Chimeric Oligomeric Compounds Comprising Alternating Regions Of Northern And Southern Conformational Geometry

Monia; Brett P. ;   et al.

Patent Application Summary

U.S. patent application number 14/304433 was filed with the patent office on 2014-12-04 for chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry. This patent application is currently assigned to ISIS PHARMACEUTICALS, INC.. The applicant listed for this patent is Isis Pharmaceuticals, Inc.. Invention is credited to Brenda F. Baker, Madeline M. Butler, Robert McKay, Brett P. Monia.

Application Number20140357856 14/304433
Document ID /
Family ID34278750
Filed Date2014-12-04

United States Patent Application 20140357856
Kind Code A1
Monia; Brett P. ;   et al. December 4, 2014

CHIMERIC OLIGOMERIC COMPOUNDS COMPRISING ALTERNATING REGIONS OF NORTHERN AND SOUTHERN CONFORMATIONAL GEOMETRY

Abstract

The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3'-endo conformational geometry (3'-endo regions) or DNA like having southern or C2'-endo/O4'-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.


Inventors: Monia; Brett P.; (Encinitas, CA) ; Butler; Madeline M.; (Rancho Santa Fe, CA) ; McKay; Robert; (Poway, CA) ; Baker; Brenda F.; (Carlsbad, CA)
Applicant:
Name City State Country Type

Isis Pharmaceuticals, Inc.

Carlsbad

CA

US
Assignee: ISIS PHARMACEUTICALS, INC.
Carlsbad
CA

Family ID: 34278750
Appl. No.: 14/304433
Filed: June 13, 2014

Related U.S. Patent Documents

Application Number Filing Date Patent Number
12388856 Feb 19, 2009 8791083
14304433
10936273 Sep 8, 2004
12388856
60501719 Sep 9, 2003
60568489 May 6, 2004

Current U.S. Class: 536/24.5
Current CPC Class: C12N 2320/51 20130101; A61P 3/06 20180101; C12N 2310/3231 20130101; C12N 2310/323 20130101; C12N 15/111 20130101; C07H 21/00 20130101; A61P 3/04 20180101; C12N 2310/32 20130101; C12N 15/113 20130101; C12N 2310/321 20130101
Class at Publication: 536/24.5
International Class: C12N 15/113 20060101 C12N015/113

Claims



1-67. (canceled)

68. A chimeric oligomeric compound comprising from about 5 to about 80 linked nucleosides, wherein the chimeric oligomeric compound is divided into at least 5 separate regions, wherein each of the regions is a continuous sequence from 1 to about 5 nucleosides each comprising a 3'-endo sugar conformational geometry or a continuous sequence of from 1 to about 5 2'-deoxyribonucleosides, and wherein each of the regions comprising from 1 to about 5 2'-deoxyribonucleosides is internally located between two of the regions comprising 1 to about 5 nucleosides each comprising a 3'-endo sugar conformational geometry or at one of the 3' or 5'-termini.

69. The compound of claim 68 comprising 5 separate regions.

70. The compound of claim 68 comprising 7 separate regions.

71. The compound of claim 68 comprising 9 separate regions.

72. The compound of claim 68 comprising 11 separate regions.

73. The compound of claim 68 comprising 13 separate regions.

74. The compound of claim 68 comprising 15 separate regions.

75. The compound of claim 68 comprising 17 separate regions.

76. The compound of claim 68 wherein each of the regions is from 1 to 4 nucleosides in length.

77. The compound of claim 68 wherein each of the nucleosides comprising a 3'-endo sugar conformational geometry is, independently, a sugar modified nucleoside, a base modified nucleoside, or a nucleoside having one or more modifications that include both the base and the sugar.

78. The compound of claim 77 wherein each of the nucleosides comprising a 3'-endo sugar conformational geometry is a sugar modified nucleoside.

79. The compound of claim 77 wherein each of the sugar modified nucleosides, independently, comprises a 2'-substituent group.

80. The compound of claim 79 wherein each of the 2'-substituent groups is, independently, O(CH.sub.2).sub.2OCH.sub.3, O(CH.sub.2).sub.2SCH.sub.3, O(CH.sub.2).sub.2ON(CH.sub.3).sub.2, O(CH.sub.2).sub.2--O--(CH.sub.2).sub.2N(CH.sub.3).sub.2, OCH.sub.2C(.dbd.O)N(H)CH.sub.3, OCH.sub.3, O(CH.sub.2).sub.2NH.sub.2, O(CH.sub.2).sub.2N(CH.sub.3).sub.2, O(CH.sub.2).sub.3NH.sub.2, O(CH.sub.2).sub.3N(H)CH.sub.3, CH.sub.2CH.dbd.CH.sub.2, or O(CH.sub.2).sub.2S(O)CH.sub.3.

81. The compound of claim 77 wherein at least one of the nucleosides of one of the regions comprising 3'-endo sugar conformational geometry has a bicyclic sugar moiety.

82. The compound of claim 81 wherein at least one of the bicyclic sugar moieties is a locked nucleic acid (LNA).

83. The compound of claim 68 comprising from about 12 to 30 nucleosides in length.

84. The compound of claim 68 comprising from about 15 to 25 nucleosides in length.

85. The compound of claim 68 comprising from about 21 to 25 nucleosides in length.

86. The compound of claim 68 wherein each of the nucleosides is, independently, linked by phosphodiester or phosphorothioate.

87. The compound of claim 68 wherein each of the nucleosides is linked by a phosphorothioate internucleoside linking group.
Description



CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No. 12/388,856 filed Feb. 19, 2009, which is a continuation of U.S. application Ser. No. 10/936,273, filed Sep. 8, 2004, which claims priority to U.S. Provisional Application No. 60/501,719 filed Sep. 9, 2003 and to U.S. Provisional Application No. 60/568,489 filed May 6, 2004, each which is incorporated herein by reference in its entirety.

SEQUENCE LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled CORE0026USC2SEQ_ST25, created May 30, 2014, which is 564 Kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0003] The present invention relates to novel chimeric oligomeric compounds having regions of nucleosides that are RNA like having northern or 3'-endo conformational geometry (3'-endo regions) and regions of nucleosides that are DNA like having southern or C2'-endo/04'-endo conformational geometry. In certain embodiments the nucleosides that comprise the DNA like regions are 2'-deoxyribonucleosides. Chimeric oligomeric compounds include those having 3'-endo regions positioned at the 3' and 5'-termini with at least two internal C2'-endo/04'-endo regions that are separated by at least one 3'-endo region. In other embodiments there are at least 5 separate regions that alternate between C2'-endo/04'-endo and 3'-endo regions. The oligomeric compounds of the present invention are useful in the regulation of gene expression. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems. The chimeric oligomeric compounds of the present invention are useful, for example, for investigative and therapeutic purposes.

BACKGROUND OF THE INVENTION

[0004] Nearly all disease states in multicellular organisms involve the action of proteins. Classic therapeutic approaches have focused on the interaction of proteins with other molecules in efforts to moderate the proteins' disease-causing or disease-potentiating activities. In newer therapeutic approaches, modulation of the production of proteins has been sought. A general object of some current therapeutic approaches is to interfere with or otherwise modulate gene expression.

[0005] One method for inhibiting the expression of specific genes involves the use of oligonucleotides, particularly oligonucleotides that are complementary to a specific target messenger RNA (mRNA) sequence. Due to promising research results in recent years, oligonucleotides and oligonucleotide analogs are now accepted as therapeutic agents holding great promise for therapeutic and diagnostic methods.

[0006] Oligonucleotides and their analogs can be designed to have particular properties. A number of chemical modifications have been introduced into oligomeric compounds to increase their usefulness as therapeutic agents. Such modifications include those designed to increase binding affinity to a target strand, to increase cell penetration, to stabilize against nucleases and other enzymes that degrade or interfere with the structure or activity of the oligonucleotide, to provide a mode of disruption (terminating event) once the oligonucleotide is bound to a target, and to improve the pharmacokinetic properties of the oligonucleotide.

[0007] Despite these advances, a need exists in the art for the development of means to improve the binding affinity and nuclease resistance properties of oligomeric compounds. The present invention meets these needs as well as other needs.

SUMMARY OF THE INVENTION

[0008] The present invention provides chimeric oligomeric compounds comprising from about 5 to about 80 linked nucleosides wherein the chimeric oligomeric compounds are divided into at least 5 separate regions and each of these regions is a continuous sequence of from 1 to about 5 nucleosides each having a 3'-endo sugar conformational geometry or a continuous sequence of from 1 to about 5 2'-deoxyribonucleosides and wherein each of these regions comprising from 1 to about 5 2'-deoxyribonucleosides is internally located between two of said regions comprising 1 to about 5 nucleosides each having a 3'-endo sugar conformational geometry or at one of the 3' or 5' termini.

BRIEF DESCRIPTION OF THE FIGURES

[0009] FIG. 1 shows scheme I depicting iterative synthesis of compound 10.

[0010] FIG. 2 shows scheme I (continued) depicting iterative synthesis of compound 17.

[0011] FIG. 3 shows scheme I (continued) depicting iterative synthesis of compound I.

[0012] FIG. 4 shows scheme II depicting an alternate iterative synthesis of compound I starting with compound 20.

[0013] FIG. 5 shows scheme III depicting iterative synthesis of compound 33.

[0014] FIG. 6 shows scheme IV depicting iterative synthesis of compound 40.

[0015] FIG. 7 shows scheme V depicting iterative synthesis of compound 47.

DETAILED DESCRIPTION OF THE INVENTION

[0016] The present invention provides novel chimeric oligomeric compounds comprising regions that alternate between 3'-endo sugar conformational geometry (3'-endo regions) and 2'-endo/O4'-endo sugar conformational geometry (2'-endo regions). Each of the alternating regions comprise from 1 to about 5 nucleosides. The chimeric oligomeric compounds can start (5'-end) or end (3'-end) with either of the 2 regions and can have from about 5 to about 20 separate regions. One or more of the nucleosides of the chimeric oligomeric compound can further comprise a conjugate group. In one aspect of the present invention chimeric oligomeric compounds have the formula: T.sub.1-(3'-endo region)-[(2'-endo region)-(3'-endo region)].sub.n-T.sub.2 wherein n is at least two and each T.sub.1 and T.sub.2 is independently an optional conjugate group.

[0017] Each of the regions can range from 1 to about 5 nucleosides in length allowing for a plurality of motifs for oligonucleotides having the same length. Such as for example a chimeric oligomeric compound of the present invention having a length of 20 base pairs (bp) would include such motifs as 3-3-2-4-2-3-3,3-4-1-4-1-4-3 and 4-3-1-4-1-3-4 where each motif has the same number and orientation of regions (bold and italicized numbers are 3'-endo regions, unbold and not underlined numbers are 2'-endo regions and the number corresponding to each region representing the number of base pairs for that particular region).

[0018] A plurality of motifs for the chimeric oligomeric compounds of the present invention has been prepared and has shown activity in a plurality of assays against various targets. In addition to in vitro assays some positive data have also been obtained through in vivo assays. A list of motifs is shown below. This list is meant to be representative and not limiting.

TABLE-US-00001 Motifs # bp's Regions Motif 20 mer 5 1-8-2-8-1 20 mer 5 2-6-4-6-2 20 mer 5 2-7-2-7-2 20 mer 5 3-5-4-5-3 20 mer 5 3-6-1-7-3 20 mer 5 3-7-1-6-3 20 mer 7 3-3-2-4-2-3-3 20 mer 7 3-4-1-4-1-4-3 20 mer 7 4-3-1-4-1-3-4 18 mer 9 2-2-1-3-1-2-1-3-3 20 mer 9 3-2-1-3-1-3-1-3-3 20 mer 9 3-2-1-3-1-2-1-3-4 18 mer 9 3-3-1-2-1-3-1-2-2 20 mer 9 3-3-1-2-1-3-1-3-3 20 mer 9 3-3-1-2-1-2-1-3-4 20 mer 9 3-3-1-3-1-2-1-2-4 20 mer 9 3-3-1-3-1-2-1-3-3 20 mer 9 5-2-1-2-1-2-1-1-5 20 mer 11 3-2-2-1-2-1-2-1-1-2-3 20 mer 11 3-1-3-1-2-1-2-1-2-1-3 20 mer 11 3-1-2-1-2-1-2-1-2-1-4 20 mer 11 3-2-1-2-1-2-1-2-1-2-3 20 mer 11 3-2-1-2-1-3-1-2-1-1-3 20 mer 15 2-1-1-2-1-1-1-1-1-1-1-1-1-3-2 20 mer 15 3-1-1-1-1-1-1-1-1-1-1-1-1-1-4 20 mer 19 1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-2 # = number of 3'-endo nucleosides in the region (bolded) # = number of 2'-deoxy ribonucleotides in the region

Compounds of the Invention

[0019] The present invention provides chimeric oligomeric compounds that have at least 5 regions that alternate between 3'-endo and 2'-endo in conformational geometry. The nucleoside or nucleosides of a particular region can be modified in a variety of ways to give the region either a 3'-endo or a 2'-endo conformational geometry. The conformational geometry of a selected nucleoside can be modulated in one aspect by modifying the sugar the base or both the sugar and the base. Modifications include attachment of substituent groups or conjugate groups or by directly modifying the base or the sugar.

[0020] The sugar conformational geometry (puckering) plays a central role in determining the duplex conformational geometry between an oligonucleotide and its nucleic acid target. By controlling the sugar puckering independently at each position of an oligonucleotide the duplex geometry can be modulated to help maximize desired properties of the resulting chimeric oligomeric compound. Modulation of sugar geometry has been shown to enhance properties such as for example increased lipohpilicity, binding affinity to target nucleic acid (e.g. mRNA), chemical stability and nuclease resistance.

[0021] The present invention discloses novel chimeric oligomeric compounds comprised of a plurality of alternating 3'-endo and 2'-endo (including 2'-deoxy) regions wherein each of the regions are independently from about 1 to about 5 nucleosides in length. The chimeric oligomeric compounds can start and end with either 3'-endo or 2'-endo regions and have from about 5 to about 19 regions in total. The nucleosides of each region can be selected to be uniform such as for example uniform 2'-O-MOE nucleosides for one or more of the 3'-endo regions and 2'-deoxynucleosides for the 2'-endo regions. Alternatively the nucleosides can be mixed such that any nucleoside having 3'-endo conformational geometry can be used in any position of any 3'-endo region and any nucleoside having 2'-endo conformational geometry can be used in any position of any 2'-endo region. In some embodiments a 5'-conjugate group is used as a 5'-cap as a method of increasing the 5'-exonuclease resistance but conjugate groups can be used at any position within the chimeric oligomeric compounds of the invention.

3'-Endo Regions

[0022] The present invention provides chimeric oligomeric compounds having alternating regions wherein one of the alternating regions has 3'-endo conformational geometry. These 3'-endo regions include nucleosides synthetically modified to induce a 3'-endo sugar conformation. A nucleoside can incorporate synthetic modifications of the heterocyclic base, the sugar moiety or both to induce a desired 3'-endo sugar conformation. These modified nucleosides are used to mimic RNA like nucleosides so that particular properties of an oligomeric compound can be enhanced while maintaining the desirable 3'-endo conformational geometry. Properties that are enhanced by using more stable 3'-endo nucleosides include but aren't limited to modulation of pharmacokinetic properties through modification of protein binding, protein off-rate, absorption and clearance; modulation of nuclease stability as well as chemical stability; modulation of the binding affinity and specificity of the oligomer (affinity and specificity for enzymes as well as for complementary sequences); and increasing efficacy of RNA cleavage. The present invention provides regions of nucleosides modified in such a way as to favor a C3'-endo type conformation.

##STR00001##

[0023] Nucleoside conformation is influenced by various factors including substitution at the 2', 3' or 4'-positions of the pentofuranosyl sugar. Electronegative substituents generally prefer the axial positions, while sterically demanding substituents generally prefer the equatorial positions (Principles of Nucleic Acid Structure, Wolfgang Sanger, 1984, Springer-Verlag.) Modification of the 2' position to favor the 3'-endo conformation can be achieved while maintaining the 2'-OH as a recognition element (Gallo et al., Tetrahedron (2001), 57, 5707-5713. Harry-O' kuru et al., J. Org. Chem., (1997), 62(6), 1754-1759 and Tang et al., J. Org. Chem. (1999), 64, 747-754.)

[0024] Alternatively, preference for the 3'-endo conformation can be achieved by deletion of the 2'-OH as exemplified by 2' deoxy-2'F-nucleosides (Kawasaki et al., J. Med. Chem. (1993), 36, 831-841), which adopts the 3'-endo conformation positioning the electronegative fluorine atom in the axial position. Other modifications of the ribose ring, for example substitution at the 4'-position to give 4'-F modified nucleosides (Guillerm et al., Bioorganic and Medicinal Chemistry Letters (1995), 5, 1455-1460 and Owen et al., J. Org. Chem. (1976), 41, 3010-3017), or for example modification to yield methanocarba nucleoside analogs (Jacobson et al., J. Med. Chem. Lett. (2000), 43, 2196-2203 and Lee et al., Bioorganic and Medicinal Chemistry Letters (2001), 11, 1333-1337) also induce preference for the 3'-endo conformation. Along similar lines, 3'-endo regions can include one or more nucleosides modified in such a way that conformation is locked into a C3'-endo type conformation, i.e. Locked Nucleic Acid (LNA, Singh et al, Chem. Commun. (1998), 4, 455-456), and ethylene bridged Nucleic Acids (ENA, Morita et al, Bioorganic & Medicinal Chemistry Letters (2002), 12, 73-76.)

[0025] Examples of modified nucleosides amenable to the present invention are shown below in Table 1. These examples are meant to be representative and not exhaustive.

TABLE-US-00002 TABLE 1 ##STR00002## ##STR00003## ##STR00004## ##STR00005## ##STR00006## ##STR00007## ##STR00008## ##STR00009## ##STR00010## ##STR00011## ##STR00012## ##STR00013## ##STR00014## ##STR00015## ##STR00016## ##STR00017## ##STR00018## ##STR00019## ##STR00020##

[0026] The preferred conformation of modified nucleosides and their oligomers can be estimated by various methods such as molecular dynamics calculations, nuclear magnetic resonance spectroscopy and CD measurements. Hence, modifications predicted to induce RNA like conformations, A-form duplex geometry in an oligomeric context, are selected for use in the modified oligoncleotides of the present invention. The synthesis of numerous of the modified nucleosides amenable to the present invention are known in the art (see for example, Chemistry of Nucleosides and Nucleotides Vol 1-3, ed. Leroy B. Townsend, 1988, Plenum press., and the examples section below). Nucleosides known to be inhibitors/substrates for RNA dependent RNA polymerases (for example HCV NS5B).

[0027] The terms used to describe the conformational geometry of homoduplex nucleic acids are "A Form" for RNA and "B Form" for DNA. The respective conformational geometry for RNA and DNA duplexes was determined from X-ray diffraction analysis of nucleic acid fibers (Arnott and Hukins, Biochem. Biophys. Res. Comm., 1970, 47, 1504.) In general, RNA:RNA duplexes are more stable and have higher melting temperatures (T.sub.ms) than DNA:DNA duplexes (Sanger et al., Principles of Nucleic Acid Structure, 1984, Springer-Verlag; New York, N.Y.; Lesnik et al., Biochemistry, 1995, 34, 10807-10815; Conte et al., Nucleic Acids Res., 1997, 25, 2627-2634). The increased stability of RNA has been attributed to several structural features, most notably the improved base stacking interactions that result from an A-form geometry (Searle et al., Nucleic Acids Res., 1993, 21, 2051-2056). The presence of the 2' hydroxyl in RNA biases the sugar toward a C3' endo pucker, i.e., also designated as Northern pucker, which causes the duplex to favor the A-form geometry. In addition, the 2' hydroxyl groups of RNA can form a network of water mediated hydrogen bonds that help stabilize the RNA duplex (Egli et al., Biochemistry, 1996, 35, 8489-8494). On the other hand, deoxy nucleic acids prefer a C2' endo sugar pucker, i.e., also known as Southern pucker, which is thought to impart a less stable B-form geometry (Sanger, W. (1984) Principles of Nucleic Acid Structure, Springer-Verlag, New York, N.Y.). As used herein, B-form geometry is inclusive of both C2'-endo pucker and 04'-endo pucker. This is consistent with Berger, et. al., Nucleic Acids Research, 1998, 26, 2473-2480, who pointed out that in considering the furanose conformations which give rise to B-form duplexes consideration should also be given to a 04'-endo pucker contribution.

[0028] DNA:RNA hybrid duplexes, however, are usually less stable than pure RNA:RNA duplexes, and depending on their sequence may be either more or less stable than DNA:DNA duplexes (Searle et al., Nucleic Acids Res., 1993, 21, 2051-2056). The structure of a hybrid duplex is intermediate between A- and B-form geometries, which may result in poor stacking interactions (Lane et al., Eur. J. Biochem., 1993, 215, 297-306; Fedoroff et al., J. Mol. Biol., 1993, 233, 509-523; Gonzalez et al., Biochemistry, 1995, 34, 4969-4982; Horton et al., J. Mol. Biol., 1996, 264, 521-533). The stability of the duplex formed between a target RNA and a synthetic sequence is central to therapies such as, but not limited to, antisense and RNA interference as these mechanisms require the binding of an oligonucleotide strand to an RNA target strand. In the case of antisense, effective inhibition of the mRNA requires that the antisense DNA have a minimum binding affinity with the mRNA. Otherwise, the desired interaction between the oligonucleotide strand and target mRNA strand will occur infrequently, resulting in decreased efficacy.

[0029] One routinely used method of modifying the sugar puckering is the substitution on the sugar at the 2'-position with a substituent group that influences the sugar geometry. The influence on ring conformation is dependant on the nature of the substituent at the 2'-position. A number of different substituents have been studied to determine their sugar puckering effect. For example, 2'-halogens have been studied showing that the 2'-fluoro derivative exhibits the largest population (65%) of the C3'-endo form, and the 2'-iodo exhibits the lowest population (7%). The populations of adenosine (2'-OH) versus deoxyadenosine (2'-H) are 36% and 19%, respectively. Furthermore, the effect of the 2'-fluoro group of adenosine dimers (2'-deoxy-2'-fluoroadenosine-2'-deoxy-2'-fluoro-adenosine) is further correlated to the stabilization of the stacked conformation.

[0030] As expected, the relative duplex stability can be enhanced by replacement of 2'-OH groups with 2'-F groups thereby increasing the C3'-endo population. It is assumed that the highly polar nature of the 2'-F bond and the extreme preference for C3'-endo puckering may stabilize the stacked conformation in an A-form duplex. Data from UV hypochromicity, circular dichroism, and .sup.1H NMR also indicate that the degree of stacking decreases as the electronegativity of the halo substituent decreases. Furthermore, steric bulk at the 2'-position of the sugar moiety is better accommodated in an A-form duplex than a B-form duplex. Thus, a 2'-substituent on the 3'-terminus of a dinucleoside monophosphate is thought to exert a number of effects on the stacking conformation: steric repulsion, furanose puckering preference, electrostatic repulsion, hydrophobic attraction, and hydrogen bonding capabilities. These substituent effects are thought to be determined by the molecular size, electronegativity, and hydrophobicity of the substituent. Melting temperatures of complementary strands is also increased with the 2'-substituted adenosine diphosphates. It is not clear whether the 3'-endo preference of the conformation or the presence of the substituent is responsible for the increased binding. However, greater overlap of adjacent bases (stacking) can be achieved with the 3'-endo conformation.

[0031] One synthetic 2'-modification that imparts increased nuclease resistance and a very high binding affinity to nucleotides is the 2-methoxyethoxy (2'-MOE, 2'-OCH.sub.2CH.sub.2OCH.sub.3) side chain (Baker et al., J. Biol. Chem., 1997, 272, 11944-12000). One of the immediate advantages of the 2'-MOE substitution is the improvement in binding affinity, which is greater than many similar 2' modifications such as O-methyl, O-propyl, and O-aminopropyl. Oligonucleotides having the 2'-.beta.-methoxyethyl substituent also have been shown to be antisense inhibitors of gene expression with promising features for in vivo use (Martin, P., Helv. Chim. Acta, 1995, 78, 486-504; Altmann et al., Chimia, 1996, 50, 168-176; Altmann et al., Biochem. Soc. Trans., 1996, 24, 630-637; and Altmann et al., Nucleosides Nucleotides, 1997, 16, 917-926). Relative to DNA, the oligonucleotides having the 2'-MOE modification displayed improved RNA affinity and higher nuclease resistance. Chimeric oligomeric compounds having 2'-MOE substituents in the wing nucleosides and an internal region of deoxy-phosphorothioate nucleotides (also termed a gapped oligonucleotide or gapmer) have shown effective reduction in the growth of tumors in animal models at low doses. 2'-MOE substituted oligonucleotides have also shown outstanding promise as antisense agents in several disease states. One such MOE substituted oligonucleotide is presently being investigated in clinical trials for the treatment of CMV retinitis.

[0032] To better understand the higher RNA affinity of 2'-O-methoxyethyl substituted RNA and to examine the conformational properties of the 2'-O-methoxyethyl substituent, two dodecamer oligonucleotides were synthesized having SEQ ID NO: 1 (CGC GAA UUC GCG) and SEQ ID NO: 2 (GCG CUU AAG CGC). These self-complementary strands have every 2'-position modified with a 2'-O-methoxyethyl. The duplex was crystallized at a resolution of 1.7 Angstrom and the crystal structure was determined. The conditions used for the crystallization were 2 mM oligonucleotide, 50 mM Na Hepes pH 6.2-7.5, 10.50 mM MgCl.sub.2, 15% PEG 400. The crystal data showed: space group C2, cell constants a=41.2 .ANG., b=34.4 .ANG., c=46.6 .ANG., .quadrature.=92.4.degree.. The resolution was 1.7 .ANG. at -170.degree. C. The current R=factor was 20% (R.sub.free 26%).

[0033] This crystal structure is believed to be the first crystal structure of a fully modified RNA oligonucleotide analogue. The duplex adopts an overall A-form conformation and all modified sugars display C3'-endo pucker. In most of the 2'-O-substituents, the torsion angle around the A'-B' bond, as depicted in Structure II below, of the ethylene glycol linker has a gauche conformation. For 2'-O-MOE, A' and B' of Structure II below are methylene moieties of the ethyl portion of the MOE and R' is the methoxy portion.

##STR00021##

[0034] In the crystal, the 2'-O-MOE RNA duplex adopts a general orientation such that the crystallographic 2-fold rotation axis does not coincide with the molecular 2-fold rotation axis. The duplex adopts the expected A-type geometry and all of the 24 2'-O-MOE substituents were visible in the electron density maps at full resolution. The electron density maps as well as the temperature factors of substituent atoms indicate flexibility of the 2'-O-MOE substituent in some cases.

[0035] Most of the 2'-O-MOE substituents display a gauche conformation around the C--C bond of the ethyl linker. However, in two cases, a trans conformation around the C--C bond is observed. The lattice interactions in the crystal include packing of duplexes against each other via their minor grooves. Therefore, for some residues, the conformation of the 2'-O-substituent is affected by contacts to an adjacent duplex. In general, variations in the conformation of the substituents (e.g. g' or g.sup.- around the C--C bonds) create a range of interactions between substituents, both inter-strand, across the minor groove, and intra-strand. At one location, atoms of substituents from two residues are in van der Waals contact across the minor groove. Similarly, a close contact occurs between atoms of substituents from two adjacent intra-strand residues.

[0036] Previously determined crystal structures of A-DNA duplexes were for those that incorporated isolated 2'-O-methyl T residues. In the crystal structure noted above for the 2'-O-MOE substituents, a conserved hydration pattern has been observed for the 2'-O-MOE residues. A single water molecule is seen located between O2', O3' and the methoxy oxygen atom of the substituent, forming contacts to all three of between 2.9 and 3.4 .ANG.. In addition, oxygen atoms of substituents are involved in several other hydrogen bonding contacts. For example, the methoxy oxygen atom of a particular 2'-O-substituent forms a hydrogen bond to N3 of an adenosine from the opposite strand via a bridging water molecule.

[0037] In several cases a water molecule is trapped between the oxygen atoms O2', O3' and OC' of modified nucleosides. 2'-O-MOE substituents with trans conformation around the C--C bond of the ethylene glycol linker are associated with close contacts between OC' and N2 of a guanosine from the opposite strand, and, water-mediated, between OC' and N3(G). When combined with the available thermodynamic data for duplexes containing 2'-O-MOE modified strands, this crystal structure allows for further detailed structure-stability analysis of other modifications.

[0038] In extending the crystallographic structure studies, molecular modeling experiments were performed to study further enhanced binding affinity of oligonucleotides having 2'-O-modifications of the invention. The computer simulations were conducted on compounds of SEQ ID NO: 1, above, having 2'-O-modifications of the invention located at each of the nucleoside of the oligonucleotide. The simulations were performed with the oligonucleotide in aqueous solution using the AMBER force field method (Cornell et al., J. Am. Chem. Soc., 1995, 117, 5179-5197)(modeling software package from UCSF, San Francisco, Calif.). The calculations were performed on an Indigo2 SGI machine (Silicon Graphics, Mountain View, Calif.).

[0039] Further 2'-O-modifications that will have a 3'-endo sugar influence include those having a ring structure that incorporates a two atom portion corresponding to the A' and B' atoms of Structure II. The ring structure is attached at the 2' position of a sugar moiety of one or more nucleosides that are incorporated into an oligonucleotide. The 2'-oxygen of the nucleoside links to a carbon atom corresponding to the A' atom of Structure II. These ring structures can be aliphatic, unsaturated aliphatic, aromatic or heterocyclic. A further atom of the ring (corresponding to the B' atom of Structure II), bears a further oxygen atom, or a sulfur or nitrogen atom. This oxygen, sulfur or nitrogen atom is bonded to one or more hydrogen atoms, alkyl moieties, or haloalkyl moieties, or is part of a further chemical moiety such as a ureido, carbamate, amide or amidine moiety. The remainder of the ring structure restricts rotation about the bond joining these two ring atoms. This assists in positioning the "further oxygen, sulfur or nitrogen atom" (part of the R position as described above) such that the further atom can be located in close proximity to the 3'-oxygen atom (O3') of the nucleoside.

[0040] Another 2'-sugar substituent group that gives a 3'-endo sugar conformational geometry is the 2'-OMe group. 2'-Substitution of guanosine, cytidine, and uridine dinucleoside phosphates with the 2'-OMe group showed enhanced stacking effects with respect to the corresponding native (2'-OH) species leading to the conclusion that the sugar is adopting a C3'-endo conformation. In this case, it is believed that the hydrophobic attractive forces of the methyl group tend to overcome the destabilizing effects of its steric bulk.

[0041] The ability of oligonucleotides to bind to their complementary target strands is compared by determining the melting temperature (T.sub.m) of the hybridization complex of the oligonucleotide and its complementary strand. The melting temperature (T.sub.m), a characteristic physical property of double helices, denotes the temperature (in degrees centigrade) at which 50% helical (hybridized) versus coil (unhybridized) forms are present. T.sub.m is measured by using the UV spectrum to determine the formation and breakdown (melting) of the hybridization complex. Base stacking, which occurs during hybridization, is accompanied by a reduction in UV absorption (hypochromicity). Consequently, a reduction in UV absorption indicates a higher T.sub.m. The higher the T.sub.m, the greater the strength of the bonds between the strands.

[0042] Freier and Altmann, Nucleic Acids Research, (1997) 25:4429-4443, have previously published a study on the influence of structural modifications of oligonucleotides on the stability of their duplexes with target RNA. In this study, the authors reviewed a series of oligonucleotides containing more than 200 different modifications that had been synthesized and assessed for their hybridization affinity and T.sub.m. Sugar modifications studied included substitutions on the 2'-position of the sugar, 3'-substitution, replacement of the 4'-oxygen, the use of bicyclic sugars, and four member ring replacements. Several nucleobase modifications were also studied including substitutions at the 5, or 6 position of thymine, modifications of pyrimidine heterocycle and modifications of the purine heterocycle. Modified internucleoside linkages were also studied including neutral, phosphorus and non-phosphorus containing internucleoside linkages.

[0043] Increasing the percentage of C3'-endo sugars in a modified oligonucleotide targeted to an RNA target strand should preorganize this strand for binding to RNA. Of the several sugar modifications that have been reported and studied in the literature, the incorporation of electronegative substituents such as 2'-fluoro or 2'-alkoxy shift the sugar conformation towards the 3' endo (northern) pucker conformation. This preorganizes an oligonucleotide that incorporates such modifications to have an A-form conformational geometry. This A-form conformation results in increased binding affinity of the oligonucleotide to a target RNA strand.

[0044] Molecular modeling experiments were performed to study further enhanced binding affinity of oligonucleotides having 2'-O-modifications. Computer simulations were conducted on compounds having SEQ ID NO: 1, r(CGC GAA UUC GCG), having 2'-O-modifications of the invention located at each of the nucleoside of the oligonucleotide. The simulations were performed with the oligonucleotide in aqueous solution using the AMBER force field method (Cornell et al., J. Am. Chem. Soc., 1995, 117, 5179-5197)(modeling software package from UCSF, San Francisco, Calif.). The calculations were performed on an Indigo2 SGI machine (Silicon Graphics, Mountain View, Calif.).

[0045] In addition, for 2'-substituents containing an ethylene glycol motif, a gauche interaction between the oxygen atoms around the O--C--C--O torsion of the side chain may have a stabilizing effect on the duplex (Freier and Altmann, Nucleic Acids Research, 1997, 25, 4429-4443). Such gauche interactions have been observed experimentally for a number of years (Wolfe et al., Acc. Chem. Res., 1972, 5, 102; Abe et al., J. Am. Chem. Soc., 1976, 98, 468). This gauche effect may result in a configuration of the side chain that is favorable for duplex formation. The exact nature of this stabilizing configuration has not yet been explained. While not wishing to be bound by theory, it may be that holding the O--C--C--O torsion in a single gauche configuration, rather than a more random distribution seen in an alkyl side chain, provides an entropic advantage for duplex formation.

[0046] Representative 2'-substituent groups amenable to the present invention that give A-form conformational properties (3'-endo) to the resultant duplexes include 2'-O-alkyl, 2'-O-substituted alkyl and 2'-fluoro substituent groups. Substituent groups can be various alkyl and aryl ethers and thioethers, amines and monoalkyl and dialkyl substituted amines. It is further intended that multiple modifications can be made to one or more nucleosides and or internucleoside linkages within an oligonucleotide of the invention to enhance activity of the oligonucleotide. Tables 2 through 8 list nucleoside and internucleotide linkage modifications/replacements that have been shown to give a positive .epsilon.T.sub.m per modification when the modification/replacement was made to a DNA strand that was hybridized to an RNA complement.

TABLE-US-00003 TABLE 2 Modified DNA strand having 2'-substituent groups that gave an overall increase in T.sub.m against an RNA complement: Positive .epsilon. T.sub.m/mod 2'-substituents 2'-OH 2'-O--C.sub.1-C.sub.4 alkyl 2'-O--(CH.sub.2).sub.2CH.sub.3 2'-O--CH.sub.2CH.dbd.CH.sub.2 2'-F 2'-O--(CH.sub.2).sub.2--O--CH.sub.3 2'-[O--(CH.sub.2).sub.2].sub.2--O--CH.sub.3 2'-[O--(CH.sub.2).sub.2].sub.3--O--CH.sub.3 2'-[O--(CH.sub.2).sub.2].sub.4--O--CH.sub.3 2'-[O--(CH.sub.2).sub.2].sub.3--O--(CH.sub.2).sub.8CH.sub.3 2'-O--(CH.sub.2).sub.2CF.sub.3 2'-O--(CH.sub.2).sub.2OH 2'-O--(CH.sub.2).sub.2F 2'-O--CH.sub.2CH(CH.sub.3)F 2'-O--CH.sub.2CH(CH.sub.2OH)OH 2'-O--CH.sub.2CH(CH.sub.2OCH.sub.3)OCH.sub.3 2'-O--CH.sub.2CH(CH.sub.3)OCH.sub.3 2'-O--CH.sub.2--C.sub.14H.sub.7O.sub.2(--C.sub.14H.sub.7O.sub.2 = Anthraquinone) 2'-O--(CH.sub.2).sub.3--NH.sub.2* 2'-O--(CH.sub.2).sub.4--NH.sub.2* *These modifications can increase the T.sub.m of oligonucleotides but can also decrease the T.sub.m depending on positioning and number (motif dependant).

TABLE-US-00004 TABLE 3 Modified DNA strand having modified sugar ring (see structure) that give an overall increase in T.sub.m against an RNA complement: ##STR00022## Positive .epsilon.T.sub.m/mod Q --S-- --CH.sub.2-- Note: In general ring oxygen substitution with sulfur or methylene had only a minor effect on T.sub.m for the specific motiffs studied. Substitution at the 2'-position with groups shown to stabilize the duplex were destabilizing when CH.sub.2 replaced the ring O. This is thought to be due to the necessary gauche interaction between the ring O with particular 2'- substituents (for example --O--CH.sub.3 and --(O--CH.sub.2CH.sub.2).sub.3--O--CH.sub.3.

TABLE-US-00005 TABLE 4 Modified DNA strand having modified sugar ring that give an overall increase in T.sub.m against an RNA complement: ##STR00023## Positive .epsilon.T.sub.m/mod --C(H)R.sub.1 effects OH (R.sub.2, R.sub.3 both = H) CH.sub.3* CH.sub.2OH* OCH.sub.3* *These modifications can increase the T.sub.m of oligonucleotides but can also decrease the T.sub.m depending on positioning and number (motif dependant).

TABLE-US-00006 TABLE 5 Modified DNA strand having bicyclic substitute sugar modifications that give an overall increase in T.sub.m against an RNA complement: Formula Positive .epsilon.T.sub.m/mod I + II + ##STR00024## ##STR00025##

TABLE-US-00007 TABLE 6 Modified DNA strand having modified heterocyclic base moieties that give an overall increase in T.sub.m against an RNA complement: Modification/Formula Positive .epsilon.T.sub.m/mod Heterocyclic base 2-thioT modifications 2'-O-methylpseudoU 7-halo-7-deaza purines 7-propyne-7-deaza purines 2-aminoA(2,6-diaminopurine) ##STR00026## (R.sub.2, R.sub.3 = H), R1 = Br C/C--CH.sub.3 (CH.sub.2).sub.3NH.sub.2 CH.sub.3 Motiffs-disubstitution R.sub.1 = C/C--CH.sub.3, R.sub.2 = H, R.sub.3 = F R.sub.1 = C/C--CH.sub.3, R.sub.2 = H R.sub.3 = O--(CH.sub.2).sub.2--O--CH.sub.3 R.sub.1 = O--CH.sub.3, R.sub.2 = H, R.sub.3 = O--(CH.sub.2).sub.2--O--CH.sub.3* *This modification can increase the T.sub.m of oligonucleotides but can also decrease the T.sub.m depending on positioning and number (motif dependant).

[0047] Substitution at R.sub.1 can be stabilizing, substitution at R.sub.2 is generally greatly destabilizing (unable to form anti conformation), motiffs with stabilizing 5 and 2'-substituent groups are generally additive e.g. increase stability.

[0048] Substitution of the O4 and O2 positions of 2'-O-methyl uridine was greatly duplex destabilizing as these modifications remove hydrogen binding sites that would be an expected result. 6-Aza T also showed extreme destabilization as this substitution reduces the pK.sub.a and shifts the nucleoside toward the enol tautomer resulting in reduced hydrogen bonding.

TABLE-US-00008 TABLE 7 DNA strand having at least one modified phosphorus containing internucleoside linkage and the effect on the T.sub.m against an RNA complement: .epsilon.T.sub.m/mod + .epsilon.T.sub.m/mod - phosphorothioate.sup.1 phosphoramidate.sup.1 methyl phosphonates.sup.1 (.sup.1one of the non-bridging oxygen atoms replaced with S, N(H)R or --CH.sub.3) phosphoramidate (the 3'-bridging atom replaced with an N(H)R group, stabilization effect enhanced when also have 2'-F)

TABLE-US-00009 TABLE 8 DNA strand having at least one non-phosphorus containing internucleoside linkage and the effect on the T.sub.m against an RNA complement: Positive .epsilon. T.sub.m/mod --CH.sub.2C(.dbd.O)NHCH.sub.2--* --CH.sub.2C(.dbd.O)N(CH.sub.3)CH.sub.2--* --CH.sub.2C(.dbd.O)N(CH.sub.2CH.sub.2CH.sub.3)CH.sub.2--* --CH.sub.2C(.dbd.O)N(H)CH.sub.2-- (motif with 5'-propyne on T's) --CH.sub.2N(H)C(.dbd.O)CH.sub.2--* --CH.sub.2N(CH.sub.3)OCH.sub.2--* --CH.sub.2N(CH.sub.3)N(CH.sub.3)CH.sub.2--* * This modification can increase the T.sub.m of oligonucleotides but can also decrease the T.sub.m depending on positioning and number (motif dependant). Notes: In general carbon chain internucleotide linkages were destabilizing to duplex formation. This destabilization was not as severe when double and tripple bonds were utilized. The use of glycol and flexible ether linkages were also destabilizing.

[0049] Suitable ring structures of the invention for inclusion as a 2'-O modification include cyclohexyl, cyclopentyl and phenyl rings as well as heterocyclic rings having spacial footprints similar to cyclohexyl, cyclopentyl and phenyl rings. Particularly suitable 2'-O-substituent groups of the invention are listed below including an abbreviation for each:

[0050] 2'-O-(trans 2-methoxy cyclohexyl)-2'-O-(TMCHL)

[0051] 2'-O-(trans 2-methoxy cyclopentyl)-2'-O-(TMCPL)

[0052] 2'-O-(trans 2-ureido cyclohexyl)-2'-O-(TUCHL)

[0053] 2'-O-(trans 2-methoxyphenyl)-2'-O-(2 MP)

[0054] Structural details for duplexes incorporating such 2-O-substituents were analyzed using the described AMBER force field program on the Indigo2 SGI machine. The simulated structure maintained a stable A-form geometry throughout the duration of the simulation. The presence of the 2' substitutions locked the sugars in the C3'-endo conformation.

[0055] The simulation for the TMCHL modification revealed that the 2'-O-(TMCHL) side chains have a direct interaction with water molecules solvating the duplex. The oxygen atoms in the 2'-O-(TMCHL) side chain are capable of forming a water-mediated interaction with the 3' oxygen of the phosphate backbone. The presence of the two oxygen atoms in the 2'-O-(TMCHL) side chain gives rise to favorable gauche interactions. The barrier for rotation around the O--C--C--O torsion is made even larger by this novel modification. The preferential preorganization in an A-type geometry increases the binding affinity of the 2'-O-(TMCHL) to the target RNA. The locked side chain conformation in the 2'-O-(TMCHL) group created a more favorable pocket for binding water molecules. The presence of these water molecules played a key role in holding the side chains in the preferable gauche conformation. While not wishing to be bound by theory, the bulk of the substituent, the diequatorial orientation of the substituents in the cyclohexane ring, the water of hydration and the potential for trapping of metal ions in the conformation generated will additionally contribute to improved binding affinity and nuclease resistance of oligonucleotides incorporating nucleosides having this 2'-O-modification.

[0056] As described for the TMCHL modification above, identical computer simulations of the 2'-O-(TMCPL), the 2'-O-(2 MP) and 2'-O-(TUCHL) modified oligonucleotides in aqueous solution also illustrate that stable A-form geometry will be maintained throughout the duration of the simulation. The presence of the 2' substitution will lock the sugars in the C3'-endo conformation and the side chains will have direct interaction with water molecules solvating the duplex. The oxygen atoms in the respective side chains are capable of forming a water-mediated interaction with the 3' oxygen of the phosphate backbone. The presence of the two oxygen atoms in the respective side chains give rise to the favorable gauche interactions. The barrier for rotation around the respective O--C--C--O torsions will be made even larger by respective modification. The preferential preorganization in A-type geometry will increase the binding affinity of the respective 2'-.beta.-modified oligonucleotides to the target RNA. The locked side chain conformation in the respective modifications will create a more favorable pocket for binding water molecules. The presence of these water molecules plays a key role in holding the side chains in the preferable gauche conformation. The bulk of the substituent, the diequatorial orientation of the substituents in their respective rings, the water of hydration and the potential trapping of metal ions in the conformation generated will all contribute to improved binding affinity and nuclease resistance of oligonucleotides incorporating nucleosides having these respective 2'-O-modification.

[0057] Ribose conformations in C2'-modified nucleosides containing S-methyl groups were examined. To understand the influence of 2'-O-methyl and 2'-S-methyl groups on the conformation of nucleosides, we evaluated the relative energies of the 2'-O-- and 2'-S-methylguanosine, along with normal deoxyguanosine and riboguanosine, starting from both C2'-endo and C3'-endo conformations using ab initio quantum mechanical calculations. All the structures were fully optimized at HF/6-31G* level and single point energies with electron-correlation were obtained at the MP2/6-31G*//HF/6-31G* level. As shown in Table 9, the C2'-endo conformation of deoxyguanosine is estimated to be 0.6 kcal/mol more stable than the C3'-endo conformation in the gas-phase. The conformational preference of the C2'-endo over the C3'-endo conformation appears to be less dependent upon electron correlation as revealed by the MP2/6-31G*//HF/6-31G* values which also predict the same difference in energy. The opposite trend is noted for riboguanosine. At the HF/6-31G* and MP2/6-31G*//HF/6-31G* levels, the C3'-endo form of riboguanosine is shown to be about 0.65 and 1.41 kcal/mol more stable than the C2' endo form, respectively.

TABLE-US-00010 TABLE 9 Relative energies* of the C3'-endo and C2'-endo conformations of representative nucleosides Continuum HF/6-31G MP2/6-31-G Model Amber dG 0.60 0.56 0.88 0.65 rG -0.65 -1.41 -0.28 -2.09 2'-O--MeG -0.89 -1.79 -0.36 -0.86 2'-S--MeG 2.55 1.41 3.16 2.43 *energies are in kcal/mol relative to the C2'-endo conformation

[0058] Table 9 also includes the relative energies of 2'-O-methylguanosine and 2'-S-methylguanosine in C2'-endo and C3'-endo conformation. This data indicates the electronic nature of C2'-substitution has a significant impact on the relative stability of these conformations. Substitution of the 2'-O-methyl group increases the preference for the C3'-endo conformation (when compared to riboguanosine) by about 0.4 kcal/mol at both the HF/6-31G* and MP2/6-31G*//HF/6-31G* levels. In contrast, the 2'-S-methyl group reverses the trend. The C2'-endo conformation is favored by about 2.6 kcal/mol at the HF/6-31G* level, while the same difference is reduced to 1.41 kcal/mol at the MP2/6-31G*//HF/6-31G* level. For comparison, and also to evaluate the accuracy of the molecular mechanical force-field parameters used for the 2'-O-methyl and 2'-S-methyl substituted nucleosides, we have calculated the gas phase energies of the nucleosides. The results reported in Table 9 indicate that the calculated relative energies of these nucleosides compare qualitatively well with the ab initio calculations.

[0059] Additional calculations were also performed to gauge the effect of solvation on the relative stability of nucleoside conformations. The estimated solvation effect using HF/6-31G* geometries confirms that the relative energetic preference of the four nucleosides in the gas-phase is maintained in the aqueous phase as well (Table 9). Solvation effects were also examined using molecular dynamics simulations of the nucleosides in explicit water. From these trajectories, one can observe the predominance of C2'-endo conformation for deoxyriboguanosine and 2'-S-methylriboguanosine while riboguanosine and 2'-O-methylriboguanosine prefer the C3'-endo conformation. These results are in much accord with the available NMR results on 2'-S-methylribonucleosides. NMR studies of sugar puckering equilibrium using vicinal spin-coupling constants have indicated that the conformation of the sugar ring in 2'-S-methylpyrimidine nucleosides show an average of >75% S-character, whereas the corresponding purine analogs exhibit an average of >90% S-pucker (Fraser, A., Wheeler, P., Cook, P. D. and Sanghvi, Y. S., J. Heterocycl. Chem., 1993, 30, 1277-1287). It was observed that the 2'-S-methyl substitution in deoxynucleoside confers more conformational rigidity to the sugar conformation when compared with deoxyribonucleosides.

[0060] Structural features of DNA:RNA, OMe-DNA:RNA and SMe-DNA:RNA hybrids were also observed. The average RMS deviation of the DNA:RNA structure from the starting hybrid coordinates indicate the structure is stabilized over the length of the simulation with an approximate average RMS deviation of 1.0 .ANG.. This deviation is due, in part, to inherent differences in averaged structures (i.e. the starting conformation) and structures at thermal equilibrium. The changes in sugar pucker conformation for three of the central base pairs of this hybrid are in good agreement with the observations made in previous NMR studies. The sugars in the RNA strand maintain very stable geometries in the C3'-endo conformation with ring pucker values near 0.degree.. In contrast, the sugars of the DNA strand show significant variability.

[0061] The average RMS deviation of the OMe-DNA:RNA is approximately 1.2 .ANG. from the starting A-form conformation; while the SMe-DNA:RNA shows a slightly higher deviation (approximately 1.8 .ANG.) from the starting hybrid conformation. The SMe-DNA strand also shows a greater variance in RMS deviation, suggesting the S-methyl group may induce some structural fluctuations. The sugar puckers of the RNA complements maintain C3'-endo puckering throughout the simulation. As expected from the nucleoside calculations, however, significant differences are noted in the puckering of the OMe-DNA and SMe-DNA strands, with the former adopting C3'-endo, and the latter, C1'-exo/C2'-endo conformations.

[0062] An analysis of the helicoidal parameters for all three hybrid structures has also been performed to further characterize the duplex conformation. Three of the more important axis-basepair parameters that distinguish the different forms of the duplexes, X-displacement, propeller twist, and inclination, are reported in Table 10. Usually, an X-displacement near zero represents a B-form duplex; while a negative displacement, which is a direct measure of deviation of the helix from the helical axis, makes the structure appear more A-like in conformation. In A-form duplexes, these values typically vary from -4 .ANG. to -5 .ANG.. In comparing these values for all three hybrids, the SMe_DNA:RNA hybrid shows the most deviation from the A-form value, the OMe_DNA:RNA shows the least, and the DNA:RNA is intermediate. A similar trend is also evident when comparing the inclination and propeller twist values with ideal A-form parameters. These results are further supported by an analysis of the backbone and glycosidic torsion angles of the hybrid structures. Glycosidic angles (X) of A-form geometries, for example, are typically near -159.degree. while B form values are near -102.degree.. These angles are found to be -162.degree., -133.degree., and -108.degree. for the OMe-DNA, DNA, and SMe-DNA strands, respectively. All RNA complements adopt an X angle close to -160.degree.. In addition, "crankshaft" transitions were also noted in the backbone torsions of the central UpU steps of the RNA strand in the SMe-DNA:RNA and DNA;RNA hybrids. Such transitions suggest some local conformational changes may occur to relieve a less favorable global conformation. Taken overall, the results indicate the amount of A-character decreases as OMe-DNA:RNA>DNA:RNA>SMe-DNA:RNA, with the latter two adopting more intermediate conformations when compared to A- and B-form geometries.

TABLE-US-00011 TABLE 10 Average helical parameters derived from the last 500 ps of simulation time (canonical A-and B-form values are given for comparison) OMe_ SMe_ Helicoidal B-DNA B-DNA A-DNA DNA: DNA: DNA: Parameter (x-ray) (fibre) (fibre) RNA RNA RNA X-disp 1.2 0.0 -5.3 -4.5 -5.4 -3.5 Inclination -2.3 1.5 20.7 11.6 15.1 0.7 Propeller -16.4 -13.3 -7.5 -12.7 -15.8 -10.3

Stability of C2'-modified DNA:RNA hybrids was determined. Although the overall stability of the DNA:RNA hybrids depends on several factors including sequence-dependencies and the purine content in the DNA or RNA strands DNA:RNA hybrids are usually less stable than RNA:RNA duplexes and, in some cases, even less stable than DNA:DNA duplexes. Available experimental data attributes the relatively lowered stability of DNA:RNA hybrids largely to its intermediate conformational nature between DNA:DNA (B-family) and RNA:RNA (A-family) duplexes. The overall thermodynamic stability of nucleic acid duplexes may originate from several factors including the conformation of backbone, base-pairing and stacking interactions. While it is difficult to ascertain the individual thermodynamic contributions to the overall stabilization of the duplex, it is reasonable to argue that the major factors that promote increased stability of hybrid duplexes are better stacking interactions (electrostatic .pi.-.pi. interactions) and more favorable groove dimensions for hydration. The C2'-S-methyl substitution has been shown to destabilize the hybrid duplex. The notable differences in the rise values among the three hybrids may offer some explanation. While the 2'-S-methyl group has a strong influence on decreasing the base-stacking through high rise values (.about.3.2 .ANG.), the 2'-O-methyl group makes the overall structure more compact with a rise value that is equal to that of A-form duplexes (.about.2.6 .ANG.). Despite its overall A-like structural features, the SMe DNA:RNA hybrid structure possesses an average rise value of 3.2 .ANG. which is quite close to that of B-family duplexes. In fact, some local base-steps (CG steps) may be observed to have unusually high rise values (as high as 4.5 .ANG.). Thus, the greater destabilization of 2'-S-methyl substituted DNA:RNA hybrids may be partly attributed to poor stacking interactions.

[0063] It has been postulated that RNase H binds to the minor groove of RNA:DNA hybrid complexes, requiring an intermediate minor groove width between ideal A- and B-form geometries to optimize interactions between the sugar phosphate backbone atoms and RNase H. A close inspection of the averaged structures for the hybrid duplexes using computer simulations reveals significant variation in the minor groove width dimensions as shown in Table 11. Whereas the O-methyl substitution leads to a slight expansion of the minor groove width when compared to the standard DNA:RNA complex, the S-methyl substitution leads to a general contraction (approximately 0.9 .ANG.). These changes are most likely due to the preferred sugar puckering noted for the antisense strands which induce either A- or B-like single strand conformations. In addition to minor groove variations, the results also point to potential differences in the steric makeup of the minor groove. The O-methyl group points into the minor groove while the S-methyl is directed away towards the major groove. Essentially, the S-methyl group has flipped through the bases into the major groove as a consequence of C2'-endo puckering.

TABLE-US-00012 TABLE 11 Minor groove widths averaged over the last 500 ps of simulation time Phosphate DNA: OMe_DNA: SMe_DNA: DNA: RNA RNA: RNA Distance RNA RNA RNA (B-form) (A-form) P5-P20 15.27 16.82 13.73 14.19 17.32 P6-P19 15.52 16.79 15.73 12.66 17.12 P7-P18 15.19 16.40 14.08 11.10 16.60 P8-P17 15.07 16.12 14.00 10.98 16.14 P9-P16 15.29 16.25 14.98 11.65 16.93 P10-P15 15.37 16.57 13.92 14.05 17.69

[0064] In addition to the modifications described above, the nucleotides of the chimeric oligomeric compounds of the invention can have a variety of other modification so long as these other modifications do not significantly detract from the properties described above. Thus, for nucleotides that are incorporated into oligonucleotides of the invention, these nucleotides can have sugar portions that correspond to naturally-occurring sugars or modified sugars. Representative modified sugars include carbocyclic or acyclic sugars, sugars having substituent groups at their 2' position, sugars having substituent groups at their 3' position, and sugars having substituents in place of one or more hydrogen atoms of the sugar. Other altered base moieties and altered sugar moieties are disclosed in U.S. Pat. No. 3,687,808 and PCT application PCT/US89/02323.

2'-Endo Regions

[0065] A number of different nucleosides can be used independently or exclusively to create one or more of the C2'-endo regions to prepare chimeric oligomeric compounds of the present invention. For the purpose of the present invention the terms 2'-endo and C2'-endo are meant to include 04'-endo and 2'-deoxy nucleosides. 2'-Deoxy nucleic acids prefer both C2'-endo sugar pucker and O4'-endo sugar, i.e., also known as Southern pucker, which is thought to impart a less stable B-form geometry (Sanger, W. (1984) Principles of Nucleic Acid Structure, Springer-Verlag, New York, N.Y. and Berger, et. al., Nucleic Acids Research, 1998, 26, 2473-2480). The 2'-deoxyribonucleoside is one suitable nucleoside for the 2'-endo regions but all manner of nucleosides known in the art that have a preference for 2'-endo sugar conformational geometry are amenable to the present invention. Such nucleosides include without limitation 2'-modified ribonucleosides such as for example: 2'-SCH.sub.3, 2'-NH.sub.2, 2'-NH(C.sub.1-C.sub.2 alkyl), 2'-N(C.sub.1-C.sub.2 alkyl).sub.2, 2'-CF.sub.3, 2'=CH.sub.2, 2'=CHF, 2'=CF.sub.2, 2'-CH.sub.3, 2'-C.sub.2H.sub.5, 2'-CH.dbd.CH.sub.2 or 2'-C.ident.CH. Also amenable to the present invention are modified 2'-arabinonucleosides including without limitation: 2'-CN, 2'-F, 2'-Cl, 2'-Br, 2'-N.sub.3 (azido), 2'-OH, 2'-O--CH.sub.3 or 2'-dehydro-2'-CH.sub.3.

[0066] Suitable sugar modifications for the 2'-endo regions of the present invention include without limitation 2'-deoxy-2'-S-methyl, 2'-deoxy-2'-methyl, 2'-deoxy-2'-amino, 2'-deoxy-2'-mono or dialkyl substituted amino, 2'-deoxy-2'-fluoromethyl, 2'-deoxy-2'-difluoromethyl, 2'-deoxy-2'-trifluoromethyl, 2'-deoxy-2'-methylene, 2'-deoxy-2'-fluoromethylene, 2'-deoxy-2'-difluoromethylene, 2'-deoxy-2'-ethyl, 2'-deoxy-2'-ethylene and 2'-deoxy-2'-acetylene. These nucleotides can alternately be described as 2'-SCH.sub.3 ribonucleotide, 2'-CH.sub.3 ribonucleotide, 2'--NH.sub.2 ribonucleotide 2'--NH(C.sub.1-C.sub.2 alkyl) ribonucleotide, 2'-N(C.sub.1-C.sub.2 alkyl).sub.2 ribonucleotide, 2'-CH.sub.2F ribonucleotide, 2'-CHF.sub.2 ribonucleotide, 2'-CF.sub.3 ribonucleotide, 2'=CH.sub.2 ribonucleotide, 2'=CHF ribonucleotide, 2'=CF.sub.2 ribonucleotide, 2'-C.sub.2H.sub.5 ribonucleotide, 2'-CH.dbd.CH.sub.2 ribonucleotide, 2'-C.quadrature.CH ribonucleotide. A further useful sugar modification is one having a ring located on the ribose ring in a cage-like structure including 3',O,4'-C-methyleneribonucleotides. Such cage-like structures will physically fix the ribose ring in the desired conformation.

[0067] Additionally, suitable sugar modifications for the 2'-endo regions of the present invention include without limitation are arabino nucleotides having 2'-deoxy-2'-cyano, 2'-deoxy-2'-fluoro, 2'-deoxy-2'-chloro, 2'-deoxy-2'-bromo, 2'-deoxy-2'-azido, 2'-methoxy and the unmodified arabino nucleotide (that includes a 2'-OH projecting upwards towards the base of the nucleotide). These arabino nucleotides can alternately be described as 2'-CN arabino nucleotide, 2'-F arabino nucleotide, 2'-C1 arabino nucleotide, 2'-Br arabino nucleotide, 2'-N.sub.3 arabino nucleotide, 2'-O--CH.sub.3 arabino nucleotide and arabino nucleotide.

[0068] Such nucleotides are linked together via phosphorothioate, phosphorodithioate, boranophosphate or phosphodiester linkages. Particularly suitable is the phosphorothioate linkage.

Internucleoside Linkages

[0069] Specific examples of chimeric oligomeric compounds useful in this invention include oligonucleotides containing modified e.g. non-naturally occurring internucleoside linkages. As defined in this specification, oligonucleotides having modified internucleoside linkages include internucleoside linkages that retain a phosphorus atom and internucleoside linkages that do not have a phosphorus atom. For the purposes of this specification, and as sometimes referenced in the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. Modified internucleoside linkages containing a phosphorus atom therein include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates, 5'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, selenophosphates and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein one or more internucleotide linkages is a 3' to 3', 5' to 5' or 2' to 2' linkage. Oligonucleotides having inverted polarity comprise a single 3' to 3' linkage at the 3'-most internucleotide linkage i.e. a single inverted nucleoside residue which may be abasic (the nucleobase is missing or has a hydroxyl group in place thereof). Various salts, mixed salts and free acid forms are also included.

[0070] Representative United States patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; 5,194,599; 5,565,555; 5,527,899; 5,721,218; 5,672,697 and 5,625,050, each of which is herein incorporated by reference.

[0071] In other embodiments of the invention, chimeric oligomeric compounds include one or more phosphorothioate and/or heteroatom internucleoside linkages, in particular --CH.sub.2--NH--O--CH.sub.2--, --CH.sub.2--N(CH.sub.3)--O--CH.sub.2-- [known as a methylene (methylimino) or MMI backbone], --CH.sub.2--O--N(CH.sub.3)--CH.sub.2--, --CH.sub.2--N(CH.sub.3)--N(CH.sub.3)--CH.sub.2-- and --O--N(CH.sub.3)--CH.sub.2--CH.sub.2-- [wherein the native phosphodiester internucleotide linkage is represented as --O--P(.dbd.O)(OH)--O--CH.sub.2--]. The MMI type internucleoside linkages are disclosed in the above referenced U.S. Pat. No. 5,489,677. Amide internucleoside linkages are disclosed in the above referenced U.S. Pat. No. 5,602,240.

[0072] Modified internucleoside linkages that do not include a phosphorus atom therein include those formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; riboacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH.sub.2 component parts.

[0073] Representative United States patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and 5,677,439, each of which is herein incorporated by reference.

Conjugate Groups

[0074] An additional substitution that can be appended to the oligomeric compounds of the invention involves the linkage of one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the resulting oligomeric compounds. In one embodiment such modified oligomeric compounds are prepared by covalently attaching conjugate groups to functional groups such as hydroxyl or amino groups. Conjugate groups of the invention include intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, polyethers, groups that enhance the pharmacodynamic properties of oligomers, and groups that enhance the pharmaco-kinetic properties of oligomers. Typical conjugates groups include cholesterols, lipids, phospho-lipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, fluoresceins, rhodamines, coumarins, and dyes. Groups that enhance the pharmacodynamic properties, in the context of this invention, include groups that improve oligomer uptake, enhance oligomer resistance to degradation, and/or strengthen sequence-specific hybridization with RNA. Groups that enhance the pharmacokinetic properties, in the context of this invention, include groups that improve oligomer uptake, distribution, metabolism or excretion. Representative conjugate groups are disclosed in International Patent Application PCT/US92/09196, filed Oct. 23, 1992 the entire disclosure of which is incorporated herein by reference. Conjugate moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994, 4, 1053-1060), a thioether, e.g., hexyl-5-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids

[0075] Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937.

[0076] The chimeric oligomeric compounds of the invention may also be conjugated to active drug substances, for example, aspirin, warfarin, phenylbutazone, ibuprofen, naproxen, suprofen, fenbufen, ketoprofen, (S)-(+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, flufenamic acid, folinic acid, a benzothiadiazide, chlorothiazide, a diazepine, indomethicin, a barbiturate, a cephalosporin, a sulfa drug, an antidiabetic, an antibacterial or an antibiotic. Oligonucleotide-drug conjugates and their preparation are described in U.S. patent application Ser. No. 09/334,130 which is incorporated herein by reference in its entirety.

[0077] Representative United States patents that teach the preparation of such oligonucleotide conjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporated by reference.

[0078] Oligomeric compounds used in the compositions of the present invention can also be modified to have one or more stabilizing groups that are generally attached to one or both termini of oligomeric compounds to enhance properties such as for example nuclease stability. Included in stabilizing groups are cap structures. By "cap structure or terminal cap moiety" is meant chemical modifications, which have been incorporated at either terminus of oligonucleotides (see for example Wincott et al., WO 97/26270, incorporated by reference herein). These terminal modifications protect the oligomeric compounds having terminal nucleic acid molecules from exonuclease degradation, and can help in delivery and/or localization within a cell. The cap can be present at the 5'-terminus (5'-cap) or at the 3'-terminus (3'-cap) or can be present on both termini. In non-limiting examples, the 5'-cap includes inverted 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 riucleotide, 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 (for more details see Wincott et al., International PCT publication No. WO 97/26270, which is incorporated by reference herein.

[0079] Particularly suitable 3'-cap structures of the present invention include, for example 4',5'-methylene nucleotide; 1-(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 Tyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).

[0080] Further 3' and 5'-stabilizing groups that can be used to cap one or both ends of an oligomeric compound to impart nuclease stability include those disclosed in WO 03/004602.

Oligomeric Compounds

[0081] In the context of the present invention, the term "oligomeric compound" refers to a polymeric structure capable of hybridizing a region of a nucleic acid molecule. This term includes oligonucleotides, oligonucleosides, oligonucleotide analogs, oligonucleotide mimetics and combinations of these. Oligomeric compounds routinely prepared linearly but can be joined or otherwise prepared to be circular and may also include branching. Oligomeric compounds can hybridized to form double stranded compounds which can be blunt ended or may include overhangs. In general an oligomeric compound comprises a backbone of linked momeric subunits where each linked momeric subunit is directly or indirectly attached to a heterocyclic base moiety. The linkages joining the monomeric subunits, the sugar moieties or surrogates and the heterocyclic base moieties can be independently modified giving rise to a plurality of motifs for the resulting oligomeric compounds including hemimers, gapmers and chimeras.

[0082] As is known in the art, a nucleoside is a base-sugar combination. The base portion of the nucleoside is normally a heterocyclic base moiety. The two most common classes of such heterocyclic bases are purines and pyrimidines. Nucleotides are nucleosides that further include a phosphate group covalently linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be linked to the 2', 3' or 5' hydroxyl moiety of the sugar. In forming oligonucleotides, the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound. The respective ends of this linear polymeric structure can be joined to form a circular structure by hybridization or by formation of a covalent bond, however, open linear structures are generally suitable. Within the oligonucleotide structure, the phosphate groups are commonly referred to as forming the internucleoside linkages of the oligonucleotide. The normal internucleoside linkage of RNA and DNA is a 3' to 5' phosphodiester linkage.

[0083] In the context of this invention, the term "oligonucleotide" refers to an oligomer or polymer of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA). This term includes oligonucleotides composed of naturally-occurring nucleobases, sugars and covalent internucleoside linkages. The term "oligonucleotide analog" refers to oligonucleotides that have one or more non-naturally occurring portions which function in a similar manner to oligonulceotides. Such non-naturally occurring oligonucleotides are often desired, the naturally occurring forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic acid target and increased stability in the presence of nucleases.

[0084] In the context of this invention, the term "oligonucleoside" refers to nucleosides that are joined by internucleoside linkages that do not have phosphorus atoms. Internucleoside linkages of this type include short chain alkyl, cycloalkyl, mixed heteroatom alkyl, mixed heteroatom cycloalkyl, one or more short chain heteroatomic and one or more short chain heterocyclic. These internucleoside linkages include but are not limited to siloxane, sulfide, sulfoxide, sulfone, acetyl, formacetyl, thioformacetyl, methylene formacetyl, thioformacetyl, alkeneyl, sulfamate; methyleneimino, methylenehydrazino, sulfonate, sulfonamide, amide and others having mixed N, O, S and CH.sub.2 component parts.

[0085] Representative United States patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and 5,677,439, each of which is herein incorporated by reference.

[0086] Further included in the present invention are oligomeric compounds such as antisense oligomeric compounds, antisense oligonucleotides, alternate splicers and other oligomeric compounds which hybridize to at least a portion of the target nucleic acid. As such, these oligomeric compounds may be introduced in the form of single-stranded, double-stranded, circular or hairpin oligomeric compounds and may contain structural elements such as internal or terminal bulges or loops or mismatches. Once introduced to a system, the oligomeric compounds of the invention may elicit the action of one or more enzymes or structural proteins to effect modification of the target nucleic acid.

[0087] One non-limiting example of such an enzyme is RNAse H, a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. It is known in the art that single-stranded antisense oligomeric compounds which are "DNA-like" or have "DNA-like" regions elicit RNAse H. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of oligonucleotide-mediated inhibition of gene expression. Similar roles have been postulated for other ribonucleases such as those in the RNase III and ribonuclease L family of enzymes.

[0088] While one form of antisense acting chimeric oligomeric compound is a single-stranded chimeric oligonucleotide, in many species the introduction of double-stranded structures, such as double-stranded RNA (dsRNA) molecules, has been shown to induce potent and specific antisense-mediated reduction of the function of a gene or its associated gene products. This phenomenon, which has been designated RNA interference (RNAi), occurs in both plants and animals and is believed to have an evolutionary connection to viral defense and transposon silencing. The term RNAi has been generalized to mean antisense-mediated gene silencing involving the introduction of dsRNA leading to the sequence-specific reduction of endogenous targeted mRNA levels (Fire et al., Nature, 1998, 391, 806-811). It has been shown that it is, in fact, the single-stranded RNA oligomers of antisense polarity of the dsRNAs which are the potent inducers of RNAi (Tijsterman et al., Science, 2002, 295, 694-697). The primary interference effects of dsRNAs are posttranscriptional (Montgomery et al., Proc. Natl. Acad. Sci. USA, 1998, 95, 15502-15507).

[0089] In addition to the modifications described above, the nucleosides of the oligomeric compounds of the invention can have a variety of other modifications. These modifications either alone or in combination with other nucleosides may enhance one or more of the desired properties described above. Thus, for nucleotides that are incorporated into oligonucleotides of the invention, these nucleotides can have sugar portions that correspond to naturally-occurring sugars or modified sugars. Representative modified sugars include carbocyclic or acyclic sugars, sugars having substituent groups at one or more of their 2', 3' or 4' positions and sugars having substituents in place of one or more hydrogen atoms of the sugar. Additional nucleosides amenable to the present invention having altered base moieties and or altered sugar moieties are disclosed in U.S. Pat. No. 3,687,808 and PCT application PCT/US89/02323.

[0090] The oligomeric compounds in accordance with this invention comprise from about 5 to about 80 nucleobases (i.e. from about 5 to about 80 linked nucleosides). One of ordinary skill in the art will appreciate that the invention embodies oligomeric compounds of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, or 80 nucleobases in length, or any sub-range therewithin.

[0091] In a further embodiment, the oligomeric compounds of the invention are 5 to 50 nucleobases in length. One of ordinary skill in the art will appreciate that the invention embodies oligomeric compounds of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 nucleobases in length, or any sub-range therewithin.

[0092] In another embodiment, the oligomeric compounds of the invention are 12 to 50 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleobases in length, or any sub-range therewithin.

[0093] In another embodiment, the oligomeric compounds of the invention are 12 to 30 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleobases in length, or any sub-range therewithin.

[0094] In a further embodiment, the oligomeric compounds of the invention are 13 to 40 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 nucleobases in length, or any sub-range therewithin.

[0095] In another embodiment, the oligomeric compounds of the invention are 15 to 30 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleobases in length, or any sub-range therewithin.

[0096] In another embodiment, the oligomeric compounds of the invention are 15 to 25 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleobases in length, or any sub-range therewithin.

[0097] In a further embodiment, the oligomeric compounds of the invention are 21 to 25 nucleobases in length. One having ordinary skill in the art will appreciate that this embodies oligomeric compounds of 21, 22, 23, 24 or 25 nucleobases in length, or any sub-range therewithin.

[0098] Particularly suitable oligomeric compounds are oligonucleotides comprising from about 12 to about 50 nucleobases, from about 13 to 40 nucleobases, or from about 15 to about 30 nucleobases.

Oligomer Synthesis

[0099] Oligomerization of modified and unmodified nucleosides is performed according to literature procedures for DNA (Protocols for Oligonucleotides and Analogs, Ed. Agrawal (1993), Humana Press) and/or RNA (Scaringe, Methods (2001), 23, 206-217. Gait et al., Applications of Chemically synthesized RNA in RNA:Protein Interactions, Ed. Smith (1998), 1-36. Gallo et al., Tetrahedron (2001), 57, 5707-5713) synthesis as appropriate. In addition specific protocols for the synthesis of oligomeric compounds of the invention are illustrated in the examples below.

[0100] The oligomeric compounds used in accordance with this invention may be conveniently and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, Calif.). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives.

[0101] The present invention is also useful for the preparation of oligomeric compounds incorporating at least one 2'-O-protected nucleoside. After incorporation and appropriate deprotection the 2'-O-protected nucleoside will be converted to a ribonucleoside at the position of incorporation. The number and position of the 2-ribonucleoside units in the final oligomeric compound can vary from one at any site or the strategy can be used to prepare up to a full 2'-OH modified oligomeric compound. All 2'-O-protecting groups amenable to the synthesis of oligomeric compounds are included in the present invention. In general a protected nucleoside is attached to a solid support by for example a succinate linker. Then the oligonucleotide is elongated by repeated cycles of deprotecting the 5'-terminal hydroxyl group, coupling of a further nucleoside unit, capping and oxidation (alternatively sulfurization). In a more frequently used method of synthesis the completed oligonucleotide is cleaved from the solid support with the removal of phosphate protecting groups and exocyclic amino protecting groups by treatment with an ammonia solution. Then a further deprotection step is normally required for the more specialized protecting groups used for the protection of 2'-hydroxyl groups which will give the fully deprotected oligonucleotide.

[0102] A large number of 2'-O-protecting groups have been used for the synthesis of oligoribo-nucleotides but over the years more effective groups have been discovered. The key to an effective 2'-O-protecting group is that it is capable of selectively being introduced at the 2'-O-position and that it can be removed easily after synthesis without the formation of unwanted side products. The protecting group also needs to be inert to the normal deprotecting, coupling, and capping steps required for oligoribonucleotide synthesis. Some of the protecting groups used initially for oligoribonucleotide synthesis included tetrahydropyran-1-yl and 4-methoxytetrahydropyran-4-yl. These two groups are not compatible with all 5'-O-protecting groups so modified versions were used with 5'-DMT groups such as 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp). Reese has identified a number of piperidine derivatives (like Fpmp) that are useful in the synthesis of oligoribonucleotides including 1-[(chloro-4-methyl)phenyl]-4'-methoxypiperidin-4-yl (Reese et al., Tetrahedron Lett., 1986, (27), 2291). Another approach was to replace the standard 5'-DMT (dimethoxytrityl) group with protecting groups that were removed under non-acidic conditions such as levulinyl and 9-fluorenylmethoxycarbonyl. Such groups enable the use of acid labile 2'-protecting groups for oligoribonucleotide synthesis. Another more widely used protecting group initially used for the synthesis of oligoribonucleotides was the t-butyldimethylsilyl group (Ogilvie et al., Tetrahedron Lett., 1974, 2861; Hakimelahi et al., Tetrahedron Lett., 1981, (22), 2543; and Jones et al., J. Chem. Soc. Perkin I, 2762). The 2'-O-protecting groups can require special reagents for their removal such as for example the t-butyldimethylsilyl group is normally removed after all other cleaving/deprotecting steps by treatment of the oligomeric compound with tetrabutylammonium fluoride (TBAF).

[0103] One group of researchers examined a number of 2'-O-protecting groups (Pitsch, S., Chimia, 2001, (55), 320-324.) The group examined fluoride labile and photolabile protecting groups that are removed using moderate conditions. One photolabile group that was examined was the [2-(nitrobenzyl)oxy]methyl (nbm) protecting group (Schwartz et al., Bioorg. Med. Chem. Lett., 1992, (2), 1019.) Other groups examined included a number structurally related formaldehyde acetal-derived, 2'-O-protecting groups. Also prepared were a number of related protecting groups for preparing 2'-O-alkylated nucleoside phosphoramidites including 2'-O--[(triisopropylsilyl)oxy]methyl (2'-O--CH.sub.2--O--Si(iPr).sub.3, TOM). One 2'-O-protecting group that was prepared to be used orthogonally to the TOM group was 2'-O--[(R)-1-(2-nitrophenyl)ethyloxy)methyl] ((R)-mnbm).

[0104] Another strategy using a fluoride labile 5'-O-protecting group (non-acid labile) and an acid labile 2'-O-protecting group has been reported (Scaringe, Stephen A., Methods, 2001, (23) 206-217). A number of possible silyl ethers were examined for 5'-O-protection and a number of acetals and orthoesters were examined for 2'-O-protection. The protection scheme that gave the best results was 5'-O-silyl ether-2'-ACE (5'-O-bis(trimethylsiloxy)cyclododecyloxysilyl ether (DOD)-2'-O-bis(2-acetoxyethoxy)methyl (ACE). This approach uses a modified phosphoramidite synthesis approach in that some different reagents are required that are not routinely used for RNA/DNA synthesis.

[0105] Although a lot of research has focused on the synthesis of oligoribonucleotides the main RNA synthesis strategies that are presently being used commercially include 5'-O-DMT-2'-O-t-butyldimethylsilyl (TBDMS), 5'-O-DMT-2'-O-[1 (2-fluorophenyl)-4-methoxypiperidin-4-yl] (FPMP), 2'-O-[(triisopropylsilyl)oxy]methyl (2'-O--CH.sub.2--O--Si(iPr).sub.3 (TOM), and the 5'-O-silyl ether-2'-ACE (5'-O-bis(trimethylsiloxy)cyclododecyloxysilyl ether (DOD)-2'-O-bis(2-acetoxyethoxy)methyl (ACE). A current list of some of the major companies currently offering RNA products include Pierce Nucleic Acid Technologies, Dharmacon Research Inc., Ameri Biotechnologies Inc., and Integrated DNA Technologies, Inc. One company, Princeton Separations, is marketing an RNA synthesis activator advertised to reduce coupling times especially with TOM and TBDMS chemistries. Such an activator would also be amenable to the present invention.

[0106] The primary groups being used for commercial RNA synthesis are: [0107] TBDMS=5'-O-DMT-2'-O-t-butyldimethylsilyl; [0108] TOM=2'-O-[(triisopropylsilyl)oxy]methyl; [0109] DOD/ACE=(5'-O-bis(trimethylsiloxy)cyclododecyloxysilyl ether-2'-O-bis(2-acetoxyethoxy)methyl [0110] FPMP=5'-O-DMT-2'-O-[1(2-fluorophenyl)-4-methoxypiperidin-4-yl].

[0111] All of the aforementioned RNA synthesis strategies are amenable to the present invention. Strategies that would be a hybrid of the above e.g. using a 5'-protecting group from one strategy with a 2'-O-protecting from another strategy is also amenable to the present invention.

[0112] The preparation of ribonucleotides and oligomeric compounds having at least one ribonucleoside incorporated and all the possible configurations falling in between these two extremes are encompassed by the present invention. The corresponding oligomeric compounds can be hybridized to further oligomeric compounds including oligoribonucleotides having regions of complementarity to form double-stranded (duplexed) oligomeric compounds, which are commonly referred to as dsRNAs in the art. Such double stranded oligonucleotide moieties have been shown in the art to modulate target expression and regulate translation as well as RNA processsing via an antisense mechanism. Moreover, the double-stranded moieties may be subject to chemical modifications (Fire et al., Nature, 1998, 391, 806-811; Timmons and Fire, Nature 1998, 395, 854; Timmons et al., Gene, 2001, 263, 103-112; Tabara et al., Science, 1998, 282, 430-431; Montgomery et al., Proc. Natl. Acad. Sci. USA, 1998, 95, 15502-15507; Tuschl et al., Genes Dev., 1999, 13, 3191-3197; Elbashir et al., Nature, 2001, 411, 494-498; Elbashir et al., Genes Dev. 2001, 15, 188-200). For example, such double-stranded moieties have been shown to inhibit the target by the classical hybridization of antisense strand of the duplex to the target, thereby triggering enzymatic degradation of the target (Tijsterman et al., Science, 2002, 295, 694-697). The effects of nucleoside modifications on RNAi activity are evaluated according to existing literature (Elbashir et al., Nature (2001), 411, 494-498; Nishikura et al., Cell (2001), 107, 415-416; and Bass et al., Cell (2000), 101, 235-238.)

[0113] The methods of preparing oligomeric compounds of the present invention can also be applied in the areas of drug discovery and target validation.

Oligomer Mimetics (Oligonucleotide Mimics)

[0114] Another group of oligomeric compounds amenable to the present invention includes oligonucleotide mimetics. The term mimetic as it is applied to oligonucleotides is intended to include oligomeric compounds wherein only the furanose ring or both the furanose ring and the internucleotide linkage are replaced with novel groups, replacement of only the furanose ring is also referred to in the art as being a sugar surrogate. The heterocyclic base moiety or a modified heterocyclic base moiety is maintained for hybridization with an appropriate target nucleic acid. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA oligomeric compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative United States patents that teach the preparation of PNA oligomeric compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA oligomeric compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.

