
GAGCCCTCGTCTGACTTTG


 


4265
AAAGTCAGACGAGGGCTCT
AGAGCCCTCGTCTGACTTT


 


4266
AAGTCAGACGAGGGCTCTG
CAGAGCCCTCGTCTGACTT


 


4267
AGTCAGACGAGGGCTCTGT
ACAGAGCCCTCGTCTGACT


 


4268
GTCAGACGAGGGCTCTGTC
GACAGAGCCCTCGTCTGAC


 


4269
TCAGACGAGGGCTCTGTCC
GGACAGAGCCCTCGTCTGA


 


4270
CAGACGAGGGCTCTGTCCT
AGGACAGAGCCCTCGTCTG


 


4271
AGACGAGGGCTCTGTCCTC
GAGGACAGAGCCCTCGTCT


 


4272
GACGAGGGCTCTGTCCTCC
GGAGGACAGAGCCCTCGTC


 


4273
ACGAGGGCTCTGTCCTCCT
AGGAGGACAGAGCCCTCGT


 


4274
CGAGGGCTCTGTCCTCCTG
CAGGAGGACAGAGCCCTCG


 


4275
GAGGGCTCTGTCCTCCTGC
GCAGGAGGACAGAGCCCTC


 


4276
AGGGCTCTGTCCTCCTGCT
AGCAGGAGGACAGAGCCCT


 


4277
GGGCTCTGTCCTCCTGCTG
CAGCAGGAGGACAGAGCCC


 


4278
GGCTCTGTCCTCCTGCTGC
GCAGCAGGAGGACAGAGCC


 


4279
GCTCTGTCCTCCTGCTGCA
TGCAGCAGGAGGACAGAGC


 


4280
CTCTGTCCTCCTGCTGCAC
GTGCAGCAGGAGGACAGAG


 


4281
TCTGTCCTCCTGCTGCACC
GGTGCAGCAGGAGGACAGA


 


4282
CTGTCCTCCTGCTGCACCG
CGGTGCAGCAGGAGGACAG


 


4283
TGTCCTCCTGCTGCACCGA
TCGGTGCAGCAGGAGGACA


 


4284
GTCCTCCTGCTGCACCGAG
CTCGGTGCAGCAGGAGGAC


 


4285
TCCTCCTGCTGCACCGAGC
GCTCGGTGCAGCAGGAGGA


 


4286
CCTCCTGCTGCACCGAGCT
AGCTCGGTGCAGCAGGAGG


 


4287
CTCCTGCTGCACCGAGCTT
AAGCTCGGTGCAGCAGGAG


 


4288
TCCTGCTGCACCGAGCTTT
AAAGCTCGGTGCAGCAGGA


 


4289
CCTGCTGCACCGAGCTTTG
CAAAGCTCGGTGCAGCAGG


 


4290
CTGCTGCACCGAGCTTTGG
CCAAAGCTCGGTGCAGCAG


 


4291
TGCTGCACCGAGCTTTGGG
CCCAAAGCTCGGTGCAGCA


 


4292
GCTGCACCGAGCTTTGGGG
CCCCAAAGCTCGGTGCAGC


 


4293
CTGCACCGAGCTTTGGGGG
CCCCCAAAGCTCGGTGCAG


 


4294
TGCACCGAGCTTTGGGGGA
TCCCCCAAAGCTCGGTGCA


 


4295
GCACCGAGCTTTGGGGGAT
ATCCCCCAAAGCTCGGTGC


 


4296
CACCGAGCTTTGGGGGATG
CATCCCCCAAAGCTCGGTG


 


4297
ACCGAGCTTTGGGGGATGA
TCATCCCCCAAAGCTCGGT


 


4298
CCGAGCTTTGGGGGATGAG
CTCATCCCCCAAAGCTCGG


 


4299
CGAGCTTTGGGGGATGAGG
CCTCATCCCCCAAAGCTCG


 


4300
GAGCTTTGGGGGATGAGGA
TCCTCATCCCCCAAAGCTC


 


4301
AGCTTTGGGGGATGAGGAC
GTCCTCATCCCCCAAAGCT


 


4302
GCTTTGGGGGATGAGGACA
TGTCCTCATCCCCCAAAGC


 


4303
CTTTGGGGGATGAGGACAC
GTGTCCTCATCCCCCAAAG


 


4304
TTTGGGGGATGAGGACACC
GGTGTCCTCATCCCCCAAA


 


4305
TTGGGGGATGAGGACACCA
TGGTGTCCTCATCCCCCAA


 


4306
TGGGGGATGAGGACACCAG
CTGGTGTCCTCATCCCCCA


 


4307
GGGGGATGAGGACACCAGC
GCTGGTGTCCTCATCCCCC


 


4308
GGGGATGAGGACACCAGCA
TGCTGGTGTCCTCATCCCC


 


4309
GGGATGAGGACACCAGCAG
CTGCTGGTGTCCTCATCCC


 


4310
GGATGAGGACACCAGCAGG
CCTGCTGGTGTCCTCATCC


 


4311
GATGAGGACACCAGCAGGG
CCCTGCTGGTGTCCTCATC


 


4312
ATGAGGACACCAGCAGGGT
ACCCTGCTGGTGTCCTCAT


 


4313
TGAGGACACCAGCAGGGTG
CACCCTGCTGGTGTCCTCA


 


4314
GAGGACACCAGCAGGGTGG
CCACCCTGCTGGTGTCCTC


 


4315
AGGACACCAGCAGGGTGGA
TCCACCCTGCTGGTGTCCT


 


4316
GGACACCAGCAGGGTGGAG
CTCCACCCTGCTGGTGTCC


 


4317
GACACCAGCAGGGTGGAGA
TCTCCACCCTGCTGGTGTC


 


4318
ACACCAGCAGGGTGGAGAA
TTCTCCACCCTGCTGGTGT


 


4319
CACCAGCAGGGTGGAGAAC
GTTCTCCACCCTGCTGGTG


 


4320
ACCAGCAGGGTGGAGAACC
GGTTCTCCACCCTGCTGGT


 


4321
CCAGCAGGGTGGAGAACCT
AGGTTCTCCACCCTGCTGG


 


4322
CAGCAGGGTGGAGAACCTA
TAGGTTCTCCACCCTGCTG


 


4323
AGCAGGGTGGAGAACCTAG
CTAGGTTCTCCACCCTGCT


 


4324
GCAGGGTGGAGAACCTAGC
GCTAGGTTCTCCACCCTGC


 


4325
CAGGGTGGAGAACCTAGCT
AGCTAGGTTCTCCACCCTG


 


4326
AGGGTGGAGAACCTAGCTG
CAGCTAGGTTCTCCACCCT


 


4327
GGGTGGAGAACCTAGCTGC
GCAGCTAGGTTCTCCACCC


 


4328
GGTGGAGAACCTAGCTGCC
GGCAGCTAGGTTCTCCACC


 


4329
GTGGAGAACCTAGCTGCCA
TGGCAGCTAGGTTCTCCAC


 


4330
TGGAGAACCTAGCTGCCAG
CTGGCAGCTAGGTTCTCCA


 


4331
GGAGAACCTAGCTGCCAGT
ACTGGCAGCTAGGTTCTCC


 


4332
GAGAACCTAGCTGCCAGTC
GACTGGCAGCTAGGTTCTC


 


4333
AGAACCTAGCTGCCAGTCT
AGACTGGCAGCTAGGTTCT


 


4334
GAACCTAGCTGCCAGTCTG
CAGACTGGCAGCTAGGTTC


 


4335
AACCTAGCTGCCAGTCTGC
GCAGACTGGCAGCTAGGTT


 


4336
ACCTAGCTGCCAGTCTGCC
GGCAGACTGGCAGCTAGGT


 


4337
CCTAGCTGCCAGTCTGCCA
TGGCAGACTGGCAGCTAGG


 


4338
CTAGCTGCCAGTCTGCCAC
GTGGCAGACTGGCAGCTAG


 


4339
TAGCTGCCAGTCTGCCACT
AGTGGCAGACTGGCAGCTA


 


4340
AGCTGCCAGTCTGCCACTT
AAGTGGCAGACTGGCAGCT


 


4341
GCTGCCAGTCTGCCACTTC
GAAGTGGCAGACTGGCAGC


 


4342
CTGCCAGTCTGCCACTTCC
GGAAGTGGCAGACTGGCAG


 


4343
TGCCAGTCTGCCACTTCCG
CGGAAGTGGCAGACTGGCA


 


4344
GCCAGTCTGCCACTTCCGG
CCGGAAGTGGCAGACTGGC


 


4345
CCAGTCTGCCACTTCCGGA
TCCGGAAGTGGCAGACTGG


 


4346
CAGTCTGCCACTTCCGGAG
CTCCGGAAGTGGCAGACTG


 


4347
AGTCTGCCACTTCCGGAGT
ACTCCGGAAGTGGCAGACT


 


4348
GTCTGCCACTTCCGGAGTA
TACTCCGGAAGTGGCAGAC


 


4349
TCTGCCACTTCCGGAGTAC
GTACTCCGGAAGTGGCAGA


 


4350
CTGCCACTTCCGGAGTACT
AGTACTCCGGAAGTGGCAG


 


4351
TGCCACTTCCGGAGTACTG
CAGTACTCCGGAAGTGGCA


 


4352
GCCACTTCCGGAGTACTGC
GCAGTACTCCGGAAGTGGC


 


4353
CCACTTCCGGAGTACTGCG
CGCAGTACTCCGGAAGTGG


 


4354
CACTTCCGGAGTACTGCGC
GCGCAGTACTCCGGAAGTG


 


4355
ACTTCCGGAGTACTGCGCC
GGCGCAGTACTCCGGAAGT


 


4356
CTTCCGGAGTACTGCGCCC
GGGCGCAGTACTCCGGAAG


 


4357
TTCCGGAGTACTGCGCCCT
AGGGCGCAGTACTCCGGAA


 


4358
TCCGGAGTACTGCGCCCTC
GAGGGCGCAGTACTCCGGA


 


4359
CCGGAGTACTGCGCCCTCC
GGAGGGCGCAGTACTCCGG


 


4360
CGGAGTACTGCGCCCTCCA
TGGAGGGCGCAGTACTCCG


 


4361
GGAGTACTGCGCCCTCCAT
ATGGAGGGCGCAGTACTCC


 


4362
GAGTACTGCGCCCTCCATG
CATGGAGGGCGCAGTACTC


 


4363
AGTACTGCGCCCTCCATGG
CCATGGAGGGCGCAGTACT


 


4364
GTACTGCGCCCTCCATGGA
TCCATGGAGGGCGCAGTAC


 


4365
TACTGCGCCCTCCATGGAA
TTCCATGGAGGGCGCAGTA


 


4366
ACTGCGCCCTCCATGGAAA
TTTCCATGGAGGGCGCAGT


 


4367
CTGCGCCCTCCATGGAAAA
TTTTCCATGGAGGGCGCAG


 


4368
TGCGCCCTCCATGGAAAAC
GTTTTCCATGGAGGGCGCA


 


4369
GCGCCCTCCATGGAAAACT
AGTTTTCCATGGAGGGCGC


 


4370
CGCCCTCCATGGAAAACTC
GAGTTTTCCATGGAGGGCG


 


4371
GCCCTCCATGGAAAACTCA
TGAGTTTTCCATGGAGGGC


 


4372
CCCTCCATGGAAAACTCAA
TTGAGTTTTCCATGGAGGG


 


4373
CCTCCATGGAAAACTCAAC
GTTGAGTTTTCCATGGAGG


 


4374
CTCCATGGAAAACTCAACC
GGTTGAGTTTTCCATGGAG


 


4375
TCCATGGAAAACTCAACCT
AGGTTGAGTTTTCCATGGA


 


4376
CCATGGAAAACTCAACCTG
CAGGTTGAGTTTTCCATGG


 


4377
CATGGAAAACTCAACCTGG
CCAGGTTGAGTTTTCCATG


 


4378
ATGGAAAACTCAACCTGGC
GCCAGGTTGAGTTTTCCAT


 


4379
TGGAAAACTCAACCTGGCT
AGCCAGGTTGAGTTTTCCA


 


4380
GGAAAACTCAACCTGGCTT
AAGCCAGGTTGAGTTTTCC


 


4381
GAAAACTCAACCTGGCTTC
GAAGCCAGGTTGAGTTTTC


 


4382
AAAACTCAACCTGGCTTCC
GGAAGCCAGGTTGAGTTTT


 


4383
AAACTCAACCTGGCTTCCT
AGGAAGCCAGGTTGAGTTT


 


4384
AACTCAACCTGGCTTCCTA
TAGGAAGCCAGGTTGAGTT


 


4385
ACTCAACCTGGCTTCCTAC
GTAGGAAGCCAGGTTGAGT


 


4386
CTCAACCTGGCTTCCTACC
GGTAGGAAGCCAGGTTGAG


 


4387
TCAACCTGGCTTCCTACCT
AGGTAGGAAGCCAGGTTGA


 


4388
CAACCTGGCTTCCTACCTC
GAGGTAGGAAGCCAGGTTG


 


4389
AACCTGGCTTCCTACCTCC
GGAGGTAGGAAGCCAGGTT


 


4390
ACCTGGCTTCCTACCTCCC
GGGAGGTAGGAAGCCAGGT


 


4391
CCTGGCTTCCTACCTCCCA
TGGGAGGTAGGAAGCCAGG


 


4392
CTGGCTTCCTACCTCCCAC
GTGGGAGGTAGGAAGCCAG


 


4393
TGGCTTCCTACCTCCCACC
GGTGGGAGGTAGGAAGCCA


 


4394
GGCTTCCTACCTCCCACCG
CGGTGGGAGGTAGGAAGCC


 


4395
GCTTCCTACCTCCCACCGG
CCGGTGGGAGGTAGGAAGC


 


4396
CTTCCTACCTCCCACCGGG
CCCGGTGGGAGGTAGGAAG


 


4397
TTCCTACCTCCCACCGGGC
GCCCGGTGGGAGGTAGGAA


 


4398
TCCTACCTCCCACCGGGCC
GGCCCGGTGGGAGGTAGGA


 


4399
CCTACCTCCCACCGGGCCT
AGGCCCGGTGGGAGGTAGG


 


4400
CTACCTCCCACCGGGCCTT
AAGGCCCGGTGGGAGGTAG


 


4401
TACCTCCCACCGGGCCTTG
CAAGGCCCGGTGGGAGGTA


 


4402
ACCTCCCACCGGGCCTTGC
GCAAGGCCCGGTGGGAGGT


 


4403
CCTCCCACCGGGCCTTGCC
GGCAAGGCCCGGTGGGAGG


 


4404
CTCCCACCGGGCCTTGCCC
GGGCAAGGCCCGGTGGGAG


 


4405
TCCCACCGGGCCTTGCCCT
AGGGCAAGGCCCGGTGGGA


 


4406
CCCACCGGGCCTTGCCCTG
CAGGGCAAGGCCCGGTGGG


 


4407
CCACCGGGCCTTGCCCTGC
GCAGGGCAAGGCCCGGTGG


 


4408
CACCGGGCCTTGCCCTGCG
CGCAGGGCAAGGCCCGGTG


 


4409
ACCGGGCCTTGCCCTGCGT
ACGCAGGGCAAGGCCCGGT


 


4410
CCGGGCCTTGCCCTGCGTC
GACGCAGGGCAAGGCCCGG


 


4411
CGGGCCTTGCCCTGCGTCC
GGACGCAGGGCAAGGCCCG


 


4412
GGGCCTTGCCCTGCGTCCA
TGGACGCAGGGCAAGGCCC


 


4413
GGCCTTGCCCTGCGTCCAC
GTGGACGCAGGGCAAGGCC


 


4414
GCCTTGCCCTGCGTCCACT
AGTGGACGCAGGGCAAGGC


 


4415
CCTTGCCCTGCGTCCACTG
CAGTGGACGCAGGGCAAGG


 


4416
CTTGCCCTGCGTCCACTGG
CCAGTGGACGCAGGGCAAG


 


4417
TTGCCCTGCGTCCACTGGA
TCCAGTGGACGCAGGGCAA


 


4418
TGCCCTGCGTCCACTGGAG
CTCCAGTGGACGCAGGGCA


 


4419
GCCCTGCGTCCACTGGAGC
GCTCCAGTGGACGCAGGGC


 


4420
CCCTGCGTCCACTGGAGCC
GGCTCCAGTGGACGCAGGG


 


4421
CCTGCGTCCACTGGAGCCC
GGGCTCCAGTGGACGCAGG


 


4422
CTGCGTCCACTGGAGCCCC
GGGGCTCCAGTGGACGCAG


 


4423
TGCGTCCACTGGAGCCCCA
TGGGGCTCCAGTGGACGCA


 


4424
GCGTCCACTGGAGCCCCAG
CTGGGGCTCCAGTGGACGC


 


4425
CGTCCACTGGAGCCCCAGC
GCTGGGGCTCCAGTGGACG


 


4426
GTCCACTGGAGCCCCAGCT
AGCTGGGGCTCCAGTGGAC


 


4427
TCCACTGGAGCCCCAGCTC
GAGCTGGGGCTCCAGTGGA


 


4428
CCACTGGAGCCCCAGCTCT
AGAGCTGGGGCTCCAGTGG


 


4429
CACTGGAGCCCCAGCTCTG
CAGAGCTGGGGCTCCAGTG


 


4430
ACTGGAGCCCCAGCTCTGG
CCAGAGCTGGGGCTCCAGT


 


4431
CTGGAGCCCCAGCTCTGGG
CCCAGAGCTGGGGCTCCAG


 


4432
TGGAGCCCCAGCTCTGGGC
GCCCAGAGCTGGGGCTCCA


 


4433
GGAGCCCCAGCTCTGGGCA
TGCCCAGAGCTGGGGCTCC


 


4434
GAGCCCCAGCTCTGGGCAG
CTGCCCAGAGCTGGGGCTC


 


4435
AGCCCCAGCTCTGGGCAGC
GCTGCCCAGAGCTGGGGCT


 


4436
GCCCCAGCTCTGGGCAGCC
GGCTGCCCAGAGCTGGGGC


 


4437
CCCCAGCTCTGGGCAGCCT
AGGCTGCCCAGAGCTGGGG


 


4438
CCCAGCTCTGGGCAGCCTA
TAGGCTGCCCAGAGCTGGG


 


4439
CCAGCTCTGGGCAGCCTAT
ATAGGCTGCCCAGAGCTGG


 


4440
CAGCTCTGGGCAGCCTATG
CATAGGCTGCCCAGAGCTG


 


4441
AGCTCTGGGCAGCCTATGG
CCATAGGCTGCCCAGAGCT


 


4442
GCTCTGGGCAGCCTATGGT
ACCATAGGCTGCCCAGAGC


 


4443
CTCTGGGCAGCCTATGGTG
CACCATAGGCTGCCCAGAG


 


4444
TCTGGGCAGCCTATGGTGT
ACACCATAGGCTGCCCAGA


 


4445
CTGGGCAGCCTATGGTGTG
CACACCATAGGCTGCCCAG


 


4446
TGGGCAGCCTATGGTGTGA
TCACACCATAGGCTGCCCA


 


4447
GGGCAGCCTATGGTGTGAG
CTCACACCATAGGCTGCCC


 


4448
GGCAGCCTATGGTGTGAGC
GCTCACACCATAGGCTGCC


 


4449
GCAGCCTATGGTGTGAGCC
GGCTCACACCATAGGCTGC


 


4450
CAGCCTATGGTGTGAGCCC
GGGCTCACACCATAGGCTG


 


4451
AGCCTATGGTGTGAGCCCG
CGGGCTCACACCATAGGCT


 