[0115] PNA has been modified in the art to incorporate numerous modifications since the basic PNA structure was first prepared. The basic structure is shown below:

##STR00027##

wherein

[0116] Bx is a heterocyclic base moiety;

[0117] T.sub.4 is hydrogen, an amino protecting group, --C(O)R.sub.5, substituted or unsubstituted C.sub.1-C.sub.12 alkyl, substituted or unsubstituted C.sub.2-C.sub.12 alkenyl, substituted or unsubstituted C.sub.2-C.sub.12 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L .alpha.-amino acid linked via the .alpha.-carboxyl group or optionally through the .omega.-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;

[0118] T.sub.5 is --OH, --N(Z.sub.1)Z.sub.2, R.sub.5, D or L .alpha.-amino acid linked via the .alpha.-amino group or optionally through the .omega.-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;

[0119] Z.sub.1 is hydrogen, C.sub.1-C.sub.6 alkyl, or an amino protecting group;

[0120] Z.sub.2 is hydrogen, C.sub.1-C.sub.6 alkyl, an amino protecting group, --C(.dbd.O)--(CH.sub.2).sub.n-J-Z.sub.3, a D or L .alpha.-amino acid linked via the .alpha.-carboxyl group or optionally through the .omega.-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;

[0121] Z.sub.3 is hydrogen, an amino protecting group, --C.sub.1-C.sub.6 alkyl, --C(.dbd.O)--CH.sub.3, benzyl, benzoyl, or --(CH.sub.2).sub.n--N(H)Z.sub.1;

[0122] each J is O, S or NH;

[0123] R.sub.5 is a carbonyl protecting group; and

[0124] n is from 2 to about 50.

[0125] Another class of oligonucleotide mimetic that has been studied is based on linked morpholino units (morpholino nucleic acid) having heterocyclic bases attached to the morpholino ring. A number of linking groups have been reported that link the morpholino monomeric units in a morpholino nucleic acid. One class of linking groups has been selected to give a non-ionic oligomeric compound. The non-ionic morpholino-based oligomeric compounds are less likely to have undesired interactions with cellular proteins. Morpholino-based oligomeric compounds are non-ionic mimics of oligonucleotides which are less likely to form undesired interactions with cellular proteins (Dwaine A. Braasch and David R. Corey, Biochemistry, 2002, 41(14), 4503-4510). Morpholino-based oligomeric compounds are disclosed in U.S. Pat. No. 5,034,506, issued Jul. 23, 1991. The morpholino class of oligomeric compounds has been prepared having a variety of different linking groups joining the monomeric subunits.

[0126] Morpholino nucleic acids have been prepared having a variety of different linking groups (L.sub.2) joining the monomeric subunits. The basic formula is shown below:

##STR00028##

wherein

[0127] T.sub.1 is hydroxyl or a protected hydroxyl;

[0128] T.sub.5 is hydrogen or a phosphate or phosphate derivative;

[0129] L.sub.2 is a linking group; and

[0130] n is from 2 to about 50.

[0131] A further class of oligonucleotide mimetic is referred to as cyclohexenyl nucleic acids (CeNA). The furanose ring normally present in an DNA/RNA molecule is replaced with a cyclohenyl ring. CeNA DMT protected phosphoramidite monomers have been prepared and used for oligomeric compound synthesis following classical phosphoramidite chemistry. Fully modified CeNA oligomeric compounds and oligonucleotides having specific positions modified with CeNA have been prepared and studied (see Wang et al., J. Am. Chem. Soc., 2000, 122, 8595-8602). In general the incorporation of CeNA monomers into a DNA chain increases its stability of a DNA/RNA hybrid. CeNA oligoadenylates formed complexes with RNA and DNA complements with similar stability to the native complexes. The study of incorporating CeNA structures into natural nucleic acid structures was shown by NMR and circular dichroism to proceed with easy conformational adaptation. Furthermore the incorporation of CeNA into a sequence targeting RNA was stable to serum and able to activate E. coli RNase resulting in cleavage of the target RNA strand.

[0132] The general formula of CeNA is shown below:

##STR00029##

wherein

[0133] each Bx is a heterocyclic base moiety;

[0134] T.sub.1 is hydroxyl or a protected hydroxyl; and

[0135] T2 is hydroxyl or a protected hydroxyl.

[0136] Another class of oligonucleotide mimetic (anhydrohexitol nucleic acid) can be prepared from one or more anhydrohexitol nucleosides (see, Wouters and Herdewijn, Bioorg. Med. Chem. Lett., 1999, 9, 1563-1566) and would have the general formula:

##STR00030##

[0137] Another group of modifications includes nucleosides having sugar moieties that are bicyclic thereby locking the sugar conformational geometry. The most studied of these nucleosides having a bicyclic sugar moiety is locked nucleic acid or LNA. As can be seen in the structure below the 2'-O-has been linked via a methylene group to the 4' carbon. This bridge attaches under the 3' bonds forcing the sugar ring into a locked 3'-endo conformation geometry. The linkage can be a methylene (--CH.sub.2--).sub.n group bridging the 2' oxygen atom and the 4' carbon atom wherein n is 1 for LNA. LNA and LNA analogs display very high duplex thermal stabilities with complementary DNA and RNA (T.sub.m=+3 to +10 C), stability towards 3'-exonucleolytic degradation and good solubility properties.

[0138] An LNA analog that also has been looked at is ENA wherein an additional methylene group has been added to the bridge between the 2' and the 2' carbons (4'-CH.sub.2--CH.sub.2--O-2', Kaneko et al., United States Patent Application Publication No.: US 2002/0147332, Singh et al., Chem. Commun., 1998, 4, 455-456, also see Japanese Patent Application HEI-11-33863, Feb. 12, 1999).

[0139] In another publication a large genus of nucleosides having bicyclic sugar moieties is disclosed. The bridging group is variable as are the points of attachment (United States Patent Application Publication No.: U.S. 2002/0068708).

[0140] The basic structure of LNA showing the bicyclic ring system is shown below:

##STR00031##

[0141] The conformations of LNAs determined by 2D NMR spectroscopy have shown that the locked orientation of the LNA nucleotides, both in single-stranded LNA and in duplexes, constrains the phosphate backbone in such a way as to introduce a higher population of the N-type conformation (Petersen et al., J. Mol. Recognit., 2000, 13, 44-53). These conformations are associated with improved stacking of the nucleobases (Wengel et al., Nucleosides Nucleotides, 1999, 18, 1365-1370).

[0142] LNA has been shown to form exceedingly stable LNA:LNA duplexes (Koshkin et al., J. Am. Chem. Soc., 1998, 120, 13252-13253). LNA:LNA hybridization was shown to be the most thermally stable nucleic acid type duplex system, and the RNA-mimicking character of LNA was established at the duplex level. Introduction of 3 LNA monomers (T or A) significantly increased melting points (T.sub.m=+15/+11) toward DNA complements. The universality of LNA-mediated hybridization has been stressed by the formation of exceedingly stable LNA:LNA duplexes. The RNA-mimicking of LNA was reflected with regard to the N-type conformational restriction of the monomers and to the secondary structure of the LNA:RNA duplex.

[0143] LNAs also form duplexes with complementary DNA, RNA or LNA with high thermal affinities. Circular dichroism (CD) spectra show that duplexes involving fully modified LNA (esp. LNA:RNA) structurally resemble an A-form RNA:RNA duplex. Nuclear magnetic resonance (NMR) examination of an LNA:DNA duplex confirmed the 3'-endo conformation of an LNA monomer. Recognition of double-stranded DNA has also been demonstrated suggesting strand invasion by LNA. Studies of mismatched sequences show that LNAs obey the Watson-Crick base pairing rules with generally improved selectivity compared to the corresponding unmodified reference strands.

[0144] Novel types of LNA-oligomeric compounds, as well as the LNAs, are useful in a wide range of diagnostic and therapeutic applications. Among these are antisense applications, PCR applications, strand-displacement oligomers, substrates for nucleic acid polymerases and generally as nucleotide based drugs.

[0145] Potent and nontoxic antisense oligonucleotides containing LNAs have been described (Wahlestedt et al., Proc. Natl. Acad. Sci. U.S.A., 2000, 97, 5633-5638.) The authors have demonstrated that LNAs confer several desired properties to antisense agents. LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. LNA/DNA copolymers exhibited potent antisense activity in assay systems as disparate as G-protein-coupled receptor signaling in living rat brain and detection of reporter genes in Escherichia coli. Lipofectin-mediated efficient delivery of LNA into living human breast cancer cells has also been accomplished.

[0146] The synthesis and preparation of the LNA monomers adenine, cytosine, guanine, 5-methyl-cytosine, thymine and uracil, along with their oligomerization, and nucleic acid recognition properties have been described (Koshkin et al., Tetrahedron, 1998, 54, 3607-3630). LNAs and preparation thereof are also described in WO 98/39352 and WO 99/14226.

[0147] The first analogs of LNA, phosphorothioate-LNA and 2'-thio-LNAs, have also been prepared (Kumar et al., Bioorg. Med. Chem. Lett., 1998, 8, 2219-2222). Preparation of locked nucleoside analogs containing oligodeoxyribonucleotide duplexes as substrates for nucleic acid polymerases has also been described (Wengel et al., PCT International Application WO 98-DK393 19980914). Furthermore, synthesis of 2'-amino-LNA, a novel conformationally restricted high-affinity oligonucleotide analog with a handle has been described in the art (Singh et al., J. Org. Chem., 1998, 63, 10035-10039). In addition, 2'-Amino- and 2'-methylamino-LNA's have been prepared and the thermal stability of their duplexes with complementary RNA and DNA strands has been previously reported.

[0148] One group has added an additional methylene group to the LNA 2',4'-bridging group (e.g. 4'-CH.sub.2--CH.sub.2--O-2' (ENA), Kaneko et al., United States Patent Application Publication No.: US 2002/0147332, also see Japanese Patent Application HEI-11-33863, Feb. 12, 1999).

[0149] Further oligonucleotide mimetics have been prepared to include bicyclic and tricyclic nucleoside analogs having the formulas (amidite monomers shown):

##STR00032##

(see Steffens et al., Helv. Chim. Acta, 1997, 80, 2426-2439; Steffens et al., J. Am. Chem. Soc., 1999, 121, 3249-3255; and Renneberg et al., J. Am. Chem. Soc., 2002, 124, 5993-6002). These modified nucleoside analogs have been oligomerized using the phosphoramidite approach and the resulting oligomeric compounds containing tricyclic nucleoside analogs have shown increased thermal stabilities (T.sub.m's) when hybridized to DNA, RNA and itself. Oligomeric compounds containing bicyclic nucleoside analogs have shown thermal stabilities approaching that of DNA duplexes.

[0150] Another class of oligonucleotide mimetic is referred to as phosphonomonoester nucleic acids incorporate a phosphorus group in a backbone the backbone. This class of olignucleotide mimetic is reported to have useful physical and biological and pharmacological properties in the areas of inhibiting gene expression (antisense oligonucleotides, ribozymes, sense oligonucleotides and triplex-forming oligonucleotides), as probes for the detection of nucleic acids and as auxiliaries for use in molecular biology.

[0151] The general formula (for definitions of Markush variables see: U.S. Pat. Nos. 5,874,553 and 6,127,346 herein incorporated by reference in their entirety) is shown below.

##STR00033##

[0152] Another oligonucleotide mimetic has been reported wherein the furanosyl ring has been replaced by a cyclobutyl moiety.

Modified Sugars

[0153] Oligomeric compounds of the invention may also contain one or more substituted sugar moieties. Oligomeric compounds comprise a sugar substituent group selected from: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C.sub.1 to C.sub.12 alkyl or C.sub.2 to C.sub.12 alkenyl and alkynyl. Particularly suitable are O[(CH.sub.2).sub.nO].sub.mCH.sub.3, O(CH.sub.2).sub.nOCH.sub.3, O(CH.sub.2).sub.nNH.sub.2, O(CH.sub.2).sub.nCH.sub.3, O(CH.sub.2).sub.nONH.sub.2, and O(CH.sub.2).sub.nON[(CH.sub.2).sub.nCH.sub.3].sub.2, where n and m are from 1 to about 10. Other oligonucleotides comprise a sugar substituent group selected from: C.sub.1 to C.sub.12 lower alkyl, substituted lower alkyl, alkenyl, alkynyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH.sub.3, OCN, Cl, Br, CN, CF.sub.3, OCF.sub.3, SOCH.sub.3, SO.sub.2CH.sub.3, ONO.sub.2, NO.sub.2, N.sub.3, NH.sub.2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. One modification includes 2'-methoxyethoxy (2'-O--CH.sub.2CH.sub.2OCH.sub.3, also known as 2'-O-(2-methoxyethyl) or 2'-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78, 486-504) i.e., an alkoxyalkoxy group. Another modification includes 2'-dimethylaminooxyethoxy, i.e., a O(CH.sub.2).sub.2ON(CH.sub.3).sub.2 group, also known as 2'-DMAOE, as described in examples hereinbelow, and 2'-dimethylaminoethoxyethoxy (also known in the art as 2'-O-dimethyl-amino-ethoxy-ethyl or 2'-DMAEOE), i.e., 2'-O--CH.sub.2--O--CH.sub.2--N(CH.sub.3).sub.2.

[0154] Other sugar substituent groups include methoxy (--O--CH.sub.3), aminopropoxy (--OCH.sub.2CH.sub.2CH.sub.2NH.sub.2), allyl (--CH.sub.2--CH.dbd.CH.sub.2), --O-allyl (--O--CH.sub.2--CH.dbd.CH.sub.2) and fluoro (F). 2'-Sugar substituent groups may be in the arabino (up) position or ribo (down) position. One 2'-arabino modification is 2'-F. Similar modifications may also be made at other positions on the oligomeric compound, particularly the 3' position of the sugar on the 3' terminal nucleoside or in 2'-5' linked oligonucleotides and the 5' position of 5' terminal nucleotide. Oligomeric compounds may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative United States patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; 5,792,747; and 5,700,920, each of which is herein incorporated by reference in its entirety.

[0155] Further representative sugar substituent groups include groups of formula I.sub.a or II.sub.a:

##STR00034##

wherein:

[0156] R.sub.b is O, S or NH;

[0157] R.sub.d is a single bond, O, S or C(.dbd.O);

[0158] R.sub.e is C.sub.1-C.sub.12 alkyl, N(R.sub.k)(R.sub.m), N(R.sub.k)(R.sub.n), N.dbd.C(R.sub.p)(R.sub.q), N.dbd.C(R.sub.p)(R.sub.r) or has formula III.sub.a;

##STR00035##

[0159] R.sub.p and R.sub.q are each independently hydrogen or C.sub.1-C.sub.12 alkyl;

[0160] R.sub.r is --R.sub.x--R.sub.y;

[0161] each R.sub.s, R.sub.t, R.sub.u and R.sub.v is, independently, hydrogen, C(O)R.sub.w, substituted or unsubstituted C.sub.1-C.sub.12 alkyl, substituted or unsubstituted C.sub.2-C.sub.12 alkenyl, substituted or unsubstituted C.sub.2-C.sub.12 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group or a conjugate group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;

[0162] or optionally, R.sub.u and R.sub.v, together form a phthalimido moiety with the nitrogen atom to which they are attached;

[0163] each R.sub.w is, independently, substituted or unsubstituted C.sub.1-C.sub.12alkyl, trifluoromethyl, cyanoethyloxy, methoxy, ethoxy, t-butoxy, allyloxy, 9-fluorenylmethoxy, 2-(trimethylsilyl)-ethoxy, 2,2,2-trichloroethoxy, benzyloxy, butyryl, iso-butyryl, phenyl or aryl;

[0164] R.sub.k is hydrogen, a nitrogen protecting group or --R.sub.x--R.sub.y;

[0165] R.sub.p is hydrogen, a nitrogen protecting group or --R.sub.x--R.sub.y;

[0166] R.sub.x is a bond or a linking moiety;

[0167] R.sub.y is a chemical functional group, a conjugate group or a solid support medium;

[0168] each R.sub.m and R.sub.n is, independently, H, a nitrogen protecting group, substituted or unsubstituted C.sub.1-C.sub.12 alkyl, substituted or unsubstituted C.sub.2-C.sub.12 alkenyl, substituted or unsubstituted C.sub.2-C.sub.12 alkynyl, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl, alkynyl; NH.sub.3.sup.+, N(R.sub.u)(R.sub.v), guanidino and acyl where said acyl is an acid amide or an ester;

[0169] or R.sub.m and R.sub.n, together, are a nitrogen protecting group, are joined in a ring structure that optionally includes an additional heteroatom selected from N and O or are a chemical functional group;

[0170] R.sub.i is OR.sub.z, SR.sub.z, or N(R.sub.z).sub.2;

[0171] each R.sub.z is, independently, H, C.sub.1-C.sub.8 alkyl, C.sub.1-C.sub.8 haloalkyl, C(.dbd.NH)N(H)R.sub.u, C(.dbd.O)N(H)R.sub.u or OC(.dbd.O)N(H)R.sub.u;

[0172] R.sub.f, R.sub.g and R.sub.h comprise a ring system having from about 4 to about 7 carbon atoms or having from about 3 to about 6 carbon atoms and 1 or 2 heteroatoms wherein said heteroatoms are selected from oxygen, nitrogen and sulfur and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;

[0173] R.sub.j is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(R.sub.k)(R.sub.m)OR.sub.k, halo, SR.sub.k or CN;

[0174] m.sub.a is 1 to about 10;

[0175] each mb is, independently, 0 or 1;

[0176] mc is 0 or an integer from 1 to 10;

[0177] md is an integer from 1 to 10;

[0178] me is from 0, 1 or 2; and

[0179] provided that when mc is 0, md is greater than 1.

[0180] Representative substituents groups of Formula Ia are disclosed in U.S. patent application Ser. No. 09/130,973, filed Aug. 7, 1998, entitled "Capped 2'-Oxyethoxy Oligonucleotides," hereby incorporated by reference in its entirety.

[0181] Representative cyclic substituent groups of Formula IIa are disclosed in U.S. patent application Ser. No. 09/123,108, filed Jul. 27, 1998, entitled "RNA Targeted 2'-Oligomeric compounds that are Conformationally Preorganized," hereby incorporated by reference in its entirety.

[0182] Sugar substituent groups include O[(CH.sub.2).sub.nO].sub.mCH.sub.3, O(CH.sub.2).sub.nCH.sub.3, O(CH.sub.2).sub.nNH.sub.2, O(CH.sub.2).sub.nCH.sub.3, O(CH.sub.2).sub.nNH.sub.2, and O(CH.sub.2).sub.nON[(CH.sub.2).sub.nCH.sub.3)].sub.2, where n and m are from 1 to about 10.

[0183] Representative guanidino substituent groups that are shown in formula IIIa disclosed in co-owned U.S. patent application Ser. No. 09/349,040, entitled "Functionalized Oligomers", filed Jul. 7, 1999, hereby incorporated by reference in its entirety.

[0184] Representative acetamido substituent groups are disclosed in U.S. Pat. No. 6,147,200 which is hereby incorporated by reference in its entirety.

[0185] Representative dimethylaminoethyloxyethyl substituent groups are disclosed in International Patent Application PCT/US99/17895, entitled "2'-O-Dimethylaminoethyloxyethyl-Oligomeric compounds", filed Aug. 6, 1999, hereby incorporated by reference in its entirety.

Modified Nucleobases/Naturally Occurring Nucleobases

[0186] Chimeric oligomeric compounds of the invention may also include nucleobase (often referred to in the art simply as "base" or "heterocyclic base moiety") modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases also referred herein as heterocyclic base moieties include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (--C.ident.C--CH.sub.3) uracil and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine.

[0187] Heterocyclic base moieties may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. I., ed. John Wiley & Sons, 1990, those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y. S., Chapter 15, Antisense Research and Applications, pages 289-302, Crooke, S.T. and Lebleu, B., ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2.degree. C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., eds., Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently suitable base substitutions, even more particularly when combined with 2'-O-methoxyethyl sugar modifications.

[0188] In one aspect of the present invention chimeric oligomeric compounds are prepared having polycyclic heterocyclic compounds in place of one or more heterocyclic base moieties. A number of tricyclic heterocyclic compounds have been previously reported. These compounds are routinely used in antisense applications to increase the binding properties of the modified strand to a target strand. The most studied modifications are targeted to guanosines hence they have been termed G-clamps or cytidine analogs. Many of these polycyclic heterocyclic compounds have the general formula:

##STR00036##

[0189] Representative cytosine analogs that make 3 hydrogen bonds with a guanosine in a second strand include 1,3-diazaphenoxazine-2-one (R.sub.10.dbd.O, R.sub.11-R.sub.14.dbd.H) (Kurchavov, et al., Nucleosides and Nucleotides, 1997, 16, 1837-1846), 1,3-diazaphenothiazine-2-one (R.sub.10.dbd.S, R.sub.11-R.sub.14.dbd.H), (Lin, K.-Y.; Jones, R. J.; Matteucci, M. J. Am. Chem. Soc. 1995, 117, 3873-3874) and 6,7,8,9-tetrafluoro-1,3-diazaphenoxazine-2-one (R.sub.10.dbd.O, R.sub.11-R.sub.14.dbd.F) (Wang, J.; Lin, K.-Y., Matteucci, M. Tetrahedron Lett. 1998, 39, 8385-8388). Incorporated into oligonucleotides these base modifications were shown to hybridize with complementary guanine and the latter was also shown to hybridize with adenine and to enhance helical thermal stability by extended stacking interactions (also see U.S. patent application entitled "Modified Peptide Nucleic Acids" filed May 24, 2002, Ser. No. 10/155,920; and U.S. patent application entitled "Nuclease Resistant Chimeric oligomeric compounds" filed May 24, 2002, Ser. No. 10/013,295, both of which are herein incorporated by reference in their entirety).

[0190] Further helix-stabilizing properties have been observed when a cytosine analog/substitute has an aminoethoxy moiety attached to the rigid 1,3-diazaphenoxazine-2-one scaffold (R.sub.10.dbd.O, R.sub.11.dbd.--O--(CH.sub.2).sub.2--NH.sub.2, R.sub.12-14.dbd.H) (Lin, K.-Y.; Matteucci, M. J. Am. Chem. Soc. 1998, 120, 8531-8532). Binding studies demonstrated that a single incorporation could enhance the binding affinity of a model oligonucleotide to its complementary target DNA or RNA with a .DELTA.T.sub.m of up to 18.degree. relative to 5-methyl cytosine (dC5.sup.me), which is the highest known affinity enhancement for a single modification. On the other hand, the gain in helical stability does not compromise the specificity of the oligonucleotides. The T.sub.m data indicate an even greater discrimination between the perfect match and mismatched sequences compared to dC5.sup.me. It was suggested that the tethered amino group serves as an additional hydrogen bond donor to interact with the Hoogsteen face, namely the O6, of a complementary guanine thereby forming 4 hydrogen bonds. This means that the increased affinity of G-clamp is mediated by the combination of extended base stacking and additional specific hydrogen bonding.

[0191] Further tricyclic heterocyclic compounds and methods of using them that are amenable to the present invention are disclosed in U.S. Pat. No. 6,028,183 and U.S. Pat. No. 6,007,992, each of which is incorporated herein in its entirety.

[0192] The enhanced binding affinity of the phenoxazine derivatives together with their uncompromised sequence specificity makes them valuable nucleobase analogs for the development of more potent antisense-based drugs. In fact, promising data have been derived from in vitro experiments demonstrating that heptanucleotides containing phenoxazine substitutions are capable to activate RNaseH, enhance cellular uptake and exhibit an increased antisense activity (Lin, K-Y; Matteucci, M. J. Am. Chem. Soc. 1998, 120, 8531-8532). The activity enhancement was even more pronounced in case of G-clamp, as a single substitution was shown to significantly improve the in vitro potency of a 20mer 2'-deoxyphosphorothioate oligonucleotides (Flanagan, W. M.; Wolf, J. J.; Olson, P.; Grant, D.; Lin, K.-Y.; Wagner, R. W.; Matteucci, M. Proc. Natl. Acad. Sci. USA, 1999, 96, 3513-3518). Nevertheless, to optimize oligonucleotide design and to better understand the impact of these heterocyclic modifications on the biological activity, it is important to evaluate their effect on the nuclease stability of the oligomers.

[0193] Further modified polycyclic heterocyclic compounds useful as heterocyclcic bases are disclosed in but not limited to, the above noted U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,434,257; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091; 5,614,617; 5,645,985; 5,646,269; 5,750,692; 5,830,653; 5,763,588; 6,005,096; and 5,681,941, and Unites States patent application Ser. No. 09/996,292 filed Nov. 28, 2001, each of which is herein incorporated by reference.

Activated Phosphorus Groups

[0194] The compositions of the present invention illustrate the use of activated phosphorus compositions (e.g. compounds having activated phosphorus-containing substituent groups) in coupling reactions. As used herein, the term activated phosphorus composition includes monomers and oligomers that have an activated phosphorus-containing substituent group that is reactive with a hydroxyl group of another monomeric or oligomeric compound to form a phosphorus-containing internucleotide linkage. Such activated phosphorus groups contain activated phosphorus atoms in P.sup.III valence state and are known in the art and include, but are not limited to, phosphoramidite, H-phosphonate, phosphate triesters and chiral auxiliaries. One synthetic solid phase synthesis utilizes phosphoramidites as activated phosphates. The phosphoramidites utilize P.sup.III chemistry. The intermediate phosphite compounds are subsequently oxidized to the P.sup.V state using known methods to yield, in one embodiment, phosphodiester or phosphorothioate internucleotide linkages. Additional activated phosphates and phosphites are disclosed in Tetrahedron Report Number 309 (Beaucage and Iyer, Tetrahedron, 1992, 48, 2223-2311).

[0195] Activated phosphorus groups are useful in the preparation of a wide range of oligomeric compounds including but not limited to oligonucleosides and oligonucleotides as well as oligonucleotides that have been modified or conjugated with other groups at the base or sugar or both. Also included are oligonucleotide mimetics including but not limited to peptide nucleic acids (PNA), morpholino nucleic acids, cyclohexenyl nucleic acids (CeNA), anhydrohexitol nucleic acids, locked nucleic acids (LNA and ENA), bicyclic and tricyclic nucleic acids, phosphonomonoester nucleic acids and cyclobutyl nucleic acids. A representative example of one type of oligomer synthesis that utilizes the coupling of an activated phosphorus group with a reactive hydroxyl group is the widely used phosphoramidite approach. A phosphoramidite synthon is reacted under appropriate conditions with a reactive hydroxyl group to form a phosphite linkage that is further oxidized to a phosphodiester or phosphorothioate linkage. This approach commonly utilizes nucleoside phosphoramidites of the formula:

##STR00037##

wherein each Bx' is an optionally protected heterocyclic base moiety; each R.sub.1' is, independently, H or an optionally protected sugar substituent group; T.sub.3' is H, a hydroxyl protecting group, a nucleoside, a nucleotide, an oligonucleoside or an oligonucleotide;

L.sub.1 is N(R.sub.1)R.sub.2;

[0196] each R.sub.2 and R.sub.3 is, independently, C.sub.1-C.sub.12 straight or branched chain alkyl; or R.sub.2 and R.sub.3 are joined together to form a 4- to 7-membered heterocyclic ring system including the nitrogen atom to which R.sub.2 and R.sub.3 are attached, wherein said ring system optionally includes at least one additional heteroatom selected from O, N and S; L.sub.2 is Pg-O--, Pg-S--, C.sub.1-C.sub.12 straight or branched chain alkyl, CH.sub.3(CH.sub.2).sub.0-10--O-- or --NR.sub.5R.sub.6; Pg is a protecting/blocking group; and each R.sub.5 and R.sub.6 is, independently, hydrogen, C.sub.1-C.sub.12 straight or branched chain alkyl, cycloalkyl or aryl; or optionally, R.sub.5 and R.sub.6, together with the nitrogen atom to which they are attached form a cyclic moiety that may include an additional heteroatom selected from O, S and N; or

[0197] L.sub.1 and L.sub.2 together with the phosphorus atom to which L.sub.1 and L.sub.2 are attached form a chiral auxiliary.

[0198] Groups that are attached to the phosphorus atom of internucleotide linkages before and after oxidation (L.sub.1 and L.sub.2) can include nitrogen containing cyclic moieties such as morpholine. Such oxidized internucleoside linkages include a phosphoromorpholidothioate linkage (Wilk et al., Nucleosides and nucleotides, 1991, 10, 319-322). Further cyclic moieties amenable to the present invention include mono-, bi- or tricyclic ring moieties which may be substituted with groups such as oxo, acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, ODMT, alkylsulfonyl, nitro, sulfide, sulfone, sulfonamide, thiol and thioalkoxy. A bicyclic ring structure that includes nitrogen is phthalimido.

[0199] Unless otherwise defined herein, alkyl means C.sub.1-C.sub.12, C.sub.1-C.sub.8, or C.sub.1-C.sub.6, straight or (where possible) branched chain aliphatic hydrocarbyl.

[0200] Unless otherwise defined herein, heteroalkyl means C.sub.1-C.sub.12, C.sub.1-C.sub.8, or C.sub.1-C.sub.6, straight or (where possible) branched chain aliphatic hydrocarbyl containing at least one or about 1 to about 3, hetero atoms in the chain, including the terminal portion of the chain. Suitable heteroatoms include N, O and S.

[0201] Unless otherwise defined herein, cycloalkyl means C.sub.3-C.sub.12, C.sub.3-C.sub.8, or C.sub.3-C.sub.6, aliphatic hydrocarbyl ring.

[0202] Unless otherwise defined herein, alkenyl means C.sub.2-C.sub.12, C.sub.2-C.sub.8, or C.sub.2-C.sub.6 alkenyl, which may be straight or (where possible) branched hydrocarbyl moiety, which contains at least one carbon-carbon double bond.

[0203] Unless otherwise defined herein, alkynyl means C.sub.2-C.sub.12, C.sub.2-C.sub.8, or C.sub.2-C.sub.6 alkynyl, which may be straight or (where possible) branched hydrocarbyl moiety, which contains at least one carbon-carbon triple bond.

[0204] Unless otherwise defined herein, heterocycloalkyl means a ring moiety containing at least three ring members, at least one of which is carbon, and of which 1, 2 or three ring members are other than carbon. The number of carbon atoms can vary from 1 to about 12, or from 1 to about 6, and the total number of ring members can vary from three to about 15, or from about 3 to about 8. Ring heteroatoms can be N, O and S. Heterocycloalkyl groups include morpholino, thiomorpholino, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, homomorpholino, homothiomorpholino, pyrrolodinyl, tetrahydrooxazolyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydroisoxazolyl, tetrahydropyrrazolyl, furanyl, pyranyl, and tetrahydroisothiazolyl.

[0205] Unless otherwise defined herein, aryl means any hydrocarbon ring structure containing at least one aryl ring. Ayl rings can have about 6 to about 20 ring carbons. Aryl rings can include phenyl, napthyl, anthracenyl, and phenanthrenyl.

[0206] Unless otherwise defined herein, hetaryl means a ring moiety containing at least one fully unsaturated ring, the ring consisting of carbon and non-carbon atoms. The ring system can contain about 1 to about 4 rings. The number of carbon atoms can vary from 1 to about 12, or from 1 to about 6, and the total number of ring members can vary from three to about 15, or from about 3 to about 8. Ring heteroatoms are N, O and S. Hetaryl moieties include pyrazolyl, thiophenyl, pyridyl, imidazolyl, tetrazolyl, pyridyl, pyrimidinyl, purinyl, quinazolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl, etc.

[0207] Unless otherwise defined herein, where a moiety is defined as a compound moiety, such as hetarylalkyl (hetaryl and alkyl), aralkyl (aryl and alkyl), etc., each of the sub-moieties is as defined herein.

[0208] Unless otherwise defined herein, an electron withdrawing group is a group, such as the cyano or isocyanato group that draws electronic charge away from the carbon to which it is attached. Other electron withdrawing groups of note include those whose electronegativities exceed that of carbon, for example halogen, nitro, or phenyl substituted in the ortho- or para-position with one or more cyano, isothiocyanato, nitro or halo groups.

[0209] Unless otherwise defined herein, the terms halogen and halo have their ordinary meanings Halo (halogen) substituents can be Cl, Br, and I.

[0210] The aforementioned optional substituents are, unless otherwise herein defined, suitable substituents depending upon desired properties. Included are halogens (Cl, Br, I), alkyl, alkenyl, and alkynyl moieties, NO.sub.2, NH.sub.3 (substituted and unsubstituted), acid moieties (e.g. --CO.sub.2H, --OSO.sub.3H.sub.2, etc.), heterocycloalkyl moieties, hetaryl moieties, aryl moieties, etc.

[0211] In all the preceding formulae, the squiggle (.about.) indicates a bond to an oxygen or sulfur of the 5'-phosphate.

[0212] Phosphate protecting groups include those described in U.S. Pat. No. 5,760,209, U.S. Pat. No. 5,614,621, U.S. Pat. No. 6,051,699, U.S. Pat. No. 6,020,475, U.S. Pat. No. 6,326,478, U.S. Pat. No. 6,169,177, U.S. Pat. No. 6,121,437, U.S. Pat. No. 6,465,628 each of which is expressly incorporated herein by reference in its entirety.

Hybridization

[0213] In the context of this invention, "hybridization" means the pairing of complementary strands of oligomeric compounds. In the present invention, one mechanism of pairing involves hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases (nucleobases) of the strands of oligomeric compounds. For example, adenine and thymine are complementary nucleobases which pair through the formation of hydrogen bonds. Hybridization can occur under varying circumstances.

[0214] An oligomeric compound is specifically hybridizable when binding of the compound to the target nucleic acid interferes with the normal function of the target nucleic acid to cause a reduction in activity, and there is a sufficient degree of complementarity to avoid off-target effects (non-specific binding of the antisense oligomeric compound to non-target nucleic acid sequences under conditions in which specific binding is desired, i.e., under physiological conditions in the case of in vivo assays or therapeutic treatment, or under conditions in which assays are performed in the case of in vitro assays).

[0215] In the present invention the phrase "stringent hybridization conditions" or "stringent conditions" refers to conditions under which an oligomeric compound of the invention will hybridize to its target sequence, but to a minimal number of other sequences. Stringent conditions are sequence-dependent and will vary with different circumstances and in the context of this invention, "stringent conditions" under which oligomeric compounds hybridize to a target sequence are determined by the nature and composition of the oligomeric compounds and the assays in which they are being investigated.

[0216] "Complementary," as used herein, refers to the capacity for precise pairing of two nucleobases regardless of where the two are located. For example, if a nucleobase at a certain position of an oligomeric compound is capable of hydrogen bonding (pairing) with a nucleobase at a certain position of a target nucleic acid, the target nucleic acid being a DNA, RNA, or oligonucleotide molecule, then the position of hydrogen bonding between the oligonucleotide and the target nucleic acid is considered to be a complementary position. The oligomeric compound and the further DNA, RNA, or oligonucleotide molecule are complementary to each other when a sufficient number of complementary positions in each molecule are occupied by nucleobases which can hydrogen bond with each other. Thus, "specifically hybridizable" and "complementary" are terms which are used to indicate a sufficient degree of precise pairing or complementarity over a sufficient number of nucleobases such that stable and specific binding occurs between the oligonucleotide and a target nucleic acid.

[0217] It is understood in the art that the sequence of a chimeric oligomeric compound compound need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable. Moreover, an oligonucleotide may hybridize over one or more segments such that intervening or adjacent segments are not involved in the hybridization event (e.g., a loop structure or hairpin structure). It may be desirable that the chimeric oligomeric compounds of the present invention comprise at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% sequence complementarity to a target region within the target nucleic acid to which they are targeted. For example, a chimeric oligomeric compound in which 18 of 20 nucleobases are complementary (the remaining 2 being mismatches) to a target region, which specifically hybridizes, would represent 90 percent complementarity. In this example, the remaining noncomplementary nucleobases may be clustered or interspersed with complementary nucleobases and need not be contiguous to each other or to complementary nucleobases. As such, a chimeric oligomeric compound which is 18 nucleobases in length having 4 (four) noncomplementary nucleobases which are flanked by two regions of complete complementarity with the target nucleic acid would have 77.8% overall complementarity with the target nucleic acid and would thus fall within the scope of the present invention. Percent complementarity of a chimeric oligomeric compound with a region of a target nucleic acid can be determined routinely using BLAST programs (basic local alignment search tools) and PowerBLAST programs known in the art (Altschul et al., J. Mol. Biol., 1990, 215, 403-410; Zhang and Madden, Genome Res., 1997, 7, 649-656).

Targets of the Invention

[0218] The chimeric oligomeric compounds of the present invention are targeted to nucleic acid targets in a sequence dependent manner. One nucleic acid target is messenger RNA. More specifically, chimeric oligomeric compounds of the invention will modulate gene expression by hybridizing to a nucleic acid target resulting in alteration of or reduction in normal function of the target nucleic acid. As used herein, the term "target nucleic acid" or "nucleic acid target" is used for convenience to encompass any nucleic acid capable of being targeted including without limitation DNA, RNA (including pre-mRNA and mRNA or portions thereof) transcribed from such DNA, and also cDNA derived from such RNA. In one embodiment of the invention the target nucleic acid is a messenger RNA. The inhibition of the target is typically based upon hydrogen bonding-based hybridization of the chimeric oligomeric compound strands or segments such that at least one strand or segment is cleaved, degraded, or otherwise rendered inoperable. In this regard, it is presently suitable to target specific nucleic acid molecules and their functions for such inhibition.

[0219] The functions of DNA to be interfered with can include replication and transcription. Replication and transcription, for example, can be from an endogenous cellular template, a vector, a plasmid construct or otherwise. The functions of RNA to be interfered with can include functions such as translocation of the RNA to a site of protein translation, translocation of the RNA to sites within the cell which are distant from the site of RNA synthesis, translation of protein from the RNA, splicing of the RNA to yield one or more RNA species, and catalytic activity or complex formation involving the RNA which may be engaged in or facilitated by the RNA. In the context of the present invention, "modulation" and "modulation of expression" mean either an increase (stimulation) or a decrease (inhibition) in the amount or levels of a nucleic acid molecule encoding the gene, e.g., DNA or RNA Inhibition is often the desired form of modulation of expression and mRNA is often a suitable target nucleic acid.

[0220] In one aspect, the present invention is directed to chimeric oligomeric compounds that are prepared having enhanced activity against nucleic acid targets. As used herein the phrase "enhanced activity" can indicate upregulation or downregulation of a system. A target and a mechanism for its modulation is determined. An oligonucleotide is selected having an effective length and sequence that is complementary to a portion of the target sequence. The selected sequence is divided into regions and the nucleosides of each region are modified to enhance the desired properties of the respective region. Consideration is also given to the 5' and 3'-termini as there are often advantageous modifications that can be made to one or more of the terminal nucleosides. Further modifications are also considered such as internucleoside linkages, conjugate groups, substitute sugars or bases, substitution of one or more nucleosides with nucleoside mimetics and any other modification that can enhance the selected sequence for its intended target.

[0221] "Targeting" a chimeric oligomeric compound of the invention to a particular nucleic acid molecule, in the context of this invention, can be a multistep process. The process usually begins with the identification of a target nucleic acid whose function is to be modulated. This target nucleic acid may be, for example, a cellular gene (or mRNA transcribed from the gene) whose expression is associated with a particular disorder or disease state, or a nucleic acid molecule from an infectious agent.

[0222] The targeting process usually also includes determination of at least one target region, target segment, or target site within the target nucleic acid for the antisense interaction to occur (hybridization of the chimeric oligomeric compound to its complementary sense target) such that the desired effect, e.g., modulation of expression, will result. Within the context of the present invention, the term "target region" is defined as a portion of the target nucleic acid having at least one identifiable structure, function, or characteristic. Within regions of target nucleic acids are segments. "Target segments" are defined as smaller or sub-portions of regions within a target nucleic acid. "Target sites," as used in the present invention, are defined as positions within a target nucleic acid. Since, as is known in the art, the translation initiation codon is typically 5'-AUG (in transcribed mRNA molecules; 5'-ATG in the corresponding DNA molecule), the translation initiation codon is also referred to as the "AUG codon," the "start codon" or the "AUG start codon". A minority of genes has a translation initiation codon having the RNA sequence 5'-GUG, 5'-UUG or 5'-CUG, and 5'-AUA, 5'-ACG and 5'-CUG have been shown to function in vivo. Thus, the terms "translation initiation codon" and "start codon" can encompass many codon sequences, even though the initiator amino acid in each instance is typically methionine (in eukaryotes) or formylmethionine (in prokaryotes). It is also known in the art that eukaryotic and prokaryotic genes may have two or more alternative start codons, any one of which may be preferentially utilized for translation initiation in a particular cell type or tissue, or under a particular set of conditions. In the context of the invention, "start codon" and "translation initiation codon" refer to the codon or codons that are used in vivo to initiate translation of an mRNA transcribed from a gene encoding a nucleic acid target, regardless of the sequence(s) of such codons. It is also known in the art that a translation termination codon (or "stop codon") of a gene may have one of three sequences, i.e., 5'-UAA, 5'-UAG and 5'-UGA (the corresponding DNA sequences are 5'-TAA, 5'-TAG and 5'-TGA, respectively).

[0223] The terms "start codon region" and "translation initiation codon region" refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation initiation codon. Similarly, the terms "stop codon region" and "translation termination codon region" refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation termination codon. Consequently, the "start codon region" (or "translation initiation codon region") and the "stop codon region" (or "translation termination codon region") are all regions which may be targeted effectively with the chimeric oligomeric compounds of the present invention.

[0224] The open reading frame (ORF) or "coding region," which is known in the art to refer to the region between the translation initiation codon and the translation termination codon, is also a region which may be targeted effectively. Within the context of the present invention, one region is the intragenic region encompassing the translation initiation or termination codon of the open reading frame (ORF) of a gene.

[0225] Other target regions include the 5' untranslated region (5'UTR), known in the art to refer to the portion of an mRNA in the 5' direction from the translation initiation codon, and thus including nucleotides between the 5' cap site and the translation initiation codon of an mRNA (or corresponding nucleotides on the gene), and the 3' untranslated region (3'UTR), known in the art to refer to the portion of an mRNA in the 3' direction from the translation termination codon, and thus including nucleotides between the translation termination codon and 3' end of an mRNA (or corresponding nucleotides on the gene). The 5' cap site of an mRNA comprises an N7-methylated guanosine residue joined to the 5'-most residue of the mRNA via a 5'-5' triphosphate linkage. The 5' cap region of an mRNA is considered to include the 5' cap structure itself as well as the first 50 nucleotides adjacent to the cap site. It is also suitable to target the 5' cap region.

[0226] Although some eukaryotic mRNA transcripts are directly translated, many contain one or more regions, known as "introns," which are excised from a transcript before it is translated. The remaining (and therefore translated) regions are known as "exons" and are spliced together to form a continuous mRNA sequence, resulting in exon-exon junctions at the sites where exons are joined. Targeting exon-exon junctions can be useful in situations where the overproduction of a normal splice product is implicated in disease, or where the overproduction of an aberrant splice product is implicated in disease. Targeting splice sites, i.e., intron-exon junctions or exon-intron junctions, may also be particularly useful in situations where aberrant splicing is implicated in disease, or where an overproduction of a particular splice product is implicated in disease. Aberrant fusion junctions due to rearrangements or deletions are also suitable target sites. mRNA transcripts produced via the process of splicing of two (or more) mRNAs from different gene sources known as "fusion transcripts" are also suitable target sites. It is also known that introns can be effectively targeted using chimeric oligomeric compounds targeted to, for example, DNA or pre-mRNA.

[0227] It is also known in the art that alternative RNA transcripts can be produced from the same genomic region of DNA. These alternative transcripts are generally known as "variants". More specifically, "pre-mRNA variants" are transcripts produced from the same genomic DNA that differ from other transcripts produced from the same genomic DNA in either their start or stop position and contain both intronic and exonic sequences.

[0228] Upon excision of one or more exon or intron regions, or portions thereof during splicing, pre-mRNA variants produce smaller "mRNA variants". Consequently, mRNA variants are processed pre-mRNA variants and each unique pre-mRNA variant must always produce a unique mRNA variant as a result of splicing. These mRNA variants are also known as "alternative splice variants". If no splicing of the pre-mRNA variant occurs then the pre-mRNA variant is identical to the mRNA variant.

[0229] It is also known in the art that variants can be produced through the use of alternative signals to start or stop transcription and that pre-mRNAs and mRNAs can possess more that one start codon or stop codon. Variants that originate from a pre-mRNA or mRNA that use alternative start codons are known as "alternative start variants" of that pre-mRNA or mRNA. Those transcripts that use an alternative stop codon are known as "alternative stop variants" of that pre-mRNA or mRNA. One specific type of alternative stop variant is the "polyA variant" in which the multiple transcripts produced result from the alternative selection of one of the "polyA stop signals" by the transcription machinery, thereby producing transcripts that terminate at unique polyA sites. Within the context of the invention, the types of variants described herein are also suitable target nucleic acids.

[0230] The locations on the target nucleic acid to which the chimeric oligomeric compounds hybridize are hereinbelow referred to as "suitable target segments." As used herein the term "suitable target segment" is defined as at least a 5-nucleobase portion of a target region to which an active chimeric oligomeric compound of the present invention is targeted. While not wishing to be bound by theory, it is presently believed that these target segments represent portions of the target nucleic acid which are accessible for hybridization.

[0231] Exemplary chimeric oligomeric compounds include at least the 5 consecutive nucleobases from the 5'-terminus of a targeted nucleic acid e.g. a cellular gene or mRNA transcribed from the gene (the remaining nucleobases being a consecutive stretch of the same oligonucleotide beginning immediately upstream of the 5'-terminus of the chimeric oligomeric compound which is specifically hybridizable to the target nucleic acid and continuing until the oligonucleotide contains from about 5 to about 80 nucleobases). Similarly, chimeric oligomeric compounds comprise at least the 5 consecutive nucleobases from the 3'-terminus of one of the illustrative chimeric oligomeric compounds (the remaining nucleobases being a consecutive stretch of the same oligonucleotide beginning immediately downstream of the 3'-terminus of the chimeric oligomeric compound which is specifically hybridizable to the target nucleic acid and continuing until the chimeric oligomeric compound contains from about 5 to about 80 nucleobases). One having skill in the art armed with the chimeric oligomeric compounds illustrated herein will be able, without undue experimentation, to identify further chimeric oligomeric compounds.

[0232] Once one or more target regions, target segments or target sites have been identified, chimeric oligomeric compounds of the invention are chosen which are sufficiently complementary to the target, i.e., hybridize sufficiently well and with sufficient specificity, to give the desired effect.

[0233] The oligomeric antisense compounds can also be targeted to regions of a target nucleobase sequence, such as those disclosed herein. All regions of a nucleobase sequence to which an oligomeric antisense compound can be targeted, wherein the regions are greater than or equal to 5 and less than or equal to 80 nucleobases, are described as follows:

[0234] Let R(m, n+m-1) be a region from a target nucleobase sequence, where "n" is the 5'-most nucleobase position of the region, where "n+m-1" is the 3'-most nucleobase position of the region and where "m" is the length of the region. A set "S(m)", of regions of length "m" is defined as the regions where n ranges from 1 to L-m+1, where L is the length of the target nucleobase sequence and L>m. A set, "A", of all regions can be constructed as a union of the sets of regions for each length from where m is greater than or equal to 5 and is less than or equal to 80.

[0235] This set of regions can be represented using the following mathematical notation:

A = m S ( m ) ##EQU00001## where m .di-elect cons. N | 5 .ltoreq. m .ltoreq. 80 ##EQU00001.2## and ##EQU00001.3## S ( m ) = { R n , n + m - 1 | n .di-elect cons. { 1 , 2 , 3 , , L - m + 1 } } ##EQU00001.4##

[0236] where the mathematical operator | indicates "such that",

[0237] where the mathematical operator .epsilon. indicates "a member of a set" (e.g. y.epsilon.Z indicates that element y is a member of set Z), [0238] where x is a variable,

[0239] where N indicates all natural numbers, defined as positive integers, [0240] and where the mathematical operator .orgate. indicates "the union of sets".

[0241] For example, the set of regions for m equal to 5, 20 and 80 can be constructed in the following manner. The set of regions, each 5 nucleobases in length, S(m=5), in a target nucleobase sequence 100 nucleobases in length (L=100), beginning at position 1 (n=1) of the target nucleobase sequence, can be created using the following expression:

S(5)={R.sub.1,5|n.epsilon.{1,2,3, . . . , 96}}

and describes the set of regions comprising nucleobases 1-5, 2-6, 3-7, 4-8, 5-9, 6-10, 7-11, 8-12, 9-13, 10-14, 11-15, 12-16, 13-17, 14-18, 15-19, 16-20, 17-21, 18-22, 19-23, 20-24, 21-25, 22-26, 23-27, 24-28, 25-29, 26-30, 27-31, 28-32, 29-33, 30-34, 31-35, 32-36, 33-37, 34-38, 35-39, 36-40, 37-41, 38-42, 39-43, 40-44, 41-45, 42-46, 43-47, 44-48, 45-49, 46-50, 47-51, 48-52, 49-53, 50-54, 51-55, 52-56, 53-57, 54-58, 55-59, 56-60, 57-61, 58-62, 59-63, 60-64, 61-65, 62-66, 63-67, 64-68, 65-69, 66-70, 67-71, 68-72, 69-73, 70-74, 71-75, 72-76, 73-77, 74-78, 75-79, 76-80, 77-81, 78-82, 79-83, 80-84, 81-85, 82-86, 83-87, 84-88, 85-89, 86-90, 87-91, 88-92, 89-93, 90-94, 91-95, 92-96, 93-97, 94-98, 95-99, 96-100.

[0242] An additional set for regions 20 nucleobases in length, in a target sequence 100 nucleobases in length, beginning at position 1 of the target nucleobase sequence, can be described using the following expression:

S(20)={R.sub.1,20|n.epsilon.{1,2,3, . . . , 81}}

and describes the set of regions comprising nucleobases 1-20, 2-21, 3-22, 4-23, 5-24, 6-25, 7-26, 8-27, 9-28, 10-29, 11-30, 12-31, 13-32, 14-33, 15-34, 16-35, 17-36, 18-37, 19-38, 20-39, 21-40, 22-41, 23-42, 24-43, 25-44, 26-45, 27-46, 28-47, 29-48, 30-49, 31-50, 32-51, 33-52, 34-53, 35-54, 36-55, 37-56, 38-57, 39-58, 40-59, 41-60, 42-61, 43-62, 44-63, 45-64, 46-65, 47-66, 48-67, 49-68, 50-69, 51-70, 52-71, 53-72, 54-73, 55-74, 56-75, 57-76, 58-77, 59-78, 60-79, 61-80, 62-81, 63-82, 64-83, 65-84, 66-85, 67-86, 68-87, 69-88, 70-89, 71-90, 72-91, 73-92, 74-93, 75-94, 76-95, 77-96, 78-97, 79-98, 80-99, 81-100.

[0243] An additional set for regions 80 nucleobases in length, in a target sequence 100 nucleobases in length, beginning at position 1 of the target nucleobase sequence, can be described using the following expression:

S(80)={R.sub.1,80/n.epsilon.{1,2,3, . . . , 21}}

and describes the set of regions comprising nucleobases 1-80, 2-81, 3-82, 4-83, 5-84, 6-85, 7-86, 8-87, 9-88, 10-89, 11-90, 12-91, 13-92, 14-93, 15-94, 16-95, 17-96, 18-97, 19-98, 20-99, 21-100.

[0244] Thus, in this example, A would include regions 1-5, 2-6, 3-7 . . . 93-100, 1-20, 2-21, 3-22 . . . 81-100, 1-80, 2-81, 3-82 . . . 21-100.

[0245] The union of these aforementioned example sets and other sets for lengths from 10 to 19 and 21 to 79 can be described using the mathematical expression

A = m S ( m ) ##EQU00002##

[0246] where .orgate. represents the union of the sets obtained by combining all members of all sets.

[0247] The mathematical expressions described herein defines all possible target regions in a target nucleobase sequence of any length L, where the region is of length m, and where m is greater than or equal to 5 and less than or equal to 80 nucleobases and, and where m is less than L, and where n is less than L-m+1.

[0248] In accordance with one embodiment of the present invention, a series of nucleic acid duplexes comprising the chimeric oligomeric compounds of the present invention and their complements can be designed for a specific target or targets. These nucleic acid duplexes are commonly referred to in the art as double-strand RNAs (dsRNAs) or small interfering RNAs (siRNAs). As described herein, such duplexes have been shown in the art to modulate target expression and regulate translation as well as RNA processing via an antisense mechanism. Within a duplex, the ends of the strands may be modified by the addition of one or more natural or modified nucleobases to form an overhang. The sense strand of the duplex is then designed and synthesized as the complement of the antisense strand and may also contain modifications or additions to either terminus. For example, in one embodiment, both strands of the duplex would be complementary over the central nucleobases, each having overhangs at one or both termini. The antisense and sense strands of the duplex comprise from about 17 to 25 nucleotides, or from about 19 to 23 nucleotides. Alternatively, the antisense and sense strands comprise 20, 21 or 22 nucleotides.

[0249] For example, a duplex comprising a chimeric oligomeric compound having the sequence CGAGAGGCGGACGGGACCG (SEQ ID NO: 3) and having a two-nucleobase overhang of deoxythymidine(dT) would have the following structure:

##STR00038##

[0250] Overhangs can range from 1 to 6 nucleobases and these nucleobases may or may not be complementary to the target nucleic acid. One of skill in the art will understand that the overhang may be 1, 2, 3, 4, 5 or 6 nucleobases in length. In another embodiment, the duplexes may have an overhang on only on terminus.

[0251] In another embodiment, a duplex comprising an antisense strand having the same sequence CGAGAGGCGGACGGGACCG (SEQ ID NO: 3) may be prepared with blunt ends (no single stranded overhang) as shown:

##STR00039##

[0252] The RNA duplex can be unimolecular or bimolecular; i.e., the two strands can be part of a single molecule or may be separate molecules. These sequences are shown to contain thymine (T), but one of skill in the art will appreciate that thymine (T) can generally be replaced with uracil (U) in RNA sequences.

Screening and Target Validation

[0253] In a further embodiment, "suitable target segments" may be employed in a screen for additional oligomeric compounds that modulate the expression of a selected protein. "Modulators" are those oligomeric compounds that decrease or increase the expression of a nucleic acid molecule encoding a protein and which comprise at least an 8-nucleobase portion which is complementary to a suitable target segment. The screening method comprises the steps of contacting a suitable target segment of a nucleic acid molecule encoding a protein with one or more candidate modulators, and selecting for one or more candidate modulators which decrease or increase the expression of a nucleic acid molecule encoding a protein. Once it is shown that the candidate modulator or modulators are capable of modulating (e.g. either decreasing or increasing) the expression of a nucleic acid molecule encoding a peptide, the modulator may then be employed in further investigative studies of the function of the peptide, or for use as a research, diagnostic, or therapeutic agent in accordance with the present invention.

[0254] The suitable target segments of the present invention may also be combined with their respective complementary chimeric oligomeric compounds of the present invention to form stabilized double-stranded (duplexed) oligonucleotides. Such double-stranded oligonucleotide moieties have been shown in the art to modulate target expression and regulate translation as well as RNA processing via an antisense mechanism.

[0255] The oligomeric compounds of the present invention can also be applied in the areas of drug discovery and target validation. The present invention comprehends the use of the oligomeric compounds and suitable targets identified herein in drug discovery efforts to elucidate relationships that exist between proteins and a disease state, phenotype, or condition. These methods include detecting or modulating a target peptide comprising contacting a sample, tissue, cell, or organism with the oligomeric compounds of the present invention, measuring the nucleic acid or protein level of the target and/or a related phenotypic or chemical endpoint at some time after treatment, and optionally comparing the measured value to a non-treated sample or sample treated with a further oligomeric compound of the invention. These methods can also be performed in parallel or in combination with other experiments to determine the function of unknown genes for the process of target validation or to determine the validity of a particular gene product as a target for treatment or prevention of a particular disease, condition, or phenotype.

Kits, Research Reagents, Diagnostics, and Therapeutics

[0256] The oligomeric compounds of the present invention can be utilized for diagnostics, therapeutics, prophylaxis and as research reagents and kits. Furthermore, antisense oligonucleotides, which are able to inhibit gene expression with exquisite specificity, are often used by those of ordinary skill to elucidate the function of particular genes or to distinguish between functions of various members of a biological pathway.

[0257] For use in kits and diagnostics, the oligomeric compounds of the present invention, either alone or in combination with other oligomeric compounds or therapeutics, can be used as tools in differential and/or combinatorial analyses to elucidate expression patterns of a portion or the entire complement of genes expressed within cells and tissues.

[0258] As one nonlimiting example, expression patterns within cells or tissues treated with one or more chimeric oligomeric compounds are compared to control cells or tissues not treated with chimeric oligomeric compounds and the patterns produced are analyzed for differential levels of gene expression as they pertain, for example, to disease association, signaling pathway, cellular localization, expression level, size, structure or function of the genes examined. These analyses can be performed on stimulated or unstimulated cells and in the presence or absence of other compounds and or oligomeric compounds which affect expression patterns.

[0259] Examples of methods of gene expression analysis known in the art include DNA arrays or microarrays (Brazma and Vilo, FEBS Lett., 2000, 480, 17-24; Celis, et al., FEBS Lett., 2000, 480, 2-16), SAGE (serial analysis of gene expression)(Madden, et al., Drug Discov. Today, 2000, 5, 415-425), READS (restriction enzyme amplification of digested cDNAs) (Prashar and Weissman, Methods Enzymol., 1999, 303, 258-72), TOGA (total gene expression analysis) (Sutcliffe, et al., Proc. Natl. Acad. Sci. U.S.A., 2000, 97, 1976-81), protein arrays and proteomics (Celis, et al., FEBS Lett., 2000, 480, 2-16; Jungblut, et al., Electrophoresis, 1999, 20, 2100-10), expressed sequence tag (EST) sequencing (Celis, et al., FEBS Lett., 2000, 480, 2-16; Larsson, et al., J. Biotechnol., 2000, 80, 143-57), subtractive RNA fingerprinting (SuRF) (Fuchs, et al., Anal. Biochem., 2000, 286, 91-98; Larson, et al., Cytometry, 2000, 41, 203-208), subtractive cloning, differential display (DD) (Jurecic and Belmont, Curr. Opin. Microbiol., 2000, 3, 316-21), comparative genomic hybridization (Carulli, et al., J. Cell Biochem. Suppl., 1998, 31, 286-96), FISH (fluorescent in situ hybridization) techniques (Going and Gusterson, Eur. J. Cancer, 1999, 35, 1895-904) and mass spectrometry methods (To, Comb. Chem. High Throughput Screen, 2000, 3, 235-41).

[0260] The oligomeric compounds of the invention are useful for research and diagnostics, because these oligomeric compounds hybridize to nucleic acids encoding proteins. The primers and probes disclosed herein are useful in methods requiring the specific detection of nucleic acid molecules encoding proteins and in the amplification of the nucleic acid molecules for detection or for use in further studies. Hybridization of the primers and probes with a nucleic acid can be detected by means known in the art. Such means may include conjugation of an enzyme to the primer or probe, radiolabelling of the primer or probe or any other suitable detection means. Kits using such detection means for detecting the level of selected proteins in a sample may also be prepared.

[0261] The specificity and sensitivity of antisense is also harnessed by those of skill in the art for therapeutic uses. Antisense oligomeric compounds have been employed as therapeutic moieties in the treatment of disease states in animals, including humans. Antisense oligonucleotide drugs, including ribozymes, have been safely and effectively administered to humans and numerous clinical trials are presently underway. It is thus established that antisense oligomeric compounds can be useful therapeutic modalities that can be configured to be useful in treatment regimes for the treatment of cells, tissues and animals, especially humans.

[0262] For therapeutics, an animal, such as a human, suspected of having a disease or disorder which can be treated by modulating the expression of a selected protein is treated by administering chimeric oligomeric compounds in accordance with this invention. For example, in one non-limiting embodiment, the methods comprise the step of administering to the animal in need of treatment, a therapeutically effective amount of a protein inhibitor. The protein inhibitors of the present invention effectively inhibit the activity of the protein or inhibit the expression of the protein. In one embodiment, the activity or expression of a protein in an animal is inhibited by about 10% or more, by about 20% or more, by about 30% or more, by about 40% or more, by about 50% or more, by about 60% or more, by about 70% or more, by about 80% or more, by about 90% or more, by about 95% or more, or by about 99% or more. For example, the reduction of the expression of a protein may be measured in serum, adipose tissue, liver or any other body fluid, tissue or organ of the animal. The cells contained within the fluids, tissues or organs being analyzed can contain a nucleic acid molecule encoding a protein and/or the protein itself.

[0263] The oligomeric compounds of the invention can be utilized in pharmaceutical compositions by adding an effective amount of an oligomeric compound to a suitable pharmaceutically acceptable diluent or carrier. Use of the oligomeric compounds and methods of the invention may also be useful prophylactically.

Formulations

[0264] The oligomeric compounds of the invention may also be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecule structures or mixtures of compounds, as for example, liposomes, receptor-targeted molecules, oral, rectal, topical or other formulations, for assisting in uptake, distribution and/or absorption. Representative United States patents that teach the preparation of such uptake, distribution and/or absorption-assisting formulations include, but are not limited to, U.S. Pat. Nos. 5,108,921; 5,354,844; 5,416,016; 5,459,127; 5,521,291; 5,543,158; 5,547,932; 5,583,020; 5,591,721; 4,426,330; 4,534,899; 5,013,556; 5,108,921; 5,213,804; 5,227,170; 5,264,221; 5,356,633; 5,395,619; 5,416,016; 5,417,978; 5,462,854; 5,469,854; 5,512,295; 5,527,528; 5,534,259; 5,543,152; 5,556,948; 5,580,575; and 5,595,756, each of which is herein incorporated by reference.

[0265] The chimeric oligomeric compounds of the invention encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other compound which, upon administration to an animal, including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. Accordingly, for example, the disclosure is also drawn to prodrugs and pharmaceutically acceptable salts of the oligomeric compounds of the invention, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents. The term "prodrug" indicates a therapeutic agent that is prepared in an inactive form that is converted to an active form (i.e., drug) within the body or cells thereof by the action of endogenous enzymes or other chemicals and/or conditions. In particular, prodrug versions of the oligomeric compounds of the invention are prepared as SATE[(S-acetyl-2-thioethyl)phosphate]derivatives according to the methods disclosed in WO 93/24510 to Gosselin et al., published Dec. 9, 1993 or in WO 94/26764 and U.S. Pat. No. 5,770,713 to Imbach et al.

[0266] The term "pharmaceutically acceptable salts" refers to physiologically and pharmaceutically acceptable salts of the compounds of the invention: i.e., salts that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects thereto.

[0267] Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Examples of metals used as cations are sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines are N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge et al., "Pharmaceutical Salts," J. of Pharma Sci., 1977, 66, 1-19). The base addition salts of said acidic compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner. The free acid form may be regenerated by contacting the salt form with an acid and isolating the free acid in the conventional manner. The free acid forms differ from their respective salt forms somewhat in certain physical properties such as solubility in polar solvents, but otherwise the salts are equivalent to their respective free acid for purposes of the present invention. As used herein, a "pharmaceutical addition salt" includes a pharmaceutically acceptable salt of an acid form of one of the components of the compositions of the invention. These include organic or inorganic acid salts of the amines. Acid salts are the hydrochlorides, acetates, salicylates, nitrates and phosphates. Other suitable pharmaceutically acceptable salts are well known to those skilled in the art and include basic salts of a variety of inorganic and organic acids, such as, for example, with inorganic acids, such as for example hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid; with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, lactic acid, oxalic acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid; and with amino acids, such as the 20 alpha-amino acids involved in the synthesis of proteins in nature, for example glutamic acid or aspartic acid, and also with phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate, N-cyclohexylsulfamic acid (with the formation of cyclamates), or with other acid organic compounds, such as ascorbic acid. Pharmaceutically acceptable salts of compounds may also be prepared with a pharmaceutically acceptable cation. Suitable pharmaceutically acceptable cations are well known to those skilled in the art and include alkaline, alkaline earth, ammonium and quaternary ammonium cations. Carbonates or hydrogen carbonates are also possible.

[0268] For oligonucleotides, examples of pharmaceutically acceptable salts include but are not limited to (a) salts formed with cations such as sodium, potassium, ammonium, magnesium, calcium, polyamines such as spermine and spermidine, etc.; (b) acid addition salts formed with inorganic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; (c) salts formed with organic acids such as, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (d) salts formed from elemental anions such as chlorine, bromine, and iodine.

Pharmaceutical Compositions and Routes of Administration

[0269] The present invention also includes pharmaceutical compositions and formulations which include the oligomeric compounds of the invention. The pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (including ophthalmic and to mucous membranes including vaginal and rectal delivery), pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Oligonucleotides with at least one 2'-O-methoxyethyl modification are believed to be particularly useful for oral administration.

[0270] Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. Topical formulations include those in which the oligonucleotides of the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Lipids and liposomes include neutral (e.g. dioleoylphosphatidyl DOPE ethanolamine, dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g. dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g. dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA). Oligonucleotides of the invention may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, oligonucleotides may be complexed to lipids, in particular to cationic lipids. Fatty acids and esters include but are not limited arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C.sub.1-10 alkyl ester (e.g. isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof. Topical formulations are described in detail in U.S. patent application Ser. No. 09/315,298 filed on May 20, 1999 which is incorporated herein by reference in its entirety.

[0271] In some embodiments, an oligonucleotide may be administered to a subject via an oral route of administration. The subjects of the present invention comprise animals. An animal subject may be a mammal, such as a mouse, a rat, a dog, a guinea pig, a monkey, a human, a non-human primate, a cat or a pig. Non-human primates include monkeys and chimpanzees. A suitable animal subject may be an experimental animal, such as a mouse, a rat, a dog, a non-human primate, a cat or a pig.

[0272] In some embodiments, the subject may be a human. In certain embodiments, the subject may be a human patient as discussed in more detail herein. In certain embodiments, it may be necessary to modulate the expression of one or more genes of the human patient. In some particular embodiments, it may be necessary to inhibit expression of one or more genes of the human patient. In particular embodiments, it may be necessary to modulate, i e inhibit or enhance, the expression of one or more genes in order to obtain therapeutic outcomes discussed herein.

[0273] In some embodiments, non-parenteral (e.g. oral) oligonucleotide formulations according to the present invention result in enhanced bioavailability of the oligonucleotide. In this context, the term "bioavailability" refers to a measurement of that portion of an administered drug which reaches the circulatory system (e.g. blood, especially blood plasma) when a particular mode of administration is used to deliver the drug. Enhanced bioavailability refers to a particular mode of administration's ability to deliver oligonucleotide to the peripheral blood plasma of a subject relative to another mode of administration. For example, when a non-parenteral mode of administration (e.g. an oral mode) is used to introduce the drug into a subject, the bioavailability for that mode of administration may be compared to a different mode of administration, e.g. an IV mode of administration. In some embodiments, the area under a compound's blood plasma concentration curve (AUC.sub.0) after non-parenteral administration may be divided by the area under the drug's plasma concentration curve after intravenous (i.v.) administration (AUC.sub.iv) to provide a dimensionless quotient (relative bioavailability, RB) that represents fraction of compound absorbed via the non-parenteral route as compared to the IV route. A composition's bioavailability is said to be enhanced in comparison to another composition's bioavailability when the first composition's relative bioavailability (RB.sub.1) is greater than the second composition's relative bioavailability (RB.sub.2).

[0274] In general, bioavailability correlates with therapeutic efficacy when a compound's therapeutic efficacy is related to the blood concentration achieved, even if the drug's ultimate site of action is intracellular (van Berge-Henegouwen et al., Gastroenterol., 1977, 73, 300). Bioavailability studies have been used to determine the degree of intestinal absorption of a drug by measuring the change in peripheral blood levels of the drug after an oral dose (DiSanto, Chapter 76 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 1451-1458).

[0275] In general, an oral composition (comprising an oligonucleotide) bioavailability is said to be "enhanced" when its relative bioavailability is greater than the bioavailability of a composition substantially consisting of pure oligonucleotide, i.e. oligonucleotide in the absence of a penetration enhancer.

[0276] Organ bioavailability refers to the concentration of compound in an organ. Organ bioavailability may be measured in test subjects by a number of means, such as by whole-body radiography. Organ bioavailability may be modified, e.g. enhanced, by one or more modifications to the oligonucleotide, by use of one or more carrier compounds or excipients, etc. as discussed in more detail herein. In general, an increase in bioavailability will result in an increase in organ bioavailability.

[0277] Oral oligonucleotide compositions according to the present invention may comprise one or more "mucosal penetration enhancers," also known as "absorption enhancers" or simply as "penetration enhancers." Accordingly, some embodiments of the invention comprise at least one oligonucleotide in combination with at least one penetration enhancer. In general, a penetration enhancer is a substance that facilitates the transport of a drug across mucous membrane(s) associated with the desired mode of administration, e.g. intestinal epithelial membranes. Accordingly it is desirable to select one or more penetration enhancers that facilitate the uptake of an oligonucleotide, without interfering with the activity of the oligonucleotide, and in such a manner the oligonucleotide can be introduced into the body of an animal without unacceptable degrees of side-effects such as toxicity, irritation or allergic response.

[0278] Embodiments of the present invention provide compositions comprising one or more pharmaceutically acceptable penetration enhancers, and methods of using such compositions, which result in the improved bioavailability of oligonucleotides administered via non-parenteral modes of administration. Heretofore, certain penetration enhancers have been used to improve the bioavailability of certain drugs. See Muranishi, Crit. Rev. Ther. Drug Carrier Systems, 1990, 7, 1 and Lee et al., Crit. Rev. Ther. Drug Carrier Systems, 1991, 8, 91. It has been found that the uptake and delivery of oligonucleotides can be greatly improved even when administered by non-parenteral means through the use of a number of different classes of penetration enhancers.

[0279] In some embodiments, compositions for non-parenteral administration include one or more modifications to naturally-occurring oligonucleotides (i.e. full-phosphodiester deoxyribosyl or full-phosphodiester ribosyl oligonucleotides). Such modifications may increase binding affinity, nuclease stability, cell or tissue permeability, tissue distribution, or other biological or pharmacokinetic property. Modifications may be made to the base, the linker, or the sugar, in general, as discussed in more detail herein with regards to oligonucleotide chemistry. In some embodiments of the invention, compositions for administration to a subject, and in particular oral compositions for administration to an animal (human or non-human) subject, will comprise modified oligonucleotides having one or more modifications for enhancing affinity, stability, tissue distribution, or other biological property.

[0280] Suitable modified linkers include phosphorothioate linkers. In some embodiments according to the invention, the oligonucleotide has at least one phosphorothioate linker. Phosphorothioate linkers provide nuclease stability as well as plasma protein binding characteristics to the oligonucleotide. Nuclease stability is useful for increasing the in vivo lifetime of oligonucleotides, while plasma protein binding decreases the rate of first pass clearance of oligonucleotide via renal excretion. In some embodiments according to the present invention, the oligonucleotide has at least two phosphorothioate linkers. In some embodiments, wherein the oligonucleotide has exactly n nucleosides, the oligonucleotide has from one to n-1 phosphorothioate linkages. In some embodiments, wherein the oligonucleotide has exactly n nucleosides, the oligonucleotide has n-1 phosphorothioate linkages. In other embodiments wherein the oligonucleotide has exactly n nucleoside, and n is even, the oligonucleotide has from 1 to n/2 phosphorothioate linkages, or, when n is odd, from 1 to (n-1)/2 phosphorothioate linkages. In some embodiments, the oligonucleotide has alternating phosphodiester (PO) and phosphorothioate (PS) linkages. In other embodiments, the oligonucleotide has at least one stretch of two or more consecutive PO linkages and at least one stretch of two or more PS linkages. In other embodiments, the oligonucleotide has at least two stretches of PO linkages interrupted by at least on PS linkage.

[0281] In some embodiments, at least one of the nucleosides is modified on the ribosyl sugar unit by a modification that imparts nuclease stability, binding affinity or some other beneficial biological property to the sugar. In some cases, the sugar modification includes a 2'-modification, e.g. the 2'-OH of the ribosyl sugar is replaced or substituted. Suitable replacements for 2'-OH include 2'-F and 2'-arabino-F. Suitable substitutions for OH include 2'-O-alkyl, e.g. 2-O-methyl, and 2'-O-substituted alkyl, e.g. 2'-O-methoxyethyl, 2'--NH.sub.2, 2'-O-aminopropyl, etc. In some embodiments, the oligonucleotide contains at least one 2'-modification. In some embodiments, the oligonucleotide contains at least two 2'-modifications. In some embodiments, the oligonucleotide has at least one 2'-modification at each of the termini (i.e. the 3'- and 5'-terminal nucleosides each have the same or different 2'-modifications). In some embodiments, the oligonucleotide has at least two sequential 2'-modifications at each end of the oligonucleotide. In some embodiments, oligonucleotides further comprise at least one deoxynucleoside. In particular embodiments, oligonucleotides comprise a stretch of deoxynucleosides such that the stretch is capable of activating RNase (e.g. RNase H) cleavage of an RNA to which the oligonucleotide is capable of hybridizing. In some embodiments, a stretch of deoxynucleosides capable of activating RNase-mediated cleavage of RNA comprises about 6 to about 16, e.g. about 8 to about 16 consecutive deoxynucleosides. In further embodiments, oligonucleotides are capable of eliciting cleaveage by dsRNAse enzymes which act on RNA:RNA hybrids.

[0282] Oligonucleotide compositions of the present invention may be formulated in various dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, and enemas. The term "alimentary delivery" encompasses e.g. oral, rectal, endoscopic and sublingual/buccal administration. A common requirement for these modes of administration is absorption over some portion or all of the alimentary tract and a need for efficient mucosal penetration of the oligonucleotides or mimetics thereof so administered.

[0283] Delivery of a drug via the oral mucosa, as in the case of buccal and sublingual administration, has several desirable features, including, in many instances, a more rapid rise in plasma concentration of the drug (Harvey, Chapter 35 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, page 711).

[0284] Endoscopy may be used for drug delivery directly to an interior portion of the alimentary tract. For example, endoscopic retrograde cystopancreatography (ERCP) takes advantage of extended gastroscopy and permits selective access to the biliary tract and the pancreatic duct (Hirahata et al., Gan To Kagaku Ryoho, 1992, 19(10 Suppl.), 1591). Pharmaceutical compositions, including liposomal formulations, can be delivered directly into portions of the alimentary canal, such as, e.g., the duodenum (Somogyi et al., Pharm. Res., 1995, 12, 149) or the gastric submucosa (Akamo et al., Japanese J. Cancer Res., 1994, 85, 652) via endoscopic means. Gastric lavage devices (Inoue et al., Artif. Organs, 1997, 21, 28) and percutaneous endoscopic feeding devices (Pennington et al., Ailment Pharmacol. Ther., 1995, 9, 471) can also be used for direct alimentary delivery of pharmaceutical compositions.

[0285] In some embodiments, oligonucleotide formulations may be administered through the anus into the rectum or lower intestine. Rectal suppositories, retention enemas or rectal catheters can be used for this purpose and may be desired when patient compliance might otherwise be difficult to achieve (e.g., in pediatric and geriatric applications, or when the patient is vomiting or unconscious). Rectal administration can result in more prompt and higher blood levels than the oral route. (Harvey, Chapter 35 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, page 711). Because about 50% of the drug that is absorbed from the rectum will likely bypass the liver, administration by this route significantly reduces the potential for first-pass metabolism (Benet et al., Chapter 1 In: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al., eds., McGraw-Hill, New York, N.Y., 1996).

[0286] Some embodiments employ various penetration enhancers in order to effect transport of oligonucleotides and other nucleic acids across mucosal and epithelial membranes. Penetration enhancers may be classified as belonging to one of five broad categories--surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Accordingly, some embodiments comprise oral oligonucleotide compositions comprising at least one member of the group consisting of surfactants, fatty acids, bile salts, chelating agents, and non-chelating surfactants. Further embodiments comprise oral oligonucleotide compositions comprising at least one fatty acid, e.g. capric or lauric acid, or combinations or salts thereof. Other embodiments comprise methods of enhancing the oral bioavailability of an oligonucleotide, the method comprising co-administering the oligonucleotide and at least one penetration enhancer.

[0287] Other excipients that may be added to oral oligonucleotide compositions include surfactants (or "surface-active agents"). These are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of oligonucleotides through the alimentary mucosa and other epithelial membranes is enhanced. In addition to bile salts and fatty acids, surfactants include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and perfluorohemical emulsions, such as FC-43 (Takahashi et al., J. Pharm. Phamacol., 1988, 40, 252).

[0288] Fatty acids and their derivatives which act as penetration enhancers and may be used in compositions of the present invention include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines and mono- and di-glycerides thereof and/or physiologically acceptable salts thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1; El-Hariri et al., J. Pharm. Pharmacol., 1992, 44, 651).

[0289] In some embodiments, oligonucleotide compositions for oral delivery comprise at least two discrete phases, which phases may comprise particles, capsules, gel-capsules, microspheres, etc. Each phase may contain one or more oligonucleotides, penetration enhancers, surfactants, bioadhesives, effervescent agents, or other adjuvant, excipient or diluent. In some embodiments, one phase comprises at least one oligonucleotide and at lease one penetration enhancer. In some embodiments, a first phase comprises at least one oligonucleotide and at least one penetration enhancer, while a second phase comprises at least one penetration enhancer. In some embodiments, a first phase comprises at least one oligonucleotide and at least one penetration enhancer, while a second phase comprises at least one penetration enhancer and substantially no oligonucleotide. In some embodiments, at least one phase is compounded with at least one degradation retardant, such as a coating or a matrix, which delays release of the contents of that phase. In some embodiments, at least one phase In some embodiments, a first phase comprises at least one oligonucleotide, at least one penetration enhancer, while a second phase comprises at least one penetration enhancer and a release-retardant. In particular embodiments, an oral oligonucleotide composition comprises a first phase comprising particles containing an oligonucleotide and a penetration enhancer, and a second phase comprising particles coated with a release-retarding agent and containing penetration enhancer.

[0290] A variety of bile salts also function as penetration enhancers to facilitate the uptake and bioavailability of drugs. The physiological roles of bile include the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (Brunton, Chapter 38 In: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al., eds., McGraw-Hill, New York, N.Y., 1996, pages 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus, the term "bile salt" includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. The bile salts of the invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (CDCA, sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579).

[0291] In some embodiments, penetration enhancers of the present invention are mixtures of penetration enhancing compounds. One such penetration mixture is UDCA (and/or CDCA) with capric and/or lauric acids or salts thereof e.g. sodium. Such mixtures are useful for enhancing the delivery of biologically active substances across mucosal membranes, in particular intestinal mucosa. Other penetration enhancer mixtures comprise about 5-95% of bile acid or salt(s) UDCA and/or CDCA with 5-95% capric and/or lauric acid. Particular penetration enhancers are mixtures of the sodium salts of UDCA, capric acid and lauric acid in a ratio of about 1:2:2 respectively. Anther such penetration enhancer is a mixture of capric and lauric acid (or salts thereof) in a 0.01:1 to 1:0.01 ratio (mole basis). In particular embodiments capric acid and lauric acid are present in molar ratios of e.g. about 0.1:1 to about 1:0.1, in particular about 0.5:1 to about 1:0.5.

[0292] Other excipients include chelating agents, i.e. compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of oligonucleotides through the alimentary and other mucosa is enhanced. With regards to their use as penetration enhancers in compositions containing DNA-like oligonucleotides in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315). Chelating agents of the invention include, but are not limited to, disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines)(Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1; Buur et al., J. Control Rel., 1990, 14, 43).

[0293] As used herein, non-chelating non-surfactant penetration enhancers may be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of oligonucleotides through the alimentary and other mucosal membranes (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1). This class of penetration enhancers includes, but is not limited to, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621).

[0294] Agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical, therapeutic and other compositions of the present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), can be used.

[0295] A "pharmaceutical carrier" or "excipient" may be a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a an oligonucleotide and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, EXPLOTAB); and wetting agents (e.g., sodium lauryl sulphate, etc.).

[0296] Oral oligonucleotide compositions may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the composition of present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention.

[0297] Compositions and formulations for parenteral, intrathecal or intraventricular administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients.

[0298] Pharmaceutical compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids.

[0299] The pharmaceutical formulations of the present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.

[0300] The compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.

[0301] In one embodiment of the present invention the pharmaceutical compositions may be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency of the final product. The preparation of such compositions and formulations is generally known to those skilled in the pharmaceutical and formulation arts and may be applied to the formulation of the compositions of the present invention.

Emulsions

[0302] The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 um in diameter (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systems comprising of two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be either water-in-oil (w/o) or of the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous provides an o/w/o emulsion.

[0303] Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).

[0304] Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).

[0305] Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.

[0306] A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.

[0307] Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.

[0308] The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of reasons of ease of formulation, efficacy from an absorption and bioavailability standpoint. (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.

[0309] In one embodiment of the present invention, the compositions of oligonucleotides are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 271).

[0310] The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.

[0311] Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (SO750), decaglycerol decaoleate (DAO750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.

[0312] Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or oligonucleotides. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of oligonucleotides from the gastrointestinal tract, as well as improve the local cellular uptake of oligonucleotides within the gastrointestinal tract, vagina, buccal cavity and other areas of administration.

[0313] Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the oligonucleotides and nucleic acids of the present invention. Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories--surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.

Liposomes

[0314] There are many organized surfactant structures besides microemulsions that have been studied and used in the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term "liposome" means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers.

[0315] Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo.

[0316] In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores.

[0317] Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes.

[0318] Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes. As the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act.

[0319] Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.

[0320] Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis.

[0321] Liposomes fall into two broad classes and are useful for the delivery of DNA, RNA or any nucleic acid-based construct. Cationic liposomes are positively charged liposomes which interact with negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).

[0322] Liposomes which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).

[0323] One major type of liposomal composition includes phospholipids other than naturally-derived phosphatidylcholine. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.

[0324] Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g. as a solution or as an emulsion) were ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265).

[0325] Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome.TM. I (glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether) and Novasome.TM. II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P.Pharma. Sci., 1994, 4, 6, 466).

[0326] Liposomes also include "sterically stabilized" liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside G.sub.M1, or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).

[0327] Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. (Ann. N.Y. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside G.sub.M1, galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside G.sub.M1 or a galactocerebroside sulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphatidylcholine are disclosed in WO 97/13499 (Lim et al.).

[0328] Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C.sub.1215G, that contains a PEG moiety. Illum et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEG-derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al.). U.S. Pat. No. 5,540,935 (Miyazaki et al.) and U.S. Pat. No. 5,556,948 (Tagawa et al.) describe PEG-containing liposomes that can be further derivatized with functional moieties on their surfaces.

[0329] WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include an antisense RNA. U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising antisense oligonucleotides targeted to the raf gene.

[0330] Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g. they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.

[0331] Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the "head") provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).

[0332] If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class.

[0333] If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps.

[0334] If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.

[0335] If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides. The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).

[0336] Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.

[0337] Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.

[0338] Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.

Pulsatile Delivery

[0339] The compounds of the present invention may also be administered by pulsatile delivery. "Pulsatile delivery" refers to a pharmaceutical formulation that delivers a first pulse of drug (e.g. an antisense compound) combined with a penetration enhancer and a second pulse of penetration enhancer to promote absorption of drug which is not absorbed upon release with the first pulse of penetration enhancer.

[0340] One embodiment of the present invention is a delayed release oral formulation for enhanced intestinal drug absorption, comprising:

[0341] (a) a first population of carrier particles comprising said drug and a penetration enhancer, wherein said drug and said penetration enhancer are released at a first location in the intestine; and

[0342] (b) a second population of carrier particles comprising a penetration enhancer and a delayed release coating or matrix, wherein the penetration enhancer is released at a second location in the intestine downstream from the first location, whereby absorption of the drug is enhanced when the drug reaches the second location.

[0343] Alternatively, the penetration enhancer in (a) and (b) is different.

[0344] This enhancement is obtained by encapsulating at least two populations of carrier particles. The first population of carrier particles comprises a biologically active substance and a penetration enhancer, and the second (and optionally additional) population of carrier particles comprises a penetration enhancer and a delayed release coating or matrix.

[0345] A "first pass effect" that applies to orally administered drugs is degradation due to the action of gastric acid and various digestive enzymes. One means of ameliorating first pass clearance effects is to increase the dose of administered drug, thereby compensating for proportion of drug lost to first pass clearance. Although this may be readily achieved with i.v. administration by, for example, simply providing more of the drug to an animal, other factors influence the bioavailability of drugs administered via non-parenteral means. For example, a drug may be enzymatically or chemically degraded in the alimentary canal or blood stream and/or may be impermeable or semipermeable to various mucosal membranes.

[0346] It is also contemplated that these pharmaceutical compositions are capable of enhancing absorption of biologically active substances when administered via the rectal, vaginal, nasal or pulmonary routes. It is also contemplated that release of the biologically active substance can be achieved in any part of the gastrointestinal tract.

[0347] Liquid pharmaceutical compositions of oligonucleotide can be prepared by combining the oligonucleotide with a suitable vehicle, for example sterile pyrogen free water, or saline solution. Other therapeutic compounds may optionally be included.

[0348] The present invention also contemplates the use of solid particulate compositions. Such compositions comprise particles of oligonucleotide that are of respirable size. Such particles can be prepared by, for example, grinding dry oligonucleotide by conventional means, fore example with a mortar and pestle, and then passing the resulting powder composition through a 400 mesh screen to segregate large particles and agglomerates. A solid particulate composition comprised of an active oligonucleotide can optionally contain a dispersant which serves to facilitate the formation of an aerosol, for example lactose.

[0349] In accordance with the present invention, oligonucleotide compositions can be aerosolized. Aerosolization of liquid particles can be produced by any suitable means, such as with a nebulizer. See, for example, U.S. Pat. No. 4,501,729. Nebulizers are commercially available devices which transform solutions or suspensions into a therapeutic aerosol mist either by means of acceleration of a compressed gas, typically air or oxygen, through a narrow venturi orifice or by means of ultrasonic agitation. Suitable nebulizers include those sold by Blairex.RTM. under the name PARI LC PLUS, PARI DURA-NEB 2000, PARI-BABY Size, PARI PRONEB Compressor with LC PLUS, PARI WALKHALER Compressor/Nebulizer System, PARI LC PLUS Reusable Nebulizer, and PARI LC Jet+.RTM.Nebulizer.

[0350] Formulations for use in nebulizers may consist of an oligonucleotide in a liquid, such as sterile, pyragen free water, or saline solution, wherein the oligonucleotide comprises up to about 40% w/w of the formulation. The oligonucleotide can comprise less than 20% w/w. If desired, further additives such as preservatives (for example, methyl hydroxybenzoate) antioxidants, and flavoring agents can be added to the composition.

[0351] Solid particles comprising an oligonucleotide can also be aerosolized using any solid particulate medicament aerosol generator known in the art. Such aerosol generators produce respirable particles, as described above, and further produce reproducible metered dose per unit volume of aerosol. Suitable solid particulate aerosol generators include insufflators and metered dose inhalers. Metered dose inhalers are used in the art and are useful in the present invention.

[0352] Liquid or solid aerosols are produced at a rate of from about 10 to 150 liters per minute, from about 30 to 150 liters per minute, or from about 60 to 150 liters per minute.

[0353] Enhanced bioavailability of biologically active substances is also achieved via the oral administration of the compositions and methods of the present invention.

Other Components

[0354] The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.

[0355] Aqueous suspensions may contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.

[0356] Certain embodiments of the invention provide pharmaceutical compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism. Examples of such chemotherapeutic agents include but are not limited to daunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the compounds of the invention, such chemotherapeutic agents may be used individually (e.g., 5-FU and oligonucleotide), sequentially (e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide), or in combination with one or more other such chemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide). Anti-inflammatory drugs, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions of the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.

[0357] In another related embodiment, compositions of the invention may contain one or more antisense compounds, particularly oligonucleotides, targeted to a first nucleic acid and one or more additional antisense compounds targeted to a second nucleic acid target. Two or more antisense compounds may be used together or sequentially.

Dosing

[0358] The formulation of therapeutic compositions and their subsequent administration (dosing) is believed to be within the skill of those in the art. Dosing is dependent on severity and responsiveness of the disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution of the disease state is achieved. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient. Persons of ordinary skill can easily determine optimum dosages, dosing methodologies and repetition rates. Optimum dosages may vary depending on the relative potency of individual oligonucleotides, and can generally be estimated based on EC.sub.50s found to be effective in in vitro and in vivo animal models. In general, dosage is from 0.01 .mu.g to 100 g per kg of body weight, from 0.1 .mu.g to 10 g per kg of body weight, from 1.0 .mu.g to 1 g per kg of body weight, from 10.0 .mu.g to 100 mg per kg of body weight, from 100 .mu.g to 10 mg per kg of body weight, or from 1 mg to 5 mg per kg of body weight, and may be given once or more daily, weekly, monthly or yearly, or even once every 2 to 20 years. Persons of ordinary skill in the art can easily estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues. Following successful treatment, it may be desirable to have the patient undergo maintenance therapy to prevent the recurrence of the disease state, wherein the oligonucleotide is administered in maintenance doses, ranging from 0.01 ug to 100 g per kg of body weight, once or more daily, to once every 20 years.

[0359] The effects of treatments with therapeutic compositions can be assessed following collection of tissues or fluids from a patient or subject receiving said treatments. It is known in the art that a biopsy sample can be procured from certain tissues without resulting in detrimental effects to a patient or subject. In certain embodiments, a tissue and its constituent cells comprise, but are not limited to, blood (e.g., hematopoietic cells, such as human hematopoietic progenitor cells, human hematopoietic stem cells, CD34+ cells CD4+ cells), lymphocytes and other blood lineage cells, bone marrow, breast, cervix, colon, esophagus, lymph node, muscle, peripheral blood, oral mucosa and skin. In other embodiments, a fluid and its constituent cells comprise, but are not limited to, blood, urine, semen, synovial fluid, lymphatic fluid and cerebro-spinal fluid. Tissues or fluids procured from patients can be evaluated for expression levels of the target mRNA or protein. Additionally, the mRNA or protein expression levels of other genes known or suspected to be associated with the specific disease state, condition or phenotype can be assessed. mRNA levels can be measured or evaluated by real-time PCR, Northern blot, in situ hybridization or DNA array analysis. Protein levels can be measured or evaluated by ELISA, immunoblotting, quantitative protein assays, protein activity assays (for example, caspase activity assays) immunohistochemistry or immunocytochemistry. Furthermore, the effects of treatment can be assessed by measuring biomarkers associated with the disease or condition in the aforementioned tissues and fluids, collected from a patient or subject receiving treatment, by routine clinical methods known in the art. These biomarkers include but are not limited to: glucose, cholesterol, lipoproteins, triglycerides, free fatty acids and other markers of glucose and lipid metabolism; lipoprotein(a) particle and apolipoprotein B-100; liver transaminases, bilirubin, albumin, blood urea nitrogen, creatine and other markers of kidney and liver function; interleukins, tumor necrosis factors, intracellular adhesion molecules, C-reactive protein and other markers of inflammation; testosterone, estrogen and other hormones; tumor markers; vitamins, minerals and electrolytes.

[0360] The present invention also provides methods of reducing target RNA levels in an animal comprising contacting the animal with a gap-disabled compound comprising a gap-disabled motif listed in Table 13 or Table 26 and wherein the gap-disabled compound comprises a nucleobase sequence substantially complementary to a portion of the target RNA. These methods may also comprise identifying an animal in need of reducing target RNA levels.

[0361] The present invention also provides methods of lowering cholesterol or triglycerides in an animal comprising contacting the animal with a gap-disabled compound comprising the gap-disabled motif 3-2-1-2-1-2-1-2-1-2-3. These methods may also comprise identifying an animal in need of lowering cholesterol or triglycerides.

[0362] The present invention also provides methods of lowering plasma leptin, glucose, or plasma insulin in an animal comprising contacting the animal with a gap-disabled compound having the gap-disabled motif 3-2-1-2-1-2-1-2-1-2-3. These methods may also comprise identifying an animal in need of lowering plasma leptin, glucose, or plasma insulin.

[0363] The present invention also provides methods of lowering body weight, fat depot weight or food intake in an animal comprising contacting the animal with a gap-disabled compound comprising the gap-disabled motif 3-2-1-2-1-2-1-2-1-2-3. These methods may also comprise identifying an animal in need of lowering body weight, fat depot weight or food intake.

[0364] The present invention also provides methods of reducing serum cholesterol, triglycerides or body weight in an obese animal comprising contacting the animal with a gap-disabled compound comprising the gap-disabled motif of 3-2-1-2-1-2-1-2-1-2-3. These methods may also comprise identifying an obese animal in need of reducing serum cholesterol, triglycerides or body weight.

[0365] In order that the invention disclosed herein may be more efficiently understood, examples are provided below. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting the invention in any manner. Throughout these examples, molecular cloning reactions, and other standard recombinant DNA techniques, were carried out according to methods described in Maniatis et al., Molecular Cloning--A Laboratory Manual, 2nd ed., Cold Spring Harbor Press (1989), using commercially available reagents, except where otherwise noted.

EXAMPLES

Examples 1-17

Scheme I, FIGS. 1-3

Preparation of 1-(8-hydroxy-5-hydroxymethyl-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oct-7- -yl)-1H-pyrimidine-2,4-dione (1)

##STR00040##

[0366] Example 1

1-(3-hydroxy-5,5,7,7-tetraisopropyl-tetrahydro-1,4,6,8-tetraoxa-5,7-disila- -cyclopentacycloocten-2-yl)-1H-pyrimidine-2,4-dione (4)

[0367] The 3',5'-protected nucleoside is prepared as illustrated in Karpeisky, A., et. al., Tetrahedron Lett. 1998, 39, 1131-1134. To a solution of arabinouridine (3, 1.0 eq., 0.degree. C.) in anhydrous pyridine is added 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (1.1 eq.). The resulting solution is warmed to room temperature and stirred for two hours. The reaction mixture is subsequently quenched with methanol, concentrated to an oil, dissolved in dichloromethane, washed with aqueous NaHCO.sub.3 and saturated brine, dried over anhydrous Na.sub.2SO.sub.4, filtered, and evaporated. Purification by silica gel chromatography will yield Compound 4.

[0368] For the preparation of the corresponding cytidine and adenosine analogs, N.sup.4-benzoyl arabinocytidine and N.sup.6-benzoyl arabinoadenosine are used, respectively, both of which are prepared from the unprotected arabinonucleoside using the transient protection strategy as illustrated in Ti, et al., J. Am. Chem. Soc. 1982, 104, 1316-1319. Alternatively, the cytidine analog can also be prepared by conversion of the uridine analog as illustrated in Lin, et al., J. Med. Chem. 1983, 26, 1691.

Example 2

Acetic acid 2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-5,5,7,7-tetraisopropyl-tetrah- ydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-3-yl ester (5)

[0369] Compound 4 is O-Acetylated using well known literature procedures (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 150-160 and references cited therein and in Greene, T. W. and Wuts, P. G. M., eds, Wiley-Interscience, New York.) Acetic anhydride (2 to 2.5 eq.) and triethylamine (4 eq.) is added to a solution of 4 (1 eq.) and N,N-dimethylaminopyridine (0.1 eq.) in anhydrous pyridine. After stirring at room temperature for 1 hour the mixture is treated with methanol to quench excess acetic anhydride and evaporated. The residue is redissolved in ethyl acetate, washed extensively with aqueous NaHCO.sub.3, dried over anhydrous Na.sub.2SO.sub.4, filtered, and evaporated. The compound is used without further purification.

Example 3

Acetic acid 2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-hydroxymethyl-tet- rahydro-furan-3-yl ester (6)

[0370] The Tips protecting group is removed from Compound 5 as illustrated in the literature (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 239 and references therein, Greene, T. W. and Wuts, P. G. M., eds, Wiley-Interscience, New York). To a solution of 5 (1 eq.) in anhydrous dichloromethane is added triethylamine (2 eq.) and triethylamine trihydrofluoride (2 eq.). The reaction mixture is monitored by thin layer chromatography until complete at which point the reaction mixture is diluted with additional dichloromethane, washed with aqueous NaHCO.sub.3, dried over anhydrous Na.sub.2SO.sub.4, and evaporated. The resulting Compound 6 is optionally purified by silica gel chromatography.

Example 4

Acetic acid 5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-(2,4-dioxo-3,4-dihydro-- 2H-pyrimidin-1-yl)-4-hydroxy-tetrahydro-furan-3-yl ester (7)

[0371] Dimethoxytritylation of Compound 6 is performed using known literature procedures. Formation of the primary 4,4'-dimethoxytrityl ether should be achieved using standard conditions (Nucleic Acids in Chemistry and Biology, 1992, pp. 108-110, Blackburn, Michael G., and Gait, Michael J., eds, IRL Press, New York.) Generally, a solution of 6 (1 eq.) and N,N-dimethylaminopyridine (0.1 eq.) in anhydrous pyridine is treated with 4,4'-dimethoxytrityl chloride (DMTCl, 1.2 eq.) and triethylamine (4 eq.). After several hours at room temperature, excess 4,4'-dimethoxytrityl chloride is quenched with the addition of methanol and the mixture is evaporated. The mixture is dissolved in dichloromethane and washed extensively with aqueous NaHCO.sub.3 and dried over anhydrous Na.sub.2SO.sub.4. Purification by silica gel chromatography will yield Compound 7.

Example 5

Acetic acid 5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-diphenyl-si- lanyloxy)-2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-y- l ester (8)

[0372] The preparation of tert-butyldiphenylsilyl ethers is a common, routine procedure (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 141-144 and references therein, Greene, T. W. and Wuts, P. G. M., eds, Wiley-Interscience, New York). In general, a solution of one eq. of 7 and imidazole (3.5 eq.) in anhydrous N,N-dimethylformamide (DMF) is treated with tert-butyldiphenylsilyl chloride (1.2 eq.). After stirring at room temperature for several hours, the reaction mixture is poured into ethyl acetate and washed extensively with water and saturated brine solution. The resulting organic solution is dried over anhydrous sodium sulfate, filtered, evaporated, and purified by silica gel chromatography to give Compound 8.

Example 6

Acetic acid 4-(tert-butyl-diphenyl-silanyloxy)-2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-- 1-yl)-5-hydroxymethyl-tetrahydro-furan-3-yl ester (9)

[0373] The 5'-O-DMT group is removed as per known literature procedures 4,4'-dimethoxytrityl ethers are commonly removed under acidic conditions (Oligonucleotides and analogues, A Practical Approach, Eckstein, F., ed, IRL Press, New York.) Generally, Compound 8 (1 eq.) is dissolved in 80% aqueous acetic acid. After several hours, the mixture is evaporated, dissolved in ethyl acetate and washed with a sodium bicarbonate solution. Purification by silica gel chromatography will give compound 9.

Example 7

Acetic acid 4-(tert-butyl-diphenyl-silanyloxy)-2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-- 1-yl)-5-formyl-tetrahydro-furan-3-yl ester (10)

[0374] To a mixture of trichloroacetic anhydride (1.5 eq.) and dimethylsulfoxide (2.0 eq.) in dichloromethane at -78.degree. C. is added a solution of Compound 9 in dichloromethane. After 30 minutes, triethylamine (4.5 eq.) is added. Subsequently, the mixture is poured into ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, and evaporated to dryness. The resulting material is carried into the next step without further purification. This procedure has been used to prepare the related 4'-C-.A-inverted.-formyl nucleosides (Nomura, M., et. al., J. Med. Chem. 1999, 42, 2901-2908).

Example 8

1-[4-(tert-butyl-diphenyl-silanyloxy)-3-hydroxy-5,5-bis-hydroxymethyl-tetr- ahydro-furan-2-yl]-1H-pyrimidine-2,4-dione (11)

[0375] Hydroxymethylation of the 5'-aldehyde is performed as per the method of Cannizzaro which is well documented in the literature (Jones, G. H., et. al., J. Org. Chem. 1979, 44, 1309-1317). These condisions are expected to additionally remove the 2'-O-acetyl group. Generally, Briefly, formaldehyde (2.0 eq., 37% aq.) and NaOH (1.2 eq., 2 M) is added to a solution of Compound 10 in 1,4-dioxane. After stirring at room temperature for several hours, this mixture is neutralized with acetic acid, evaporated to dryness, suspended in methanol, and evaporated onto silica gel. The resulting mixture is added to the top of a silica gel column and eluted using an appropriate solvent system to give Compound 11.

Example 9

1-[5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-diphenyl-- silanyloxy)-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl]-1H-pyrimidine- -2,4-dione (12)

[0376] Preferential protection with DMT at the .A-inverted.-hydroxymethyl position is performed following a published literature procedure (Nomura, M., et. al., J. Med. Chem. 1999, 42, 2901-2908). Generally, a solution of Compound II (1 eq.) in anhydrous pyridine is treated with DMTC1 (1.3 eq.), then stirred at room temperature for several hours. Subsequently, the mixture is poured into ethyl acetate, washed with water, dried over anhydrous Na.sub.2SO.sub.4, filtered, and evaporated. Purification by silica gel chromatography will yield Compound 12.

Example 10

1-[5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-diphenyl-- silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxy-tetrahydro-- furan-2-yl]-1H-pyrimidine-2,4-dione (13)

[0377] The 5'-hydroxyl position is selectively protected with tert-butyldiphenylsilyl following published literature procedures (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 141-144 and references therein, Greene, T. W. and Wuts, P. G. M., eds, Wiley-Interscience, New York). Generally, a solution of Compound 12 (1 eq.) and N,N-dimethylaminopyridine (0.2 eq.) in anhydrous dichloromethane is treated with tert-butyldiphenylsilyl chloride (1.2 eq.) and triethylamine (4 eq.). After several hours at room temperature, the reaction is quenched with methanol, poured into ethyl acetate, washed with saturated NaHCO.sub.3, saturated brine, dried over anhydrous Na.sub.2SO.sub.4, filtered, and evaporated. Purification by silica gel chromatography will yield Compound 13.

Example 11

Acetic acid 5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-diphenyl-si- lanyloxy)-5-(tert-butyl-diphenyl-silanyloxymethyl)-2-(2,4-dioxo-3,4-dihydr- o-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester (14)

[0378] Compound 14 is prepared as per the procedure illustrated in Example 2 above.

Example 12

Acetic acid 4-(tert-butyl-diphenyl-silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymethy- l)-2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-5-hydroxymethyl-tetrahydro-- furan-3-yl ester (15)

[0379] Compound 15 is prepared as per the procedure illustrated in Example 9 above.

Example 13

Acetic acid 4-(tert-butyl-diphenyl-silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymethy- l)-5-(1,3-dioxo-1,3-dihydro-isoindol-2-yloxymethyl)-2-(2,4-dioxo-3,4-dihyd- ro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester (16)

[0380] The use of the Mitsunobu procedure to generate the 5'-O-phthalimido nucleosides starting with the 5'-unprotected nucleosides has been reported previously (Perbost, M., et. al., J. Org. Chem. 1995, 60, 5150-5156). Generally, a mixture of Compound 15 (1 eq.), triphenylphosphine (1.15 eq.), and N-hydroxyphthalimide (PhthNOH, 1.15 eq.) in anhydrous 1,4-dioxane is treated with diethyl azodicarboxylate (DEAD, 1.15 eq.). The reaction is stirred at room temperature for several hours until complete by thin layer chromatography. The resulting mixture is evaporated, suspended in ethyl acetate, washed with both saturated NaHCO.sub.3 and saturated brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and evaporated. Purification by silica gel chromatography will yield Compound 16.

Example 14

1-[4-(tert-butyl-diphenyl-silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymet- hyl)-3-hydroxy-5-methyleneaminooxymethyl-tetrahydro-furan-2-yl]-1H-pyrimid- ine-2,4-dione (17)

[0381] This transformation is performed smoothly in high yield using published procedures (Bhat, B., et. al., J. Org. Chem. 1996, 61, 8186-8199). Generally, a portion of Compound 16 is dissolved in dichloromethane and cooled to -10.degree. C. To this solution is added methylhydrazine (2.5 eq.). After 1-2 hours of stirring at 0.degree. C., the mixture is diluted with dichloromethane, washed with water and brine, dried with anhydrous Na.sub.2SO.sub.4, filtered, and evaporated. The resulting residue is immediately redissolved in a 1:1 mixture of ethyl acetate:methanol, and treated with 20% (w/w) aqueous formaldehyde (1.1 eq.). After an hour at room temperature, the mixture is concentrated then purified by silica gel chromatography to give Compound 17.

Example 15

Methanesulfonic acid 4-(tert-butyl-diphenyl-silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymethy- l)-2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-5-methyleneaminooxymethyl-t- etrahydro-furan-3-yl ester (18)

[0382] The mesylation of hydroxyl groups proceeds readily under these conditions (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 150-160 and references cited therein). Briefly, to a solution of Compound 17 in a 1:1 mixture of anhydrous dichloromethane and anhydrous pyridine is added methanesulfonyl chloride (1.2 eq.). After stirring at room temperature for several hours, this mixture is quenched with methanol, concentrated, diluted with dichloromethane, washed with aqueous NaHCO.sub.3 and brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and evaporated. Purification by silica gel chromatography will yield Compound 18.

Example 16

1-[8-(tert-butyl-diphenyl-silanyloxy)-5-(tert-butyl-diphenyl-silanyloxymet- hyl)-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oct-7-yl]-1H-pyrimidine-2,4-di- one (19)

[0383] The reduction of the formaldoxime moiety is performed as per known literature procedures. Generally, a solution of Compound 18 in methanol is treated with sodium cyanoborohydride (1.5 eq.). This treatment will result in quantitative reduction of the formaldoxime moiety to yield the 4'-C-(aminooxymethyl) arabinonucleoside. The proximity of the methylated electron-rich amine to the activated 2'-O-mesylate will result in the spontaneous ring closing of this intermediate to yield bicyclic Compound 19. The reaction is monitored by thin layer chromatography until completion. The mixture is then poured into ethyl acetate, washed extensively with aqueous NaHCO.sub.3 and brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and evaporated. Purification by silica gel chromatography will yield Compound 19.

Example 17

1-(8-hydroxy-5-hydroxymethyl-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oct-7-- yl)-1H-pyrimidine-2,4-dione (1)

[0384] The tert-butyldiphenylsilyl ether protecting groups are readily cleaved by treatment with tetrabutylammonium fluoride (Protective Groups in Organic Synthesis, 3.sup.rd edition, 1999, pp. 141-144 and references therein, Greene, T. W. and Wuts, P. G. M., eds, Wiley-Interscience, New York). Briefly, a solution of Compound 19 in a minimal amount of tetrahydrofuran (THF) is treated with a 1 M solution of tetrabutylammonium fluoride (TBAF, 5-10 eq.) in THF. After several hours at room temperature, this mixture is evaporated onto silica gel and subjected to silica gel chromatography to give Compound 1.

Alternate Synthetic Route to Compound I, Synthesis of Guanosine Analog

Examples 18-25

Scheme II, FIGS. 4-7

Example 18

4-benzyloxy-5-benzyloxymethyl-5-hydroxymethyl-2-methoxy-tetrahydro-furan-3- -ol (21)

[0385] The preparation of the protected 4'-C-hydroxymethylribofuranose, Compound 20, follows published literature procedures (Koshkin, A. A., et. al., Tetrahedron 1998, 54, 3607-3630). Compound 20 (1 eq.) is dissolved in anhydrous methanol and hydrogen chloride in an anhydrous solvent (either methanol or 1,4-dioxane) is added to give a final concentration of 5% (w/v). After stirring at room temperature for several hours, the mixture is concentrated to an oil, dried under vacuum, and used in the next step without further purification.

Example 19

2-(3-benzyloxy-2-benzyloxymethyl-4-hydroxy-5-methoxy-tetrahydro-furan-2-yl- methoxy)-isoindole-1,3-dione (22)

[0386] The O-phthalimido compound is prepared following the reference cited and the procedures illustrated in Example 13 above. The reaction can be adjusted to preferentially react at the primary hydroxyl e.g. the 4'-C-hydroxymethyl group (Bhat, B., et. al., J. Org. Chem. 1996, 61, 8186-8199). Generally, a solution of 21 (1 eq.), N-hydroxyphthalimide (1.1 eq.), and triphenylphosphine (1.1 eq.) in anhydrous tetrahydrofuran is treated with diethyl azodicarboxylate (1.1 eq.). After several hours at room temperature, the mixture is concentrated and subjected to silica gel chromatography to give Compound 22.

Example 20

Formaldehyde O-(3-benzyloxy-2-benzyloxymethyl-4-hydroxy-5-methoxy-tetrahydro-furan-2-y- lmethyl)-oxime (23)

[0387] Compound 23 is prepared as per the procedure illustrated in Example 14 above.

Example 21

Methanesulfonic acid 4-benzyloxy-5-benzyloxymethyl-2-methoxy-5-methylene-aminooxymethyl-tetrah- ydro-furan-3-yl ester (24)

[0388] Mesylation is achieved with inversion of configuration using Mitsunobu conditions (Anderson, N. G., et. al., J. Org. Chem. 1996, 60, 7955). Generally, a mixture of Compound 23 (1 eq.), triphenylphosphine (1.2 eq.) and methanesulfonic acid (1.2 eq.) in anhydrous 1,4-dioxane is treated with diethyl azodicarboxylate (1.2 eq.). After stirring at room temperature for several hours, the resulting mixture is concentrated and subjected to silica gel chromatography to give Compound 24.

Example 22

8-benzyloxy-5-benzyloxymethyl-7-methoxy-2-methyl-3,6-dioxa-2-aza-bicyclo[3- .2.1]octane (25)

[0389] Compound 25 is prepared as per the procedure illustrated in Example 16 above.

Example 23

Acetic acid 8-benzyloxy-5-benzyloxymethyl-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oct-- 7-yl ester (26)

[0390] Compound 25 is dissolved in 80% (v/v) aqueous acetic acid. After 1-2 hours at room temperature, the solution is concentrated, then dissolved in dichloromethane and washed with saturated aqueous NaHCO.sub.3 and brine. The organic portion is subsequently dried over anhydrous Na.sub.2SO.sub.4, filtered, and concentrated. The resulting mixture is coevaporated from anhydrous pyridine, then dissolved in anhydrous pyridine and treated with acetic anhydride (2 eq.). The solution is stirred overnight, quenched with methanol, dissolved in ethyl acetate and washed extensively with saturated NaHCO.sub.3. The organic portion is then dried (Na.sub.2SO.sub.4), filtered and evaporated without further purification.

Example 24

1-(8-benzyloxy-5-benzyloxymethyl-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oc- t-7-yl)-1H-pyrimidine-2,4-dione (27)

[0391] Compound 26 is converted to one of several N-glycosides (nucleosides) using published chemistry procedures including either Vorbruggen chemistry or one of several other methods (Chemistry of Nucleosides and Nucleotides, Volume 1, 1988, edited by Leroy B. Townsend, Plenum Press, New York). To prepare the uradinyl analog, a mixture of Compound 26 (1 eq.) and uracil (1.3 eq.) is suspended in anhydrous acetonitrile. To the suspension is added N,O-bis-(trimethylsilyl)-acetamide (BSA, 4 eq.). The suspension is heated to 70.degree. C. for 1 hour, then cooled to 0.degree. C. and treated with trimethylsilyl-trifluoromethanesulfonate (TMSOTf, 1.6 eq.). The resulting solution is heated at 55.degree. C. until the reaction appears complete by TLC. The reaction mixture is poured into ethyl acetate and washed extensively with saturated NaHCO.sub.3, dried over anhydrous Na.sub.2SO.sub.4, filtered, evaporated, and purified by silica gel chromatography to give Compound 24.

[0392] In order to use the above preparation with nucleobases with reactive functional groups the reactive functional groups are protected prior to use. For example such protected nucleobases include naturally occurring nucleobases such as N.sup.4-benzoyl cytosine, N.sup.6-benzoyl adenine and N.sup.2-isobutyryl guanine

Example 25

1-(8-hydroxy-5-hydroxymethyl-2-methyl-3,6-dioxa-2-aza-bicyclo[3.2.1]oct-7-- yl)-1H-pyrimidine-2,4-dione (1)

[0393] To give the desired product, Compound I the benzyl ethers protecting groups are removed following published literature procedures (Koshkin, A. A., et. al., Tetrahedron 1998, 54, 3607-3630).

[0394] Generally, the bis-O-benzylated bicyclic Compound 27 is dissolved in methanol. To this solution is added 20% Pd(OH).sub.2/C, and the resulting suspension is maintained under an atmosphere of H.sub.2 at 1-2 atm pressure. This mixture is stirred at room temperature for several hours until complete by TLC, at which point the Pd(OH).sub.2/C is removed by filtration, and the filtrate is concentrated and purified by silica gel chromatography, if necessary, to give Compound 1.

Example 26

2'-O-tert-butyldimethylsilyl-3'-C-styryluridine (33)

[0395] Compound 28 is treated with DMTCl, in pyridine in presence of DMAP to get 5'-DMT derivative, Compound 29. Compound 29 is treated with TBDMSCl in pyridine to which yields both the 2' and the 3'-silyl derivative. The 3'-TBDMS derivative is isolated by silica gel flash column chromatography and further heated with phenyl chlorothionoformate and N-chlorosuccinimide in a solution of pyridine in benzene 60.degree. C. to give Compound 31. Compound 31 is treated with .beta.-tributylstannylstyrene and AIBN in benzene give Compound 32. Compound 32 is detritylated with dichloroacetic acid in dichloromethane give compound 33.

Example 27

1-[(1R,3R,8S)-8-[(2-cyanoethyl)bis(1-methylethyl)phosphoramidite)-3-[(4,4'- -dimethoxytrityloxy)methyl]-5-methyl-2-oxo-5-azabicyclo[2.3.1]octane-5-met- hyl-2,4-(1H,3H)-pyrimidinedione (40)

[0396] Compound 33 is treated with oxalyl chloride in DMSO in the presence of ethyl diisopropylamine to give the 5'-aldehyde which is then subjected to a tandem aldol condensation and Cannizzaro reaction using aqueous formaldehyde and 1 M NaOH in 1,4-dioxane to yield the diol, Compound 34. Selective silylation with TBDMSCl in pyridine and isolation of the required isomer will give Compound 35. Compound 35 is treated with methanesulfonyl chloride in pyridine to give the methane sulfonyl derivative which is treated with methanolic ammonia to give compound 36. The double bond of Compound 36 is oxidatively cleaved by oxymylation go give the diol and then by cleavage of the diol with sodium periodate to give the aldehyde, Compound 37. The amino and aldehyde groups in Compound 37 are cross coupled under reductive condition followed by methylation of the amino group with formaldehyde in the presence of sodium borohydride will give the Compound 38. Treatment of Compound 38 with triethylamine trihydrofluoride and triethylamine in THF will give Compound 39. The primary alcohol of Compound 39 is selectively titylated with DMTCl in pyridine followed by phosphytilation at 8-position to give Compound 40.

Example 28

1-[(1R,3R,8S)-8-[(2-cyanoethyl)bis(1-methylethyl)phosphoramidite)-3-[(4,4'- -dimethoxytrityloxy)methyl]-5-methyl-2-oxo-5-azabicyclo[3.2.1]octan-4-one-- 5-methyl-2,4-(1H,3H)-pyrimidinedione (47)

[0397] Compound 35 is benzylated with benzyl bromide in DMF and sodium hydride to give Compound 41. Oxidative cleavage of Compound 41 will give an aldehyde at the 2'-position which is reduced to the corresponding alcohol using sodium borohydride in methanol to give Compound 42. Compound 42 is converted into the 3'-C-aminomethyl derivative, Compound 43 by in situ generation of the methane sulfonyl derivative and treatment with ammonia. The amino group in Compound 43 is protected with an Fmoc protecting group using Fmoc-Cl and sodium bicarbonate in aqueous dioxane to give Compound 44. Deprotection of the benzyl group is achieved with BCl.sub.3 in dichloromethane at -78.degree. C. followed by oxidation of the alcohol with pyridinium dichromate in DMF give the corresponding carboxylic acid. The deprotection of the Fmoc group releases the amino group at the 2'-position to give Compound 45. Compound 45 is treated with TBTU (2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumtetrafluorobora- te) and triethylamine in DMF to yield Compound 46. Compound 46 is desilylated with triethylamine trihydrofluoride in triethylamine in THF followed by tritylation at 3 position to give the 3-trityloxymethyl derivative followed by phosphytilation at 8-position to give Compound 47. The DMT phosphoramidite bicyclic nucleoside, Compound 47 is purified by silica gel flash column chromatography.

Example 29

Synthesis of Nucleoside Phosphoramidites

[0398] The following compounds, including amidites and their intermediates were prepared as described in U.S. Pat. No. 6,426,220 and published PCT WO 02/36743; 5'-O-Dimethoxytrityl-thymidine intermediate for 5-methyl dC amidite, 5'-O-Dimethoxytrityl-2'-deoxy-5-methylcytidine intermediate for 5-methyl-dC amidite, 5'-O-Dimethoxytrityl-2'-deoxy-N4-benzoyl-5-methylcytidine penultimate intermediate for 5-methyl dC amidite, [5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-deoxy-N.sup.4-benzoyl-5-methylcy- tidin-3'-O-yl]-2-cyanoethyl-N,N-diisopropylphosphoramidite (5-methyl dC amidite), 2'-Fluorodeoxyadenosine, 2'-Fluorodeoxyguanosine, 2'-Fluorouridine, 2'-Fluorodeoxycytidine, 2'-O-(2-Methoxyethyl) modified amidites, 2'-O-(2-methoxyethyl)-5-methyluridine intermediate, 5'-O-DMT-2'-O-(2-methoxyethyl)-5-methyluridine penultimate intermediate, [5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-(2-methoxyethyl)-5-methyluridi- n-3'-O-yl]-2-cyanoethyl-N,N-diisopropylphosphoramidite (MOE T amidite), 5'-O-Dimethoxytrityl-2'-O-(2-methoxyethyl)-5-methylcytidine intermediate, 5'-O-dimethoxytrityl-2'-O-(2-methoxyethyl)-N.sup.4-benzoyl-5-methyl-cytid- ine penultimate intermediate, [5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-.beta.-(2-methoxyethyl)-N.sup.4-- benzoyl-5-methylcytidin-3'-O-yl]-2-cyanoethyl-N,N-diisopropylphosphoramidi- te (MOE 5-Me-C amidite), [5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-.beta.-(2-methoxyethyl)-N.sup.6-- benzoyladenosin-3'-O-yl]-2-cyanoethyl-N,N-diisopropylphosphoramidite (MOE A amdite), [5'-O-(4,4'-Dimethoxytriphenylmethyl)-2'-O-(2-methoxyethyl)-N.sup.4-isobu- tyrylguanosin-3'-O-yl]-2-cyanoethyl-N,N-diisopropylphosphoramidite (MOE G amidite), 2'-O-(Aminooxyethyl)nucleoside amidites and 2'-O-(dimethylaminooxyethyl)nucleoside amidites, 2'-(Dimethylaminooxyethoxy)nucleoside amidites, 5'-O-tert-Butyldiphenylsilyl-O.sup.2-2'-anhydro-5-methyluridine, 5'-O-tert-Butyldiphenylsilyl-2'-O-(2-hydroxyethyl)-5-methyluridine, 2'-O-([[2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5-methyluridine, 5'-O-tert-butyldiphenylsilyl-2'-O-[(2-formadoximinooxy)ethyl]-5-methyluri- dine, 5'-O-tert-Butyldiphenylsilyl-2'-O--[N,N dimethylaminooxyethyl]-5-methyluridine, 2'-O-(dimethylaminooxyethyl)-5-methyluridine, 5'-O-DMT-2'-O-(dimethylaminooxyethyl)-5-methyluridine, 5'-O-DMT-2'-O-(2-N,N-dimethylaminooxyethyl)-5-methyluridine-3'-[(2-cyanoe- thyl)-N,N-diisopropylphosphoramidite], 2'-(Aminooxyethoxy)nucleoside amidites, N2-isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5'-O-(- 4,4'-dimethoxytrityl)guanosine-3'-[(2-cyanoethyl)-N,N-diisopropylphosphora- midite], 2'-dimethylaminoethoxyethoxy (2'-DMAEOE) nucleoside amidites, 2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl]-5-methyl uridine, 5'-O-dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy)-ethyl)]-5-methyl uridine and 5'-O-Dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy)-ethyl)]-5-methyl uridine-3'-O-(cyanoethyl-N,N-diisopropyl)phosphoramidite.

Example 30

Oligonucleotide and Oligonucleoside Synthesis

[0399] The chimeric oligomeric compounds used in accordance with this invention may be conveniently and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, Calif.). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives.

[0400] Oligonucleotides: Unsubstituted and substituted phosphodiester (P.dbd.O) oligonucleotides are synthesized on an automated DNA synthesizer (Applied Biosystems model 394) using standard phosphoramidite chemistry with oxidation by iodine.

[0401] Phosphorothioates (P.dbd.S) are synthesized similar to phosphodiester oligonucleotides with the following exceptions: thiation was effected by utilizing a 10% w/v solution of 3,H-1,2-benzodithiole-3-one 1,1-dioxide in acetonitrile for the oxidation of the phosphite linkages. The thiation reaction step time was increased to 180 sec and preceded by the normal capping step. After cleavage from the CPG column and deblocking in concentrated ammonium hydroxide at 55.degree. C. (12-16 hr), the oligonucleotides were recovered by precipitating with >3 volumes of ethanol from a 1 M NH.sub.4OAc solution. Phosphinate oligonucleotides are prepared as described in U.S. Pat. No. 5,508,270, herein incorporated by reference.

[0402] Alkyl phosphonate oligonucleotides are prepared as described in U.S. Pat. No. 4,469,863, herein incorporated by reference.

[0403] 3'-Deoxy-3'-methylene phosphonate oligonucleotides are prepared as described in U.S. Pat. No. 5,610,289 or 5,625,050, herein incorporated by reference.

[0404] Phosphoramidite oligonucleotides are prepared as described in U.S. Pat. No. 5,256,775 or U.S. Pat. No. 5,366,878, herein incorporated by reference.

[0405] Alkylphosphonothioate oligonucleotides are prepared as described in published PCT applications PCT/US94/00902 and PCT/US93/06976 (published as WO 94/17093 and WO 94/02499, respectively), herein incorporated by reference.

[0406] 3'-Deoxy-3'-amino phosphoramidate oligonucleotides are prepared as described in U.S. Pat. No. 5,476,925, herein incorporated by reference.

[0407] Phosphotriester oligonucleotides are prepared as described in U.S. Pat. No. 5,023,243, herein incorporated by reference.

[0408] Borano phosphate oligonucleotides are prepared as described in U.S. Pat. Nos. 5,130,302 and 5,177,198, both herein incorporated by reference.

[0409] Oligonucleosides: Methylenemethylimino linked oligonucleosides, also identified as MMI linked oligonucleosides, methylenedimethylhydrazo linked oligonucleosides, also identified as MDH linked oligonucleosides, and methylenecarbonylamino linked oligonucleosides, also identified as amide-3 linked oligonucleosides, and methyleneaminocarbonyl linked oligonucleosides, also identified as amide-4 linked oligonucleosides, as well as mixed backbone oligomeric compounds having, for instance, alternating MMI and P.dbd.O or P.dbd.S linkages are prepared as described in U.S. Pat. Nos. 5,378,825, 5,386,023, 5,489,677, 5,602,240 and 5,610,289, all of which are herein incorporated by reference.

[0410] Formacetal and thioformacetal linked oligonucleosides are prepared as described in U.S. Pat. Nos. 5,264,562 and 5,264,564, herein incorporated by reference.

[0411] Ethylene oxide linked oligonucleosides are prepared as described in U.S. Pat. No. 5,223,618, herein incorporated by reference.

Example 31

RNA Synthesis

[0412] In general, RNA synthesis chemistry is based on the selective incorporation of various protecting groups at strategic intermediary reactions. Although one of ordinary skill in the art will understand the use of protecting groups in organic synthesis, a useful class of protecting groups includes silyl ethers. In particular bulky silyl ethers are used to protect the 5''-hydroxyl in combination with an acid-labile orthoester protecting group on the 2'-hydroxyl. This set of protecting groups is then used with standard solid-phase synthesis technology. It is important to lastly remove the acid labile orthoester protecting group after all other synthetic steps. Moreover, the early use of the silyl protecting groups during synthesis ensures facile removal when desired, without undesired deprotection of 2' hydroxyl.

[0413] Following this procedure for the sequential protection of the 5'-hydroxyl in combination with protection of the 2'-hydroxyl by protecting groups that are differentially removed and are differentially chemically labile, RNA oligonucleotides were synthesized.

[0414] RNA oligonucleotides are synthesized in a stepwise fashion. Each nucleotide is added sequentially (3'- to 5''-direction) to a solid support-bound oligonucleotide. The first nucleoside at the 3''-end of the chain is covalently attached to a solid support. The nucleotide precursor, a ribonucleoside phosphoramidite, and activator are added, coupling the second base onto the 5''-end of the first nucleoside. The support is washed and any unreacted 5''-hydroxyl groups are capped with acetic anhydride to yield 5'-acetyl moieties. The linkage is then oxidized to the more stable and ultimately desired P(V) linkage. At the end of the nucleotide addition cycle, the 5''-silyl group is cleaved with fluoride. The cycle is repeated for each subsequent nucleotide.

[0415] Following synthesis, the methyl protecting groups on the phosphates are cleaved in 30 minutes utilizing 1 M disodium-2-carbamoyl-2-cyanoethylene-1,1-dithiolate trihydrate (S.sub.2Na.sub.2) in DMF. The deprotection solution is washed from the solid support-bound oligonucleotide using water. The support is then treated with 40% methylamine in water for 10 minutes at 55.degree. C. This releases the RNA oligonucleotides into solution, deprotects the exocyclic amines, and modifies the 2'-groups. The oligonucleotides can be analyzed by anion exchange HPLC at this stage.

[0416] The 2'-orthoester groups are the last protecting groups to be removed. The ethylene glycol monoacetate orthoester protecting group developed by Dharmacon Research, Inc. (Lafayette, Colo.), is one example of a useful orthoester protecting group which, has the following important properties. It is stable to the conditions of nucleoside phosphoramidite synthesis and oligonucleotide synthesis. However, after oligonucleotide synthesis the oligonucleotide is treated with methylamine which not only cleaves the oligonucleotide from the solid support but also removes the acetyl groups from the orthoesters. The resulting 2-ethyl-hydroxyl substituents on the orthoester are less electron withdrawing than the acetylated precursor. As a result, the modified orthoester becomes more labile to acid-catalyzed hydrolysis. Specifically, the rate of cleavage is approximately 10 times faster after the acetyl groups are removed. Therefore, this orthoester possesses sufficient stability in order to be compatible with oligonucleotide synthesis and yet, when subsequently modified, permits deprotection to be carried out under relatively mild aqueous conditions compatible with the final RNA oligonucleotide product.

[0417] Additionally, methods of RNA synthesis are well known in the art (Scaringe, S. A. Ph.D. Thesis, University of Colorado, 1996; Scaringe, S. A., et al., J. Am. Chem. Soc., 1998, 120, 11820-11821; Matteucci, M. D. and Caruthers, M. H. J. Am. Chem. Soc., 1981, 103, 3185-3191; Beaucage, S. L. and Caruthers, M. H. Tetrahedron Lett., 1981, 22, 1859-1862; Dahl, B. J., et al., Acta Chem. Scand,. 1990, 44, 639-641; Reddy, M. P., et al., Tetrahedrom Lett., 1994, 25, 4311-4314; Wincott, F. et al., Nucleic Acids Res., 1995, 23, 2677-2684; Griffin, B. E., et al., Tetrahedron, 1967, 23, 2301-2313; Griffin, B. E., et al., Tetrahedron, 1967, 23, 2315-2331).

[0418] RNA oligomeric compounds (RNA oligonucleotides) for use in the present invention can be synthesized by the methods herein or purchased from Dharmacon Research, Inc (Lafayette, Colo.). Once synthesized, complementary RNA oligomeric compounds can then be annealed by methods known in the art to form double stranded (duplexed) oligomeric compounds. For example, duplexes can be formed by combining 30 .mu.l of each of the complementary strands of RNA oligonucleotides (50 uM RNA oligonucleotide solution) and 15 .mu.l of 5.times. annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH pH 7.4, 2 mM magnesium acetate) followed by heating for 1 minute at 90.degree. C., then 1 hour at 37.degree. C. The resulting duplexed oligomeric compounds can be used in kits, assays, screens, or other methods to investigate the role of a target nucleic acid.

Example 32

Synthesis of Chimeric Oligomeric Compounds

[0419] Chimeric oligomeric compounds, oligonucleosides or mixed oligonucleotides/oligonucleosides of the invention can be of several different types. These include a first type wherein the "gap" segment of linked nucleosides is positioned between 5' and 3' "wing" segments of linked nucleosides and a second "open end" type wherein the "gap" segment is located at either the 3' or the 5' terminus of the oligomeric compound. Oligonucleotides of the first type are also known in the art as "gapmers" or gapped oligonucleotides. Oligonucleotides of the second type are also known in the art as "hemimers" or "wingmers".

[2'-O-Me]-[2'-deoxyl]-[2'-O-Me] Chimeric Phosphorothioate Oligonucleotides

[0420] Chimeric oligomeric compounds having 2'-O-alkyl phosphorothioate and 2'-deoxy phosphorothioate oligonucleotide segments are synthesized using an Applied Biosystems automated DNA synthesizer Model 394, as above. Oligonucleotides are synthesized using the automated synthesizer and 2'-deoxy-5'-dimethoxytrityl-3'-O-phosphoramidite for the DNA portion and 5'-dimethoxytrityl-2'-O-methyl-3'-O-phosphoramidite for 5' and 3' wings. The standard synthesis cycle is modified by incorporating coupling steps with increased reaction times for the 5'-dimethoxytrityl-2'-O-methyl-3'-O-phosphoramidite. The fully protected oligonucleotide is cleaved from the support and deprotected in concentrated ammonia (NH.sub.4OH) for 12-16 hr at 55.degree. C. The deprotected oligonucleotide is then recovered by an appropriate method (precipitation, column chromatography, volume reduced in vacuo and analyzed spetrophotometrically for yield and for purity by capillary electrophoresis and by mass spectrometry.

[2'-O-(2-Methoxyethyl)]-[2'-deoxy]-[2'-O-(Methoxyethyl)]Chimeric Phosphorothioate Oligonucleotides

[0421] [2'-O-(2-methoxyethyl)]-[2'-deoxy]-[-2'-O-(methoxyethyl)]chimeric phosphorothioate oligonucleotides were prepared as per the procedure above for the 2'-O-methyl chimeric oligomeric compound, with the substitution of 2'-O-(methoxyethyl)amidites for the 2'-O-methyl amidites.

[2'-O-(2-Methoxyethyl)Phosphodiester]-[2'-deoxy Phosphorothioate]-[2'-O-(2-Methoxyethyl)Phosphodiester] Chimeric oligomeric compounds

[0422] [2'-O-(2-methoxyethyl phosphodiester]-[2'-deoxy phosphorothioate]-[2'-O-(methoxyethyl)phosphodiester] chimeric oligomeric compounds are prepared as per the above procedure for the 2'-O-methyl chimeric oligomeric compound with the substitution of 2'-O-(methoxyethyl)amidites for the 2'-O-methyl amidites, oxidation with iodine to generate the phosphodiester internucleotide linkages within the wing portions of the chimeric structures and sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) to generate the phosphorothioate internucleotide linkages for the center gap.

[0423] The above methods are also applicable to the synthesis of chimeric oligomeric compounds having multiple alternating regions such as olignucleotides having the formula: T.sub.1-(3'-endo region)-[(2'-deoxy region)-(3'-endo region)].sub.n-T.sub.2. The use of 2'-MOE or other nucleoside amidites will enable the preparation of a myriad of different oligonucleotides.

[0424] Other chimeric oligomeric compounds, chimeric oligonucleosides and mixed chimeric oligomeric compounds/oligonucleosides are synthesized according to U.S. Pat. No. 5,623,065, herein incorporated by reference.

Example 33

Screening of Duplexed Oligomeric Compounds of the Invention

[0425] In accordance with the present invention, nucleic acid duplexes comprising the oligonucleotides of the invention and their complements are tested for their ability to modulate the expression of the nucleic acid molecule to which they are targeted. The desired RNA strand(s) of the duplex can be synthesized by methods disclosed herein or purchased from various RNA synthesis companies such as for example Dharmacon Research Inc., (Lafayette, Colo.). Once synthesized, the complementary strands are annealed. The single strands are aliquoted and diluted to a concentration of 50 uM. Once diluted, 30 uL of each strand is combined with 15 uL of a 5.times. solution of annealing buffer. The final concentration of the buffer is 100 mM potassium acetate, 30 mM HEPES-KOH pH 7.4, and 2 mM magnesium acetate. The final volume is 75 uL. This solution is incubated for 1 minute at 90.degree. C. and then centrifuged for 15 seconds. The tube is allowed to sit for 1 hour at 37.degree. C. at which time the dsRNA duplexes are used in experimentation. The final concentration of the dsRNA compound is 20 uM. This solution can be stored frozen (-20.degree. C.) and freeze-thawed up to 5 times.

[0426] Once prepared, the desired synthetic duplexes are evaluated for their ability to modulate target expression. When cells reach approximately 60-80% confluency, they are treated with synthetic duplexes comprising at least one oligomeric compound of the invention. The duplexes are mixed with LIPOFECTIN.TM. (Invitrogen Life Technologies, Carlsbad, Calif.) in 1 mL of Opti-MEM.TM.-1 reduced serum medium (Invitrogen Life Technologies, Carlsbad, Calif.) to achieve the desired final concentration of duplex. This transfection mixture was incubated at room temperature for approximately 0.5 hours. The final concentration of duplex ranges from 10 to 200 nM. LIPOFECTIN.TM. is used at a concentration of 5 or 6 .mu.g/mL LIPOFECTIN.TM. per 200 nM of duplex. For cells grown in 96-well plates, wells were washed once with 100 .mu.L OPTI-MEM.TM.-1 and then treated with 130 .mu.L of the transfection mixture. Cells grown in 24-well plates or other standard tissue culture plates are treated similarly, using appropriate volumes of medium and oligonucleotide. Cells are treated and data are obtained in duplicate or triplicate. After approximately 4-7 hours of treatment at 37.degree. C., the medium containing the transfection mixture was replaced with fresh medium. Cells were harvested 16-24 hours after oligonucleotide treatment, at which time RNA is isolated and target reduction is measured by real-time PCR or Northern blot.

Example 34

Oligonucleotide Isolation

[0427] After cleavage from the controlled pore glass solid support and deblocking in concentrated ammonium hydroxide at 55.degree. C. for 12-16 hours, the oligonucleotides or oligonucleosides are recovered by precipitation out of 1 M NH.sub.4OAc with >3 volumes of ethanol. Synthesized oligonucleotides were analyzed by electrospray mass spectroscopy (molecular weight determination) and by capillary gel electrophoresis and judged to be at least 70% full length material. The relative amounts of phosphorothioate and phosphodiester linkages obtained in the synthesis was determined by the ratio of correct molecular weight relative to the -16 amu product (+/-32+/-48). For some studies oligonucleotides were purified by HPLC, as described by Chiang et al., J. Biol. Chem. 1991, 266, 18162-18171. Results obtained with HPLC-purified material were similar to those obtained with non-HPLC purified material.

Example 35

Oligonucleotide Synthesis--96 Well Plate Format

[0428] Oligonucleotides were synthesized via solid phase P(III) phosphoramidite chemistry on an automated synthesizer capable of assembling 96 sequences simultaneously in a 96-well format. Phosphodiester internucleotide linkages were afforded by oxidation with aqueous iodine. Phosphorothioate internucleotide linkages were generated by sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) in anhydrous acetonitrile. Standard base-protected beta-cyanoethyl-diiso-propyl phosphoramidites were purchased from commercial vendors (e.g. PE-Applied Biosystems, Foster City, Calif., or Pharmacia, Piscataway, N.J.). Non-standard nucleosides are synthesized as per standard or patented methods. They are utilized as base protected beta-cyanoethyldiisopropyl phosphoramidites.

[0429] Oligonucleotides were cleaved from support and deprotected with concentrated NH.sub.4OH at elevated temperature (55-60.degree. C.) for 12-16 hours and the released product then dried in vacuo. The dried product was then re-suspended in sterile water to afford a master plate from which all analytical and test plate samples are then diluted utilizing robotic pipettors.

Example 36

Oligonucleotide Analysis--96-Well Plate Format

[0430] The concentration of oligonucleotide in each well was assessed by dilution of samples and

[0431] UV absorption spectroscopy. The full-length integrity of the individual products was evaluated by capillary electrophoresis (CE) in either the 96-well format (Beckman P/ACE.TM. MDQ) or, for individually prepared samples, on a commercial CE apparatus (e.g., Beckman P/ACE.TM. 5000, ABI 270). Base and backbone composition was confirmed by mass analysis of the oligomeric compounds utilizing electrospray-mass spectroscopy. All assay test plates were diluted from the master plate using single and multi-channel robotic pipettors. Plates were judged to be acceptable if at least 85% of the oligomeric compounds on the plate were at least 85% full length.

Example 37

Cell Culture and Oligonucleotide Treatment

[0432] The effect of chimeric oligomeric compounds on target nucleic acid expression can be tested in any of a variety of cell types provided that the target nucleic acid is present at measurable levels. This can be routinely determined using, for example, PCR or Northern blot analysis. The following cell types are provided for illustrative purposes, but other cell types can be routinely used, provided that the target is expressed in the cell type chosen. This can be readily determined by methods routine in the art, for example Northern blot analysis, ribonuclease protection assays, or real-time PCR.

T-24 Cells:

[0433] The human transitional cell bladder carcinoma cell line T-24 was obtained from the American Type Culture Collection (ATCC) (Manassas, Va.). T-24 cells were routinely cultured in complete McCoy's 5A basal media (Invitrogen Corporation, Carlsbad, Calif.) supplemented with 10% fetal bovine serum (Invitrogen Corporation, Carlsbad, Calif.), 100 units per mL penicillin and 100 micrograms per mL streptomycin (Invitrogen Corporation, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached approximately 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) at a density of approximately 4000-6000 cells/well for use in oligomeric compound transfection experiments.

A549 Cells:

[0434] The human lung carcinoma cell line A549 was obtained from the American Type Culture Collection (Manassas, Va.). A549 cells were routinely cultured in DMEM, high glucose (Invitrogen Life Technologies, Carlsbad, Calif.) supplemented with 10% fetal bovine serum, 100 units per ml penicillin, and 100 micrograms per ml streptomycin (Invitrogen Life Technologies, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached approximately 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) at a density of approximately 5000 cells/well for use in oligomeric compound transfection experiments.

NHDF Cells:

[0435] Human neonatal dermal fibroblast (NHDF) were obtained from the Clonetics Corporation (Walkersville, Md.). NHDFs were routinely maintained in Fibroblast Growth Medium (Clonetics Corporation, Walkersville, Md.) supplemented as recommended by the supplier. Cells were maintained for up to 10 passages as recommended by the supplier.

HEK Cells:

[0436] Human embryonic keratinocytes (HEK) were obtained from the Clonetics Corporation (Walkersville, Md.). HEKs were routinely maintained in Keratinocyte Growth Medium (Clonetics Corporation, Walkersville, Md.) formulated as recommended by the supplier. Cells were routinely maintained for up to 10 passages as recommended by the supplier.

HeLa Cells:

[0437] The human epitheloid carcinoma cell line HeLa was obtained from the American Tissue Type Culture Collection (Manassas, Va.). HeLa cells were routinely cultured in DMEM, high glucose (Invitrogen Corporation, Carlsbad, Calif.) supplemented with 10% fetal bovine serum (Invitrogen Corporation, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached approximately 90% confluence. Cells were seeded into 24-well plates (Falcon-Primaria #353846, BD Biosciences, Bedford, Mass.) at a density of 50,000 cells/well or in 96-well plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) at a density of 5,000 cells/well for use in oligomeric compound transfection experiments. For Northern blotting or other analyses, cells were harvested when they reached approximately 90% confluence.

NIH3T3 cells:

[0438] The mouse embryo-derived NIH3T3 cell line was obtained from American Type Culture Collection (Manassas, Va.). NIH3T3 cells were routinely cultured in DMEM, high glucose (Invitrogen Life Technologies, Carlsbad, Calif.) supplemented with 10% fetal bovine serum, (Invitrogen Life Technologies, Carlsbad, Calif.), 100 .mu.g/ml penicillin and 100 .mu.g/ml streptomycin (Invitrogen Life Technologies, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached 80% confluencey. Cells were seeded into 96-well plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) at a density of 3000 cells/well for use in oligomeric compound transfection experiments.

b.END Cells:

[0439] The mouse brain endothelial cell line b.END was obtained from Dr. Werner Risau at the Max Plank Institute (Bad Nauheim, Germany). b.END cells were routinely cultured in DMEM, high glucose (Invitrogen Life Technologies, Carlsbad, Calif.) supplemented with 10% fetal bovine serum (Invitrogen Life Technologies, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached approximately 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #3872) at a density of approximately 3000 cells/well for use in oligomeric compound transfection experiments.

Primary Mouse Hepatocytes:

[0440] Primary mouse hepatocytes were prepared from CD-1 mice purchased from Charles River Labs. Primary mouse hepatocytes were routinely cultured in Hepatocyte Attachment Media supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin, 1% antibiotic-antimycotic (Invitrogen Life Technologies, Carlsbad, Calif.) and 10 nM bovine insulin (Sigma-Aldrich, St. Louis, Mo.). Cells were seeded into 96-well plates (Falcon-Primaria #3872) coated with 0.1 mg/ml collagen at a density of approximately 10,000 cells/well for use in oligomeric compound transfection experiments.

Primary Rat Hepatocytes:

[0441] Primary rat hepatocytes are prepared from Sprague-Dawley rats purchased from Charles River Labs (Wilmington, Mass.) and are routinely cultured in DMEM, high glucose (Invitrogen Life Technologies, Carlsbad, Calif.) supplemented with 10% fetal bovine serum (Invitrogen Life Technologies, Carlsbad, Calif.), 100 units per mL penicillin, and 100 .mu.g/mL streptomycin (Invitrogen Life Technologies, Carlsbad, Calif.). Cells are seeded into 96-well plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) at a density of 4000-6000 cells/well for use in oligomeric compound transfection experiments.

MH-S Cells:

[0442] The mouse alveolar macrophage cell line was obtained from American Type Culture Collection (Manassas, Va.). MH-S cells were cultured in RPMI Medium 1640 with L-glutamine (Invitrogen Life Technologies, Carlsbad, Calif.), supplemented with 10% fetal bovine serum, 1 mM sodium pyruvate and 10 mM HEPES (all supplements from Invitrogen Life Technologies, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached 70-80% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #353047, BD Biosciences, Bedford, Mass.) at a density of 6500 cells/well for use in oligomeric compound transfection experiments.

Treatment with Oligomeric Compounds:

[0443] When cells reached approximately 65-90% confluency, they were treated with oligomeric compound. Oligomeric compounds were mixed with LIPOFECTIN.TM. (Invitrogen Life Technologies, Carlsbad, Calif.) in 1 mL of Opti-MEM.TM.-1 reduced serum medium (Invitrogen Life Technologies, Carlsbad, Calif.) to achieve the desired concentration of oligomeric compound. The concentration of oligomeric compound used herein ranges from 5 to 300 nM. This transfection mixture was incubated at room temperature for approximately 0.5 hours. LIPOFECTIN.TM. is used at a concentration of 2.5 or 3 .mu.g/mL LIPOFECTIN.TM. per 100 nM oligomeric compound. For cells grown in 96-well plates, wells were washed once with 100 .mu.L OPTI-MEM.TM.-1 and then treated with 130 .mu.L of the transfection mixture. Cells grown in 24-well plates or other standard tissue culture plates are treated similarly, using appropriate volumes of medium and oligonucleotide. Cells are treated and data are obtained in duplicate or triplicate. After approximately 4-7 hours of treatment at 37.degree. C., the medium containing the transfection mixture was replaced with fresh medium. Cells were harvested 16-24 hours after oligonucleotide treatment, at which time RNA was isolated and target expression was measured by real-time PCR.

[0444] The concentration of oligonucleotide used varies from cell line to cell line. To determine the optimal oligonucleotide concentration for a particular cell line, the cells are treated with a positive control oligonucleotide at a range of concentrations. For human cells the positive control oligonucleotide is selected from either ISIS 13920 (TCCGTCATCGCTCCTCAGGG, SEQ ID NO: 7) which is targeted to human H-ras, or ISIS 18078 (GTGCGCGCGAGCCCGAAATC, SEQ ID NO: 8) which is targeted to human Jun-N-terminal kinase-2 (JNK2). Both controls are chimeric oligomeric compounds composed of a central "gap" segment comprising 2'-deoxynucleotides, which is flanked on both sides (5' and 3') by "wing" segments comprising 2'-O-methoxyethyl nucleotides (2'-O-methoxyethyls shown in emboldened, underlined type). Internucleoside linkages are phosphorothioate throughout both compounds. All cytosine residues in the wing segments are 5-methylcytosines. For mouse or rat cells the positive control oligonucleotide is ISIS 15770 (ATGCATTCTGCCCCCAAGGA, SEQ ID NO: 9) is targeted to both mouse and rat C-raf. ISIS 15770 is a chimeric oligomeric compound composed of a central "gap" segment comprising 2'-deoxynucleotides, which is flanked on both sides (5' and 3') by "wing" segments comprising 2'-.beta.-methoxyethyl nucleotides (2'-O-methoxyethyls shown in emboldened, underlined type). Internucleoside linkages are phosphorothioate throughout the compound. The cytosine residue in the 5' wing segment is a 5-methylcytosine. The concentration of positive control oligonucleotide that results in 80% inhibition of c-H-ras (for ISIS 13920), JNK2 (for ISIS 18078) or C-raf (for ISIS 15770) mRNA is then utilized as the screening concentration for new oligonucleotides in subsequent experiments for that cell line. If 80% inhibition is not achieved, the lowest concentration of positive control oligonucleotide that results in 60% inhibition of c-H-ras, JNK2 or C-raf mRNA is then utilized as the oligonucleotide screening concentration in subsequent experiments for that cell line. If 60% inhibition is not achieved, that particular cell line is deemed as unsuitable for oligonucleotide transfection experiments. The concentrations of antisense oligonucleotides used herein are from 50 nM to 300 nM.

Example 38

Analysis of Oligonucleotide Inhibition of a Target Expression

[0445] Antisense modulation of a target expression can be assayed in a variety of ways known in the art. For example, a target mRNA levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or real-time PCR. Real-time quantitative PCR is presently preferred. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. One method of RNA analysis of the present invention is the use of total cellular RNA as described in other examples herein. Methods of RNA isolation are well known in the art. Northern blot analysis is also routine in the art. Quantitative real-time PCR can be conveniently accomplished using the commercially available ABI PRISM.TM. 7600, 7700, or 7900 Sequence Detection System, available from PE-Applied Biosystems, Foster City, Calif. and used according to manufacturer's instructions.

[0446] Protein levels of a target can be quantitated in a variety of ways well known in the art, such as immunoprecipitation, Western blot analysis (immunoblotting), enzyme-linked immunosorbent assay (ELISA) or fluorescence-activated cell sorting (FACS). Antibodies directed to a target can be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Corporation, Birmingham, Mich.), or can be prepared via conventional monoclonal or polyclonal antibody generation methods well known in the art.

Example 39

Design of Phenotypic Assays for the Use of Target Inhibitors

[0447] Once a target inhibitors have been identified by the methods disclosed herein, the oligomeric compounds are further investigated in one or more phenotypic assays, each having measurable endpoints predictive of efficacy in the treatment of a particular disease state or condition.

[0448] Phenotypic assays, kits and reagents for their use are well known to those skilled in the art and are herein used to investigate the role and/or association of a target in health and disease. Representative phenotypic assays, which can be purchased from any one of several commercial vendors, include those for determining cell viability, cytotoxicity, proliferation or cell survival (Molecular Probes, Eugene, Oreg.; PerkinElmer, Boston, Mass.), protein-based assays including enzymatic assays (Panvera, LLC, Madison, Wis.; BD Biosciences, Franklin Lakes, N.J.; Oncogene Research Products, San Diego, Calif.), cell regulation, signal transduction, inflammation, oxidative processes and apoptosis (Assay Designs Inc., Ann Arbor, Mich.), triglyceride accumulation (Sigma-Aldrich, St. Louis, Mo.), angiogenesis assays, tube formation assays, cytokine and hormone assays and metabolic assays (Chemicon International Inc., Temecula, Calif.; Amersham Biosciences, Piscataway, N.J.).

[0449] In one non-limiting example, cells determined to be appropriate for a particular phenotypic assay (i.e., MCF-7 cells selected for breast cancer studies; adipocytes for obesity studies) are treated with a target inhibitors identified from the in vitro studies as well as control compounds at optimal concentrations which are determined by the methods described above. At the end of the treatment period, treated and untreated cells are analyzed by one or more methods specific for the assay to determine phenotypic outcomes and endpoints.

[0450] Phenotypic endpoints include changes in cell morphology over time or treatment dose as well as changes in levels of cellular components such as proteins, lipids, nucleic acids, hormones, saccharides or metals. Measurements of cellular status which include pH, stage of the cell cycle, intake or excretion of biological indicators by the cell, are also endpoints of interest.

[0451] Measurement of the expression of one or more of the genes of the cell after treatment is also used as an indicator of the efficacy or potency of the target inhibitors. Hallmark genes, or those genes suspected to be associated with a specific disease state, condition, or phenotype, are measured in both treated and untreated cells.

Example 40

RNA Isolation

[0452] Poly(A)+ mRNA Isolation

[0453] Poly(A)+ mRNA was isolated according to Miura et al., (Clin. Chem., 1996, 42, 1758-1764). Other methods for poly(A)+ mRNA isolation are routine in the art. Briefly, for cells grown on 96-well plates, growth medium was removed from the cells and each well was washed with 200 .mu.L cold PBS. 60 .mu.L lysis buffer (10 mM Tris-HCl, pH 7.6, 1 mM EDTA, 0.5 M NaCl, 0.5% NP-40, 20 mM vanadyl-ribonucleoside complex) was added to each well, the plate was gently agitated and then incubated at room temperature for five minutes. 55 .mu.L of lysate was transferred to Oligo d(T) coated 96-well plates (AGCT Inc., Irvine Calif.). Plates were incubated for 60 minutes at room temperature, washed 3 times with 200 .mu.L of wash buffer (10 mM Tris-HCl pH 7.6, 1 mM EDTA, 0.3 M NaCl). After the final wash, the plate was blotted on paper towels to remove excess wash buffer and then air-dried for 5 minutes. 60 .mu.L of elution buffer (5 mM Tris-HCl pH 7.6), preheated to 70.degree. C., was added to each well, the plate was incubated on a 90.degree. C. hot plate for 5 minutes, and the eluate was then transferred to a fresh 96-well plate.

[0454] Cells grown on 100 mm or other standard plates may be treated similarly, using appropriate volumes of all solutions.

Total RNA Isolation

[0455] Total RNA was isolated using an RNEASY 96.TM. kit and buffers purchased from Qiagen Inc. (Valencia, Calif.) following the manufacturer's recommended procedures. Briefly, for cells grown on 96-well plates, growth medium was removed from the cells and each well was washed with 200 .mu.L cold PBS. 150 .mu.L Buffer RLT was added to each well and the plate vigorously agitated for 20 seconds. 150 .mu.L of 70% ethanol was then added to each well and the contents mixed by pipetting three times up and down. The samples were then transferred to the RNEASY 96.TM. well plate attached to a QIAVAC.TM. manifold fitted with a waste collection tray and attached to a vacuum source. Vacuum was applied for 1 minute. 500 .mu.L of Buffer RW1 was added to each well of the RNEASY 96.TM. plate and incubated for 15 minutes and the vacuum was again applied for 1 minute. An additional 500 .mu.L of Buffer RW1 was added to each well of the RNEASY 96.TM. plate and the vacuum was applied for 2 minutes. 1 mL of Buffer RPE was then added to each well of the RNEASY 96.TM. plate and the vacuum applied for a period of 90 seconds. The Buffer RPE wash was then repeated and the vacuum was applied for an additional 3 minutes. The plate was then removed from the QIAVAC.TM. manifold and blotted dry on paper towels. The plate was then re-attached to the QIAVAC.TM. manifold fitted with a collection tube rack containing 1.2 mL collection tubes. RNA was then eluted by pipetting 140 .mu.L of RNAse free water into each well, incubating 1 minute, and then applying the vacuum for 3 minutes.

[0456] The repetitive pipetting and elution steps may be automated using a QIAGEN Bio-Robot 9604 (Qiagen, Inc., Valencia Calif.). Essentially, after lysing of the cells on the culture plate, the plate is transferred to the robot deck where the pipetting, DNase treatment and elution steps are carried out.

Example 41

Real-Time Quantitative PCR Analysis of a Target mRNA Levels

[0457] Quantitation of a target mRNA levels was accomplished by real-time quantitative PCR using the ABI PRISM.TM. 7600, 7700, or 7900 Sequence Detection System (PE-Applied Biosystems, Foster City, Calif.) according to manufacturer's instructions. This is a closed-tube, non-gel-based, fluorescence detection system which allows high-throughput quantitation of polymerase chain reaction (PCR) products in real-time. As opposed to standard PCR in which amplification products are quantitated after the PCR is completed, products in real-time PCR are quantitated as they accumulate. This is accomplished by including in the PCR reaction an oligonucleotide probe that anneals specifically between the forward and reverse PCR primers, and contains two fluorescent dyes. A reporter dye (e.g., FAM or JOE, obtained from either PE-Applied Biosystems, Foster City, Calif., Operon Technologies Inc., Alameda, Calif. or Integrated DNA Technologies Inc., Coralville, Iowa) is attached to the 5' end of the probe and a quencher dye (e.g., TAMRA, obtained from either PE-Applied Biosystems, Foster City, Calif., Operon Technologies Inc., Alameda, Calif. or Integrated DNA Technologies Inc., Coralville, Iowa) is attached to the 3' end of the probe. When the probe and dyes are intact, reporter dye emission is quenched by the proximity of the 3' quencher dye. During amplification, annealing of the probe to the target sequence creates a substrate that can be cleaved by the 5'-exonuclease activity of Taq polymerase. During the extension phase of the PCR amplification cycle, cleavage of the probe by Taq polymerase releases the reporter dye from the remainder of the probe (and hence from the quencher moiety) and a sequence-specific fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes, and the fluorescence intensity is monitored at regular intervals by laser optics built into the ABI PRISM.TM. Sequence Detection System. In each assay, a series of parallel reactions containing serial dilutions of mRNA from untreated control samples generates a standard curve that is used to quantitate the percent inhibition after antisense oligonucleotide treatment of test samples.

[0458] Prior to quantitative PCR analysis, primer-probe sets specific to the target gene being measured are evaluated for their ability to be "multiplexed" with a GAPDH amplification reaction. In multiplexing, both the target gene and the internal standard gene GAPDH are amplified concurrently in a single sample. In this analysis, mRNA isolated from untreated cells is serially diluted. Each dilution is amplified in the presence of primer-probe sets specific for GAPDH only, target gene only ("single-plexing"), or both (multiplexing). Following PCR amplification, standard curves of GAPDH and target mRNA signal as a function of dilution are generated from both the single-plexed and multiplexed samples. If both the slope and correlation coefficient of the GAPDH and target signals generated from the multiplexed samples fall within 10% of their corresponding values generated from the single-plexed samples, the primer-probe set specific for that target is deemed multiplexable. Other methods of PCR are also known in the art.

[0459] Gene target quantities are obtained by real-time PCR. Prior to the real-time PCR, isolated RNA is subjected to a reverse transcriptase (RT) reaction, for the purpose of generating complementary DNA (cDNA). Reverse transcriptase and PCR reagents were obtained from Invitrogen Corporation (Carlsbad, Calif.). RT, real-time PCR reactions were carried out by adding 20 .mu.L PCR cocktail (2.5.times. PCR buffer minus MgCl.sub.2, 6.6 mM MgCl.sub.2, 375 .mu.M each of dATP, dCTP, dCTP and dGTP, 375 nM each of forward primer and reverse primer, 125 nM of probe, 4 Units RNAse inhibitor, 1.25 Units PLATINUM.RTM. Taq, 5 Units MuLV reverse transcriptase, and 2.5.times. ROX dye) to 96-well plates containing 30 .mu.L total RNA solution (20-200 ng). The RT reaction was carried out by incubation for 30 minutes at 48.degree. C. Following a 10 minute incubation at 95.degree. C. to activate the PLATINUM.RTM. Taq, 40 cycles of a two-step PCR protocol were carried out: 95.degree. C. for 15 seconds (denaturation) followed by 60.degree. C. for 1.5 minutes (annealing/extension).

[0460] Gene target quantities obtained by real-time PCR are normalized using either the expression level of GAPDH or cyclophilin A, genes whose expression levels are constant, or by quantifying total RNA. GAPDH expression is quantified by real-time PCR, by being run simultaneously with the target, multiplexing, or separately. Total RNA is quantified using RiboGreen.TM. RNA quantification reagent (Molecular Probes, Inc. Eugene, Oreg.). Methods of RNA quantification by RiboGreen.TM. are taught in Jones, L. J., et al, (Analytical Biochemistry, 1998, 265, 368-374).

[0461] In this assay, 170 .mu.L of RiboGreen.TM. working reagent (RiboGreen.TM. reagent diluted 1:350 in 10 mM Tris-HCl, 1 mM EDTA, pH 7.5) is pipetted into a 96-well plate containing 30 .mu.L purified, cellular RNA. The plate is read in a CytoFluor 4000 (PE Applied Biosystems) with excitation at 485 nm and emission at 530 nm.

[0462] Primers and probes used in real-time PCR are designed with the aid of computer software, for example, Primer Express.RTM. Software (PE-Applied Biosystems, Foster City, Calif., Operon Technologies Inc., Alameda, Calif.), using publicly available sequence information. It is understood that one of skill in the art will readily be able to design such primers and probes.

Example 42

Northern Blot Analysis of a Target mRNA Levels

[0463] Eighteen hours after antisense treatment, cell monolayers were washed twice with cold PBS and lysed in 1 mL RNAZOL.TM. (TEL-TEST "B" Inc., Friendswood, Tex.). Total RNA was prepared following manufacturer's recommended protocols. Twenty micrograms of total RNA was fractionated by electrophoresis through 1.2% agarose gels containing 1.1% formaldehyde using a MOPS buffer system (AMRESCO, Inc. Solon, Ohio). RNA was transferred from the gel to HYBONDT.TM.-N+ nylon membranes (Amersham Pharmacia Biotech, Piscataway, N.J.) by overnight capillary transfer using a Northern/Southern Transfer buffer system (TEL-TEST "B" Inc., Friendswood, Tex.). RNA transfer was confirmed by UV visualization. Membranes were fixed by UV cross-linking using a STRATALINKERT.TM. UV Crosslinker 2400 (Stratagene, Inc, La Jolla, Calif.) and then probed using QUICKHYB.TM. hybridization solution (Stratagene, La Jolla, Calif.) using manufacturer's recommendations for stringent conditions.

[0464] To detect human a target, a human target-specific probe is prepared by PCR. To normalize for variations in loading and transfer efficiency membranes are stripped and probed for human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA (Clontech, Palo Alto, Calif.).

[0465] Hybridized membranes were visualized and quantitated using a PhosphorImager.TM. and IMAGEQUANT.TM. Software V3.3 (Molecular Dynamics, Sunnyvale, Calif.). Data was normalized to GAPDH levels in untreated controls.

Example 43

Western Blot Analysis of a Target Protein Levels

[0466] Western blot analysis (immunoblot analysis) is carried out using standard methods. Cells are harvested 16-20 h after oligonucleotide treatment, washed once with PBS, suspended in Laemmli buffer (100 ul/well), boiled for 5 minutes and loaded on a 16% SDS-PAGE gel. Gels are run for 1.5 hours at 150 V, and transferred to membrane for western blotting. Appropriate primary antibody directed to a target is used, with a radiolabeled or fluorescently labeled secondary antibody directed against the primary antibody species. Bands are visualized using a PhosphorImager.TM. (Molecular Dynamics, Sunnyvale Calif.).

Example 44

Gene Target Sequences

[0467] In accordance with the present invention, a series of oligomeric compounds was designed to hybridize to different regions of target genes or targets. Presented in Table 12 are the target genes, as well as the corresponding sequences, identified by GenBank.RTM. accession number, used to design the oligomeric compounds of the invention and other compounds described herein. "Gene symbol" indicates the name used to herein to describe the target nucleic acid molecule, and "Gene Name" indicates an additional name by which the gene target is known.

TABLE-US-00013 TABLE 12 Gene target sequences SEQ Gene ID Symbol Gene Name GenBank .RTM. Accession # NO CD86 CD86 S70108.1 10 DGAT2 Diacylglycerol Acyltransferase 2 AK002443.1 11 FAS Fatty Acid Synthase AF127033.1 12 FAS Fatty Acid Synthase X62889.1 13 FACL2 Fatty-Acid-Coenzyme A Ligase, Long-Chain 2 NM_007981.1 14 GCGR Glucagon Receptor NM_000160.1 15 GCGR Glucagon Receptor NM_008101.1 16 HSL Hormone-Sensitive Lipase U08188.1 17 HSD11 Hydroxysteroid 11-Beta Dehydrogenase 1 X83202.1 18 JNK1 Jun N-Terminal Kinase-1 L26318.1 19 PP2A- Protein Phosphatase 2 Catalytic Subunit Alpha NM_002715.1 20 alpha PTEN Phosphatase And Tensin Homologue U92436.1 21 PTP1B Protein Tyrosine Phosphatase 1b M33962.1 22 NaDC1 Solute Carrier Family 13 (Sodium-Dependent AF201903.1 23 Dicarboxylate Transporter), Member 2 SCD1 Stearoyl-Coenzyme A Desaturase 1 1850_038A 24 Survivin Survivin U75285.1 25 Survivin Survivin AA717921.1 26 Survivin Survivin AB013819.1 27 TRADD Tumor Necrosis Factor Receptor Associated L41690.1 28 Death Domain C-raf Raf kinase C X03484.1 29 C-raf Raf kinase C assembled from 30 AC026153.10 and AC018500.2 SRC-2 steroid receptor coactivator 2 U39060.1 31 SRC-2 steroid receptor coactivator 2 complement of nucleotides 32 10220000 to 10460000 of NW_000149.1 SRC-2 steroid receptor coactivator 2 AK028964.1 33

Example 45

Chimeric Oligomeric Compounds Having Alternating 3'-Endo and 2'-Endo Regions

[0468] In one embodiment of the invention, the target sequences presented in Table 12 were used as targets to which oligomeric compounds were designed. These compounds have regions of nucleosides that are "RNA-like", having northern or 3'-endo conformational geometry (3'-endo regions), and regions of nucleosides that are "DNA-like", having southern or C2'-endo/04'-endo conformational geometry. Each of the regions ranges from 1 to 8 nucleosides in length. The motif of each oligomeric compound is illustrated in Table 13, where 3'-endo regions are indicated by bold, underlined type, or by italicized, underlined type in the case of ISIS 199043, and 2'-endo regions are indicated by plain type. The number corresponding to each region represents the number of base pairs for that particular region. The motif further indicates the total number of regions in the compound, for example, a compound having the motif "3-3-1-2-1-2-1-3-4" has a total of 9 regions, with each region ranging from 1 to 4 nucleotides. In the compounds shown in Table 13, the 3'-endo regions shown in bold, underlined type comprise 2'-O-methoxyethyl (2'-MOE) nucleotides; the 3'-endo regions in italicized, underlined type comprise 2'-O-methyl nucleotides; and the 2'-endo regions comprise 2'-deoxynucleotides. Internucleoside linkages are phosphorothioate throughout all compound in Table 13, except where an asterisk "*" is present to indicate a phosphodiester internucleoside linkage. All cytosines are 5-methylcytosines, unless otherwise indicated by a superscript "U" preceding the nucleobase, for example, .sup.uC, which indicates a natural or unmodified cytosine.