4452
GCCTATGGTGTGAGCCCGC
GCGGGCTCACACCATAGGC


 


4453
CCTATGGTGTGAGCCCGCA
TGCGGGCTCACACCATAGG


 


4454
CTATGGTGTGAGCCCGCAC
GTGCGGGCTCACACCATAG


 


4455
TATGGTGTGAGCCCGCACC
GGTGCGGGCTCACACCATA


 


4456
ATGGTGTGAGCCCGCACCG
CGGTGCGGGCTCACACCAT


 


4457
TGGTGTGAGCCCGCACCGG
CCGGTGCGGGCTCACACCA


 


4458
GGTGTGAGCCCGCACCGGG
CCCGGTGCGGGCTCACACC


 


4459
GTGTGAGCCCGCACCGGGG
CCCCGGTGCGGGCTCACAC


 


4460
TGTGAGCCCGCACCGGGGA
TCCCCGGTGCGGGCTCACA


 


4461
GTGAGCCCGCACCGGGGAC
GTCCCCGGTGCGGGCTCAC


 


4462
TGAGCCCGCACCGGGGACA
TGTCCCCGGTGCGGGCTCA


 


4463
GAGCCCGCACCGGGGACAC
GTGTCCCCGGTGCGGGCTC


 


4464
AGCCCGCACCGGGGACACC
GGTGTCCCCGGTGCGGGCT


 


4465
GCCCGCACCGGGGACACCT
AGGTGTCCCCGGTGCGGGC


 


4466
CCCGCACCGGGGACACCTG
CAGGTGTCCCCGGTGCGGG


 


4467
CCGCACCGGGGACACCTGG
CCAGGTGTCCCCGGTGCGG


 


4468
CGCACCGGGGACACCTGGG
CCCAGGTGTCCCCGGTGCG


 


4469
GCACCGGGGACACCTGGGG
CCCCAGGTGTCCCCGGTGC


 


4470
CACCGGGGACACCTGGGGA
TCCCCAGGTGTCCCCGGTG


 


4471
ACCGGGGACACCTGGGGAC
GTCCCCAGGTGTCCCCGGT


 


4472
CCGGGGACACCTGGGGACC
GGTCCCCAGGTGTCCCCGG


 


4473
CGGGGACACCTGGGGACCA
TGGTCCCCAGGTGTCCCCG


 


4474
GGGGACACCTGGGGACCAA
TTGGTCCCCAGGTGTCCCC


 


4475
GGGACACCTGGGGACCAAG
CTTGGTCCCCAGGTGTCCC


 


4476
GGACACCTGGGGACCAAGA
TCTTGGTCCCCAGGTGTCC


 


4477
GACACCTGGGGACCAAGAA
TTCTTGGTCCCCAGGTGTC


 


4478
ACACCTGGGGACCAAGAAC
GTTCTTGGTCCCCAGGTGT


 


4479
CACCTGGGGACCAAGAACC
GGTTCTTGGTCCCCAGGTG


 


4480
ACCTGGGGACCAAGAACCT
AGGTTCTTGGTCCCCAGGT


 


4481
CCTGGGGACCAAGAACCTC
GAGGTTCTTGGTCCCCAGG


 


4482
CTGGGGACCAAGAACCTCT
AGAGGTTCTTGGTCCCCAG


 


4483
TGGGGACCAAGAACCTCTG
CAGAGGTTCTTGGTCCCCA


 


4484
GGGGACCAAGAACCTCTGT
ACAGAGGTTCTTGGTCCCC


 


4485
GGGACCAAGAACCTCTGTG
CACAGAGGTTCTTGGTCCC


 


4486
GGACCAAGAACCTCTGTGT
ACACAGAGGTTCTTGGTCC


 


4487
GACCAAGAACCTCTGTGTG
CACACAGAGGTTCTTGGTC


 


4488
ACCAAGAACCTCTGTGTGG
CCACACAGAGGTTCTTGGT


 


4489
CCAAGAACCTCTGTGTGGA
TCCACACAGAGGTTCTTGG


 


4490
CAAGAACCTCTGTGTGGAG
CTCCACACAGAGGTTCTTG


 


4491
AAGAACCTCTGTGTGGAGG
CCTCCACACAGAGGTTCTT


 


4492
AGAACCTCTGTGTGGAGGT
ACCTCCACACAGAGGTTCT


 


4493
GAACCTCTGTGTGGAGGTG
CACCTCCACACAGAGGTTC


 


4494
AACCTCTGTGTGGAGGTGG
CCACCTCCACACAGAGGTT


 


4495
ACCTCTGTGTGGAGGTGGC
GCCACCTCCACACAGAGGT


 


4496
CCTCTGTGTGGAGGTGGCC
GGCCACCTCCACACAGAGG


 


4497
CTCTGTGTGGAGGTGGCCG
CGGCCACCTCCACACAGAG


 


4498
TCTGTGTGGAGGTGGCCGA
TCGGCCACCTCCACACAGA


 


4499
CTGTGTGGAGGTGGCCGAC
GTCGGCCACCTCCACACAG


 


4500
TGTGTGGAGGTGGCCGACC
GGTCGGCCACCTCCACACA


 


4501
GTGTGGAGGTGGCCGACCT
AGGTCGGCCACCTCCACAC


 


4502
TGTGGAGGTGGCCGACCTG
CAGGTCGGCCACCTCCACA


 


4503
GTGGAGGTGGCCGACCTGG
CCAGGTCGGCCACCTCCAC


 


4504
TGGAGGTGGCCGACCTGGT
ACCAGGTCGGCCACCTCCA


 


4505
GGAGGTGGCCGACCTGGTC
GACCAGGTCGGCCACCTCC


 


4506
GAGGTGGCCGACCTGGTCA
TGACCAGGTCGGCCACCTC


 


4507
AGGTGGCCGACCTGGTCAG
CTGACCAGGTCGGCCACCT


 


4508
GGTGGCCGACCTGGTCAGC
GCTGACCAGGTCGGCCACC


 


4509
GTGGCCGACCTGGTCAGCA
TGCTGACCAGGTCGGCCAC


 


4510
TGGCCGACCTGGTCAGCAT
ATGCTGACCAGGTCGGCCA


 


4511
GGCCGACCTGGTCAGCATC
GATGCTGACCAGGTCGGCC


 


4512
GCCGACCTGGTCAGCATCC
GGATGCTGACCAGGTCGGC


 


4513
CCGACCTGGTCAGCATCCT
AGGATGCTGACCAGGTCGG


 


4514
CGACCTGGTCAGCATCCTG
CAGGATGCTGACCAGGTCG


 


4515
GACCTGGTCAGCATCCTGG
CCAGGATGCTGACCAGGTC


 


4516
ACCTGGTCAGCATCCTGGT
ACCAGGATGCTGACCAGGT


 


4517
CCTGGTCAGCATCCTGGTG
CACCAGGATGCTGACCAGG


 


4518
CTGGTCAGCATCCTGGTGC
GCACCAGGATGCTGACCAG


 


4519
TGGTCAGCATCCTGGTGCA
TGCACCAGGATGCTGACCA


 


4520
GGTCAGCATCCTGGTGCAT
ATGCACCAGGATGCTGACC


 


4521
GTCAGCATCCTGGTGCATG
CATGCACCAGGATGCTGAC


 


4522
TCAGCATCCTGGTGCATGC
GCATGCACCAGGATGCTGA


 


4523
CAGCATCCTGGTGCATGCC
GGCATGCACCAGGATGCTG


 


4524
AGCATCCTGGTGCATGCCG
CGGCATGCACCAGGATGCT


 


4525
GCATCCTGGTGCATGCCGA
TCGGCATGCACCAGGATGC


 


4526
CATCCTGGTGCATGCCGAC
GTCGGCATGCACCAGGATG


 


4527
ATCCTGGTGCATGCCGACA
TGTCGGCATGCACCAGGAT


 


4528
TCCTGGTGCATGCCGACAC
GTGTCGGCATGCACCAGGA


 


4529
CCTGGTGCATGCCGACACA
TGTGTCGGCATGCACCAGG


 


4530
CTGGTGCATGCCGACACAC
GTGTGTCGGCATGCACCAG


 


4531
TGGTGCATGCCGACACACC
GGTGTGTCGGCATGCACCA


 


4532
GGTGCATGCCGACACACCA
TGGTGTGTCGGCATGCACC


 


4533
GTGCATGCCGACACACCAC
GTGGTGTGTCGGCATGCAC


 


4534
TGCATGCCGACACACCACT
AGTGGTGTGTCGGCATGCA


 


4535
GCATGCCGACACACCACTG
CAGTGGTGTGTCGGCATGC


 


4536
CATGCCGACACACCACTGC
GCAGTGGTGTGTCGGCATG


 


4537
ATGCCGACACACCACTGCC
GGCAGTGGTGTGTCGGCAT


 


4538
TGCCGACACACCACTGCCT
AGGCAGTGGTGTGTCGGCA


 


4539
GCCGACACACCACTGCCTG
CAGGCAGTGGTGTGTCGGC


 


4540
CCGACACACCACTGCCTGC
GCAGGCAGTGGTGTGTCGG


 


4541
CGACACACCACTGCCTGCC
GGCAGGCAGTGGTGTGTCG


 


4542
GACACACCACTGCCTGCCT
AGGCAGGCAGTGGTGTGTC


 


4543
ACACACCACTGCCTGCCTG
CAGGCAGGCAGTGGTGTGT


 


4544
CACACCACTGCCTGCCTGG
CCAGGCAGGCAGTGGTGTG


 


4545
ACACCACTGCCTGCCTGGC
GCCAGGCAGGCAGTGGTGT


 


4546
CACCACTGCCTGCCTGGCA
TGCCAGGCAGGCAGTGGTG


 


4547
ACCACTGCCTGCCTGGCAC
GTGCCAGGCAGGCAGTGGT


 


4548
CCACTGCCTGCCTGGCACC
GGTGCCAGGCAGGCAGTGG


 


4549
CACTGCCTGCCTGGCACCG
CGGTGCCAGGCAGGCAGTG


 


4550
ACTGCCTGCCTGGCACCGG
CCGGTGCCAGGCAGGCAGT


 


4551
CTGCCTGCCTGGCACCGGG
CCCGGTGCCAGGCAGGCAG


 


4552
TGCCTGCCTGGCACCGGGC
GCCCGGTGCCAGGCAGGCA


 


4553
GCCTGCCTGGCACCGGGCA
TGCCCGGTGCCAGGCAGGC


 


4554
CCTGCCTGGCACCGGGCAC
GTGCCCGGTGCCAGGCAGG


 


4555
CTGCCTGGCACCGGGCACA
TGTGCCCGGTGCCAGGCAG


 


4556
TGCCTGGCACCGGGCACAG
CTGTGCCCGGTGCCAGGCA


 


4557
GCCTGGCACCGGGCACAGA
TCTGTGCCCGGTGCCAGGC


 


4558
CCTGGCACCGGGCACAGAA
TTCTGTGCCCGGTGCCAGG


 


4559
CTGGCACCGGGCACAGAAA
TTTCTGTGCCCGGTGCCAG


 


4560
TGGCACCGGGCACAGAAAG
CTTTCTGTGCCCGGTGCCA


 


4561
GGCACCGGGCACAGAAAGA
TCTTTCTGTGCCCGGTGCC


 


4562
GCACCGGGCACAGAAAGAC
GTCTTTCTGTGCCCGGTGC


 


4563
CACCGGGCACAGAAAGACT
AGTCTTTCTGTGCCCGGTG


 


4564
ACCGGGCACAGAAAGACTT
AAGTCTTTCTGTGCCCGGT


 


4565
CCGGGCACAGAAAGACTTC
GAAGTCTTTCTGTGCCCGG


 


4566
CGGGCACAGAAAGACTTCC
GGAAGTCTTTCTGTGCCCG


 


4567
GGGCACAGAAAGACTTCCT
AGGAAGTCTTTCTGTGCCC


 


4568
GGCACAGAAAGACTTCCTT
AAGGAAGTCTTTCTGTGCC


 


4569
GCACAGAAAGACTTCCTTT
AAAGGAAGTCTTTCTGTGC


 


4570
CACAGAAAGACTTCCTTTC
GAAAGGAAGTCTTTCTGTG


 


4571
ACAGAAAGACTTCCTTTCA
TGAAAGGAAGTCTTTCTGT


 


4572
CAGAAAGACTTCCTTTCAG
CTGAAAGGAAGTCTTTCTG


 


4573
AGAAAGACTTCCTTTCAGG
CCTGAAAGGAAGTCTTTCT


 


4574
GAAAGACTTCCTTTCAGGC
GCCTGAAAGGAAGTCTTTC


 


4575
AAAGACTTCCTTTCAGGCC
GGCCTGAAAGGAAGTCTTT


 


4576
AAGACTTCCTTTCAGGCCT
AGGCCTGAAAGGAAGTCTT


 


4577
AGACTTCCTTTCAGGCCTG
CAGGCCTGAAAGGAAGTCT


 


4578
GACTTCCTTTCAGGCCTGG
CCAGGCCTGAAAGGAAGTC


 


4579
ACTTCCTTTCAGGCCTGGA
TCCAGGCCTGAAAGGAAGT


 


4580
CTTCCTTTCAGGCCTGGAC
GTCCAGGCCTGAAAGGAAG


 


4581
TTCCTTTCAGGCCTGGACG
CGTCCAGGCCTGAAAGGAA


 


4582
TCCTTTCAGGCCTGGACGG
CCGTCCAGGCCTGAAAGGA


 


4583
CCTTTCAGGCCTGGACGGG
CCCGTCCAGGCCTGAAAGG


 


4584
CTTTCAGGCCTGGACGGGG
CCCCGTCCAGGCCTGAAAG


 


4585
TTTCAGGCCTGGACGGGGA
TCCCCGTCCAGGCCTGAAA


 


4586
TTCAGGCCTGGACGGGGAG
CTCCCCGTCCAGGCCTGAA


 


4587
TCAGGCCTGGACGGGGAGG
CCTCCCCGTCCAGGCCTGA


 


4588
CAGGCCTGGACGGGGAGGG
CCCTCCCCGTCCAGGCCTG


 


4589
AGGCCTGGACGGGGAGGGG
CCCCTCCCCGTCCAGGCCT


 


4590
GGCCTGGACGGGGAGGGGC
GCCCCTCCCCGTCCAGGCC


 


4591
GCCTGGACGGGGAGGGGCT
AGCCCCTCCCCGTCCAGGC


 


4592
CCTGGACGGGGAGGGGCTC
GAGCCCCTCCCCGTCCAGG


 


4593
CTGGACGGGGAGGGGCTCT
AGAGCCCCTCCCCGTCCAG


 


4594
TGGACGGGGAGGGGCTCTG
CAGAGCCCCTCCCCGTCCA


 


4595
GGACGGGGAGGGGCTCTGG
CCAGAGCCCCTCCCCGTCC


 


4596
GACGGGGAGGGGCTCTGGT
ACCAGAGCCCCTCCCCGTC


 


4597
ACGGGGAGGGGCTCTGGTC
GACCAGAGCCCCTCCCCGT


 


4598
CGGGGAGGGGCTCTGGTCT
AGACCAGAGCCCCTCCCCG


 


4599
GGGGAGGGGCTCTGGTCTC
GAGACCAGAGCCCCTCCCC


 


4600
GGGAGGGGCTCTGGTCTCC
GGAGACCAGAGCCCCTCCC


 


4601
GGAGGGGCTCTGGTCTCCG
CGGAGACCAGAGCCCCTCC


 


4602
GAGGGGCTCTGGTCTCCGG
CCGGAGACCAGAGCCCCTC


 


4603
AGGGGCTCTGGTCTCCGGG
CCCGGAGACCAGAGCCCCT


 


4604
GGGGCTCTGGTCTCCGGGC
GCCCGGAGACCAGAGCCCC


 


4605
GGGCTCTGGTCTCCGGGCA
TGCCCGGAGACCAGAGCCC


 


4606
GGCTCTGGTCTCCGGGCAG
CTGCCCGGAGACCAGAGCC


 


4607
GCTCTGGTCTCCGGGCAGC
GCTGCCCGGAGACCAGAGC


 


4608
CTCTGGTCTCCGGGCAGCC
GGCTGCCCGGAGACCAGAG


 


4609
TCTGGTCTCCGGGCAGCCA
TGGCTGCCCGGAGACCAGA


 


4610
CTGGTCTCCGGGCAGCCAG
CTGGCTGCCCGGAGACCAG


 


4611
TGGTCTCCGGGCAGCCAGG
CCTGGCTGCCCGGAGACCA


 


4612
GGTCTCCGGGCAGCCAGGT
ACCTGGCTGCCCGGAGACC


 


4613
GTCTCCGGGCAGCCAGGTC
GACCTGGCTGCCCGGAGAC


 


4614
TCTCCGGGCAGCCAGGTCA
TGACCTGGCTGCCCGGAGA


 


4615
CTCCGGGCAGCCAGGTCAG
CTGACCTGGCTGCCCGGAG


 


4616
TCCGGGCAGCCAGGTCAGC
GCTGACCTGGCTGCCCGGA


 


4617
CCGGGCAGCCAGGTCAGCA
TGCTGACCTGGCTGCCCGG


 


4618
CGGGCAGCCAGGTCAGCAC
GTGCTGACCTGGCTGCCCG


 


4619
GGGCAGCCAGGTCAGCACT
AGTGCTGACCTGGCTGCCC


 


4620
GGCAGCCAGGTCAGCACTG
CAGTGCTGACCTGGCTGCC


 


4621
GCAGCCAGGTCAGCACTGT
ACAGTGCTGACCTGGCTGC


 


4622
CAGCCAGGTCAGCACTGTG
CACAGTGCTGACCTGGCTG


 


4623
AGCCAGGTCAGCACTGTGT
ACACAGTGCTGACCTGGCT


 


4624
GCCAGGTCAGCACTGTGTG
CACACAGTGCTGACCTGGC


 


4625
CCAGGTCAGCACTGTGTGG
CCACACAGTGCTGACCTGG


 


4626
CAGGTCAGCACTGTGTGGC
GCCACACAGTGCTGACCTG


 


4627
AGGTCAGCACTGTGTGGCA
TGCCACACAGTGCTGACCT


 


4628
GGTCAGCACTGTGTGGCAC
GTGCCACACAGTGCTGACC


 


4629
GTCAGCACTGTGTGGCACG
CGTGCCACACAGTGCTGAC


 


4630
TCAGCACTGTGTGGCACGT
ACGTGCCACACAGTGCTGA


 


4631
CAGCACTGTGTGGCACGTG
CACGTGCCACACAGTGCTG


 


4632
AGCACTGTGTGGCACGTGT
ACACGTGCCACACAGTGCT


 


4633
GCACTGTGTGGCACGTGTT
AACACGTGCCACACAGTGC


 


4634
CACTGTGTGGCACGTGTTC
GAACACGTGCCACACAGTG


 


4635
ACTGTGTGGCACGTGTTCC
GGAACACGTGCCACACAGT


 


4636
CTGTGTGGCACGTGTTCCG
CGGAACACGTGCCACACAG


 


4637
TGTGTGGCACGTGTTCCGG
CCGGAACACGTGCCACACA


 


4638
GTGTGGCACGTGTTCCGGG
CCCGGAACACGTGCCACAC


 


4639
TGTGGCACGTGTTCCGGGC
GCCCGGAACACGTGCCACA


 


4640
GTGGCACGTGTTCCGGGCA
TGCCCGGAACACGTGCCAC


 


4641
TGGCACGTGTTCCGGGCAC
GTGCCCGGAACACGTGCCA


 


4642
GGCACGTGTTCCGGGCACA
TGTGCCCGGAACACGTGCC


 


4643
GCACGTGTTCCGGGCACAG
CTGTGCCCGGAACACGTGC


 


4644
CACGTGTTCCGGGCACAGG
CCTGTGCCCGGAACACGTG


 


4645
ACGTGTTCCGGGCACAGGA
TCCTGTGCCCGGAACACGT


 


4646
CGTGTTCCGGGCACAGGAC
GTCCTGTGCCCGGAACACG


 


4647
GTGTTCCGGGCACAGGACG
CGTCCTGTGCCCGGAACAC


 


4648
TGTTCCGGGCACAGGACGC
GCGTCCTGTGCCCGGAACA


 


4649
GTTCCGGGCACAGGACGCC
GGCGTCCTGTGCCCGGAAC


 


4650
TTCCGGGCACAGGACGCCC
GGGCGTCCTGTGCCCGGAA


 


4651
TCCGGGCACAGGACGCCCA
TGGGCGTCCTGTGCCCGGA


 


4652
CCGGGCACAGGACGCCCAG
CTGGGCGTCCTGTGCCCGG


 


4653
CGGGCACAGGACGCCCAGC
GCTGGGCGTCCTGTGCCCG


 


4654
GGGCACAGGACGCCCAGCG
CGCTGGGCGTCCTGTGCCC


 


4655
GGCACAGGACGCCCAGCGC
GCGCTGGGCGTCCTGTGCC


 


4656
GCACAGGACGCCCAGCGCA
TGCGCTGGGCGTCCTGTGC


 


4657
CACAGGACGCCCAGCGCAT
ATGCGCTGGGCGTCCTGTG


 


4658
ACAGGACGCCCAGCGCATC
GATGCGCTGGGCGTCCTGT


 


4659
CAGGACGCCCAGCGCATCC
GGATGCGCTGGGCGTCCTG


 


4660
AGGACGCCCAGCGCATCCG
CGGATGCGCTGGGCGTCCT


 


4661
GGACGCCCAGCGCATCCGC
GCGGATGCGCTGGGCGTCC


 


4662
GACGCCCAGCGCATCCGCC
GGCGGATGCGCTGGGCGTC


 


4663
ACGCCCAGCGCATCCGCCG
CGGCGGATGCGCTGGGCGT


 


4664
CGCCCAGCGCATCCGCCGC
GCGGCGGATGCGCTGGGCG


 


4665
GCCCAGCGCATCCGCCGCT
AGCGGCGGATGCGCTGGGC


 


4666
CCCAGCGCATCCGCCGCTT
AAGCGGCGGATGCGCTGGG


 


4667
CCAGCGCATCCGCCGCTTT
AAAGCGGCGGATGCGCTGG


 


4668
CAGCGCATCCGCCGCTTTC
GAAAGCGGCGGATGCGCTG


 


4669
AGCGCATCCGCCGCTTTCT
AGAAAGCGGCGGATGCGCT


 


4670
GCGCATCCGCCGCTTTCTC
GAGAAAGCGGCGGATGCGC


 


4671
CGCATCCGCCGCTTTCTCC
GGAGAAAGCGGCGGATGCG


 


4672
GCATCCGCCGCTTTCTCCA
TGGAGAAAGCGGCGGATGC


 


4673
CATCCGCCGCTTTCTCCAG
CTGGAGAAAGCGGCGGATG


 


4674
ATCCGCCGCTTTCTCCAGA
TCTGGAGAAAGCGGCGGAT


 


4675
TCCGCCGCTTTCTCCAGAT
ATCTGGAGAAAGCGGCGGA


 


4676
CCGCCGCTTTCTCCAGATG
CATCTGGAGAAAGCGGCGG


 


4677
CGCCGCTTTCTCCAGATGG
CCATCTGGAGAAAGCGGCG


 


4678
GCCGCTTTCTCCAGATGGT
ACCATCTGGAGAAAGCGGC


 


4679
CCGCTTTCTCCAGATGGTG
CACCATCTGGAGAAAGCGG


 


4680
CGCTTTCTCCAGATGGTGT
ACACCATCTGGAGAAAGCG


 


4681
GCTTTCTCCAGATGGTGTG
CACACCATCTGGAGAAAGC


 


4682
CTTTCTCCAGATGGTGTGC
GCACACCATCTGGAGAAAG


 


4683
TTTCTCCAGATGGTGTGCC
GGCACACCATCTGGAGAAA


 


4684
TTCTCCAGATGGTGTGCCC
GGGCACACCATCTGGAGAA


 


4685
TCTCCAGATGGTGTGCCCG
CGGGCACACCATCTGGAGA


 


4686
CTCCAGATGGTGTGCCCGG
CCGGGCACACCATCTGGAG


 


4687
TCCAGATGGTGTGCCCGGC
GCCGGGCACACCATCTGGA


 


4688
CCAGATGGTGTGCCCGGCC
GGCCGGGCACACCATCTGG


 


4689
CAGATGGTGTGCCCGGCCG
CGGCCGGGCACACCATCTG


 


4690
AGATGGTGTGCCCGGCCGG
CCGGCCGGGCACACCATCT


 


4691
GATGGTGTGCCCGGCCGGG
CCCGGCCGGGCACACCATC


 


4692
ATGGTGTGCCCGGCCGGGG
CCCCGGCCGGGCACACCAT


 


4693
TGGTGTGCCCGGCCGGGGC
GCCCCGGCCGGGCACACCA


 


4694
GGTGTGCCCGGCCGGGGCA
TGCCCCGGCCGGGCACACC


 


4695
GTGTGCCCGGCCGGGGCAG
CTGCCCCGGCCGGGCACAC


 


4696
TGTGCCCGGCCGGGGCAGG
CCTGCCCCGGCCGGGCACA


 


4697
GTGCCCGGCCGGGGCAGGC
GCCTGCCCCGGCCGGGCAC


 


4698
TGCCCGGCCGGGGCAGGCG
CGCCTGCCCCGGCCGGGCA


 


4699
GCCCGGCCGGGGCAGGCGC
GCGCCTGCCCCGGCCGGGC


 


4700
CCCGGCCGGGGCAGGCGCC
GGCGCCTGCCCCGGCCGGG


 


4701
CCGGCCGGGGCAGGCGCCC
GGGCGCCTGCCCCGGCCGG


 


4702
CGGCCGGGGCAGGCGCCCT
AGGGCGCCTGCCCCGGCCG


 


4703
GGCCGGGGCAGGCGCCCTG
CAGGGCGCCTGCCCCGGCC


 


4704
GCCGGGGCAGGCGCCCTGG
CCAGGGCGCCTGCCCCGGC


 


4705
CCGGGGCAGGCGCCCTGGA
TCCAGGGCGCCTGCCCCGG


 


4706
CGGGGCAGGCGCCCTGGAG
CTCCAGGGCGCCTGCCCCG


 


4707
GGGGCAGGCGCCCTGGAGC
GCTCCAGGGCGCCTGCCCC


 


4708
GGGCAGGCGCCCTGGAGCC
GGCTCCAGGGCGCCTGCCC


 


4709
GGCAGGCGCCCTGGAGCCT
AGGCTCCAGGGCGCCTGCC


 


4710
GCAGGCGCCCTGGAGCCTG
CAGGCTCCAGGGCGCCTGC


 


4711
CAGGCGCCCTGGAGCCTGG
CCAGGCTCCAGGGCGCCTG


 


4712
AGGCGCCCTGGAGCCTGGC
GCCAGGCTCCAGGGCGCCT


 


4713
GGCGCCCTGGAGCCTGGCG
CGCCAGGCTCCAGGGCGCC


 


4714
GCGCCCTGGAGCCTGGCGC
GCGCCAGGCTCCAGGGCGC


 


4715
CGCCCTGGAGCCTGGCGCC
GGCGCCAGGCTCCAGGGCG


 


4716
GCCCTGGAGCCTGGCGCCC
GGGCGCCAGGCTCCAGGGC


 


4717
CCCTGGAGCCTGGCGCCCC
GGGGCGCCAGGCTCCAGGG


 


4718
CCTGGAGCCTGGCGCCCCA
TGGGGCGCCAGGCTCCAGG


 


4719
CTGGAGCCTGGCGCCCCAG
CTGGGGCGCCAGGCTCCAG


 


4720
TGGAGCCTGGCGCCCCAGG
CCTGGGGCGCCAGGCTCCA


 


4721
GGAGCCTGGCGCCCCAGGC
GCCTGGGGCGCCAGGCTCC


 


4722
GAGCCTGGCGCCCCAGGCA
TGCCTGGGGCGCCAGGCTC


 


4723
AGCCTGGCGCCCCAGGCAG
CTGCCTGGGGCGCCAGGCT


 


4724
GCCTGGCGCCCCAGGCAGC
GCTGCCTGGGGCGCCAGGC


 


4725
CCTGGCGCCCCAGGCAGCT
AGCTGCCTGGGGCGCCAGG


 


4726
CTGGCGCCCCAGGCAGCTG
CAGCTGCCTGGGGCGCCAG


 


4727
TGGCGCCCCAGGCAGCTGC
GCAGCTGCCTGGGGCGCCA


 


4728
GGCGCCCCAGGCAGCTGCT
AGCAGCTGCCTGGGGCGCC


 


4729
GCGCCCCAGGCAGCTGCTA
TAGCAGCTGCCTGGGGCGC


 


4730
CGCCCCAGGCAGCTGCTAC
GTAGCAGCTGCCTGGGGCG


 


4731
GCCCCAGGCAGCTGCTACC
GGTAGCAGCTGCCTGGGGC


 


4732
CCCCAGGCAGCTGCTACCT
AGGTAGCAGCTGCCTGGGG


 


4733
CCCAGGCAGCTGCTACCTG
CAGGTAGCAGCTGCCTGGG


 


4734
CCAGGCAGCTGCTACCTGG
CCAGGTAGCAGCTGCCTGG


 


4735
CAGGCAGCTGCTACCTGGA
TCCAGGTAGCAGCTGCCTG


 


4736
AGGCAGCTGCTACCTGGAT
ATCCAGGTAGCAGCTGCCT


 


4737
GGCAGCTGCTACCTGGATG
CATCCAGGTAGCAGCTGCC


 


4738
GCAGCTGCTACCTGGATGC
GCATCCAGGTAGCAGCTGC


 


4739
CAGCTGCTACCTGGATGCA
TGCATCCAGGTAGCAGCTG


 


4740
AGCTGCTACCTGGATGCAG
CTGCATCCAGGTAGCAGCT


 


4741
GCTGCTACCTGGATGCAGG
CCTGCATCCAGGTAGCAGC


 


4742
CTGCTACCTGGATGCAGGG
CCCTGCATCCAGGTAGCAG


 


4743
TGCTACCTGGATGCAGGGC
GCCCTGCATCCAGGTAGCA


 


4744
GCTACCTGGATGCAGGGCT
AGCCCTGCATCCAGGTAGC


 


4745
CTACCTGGATGCAGGGCTG
CAGCCCTGCATCCAGGTAG


 


4746
TACCTGGATGCAGGGCTGC
GCAGCCCTGCATCCAGGTA


 


4747
ACCTGGATGCAGGGCTGCG
CGCAGCCCTGCATCCAGGT


 


4748
CCTGGATGCAGGGCTGCGG
CCGCAGCCCTGCATCCAGG


 


4749
CTGGATGCAGGGCTGCGGC
GCCGCAGCCCTGCATCCAG


 


4750
TGGATGCAGGGCTGCGGCG
CGCCGCAGCCCTGCATCCA


 


4751
GGATGCAGGGCTGCGGCGG
CCGCCGCAGCCCTGCATCC


 


4752
GATGCAGGGCTGCGGCGGC
GCCGCCGCAGCCCTGCATC


 


4753
ATGCAGGGCTGCGGCGGCG
CGCCGCCGCAGCCCTGCAT


 


4754
TGCAGGGCTGCGGCGGCGC
GCGCCGCCGCAGCCCTGCA


 


4755
GCAGGGCTGCGGCGGCGCC
GGCGCCGCCGCAGCCCTGC


 


4756
CAGGGCTGCGGCGGCGCCT
AGGCGCCGCCGCAGCCCTG


 


4757
AGGGCTGCGGCGGCGCCTG
CAGGCGCCGCCGCAGCCCT


 


4758
GGGCTGCGGCGGCGCCTGC
GCAGGCGCCGCCGCAGCCC


 


4759
GGCTGCGGCGGCGCCTGCG
CGCAGGCGCCGCCGCAGCC


 


4760
GCTGCGGCGGCGCCTGCGG
CCGCAGGCGCCGCCGCAGC


 


4761
CTGCGGCGGCGCCTGCGGG
CCCGCAGGCGCCGCCGCAG


 


4762
TGCGGCGGCGCCTGCGGGA
TCCCGCAGGCGCCGCCGCA


 


4763
GCGGCGGCGCCTGCGGGAG
CTCCCGCAGGCGCCGCCGC


 


4764
CGGCGGCGCCTGCGGGAGG
CCTCCCGCAGGCGCCGCCG


 


4765
GGCGGCGCCTGCGGGAGGA
TCCTCCCGCAGGCGCCGCC


 


4766
GCGGCGCCTGCGGGAGGAG
CTCCTCCCGCAGGCGCCGC


 


4767
CGGCGCCTGCGGGAGGAGT
ACTCCTCCCGCAGGCGCCG


 


4768
GGCGCCTGCGGGAGGAGTG
CACTCCTCCCGCAGGCGCC


 


4769
GCGCCTGCGGGAGGAGTGG
CCACTCCTCCCGCAGGCGC


 


4770
CGCCTGCGGGAGGAGTGGG
CCCACTCCTCCCGCAGGCG


 


4771
GCCTGCGGGAGGAGTGGGG
CCCCACTCCTCCCGCAGGC


 


4772
CCTGCGGGAGGAGTGGGGC
GCCCCACTCCTCCCGCAGG


 


4773
CTGCGGGAGGAGTGGGGCG
CGCCCCACTCCTCCCGCAG


 


4774
TGCGGGAGGAGTGGGGCGT
ACGCCCCACTCCTCCCGCA


 


4775
GCGGGAGGAGTGGGGCGTG
CACGCCCCACTCCTCCCGC


 


4776
CGGGAGGAGTGGGGCGTGA
TCACGCCCCACTCCTCCCG


 


4777
GGGAGGAGTGGGGCGTGAG
CTCACGCCCCACTCCTCCC


 


4778
GGAGGAGTGGGGCGTGAGC
GCTCACGCCCCACTCCTCC


 


4779
GAGGAGTGGGGCGTGAGCT
AGCTCACGCCCCACTCCTC


 


4780
AGGAGTGGGGCGTGAGCTG
CAGCTCACGCCCCACTCCT


 


4781
GGAGTGGGGCGTGAGCTGC
GCAGCTCACGCCCCACTCC


 


4782
GAGTGGGGCGTGAGCTGCT
AGCAGCTCACGCCCCACTC


 


4783
AGTGGGGCGTGAGCTGCTG
CAGCAGCTCACGCCCCACT


 


4784
GTGGGGCGTGAGCTGCTGG
CCAGCAGCTCACGCCCCAC


 


4785
TGGGGCGTGAGCTGCTGGA
TCCAGCAGCTCACGCCCCA


 


4786
GGGGCGTGAGCTGCTGGAC
GTCCAGCAGCTCACGCCCC


 


4787
GGGCGTGAGCTGCTGGACC
GGTCCAGCAGCTCACGCCC


 


4788
GGCGTGAGCTGCTGGACCC
GGGTCCAGCAGCTCACGCC


 


4789
GCGTGAGCTGCTGGACCCT
AGGGTCCAGCAGCTCACGC


 


4790
CGTGAGCTGCTGGACCCTG
CAGGGTCCAGCAGCTCACG


 


4791
GTGAGCTGCTGGACCCTGC
GCAGGGTCCAGCAGCTCAC


 


4792
TGAGCTGCTGGACCCTGCT
AGCAGGGTCCAGCAGCTCA


 


4793
GAGCTGCTGGACCCTGCTC
GAGCAGGGTCCAGCAGCTC


 


4794
AGCTGCTGGACCCTGCTCC
GGAGCAGGGTCCAGCAGCT


 


4795
GCTGCTGGACCCTGCTCCA
TGGAGCAGGGTCCAGCAGC


 


4796
CTGCTGGACCCTGCTCCAG
CTGGAGCAGGGTCCAGCAG


 


4797
TGCTGGACCCTGCTCCAGG
CCTGGAGCAGGGTCCAGCA


 


4798
GCTGGACCCTGCTCCAGGC
GCCTGGAGCAGGGTCCAGC


 


4799
CTGGACCCTGCTCCAGGCC
GGCCTGGAGCAGGGTCCAG


 


4800
TGGACCCTGCTCCAGGCCC
GGGCCTGGAGCAGGGTCCA


 


4801
GGACCCTGCTCCAGGCCCC
GGGGCCTGGAGCAGGGTCC


 


4802
GACCCTGCTCCAGGCCCCC
GGGGGCCTGGAGCAGGGTC


 


4803
ACCCTGCTCCAGGCCCCCG
CGGGGGCCTGGAGCAGGGT


 


4804
CCCTGCTCCAGGCCCCCGG
CCGGGGGCCTGGAGCAGGG


 


4805
CCTGCTCCAGGCCCCCGGA
TCCGGGGGCCTGGAGCAGG


 


4806
CTGCTCCAGGCCCCCGGAG
CTCCGGGGGCCTGGAGCAG


 


4807
TGCTCCAGGCCCCCGGAGA
TCTCCGGGGGCCTGGAGCA


 


4808
GCTCCAGGCCCCCGGAGAG
CTCTCCGGGGGCCTGGAGC


 


4809
CTCCAGGCCCCCGGAGAGG
CCTCTCCGGGGGCCTGGAG


 


4810
TCCAGGCCCCCGGAGAGGC
GCCTCTCCGGGGGCCTGGA


 


4811
CCAGGCCCCCGGAGAGGCC
GGCCTCTCCGGGGGCCTGG


 


4812
CAGGCCCCCGGAGAGGCCG
CGGCCTCTCCGGGGGCCTG


 


4813
AGGCCCCCGGAGAGGCCGT
ACGGCCTCTCCGGGGGCCT


 


4814
GGCCCCCGGAGAGGCCGTG
CACGGCCTCTCCGGGGGCC


 


4815
GCCCCCGGAGAGGCCGTGC
GCACGGCCTCTCCGGGGGC


 


4816
CCCCCGGAGAGGCCGTGCT
AGCACGGCCTCTCCGGGGG


 


4817
CCCCGGAGAGGCCGTGCTG
CAGCACGGCCTCTCCGGGG


 


4818
CCCGGAGAGGCCGTGCTGG
CCAGCACGGCCTCTCCGGG


 


4819
CCGGAGAGGCCGTGCTGGT
ACCAGCACGGCCTCTCCGG


 


4820
CGGAGAGGCCGTGCTGGTG
CACCAGCACGGCCTCTCCG


 


4821
GGAGAGGCCGTGCTGGTGC
GCACCAGCACGGCCTCTCC


 


4822
GAGAGGCCGTGCTGGTGCC
GGCACCAGCACGGCCTCTC


 


4823
AGAGGCCGTGCTGGTGCCT
AGGCACCAGCACGGCCTCT


 


4824
GAGGCCGTGCTGGTGCCTG
CAGGCACCAGCACGGCCTC


 


4825
AGGCCGTGCTGGTGCCTGC
GCAGGCACCAGCACGGCCT


 


4826
GGCCGTGCTGGTGCCTGCA
TGCAGGCACCAGCACGGCC


 


4827
GCCGTGCTGGTGCCTGCAG
CTGCAGGCACCAGCACGGC


 