[0469] The nucleic acid molecule to which each compound is targeted is indicated by SEQ ID NO. "Target site" indicates the first (5'-most) nucleotide number on the particular target nucleic acid to which the compound binds. Where present, "NA" indicates that "Target SEQ ID NO:" and "Target site" do not apply to a particular oligomeric compound due to its lack of perfect complementarity to any known gene (i.e., it is a mismatched oligomeric compound).

[0470] The chimeric oligomeric compounds of the invention, comprising at least 5 regions that alternate between 3'-endo regions and 2'-endo regions, are herein referred to as "gap-disabled" oligomeric compounds. Also described herein are "gapmers", chimeric oligomeric compounds having 3 regions, where one 2'-endo region comprised of 2'-deoxynucleotides is flanked on both sides (5' and 3' directions) by a 3'-endo region.

TABLE-US-00014 TABLE 13 Oligomeric compounds TARGET SEQ SEQ ID TARGET ID ISIS # NO SITE SEQUENCE MOTIF NO 113715 22 980 GCTCCTTCCACTGATCCTGC 5-10-5 45 114905 26 296 GTTGGTCTCCTTTGCCTGGA 5-10-5 49 116847 21 2097 CTGCTAGCCTCTGGATTTGA 5-10-5 42 118929 20 1492 TCTACAGTCATGCTGAGTAA 5-10-5 53 121874 10 289 TCAAGTTTCTCTGTGCCCAA 5-10-5 51 121875 10 335 GTTCCTGTCAAAGCTCGTGC 5-10-5 48 126965 17 2263 CCAGGGCTGCCTCAGACACA 5-10-5 39 129605 NA NA CCTGCTCCCTCTAATGCTGC 5-10-5 63 129686 NA NA CGTTATTAACCTCCGTTGAA 5-10-5 65 131906 NA NA TCAAGTCCTTCCACACCCAA 5-10-5 70 141923 NA NA CCTTCCCTGAAGGTTCCTCC 5-10-5 64 146038 18 1107 TTCTCATGATGAGGTGTACC 5-10-5 58 146039 18 1119 TGTTGCAAGAATTTCTCATG 5-10-5 56 148529 12 630 TTCATGAACTGCACAGAGGT 5-10-5 57 148548 12 2238 TTGTTGACATTGTACTCGGC 5-10-5 59 166659 22 980 GCTCCTTCCACTGATCCTGC 3-3-1-2-1-2-1-3-4 45 180475 16 1348 GAGCTTTGCCTTCTTGCCAT 5-10-5 43 189525 NA NA .sup.uC.sup.uCTG.sup.uCT.sup.uC.sup.uC.sup.uCT.sup.uCTAATG 5-10-5 63 .sup.uCTG.sup.uC 194563 NA NA CCTGCTCCCTCTAATGCTGC 2-1-1-2-1-1-1-1-1-1-1- 63 1-1-3-2 199041 NA NA CCTGCTCCCTCTAATGCTGC Uniform 2'-MOE 63 199042 NA NA CCTGCTCCCTCTAATGCTGC 5-2-1-2-1-2-1-1-5 63 199043 NA NA CCTGCTCCCTCTAATGCTGC Uniform 2'-deoxy 63 199044 NA NA CCTGCTCCCTCTAATGCTGC 5-10-5 63 199046 NA NA C*C*T*G*CTCCCTCTAATG* 5-10-5 63 C*T*G*C 199047 NA NA CCTGATCCCTCTAATGATGC 5-10-5 61 199048 NA NA CCTGCTCACTCTAATGCTGC 5-10-5 62 217352 11 1424 ATGCACTCAAGAACTCGGTA 5-10-5 35 217376 11 2230 TCCATTTATTAGTCTAGGAA 5-10-5 52 244504 24 1329 GTGTTTCTGAGAACTTGTGG 5-10-5 47 244541 24 1435 ATGTCCAGTTTTCCGCCCTT 5-10-5 36 249375 23 846 GGACCTGTAGCCATAGCCAA 5-10-5 46 249386 23 1021 CTCGTGAACCAGAGCACCAC 5-10-5 41 256899 13 12343 TTGTTGACGTTGTACTCAGC 5-10-5 60 283586 22 980 GCTCCTTCCACTGATCCTGC Uniform 2'-MOE 45 284346 NA NA CTTCTAGCCTCTGGATTGGA 5-10-5 66 291452 14 214 TCAAGGACTGCTGATCTTCG 5-10-5 50 298682 NA NA GCGATTTCCCGTTTTCACCT 5-10-5 67 298683 16 1348 GAGCTTTGCCTTCTTGCCAT Uniform 2'-MOE 43 298683 16 1348 GAGCTTTGCCTTCTTGCCAT Uniform 2'-MOE 43 299228 25 12665 TGTGCTATTCTGTGAATT 2-2-1-3-1-2-1-3-3 55 299229 25 12665 TGTGCTATTCTGTGAATT 3-3-1-2-1-3-1-2-2 55 299230 27 856 AACCACACTTACCCATGGGC 3-2-1-3-1-2-1-3-4 34 299231 26 296 GTTGGTCTCCTTTGCCTGGA 3-2-1-3-1-2-1-3-4 49 299232 27 303 TGTCATCGGGTTCCCAGCCT 3-2-1-3-1-2-1-3-4 54 300861 16 1348 GAGCTTTGCCTTCTTGCCAT 3-2-1-3-1-3-1-3-3 43 303767 NA NA GTTCGTGTTCTCTGGCTCGA 5-10-5 68 304170 13 12343 TTGTTGACGTTGTACTCAGC 3-2-1-2-1-2-1-2-1-2-3 60 304171 12 2238 TTGTTGACATTGTACTCGGC 3-2-1-2-1-2-1-2-1-2-3 59 306058 10 289 TCAAGTTTCTCTGTGCCCAA 3-2-1-2-1-3-1-2-1-1-3 51 307754 19 341 ATTTGCATCCATGAGCTCCA 5-10-5 37 310456 15 500 CAGGAGATGTTGGCCGTGGT 5-10-5 38 310457 15 532 GCACTTTGTGGTGCCAAGGC 5-10-5 44 310514 11 1424 ATGCACTCAAGAACTCGGTA 3-2-1-2-1-2-1-2-1-2-3 35 310515 11 2230 TCCATTTATTAGTCTAGGAA 3-2-1-2-1-2-1-2-1-2-3 52 310516 18 1107 TTCTCATGATGAGGTGTACC 3-2-1-2-1-2-1-2-1-2-3 58 310517 18 1119 TGTTGCAAGAATTTCTCATG 3-2-1-2-1-2-1-2-1-2-3 56 312837 23 846 GGACCTGTAGCCATAGCCAA 3-2-1-2-1-2-1-2-1-2-3 46 312844 24 1329 GTGTTTCTGAGAACTTGTGG 3-2-1-2-1-2-1-2-1-2-3 47 319162 14 214 TCAAGGACTGCTGATCTTCG 3-2-1-2-1-2-1-2-1-2-3 50 319237 NA NA TTGTTAACGGTGTTCTCAGC 5-10-5 71 319238 NA NA TTTGTAACGGTGTTCACTGA 5-10-5 72 319239 12 630 TTCATGAACTGCACAGAGGT 3-2-1-2-1-2-1-2-1-2-3 57 319240 NA NA TACTTGACCTACAGAGTGGA 5-10-5 69 330693 17 2263 CCAGGGCTGCCTCAGACACA 2-1-1-2-1-1-1-1-1-1-1- 39 1-1-3-2 332520 15 532 GCACTTTGTGGTGCCAAGGC Uniform 2'-MOE 44 332521 15 532 GCACTTTGTGGTGCCAAGGC Uniform 2'-deoxy 44 332522 15 532 GCACTTTGTGGTGCCAAGGC 3-2-1-2-1-2-1-2-1-2-3 44 332864 16 1348 GAGCTTTGCCTTCTTGCCAT 4-3-1-4-1-3-4 43 332865 16 1348 GAGCTTTGCCTTCTTGCCAT 3-2-1-2-1-2-1-2-1-2-3 43 332866 16 1348 GAGCTTTGCCTTCTTGCCAT 3-5-4-5-3 43 332867 16 1348 GAGCTTTGCCTTCTTGCCAT 3-14-3 43 332868 16 1348 GAGCTTTGCCTTCTTGCCAT 3-3-2-4-2-3-3 43 332869 16 1348 GAGCTTTGCCTTCTTGCCAT 3-1-1-1-1-1-1-1-1-1-1- 43 1-1-1-4 333022 15 500 CAGGAGATGTTGGCCGTGGT Uniform 2'-MOE 38 333023 15 500 CAGGAGATGTTGGCCGTGGT Uniform 2'-deoxy 38 333024 15 500 CAGGAGATGTTGGCCGTGGT 3-2-1-2-1-2-1-2-1-2-3 38 334269 21 2097 CTGCTAGCCTCTGGATTTGA 3-14-3 42 334270 21 2097 CTGCTAGCCTCTGGATTTGA 3-6-1-7-3 42 334271 21 2097 CTGCTAGCCTCTGGATTTGA 3-7-1-6-3 42 334272 21 2097 CTGCTAGCCTCTGGATTTGA 3-4-1-4-1-4-3 42 334273 21 2097 CTGCTAGCCTCTGGATTTGA 3-3-1-2-1-3-1-3-3 42 334274 21 2097 CTGCTAGCCTCTGGATTTGA 3-3-1-3-1-2-1-3-3 42 334275 21 2097 CTGCTAGCCTCTGGATTTGA 3-2-1-2-1-2-1-2-1-2-3 42 334276 21 2097 C*T*G*C*T*A*G*C*C*T* Uniform 2'-deoxy 42 C*T*G*G*A*T*T*T*G*A 335032 16 1348 GAGCTTTGCCTTCTTGCCAT Uniform 2'-deoxy 43 335033 16 1348 G*A*G*C*T*T*T*G*C*C* Uniform 2'-deoxy 43 T*T*C*T*T*G*C*C*A*T 335112 16 1348 G*A*G*C*T*T*T*G*C*C* 5-10-5 43 T*T*C*T*T*G*C*C*A*T 335114 16 1348 G*A*G*C*T*T*T*G*C*C* 3-2-1-3-1-3-1-3-3 43 T*T*C*T*T*G*C*C*A*T 337205 11 1424 ATGCACTCAAGAACTCGGTA 3-14-3 35 337206 11 1424 ATGCACTCAAGAACTCGGTA 3-6-1-7-3 35 337207 11 1424 ATGCACTCAAGAACTCGGTA 3-7-1-6-3 35 337208 11 1424 ATGCACTCAAGAACTCGGTA 3-4-1-4-1-4-3 35 337209 11 1424 ATGCACTCAAGAACTCGGTA 3-3-1-2-1-3-1-3-3 35 337210 11 1424 ATGCACTCAAGAACTCGGTA 3-3-1-3-1-2-1-3-3 35 337211 11 1424 A*T*G*C*A*C*T*C*A*A* Uniform 2'-deoxy 35 G*A*A*C*T*C**G*G*T*A 337212 11 1424 ATGCACTCAAGAACTCGGTA 3-2-2-1-2-1-2-1-1-2-3 35 337213 11 1424 ATGCACTCAAGAACTCGGTA 3-1-3-1-2-1-2-1-2-1-3 35 337214 11 1424 ATGCACTCAAGAACTCGGTA 3-1-2-1-2-1-2-1-2-1-4 35 337215 11 1424 ATGCACTCAAGAACTCGGTA 3-1-1-1-1-1-1-1-1-1-1- 35 1-1-1-4 337216 11 1424 ATGCACTCAAGAACTCGGTA 1-1-1-1-1-1-1-1-1-1-1- 35 1-1-1-1-1-1-1-2 337217 21 2097 CTGCTAGCCTCTGGATTTGA 3-2-2-1-2-1-2-1-1-2-3 42 337218 21 2097 CTGCTAGCCTCTGGATTTGA 3-1-3-1-2-1-2-1-2-1-3 42 337219 21 2097 CTGCTAGCCTCTGGATTTGA 3-1-2-1-2-1-2-1-2-1-4 42 337220 21 2097 CTGCTAGCCTCTGGATTTGA 3-1-1-1-1-1-1-1-1-1-1- 42 1-1-1-4 337221 21 2097 CTGCTAGCCTCTGGATTTGA 1-1-1-1-1-1-1-1-1-1-1- 42 1-1-1-1-1-1-1-2 337222 11 1424 ATGCACTCAAGAACTCGGTA Uniform 2'-MOE 35 338173 28 802 CGCTCGTACTCGTAGGCCAG 5-10-5 40 338174 28 802 CGCTCGTACTCGTAGGCCAG Uniform 2'-MOE 40 338175 28 802 CGCTCGTACTCGTAGGCCAG 4-3-1-4-1-3-4 40 338176 28 802 CGCTCGTACTCGTAGGCCAG 3-2-1-2-1-2-1-2-1-2-3 40 338177 28 802 CGCTCGTACTCGTAGGCCAG 3-5-4-5-3 40 338178 28 802 CGCTCGTACTCGTAGGCCAG 3-14-3 40 338179 28 802 CGCTCGTACTCGTAGGCCAG 3-3-2-4-2-3-3 40 338180 28 802 CGCTCGTACTCGTAGGCCAG 3-1-1-1-1-1-1-1-1-1-1- 40 1-1-1-4

345888 19 341 ATTTGCATCCATGAGCTCCA 3-2-1-2-1-2-1-2-1-2-3 37 352426 16 1348 GAGCTTTGCCTTCTTGCCAT 2-6-4-6-2 43 352427 16 1348 GAGCTTTGCCTTCTTGCCAT 2-7-2-7-2 43 352428 16 1348 GAGCTTTGCCTTCTTGCCAT 1-8-2-8-1 43

[0471] The target regions to which these sequences are complementary are herein referred to as "target segments" and are therefore suitable for targeting by oligomeric compounds of the present invention. The target segment sequences represent the reverse complement of the chimeric oligomeric compounds.

[0472] As these "target segments" have been found by experimentation to be open to, and accessible for, hybridization with the chimeric oligomeric compounds of the present invention, one of skill in the art will recognize or be able to ascertain, using no more than routine experimentation, further embodiments of the invention that encompass other oligomeric compounds that specifically hybridize to these target segments and consequently inhibit the expression of a target.

[0473] According to the present invention, chimeric oligomeric compounds include antisense oligomeric compounds, antisense oligonucleotides, siRNAs, alternate splicers and other short oligomeric compounds which hybridize to at least a portion of the target nucleic acid.

Example 46

In Vitro Analysis of Chimeric Oligomeric Compounds Having Alternating 3'-Endo and 2'-Endo Regions

[0474] In one embodiment, gap-disabled oligomeric compounds were selected from Table 13 and tested for their effects on target expression in cultured cells. Gapmer compounds were also tested in each in vitro assay and served as the positive control for target reduction.

[0475] To test the effects of gap-disabled compounds of the invention on mouse survivin expression, NIH 3T3 cells were treated 6.25, 25, 100 and 200 nM of the oligomeric compounds shown in Table 13. ISIS 303767, which contains 6 mismatches to mouse survivin, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 14. Data are averages from two or more experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 14, the gap-disabled compounds ISIS 299230 and ISIS 229231 and the gapmer ISIS 114905 inhibited mouse survivin expression in a dose-dependent manner. The gap-disabled compounds ISIS 299229 and ISIS 299232 inhibited mouse survivin expression at the 100 and 200 nM doses.

TABLE-US-00015 TABLE 14 Inhibition of mouse survivin expression in NIH 3T3 cells: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 6.25 25 100 200 299228 55 0 0 0 9 299229 55 0 0 10 17 299230 34 23 28 64 72 299231 49 22 44 78 83 299232 54 0 0 38 59 114905 49 0 51 82 91 303767 68 0 0 10 60

[0476] Oligomeric compounds targeting mouse SCD1 were also tested. Primary mouse hepatocytes were treated with 15, 44, 133 and 400 nM of the oligomeric compounds shown in Table 15, or the control oligomeric compound ISIS 141923, which does not target mouse SCD1. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 15. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 15, the gap-disabled compound ISIS 312844 inhibited SCD1 expression in a dose-dependent manner. The gapmer compounds also inhibited SCD1 expression in a dose-dependent manner.

TABLE-US-00016 TABLE 15 Inhibition of mouse SCD1 expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 15 44 133 400 312844 47 0 15 40 69 244504 47 15 32 65 83 244541 36 0 1 46 78 141923 64 0 0 0 0

[0477] To evaluate the effects of oligomeric compounds of the invention on mouse PTEN expression, b.END cells were treated with 12.5, 25, 50 or 100 nM of the oligomeric compounds shown in Table 16. ISIS 141923, which does not target PTEN, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 16. Data are averages from two or more experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 16, the gap-disabled compounds ISIS 334269, ISIS 334270, ISIS 334271, ISIS 334272, ISIS 334273, ISIS 334274 and ISIS 334275 inhibited mouse PTEN mRNA expression in a dose-dependent manner, as did the gapmer compound ISIS 116847. ISIS 334269, a gapmer compound with a gap segment 14 nucleotides in length and wing segments 3 nucleotides in length, also inhibited PTEN expression in a dose-dependent manner. The uniform 2'-deoxy compound ISIS 334276 did not exhibit target inhibition greater than 9%.

TABLE-US-00017 TABLE 16 Inhibition of mouse PTEN mRNA expression in b.END cells: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 12.5 25 50 100 334269 42 9 29 56 71 334270 42 31 29 63 75 334271 42 18 46 59 66 334272 42 0 31 57 64 334273 42 19 31 47 60 334274 42 9 26 47 50 334275 42 10 30 43 63 334276 42 3 9 8 0 116847 42 12 45 62 75 141923 64 0 0 0 0

[0478] Additional compounds targeted to mouse PTEN were tested in a similar assay in b.END cells. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. ISIS 337217 inhibited target expression 10% and 15% at doses of 25 and 50 nM, respectively. ISIS 331218 inhibited PTEN expression by 17% at a dose of 100 nM. ISIS 337219, ISIS 337220 and ISIS 337221 did not significantly inhibit PTEN expression in b.END cells in this assay.

[0479] Oligomeric compounds targeted to NaDC1 were also tested in an in vitro assay. Primary mouse hepatocytes were treated with 15, 44, 133 or 400 nM of the oligomeric compounds shown in Table 17. ISIS 141923, which does not target mouse NaDC1, was used as a negative control compound in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 17. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 17 the gap-disabled compound ISIS 312387 inhibited mouse NaDC1 in a dose-dependent manner, as did the gapmer compounds targeted to NaDC1.

TABLE-US-00018 TABLE 17 Inhibition of mouse NaDC1 mRNA expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS NO NO 15 44 133 400 312837 46 16 55 61 79 249375 46 29 59 71 90 249386 41 0 9 38 76 141923 64 0 0 0 0

[0480] Primary mouse hepatocytes were treated for 4 hours with 15, 44, 133, and 400 nM of the oligomeric compounds shown in Table 18. ISIS 141923, which does not target mouse HSD11, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 18. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 18, the gap-disabled compound ISIS 310516 inhibited HSD11 expression in a dose-dependent manner, as did the gapmer compound.

TABLE-US-00019 TABLE 18 Inhibition of mouse HSD11 mRNA expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS NO NO 15 44 133 400 310516 58 0 40 69 95 146038 58 37 70 94 97 141923 64 0 0 0 0

[0481] Gap-disabled compound targeting the mouse glucagon receptor RNA were also tested in an in vitro assay. Primary mouse hepatocytes were treated with 0.5, 1, 5, 10, 25 or 50 nM of the oligomeric compounds shown in Table 19. ISIS 116847, which does not target the mouse glucagon receptor, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein.

[0482] Results of these studies are shown in Table 19. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. "IC.sub.50" indicates the concentration of oligomeric compound required to inhibit glucagon receptor mRNA expression by 50%. Where present, "ND" indicates "not determined." As demonstrated in Table 19, the gap-disabled compounds ISIS 300861, ISIS 332864, ISIS 332865, ISIS 332866, ISIS 332897 and ISIS 332868 inhibited mouse glucagon receptor expression in a dose-dependent manner, as did the gapmer compound. ISIS 332867, a gap-disabled compound, inhibited mouse glucagon receptor expression. ISIS 332869, a gapmer compound with a gap segment of 14 nucleotides in length and wing segments of 3 nucleotides in length, exhibited dose-dependent inhibition of mouse glucagon receptor mRNA at doses of 5, 10 and 25 nM.

TABLE-US-00020 TABLE 19 Inhibition of mouse glucagon receptor mRNA expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) IC.sub.50 ISIS # NO 0.5 1 5 10 25 50 (nM) 300861 43 1 15 32 20 51 67 24 332864 43 10 30 52 45 63 70 14 332865 43 6 10 29 36 49 53 33 332866 43 27 42 ND 58 70 75 6 332867 43 37 48 66 74 74 77 1 332868 43 7 34 52 58 68 ND 5 332869 43 15 2 5 12 24 25 >50 180475 43 3 43 58 68 78 80 3 116847 42 11 13 0 0 0 0 >50

[0483] To evaluate the effects of gap-disabled compounds targeted to mouse DGAT2, primary mouse hepatocytes were treated with 15, 44, 133, and 400 nM of the oligomeric compounds shown in Table 20. ISIS 116847, which does not target the mouse glucagon receptor, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 20. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. As demonstrated in Table 2 the gap-disabled compounds ISIS 310514 and ISIS 310515, like the gapmer compounds, inhibited mouse DGAT2 expression in a dose-dependent manner.

TABLE-US-00021 TABLE 20 Inhibition of mouse DGAT2 expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS NO NO 15 44 133 400 310514 35 32 64 78 88 310515 52 0 39 45 66 217352 35 71 87 94 95 217376 52 65 75 91 98 141923 64 43 44 0 0

[0484] An additional assay tested a gap-disabled compound targeted to mouse CD86. MH-S cells were treated with 0.12, 0.37, 1, 1, 3.3, 10 and 30 nM of the oligomeric compounds shown in Table 21. ISIS 131906, which contains seven mismatched bases to mouse CD86, served as the negative control compound in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Data are averages from two or more experiments and are expressed as percent inhibition relative to untreated control. Results of these studies are shown in Table 21 and demonstrate that the gap-disabled compound ISIS 306058, inhibited CD86 mRNA expression in a dose-dependent manner at doses of 3.3, 10 and 30 nM.

TABLE-US-00022 TABLE 21 Inhibition of mouse CD86 mRNA expression in MH-S cells: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 0.12 0.37 1.1 3.3 10 30 306058 51 0 6 0 17 32 45 121874 51 0 27 42 61 74 70 121875 48 0 25 43 62 78 81 131906 70 0 1 0 0 0 21

[0485] In a further embodiment, ISIS 306058 was tested for its ability to modulate cell surface expression of CD86 protein. MH-S cells were treated with 0.1, 0.4, 1.2, 3.7, 11.1, 33.3 and 100 nM of the oligomeric compounds shown in Table 22. ISIS 131906, which contains seven mismatched bases to mouse CD86, served as the negative control compound in this assay. Cells were transfected using LIPOFECTINT.TM. as described in other examples herein. Cell surface expression of CD86 protein was measured by flow cytometry. Cell surface expression of CD80, which shares sequence identify with CD86 at the nucleic acid level, was also measured. Cells were harvested by brief trypsinization, washed with PBS, then resuspended in 100 .mu.L of staining buffer (PBS, 0.2% BSA) containing both 10 .mu.L of FITC-conjugated anti-CD86 antibody (FITC-anti-hCD86; FITC: fluorescien isothiocyanate; BD Biosciences, San Jose, Calif.) and 10 ul of PE-conjugated anti-CD80 antibody (PE: phycoerythrin; PE-anti-hCD80, BD Biosciences, San Jose, Calif.). The cells were stained for 30 minutes at 4.degree. C., washed with PBS, resuspended in 300 .mu.L PBS containing 0.5% paraformaldehyde. Measurements of mean fluorescence activity were made by flow cytometry using the FL-1 and FL-2 channels of a BD Biosciences FACScan (BD Biosciences, San Jose, Calif.). With this method, both CD86 and CD80 protein expression on the surface of the same cell was measured. Data were averaged from two or more experiments and are expressed as percent inhibition relative to untreated control. As shown in Table 22, the gap-disabled compound ISIS 306058 exhibited inhibition of CD86 protein expression in a pattern similar to that observed in cells treated with the gapmer compounds, with dose-dependent inhibition limited to the 5 lower doses. CD80 protein levels were not lowered by the gap-disabled or gapmer compounds targeted to CD86.

TABLE-US-00023 TABLE 22 Inhibition of mouse CD86 protein expression in MH-S cells: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 0.1 0.4 1.2 3.7 11.1 33.3 100 306058 51 4 6 12 19 30 31 31 121874 51 10 22 43 56 57 57 57 121875 48 9 21 34 46 57 55 54 131906 70 0 6 9 3 3 15 30

[0486] A gap-disabled compound targeted to mouse ACS1 was tested for its effects on target mRNA expression. Primary mouse hepatocytes were treated with 15, 44, 133 and 400 nM of the oligomeric compounds shown in Table 23. ISIS 141923, which does not target mouse ACS1, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Data were averaged from three experiments and are expressed as percent inhibition relative to untreated control. Results of these studies are shown in Table 23 and demonstrate that the gap-disabled compound ISIS 319962 inhibited mouse ACS1 in a dose-dependent manner, as the gapmer compound.

TABLE-US-00024 TABLE 23 Inhibition of mouse ACS1 expression in mouse primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS # NO 15 44 133 400 319162 50 9 12 45 77 291452 50 20 38 63 90 141923 64 32 5 17 29

[0487] An additional in vitro assay was performed to test a gap-disabled compound targeted to rat HSD11. Primary rat hepatocytes were treated for 4 hours with 15, 44, 133 and 400 nM of the oligomeric compounds shown in Table 24. ISIS 141923, which does not target rat HSD11, was used as a negative control in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Data were averaged from three experiments and are expressed as percent inhibition relative to untreated control. Results of these studies are shown in Table 24 and demonstrate that the gap-disabled compound ISIS 310517 inhibited target mRNA expression in a dose-dependent manner at the 3 higher doses of oligomeric compound.

TABLE-US-00025 TABLE 24 Inhibition of rat HSD11 mRNA expression in rat primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nM) ISIS NO NO 15 44 133 400 146039 56 31 53 76 92 310517 56 0 20 54 79 141923 64 7 9 0 0

[0488] Gap-disabled compounds targeted to rat FAS were tested for their effects on target mRNA expression. Primary rat hepatocytes were treated with 5, 10, 25, 50, 100, and 200 nM of the oligomeric compounds shown in Table 25. ISIS 319237, ISIS 319238, or ISIS 319240, which contain 3, 8 and 7 mismatches to rat FAS, respectively, were used as negative control compounds in this assay. Cells were transfected using LIPOFECTINT.TM. and mRNA levels were measured using real-time PCR as described in other examples herein. Results of these studies are shown in Table 25. Data are averages from three experiments and are expressed as percent inhibition relative to untreated control. "IC.sub.50" indicates the concentration of oligomeric compound required to inhibit FAS mRNA expression by 50%. Where present, "ND" indicates "not determined." The data illustrate that the gap-disabled compound ISIS 304170 inhibited rat FAS mRNA in a dose-dependent manner. With the exception of the 25 nM dose, the treatments with ISIS 319239 inhibited rat FAS expression in a dose-dependent manner. The gapmer compounds also inhibited target expression, whereas the mismatched compounds did not.

TABLE-US-00026 TABLE 25 Inhibition of rat FAS mRNA expression in rat primary hepatocytes: dose response % Inhibition SEQ ID Dose of oligonucleotide (nm) IC.sub.50 ISIS # NO 5 10 25 50 100 200 (nM) 304170 60 1 12 9 13 42 71 104 319239 57 4 14 0 38 62 76 67 148529 57 0 0 8 28 61 70 75 256899 60 17 16 3 25 52 73 97 319237 71 0 0 0 0 0 5 N.D. 319238 72 0 0 0 0 0 0 N.D. 319240 69 0 0 0 0 0 13 N.D.

[0489] From the data from the in vitro assays presented in Tables 14-25, it is evident that gap-disabled compounds effectively inhibited the expression of the nucleic acid molecules to which they are targeted.

Example 47

Chimeric Oligomeric Gap-Disabled Compounds Having Varying 2' Sugar Modifications

[0490] The data described herein demonstrate that gap-disabled oligomeric compounds having 2'-MOE nucleotides in the 3'-endo regions are able to inhibit expression of a target gene. In a further embodiment, a series of oligomeric compounds was designed, using various 2' sugar modifications in the 3'-endo region. The oligomeric compounds were designed using SEQ ID NO: 43, which targets the mouse glucagon receptor RNA. The compounds are shown in Table 26. All compounds in Table 26 are chimeric oligomeric compounds comprising regions that alternate between 3'-endo regions and 2'-endo regions. The motif of each oligomeric compound is illustrated in Table 26, where 3'-endo regions are indicated by bold, underlined type and 2'-endo regions are indicated by plain type. The number corresponding to each region represents the number of base pairs for that particular region. The 3'-endo modification of each oligomeric compound is also indicated in Table 26. All internucleoside linkages are phosphorothioate throughout each compound in Table 26. Unmodified cytosines are indicated by a superscript "U" preceding the nucleobase, for example, ".sup.UC"; all other cytosines are 5-methylcytosines. The 2'-endo regions of ISIS 340662 are comprised of 2'-ribonucleotides. The 2'-endo regions of all other compounds in Table 26 are comprised of 2'-deoxynucleotides. Where indicated by "U" at the 3'-terminal nucleobase position of ISIS 340658, ISIS 340661, ISIS 340663 and ISIS 358699, uracil was used in place of thymidine, making the compounds hybrids of DNA and RNA.

TABLE-US-00027 TABLE 26 Gap-disabled oligomeric compounds targeted to mouse glucagon receptor: varying motifs and 3'-endo nucleosides SEQ ISIS ID 3'-endo NO NO Sequence (5' to 3') Motif modification 180475 43 GAGCTTTGCCTTCTTGCCAT 5-10-5 2'-MOE 298683 43 GAGCTTTGCCTTCTTGCCAT Uniform 2'-MOE 2'-MOE 300861 43 GAGCTTTGCCTTCTTGCCAT 3-2-1-3-1-3-1-3-3 2'-MOE 340658 43 GAGCTTTGCCTTCTTGCCAU 3-2-1-3-1-3-1-3-3 2'-O-methyl 340659 43 GAGCTTTGCCTTCTTGCCAT 3-2-1-3-1-3-1-3-3 2'-fluoro 340660 43 GAGCTTTGCCTTCTTGCCAT 3-2-1-3-1-3-1-3-3 LNA 340661 43 GAGCTUTGC.sup.UCTTCUTGC.sup.UCAU 3-2-1-3-1-3-1-3-3 2'-OH 340662 43 GAG.sup.UCUTUG.sup.UCCUU.sup.UCTUG.sup.UCCAT 3-2-1-3-1-3-1-3-3 2'-MOE 332866 43 GAGCTTTGCCTTCTTGCCAT 3-5-4-5-3 2'-MOE 340663 43 GAGCTTTGCCTTCTTGCCAU 3-5-4-5-3 2'-O-methyl 340673 43 GAGCTTTGCCTTCTTGCCAT 3-5-4-5-3 LNA 358699 43 GAGCTTTGCCTTCTTGCCAU 3-5-4-5-3 2'-fluoro

[0491] The compounds were tested for their ability to modulate the expression of glucagon receptor mRNA in mouse primary hepatocytes. Cells, cultured as described herein, were treated with 0.1, 0.316, 1, 3.16, 10, 31.6 or 100 nM of oligomeric compounds. Untreated cells served as a control group to which all other data were normalized. Cells were transfected and mRNA was measured as described herein. The data, shown in Table 27, are the average of 3 experiments and are presented as percent of control cell mRNA expression. A number less than or greater than 100% indicates a decrease or increase in mRNA expression, respectively.

TABLE-US-00028 TABLE 27 Oligomeric compounds of varying motifs and 3'-endo regions: effects on mouse glucagon receptor mRNA Dose of oligomeric compound (nM) 100 31.6 10 3.16 1 0.316 0.1 3'-endo ISIS # % Control expression Motif modification 180475 16 58 84 130 140 141 103 5-10-5 2'-MOE 298683 105 133 149 167 150 133 144 Uniform 2'-MOE 2'-MOE 300861 58 109 116 145 151 162 132 3-2-1-3-1-3-1-3-3 2'-MOE 340658 78 100 131 141 171 160 119 3-2-1-3-1-3-1-3-3 2'-O-methyl 340659 62 85 118 131 138 154 134 3-2-1-3-1-3-1-3-3 2'-fluoro 340660 38 61 97 121 134 146 154 3-2-1-3-1-3-1-3-3 LNA 340661 93 129 129 124 165 146 116 3-2-1-3-1-3-1-3-3 2'-OH 340662 99 151 145 149 163 168 128 3-2-1-3-1-3-1-3-3 2'-MOE 332866 20 64 83 146 133 128 144 3-5-4-5-3 2'-MOE 340663 25 76 112 123 137 138 137 3-5-4-5-3 2'-O-methyl 340673 45 59 87 112 128 125 99 3-5-4-5-3 LNA 358699 42 75 113 118 158 115 147 3-5-4-5-3 2'-fluoro

[0492] These data demonstrate that gap-disabled compounds, having a plurality of motifs and 3'-endo modifications, exhibit target reduction activity in this assay. For example, ISIS 300861 (2'-MOE), ISIS 340658 (2'-O-methyl), ISIS 340659 (2'-fluoro), ISIS 340660 (LNA), ISIS 332866 (2'-MOE), ISIS 340663 (2'-O-methyl), ISIS 340673 (LNA) and ISIS 359699 (2'-fluoro) inhibited target expression at the 100 nM dose.

Example 48

Comparison of Gapmers and Gap-Disabled Oligomeric Compounds: Influence on Apoptosis Induction and Cell Viability

[0493] Programmed cell death, or apoptosis, is an important aspect of various biological processes, including normal cell turnover, as well as immune system and embryonic development. Apoptosis involves the activation of caspases, a family of intracellular proteases through which a cascade of events leads to the cleavage of a select set of proteins. The caspase family can be divided into two groups: the initiator caspases, such as caspase-8 and -9, and the executioner caspases, such as caspase-3, -6 and -7, which are activated by the initiator caspases. The caspase family contains at least 14 members, with differing substrate preferences (Thornberry and Lazebnik, Science, 1998, 281, 1312-1316). Measuring caspase-3 activity is one manner in which caspase activity is evaluated. Changes in nucleic acid content also serve as an indicator of cell viability, as well as cytotoxic events or pathological abnormalities that affect cell proliferation.

[0494] The ability of gap-disabled and gapmer oligomeric compounds to affect apoptosis and viability in cultured cells was assayed using gap-disabled compounds and their corresponding gapmer compounds. The nucleic acid molecules to which these compounds are targeted, as well as the sequence and motif of each compound, are shown in Table 13. The gap-disabled compounds were: ISIS 330693, ISIS 194563, ISIS 300861 and ISIS 304170. The gapmer compounds were: ISIS 126965, ISIS 129605, ISIS 180475 and ISIS 256899.

[0495] These were tested for their effects on caspase-3 activity and cell viability in the human lung carcinoma cell line A549 (American Type Culture Collection; Manassas, Va.). A549 cells were routinely cultured in DMEM basal media (Invitrogen Corporation, Carlsbad, Calif.) supplemented with 10% fetal bovine serum (Invitrogen Corporation, Carlsbad, Calif.) and lx antibiotic-antimycotic mix (Invitrogen Corporation, Carlsbad, Calif.). Cells were routinely passaged by trypsinization and dilution when they reached approximately 100% confluence. For LIPOFECTINT.TM.-mediated transfection A549 cells were plated on 96-well microtiter plates (Falcon-Primaria #353872, BD Biosciences, Bedford, Mass.) precoated with rat tail collagen (BD Biosciences, Bedford Mass.) at a density of approximately 2*10.sup.5 cells/ml in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum and antibiotic-antimycotic mix. Cells were cultured overnight at 37.degree. C. in the presence of 5% CO.sub.2. The following day the media was aspirated and replaced with prewarmed OPTI-MEM.TM. (Invitrogen Corporation, Carlsbad, Calif.) containing 300 nM oligonucleotide and 9 .mu.g/mL LIPOFECTINT.TM. (Invitrogen Corporation, Carlsbad, Calif.). Cells incubated with OPTI-MEM.TM. alone served as untreated control cells. After four hours the transfection mix was exchanged for fresh culture medium and cells were incubated for an additional 44 hours at 37.degree. C. in the presence of 5% CO.sub.2.

[0496] Caspase-3 activity was evaluated with a fluorometric HTS Caspase-3 assay (Oncogene Research Products, San Diego, Calif.) that detects cleavage after aspartate residues in the peptide sequence DEVD. The DEVD substrate is labeled with a fluorescent molecule, which exhibits a blue to green shift in fluorescence upon cleavage. Active caspase-3 in the oligonucleotide treated cells is measured by this assay according to the manufacturer's instructions. 48 hours after oligonucleotide treatment, 50 uL of assay buffer was added to each well, followed by addition 20 uL of the caspase-3 fluorescent substrate conjugate. Data were obtained in triplicate. Fluorescence in wells was immediately detected (excitation/emission 400/505 nm) using a fluorescent plate reader (SpectraMAX GeminiXS, Molecular Devices, Sunnyvale, Calif.). The plate was covered and incubated at 37.degree. C. for and additional three hours, after which the fluorescence was again measured (excitation/emission 400/505 nm). The value at time zero was subtracted from the measurement obtained at 3 hours. The measurement obtained from the untreated control cells was designated as 100% activity. The data are presented in Table 28. Values above or below 100% indicate an increase or decrease in caspase-3 activity, respectively.

[0497] Cell proliferation and viability were measured using the CyQuant Cell Proliferation Assay Kit (Molecular Probes, Eugene, Oreg.) utilizing the CyQuant GR green fluorescent dye which exhibits strong fluorescence enhancement when bound to cellular nucleic acids. After the 48 hour oligonucleotide treatment, the microplate was gently inverted to remove the medium from the wells, which were each washed once with 200 uL of phosphate-buffered saline. Plates were frozen at -70.degree. C. and then thawed. A volume of 200 uL of the CyQUANT GR dye/cell-lysis buffer was added to each well. The microplate was incubated for 5 minutes at room temperature, protected from light. Data were obtained in triplicate. Fluorescence in wells was immediately detected (excitation/emission 480/520 nm) using a fluorescent plate reader (SpectraMAX GeminiXS, Molecular Devices, Sunnyvale, Calif.). The measurement obtained from the untreated control cells was designated as 100% activity. The data are presented in Table 28. Values above or below 100% indicate an increase or decrease in caspase-3 activity, respectively.

TABLE-US-00029 TABLE 28 Apoptosis and cell viability: comparison of gapmer and gap-disabled oligomeric compounds % cell % caspase- SEQ ISIS # Motif viability 3 activity ID NO 126965 5-10-5 27 2408 39 330693 2-1-1-2-1-1-1-1-1-1-1-1-1-3-2 76 119 39 129605 5-10-5 60 156 63 194563 2-1-1-2-1-1-1-1-1-1-1-1-1-3-2 51 67 63 180475 5-10-5 30 436 43 300861 3-2-1-3-1-3-1-3-3 43 94 43 256899 5-10-5 68 110 60 304170 3-2-1-2-1-2-1-2-1-2-3 58 72 60

[0498] These data demonstrate that when cells were treated with compounds have the nucleobase sequence of SEQ ID NOs: 39 and 43, cell viability was higher and caspase-3 activity was lowered in cells treated with the gap-disabled compounds, as compared to cells treated with the gapmer compounds. Comparison of gap-disabled and gapmer compounds having the nucleobase sequence of SEQ ID NOs: 63 and 60 reveals that both cell viability and caspase-3 activity were lowered in the cells treated with the gap-disabled compounds, as compared to cells treated with the gapmer compounds. These data further illustrate that gap-disabled compounds, like gapmer compounds, are able to modulate cellular pathways.

Example 49

Gap-Disabled vs. Gapmer Oligomeric Compounds: Hepatotoxic Effects

[0499] A number of chemical modifications have been introduced into oligomeric compounds to increase their usefulness as therapeutic agents and improve their pharmacokinetic properties. Of particular interest is the elimination of toxicity caused by oligomeric compounds, which can be significant in the liver and kidney due to the relatively high accumulation of oligomeric compounds in these organs. In a further embodiment, the hepatotoxic effects of the gapmer compound ISIS 129605 (SEQ ID NO: 63; no known target) and the gap-disabled compound ISIS 194563 (SEQ ID NO: 63; no known target) were tested in normal mice. Other oligomeric compounds tested included ISIS 118929 (SEQ ID NO: 53), a randomized control ISIS 29848, where N is A, T, C or G, SEQ ID NO: 75); and ISIS 148548 (SEQ ID NO: 59), all three of which are gapmer oligomeric compounds with 5-methylcytidines and phosphorothioate internucleoside linkages throughout.

[0500] Normal mice, maintained on a lean diet, were injected with 50 mg/kg of each oligomeric compound, twice weekly for 2 weeks. Saline-injected animals served as a control group. Each treatment group contained 4 animals. Animals were sacrificed at the end of the treatment period. Liver weights were determined at necropsy, and serum was collected for analysis of liver transaminase levels determined by routine clinical assays.

[0501] The serum transaminases ALT and AST are frequently used as indicators of hepatotoxicity. ISIS 129605 caused marked increases in both AST and ALT levels, which were 20 and 17 times, respectively, that observed in saline-treated mice. Conversely, ISIS 194563, which has the same nucleotide sequence as ISIS 129605 but is a gap-disabled compound, caused no increase in ALT and AST levels relative to saline-treated animals. Similarly, treatment ISIS 118929, ISIS 148548 or ISIS 29848 did not result in elevated ALT and AST levels. Increases in liver and spleen weights can also indicate the presence of toxicity. Treatment with ISIS 129605 resulted in an increase in liver weight approximately 1.6 times that of livers from saline-treated animals. Conversely, treatment with ISIS 194563 did not elevate or reduce liver weight. Serum transaminase levels and liver weight data demonstrate that introduction of 2'-MOE nucleotides into the gap segment of ISIS 129605 reduced the toxicity of that compound. Liver weights following treatment with the other gamper compounds were not significantly increased. None of the compounds resulted in significantly elevated spleen weights.

[0502] An additional in vivo experiment was performed, using oligomeric compounds described herein: ISIS 129605 (SEQ ID NO: 63), a gapmer having the motif 5-10-5 wherein the wing segments are composed of 2'-MOE nucleotides; ISIS 189525 (SEQ ID NO: 63), a gapmer having the motif 5-10-5, wherein the wings are composed of 2'-MOE nucleotides, and also having unmodified cytosines (rather than 5-methylcytosines); ISIS 199041 (SEQ ID NO: 63), uniformly composed of 2'-MOE nucleotides; ISIS 199042 (SEQ ID NO: 63), a gap-disabled compound having the motif 5-2-1-2-1-2-1-1-5; ISIS 199043 (SEQ ID NO: 63), uniformly composed of 2'-deoxynucleotides; ISIS 199044 (SEQ ID NO: 63), a 5-10-5 gapmer wherein the wing segments are composed of 2'-O-methyl nucleotides and the gap is composed of 2'-deoxynucleotides; and ISIS 199046 (SEQ ID NO: 63), a 5-10-5 gapmer wherein the wing segments are composed of 2'-MOE nucleotides, and wherein the internucleoside linkages in the wings are phosphodiester and the internucleoside linkages in the gap are phosphorothioate. Also tested were ISIS 199047 (SEQ ID NO: 61) and ISIS 199048 (SEQ ID NO: 62), both gapmer compounds with the motif 5-10-5, having wing segments composed of 2'-MOE nucleotides. Unless otherwise noted, internucleoside linkages are phosphorothioate and cytosines are 5-methylcytosines. For each motif presented, emboldened, underlined type indicates 2'-MOE nucleotides and plain type indicated 2'-deoxynucleotides. SEQ ID NOs: 63, 61 and 62 are not perfectly complementary to any known target.

[0503] Lean mice were treated with 50 mg/kg oligomeric compound, twice weekly for 3 weeks. The serum transaminases ALT and AST, indicators of toxicity, were measured by routine clinical analysis at the end of the study. ISIS 129605 treatment resulted in AST and ALT levels approximately 6 and 5 times those of saline-treated mice, respectively. ISIS 199044 resulted in dramatically elevated AST and ALT, approximately 15 and 9 times those of saline-treated mice, respectively. Treatment with ISIS 199048 also resulted in elevated AST and ALT, approximately 10 and 15 times those of saline-treated mice, respectively. The gap-disabled compound ISIS 199042 did not significantly elevate ALT and AST levels, demonstrating that an additional gap-disabled compound exhibits significantly fewer toxic properties than the gapmer version having the same nucleotide sequence. ISIS 189525, ISIS 199041, ISIS 199043, ISIS 199046 and ISIS 199047 similarly did not cause significantly elevated ALT and AST levels, illustrating that various chemical modifications of SEQ ID NO: 63 exhibit fewer toxic properties relative to ISIS 129605.

[0504] Liver weights, increases in which can also indicate toxicity, were also measured at the end of the study. In accordance with the observation that ISIS 199042 did not elevate ALT and AST levels, this compound did not significantly change liver weight. ISIS 199041 and ISIS 199046 did not cause increases in liver weight. However, ISIS 129605 and ISIS 199044, which did exhibit toxic properties as judged by ALT and AST levels, increased liver weight by approximately 1.6 and 1.8 times that of liver weights from saline-treated mice. These data further demonstrate the toxic properties of these compounds. Although ISIS 189525 and ISIS 199043 did not elevate ALT and AST levels, treatment with these compounds resulted in approximately 1.4-fold increases in liver weights relative to livers from saline-treated mice.

[0505] These in vivo studies illustrate that chimeric oligomeric compounds having at least 9 alternating 3'-endo and 2'-endo regions ameliorate hepatotoxicity, thereby improving the pharmacokinetic properties of the compounds. Thus, these compounds have applications in the development of therapeutic agents.

Example 50

In Vivo Comparison of Gapmer and Gap-Disabled Oligomeric Compounds Targeted to JNK1: Target Reduction and Toxicity

[0506] In a further embodiment, gap-disabled and gapmer oligomeric compounds targeted to both human and mouse jun N-terminal kinase-1 (JNK1) were tested for their effects on both toxicity and target reduction in vivo. The gap-disabled compound ISIS 345888 (SEQ ID NO: 37) and the gapmer compound ISIS 307754 (SEQ ID NO: 37) are both shown in Table 13 and were selected for this study.

[0507] Male Balb/c mice, 6 to 7 weeks of age, received twice weekly intraperitoneal injections of 12.5, 25 or 50 mg/kg of either ISIS 307754 or ISIS 345888, for a period of three weeks. ISIS 141923 (SEQ ID NO: 64) was used as a negative control oligomeric compound and was injected at 50 mg/kg. Saline-injected animals served as a control group and were injected in the same manner as the oligomeric compounds. Each treatment group contained 4 animals. Body weights were monitored throughout the study (Days 1, 5, 8, 12, 15 and 19). Two days following the final injection, animals were sacrificed (Day 20). Liver and spleen weights, increases in which can indicate toxicity, were determined at time of necropsy. Serum was collected for analysis of the liver transaminase ALT, an indicator of toxicity. ALT levels were determined by routine clinical analysis. Liver tissue was collected for measurement of target mRNA expression by real-time PCR. Liver and kidney tissue were evaluated for concentration of total and full-length oligomeric compound by capillary gel electrophoresis.

[0508] ALT levels are shown in Table 29, in international units per liter (IU/L), with the saline control levels included for comparison. Body, liver and spleen weights are also presented in Table 29. Body weights are shown as percentage relative to the weight of each animal at the start of the study. Liver and spleen weights are normalized to saline-treated control weights.

TABLE-US-00030 TABLE 29 Indicators of toxicity: gap-disabled vs. gapmer oligomeric compounds targeted to JNK1 Liver Spleen ALT Body Weights Weight Weight IU/L % relative to Day 1 % relative to saline Dose, Day Day Day Day Day Day Day Day Treatment mg/kg 20 5 8 12 15 19 20 20 Saline none 46 100 106 104 108 108 100 100 141923 50 64 100 104 105 107 109 99 106 307754 50 292 101 102 103 102 105 131 147 307754 25 218 98 101 101 105 107 118 122 307754 12.5 40 101 105 106 106 109 109 120 345888 50 58 100 104 103 106 106 101 125 345888 25 103 102 105 105 107 110 110 124 345888 12.5 48 98 103 103 107 110 107 119

[0509] From these data, it is evident that at doses of 25 or 50 mg/kg, treatment with the gap-disabled compound ISIS 345888 resulted in markedly lower ALT levels, relative to treatment with the gapmer compound ISIS 307754. These data further reveal that at the 25 and 50 mg/kg doses, ISIS 307754 caused increases in liver weight, relative to saline-treatment. The 12.5 mg/kg dose of ISIS 307754 did not increase liver weight, relative to saline-treatment. None of the doses of the gap-disabled compound ISIS 345888 resulted in an increase in liver weight, relative to saline-treatment. Thus, ISIS 345888 exhibits fewer toxic properties than ISIS 307754.

[0510] Oligomeric compounds isolated from kidney and liver tissue were subjected to capillary gel electrophoresis, to determine the concentrations of total and full-length oligomeric compound. The total concentration of oligomeric compound following treatment with ISIS 307754 (gapmer) was 163 .mu.g/g in kidney and 176 .mu.g/g in liver. Full-length ISIS 307754 represented 94% of the total compound present in kidney and 98% of the total compound present in liver. The total concentration following treatment with ISIS 345888 was 126 .mu.g/g in kidney and 174 .mu.g/g in liver. Full-length ISIS 345888 represented 82% of the total compound present in kidney and 78% of the total compound present in liver. These data demonstrate that full-length ISIS 345888 accumulates in liver and kidney tissue.

[0511] Liver RNA was analyzed for JNK1 expression levels by quantitative real-time PCR as described by other examples herein, using the housekeeping gene cyclophilin A to normalize RNA levels among samples. In Table 30, JNK1 mRNA expression levels are shown as normalized to saline-treated control JNK1 levels.

TABLE-US-00031 TABLE 30 Target reduction and serum transaminases: gap-disabled vs. gapmer oligomeric compounds targeted to JNK1 JNK1 Dose, mRNA % Treatment mg/kg control 141923 50 93 307754 50 15 307754 25 16 307754 12.5 31 345888 50 23 345888 25 26 345888 12.5 49

[0512] These results demonstrate a substantial reduction in target expression following treatment with both the gap-disabled and gapmer compounds. Furthermore, the hepatoxicity caused by the gapmer, as judged by liver weights and ALT levels, is ameliorated by the introduction of 2'-MOE nucleotides into the gap segment. The significant reduction of JNK1 mRNA in livers of mice treated with ISIS 345888 also illustrates that the concentration of ISIS 345888 accumulated in the liver is an amount sufficient to elicit substantial target reduction.

Example 51

Antisense Inhibition by Gap-Disabled Oligomeric Compounds Target to Human C-Raf

[0513] In a further embodiment, a series of oligomeric compounds was designed to target human C-raf RNA, using publicly available sequences (GenBank accession number X03484.1, incorporated herein as SEQ ID NO: 29; and a sequence assembled from GenBank accession numbers AC026153.10 and AC018500.2, incorporated herein as SEQ ID NO: 30). The compounds are shown in Table 31. "Target site" indicates the first (5'-most) nucleotide number on the particular target sequence to which the compound binds. All compounds in Table 31 are chimeric oligomeric compounds, comprising regions that alternate between 3'-endo regions and 2'-endo regions, also known as gap-disabled compounds. The motif of each compound in Table 31 is 3-2-1-2-1-2-1-2-1-2-3, where the number indicates the number of nucleosides in that region. Regions consisting of 2'-MOE nucleotides are indicated by bold, underlined type and the remaining regions in plain type consist of 2'-deoxynucleotides. All internucleoside linkages are phosphorothioate linkages, and all cytosines are 5-methylcytosines.

[0514] The compounds were tested for their effect on human C-raf mRNA levels by quantitative real-time PCR as described in other examples herein. Data are averages from two experiments in which A549 cells were treated with 75 nM of the compounds in Table 31. ISIS 18078 (SEQ ID NO: 8), which does not target Raf kinase C, was used as a negative control oligonucleotide in this assay.

TABLE-US-00032 TABLE 31 Antisense inhibition by gap-disabled oligomeric compounds targeted to human C-raf Target Seq SEQ Target % ID Isis # Region ID NO Site Sequence 5' to 3' Inhib NO 336818 Coding 29 94 attcttaaacctgagggagc 26 76 336819 Coding 29 144 tgatcgtcttccaagctccc 46 77 336820 Coding 29 198 gagagatgcagctggagcca 61 78 336821 Coding 29 249 tgccatcatctgatgcccgg 77 79 336822 Coding 29 268 ttagaaggatctgtgagttt 67 80 336823 Coding 29 327 gcacattgaccactgttctt 43 81 336824 Coding 29 367 agtgctttcataaggcagtc 38 82 336825 Coding 29 392 ctctggttgcaggcccctca 59 83 336826 Coding 29 413 aagtctgaacactgcacagc 57 84 336827 Coding 29 433 ttacctttgtgttcgtggag 75 85 336828 Coding 29 466 gcagcatcagtattccaatc 58 86 336829 Coding 29 543 tcttccgagcaaagttgtgt 35 87 336830 Coding 29 591 tgagcaggaatttctgacag 53 88 336831 Coding 29 701 tggaaacaataagagttgtc 40 89 336832 Coding 29 776 ggaaacagactctcgcatac 38 90 336833 Coding 29 800 gtgctgagaactaacaggca 78 91 336834 Coding 29 909 tgaccatgtggacattaggt 70 92 336835 Coding 29 931 ctgtccacaggcagcgtggt 40 93 336837 Coding 29 954 gaaggtgaggctgattcgct 43 94 336838 Coding 29 982 cacgaggcctaattttgttt 91 95 336839 Coding 29 1110 atttcccaataatagcttga 68 96 336840 Coding 29 1141 gcaacatctccgtgccattt 48 97 336841 Coding 29 1228 tcctgaaggcctggaattgc 53 98 336842 Coding 29 1284 ccgtgttttgcgcagaacag 50 99 336843 Coding 29 1313 caggttgtcctttgtcatgt 17 100 336844 Coding 29 1361 ggacatgcaggtgtttgtag 27 101 336845 Coding 29 1416 attagctggaacatctgaaa 19 102 336846 Coding 29 1447 atgcaaatagtccattccct 21 103 336847 Coding 29 1490 gaaatatattgttggatttc 61 104 336848 Coding 29 1536 cgtgactttactgttgccaa 34 105 336849 Coding 29 1594 gggccatccagaggacagag 58 106 336850 Coding 29 1650 tgaagatgatctgatctcgg 31 107 336851 Coding 29 1788 atatagcttactaagatctg 33 108 336852 Coding 29 1832 aatggaagacaggatctggg 34 109 336853 Coding 29 1928 cttcggtagagagtgttgga 52 110 336854 Coding 29 1955 tatcctcagtgtgggctgcc 39 111 336855 Coding 29 2010 tgcaaagtcaactagaagac 49 112 336856 Coding 29 2068 ttctgcctctggagaaaggg 20 113 336857 Intron 29 2144 aggtccttagcagagcttct 33 114 336858 Intron 29 2177 aaatggcttccttctcccag 13 115 336859 Intron 29 2255 tacagaaggctgggccttga 67 116 336860 Intron 29 2317 tttttgtactaccatcaaca 50 117 336861 Intron 29 2351 acttcctctaaatactcatg 24 118 336862 Intron 29 2399 tccacatcagggctggactg 32 119 336863 Intron 29 2430 gaagctgatttccaaaatcc 14 120 336864 Intron 29 2458 tcccgcctgtgacatgcatt 39 121 336865 Intron 29 2484 accactctctgaagaaagtc 25 122 336866 Intron 29 2502 gtgccttatgtgcaaaatgt 36 123 336867 Intron 29 2532 ggcggccagagtctcggcag 13 124 336868 Intron 29 2566 ctaagaaaagttccatagta 14 125 336869 Intron 29 2604 gaagctgtgaaaggaggacg 9 126 336870 Intron 29 2630 gggcagctcctggaagacaa 31 127 336871 Intron 29 2746 tgtatacacatgatgtgact 25 128 336872 Intron 30 2834 aacatagctatttgaagcta 47 129 336873 Intron 30 27366 aagcaataatttcaatttct 35 130 336874 Intron 30 27473 gcccagcttaacgtgtattt 12 131 336875 Intron 30 27513 tcatcaggcccagcttaacg 52 132 336876 Intron 30 27520 ccatccatggaaacattatc 35 133 336877 Intron 30 28081 acagcatctaacatcactgt 24 134 336878 Intron 30 28103 agtcaatctcccgaggatag 38 135 336879 Intron 30 28215 agtgacgctttccaagaaga 27 136 336880 Intron 30 28503 atgtaagctaacgatgaata 10 137 336881 Exon-Exon Junction 30 28528 ttccctgggctattctccca 51 138 336882 Exon-Exon Junction 30 28577 aattgagaattacactcacc 55 139 336883 Exon-Exon Junction 30 28613 aacgcctcctaaattgagaa 27 140 336884 Exon-Exon Junction 30 28624 tggattggcttagggaccca 25 141 336885 Exon-Exon Junction 30 28700 actattttgcccttatgaag 81 142 336886 Exon-Exon Junction 30 28886 tcttaaaatctactctgaaa 29 143 336887 Exon-Exon Junction 30 29191 cttaactgtcttaaaatcta 47 144 336888 Exon-Exon Junction 30 29199 tgaaaaatgtacttttctat 51 145 336889 Exon-Exon Junction 30 29273 aaagttttctttaaacaatg 44 146 336890 Exon-Exon Junction 30 29462 gcccatgttctcagaataaa 63 147 336891 Exon-Exon Junction 30 29641 aatctaggtctgttgaactc 6 148 336892 Exon-Exon Junction 30 29665 aaggtaatttgctcaaggcc 46 149 336893 Exon-Exon Junction 30 29713 agaaaactgggactctaaga 60 150 336894 Exon-Exon Junction 30 29732 tatttctatctgaaaaataa 48 151 336895 Exon-Exon Junction 30 29751 aacaaacctatgaagtaggt 59 152 337561 Exon 1: Intron 1 30 29773 tgccacctacctgagggagc 43 153 337562 Exon 10: Intron 10 30 20510 attcttaaacctggtaagaa 64 154 337563 Exon 11: Intron 11 30 20743 gttcacataccactgttctt 48 155 337564 Exon 12: Intron 12 30 27195 gcacattgacctacaaacaa 57 156 337565 Exon 13: Intron 13 30 27308 gagctcttaccctttgtgtt 45 157 337566 Exon 14: Intron 14 30 30025 tgcaacttacaaagttgtgt 67 158 337567 Exon 15: Intron 15 30 30334 tcttccgagcctacaacaag 43 159 337568 Exon 2: Intron 2 30 30492 aatgccttacaagagttgtc 48 160 337569 Exon 3: Intron 3 30 34981 gtgctgagaactaggaggag 63 161 337570 Exon 4: Intron 4 30 35135 gccctattacctcaatcatc 48 162 337571 Exon 5: Intron 5 30 38855 gaattgcatcctgaaacaga 69 163 337572 Exon 7: Intron 7 30 38883 ggaaaagtacctgattcgct 43 164 337573 Exon 8: Intron 8 30 38991 gaaggtgaggcttaatagac 84 165 337574 Intron 1: Exon 2 30 39462 cacgaggcctctgaaacaag 60 166 337575 Intron 10: Exon 11 30 39580 ccaagcttaccgtgccattt 65 167 337576 Intron 12: Exon 13 30 47482 gcaacatctcctgcaaaatt 40 168 337577 Intron 13: Exon 14 30 47567 ttctactcaccgcagaacag 28 169 337578 Intron 15: Exon 16 30 48476 tctactcactccattccctg 38 170 337579 Intron 16: Exon 17 30 51633 atgcaaatagctgtgaaggg 58 171 337580 Intron 2: Exon 3 30 51680 caaaggatactgttggattt 76 172 337581 Intron 4: Exon 5 30 53471 agaaatatatctcaatgctt 58 173 337582 Intron 6: Exon 7 30 53590 agattctcaccatccagagg 79 174 337583 Intron 7: Exon 8 30 54149 acagacttacctgatctcgg 44 175 337584 Intron 8: Exon 9 30 54289 tgaagatgatctaagggaaa 65 176 337585 Intron 9: Exon 10 30 54615 ggaagacaggatctgaaaca 56 177

[0515] These data reveal that SEQ ID NOs 77, 78, 79, 80, 81, 83, 84, 85, 86, 88, 91, 92, 94, 95, 96, 97, 98, 99, 104, 106, 110, 112, 116, 117, 129, 132, 138, 139, 142, 144, 145, 146, 147, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 171, 172, 173, 174, 175, 176 and 177 exhibited at least 43% inhibition of human C-raf mRNA expression in this assay.

Example 52

Antisense Inhibition by Gap-Disabled Oligomeric Compounds Target to Mouse SRC-2

[0516] In a further embodiment, a series of oligomeric compounds was designed to target mouse SRC-2 RNA, using publicly available sequences (GenBank accession number U39060.1, incorporated herein as SEQ ID NO: 31; the complement of nucleotides 10220000 to 10460000 of the sequence with GenBank accession number NW.sub.--000149.1, incorporated herein as SEQ ID NO: 32; and GenBank accession number AK028964.1, incorporated herein as SEQ ID NO: 33). The compounds are shown in Table 32. "Target site" indicates the first (5'-most) nucleotide number on the particular target sequence to which the compound binds. All compounds in Table 32 are chimeric oligomeric compounds, comprising alternating 3'-endo regions and 2'-endo regions, also known as gap disabled compounds. The motif of each compound in Table 19 is 3-2-1-2-1-2-1-2-1-2-3, where the number indicates the number of nucleosides in that region. Regions consisting of 2'-MOE nucleotides are indicated by bold, underlined type and the remaining regions in plain type consist of 2'-deoxynucleotides. All internucleoside linkages are phosphorothioate linkages, and all cytosines are 5-methylcytosines.

[0517] The compounds were tested for their effect on mouse SRC-2 mRNA levels by quantitative real-time PCR as described in other examples herein. Data are averages from two experiments in which b.END cells were treated with 50 nM of the compounds in Table 32. ISIS 337599 (GTGCGCGCGAGCCCGAAATC, SEQ ID NO: 178), which does not target Raf kinase C, is a gap-disabled compound having the same motif as the compounds in Table 32 and was used as a negative control compound in this assay.

TABLE-US-00033 TABLE 32 Antisense inhibition by gap-disabled oligomeric compounds targeted to human Raf kinase C TARGET SEQ SEQ ID TARGET % ID ISIS # Region NO SITE SEQUENCE (5' to 3') INHIB NO 337600 5' UTR 31 174 tatcagcaactgtgcctgta 6 179 337601 5' UTR 31 193 cccactcatcttgaacacat 21 180 337602 Coding 31 479 tctgcacttcatctatgttg 45 181 337603 Coding 31 646 cagctcttcttggttatacc 37 182 337604 Coding 31 1170 tgtctcagaacttcatggtg 34 183 337605 Coding 31 1257 gaacggatgagtttgctctt 9 184 337606 Coding 31 1272 tcattagtagtctgagaacg 0 185 337607 Coding 31 1426 acctgggttcccactgcaca 49 186 337608 Coding 31 1462 gggaaaatttatattgctac 9 187 337609 Coding 31 1491 atgcccatttgttcctttgg 22 188 337610 Coding 31 2244 tgcttctccttgagcgaggt 31 189 337611 Coding 31 2509 aggatctgtcttactgtcca 53 190 337612 Coding 31 2519 tgttactggcaggatctgtc 20 191 337613 Coding 31 2625 tgcaaatcatccaaaatctc 26 192 337614 Coding 31 2700 atggcttgcttgtcaactga 53 193 337615 Coding 31 2705 tgatgatggcttgcttgtca 35 194 337616 Coding 31 2720 gttgcatgaggtcattgatg 31 195 337617 Coding 31 2804 gtgggttattaaaagtgctc 7 196 337618 Coding 31 2809 tggtcgtgggttattaaaag 16 197 337619 Coding 31 2819 ccagttgccctggtcgtggg 39 198 337620 Coding 31 2824 cctgcccagttgccctggtc 10 199 337621 Coding 31 2839 ctggtttggcaataacctgc 1 200 337622 Coding 31 2885 gtccagcaccagttgggctt 27 201 337623 Coding 31 2890 gaaaggtccagcaccagttg 33 202 337624 Coding 31 2900 tgattggtgggaaaggtcca 11 203 337625 Coding 31 2910 ctactgtttctgattggtgg 33 204 337626 Coding 31 2934 ggctgaggtatcactgagta 62 205 337627 Coding 31 2939 ttcctggctgaggtatcact 34 206 337628 Coding 31 2949 ttacccatcattcctggctg 36 207 337629 Coding 31 3182 gtctttggccaggctggctg 27 208 337630 Coding 31 3513 tggctctggctgaccagttc 20 209 337631 Coding 31 3650 agtttggatcttgcatggga 28 210 337632 Coding 31 3789 ttctgctgtgcttggaggcg 24 211 337633 Coding 31 4137 gtcgtagccccagtaaagcc 2 212 337634 3' UTR 31 4833 agttgcactacggtgaatgc 43 213 337635 Exon 1a: 32 77182 gcatctttaccacttcagga 39 214 Intron 1c 337636 Exon 11: 32 200699 gaaaactcacctggtcactg 0 215 Intron 11 337637 3' UTR 33 2520 aacaggtcgagctcagtagt 34 216

[0518] These data demonstrate that SEQ ID NOs 180, 181, 182, 183, 186, 188, 189, 190, 191, 192, 193, 194, 195, 198, 201, 202, 204, 205, 206, 207, 208, 209, 210, 211, 213, 214 and 216 demonstrated at least 20% inhibition of mouse SRC-2 in this assay. These results provide another example of target inhibition by gap-disabled oligomeric compounds.

Example 53

Recombinant Human RNase H Analysis

[0519] RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. It is known in the art that single-stranded antisense oligomeric compounds which are "DNA-like" or have DNA-like regions elicit RNase H activity. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby allowing oligonucleotide-mediated inhibition of gene expression.

[0520] In a further embodiment, the ability of oligomeric compounds to elicit RNase H activity was tested using RNase H activity assays. Where the motif of each compound is indicated, 2'-MOE nucleotides are in bold, underlined type and 2'-deoxynucleotide regions are in plain type. The number in each region represents the number of nucleotides in that region. Oligomeric compounds tested included ISIS 300861 (SEQ ID NO: 43), a gap-disabled compound having the motif 3-2-1-3-1-3-1-3-3 and phosphorothioate (P.dbd.S) internucleoside linkages throughout the compound, and ISIS 335114 (SEQ ID NO: 43), also a gap-disabled compound having the motif 3-2-1-3-1-3-1-3-3 and phosphodiester (P=0) internucleoside linkages throughout the compound. Also tested was ISIS 335112 (SEQ ID NO: 43), a chimeric oligonucleotide 20 nucleotides in length, having a 10-nucleotide gap segment flanked on both sides (5' and 3') by 5-nucleotide wing segments, wherein the gap segment consists of 2'-deoxynucleotides and the wing segments consist of 2'-MOE nucleotides. Internucleoside linkages are phosphodiester (P.dbd.O) throughout the compound. An additional oligomeric compound tested was ISIS 335033 (SEQ ID NO: 43), uniformly composed of 2'-deoxynucleotides with phosphodiester (P.dbd.O) internucleoside linkages throughout the compound. In these compounds, all cytosines are 5-methylcytosines.

[0521] RNase H1 activity was evaluated using 40 oligoribonucleotides of mouse glucagon receptor RNA (GTTGGAGGCAATGGCAAGAAGGCAAAGCTCTTCAGGAGGA, incorporated herein as SEQ ID NO: 217) as the target RNA. This target RNA was radiolabelled with .sup.32P at the 5'-end as described by Wu et al. (J. Biol. Chem., 2001, 276, 23547-23553). In a volume of 100 .mu.A, 100 nM of radiolabelled RNA and 200 nM of oligomeric compound were incubated in a reaction containing 20 mM Tris HCl, pH 7.5, 20 mM KCl, 1 mM MgCL.sub.2, 0.1 mM Tris(2-carboxyethyl)phosphine hydrochloride (TCEP) and 4% RNaseOUT.TM. (Invitrogen Corporation, Carlsbad, Calif.). Reactions were melted by heating to 95.degree. C. for 5 minutes then allowed to cool slowly to room temperature. Formation of the heteroduplex between the target RNA and an oligomeric compound was confirmed by the shift in mobility between the single-stranded end labeled sense RNA and the annealed duplex on non-denaturing polyacrylamide gels. The resulting heteroduplexes were tested as substrates for digestion by recominant human RNase H1, which was expressed and purified as described by Wu et al. (J. Biol. Chem., 2004, 279, 17181-17189). An aliquot of annealed heteroduplex reaction was removed for use as the t=0 timepoint. 70 ng of purified recombinant RNase H1 in a solution of 50 mM Tris HCl, pH 7.5, 50 mM NaCl, 50% glycerol, 1 mM TCEP and 4% RNaseOUT.TM. was added to 100 .mu.L of the duplex reaction and was incubated at 37.degree. C. The reaction was terminated at 15, 60 and 240 minute timepoints by the addition of 4M Urea and 20 mM EDTA. The reactions were heated at 90.degree. C. for 2 minutes and the reaction products were resolved on a 12% polyacrylamide gel containing 7 M Urea and visualized and quantitated using a PhosphorImager.TM. and IMAGEQUANT.TM. Software (Molecular Dynamics, Sunnyvale, Calif.).

[0522] Recombinant human RNase H1 was tested for its ability to cleave four different heteroduplexes formed between the target RNA and each of the oligomeric compounds ISIS 335112, ISIS 335033, ISIS 335114 and ISIS 300861. The percentage of target RNA cleaved was calculated using the following formula: [(fraction of RNA cleaved/total RNA input).times.100]-% background. The data from the 15, 60 and 240 minute time points were normalized to the data from the t=0 timepoint. The results are shown in Table 33.

TABLE-US-00034 TABLE 33 Recombinant human Rnase-H1 mediated cleavage of heteroduplexes % target mRNA cleavage Reaction ISIS 335112 ISIS 335033 ISIS 335114 ISIS 300861 time Gapmer 2'-deoxy Gap-disabled Gap-disabled (minutes) P = O P = O P = O P = S 15 3 5 1 0 60 15 30 1 1 240 38 74 1 1

[0523] These data demonstrate that whereas ISIS 335112 (gapmer) and ISIS 335033 (uniform 2'-deoxy) oligomeric compounds elicited RNase H1-mediated cleavage, the gap-disabled compounds (ISIS 335114 or ISIS 300861) were unable to utilize recombinant RNase H1 to effect the detectable cleavage of target mRNA in this assay.

Example 54

Immunoprecipitated RNase H Activity

[0524] In a further embodiment, the ability of gap-disabled oligomeric compounds to utilize immunoprecipitated RNase H1 and RNase H2 to direct the cleavage of target RNA was tested. Polyclonal antibodies were generated by Biosolutions (Ramona, Calif.) using RNase H1 and RNase H2 proteins purified as described by Wu, et al. (J. Biol. Chem., 2004, 279, 17181-17189). Immunoprecipitations were also performed as described by Wu, et al. (J. Biol. Chem., 2004, 279, 17181-17189). Duplex formation was performed as described herein, using ISIS 300861 (SEQ ID NO: 43, gap-disabled), ISIS 335112 (SEQ ID NO: 43, gapmer) and ISIS 335033 (SEQ ID NO: 43, uniform 2'-deoxy) as the oligomeric compounds and the mouse glucagon receptor (SEQ ID NO: 217) as the target RNA. The cleavage assay was performed as described herein for recombinant RNase H1, using RNase H1 or RNase H2 immunoprecipitated with 10 .mu.g of the respective antibody per 1 mg total cellular protein. Samples of the cleavage assay were collected at t=0 (start of the reaction), 15, 60 and 180 minutes and products were resolved by denaturing polyacrylamide electrophoresis and visualized by using a PhosphorImager.TM. and IMAGEQUANT.TM. Software (Molecular Dynamics, Sunnyvale, Calif.). Whereas both ISIS 335033 (uniform 2' deoxy) and ISIS 335112 (gapmer) were able to direct cleavage of the target RNA by both immunoprecipitated RNase H1 and RNase H2, ISIS 300861 (gap-disabled) did not elicit detectable cleavage of the target RNA by immunoprecipitated RNase H1 or RNase H2 in this assay.

Example 55

In Vitro Nuclease Assay

[0525] In a further embodiment, the ability of gap-disabled compounds to elicit target cleavage in subcellular fractions was evaluated. HeLa cell nuclear, nuclear membrane and cytosolic fractions were isolated as described previously (Dignam, et al., Nucleic Acids Research., 1983, 11, 1475-1489) and used to test the ability of gap-disabled oligomeric compounds to elicit target reduction. Following isolation of the subcellular fractions, the cleavage assay was performed as described for recombinant RNase H1.

[0526] Duplexes between the mouse glucagon receptor RNA and oligomeric compound were prepared as described herein, using as the oligomeric compounds ISIS 335033 (SEQ ID NO: 43, uniform 2'-deoxy), ISIS 335112 (SEQ ID NO: 43, gapmer), ISIS 300861 (SEQ ID NO: 43, gap-disabled) and ISIS 298683 (SEQ ID NO: 43, uniform 2'-MOE). Annealed duplexes (10 .mu.l) were incubated with 3 .mu.g of the HeLa cytosolic extract at 37.degree. C. The assay was also performed with a 4-fold higher concentration of cytosolic extract. Samples were collected at t=0 (reaction start time), 15, 60 and 180 minutes. The reaction was terminated by phenol/chloroform extraction and ethanol precipitated with the addition of 10 .mu.g of tRNA as a carrier. Pellets were resuspended in 10 .mu.l of denaturing loading dye and products were resolved on 12% denaturing acrylamide gels as described herein. Visualization of cleavage patterns by PhosphorImager.TM. detection revealed that while HeLa cytosolic extracts were capable of supporting target cleavage mediated by ISIS 335112 (gapmer) and ISIS 335033 (uniform 2'-deoxy) in a time-dependent manner, this fraction was unable to support target reduction by ISIS 300861 (gap-disabled). Additionally, ISIS 298683 (uniform 2'-MOE) was unable to direct cleavage in the cytosolic extracts.

[0527] The ability of ISIS 300861 (gap-disabled) and ISIS 335112 (gapmer) to mediate target cleavage was also tested in the nuclear fraction isolated from HeLa cells. In this assay, the mouse glucagon receptor target RNA contained a 3' phosphorothioate cap, to improve its resistance to exonuclease activity, which, as is known in the art, is present in nuclear extracts and results in non-specific degradation of the target RNA. Annealed duplexes (10 .mu.l) were incubated with 3 .mu.g of the HeLa nuclear extract at 37.degree. C. The assay was performed both in the presence and absence of beta-mercapoethanol. Samples were collected at t=0 (start of the reaction), 10 and 60 minutes. Resolution of the products on a denaturing polyacrylamide gel, followed by PhosphorImager.TM. detection, revealed that ISIS 300861 (gap-disabled) and ISIS 355112 (gapmer) elicited target cleavage in HeLa nuclear extracts in a time-dependent manner, both in the presence and absence of beta-mercaptoethanol. A four-fold higher concentration of nuclear extract was also able to support cleavage by both compounds.

[0528] The assay was also performed using HeLa nuclear membrane extract as source of RNase activity. Annealed duplexes (10 .mu.l) were incubated with 3 .mu.g of the HeLa nuclear membrane extract at 37.degree. C. Neither ISIS 331112 (gapmer) nor ISIS 335114 (gap-disabled) was able to elicit cleavage of the target RNA in HeLa nuclear membrane extracts.

[0529] Together, these data reveal that the enzyme activity responsible for the cleavage of duplexes formed between gap-disabled oligomeric compounds and target RNAs resides in the nuclear fraction of the cell, not in the cytosolic or nuclear membrane fractions.

[0530] In the nuclear extracts, comparison of the target RNA cleavage pattern to a molecular weight ladder revealed that cleavage of the target RNA occurred only at nucleobase positions complementary to a 2' deoxynucleotide of the gap-disabled oligomeric compound, i.e. the cleavage sites were positioned within the 2'-deoxynucleotide gaps. Furthermore, within the target site for ISIS 300861, cleavage occurred preferentially at guanines

Example 56

Influence of Divalent Cations on RNase Activity in Subcellular Extracts

[0531] Multiple RNase H-like activities exist in human cells, and these activities are differentially activated by magnesium and manganese (Wu et al., J. Biol. Chem., 2004, 279, 17181-17189). Thus, it was of interest to determine the influence of these divalent cations on the ability of RNase enzymes to cleave heteroduplexes comprising gap-disabled oligomeric compounds.

[0532] ISIS 300861 (SEQ ID NO: 43, gap-disabled) and ISIS 335112 (SEQ ID NO: 43, gapmer) were tested for their ability to direct RNase mediated cleavage in the presence of manganese or magnesium. Duplex formation and subcellular fractionation of HeLa cells were performed as described herein. The cleavage assay was also conducted as described herein, with the addition of 0.05 mM magnesium, 5 mM magnesium, 0.05 mM manganese or 5 mM manganese. The cleavage reaction was terminated at t=0 (start of the reaction), 15, 60 and 120 minutes, and samples from each of these timepoints were resolved on a denaturing polyacrylamide gel. Cleavage products were detected using a PhosphorImager.TM..

[0533] In nuclear extracts, prepared as described herein, both magnesium- and manganese-dependent degradation of ISIS 300861 (gap-disabled) and ISIS 335112 (gapmer) heteroduplexes was observed. The cleavage activity in the presence of 0.05 mM manganese was approximately equal to that observed in the presence of 5 mM magnesium, demonstrating that manganese is more effective than magnesium at enhancing RNase activity in HeLa cell nuclear extracts.

[0534] The influence of divalent cations on cleavage activity was similarly tested in cytosolic extracts. The assay was performed as described herein. In the presence of either 5 mM magnesium or 5 mM manganese, ISIS 300861 (gap-disabled) did not elicit cleavage of the target RNA. ISIS 335112 (gapmer) was, however, able to direct cleavage of the target RNA in cytosolic extracts.

[0535] The effects of divalent cations on cleavage by immunoprecipitated RNase H1 were also evaluated. Duplex formation between the target RNA and ISIS 300861(gap-disabled) or ISIS 335112 (gapmer) was conducted as described herein. Immunoprecipitation and the cleavage assay were performed as described herein, with the addition of 0.05 mM magnesium, 5 mM magnesium, 0.05 mM manganese or 5 mM manganese to the cleavage assay. ISIS 335112 (gapmer) resulted in target RNA cleavage in the presence of either divalent cation at all concentrations. In contrast to the results observed in the absence of divalent cation, the addition of 5 mM manganese allowed the gap-disabled compound ISIS 300861 to direct the cleavage of the target RNA by immunoprecipitated RNase H1 in a pattern consistent with that observed for gap-disabled cleavage activity in nuclear extracts. Coupled with the observation that without additional manganese, a gap-disabled compound was unable to utilize immunoprecipitated RNase H1 to effect target RNA cleavage, these data demonstrate that additional manganese is required for immunoprecipitated RNase H1 to cleave heteroduplexes formed between a gap-disabled oligomeric compound and a target RNA.

[0536] A similar assay was performed using immunoprecipitated RNase H2, however, neither the gap-disabled nor gapmer oligomeric compound elicited target RNA cleavage by immunoprecipitated RNase H2, regardless of the presence of a divalent cation in the cleavage assay.

[0537] Further tested was the effect of divalent cations on the activity of recombinant human RNase H1. The assay was performed as described herein, using ISIS 300861 as the gap-disabled compound and ISIS 335112 as the gapmer compound. Manganese at a concentration of 5 mM was added to the cleavage assay. In contrast to the results described for the activity of recombinant RNase H1 in the absence of additional manganese, in the presence of 5 mM manganese ISIS 300861 was able to direct cleavage of its target RNA by recombinant RNase H1. The cleavage pattern mimicked those observed for nuclear extracts and for immunoprecipitated RNase H1 in the presence of manganese. These data demonstrate that manganese is required for recombinant RNase H1 to cleave heteroduplexes formed between a gap-disabled oligomeric compound and a target RNA.

[0538] To extend the observation that the presence of manganese influences the potency of gap-disabled oligomeric compounds, the extent of cleavage and the rate at which it occurs were evaluated as a function of manganese concentration. Duplex formation between ISIS 300861 and the mouse glucagon target RNA was performed as described herein. A cleavage assay was performed as described herein using recombinant human RNase H1, with the addition of manganese at 0.5, 1, 5, 20 or 50 mM. To measure the rate at which cleavage occurs, reactions were terminated at t=0 (start of the reaction), 10, 60 and 180 minutes and the percentage of RNA cleaved was calculated as described herein, using the t=0 timepoint to normalize the data from the 10, 60 and 180 minute timepoints. The data are shown in Table 34.

TABLE-US-00035 TABLE 34 Dependence of RNA cleavage by recombinant RNase H1 on manganese concentration Time Concentration of manganese (mM) (minutes) 0.5 1 5 20 50 10 3 56 68 63 0 60 6 69 74 69 0 180 12 75 75 70 12

[0539] These data demonstrate concentration-dependent cleavage at 0.5 and 1 mM manganese, however, the addition of 5 or 20 nM manganese did not further increase target cleavage. The addition of 50 mM manganese inhibited cleavage of the target RNA.

[0540] A comparison of cleavage rates achieved by ISIS 335112 (gapmer) and ISIS 300861 (gap-disabled) was conducted. Duplexes formed with the target RNA and ISIS 335112 were cleaved at rates of 0.7 and 1.3 nM per minute in the presence of 50 and 500 uM manganese, respectively. Duplexes formed with the target RNA and ISIS 300861 were cleaved at 0.1 and 0.3 uM per minute at manganese concentrations of 50 and 500 uM, respectively. These data demonstrate that cleavage elicited by the gapmer oligomeric compound occurs at a higher rate than that elicited by the gap-disabled oligomeric compound.

Example 57

[0541] siRNA-Mediated Disruption of RNase H1 Activity: Influence on Gap-Disabled Oligomeric Compound Potency

[0542] In a further embodiment, the participation of RNase H1 in the cleavage of target RNA mediated by gap-disabled oligomeric compounds was tested following disruption of cellular RNase H1 mRNA by siRNAs. Because siRNAs elicit target reduction through mechanisms not dependent on RNase H1, the use of siRNAs to disrupt the expression of RNase H1 is a method by which the activity of RNase H1 can be reduced, while not interfering with the pathway through which it acts. In this assay, cells receive a first treatment with an siRNA to reduce RNase H1 mRNA, followed by a second treatment with a known or putative RNase Hl-dependent compound. The target RNA cleavage following the second treatment is used to assess whether the siRNA affected the enzyme activity stimulated by the addition of the oligomeric compound.

[0543] A549 cells were treated with 100 nM of an siRNA directed to RNase H1, comprised of the antisense strand with the sequence CUCAUCCUCUGUGGCAAACUU (SEQ ID NO: 218) annealed to the complementary sense strand (AAGUUUGCCACAGAGGAUGAG, SEQ ID NO: 219). Both strands are oligoribonucleotides with phosphodiester linkages throughout the compounds. As controls, cells were treated with 100 nM of the single-strand sense RNA (SEQ ID NO: 219) or were left untreated. Following 10 hours of treatment, RNase H1 mRNA expression was measured by quantitative real-time PCR and was reduced by 49% in cells treated with the RNase H1 siRNA. Untreated cells and cells treated with the control siRNA showed no reduction in RNase H1 mRNA expression. Cells were split into 96-well format cell culture plates at a density of 6000 cells per well and were cultured for an additional 10 hours. Next, cells were treated with ISIS 336848 (SEQ ID NO: 105) at 5, 10 or 30 nM. ISIS 336848 is a gap-disabled compound targeted to C-raf and having the motif 3-2-1-2-1-2-1-2-1-2-3; internucleoside linkages are phosphorothioate throughout the compound and all cytosines are 5-methylcytosines. C-raf mRNA was measured by quantitative real-time PCR as described herein. Untreated cells served as the control to which data were normalized. The data are presented in Table 35 as percentage reduction in C-raf mRNA.

TABLE-US-00036 TABLE 35 Gap-disabled mediated reduction of C-raf mRNA in A549 cells with lowered RNase H1 activity Reduction in C-raf mRNA Concentration of gap-disabled compound (nM) 5 10 30 Single-strand sense RNA 40 61 89 No siRNA 39 55 89 RNase H1 siRNA 32 48 83

[0544] These data demonstrate that, in comparison to cells treated with a control sense RNA or cells left untreated, the reduction in expression of RNase H1 mRNA results in a decrease in the ability of the gap-disabled oligomeric compound to result in cleavage of its target mRNA. For example, whereas a dose of 5 nM of ISIS 336848 results in 39% and 40% reductions in target mRNA in cells receiving no siRNA or single-strand sense RNA, respectively, C-raf mRNA is reduced by only 32% in cells in which RNase H1 has been reduced by siRNA treatment.

[0545] This assay was also performed in HeLa cells, in which either RNase H1 or RNase H2 was disrupted using siRNAs directed to the mRNA sequence encoding each respective enzyme. The siRNA directed to RNase H1 was comprised of SEQ ID NOs: 218 and 219. The siRNA directed to RNase H2 was comprised of the antisense strand with the sequence GGAGCCUUGCGUCCUGGGCTT (SEQ ID NO: 220), annealed to the complementary sense strand GCCCAGGACGCAAGGCTCCTT (SEQ ID NO: 221). SEQ ID NOs 220 and 221 are oligoribonucleotides 19 nucleobases in length each having a two-nucleobase overhang of deoxythymidine. In cells receiving no first treatment with siRNA, the second treatment with 5, 10 or 30 nM of ISIS 336848 (gap-disabled) resulted in 18, 32 and 75% reductions in C-raf mRNA. In cells in which RNase H2 was disrupted, a second treatment with 5, 10 or 30 nM of ISIS 336848 (gap-disabled) resulted in 23, 38 and 73% reductions in C-raf mRNA. Thus, disruption of RNase H2 did not significantly affect gap-disabled oligomeric compound activity. However, in cells in which RNase H1 was disrupted, a second treatment with 5, 10 or 30 nM of the gap-disabled oligomeric compound resulted in 14, 28 and 58% reductions in C-raf mRNA. These data illustrate that siRNA-mediated reduction of RNase H1 mRNA reduced the potency of the gap-disabled compound. Thus, gap-disabled compounds elicit target RNA cleavage through the activity of RNase H1.

Example 58

Overexpression of RNase H

[0546] In a further embodiment, RNase H overexpression in cultured cells was tested for its effects on the potency of gap-disabled oligomeric compounds. RNase H overexpression was accomplished using the RNase H full-length coding regions packaged in adenoviral vectors, which were prepared as previously described (Wu et al., J. Biol. Chem., 2004, 279, 17181-17189). An RNase H1 adenoviral vector was prepared using the full-length RNase H1 coding region. An RNase H2 adenoviral vector was prepared in the same manner, using the RNase H2 full-length coding region. An additional vector was prepared using a truncated human RNase H1 cDNA that encodes a protein lacking the 26 N-terminal amino acids; this construct is named RNase H1(-26). Two native isoforms of human RNase H1 exist in the cell: a full length RNase H1 and the truncated RNase Hl. The N-terminal 26 amino acids of human RNase H1 comprise a mitochondial localization signal, thus the full-length isoform is found predominantly in the cytosol and mitochondria and the truncated protein (lacking the localization signal) is found predominantly in the nucleus. When compared in the in vitro assays described herein, both isoforms behave similarly with respects to enzyme kinetics. A control vector, pLox, contained the shuttle vector used in preparation of the RNase H-containing viruses and lacked the inserted genes.

[0547] In this assay, HeLa cells were cultured in DMEM supplemented with 10% fetal bovine serum, 0.005 mg/mL insulin, 0.005 mg/mL transferring, 5 ng/mL selenium, 40 ng/mL dexamethasone (medium and all supplements from Invitrogen Corporation, Carlsbad, Calif.). Cells were plated at a density of approximately 6000 cells per well in 96-well plates and infected with RNase H1, RNase H2, RNase H1(-26) or pLox adenovirus at 200 plaque forming units per cell (pfu/cell). After 12 hours, cells transfected with each virus were collected for RNA isolation and real-time PCR quantitation of RNase H mRNA. The remaining cells were transfected with the gap-disabled compound ISIS 336848 (SEQ ID NO: 105) at concentrations of 15, 30 and 45 nM, using LIPOFECTINT.TM. as described herein. Cells were harvested 24 hours later, RNA was isolated and C-raf mRNA levels were measured using real-time PCR, as described herein. Real-time PCR measurements of RNase H1, RNase H2, RNase H1(-26) and C-raf were normalized using the housekeeping gene cyclophilin. The results of this assay are shown in Table 36. RNases H mRNA levels are shown as percent relative to RNase H expression in pLox-infected cells. C-raf mRNA levels are presented as percent reduction relative to cells that did not receive oligomeric compound treatment.

TABLE-US-00037 TABLE 36 Gap-disabled compound potency in cells overexpressing RNases H Virus pLox RNase H1 RNase H1(-26) RNase H2 RNase H 100% 2938% 801% 1216% level Dose of ISIS 336848 % Reduction in C-raf mRNA 15 nM 30 45 37 26 30 nM 54 55 56 46 45 nM 63 67 74 60

[0548] These data demonstrate that when RNase H1 is present at a level approximately 30 times higher than that in pLox-infected cells, treatment with a 15 nM dose of the gap-disabled compound resulted in a 45% reduction in C-raf mRNA, whereas target mRNA was reduced by only 30% in pLox-infected cells. Overexpression of RNase H1(-26) to levels approximately 8 times higher than that in p-Lox-infected cells also improved the potency of the gap-disabled compound. An excess of RNase H2 did not improve the activity of the gap-disabled compound. When the % reduction in C-raf mRNA is plotted against the base-10 logarithm of the gap-disabled compound concentration, an increase in gap-disabled compound activity is apparent at all oligomeric compound concentrations tested in this assay. Similar observations were made in cells expressing any of the RNases H at levels 5 to 7 times that of the p-Lox-infected cells. These data suggest that overexpression of either isoform improves gap-disabled oligomeric compound activity and that gap-disabled oligomeric compounds are active in both the nucleus and cytosol. These data further illustrate that gap-disabled compounds elicit target RNA cleavage through RNase Hi.

Example 59

In Vivo Analysis of Gap-Disabled Compounds Targeted to Mouse Glucagon Receptor

[0549] In a further embodiment, gap-disabled chimeric oligomeric compounds targeted to mouse glucagon receptor were tested for their effects on target reduction in vivo. The gap-disabled compounds were: ISIS 332866, ISIS 332868, ISIS 352426 and ISIS 352427 (all with the nucleotide sequence of SEQ ID NO: 43). Also tested were ISIS 180475 (SEQ ID NO: 43), a gapmer compound; ISIS 332867, also a gapmer compound; ISIS 335032 (SEQ ID NO: 43), an oligomeric compound uniformly comprised of 2'-deoxynucleotides and ISIS 298683 (SEQ ID NO: 43), an oligomeric compound uniformly comprised of 2'-MOE nucleotides. The motif of each compound is shown in Table 37 as described for other compounds herein. Male Balb/c mice, 6 to 7 weeks of age, received twice weekly intraperitoneal injections of approximately 1, 3 or 10 mg/kg of the compounds shown in Table 37. Saline-injected animals served as a control group and were injected in the same manner as the oligomeric compounds. Each treatment group contained 4 animals.

[0550] Liver RNA was analyzed for glucagon receptor expression levels by quantitative real-time PCR as described by other examples herein, using the housekeeping gene cyclophilin A to normalize RNA levels among samples. In Table 37, glucagon receptor mRNA expression levels are shown as percentage of saline-treated control glucagon receptor levels. A value less than or greater than 100 indicates a decrease or increase in mRNA expression, respectively. If present, "ND" indicates "not determined".

TABLE-US-00038 TABLE 37 Target reduction following treatment with chimeric oligomeric compounds targeted to mouse glucagon receptor % Control SEQ Dose of oligonucleotide ISIS # ID NO Motif 10 mg/kg 3 mg/kg 1 mg/kg 335032 43 Uniform 2'-deoxy 10 85 117 332866 43 3-5-4-5-3 27 53 115 332867 43 3-14-3 12 111 112 332868 43 3-3-2-4-2-3-3 40 77 107 352426 43 2-6-4-6-2 21 66 115 352427 43 2-7-2-7-2 9 48 122 298683 43 Uniform 2'-MOE 84 ND ND 180475 43 5-10-5 15 53 93

[0551] These results demonstrate that treatment with 3 mg/kg and 10 mg/kg doses of the gap-disabled compounds ISIS 332866, ISIS 332868, ISIS 352426 and ISIS 352427, in addition to the gapmer compound ISIS 180475 and the uniform 2'-deoxy compound ISIS 335032, inhibited mouse glucagon receptor mRNA expression in a dose-dependent manner in vivo. ISIS 332867 inhibited mouse glucagon receptor mRNA expression at the 10 mg/kg dose.

Example 60

In Vivo Analysis of Chimeric Oligomeric Compounds Targeted to FAS: Levin Rat Model

[0552] The Levin model is a polygenic model of rats selectively bred to develop diet-induced obesity (DIO) associated with impaired glucose tolerance, dyslipidemia and insulin resistance when fed a high-fat diet. The advantage of this model is that it displays traits more similar to human obesity and glucose intolerance than in animals that are obese/hyperinsulinemic due to genetic defects, for example, a defect in leptin signaling. In a further embodiment, the gap-disabled compound ISIS 304170 (SEQ ID NO: 60), targeted to rat fatty acid synthase (FAS), was tested for its effects on target reduction in the Levin rat model. Male Levin rats were purchases from Charles River Laboratories at approximately 8 weeks of age. Rats were fed a high-fat diet (60% fat) for 8 weeks, after which the animals were divided into three groups and treated with saline, ISIS 304170 or the gapmer ISIS 256899 (SEQ ID NO: 60). ISIS 256899, also targeted to rat FAS, was used as a positive control for target reduction. Treatments were administered subcutaneously at a dose of 25 mg/kg, twice weekly, for 8 weeks. Control groups consisted of animals on the high-fat diet receiving saline treatment and animals on a standard rodent diet receiving saline treatment. Each treatment group included 5 to 6 animals.

[0553] At the end of the 8 week treatment period, animals were sacrificed and liver was collected for FAS protein analysis and white adipose tissue (WAT) and brown adipose tissue (BAT) were collected for measurement of FAS mRNA expression. mRNA was measured by real-time PCR as described herein and were normalized to levels in saline treated animals that received a high-fat diet. Protein levels were measured by western blot as described herein, using an antibody recognizing rodent FAS (BD Transduction Laboratories of the BD Pharmingen Unit, San Diego, Calif.) and were normalized to levels in saline treated animals that received a high-fat diet. Data are shown in Table 38 and are expressed as percentage of high-fat diet saline control. If present, "ND" indicates "not determined". Also shown in Table 38 are serum cholesterol (mg/dL), triglyceride (mg/dL) and liver transaminase (ALT and AST, IU/L) levels, which were measured at the end of the study using routine clinical analyzer instruments (e.g. Olympus Clinical Analyzer, Melville, N.Y.).

TABLE-US-00039 TABLE 38 FAS, cholesterol and triglycerides in Levin rats treated with chimeric oligomeric compounds High High High Standard Fat Fat Fat Treatment Saline Saline ISIS ISIS 304170 256899 % FAS protein, Liver 110 100 55 39 % FAS mRNA, WAT ND 100 21 17 % FAS mRNA, BAT ND 100 5 6 Serum Cholesterol (mg/dL) 81 81 69 160 Serum Triglyceride (mg/dL) 269 377 104 607 ALT (IU/L) 79 73 158 61 AST (IU/L) 45 30 51 32

[0554] These data demonstrate that the gap-disabled compound ISIS 304170 resulted in a marked reduction in rat FAS mRNA expression in both white and brown adipose tissue. Furthermore, rat FAS protein levels were reduced in liver following treatment with ISIS 304170. FAS mRNA and protein levels were similar to those observed following treatment with the gapmer compound. Furthermore, cholesterol and triglycerides in Levin rats receiving a high-fat diet were markedly lowered by treatment with ISIS 304170, whereas ISIS 256899 did not lower cholesterol and triglycerides in Levin rats receiving a high-fat diet. AST and ALT levels were not at levels considered indicative of toxicity.

[0555] Plasma glucose concentrations were measured at 0 (beginning of study) and 8 (end of study) weeks of treatment by routine clinical analysis using a Y512700 Select.TM. Biochemistry Analyzer (YSI Inc., Yellow Spring, Ohio). Plasma insulin levels were measured at 0 and 8 weeks of treatment using an insulin ELISA kit (ALPCO Diagnostics, Windham, N.H.) according to the manufacturer's instructions. Plasma leptin levels were measured at 0 and 8 weeks using a rat leptin ELISA kit (Crystal Chem. Inc., Downer's Grove, Ill.). Leptin is a hormone that regulates appetite. Plasma insulin, glucose and leptin levels are shown in Table 39.

TABLE-US-00040 TABLE 39 Plasma leptin, glucose and insulin in Levin rats treated with chimeric oligomeric compounds Diet and Treatment Study High High High week Standard Fat Fat Fat Saline Saline 304170 256899 Plasma Leptin (ng/mL) 0 11 42 46 46 Plasma Leptin (ng/mL) 8 10 57 8 24 Plasma Glucose (mg/dL) 0 106 103 100 105 Plasma Glucose (mg/dL) 8 95 115 106 98 Plasma Insulin (ng/mL) 0 1.3 3.3 3.6 2.9 Plasma Insulin (ng/mL) 8 1.0 1.8 0.9 0.8

[0556] These data demonstrate that after 8 weeks, relative to animals receiving a high-fat diet and saline treatment, treatment with ISIS 304170 and ISIS 256899 lowered plasma leptin, glucose and insulin levels. ISIS 304170 lowered plasma leptin and insulin levels to those observed in rats on a standard diet. ISIS 256899 lowered plasma glucose levels to those observed in rats on a standard diet.

[0557] After 4 weeks of treatment, an insulin tolerance test was performed. After 7 weeks of treatment, a glucose tolerance test was performed. For the tolerance tests, a baseline tail blood glucose measurement was obtained, after which 1.0 g/kg glucose or 0.5 units/kg insulin was administered orally or intraperitoneally, respectively. Tail blood glucose levels were measured using a Glucometer.RTM. instrument (Abbott Laboratories, Bedford, Mass.) at 15, 30, 60, 90, 120, 150 and 180 minutes following the challenge with insulin and 30, 60, 90 and 120 minutes following the glucose challenge. Insulin sensitivity in the animals receiving ISIS 304170 and ISIS 256899 was similar to animals on a standard diet receiving saline treatment and was improved relative to saline-treated animals on a high-fat diet. Glucose tolerance was not improved by treatment with ISIS 304170 or ISIS 256899.

[0558] Body weight and food intake were measured weekly throughout the study. At the beginning of the study, animals on the high-fat diet weighed approximately 670 grams. Whereas the saline-treated rats maintained this weight throughout the treatment period, the body weights of rats treated with ISIS 304170 and ISIS 256899 dropped to approximately 500 g, the same body weight as the rats on a standard rodent diet, by the end of the study. Throughout the study, food intake among rats treated with ISIS 304170 and ISIS 256899 was approximately half that among saline treated rats. Thus, concomitant with a reduction in FAS mRNA and protein, body weight and food intake were lowered.

[0559] At the end of the study, liver and spleen weights, increases in which can indicate toxicity, were measured. Relative to saline-treated rats on a high-fat diet, liver weights were lower in rats receiving ISIS 304170 and slightly higher in rats receiving ISIS 256899. The converse was true for spleen weights, which were slightly raised in rats receiving ISIS 304170. Fat depot weights were also determined. Treatment with ISIS 304170 and ISIS 256899 prevented increases in brown adipose tissue and intra-abdominal white adipose tissue (both epididymal and perinephric fat) weights, which were all significantly raised in saline-treated rats on a high-fat diet.

[0560] Metabolic rate was measured after 4 weeks and 8 weeks of oligomeric compound treatment using indirect calorimetry in a metabolic chamber (Oxymax System, Columbus Instruments, Columbus, Ohio). No significant differenced in metabolic rates were observed when oligomeric compound-treated mice were compared to saline-treated mice.

[0561] This study in a rat model of diabetes and obesity illustrates that treatment with the gap-disabled compound ISIS 304170 reduces rat FAS protein expression. Concomitant reductions are observed in body weight, fat depot weight, food intake, plasma leptin, plasma insulin, serum cholesterol, serum triglycerides and insulin sensitivity. Thus, this compound has applications in the treatment of diabetes, obesity and related conditions.

Example 61

In Vivo Analysis of Chimeric Oligomeric Compounds Targeted to FAS: Mouse Model of Diabetes and Obesity

[0562] Leptin is a hormone produced by fat that regulates appetite. Deficiencies in this hormone lead to obesity in animals. ob/ob mice have a mutation in the leptin gene which results in obesity and hyperglycemia. As such, these mice are a useful model for the investigation of obesity and diabetes and treatments designed to treat these conditions. ob/ob mice have higher circulating levels of insulin and are less hyperglycemic than db/db mice, which harbor a mutation in the leptin receptor. In accordance with the present invention, the oligomeric compounds of the invention are tested in the ob/ob model of obesity and diabetes.

[0563] Seven-week old male C57B1/6J-Lep ob/ob mice (Jackson Laboratory, Bar Harbor, Me.) were fed a diet with a fat content of approximately 11% and were subcutaneously injected with ISIS 304171 (SEQ ID NO: 59) or ISIS 148548 (SEQ ID NO: 59) at a dose of 25 mg/kg two times per week for 8 weeks. Saline-injected animals served as a control group. Each treatment group contained 8 mice.

[0564] After the treatment period, mice were sacrificed and FAS protein levels were measured by western blot in liver and white adipose tissue (WAT), using an antibody that recognizes mouse FAS (BD Transduction Laboratories of the BD Pharmingen Unit, San Diego, Calif.). Relative to FAS protein levels in saline-treated mice, treatment with ISIS 304171 reduced protein expression by 66% in liver and by 62% in white adipose tissue. Treatment with ISIS 148548 resulted in 93% and 81% reductions in fatty acid protein in liver and white adipose tissue, respectively.

[0565] To assess the physiological effects resulting from reduction of FAS expression, the mice were further evaluated at the end of the treatment period for serum triglycerides, serum cholesterol, and serum transaminase levels. Triglycerides, cholesterol and transaminases were measured by routine clinical analyzer instruments (e.g. Olympus Clinical Analyzer, Melville, N.Y.). Triglyceride levels were 173, 101 and 118 mg/dL in mice receiving treatment with saline, ISIS 304171 or ISIS 148548, respectively. Cholesterol levels were 312, 221 and 218 mg/dL in mice receiving treatment with saline, ISIS 304171 or ISIS 148548, respectively. These data demonstrate that treatment with either the gap-disabled compound or gapmer compound targeted to FAS reduced both cholesterol and triglyceride levels in ob/ob mice on a high fat diet. Also reduced were the liver transaminases ALT and AST (measured in international units/liter, or IU/L), indicating an improvement in liver function following treatment of ob/ob animals with a gap-disabled or gapmer compound. AST levels were 511, 277 and 334 IU/L in mice receiving treatment with saline, ISIS 304171 or ISIS 148548, respectively. ALT levels were 751, 481 and 344 IU/L in mice receiving treatment with saline, ISIS 304171 or ISIS 148548, respectively.

[0566] Body weight was monitored throughout the study. Body weights in all 3 treatment groups increased steadily throughout the first 5 weeks. After 6, 7 and 8 weeks of treatment, the average body weight in ISIS 304171-treated mice was 59 grams. The average body weight in ISIS 148548-treated mice after 6, 7 and 8 weeks of treatment was 58 grams. However, in the saline-treated mice, the average body weight at 6, 7 and 8 weeks was 64 grams. Thus, treatment with the gap-disabled or gapmer compound targeted to FAS resulted in reduced weight gain in ob/ob mice on a high fat diet.

[0567] Metabolic rate was measured after 5 weeks of oligomeric compound treatment using indirect calorimetry in a metabolic chamber (Oxymax System, Columbus Instruments, Columbus, Ohio). No significant differenced in metabolic rates were observed when oligomeric compound-treated mice were compared to saline-treated mice.

[0568] Adipose tissue weight was also measured at the end of the study. No significant differences were observed when the oligomeric compound-treated mice were compared to saline-treated mice.

[0569] The effects of target inhibition on glucose metabolism were also evaluated. After 7 weeks of treatment with oligomeric compounds, an oral glucose tolerance test was performed. Mice received an oral dose of approximately 1 g/kg of glucose, and blood glucose levels were measured at 30 minute intervals for up to 2 hours. Glucose levels are measured using a YSI glucose analyzer (YSI Scientific, Yellow Springs, Ohio). No differences in glucose tolerance were observed when oligomeric compound-treated mice were compared to saline-treated mice.

[0570] These data demonstrate that the gap-disabled compound ISIS 304171, like the gapmer compound ISIS 148548, reduced FAS expression in the livers of ob/ob mice. Furthermore, reductions were observed in serum cholesterol and triglycerides, body weight and liver transaminases.

[0571] Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference (including, but not limited to, journal articles, U.S. and non-U.S. patents, patent application publications, international patent application publications, gene bank accession numbers, and the like) cited in the present application is incorporated herein by reference in its entirety.