4828
CCGTGCTGGTGCCTGCAGG
CCTGCAGGCACCAGCACGG


 


4829
CGTGCTGGTGCCTGCAGGG
CCCTGCAGGCACCAGCACG


 


4830
GTGCTGGTGCCTGCAGGGG
CCCCTGCAGGCACCAGCAC


 


4831
TGCTGGTGCCTGCAGGGGC
GCCCCTGCAGGCACCAGCA


 


4832
GCTGGTGCCTGCAGGGGCT
AGCCCCTGCAGGCACCAGC


 


4833
CTGGTGCCTGCAGGGGCTC
GAGCCCCTGCAGGCACCAG


 


4834
TGGTGCCTGCAGGGGCTCC
GGAGCCCCTGCAGGCACCA


 


4835
GGTGCCTGCAGGGGCTCCC
GGGAGCCCCTGCAGGCACC


 


4836
GTGCCTGCAGGGGCTCCCC
GGGGAGCCCCTGCAGGCAC


 


4837
TGCCTGCAGGGGCTCCCCA
TGGGGAGCCCCTGCAGGCA


 


4838
GCCTGCAGGGGCTCCCCAC
GTGGGGAGCCCCTGCAGGC


 


4839
CCTGCAGGGGCTCCCCACC
GGTGGGGAGCCCCTGCAGG


 


4840
CTGCAGGGGCTCCCCACCA
TGGTGGGGAGCCCCTGCAG


 


4841
TGCAGGGGCTCCCCACCAG
CTGGTGGGGAGCCCCTGCA


 


4842
GCAGGGGCTCCCCACCAGG
CCTGGTGGGGAGCCCCTGC


 


4843
CAGGGGCTCCCCACCAGGT
ACCTGGTGGGGAGCCCCTG


 


4844
AGGGGCTCCCCACCAGGTG
CACCTGGTGGGGAGCCCCT


 


4845
GGGGCTCCCCACCAGGTGC
GCACCTGGTGGGGAGCCCC


 


4846
GGGCTCCCCACCAGGTGCA
TGCACCTGGTGGGGAGCCC


 


4847
GGCTCCCCACCAGGTGCAG
CTGCACCTGGTGGGGAGCC


 


4848
GCTCCCCACCAGGTGCAGG
CCTGCACCTGGTGGGGAGC


 


4849
CTCCCCACCAGGTGCAGGG
CCCTGCACCTGGTGGGGAG


 


4850
TCCCCACCAGGTGCAGGGC
GCCCTGCACCTGGTGGGGA


 


4851
CCCCACCAGGTGCAGGGCC
GGCCCTGCACCTGGTGGGG


 


4852
CCCACCAGGTGCAGGGCCT
AGGCCCTGCACCTGGTGGG


 


4853
CCACCAGGTGCAGGGCCTG
CAGGCCCTGCACCTGGTGG


 


4854
CACCAGGTGCAGGGCCTGG
CCAGGCCCTGCACCTGGTG


 


4855
ACCAGGTGCAGGGCCTGGT
ACCAGGCCCTGCACCTGGT


 


4856
CCAGGTGCAGGGCCTGGTG
CACCAGGCCCTGCACCTGG


 


4857
CAGGTGCAGGGCCTGGTGA
TCACCAGGCCCTGCACCTG


 


4858
AGGTGCAGGGCCTGGTGAG
CTCACCAGGCCCTGCACCT


 


4859
GGTGCAGGGCCTGGTGAGC
GCTCACCAGGCCCTGCACC


 


4860
GTGCAGGGCCTGGTGAGCA
TGCTCACCAGGCCCTGCAC


 


4861
TGCAGGGCCTGGTGAGCAC
GTGCTCACCAGGCCCTGCA


 


4862
GCAGGGCCTGGTGAGCACA
TGTGCTCACCAGGCCCTGC


 


4863
CAGGGCCTGGTGAGCACAG
CTGTGCTCACCAGGCCCTG


 


4864
AGGGCCTGGTGAGCACAGT
ACTGTGCTCACCAGGCCCT


 


4865
GGGCCTGGTGAGCACAGTC
GACTGTGCTCACCAGGCCC


 


4866
GGCCTGGTGAGCACAGTCA
TGACTGTGCTCACCAGGCC


 


4867
GCCTGGTGAGCACAGTCAG
CTGACTGTGCTCACCAGGC


 


4868
CCTGGTGAGCACAGTCAGC
GCTGACTGTGCTCACCAGG


 


4869
CTGGTGAGCACAGTCAGCG
CGCTGACTGTGCTCACCAG


 


4870
TGGTGAGCACAGTCAGCGT
ACGCTGACTGTGCTCACCA


 


4871
GGTGAGCACAGTCAGCGTC
GACGCTGACTGTGCTCACC


 


4872
GTGAGCACAGTCAGCGTCA
TGACGCTGACTGTGCTCAC


 


4873
TGAGCACAGTCAGCGTCAC
GTGACGCTGACTGTGCTCA


 


4874
GAGCACAGTCAGCGTCACT
AGTGACGCTGACTGTGCTC


 


4875
AGCACAGTCAGCGTCACTC
GAGTGACGCTGACTGTGCT


 


4876
GCACAGTCAGCGTCACTCA
TGAGTGACGCTGACTGTGC


 


4877
CACAGTCAGCGTCACTCAG
CTGAGTGACGCTGACTGTG


 


4878
ACAGTCAGCGTCACTCAGC
GCTGAGTGACGCTGACTGT


 


4879
CAGTCAGCGTCACTCAGCA
TGCTGAGTGACGCTGACTG


 


4880
AGTCAGCGTCACTCAGCAC
GTGCTGAGTGACGCTGACT


 


4881
GTCAGCGTCACTCAGCACT
AGTGCTGAGTGACGCTGAC


 


4882
TCAGCGTCACTCAGCACTT
AAGTGCTGAGTGACGCTGA


 


4883
CAGCGTCACTCAGCACTTC
GAAGTGCTGAGTGACGCTG


 


4884
AGCGTCACTCAGCACTTCC
GGAAGTGCTGAGTGACGCT


 


4885
GCGTCACTCAGCACTTCCT
AGGAAGTGCTGAGTGACGC


 


4886
CGTCACTCAGCACTTCCTC
GAGGAAGTGCTGAGTGACG


 


4887
GTCACTCAGCACTTCCTCT
AGAGGAAGTGCTGAGTGAC


 


4888
TCACTCAGCACTTCCTCTC
GAGAGGAAGTGCTGAGTGA


 


4889
CACTCAGCACTTCCTCTCC
GGAGAGGAAGTGCTGAGTG


 


4890
ACTCAGCACTTCCTCTCCC
GGGAGAGGAAGTGCTGAGT


 


4891
CTCAGCACTTCCTCTCCCC
GGGGAGAGGAAGTGCTGAG


 


4892
TCAGCACTTCCTCTCCCCT
AGGGGAGAGGAAGTGCTGA


 


4893
CAGCACTTCCTCTCCCCTG
CAGGGGAGAGGAAGTGCTG


 


4894
AGCACTTCCTCTCCCCTGA
TCAGGGGAGAGGAAGTGCT


 


4895
GCACTTCCTCTCCCCTGAG
CTCAGGGGAGAGGAAGTGC


 


4896
CACTTCCTCTCCCCTGAGA
TCTCAGGGGAGAGGAAGTG


 


4897
ACTTCCTCTCCCCTGAGAC
GTCTCAGGGGAGAGGAAGT


 


4898
CTTCCTCTCCCCTGAGACC
GGTCTCAGGGGAGAGGAAG


 


4899
TTCCTCTCCCCTGAGACCT
AGGTCTCAGGGGAGAGGAA


 


4900
TCCTCTCCCCTGAGACCTC
GAGGTCTCAGGGGAGAGGA


 


4901
CCTCTCCCCTGAGACCTCT
AGAGGTCTCAGGGGAGAGG


 


4902
CTCTCCCCTGAGACCTCTG
CAGAGGTCTCAGGGGAGAG


 


4903
TCTCCCCTGAGACCTCTGC
GCAGAGGTCTCAGGGGAGA


 


4904
CTCCCCTGAGACCTCTGCC
GGCAGAGGTCTCAGGGGAG


 


4905
TCCCCTGAGACCTCTGCCC
GGGCAGAGGTCTCAGGGGA


 


4906
CCCCTGAGACCTCTGCCCT
AGGGCAGAGGTCTCAGGGG


 


4907
CCCTGAGACCTCTGCCCTC
GAGGGCAGAGGTCTCAGGG


 


4908
CCTGAGACCTCTGCCCTCT
AGAGGGCAGAGGTCTCAGG


 


4909
CTGAGACCTCTGCCCTCTC
GAGAGGGCAGAGGTCTCAG


 


4910
TGAGACCTCTGCCCTCTCT
AGAGAGGGCAGAGGTCTCA


 


4911
GAGACCTCTGCCCTCTCTG
CAGAGAGGGCAGAGGTCTC


 


4912
AGACCTCTGCCCTCTCTGC
GCAGAGAGGGCAGAGGTCT


 


4913
GACCTCTGCCCTCTCTGCT
AGCAGAGAGGGCAGAGGTC


 


4914
ACCTCTGCCCTCTCTGCTC
GAGCAGAGAGGGCAGAGGT


 


4915
CCTCTGCCCTCTCTGCTCA
TGAGCAGAGAGGGCAGAGG


 


4916
CTCTGCCCTCTCTGCTCAG
CTGAGCAGAGAGGGCAGAG


 


4917
TCTGCCCTCTCTGCTCAGC
GCTGAGCAGAGAGGGCAGA


 


4918
CTGCCCTCTCTGCTCAGCT
AGCTGAGCAGAGAGGGCAG


 


4919
TGCCCTCTCTGCTCAGCTC
GAGCTGAGCAGAGAGGGCA


 


4920
GCCCTCTCTGCTCAGCTCT
AGAGCTGAGCAGAGAGGGC


 


4921
CCCTCTCTGCTCAGCTCTG
CAGAGCTGAGCAGAGAGGG


 


4922
CCTCTCTGCTCAGCTCTGC
GCAGAGCTGAGCAGAGAGG


 


4923
CTCTCTGCTCAGCTCTGCC
GGCAGAGCTGAGCAGAGAG


 


4924
TCTCTGCTCAGCTCTGCCA
TGGCAGAGCTGAGCAGAGA


 


4925
CTCTGCTCAGCTCTGCCAC
GTGGCAGAGCTGAGCAGAG


 


4926
TCTGCTCAGCTCTGCCACC
GGTGGCAGAGCTGAGCAGA


 


4927
CTGCTCAGCTCTGCCACCA
TGGTGGCAGAGCTGAGCAG


 


4928
TGCTCAGCTCTGCCACCAG
CTGGTGGCAGAGCTGAGCA


 


4929
GCTCAGCTCTGCCACCAGG
CCTGGTGGCAGAGCTGAGC


 


4930
CTCAGCTCTGCCACCAGGG
CCCTGGTGGCAGAGCTGAG


 


4931
TCAGCTCTGCCACCAGGGA
TCCCTGGTGGCAGAGCTGA


 


4932
CAGCTCTGCCACCAGGGAC
GTCCCTGGTGGCAGAGCTG


 


4933
AGCTCTGCCACCAGGGACC
GGTCCCTGGTGGCAGAGCT


 


4934
GCTCTGCCACCAGGGACCC
GGGTCCCTGGTGGCAGAGC


 


4935
CTCTGCCACCAGGGACCCA
TGGGTCCCTGGTGGCAGAG


 


4936
TCTGCCACCAGGGACCCAG
CTGGGTCCCTGGTGGCAGA


 


4937
CTGCCACCAGGGACCCAGC
GCTGGGTCCCTGGTGGCAG


 


4938
TGCCACCAGGGACCCAGCC
GGCTGGGTCCCTGGTGGCA


 


4939
GCCACCAGGGACCCAGCCT
AGGCTGGGTCCCTGGTGGC


 


4940
CCACCAGGGACCCAGCCTT
AAGGCTGGGTCCCTGGTGG


 


4941
CACCAGGGACCCAGCCTTC
GAAGGCTGGGTCCCTGGTG


 


4942
ACCAGGGACCCAGCCTTCC
GGAAGGCTGGGTCCCTGGT


 


4943
CCAGGGACCCAGCCTTCCC
GGGAAGGCTGGGTCCCTGG


 


4944
CAGGGACCCAGCCTTCCCC
GGGGAAGGCTGGGTCCCTG


 


4945
AGGGACCCAGCCTTCCCCC
GGGGGAAGGCTGGGTCCCT


 


4946
GGGACCCAGCCTTCCCCCT
AGGGGGAAGGCTGGGTCCC


 


4947
GGACCCAGCCTTCCCCCTG
CAGGGGGAAGGCTGGGTCC


 


4948
GACCCAGCCTTCCCCCTGA
TCAGGGGGAAGGCTGGGTC


 


4949
ACCCAGCCTTCCCCCTGAC
GTCAGGGGGAAGGCTGGGT


 


4950
CCCAGCCTTCCCCCTGACT
AGTCAGGGGGAAGGCTGGG


 


4951
CCAGCCTTCCCCCTGACTG
CAGTCAGGGGGAAGGCTGG


 


4952
CAGCCTTCCCCCTGACTGC
GCAGTCAGGGGGAAGGCTG


 


4953
AGCCTTCCCCCTGACTGCC
GGCAGTCAGGGGGAAGGCT


 


4954
GCCTTCCCCCTGACTGCCA
TGGCAGTCAGGGGGAAGGC


 


4955
CCTTCCCCCTGACTGCCAC
GTGGCAGTCAGGGGGAAGG


 


4956
CTTCCCCCTGACTGCCACC
GGTGGCAGTCAGGGGGAAG


 


4957
TTCCCCCTGACTGCCACCT
AGGTGGCAGTCAGGGGGAA


 


4958
TCCCCCTGACTGCCACCTG
CAGGTGGCAGTCAGGGGGA


 


4959
CCCCCTGACTGCCACCTGC
GCAGGTGGCAGTCAGGGGG


 


4960
CCCCTGACTGCCACCTGCT
AGCAGGTGGCAGTCAGGGG


 


4961
CCCTGACTGCCACCTGCTT
AAGCAGGTGGCAGTCAGGG


 


4962
CCTGACTGCCACCTGCTTT
AAAGCAGGTGGCAGTCAGG


 


4963
CTGACTGCCACCTGCTTTA
TAAAGCAGGTGGCAGTCAG


 


4964
TGACTGCCACCTGCTTTAT
ATAAAGCAGGTGGCAGTCA


 


4965
GACTGCCACCTGCTTTATG
CATAAAGCAGGTGGCAGTC


 


4966
ACTGCCACCTGCTTTATGC
GCATAAAGCAGGTGGCAGT


 


4967
CTGCCACCTGCTTTATGCC
GGCATAAAGCAGGTGGCAG


 


4968
TGCCACCTGCTTTATGCCC
GGGCATAAAGCAGGTGGCA


 


4969
GCCACCTGCTTTATGCCCA
TGGGCATAAAGCAGGTGGC


 


4970
CCACCTGCTTTATGCCCAG
CTGGGCATAAAGCAGGTGG


 


4971
CACCTGCTTTATGCCCAGA
TCTGGGCATAAAGCAGGTG


 


4972
ACCTGCTTTATGCCCAGAT
ATCTGGGCATAAAGCAGGT


 


4973
CCTGCTTTATGCCCAGATG
CATCTGGGCATAAAGCAGG


 


4974
CTGCTTTATGCCCAGATGG
CCATCTGGGCATAAAGCAG


 


4975
TGCTTTATGCCCAGATGGA
TCCATCTGGGCATAAAGCA


 


4976
GCTTTATGCCCAGATGGAC
GTCCATCTGGGCATAAAGC


 


4977
CTTTATGCCCAGATGGACT
AGTCCATCTGGGCATAAAG


 


4978
TTTATGCCCAGATGGACTG
CAGTCCATCTGGGCATAAA


 


4979
TTATGCCCAGATGGACTGG
CCAGTCCATCTGGGCATAA


 


4980
TATGCCCAGATGGACTGGG
CCCAGTCCATCTGGGCATA


 


4981
ATGCCCAGATGGACTGGGC
GCCCAGTCCATCTGGGCAT


 


4982
TGCCCAGATGGACTGGGCT
AGCCCAGTCCATCTGGGCA


 


4983
GCCCAGATGGACTGGGCTG
CAGCCCAGTCCATCTGGGC


 


4984
CCCAGATGGACTGGGCTGT
ACAGCCCAGTCCATCTGGG


 


4985
CCAGATGGACTGGGCTGTG
CACAGCCCAGTCCATCTGG


 


4986
CAGATGGACTGGGCTGTGT
ACACAGCCCAGTCCATCTG


 


4987
AGATGGACTGGGCTGTGTT
AACACAGCCCAGTCCATCT


 


4988
GATGGACTGGGCTGTGTTC
GAACACAGCCCAGTCCATC


 


4989
ATGGACTGGGCTGTGTTCC
GGAACACAGCCCAGTCCAT


 


4990
TGGACTGGGCTGTGTTCCA
TGGAACACAGCCCAGTCCA


 


4991
GGACTGGGCTGTGTTCCAA
TTGGAACACAGCCCAGTCC


 


4992
GACTGGGCTGTGTTCCAAG
CTTGGAACACAGCCCAGTC


 


4993
ACTGGGCTGTGTTCCAAGC
GCTTGGAACACAGCCCAGT


 


4994
CTGGGCTGTGTTCCAAGCA
TGCTTGGAACACAGCCCAG


 


4995
TGGGCTGTGTTCCAAGCAG
CTGCTTGGAACACAGCCCA


 


4996
GGGCTGTGTTCCAAGCAGT
ACTGCTTGGAACACAGCCC


 


4997
GGCTGTGTTCCAAGCAGTG
CACTGCTTGGAACACAGCC


 


4998
GCTGTGTTCCAAGCAGTGA
TCACTGCTTGGAACACAGC


 


4999
CTGTGTTCCAAGCAGTGAA
TTCACTGCTTGGAACACAG


 


5000
TGTGTTCCAAGCAGTGAAG
CTTCACTGCTTGGAACACA


 


5001
GTGTTCCAAGCAGTGAAGG
CCTTCACTGCTTGGAACAC


 


5002
TGTTCCAAGCAGTGAAGGT
ACCTTCACTGCTTGGAACA


 


5003
GTTCCAAGCAGTGAAGGTG
CACCTTCACTGCTTGGAAC


 


5004
TTCCAAGCAGTGAAGGTGG
CCACCTTCACTGCTTGGAA


 


5005
TCCAAGCAGTGAAGGTGGC
GCCACCTTCACTGCTTGGA


 


5006
CCAAGCAGTGAAGGTGGCC
GGCCACCTTCACTGCTTGG


 


5007
CAAGCAGTGAAGGTGGCCG
CGGCCACCTTCACTGCTTG


 


5008
AAGCAGTGAAGGTGGCCGT
ACGGCCACCTTCACTGCTT


 


5009
AGCAGTGAAGGTGGCCGTG
CACGGCCACCTTCACTGCT


 


5010
GCAGTGAAGGTGGCCGTGG
CCACGGCCACCTTCACTGC


 


5011
CAGTGAAGGTGGCCGTGGG
CCCACGGCCACCTTCACTG


 


5012
AGTGAAGGTGGCCGTGGGG
CCCCACGGCCACCTTCACT


 


5013
GTGAAGGTGGCCGTGGGGA
TCCCCACGGCCACCTTCAC


 


5014
TGAAGGTGGCCGTGGGGAC
GTCCCCACGGCCACCTTCA


 