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 221 <210> SEQ ID NO 1 <211> LENGTH: 12 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 1 cgcgaauucg cg 12 <210> SEQ ID NO 2 <211> LENGTH: 12 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 2 gcgcuuaagc gc 12 <210> SEQ ID NO 3 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 3 cgagaggcgg acgggaccg 19 <210> SEQ ID NO 4 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 4 cgagaggcgg acgggaccgt t 21 <210> SEQ ID NO 5 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 5 ttgctctccg cctgccctgg c 21 <210> SEQ ID NO 6 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 6 gctctccgcc tgccctggc 19 <210> SEQ ID NO 7 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 7 tccgtcatcg ctcctcaggg 20 <210> SEQ ID NO 8 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 8 gtgcgcgcga gcccgaaatc 20 <210> SEQ ID NO 9 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 9 atgcattctg cccccaagga 20 <210> SEQ ID NO 10 <211> LENGTH: 1115 <212> TYPE: DNA <213> ORGANISM: M. spretus <400> SEQUENCE: 10 aagagtggct cctgtaggca gcacggactt gaacaaccag actcctgtag acgtgttcca 60 gaacttacgg aagcacccac gatggacccc agatgcacca tgggcttggc aatccttatc 120 tttgtgacag tcttgctgat ctcagatgct gtttccgtgg agacgcaagc ttatttcaat 180 gggactgcat atctgccgtg cccatttaca aaggctcaaa acataagcct gagtgagctg 240 gtagtatttt ggcaggacca gcaaaagttg gttctgtacg agcactattt gggcacagag 300 aaacttgata gtgtgaatgc caagtacctg ggccgcacga gctttgacag gaacaactgg 360 actctacgac ttcacaatgt tcagatcaag gacatgggct cgtatgattg ttttatacaa 420 aaaaagccac ccacaggatc aattatcctc caacagacat taacagaact gtcagtgatc 480 gccaacttca gtgaacctga aataaaactg gctcagaatg taacaggaaa ttctggcata 540 aatttgacct gcacgtctaa gcaaggtcac ccgaaaccta agaagatgta ttttctgata 600 actaattcaa ctaatgagta tggtgataac atgcagatat cacaagataa tgtcacagaa 660 ctgttcagta tctccaacag cctctctctt tcattcccgg atggtgtgtg gcatatgacc 720 gttgtgtgtg ttctggaaac ggagtcaatg aagatttcct ccaaacctct caatttcact 780 caagagtttc catctcctca aacgtattgg aaggagatta cagcttcagt tactgtggcc 840 ctcctccttg tgatgctgct catcattgta tgtcacaaga agccgaatca gcctagcagg 900 cccagcaaca cagcctctaa gttagagcgg gatagtaacg ctgacagaga gactatcaac 960 ctgaaggaac ttgaacccca aattgcttca gcaaaaccaa atgcagagtg aaggcagtga 1020 gagcctgagg aaagagttaa aaattgcttt gcctgaaata agaagtgcag agtttctcag 1080 aattcaaaaa tgttctcagc tgattggaat tctac 1115 <210> SEQ ID NO 11 <211> LENGTH: 2262 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 11 ggtggccgcg cttcgctggc tttctgctca tctagggtgg cagcggctac ctacctcagc 60 tctcgccctg ctgccgccac ggcctgggcg ctgtccctca gctcccggag ctcagcgcga 120 agccctggcc ccggcggccg gggcatgggt caggggcgcg gcgtgaggcg gctttctgca 180 cggccgtgac gtgcattggc ttcagcatga agaccctcat cgccgcctac tccggggtcc 240 tgcggggtga gcgtcgggcg gaagctgccc gcagcgaaaa caagaataaa ggatctgccc 300 tgtcacgcga ggggtctggg cgatggggca ctggctccag catcctctca gccctccaag 360 acatcttctc tgtcacctgg ctcaacagat ctaaggtgga aaaacagctg caggtcatct 420 cagtactaca atgggtccta tccttcctgg tgctaggagt ggcctgcagt gtcatcctca 480 tgtacacctt ctgcacagac tgctggctga tagctgtgct ctacttcacc tggctggcat 540 ttgactggaa cacgcccaag aaaggtggca ggagatcgca gtgggtgcga aactgggccg 600 tgtggcgcta cttccgagac tactttccca tccagctggt gaagacacac aacctgctga 660 ccaccaggaa ctatatcttt ggataccacc cccatggcat catgggcctg ggtgccttct 720 gtaacttcag cacagaggct actgaagtca gcaagaagtt tcctggcata aggccctatt 780 tggctacgtt ggctggtaac ttccggatgc ctgtgcttcg cgagtacctg atgtctggag 840 gcatctgccc tgtcaaccga gacaccatag actacttgct ctccaagaat gggagtggca 900 atgctatcat catcgtggtg ggaggtgcag ctgagtccct gagctccatg cctggcaaga 960 acgcagtcac cctgaagaac cgcaaaggct ttgtgaagct ggccctgcgc catggagctg 1020 atctggttcc cacttattcc tttggagaga atgaggtata caagcaggtg atctttgagg 1080 agggttcctg gggccgatgg gtccagaaga agttccagaa gtatattggt ttcgccccct 1140 gcatcttcca tggccgaggc ctcttctcct ctgacacctg ggggctggtg ccctactcca 1200 agcccatcac caccgtcgtg ggggagccca tcactgtccc caagctggag cacccgaccc 1260 agaaagacat cgacctgtac catgccatgt acatggaggc cctggtgaag ctctttgaca 1320 atcacaagac caaatttggc cttccagaga ctgaggtgct ggaggtgaac tgacccagcc 1380 ctcgcgtgcc agctcctggg agggacgact gcagatcctt ttctaccgag ttcttgagtg 1440 cattttgttc tgtaaatttg gaagcgtcat gggtgtctgt gggttattta aaagaaatta 1500 taatgtgtta aaccattgca atgttagatg tttttttaag aagggaagag tcagtatttt 1560 aagctcactt ctagtgtgtc ctgctcaagg tggaggctga tatttatggg ccttggtggt 1620 ttcttaccca ccccttctag cgttccccag acgacagaca cttggccctg gctagctggg 1680 caagggcagt ccttagtgac tccagggatt cttgagaggc agaggccatg tcccacccgt 1740 ggctgcaggt cgggttcctc gtaccaaggg gaggctgagg gcacagctgg ccccacttgg 1800 ggagggtaga taacatctgg actgcccggc ttgggtctct gctcctcacc ctagccctct 1860 tctccaatct gagcctaccc tggcctcctg tctcctggct agggacacgg ctgtcccaca 1920 ggtgccgtct tgggttatct cgctgctgtt ggctggtttc actctggagg ttggcaccat 1980 ggacacagct cagcgttgct ctggcgcata tcctcctgag ccacacccca agtctggtgt 2040 gaggaagggc ttctcttctc ttcacagagg tgcctggctt cctgtgcagc acactgggtc 2100 caggacagga ggcccccccc ccaaaccaag cctcacgtgt gtgcctttat gaggcgttgg 2160 gagaaagcta ccctcctgtg tattctgttt tctccatgag attgttgtgc catgtcacac 2220 ttttgtatat tcctagacta ataaatggaa acaagaacag cc 2262 <210> SEQ ID NO 12 <211> LENGTH: 8363 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 12 tcctcgcttg tcgtctgcct ccagagccca gacagagaag agccatggag gaggtggtga 60 tagccggtat gtcggggaag ttgcccgagt cagagaacct acaggagttc tgggccaacc 120 tcattggtgg tgtggacatg gtcacagatg atgacaggag atggaaggct gggctctatg 180 gattacccaa gcggtctgga aagctgaagg atctctccaa gttcgacgcc tccttttttg 240 gggtccaccc caagcaggca cacacaatgg acccccagct tcggctgctg ttggaagtca 300 gctatgaagc aattgtggat ggaggtatca acccagcctc actccgagga acgaacactg 360 gcgtctgggt gggtgtgagt ggttcagagg catccgaggc ccttagcaga gatcccgaga 420 cgcttctggg ctacagcatg gtgggctgcc agcgtgcaat gatggccaac cggctctctt 480 tcttcttcga cttcaaagga ccaagcattg ccctggacac agcctgctcc tccagcttgc 540 tggcactaca gaatgcctac caggccatcc gtagtgggga atgccccgcg gcccttgtgg 600 gtgggatcaa cctgctcctg aagccgaaca cctctgtgca gttcatgaag ctgggcatgc 660 tcagcccgga cggcacctgc agatcctttg atgattcagg gagtggatat tgtcgctctg 720 aggctgttgt agcagttctg ctgactaaga agtccctggc tcggcgggtc tatgccacga 780 ttctgaatgc cggcaccaat acagatggca gcaaggagca aggtgtaaca ttcccctctg 840 gagaagtcca agaacaactc atctgctctc tgtatcagcc agctggtctg gccccggagt 900 cgcttgagta tattgaagcc catggcacgg gcaccaaggt gggtgacccc caggaactga 960 atggcattac tcggtccctg tgcgccttcc gccaggcccc tctgttaatt ggctccacca 1020 aatccaacat gggacaccct gagcctgcct ctgggcttgc agccctgacc aaggtgctgt 1080 tatccctgga gcatggggtc tgggccccta acctgcactt ccacaacccc aaccctgaga 1140 tcccagcact tcttgatggg cggctgcagg tggtcgatag gcccctgcct gttcgtggtg 1200 gcaacgtggg catcaactca tttggcttcg gaggctccaa tgttcatgtc atcctccagc 1260 ccaacacacg gcaggcccct gcgcccactg cacacgctgc ccttccccat ttgctgcacg 1320 ccagtggacg caccttagag gcagtgcagg acctgctgga acagggccgc cagcacagcc 1380 aggacctggc ctttgtgagc atgctcaatg acattgcggc aacccctaca gcagccatgc 1440 ccttcagggg ttacactgtg ctaggtgttg agggccgtgt ccaagaagtg cagcaagtgt 1500 ccaccaacaa gcgcccactc tggttcatct gctcagggat gggcacgcag tggcgcggga 1560 tggggctgag cctcatgcgc ctggacagct tccgtgagtc tatcctgcgc tccgatgagg 1620 ctgtgaagcc gttgggagtg aaagtgtcag atctgctgtt gagcacagat gagcgcacct 1680 ttgatgacat cgtgcatgcc tttgtgagcc tcactgccat ccagattgcc ctcatcgacc 1740 tactgacttc tgtgggactg aaacctgacg gcatcattgg gcactccttg ggagaggttg 1800 cctgtggcta tgcagatggc tgtctctccc agagagaggc tgtgcttgca gcttactggc 1860 gaggccagtg catcaaagat gcccacctcc cgcctggatc catggcagct gttggtttgt 1920 cctgggagga atgtaaacag cgctgccccg ctggcgtggt gcctgcctgc cacaactctg 1980 aggacaccgt gaccatctct ggacctcagg ctgcagtgaa tgaatttgtg gagcagctaa 2040 agcaagaagg tgtgtttgcc aaggaggtac gaacaggagg cctggctttc cactcctact 2100 tcatggaagg aattgccccc acattgctgc aggctctcaa gaaggtgatc cgggaaccac 2160 ggccgcgctc ggctcgatgg ctcagcacct ctatccctga ggcccagtgg cagagcagcc 2220 tggcccgcac atcttctgcc gagtacaatg tcaacaacct ggtgagccct gtgctcttcc 2280 aggaagcact gtggcacatc cctgagcatg ccgtggtgct ggagattgcg ccccacgcac 2340 tgttgcaggc tgtcctgaag cgaggcgtga agtccagctg caccatcatt cccttgatga 2400 agagggatca taaagataac ttggagttct ttctcaccaa ccttggcaag gtgcacctca 2460 caggcatcaa tgtcaaccct aacgccttgt tcccacctgt ggagttcccg gctccccgag 2520 ggactcctct catctcccct cacatcaagt gggaccacag tcagacttgg gatgtcccgg 2580 ttgctgagga cttcccaaac ggctccagct cctcctctgc tacagtctac agcatcgacg 2640 ccagtcctga gtcgcccgac cactacctgg tagaccactg cattgacggc cgggtcatct 2700 tccctggcac tggctacctg tgcctggtgt ggaagacact ggctcgcagc ctgggcttgt 2760 ccctagaaga gacccctgtg gtatttgaga atgtgtcgtt tcatcaggcc actatactac 2820 ccaagacagg aaccgtggcg ctggaggtga ggctgctaga ggcctcccat gcctttgagg 2880 tgtctgacac tggcaatctg attgtgagcg gaaaagtgta cctgtgggaa gacccgaact 2940 ccaagttatt cgaccaccca gaagtcccaa caccccctga gtctgcatcg gtctcccgcc 3000 tgacccaggg agaagtatac aaggagctgc ggctgcgtgg ctatgattat ggccctcagt 3060 tccagggcat ctgtgaggcc acccttgaag gtgaacaagg caagctgctc tggaaagata 3120 actgggtgac cttcatggac acaatgctgc aggtatccat tctgggttct agccagcaga 3180 gtctacagct acctacccgt gtgaccgcca tctatatcga ccctgccacc caccgtcaga 3240 aggtgtacag gctgaaggag gacactcaag tggctgatgt gacaacgagc cgctgtctgg 3300 gcataacggt ctctggtggt atccacatct caagactaca gacgacagca acctcacggc 3360 ggcagcaaga acagctggtc cccaccttgg aaaagttcgt tttcacaccg cacatggagg 3420 ctgagtgcct gtctgagagc actgccctgc agaaggagct gcaactgtgc aagggtctgg 3480 cacgggctct gcagaccaag gccacccagc aagggctgaa ggcggcaatg cttgggcaag 3540 aggaccctcc acagcacggg ctgcctcgac tcctggcagc tgcttgccag ttgcagctca 3600 acgggaacct gcagctggag ctgggagaag cgctggctca agagaggctc ctgctgccag 3660 aagaccctct gatcagtggc ctcctcaact cccaggccct caaggcctgc gtagacacag 3720 ccctggagaa cttgtctact ctcaagatga aggtggcaga ggtgctggct ggagaaggcc 3780 acttgtattc ccgaatcccg gcactgctca acacccagcc catgctacaa ctggaataca 3840 cagccaccga ccggcacccc caggccctga aggatgttca gaccaaactg cagcagcatg 3900 atgtggcgca gggccagtgg aacccttccg accctgcgcc cagcagcctg ggtgcccttg 3960 accttctggt gtgcaactgt gcattagcca ccctggggga tccagccttg gccctggaca 4020 acatggtagc tgccctcaag gaaggtggtt tcctgctagt gcacacagtg ctcaaaggac 4080 atgcccttgg ggagaccctg gcctgcctac cctctgaggt gcagcctgcg cccagcctcc 4140 taagccagga ggagtgggag agcctgttct cgaggaaggc actacacctg gtgggcctta 4200 aaaggtcctt ctacggtact gcgctgttcc tgtgccggcg agccatccca caggagaaac 4260 ctatcttcct gtctgtggag gataccagct tccagtgggt ggactctctg aagagcactc 4320 tggccacgtc ctcctcccag cctgtgtggc taacggccat ggactgcccc acctcgggtg 4380 tggtgggttt ggtgaattgt ctccgaaaag agccgggtgg acaccggatt cggtgtatcc 4440 tgctgtccaa cctcagcaac acatctcacg cccccaagtt ggaccctggc tctccagagc 4500 tacagcaggt gctaaagcat gacctcgtga tgaacgtgta ccgggacggg gcctggggtg 4560 ccttccgtca cttccagtta gagcaggaca agcccaagga gcagacagcg catgcctttg 4620 taaacgtcct cacccgaggg gacctcgcct ccatccgctg ggtctcctcc cccctgaagc 4680 acacgcagcc ctcgagctca ggagcacagc tctgcactgt ctactacgcc tcactgaact 4740 tccgagacat catgctggcc acgggcaagc tgtcccctga tgccattcca ggtaaatggg 4800 ccagccgaga ctgcatgctc ggcatggagt tctcaggccg ggataggtgt ggccggcgtg 4860 tgatggggct ggttcctgca gaaggcctgg ccacctcagt cctgctatca tctgacttcc 4920 tctgggatgt accctccagc tggaccctgg aggaggcggc ctctgtgccc gtcgtctata 4980 ccactgctta ctactcgtta gtggttcgcg ggcgcatcca gcgtggggag accgtgctca 5040 tccactcagg ttcaggtggt gtgggccaag cggccatttc cattgccctc agtctgggct 5100 gccgcgtctt caccactgtg ggctctgcag agaagcgagc atacctccag gccaggttcc 5160 ctcagcttga tgacaccagc tttgccaact cgagggacac atcatttgag cagcacgtgt 5220 tactgcacac aggtggcaaa ggggtcgacc tggtcctcaa ctcactggca gaagagaagc 5280 tgcaggccag tgtgcggtgc ttggctcagc atggtcgctt cttagagatt ggcaaatttg 5340 atctttctaa caaccaccct ctgggcatgg ctatcttctt gaagaacgtc actttccatg 5400 ggatcctgct ggacgccctt tttgaggagg ccaatgacag ctggcgggag gtggcggcac 5460 tcctgaaggc tggcattcgt gatggagtcg tgaagcccct caagtgcaca gtgtttccca 5520 aggcccaggt ggaagatgcc ttccgctaca tggctcaggg gaaacacatt ggcaaagtcc 5580 ttgtccaggt acgggaggag gagcctgagg ctgtgctgcc aggggctcag cccaccctga 5640 tttctgccat ctccaagacc ttctgcccag cccataagag ttacatcatc actggtggcc 5700 taggtggctt tggcctggag ctggcccggt ggctcgtgct tcgcggagcc cagaggcttg 5760 tgctgacttc ccgatctgga atccgcaccg gctaccaagc caagcacatt cgggagtgga 5820 gacgccaggg catccaagtg ctcgtgtcaa caagcaacgt gagctcactg gagggggccc 5880 gtgctctcat cgccgaagcc acaaagctgg ggcccgttgg gggtgtcttc aacctggcca 5940 tggttttgag ggatgccatg ctggagaacc agaccccaga gctcttccag gatgtcaaca 6000 agcccaaata caatggcacc ctgaaccttg acagggcaac ccgggaagcc tgccctgagc 6060 tggactactt tgtggccttc tcctctgtaa gctgcgggcg tggtaatgct ggccaaacta 6120 actacggctt cgccaactct accatggagc gtatatgtga acagcgcagg cacgatggcc 6180 tcccaggcct tgccgtgcag tggggtgcca ttggtgacgt gggcattgtc ctggaagcga 6240 tgggcaccaa tgacacagtc atcggaggta cgctgcctca gcgcatctcc tcctgcatgg 6300 aggtactgga cctcttcctg aatcagcccc acgcagtcct gagcagcttt gtgctggcag 6360 agaagaaagc tgtggcccat ggggacgggg acacccagag ggatctggtg aaagctgtag 6420 cacacatcct aggcatccga gacctcgcag gtattaacct ggacagcacg ctggcagacc 6480 tcggcctgga ctcgctcatg ggtgtggaag ttcgtcagat cctggaacga gaacacgatc 6540 tggtgctgcc catgcgtgag gtgcggcagc tcacgctgcg gaaacttcag gaaatgtcct 6600 ccaagactga ctcggctact gacacgacag cccccaagtc caggagtgac acgtctctga 6660 agcagaacca actgaacctg agcacactgc tggtgaaccc tgagggtcct accctaaccc 6720 agctcaactc ggtgcagagc tctgagcggc ctctgttcct tgtgcacccc attgagggtt 6780 ccaccaccgt gttccacagt ctggctgcca agctcagtgt gcccacctac ggcctgcagt 6840 gcacccaagc tgcccccctg gatagcattc cgaacctggc tgcctactac atagattgca 6900 tcaagcaagt gcagcctgag ggaccctacc gcatagctgg gtactcattt ggagcctgtg 6960 tagccttcga gatgtgctcc cagctgcagg cccagcaggg cccagccccg acccacaaca 7020 acctcttcct gtttgacggc tcacacacct acgtgttggc ctacacccag agctaccggg 7080 caaagatgac cccaggctgt gaagccgagg ccgaggctga ggccttatgc ttcttcataa 7140 agcagtttct tgatgtggaa cacagcaagg tgctggaggc cctgctgcca ctgaagagcc 7200 tggaagatcg ggtggctgcc tccgtggacc ttatcactaa gagtcaccac agcctggacc 7260 gccgagagct gagctttgct gccgtgtcct tctaccacaa gctccgggca gctgatcagt 7320 ataagcccaa ggccaagtac catggcaacg tgacactgct gcgtgccaag acaggcggca 7380 cctatggcga ggacttgggt gctgactaca acctctccca ggtgtgtgac gggaaggtgt 7440 ctgtgcacat cattgagggt gaccaccgca cactgctgga gggcagtggc ctggaatcca 7500 tcatcaacat catccatagc tccctggctg agccacgagt gagtgtacgg gagggctaga 7560 cctgccgacc accatgaagc cacgctccac acctgccacc agagatgctc cgatccccac 7620 cacaccctga gtgcaggaac tggggagggt cctgctggtg ggacccctcc ccccagtggc 7680 ccagcaccac ccgctcccct ggtggctgct acaaacagac catcacgcgt gtgtttccca 7740 gccgcgtagt ggggttccca gagccactga cttggagaca ccctggtctg tgaagagtca 7800 gtggaggcag gagccaaact gagccttttc taccgtgtgg catttgccac gctggtcgtt 7860 tctccattaa attctcatat ttattgcatt gctgggaaag acccccaggg gtgactcatt 7920 ccagaacccc ctaaaatggg agaagccatg tggggaagat ttctgggaaa gtttctagac 7980 tcaatacaca ggctgctggc tggagcccct ttttgtcttg tcctgtccct gctcactgca 8040 gggcaggata tggagagggc tggttcccag ggaacaagga ccccagcaga cactgtagcc 8100 cgtggccctt ggtccccagc atccccggct gccccatgat gcagggccat cctgactctg 8160 cggaccgcac cgggcactga ctgtctgttt tccaagacga aaatgatgct tgggttttga 8220 cttttctgca gctgtcagtg tgaagaagtg tctggactgt gtcattttta caccaacctg 8280 gtaaaaatgc tgctcttgat gctctcctga tcccacaatt aaactgcacg tgagcgaaaa 8340 aaaaaaaaaa aaaaaaaaaa aaa 8363 <210> SEQ ID NO 13 <211> LENGTH: 23713 <212> TYPE: DNA <213> ORGANISM: R. norvegicus <400> SEQUENCE: 13 ggtacctcct tcccccacac agggaggact gtctaaagag aggccaccaa gaagagtgtc 60 ctgttcttcc tttaactaga cctacttagg aacagctcaa gtaagtgtgt ctagctcttg 120 gtgccagtta gaagctactt gtctgacact ggcctgagtc atgaacagct ccactgtgac 180 cactggttag atcaggctag ttccttcctt ggcctttgct cctacctggc tgggccaggt 240 cggcagcaag aggacctagc atggagccct tctatgattc ctgccctcca tgatgccttc 300 tggaagactt agaggagaag agccatgtga tatggttagc tggtgctggg aggaacatgt 360 gtataagagg agggtggtct aggtttggag aaccaggcat agctagcagg tgtcctcagg 420 atcctgagtc agcacagcct tgtcctgcag gagctagggc agaaatgacc ctaatgaggt 480 tgctgcttct aaatgtttca aaaagttcct tcctcagaaa gctgggcatg gtatcacata 540 ctgcgttctc acaagcctga agcaagagga ttgccatgac tccagcctgc attacaaagc 600 aagaccctga tttaaaagaa accaaagaaa aagagaccca cacagtctca ggacagggag 660 gagggcagct cacttctctg gagcctatgc aagcactcag gctccatgcc cacagcacat 720 tagattctgc caggcactct gtggctctac tgactcttac cctacctacc ctgtgcccat 780 gcggcatgtt ccaggtccac gggagtcaca gagataggct cctcagctct ggacagacat 840 gcacataaga cagctgagct aagactggca agcagtgggc tgtgtcccca agacaccaga 900 ctctgctgta agatatagtg catggtgttg tgttgcatgc tcttaatccc tccacttggg 960 aggcagaggc aggtgtgtcc ctaatgtcta ggccaagcag tttacatagt gagttccagg 1020 taaaccagaa ctgcatagta gttcctgtct aaaaaggagg gaaaaaaaag tataaaaatg 1080 caaaagcccc agaagcttcc tgtctgctgg gccaggttgc cagggaggaa ggataggtct 1140 gtctgtgtgc ctgagggagg tgaaatagtt ttagaaaaga tagacattgg ggttggggat 1200 ttagctcagt ggtagagcgc ttgcctagga agcgcaaggc cctgggttcg gtccccagct 1260 ccgaaaaaaa gaaccaaaaa aaaaaaaaaa aaagataaga catttttagt atcaaagatt 1320 caaagtacac aaaagatcaa aagataaaga tgatcatcta caaaagctag tgggacttac 1380 tagtgggcta actagtgggg cttactaact agtggggctt actaactagt ggggcttact 1440 aactagtggg gcttactagc aggcccttac ccatgaagtc tgggttctag cagcagccgc 1500 agcagcggca ataaagtgac cactttgact acggctcaag tggactctgg cagagctgct 1560 ctaggcttta acctgtgcct gtgtgtgtgg tacagcttac cagacagtcc ttggcctgtc 1620 tgtgtcagaa gtgttcacga acactccctg tacacgcaag ccccaagcac aggacaactc 1680 actgaactct cgatgaggtg gcttggcttg aatgggaggt ggggccacct gcccccatgc 1740 ccttaggaaa tggttataac agctcagggt gttttgttca gtgctttctt ttgtttccag 1800 agcccagatt tctgtgcggt agggaagagg caggcccagg atcagttgaa gatatgtgaa 1860 gcctgtgccc acacagacct cctacaccct agtcaggacc caataccgtt gctgccactg 1920 gccagggcta gggcactccg gaggcctgct ggcctgtata ggctcctgca gagaaaagca 1980 gactgagtcc ttacaggctg ctgattatga tatgaccaac tctgggcaca tacccacctc 2040 cgtttcctgt gatcctaacc tacatctttt tctacttctt gcctgtagag tgtcccgcac 2100 ctctgggacc cagctgtttc caaaaggtca gccggagccc tgtccccaca caaagggtca 2160 gccggagccc tgtccccaca caaagggcct ttgctgtcaa agggctaaag atggaagctc 2220 agccaaaagc ctcacacccc agacccagca agtcgcatcc agcaaagcct gcaaactgcc 2280 agccacagcg gcacccaagg atccgcaact acaacctcaa ggactagatc tcagcctcct 2340 gcagggcact gcacaggggc ctccaccttg gtccacgggg cctgtgcatg tacaagttgg 2400 gagtgagtac acacataata cacaggtgga ctgtgacaca ggacagactc ccaaatgctg 2460 gcctgcctga tactaaagag aaattaaaac cctcctccat ctgcttggcc tgtgaagttg 2520 tctgtcttgt cctacttggg aaatgaagta tcaacatgca ggctagatcc tgggctggtc 2580 tctgccacct gcctgtgtca ccacccacag ccactgtgca ctgaccctgt cagtgacact 2640 attcttctct agaatctggt gggcagaata gagtggccac ctgcaaagta tgtccccaag 2700 gaacattgtg agagaggtcc tcccaggagc atgagcctgg ccgaggccct atctcagaaa 2760 tatactcatc tgccgactga aaacctcatc aagggacctg cctgaccatt cctgcccaca 2820 gtagatctta aagagggtca tggccttagc cttgctgggc ataagacaca cagggctgca 2880 ggggtggaag cagctcccag gtccaggttg ctgtgtgtcc ctgattaatc atgtgactct 2940 tacagcttca ttttgcatct gtgtaaaatc ctgatagtgg ttcccgctgg ctggctcaca 3000 tgtgtgggcc acacaaacat cacaagaaag cccacgctca gtaatgtggt cttgggacgc 3060 tagctgaaac cctcaggcct aggtatcaca caactgcaga tcactcttgc tgtgtctgta 3120 gtaggctgct ctcgaggtgc atacgccaag agacatagga tgatgtcttc acaacagccc 3180 acctaggcac actgtgcttt caagaccagc aagggcaatg gcaggccatc ttgatgtggc 3240 tctcccacat ccacatctgg cagtccactc tctttgctga gatgtagcct gcaacctcta 3300 tgggtaaaaa gatgagcaga gaagtctgct gaccccagca tcctcctctg cacaggccca 3360 tactctgcat tccagcctgc tctccttggt tacaacccct ccactgaaga ccccagtagc 3420 tgcagagggc agagctctgc tgaccaagta tggttagcca gcagcctggc cagcgagaag 3480 gcaaacacag ggcacctgga ggtggggtgg gacagctctg gctggcacat gcacaagcca 3540 tttataaaac tctcctaggc tgaccctgaa acccaaagac acaacaaagt gaagaccctc 3600 caatagagag agtgcaggac ctgggtcctg cactcctcac ctccatagaa tacacattac 3660 aacaagagat gccatcagta ggccatggaa caggccctaa agacacaggg gcactaatag 3720 gagaacttgg gggcaagccg gcatgtgggc agaatacacc tgccagtcct acaggctgcc 3780 cttcagggtc cccacttagc ctccttccac agagagcctg tggacagcca agctggagaa 3840 gctagaagcc agggttgaca agcaaggctc tgaggctctg gcttttgcta tagacatgca 3900 gtcaaggacc actgacacta ctccctcctt agcgcccccc ccccccaaag ccactgccca 3960 taaggttggt cttagtggcc tgggcctgta gtggaagggc agaaggaaag ggatcaactc 4020 tgagcagtct gtgtcttttt ggtcggtgag ttttcatcat ctcccgtccc caaattcgat 4080 aaccctttca aaagaggaat ttaaagggag ggagggtgag ggtcccggaa accagcaact 4140 cagggaggcg cgcagacgct cctttgttcc caccaggcgg gggaggggtg gtatcccgct 4200 cgccagatgg ccgcgcctgg acactgaacg gactcaggag accgcggcac gcgcccgtca 4260 gtgttcccta tcctgcctac tgctctcgtc cctgcccgca tcctggtctc caaggcggcc 4320 acagaaaggg tgggtgtctg agaaagctgg gccacgatga ccggtagtaa ccccgcctga 4380 ggcgccctcc gccagggtca acgaccgcgc ttgcgcgggg gcccgagaag cgctttgccg 4440 cttttgccgg cccatcaccc tattgcctag caacgcccac ccgcgcgcca ccattgggcc 4500 accgagaacg gcctcggtgt ccaattggtc tcgatgtgga gcaggccacg cccctcggct 4560 ctgcgcgcgc tacgatcacg gcgtggaatc gcagcgacac ggacctgttc tgttcccccg 4620 cgtggcccca gtgtcctcag tgcagttccc agtgtgacca agcacgcccg acccacactg 4680 cgcgcgcaca gtgcacacct ggccccggcc gcgggggtgg gggggtgaga gaaaggacag 4740 agatgagggc gtcgggatga gccccgcgtg gcccgcggga ggccgggggc ggggacggaa 4800 gcgggcgggg gctgcgcgtt ccttgtgctc cagcgcgcgc ctgtgcaggg tcccggctgg 4860 gggcggcgcg cgcgggcatc accccaccga cggcggcgcg ccgggtcccg gggcgcagcc 4920 ccgacgctca ttggcctggg cggcgcagcc aagctgtcag cccatgtggc gtggccgcgc 4980 ggggatggcc gcggtttaaa tagcgccggc gcggcctaga gggagccaga gagacggcag 5040 cagcgtcccg tccagttcgc ctgccgcgct cctcgcttgt cgtctgcctc cagatcccag 5100 acaggtacgc cgctgcgttc ggggttccgg gatggcaggc cggtgtcggg gtgccgcggc 5160 tccagtggga ggacaggcgg gcgcccatcc tcaacagccc tgcgctcaca aaagcgccgc 5220 cgcgcccctc cgacagccaa ccacccggct gtgcgccgcg gtccggccga gaggggcgcg 5280 ggaggggtgt gcggagagcc agcgcggcgg gccgctgtca cgtgggcgcc gcgccagccg 5340 ggtgcaggag gctgggtgcc tcgtggatgg ggccggggcc tccactctca tccggaggct 5400 ttggcagggc acaggaggcc gcggtggtac ccgggctcca gtttggagag gccagttgtg 5460 ggtctgggag cgcacgaggc cccaggggcc tcagcggaag tcatcagacc atccaggcct 5520 caccggctgg gtggcgcgga agccttctcc ttggactacg gctgcaaggc ctgaactgcc 5580 ctgggcaagt gccttaggga ccagaggatc tatcaaaccc ttcagctggc tcagccaggt 5640 tacaaggtgt tcgaccaaat ggcgagaggc ttctcctgtc ccggatccgc acctagttag 5700 gagtggtact ctaggtcgga tcttgctgaa aggatccgtt ggcaggggat cggtttgcct 5760 cagccctgct aggcctgagc actaagtagt cgggcctgtt ctctctgggt ccttaccatg 5820 cctggcgttc tggctggccc tgcagggcag tcagtctcca ccctcatcat gaaagggaag 5880 cgttggcttc cccgtggctt gaggtgagag tgtcccagac cctgcttctt gaagccccac 5940 ttctgtttgc aagttcctta tgattgggat ggagcaccca gtaggcaact ggagatcata 6000 tggtcccagg taactagcaa ggcatggtag ggtcaggcca ggtcatgtgt ctggaaggga 6060 ttaaaaacct cagaagtagc tatcccgtgc aagggaaccc gagcacccgg gctcatccat 6120 tgattatagc tgggtcctgc tagtttccac cactgggggg ctttctgagc cctttgctct 6180 cagaaagtca gggcctggct gtgaggtgtg ctacctgtgg attcaggtgg ctgtagctgg 6240 gaatgactct atgagggagg cccaccaggc tacctacctt cccccacaga gaagagccat 6300 ggaggaggtg gtgatagccg gtatgtccgg gaaattgccc gagtcagaga acctgcagga 6360 gttctgggcc aacctcattg gcggtgtgga catggtcaca gacgatgaca ggaggtggaa 6420 ggctggtgag tgtcccctcg ggatcaggca gcaggacaga ctgagagtct cacccaagat 6480 gcttctagag acagtgaact ccctgtagag ctgtgaggtt gagaaccggt tagaatgaga 6540 agggacaggt gtcttggttg gttccgcatg caagacaccc aaggtgggcc gtagaagagg 6600 actggccctt tggatctccc atctgtaacc tctgccctga gctggcggat agtgtctaag 6660 atgacgctca cacccagtgg attctaacag tgccatagag cagctagctc tacctgatgg 6720 gcaggtgtga gtcagcactg ggctggcctg gccagcctcg gagtaggcag agggtctccc 6780 agtcaggtcg gggttaccag ggggtgatcg ccagcctcac ttcctgctcc tacaggtttt 6840 gctttgggtc acccacatgt ggcggttttg gggctcctca ttagcagtga ggctgggtca 6900 ctctctggga accttcctcc aggagaggtt ggttccctgg cctcagactg tgatgttcca 6960 cagggctcta tgggttgcct aagcggtctg gaaagctgaa ggatctgtcc aagttcgacg 7020 cctccttttt tggggtccac cccaagcagg cacacacaat ggacccgcag ctccggctgc 7080 tgctggaagt cagctatgaa gctattgtgg acggaggtgg gtcattgggg tattattatt 7140 gcccttttta ggacttactg tcatgagggc tggggacgta gtccagtggg agagcacttg 7200 cctagtatgc acaaggacct gggaacatca tcatccccag tccaggaaaa ggaaacacaa 7260 caatgatacc ttcttggctc tgagatgtca agagctcaga gacaggcatg gatggcatgg 7320 gtccctctag ctatgtcccc aaccctgatg tagggccagt ggctcaggag gcgggggccc 7380 tgagcagggc acgggtttca caaccacaca cttagtgtcc caggcgcgcc ctgttacccc 7440 agttacttca ctccccgacg tctggttgtt cttggactga gggcggggct tacagcaggt 7500 agcactgcag gggctcagcc tcagctttgg caacaaccca gtcccactgg ctgtctctca 7560 ctctggatcc tgctgcttgg gtcatggacg tgtccccagg gatagaaggc cccatagtgg 7620 gcagccagtg tgggttagta tggcgggggt gagcttcagg ttggtagatg ctaattaacc 7680 ctgtacttga taaacagctt gatgtataac tgccctgggg tagagtagaa gaccagagga 7740 tgcaggatcc tggtaacctc ggtggtgaaa atgaaggtcc tcaccttggg cctgtctggc 7800 tgcccaggct ctatcaatgg ctgggcacag ctcccagggg gttacccact gtcctctgct 7860 ttcccagctt ggacacttgg tctttgtctt cttgtatctc cttatcacag cctgtcccag 7920 ggcaggctgc ccttggcact agagaactca ttggccagcg gcctctcgag acccaccagt 7980 aacaccagag cccgagggag ttgccctcag acaatgctgt cctctgtctt aactatagcc 8040 tcctatggtt gcagctctga cccagacctt agaggtccac tgtggcccct atggtacccc 8100 tctgacccaa acccatgtgg ttattgctgc ccccggcagg tatcaacccg gcctcactcc 8160 gaggaacaaa cactggtgtc tgggtgggtg tgagtggttc cgaggcgtcg gaggccctga 8220 gcagagatcc tgagactctt ctgggctaca gcatggtggg ctgccagaga gcaatgatgg 8280 ccaaccggct ctctttcttc ttcgacttca aaggtgggtg ggcagcccag ctctgggcac 8340 gacccagctg tatgtgcatt cacctacaca acccttttgg actcagactt ccttattcct 8400 ggggaaggca ctgagtgggg tactcacagc ccgggaggcg gggggtgtgg gacagcatct 8460 gcccaagggt acccacaccc actttatgac cttgtccaca ggacccagca ttgccctgga 8520 cacagcctgc tcctctagcc tactggcact acagaatgcc tatcaggcta tccgcagtgg 8580 ggagtgccct gctgccattg tgggcgggat caacctgctg ctaaagccta acacctctgt 8640 gcagttcatg aagctaggca tgctcagccc cgatggcacc tgcagatcct ttgatgattc 8700 aggtaaggtt ggcctgggta gggatcgtta ggctctactt tgcagggctc cagcctgtac 8760 cctgagtggc atctgggctc ctggtggtgt ggggaaggga ggacgtgtgc atgtatagac 8820 tcatagcaca caccccatca caccagagca cctagctgag gtgttgatct actctaggga 8880 acgggtattg ccgtgctgag gctgtcgtgg cagttctgct gactaagaag tccttggctc 8940 ggcgagtcta tgccactatt ctgaatgccg ggacgaacac agatggctgc aaggagcaag 9000 gtgggcatgg agggaaagag catggggaat ggggacgtgg agcacacaag gcttgacacc 9060 gtactgtacc attacccatc tccgtaggcg tgacattccc ctctggagaa gcccaggaac 9120 aactcatccg ttctctgtat cagccgggcg gtgtggcccc cgagtctctt gaatatattg 9180 aagcccatgg cacgggcacc aaggtgaaag ccctttccag cccatacctg ccactcctct 9240 atcctcacta gagggacctg gctgcagcct taacctactc tgtcccctgc aggtggggga 9300 cccccaggaa ctgaacggca ttactcggtc cctgtgtgct ttccgccaga gccctttgtt 9360 aattggctcc accaaatcca acatgggaca ccctgagcct gcctcggggc ttgcagccct 9420 gaccaaggtg agcaggctgg gggctctgag tcaagaatga tgtggatagg tctgtactgt 9480 gaccaccact tgacctaccc cggggctcct gcctgctcac caaccagccc tttggctgta 9540 ccgttgctga agtggcaggg agactgggta cactccctgt ggttgctgtg ctgacttaca 9600 tagcttctgg ctgaaggaaa cacttggctg cataaaggac aggtgcagtt ctgaggaagt 9660 atctaggcag ccaggtctag cagaatgccc cattctgaga tgaggagaga ggagcgagcc 9720 agtgtctgat ctggtgtgtt ctttccctgg gtgaccctgc acgtgtaggc accttcagct 9780 tgtttctatg ctgggaggtg tgcggttgtc tggatgacct atctgttggg gcttctgggc 9840 ctggcttcag agtttgtgcg ctcaggccta ctgccccttg acttgggcac catgcaccct 9900 ggaccactgg tggcaaggcc agagaagaca agggtcttgg tgcccagtac catacacagc 9960 tcatgggccc tggggaggta ggtggccacg cttggtgggg acagctgccc agtaaccatg 10020 tgttttgtct acaggtgctg ttatccctag aaaatggggt ttgggccccc aacctgcatt 10080 tccacaaccc caaccctgaa atcccagcac ttcttgatgg gcggctgcag gtggtcgata 10140 ggcccctgcc tgttcgtggt ggcatcgtgg gcatcaactc gtttggcttc ggaggtgcca 10200 atgttcacgt catcctccag cccaacacac agcaggcccc agcacctgcc ccacatgctg 10260 ccctaccgca tttgctgcat gccagtggac ggaccatgga ggcagtgcag ggcctgctgg 10320 aacagggccg ccagcacagt caggacttgg cctttgtgag catgctcaat gacattgcag 10380 caacccctac agcagccatg cccttcagag gttacactgt gttaggtgtt gagggccatg 10440 tccaggaagt gcagcaagtg cctgccagcc agcgcccact ctggttcatc tgctcaggtg 10500 agcctgctcc catgttccca ggctggcccc aaaggaggag gggagtcggt cccttttctt 10560 gagggtgagg ctggaggttg gccatgctat ggccctgata agctttctgg tacagggatg 10620 ggcacacagt ggcgtggaat ggggctgagc cttatgcgcc tggacagttt ccgtgagtcc 10680 atcctgcgct ctgatgaggc tctgaagccc ttgggagtca aagtgtcaga cctgctgctg 10740 agcactgatg agcacacctt tgatgacatc gtgcattcct ttgtgagcct caccgccatc 10800 caggtatgcc accttcgtgg tactcggacc ccgggacact ccacaccaga gtcacgtagt 10860 cctggccctg actggtatgt aggcagagcc ttaaataggt acacctgagg aggagcaggg 10920 tcttctcaga ggaccctaag agaggcttgg cgtgcttggt gtgctcagct ttactgtgag 10980 ggatggtcag gctagtgatc tagggtctac gtgacatggc ttatatcccc acttcgcaga 11040 ttgccctcat cgacctgctg acgtctatgg ggctgaaacc tgatggcatc attgggcact 11100 ccttgggaga ggttgcctgt ggctatgcag atggctgtct ctcccagaga gaggctgtgc 11160 ttgcagccta ctggagaggc cagtgcatta aggatgccaa ccttccggct ggatccatgg 11220 cagctgttgg taggtatcct ctcaagggcc cccgacctca ttaggcacca ggatcttctt 11280 ggaaggggtt tctgtcctgg gtcctccaaa agaatcagtt gctttgttgt gagacatggg 11340 gttgcaaagg gagaagtcac tctgctcaga ttatctttat aggaggcttc agttctgacc 11400 ccacaggccc gagcaaggta tgaaacacca tacacatcag atgagggttc caggagctga 11460 ggagagccac ttaccaaccc taggtgttca tcgcccagct tctcagctgc ttacccccta 11520 caccacttag gtgtcatttc tgaggtccgg ctcctttcct acactccctc cataatgaca 11580 cctctcttga gatcagaaac agcagggagg gagtaaaggt gccctggaag gtcgactctt 11640 agcatcccaa caccattggc tctaagtagt gctcatggtc caggaggatg ggctgagttc 11700 gggccagctc tgaggccagc ctctctgctt ataggtttgt cctgggaaga atgtaaacaa 11760 cgctgccctc ctggtgtggt gcctgcctgc cacaactctg aggacactgt gaccatctct 11820 ggacctcagg taggccctgc aatcatagca ggacttctgt tccctgcaat tttgccctgg 11880 ccctgcctag gaggcaaggc ctcctcagtc tgtgtccacc aagttctgaa gggcccagct 11940 ggtgagctac acttgtcgca ggccctctgg gtggactgtg tccctgacca gggaaagcca 12000 gtccaggccc cctgaccact ggccttgatg cctgcaggct gcagtgaatg aatttgtgga 12060 gcagctaaag caagagggcg tgtttgccaa ggaggtgcga acaggtggcc tggccttcca 12120 ctcctacttc atggaaggaa ttgcccccac gctgctgcag gctctcaaga aggtgagtac 12180 ctggccatgt gcttggaccc cagggcacgg tgacttgacc tcactcgcta accaagcgtc 12240 tgtgtgcagg tgatccggga gccacggcca cgctcagcac gctggctcag cacctctatc 12300 cctgaggccc agtggcagag cagcctggcc cgcacatctt ctgctgagta caacgtcaac 12360 aacctggtga gccctgtgct cttccaggaa gcactgtggc acgtccccga gcacgccgtg 12420 gtgctggaga ttgcacccca tgcactgttg caggtgagca ctggtccgcc tgggatgggg 12480 cacatcagcc tgccagtcac tggcgaaggc gagtggcacg gaaggggtcg gagcctagct 12540 ctcctttgct atgtgtaggc tgtcctgaag cgaggcgtga agcctagctg caccatcatc 12600 cccttgatga agagggacca taaagataac ttggagttct tcctcaccaa cctcggcaag 12660 gtgcacctca cagggtaggt ctcccttctg tctgctgctc gtgtgcaggc ccacaccaac 12720 ccccatgaga ggggttgctg tggcctagct cagtgctggc cctcggtcct catcttggcc 12780 atcttggggt cttagagcaa aactagggcc acagactctc agggacaggt gtgtcactta 12840 acttgtttgt caccagcatc gacatcaacc ctaatgcctt gttcccacct gtggaattcc 12900 cggttccccg agggactcct ctcatctccc ctcacatcaa gtgggaccac agtcagactt 12960 gggatatccc agttgctgaa gacttcccca acggttccag ctcctcctca gctacagtct 13020 acaacattgg tgagccaggc tccgtggtca gtgggttcct cccaggcctg tgggcccgtg 13080 ctgaggcatt gtccttacag acgccagttc cgagtcatct gaccactacc tggtcgacca 13140 ctgcattgac ggccgtgtcc tcttccctgg cactggctac ctgtacctgg tgtggaagac 13200 actggctcga agcctgagct tgtccctaga agagacccct gtggtgtttg agaacgtgac 13260 atttcatcag gccaccatcc tgcccaggac aggtaagagg cccttcagtg ggggctggtg 13320 aggtggttgt gactactccg ctctgacctt ctttttttct ctgcaggaac cgtgcctctg 13380 gaggtgcggc tgctagaggc ctcacatgca tttgaggtgt ctgacagtgg caacctgata 13440 gtgagcggtg agtagtacct ggctgggcct gtgtggctga ggacctcagc tcctagcctg 13500 ccccatgctc agaccctcct gttgccctgc ctcctacagg gaaagtgtac cagtgggaag 13560 accctgactc caagttattc gaccacccag aagtcccgat ccccgccgag tccgagtctg 13620 tctcccgctt gacgcaggga gaagtataca aggagctgcg gctacgtggc tatgactatg 13680 gccctcattt ccagggcgtc tatgaggcca ccctcgaagg tgggcaggag caatccccga 13740 gtcagtgagc atgatgacca ggagccattg tcactcctgg gccatgtctt gctgggggtc 13800 agggaagacg gaggaagggt agtagaggcc ctggagcagg tgaggcctcg tgtgctgagc 13860 agccccccta ctgcaggtga gcaaggcaag ctgctctgga aagacaactg ggtgaccttc 13920 atggacacaa tgctgcagat atccatcctg ggcttcagca agcagagtct gcagctaccc 13980 acccgtgtga ctgccatcta tattgaccct gcaacccacc tgcagaaggt gtacatgctg 14040 gagggagaca ctcaaggtag ctctggccct cgctctgtcc acttgtcctg gactgagcat 14100 tgcctacact gaccagtgtg tctcatagtg gctgacgtga ccacgagccg ctgtctgggc 14160 gtgaccgtct ctggtggtgt ctacatttcg agactacaga caacagcaac ctcacggcgg 14220 cagcaggaac agctggtccc caccctggag aagtttgtct tcacacccca tgtggagcct 14280 gagtgcctgt ctgagagtgc tatcctgcag aaagagctgc agctgtgcaa gggttgagga 14340 tccaaacctt ccctcttctt cctcagtctt tgcctttgaa actcctgagg caaggcctgg 14400 atggcgggga gctcagggtt ggtgagagca cagcctacct tccatgggta gcacggcact 14460 gctgcatcct tcctattgag tttccgctct tcccattgct gtgggcttgt cctgtggaca 14520 cgctagaagc aggccctggc agtaggctgg aggccgtaga gagagaacgt aggcctttct 14580 ttgtccctcc caggtctggc aaaggctctg cagaccaagg ccacccagca agggctgaag 14640 atgacagtgc ctgggctaga ggaccttccc cagcatggac tgcctcgact cttggctgct 14700 gcctgccagc tgcagctcaa cgggaacctg caactggagt taggtgaggt actggctcga 14760 gagaggctcc tgctgccaga agaccctctg atcagtggcc tccttaactc ccaggccctc 14820 aaggcctgca tagacacagc cctggagaac ttgtctactc tcaagatgaa ggtggtggag 14880 gtgagtgctg ggaaggtaga caggccatgt gcgtggatcc agggcaatct cagacccgag 14940 cccaaggcag gcagccatga tgtagcagct ttctatggcc tttgtgcttt ggtttgttcc 15000 accctaaaag attgtgggga acttttcact gctaccagtc caggggatga gatatcagaa 15060 ggaaggcttc tgggaaagaa tcctgggatg ctctgagctc tagcctggga tgtcgcagac 15120 agtctccaca ggagagtaga ggagaacact ggaagagcct cccggccagc attgccacaa 15180 aactgagcat gagcagcacg gagaggctca cccaggcccc agggttttct gcctcctaga 15240 aacaacagat ctaagatgct ctcccacacc aggtgctggc tggagaaggc cacttgtatt 15300 cccacatctc agcactgctc aacacccagc ctatgctgca actggagtat acagccaccg 15360 accggcaccc ccaggccctg aaggatgttc agaccaagct gcagcagcat gatgtagcac 15420 agggccagtg ggacccttct ggtcctgctc ctaccaacct gggtgctctt gaccttgtgg 15480 tgtgcaactg tgcgttagcc accctggggg atccagccct ggccctggac aacatggtag 15540 ctgccctcaa ggatggtggt ttcctgctaa tgcacacagt gctcaaagga catgcccttg 15600 gggagaccct ggcctgcctc ccttctgagg tgcagcctgg gcccagcttc ttaagccagg 15660 tactgctcct gggcatgcag ggcaggtaag ggctgggtat ggttccgcca gttcagtact 15720 tacaagactt catacacata ggaagagtgg gagagcctgt tctcaaggaa ggcactgcac 15780 ctggtgggcc ttaaaaagtc attctacggt actgcgctgt tcctgtgccg ccgtctcagc 15840 ccacaggaca agcccatctt cctgcctgtg gaggatacta gtttccagtg ggtggactct 15900 ctgaaggtca ggctctgggg ctgggtacct tggcttcccc tgacgtatga tcaccctaga 15960 ggctgaccct actttatcct gcagagcatt ctggccacat cctcctccca gcctgtgtgg 16020 ctaacagcca tgaactgccc cacctcaggt gtggtaggct tggtgaactg tctccgaaaa 16080 gagccgggtg gacaccggat tcggtaggaa aggccctgag aggtgcctac ccttcctccc 16140 tcaccccctc cattcttggt atccttaccc actttgcccc cacaggtgta tcctgctgtc 16200 caacctcagc agcacatctc acgtccccaa gctggaccct ggctcttcag agctacagaa 16260 ggtgctagag agtgatctgg tgatgaacgt gtacagggac ggtgcctggg gtgccttccg 16320 tcacttccag ttagagcagg gtaagcctgt ccatgcccta tatacttaat aggcttgtga 16380 ggtggcaggg gaacaaggag ctggccaggt aggcccctgt ggcatccttg ctttctttcc 16440 cctcagacaa gcccgaggag cagacagcac atgcctttgt aaacgtcctt acccgagggg 16500 accttgcctc catccgctgg gtctcttctc ccctgaaaca catgcagccg ccctcgagct 16560 caggagcaca gctctgcact gtctactatg cctcactgaa cttccgagat atcatgctgg 16620 ccacgggcaa gctgtcccct gatgccattc caggtgccaa ccaggatggg ggcttatgat 16680 tgggttgctg ggagtagaga aggtgcctgt actgtagcag cccagtgagg aggagtcctg 16740 cccggctcct ggggaagaga gggttcccag caccagaggc tgcacttgca tcctgctccc 16800 ctgacaacct gtcctagggt ctgggctaac aggagcctcc ctctgtctac acacaggtaa 16860 atgggccagc cgggactgca tgcttggcat ggagttctca ggccgtgata agtgcggccg 16920 gcgtgtgatg gggctggtac ccgcagaagg cctggccacc tcagtcctgt tatcacccga 16980 cttcctctgg gatgtaccct ctagctggtg agtggctggc tgcagttggg ggttatgtga 17040 tcttagttgg tggccaggct gaattgatcc tgtgctccgt tccctcagga ccctggagga 17100 ggcggcttct gtgcctgttg tctacaccac cgcctactac tccttagtag tgcgtggtcg 17160 tattcagcac ggggaaactg tgctcattca ctcgggctcc ggtggtgtgg gccaagcggc 17220 catttccatt gcccttagcc tgggctgccg agtcttcacc actgtgggta aggccctcac 17280 cccctcccga tcccaatcaa ggagcttctt gaaccctgtg ggccaaactt actggggtct 17340 cccttgactg acaggctccg ctgagaagcg agcttacctc caggccagat tccctcagct 17400 ggatgacacc agctttgcta actctcgaga cacatcgttt gagcagcatg tgttactgca 17460 cacaggtggc aaaggtaaat accccctggg ccattgcctg agagtgagtg ggtcacatag 17520 tcagtccagc gctgaggact gaggtacagg tgagcccagt atgaccgact gacatgtttg 17580 ccaccgtagg ggtggacctg gtcctcaact ccctggcaga agagaagctg caggccagtg 17640 tgcggtgctt ggctcagcat ggccgcttcc tagagatcgg caaatttgat ctttctaaca 17700 accaccctct gggtatgact cgtagtcagg agcaggggtg ggcgctggtg ttggggccag 17760 gggcatccca cagtgaacag gattctcgaa tacaggcatg gccatcttct tgaagaacgt 17820 cactttccat gggatcctgc tggatgcact ttttgagggg gccaacgaca gctggcggga 17880 ggtggcagag ctgctgaagg ccggcatccg tgatggggtt gtgaagcctc tcaagtgtac 17940 agtgtttccc aaggcccagg tggaggacgc cttccgatac atggctcaag gaaaacatat 18000 tggcaaagtc cttgtccagg tgaagtgagg ccctcgggca ccaagcctgg tttcgccttt 18060 tgtagtgcat tttttttcta attatattta cttacttttg atggttgtga gtggcatgtg 18120 tgggtaccag aggacaactt gcaggagttg gttctcctcc atgggtcatc aggttttttt 18180 ttattttttt ggttcttttt tttcggagct ggggaccgaa cccagggcct tgcgcttctt 18240 aggtaagcgc tctaccactg agctaaatcc ccagcccggg tcatcaggtt tgatagaagc 18300 actgttaact acccagctgt ctcgctggtc ctgggacagc ttctgaacca ctgctacttg 18360 tatgcaggta cgggaggagg agcccgaggc tatgctgcca ggggctcagc ccaccctgat 18420 ttccgccatc tccaagacct tctgcccaga gcataagagt tacatcatca ctggtggcct 18480 aggtggcttt ggcctggaac tggcccggtg gcttgtgctt cgtggggccc aaaggcttgt 18540 actaacttcc cgatctggaa tccgcacagg taggcaagta gaagcagttg gtagtgtagg 18600 cttcccttca gtggaaagtg tcctgggagg gctgtaggcc actgctttcc tctggtgcag 18660 ccccatttcc ctgtgtccca taggctacca agccaagcac gttcgggagt ggaggcgcca 18720 gggcatccat gtgctagtgt cgacaagcaa tgtcagttca ctggaggggg cccgtgctct 18780 catcgctgaa gccacaaagc ttgggcccgt tggaggtgtc ttcaacctgg ccatggtgag 18840 aaaagcatgc agggctctgc gtacctccag agcctgagac ccaggctgct gctaagtggg 18900 gttagaacct cagagctgca gcagacacta aaaccccttc ttctaggttt taagggatgc 18960 catgctggag aaccagactc cagaactctt ccaggatgtc aacaagccca agtacaatgg 19020 caccctgaac cttgacaggt aggcagttgg tccctctgct gagtttcatg tatgcttgca 19080 atgtatactg gtccctgctg gacttgaggg tctggggaag tgaaactgtg ccacccgtgg 19140 ccttctgggc ctgccctggg gaggtacgga catgaaagtt atcagactga catgagtacc 19200 cacagggcga cccgggaagc ctgtcctgag ctggactact ttgtggcctt ctcctctgta 19260 agctgcgggc gtggtaatgc tggccaatcc aactatggct tcgccaactc taccatggag 19320 cgtatttgcg aacagcgccg gcacgatggc ctcccaggtg ggcctctttg tctagcccac 19380 ccctgcttgt ggtctcactc cccaaagcac ctcaccggct gcctcccttg ctctcaggtc 19440 ttgccgtgca atggggtgcc attggtgacg tgggcattat cttggaagcg atgggtacca 19500 atgacacagt cgttggcggc acactgccac agcgcatctc ctcctgcatg gaggtgctgg 19560 acctcttcct gaatcagccc cacgcagtcc tgagcagttt tgtgctggct gagaagaaag 19620 ctgtggccca tggtgatggt gaagcccaga gggatctggt gaaagcagtg gcacacatcc 19680 taggtaagcc agcttccggg accttcccgg cttaggtgac ttggagcctt agttttccca 19740 tctgtagaag cagacgacag agttctgtgg tctgaatgct ggccaggcca ggtgattggc 19800 agtgatgctg gagagccaca gtatgtacct ggttcccacg tccccttctc agtaatgacc 19860 agttacccat cccctttgtt aggcatccgc gacctcgcag ggattaacct ggacagctcg 19920 ctggcagacc tcggcctgga ctcgctcatg ggtgtggaag tgcgccagat cctggaacgt 19980 gaacatgatc tggtgctacc cattcgtgaa gtacggcaac tcacactgcg gaagcttcag 20040 gaaatgtcct ccaaggctgg ctcagacact ggtgcgtacc aggcagcagg ctgtgagaga 20100 cacaagtgca tcctagtatt gtaggcagca gcgctgccct tttgcaaaga acacatgggc 20160 ctgtgcttaa tctgtgtgtg tatgacctca caaggggatg tgtaccagag cccatgtgcc 20220 aaggctaccc tacaccctct gtctttacag agttggcagc ccccaagtcc aagaatgata 20280 catccctgaa gcaggcccag ctgaatctga gtatcctgct ggtgaaccct gagggcccta 20340 ccttaacacg actcaactca gtgcagagct ctgagcggcc tctgttcctg gtgcacccca 20400 ttgaaggttc catcactgtg ttccacagcc tggctgccaa gctcagtgtg cccacctacg 20460 gtctgcagtg cacccaaggt actgtgcaca tggcgaagca gtacatgctg ccttgggcct 20520 ccgttcctca ctgactgctg gctgagtcct ctgtttgtcc ttacagcggc ccccctggac 20580 agcattccaa acctggctgc ctactacatt gattgcatca agcaggtgca gcctgagggg 20640 ccctaccgag tggctgggta ttcttttgga gcttgtgtag ccttcgagat gtgctcccag 20700 ctgcaggccc agcagggccc agcccccgcc cacaacaacc tcttcttgtt tgatggctca 20760 cacacctacg tattggcgta cacccaggtg agagccgggc caactggtcc taagcattgc 20820 cgcctatgtc ttggctctga acacacttct gggagggtcc tggttacttt agcccttgca 20880 gcatcaatct ctccttccct gacagagcta ccgggcaaag ctgaccccag gctgtgaggc 20940 tgaggctgaa gctgaagcca tatgcttctt cattaagcag tttgttgatg cagagcatag 21000 caaggtgggc ctggacacac cctagagagg gcaggaaagg caaggctggg agggttgggg 21060 tctctgtgcc tttaaaatgg agcagggaaa tccaagcgct tcttcagaaa cccgtctgcc 21120 cagagaaggc agggcagacc gtgtagcccc ccatcccacc ccacatgctc agagctgttg 21180 cttttaggtg ctagaggccc tgctaccact gaagagcctg gaggaccggg ttgctgctgc 21240 tgtggacctc atcactagaa gccaccagag cctggaccgc cgtgacctga gctttgctgc 21300 cgtgtccttc tactacaagc ttcgagccgc cgaccagtat aaacccaagg ccaagtacca 21360 cggcaatgtg atcctgctgc gggccaagac aggtggcacc tacggcgagg acttgggtgc 21420 cgattacaac ctgtcccagg taagcgagtg agtggggcag acgaggcggt gtgggacgga 21480 cgcctgctgg tggtcacaga atgacacctg aatgtttaca ggtgtgtgat gggaaggtgt 21540 ctgtgcacat cattgagggt gaccaccgta cgctgctgga gggcaggggc ctggagtcta 21600 tcatcaacat catccacagc tccctggctg agcctcgagt gagtgtacgg gagggctaga 21660 cctgcctacc atgaagccac gacccacacc ggccaccaga gatgctccga tccccaccac 21720 accctgagtg cagggactgg ggagggtcct gctggtggga ccccctcacc ccagtggccc 21780 agcaccaccc cctcccctgg tggctgctac aaacaggacc atcacatgtg tcccagccac 21840 ttagtggggt tcccagagcc actgacttgg aggcaccctg gtctgtgaag agtcagtgga 21900 ggccagcaag agccaaactg agccttttct gccaagtgac atttgtcaca ctggttgttt 21960 ctccattaaa ttctcatatt tattgcattg ctgggaaaga ccgcccaccc cagggttaac 22020 tcattccaga acccctaaag tgggaaaagc catgtgggga aggctgctgg ctggagcccc 22080 tttttgtctt agccctgtac ccgctcactg cagggcaggg tatggagagg gctggttcgc 22140 ggggaacgag gaccccagca gacactgtag cccatggccc ttggtcccca gcactcccgg 22200 ctgcacccat gatgcagggc ctaccagact ctgcggaccg caccgggcac tcactgtatt 22260 tgttttccaa gattcaaatt gctgcttggg ttttgaattt actgcagctg tcagtgtaaa 22320 gaaacatgtc tgaactgtgt cctttttaca ccaacctggt aaaaatgctc ttgatgctgt 22380 cccgttgcca caattaaact gcacgtgagc tctggcttcc gttcagtctc tttccagtcc 22440 cagacctgag tccccagagc ctccacagct cttacagtga gaatcaaatt ggcccactcc 22500 ttggaaggcg tggcattctg tcagagtaaa aggaaagtag agtgtgctga ttcacgttca 22560 gcgtgtgggg ctggctagag accttggcac tgtagtgaac agaatgtgtc cacctttaag 22620 tcaccctgaa ggcatcacca tagctacagc ctcacccagg ggtagagaat agtactgtct 22680 acttgttgac tacctggcag ttggtgccag cccctataga ggaaaacagc agtgtgtggc 22740 cactgtgaga agcatatccc tggaaacagg tgaccagagc agagggctaa cgcctacctg 22800 agtcacacaa aactgaccag gcttgagtgt ccagaagagt ctatcagaag gccacagcat 22860 tcagtcctat ccacagagag cagcagacta agttgtctcc ttgccagctt agaaaactgc 22920 agtgctgggg tacaggtagg gtgttcagga ggtccgggcc ccagtgatta gtctaagact 22980 gaagcatctg gttggctgtg gtcccaccta gaaaattctt aaagctcttg tcatgtactt 23040 cctgggaagg acctaccctg tctcaataat gtctctagct cgttggagtc tactgactca 23100 aacatttata aagtgtccta gaaaggcctg actcccctac aaggctgtgt gatccttcaa 23160 actcacatat gtgagccaat aaaaccttga gactctagtc ttatggccac cttgctcctt 23220 cctgctcttc gtgctcatgt aacaagactt ccactgcgtc tgatgagatt gctctgggta 23280 gagtcggagt ttgatcactg gaacccacgt aaaggttgtc atctgacttc cacacgtgtt 23340 gagtggagca atactaaaat gaaaatttaa aagagcagtt gctgttcatg gggatcttaa 23400 aatacaggta gaggaccaaa tttagcatct ggcttgttgg tacgacactg agttcttaca 23460 tcagtcagga ataggagtgc tcctaggaac ttcagcaata aaaatgacta agagggtaga 23520 gaagcgactc tacagttaaa ggacccagat taggttccca gcaaccatag caactccagc 23580 cccaagggac ctgacaccct gtgcaggaac cactgagagt actcagacat gcatgcaagc 23640 aaaatgttca cacacataaa actaattaaa cttttaaaca aaagctcaaa gagcttaaag 23700 gtcaaagttt ctg 23713 <210> SEQ ID NO 14 <211> LENGTH: 2848 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 14 ggtggattgc agtgacagcc gcctgtggag cagcccgggc agcggaggag aattctgcat 60 agagaaccac caacccagaa ccatggaagt ccatgaattg ttccggtatt ttcgaatgcc 120 agagctgatt gacattcggc agtacgtgcg cacccttcca accaacaccc tcatggggtt 180 tggggctttt gcagcgctca ccaccttctg gtatgccacc aggcctaagg ccctgaagcc 240 accatgtgac ctctccatgc agtcagtgga aatagcgggt accactgatg gtattcgaag 300 atcagcagtc cttgaagatg acaagctctt ggtgtactac tacgacgatg tcagaaccat 360 gtacgatggc ttccagaggg ggattcaggt gtcaaataat ggtccttgtt taggttctcg 420 gaagccaaac cagccctatg agtggatttc ctacaaagag gtggcagaac tggctgagtg 480 cataggctcc gggctgatcc agaaggggtt caagccttgc tccgagcagt tcatcggcct 540 cttctctcaa aacagacccg agtgggtgat cgtcgagcaa ggatgcttct cttactcaat 600 ggtggtcgtc ccgctctatg acacccttgg agctgacgcc atcacctaca tagtgaacaa 660 agctgaactc tctgtgattt ttgctgacaa gccagaaaaa gccaaactct tattagaagg 720 tgtagaaaac aagttaacac catgccttaa aatcatagtc atcatggact cctacggcag 780 tgatctggtg gaacgaggca agaagtgtgg ggtggaaatc atcagcctca aagctctgga 840 ggaccttgga agagtgaaca gagtgaagcc caagcctcca gaacccgaag atcttgcgat 900 aatttgtttc acaagtggaa ctacaggcaa ccccaaagga gcaatgatca ctcaccaaaa 960 cattataaac gactgctcag gttttataaa agcaacagag agtgcattca tcgcttccac 1020 agatgatgtg ctgatatctt tcttgcctct cgcccatatg tttgagaccg ttgtagagtg 1080 tgtaatgctg tgtcatggag ctaagatagg atttttccaa ggagatatca ggctgcttat 1140 ggacgacctc aaggtgcttc agcccaccat cttccctgtg gttcccaggc tgctgaaccg 1200 gatgttcgac agaatttttg gacaagcaaa cacttccttg aagcgatggc tgttggactt 1260 tgcctccaaa aggaaagagg cggagcttcg cagtggcatc gtcagaaaca acagcctgtg 1320 ggataaactc atcttccaca agatacagtc gagcctgggt gggaaagtcc ggctgatgat 1380 cacaggagca gccccggtgt ctgccacagt gctgacgttt ctgaggacag cgctcggctg 1440 ccagttctat gaaggctacg gacagaccga gtgcactgct ggttgctgcc tgagcttgcc 1500 cggagactgg acggcaggcc atgttggagc ccccatgcct tgcaattatg taaagcttgt 1560 ggatgtggaa gaaatgaatt acctggcatc caagggcgag ggtgaggtgt gtgtgaaagg 1620 ggcaaatgtg ttcaaaggct acttgaaaga cccagcaaga acagctgaag ccctggataa 1680 agatggctgg ttacacacgg gggacattgg aaaatggctg ccaaatggca ccttgaagat 1740 tatcgacagg aaaaagcaca tatttaaact agcccaagga gagtacatag caccagaaaa 1800 gattgaaaat atctacctgc ggagtgaagc cgtggcccag gtgtttgtcc acggagaaag 1860 cttgcaggcc tttctcatag cagttgtggt acccgacgtt gagagcctac cgtcctgggc 1920 acagaagaga ggcttacaag ggtccttcga agaactgtgc aggaacaagg atatcaataa 1980 agctatcctg gacgacttgt tgaaacttgg gaaggaagcc ggtctgaagc catttgaaca 2040 ggtcaaaggc attgctgtgc acccggaatt attttctatt gacaacggcc ttctgactcc 2100 aacactgaag gcgaagaggc cagagctacg gaactatttc aggtcgcaga tagatgaact 2160 gtacgccacc atcaagatct aacgtgagga aggatactta gaagaaatgg cgcatctcca 2220 caatcctcct cgtaccaatg gccttcgagt tggtaacttt gcctgcagcg agtgtgggaa 2280 aggaaatgcc ctgccgccgg acttgtccac ggggtcttac catagggata gtcgagggca 2340 cggaacactg ccttacttac agtcacctgt gttgcagccc atgatcccgg ggacacacaa 2400 tttccaaaac gagccttaaa cattgtaaag gggaacccat aaaagtgcta agttatttaa 2460 gacttcttca accaataagg tggatgctac aagttctgtc tcctgttttt ctaactgagg 2520 ggttaggact tattctttct gatatgtctg ctgcttgctg cgcgttttgc agctgtctgc 2580 tgctctgaag agcaccgtac actggaggaa agctgtccct ttaagaacaa ctgtccaggc 2640 tgaagaaagt cacagtggac cagaggtttt ccttttgaac ccctcctccc ccttgcccct 2700 ttccctcacc acctcacata cagtacactc acatgacctt tctggtttgt aagggttcca 2760 cacggtccct gtttgcgcct gctggaacat gaggttttca gtaaactaaa gagcagaccc 2820 tcttcagaac atgtgggtgt ccagtctc 2848 <210> SEQ ID NO 15 <211> LENGTH: 2034 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 15 ggatctggca gcgccgcgaa gacgagcggt caccggcgcc cgacccgagc gcgcccagag 60 gacggcgggg agccaagccg acccccgagc agcgccgcgc gggccctgag gctcaaaggg 120 gcagcttcag gggaggacac cccactggcc aggacgcccc aggctctgct gctctgccac 180 tcagctgccc tcggaggagc gtacacacac accaggactg cattgcccca gtgtgcagcc 240 cctgccagat gtgggaggca gctagctgcc cagaggcatg cccccctgcc agccacagcg 300 acccctgctg ctgttgctgc tgctgctggc ctgccagcca caggtcccct ccgctcaggt 360 gatggacttc ctgtttgaga agtggaagct ctacggtgac cagtgtcacc acaacctgag 420 cctgctgccc cctcccacgg agctggtgtg caacagaacc ttcgacaagt attcctgctg 480 gccggacacc cccgccaata ccacggccaa catctcctgc ccctggtacc tgccttggca 540 ccacaaagtg caacaccgct tcgtgttcaa gagatgcggg cccgacggtc agtgggtgcg 600 tggaccccgg gggcagcctt ggcgtgatgc ctcccagtgc cagatggatg gcgaggagat 660 tgaggtccag aaggaggtgg ccaagatgta cagcagcttc caggtgatgt acacagtggg 720 ctacagcctg tccctggggg ccctgctcct cgccttggcc atcctggggg gcctcagcaa 780 gctgcactgc acccgcaatg ccatccacgc gaatctgttt gcgtccttcg tgctgaaagc 840 cagctccgtg ctggtcattg atgggctgct caggacccgc tacagccaga aaattggcga 900 cgacctcagt gtcagcacct ggctcagtga tggagcggtg gctggctgcc gtgtggccgc 960 ggtgttcatg caatatggca tcgtggccaa ctactgctgg ctgctggtgg agggcctgta 1020 cctgcacaac ctgctgggcc tggccaccct ccccgagagg agcttcttca gcctctacct 1080 gggcatcggc tggggtgccc ccatgctgtt cgtcgtcccc tgggcagtgg tcaagtgtct 1140 gttcgagaac gtccagtgct ggaccagcaa tgacaacatg ggcttctggt ggatcctgcg 1200 gttccccgtc ttcctggcca tcctgatcaa cttcttcatc ttcgtccgca tcgttcagct 1260 gctcgtggcc aagctgcggg cacggcagat gcaccacaca gactacaagt tccggctggc 1320 caagtccacg ctgaccctca tccctctgct gggcgtccac gaagtggtct ttgccttcgt 1380 gacggacgag cacgcccagg gcaccctgcg ctccgccaag ctcttcttcg acctcttcct 1440 cagctccttc cagggcctgc tggtggctgt cctctactgc ttcctcaaca aggaggtgca 1500 gtcggagctg cggcggcgtt ggcaccgctg gcgcctgggc aaagtgctat gggaggagcg 1560 gaacaccagc aaccacaggg cctcatcttc gcccggccac ggccctccca gcaaggagct 1620 gcagtttggg aggggtggtg gcagccagga ttcatctgcg gagaccccct tggctggtgg 1680 cctccctaga ttggctgaga gccccttctg aaccctgctg ggaccccagc tagggctgga 1740 ctctggcacc cagaggcgtc gctggacaac ccagaactgg acgcccagct gaggctgggg 1800 gcgggggagc caacagcagc ccccacctac cccccacccc cagtgtggct gtctgcgaga 1860 ttgggcctcc tctccctgca cctgccttgt ccctggtgca gaggtgagca gaggagtcca 1920 gggcgggagt gggggctgtg ccgtgaactg cgtgccagtg tccccacgta tgtcggcacg 1980 tcccatgtgc atggaaatgt cctccaacaa taaagagctc aagtggtcac cgtg 2034 <210> SEQ ID NO 16 <211> LENGTH: 1944 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 16 cagggtctcc cttgcaacct gaggagaggt gcacacactc tgaggaccta ggtgtgcaac 60 ctctgccaga tgtggggcgt ggctacccag aggcatgccc ctcacccagc tccactgtcc 120 ccacctgctg ctgctgctgt tggtgctgtc atgtctgcca gaggcaccct ctgcccaggt 180 aatggacttt ttgtttgaga agtggaagct ctatagtgac caatgtcacc acaacctaag 240 cctgctgccc ccacctactg agctggtctg taacagaacc ttcgacaact actcctgctg 300 gcctgacacc cctcccaaca ccactgccaa catttcctgc ccctggtacc taccttggtg 360 ccacaaagtg cagcaccgcc tagtgttcaa gaggtgtggg cccgatgggc agtgggttcg 420 agggccacgg gggcagccgt ggcgcaacgc ctcccaatgt cagttggatg atgaagagat 480 cgaggtccag aagggggtgg ccaagatgta tagcagccag caggtgatgt acaccgtggg 540 ctacagtctg tccctggggg ccttgctcct tgcgctggtc atcctgctgg gcctcaggaa 600 gctgcactgc acccgaaact acatccatgg gaacctgttt gcgtcctttg tgctcaaggc 660 tggctctgtg ttggtcatcg attggctgct gaagacacgg tacagccaga agattggcga 720 tgacctcagt gtgagcgtct ggctcagtga cggggcgatg gccggctgca gagtggccac 780 agtgatcatg cagtacggca tcatacccaa ctattgctgg ttgctggtag agggcgtgta 840 cctgtacagc ctgctgagcc ttgccacctt ctctgagagg agcttctttt ccctctacct 900 gggcattggc tggggtgcgc ccctgctgtt tgtcatcccc tgggtggtgg tcaagtgtct 960 gtttgagaat gttcagtgct ggaccagcaa tgacaacatg ggattctggt ggatcctgcg 1020 tattcctgtc ttcctggcct tactgatcaa ttttttcatc tttgtccaca tcattcaact 1080 tcttgtggcc aagctgcgtg cccatcagat gcactatgct gattacaagt tccggctggc 1140 caggtccacg ctgaccctca tccctctgct gggggtccac gaggtggtct ttgcctttgt 1200 gactgacgag catgcccaag gcaccctgcg ctccaccaag ctcttttttg acctgttcct 1260 cagctccttc cagggtctgc tggtggctgt tctctactgt ttcctcaaca aggaggtgca 1320 ggcagagctg atgcggcgtt ggaggcaatg gcaagaaggc aaagctcttc aggaggaaag 1380 gttggccagc agccatggca gccacatggc cccagcaggg ccttgtcatg gtgatccctg 1440 tgagaaactt cagcttatga gtgcaggcag cagcagtggg actggctgtg tgccctctat 1500 ggagacctcg ctggccagta gtctcccaag gttggctgac agccccacct gaatctccac 1560 ttggagccta ggcaggttgt gttcaagaaa gggcctcaga ggacaaccca gagccagatg 1620 cccggccaag gttgaagagc caaagcagca agacagcagc ttgtactgtg cacactcccc 1680 taacctgtcc tagcctggca caggccacag tgacagagta ggggttggat atgatggaga 1740 agccatgtta tctatgaact ctgagtgttc ccatgtgtgt tgacatggtc cctgtaccca 1800 gatatgtcct tcagtaaaaa gctcgagtgg agctgctgca cagctcgtgg acagcaggct 1860 tgaagccccc agggacgggg tttgggaggc cggggatgag cagcacactc agcaggtgga 1920 gcgctagtgc aacccaggaa agaa 1944 <210> SEQ ID NO 17 <211> LENGTH: 3172 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 17 ctgagaagga aacttggagt gggacttgaa tgcgtgggtc ttcagaagga gaaccgctaa 60 gcatcccgat ttcccagaac aagaaggaca agtccaaaga cagtaaacaa agataggagt 120 tcacccttga atacctggaa ggaagaagga agagggtggg cccgcctctg gaatagaggg 180 ctcaggagat tggactccta gatccaggaa gaaggccaaa agacctggtc agtgggtttc 240 taattctgaa gaggagctag tcagggtctg ctcagtctga gggcttcgac tcccagctgc 300 tagaaagagg atgaggatgc agccgcaggc ttctagaaga caaggagata aattcctagg 360 tgtgagagag aagataatag gaaggcccct gcgtctccag gaggattggg acagacctga 420 ggaaggagag ggctcggctt tggactcctg catctcagca aggacggtcc taggtttgaa 480 tacttggttg gcctagggaa agagaggaag ggcatggact cctgggcctg acagagcaaa 540 gggtaaccac agaccttccc atcttctcac agcctcagcg ttctcacaca gcatggattt 600 acgcacgatg acacagtcgc tggtgacact cgcagaagac aatatggcct tcttctcaag 660 ccagggccca ggagagacag cacggcggct gtctaatgtc tttgcaggtg ttcgggaaca 720 ggcactgggg ctggaaccaa ccctaggcca actgttgggt gtggcacacc attttgacct 780 ggacacagag acaccagcca acggataccg tagtttggtg cacacagccc gatgctgcct 840 ggcacaccta ctacacaaat cccgctatgt ggcttctaac cgcaaaagta tcttcttccg 900 tgccagccac aacctagcag agctggaggc ctacctggcc gccctcaccc agctccgtgc 960 tatggcctac tatgcccagc gcctgctgac catcaaccga ccaggagtgc tcttcttcga 1020 gggtgatgaa ggactcaccg ctgacttcct gcaagagtat gtcacgctac acaaaggctg 1080 cttctacggc cgctgcctgg gcttccagtt cacacctgcc atccggccgt tcctgcagac 1140 tctctccatc gggctggtgt ccttcgggga gcactacaaa cgcaacgaga caggcctcag 1200 tgtgaccgcc agttccctct ttaccggtgg ccgattcgcc atagacccag agttgcgtgg 1260 ggctgaattt gaacgcatca tacagaacct ggatgtgcac ttctggaaag ccttctggaa 1320 catcactgag attgaggtgc tgtcgtctct ggccaacatg gcatcaacca ctgtgagggt 1380 aagccgcctg ctcagcttgc cacctgaggc ctttgagatg ccactcacct ctgatcccag 1440 gctcacagtt accatctcac ctcccttggc acacacggga ccagctcctg tgctagccag 1500 gctcatctcc tatgacctac gggaaggaca ggacagcaag gtactcaaca gcctggcaaa 1560 atctgagggc ccacgcctgg acgtgcgccc acggcctcac caagcacccc gttcacgggc 1620 cctggttgtt cacatccacg gaggcggctt tgtggcacag acctctaaat cccacgagcc 1680 ctacctcaag aactgggccc aggagctagg agtccctatc ttctccatcg actactccct 1740 ggcccccgag gctccctttc cccgagcgct ggaggagtgt ttttttgcct actgctgggc 1800 tgtcaagcac tgtgacctgc ttggttcaac tggagagcgg atatgccttg caggggacag 1860 tgcaggtggg aatctctgca tcactgtgtc ccttcgggca gcagcctatg gagtgagggt 1920 gccagatggc atcatggcag cctacccagt taccaccctg cagtcctctg cttctccctc 1980 tcgtctgctg agcctcatgg accctcttct accactgagc gtactctcta agtgtgtcag 2040 tgcctattca gggacagagg cagaggacca ttttgactca gaccagaagg cactaggcgt 2100 gatggggctg gtgcagagag acacttcgct gttcctcaga gacctccgac tgggtgcctc 2160 ctcatggctc aactccttcc cggaactaag tggacgcaag ccccaaaaga ccacatcgcc 2220 cacagcagag tctgtgcgcc ccacggagtc tatgcgcagg agtgtgtctg aggcagccct 2280 ggcccagcct gagggcttac tgggcacaga taccttgaag aagctgacaa taaaggactt 2340 gagcaactca gagccttcag acagccccga gatgtcacag tcaatggaga cacttggccc 2400 ctccacaccc tctgatgtca acttttttct gcggcctggg aattcccagg aagaggctga 2460 agccaaagat gaagtgagac ccatggacgg agtcccccgc gtgcgcgctg ctttccctga 2520 ggggtttcac ccccggcgct caagccaagg tgtcctccac atgcccctct acacgtcacc 2580 catagtcaag aaccccttca tgtctcctct gctggcccct gacagcatgc tgaagacctt 2640 gccgcctgtg caccttgtgg cttgcgctct ggaccccatg ctagatgact cggtcatgtt 2700 cgcgcggcga ctgcgcgacc tgggccagcc ggtgacgctg aaagtggtag aagatctgcc 2760 gcatggcttc ctgagcctgg cggcactgtg tcgcgagacc cggcaggcca cggagttctg 2820 cgtgcagcgc atccggctga tcctcacccc gcctgctgca ccactgaact gagctgggga 2880 cggcgggggg cggcactaaa agacctcttg ctcccatctg cgcgggcttc cgttatgagt 2940 gcgctccgag atgggctcca ggccccctca gtcgggctgg gcgggcggga gtgggctgtg 3000 cttaacttga gacagtaagt ggggcgggac aggggccaaa agctgaacct gggggaggga 3060 cacacacaca cctgtcactg agacagctgg atctgcactc taccactgcc ttctgctgct 3120 gtgaccgacc cggctagtcg gttttgcctt tttgtaaata aaagttattt aa 3172 <210> SEQ ID NO 18 <211> LENGTH: 1350 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 18 ggatgagaca gaaggataga gaggaggaga gagagagaga gaagagaagc aaccagaaat 60 aggcagccaa taaaaaggag ccgcacttat ctgaagcctc aaggggcctg agccaggtcc 120 ctgtttgatg gcagttatga aaaattacct cctcccgatc ctggtgctct ccctggccta 180 ctactactat tctacaaatg aagagttcag accagaaatg ctccagggaa agaaagtgat 240 tgtcactggg gccagcaaag ggattggaag agaaatggca tatcatctgt caaaaatggg 300 agcccatgtg gtattgactg ccaggtcgga ggaaggtctc cagaaggtag tgtctcgctg 360 ccttgaactc ggagcagcct ctgctcacta cattgctggc actatggaag acatgacatt 420 tgcggagcaa tttattgtca aggcgggaaa gctcatgggc ggactggaca tgcttattct 480 aaaccacatc actcagacct cgctgtctct cttccatgac gacatccact ctgtgcgaag 540 agtcatggag gtcaacttcc tcagctacgt ggtcatgagc acagccgcct tgcccatgct 600 gaagcagagc aatggcagca ttgccgtcat ctcctccttg gctgggaaaa tgacccagcc 660 tatgattgct ccctactctg caagcaagtt tgctctggat gggttctttt ccaccattag 720 aacagaactc tacataacca aggtcaacgt gtccatcact ctctgtgtcc ttggcctcat 780 agacacagaa acagctatga aggaaatctc tgggataatt gacgccctag cttctcccaa 840 ggaggagtgc gccctggaga tcatcaaagg cacagctcta cgcaaaagcg aggtgtacta 900 tgacaaattg cctttgactc caatcctgct tgggaaccca ggaaggaaga tcatggaatt 960 tttttcatta cgatattata ataaggacat gtttgtaagt aactaggaac tcctgagccc 1020 tggtgagtgg tcttagaaca gtcctgcctc atacttcagt aagccctacc cacaaaagta 1080 tctttccaga gatacacaaa ttttggggta cacctcatca tgagaaattc ttgcaacact 1140 tgcacagtga aaatgtaatt gtaataaatg tcacaaacca ctttgggcct gcagttgtga 1200 acttgattgt aactatggat ataaacacat agtggttgta tcggctttac ctcacactga 1260 atgaaacaat gataactaat gtaacattaa atataataaa ggtaatatca acttcgtaaa 1320 tgcaaaaaaa aaaaaaaaaa aaaaaaaaaa 1350 <210> SEQ ID NO 19 <211> LENGTH: 1418 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 19 cattaattgc ttgccatcat gagcagaagc aagcgtgaca acaattttta tagtgtagag 60 attggagatt ctacattcac agtcctgaaa cgatatcaga atttaaaacc tataggctca 120 ggagctcaag gaatagtatg cgcagcttat gatgccattc ttgaaagaaa tgttgcaatc 180 aagaagctaa gccgaccatt tcagaatcag actcatgcca agcgggccta cagagagcta 240 gttcttatga aatgtgttaa tcacaaaaat ataattggcc ttttgaatgt tttcacacca 300 cagaaatccc tagaagaatt tcaagatgtt tacatagtca tggagctcat ggatgcaaat 360 ctttgccaag tgattcagat ggagctagat catgaaagaa tgtcctacct tctctatcag 420 atgctgtgtg gaatcaagca ccttcattct gctggaatta ttcatcggga cttaaagccc 480 agtaatatag tagtaaaatc tgattgcact ttgaagattc ttgacttcgg tctggccagg 540 actgcaggaa cgagttttat gatgacgcct tatgtagtga ctcgctacta cagagcaccc 600 gaggtcatcc ttggcatggg ctacaaggaa aacgtggatt tatggtctgt ggggtgcatt 660 atgggagaaa tggtttgcca caaaatcctc tttccaggaa gggactatat tgatcagtgg 720 aataaagtta ttgaacagct tggaacacca tgtcctgaat tcatgaagaa actgcaacca 780 acagtaagga cttacgttga aaacagacct aaatatgctg gatatagctt tgagaaactc 840 ttccctgatg tccttttccc agctgactca gaacacaaca aacttaaagc cagtcaggca 900 agggatttgt tatccaaaat gctggtaata gatgcatcta aaaggatctc tgtagatgaa 960 gctctccaac acccgtacat caatgtctgg tatgatcctt ctgaagcaga agctccacca 1020 ccaaagatcc ctgacaagca gttagatgaa agggaacaca caatagaaga gtggaaagaa 1080 ttgatatata aggaagttat ggacttggag gagagaacca agaatggagt tatacggggg 1140 cagccctctc ctttagcaca ggtgcagcag tgatcaatgg ctctcagcat ccatcatcat 1200 cgtcgtctgt caatgatgtg tcttcaatgt caacagatcc gactttggcc tctgatacag 1260 acagcagtct agaagcagca gctgggcctc tgggctgctg tagatgacta cttgggccat 1320 cggggggtgg gagggatggg gagtcggtta gtcattgata gaactacttt gaaaacaatt 1380 cagtggtctt atttttgggt gatttttcaa aaaatgta 1418 <210> SEQ ID NO 20 <211> LENGTH: 2181 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 20 agagagccga gctctggagc ctcagcgagc ggaggaggag gcgcagggcc gacggccgag 60 tactgcggtg agagccagcg ggccagcgcc agcctcaaca gccgccagaa gtacacgagg 120 aaccggcggc ggcgtgtgcg tgtaggcccg tgtgcgggcg gcggcgcggg aggagcgcgg 180 agcggcagcc ggctggggcg ggtggcatca tggacgagaa ggtgttcacc aaggagctgg 240 accagtggat cgagcagctg aacgagtgca agcagctgtc cgagtcccag gtcaagagcc 300 tctgcgagaa ggctaaagaa atcctgacaa aagaatccaa cgtgcaagag gttcgatgtc 360 cagttactgt ctgtggagat gtgcatgggc aatttcatga tctcatggaa ctgtttagaa 420 ttggtggcaa atcaccagat acaaattact tgtttatggg agattatgtt gacagaggat 480 attattcagt tgaaacagtt acactgcttg tagctcttaa ggttcgttac cgtgaacgca 540 tcaccattct tcgagggaat catgagagca gacagatcac acaagtttat ggtttctatg 600 atgaatgttt aagaaaatat ggaaatgcaa atgtttggaa atattttaca gatctttttg 660 actatcttcc tctcactgcc ttggtggatg ggcagatctt ctgtctacat ggtggtctct 720 cgccatctat agatacactg gatcatatca gagcacttga tcgcctacaa gaagttcccc 780 atgagggtcc aatgtgtgac ttgctgtggt cagatccaga tgaccgtggt ggttggggta 840 tatctcctcg aggagctggt tacacctttg ggcaagatat ttctgagaca tttaatcatg 900 ccaatggcct cacgttggtg tctagagctc accagctagt gatggaggga tataactggt 960 gccatgaccg gaatgtagta acgattttca gtgctccaaa ctattgttat cgttgtggta 1020 accaagctgc aatcatggaa cttgacgata ctctaaaata ctctttcttg cagtttgacc 1080 cagcacctcg tagaggcgag ccacatgtta ctcgtcgtac cccagactac ttcctgtaat 1140 gaaattttaa acttgtacag tattgccatg aaccatatat cgacctaatg gaaatgggaa 1200 gagcaacagt aactccaaag tgtcagaaaa tagttaacat tcaaaaaact tgttttcaca 1260 tggaccaaaa gatgtgccat ataaaaatac aaagcctctt gtcatcaaca gccgtgacca 1320 ctttagaatg aaccagttca ttgcatgctg aagcgacatt gttggtcaag aaaccagttt 1380 ctggcatagc gctatttgta gttacttttg ctttctctga gagactgcag ataataagat 1440 gtaaacatta acacctcgtg aatacaattt aacttccatt tagctatagc tttactcagc 1500 atgactgtag ataaggatag cagcaaacaa tcattggagc ttaatgaaca tttttaaaaa 1560 taattaccaa ggcctccctt ctacttgtga gttttgaaat tgttcttttt attttcaggg 1620 ataccgttta atttaattat atgatttgtc tgcactcagt ttattcccta ctcaaatctc 1680 agccccatgt tgttctttgt tattgtcaga acctggtgag ttgttttgaa cagaactgtt 1740 ttttcccctt cctgtaagac gatgtgactg cacaagagca ctgcagtgtt tttcataata 1800 aacttgtgaa ctaagaactg agaaggtcaa attttaattg tatcaatggg caagactggt 1860 gctgtttatt aaaaaagtta aatcaattga gtaaatttta gaatttgtag acttgtaggt 1920 aaaataaaaa tcaagggcac tacataacct ctctggtaac tccttgacat tcttcagatt 1980 aacttcagga tttatttgta tttcacatat tacaatttgt cacattgttg gtgtgcactt 2040 tgtgggttct tcctgcatat taacttgttt gtaagaaagg aaatctgtgc tgcttcagta 2100 agacttaatt gtaaaaccat ataacttgag atttaagtct ttgggttgtg ttttaataaa 2160 acagcatgtt ttcaggtaga g 2181 <210> SEQ ID NO 21 <211> LENGTH: 3160 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 21 cctcccctcg cccggcgcgg tcccgtccgc ctctcgctcg cctcccgcct cccctcggtc 60 ttccgaggcg cccgggctcc cggcgcggcg gcggaggggg cgggcaggcc ggcgggcggt 120 gatgtggcag gactctttat gcgctgcggc aggatacgcg ctcggcgctg ggacgcgact 180 gcgctcagtt ctctcctctc ggaagctgca gccatgatgg aagtttgaga gttgagccgc 240 tgtgaggcga ggccgggctc aggcgaggga gatgagagac ggcggcggcc gcggcccgga 300 gcccctctca gcgcctgtga gcagccgcgg gggcagcgcc ctcggggagc cggccggcct 360 gcggcggcgg cagcggcggc gtttctcgcc tcctcttcgt cttttctaac cgtgcagcct 420 cttcctcggc ttctcctgaa agggaaggtg gaagccgtgg gctcgggcgg gagccggctg 480 aggcgcggcg gcggcggcgg cggcacctcc cgctcctgga gcggggggga gaagcggcgg 540 cggcggcggc cgcggcggct gcagctccag ggagggggtc tgagtcgcct gtcaccattt 600 ccagggctgg gaacgccgga gagttggtct ctccccttct actgcctcca acacggcggc 660 ggcggcggcg gcacatccag ggacccgggc cggttttaaa cctcccgtcc gccgccgccg 720 caccccccgt ggcccgggct ccggaggccg ccggcggagg cagccgttcg gaggattatt 780 cgtcttctcc ccattccgct gccgccgctg ccaggcctct ggctgctgag gagaagcagg 840 cccagtcgct gcaaccatcc agcagccgcc gcagcagcca ttacccggct gcggtccaga 900 gccaagcggc ggcagagcga ggggcatcag ctaccgccaa gtccagagcc atttccatcc 960 tgcagaagaa gccccgccac cagcagcttc tgccatctct ctcctccttt ttcttcagcc 1020 acaggctccc agacatgaca gccatcatca aagagatcgt tagcagaaac aaaaggagat 1080 atcaagagga tggattcgac ttagacttga cctatattta tccaaacatt attgctatgg 1140 gatttcctgc agaaagactt gaaggcgtat acaggaacaa tattgatgat gtagtaaggt 1200 ttttggattc aaagcataaa aaccattaca agatatacaa tctttgtgct gaaagacatt 1260 atgacaccgc caaatttaat tgcagagttg cacaatatcc ttttgaagac cataacccac 1320 cacagctaga acttatcaaa cccttttgtg aagatcttga ccaatggcta agtgaagatg 1380 acaatcatgt tgcagcaatt cactgtaaag ctggaaaggg acgaactggt gtaatgatat 1440 gtgcatattt attacatcgg ggcaaatttt taaaggcaca agaggcccta gatttctatg 1500 gggaagtaag gaccagagac aaaaagggag taactattcc cagtcagagg cgctatgtgt 1560 attattatag ctacctgtta aagaatcatc tggattatag accagtggca ctgttgtttc 1620 acaagatgat gtttgaaact attccaatgt tcagtggcgg aacttgcaat cctcagtttg 1680 tggtctgcca gctaaaggtg aagatatatt cctccaattc aggacccaca cgacgggaag 1740 acaagttcat gtactttgag ttccctcagc cgttacctgt gtgtggtgat atcaaagtag 1800 agttcttcca caaacagaac aagatgctaa aaaaggacaa aatgtttcac ttttgggtaa 1860 atacattctt cataccagga ccagaggaaa cctcagaaaa agtagaaaat ggaagtctat 1920 gtgatcaaga aatcgatagc atttgcagta tagagcgtgc agataatgac aaggaatatc 1980 tagtacttac tttaacaaaa aatgatcttg acaaagcaaa taaagacaaa gccaaccgat 2040 acttttctcc aaattttaag gtgaagctgt acttcacaaa aacagtagag gagccgtcaa 2100 atccagaggc tagcagttca acttctgtaa caccagatgt tagtgacaat gaacctgatc 2160 attatagata ttctgacacc actgactctg atccagagaa tgaacctttt gatgaagatc 2220 agcatacaca aattacaaaa gtctgaattt ttttttatca agagggataa aacaccatga 2280 aaataaactt gaataaactg aaaatggacc tttttttttt taatggcaat aggacattgt 2340 gtcagattac cagttatagg aacaattctc ttttcctgac caatcttgtt ttaccctata 2400 catccacagg gttttgacac ttgttgtcca gttgaaaaaa ggttgtgtag ctgtgtcatg 2460 tatatacctt tttgtgtcaa aaggacattt aaaattcaat taggattaat aaagatggca 2520 ctttcccgtt ttattccagt tttataaaaa gtggagacag actgatgtgt atacgtagga 2580 attttttcct tttgtgttct gtcaccaact gaagtggcta aagagctttg tgatatactg 2640 gttcacatcc tacccctttg cacttgtggc aacagataag tttgcagttg gctaagagag 2700 gtttccgaaa ggttttgcta ccattctaat gcatgtattc gggttagggc aatggagggg 2760 aatgctcaga aaggaaataa ttttatgctg gactctggac catataccat ctccagctat 2820 ttacacacac ctttctttag catgctacag ttattaatct ggacattcga ggaattggcc 2880 gctgtcactg cttgttgttt gcgcattttt ttttaaagca tattggtgct agaaaaggca 2940 gctaaaggaa gtgaatctgt attggggtac aggaatgaac cttctgcaac atcttaagat 3000 ccacaaatga agggatataa aaataatgtc ataggtaaga aacacagcaa caatgactta 3060 accatataaa tgtggaggct atcaacaaag aatgggcttg aaacattata aaaattgaca 3120 atgatttatt aaatatgttt tctcaattgt aaaaaaaaaa 3160 <210> SEQ ID NO 22 <211> LENGTH: 4127 <212> TYPE: DNA <213> ORGANISM: R. norvegicus <400> SEQUENCE: 22 agccgctgct ggggaggttg gggctgaggt ggtggcgggc gacgggcctc gagacgcgga 60 gcgacgcggc ctagcgcggc ggacggccga gggaactcgg gcagtcgtcc cgtcccgcca 120 tggaaatgga gaaggaattc gagcagatcg ataaggctgg gaactgggcg gctatttacc 180 aggatattcg acatgaagcc agtgacttcc catgcagaat agcgaaactt cctaagaaca 240 aaaaccggaa caggtaccga gatgtcagcc cttttgacca cagtcggatt aaattgcatc 300 aggaagataa tgactatatc aatgccagct tgataaaaat ggaggaagcc cagaggagct 360 atatcctcac ccagggccct ttaccaaaca cgtgcgggca cttctgggag atggtgtggg 420 agcagaagag caggggcgtg gtcatgctca accgcatcat ggagaaaggc tcgttaaaat 480 gtgcccagta ttggccacag aaagaagaaa aagagatggt cttcgatgac accaatttga 540 agctgacact gatctctgaa gatgtcaagt catattacac agtacggcag ttggagttgg 600 agaacctggc tacccaggag gctcgagaga tcctgcattt ccactacacc acctggcctg 660 actttggagt ccctgagtca cctgcctctt tcctcaattt cctattcaaa gtccgagagt 720 caggctcact cagcccagag cacggcccca ttgtggtcca ctgcagtgct ggcattggca 780 ggtcagggac cttctgcctg gctgacacct gcctcttact gatggacaag aggaaagacc 840 cgtcctctgt ggacatcaag aaagtgctgt tggagatgcg caggttccgc atggggctca 900 tccagacggc cgaccaactg cgcttctcct acctggctgt gatcgagggt gcaaagttca 960 tcatgggcga ctcgtcagtg caggatcagt ggaaggagct ttcccatgaa gacctggagc 1020 ctccccctga gcacgtgccc ccacctcccc ggccacccaa acgcacattg gagcctcaca 1080 atggcaagtg caaggagctc ttctccaacc accagtgggt gagcgaggag agctgtgagg 1140 atgaggacat cctggccaga gaggaaagca gagccccctc aattgctgtg cacagcatga 1200 gcagtatgag tcaagacact gaagttagga aacggatggt gggtggaggt cttcaaagtg 1260 ctcaggcatc tgtccccact gaggaagagc tgtccccaac cgaggaggaa caaaaggcac 1320 acaggccagt tcactggaag cccttcctgg