5015
GAAGGTGGCCGTGGGGACA
TGTCCCCACGGCCACCTTC


 


5016
AAGGTGGCCGTGGGGACAT
ATGTCCCCACGGCCACCTT


 


5017
AGGTGGCCGTGGGGACATT
AATGTCCCCACGGCCACCT


 


5018
GGTGGCCGTGGGGACATTA
TAATGTCCCCACGGCCACC


 


5019
GTGGCCGTGGGGACATTAC
GTAATGTCCCCACGGCCAC


 


5020
TGGCCGTGGGGACATTACA
TGTAATGTCCCCACGGCCA


 


5021
GGCCGTGGGGACATTACAG
CTGTAATGTCCCCACGGCC


 


5022
GCCGTGGGGACATTACAGG
CCTGTAATGTCCCCACGGC


 


5023
CCGTGGGGACATTACAGGA
TCCTGTAATGTCCCCACGG


 


5024
CGTGGGGACATTACAGGAG
CTCCTGTAATGTCCCCACG


 


5025
GTGGGGACATTACAGGAGG
CCTCCTGTAATGTCCCCAC


 


5026
TGGGGACATTACAGGAGGC
GCCTCCTGTAATGTCCCCA


 


5027
GGGGACATTACAGGAGGCC
GGCCTCCTGTAATGTCCCC


 


5028
GGGACATTACAGGAGGCCA
TGGCCTCCTGTAATGTCCC


 


5029
GGACATTACAGGAGGCCAA
TTGGCCTCCTGTAATGTCC


 


5030
GACATTACAGGAGGCCAAA
TTTGGCCTCCTGTAATGTC


 


5031
ACATTACAGGAGGCCAAAT
ATTTGGCCTCCTGTAATGT


 


5032
CATTACAGGAGGCCAAATA
TATTTGGCCTCCTGTAATG


 


5033
ATTACAGGAGGCCAAATAG
CTATTTGGCCTCCTGTAAT


 


5034
TTACAGGAGGCCAAATAGA
TCTATTTGGCCTCCTGTAA


 


5035
TACAGGAGGCCAAATAGAG
CTCTATTTGGCCTCCTGTA


 


5036
ACAGGAGGCCAAATAGAGG
CCTCTATTTGGCCTCCTGT


 


5037
CAGGAGGCCAAATAGAGGG
CCCTCTATTTGGCCTCCTG


 


5038
AGGAGGCCAAATAGAGGGA
TCCCTCTATTTGGCCTCCT


 


5039
GGAGGCCAAATAGAGGGAT
ATCCCTCTATTTGGCCTCC


 


5040
GAGGCCAAATAGAGGGATG
CATCCCTCTATTTGGCCTC


 


5041
AGGCCAAATAGAGGGATGC
GCATCCCTCTATTTGGCCT


 


5042
GGCCAAATAGAGGGATGCT
AGCATCCCTCTATTTGGCC


 


5043
GCCAAATAGAGGGATGCTA
TAGCATCCCTCTATTTGGC


 


5044
CCAAATAGAGGGATGCTAG
CTAGCATCCCTCTATTTGG


 


5045
CAAATAGAGGGATGCTAGG
CCTAGCATCCCTCTATTTG


 


5046
AAATAGAGGGATGCTAGGT
ACCTAGCATCCCTCTATTT


 


5047
AATAGAGGGATGCTAGGTG
CACCTAGCATCCCTCTATT


 


5048
ATAGAGGGATGCTAGGTGT
ACACCTAGCATCCCTCTAT


 


5049
TAGAGGGATGCTAGGTGTC
GACACCTAGCATCCCTCTA


 


5050
AGAGGGATGCTAGGTGTCT
AGACACCTAGCATCCCTCT


 


5051
GAGGGATGCTAGGTGTCTG
CAGACACCTAGCATCCCTC


 


5052
AGGGATGCTAGGTGTCTGG
CCAGACACCTAGCATCCCT


 


5053
GGGATGCTAGGTGTCTGGG
CCCAGACACCTAGCATCCC


 


5054
GGATGCTAGGTGTCTGGGA
TCCCAGACACCTAGCATCC


 


5055
GATGCTAGGTGTCTGGGAT
ATCCCAGACACCTAGCATC


 


5056
ATGCTAGGTGTCTGGGATC
GATCCCAGACACCTAGCAT


 


5057
TGCTAGGTGTCTGGGATCG
CGATCCCAGACACCTAGCA


 


5058
GCTAGGTGTCTGGGATCGG
CCGATCCCAGACACCTAGC


 


5059
CTAGGTGTCTGGGATCGGG
CCCGATCCCAGACACCTAG


 


5060
TAGGTGTCTGGGATCGGGG
CCCCGATCCCAGACACCTA


 


5061
AGGTGTCTGGGATCGGGGT
ACCCCGATCCCAGACACCT


 


5062
GGTGTCTGGGATCGGGGTG
CACCCCGATCCCAGACACC


 


5063
GTGTCTGGGATCGGGGTGG
CCACCCCGATCCCAGACAC


 


5064
TGTCTGGGATCGGGGTGGG
CCCACCCCGATCCCAGACA


 


5065
GTCTGGGATCGGGGTGGGG
CCCCACCCCGATCCCAGAC


 


5066
TCTGGGATCGGGGTGGGGA
TCCCCACCCCGATCCCAGA


 


5067
CTGGGATCGGGGTGGGGAC
GTCCCCACCCCGATCCCAG


 


5068
TGGGATCGGGGTGGGGACA
TGTCCCCACCCCGATCCCA


 


5069
GGGATCGGGGTGGGGACAG
CTGTCCCCACCCCGATCCC


 


5070
GGATCGGGGTGGGGACAGG
CCTGTCCCCACCCCGATCC


 


5071
GATCGGGGTGGGGACAGGT
ACCTGTCCCCACCCCGATC


 


5072
ATCGGGGTGGGGACAGGTA
TACCTGTCCCCACCCCGAT


 


5073
TCGGGGTGGGGACAGGTAG
CTACCTGTCCCCACCCCGA


 


5074
CGGGGTGGGGACAGGTAGA
TCTACCTGTCCCCACCCCG


 


5075
GGGGTGGGGACAGGTAGAC
GTCTACCTGTCCCCACCCC


 


5076
GGGTGGGGACAGGTAGACC
GGTCTACCTGTCCCCACCC


 


5077
GGTGGGGACAGGTAGACCA
TGGTCTACCTGTCCCCACC


 


5078
GTGGGGACAGGTAGACCAG
CTGGTCTACCTGTCCCCAC


 


5079
TGGGGACAGGTAGACCAGG
CCTGGTCTACCTGTCCCCA


 


5080
GGGGACAGGTAGACCAGGT
ACCTGGTCTACCTGTCCCC


 


5081
GGGACAGGTAGACCAGGTG
CACCTGGTCTACCTGTCCC


 


5082
GGACAGGTAGACCAGGTGC
GCACCTGGTCTACCTGTCC


 


5083
GACAGGTAGACCAGGTGCT
AGCACCTGGTCTACCTGTC


 


5084
ACAGGTAGACCAGGTGCTC
GAGCACCTGGTCTACCTGT


 


5085
CAGGTAGACCAGGTGCTCA
TGAGCACCTGGTCTACCTG


 


5086
AGGTAGACCAGGTGCTCAG
CTGAGCACCTGGTCTACCT


 


5087
GGTAGACCAGGTGCTCAGC
GCTGAGCACCTGGTCTACC


 


5088
GTAGACCAGGTGCTCAGCC
GGCTGAGCACCTGGTCTAC


 


5089
TAGACCAGGTGCTCAGCCC
GGGCTGAGCACCTGGTCTA


 


5090
AGACCAGGTGCTCAGCCCA
TGGGCTGAGCACCTGGTCT


 


5091
GACCAGGTGCTCAGCCCAG
CTGGGCTGAGCACCTGGTC


 


5092
ACCAGGTGCTCAGCCCAGG
CCTGGGCTGAGCACCTGGT


 


5093
CCAGGTGCTCAGCCCAGGC
GCCTGGGCTGAGCACCTGG


 


5094
CAGGTGCTCAGCCCAGGCA
TGCCTGGGCTGAGCACCTG


 


5095
AGGTGCTCAGCCCAGGCAC
GTGCCTGGGCTGAGCACCT


 


5096
GGTGCTCAGCCCAGGCACA
TGTGCCTGGGCTGAGCACC


 


5097
GTGCTCAGCCCAGGCACAA
TTGTGCCTGGGCTGAGCAC


 


5098
TGCTCAGCCCAGGCACAAC
GTTGTGCCTGGGCTGAGCA


 


5099
GCTCAGCCCAGGCACAACT
AGTTGTGCCTGGGCTGAGC


 


5100
CTCAGCCCAGGCACAACTT
AAGTTGTGCCTGGGCTGAG


 


5101
TCAGCCCAGGCACAACTTC
GAAGTTGTGCCTGGGCTGA


 


5102
CAGCCCAGGCACAACTTCA
TGAAGTTGTGCCTGGGCTG


 


5103
AGCCCAGGCACAACTTCAG
CTGAAGTTGTGCCTGGGCT


 


5104
GCCCAGGCACAACTTCAGC
GCTGAAGTTGTGCCTGGGC


 


5105
CCCAGGCACAACTTCAGCA
TGCTGAAGTTGTGCCTGGG


 


5106
CCAGGCACAACTTCAGCAG
CTGCTGAAGTTGTGCCTGG


 


5107
CAGGCACAACTTCAGCAGG
CCTGCTGAAGTTGTGCCTG


 


5108
AGGCACAACTTCAGCAGGG
CCCTGCTGAAGTTGTGCCT


 


5109
GGCACAACTTCAGCAGGGG
CCCCTGCTGAAGTTGTGCC


 


5110
GCACAACTTCAGCAGGGGA
TCCCCTGCTGAAGTTGTGC


 


5111
GACAACTTCAGCAGGGGAT
ATCCCCTGCTGAAGTTGTG


 


5112
ACAACTTCAGCAGGGGATG
CATCCCCTGCTGAAGTTGT


 


5113
CAACTTCAGCAGGGGATGG
CCATCCCCTGCTGAAGTTG


 


5114
AACTTCAGCAGGGGATGGC
GCCATCCCCTGCTGAAGTT


 


5115
ACTTCAGCAGGGGATGGCG
CGCCATCCCCTGCTGAAGT


 


5116
CTTCAGCAGGGGATGGCGC
GCGCCATCCCCTGCTGAAG


 


5117
TTCAGCAGGGGATGGCGCT
AGCGCCATCCCCTGCTGAA


 


5118
TCAGCAGGGGATGGCGCTA
TAGCGCCATCCCCTGCTGA


 


5119
CAGCAGGGGATGGCGCTAG
CTAGCGCCATCCCCTGCTG


 


5120
AGCAGGGGATGGCGCTAGG
CCTAGCGCCATCCCCTGCT


 


5121
GCAGGGGATGGCGCTAGGG
CCCTAGCGCCATCCCCTGC


 


5122
CAGGGGATGGCGCTAGGGG
CCCCTAGCGCCATCCCCTG


 


5123
AGGGGATGGCGCTAGGGGA
TCCCCTAGCGCCATCCCCT


 


5124
GGGGATGGCGCTAGGGGAC
GTCCCCTAGCGCCATCCCC


 


5125
GGGATGGCGCTAGGGGACT
AGTCCCCTAGCGCCATCCC


 


5126
GGATGGCGCTAGGGGACTT
AAGTCCCCTAGCGCCATCC


 


5127
GATGGCGCTAGGGGACTTG
CAAGTCCCCTAGCGCCATC


 


5128
ATGGCGCTAGGGGACTTGG
CCAAGTCCCCTAGCGCCAT


 


5129
TGGCGCTAGGGGACTTGGG
CCCAAGTCCCCTAGCGCCA


 


5130
GGCGCTAGGGGACTTGGGG
CCCCAAGTCCCCTAGCGCC


 


5131
GCGCTAGGGGACTTGGGGA
TCCCCAAGTCCCCTAGCGC


 


5132
CGCTAGGGGACTTGGGGAT
ATCCCCAAGTCCCCTAGCG


 


5133
GCTAGGGGACTTGGGGATT
AATCCCCAAGTCCCCTAGC


 


5134
CTAGGGGACTTGGGGATTT
AAATCCCCAAGTCCCCTAG


 


5135
TAGGGGACTTGGGGATTTC
GAAATCCCCAAGTCCCCTA


 


5136
AGGGGACTTGGGGATTTCT
AGAAATCCCCAAGTCCCCT


 


5137
GGGGACTTGGGGATTTCTG
CAGAAATCCCCAAGTCCCC


 


5138
GGGACTTGGGGATTTCTGG
CCAGAAATCCCCAAGTCCC


 


5139
GGACTTGGGGATTTCTGGT
ACCAGAAATCCCCAAGTCC


 


5140
GACTTGGGGATTTCTGGTC
GACCAGAAATCCCCAAGTC


 


5141
ACTTGGGGATTTCTGGTCA
TGACCAGAAATCCCCAAGT


 


5142
CTTGGGGATTTCTGGTCAA
TTGACCAGAAATCCCCAAG


 


5143
TTGGGGATTTCTGGTCAAC
GTTGACCAGAAATCCCCAA


 


5144
TGGGGATTTCTGGTCAACC
GGTTGACCAGAAATCCCCA


 


5145
GGGGATTTCTGGTCAACCC
GGGTTGACCAGAAATCCCC


 


5146
GGGATTTCTGGTCAACCCC
GGGGTTGACCAGAAATCCC


 


5147
GGATTTCTGGTCAACCCCA
TGGGGTTGACCAGAAATCC


 


5148
GATTTCTGGTCAACCCCAC
GTGGGGTTGACCAGAAATC


 


5149
ATTTCTGGTCAACCCCACA
TGTGGGGTTGACCAGAAAT


 


5150
TTTCTGGTCAACCCCACAA
TTGTGGGGTTGACCAGAAA


 


5151
TTCTGGTCAACCCCACAAG
CTTGTGGGGTTGACCAGAA


 


5152
TCTGGTCAACCCCACAAGC
GCTTGTGGGGTTGACCAGA


 


5153
CTGGTCAACCCCACAAGCA
TGCTTGTGGGGTTGACCAG


 


5154
TGGTCAACCCCACAAGCAC
GTGCTTGTGGGGTTGACCA


 


5155
GGTCAACCCCACAAGCACC
GGTGCTTGTGGGGTTGACC


 


5156
GTCAACCCCACAAGCACCA
TGGTGCTTGTGGGGTTGAC


 


5157
TCAACCCCACAAGCACCAC
GTGGTGCTTGTGGGGTTGA


 


5158
CAACCCCACAAGCACCACT
AGTGGTGCTTGTGGGGTTG


 


5159
AACCCCACAAGCACCACTC
GAGTGGTGCTTGTGGGGTT


 


5160
ACCCCACAAGCACCACTCT
AGAGTGGTGCTTGTGGGGT


 


5161
CCCCACAAGCACCACTCTG
CAGAGTGGTGCTTGTGGGG


 


5162
CCCACAAGCACCACTCTGG
CCAGAGTGGTGCTTGTGGG


 


5163
CCACAAGCACCACTCTGGG
CCCAGAGTGGTGCTTGTGG


 


5164
CACAAGCACCACTCTGGGC
GCCCAGAGTGGTGCTTGTG


 


5165
ACAAGCACCACTCTGGGCA
TGCCCAGAGTGGTGCTTGT


 


5166
CAAGCACCACTCTGGGCAC
GTGCCCAGAGTGGTGCTTG


 


5167
AAGCACCACTCTGGGCACA
TGTGCCCAGAGTGGTGCTT


 


5168
AGCACCACTCTGGGCACAA
TTGTGCCCAGAGTGGTGCT


 


5169
GCACCACTCTGGGCACAAG
CTTGTGCCCAGAGTGGTGC


 


5170
CACCACTCTGGGCACAAGC
GCTTGTGCCCAGAGTGGTG


 


5171
ACCACTCTGGGCACAAGCA
TGCTTGTGCCCAGAGTGGT


 


5172
CCACTCTGGGCACAAGCAG
CTGCTTGTGCCCAGAGTGG


 


5173
CACTCTGGGCACAAGCAGG
CCTGCTTGTGCCCAGAGTG


 


5174
ACTCTGGGCACAAGCAGGG
CCCTGCTTGTGCCCAGAGT


 


5175
CTCTGGGCACAAGCAGGGC
GCCCTGCTTGTGCCCAGAG


 


5176
TCTGGGCACAAGCAGGGCA
TGCCCTGCTTGTGCCCAGA


 


5177
CTGGGCACAAGCAGGGCAC
GTGCCCTGCTTGTGCCCAG


 


5178
TGGGCACAAGCAGGGCACT
AGTGCCCTGCTTGTGCCCA


 


5179
GGGCACAAGCAGGGCACTC
GAGTGCCCTGCTTGTGCCC


 


5180
GGCACAAGCAGGGCACTCT
AGAGTGCCCTGCTTGTGCC


 


5181
GCACAAGCAGGGCACTCTG
CAGAGTGCCCTGCTTGTGC


 


5182
CACAAGCAGGGCACTCTGT
ACAGAGTGCCCTGCTTGTG


 


5183
ACAAGCAGGGCACTCTGTT
AACAGAGTGCCCTGCTTGT


 


5184
CAAGCAGGGCACTCTGTTC
GAACAGAGTGCCCTGCTTG


 


5185
AAGCAGGGCACTCTGTTCC
GGAACAGAGTGCCCTGCTT


 


5186
AGCAGGGCACTCTGTTCCC
GGGAACAGAGTGCCCTGCT


 


5187
GCAGGGCACTCTGTTCCCC
GGGGAACAGAGTGCCCTGC


 


5188
CAGGGCACTCTGTTCCCCT
AGGGGAACAGAGTGCCCTG


 


5189
AGGGCACTCTGTTCCCCTC
GAGGGGAACAGAGTGCCCT


 


5190
GGGCACTCTGTTCCCCTCC
GGAGGGGAACAGAGTGCCC


 


5191
GGCACTCTGTTCCCCTCCC
GGGAGGGGAACAGAGTGCC


 


5192
GCACTCTGTTCCCCTCCCC
GGGGAGGGGAACAGAGTGC


 


5193
CACTCTGTTCCCCTCCCCC
GGGGGAGGGGAACAGAGTG


 


5194
ACTCTGTTCCCCTCCCCCT
AGGGGGAGGGGAACAGAGT


 


5195
CTCTGTTCCCCTCCCCCTT
AAGGGGGAGGGGAACAGAG


 


5196
TCTGTTCCCCTCCCCCTTA
TAAGGGGGAGGGGAACAGA


 


5197
CTGTTCCCCTCCCCCTTAA
TTAAGGGGGAGGGGAACAG


 


5198
TGTTCCCCTCCCCCTTAAG
CTTAAGGGGGAGGGGAACA


 


5199
GTTCCCCTCCCCCTTAAGC
GCTTAAGGGGGAGGGGAAC


 


5200
TTCCCCTCCCCCTTAAGCC
GGCTTAAGGGGGAGGGGAA


 


5201
TCCCCTCCCCCTTAAGCCA
TGGCTTAAGGGGGAGGGGA


 


5202
CCCCTCCCCCTTAAGCCAA
TTGGCTTAAGGGGGAGGGG


 


5203
CCCTCCCCCTTAAGCCAAC
GTTGGCTTAAGGGGGAGGG


 


5204
CCTCCCCCTTAAGCCAACA
TGTTGGCTTAAGGGGGAGG


 


5205
CTCCCCCTTAAGCCAACAA
TTGTTGGCTTAAGGGGGAG


 


5206
TCCCCCTTAAGCCAACAAC
GTTGTTGGCTTAAGGGGGA


 


5207
CCCCCTTAAGCCAACAACC
GGTTGTTGGCTTAAGGGGG


 


5208
CCCCTTAAGCCAACAACCA
TGGTTGTTGGCTTAAGGGG


 


5209
CCCTTAAGCCAACAACCAC
GTGGTTGTTGGCTTAAGGG


 


5210
CCTTAAGCCAACAACCACA
TGTGGTTGTTGGCTTAAGG


 


5211
CTTAAGCCAACAACCACAG
CTGTGGTTGTTGGCTTAAG


 


5212
TTAAGCCAACAACCACAGT
ACTGTGGTTGTTGGCTTAA


 


5213
TAAGCCAACAACCACAGTG
CACTGTGGTTGTTGGCTTA


 


5214
AAGCCAACAACCACAGTGC
GCACTGTGGTTGTTGGCTT


 


5215
AGCCAACAACCACAGTGCC
GGCACTGTGGTTGTTGGCT


 


5216
GCCAACAACCACAGTGCCA
TGGCACTGTGGTTGTTGGC


 


5217
CCAACAACCACAGTGCCAC
GTGGCACTGTGGTTGTTGG


 


5218
CAACAACCACAGTGCCACC
GGTGGCACTGTGGTTGTTG


 


5219
AACAACCACAGTGCCACCA
TGGTGGCACTGTGGTTGTT


 


5220
ACAACCACAGTGCCACCAA
TTGGTGGCACTGTGGTTGT


 


5221
CAACCACAGTGCCACCAAG
CTTGGTGGCACTGTGGTTG


 


5222
AACCACAGTGCCACCAAGC
GCTTGGTGGCACTGTGGTT


 


5223
ACCACAGTGCCACCAAGCT
AGCTTGGTGGCACTGTGGT


 


5224
CCACAGTGCCACCAAGCTC
GAGCTTGGTGGCACTGTGG


 


5225
CACAGTGCCACCAAGCTCA
TGAGCTTGGTGGCACTGTG


 


5226
ACAGTGCCACCAAGCTCAC
GTGAGCTTGGTGGCACTGT


 


5227
CAGTGCCACCAAGCTCACA
TGTGAGCTTGGTGGCACTG


 


5228
AGTGCCACCAAGCTCACAC
GTGTGAGCTTGGTGGCACT


 


5229
GTGCCACCAAGCTCACACC
GGTGTGAGCTTGGTGGCAC


 


5230
TGCCACCAAGCTCACACCT
AGGTGTGAGCTTGGTGGCA


 


5231
GCCACCAAGCTCACACCTG
CAGGTGTGAGCTTGGTGGC


 


5232
CCACCAAGCTCACACCTGT
ACAGGTGTGAGCTTGGTGG


 


5233
CACCAAGCTCACACCTGTC
GACAGGTGTGAGCTTGGTG


 


5234
ACCAAGCTCACACCTGTCC
GGACAGGTGTGAGCTTGGT


 


5235
CCAAGCTCACACCTGTCCT
AGGACAGGTGTGAGCTTGG


 


5236
CAAGCTCACACCTGTCCTT
AAGGACAGGTGTGAGCTTG


 


5237
AAGCTCACACCTGTCCTTC
GAAGGACAGGTGTGAGCTT


 


5238
AGCTCACACCTGTCCTTCT
AGAAGGACAGGTGTGAGCT


 


5239
GCTCACACCTGTCCTTCTC
GAGAAGGACAGGTGTGAGC


 


5240
CTCACACCTGTCCTTCTCA
TGAGAAGGACAGGTGTGAG


 


5241
TCACACCTGTCCTTCTCAG
CTGAGAAGGACAGGTGTGA


 


5242
CACACCTGTCCTTCTCAGG
CCTGAGAAGGACAGGTGTG


 


5243
ACACCTGTCCTTCTCAGGC
GCCTGAGAAGGACAGGTGT


 


5244
CACCTGTCCTTCTCAGGCT
AGCCTGAGAAGGACAGGTG


 


5245
ACCTGTCCTTCTCAGGCTG
CAGCCTGAGAAGGACAGGT


 


5246
CCTGTCCTTCTCAGGCTGG
CCAGCCTGAGAAGGACAGG


 


5247
CTGTCCTTCTCAGGCTGGC
GCCAGCCTGAGAAGGACAG


 


5248
TGTCCTTCTCAGGCTGGCA
TGCCAGCCTGAGAAGGACA


 


5249
GTCCTTCTCAGGCTGGCAT
ATGCCAGCCTGAGAAGGAC


 


5250
TCCTTCTCAGGCTGGCATC
GATGCCAGCCTGAGAAGGA


 


5251
CCTTCTCAGGCTGGCATCT
AGATGCCAGCCTGAGAAGG


 


5252
CTTCTCAGGCTGGCATCTC
GAGATGCCAGCCTGAGAAG


 


5253
TTCTCAGGCTGGCATCTCC
GGAGATGCCAGCCTGAGAA


 


5254
TCTCAGGCTGGCATCTCCC
GGGAGATGCCAGCCTGAGA


 


5255
CTCAGGCTGGCATCTCCCC
GGGGAGATGCCAGCCTGAG


 


5256
TCAGGCTGGCATCTCCCCC
GGGGGAGATGCCAGCCTGA


 


5257
CAGGCTGGCATCTCCCCCA
TGGGGGAGATGCCAGCCTG


 


5258
AGGCTGGCATCTCCCCCAC
GTGGGGGAGATGCCAGCCT


 


5259
GGCTGGCATCTCCCCCACC
GGTGGGGGAGATGCCAGCC


 


5260
GCTGGCATCTCCCCCACCC
GGGTGGGGGAGATGCCAGC


 


5261
CTGGCATCTCCCCCACCCT
AGGGTGGGGGAGATGCCAG


 


5262
TGGCATCTCCCCCACCCTG
CAGGGTGGGGGAGATGCCA


 


5263
GGCATCTCCCCCACCCTGT
ACAGGGTGGGGGAGATGCC


 


5264
GCATCTCCCCCACCCTGTG
CACAGGGTGGGGGAGATGC


 


5265
CATCTCCCCCACCCTGTGC
GCACAGGGTGGGGGAGATG


 


5266
ATCTCCCCCACCCTGTGCC
GGCACAGGGTGGGGGAGAT


 


5267
TCTCCCCCACCCTGTGCCC
GGGCACAGGGTGGGGGAGA


 


5268
CTCCCCCACCCTGTGCCCC
GGGGCACAGGGTGGGGGAG


 


5269
TCCCCCACCCTGTGCCCCT
AGGGGCACAGGGTGGGGGA


 


5270
CCCCCACCCTGTGCCCCTT
AAGGGGCACAGGGTGGGGG


 


5271
CCCCACCCTGTGCCCCTTT
AAAGGGGCACAGGGTGGGG


 


5272
CCCACCCTGTGCCCCTTTT
AAAAGGGGCACAGGGTGGG


 


5273
CCACCCTGTGCCCCTTTTC
GAAAAGGGGCACAGGGTGG


 


5274
CACCCTGTGCCCCTTTTCA
TGAAAAGGGGCACAGGGTG


 


5275
ACCCTGTGCCCCTTTTCAT
ATGAAAAGGGGCACAGGGT


 


5276
CCCTGTGCCCCTTTTCATG
CATGAAAAGGGGCACAGGG


 


5277
CCTGTGCCCCTTTTCATGG
CCATGAAAAGGGGCACAGG


 


5278
CTGTGCCCCTTTTCATGGT
ACCATGAAAAGGGGCACAG


 


5279
TGTGCCCCTTTTCATGGTA
TACCATGAAAAGGGGCACA


 


5280
GTGCCCCTTTTCATGGTAC
GTACCATGAAAAGGGGCAC


 


5281
TGCCCCTTTTCATGGTACC
GGTACCATGAAAAGGGGCA


 


5282
GCCCCTTTTCATGGTACCA
TGGTACCATGAAAAGGGGC


 


5283
CCCCTTTTCATGGTACCAG
CTGGTACCATGAAAAGGGG


 


5284
CCCTTTTCATGGTACCAGG
CCTGGTACCATGAAAAGGG


 


5285
CCTTTTCATGGTACCAGGC
GCCTGGTACCATGAAAAGG


 


5286
CTTTTCATGGTACCAGGCC
GGCCTGGTACCATGAAAAG


 


5287
TTTTCATGGTACCAGGCCC
GGGCCTGGTACCATGAAAA


 


5288
TTTCATGGTACCAGGCCCG
CGGGCCTGGTACCATGAAA


 


5289
TTCATGGTACCAGGCCCGC
GCGGGCCTGGTACCATGAA


 


5290
TCATGGTACCAGGCCCGCA
TGCGGGCCTGGTACCATGA


 


5291
CATGGTACCAGGCCCGCAC
GTGCGGGCCTGGTACCATG


 


5292
ATGGTACCAGGCCCGCACT
AGTGCGGGCCTGGTACCAT


 


5293
TGGTACCAGGCCCGCACTG
CAGTGCGGGCCTGGTACCA


 


5294
GGTACCAGGCCCGCACTGG
CCAGTGCGGGCCTGGTACC


 


5295
GTACCAGGCCCGCACTGGG
CCCAGTGCGGGCCTGGTAC


 


5296
TACCAGGCCCGCACTGGGG
CCCCAGTGCGGGCCTGGTA


 


5297
ACCAGGCCCGCACTGGGGG
CCCCCAGTGCGGGCCTGGT


 


5298
CCAGGCCCGCACTGGGGGC
GCCCCCAGTGCGGGCCTGG


 


5299
CAGGCCCGCACTGGGGGCA
TGCCCCCAGTGCGGGCCTG


 


5300
AGGCCCGCACTGGGGGCAA
TTGCCCCCAGTGCGGGCCT


 


5301
GGCCCGCACTGGGGGCAAT
ATTGCCCCCAGTGCGGGCC


 


5302
GCCCGCACTGGGGGCAATT
AATTGCCCCCAGTGCGGGC


 


5303
CCCGCACTGGGGGCAATTG
CAATTGCCCCCAGTGCGGG


 


5304
CCGCACTGGGGGCAATTGA
TCAATTGCCCCCAGTGCGG


 


5305
CGCACTGGGGGCAATTGAC
GTCAATTGCCCCCAGTGCG


 


5306
GCACTGGGGGCAATTGACT
AGTCAATTGCCCCCAGTGC


 


5307
CACTGGGGGCAATTGACTT
AAGTCAATTGCCCCCAGTG


 


5308
ACTGGGGGCAATTGACTTC
GAAGTCAATTGCCCCCAGT


 


5309
CTGGGGGCAATTGACTTCC
GGAAGTCAATTGCCCCCAG


 


5310
TGGGGGCAATTGACTTCCT
AGGAAGTCAATTGCCCCCA


 


5311
GGGGGCAATTGACTTCCTC
GAGGAAGTCAATTGCCCCC


 


5312
GGGGCAATTGACTTCCTCC
GGAGGAAGTCAATTGCCCC


 


5313
GGGCAATTGACTTCCTCCA
TGGAGGAAGTCAATTGCCC


 


5314
GGCAATTGACTTCCTCCAA
TTGGAGGAAGTCAATTGCC


 


5315
GCAATTGACTTCCTCCAAT
ATTGGAGGAAGTCAATTGC


 


5316
CAATTGACTTCCTCCAATC
GATTGGAGGAAGTCAATTG


 


5317
AATTGACTTCCTCCAATCC
GGATTGGAGGAAGTCAATT


 


5318
ATTGACTTCCTCCAATCCC
GGGATTGGAGGAAGTCAAT


 


5319
TTGACTTCCTCCAATCCCC
GGGGATTGGAGGAAGTCAA


 


5320
TGACTTCCTCCAATCCCCA
TGGGGATTGGAGGAAGTCA


 


5321
GACTTCCTCCAATCCCCAC
GTGGGGATTGGAGGAAGTC


 


5322
ACTTCCTCCAATCCCCACT
AGTGGGGATTGGAGGAAGT


 


5323
CTTCCTCCAATCCCCACTC
GAGTGGGGATTGGAGGAAG


 


5324
TTCCTCCAATCCCCACTCC
GGAGTGGGGATTGGAGGAA


 


5325
TCCTCCAATCCCCACTCCT
AGGAGTGGGGATTGGAGGA


 


5326
CCTCCAATCCCCACTCCTC
GAGGAGTGGGGATTGGAGG


 


5327
CTCCAATCCCCACTCCTCC
GGAGGAGTGGGGATTGGAG


 


5328
TCCAATCCCCACTCCTCCG
CGGAGGAGTGGGGATTGGA


 


5329
CCAATCCCCACTCCTCCGA
TCGGAGGAGTGGGGATTGG


 


5330
CAATCCCCACTCCTCCGAG
CTCGGAGGAGTGGGGATTG


 


5331
AATCCCCACTCCTCCGAGA
TCTCGGAGGAGTGGGGATT


 


5332
ATCCCCACTCCTCCGAGAC
GTCTCGGAGGAGTGGGGAT


 


5333
TCCCCACTCCTCCGAGACC
GGTCTCGGAGGAGTGGGGA


 


5334
CCCCACTCCTCCGAGACCC
GGGTCTCGGAGGAGTGGGG


 


5335
CCCACTCCTCCGAGACCCA
TGGGTCTCGGAGGAGTGGG


 


5336
CCACTCCTCCGAGACCCAG
CTGGGTCTCGGAGGAGTGG


 


5337
CACTCCTCCGAGACCCAGG
CCTGGGTCTCGGAGGAGTG


 


5338
ACTCCTCCGAGACCCAGGA
TCCTGGGTCTCGGAGGAGT


 


5339
CTCCTCCGAGACCCAGGAG
CTCCTGGGTCTCGGAGGAG


 


5340
TCCTCCGAGACCCAGGAGA
TCTCCTGGGTCTCGGAGGA


 


5341
CCTCCGAGACCCAGGAGAC
GTCTCCTGGGTCTCGGAGG


 


5342
CTCCGAGACCCAGGAGACA
TGTCTCCTGGGTCTCGGAG


 


5343
TCCGAGACCCAGGAGACAA
TTGTCTCCTGGGTCTCGGA


 


5344
CCGAGACCCAGGAGACAAA
TTTGTCTCCTGGGTCTCGG


 


5345
CGAGACCCAGGAGACAAAC
GTTTGTCTCCTGGGTCTCG


 


5346
GAGACCCAGGAGACAAACA
TGTTTGTCTCCTGGGTCTC


 


5347
AGACCCAGGAGACAAACAG
CTGTTTGTCTCCTGGGTCT


 


5348
GACCCAGGAGACAAACAGC
GCTGTTTGTCTCCTGGGTC


 


5349
ACCCAGGAGACAAACAGCC
GGCTGTTTGTCTCCTGGGT


 


5350
CCCAGGAGACAAACAGCCC
GGGCTGTTTGTCTCCTGGG


 


5351
CCAGGAGACAAACAGCCCT
AGGGCTGTTTGTCTCCTGG


 


5352
CAGGAGACAAACAGCCCTT
AAGGGCTGTTTGTCTCCTG


 


5353
AGGAGACAAACAGCCCTTC
GAAGGGCTGTTTGTCTCCT


 


5354
GGAGACAAACAGCCCTTCC
GGAAGGGCTGTTTGTCTCC


 


5355
GAGACAAACAGCCCTTCCT
AGGAAGGGCTGTTTGTCTC


 


5356
AGACAAACAGCCCTTCCTT
AAGGAAGGGCTGTTTGTCT


 


5357
GACAAACAGCCCTTCCTTG
CAAGGAAGGGCTGTTTGTC


 


5358
ACAAACAGCCCTTCCTTGG
CCAAGGAAGGGCTGTTTGT


 


5359
CAAACAGCCCTTCCTTGGG
CCCAAGGAAGGGCTGTTTG


 


5360
AAACAGCCCTTCCTTGGGG
CCCCAAGGAAGGGCTGTTT


 


5361
AACAGCCCTTCCTTGGGGA
TCCCCAAGGAAGGGCTGTT


 


5362
ACAGCCCTTCCTTGGGGAA
TTCCCCAAGGAAGGGCTGT


 


5363
CAGCCCTTCCTTGGGGAAA
TTTCCCCAAGGAAGGGCTG


 


5364
AGCCCTTCCTTGGGGAAAC
GTTTCCCCAAGGAAGGGCT


 


5365
GCCCTTCCTTGGGGAAACT
AGTTTCCCCAAGGAAGGGC


 


5366
CCCTTCCTTGGGGAAACTT
AAGTTTCCCCAAGGAAGGG


 


5367
CCTTCCTTGGGGAAACTTG
CAAGTTTCCCCAAGGAAGG


 


5368
CTTCCTTGGGGAAACTTGG
CCAAGTTTCCCCAAGGAAG


 


5369
TTCCTTGGGGAAACTTGGG
CCCAAGTTTCCCCAAGGAA


 


5370
TCCTTGGGGAAACTTGGGA
TCCCAAGTTTCCCCAAGGA


 


5371
CCTTGGGGAAACTTGGGAA
TTCCCAAGTTTCCCCAAGG


 


5372
CTTGGGGAAACTTGGGAAT
ATTCCCAAGTTTCCCCAAG


 


5373
TTGGGGAAACTTGGGAATC
GATTCCCAAGTTTCCCCAA


 


5374
TGGGGAAACTTGGGAATCA
TGATTCCCAAGTTTCCCCA


 


5375
GGGGAAACTTGGGAATCAT
ATGATTCCCAAGTTTCCCC


 


5376
GGGAAACTTGGGAATCATT
AATGATTCCCAAGTTTCCC


 


5377
GGAAACTTGGGAATCATTC
GAATGATTCCCAAGTTTCC


 


5378
GAAACTTGGGAATCATTCT
AGAATGATTCCCAAGTTTC


 


5379
AAACTTGGGAATCATTCTG
CAGAATGATTCCCAAGTTT


 


5380
AACTTGGGAATCATTCTGG
CCAGAATGATTCCCAAGTT


 


5381
ACTTGGGAATCATTCTGGC
GCCAGAATGATTCCCAAGT


 


5382
CTTGGGAATCATTCTGGCT
AGCCAGAATGATTCCCAAG


 


5383
TTGGGAATCATTCTGGCTT
AAGCCAGAATGATTCCCAA


 


5384
TGGGAATCATTCTGGCTTA
TAAGCCAGAATGATTCCCA


 


5385
GGGAATCATTCTGGCTTAA
TTAAGCCAGAATGATTCCC


 


5386
GGAATCATTCTGGCTTAAA
TTTAAGCCAGAATGATTCC


 


5387
GAATCATTCTGGCTTAAAC
GTTTAAGCCAGAATGATTC


 


5388
AATCATTCTGGCTTAAACA
TGTTTAAGCCAGAATGATT


 


5389
ATCATTCTGGCTTAAACAA
TTGTTTAAGCCAGAATGAT


 


5390
TCATTCTGGCTTAAACAAC
GTTGTTTAAGCCAGAATGA


 


5391
CATTCTGGCTTAAACAACA
TGTTGTTTAAGCCAGAATG


 


5392
ATTCTGGCTTAAACAACAC
GTGTTGTTTAAGCCAGAAT


 


5393
TTCTGGCTTAAACAACACC
GGTGTTGTTTAAGCCAGAA


 


5394
TCTGGCTTAAACAACACCT
AGGTGTTGTTTAAGCCAGA


 


5395
CTGGCTTAAACAACACCTC
GAGGTGTTGTTTAAGCCAG


 


5396
TGGCTTAAACAACACCTCC
GGAGGTGTTGTTTAAGCCA


 