tcaacgtgtg catggccacg gccctggcga 1380 ctggcgcgta cctctgttac cgggtatgtt ttcactgaca gactgctgtg aggcatgagc 1440 gtggtgggcg ctgccactgc ccaggttagg atttggtctg cggcgtctaa cctggtgtag 1500 aagaaacaac agcttacaag cctgtggtgg aactggaagg gccagcccca ggaggggcat 1560 ctgtgcactg ggctttgaag gagcccctgg tcccaagaac agagtctaat ctcagggcct 1620 taacctgttc aggagaagta gaggaaatgc caaatactct tcttgctctc acctcactcc 1680 tcccctttct ctggttcgtt tgtttttgga aaaaaaaaaa aaagaattac aacacattgt 1740 tgtttttaac atttataaag gcaggttttt gttattttta gagaaaacaa aagatgctag 1800 gcactggtga gattctcttg tgccctttgg catgtgatca gattcacgat ttacgtttat 1860 ttccggggga gggtcccacc tgtcaggact gtaaagttcc tgctggcttg gtcagccccc 1920 ccaccccccc accccgagct tgcaggtgcc ctgctgtgag gagagcagca gcagaggctg 1980 cccctggaca gaagcccagc tctgcttccc tcaggtgtcc ctgcgtttcc atcctccttc 2040 tttgtgaccg ccatcttgca gatgacccag tcctcagcac cccacccctg cagatgggtt 2100 tctccgaggg cctgcctcag ggtcatcaga ggttggctgc cagcttagag ctggggcttc 2160 catttgattg gaaagtcatt actattctat gtagaagcca ctccactgag gtgtaaagca 2220 agactcataa aggaggagcc ttggtgtcat ggaagtcact ccgcgcgcag gacctgtaac 2280 aacctctgaa acactcagtc ctgctgcagt gacgtccttg aaggcatcag acagatgatt 2340 tgcagactgc caagacttgt cctgagccgt gatttttaga gtctggactc atgaaacacc 2400 gccgagcgct tactgtgcag cctctgatgc tggttggctg aggctgcggg gaggtggaca 2460 ctgtgggtgc atccagtgca gttgcttttg tgcagttggg tccagcagca cagcccgcac 2520 tccagcctca gctgcaggcc acagtggcca tggaggccgc cagagcgagc tggggtggat 2580 gcttgttcac ttggagcagc cttcccagga cgtgcagctc ccttcctgct ttgtccttct 2640 gcttccttcc ctggagtagc aagcccacga gcaatcgtga ggggtgtgag ggagctgcag 2700 aggcatcaga gtggcctgca gcggcgtgag gccccttccc ctccgacacc cccctccaga 2760 ggagccgctc cactgttatt tattcacttt gcccacagac acccctgagt gagcacaccc 2820 tgaaactgac cgtgtaaggt gtcagcctgc acccaggacc gtcaggtgca gcaccgggtc 2880 agtcctaggg ttgaggtagg actgacacag ccactgtgtg gctggtgctg gggcaggggc 2940 aggagctgag ggtcttagaa gcaatcttca ggaacagaca acagtggtga catgtaaagt 3000 ccctgtggct actgatgaca tgtgtaggat gaaggctggc ctttctccca tgactttcta 3060 gatcccgttc cccgtctgct ttccctgtga gttagaaaac acacaggctc ctgtcctggt 3120 ggtgccgtgt gcttgacatg ggaaacttag atgcctgctc actggcgggc acctcggcat 3180 cgccaccact cagagtgaga gcagtgctgt ccagtgccga ggccgcctga ctcccggcag 3240 gactcttcag gctctggcct gccccagcac accccgctgg atctcagaca ttccacaccc 3300 acacctcatt ccctggacac ttgggcaagc aggcccgccc ttccacctct ggggtcagcc 3360 cctccattcc gagttcacac tgctctggag caggccagga ccggaagcaa ggcagctggt 3420 gaggagcacc ctcctgggaa cagtgtaggt gacagtcctg agagtcagct tgctagcgct 3480 gctggcacca gtcaccttgc tcagaagtgt gtggctcttg aggctgaaga gactgatgat 3540 ggtgctcatg actcttctgt gaggggaact tgaccttcac attgggtggc tttttttaaa 3600 ataagcgaag gcagctggaa ctccagtctg cctcttgcca gcacttcaca ttttgccttt 3660 cacccagaga agccagcaca gagccactgg ggaaggcgat ggccttgcct gcacaggctg 3720 aggagatggc tcagccggcg tccaggctgt gtctggagca gggggtgcac agcagcctca 3780 caggtggggg cctcagagca ggcgctgccc tgtcccctgc cccgctggag gcagcaaagc 3840 tgctgcatgc cttaagtcaa tacttactca gcagggcgct ctcgttctct ctctctctct 3900 ctctctctct ctctctctct ctctctctct ctctaaatgg ccatagaata aaccatttta 3960 caaaaataaa agccaacaac aaagtgctct ggaatagcac ctttgcagga gcggggggtg 4020 tctcagggtc ttctgtgacc tcaccgaact gtccgactgc accgtttcca acttgtgtct 4080 cactaatggg tctgcattag ttgcaacaat aaatgttttt aaagaac 4127 <210> SEQ ID NO 23 <211> LENGTH: 2194 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 23 gacaggctgg tcctcaccat ggccacctgc tggcaggcac tatgggccta tcgctcctac 60 ctgattgtgc tatgtctgcc cattttcctg ttgcctctgc cactcattgt ccaaactaag 120 gaagcctact gtgcttactc catcatcctc atggcgctgc tgtggtgtac agaggccctg 180 cccttggctg tcaccgccct cttccccatc atcctcttcc ctttgatggg tatcatggaa 240 gcctccaagg tctgcttaga gtacttcaag gacaccaaca tattgttcgt cgggggtctg 300 atggtggcca tcgccgtgga gcactggaac ctgcacaagc gcattgccct tggagtgctc 360 cttatcatag gagtgcggcc cgccctgctg cttctgggct tcatgttggt cacagccttc 420 ctctccatgt ggatcagcaa cacagccacc acagccatga tgctgcccat cgggtatgca 480 gtcctggagc agctgcaggg ctcacaaaag gatgtggagg aaggcaatag taacccttcc 540 tttgagctcc aggaagcaag tccccagaag gaggagacca agcttgataa cggtcaggct 600 gtatctgttt cttcggagcc aagagctcag aagaccaaag agcatcaccg cttcagccag 660 ggcctgagtc tctgcatctg ctactcagcc agcattgggg gcattgccac cctgacgggt 720 accacaccca acctggtgct ccaaggccag gtcaactcga tcttccctga aaatagtaac 780 gtggtgaact ttgcttcatg gtttggtttt gccttcccca ccatggtgat cttgctgcta 840 ctggcttggc tatggctaca ggtcctcttc ctgggtgtca acttccggaa gaactttggc 900 tttggggaag gggaagagga acggaagcag gctgccttcc aggtcatcaa gacccagcac 960 aggctgctgg gccccatgag ttttgcagag aaggctgtca ctttcctgtt tgtcctgcta 1020 gtggtgctct ggttcacgag ggagccgggc ttcttcccag gctggggtga cacagctttc 1080 gccaataaaa aagggcaaag catggtatca gatgggacag tggccatctt tatcagcctg 1140 attatgttca tcataccctc caagattcca ggactaaccg aggacccaaa aaaaccaggg 1200 aagctgaagg ctcctcctgc catcctcacc tggaagacag tgaacgataa gatgccctgg 1260 aatatcctga tcttgctggg tgggggcttt gccctggcca aaggcagtga ggaatcaggt 1320 ttgtctaagt ggctgggaga caaactgacc ccgctgcagc acgtaccgcc atcagccacc 1380 gtgctcatcc tctctctatt ggtggccatc ttcactgagt gcaccagcaa cgtggccacc 1440 actacactat ttctgcccat cctggcctcc atggcacagg ccatctgcct tcacccgctt 1500 tatgtcatgc ttccctgcac cctggctgcc tccctagctt tcatgctacc cgtggccact 1560 ccacccaacg ccattgtctt ctcttttgga ggcctcaaag tgtctgatat ggcccgtgca 1620 ggattcctgc tcaatatcat cggagtgctg actatcacat tatccataaa cagctggagt 1680 atccctatct tcaagctgga cacatttccc acctgggcct actccaacac aagccagtgc 1740 cttctcaatc cgcctaattc cactgtacca ggccactaga ctatggtaca acctagctct 1800 gctaggggaa aagccgctgg tgccactcct cggagccagg agagggcgct ccaaactcca 1860 agtcccggga cagaggtgca gaatcggctg gcgcatgcga aatcatgtat tcgtgtgttt 1920 gcctacatcc tgtatgtgtg ctctccggtg aagaggaaga tgctcgtgtc tccgtgtggt 1980 gtgcgtggac gcttgcgtgt ggtgtggcct gagggctcct cagtagttgt atgcatggca 2040 accgcgcccg ccctctgact cccagctagg cctccagatc tctttgccct gtatttattg 2100 aaactctggg caggaggccc ctgggagcag gaactccaaa gttcattaaa ggctttttca 2160 gtagagtccg ggtgtgtttc ccggtgttca gaag 2194 <210> SEQ ID NO 24 <211> LENGTH: 5383 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 24 tcccagtctc ccggggtttc tctttgctgg tgcctggaag tgggggtaga tgtgaagtta 60 gaccgagttg tgagtggcgg tagccagtgt cttcctcact tctttcgatg cgatttcccc 120 agtgaaccat ttgctaagcg ccagaccaaa gtcctaggct tgcacacaat tcctacttgg 180 aatcacgtta tcctgctctt aaagaaaagt cacccatcag cccacagcaa agaggataag 240 gagaaaaaga ggggaggaga gacggagaag ctagaggcag agggaacagc agattgcgcc 300 tagccaatgg aaaaggcagg acaaggtggc accaaattct ctttggccaa tgacaagacg 360 ggcttcacag gaggcacatt agcatttatc cccaggcagg gggttggagc agcgcgccct 420 gttgatgcct tcagcatccc ggcgcctcca aggtctactc tggaatctac ttggctttct 480 ttcccgttct tggtcccgcc ctctctctct ccctccctcc ctccctccct tcctccctcc 540 ctccctccct ccctccctcc ctcacctcca cgcctggctt ccttggctag ctatctctgc 600 gctctttacc ctttgctggc agccgataaa agggggctga ggaaatactg aacacggtca 660 tcccatcgcc tgctctaccc tttaaaatcc cagcccagga gatctgtgca cagccagacc 720 gggctgaaca cccatcccga gagtcaggag ggcaggtttc caagcgcagt tccgccactc 780 gcctacacca acgggctccg gaaccgaagt ccacgctcga tctcagcact gggaaagtga 840 ggcgagcaac tgactatcat catgccggcc cacatgctcc aagagatctc cagttcttac 900 acgaccacca ccaccatcac tgcacctccc tccggaaatg aacgagagaa ggtgaagaca 960 gtgcccctcc acctggaaga agacatccgt cctgaaatga aagaagatat tcacgacccc 1020 acctatcagg atgaggaggg acccccgccc aagctggagt acgtctggag gaacatcatt 1080 ctcatggtcc tgctgcactt gggaggcctg tacgggatca tactggttcc ctcctgcaag 1140 ctctacactg ccctcttcgg gattttctac tacatgacca gcgctctggg catcacagcc 1200 ggggctcatc gcctctggag ccacagaact tacaaggctc ggctgcccct gcggatcttc 1260 ctaatcattg ccaacaccat ggcgttccaa aatgacgtgt acgactgggc ccgagatcac 1320 cgcgcccacc acaagttctc agaaacacac gccgaccctc acaattcccg ccgtggcttc 1380 ttcttctctc acgtgggttg gctgcttgtg cgcaaacacc cggctgtcaa agagaagggc 1440 ggaaaactgg acatgtctga cctgaaagcc gagaagctgg tgatgttcca gaggaggtac 1500 tacaagcccg gcctcctgct gatgtgcttc atcctgccca cgctggtgcc ctggtactgc 1560 tggggcgaga cttttgtaaa cagcctgttc gttagcacct tcttgcgata cactctggtg 1620 ctcaacgcca cctggctggt gaacagtgcc gcgcatctct atggatatcg cccctacgac 1680 aagaacattc aatcccggga gaatatcctg gtttccctgg gtgccgtggg cgagggcttc 1740 cacaactacc accacacctt ccccttcgac tactctgcca gtgagtaccg ctggcacatc 1800 aacttcacca cgttcttcat cgactgcatg gctgccctgg gcctggctta cgaccggaag 1860 aaagtttcta aggctactgt cttagccagg attaagagaa ctggagacgg gagtcacaag 1920 agtagctgag ctttgggctt ctgagttcct gtttcaaacg ttttctggca gagatttaat 1980 attctgttga ttaactaaca actggatatt gctatcgggg tgttaatgat gcatttaacc 2040 tattccggta cagtattctt ataaaatgag aaagctttga tcacgttttg aggtaataaa 2100 tattttattt agctaggatt aaccatgcca caagacatta tatatttcta agcacacatg 2160 ataaatgcat atacaatttt gcacaacagc tttaaataat aacaataaat ttgaacattc 2220 tatacagaga ggatcaaagc caaggaacat gctgttttga tgctagggtg agcatggtgc 2280 tcagtccctg tttgtttgca tggtgtccag ctttgtttct tctctgtcat caccaccttc 2340 aggcaaatag ttgaccaacc actggcctgt gtctgtccac cctccaaagc ccaggccacc 2400 tttctgtttt ctgaaatact gatccttcct cctgaataca tccctccttg ttcctagctt 2460 caagactgct gcctcaaata gggatagagc aagtccccgc tgcaggttgt gctagatggg 2520 atggagaaat tatcttcatt tgatacagag caagtagatt gtctcgagag aaaagttagc 2580 atgcgtggta tgatttgtaa gtaaagatgg aagagagaga gagagagaga gagagagaga 2640 gagagagaga gagagaggta gccatatcta acagcctact taccaaagac cccaggcctc 2700 tctgcttggc atgcctcctt tctgtccatc ctctgaaccc cagagattag tgagatttga 2760 ataattaaat cattttcaga gtgaaggggg ttaatgcagg gtctgtgcta ggggagggtt 2820 ttagcttttg gtaactgaag attttttcat ggaaaaagtc ttcgtgttca atgtgcctag 2880 aactgataac taaacagctg acatttgtcg gggacagata tggtgtgaaa ctatgaaaat 2940 ataagcaaaa tcttcacttg gaacatgaaa ctatttcact tagaaaataa tcgaaggacc 3000 cgaggtgttg cctgggttgc cagtttcttt cgtggctggg caggaactag tgaggttgag 3060 gggcagtgtc tgtaagtagc tgctaagagg tgcatttcca gatgaagccc ttggggaaca 3120 tctgccaggg atccgcatgg tgttggctcc atccattgct ttagtttcct ccttggattg 3180 tgtagaaact tggcttccca tggttttgaa ccttccatgc cttctttgct ttgtggccac 3240 ccagcctgcc tagtgctgcc taggaagctc ttacccacct gatttcttct gacatttctt 3300 tctttggcct ttttttcttt ctccggacat gcagctagtt gcctgagtgt atcaagagca 3360 cccaggactt gctgctgtcc aggcctgttc ctcccccagt atccgtgggt gtggaagagc 3420 tgtgtagctt caggaagcag agccaggtgc cacctttctg tggcttccag atcctcccta 3480 cctccaactc atgtgcctct gtcacagtga tttcaggaaa gcttggtaga ccctctagca 3540 acatctcggt tcagaaagtc tctctggttt gtgagttaac agctcagcta agtgctgttt 3600 tgtctcagtg agttaaccac tgaatgcgag ggttggttgt tgatctgtct cggtgtgtgt 3660 cggagtagac agcatatgca cttctccctg tgcgctttgc aaggtaatgt ggctttggct 3720 gatccatgca ggcaggtagt ggtacagtgc tgctgaaagg aagaagttcc ccattttatc 3780 tgttaaaaca ccagagacat gggcaagtgc taatggacct cacttcagga agagggtctg 3840 cttcctgaag ccagtgtgtg atgaaaagtg actgagacct gatatctaag gtgagacctg 3900 atacctaaca ctctgtcaca cagtccaggg ccaacagtgc tataggaaag tctagaagaa 3960 aacatcacat cagtatttta gaaccatcaa ccatctcttg tccctatagc ccaatccaga 4020 ggcctggttt ttagaactgg ctgtgtaagg tgccaaacac tcagttcact tgtagaatca 4080 gagccttttt tcccccctat gttaattgaa cacgcgctct gagctgtttt gttgaagtag 4140 aaaatctcat agaaaaatca ctgtagatct actgacctat agccctctgg aaatgccttt 4200 gagatggttt tacttttcta ggtcatagat gcctgattat aaagatgaac aataaaatca 4260 gctttctttc tttctcttct gatcttattc cccagatctg attcaggcca tgttccaaag 4320 caaggctaca ttgaggtcct ggtgtcttta agtaaaggac atctttcaga tcctctcaaa 4380 gaaggattta taacagtttc cagatgaatg tactaatagc tttgggtgcc ttatctcttt 4440 cctaatctgt agtgcctgtg agctcagtct cactccttcc cttagcccgg agacccctta 4500 gatcgagtgg gaatagtcaa gaggctggct ggagagtcat cagtacattg gtttgcagaa 4560 atcttttaca ggctacattt tggaattttt ttttttttag taagtgatca aatttggtgg 4620 gaagtaattc gagtgtattc gattgtattg tcgtcctcgt tatcattgtc aaacatgtta 4680 tagacggcag ttggcactgg ggctgctaat ctctgggtgt agtctctgaa actgtagctc 4740 cagtgaggtg gtgtgaaagg ttagcaaagc caccatctgc tggtgctcca gccaaggtgc 4800 ctcttagcca ctgaattgct atgttatcct ttctcttgta acaaacccac cccagagata 4860 aagcctttaa tcaacccaag aaactcctgg gctaagtatc tgacagtctc acatctcaac 4920 agtgtgaatt aagtgtccat agcatcagct caggaggaca ctctgggaga gtgctgacaa 4980 aaaagggtta ttaatactga cctactactt caagggcagt tctgaggtga ttagagcttt 5040 ttttaaaaac caagtatttg gggatcctca gcagaggtat tcatacagac tcccaaagaa 5100 ctatatatgt tcctgagacc atcgtttagt ctacattgct cttcccagag actgacagat 5160 atgaccagtc aaagtgcaag actacctacc cactgccatg aaaaccattg caggaaacct 5220 ttcccttcct gaatgagatt ttttttttcc ctttttatgt ggggtaatta tttgtgaccc 5280 aagtgtaatt tggatgattt ccattaatat caactcttga agcctacttg tactgattga 5340 gattgtattt gttcctaata aaagtggatc tggttgtact gtc 5383 <210> SEQ ID NO 25 <211> LENGTH: 14796 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 25 tctagacatg cggatatatt caagctgggc acagcacagc agccccaccc caggcagctt 60 gaaatcagag ctggggtcca aagggaccac accccgaggg actgtgtggg ggtcggggca 120 cacaggccac tgcttccccc cgtctttctc agccattcct gaagtcagcc tcactctgct 180 tctcagggat ttcaaatgtg cagagactct ggcacttttg tagaagcccc ttctggtcct 240 aacttacacc tggatgctgt ggggctgcag ctgctgctcg ggctcgggag gatgctgggg 300 gcccggtgcc catgagcttt tgaagctcct ggaactcggt tttgagggtg ttcaggtcca 360 ggtggacacc tgggctgtcc ttgtccatgc atttgatgac attgtgtgca gaagtgaaaa 420 ggagttaggc cgggcatgct ggcttatgcc tgtaatccca gcactttggg aggctgaggc 480 gggtggatca cgaggtcagg agttcaatac cagcctggcc aagatggtga aaccccgtct 540 ctactaaaaa tacaaaaaaa ttagccgggc atggtggcgg gcgcatgtaa tcccagctac 600 tgggggggct gaggcagaga attgctggaa cccaggagat ggaggttgca gtgagccaag 660 attgtgccac tgcactgcac tccagcctgg cgacagagca agactctgtc tcaaaaaaaa 720 aaaaaaaaag tgaaaaggag ttgttccttt cctccctcct gagggcaggc aactgctgcg 780 gttgccagtg gaggtggtgc gtccttggtc tgtgcctggg ggccacccca gcagaggcca 840 tggtggtgcc agggcccggt tagcgagcca atcagcagga cccaggggcg acctgccaaa 900 gtcaactgga tttgataact gcagcgaagt taagtttcct gattttgatg attgtgttgt 960 ggttgtgtaa gagaatgaag tatttcgggg tagtatggta atgccttcaa cttacaaacg 1020 gttcaggtaa accacccata tacatacata tacatgcatg tgatatatac acatacaggg 1080 atgtgtgtgt gttcacatat atgaggggag agagactagg ggagagaaag taggttgggg 1140 agagggagag agaaaggaaa acaggagaca gagagagagc ggggagtaga gagagggaag 1200 gggtaagaga gggagaggag gagagaaagg gaggaagaag cagagagtga atgttaaagg 1260 aaacaggcaa aacataaaca gaaaatctgg gtgaagggta tatgagtatt ctttgtacta 1320 ttcttgcaat tatcttttat ttaaattgac atcgggccgg gcgcagtggc tcacatctgt 1380 aatcccagca ctttgggagg ccgaggcagg cagatcactt gaggtcagga gtttgagacc 1440 agcctggcaa acatggtgaa accccatctc tactaaaaat acaaaaatta gcctggtgtg 1500 gtggtgcatg cctttaatct cagctactcg ggaggctgag gcaggagaat cgcttgaacc 1560 cgtggcgggg aggaggttgc agtgagctga gatcatgcca ctgcactcca gcctgggcga 1620 tagagcgaga ctcagtttca aataaataaa taaacatcaa aataaaaagt tactgtatta 1680 aagaatgggg gcggggtggg aggggtgggg agaggttgca aaaataaata aataaataaa 1740 taaaccccaa aatgaaaaag acagtggagg caccaggcct gcgtggggct ggagggctaa 1800 taaggccagg cctcttatct ctggccatag aaccagagaa gtgagtggat gtgatgccca 1860 gctccagaag tgactccaga acaccctgtt ccaaagcaga ggacacactg attttttttt 1920 taataggctg caggacttac tgttggtggg acgccctgct ttgcgaaggg aaaggaggag 1980 tttgccctga gcacaggccc ccaccctcca ctgggctttc cccagctccc ttgtcttctt 2040 atcacggtag tggcccagtc cctggcccct gactccagaa ggtggccctc ctggaaaccc 2100 aggtcgtgca gtcaacgatg tactcgccgg gacagcgatg tctgctgcac tccatccctc 2160 ccctgttcat ttgtccttca tgcccgtctg gagtagatgc tttttgcaga ggtggcaccc 2220 tgtaaagctc tcctgtctga cttttttttt ttttttagac tgagttttgc tcttgttgcc 2280 taggctggag tgcaatggca caatctcagc tcactgcacc ctctgcctcc cgggttcaag 2340 cgattctcct gcctcagcct cccgagtagt tgggattaca ggcatgcacc accacgccca 2400 gctaattttt gtatttttag tagagacaag gtttcaccgt gatggccagg ctggtcttga 2460 actccaggac tcaagtgatg ctcctgccta ggcctctcaa agtgttggga ttacaggcgt 2520 gagccactgc acccggcctg cacgcgttct ttgaaagcag tcgagggggc gctaggtgtg 2580 ggcagggacg agctggcgcg gcgtcgctgg gtgcaccgcg accacgggca gagccacgcg 2640 gcgggaggac tacaactccc ggcacacccc gcgccgcccc gcctctactc ccagaaggcc 2700 gcggggggtg gaccgcctaa gagggcgtgc gctcccgaca tgccccgcgg cgcgccatta 2760 accgccagat ttgaatcgcg ggacccgttg gcagaggtgg cggcggcggc atgggtgccc 2820 cgacgttgcc ccctgcctgg cagccctttc tcaaggacca ccgcatctct acattcaaga 2880 actggccctt cttggagggc tgcgcctgca ccccggagcg ggtgagactg cccggcctcc 2940 tggggtcccc cacgcccgcc ttgccctgtc cctagcgagg ccactgtgac tgggcctcgg 3000 gggtacaagc cgccctcccc tccccgtcct gtccccagcg aggccactgt ggctgggccc 3060 cttgggtcca ggccggcctc ccctccctgc tttgtcccca tcgaggcctt tgtggctggg 3120 cctcggggtt ccgggctgcc acgtccactc acgagctgtg ctgtcccttg cagatggccg 3180 aggctggctt catccactgc cccactgaga acgagccaga cttggcccag tgtttcttct 3240 gcttcaagga gctggaaggc tgggagccag atgacgaccc catgtaagtc ttctctggcc 3300 agcctcgatg ggctttgttt tgaactgagt tgtcaaaaga tttgagttgc aaagacactt 3360 agtatgggag ggttgctttc caccctcatt gcttcttaaa cagctgttgt gaacggatac 3420 ctctctatat gctggtgcct tggtgatgct tacaacctaa ttaaatctca tttgaccaaa 3480 atgccttggg gtggacgtaa gatgcctgat gcctttcatg ttcaacagaa tacatcagca 3540 gaccctgttg ttgtgaactc ccaggaatgt ccaagtgctt tttttgagat tttttaaaaa 3600 acagtttaat tgaaatataa cctacacagc acaaaaatta ccctttgaaa gtgtgcactt 3660 cacactttcg gaggctgagg cgggcggatc acctgaggtc aggagttcaa gacctgcctg 3720 gccaacttgg cgaaaccccg tctctactaa aaatacaaaa attagccggg catggtagcg 3780 cacgcccgta atcccagcta ctcgggaggc taaggcagga gaatcgcttg aacctgggag 3840 gcggaggttg cagtgagccg agattgtgcc aatgcactcc agcctcggcg acagagcgag 3900 actccgtcat aaaaataaaa aattgaaaaa aaaaaaagaa agaaagcata tacttcagtg 3960 ttgttctgga tttttttctt caagatgcct agttaatgac aatgaaattc tgtactcgga 4020 tggtatctgt ctttccacac tgtaatgcca tattcttttc tcaccttttt ttctgtcgga 4080 ttcagttgct tccacagctt taattttttt cccctggaga atcaccccag ttgtttttct 4140 ttttggccag aagagagtag ctgttttttt tcttagtatg tttgctatgg tggttatact 4200 gcatccccgt aatcactggg aaaagatcag tggtattctt cttgaaaatg aataagtgtt 4260 atgatatttt cagattagag ttacaactgg ctgtcttttt ggactttgtg tggccatgtt 4320 ttcattgtaa tgcagttctg gtaacggtga tagtcagtta tacagggaga ctcccctagc 4380 agaaaatgag agtgtgagct agggggtccc ttggggaacc cggggcaata atgcccttct 4440 ctgcccttaa tccttacagt gggccgggca cggtggctta cgcctgtaat accagcactt 4500 tgggaggccg aggcgggcgg atcacgaggt caggagatcg agaccatctt ggctaatacg 4560 gtgaaacccc gtctccacta aaaatacaaa aaattagccg ggcgtggtgg tgggcgcctg 4620 tagtcccagc tactcgggag gctgaggcag gagaatggcg tgaacccagg aggcggagct 4680 tgcagtgagc cgagattgca ccactgcact ccagcctggg cgacagaatg agactccgtc 4740 tcaaaaaaaa aaaaaaaaga aaaaaatctt tacagtggat tacataacaa ttccagtgaa 4800 atgaaattac ttcaaacagt tccttgagaa tgttggaggg atttgacatg taattccttt 4860 ggacatatac catgtaacac ttttccaact aattgctaag gaagtccaga taaaatagat 4920 acattagcca cacagatgtg gggggagatg tccacaggga gagagaaggt gctaagaggt 4980 gccatatggg aatgtggctt gggcaaagca ctgatgccat caacttcaga cttgacgtct 5040 tactcctgag gcagagcagg gtgtgcctgt ggagggcgtg gggaggtggc ccgtggggag 5100 tggactgccg ctttaatccc ttcagctgcc tttccgctgt tgttttgatt tttctagaga 5160 ggaacataaa aagcattcgt ccggttgcgc tttcctttct gtcaagaagc agtttgaaga 5220 attaaccctt ggtgaatttt tgaaactgga cagagaaaga gccaagaaca aaattgtatg 5280 tattgggaat aagaactgct caaaccctgt tcaatgtctt tagcactaaa ctacctagtc 5340 cctcaaaggg actctgtgtt ttcctcagga agcatttttt ttttttttct gagatagagt 5400 ttcactcttg ttgcccaggc tggagtgcaa tggtgcaatc ttggctcact gcaacctctg 5460 cctctcgggt tcaagtgatt ctcctgcctc agcctcccaa gtaactggga ttacagggaa 5520 gtgccaccac acccagctaa tttttgtatt tttagtagag atggggtttc accacattgc 5580 ccaggctggt cttgaactcc tgacctcgtg attcgcccac cttggcctcc caaagtgctg 5640 ggattacagg cgtgaaccac cacgcctggc tttttttttt ttgttctgag acacagtttc 5700 actctgttac ccaggctgga gtagggtggc ctgatctcgg atcactgcaa cctccgcctc 5760 ctgggctcaa gtgatttgcc tgcttcagcc tcccaagtag ccgagattac aggcatgtgc 5820 caccacaccc aggtaatttt tgtatttttg gtagagacga ggtttcacca tgttggccag 5880 gctggttttg aactcctgac ctcaggtgat ccacccgcct cagcctccca aagtgctgag 5940 attataggtg tgagccacca cacctggcct caggaagtat ttttattttt aaatttattt 6000 atttatttga gatggagtct tgctctgtcg cccaggctag agtgcagcga cgggatctcg 6060 gctcactgca agctccgccc cccaggttca agccattctc ctgcctcagc ctcccgagta 6120 gctgggacta caggcgcccg ccaccacacc cggctaattt ttttgtattt ttagtagaga 6180 cgggttttca ccgtgttagc caggagggtc ttgatctcct gacctcgtga tctgcctgcc 6240 tcggcctccc aaagtgctgg gattacaggt gtgagccacc acacccggct atttttattt 6300 ttttgagaca gggactcact ctgtcacctg ggctgcagtg cagtggtaca ccatagctca 6360 ctgcagcctc gaactcctga gctcaagtga tcctcccacc tcatcctcac aagtaattgg 6420 gactacaggt gcaccccacc atgcccacct aatttattta tttatttatt tatttatttt 6480 catagagatg agggttccct gtgttgtcca ggctggtctt gaactcctga gctcacggga 6540 tccttttgcc tgggcctccc aaagtgctga gattacaggc atgagccacc gtgcccagct 6600 aggaatcatt tttaaagccc ctaggatgtc tgtgtgattt taaagctcct ggagtgtggc 6660 cggtataagt atataccggt ataagtaaat cccacatttt gtgtcagtat ttactagaaa 6720 cttagtcatt tatctgaagt tgaaatgtaa ctgggcttta tttatttatt tatttattta 6780 tttattttta attttttttt ttgagacgag tctcactttg tcacccaggc tggagtgcag 6840 tggcacgatc tcggctcact gcaacctctg cctcccgggg tcaagcgatt ctcctgcctt 6900 agcctcccga gtagctggga ctacaggcac gcaccaccat gcctggctaa tttttgtatt 6960 tttagtagac ggggtttcac catgctggcc aagctggtct caaactcctg accttgtgat 7020 ctgcccgctt tagcctccca gagtgctggg attacaggca tgagccacca tgcgtggtct 7080 ttttaaaatt ttttgatttt tttttttttt gagacagagc cttgctctgt cgcccaggct 7140 ggagtgcagt ggcacgatct cagctcacta caagctccgc ctcccgggtt cacgccattc 7200 ttctgcctca gcctcctgag tagctgggac tacaggtgcc caccaccacg cctggctaat 7260 tttttttggt atttttatta gagacaaggt ttcatcatgt tggccaggct ggtctcaaac 7320 tcctgacctc aagtgatctg cctgcctcgg cctcccaaag cgctgagatt acaggtgtga 7380 tctactgcgc caggcctggg cgtcatatat tcttatttgc taagtctggc agccccacac 7440 agaataagta ctgggggatt ccatatcctt gtagcaaagc cctgggtgga gagtcaggag 7500 atgttgtagt tctgtctctg ccacttgcag actttgagtt taagccagtc gtgctcatgc 7560 tttccttgct aaatagaggt tagaccccct atcccatggt ttctcaggtt gcttttcagc 7620 ttgaaaattg tattcctttg tagagatcag cgtaaaataa ttctgtcctt atatgtggct 7680 ttattttaat ttgagacaga gtgtcactca gtcgcccagg ctggagtgtg gtggtgcgat 7740 cttggctcac tgcgacctcc acctcccagg ttcaagcgat tctcgtgcct caggctccca 7800 agtagctgag attataggtg tgtgccacca ggcccagcta acttttgtat ttttagtaga 7860 gacagggttt tgccatgttg gctaagctgg tctcgaactc ctggcctcaa gtgatctgcc 7920 cgccttggca tcccaaagtg ctgggattac aggtgtgaac caccacacct ggcctcaata 7980 tagtggcttt taagtgctaa ggactgagat tgtgttttgt caggaagagg ccagttgtgg 8040 gtgaagcatg ctgtgagaga gcttgtcacc tggttgaggt tgtgggagct gcagcgtggg 8100 aactggaaag tgggctgggg atcatctttt tccaggtcag gggtcagcca gcttttctgc 8160 agcgtgccat agaccatctc ttagccctcg tgggtcagag tctctgttgc atattgtctt 8220 ttgttgtttt tcacaacctt ttagaaacat aaaaagcatt cttagcccgt gggctggaca 8280 aaaaaaggcc atgacgggct gtatggattt ggcccagcag gcccttgctt gccaagccct 8340 gttttagaca aggagcagct tgtgtgcctg gaaccatcat gggcacaggg gaggagcaga 8400 gtggatgtgg aggtgtgagc tggaaaccag gtcccagagc gctgagaaag acagagggtt 8460 tttgcccttg caagtagagc aactgaaatc tgacaccatc cagttccaga aagccctgaa 8520 gtgctggtgg acgctgcggg gtgctccgct ctagggttac agggatgaag atgcagtctg 8580 gtagggggag tccactcacc tgttggaaga tgtgattaag aaaagtagac tttcagggcc 8640 gggcatggtg gctcacgcct gtaatcccag cactttggga ggccgaggcg ggtggatcac 8700 gaggtcagga gatcgagacc atcctggcta acatggtgaa accccgtctt tactaaaaat 8760 acaaaaaatt agctgggcgt ggtggcgggc gcctgtagtc ccagctactc gggaggctga 8820 ggcaggagaa tggcgtgaac ctgggaggtg gagcttgctg tgagccgaga tcgcgccact 8880 gcactccagc ctgggcgaca gagcgagact ccgtctcaaa aaaaaaaaaa aaagtaggct 8940 ttcatgatgt gtgagctgaa ggcgcagtag gcagaagtag aggcctcagt ccctgcagga 9000 gacccctcgg tctctatctc ctgatagtca gacccagcca cactggaaag aggggagaca 9060 ttacagcctg cgagaaaagt agggagattt aaaaactgct tggcttttat tttgaactgt 9120 tttttttgtt tgtttgtttt ccccaattca gaatacagaa tacttttatg gatttgtttt 9180 tattacttta attttgaaac aatataatct tttttttgtt gtttttttga gacagggtct 9240 tactctgtca cccaggctga gtgcagtggt gtgatcttgg ctcacctcag cctcgacccc 9300 ctgggctcaa atgattctcc cacctcagct tcccaagtag ctgggaccac aggtgcgtgt 9360 gttgcgctat acaaatcctg aagacaagga tgctgttgct ggtgatgctg gggattccca 9420 agatcccaga tttgatggca ggatgcccct gtctgctgcc ttgccagggt gccaggaggg 9480 cgctgctgtg gaagctgagg cccggccatc cagggcgatg cattgggcgc tgattcttgt 9540 tcctgctgct gcctcggtgc ttagcttttg aaacaatgaa ataaattaga accagtgtga 9600 aaatcgatca gggaataaat ttaatgtgga aataaactga acaacttagt tcttcataag 9660 agtttacttg gtaaatactt gtgatgagga caaaacgaag cactagaagg agaggcgagt 9720 tgtagacctg ggtggcagga gtgttttgtt tgttttcttt ggcagggtct tgctctgttg 9780 ctcaggctgg agtacagtgg cacaatcaca gctcactata gcctcgacct cctggactca 9840 agcaatcctc ctgcctcagc ctcccagtag ctgggactac aggcgcatgc caccatgcct 9900 ggctaatttt aaattttttt ttttctcttt tttgagatgg aatctcactc tgtcgcccag 9960 gctggagtgc agtggcgtga tctcggctga cggcaagctc cgcctcccag gttcactcca 10020 ttcgcctgcc tcagcctccc aagtagctgg gactacaggc gctgggatta caaacccaaa 10080 cccaaagtgc tgggattaca ggcgtgagcc actgcacccg gcctgttttg tctttcaata 10140 gcaagagttg tgtttgcttc gcccctacct ttagtggaaa aatgtataaa atggagatat 10200 tgacctccac attggggtgg ttaaattata gcatgtatgc aaaggagctt cgctaattta 10260 aggctttttt gaaagagaag aaactgaata atccatgtgt gtatatatat tttaaaagcc 10320 atggtcatct ttccatatca gtaaagctga ggctccctgg gactgcagag ttgtccatca 10380 cagtccatta taagtgcgct gctgggccag gtgcagtggc ttgtgcctga atcccagcac 10440 tttgggaggc caaggcagga ggattcattg agcccaggag ttttgaggcg agcctgggca 10500 atgtggccag acctcatctc ttcaaaaaat acacaaaaaa ttagccaggc atggtggcac 10560 gtgcctgtag tctcagctac tcaggaggct gaggtgggag gatcactttg agccttgcag 10620 gtcaaagctg cagtaagcca tgatcttgcc actgcattcc agcctggatg acagagcgag 10680 accctgtctc taaaaaaaaa aaaaaccaaa cggtgcactg ttttcttttt tcttatcaat 10740 ttattatttt taaattaaat tttcttttaa taatttataa attataaatt tatattaaaa 10800 aatgacaaat ttttattact tatacatgag gtaaaactta ggatatataa agtacatatt 10860 gaaaagtaat tttttggctg gcacagtggc tcacacctgt aatcccagca ctttgggagg 10920 ccgtggcggg cagatcacat gagatcatga gttcgagacc aacctgacca acatggagag 10980 accccatctc tactaaaaat acaaaattag ccggggtggt ggcgcatgcc tgtaatccca 11040 gctactcggg aggctgaggc aggagaatct cttgaacccg ggaggcagag gttgcggtga 11100 gccaagatcg tgcctttgca caccagccta ggcaacaaga gcgaaagtcc gtctcaaaaa 11160 aaaagtaatt ttttttaagt taacctctgt cagcaaacaa atttaaccca ataaaggtct 11220 ttgtttttta atgtagtaga ggagttaggg tttataaaaa atatggtagg gaagggggtc 11280 cctggatttg ctaatgtgat tgtcatttgc cccttaggag agagctctgt tagcagaatg 11340 aaaaaattgg aagccagatt cagggaggga ctggaagcaa aagaatttct gttcgaggaa 11400 gagcctgatg tttgccaggg tctgtttaac tggacatgaa gaggaaggct ctggactttc 11460 ctccaggagt ttcaggagaa aggtagggca gtggttaaga gcagagctct gcctagacta 11520 gctggggtgc ctagactagc tggggtgccc agactagctg gggtgcctag actagctggg 11580 tactttgagt ggctccttca gcctggacct cggtttcctc acctgtatag tagagatatg 11640 ggagcaccca gcgcaggatc actgtgaaca taaatcagtt aatggaggaa gcaggtagag 11700 tggtgctggg tgcataccaa gcactccgtc agtgtttcct gttattcgat gattaggagg 11760 cagcttaaac tagagggagt tgagctgaat caggatgttt gtcccaggta gctgggaatc 11820 tgcctagccc agtgcccagt ttatttaggt gctctctcag tgttccctga ttgttttttc 11880 ctttgtcatc ttatctacag gatgtgactg ggaagctctg gtttcagtgt catgtgtcta 11940 ttctttattt ccaggcaaag gaaaccaaca ataagaagaa agaatttgag gaaactgcga 12000 agaaagtgcg ccgtgccatc gagcagctgg ctgccatgga ttgaggcctc tggccggagc 12060 tgcctggtcc cagagtggct gcaccacttc cagggtttat tccctggtgc caccagcctt 12120 cctgtgggcc ccttagcaat gtcttaggaa aggagatcaa cattttcaaa ttagatgttt 12180 caactgtgct cctgttttgt cttgaaagtg gcaccagagg tgcttctgcc tgtgcagcgg 12240 gtgctgctgg taacagtggc tgcttctctc tctctctctc ttttttgggg gctcattttt 12300 gctgttttga ttcccgggct taccaggtga gaagtgaggg aggaagaagg cagtgtccct 12360 tttgctagag ctgacagctt tgttcgcgtg ggcagagcct tccacagtga atgtgtctgg 12420 acctcatgtt gttgaggctg tcacagtcct gagtgtggac ttggcaggtg cctgttgaat 12480 ctgagctgca ggttccttat ctgtcacacc tgtgcctcct cagaggacag tttttttgtt 12540 gttgtgtttt tttgtttttt ttttttggta gatgcatgac ttgtgtgtga tgagagaatg 12600 gagacagagt ccctggctcc tctactgttt aacaacatgg ctttcttatt ttgtttgaat 12660 tgttaattca cagaatagca caaactacaa ttaaaactaa gcacaaagcc attctaagtc 12720 attggggaaa cggggtgaac ttcaggtgga tgaggagaca gaatagagtg ataggaagcg 12780 tctggcagat actccttttg ccactgctgt gtgattagac aggcccagtg agccgcgggg 12840 cacatgctgg ccgctcctcc ctcagaaaaa ggcagtggcc taaatccttt ttaaatgact 12900 tggctcgatg ctgtggggga ctggctgggc tgctgcaggc cgtgtgtctg tcagcccaac 12960 cttcacatct gtcacgttct ccacacgggg gagagacgca gtccgcccag gtccccgctt 13020 tctttggagg cagcagctcc cgcagggctg aagtctggcg taagatgatg gatttgattc 13080 gccctcctcc ctgtcataga gctgcagggt ggattgttac agcttcgctg gaaacctctg 13140 gaggtcatct cggctgttcc tgagaaataa aaagcctgtc atttcaaaca ctgctgtgga 13200 ccctactggg tttttaaaat attgtcagtt tttcatcgtc gtccctagcc tgccaacagc 13260 catctgccca gacagccgca gtgaggatga gcgtcctggc agagacgcag ttgtctctgg 13320 gcgcttgcca gagccacgaa ccccagacct gtttgtatca tccgggctcc ttccgggcag 13380 aaacaactga aaatgcactt cagacccact tatttatgcc acatctgagt cggcctgaga 13440 tagacttttc cctctaaact gggagaatat cacagtggtt tttgttagca gaaaatgcac 13500 tccagcctct gtactcatct aagctgctta tttttgatat ttgtgtcagt ctgtaaatgg 13560 atacttcact ttaataactg ttgcttagta attggctttg tagagaagct ggaaaaaaat 13620 ggttttgtct tcaactcctt tgcatgccag gcggtgatgt ggatctcggc ttctgtgagc 13680 ctgtgctgtg ggcagggctg agctggagcc gcccctctca gcccgcctgc cacggccttt 13740 ccttaaaggc catccttaaa accagaccct catggctgcc agcacctgaa agcttcctcg 13800 acatctgtta ataaagccgt aggcccttgt ctaagcgcaa ccgcctagac tttctttcag 13860 atacatgtcc acatgtccat ttttcaggtt ctctaagttg gagtggagtc tgggaagggt 13920 tgtgaatgag gcttctgggc tatgggtgag gttccaatgg caggttagag cccctcgggc 13980 caactgccat cctggaaagt agagacagca gtgcccgctg cccagaagag accagcaagc 14040 caaactggag cccccattgc aggctgtcgc catgtggaaa gagtaactca caattgccaa 14100 taaagtctca tgtggtttta tctacttttt ttttcttttt cttttttttt gagacaaggc 14160 cttgccctcc caggctggag tgcagtggaa tgaccacagc tcaccgcaac ctcaaattct 14220 tgcgttcaag tgaacctccc actttagcct cccaagtagc tgggactaca ggcgcacgcc 14280 atcacacccg gctaattgaa aaattttttt ttttgtttag atggaatctc actttgttgc 14340 ccaggctggt ctcaaactcc tgggctcaag tgatcatcct gcttcagcgt ccgacttgtt 14400 ggtattatag gcgtgagcca ctgggcctga cctagctacc attttttaat gcagaaatga 14460 agacttgtag aaatgaaata acttgtccag gatagtcgaa taagtaactt ttagagctgg 14520 gatttgaacc caggcaatct ggctccagag ctgggccctc actgctgaag gacactgtca 14580 gcttgggagg gtggctatgg tcggctgtct gattctaggg agtgagggct gtctttaaag 14640 caccccattc cattttcaga cagctttgtc agaaaggctg tcatatggag ctgacacctg 14700 cctccccaag gcttccatag atcctctctg tacattgtaa ccttttattt tgaaatgaaa 14760 attcacagga agttgtaagg ctagtacagg ggatcc 14796 <210> SEQ ID NO 26 <211> LENGTH: 515 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (266)..(266) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 26 ttcggatcct tggctgggat taaaggtgtg agccaccacg cccggcttga aaaaacatgt 60 ttatatatat atatgtatat atataaaaaa tcaaggaagg aaaattccag tttgtagctc 120 agtaagtatt tgcttattac tattgaggcc ctaggttcaa ttcccagcaa tacaaaaata 180 ataactttcc ttttaatgat ttatcttgcc acgatggtga tgacactagc atctcaccct 240 ggacaggcaa gcctggccct ctggcnaccc cagccccttc gtgtctgttc atcattccag 300 gcaaaggaga ccaacaacaa gcaaaaagag tttgaagaga ctgcaaagac tacccgtcag 360 tcaattgagc agctggctgc ctaatgctga gcctttgctg agataacttg gacctgagtg 420 acatgccaca tctaagccac gcatcccagc ttttccagcc agggcctcct agcaggatct 480 tagagcagga gacagtggta ttttgaaact ggata 515 <210> SEQ ID NO 27 <211> LENGTH: 955 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 27 ggcacgaggg ggccggggct ctcccggcat gctctgcggc gcgcctccgc ccgcgcgatt 60 tgaatcctgc gtttgagtcg tcttggcgga ggttgtggtg acgccatcat gggagctccg 120 gcgctgcccc agatctggca gctgtacctc aagaactacc gcatcgccac cttcaagaac 180 tggcccttcc tggaggactg cgcctgcacc ccagagcgaa tggcggaggc tggcttcatc 240 cactgcccta ccgagaacga gcctgatttg gcccagtgtt ttttctgctt taaggaattg 300 gaaggctggg aacccgatga caacccgata gaggagcata gaaagcactc ccctggctgc 360 gccttcctca ctgtcaagaa gcagatggaa gaactaaccg tcagtgaatt cttgaaactg 420 gacagacaga gagccaagaa caaaattgca aaggagacca acaacaagca aaaagagttt 480 gaagagactg caaagactac ccgtcagtca attgagcagc tggctgccta atgctgagcc 540 tttgctgaga taacttggac ctgagtgaca tgccacatct aagccacgca tcccagcttt 600 tccagccagg gcctcctagc aggatcttag agaaggagac agtggtattt tgaaactgga 660 tatcaaatat ttttggtttt gctttaaagt ggctacctct ctttggtttt gtggctttgc 720 tctattgtga cgtggactta agcaataagg aagtgatgaa gggacagtgt tctctgacag 780 gacctgtggg ggtcggggtg cctgtgcaag gtcttggttc tgattgtgat atttccatac 840 agggctgcta atgcagccca tgggtaagtg tggttatatg tgtttgtgct gataattttg 900 tcctgatgag ttttcctacc acggggtaac ggaataaaat cacttgaaaa agtgg 955 <210> SEQ ID NO 28 <211> LENGTH: 1435 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 28 ctggcgggcg tgggaaccca ggccccgccg aggcggccag gaggtgagat ggcagctggg 60 caaaatgggc acgaagagtg ggtgggcagc gcatacctgt ttgtggagtc ctcgctggac 120 aaggtggtcc tgtcggatgc ctacgcgcac ccccagcaga aggtggcagt gtacagggct 180 ctgcaggctg ccttggcaga gagcggcggg agcccggacg tgctgcagat gctgaagatc 240 caccgcagcg acccgcagct gatcgtgcag ctgcgattct gcgggcggca gccctgtggc 300 cgcttcctcc gcgcctaccg cgagggggcg ctgcgcgccg cgctgcagag gagcctggcg 360 gccgcgctcg cccagcactc ggtgccgctg caactggagc tgcgcgccgg cgccgagcgg 420 ctggacgctt tgctggcgga cgaggagcgc tgtttgagtt gcatcctagc ccagcagccc 480 gaccggctcc gggatgaaga actggctgag ctggaggatg cgctgcgaaa tctgaagtgc 540 ggctcggggg cccggggtgg cgacggggag gtcgcttcgg cccccttgca gcccccggtg 600 ccctctctgt cggaggtgaa gccgccgccg ccgccgccac ctgcccagac ttttctgttc 660 cagggtcagc ctgtagtgaa tcggccgctg agcctgaagg accaacagac gttcgcgcgc 720 tctgtgggtc tcaaatggcg caaggtgggg cgctcactgc agcgaggctg ccgggcgctg 780 cgggacccgg cgctggactc gctggcctac gagtacgagc gcgagggact gtacgagcag 840 gccttccagc tgctgcggcg cttcgtgcag gccgagggcc gccgcgccac gctgcagcgc 900 ctggtggagg cactcgagga gaacgagctc accagcctgg cagaggactt gctgggcctg 960 accgatccca atggcggcct ggcctagacc aggggtgcag ccagcttttg gagaacctgg 1020 atggccttag ggttccttct gcggctattg ctgaacccct gtccatccac gggaccctga 1080 aactccactt ggcctatctg ctggacctgc tggggcagag ttgattgcct tccccaggag 1140 ccagaccact gggggtgcat cattggggat tctgcctcag gtactttgat agagtgtggg 1200 gtggggggga cttgctttgg agatcagcct caccttctcc catcccagaa gcggggctta 1260 cagccagccc ttacagtttc actcatgaag caccttgatc tttggtgtcc tggacttcat 1320 cctgggtgct gcagatactg cagtgaagta aaacaggaat caatcttgcc tgcccccagc 1380 tcacactcag cgtgggaccc cgaatgttaa gcaatgataa taaagtataa cacgg 1435 <210> SEQ ID NO 29 <211> LENGTH: 2977 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 29 ccgaatgtga ccgcctcccg ctccctcacc cgccgcgggg aggaggagcg ggcgagaagc 60 tgccgccgaa cgacaggacg ttggggcggc ctggctccct caggtttaag aattgtttaa 120 gctgcatcaa tggagcacat acagggagct tggaagacga tcagcaatgg ttttggattc 180 aaagatgccg tgtttgatgg ctccagctgc atctctccta caatagttca gcagtttggc 240 tatcagcgcc gggcatcaga tgatggcaaa ctcacagatc cttctaagac aagcaacact 300 atccgtgttt tcttgccgaa caagcaaaga acagtggtca atgtgcgaaa tggaatgagc 360 ttgcatgact gccttatgaa agcactcaag gtgaggggcc tgcaaccaga gtgctgtgca 420 gtgttcagac ttctccacga acacaaaggt aaaaaagcac gcttagattg gaatactgat 480 gctgcgtctt tgattggaga agaacttcaa gtagatttcc tggatcatgt tcccctcaca 540 acacacaact ttgctcggaa gacgttcctg aagcttgcct tctgtgacat ctgtcagaaa 600 ttcctgctca atggatttcg atgtcagact tgtggctaca aatttcatga gcactgtagc 660 accaaagtac ctactatgtg tgtggactgg agtaacatca gacaactctt attgtttcca 720 aattccacta ttggtgatag tggagtccca gcactacctt ctttgactat gcgtcgtatg 780 cgagagtctg tttccaggat gcctgttagt tctcagcaca gatattctac acctcacgcc 840 ttcaccttta acacctccag tccctcatct gaaggttccc tctcccagag gcagaggtcg 900 acatccacac ctaatgtcca catggtcagc accacgctgc ctgtggacag caggatgatt 960 gaggatgcaa ttcgaagtca cagcgaatca gcctcacctt cagccctgtc cagtagcccc 1020 aacaatctga gcccaacagg ctggtcacag ccgaaaaccc ccgtgccagc acaaagagag 1080 cgggcaccag tatctgggac ccaggagaaa aacaaaatta ggcctcgtgg acagagagat 1140 tcaagctatt attgggaaat agaagccagt gaagtgatgc tgtccactcg gattgggtca 1200 ggctcttttg gaactgttta taagggtaaa tggcacggag atgttgcagt aaagatccta 1260 aaggttgtcg acccaacccc agagcaattc caggccttca ggaatgaggt ggctgttctg 1320 cgcaaaacac ggcatgtgaa cattctgctt ttcatggggt acatgacaaa ggacaacctg 1380 gcaattgtga cccagtggtg cgagggcagc agcctctaca aacacctgca tgtccaggag 1440 accaagtttc agatgttcca gctaattgac attgcccggc agacggctca gggaatggac 1500 tatttgcatg caaagaacat catccataga gacatgaaat ccaacaatat atttctccat 1560 gaaggcttaa cagtgaaaat tggagatttt ggtttggcaa cagtaaagtc acgctggagt 1620 ggttctcagc aggttgaaca acctactggc tctgtcctct ggatggcccc agaggtgatc 1680 cgaatgcagg ataacaaccc attcagtttc cagtcggatg tctactccta tggcatcgta 1740 ttgtatgaac tgatgacggg ggagcttcct tattctcaca tcaacaaccg agatcagatc 1800 atcttcatgg tgggccgagg atatgcctcc ccagatctta gtaagctata taagaactgc 1860 cccaaagcaa tgaagaggct ggtagctgac tgtgtgaaga aagtaaagga agagaggcct 1920 ctttttcccc agatcctgtc ttccattgag ctgctccaac actctctacc gaagatcaac 1980 cggagcgctt ccgagccatc cttgcatcgg gcagcccaca ctgaggatat caatgcttgc 2040 acgctgacca cgtccccgag gctgcctgtc ttctagttga ctttgcacct gtcttcaggc 2100 tgccagggga ggaggagaag ccagcaggca ccacttttct gctccctttc tccagaggca 2160 gaacacatgt tttcagagaa gctctgctaa ggaccttcta gactgctcac agggccttaa 2220 cttcatgttg ccttcttttc tatccctttg ggccctggga gaaggaagcc atttgcagtg 2280 ctggtgtgtc ctgctccctc cccacattcc ccatgctcaa ggcccagcct tctgtagatg 2340 cgcaagtgga tgttgatggt agtacaaaaa gcaggggccc agccccagct gttggctaca 2400 tgagtattta gaggaagtaa ggtagcaggc agtccagccc tgatgtggag acacatggga 2460 ttttggaaat cagcttctgg aggaatgcat gtcacaggcg ggactttctt cagagagtgg 2520 tgcagcgcca gacattttgc acataaggca ccaaacagcc caggactgcc gagactctgg 2580 ccgcccgaag gagcctgctt tggtactatg gaacttttct taggggacac gtcctccttt 2640 cacagcttct aaggtgtcca gtgcattggg atggttttcc aggcaaggca ctcggccaat 2700 ccgcatctca gccctctcag gagcagtctt ccatcatgct gaattttgtc ttccaggagc 2760 tgcccctatg gggcgggccg cagggccagc ctgtttctct aacaaacaaa caaacaaaca 2820 gccttgtttc tctagtcaca tcatgtgtat acaaggaagc caggaataca ggttttcttg 2880 atgatttggg ttttaatttt gtttttattg cacctgacaa aatacagtta tctgatggtc 2940 cctcaattat gttattttaa taaaataaat taaattt 2977 <210> SEQ ID NO 30 <211> LENGTH: 76698 <212> TYPE: DNA <213> ORGANISM: H. sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15311)..(15410) <223> OTHER INFORMATION: n = A,T,C or G <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15414)..(15414) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 30 cgcggaattc cagacctcag gtgatccacc cacctcggcc tcccaaggtg ctgggattac 60 aggcgtgagc caccatgcct ggccgattgt tccaatgtat atgcacccca gtaatttatg 120 agagagccca ggtcttaatt tttaattgtt ttccaagatg gctgtactag gctttcctgc 180 aaatgacacc atagcatata ttgtggttgc caccccagca accaggccct caccctccat 240 catgggctgc ccattatggc atgaggggga ttgacactgg gccaggtatc ttttgcccct 300 ctaggattcc ccttcatcat tctctccatg ccgtctgccc caggaaggcg atctccaacc 360 tcagagacct gcttgctgtt tcccaaactt atgctaatca cacctctatg cctttgccca 420 tactgttccc acctcttgcc ctgcactcct tcccttctca gtctggaaca ttctgaagtt 480 gtcctcacag gattaacaag aattttggac aaaaatatat taatagttat aattaagcat 540 tacttaggct gcactttgac ccactttctt gtaactgaaa attacagggc actagatact 600 gaccatttgc atccccattg ttcctacaga taggtttttt tttttttttt tgacaaggtc 660 tcactctgtc acccaggctg gagtgcagtg gtacaatcat ggctcactgc agtcttgacc 720 tcccacactc aagcaatcct cccgcctcaa cttcctgagt agcccagtct acaggtgtag 780 gctaccacac ctcgctaatt tttaaatttt tttgtagaga caggggtctc cctatgttgc 840 ccagaatggt cttgaactct tgggctaaga ggtcctccca cctcagcctc ccaaagtgct 900 aggattacaa gtgtgagccg ccaccacacc tggcctatag atcagctttc tgatgctaga 960 ataataagcc ttttatttaa gataggtaga atctctgaca ttagaatcat aaggtttttg 1020 tttaagaatt tcttaagatg ttttttagat cctgaattcc agcaagacag ctgacctcaa 1080 atagtctgaa gacccactga cccctacaga ggaatggaat cagcatgaga atacagtttc 1140 ttcatctccc tgttccatga ctttgccctg tgccctttga gcaatcaagg atctccacac 1200 tttggctgat tcccaaaccc ctgaaaaccc tagccccaaa ctctgtggag acggatttga 1260 ggtttcctcc catctcctgg ttcagcatcc ctagaaataa acctctttca ctgctgcaat 1320 gtggtgaatt gacttgccac gtgcaccgga taaaggacct attatggtta caattccact 1380 catcctttaa gatagcttat atgttgtctc tggtcactgc ctccctcctc ttggtgcccc 1440 tcgcacagtt atccatgaga gcacatttgc gtcacctgct ggggcaactg tttgtttaca 1500 tggctctgtc tctcccagca cccagcccag gccagcccca cacttcaaag tccctgcagg 1560 gcaggatggc atggaaaggt cacaggtttg ggagtcagac tgaatatgac tccaccctct 1620 gtcctcagcc tcatctgctc ccccagtttt ctgtgctcta accacactgg cctgcactcc 1680 tgtctcactt catggccctt atacatgctg ttccaactgc ttagaatgct cttcctctgg 1740 ctctttttca tcctttcgtg cccagcttaa ctatcacctc ctgagacagg ccttccttga 1800 ctactgaatc taaaggcaca ccctcttccc attctgtcat tctccagcaa ttcccttcat 1860 tgatttgcca caaccctaat tatcatatta ttcatttact tgtttgctgc ttgtctcccc 1920 tgctagagct taaagtcctt gagtacatac agggactttg ccttgtttac tgctataggc 1980 ccagctctaa cacagggcct ggcatatatt aagtattaaa aaaatttaat tttagctttt 2040 tttttttttt tgtgaacgga gtttcgctct tgttgcccag gctggagtgc aatggcacga 2100 tctcgactca ccgcaacctc tgcctcccgg gttcaagcga ttctcctgcc tcagcctccc 2160 tagtagctgg gattacaggc atgtgcctcc atatctggat aattttgtac ttttagcaga 2220 gatggggttt ctccatgttg gtcaggctag tctcgaactc ccgaactcag gtgatccacc 2280 cgcctcggcc tcccaaagtc ctgggattac aggcatgagc cactgcaagc ggccaatttt 2340 agcttttttc agacaagctg gagtgcagtg gcatgatcat agctgactgc agcctctaat 2400 tcctgggctc agctgatcct cctgcctcag cctcccagga agctagaact acaggaatgt 2460 gccaccaccc ctggctaatt ttaaaaattt ttgatagaaa tggagtctca cgatgtagtc 2520 caggctggtc tcaaactcct ggtctcaagt ggttctctca ctttggcctc ctgaattgct 2580 gggattacag gtgtgagcca ccagtccacc aagaaatttt tattaactga atgaggaatg 2640 aacaaacaaa atagatccaa atccttgctc cactacttac caccagattt gtgtcttagg 2700 acaaattact taccctctcc tcatgtgaag atgaggcctc tcatgggttg tgtattggaa 2760 actgtaaaaa tgcctgatac gtgaagacat tccataaatg gccgttattt tttctttcct 2820 tcatctgaaa aatgtaccct ttttgccaag cataaagacc ttactgtaca tctttacttt 2880 ttcttttctt ttttgttttt tgagatggag tctcgctctg tagcccaggc tggagtacag 2940 tggtgtgatc ttggctcact gcaagccccg cctcctgggt tcacgccatt ctcctgcctc 3000 agcctccgga gtagctggga ctacaggcat ccgccaccac gcccagctaa ttttttgtat 3060 tttgtttagt agagacgggg tttcactgtg ttagccagga tggtctcgat ctcctgacct 3120 catgatccac ccgcctcggc ctcccaaagt gctgggatta caggcgtgag ccaccatgcc 3180 tggccaacgg tacatctttt tttttttttt ttttttttga gacagggtct ccctctgtcg 3240 cccaggctgg agtgcagtgg cacaatcttg gctcactgca acctccaact ccccggttca 3300 agcaattctt gtgcctcagc ctacagagta gctgggacta caagcatgcg ccaccatgcc 3360 cagctaattt ttgtattttt agtagagatg ggattttgtc atgttggcca ggctggtctt 3420 aaactcctga cctcagatga tctgcctgcc tcagcctccc aaagtgttgg gattacaagc 3480 gtgagccact gcgcccggcc tattttcctc ctctgatctg acatcatggg catgtctatt 3540 cttccttcaa accatttcag actcattcct tcctcctatt actcttctga gacctttcct 3600 aataacttta gcacacttga cctctcctac caccaaacca gaggtatcta aagtagggga 3660 tatgcaaccc agcatgtaac acacatgttt tagcacacac gatgcccaaa aaatggaaac 3720 agcccaaatg tccaccaaca gatgaatgga taaacaaaat gtggcataaa cttacaatgg 3780 gatattattc agccatgaaa atgaataaag tactgacaca tgctaccatg tggatgaacc 3840 ttgaaaacat tatgccaggt gaaagaagtc agtcacaaaa ggccacatat tgtgtgagtc 3900 catttttatg taatatccag aatagaaaaa tccatagtga cagaatgcat attggtgatt 3960 gccagacgtt caggggatgg ggaagaaact gcttgatggg taaggggttt tactttggag 4020 taatggaaat gttttggaac taggggtggt ggctgtaaaa gactgaatgt actaaatgcc 4080 actaaatgtt cagtttaaaa tggttcattt cacctcaata aattttttaa aaaatgaagt 4140 agccattctt ccaggtgagc tgaaaagttt gaatgaggca caggctcctt aaatttcttt 4200 tttttttttt tttttttttt tgagacggag tctcgctctg tcgcccaggc tggagtgcag 4260 tggcgcgatc tcggctcact gcaagctccg cctcccgggt tcacgccatt ctcctgcctc 4320 agcctcccga gtagctggga ctacaggcgc ccgccactac gcccggctaa ttttttgtat 4380 ttttagtaga gacggggttt caccgtgtta gccgggatgg tctcgatctc ctgacctcgt 4440 gatccgcccg cctcggcctc ccaaagtgct gggattacag gcgtgagcca ccttaaattt 4500 ctaagatgta aagtgctggg caaatatcag ctggggatgc tgaaggaagg aataatcaga 4560 aggtcagcaa gtgtggcttc gaaactctgc ctcaagtaat aatgataatg ataattagag 4620 atagttataa tattgacttc tttggtttcc ttgtaaacca gtgttatttt agaaaaagag 4680 ggagatagct ctagtaatta cagctaacac ttctacaatg cttaatatga ggaaggcact 4740 gttccaagta ctttacgtct aaaacttact aaatccttac aactctaaga ggtagtatca 4800 tcacatttcc attatagatg agggaatgga agaattgaga agtttaaatg agttctccaa 4860 gtcacagata aggaaatggc agagtccaaa tttgaaccca ggcaagtcag actctaggca 4920 ctgaagtctc aaccaccagg ctctgcacta agtgctctcc aggttttatc tcatttaatc 4980 ctgcaaggaa agtgttatta ttcccatttt attttattta ttatttattt atttatttat 5040 tgagacggag tttcaccctt gttgcccaag ccaaagtgca atggcacaat ctccgctcgc 5100 tgcaacttct gcctcccagg ttcaagcagt tctcctgcct cagcctcccg agtagctgag 5160 attacaggcc accatgcccg gctaattttg tatttttagt agacatgggg tttctccatg 5220 ttggtcaggc tggtctcgaa ctcccaacct caggtgatct gcctgcctca gcttcccaaa 5280 gtgctgggat tacaggcatg agccaccgtg cctggcctat tattcccatt ttaaaaatcc 5340 ccctcatgct atccacattc cacaccttct agtctttctt tttttttttt ttttttttga 5400 gacggagttt cgctctgtcg cccaggcaga cggagtgcag tggcgccatc ttggctcact 5460 gtaagctctg cctcctgggt tcacgccatt ctcctgcctc agccttccga gtagccggga 5520 ctacaggcac ccgccaccac acccggctaa ttttttgtat ttttagtaga gatgggattt 5580 caccgtgtta gccaggatgg tctcgatctc ctgacctcgt gatccgcctg ccttggcctc 5640 ccaaagtgct gggattacag gcgtgagcca ccgcgcccgg cttttttaaa aattttttta 5700 ttttttttat ttttagtaga gaccgggttt caccgtgtta gccaggaggg tctctatttc 5760 ttgaccttgt gatctgcctg cctcggcctc ccaaagggct gggattacaa gcgtgagcga 5820 ccgcgcctgg ccagtctttc tcctacattt atttttacgt tggtccacat actcctgtca 5880 ttctcacttt gcttcacttt tcctttcttc ttctttttta agagacgggg gcttgctatg 5940 ttgtccaggc tggagtgcag tgaggcaatc atagcttatg ccatccccaa ctccaagtga 6000 tcctccagcc tcagcctcct ccctagctgg attacaggag catgtcacca tgcacactaa 6060 ttttcttttc tttttttttt ttggtagaga tggggtctca tgttgctcag gctggtcttc 6120 aacatctggg ctgaagtgac cccccttcct tggcctctca aagtgctggg attagaggct 6180 ttggccacca catccaacct gaattttatt atttatattt tcttttaatc tcccattact 6240 agatggcagg gattttgatt actgttaatt ttccaatatc caaaataatg tgtggtacct 6300 aataggctct caatatcgaa aagtaatagt gcacatggca ttctgtagta ttaggtaggt 6360 atcttgtgtt cctgtgtttg cgtaaataag atcatacatt atgttctgct tttttaactt 6420 aatggctttt tttttccttt ttttgcgaca gagtctggct ctgtcaccta ggctggagtg 6480 cagtggcgct atctcggctc actgcaacct ctgcctactg ggttcaagtg attctcctgc 6540 ctcagcctcc tgagtagctg ggattacaga cgcgcaccac cacacctggc caattttttt 6600 tttttttttt ttaggcggag tctcactctg ttgtccaggc tggagtgcag tggcgcgatc 6660 tcagctcact gcaagctccg cctcccgggt tcatgccatt ctcctgcctc agcctcctga 6720 gtagctggga ctacaggggc ccgccaccac acccggctaa tcttttgtat ttttagtaga 6780 gacggggttt tactgtgtta gccaggatgg tctcgatctc ctgacttcgt gatctgcccg 6840 cctcggcctc ccaaagtgct gggattacat gtgtgagcca ccgcacccgg cctatttgtt 6900 ttgtattttt tagcagagac aggtttcacc atgttggcca ggctggtctc aaactcatga 6960 cctcaagtga tctgcccgcc tcggcctccc aaagtgctgg gattacaggc atgagccacc 7020 acgcccagcc atgtcttttt tttttttttt tttgagacaa gagtttcgct cttgttgccc 7080 aggctggagt gcaatgacgc gatttcggct caccgcaatc tccgcctcct gggtacaagc 7140 aattctcctg ccttagcctc ccgagtagat gggatgacag gcatgcacca ccatgcccag 7200 ctaatttggt atttttattt ttttatattt atttattttt tcgagacgga gtctcgctct 7260 gtcgcccagg ctggagtgta atggtgcgat ctgggctcac tgcaacctct gcctcccggg 7320 ttcaagcgat tctcctgtct cagcctcctg agtagctggg attacaggcg cccgccacca 7380 cgcccggcta atttttgtat ttttagtaga gacggggttt ctccatgttg gtcaggctgg 7440 tctcgaactc ccgacctcag gtgatccgcc tgcctcggcc ttccaaagtg ctgggattac 7500 aggagtaatc ccaaaaaaag cgccgggccc tttttttgtt gttttttaaa ttcagtaact 7560 atctagttca ttcttggatg gatgacaacc cagattggat gtgtagcagc gttctcttaa 7620 ccagtttcct attaatcttc atttcatccc cagtgtttct ccagaatgca aataatatgg 7680 cattaaatat cttcacacat agctttttgt gtatgtgtat acttatttct ctagaattag 7740 tgtctagaag tgaaactgcc gggaggaagg atatatactt ttaacatgtc caagttccac 7800 tgtgatagcg ctgcgagggc acacaacagg tttcaatata ccttggacca aaccggatat 7860 tatcagtttt tttaacttgt tgctaatgtg atgggggaaa aatgaactcg gaatttacac 7920 acaaggaaaa gaccgtttaa ggttcaggga ctgtccacat agctgtcaag tggcggagcc 7980 gtgatttggt attaaagtgc ccggagagga cgcgtcaaag ttggacactg tgccctgtgt 8040 cctgaggcac gtctggtgat cgctgggcct tgcaatgctg ggcaggcagg ccttcctctc 8100 cccttctagg cctctggcca ctcctggctg gccgaaagcc ggttcttctc gattaccgag 8160 tgcctctcct gaaagcaagt cagcgtcgcc taacctcttc agcttcgaaa tggcggccac 8220 cagatcgcta ggccacgccc cgggggcggg gcctgagttc aggccagagc gatggatgcc 8280 cgagccaagt tagaagtcga ctgccagtag ggctcgcgca gaatcggaga gccggtggcg 8340 tcgcaggtcg ggaggacgag caccgagtcg agggctcgct cgtctgggcc gcccgagagt 8400 cttaatcgcg ggcgcttggg ccgccatctt agatggcggg agtaagagga aaacgattgt 8460 gaggcgggaa cggctttctg ctgccttttt tgggccccga aaagggtcag ctggccgggc 8520 tttggggcgc gtgccctgag gcgcggagcg cgtttgctac gatgcggggg ctgctcgggg 8580 ctccgtcccc tgggctgggg acgcgccgaa tgtgaccgcc tcccgctccc tcacccgccg 8640 cggggaggag gagcgggcga gaagctgccg ccgaacgaca ggacgttggg gcggcctggc 8700 tccctcaggt aggtggcagg accgggtcgt ggatgccggg ggagccgggc ggcggggctg 8760 agggatcggc ttccagggcg accgggcctg ggtggcgctg atggagcggc cccgcggctg 8820 ccgggcagag ggcttgggcc aggccgttgt caccctgggg tagcgttggg cgggggcccc 8880 ggagtccggt gtcatggccg gcgagccgag ttcccacatc ccactcaaat ttccttgtgt 8940 ttggcggaaa cgtgccaacg ccacccttat gccatgcgca ttcctcatat ttggcagtgg 9000 gaaaatccgc ccagagctgc cccatatctg ttgtcacttg gatgggccaa ttccttttct 9060 cttgggccgc cgaatgtggg acccgggctt gcaccctttc tcagggtact tcagtcaagt 9120 gacacccttt tagagacgac gtgaggaatc gggtaagaga ggaggaaact ggccagtgcc 9180 ctaccacaaa ggcacagggg cctcttcttg ggtatcagga ctagccttgg gtatcaggac 9240 tctgggttat taatgaaagg tttgggatac ttatagagga ttggcctcag gacgctttgg 9300 aatgaagagc cagggctgtc ttttgtgtga cgcgagagcc gccgggacgc ttcagctctg 9360 cagctgctga ggctctgcga gcgagtcgat gcccaagaga gaggggtttg gacgtcgtga 9420 gaggcgaggc ggccgtgttc attcattgtt ctcgttctag ggctctgggt gtgcccctgg 9480 tattcattct gtggtgggaa gaaggaatgg aacttagtgt atccttgaga tgtgaacggg 9540 ttctaggggg tcacttaatc taagtggaaa atgaattcaa ggcacgttca ttgagcgttt 9600 ctgcttgcct ggtcctctgt gggctgagtg gagagactct gccctccctg cgctcctaag 9660 gcgtgaaaac aatgcagtgt gataagaatt ggcttatcaa gtgttatggg gatttagaac 9720 agttagtttt gcttggggag gagttgagga agcttctaca ctcgaggaga cttctgagtc 9780 gagttttgaa acacctgtga gtaagtgctc atcgggtgag gaggagctca gggaacagct 9840 ggtacaaagg cttagagcca tgtgggagtt gggatgagtt tggggagcag caaattgcct 9900 ggggtgcagg aaggaaatgg tgagagatga gagtaaaata aaagttgcta gaattgtgag 9960 ggggctgtct ttgttgtaga tagtgaacta gttgaatttg gattattgta catgggttgc 10020 cgagtcttca ttcttgctga taattttctc cctttgttga tgttgaagct gatagtgatt 10080 gaacatattt agtttaactt agttaatgac ttttaaattt ttttttattt tttcagaaca 10140 atgcaaactt tttttttttt tttttttttt tttttttttt taaaggaaca ggatctcact 10200 ctgtcgccca ggctagagtg cagtggcatg atcatagctc ggttgcagcc tctaactcct 10260 gggcttaagc agttctcctg cctttgcctc ctgagtagct gggactacag acaggtgcca 10320 ccacacatgg ctaattaaaa aaaaaatagt agagatggag tctggcagtg ttgcctaggc 10380 tggtctcaaa ctcctgggct caggcgatcc tcctgcttcc acctctccct cccaacgtgc 10440 ttgctgggat tacaggggtg agccactggc caggcagaac tttttttttt tttaaataat 10500 agagaggggg tcacactatg ttggccaggc tggtcttgaa ctcttgggct caagtgatcc 10560 tccagcttca gcctcttaaa gtgctgaaat tacaggtgtg atccactgtg cctggctagc 10620 agaacatttt tgataagtgt tttatatcaa atgttttgac ttacacagtg gtgaatgaat 10680 tgaactcata tattcctggg gattcttgca aaaaattctc ttaaagttat acttgctcac 10740 aaaaatgtta actttataaa tgtagaacac tctcctacta atttttattt tattattcta 10800 ttgtttttta tttttttgcg acggagtctc actctgttgc ccaggctggc gtgcaatgat 10860 gcgatctcgg ctcactgcaa cctctgcctc cttggttcaa gcagttctcc tgcctcaccc 10920 tcctgagtag ctgggtaggc acactccacc acgcccggct gatttttgta tttttagtag 10980 agatggggtt ttgtcgtgtt ggccaggctg gtctcgaact cctgaccgca agagatctgc 11040 ccacctcggc ctcccacggc ctcgctggga ttacaggcat gagccactgt gcctggccta 11100 aattttaaat ataagtaatg tactccccag tcttacagaa attggacgac tatagaaaac 11160 aaacatcaaa aaaagtgtag aatgtgagta tttttagttt aataagtgta ttttataaac 11220 tatttatttg tattgacttc tcggataaca acctgttata aaatctttat ccccataaac 11280 ataattttcc taaaatagct ataatattgt gattaatgtt tatgctaaag tgactattat 11340 ggaattaaca gacttcagtt gcagtttcta aatcttgctt tggttgtgat gattatatac 11400 cactgaagaa cattcaggat tattttggct tgtttttacc cttatcactc aagggctaag 11460 ctgtttaaaa tgcaacataa acatttgacc cagttgaatg ctgggatact tggaaaaata 11520 aacctgttac tgtttctgta ctaaaggctt atcttttaaa gatatgtggt gtttttttag 11580 cgcagtggtg cgatcttggc tcactgcgac ctctgcctcc tgggtttaag cattctcctg 11640 cctcagcctc ctgagtagct gggactacag gcgcctgcca ccacgcctag ccaactttta 11700 tgtttttagt agagacggga tttcaccata ttagccaggc tggtcttgaa ctcctgacct 11760 tgtgatctac ccgccttggc cttgcaaagt gctgggatta caggcgtgag ccactgtgcc 11820 tggctgatat gtggtgtttt gtgattataa attgtagtgg agttccttag ttttgttaaa 11880 gtcttgtcag tagttgtaaa aacatcagcc agttgtggtg gctcaggcct gtaagcccag 11940 cactttggga ggccgaggct ggtgaattgc tagagctcag gagtttgaga ccagcctggg 12000 caacatggtg aaaacctgtc cctacaaaaa atacacacac acaaaaagaa aaaaatcagc 12060 agggtatggt gtagtatgcc tgtagtccca gctgcttggg aggctgaggt gaaaggctca 12120 cctgagccca gggagattga ggctgcagtg agccatgttc atgccactgt actccagtgt 12180 tggtgatgga gtgagaccct gtctcaaaaa aaaaaagtgt gccttcaata gaaggcttga 12240 acgtatttta tgggatttgg tttagctgaa aaaaacagtg agaagcagat taagctggta 12300 atttctgaca aaaagtatct aaaagatgaa gtgaagaatg ttaaacatca agtattatat 12360 tacagttgct cttagactag tagcttttag tttataacat gtcatttgtt tgctctgaag 12420 attaagcaag ttcatacttc ttggaagtta aatttgactt ttccagaagc actggattat 12480 ttacgaaata aaaaatataa ttgataactt taaactacta tttcaggtag tctattacta 12540 gtaaatgtat gattctacat ttaaatttca ggtaaatctt tgttagtaac ctactgccta 12600 aaaaaatgtt acatgaggga gtacttttgt ttgcatgtta ggatcataat aggccataca 12660 taataatctt gagcttggga ggagcttgtt agccaaacag catgccttaa tgttgacttg 12720 cagaagacaa ttttaaatat tgcctttgaa aggcagtgga taatgtgaca gtgagggggt 12780 ttatgaaacc ataaaattga gctttttgac ttagtttttg tttttaagtt gttcagatct 12840 tgggagtcat ttcttcaaaa caaatgacta tgaggtggaa aattacttac cttgaataaa 12900 ttaattggaa aatcagagaa cactgggttt atttaggatg aggttgtttg gtatgtgtat 12960 gggagggtag aattcctaat tgctcatctg actgggttca aaatgtaata ctagatattt 13020 gtgttgcaat tcagttggta cttttggtat agggctaact tatcttgcgt gtaatttttt 13080 tttttttttt ttgagatgaa atctggtgct gttgcccagg ctggagtgca gtggtgtgat 13140 cttggctcac tacaacctcc gtctcccagg ttcaagggat tctcatgcct cagcctcccg 13200 agtagctggg attacaggcg ccggccacct tgcctggcta atttttgtat ttttagtaga 13260 gacgaggttt caccatgttg gccaggctgg tcttgaactc ctgacctcaa gtgatccacc 13320 tgcctcggct tcccaaagtg ctggcattac aggctcgctc aggcatcttg ccttgtaatt 13380 ctcatgatag taatggctat ttttttcttg ccttagagtt gtaagtaaaa attccttaat 13440 tacacattaa ggtttgatct ttaattttac aatgtttgag tcattttgtt acttcttttc 13500 tcccagaatg acttgcgtag ctctaaatga ttttagttaa tttcacatct gtttgccttt 13560 cttctaaaat gacccctaga atctcagctt aactaaggaa aatgtcaagt gggtgttgtt 13620 tctttgttag tggttttggc ctagactatc taaagtttgg caaattactc acaaagtatg 13680 ttaattggca tcacattcca atcagtgtac atagcatttt ttgaggaaca cttgacacac 13740 ggttttattt ttagaccaga ttctaagggg ttttactggg tggggcttaa caatcctaaa 13800 gctagtttac ggttttaaaa tctttatgat ttagaggttg tttacatttt ttgttaataa 13860 atgggaagca gcaggcagtg gcagtcaatt ttgtttgttt ctttttttgt tttttttgag 13920 acggagtttc gttcttgttg cccaggctgg agtgcagtgg catgatcttt cctcaccaca 13980 gcctctgcct cctgggttca agcgattctc ctgcctcagc ctcctgagta gctgggatta 14040 caggcatgcg ccaccacacc tggctaattt tgtattttta gtagagacag ggtttcactg 14100 tgttggtcat gctggtcttg aactccctaa ctcaggtgat ctgcctgcct cagcctccca 14160 aagtgctggg attacaggcg tgagccacca cgcccagccc tcacataact tttatgatat 14220 tatgttctta taattgttcc attattaatt ataattaatc tctcactgtg cctaatttat 14280 atgttaaact tgatcatggg tatgtatgta caggaaaaaa catagtgtat acagtatagt 14340 atactgttct tgctttcagg cattcattgg tagtcttgga acatattcca agtggatatg 14400 gaagcactac tatgtgatgg aatgttactc agtaataaaa agaaggatgt actggtgtat 14460 actacaacat tggaaacata ttaagtaaaa gaaaccatgc aggaaagacc acatattgaa 14520 ttattccatt tatatgtaat gtccagaata ggaaaatcct tagtgacaga aagtagatca 14580 ggggctgagg gatgtaggga atggtcagtg actgtgatag ggttttcttt ttgcttttga 14640 cagcggtctg cattcataat tgctaatact tggaagcaac caagatgtcc ctcagcaggc 14700 gaatggaaaa actggtacat ccagacaagg gactattgtt cagtgccaaa aagaagcaag 14760 ataccaagcc atgaaagaca tggaggaaac ttaaatgcat atcactgagt ggaagaagcc 14820 aatctaaaaa ggctgtatac ggtatgactc ccaactatat gaaactgtgg aaaaggcaaa 14880 actgctgaga caggaaaaag atcagtggtt gacggaaggg agggatacat aggcagagta 14940 cagagaattt ttagggcggt gaaactactg taatatgtca ttatacattt gtcaaaaccc 15000 atagagtaag cctgggcaaa atagcaagac cccatctcta ccaaaaattt ttaaacctag 15060 ccaggcactt gtcctccaaa agcccacttg gccctcttca agtatatttt actttctttt 15120 ccttcctgct ctgaagcttt ttataacctt tcatgctgct ggaaaacttg cctcagtttc 15180 tttatcttgc ctatgcccct catccaattc cttcttctga ggaggcaaaa atgagggtcg 15240 tgcagcctgc acggatcact tgccggaaac tcgacacccg cacgcaaaat aattcggggt 15300 gcgctcacta nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 15360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn aagnaaaagg 15420 ttaggaaaca ttaacttagc ctgcctcttt tttttttttt tttttttttg agacagagtc 15480 tcgctctgtc gcccaggctg gttggagtgc agtggcatga tctcggctca ctgcaagctc 15540 cgcctcctgg gttcatgcca ttctcctgcc tcagcctcct gagtagctgg gactacaggt 15600 gcccaccacc acgcccggct aattttttgt atttttagta gaggggtttc accctgttag 15660 ccaggatggt ctccatctcc tgacctcgtg atccatctgc ctcggcctcc ctaagtgctg 15720 ggattacagg cgtgagcccc cgcacccaac ccttagcctg cctcttaagc tgtaagtggt 15780 cttgatatgg agatagaaaa taaaatacta tgaatgacaa ataatctaaa acttgaatta 15840 aataaagtag gtgtattttt attttgtcac tttttattaa aagttattgc agtatattct 15900 ctactgagta ccagcactat attttgagtg cctgcaagac ttagaattca ttgtaaaatt 15960 actgttcttg gactgaggtt acattttagt cttatcagtg gattcttcac caatcgattg 16020 gaatcagtca attccaatac agtcttcccc cacagttgaa tatagaataa aatctattgc 16080 aagctgggtg caggggcaca agtgtggcag gagtgcttga gcctaggagt tcaagaccag 16140 cctgggcaac atagtgagac ctcatctcaa ttgaaaatat atatctatat aaaaaataaa 16200 atttattaca gttcatcttg ctggaaaaca aaatactgtt tttgtaatta aaattttttt 16260 tttaaattta gaaatggggt cttgctgtgt tgaccaggct ggtcttgaac tcttggcctc 16320 aagctgtcct cccatctggg cctcccaaag tgctgggatt acaggtgtga acaactgcgc 16380 ccggctgaca aagtattttt taaagatgta ccactaaatg gagatttgat tcacatttga 16440 tagtttttga caggtctttt ctatttaaaa acattactgt ttttgtagca ttattctggc 16500 ttttccctta atttagtaaa tatttgagtg cctttgtatt ccagatactg agcaagattg 16560 gcagggttct gcccttatgg agcagaagga aggtaggggg actgactaaa acttgaaaac 16620 tgtctaacat aagtaccatg cagaaaatga aacagtatta attggcagaa ggagagcagg 16680 ctattttggc tagtgtggtt agggaaagcc tctctaaaga gatgtctctt gggtggagac 16740 aagatgtgaa aaaaccagct tgcctgtttt tggggtttca gccttgcagg tgaagagaaa 16800 cacgaagttc agaagtcttg aggcacaaag tctggcatgt tacgaaagaa ggcctttaga 16860 cgccttgtca gggagtttag attttattct gagttttaaa acgggagtga cacaatgagt 16920 tgcattttaa gcctgttcag gctgttacat ggattattag gagctgtatc atttcaggct 16980 agtgagatgc tcagatgagt ctgccttctg tctcttccgt catctatttc tctcttatct 17040 ggtcttaagc tcctccatct tttccttttt agttggaaaa aaactcaaag atctagaaaa 17100 aagaggagct gtatgtactc ctaaaaaggg acctcatagt aacctgggga tagagttatg 17160 taggagtgag tcagggctca ggttgaggct ttagaggcag gaggcagcga gatcttgttc 17220 tgtcatcccc tcttacagaa ataaaatatg ccgataaaag tttatagtgt aatagtaaaa 17280 tataaaaaca aaaagtaagt aatgtagaaa ataaaaaccc ttcacagtcc tgctgaaatg 17340 attactgtta acactttaat tctagagttc cccatccatt tatttatttc tagatttccc 17400 tctttgtaga ttaatattaa agggttcaga cttgttcatt ttttgttgtc ttggatatct 17460 tttcccacct ctgtatatat ggatctactt tatttatcac gtggatatta acatggttta 17520 tttaattccc tattgttagg tatttggtct ttaccacagt ttttcaaggg tatgaatagt 17580 gctgcaagga atatgcttac acatgttttt atacacttgt cttaggcttc tgtaggacaa 17640 atttctggag tagaatacta ggtcattctt taagaacatt tcaaactttt aatagatatt 17700 accgtattct ttcccaaaaa gaatgtacaa agactgtatg agaataactc catgttgtga 17760 tcttaagttg tctctaaacc tctttggttt tcttagctgt catctaagaa tactaagtat 17820 ctaacctccc tcttgatttg ggcatgtgat gtgatttagc atatagtgga tattcagtta 17880 gaaacttttg gttgaaaaca aggtttggat tctgtggtct ttaattctag gccatttcag 17940 ctctgactaa aatgatttga gtgttagtgt tatatatggg aaggtaaggg ctatggagtc 18000 agtgcagccc agttcagaat cccagtttgc cacttacaag ctgtgtgtgt gagaattttc 18060 tcaactgtaa aatggggaca taattcctac ctagagtaat actgtaagta ttaaggtgga 18120 taatgattgg aatgtatgct gtgtatcctg cctcataata gtaagctttt agtaaatggt 18180 agctactgtt aataataaaa caagtttctg aaggaggaag gcttgaaaag atgggattcc 18240 ttatcaacct caaagttttc taaaggagga aaccctaccc cccttacttc tgcatggttt 18300 ctgaccatga actgaactct gaactctgaa tgaactgaac tctgaactct gaatgaactg 18360 aactctgaac tctgaatgtt atggtagaaa attcatggac tttaaattta aacagataaa 18420 gaatctggtt attttaccca ctgctggggt gttcttgggc aagtagcatg acttctgtgt 18480 ccaaaaaaga aagggtttgc agtgactgaa cctgtaatcc cagtactttg ggaggctaag 18540 gagagtggat tgcctgagct caggagttca agaccagcct gggcaacata gtgagagcct 18600 ttctcaacaa aaaaaactgt tcttaaaaat tagctgggca tggtgatgca cgtctgtggt 18660 cccagctatg tgggaagctg aggtaggaga atcatttgag cctggaaaat tgaagctgca 18720 gtgagctgtg atcatgtcac tgcaccccag cctgggcaac agagcaagac cctgtctcag 18780 aaaataaatt aattaaaaag aaagtgtgga tggaggaagg gattaaaaat ctggctgggc 18840 acggtggctc atgcctgtaa tcccaggcgt gatttgggag gccgaggcgg acagatcacg 18900 aggtcaagag attgagacca tcctggccaa catggccaac cccatctcta ctaaaaatac 18960 aaaaatcagt cgggcgtggt ggtgcatgcc tgtaatcccg gctactcggg aggctgaggc 19020 aggagaatcg cttgaacctg ggaggttcag tgagccaaga tcgcgccact acactccagc 19080 ctggcaatag agtgagactc tgtctcaaaa gaaaagaaaa gaaaagaaaa tctttggggt 19140 tcttacacaa attaaatgag ataatttatt attattattt tttttgagat ggagtcttgc 19200 tctgtccccc aggctggagt gcagtggtgc gatctcagct caccgcaagc tctgcctccc 19260 gggttcacgc cattcccctg cctcagcctc ctgagtagct gggactacag gcgcccgcca 19320 ccatgcctgg ctaatttttt gtatttttag tagagacagg gtatccctgt gttagctagg 19380 atggtctcga tctcctgacc ttgtgatccg cccatctcgg cctcccaaag tgctgggatt 19440 acaggtatga gccaccatgc ccggcttgag ataatttata aagtgcctaa aatacatcct 19500 agaaatatta gtttttcttc cttgaagtca taaattatgg cttacacttt ttttcaggta 19560 tttctcatag tactaatgtg ttgctcacac tcaagggtag tagttgctta ggaagaagag 19620 aaatgtagtt gaaaaagtaa tagactagaa gtcttgagac ctgggctcat gttccaagtt 19680 ggcttttttt tttttttttg ggagatggag tctcgctctt gtcccccagc ctggagtgca 19740 atgacacgat atcgactcac tgcaacctcc acctcctggg ttcaagtgat ttctcctgcc 19800 tcagcctccc tagtagctgg gatgacagac acccaccacc atgcctggct aatttttgta 19860 ttttaagtag tgacagcatt ttaccatgtt agccaggctg gtcttgaact cctggcctca 19920 agtgatgcgc tggcctcggc ctcccaaagt gctgggatta caggcatgag ccactgtgcc 19980 tggtcccttg ctaaatgttt tgttttgttt tgttttgttt ttgaggtgga gtcttgctct 20040 gtcacccagg ctggagtgcg gtggcatgat ctccgctcac tgcaagctcc gcctcccagg 20100 ttcccgccat tctcctgcct cagcctcccg agtagctggg actacaggcg cccgccacca 20160 cgcccggcta attttttgta tttttagtag agatggggtt tcaccgtgtt agccaggatg 20220 gtctccatct cctgacctcg tgatgcaccc acctcggcct cccaaagtgc tgggattaca 20280 ggcgtgagcc accgtgcccc gcagttgctt gctaaatctt ttaactgctg gtcccatttt 20340 cctcatctat gaaatattta atggaagtgt actattaaag aaacttttct ttgctgatga 20400 atgcaggagg tatcattaaa aacccacata gtgctatttt cataattact ctttatgtat 20460 tgtgttcttg ggttgaatac ttttgttcta gagttacaat tatttgtgtt tcttaccagg 20520 tttaagaatt gtttaagctg catcaatgga gcacatacag ggagcttgga agacgatcag 20580 caatggtttt ggattcaaag atgccgtgtt tgatggctcc agctgcatct ctcctacaat 20640 agttcagcag tttggctatc agcgccgggc atcagatgat ggcaaactca cagatccttc 20700 taagacaagc aacactatcc gtgttttctt gccgaacaag caaagaacag tggtatgtga 20760 acattctact taggaaattt agctatttat ctgcctgtgg agcacattaa ggatcatgtt 20820 caacttaaag acaggcaaaa tattcattgt catttagggt ctttattttt ttttttctaa 20880 ctgcagattt atttttttat attgctgttc cttccacacc ccctattttt tcctacctct 20940 tggccttcct tctgttactc ttgcctggaa tgtcttcctt tgtgccactt catccaaaca 21000 aatagtacat tcttatgggt atatttcaaa gacttttctt tgagaagtct ctaggccttt 21060 ccaactactt attttagaag acattttatt tcttctatta aaatattcac ctaaagcttt 21120 ttgactatta caatcaagta taaagaagaa agtaaagtta catagaaaag attatttttg 21180 tatatttcat aggcccagga ccagtctgga ggcagcttag aaatcataga atcttctttt 21240 tcagggcact gacaccagcc acttagttct gcgtagttta ttttttcagt gccagtgaca 21300 ggttcatatt ggcatcatgg caggacactg ccactaggtt ttctgataga aaatttcttt 21360 ttctttttct tttctttttt ttttttttga gacggattct cactctgtca cccaggctgg 21420 agtgcagctc actgcaacct ctgcctcctg ggttgaagtg attctcctgc ctcagcctcc 21480 caaatagctg ggactacagg cacacaccgc cacgcctggc tgatttttgt tttttgtatt 21540 tttagtagag acggggtttc accatgttaa ccaggctggt ctcaaactcc tgacctcagg 21600 taatccacct gcctcggcct cccaaactgc tgggattacc aacatgagac accacgccca 21660 gcctgataac aaaacttcaa tttttctaag aatttagctc tcaaaaagtt ttctggctgg 21720 gtgtggtgat ttatacctgt aatcccagca ctttgggaga ccgaggtggg cagattgctt 21780 gagctcagga gttcgagacc agtcgggcaa cgtggcaaac cccatctcta caaaaaaaaa 21840 ttcaaaaaag taggcctggt gcagtggctt acgcctgtaa tcctagcact ttgggaggct 21900 gaggccagct cattacttga ggtcaggagt tcgagacaag cctggccaac atggtgaaac 21960 cccatctcta ctaaaattgc aaaaattaca gccaggcatg gtgttgcacg tttgtaatcc 22020 cagctacttg ggaggctgag gcaggagaat cactcgaacc cgggaggcag aggttgcagt 22080 gggccaggat tgcgccactg cactccagcc tgggcgaaag ggtgagacta tattaaaaaa 22140 agaaataaca acaaaaatgt agccgggcgt ggtggcacac gtctgtagtc ccagctactc 22200 ggtactcggg aggctgaggt gggaggatgg cttgagccca ggaggcaaag gttgcagtga 22260 gctgagattg caccacttca ccccagcctg ggtgacagag agccagaccc cttctcaaag 22320 aaaagaaaaa caaaaaaagt tttctactat tatggataaa acaaacaaaa ccaaccacct 22380 ggccaaaaca gaaaagtgaa attgcattgg ttttgcttgg tggaactttt gagaaaactt 22440 gggttcaaaa cttccatgcc tcttcctttc ccatcctctg ttctttgtgt aaaatcaatg 22500 cattgtgttt attccatata gtcaggtgaa gcaaggttct gaggtgggga accccagtcc 22560 agagttttct gtttgcttct aacagttcca ctcttcccaa tttgttaata aattgtttat 22620 actttttttg tgaacctaag gagcctccca agtgtagtgt tgaatactta ggtgcatttt 22680 gaactgaagg caaaactcaa aagtctaact ttaattaaag tttgagtaag tttatctttg 22740 tctctcttcc taaaaatgaa aattttatgg ctggcaaaat aagcagtaat aatcccctat 22800 atctgaacaa tggtcttcca tttgcaaagt aattttgcct actgtttctc attaattttc 22860 tttgtgacct taaattgaga agtcagatag gaagtgtgtg ttatgagaag ctgaagacca 22920 tttggtgctt cttcaaagtg ttattgagac tatcttctcc atccccatct gctaccagtt 22980 tgcccagaag gctgggaaac ttaatttggc atagtgatta agtgtatgaa cctttaaaac 23040 aagaaaatcc caatttaaat cctcattgcc ttttattagc tgtatcattt agacaagttc 23100 tgtacttttt tgatcctctt tcctgacctt tatgaaatga ggcttgtact tagcacagtg 23160 gctgattcat aagtgaagtg gtagctatta ttattattat tatatgtatt ttttttagat 23220 ggaggctctc actgtcaccc aggctggagt gcagtggccc aatctcggct cactgcaacc 23280 tctacctccc aggttcaagc gattctcctt gcctcagcct cccaagtagc tgggattgca 23340 ggcacccgcc accacgcctg gctaatttgt ttgtattttt agtagagaca gggtttacca 23400 tgttggcaag gctggtctca aactcctgac cttctgatcc gcctgcctcg tcttcccaaa 23460 gtgctgggat tacagacatg agccactgca cccggctgct atgattattt cttagctttt 23520 tatacatcta tgtagtcctt gatcccctcc atttgagcac agctggtggt tggaagccaa 23580 gcttgacttc tcctacagct tatgagaagg ttgtagccta ggttagtttt gcctgtttct 23640 ttgggtaaag atgaactaac tgtggaagaa ctagctgctt tcaccaggca cgcagcttga 23700 ggaaagcggt agaagaggga agagttgctt agctaggcca gcaccatcag tcagctcttt 23760 ttactcctcc ccaggttgct ttacttcctg aacccagaat gactctcata atcactcagt 23820 gggttctaga aattatttaa ctgatttcag catgtatcca tggagggctg taaagaggag 23880 aatgagacag aggacgcgta tctgatttaa ataattttag atgtgataat taggtttttg 23940 aatgtttctt ggaattttta ttttctaaat gtgtgcctct ttgacttcct cctgctgctg 24000 ttgctgctat tgctgctgct gctactgctt ctaattatta ttagataagt gattgactgg 24060 agccgaggac cactactatt agagtcagct gaccagcagg ttaaaataca gattcattct 24120 gtatgaatgg gctttattcc atactaactg aatcagaatc cttggatgtg ttggacaggt 24180 agatggaatc tatattttct caagcttctc tgaggattct aatgccagct acatttggga 24240 atctgactgg attagatgat atttaaagaa ctgtccagct tgcagtatga tttagtgaag 24300 actgataatg taacagatat cactttatag cttagaaaac attgctatac agtatttgat 24360 gcaggtcatg attccgttag gtatgtttat tactctttgt tttcctcatt cttagtgtct 24420 tagtagttca catcagtata gcttacttgt tttgtttctg aaaagctgga agttggtggg 24480 tatcactgcg tcaagaaact tttaaaataa acttattttg gaacattaaa aaatatatac 24540 aggctgggtg cagaggctct tccctgtaat cccagcactt tgggaggctg aggtggaagg 24600 attgcttgag cccaggagtt tgagaccagc ctgggcaata tagtgagatc ttgtctctac 24660 aaaaaaaaaa aacattagct agaagtggtg ctgcccacct gtggtcccag ccgaggctga 24720 ggcaggggga