5397
GGCTTAAACAACACCTCCT
AGGAGGTGTTGTTTAAGCC


 


5398
GCTTAAACAACACCTCCTC
GAGGAGGTGTTGTTTAAGC


 


5399
CTTAAACAACACCTCCTCC
GGAGGAGGTGTTGTTTAAG


 


5400
TTAAACAACACCTCCTCCT
AGGAGGAGGTGTTGTTTAA


 


5401
TAAACAACACCTCCTCCTG
CAGGAGGAGGTGTTGTTTA


 


5402
AAACAACACCTCCTCCTGC
GCAGGAGGAGGTGTTGTTT


 


5403
AACAACACCTCCTCCTGCT
AGCAGGAGGAGGTGTTGTT


 


5404
ACAACACCTCCTCCTGCTG
CAGCAGGAGGAGGTGTTGT


 


5405
CAACACCTCCTCCTGCTGC
GCAGCAGGAGGAGGTGTTG


 


5406
AACACCTCCTCCTGCTGCT
AGCAGCAGGAGGAGGTGTT


 


5407
ACACCTCCTCCTGCTGCTC
GAGCAGCAGGAGGAGGTGT


 


5408
CACCTCCTCCTGCTGCTCA
TGAGCAGCAGGAGGAGGTG


 


5409
ACCTCCTCCTGCTGCTCAC
GTGAGCAGCAGGAGGAGGT


 


5410
CCTCCTCCTGCTGCTCACT
AGTGAGCAGCAGGAGGAGG


 


5411
CTCCTCCTGCTGCTCACTC
GAGTGAGCAGCAGGAGGAG


 


5412
TCCTCCTGCTGCTCACTCC
GGAGTGAGCAGCAGGAGGA


 


5413
CCTCCTGCTGCTCACTCCC
GGGAGTGAGCAGCAGGAGG


 


5414
CTCCTGCTGCTCACTCCCG
CGGGAGTGAGCAGCAGGAG


 


5415
TCCTGCTGCTCACTCCCGC
GCGGGAGTGAGCAGCAGGA


 


5416
CCTGCTGCTCACTCCCGCT
AGCGGGAGTGAGCAGCAGG


 


5417
CTGCTGCTCACTCCCGCTG
CAGCGGGAGTGAGCAGCAG


 


5418
TGCTGCTCACTCCCGCTGA
TCAGCGGGAGTGAGCAGCA


 


5419
GCTGCTCACTCCCGCTGAG
CTCAGCGGGAGTGAGCAGC


 


5420
CTGCTCACTCCCGCTGAGC
GCTCAGCGGGAGTGAGCAG


 


5421
TGCTCACTCCCGCTGAGCC
GGCTCAGCGGGAGTGAGCA


 


5422
GCTCACTCCCGCTGAGCCC
GGGCTCAGCGGGAGTGAGC


 


5423
CTCACTCCCGCTGAGCCCA
TGGGCTCAGCGGGAGTGAG


 


5424
TCACTCCCGCTGAGCCCAC
GTGGGCTCAGCGGGAGTGA


 


5425
CACTCCCGCTGAGCCCACT
AGTGGGCTCAGCGGGAGTG


 


5426
ACTCCCGCTGAGCCCACTC
GAGTGGGCTCAGCGGGAGT


 


5427
CTCCCGCTGAGCCCACTCT
AGAGTGGGCTCAGCGGGAG


 


5428
TCCCGCTGAGCCCACTCTA
TAGAGTGGGCTCAGCGGGA


 


5429
CCCGCTGAGCCCACTCTAC
GTAGAGTGGGCTCAGCGGG


 


5430
CCGCTGAGCCCACTCTACT
AGTAGAGTGGGCTCAGCGG


 


5431
CGCTGAGCCCACTCTACTG
CAGTAGAGTGGGCTCAGCG


 


5432
GCTGAGCCCACTCTACTGC
GCAGTAGAGTGGGCTCAGC


 


5433
CTGAGCCCACTCTACTGCC
GGCAGTAGAGTGGGCTCAG


 


5434
TGAGCCCACTCTACTGCCC
GGGCAGTAGAGTGGGCTCA


 


5435
GAGCCCACTCTACTGCCCC
GGGGCAGTAGAGTGGGCTC


 


5436
AGCCCACTCTACTGCCCCA
TGGGGCAGTAGAGTGGGCT


 


5437
GCCCACTCTACTGCCCCAG
CTGGGGCAGTAGAGTGGGC


 


5438
CCCACTCTACTGCCCCAGC
GCTGGGGCAGTAGAGTGGG


 


5439
CCACTCTACTGCCCCAGCT
AGCTGGGGCAGTAGAGTGG


 


5440
CACTCTACTGCCCCAGCTC
GAGCTGGGGCAGTAGAGTG


 


5441
ACTCTACTGCCCCAGCTCC
GGAGCTGGGGCAGTAGAGT


 


5442
CTCTACTGCCCCAGCTCCG
CGGAGCTGGGGCAGTAGAG


 


5443
TCTACTGCCCCAGCTCCGT
ACGGAGCTGGGGCAGTAGA


 


5444
CTACTGCCCCAGCTCCGTT
AACGGAGCTGGGGCAGTAG


 


5445
TACTGCCCCAGCTCCGTTT
AAACGGAGCTGGGGCAGTA


 


5446
ACTGCCCCAGCTCCGTTTC
GAAACGGAGCTGGGGCAGT


 


5447
CTGCCCCAGCTCCGTTTCT
AGAAACGGAGCTGGGGCAG


 


5448
TGCCCCAGCTCCGTTTCTA
TAGAAACGGAGCTGGGGCA


 


5449
GCCCCAGCTCCGTTTCTAC
GTAGAAACGGAGCTGGGGC


 


5450
CCCCAGCTCCGTTTCTACC
GGTAGAAACGGAGCTGGGG


 


5451
CCCAGCTCCGTTTCTACCA
TGGTAGAAACGGAGCTGGG


 


5452
CCAGCTCCGTTTCTACCAC
GTGGTAGAAACGGAGCTGG


 


5453
CAGCTCCGTTTCTACCACC
GGTGGTAGAAACGGAGCTG


 


5454
AGCTCCGTTTCTACCACCG
CGGTGGTAGAAACGGAGCT


 


5455
GCTCCGTTTCTACCACCGC
GCGGTGGTAGAAACGGAGC


 


5456
CTCCGTTTCTACCACCGCA
TGCGGTGGTAGAAACGGAG


 


5457
TCCGTTTCTACCACCGCAT
ATGCGGTGGTAGAAACGGA


 


5458
CCGTTTCTACCACCGCATC
GATGCGGTGGTAGAAACGG


 


5459
CGTTTCTACCACCGCATCC
GGATGCGGTGGTAGAAACG


 


5460
GTTTCTACCACCGCATCCT
AGGATGCGGTGGTAGAAAC


 


5461
TTTCTACCACCGCATCCTC
GAGGATGCGGTGGTAGAAA


 


5462
TTCTACCACCGCATCCTCA
TGAGGATGCGGTGGTAGAA


 


5463
TCTACCACCGCATCCTCAC
GTGAGGATGCGGTGGTAGA


 


5464
CTACCACCGCATCCTCACT
AGTGAGGATGCGGTGGTAG


 


5465
TACCACCGCATCCTCACTG
CAGTGAGGATGCGGTGGTA


 


5466
ACCACCGCATCCTCACTGG
CCAGTGAGGATGCGGTGGT


 


5467
CCACCGCATCCTCACTGGG
CCCAGTGAGGATGCGGTGG


 


5468
CACCGCATCCTCACTGGGC
GCCCAGTGAGGATGCGGTG


 


5469
ACCGCATCCTCACTGGGCT
AGCCCAGTGAGGATGCGGT


 


5470
CCGCATCCTCACTGGGCTC
GAGCCCAGTGAGGATGCGG


 


5471
CGCATCCTCACTGGGCTCA
TGAGCCCAGTGAGGATGCG


 


5472
GCATCCTCACTGGGCTCAC
GTGAGCCCAGTGAGGATGC


 


5473
CATCCTCACTGGGCTCACT
AGTGAGCCCAGTGAGGATG


 


5474
ATCCTCACTGGGCTCACTG
CAGTGAGCCCAGTGAGGAT


 


5475
TCCTCACTGGGCTCACTGC
GCAGTGAGCCCAGTGAGGA


 


5476
CCTCACTGGGCTCACTGCA
TGCAGTGAGCCCAGTGAGG


 


5477
CTCACTGGGCTCACTGCAG
CTGCAGTGAGCCCAGTGAG


 


5478
TCACTGGGCTCACTGCAGG
CCTGCAGTGAGCCCAGTGA


 


5479
CACTGGGCTCACTGCAGGC
GCCTGCAGTGAGCCCAGTG


 


5480
ACTGGGCTCACTGCAGGCA
TGCCTGCAGTGAGCCCAGT


 


5481
CTGGGCTCACTGCAGGCAT
ATGCCTGCAGTGAGCCCAG


 


5482
TGGGCTCACTGCAGGCATG
CATGCCTGCAGTGAGCCCA


 


5483
GGGCTCACTGCAGGCATGC
GCATGCCTGCAGTGAGCCC


 


5484
GGCTCACTGCAGGCATGCT
AGCATGCCTGCAGTGAGCC


 


5485
GCTCACTGCAGGCATGCTG
CAGCATGCCTGCAGTGAGC


 


5486
CTCACTGCAGGCATGCTGA
TCAGCATGCCTGCAGTGAG


 


5487
TCACTGCAGGCATGCTGAA
TTCAGCATGCCTGCAGTGA


 


5488
CACTGCAGGCATGCTGAAC
GTTCAGCATGCCTGCAGTG


 


5489
ACTGCAGGCATGCTGAACA
TGTTCAGCATGCCTGCAGT


 


5490
CTGCAGGCATGCTGAACAA
TTGTTCAGCATGCCTGCAG


 


5491
TGCAGGCATGCTGAACAAG
CTTGTTCAGCATGCCTGCA


 


5492
GCAGGCATGCTGAACAAGG
CCTTGTTCAGCATGCCTGC


 


5493
CAGGCATGCTGAACAAGGG
CCCTTGTTCAGCATGCCTG


 


5494
AGGCATGCTGAACAAGGGG
CCCCTTGTTCAGCATGCCT


 


5495
GGCATGCTGAACAAGGGGC
GCCCCTTGTTCAGCATGCC


 


5496
GCATGCTGAACAAGGGGCC
GGCCCCTTGTTCAGCATGC


 


5497
CATGCTGAACAAGGGGCCT
AGGCCCCTTGTTCAGCATG


 


5498
ATGCTGAACAAGGGGCCTC
GAGGCCCCTTGTTCAGCAT


 


5499
TGCTGAACAAGGGGCCTCC
GGAGGCCCCTTGTTCAGCA


 


5500
GCTGAACAAGGGGCCTCCA
TGGAGGCCCCTTGTTCAGC


 


5501
CTGAACAAGGGGCCTCCAA
TTGGAGGCCCCTTGTTCAG


 


5502
TGAACAAGGGGCCTCCAAC
GTTGGAGGCCCCTTGTTCA


 


5503
GAACAAGGGGCCTCCAACC
GGTTGGAGGCCCCTTGTTC


 


5504
AACAAGGGGCCTCCAACCT
AGGTTGGAGGCCCCTTGTT


 


5505
ACAAGGGGCCTCCAACCTT
AAGGTTGGAGGCCCCTTGT


 


5506
CAAGGGGCCTCCAACCTTC
GAAGGTTGGAGGCCCCTTG


 


5507
AAGGGGCCTCCAACCTTCT
AGAAGGTTGGAGGCCCCTT


 


5508
AGGGGCCTCCAACCTTCTG
CAGAAGGTTGGAGGCCCCT


 


5509
GGGGCCTCCAACCTTCTGC
GCAGAAGGTTGGAGGCCCC


 


5510
GGGCCTCCAACCTTCTGCC
GGCAGAAGGTTGGAGGCCC


 


5511
GGCCTCCAACCTTCTGCCC
GGGCAGAAGGTTGGAGGCC


 


5512
GCCTCCAACCTTCTGCCCT
AGGGCAGAAGGTTGGAGGC


 


5513
CCTCCAACCTTCTGCCCTC
GAGGGCAGAAGGTTGGAGG


 


5514
CTCCAACCTTCTGCCCTCC
GGAGGGCAGAAGGTTGGAG


 


5515
TCCAACCTTCTGCCCTCCT
AGGAGGGCAGAAGGTTGGA


 


5516
CCAACCTTCTGCCCTCCTG
CAGGAGGGCAGAAGGTTGG


 


5517
CAACCTTCTGCCCTCCTGC
GCAGGAGGGCAGAAGGTTG


 


5518
AACCTTCTGCCCTCCTGCC
GGCAGGAGGGCAGAAGGTT


 


5519
ACCTTCTGCCCTCCTGCCA
TGGCAGGAGGGCAGAAGGT


 


5520
CCTTCTGCCCTCCTGCCAA
TTGGCAGGAGGGCAGAAGG


 


5521
CTTCTGCCCTCCTGCCAAA
TTTGGCAGGAGGGCAGAAG


 


5522
TTCTGCCCTCCTGCCAAAA
TTTTGGCAGGAGGGCAGAA


 


5523
TCTGCCCTCCTGCCAAAAG
CTTTTGGCAGGAGGGCAGA


 


5524
CTGCCCTCCTGCCAAAAGA
TCTTTTGGCAGGAGGGCAG


 


5525
TGCCCTCCTGCCAAAAGAT
ATCTTTTGGCAGGAGGGCA


 


5526
GCCCTCCTGCCAAAAGATC
GATCTTTTGGCAGGAGGGC


 


5527
CCCTCCTGCCAAAAGATCT
AGATCTTTTGGCAGGAGGG


 


5528
CCTCCTGCCAAAAGATCTG
CAGATCTTTTGGCAGGAGG


 


5529
CTCCTGCCAAAAGATCTGG
CCAGATCTTTTGGCAGGAG


 


5530
TCCTGCCAAAAGATCTGGG
CCCAGATCTTTTGGCAGGA


 


5531
CCTGCCAAAAGATCTGGGG
CCCCAGATCTTTTGGCAGG


 


5532
CTGCCAAAAGATCTGGGGA
TCCCCAGATCTTTTGGCAG


 


5533
TGCCAAAAGATCTGGGGAG
CTCCCCAGATCTTTTGGCA


 


5534
GCCAAAAGATCTGGGGAGT
ACTCCCCAGATCTTTTGGC


 


5535
CCAAAAGATCTGGGGAGTG
CACTCCCCAGATCTTTTGG


 


5536
CAAAAGATCTGGGGAGTGT
ACACTCCCCAGATCTTTTG


 


5537
AAAAGATCTGGGGAGTGTG
CACACTCCCCAGATCTTTT


 


5538
AAAGATCTGGGGAGTGTGA
TCACACTCCCCAGATCTTT


 


5539
AAGATCTGGGGAGTGTGAG
CTCACACTCCCCAGATCTT


 


5540
AGATCTGGGGAGTGTGAGG
CCTCACACTCCCCAGATCT


 


5541
GATCTGGGGAGTGTGAGGA
TCCTCACACTCCCCAGATC


 


5542
ATCTGGGGAGTGTGAGGAG
CTCCTCACACTCCCCAGAT


 


5543
TCTGGGGAGTGTGAGGAGA
TCTCCTCACACTCCCCAGA


 


5544
CTGGGGAGTGTGAGGAGAG
CTCTCCTCACACTCCCCAG


 


5545
TGGGGAGTGTGAGGAGAGG
CCTCTCCTCACACTCCCCA


 


5546
GGGGAGTGTGAGGAGAGGG
CCCTCTCCTCACACTCCCC


 


5547
GGGAGTGTGAGGAGAGGGT
ACCCTCTCCTCACACTCCC


 


5548
GGAGTGTGAGGAGAGGGTG
CACCCTCTCCTCACACTCC


 


5549
GAGTGTGAGGAGAGGGTGG
CCACCCTCTCCTCACACTC


 


5550
AGTGTGAGGAGAGGGTGGC
GCCACCCTCTCCTCACACT


 


5551
GTGTGAGGAGAGGGTGGCA
TGCCACCCTCTCCTCACAC


 


5552
TGTGAGGAGAGGGTGGCAT
ATGCCACCCTCTCCTCACA


 


5553
GTGAGGAGAGGGTGGCATC
GATGCCACCCTCTCCTCAC


 


5554
TGAGGAGAGGGTGGCATCA
TGATGCCACCCTCTCCTCA


 


5555
GAGGAGAGGGTGGCATCAG
CTGATGCCACCCTCTCCTC


 


5556
AGGAGAGGGTGGCATCAGG
CCTGATGCCACCCTCTCCT


 


5557
GGAGAGGGTGGCATCAGGA
TCCTGATGCCACCCTCTCC


 


5558
GAGAGGGTGGCATCAGGAG
CTCCTGATGCCACCCTCTC


 


5559
AGAGGGTGGCATCAGGAGC
GCTCCTGATGCCACCCTCT


 


5560
GAGGGTGGCATCAGGAGCT
AGCTCCTGATGCCACCCTC


 


5561
AGGGTGGCATCAGGAGCTG
CAGCTCCTGATGCCACCCT


 


5562
GGGTGGCATCAGGAGCTGC
GCAGCTCCTGATGCCACCC


 


5563
GGTGGCATCAGGAGCTGCT
AGCAGCTCCTGATGCCACC


 


5564
GTGGCATCAGGAGCTGCTC
GAGCAGCTCCTGATGCCAC


 


5565
TGGCATCAGGAGCTGCTCA
TGAGCAGCTCCTGATGCCA


 


5566
GGCATCAGGAGCTGCTCAG
CTGAGCAGCTCCTGATGCC


 


5567
GCATCAGGAGCTGCTCAGG
CCTGAGCAGCTCCTGATGC


 


5568
CATCAGGAGCTGCTCAGGC
GCCTGAGCAGCTCCTGATG


 


5569
ATCAGGAGCTGCTCAGGCT
AGCCTGAGCAGCTCCTGAT


 


5570
TCAGGAGCTGCTCAGGCTT
AAGCCTGAGCAGCTCCTGA


 


5571
CAGGAGCTGCTCAGGCTTG
CAAGCCTGAGCAGCTCCTG


 


5572
AGGAGCTGCTCAGGCTTGG
CCAAGCCTGAGCAGCTCCT


 


5573
GGAGCTGCTCAGGCTTGGC
GCCAAGCCTGAGCAGCTCC


 


5574
GAGCTGCTCAGGCTTGGCG
CGCCAAGCCTGAGCAGCTC


 


5575
AGCTGCTCAGGCTTGGCGG
CCGCCAAGCCTGAGCAGCT


 


5576
GCTGCTCAGGCTTGGCGGA
TCCGCCAAGCCTGAGCAGC


 


5577
CTGCTCAGGCTTGGCGGAG
CTCCGCCAAGCCTGAGCAG


 


5578
TGCTCAGGCTTGGCGGAGG
CCTCCGCCAAGCCTGAGCA


 


5579
GCTCAGGCTTGGCGGAGGG
CCCTCCGCCAAGCCTGAGC


 


5580
CTCAGGCTTGGCGGAGGGA
TCCCTCCGCCAAGCCTGAG


 


5581
TCAGGCTTGGCGGAGGGAG
CTCCCTCCGCCAAGCCTGA


 


5582
CAGGCTTGGCGGAGGGAGC
GCTCCCTCCGCCAAGCCTG


 


5583
AGGCTTGGCGGAGGGAGCG
CGCTCCCTCCGCCAAGCCT


 


5584
GGCTTGGCGGAGGGAGCGG
CCGCTCCCTCCGCCAAGCC


 


5585
GCTTGGCGGAGGGAGCGGC
GCCGCTCCCTCCGCCAAGC


 


5586
CTTGGCGGAGGGAGCGGCA
TGCCGCTCCCTCCGCCAAG


 


5587
TTGGCGGAGGGAGCGGCAT
ATGCCGCTCCCTCCGCCAA


 


5588
TGGCGGAGGGAGCGGCATG
CATGCCGCTCCCTCCGCCA


 


5589
GGCGGAGGGAGCGGCATGG
CCATGCCGCTCCCTCCGCC


 


5590
GCGGAGGGAGCGGCATGGG
CCCATGCCGCTCCCTCCGC


 


5591
CGGAGGGAGCGGCATGGGC
GCCCATGCCGCTCCCTCCG


 


5592
GGAGGGAGCGGCATGGGCG
CGCCCATGCCGCTCCCTCC


 


5593
GAGGGAGCGGCATGGGCGA
TCGCCCATGCCGCTCCCTC


 


5594
AGGGAGCGGCATGGGCGAT
ATCGCCCATGCCGCTCCCT


 


5595
GGGAGCGGCATGGGCGATG
CATCGCCCATGCCGCTCCC


 


5596
GGAGCGGCATGGGCGATGT
ACATCGCCCATGCCGCTCC


 


5597
GAGCGGCATGGGCGATGTC
GACATCGCCCATGCCGCTC


 


5598
AGCGGCATGGGCGATGTCA
TGACATCGCCCATGCCGCT


 


5599
GCGGCATGGGCGATGTCAC
GTGACATCGCCCATGCCGC


 


5600
CGGCATGGGCGATGTCACT
AGTGACATCGCCCATGCCG


 


5601
GGCATGGGCGATGTCACTC
GAGTGACATCGCCCATGCC


 


5602
GCATGGGCGATGTCACTCA
TGAGTGACATCGCCCATGC


 


5603
CATGGGCGATGTCACTCAG
CTGAGTGACATCGCCCATG


 


5604
ATGGGCGATGTCACTCAGC
GCTGAGTGACATCGCCCAT


 


5605
TGGGCGATGTCACTCAGCC
GGCTGAGTGACATCGCCCA


 


5606
GGGCGATGTCACTCAGCCC
GGGCTGAGTGACATCGCCC


 


5607
GGCGATGTCACTCAGCCCC
GGGGCTGAGTGACATCGCC


 


5608
GCGATGTCACTCAGCCCCT
AGGGGCTGAGTGACATCGC


 


5609
CGATGTCACTCAGCCCCTT
AAGGGGCTGAGTGACATCG


 


5610
GATGTCACTCAGCCCCTTC
GAAGGGGCTGAGTGACATC


 


5611
ATGTCACTCAGCCCCTTCC
GGAAGGGGCTGAGTGACAT


 


5612
TGTCACTCAGCCCCTTCCC
GGGAAGGGGCTGAGTGACA


 


5613
GTCACTCAGCCCCTTCCCG
CGGGAAGGGGCTGAGTGAC


 


5614
TCACTCAGCCCCTTCCCGG
CCGGGAAGGGGCTGAGTGA


 


5615
CACTCAGCCCCTTCCCGGT
ACCGGGAAGGGGCTGAGTG


 


5616
ACTCAGCCCCTTCCCGGTC
GACCGGGAAGGGGCTGAGT


 


5617
CTCAGCCCCTTCCCGGTCC
GGACCGGGAAGGGGCTGAG


 


5618
TCAGCCCCTTCCCGGTCCG
CGGACCGGGAAGGGGCTGA


 


5619
CAGCCCCTTCCCGGTCCGC
GCGGACCGGGAAGGGGCTG


 


5620
AGCCCCTTCCCGGTCCGCC
GGCGGACCGGGAAGGGGCT


 


5621
GCCCCTTCCCGGTCCGCCC
GGGCGGACCGGGAAGGGGC


 


5622
CCCCTTCCCGGTCCGCCCG
CGGGCGGACCGGGAAGGGG


 


5623
CCCTTCCCGGTCCGCCCGC
GCGGGCGGACCGGGAAGGG


 


5624
CCTTCCCGGTCCGCCCGCT
AGCGGGCGGACCGGGAAGG


 


5625
CTTCCCGGTCCGCCCGCTT
AAGCGGGCGGACCGGGAAG


 


5626
TTCCCGGTCCGCCCGCTTC
GAAGCGGGCGGACCGGGAA


 


5627
TCCCGGTCCGCCCGCTTCC
GGAAGCGGGCGGACCGGGA


 


5628
CCCGGTCCGCCCGCTTCCC
GGGAAGCGGGCGGACCGGG


 


5629
CCGGTCCGCCCGCTTCCCT
AGGGAAGCGGGCGGACCGG


 


5630
CGGTCCGCCCGCTTCCCTC
GAGGGAAGCGGGCGGACCG


 


5631
GGTCCGCCCGCTTCCCTCC
GGAGGGAAGCGGGCGGACC


 


5632
GTCCGCCCGCTTCCCTCCT
AGGAGGGAAGCGGGCGGAC


 


5633
TCCGCCCGCTTCCCTCCTT
AAGGAGGGAAGCGGGCGGA


 


5634
CCGCCCGCTTCCCTCCTTC
GAAGGAGGGAAGCGGGCGG


 


5635
CGCCCGCTTCCCTCCTTCA
TGAAGGAGGGAAGCGGGCG


 


5636
GCCCGCTTCCCTCCTTCAT
ATGAAGGAGGGAAGCGGGC


 


5637
CCCGCTTCCCTCCTTCATG
CATGAAGGAGGGAAGCGGG


 


5638
CCGCTTCCCTCCTTCATGA
TCATGAAGGAGGGAAGCGG


 


5639
CGCTTCCCTCCTTCATGAT
ATCATGAAGGAGGGAAGCG


 


5640
GCTTCCCTCCTTCATGATT
AATCATGAAGGAGGGAAGC


 


5641
CTTCCCTCCTTCATGATTT
AAATCATGAAGGAGGGAAG


 


5642
TTCCCTCCTTCATGATTTC
GAAATCATGAAGGAGGGAA


 


5643
TCCCTCCTTCATGATTTCC
GGAAATCATGAAGGAGGGA


 


5644
CCCTCCTTCATGATTTCCA
TGGAAATCATGAAGGAGGG


 


5645
CCTCCTTCATGATTTCCAT
ATGGAAATCATGAAGGAGG


 


5646
CTCCTTCATGATTTCCATT
AATGGAAATCATGAAGGAG


 


5647
TCCTTCATGATTTCCATTA
TAATGGAAATCATGAAGGA


 


5648
CCTTCATGATTTCCATTAA
TTAATGGAAATCATGAAGG


 


5649
CTTCATGATTTCCATTAAA
TTTAATGGAAATCATGAAG


 


5650
TTCATGATTTCCATTAAAG
CTTTAATGGAAATCATGAA


 


5651
TCATGATTTCCATTAAAGT
ACTTTAATGGAAATCATGA


 


5652
CATGATTTCCATTAAAGTC
GACTTTAATGGAAATCATG


 


5653
ATGATTTCCATTAAAGTCT
AGACTTTAATGGAAATCAT


 


5654
TGATTTCCATTAAAGTCTG
CAGACTTTAATGGAAATCA


 


5655
GATTTCCATTAAAGTCTGT
ACAGACTTTAATGGAAATC


 


5656
ATTTCCATTAAAGTCTGTT
AACAGACTTTAATGGAAAT


 


5657
TTTCCATTAAAGTCTGTTG
CAACAGACTTTAATGGAAA


 


5658
TTCCATTAAAGTCTGTTGT
ACAACAGACTTTAATGGAA


 


5659
TCCATTAAAGTCTGTTGTT
AACAACAGACTTTAATGGA


 


5660
CCATTAAAGTCTGTTGTTT
AAACAACAGACTTTAATGG


 


5661
CATTAAAGTCTGTTGTTTT
AAAACAACAGACTTTAATG


 


5662
ATTAAAGTCTGTTGTTTTG
CAAAACAACAGACTTTAAT


 


5663
TTAAAGTCTGTTGTTTTGT
ACAAAACAACAGACTTTAA


 


5664
TAAAGTCTGTTGTTTTGTG
CACAAAACAACAGACTTTA
















TABLE 2







Human and Mouse Hairless Polymorphisms













mRNA
Accession
Postion




Gene
(bp)
number
(nt)
From/To
Comments















Human
5699
NM_005144
867
C/A
Homo sapiens


Hairless


1330
T/G
hairless





1677
C/T
homolog





1686
C/T
(mouse) (HR),





2437
C/A
transcript





2491
G/A
variant 1,





2671
G/A
mRNA





2672
C/T





2786
T/C





3058
T/C





3064
A/G





3208
C/T





3253
G/A





3340
G/A





3695
C/T





3812
A/T





3851
C/T





3854
C/T





4545
A/G





4715
C/G





4820
C/A


Mouse
5599
NM_021877
402
A/G
Mus musculus


hairless


535
C/A
hairless (hr),





1603
G/A
mRNA





1681
A/G





1895
C/T





2251
G/A





2482
T/C





2569
T/C





2917
T/C





3232
C/T





3371
A/T





3610
C/A





4065
T/G
















TABLE 3







Exemplary siRNA target sequences in


mammalian hairless mRNAs (shown as


cDNA sequences)











Start
Sequence
Region












Mouse (Mus musculus) hairless (hr), mRNA,



NM_021877











2023
GCAGGAGACACCGGAGACAATCATA
ORF




(SEQ ID NO: 11373)



 



2495
GGACTCTTCAACACCCACTGGAGAT
ORF




(SEQ ID NO: 11374)



 



2713
CCAAGTCTGGGCCAAGTTTGACATT
ORF




(SEQ ID NO: 11375)



 



2831
CCACAACCTTCCTGCAATGGAGATT
ORF




(SEQ ID NO: 11376)



 



2844
GCAATGGAGATTCCAATCGGACCAA
ORF




(SEQ ID NO: 11377)



 



3042
CCAGTGATGACCGCATTACCAACAT
ORF




(SEQ ID NO: 11378)



 



3085
GCAGGTAGTAGAACGGAAGATCCAA
ORF




(SEQ ID NO: 11379)



 



3750
CCTGGTATCGAGCACAGAAAGATTT
ORF




(SEQ ID NO: 11380)



 



4068
GCACAATCAGTGTCACTCAGCACTT
ORF




(SEQ ID NO: 11381)



 









Homo sapiens hairless homolog (mouse) (HR),



transcript variant 1, mRNA, NM_005144











2151
GCGGAACCTGGGTTGTTTGGCTTAA
ORF




(SEQ ID NO: 11382)



 



2831
GGACACATCGATAGGGAACAAGGAT
ORF




(SEQ ID NO: 11383)



 



3626
CCCAACTCCACAACCTTCCTGCAAT
ORF




(SEQ ID NO: 11384)



 



3796
GCCATGAGCGAATACACATGGCCTT
ORF




(SEQ ID NO: 11385)



 



4092
CCTGTGTTGGTGTCAGGGATCCAAA
ORF




(SEQ ID NO: 11386)



 









Rat (Rattus norvegicus) hairless (hr) mRNA,



NM-024364











913
CCAAGATTCTAGAGCGAGCTCCCTT
ORF




(SEQ ID NO: 11387)



 



2045
GGATTCCTGTGCCACTTCTGAGGAA
ORF




(SEQ ID NO: 11388)



 



2601
CCACAACTTTCCTGCAATGGAGATT
ORF




(SEQ ID NO: 11389)



 



2614
GCAATGGAGATTCCAATCGGACCAA
ORF




(SEQ ID NO: 11390)



 



2729
GCTGCTAGCCTCTACAGCTGTCAAA
ORF




(SEQ ID NO: 11391)



 



2765
GCATGAGCGGATTCACATGGCCTTT
ORF




(SEQ ID NO: 11392)



 



2812
CCAGTGATGACCGCATTACCAACAT
ORF




(SEQ ID NO: 11393)



 



2855
GCAGGTAGTAGAACGGAAGATCCAA
ORF




(SEQ ID NO: 11394)



 



3520
CCTGGTACCGAGCACAGAAAGATTT
ORF




(SEQ ID NO: 11395)



 



3838
GCACAATCAGTGTCACTCAGCACTT
ORF




(SEQ ID NO: 11396)



 









Monkey (Macaca mulatto) hairless mRNA,



complete cds, AF_361864











1152
GCACTCGGAGCAGTTTGAATGTCCA
ORF




(SEQ ID NO: 11397)



 



1344
GGACACATCGATAGGGAACAAGGAG
ORF




(SEQ ID NO: 11398)



 



2025
GCACCAGGTCTGGGTCAAGTTTGAT
ORF




(SEQ ID NO: 11399)



 



2172
CCACAGGACCAAGAGCATCAAAGAG
ORF




(SEQ ID NO: 113400)



 



2605
CCTGTGTTGGTGTCAGGGATCCAAA
ORF




(SEQ ID NO: 11401)



 









Pig (Sus scrofa) hairless mRNA, partical



cds, AY279972











490
CAGATATGGGCAGCCTATGGTGTGA
ORF




(SEQ ID NO: 11402)



 



918
CCTGGTAAGCACAGTGAGCATCACT
ORF




(SEQ ID NO: 11403)



 



921
GGTAAGCACAGTGAGCATCACTCAG
ORF




(SEQ ID NO: 11404)



 



926
GCACAGTGAGCATCACTCAGCACTT
ORF




(SEQ ID NO: 11405)



 



927
CACAGTGAGCATCACTCAGCACTTC
ORF




(SEQ ID NO: 11406)



 









Sheep (Ovis aries) hairless mRNA, partial



cds, AY130969











366
GGATCCTGAGCATAATGGTGGCCAT
ORF




(SEQ ID NO: 11407)



 



1140
GCTTACTCGACACTCTGAGCAGTTT
ORF




(SEQ ID NO: 11408)



 



1798
GGACTGTTCAATACCCACTGGAGAT
ORF




(SEQ ID NO: 11409)



 



1967
CCCAGTTTGTCTCCAGTCAGCCTTT
ORF




(SEQ ID NO: 11410)



 



2016
CCAGGTCTGGGTCAAGTTTGACATT
ORF




(SEQ ID NO: 11411)
















TABLE 4





Human hairless target/siRNA sequences


human hairless NM_005144


















Loop:
475-615



Loop:
651-752



Loop:
 951-1137



Loop:
1968-2183



Loop:
2348-2568



Loop:
2769-2806



Loop:
3024-3365



Loop:
3069-3277



Loop:
4577-4698



Loop:
3605-3724



Loop:
4861-5079



Loop:
310-436



Loop:
1953-2248



Loop:
 919-1265



Loop:
4286-4465



Loop:
2373-2555



Loop:
4853-5284



Loop:
1916-2288



Loop:
2739-2863



Loop:
4874-5043



Loop:
3047-3318



Loop:
 959-1123



Loop:
4477-4534



Loop:
 871-1302



Loop:
4325-4459



Loop:
4913-5029



Loop:
 940-1166



Loop:
1946-2277



Loop:
4086-4199



Loop:
5093-5247

















TABLE 5





Mouse hairless target/siRNA sequences


mouse hairless NM_021877


















Loop:
318-523



Loop:
2422-2459



Loop:
1870-1913



Loop:
5010-5089



Loop:
3614-3736



Loop:
20-23



Loop:
1048-1390



Loop:
1122-1304



Loop:
3434-3550



Loop:
3257-3337



Loop:
4272-4504



Loop:
3009-3024



Loop:
4879-4967



Loop:
668-845



Loop:
4050-4222



Loop:
1702-1800



Loop:
3364-3567



Loop:
1015-1029



Loop:
4730-4780



Loop:
1712-1792



Loop:
4540-4566



Loop:
4070-4135



Loop:
1220-1260



Loop:
3579-3701



Loop:
445-459



Loop:
3491-3516



Loop:
205-238



Loop:
1691-1926



Loop:
2320-2337



Loop:
896-951



Loop:
2212-2244



Loop:
5156-5179



Loop:
2850-3948



Loop:
1141-1201



Loop:
2588-2648



Loop:
403-518



Loop:
3370-3407



Loop:
412-510



Loop:
4517-4594



Loop:
659-871



Loop:
1087-1103



Loop:
1600-1624



Loop:
4389-4461



Loop:
3423-3561



Loop:
713-812



Loop:
176-302



Loop:
1073-1336



Loop:
675-837



Loop:
4395-4417



Loop:
1082-1316



Loop:
4152-4215



Loop:
2877-2944

## Claims

1. A method of removing hair from an area of a human, comprising:
(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:
(i) twice pulling the hair from said follicles; or
(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:
(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and
(ii) an antisense sequence complementary thereto, wherein said double stranded nucleic acid molecule inhibits expression of human hairless protein, whereby hair growth in said area is inhibited.

2. The method of claim 1, wherein inhibition of hair growth in said area persists at least one month.

3. The method of claim 1, wherein said double stranded nucleic acid comprises at least one 3′-overhang.

4. The method of claim 3, wherein said 3′-overhang is a 2- or 3′-base overhang.

5. The method of claim 3, wherein said 3′-overhang comprises at least one deoxynucleotide.

6. The method of claim 1, wherein at least one strand of said double stranded nucleic acid comprises at least one nucleotide analog or internucleotidic linkage different from unmodified RNA.

7. The method of claim 1, wherein said sense sequence comprises SEQ ID NO:11329.

8. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 19 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

9. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 20 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

10. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 21 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

11. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 22 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

12. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 23 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

13. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 24 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

14. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 25 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

15. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 26 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

16. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 27 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

17. The method of claim 1, wherein said sense sequence and said antisense sequence each comprises 28 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

18. A method for removing hair from an area of a mammal, comprising:
(A) synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:
(i) twice pulling the hair from said follicles; or
(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:
(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412 and
(ii) an antisense sequence complementary thereto, wherein said double stranded nucleic acid molecule inhibits hairless mRNA translation.

19. The method of claim 18, wherein said mammal is a human.

20. The method of claim 18, wherein inhibition of hair growth in said area persists at least one month.

21. The method of claim 18, wherein said double stranded nucleic acid comprises at least one 3′-overhang.

22. The method of claim 21 wherein said 3′-overhang is a 2- or 3′-base overhang.

23. The method of claim 22 wherein said 3′-overhang comprises at least one deoxynucleotide.

24. The method of claim 18, wherein at least one strand of said double stranded nucleic acid comprises at least one nucleotide analog or internucleotidic linkage different from unmodified RNA.

25. The method of claim 18, wherein said sense sequence comprises SEQ ID NO:11329.

26. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 19 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

27. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 20 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

28. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 21 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

29. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 22 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

30. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 23 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

31. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 24 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

32. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 25 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

33. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 26 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

34. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 27 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

35. The method of claim 18, wherein said sense sequence and said antisense sequence each comprises 28 complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.

36. A method of inhibiting expression of hairless protein in an area of a mammal, comprising:
(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:
(i) twice pulling the hair from said follicles; or
(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:
(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and
(ii) an antisense sequence complementary thereto.

37. A method for treating a human desirous of losing hair in an area, comprising:
(A) first synchronizing hair growth cycles for hair follicles in said area, wherein said synchronization is accomplished by:
(i) twice pulling the hair from said follicles; or
(ii) administering a follicle growth inducer to said area; and

(B) subsequently applying to said area a double stranded nucleic acid molecule comprising:
(i) a sense sequence corresponding to 19-29 contiguous nucleotides of SEQ ID NO: 11412; and
(ii) an antisense sequence complementary thereto.