tcacttaaac tggggtggta aagggtacat gtgtcatgat catgccattg 24780 tattccagcc tagatgacag agcaagattc tgtctcagta tatataatat agattttaca 24840 cacacacaca cacgcacgca cgtagagaaa ataacaaatc tgatgtaccc cttacccact 24900 ttcaacactt agctaaccat ggcaggcctg cttaatctgt tttcatccac tcctttccca 24960 gtgttttgac acaaatccca ggtatcattt gtctgaacta ttttggtatg tacaagaaac 25020 ttttaaagaa tgctaatttt atttattttt aaataggtaa agcattcata tgagccaaaa 25080 gtcttgggtg acccctgccc ctgtatcccc atttcttttc ctcagaggtt tcttatgatc 25140 aatctttatc tattcgaaga atcagttggt ttccccttac cctgttgttc acgacctttc 25200 ctttcttcca catctctgaa ggagaggaaa aaccatcggt agctaaggag gctatcacaa 25260 actccaaagg aacttttttc gtttggagaa tcttttcctt ctcccagatg attgatcctc 25320 ctggagaata ttccttcccc actcccatca ccttctcgac taatctgtta caagttcaaa 25380 ttcttctata ctgtactctc aatgtggagt ccatctttgg gcttcaaaga atgattactg 25440 ggcagataag tccccttcag tccctggtga tagcaaaata aagccttgtg aaaaacttct 25500 tacgttgccc ctctctgatg ttttcaaatt ccttatgctt acatgcattc ccttctttcc 25560 tagattgttt tctctgcttt gcatccacat actatgccct agtttggagc ctggtaacta 25620 gaagggccca gataactatg tcctctttct taagactttt ttctgttgta aaccagctag 25680 agaaggttgg ctggattggc attgaggtgg ctggagtaag agccaagatt aagaacactt 25740 tgggcctttt gcagccctgc tttacttcct tccccctccc cgtgtaccca cataggtaga 25800 tatatgcata cactcaccac cttctggggg cggggtgtgg ggggggatgg cggggtgggg 25860 gagcggttgg ctggctgctg tcagctgtta gcactttcaa tcagaggagg aacctggtag 25920 gcagttcaca agcactgcaa atctctgttt tgccctcctt gctggccata ctgactctag 25980 ttaccttact tttgattaat tcttggcttt gaagttaaac atggagggct tttatcaaaa 26040 ctctgaaatt ttcattcaaa tttttttaca gctgccatta attgtgagta tcctgggcac 26100 tcacacttcc cagtagggtt ctgagtacct gcctagcttt ttgaggattg agtacagggg 26160 aatatagaga agtatgtgcc actaaggctg cttggtatgg tgtgcacata tatttaaact 26220 aagattggtg tttgtcccta cagcagggct ggagttctat atcttccact tcctgctttg 26280 ccttcactag tgttaagtac ttgtgagatg gaatttttgt tagaatcatc agtcattttt 26340 gttgaaagag gttgaagtac aaattttgat cataaaaact cgtttgttta tagatcagat 26400 tggcttattt cctctctaat gaatctagtg aacatatatg tgtatacatt ctaatcacac 26460 aaaattagag acgtataaag gaaaagttta tcattttatc tttcttaacc actttctaac 26520 cactttctta actgtctctt gatgtgaaca gctaggtgta aatctttcca cttgtataac 26580 atatacagat ttcttcactt tttttttttt tttttttgag acggagtctc gttcttgtca 26640 cccaggctgg agtgcaatgg tgcgatctca gctcactgca acctctccct cctgggttcc 26700 agcaattctc ctacctcagc ctcccaagta gctgagatta caggcgtcca ccaccatgcc 26760 cggctaattt ttgtattttt agtagagacg gggtttcacc atgttggcca ggctggtctc 26820 gtactcctga cctcaggtga tccacccgcc tcggcttccc aaagtgctga gattacaggc 26880 gtgagccacc gtgcctggcc tcttcacctt taaaataatc ttactctatt attctgaagg 26940 atattttccc ccaattaata tatcatggac tcctctccat ccaggtcatt ataagtaata 27000 taatagctgc ataatgtgac ataatacaga tgtctcacac tccattcaag tactttccta 27060 ttgctggaca ttcaggttgt ttcgtatatg tgtgtgtgcg tgggccatca caagcaatac 27120 agactggtgc atttatttct gtgcccacct ttccaagggg tgctgcagcc tgtgttggtc 27180 ctaaaggtgg tcctttgttt gtaggtcaat gtgcgaaatg gaatgagctt gcatgactgc 27240 cttatgaaag cactcaaggt gaggggcctg caaccagagt gctgtgcagt gttcagactt 27300 ctccacgaac acaaagggta agagctcaaa agtcaattga cttcttcaga ctagtaagga 27360 tcttctagct tcaaatagct atgtttgtat taaattgtac tagcttccta tagaatattg 27420 tatatttcta tacctttctt tataaagaga taattcagaa aaataggtat taagaaattg 27480 aaattattgc ttggacattc tcttgaaaag ttaaatacac gttaagctgg gcctgatgac 27540 caatacctgt aatttttttt tctttttgag gtggagtctt gctctgtcgc ccaggctgga 27600 gtgcagtggc gcgatctcgg ctcaccgcaa gctccgcctc ccgggttcac gccattttcc 27660 tgcctcagcc tccggagtag ctgggactac aggcgcccac caccgcgccc ggctaatttt 27720 ttgtattttt agtagagacg gggtttcacc gtgttagcca ggatggtaat acccgtaatt 27780 ttaacactgg gaaactgagg caagagggtt gcttgaggcc aagagttcaa gaccagcctg 27840 ggcacatagc gaaggcccat ctctacaaaa gatttttaaa aattagccag gcatggtggt 27900 gcggccctgt agtcctagct gttcgaaagg ctgacgtgag aatattgcat gaccccaggg 27960 gcttgaggct gcagtgagtc atgattgtgc tactggactc cagcctgggc tggagcaaga 28020 tcctgtctat taaaaaaagc caaaaaacaa aaaaacaaaa acaaacacat gttaggtatt 28080 gataatgttt ccatggatgg aaacagtgat gttagatgct gtgttttttt gagacaaaga 28140 tttttctttg tgtttactct aatgcattat atagactggg cactcagaaa gtgcattatt 28200 ttatataaag aatgctatcc tcgggagatt gacttttctc attcactaat tttttttttt 28260 attcagttaa atgtgtacta atccctgctg tttgatagat tgtttaaaga tgcagaagca 28320 tttctgcttc agggaagatt catggtttat cctattccta atggtggtgg caagatagag 28380 gcatcccctc aaaggctagg agtaatacct caaagcagca gagctgtcca taattatcca 28440 ttatccatta ttccctccac cccgaaaata tagggaaacc tttaaagggt tcttttttac 28500 cctcttcttg gaaagcgtca cttatgttat tcatcgttag cttacatttt ttcatgtttc 28560 aaagagttct gcagtttggg agaatagccc agggaatgaa tctactcgaa ggggtgagtg 28620 taattctcaa tttaggaggc gtttgttgaa gtgcaaatct ttgaagcaga cgttaacttt 28680 tgctgaaggt agcccaggtt gggtccctaa gccaatccat agtgttcctt aaggactaga 28740 gagattctga gacagggagg gcttggtcta ctctcatcca aggctgcact ggtttggagc 28800 tactctggag tctctaggac agacagcaga ttgtcactag gatcagtctg cagattgatg 28860 agaaaataag gcttgtcctc cttctcttca taagggcaaa atagtccttt ggagttatag 28920 gaagttttcc aggtgctgta taggtaatta tattaaggaa tgtattgttt actgttggat 28980 agtgagaaaa atggcttgac taggcttctg gtagataatg gagaggcttg aatggtgcta 29040 tacatgttat tttctcttta cctgagaata ttcttccttt ggaaaatggg ccagattaac 29100 tggataaaac ataagaaagg aattgggcat tactttttac ttatgtatct attttttgtc 29160 ttatttatac tgtaggcaca gaaagtgtgg tttcagagta gattttaaga cagttaagtt 29220 tctcattgac ttatagaccc tacaactaca gatttgagtc tgttattaat taatagaaaa 29280 gtacattttt catttgtggt tcctttctat ttatctagat tgaaataggc tactgaagac 29340 taaattttgt actgcagcaa tatttataat ccattttaca ggatttgggg atttttgtaa 29400 gattttagtg ttacaaattc caatttaacg tatattgact ttattgtgag attttatata 29460 tcattgttta aagaaaactt tattctggcc agacatggtg gttcacacct gtaatcccag 29520 cactttggga ggctgaggca ggaggaccgc ttgaggccag ggattcaaga ccagcctggg 29580 caacacagca agactctctc tctaccaaaa aacatttttt taagtaaata aagagaaaac 29640 tttattctga gaacatgggc tttggagttc aacagaccta gattccaaca taggccctta 29700 aacttgctgt gtggccttga gcaaattacc ttcttagagt cccagttttc ttatttttca 29760 gatagaaata atacctactt cataggtttg ttgtatgaat taaataaatt attgttgtat 29820 ggattaaata aagttgtgtt tatatggcat gtgataaatg gtagctgttg ttatttctat 29880 tgaactttga tcttgtttaa acatttcatg ttttttttaa atcctttcta gtaaaaaagc 29940 acgcttagat tggaatactg atgctgcgtc tttgattgga gaagaacttc aagtagattt 30000 cctggatcat gttcccctca caacacacaa ctttgtaagt tgcagatctc ttctctttct 30060 ggcatgttga gggctttgcc aggcataaca gagatttctc aggtaatatg cgtatgtata 30120 tatatatata gttggattgt ttaaagttct ttatgctgtt gtttacagta aggcaattta 30180 gatttcatta gtcagagata tactctaatt tgtgattatg aattctgtac atgctggaag 30240 tatgattcat tttgtaaaaa cttttttgga ggccaagaaa tgatgttgtc ttttgtcatc 30300 ttttatttat tcagcataat ttacacctgt gttcttgttg taggctcgga agacgttcct 30360 gaagcttgcc ttctgtgaca tctgtcagaa attcctgctc aatggatttc gatgtcagac 30420 ttgtggctac aaatttcatg agcactgtag caccaaagta cctactatgt gtgtggactg 30480 gagtaacatc agacaactct tgtaaggcat tgttctttta tccaaggaag atagggatga 30540 ggagtataca tactttaaag ggtatttgtt gtagattttg actgacaggt ctggattcta 30600 gactcattta atgaattgtg atccagaaac tactttagaa acagtgataa ttctgaaact 30660 agctaggttt ggtggcattc atactccaga atgagcaggt aggagtagga cttgttatct 30720 gtcaaattga gattgacata ctgtgactgt gattcagtaa ggaaaggagc aaaaggatat 30780 gaaaacaaga agattttttg cttttcgctc ttaatagtat tatctactag ggttgctagt 30840 agacactgct ctgtattttg ttgaatatgc tgaatgagcc tttgacattg agaaggagca 30900 gaaagcacgg ttgatgctat tttcttcact tcaaactgga gaaaacttag ttgtttggac 30960 ttaaaattgt ttgaatataa aatcttgaaa gattcttgtt tctttcagga gacaatatat 31020 ttcatataga taaaatgtta ttaaagaatt taaagtttac attaaaagta catggtccaa 31080 actgcctttt aaaaactgta actaggtata tgaaaagttt aaaagttttg tccttttttg 31140 acagtactag agaaaccaag ggagtgttat tattagacca tgatgaaaac gtttttgctt 31200 tcatggtcac ttacgtattg attttgtgat gagagcttga gtagcacaaa tggcacaagc 31260 ttttaaaatt tatcttattt ttgtccccca cccttttttt tttttttttt ttttggagac 31320 aagtctcttt ctgtcattag gctggagtac agtggcatga tctcggctca ctgcaacctc 31380 tgcctcccag gttcaagtga ttctcctgcc tcagcctccc gagtagctca gactacaggc 31440 acacaccacc acgcccagct aatttttgta gttttagtag agatgaggtt tcaccatctt 31500 ggccaggatg gtctcgatct cttgacctca tgatctgccc acctcggcct cccaaagtgc 31560 tgggattaca ggcatgagcc accacgccca gccttttttt ttattattat tttttaaaga 31620 cagggtctcg ctctgtctcc cacagtggag tgcagtggca tgatcacagc tcactgtagc 31680 ctcgacctct cgggttcaag taatcctcct acctcagcct cctgagtagc tgggactaca 31740 agtgtatgcc atcatgccta gctaattttt gtattttttc tagagacggg gtttcagcat 31800 gttgcccagg ctggtctcga actcctgagc tcaagcaatc tgtccgcctt ggccttccaa 31860 agtgttgtgg ttacaggtgt gagccaccgc atccggcggc acaagctttt gagtctaaca 31920 gacatatgtc aaaatctcag tgttgtcatt aaccataacc acatctgagt tttcgttcat 31980 gcatctgaat aaaggggata ttaccttcct tgcattgttc ttatgaggct tgctgacata 32040 acctgtgaaa ttactaagca caagtgccca cctcatggaa aaaaggtgcc taattactca 32100 cttttctgtg atttattcct tctattttag tcttttatct atgcattttc aagatggaat 32160 gtttccagag aagctgtgtg tgacatagtt tgtgaaatgt tatactgtag tttgaaaaat 32220 attattttga tatagctaga cacaggacca gtatttccta gaaatgcaca ctgggccggg 32280 cgcggtggct cacgcctgta atcccagcac tttgggaggc caaggcaggt gaatcacctg 32340 aggtcaggag ttcgagacca gcctggccaa catagtgaaa ccccgtctct gctaaaaata 32400 caaaaattgg gggaagggat agcattagga gagacaccta atgttaaatg acaagttact 32460 gggtgcagca caccaacatg gcacatgtat acctatgtaa caaacctgca tgttgtgcac 32520 atgtacccta aaacttaaag tataattaaa aaaaaaatac gaaaattagc tgggcatggt 32580 ggtgtgtgcc tgtaatccca gctactcggg aggctgaggc aggagaaccc gggaggtgga 32640 ggttgcagtg agccgccatt acacctctgc actccagcct gggcaacaga gtgagactcc 32700 atcttaaaaa aaaagaaaaa gaaaaagcac acaggagcct gtatgtttat tggcaggtca 32760 gtattattca cattcaataa tcattcaaat ccagttattt ggaatattgt tccctttatt 32820 ctaggtaatg taaaacagtt gaggaaaatg tgactgggaa aagttcagtt ttagtagctc 32880 tgagtttgca aaagcaaggc atgctgattg tctctgtaag attactgcaa gcctaaaaac 32940 cagtctttcc ctgcttttgt ttagattgtt tccaaattcc actattggtg atagtggagt 33000 cccagcacta ccttctttga ctatgcgtcg tatgcgagag tctgtttcca ggatgcctgt 33060 taggtaattt tttacctata gcttttcttt tagaaagtta tttggggtgg tggggttgga 33120 agcttgaaga caaaaaataa gagtttcttc gcattccctc ctctctacgt ggaaacccct 33180 tgctgcttct gtggaacttg atactggtgg tacagcaaaa ggtagaaatt tctgtttatg 33240 gacctgtagg tcttacattc tggaaagtga ctttgactgt agcttcttct gttatcatag 33300 catatttctt aatatgtcat tacattttaa agagcttgag attctgcttt cctcagtatg 33360 tactgagttc aacctcaatg gaaagggtcc taaaacttaa tacagtgatt tgataaaaat 33420 aaaaccctta actttgaaat gcatgttgtg gccgatgcat ttgctaaaac catgtattta 33480 aatagactag tgtctttaaa aacatttaat tagattttca gcataaatat tgtttctcat 33540 gtgtctctga gtttgcatat aacttgtctt tctttactct gttttccagc tttataatca 33600 gttttgttgc gtttatctac tgctcagtgt taacacacat gaatttgaaa cctaaagtaa 33660 aatctacatc caaaatatct tactttaggc caggcacggt agctcacacc tgtaatccca 33720 gcactttggg aggccgaggc agatggacca cttgaggtca ggagttccag actagcctgg 33780 ccaacatggt gaaaccccat ctctactaaa aatacaaaaa actgggtggg tgtggtgata 33840 tgtgcctttt ggcccaggta cttgggaggc tgaagcagga gaatcttgaa cgtggtaggc 33900 agtgagctga gatggcacca ctgcactcca gccttggtga cagagcaaga ctctgtctcc 33960 aaaaaaaaat atattatgta tacacacaca cacacacaca cacacacaca cacacacaca 34020 cacacacaca taatgtgtaa tcagataatg tttaatgtga aaatactatg gaaatattaa 34080 acgcagcata tcttagaata aggaatttgc atatatctgg atatatattt ctgtatggct 34140 tttatttttc ttgataattt gaaaagcaaa tctgaccaag aatttgtagt tacctctgaa 34200 gattagaaga aaccaggcct ctgaagccat aaaacagagg attatgtggg aaggcatttt 34260 tttcaagaca atagaacaat ttcccttaga aaagctggcc tttttccctt taattcatac 34320 atgggtgtta cctgaatctg aacaaacctc gaacgaatct ttagagcaaa taatgaaaat 34380 gttatacctc ttaatgcatg ttcccagttt ggttggtggg gttggtggtg actggaagag 34440 gccagtggtt aatttcacat ttaggtattt ccatctaaaa actgaattcc catttattta 34500 ctttgtttgc tggttgtagc aggtaaggac aaacagaggg taaaatcctg gcctttttac 34560 agacatgctc agcacgtcta cttatctgtt taaataaatt ctcaaattta gtctctaaac 34620 tgggcgtgtt ccaactagct taataggtgg tagcgtggtt gtcaaatgtt aatctgttct 34680 ttcctggaga tgttgtaaaa atttggagta gagtggtgct ttatttaaaa aaagaaaact 34740 tataatgcac tctccttttc attgaattcc caatacatgt attatttcct gttccaaatt 34800 ttgtatgcaa aagcacctag acttaagata atttttagat gtcacacatt tgaaagaatc 34860 aaacattttg tcaaaggttg tacaggtaga gtttgccctt aagcatctta cttagtcaaa 34920 tatgtacttg aaagacttca ccagtatgaa agcctaagtg ccaatcatgg aattttcttt 34980 ctcctcctag ttctcagcac agatattcta cacctcacgc cttcaccttt aacacctcca 35040 gtccctcatc tgaaggttcc ctctcccaga ggcagaggtc gacatccaca cctaatgtcc 35100 acatggtcag caccaccctg cctgtggaca gcaggatgat tgaggtaata gggcaccttg 35160 ggggtggtaa tgtcagtcaa ttaatggggt gaggttgata cttatttcag agttttgggt 35220 ttcaaatctg atcaaggaat gttgcaacac tttctcaggt ctctggactt ttacagttta 35280 ttttatatcc ataatatctt cagactggct gaatagtctg gttagtatat cattcaactg 35340 gagaactaaa acttcctgaa aaaatgttaa catttgaact cttcccatta tcagatttga 35400 ataggctatt aatgaacaag tgtctaagat atttaaagag cagtttagtt ttggtgtggg 35460 acagaaatta acagtgatgg agaactacag attctctgga agacttttgt gattttattt 35520 agaaataaaa gggtggagtc ctaggacttt aataagcagg tgtttgggga gatgtcaaag 35580 tgcccaaagc tagtgttttt gaactgcttt ttcttctctt ggctttttgg ttatgtccta 35640 ttggtttaat ttgctttctg cttcatcttt aataacaact gaatacactt aaatacttcc 35700 tttgttcttt attcttcttt atttctcatt gctttggact agaataacaa cctgagtgct 35760 tctcccaggg catggtccag acgattttgt ttgaggggaa gagtaggtat ttttcttcat 35820 gcctttgctt tcttgtaatt aacaggattg ctaaaactgt cagacagcag actaccaaaa 35880 atgaaatagt tgctaagtta aatttatatt tcttgtcact tgtttccatg ttttcttttt 35940 ctttctttct ttttaaaatt ttttttggca gtagagtata tagaagtaaa aaaaatgttg 36000 tatgtggtat tgatgatagg tgaaatgaat ttctgaagtt aggccaggca tgacggtgta 36060 tgtctgttgt cccagctact ccagaggcta aggcaggagg atcactggag cccagaagtt 36120 ctaggctgta gggagctaca attgtgcctg tgaatagcca ttgcactcca actggggcaa 36180 cataataaga atccacctta aaaacaaaca aaaaatgtta agttagattt tgaggccaag 36240 ggcattaaaa agtttttttt ttaaatcaat tccaaccaaa ggctaatgtt agacttactt 36300 agttggtgct cacagcattg gtattctgtt tatacattag taaccaaatg tgtttttggt 36360 tgataaaccc tagaataaat attctttatt gaaagcttat cagagacaac tatgctctct 36420 ctcatcatgt agacacctgc tgcgttaggc acagtttatc tcattcagac ctcaaatcac 36480 tttcaacata attgtcctgc cactattgtg aggagatcat gtataagcta taaattttat 36540 tattttgact ttatcattat gattagtcct gataatacaa taatatacca gttactgcta 36600 cttctattaa atggtttgtt cctgtatgaa cactgtaata cttacaggga acagtaaagg 36660 tcagaattgg ctgggtggga agatcacttg cgaccaggag ttcaagacct acctgggcta 36720 tatgtagcaa aaccccacct ctacaaaaaa aaatgtaaaa attagctggg cttggtggtg 36780 tgcacctgca gtcctagtta ctcaggaggc ttgggcagga ggattacttg agcccaggag 36840 tttgaggttg tagtgagctg tgtatgattg tgtcaagtaa gaatttttga gtttttatta 36900 taaaagaatt agcacaattg ttgtgcctaa tcatttttta ctttagaagc agggtaaatt 36960 ttgattcctg ttaatttaat cacatataag tcagcatttt taaagtagac taattgttgc 37020 tttattcaaa ttatttgtgg gtctcaaatt attcatagtt ctcttgagta tttagactcc 37080 aggaacaata ggaaaattct ttctagaata aattgatcca actatagaaa ttagcacaga 37140 ataaaatatg ggatatttaa ttgatacagg gaagaaaatt accataacat taaggaaaat 37200 attctgctac ataggaatat aattgtggtt aataaaaata aattgtgctt tgctttaaaa 37260 acaaagaaca gcttagttgg ataatgaaat tacagctgcc gatttctatt gaaatccaca 37320 ttattttttg ccagtgtttt gcccacctgg cagttatcct gctgtactta aaaacacaca 37380 ttcctggact tctcacattc ccctccaaaa catgctcagt caatcgtggg tcggggatta 37440 ggggtggatc ttcattcttc tttccagagt cagaatcact ctccaggtaa ttctgaagac 37500 tagctagttt tgggaaccag aactaggctt tcttgttaaa ttccgaatta tgttttggga 37560 gcaggggaac agcttggttt gattcttttt atctaattat ataattagat atataatttt 37620 atctttttat ataattgagt gggagcattc tagtaatagt tgtgtggaac aagtatcttg 37680 tctatactgt agttacacaa agagaatata gtaggacttc cccccaaaaa atgtcctttt 37740 ttaggatatg ggggccaagt ggtttcatat tattctatta tactgttcta ttccaagcga 37800 tgaattttag attggggttt aggtctcatg gagccctctg caatttaaac tattttccaa 37860 acagtttcta ataaattcta aagatagcct ttgctttctc ccatgaggag aatgtaaccg 37920 atttccaaat ttacccataa ggcagtgttt tgtggtgaaa gagctgaggg ctgagatcca 37980 tatatgatgg tttctggttc tatttctgcc acctactggt tctgccaagt gaccctgcca 38040 agtctctcta cctgttcaga tgtgttttct tatatgtaaa atgtaggttt tgaacttgga 38100 tttgtggtct ttccagcttt ctgtgatttt aggcttggat aaagtatata ggctgcttac 38160 ctttttcaaa tccaacttct agtcaattta gcctaactcc ttgtggagta agagtgagct 38220 tcccccagaa tccacctccc caccctggct ttttaaaaaa agttttgagc ctcagtggaa 38280 caagaatccc aatctttgga agggtctcag ctgagagtaa ctttgctagc ttcccttgaa 38340 agagtatgtt tgttgtgtac attgctttct tttgagaaaa agaatgtggt tttcattata 38400 tatgaaaaac taataccagg cttggcacgg tggctcacgc ctgtaatccc agcactttgg 38460 gaggccgagg cgagaggatc acctcaggtc aggagttcaa gacgagcctg gccaacatgg 38520 cgaagccctg tctctactaa aaatgcaaaa attagccggg cgtgctggtg cacacctgta 38580 atcccagcta ctcgggagac tgaggcagga gaattgcttg aacctgggag gtggaatatt 38640 aaatccttct aatatttaat gaaaaatcag ccttggagat actggccact gatatttgct 38700 gaatttaatc aaggaacgtt gattagagta tgtttaggat ttctatggtt tttagaggtt 38760 tttataatct attttgttct tgcacatcct cctcctcttt tttccctccc ccagagaaaa 38820 tcttttgtgt gtaggagttg accagctttc cttttctgtt tcaggatgca attcgaagtc 38880 acagcgaatc aggtactttt ccatagtcat ttagccaaca ataatgggct ttttttcttt 38940 atgcggtgta tcttctgttg gcttatcctt gtgtggcttc tgtttgtctt gtctattaag 39000 cctcaccttc agccctgtcc agtagcccca acaatctgag cccaacaggc tggtcacagc 39060 cgaaaacccc cgtgccagca caaagagagc gggcaccagt atctgggacc caggagaaaa 39120 acaaaattgt gagtatagac aacagtacct cctgccaatt agggttcagt aagaaaaacc 39180 tcgttggaaa ttagaatact taaacttatt ttgggagaag attctaataa aatacattca 39240 atgaaggaga ttataaatgt cactgtcatt tttggcacac ttgcatcaga cagtttgcca 39300 gtgctataac taaaatggta tttctcaaaa gacaaaaatt ggaagtatgg ttaatatgtt 39360 tatctttaaa agatatggaa acagatgaca tgggttgatc ctttgatgcc ctcattatca 39420 aaagattatt accattgcat ggagtataat aatgatctct acttgtttca gaggcctcgt 39480 ggacagagag attcaagcta ttattgggaa atagaagcca gtgaagtgat gctgtccact 39540 cggattgggt caggctcttt tggaactgtt tataagggta aatggcacgg taagcttggg 39600 gccctccctt tactaactgc agggctttgg tgtgaagtca agtttcagcc cagggggcca 39660 ggaggaggag aggactgagt gctcctgggc ttatagcagt actctccctt acatacttga 39720 ttatacctga agattgaact taattctttt tagactaagt tcttataaag ctcccaggat 39780 aattagaaat tagtgaataa gacttgagcc ctataatcaa atgtcaggag tacttctcct 39840 ttaaactgat taaatacagt ctgcacatgg gtcatgcttg gaagctcctt aagtgagcaa 39900 gagtctgctg ctatggaggg agcatgggtt ctagaaactt taagctggaa aggaccttag 39960 agattgaaat ggggactgat ttgcccatgg tcatgcagtt aggcatagga aagctggaaa 40020 tctcctgaag taacttctct ttgtcctgcc ctaggattag ctgtgggtgt ccctatcaaa 40080 cagggaaggc attgacttaa ttcttgaatc tatgtggaat attaatgttc tgattttaat 40140 ggaaacactt tgtcacttgg aagaaaggta ctatttaact tatgtagtta cagcttgtgt 40200 attttggcaa cactgaacat tttggcaaca tacttagcat ttctctgtta ggtttttaat 40260 gcctctggct ttaggacttt gggaaataat aggtatttcc ttgaaaatgc tgcatgttcc 40320 caaaaagtca tctcttctaa attcagatta taataaagca aaaatcacag agtcccttgg 40380 tgcctatact actttggatg acactggaat tatctttaga gataaatgtg caaagattga 40440 gagaagttaa aagcatcaaa tgaatggagt attaaaattc aaggtactga aaatatcaaa 40500 ccccccccat ttttaggacc tgggggtttt tttttttttt tttttttttt tttttttttt 40560 tttgagatag attcttgctc tgttgcccag gctggagtac agtggcacaa tcacagctca 40620 ctgcagcctc caactcttgg gctcaaacag tcctcctgcc taagcctccc aagtagctgg 40680 gaccacaggt gaatgcccag ctaatttgtt ttaccttttg tagagacaag gtctcactat 40740 gttgcccagg ctggtctcca actcctggac tcaagcagtc ctcttgggtc tctcaaaatg 40800 ctgggattac aggcatgagc cactgtgccc agccttacca tgtgctcgtt aatgcatggt 40860 ttttaccact tgtaattaat catctgacca atttctagtt ccttaagagg attggcaccc 40920 gactgaacat ttgtaaagta catgtggaat gattcctttt cctttgaaaa ttgcatctgg 40980 ctgggcaggg tggctcacgc ctgtcatccc agcactttgg gaggctgagg caggcagaac 41040 acttgagcct aggagttcaa gaacagcttg ggcaacatcg tgaaacccca tctctaccaa 41100 aaattaggta gatgtgatgg cactcgcctg tagtcccagc tacttggaag gctgaggcag 41160 gaagattgct tgagctcagg aggcgaatgt tgtagtgagc tcaatacagt gagtacacac 41220 tactgtactc cagcctgggt gaaagggcaa gaccctgtct cagaaaaaaa aaaaaaaaga 41280 aaagaaaatt gcatctagta tgtactactg ggctgtctcc tgggtcccag agaaatgata 41340 ctgttgtaga atatttattt atatgtattt agagacaaga tctggctctg ttgcccaggc 41400 tggagtagtg gcacaatctt ggcttactgc agtctctgcc tcctgggctc aagctagcca 41460 tcctcctgcc tcagcctccc aagtagctag gactacaggc acatgccacc acacccagct 41520 aatttttgta ttttttgtag agatggggtt tcgccatgtt tcctagactg gtctcgaaat 41580 catgagctca agcgatccgc ctgcctcggc ctcccaaagt actgggattg caggtgtgag 41640 ccactgtgct cagccagttg cagaatattt tagatggcat aaatatctcc aggatttctt 41700 aggaaagaac acaagcactt tgtgggatag agcacttgtg tctgagataa caaggctgct 41760 agtagttgta ggaggcagag caatggatat tgcatttatt gcttctgtta gcattagaac 41820 atttttatat cacattttaa aagccccagc taaaagccag cggatgaagt tttaagttgt 41880 acccaagttt aattttcctc tggttgcgca ctttcatttg gggattcata atttttcaag 41940 gcattggtac gtggtactgc ttctgagctt tgtcttctct caatagagtg agctttcaaa 42000 ctgtgataaa gattatttgt tacagtgtta cttccataaa gactgctatt agaatgtaga 42060 taacttgttt ttaagattct aggtttttta ggccaggtgc ggtggctcac gcctgtaatc 42120 ccagcacttt gggaggccga ggtgggtgga tcacgaggtc agtagattga gaccatcctg 42180 gctaacacgg tgaaacccca tctctactaa aaatacaaca aattagccgg gcgtgggggt 42240 gggcgcctgt agtcccagct actttggagg ctgaggcagg agaatggcgt gaacccggga 42300 ggcagaactt acagtgagcc gagatcgtgc cactccactt cagcctgggt gacagagcga 42360 gactccgtct caaaaaaaaa aaaagattct aggtttttta agtcagaaag tctcaaaagt 42420 cagaggagtg aggagcagtg gacttttatg ccatgctttc agaaagcaag ctctggtcta 42480 tgaatgaaga agaaaaatga gtggtccagg aaacataact tctagattgt tttgtgcaat 42540 acttttttcc gccatattct ggttcctgta tacagtatat ctgttcagta tcttaaaaat 42600 tacaactgtt ttcatgattt tgattgaaga tttttttaac tcagcccacc cacttatgga 42660 agtaaagcag aaagggtctc aaagcaactc agaagcctca ggtgcatgat ttaaaactca 42720 acatatttat ttaaagcagc atctgtcagg cccaaagctc acaacctcct tttgggcatt 42780 aaatttggca tcaaggctgg gtgcggtggc tcatgcctgt aatcccagca ctttgggagg 42840 ccaaggcagg gagatcattt gaggtcagga gttcaagacc agcctgaccg acatggtgaa 42900 accctgtctc cactaaaaat aaaaaaatta gccgggtgtg atggcatgcg cctgtaatcc 42960 cagctactta ggaggctaag gcaggagaat tgcttgaacc caggaggcga ggttgcagtg 43020 agccaagatc ataccacagc actccagcct gggcgacaga acgagactct atctcaaaaa 43080 aaaaaaaaaa agaaagaaaa attctttctc taggccaggt gtggtggttc acacctgtaa 43140 tccctagcac tttgggaggc tgagttggga ggatcacttt agcccaggag atcgagacca 43200 gcctggacaa catagtgaga ccctgtctct acttaaaaca caattagctg accatggtgc 43260 tgtgtgtctg ttgtccccgc tactcgagaa actgaggcag gaggatcact tgagcctggg 43320 agatagaggc tgcagtgagc cgtgataaca ccactgcact ccagcctggg caacagaaca 43380 agaccctgtg tccaaaaaaa aaaaaaagaa acttaaggag tttatattct agtggagaca 43440 gtaaacagga aaagtagaat atatagtatg ctgtaattgc taaggagaaa aatggaggaa 43500 aggagatatg gagtggcagt cccagttcaa tgtttttaat aggttggtca gggaggaatc 43560 tgccaagaaa gtggcatttg catggagggc gagggtgggt ggtgcagata tctagggaag 43620 cagtaacatc aagtgcaaag tggaccactc acctggcctg ctccgagaac tcaaggagat 43680 cttatggctt catttagagt gagtgagagg tatactaata ggagtgaggt ccagtggtag 43740 ggtgttttag ggtcctgtaa agactatcat ttgggttaaa tgggatctgg ggttgtacga 43800 gacctttagg aggtttggca agcctttgtt tgaaaatgag tgtgatgaga gagctcatta 43860 tctgtctgag agcccattct aactccaggt agttcctact agtagaaaat agtttgattg 43920 ggtgcagtgg cccacatcta taaccccaac actttaggag gctgaggtgg gagaatcact 43980 tgaagtcagg aatttgagac cagcctgggc aacatgagac ccttgtctct acaaaaaatt 44040 ttaaaaatta ggtgggcgtg gtgatgcaca cctgtattgt agtcccagtt acttgggagg 44100 ctgaggtggg aggatccctt gagcccagga gtttgaggct gcagtgagcc gtgatggtgc 44160 tgctgcactc cagcctcggt gacagagcaa gagccagagt ggggcgaggg gagggcatgg 44220 aatagttctt tattagagtt gaaatccgtt ttcctataat gtttgctcat tgatcctagc 44280 agactgaatg aatccctttc atggcagtcc ttgggttatt tatatgtaaa tgaggggaat 44340 gctgcagtat agaacattcc ttctggattt cataagaaat tgcaaataat ctgttaccat 44400 aactgtgtta acgagagctg gctggcagat ggatccctgc aagtaccatg ggcactgtct 44460 ttggttgacc ctgttcagtc ttcccatcag tgacttaatc agaggtgtga tatgtatttg 44520 catagtagtg cggatttaga aaagcgagaa gagttcaact ggctaggatg atggaaaaaa 44580 gaaaagatca ccttttaaca gagataagtc atattcattg ttccaaaaag tagaactgga 44640 gggggaagat gtggcttaat gataacgtgt gtggaaactg ccaaggaagt tcagccgact 44700 gcaaggtcag agtaagtcac tgcgtgggct tggctctgaa ttctgaggtt atattactga 44760 ttagggccag aacaggtgac accaaagggt gggttcagtg acaactagag catgcccaga 44820 ggagagctat aagaaaggga atggactaca aaacgaggtc catgaaatag gaaggtcctt 44880 agaagcagtt ccccctgagc gatcatccag catctcccaa gccacatgcc tgaaccccta 44940 gccctgtcct gtcccctccc gttaaaggct ctgccctttt ctgggtcctg gagcctgggt 45000 catagcgttg gccattttcc cagcacttcc actcagttga ctgcctcatt gggtcagttt 45060 accttcacag gatttcttat cttcatccct tctttctgag tccccacagt caaccattct 45120 tcttgtacct ttcctgagct attgcagcag attcctctct ggtctccctc tttctctcct 45180 acaggtgtcc aaatcctacc ctagagttta ctaaacacag ctcaggtttc tctcatcccc 45240 ctcacctcac ctttatttct gatgtgccca gtctgaaaca ttctctgtcc tatttactaa 45300 aatccttccc ttggtttata gcccatttcc ttcagaaaac ctttctgtat tctctttgaa 45360 aagagattta cttaggcacc tgtagtccca gctgcttgga aggctgaggt tggaagattg 45420 cttgagccca ggagtttgag gccagcctgg gcaacatagt gaggccccat ctctaaaaaa 45480 gaaaaaaaaa aaaaaaaagg atttactccc ccatcttggg gaactcccct tctgttccag 45540 cactcctgtc ttggctccaa ctgtaccaga atggacactt atgcaaatga ttgttgtcct 45600 cctactcagg gctggttata cacgtttccc atatggtgtc ccatatggat ccatttttct 45660 agatagaagg tagctccaaa catagtgtgg atctctccca tccagtcaac agcaccttca 45720 ccggcagccc atggcaaaca catgtgcagg ttaactggat gagagccact ttggaggctg 45780 ctgttaaaac atggggactc gttgaaactt tagatgataa aaccagagat cacagggaga 45840 cagtttgggc ctatcgtgag gaccatctct ctaccaattt tcttcccaaa aatgaaatgg 45900 ggagggctgg gtggggtggc ttacgcttgt aatcccagca ctccaggagg ccgaggcagg 45960 cagatcattt gaggtcagga gtttgagacc agcctgggca acatggtgaa accccatctc 46020 cacccaaaaa tacaaaaatt agttgggcat ggtggagcat gcctgtaatc ccagctactc 46080 gggaggctga ggcaggagaa tcgcttgcgg aggttgcagt gagccaagat tgtgccactg 46140 cattccagcc taggtaacag agcgagtctc catctcaaaa aaaaaaaagg aaggaggaag 46200 gctccaacag agaggctcca gaaacacttt taaaagtggc ttttggccag gcacggtggc 46260 tcatgcctgt aatcccagca ctttgggagg ccgaggtggg aggcctcaca aggtcaggag 46320 atcgagacca tcctggctaa catggtgaaa ccccgtctct actaaaaaca cacacaaaaa 46380 attagccaga cgtggtggcg ggtgcctgta gtcccagcta ctcgggaggc tgaggcagga 46440 gaatggcgtg aacctgggag gtggagcttg cagtgagccc agatcacacc actgcactcc 46500 agcctgggtg actgagcgag actctgtctc aaaaaaaaaa aaaaaaaaaa agtggctttt 46560 aaatttatag cactctaaag tggaatggat ccctggatgt gtctaaagtt atatcaagag 46620 gctggtttta cagtgcttga caatcagttg tcagtgttat aggtagaata gcaattggag 46680 tcagactggg gttttgatcc tggctgcagc gttctttgtt ttttggctgt atgaccttgg 46740 gcaagtgact aaacttctca gcttgttgtc tgtgaagata aattatttac gtcagagggc 46800 agctgtgagg attaacagag ataaaagtat acacagtgcc aggattcagt attattagaa 46860 ttacttttta atggtattga aggcagagaa gcttaatttc aatatatatc tctgaatttt 46920 tactagggac catcttaggt ctcactgaaa tgtggattca gagttcagcc tcaatagttg 46980 ctaaatggcc tgcttcctta caccagcaac cagccccagt cattctgtat ttgccaggcc 47040 attcatatgt atgcactgat ttcatcccca caggacaagg ttttgacctg tcacacatga 47100 cctcacctct gtggcttgcc agggttggtg tgaatagttt aaccaaggct atcgaaggcc 47160 taactgtagc gatagcagtt aacctatgta acttttttga gtcatttgaa ttatgtagag 47220 attggacctg taatcccagc actttgggag gccaaggtgg gaggattgct taagccctgg 47280 aggtcaaggc tgcaatgtgc cactgcactc tagcctagac aacagagtga gaccctgtct 47340 caaaaaaaaa aaaaaaaatt ggaaatttgc cgtatctgtg taggtatgtg attctttgga 47400 taaatgattc actgtatctt cctcaaaact aggttatttg aaagactgag atcattcaac 47460 tgattgcact gactgccaac taattttgca ggagatgttg cagtaaagat cctaaaggtt 47520 gtcgacccaa ccccagagca attccaggcc ttcaggaatg aggtggctgt tctgcggtga 47580 gtagaaagct ggcggtccag tccctctgga gtgctggagt ggggagtaca aggactgtag 47640 agttagtgga ctgtgccgca ggttgggacg ggcaggcagt taggactcac tgtggagttt 47700 ctgtggttgg atgctcctcc cttgagagca aagggatgtt tcctttagtt tatgtggttg 47760 tcaagccttt cgaagagccc ctttttagga gaataccctc ctctgggcac agtaaactca 47820 atagcccaat ttctgtctct gggttttggt ttgaggtggg cagaaatagg ccctattttt 47880 acctttattt cccagaaccc ttttttttat agctgagttg ccttatttta gacttcagaa 47940 cagtcagctt tccaatcttt cagtcactat ttagacttgt aggaataagt catataatgg 48000 agacttctac aaggagtcct tgtgacctcc acaggagggt catggagtgt acattgatga 48060 aagagaatgt cctctctgta agcaaggctg gcactgaact gatggcccag tgaactaatg 48120 gtgggcttct gtttgctcag aatgccaccc gggttatcag ccgtgccatg tgtttgtttt 48180 tgggactggg ggtggtgttg ggactggggg tggtgtcgac agcacagaac ccactgtcca 48240 cgggaaagca cagtagacct ccctgagcac tttcctcctc cctctcctct cttcccctcc 48300 cctccccagc aaaacacggc atgtgaacat tctgcttttc atggggtaca tgacaaagga 48360 caacctggca attgtgaccc agtggtgcga gggcagcagc ctctacaaac acctgcatgt 48420 ccaggagacc aagtttcaga tgttccagct aattgacatt gcccggcaga cggctcaggg 48480 aatggagtga gtagatggtc tgatgcctct ctgggaccca ggcatcaaat ttgtccctaa 48540 attggaacca ggatcaggaa aagccttcta gtccattaag cgattctgtg atatctttgc 48600 acaagcctct ggcctgggct ggaggggcca attatcagga atgagttgtt caggttccag 48660 ctgggtgggg tggctcacac ctgtaatccc agcactttgg gaggccaagg ccagtggatc 48720 acttgaggcc agtagttttg agaccagcct tgccaatatg gcaaaaccct gtttctactg 48780 aaaatacaag aatgaaccag gcctggtggc acatgcctat aatcccagct actcaggagc 48840 tgggacagga gaatcgcttg aacatggaag gcagaggttg cggtgagcta agatcacgtt 48900 actgcactcc agcctgggct gcagagcgag actctgtctc aaaaaaaaaa aagagaagtt 48960 caggttcctc cttgggactg aacttccccc ttggggctca gatttgggct ctgcctgcta 49020 ccctggcttt atcagaaacc tgagaatata gtggggtgca tgtaccttct gcttggacag 49080 ctgtggcaat gccttctgct cagctgtctg aggcatggct gtcccacatg agggtttaag 49140 cagatgttgt ttttgggata attttttttt tttaattaaa aactttttcc tggccaggca 49200 cggtggctca tgcccataat cccagcactt tgggaggctg aggcgggtgg atgacgaggc 49260 caggagttcg aaaccagcct ggccaatgtg gtgaaatctc atctctacta aaaatacaaa 49320 aattagctgg ttgtggtggc aggcgcttgt aatcccagct actcgggagg ctgaggcaga 49380 agaatcactt caacccggga ggcggaggtt gcagtgagtg gagattgtgc cattgcactc 49440 tagcctgggt gacagagcca gactccatct gaaaaaaaaa aaaaaaccca aaaaaaccac 49500 acttttttcc ttagagacac aggttctcac tctgtcacct atgctagagt gcagcggcgc 49560 aatcatagct cactgcatcc ttgaactcct gggctccagc tatcctcttg gctcagtctc 49620 ataggttgct gggactgcag gcacatgcta ccgtgcccag ctaattttcg tgtattttgt 49680 agagtcggag gtctcactat gttgcccagg ctggtctcaa actggactca agtgatcctc 49740 ccacctttcc tggctagcct agggtagtgc ttctcaaact tctcctctga agtagaggag 49800 ctcctcgtac ccctagacat ctgggagtta ctaagctata gctgtgcttg caagtcctac 49860 ataaattctc acactgtctt taaaattcat atggaagttg ccttctgtgt attttaagaa 49920 atggaatgac ttttcagaaa aattgagata taattcatac atcataaaat tccccctttt 49980 aaaatgtaca cctacctcag tgtttttctg gtattgagtt gtgcagccac caccactatc 50040 taattttaga acattttcat tatcccggaa agaaacacat gcccattgta ttagtctgtt 50100 tgggttgctc taaaggaaga cctaagggtg ggtaatttat aaagaaaaga ggtttatttg 50160 actcggggtt ctgcagactg tacaaaaagc atgacaccag catctgtgtc tggtgaggcc 50220 ctcaggaagc tttcactcat ggcagaaggc aaggggagcc acgtgtgatg tggtgagaga 50280 aaggagcaag agagagagca tggagggagg tcccagactc tttaataacc aggtttcatg 50340 tgagctaata gtgtgtgaac tcactcgtta ctgcagggag gccaccgagc cgtttgtgag 50400 gaatccatcc ccatgaccca aacacctgcc acttaggtcc cacctccaac actggggatc 50460 acatttcaac ttgagatttg gagtggacag atatccaaac aatataccca ttagaggtta 50520 cccaatacct cccacccact tgcagtctac tttctgtttc tatggatttt gcctacttta 50580 tagttcaata taaatggaat catgtaagat ataatatagt caggtaacat ataatgatgt 50640 ttcggtcaat gaccacatat aggaaggtgg tcccacaaga ttataatact gtatttttac 50700 tgtgcctttt ctatgtttgg ctatgtttag agacacaaat actcaccatg ttacaaccag 50760 ctacagtatt cagtacactg agggccatac agttttgtag cctaagtgca acacgttata 50820 ccatttagcc agggtgtgta gaaggctgta ccttcttggt ttgtgtgaat acactttatg 50880 atgtgtgcat gatgacaagt tggctaacaa cacatttctc agaaggtatc cctgccgtta 50940 agtgatgctt ggctgtatat aatacataag atatggtatt gtgtgcctgg gctcttagac 51000 ctagcatagt attttcaagg ttaatgtgta gcatgagtca ctacttcatt cctttctgtg 51060 tctgagtaac attccattgt atggatatgc cacattattc attcatcatt tatggacatt 51120 gggttatcag aattacttta gagtaaaact gatgcttgaa gaagtgtcag caatggtcag 51180 gcgccagggg cccatgcctg taatccaagc attttggagg ccaacatggg aggatcactt 51240 gagcccagga gtcaagacca gcttgggcaa cagtgcaaga ccctgtatct acccaaaaaa 51300 aaaaaaaaaa aaaaaaaggc ggcatggtgg cacatgcctg tggtcccggc tactgggagg 51360 tgggaggatc acttgagccc aggaggttaa ggctgcagta agctattgac tgcactccag 51420 tctccaaaaa aaaaaaaaaa aaggtgtaag catgtttgtg ctgtggcctc accttcaggt 51480 aagcagtgat gtgaaccagg ctgaacagca cagggtctat ccctgtgtgt aacactcctt 51540 ggagccaggc cttcagtggc tttacttctt agctgtagtt taaaactgct ttctactcat 51600 gcccctcaaa cttattttta ataatttctt ttcccttcac agctatttgc atgcaaagaa 51660 catcatccat agagacatga aatccaacag tatcctttgg ttgttgagtt catttgactg 51720 ctcggttcta aatttaggga aacagaaggg aggctttcta tcacaagtgg ctctcggtgc 51780 caggggatat ctttttaagg aaagaggcag aggacaggaa aacagaaaag tcagaaaatt 51840 agtaggcttg gcctgtccct cagcagctta tgcctcacct ggactgatga gagcgatgtt 51900 taggttaggt tcctttctga gtttatctca gcaaaagtga tttggagaga tttccgtaag 51960 cttgaaatag gcataatttt atcacactat tagtaaatgt aacctgacgg ggattgggct 52020 tttgtcttaa gtttatttct agtttgtggc cagcgtgtgt atgtctatct gcttgttatg 52080 tggatagcaa gtagctacaa gccaaatgtt gaaaggtttc caaaatcact aattaaaata 52140 gtctttcttg actgggcgtg atggctcaca cctataatcc cagcactttg ggaggctgag 52200 gcaggtggat cacttgaggc taggagtttg agacttgcct ggccaatgtg gtgaaacccc 52260 atctctaaat ttaaaaatta gctgagtgtg gtggcacgta cctataatcc cagctactca 52320 ggaggctgag gcacgagaat tgcttgaacc tgggaggcag aggttgcagt gagctgagat 52380 cacgccactg cactccagcc ttggggacag agcaaggctg tgtctcaaaa aaataaataa 52440 ataaaatggt ctttctcaaa ggtacataag tgggttcttc agaagtcact attagaagag 52500 gagaggggtt gtttttatag aagagtaaat gaagaaaggt atttttaatg ctgtgaggcg 52560 tgaaatttaa caattttgaa tctgccaccc tccacgagcc tttccttgtg aaagaaagat 52620 ggcattacaa cccacgtttt gcctcttgag cagtgagagg catgatagtt gtgttggatt 52680 atgggacatg gcctatttta ggtacatgtc tgaggtgtgg aacacctttc agtggtgggg 52740 tttttagcag ccaaacatta taccatgaaa gcagacacca cagatttaag gaggtgtgaa 52800 ttcctgggca ccaacatcac aagttacttt gtgtgtgttt tgttttttaa ttttttgttc 52860 ttttttaatt tttttttcct cacaagtttg acttaaactg tatgacttct ttacccagaa 52920 gcgagccgac ttcagttctc attttgaagt cactgagtgg taccgattct agtgaggaat 52980 ttcttactac aacattgaac actcagtaag ggatttgcta ttttgttaac cactcaagtt 53040 tcagatggtg atttgagggc agaatacagg cagaaacgac tgtaagctgt caggccatcc 53100 ttggccctct ggggagcact ggagtgtggc ctctgctcat cctgttaggg tttcaagtac 53160 ctgtattatg tggaaaggtc acaaggccag agacccagca cctagatgtg caaatgggga 53220 gaagaagcag ggaagaaacg ctggcttgct tttggctagg gccaaataat ctggcacatt 53280 gaccaatccc tgcctgtctt ctggaagaag gtgcatttca aaagcacttt aaagaacttc 53340 agaaacctta ggaagttcag tgcagagagg ctgtgacaga ggtaaggtgg agagattacc 53400 gtgttataaa gaactttggg atatttttca aaattaacct gaccattctt ttgaaaccag 53460 agtccttaac aagcattgag atatatttct ccatgaaggc ttaacagtga aaattggaga 53520 ttttggtttg gcaacagtaa agtcacgctg gagtggttct cagcaggttg aacaacctac 53580 tggctctgtc ctctggatgg tgagaatctg ggctcccacc agcagtctct ggtatagggc 53640 aaaaggaatg ccttggagat ttatgtgcaa acttaaagcg tttctgtaca tttccccgaa 53700 atccacatga cccctagtga cagccagcct cagggcaatt gtagattttc ttgaggaagc 53760 tgttgatcag aaccactgtg aagcttagtg tggagaggag ttaataagct gggtgacaga 53820 aatgctgggt cttggtcctt taaagacaag gattcctgag ctgttttaac cagtgcctga 53880 gttggagtcc tttgggggaa aagctatgtg gggactgaag aatggactca ttcataacta 53940 atgaaaggga cagcctggcc cctagatgtc tgtgaggcct gtcatatggt gataaatgca 54000 cttttgtcat atggtgatac atgtaggccc cagaggtgat ccgaatgcag gataacaacc 54060 cattcagttt ccagtcggat gtctactcct atggcatcgt attgtatgaa ctgatgacgg 54120 gggagcttcc ttattctcac atcaacaacc gagatcaggt aagtctgtgc tggtgcgaaa 54180 ggacccaact cgtgggagcc cctgggcctc cgccagccta agcagctaga gggttaggac 54240 ttgttattat ctgttgttca ttcacccccc attagctcag ctgttttctt tcccttagat 54300 catcttcatg gtgggccgag gatatgcctc cccagatctt agtaagctat ataagaactg 54360 ccccaaagca atgaagaggc tggtagctga ctgtgtgaag aaagtaaagg aagagaggcc 54420 tctttttccc caggtaaggc tcagggctgc tagaatgtga ttaaagcatg ggttggttcg 54480 taaagatggc aatataaggt gggagtgttt tgttttgttt tatagggagg ggacccaggt 54540 cctctacaag atggtggggg gcagggtaca tcctgtgtct ttgagacaca gctaatgaga 54600 gcattcttgg gctttgtttc agatcctgtc ttccattgag ctgctccaac actctctacc 54660 gaagatcaac cggagcgctt ccgagccatc cttgcatcgg gcagcccaca ctgaggatat 54720 caatgcttgc acgctgacca cgtccccgag gctgcctgtc ttctagttga ctttgcacct 54780 gtcttcaggc tgccagggga ggaggagaag ccagcaggca ccacttttct gctccctttc 54840 tccagaggca gaacacatgt tttcagagaa gctgctgcta aggaccttct agactgctca 54900 cagggcctta acttcatgtt gccttctttt ctatcccttt gggccctggg agaaggaagc 54960 catttgcagt gctggtgtgt cctgctccct ccccacattc cccatgctca aggcccagcc 55020 ttctgtagat gcgcaagtgg atgttgatgg tagtacaaaa agcaggggcc cagccccagc 55080 tgttggctac atgagtattt agaggaagta aggtagcagg cagtccagcc ctgatgtgga 55140 gacacatggg attttggaaa tcagcttctg gaggaatgca tgtcacaggc gggactttct 55200 tcagagagtg gtgcagcgcc agacattttg cacataaggc accaaacagc ccaggactgc 55260 cgagactctg gccgcccgaa ggagcctgct ttggtactat ggaacttttc ttaggggaca 55320 cgtcctcctt tcacagcttc taaggtgtcc agtgcattgg gatggttttc caggcaaggc 55380 actcggccaa tccgcatctc agccctctca gggagcagtc ttccatcatg ctgaattttg 55440 tcttccagga gctgccccta tggggcgggg ccgcagggcc agccttgttt ctctaacaaa 55500 caaacaaaca aacagccttg tttctctagt cacatcatgt gtatacaagg aagccaggaa 55560 tacaggtttt cttgatgatt tgggttttaa ttttgttttt attgcacctg acaaaataca 55620 gttatctgat ggtccctcaa ttatgttatt ttaataaaat aaattaaatt taggtgtaat 55680 ggctggctgt tacctccttt taaagtaatt ctgagctcac aacttgaatg ccccatttgt 55740 tcaccctctt caggagcaga attcaagaac aggaaatgtg cccagagcct aggctgggaa 55800 tgaatttgta atttaacctt tgtactcttt gtaaacctct actgaagagt taagtataaa 55860 aattaattaa gcagaaagta ctctaaactc agctaatacc ttaagtaata cattttataa 55920 actatttatt tatttggtag gtacagcttt tttaaacaca aaaatagatt agataaattc 55980 cagcttggaa caagctagtg ctggttcaca aggttatgct cacccttcaa ttaaaatcaa 56040 aatgactaca agacttgcca tcagctctct tcaggaccac tgctgggtca gaatcagaaa 56100 ccttgggtgc catgaaattt ttacaaaatt tcaaatcaaa gccaggcttt gcagctagat 56160 aatagatcac ttgagtacga accacacatg taagtgcacg tatatttgag ttctcaatac 56220 aattaccctg atgggcaaga acccacaggt gagagcagag gcttggttcc cctagagggc 56280 cctggctgga ggccccaaca ccaaccagac gacaggaggg ccagactgct acccagtact 56340 gtacctcctg ctccttcaag agcctcccta agggagaaga agatctatac ttccactttg 56400 tttgctgcac atgtggcaac aagattgcta ccctgatttg ggacacttga gagaacttga 56460 aaaaaatgac cacccttaaa gccctagaaa aaagttgtat gtttgttaac agctatgctg 56520 cgctcacttt gcattgtgtg ttcttgaaag ctctgtataa atcaaaattt tgacgacaca 56580 ctaaatacac tagagaaata cactatagag gaatcctttt atagggctga agactccttt 56640 ggtaagaaaa atatgctgca ttaggggcag ctgcaagttt actatttctg gggaagaaaa 56700 gatcaaaggt aagagccagg tttgtttttt aaagcaatca atccaaacag tttgggtgtt 56760 tgttagttgt tacccctgag gggcttgagg tgtaactata tcagctataa aaatagcaat 56820 tccatacatt taattaggtt actttatatc tttcactctt ccccatggct gtaataatgg 56880 agattgaatg agactaaggc taagcccaac tccactcaaa tccaagtcac acgtcacctt 56940 ggctgcagta cagggaagct ccgcacaccc tggcttggga aagtttcggc cgatggagcc 57000 caagatgcag ggcaaccatc tactctttag ggttctgatg attccactcc agaaaggtgc 57060 atgaagaggt ccccgagctc tgtcatgtcg acatcttcat tgttggggac atgccggctt 57120 tctcggttct cgatgaaatc ccagagccgc actgaattaa agaactgcaa aaacagccag 57180 tggacatgcc tggttactgc taagagcaac aggaaggctg cgttccttga tcgttctttt 57240 gcctacccca tttctctgcc aggaacggta cctggaaatg cccacagctg ctaagtgtcc 57300 ccaactagag atggctaaag tccttaccct cacagtgcct tgagaactga gctgtttccg 57360 aggtttctca ggctctgcta gccgcccatc ggggtaagca tggcgataaa gacatttgct 57420 tccaaatggg caggtcccct tgccttgctc aaagtattta caggcttttt tcctgaaaag 57480 cagaaagaaa aagtcaagag gctggtggga aaatgagggg tccaaactgg gccactgcct 57540 gcctccatcc ttaccaccct tacgccagag gtaggtcagc ctcacattct aggtggggca 57600 gctgaggctg ggagaggttg agtgatttgt ctcaggtcac acacagctgg gattctgatt 57660 tccaagcagg ataggaagta tccccactta cctgcagcct tgcaaaggat attaacctgc 57720 ctggggactt gctgtgtgga gactgcagtg ctccacaggc cctccggcag ctccagagca 57780 cctcctgggt caccacagag ctaagccagg cctggtcact cctctgggca ctaagctctg 57840 aagctgggcc acttgtctct gctcaaagtt ccctaggtac cccaccaagc caactctccc 57900 cttcctcctg gccgcagtgc tgtcaaggtg gctacaggga aagcagaggg ttttagcaac 57960 tgcctaaagc cataggtctc cttccagttt tcctgtctcc aacctcggca ccagggaggg 58020 cttcttcacg ccttatgtgc tttggacccc ttctctgaac agtgtttttc aatgcataaa 58080 acatgggtct acagcataca gtgaccaaac agttcaaaat gttttccctc tctcttaatt 58140 ctaccattct ccccacagac ctctatgtta agaaccctgc ccaaggaaac tcaatcaaat 58200 gaattcccat tttgctcaaa tgaactctgg tttatccaat cataaaggat cccaaactga 58260 agttaaaaaa aaaaagatac ccaagaatcc agagggccat ctcggagtac agaggaaggg 58320 gaaagtcaca gaaataaagc caaacaacag aaagggcacg ctgctgtcag gggcagctgg 58380 ggtgtgtgac agcgggagac aagaacaggg aaaggaggct cctgaatcca gtggttttcc 58440 gtcttgtcag atgggatggc cgcaggccgg tggtgaagtt ctctgaggac ggcttcatag 58500 cagcataaag aaaagccctc tggccgggtg tggtggctca cacctgtaat tccagcattt 58560 tgggaggcca aggtgggtgg atcacttgag gtcaggagtt tgagaccagc ctggccaaca 58620 cagcgaaacc ccatctctac taaaaataca caaatgagct gggtgtggtg gctggcacct 58680 gtaatcccag ctactcggga ggctgaggct gaggcaggag aattgcttga acccaggagg 58740 tggaggctgc agtgagccaa gattgtgcca ctgcactcca gcctgggaga cagagtgaga 58800 cttcgtctca ctgggggtgg tggcgggggg gtagggtggg gggagagaga acaagctccc 58860 tggccagctg atctgatttg agcacaggtg gctggagagc aggtgtgtgg acgacacatc 58920 ctccaggccc ctgcttgcct ggagttctga gcggacttca aatgaccgtg agcagtttgc 58980 tctcaccaga gcctgctgga caactccaga gcatcctagc acactggcta tgaactcgat 59040 caggtcaaac acattatata ctggtccccc actctcacaa gaatattact ctttttcctc 59100 ccccaggctt atctggtcac caaggccaaa agcctccagt tcactctgac tcactctgtg 59160 tcctcggctc tcacacccaa ctgtgttcat tctgtttaca aatcacttcc caatctcccc 59220 ttcctttggg ttcccacact tgtggaagcc tctggggcct gcctgccagg gccacttcct 59280 cactggcctc cctcccactc ccaccagttt ccaccttcag agcagcacgg aggagcttcc 59340 caaccttttt tttttcttta aagagatgag gtctccctat gtctcccctg gacttaagca 59400 atctgccctc ctcagcctcc caaagtgctg ggattacagg cataagccac tgcgcctggc 59460 cccaacctgt tcttaaagac catggtcaca ctgggattca agtgtccctt agattccagt 59520 ctgtaggtcc caccacatcc ttctacacac ctgtttcaat gccaggagcc actcccagtg 59580 tcccccagac acaaaaccta cacccttctg tgcccatgtc cttccatcac ttccccctac 59640 agacaggtgc ttcctgcttc atggttcagg ctcccatgct gcttcccctg gcagcccccg 59700 gtggatccaa gtgctttctc tgttgtgata gatggtccct catgaagaac tggtcaccag 59760 caaacctgta tcataattgc ccttttgcag tttcccatga agttgtctta cttggcgggg 59820 cacagtggct cacacctata atcctagcac tttgggaagc tgaggtgggt agatcatctg 59880 aggccaggag ttcaagacca gcctggccaa catggcgaaa ccccatccct actaaaaaaa 59940 tacaaaaatt agctgggtgt cgtggcgcac acctgtaatc ccagctactc gggaggctga 60000 ggcagaagaa tcacttgaac cctggaggcg gaggttgcag tgagctgaaa tcatgccact 60060 gccagcctgg gtgacagagc gagactcgaa agaaaaaaga aattgtctta ctaatctcta 60120 catcccccag tggtgcttag ctagaaggta cctgacccat agtgagtact cagtaaatgt 60180 ttgtggattg caaaaaacac agtcattaaa ggaaagcaaa gcaaggaaag atccaaatag 60240 caataacaat ctccagactg cttttcagca gagccccttt ctacaggctg ggaccctttt 60300 ctacaggctg gggccctttt ctacaagctg ggacccctct gcttgccacg ccttgccctc 60360 ttgtggacac acaggaagat tgtatgagga aaaaatggta aaaaaaaaaa aaaaaaaaaa 60420 atcaagcttt agtaaactaa tatgcaacat aaaggaacca ttaaaaaagg taatgcatag 60480 tttcactttt agtatgacaa gtaaacgcct gccataccca accctcctgc agataagtct 60540 taacacaaat atttcaagaa gacctgaagg caccagagaa tgaacaaacg cagttagatt 60600 ctttggagga gtaaacacaa agaagaatag caatggcaaa ggctaagtta ccttttttaa 60660 aaaaggtagc ttttgtggct cacatctgta atcccagcat tttgggaggc cgaggcaggt 60720 ggattgcctg agctcaggag ttcaagacca gcctgggaaa cacagtgaaa ccctgtctct 60780 actaaaatac aaaaattagc caggcgtggc ggcatgcgcc tgtagtccca ccttcttggg 60840 aggctgaggc agaagtgctt gaacctggaa ggcggaggtg gcagtgagct gagactgtgc 60900 cactgcactc cagcctgggc tacaaagcaa gactccatct ccaaaaaaaa aaaaaaaaaa 60960 aaaaaaagaa gtagctctta tcctggagca ggccaaaatc ataaccacat ggggtggcta 61020 aaactccaag gggaaatcca atctttctgg cctgaagaac taaaagacaa gagttcaagg 61080 aaatcacagc cattggaaag tgaggaagca atcccacaaa gtaaggggcc tgtgaaaaag 61140 tgctcaaagg ctgtgtataa actctgccca aatctgacta actcccaaac cacacaggaa 61200 tgcgacaaag tcagctacga atgcaaaacc agaactgaga tctgaactgc tacctgggtt 61260 tgagttcaaa caatttacct gcctgttaaa aacagcaaca cttggccagg cgcagtggct 61320 catgcctgta atcccagcac tttgggaggc cgaggtgggc ggatcacctg aggtcaggag 61380 tttgagacca gccaggctaa catggtgaaa ccccgtttct actaaaaata caaaaaattg 61440 gccaggtgca gtggtgcatg cctgtaatcc ctgctactcg ggaggctgag gcaggagaat 61500 cgcttgaacc cgagaggcag aggttgcagt gagccgagat tgtgccactg cactccagct 61560 tgggcaacaa gagtgaaact ccgtctcaaa aaaaaaaaaa tcatcacttt acagataaac 61620 cataacagaa tcctaagtct ctctacaatg taatatttac aatgtcaagg ataaaatcta 61680 aaattactag acatacgaag aatcaggaaa atgtgatcca ttcttaaaag acaacagagg 61740 tcaacttcaa gataacaagg atttcaaagt agctgctaca actatgttca aggagatgaa 61800 aagaaaaaaa gattgaaaaa gaatgaatat ccccagagat ctatgaacaa tataaaaaaa 61860 ctatcataaa cggaagtaga gtcccagcag gaaaagaaaa aaacaagaca gaaaaaaagt 61920 taatgaaaca atagctaaaa tttcgctcat cttggggagt gacataagcg tagagaaaaa 61980 ccactccact cctaggcaaa atatcaacat gctgacaacc aggataaaga ggaacatttg 62040 aggccgggca cggtggctca tgcctgtaat cccagcactt tgggaggccg aggcaggagg 62100 atcacttgag cctaggagtt caagaccagc ctgggctaca tggcgaaacc ttgtctctac 62160 caaaaaaaat tagccaatta gctgggcatg gtggcgcaca ctactggtgg ccccagctac 62220 tcaagaggct cctgcttgag cccaggaggc tgaggctgca gtgagctgag attgcaccac 62280 tgcactccag cctgggcaac agagtgagac cctatctcac cgaaaaaaaa aaaaaaaaaa 62340 aaaaaacacc aaaactaaac aggtccacat caccatgtcc ttgctcattg ctgcatccca 62400 gagcccagca tggtgcctga gagaaggaag agaggaagag gcccctaaga ccacactcct 62460 gggaaggaga acgaggacac gggctgacag cagagccagg caggcagcag gggcacgtcg 62520 aaactcaaaa gcacttaccc catcccctgt ttgaaagctt caatcaactc gttcttttta 62580 ttctgatctt ccacccaata cacacttgga attacaaact ctgatatcac acggcattct 62640 ggacaagacc tgaaataaga attagattac taagggagaa gtcatgttac gaagcctggg 62700 cacactctct gctaaacctc ttgctcaact gcctcaccac tacaggcatt tccttcacca 62760 gaaattccaa aagatgaaat cacaatcatc caagaacctt atttactatt aacaaaatag 62820 ggtttcccaa tgagaacaca tggacacatg tgggggaaca tcacacaccg gggcctgtcg 62880 gtgcaggggc aaggggaggg agaacatcag cacaaacagc taatgcatgc atggctgaaa 62940 acctaggtga tgggttgaga ggtgcagaaa accaccgtgg cacatggata cccatgtaac 63000 aaagctacac attctgcaca tgtaccccag aacttaaagc aaaaaaaata cacacacaca 63060 cacacacaca cacacacaca cacacacaca tatatggttt cctcaacaaa aaagacagat 63120 gaaataaccc tcatacattg ctggtgagaa tgtaaaaggg tgcagccact ttgaacagag 63180 tctggcagat tctccaacag tttaatgtag agttattata ccataaaacc tagcaatccc 63240 acgcccaggt gtatacccaa gagaaatgaa aacacatgcc cacatgctgt gttcacaaat 63300 gttgacagca gcattattca taatagttgc aaagttaaaa cagcctaaat gtccactagc 63360 tgaggaatgg ataagggaaa tgtgctgcgt ccatacaatg gaacatattc cgccaggaga 63420 aggggactct ggcacatgct acagtcggga tgaactctga caacactatg ctcagtgaaa 63480 ggggccaggc acaaaaggcc ccaaattcta tgattccatt tataagaagt gtccagaata 63540 ggcaactctg tagagacaga aagcggatga gtggtgagtt aaattgtggg cttttatctc 63600 aatagagcag ttgtttcacc acacgatttt aggcaaatta cttgaccccc gcaccccagg 63660 cctgtttcct aatctgtaac tgaggagggt ctttgaggga atgagatgag cggacagatg 63720 tggagttctg aacagtagaa cgcgtgcagt aacctctcca catgccagct cttcccctgt 63780 cctgctggag aatttgagac tcctatgttg gccacattga gcacatccca tgtgccaggc 63840 atcatgcaga atgttttaca tgcattattc cacttcatcc tcaaataacc ctattttcgt 63900 ttttggtggg gggaaaaaac gaagctcaaa atgattaaca ggcaactggg ctacaggcag 63960 gtactactgg atttcaaaca caaggctagg agatgaaaac aggtcagtgc catttaacac 64020 ctttttacac agatcatctt tgctgagttc ctccccaaca cccagaaagc ttggtaggaa 64080 ttgttgccca tcttttatag gaacaggcac ttaggctcag gaagagtaaa tgacttgctg 64140 aagttcatgc agccaggggc cagaactcac cagttactct tgagggtaac ggagggctta 64200 aaagtggacg gaataaagtc tcaaatcaaa cattctccta gctcccacag ctaagacccc 64260 tggctgtact tacttaatga ttgggttttc aaactgtttg gcacaccgcc actgccggat 64320 gcaggacaaa cagtacgtgt gattgcaatt ggagagaatc ccaaatctcc tctcagaagc 64380 agaggccttc tccaggatca cttccatgca gatactgcac actttgtcct ggcttgcctg 64440 gaaggcaaag gccttttcca tctcgtgttc gaacgtcaac atgcagatct gaagcacaga 64500 caggaaggaa ggctttggtt gtgggccact gaggagtggc aggagcccta ggagtagctg 64560 cagccacact gccacagctg agatcaggaa ggaacactga cagcgactgc tgtgagcaaa 64620 ggcccaggct cccccaagtc aggacactga catctccctc agaccacaca aaggacttca 64680 aaccatcact ggtccagccc cttgctttcc taggaggtga catggtcacc acccatttag 64740 gactgagaac acggagatcc aaaaaggtta aactgcagtg gagtcagagt ccgtaaggac 64800 tgcggcccta gtcccccagc tcctctgggc actgtttccc ccgactctga gccatgtcta 64860 catcagagat gctgactcgt ccttaccatg aggcttgagg ctggcagcct agtcctatgt 64920 aagaagcacc acttctcccc aagaaaatga ttcaatgaat tcattcattc actaggcatg 64980 ccctgaattc cttctatgtg ctggcatttg agcaagagtg agaagaccta ggcccagccc 65040 ttgtaagctc agtctgtcca gatctgagac aagccaacac tcaccgcaga gacctcacac 65100 acttgcataa agaagacagc tctaaccctc tgcttccctg gaagacaatg gagagtgtct 65160 ccttgtccgc tgccacatgg agtcagtact aatttacctc ttgattatct aggaatacgc 65220 tgtccattta aacatgcctt aggccaggtg cagtggctca cacctgtaat cccattactc 65280 tgggaggcca tggtaagagg actgcttgat ctcaggagtt caagaccagc ctaagcaaca 65340 tagcaagacc tcacctctga aaaataaaat aatttttttt tttttttgag acagagtctc 65400 tctctgtcgt ccaggctgga gtgcggtggt gcaatctcag ctcgctgcaa gctccacctc 65460 ctgggttcag actattctcc tgcctcagcc tcccaagtag ctgggactac aggcgcccgc 65520 caccacaccc agttaacttt ttgtattttt agtagagacg gggtttcacc atgttagcca 65580 ggatggtctc aatctcctga ccttgtgatc cgcctgcctc gtcctcccaa agtgctggga 65640 ttacaggcgt gagccactgt gcccagccaa aataaaataa aattttaaaa gttagccaag 65700 ccaccacacc tggcattttt aaattttttt attattattt ttcttgagac agggtctcac 65760 tcttattgcc caggctgtag tgcagtggca caatcttggc tcactgcaac cttctgcttc 65820 ccaggctagg gtgatcctcc cacctcagtc cttgctgagt agctgggact acaggtgtgc 65880 accaccacac ctggataatg tttgtatttt tttttttttg tagagacggg gatcttacca 65940 tgttgcccag gctggtctca aactcctggg gtcaagcaat ctgcctgcct tggcctgcca 66000 aagtgctggg attacaggtg tgagtcacca tgcctggccc tcccccgcct cttatccagc 66060 ttcgtaccct ctgcatcatg catagggcct agcataaggc aaagcctccc aaaacactgc 66120 agacattaat gactttaaaa ggcccttcca acaagtggct cctcagattc tatgatttgg 66180 gctcaaatct tccaaaactt cacctagctg gatcccaacc atgaggaagt gtgaacccag 66240 ggagggagga tgctgtatct gcatgtgata gagacataca cacagacgac ataccatggt 66300 cctgagctag atctgttctt tgaacttagc atgattttat atttcagata cgacttcttt 66360 ttctctttat tctgagtaat taaaaattgg caaaataggc cgggcatggt ggctcatgcc 66420 tgtaatccca gcactttggg aggccaaggc aggcggacaa cttgaggtca ggagttcgag 66480 accagcctgg ccaacgtggt gaaaccccat ctttcctaaa aatacaaaaa gtagccgggt 66540 gtggtggtgg gcgcctgtaa tcccagctac tcggtggggc tgaggcagga ggatcacctg 66600 agccagggaa gcagaggttg cagtgagccg agattgcacc actgtactcc agcctgggtg 66660 agagggagac tccattaaaa aaaaaaaatg gcaaaatgac tgcaggaaaa agaacctgaa 66720 aacaggatgt aaatatacca gatacataat atgggtatta ctggcagggg gatgcctgtg 66780 gaaataccaa caattctgtc acttagtaca tttcagattt cttgagtgta tatggatggc 66840 cttccgtgtc ctgttcagta catttcagat ttcttaacat gagttcatgc aaaggtttgt 66900 gactttacct tttcatgagc cttcctctgc tctgggtcga atgggtgcaa gacttgcagc 66960 ctacagattt cacacacctc cccgtgcagg tagacacagg catccccaaa ccggcactcc 67020 ccagcagctg cgtaggggca cagctgctgc tcgttgctgt aggagctgct ggcctccacg 67080 tcatcaaggc cactcctgat ggcatccagg taggaatgcg gcttcatctc ggggctgggc 67140 tgggggtcgc tgcagctgcc tggattactc accatgctcg gctgggtctt cctttcagcc 67200 atgccagaga gatctgaaaa caacacacag cacacatgca catgaaaatg gccccatttt 67260 tctggtatgc cgttagccaa agcctaacat attaagctac tctgacctaa gaattccact 67320 cttgagaaca tatggcaaaa aaaacacacc gaaggggaaa aataaaagga atagtataaa 67380 atgttcatag tgacattact tataattact taaaaaaaca aaaaacaaaa aacaaaaatg 67440 gcaagacagg gaaatagcaa aacaatagga tatacttata caaaagaaca ctaaagccgt 67500 ttaaaatggc aaatatggaa atgttaacac atggaccagt taacactaaa acaaacaaaa 67560 aaacagtgag agcactagaa cacagtgttt ccttcatacc agcaaaggta aaatcatttt 67620 aagtgaacta gaatagatgt ctagagcaaa tctgtgggtc ctgaggccag tgtaaactgc 67680 cccatggtca ccccttctca cgccaggagc tgctgccttc ccactgcaca cctccgagct 67740 tgtttagagg tcacgtattc tcacaggatt actcatttgc tgaggacaga atctgcctac 67800 ctcatggtag ccaattccaa gaactagaaa tctcttcacc tggtgaggac cagccaataa 67860 aaacaacttt tatggccagg tgcagtggct cttgcctgta atcccagcac tttgggaggc 67920 cgaggcgggc ggatcatgag accaagagtt tgagaccagc ctggccaaca tagtgaaaca 67980 ctgtctctac taaaaataca aaaattagct gggcatggtg gtgggcacct gtattcccag 68040 ctactcagaa ggctgaggca agagaatccc ttgaacccgg gaggtggaga tcatgccact 68100 gcactgcagc ctaggcgaca gagcgagtct ccatctccaa aaaaaaaaca aaaacaaaac 68160 aaacaaaaaa cacaacaaaa aaacttttac aatttgtagc tttcttcctc atcaaaccct 68220 gttttaaggc acagaccatg ccccaaaccc tagtgtgcta ttcttttccc aaaggtgcaa 68280 tctaaactgt caaacactgt cagcataaaa actaagacca ttcactggcc taaaagtcaa 68340 acagtgaaac atgctcttta gcaaaatatt tagttttctt tttttttttt ttttttttga 68400 gagggagtct cactcttgtc atccaggctg gagtgcagtg gcgtgatctc agctcactac 68460 aatctttgcc tcccgggttc aagaaattct cctgcctcag cctcccaagt agctgggatt 68520 acagacacct gccactacac ccggctaatt tttgtatttt tagtagagac agggtttcta 68580 ctaaaccatg ttggccaggc tggtctcgaa ctcctgacct caggtgatcc acccgcctca 68640 gcctcccaaa gtgttggggt tataggtgtg agccacttta cccagacaaa atatttacgt 68700 ttgaaatgaa gagcttgatg cttctcacca gctggacaac caccatatga agatggaagt 68760 tacatgttga caaaaagatt gtgtttttat gttttaccag gccagtcttg gagctcaacc 68820 cagccttggg cacgagggcg aatgtatcat ttgaatgatc tgcagccaca tggagcctct 68880 tcagaacagt tctgaagtct ctccgcgcag acaatctgga ggtgtattag gttaggagtc 68940 ctcttgacaa gaggaggcta gaaaggagca ccaagcatta acaagagtgc tatgcaaaaa 69000 gacgcaacaa aaggcttccg cttactcact tcggtctcta agaaccaatg ttctcttttc 69060 acgctttccg ggttcatgtg agttagtttt cacaatggat gcagtgacct cggaaggagg 69120 gtgaggactg tggaaagctg gggagggcac actgtgggcc atggtgccca cagcacctcc 69180 agctgcagca gagggcctcg tgtggtcata tctaaacaaa acacacagca gatgcattac 69240 agacatgcca cccacacaca tctcccacac tccccagatg ccaatggccc tccttctgct 69300 gcacttgttg aggtgaagaa ggcggccatc ttttccaata tttaaactct aacaggatta 69360 tcgattatta acagatgctt ggcaattcat tgtgaggggg acatttgcta tctatcacct 69420 atgcttaagt gtctctgtgg gacttgagtg ggacagacac acagcaccag accacacaga 69480 gaacctgaaa gttccaaaca gatgttgagc taaaatctcc tgatgcctga ctgacccagt 69540 attcttttga gcaggagtcc ccaaaatgct gacaagggcc aatgatctct ccctgactgt 69600 ctctcttggc actcattgac aggggaagac caacgtgggc ctacttccat catctcccac 69660 tgcactgcag agaaaaagga gggaaggaag ctttgcagtc tagaaagaaa agatcggctc 69720 tttgctacaa aagcatgaac aagtttccgg aattgtgtac aattttataa ctatatattc 69780 ataagaataa ggctgaaaag tagttttaaa aaatgaaaat taggccaggc acggtggctc 69840 acgcctgtaa ttccagcact ttgggaagct gaggcgggag gatcacgagg tcaggagtta 69900 gagaccagcc tgaccaacat ggtgaaaccc catctctact aaaaatacaa aaaaaaaaaa 69960 aatcagccag gcgtagtggc agatgcctgt aatctcagct acttgggagg ctgaggcagg 70020 agaaccctgg aggcggaggt tgcagagaac tgagatcgca ccactgccct ccagcctggg 70080 caacagtgag agactctatc tcaaaaaaaa aaagaaaaga aaattagttt tagggtactg 70140 aaactgaggt tttaaactta tttgccatac tttttgtgat gttgccatat tacttttaca 70200 ttaaaatttc ccccttatca agacccattc tccaaatgaa atcagtgtca cagctggaat 70260 ctgttgcaga gtccttgcct gcaccgagtt ccataggcac agtagccctt ctggtagtac 70320 ttgcagatgg tggacggttt gctgtttgcc aagtcatgtg agaataggca ctgacttcct 70380 tcccgacaca caccatgcat aaaatacctg cagagacaag cacaggcata caacttttag 70440 aagcacattt tgctttataa aatcagctta ttcttgaact tagcatacaa acatttacca 70500 ggcatatatt atgtataaag gctctattag gcactggaga gagatctata tatttccttg 70560 attctacaac agtgatttca gaggcactac aactgattca atgacagctt ttctgaaaga 70620 aaaacaaatg atcccatata tttctatgtg aagatatatc ttcctgattt gagatatgtt 70680 caatgtgagc cacataattg agaaaacact ctgtgaaaaa ctgttctctc tgttctcaag 70740 gagcttaaag ggcatgacta acgaaaccag aagatctggg ctcaagaccc agctctgcca 70800 cttaagaaca tgtcacaaaa ccaacttccc tgggccttgc tacctttccc tataaaatga 70860 agattatact acccacttaa ctggtcgtgg tgaggatcaa ataccatagt gtggtatcaa 70920 aagatataca cagatgctcc ttgactaatg atggagttac atcccaataa agccactgtt 70980 ttttgttttt tgttttgaga tggagtctct ctgtcaccca ggctgaagtg caatggcaca 71040 gtctcagctc actgcaacct ctgccttccg ggttcaagcg attctcctag ctcagcctgg 71100 gctaccttac ttatgcttag aacacttaca tcagcctaca gttgggccaa atcatctaac 71160 acaaaatcta ttttacaata aagtgtagaa taatctcatg caatttattg aacaccgtac 71220 tgaaagtgag aaacagaaag gttgtatggg tacttgtagt ttttaatgaa agctgtttct 71280 catacattgt ttcagatgtt tcagaatatc agatgtatca catgttctgt atcagaatat 71340 tccactgaga tatcagatcc tggccttgaa gaataagtgg tacaggaata cctgggaggc 71400 taactctgtc cagacagggt agagagacct gagtgaatac tcaaacagta gagaccctag 71460 atgaacatgt cttgatatta aagataaact aggctgggtg tggtggctca cacctgtaat 71520 cctagtactt tgggaggcca aggcgggcgc atcacctgag gtcgggggtt ccagaccagt 71580 ctgaccaaca tggagaaacc ccgtctctac taaaaaaaat acaaaattag tcaggagtgg 71640 aggtgcatgc ctgtaatccc agctacttgg gaggctgagg caggagaatc gcttgaactc 71700 aggaggtgga ggttgcggtg agccgagatt gcgccattgc actccagcct gggtgacaag 71760 agcaaaaact ctgtctcaaa aaaaaaaaaa aaaaaaaaaa gataaactag ccagggcaac 71820 aaagggagac cctaaaattt aaaaattagc ctagcatggt ggtatgcacc tgtggttcag 71880 ctactcagga gagtgagaca ggaggattgc ttaaacccag gagttcaagg ctgcagtagc 71940 catgattgtg ccactgcact ctagcctggg tgacagcaag atcctgtctc acaaaagaaa 72000 aaaaaaaagt aaactagtgt tagagtagaa gtattttaga cacaccctaa taaggcttaa 72060 aaaaaaaaaa cacaagctga tagcaagtat ataacttact gtcagccaaa acaaacttta 72120 aaggaagaca atacaatcca aatgctcaga aactcacaat gcttggcatc caatcataaa 72180 ttactagata tgccaaaaag cagaaaataa tgtgacctat aaccaggaga aaaataaaga 72240 acaggaatta cagagatgat ggaatcagca aaataagacc ttaagaacag ctattataca 72300 tatgctcaat atgctgaaag atttaaagaa aaacataaac ataatgtgga gagaaatgga 72360 tgatttaaat aagaccaaat actaggtgtg gtggctcacg cctataatcc cagcgctttg 72420 ggagactgag gtgggtggat gaccagaggt caggagttcg aaaccagcct ggtcaacatg 72480 gtgaaacacc atctctatta aaaatacaaa aattagccag gtgtggtggc aggtgcctgt 72540 aatcccagct acttgggagg ctgaggcagg agaatcacct gaaccctgga ggcggaggtt 72600 gcagtgagcc aagatcgcgc cattgcactc cagcctgggc aataagagcg aaactccacc 72660 tcaaaacaaa acaaaacaaa aaacaaatga aacttctaga agtgaaaaat acaatgtctg 72720 aaatgagaat tacattagat gagtttagta gatgggatac tacaaaggaa aatatcagaa 72780 tacttgaaga cacagaatag aaaccatctg agagagagag agagagaaac aaacttgctt 72840 ctgactacca aggagcatgg atcttggctt ctcactgtaa aaaaacaaaa caaaacaaaa 72900 caaacccaac tgaaaaatga aacaaaatat gtgaaacaac tgctttcaga caatagaaaa 72960 aaggactggt ccttaagaga agggaaacac aggaagtaag ccccacattt agtctgactt 73020 cctacctgga ggcatattct aggtcttggt actgggagta gaacctcagg caaatcacag 73080 agattgagtt tagggaggct gcagggattc tttaaagatc cataaatagt ctgggctcag 73140 aggctcatgc ccgtaatccc accacttcag gaggccaagg tgtgaggact gcttgaaccc 73200 aggagtttga ggtcagcctg ggcaacatgg caaaacccaa tctgtataaa aaatacaaaa 73260 atcagccgtg catgatggct acttgggggc ctgaggtggg aggactgctt gagcccagaa 73320 ggagagagcc tgcagtgagc tctgtttgca ccactgtact ccagcctggg tgacaaagca 73380 agaccctgtc tcaaaacaaa caaaaaaaca aacaaaaaac cctgtaaata gaaccacaca 73440 taggccgcat gcagtggctc atgcctgtaa tcccagcact ttgggaggcc aaggtgagtg 73500 gattgcttga gctcaggagt ttgagatgag actgggcaac atggtgaaac ctcgtctcta 73560 ccaaaaaata tacaaaaaat tagccaggca cggtagcgtg cacctgtgct cccagctact 73620 tgggaagatg aggtaggagg atcgattgag cccaggaggc agtggttgca ataagccaag 73680 atcatgctgc tgcactctag cctgggtgac agagtgagac cctgtctccc aaaaaaaaaa 73740 aaaaaaaaaa aaaaaaaggt aagttgggga aagaatcttt tcaacaaatg atgctggacc 73800 caaaatcgac ttggaaaaaa cttaaatatg tacctgctga tatgacccaa aatgaagtat 73860 aaaacaacct atgacgtatt ctagccagaa acaattaatt tgaatccaca aaactccaga 73920 tctaacatcc agttcataga aaatacagga gactggggac aacctatgaa agacatctcg 73980 agaaaacaac caaataaata caaaagaggc tgtacgtggg acctaggcct actgtcttta 74040 taagtgccat gtaactaaag gaggctgagt ttggaagaca gtttgacagt ttcttaaaaa 74100 atgtaaacat aaatctacca tatgacccaa caattctacg cctaggtatg tacccaagaa 74160 aatgaaaatc tatgtccaca caaatacttg tacatgaatg tccaaagcag cactatgcat 74220 aacagccaaa aagtggaaac aatccaaatg tccatcaact gatgaacaga cagagaaaat 74280 gtgatttatc catacaatgg gctcttatcc agccataaaa aggaaagaag tactggcaca 74340 cactacaaca tgggtgaacc ttgaaaacat tacgcagagt gaaagaagct ggacacaaaa 74400 gaccacatgt tgcatgattc catttatatg caatgtcaga aaaggcaaat ctacagagac 74460 aaaaagtaga ttaagtggtt gcctagggtt gggaggagag aagtgagggt gactgttaat 74520 gggcacaagg gatcttttgg gggtgataga aatgtcctaa aatttaactg tggtgatggt 74580 tgtacaactt tgtaaattca ttaaaaagtt ttgcactgta cacttcaaac aggtaaattt 74640 tatggtatat aagttatacc tcagaaaaag ctgttaaaaa agagaaaaaa gggaagggac 74700 aatgctaggt tagcagacag aacacaaggg acataaccag atgcaatact tacctctgga 74760 ctagaatctg gtttcaacaa accagataca aaagacattt ttgaaaccag atattttgaa 74820 agatattttg aaataaatgt gagtatggac taggtataaa atgaaaattt attaatatgg 74880 aaagttaaac acaattaact gagaagagta gattataaaa cagctaatgg tgcagcttct 74940 atagaaaaac agtacggaag ttccttaaaa aattaaaaat atatttacca tatgatccgg 75000 caattccact tctgggtata gacacaaaat aattcaggcc aggcccagtg gctcacgcct 75060 gtaatcccag aactgtggga ggccgaggtg ggtggatcac ctgaggtcag gaatttgaga 75120 ccagccggat caacatggtg aaaccccatc tctactaaaa atacaaaaat tagccgggcg 75180 tggtggtggg cgcctgtaat cccagctact ttgggggccg aggcaggaga atcacttgaa 75240 cctgggaggg agaggttgca gtgagccaag atcacgccac tgcactccag cctgggcaac 75300 agagtgaatc tgtttcaaaa aaaatagaag acttcaaagt agggactcaa acaaacattt 75360 gcacacccgt gttcatacca gcattattca caatagccaa aaggtggaag caactcaagc 75420 gtgcgctaat ggacgaatgc ataaacaaga tgtggtctat ccatacaatc agccttaaaa 75480 agaaaggtga ttctggccgg gtgtggtggc tcatgcctgt aatcccagca cttagggagg 75540 ccgaggcagg cggatcatga ggtcaggaga tagagaccat cccggctaac acggtgaaac 75600 cccgtctcta tgaaaaatac aaaaaaatta gccgggcgtg gtggcaggcg cctgtagtcc 75660 cagctactcg ggaggctgag gcaggagaat ggcatgaacc cgggaggtgg agcttgcagt 75720 gggccacgat tgcgccactg cactacaacc tgggcgacag agcgagactc cgtctcaaaa 75780 aaaaaaaaaa agaaaggtga ttctgacaca cgctgcaaca tgcatgaacc ttgaggacat 75840 gacgctaagt aaaataaacc agtcacgact ccacttctgt gaggtcccta gagtagtcaa 75900 attcataggg acagacagtc gaatgccagg tgtcagaggc tggggatggg agaaatggaa 75960 gttttttaat gggtagtaca gagtttcagt tatgcaagat aaagagctct ggagattggt 76020 tacacaacaa tgtgaatgca cgtgacagaa ctataactta aaaatggtta agatggtaaa 76080 ttttatggaa attttacaat gatttttttt ttttttttga gatggagtct tgctctgtca 76140 cccaggctgg agtgtagtga catgatcttg gctcactgca acctccgcct gccaagttca 76200 agcgatcacc tgcctcagac tccgcagtag catggaaggc acactccccc aacaccgtac 76260 cagtaaaata atctcctctc tcctcccagc gcatattctc atacatacca gccaccagat 76320 tctgatactt ggaatccata ttaacccccg ccccctccgc gaacgatcgc tctccctacc 76380 cttccgcaca ccaccaccgg tgaccatccc tctacacccc cgttacccaa aactctcatc 76440 attcacggct tctgcccagt acgatgcata cctcactccc tacccaacac gagcccttca 76500 gcctccgagc atcgcctaca tcggcacttc catgcattgt ggaccaatgc tctctaattc 76560 cctccaccaa caccgaacat tctcacctct cctgtataac ccttccttcc gctatcccca 76620 tcataaaccc cgcgttgccc tctgaacggc ctctcacttt aacgagaact cttgctctcc 76680 ccatcgtcct atctcgcc 76698 <210> SEQ ID NO 31 <211> LENGTH: 4878 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4765)..(4766) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4769)..(4769) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 31 attgaaataa acaaccaggc agcagttatt aacacgggaa catggcggcc gcagcctggg 60 ctcccgcggc ggcggcggag gtcagcgccg acggcagccc gcacctgacg gcgtgacggc 120 cacattgatt ttcctcgcat ctggcttcac tgcattggct cttctgcact gtgtacaggc 180 acagttgctg atatgtgttc aagatgagtg ggatgggaga aaacacctct gacccgtcca 240 gggcagagac cagaaaacgc aaggaatgtc ccgaccagct cggacccagc cccaaaagga 300 gcactgagaa acggaaccgc gagcaggaga ataagtacat agaggagctg gccgatctga 360 tcttcgcaaa ctttaatgat attgacaact tcaacttcaa acctgacaaa tgtgccatcc 420 taaaagaaac tgtgaagcag atccgccaga tcaaagagca agagaaagca gcagctgcca 480 acatagatga agtgcagaag tcagatgtgt cgtccacggg gcagggtgtc atcgacaagg 540 atgcactggg gcccatgatg cttgaggccc tcgatgggtt cttcttcgtt gtgaacctgg 600 aaggcagtgt ggtgttcgtg tcagagaatg tgacacagta tctacggtat aaccaagaag 660 agctgatgaa caagagtgtc tacagcatcc tgcatgtcgg ggaccacact gaatttgtca 720 agaacctgct gccaaagtcc atggtgaatg gaggatcctg gtctggagaa cctcccaggc 780 ggacgagcca taccttcaac tgtcgcatgc tggtgaagcc tttgccagat tcagaagagg 840 aaggccatga tagccaggaa gcccatcaga aatacgaggc gatgcagtgc ttcgctgtgt 900 ctcagcccaa gtccatcaaa gaggaaggcg aagatttgca gtcctgcttg atttgtgtgg 960 cacgaagagt ccccatgaag gaaagaccaa ctcttccctc atcagaaagc tttaccaccc 1020 gccaggacct ccaaggcaag atcacttcac tggacactag caccatgaga gccgccatga 1080 agccgggctg ggaagatctg gtaagaagat gcattcagaa gttccacaca cagcatgaag 1140 gggagtctct atcatatgcc aagaggcatc accatgaagt tctgagacaa gggttggcgt 1200 tcagtcagat ctatcgtttt tctttgtctg atggcactct cgttgctgca caaaccaaga 1260 gcaaactcat ccgttctcag actactaatg agcctcagct tgtaatatct ttacacatgc 1320 ttcacagaga gcagaatgta tgtgtaatga atccggatct gactggacaa gcgatgggga 1380 agccattgaa tccaattagc tctagcagcc ctgcccacca ggccctgtgc agtgggaacc 1440 caggtcagga catgaccctc ggtagcaata taaattttcc catgaatggc ccaaaggaac 1500 aaatgggcat gcctatgggc aggtttggtg gttctggggg catgaaccat gtgtcaggca 1560 tgcaggcaac cactcctcag ggtagtaact atgcactcaa aatgaacagt ccctcgcaaa 1620 gcagccccgg catgaacccg gggcaagcca gctccgtgct ctccccaagg cagcgcatga 1680 gccccggcgt ggctggcagt cctcgcatcc cacccagtca gttttcccct gcaggaagct 1740 tgcattcccc tgtgggagtt tgcagcagca caggaaatag ccatagttat accaacagtt 1800 ccctcaatgc actgcaagcc ctcagcgagg gccatggggt ctcactcggg tcctcgctgg 1860 cttcaccgga cctaaaaatg ggcaatttgc aaaactcccc agttaatatg aatcctcccc 1920 cactcagcaa gatgggaagc ttggactcca aagactgttt tggactttat ggggagccct 1980 cagaaggtac aactggacaa gcagaggcca gctgccatcc tgaagaacaa aaggggccca 2040 atgattccag catgccccag gcggccagcg gggacagggc tgagggacac agccggctgc 2100 atgacagcaa agggcagacc aaactcctgc agctgctgac caccaagtcc gaccagatgg 2160 agccttcacc cttgcccagc tccttgtcgg acacaaacaa ggactcaaca gggagcttgc 2220 ctgggcctgg gtccacgcat ggcacctcgc tcaaggagaa gcataagatt ttgcacagac 2280 tcttacagga cagcagttcc cctgtggact tggccaagct gacagcagaa gccacaggca 2340 aagagctgag ccaggagtcc agcagcacag ctcctgggtc ggaagtgact gtcaaacagg 2400 agccagcgag ccccaagaag aaagagaatg cactactgcg ctatttgctc gacaaagatg 2460 atactaaaga tattggttta ccggaaataa cccccaaact cgagcgactg gacagtaaga 2520 cagatcctgc cagtaacaca aagttaattg ctatgaaaac tgtgaaggag gaggtgagct 2580 ttgagcccag tgaccagcct ggcagcgagc tggacaactt ggaagagatt ttggatgatt 2640 tgcagaacag tcagttacca cagcttttcc cagacacaag gccaggagct cctactgggt 2700 cagttgacaa gcaagccatc atcaatgacc tcatgcaact cacagctgac agcagtcccg 2760 tcccacctgc cggagcccag aaggcagcac tgcgcatgtc acagagcact tttaataacc 2820 cacgaccagg gcaactgggc aggttattgc caaaccagaa cttaccactt gacatcactt 2880 tgcaaagccc aactggtgct ggacctttcc caccaatcag aaacagtagc ccctactcag 2940 tgatacctca gccaggaatg atgggtaacc aagggatgct aggaagccaa ggaaacttag 3000 ggaacaatag cacaggaatg attggcagca gcacttcccg gcccagcatg ccttctgggg 3060 aatgggcacc acagagtcca gctgtgagag tcacttgtgc tgctaccact ggtgccatga 3120 accgaccagt ccaaggaggc atgattcgga acccaacagc cagcatcccc atgcgagcca 3180 acagccagcc tggccaaaga cagatgcttc agtctcaggt catgaacata ggcccttctg 3240 agttagagat gaacatggga ggacctcagt ataatcaaca gcaggcccct ccgaaccaaa 3300 ctgccccgtg gcctgagagc atcctgccta tagaccaggc atcgtttgcc agccagaaca 3360 ggcagccctt cggcagctcc cctgatgacc tgctgtgtcc acatcctgca gcagagtcgc 3420 caagcgatga gggcgctctt cttgaccagc tgtatctggc cttgcggaac ttcgatggcc 3480 ttgaggagat tgatagagct ctggggatac cagaactggt cagccagagc caagctgtgg 3540 atgcagagca gttctcaagt caggagtcca gcataatgct ggagcagaag ccccccgttt 3600 tcccacagca gtacgcatct caggcacaaa tggcccaggg tggctataat cccatgcaag 3660 atccaaactt tcacaccatg ggacagcggc caaattacac cacactccgt atgcagccac 3720 ggccaggcct caggcccaca ggcattgtac agaaccagcc aaaccaactg agacttcagc 3780 ttcagcaccg cctccaagca cagcagaatc gccagccgct tatgaatcag atcagcagtg 3840 tttccaatgt gaacctgact ctgaggcctg gagtgcccac tcaggctcct attaatgcac 3900 agatgctggc ccagaggcag agggaaatcc tcaaccaaca ccttcggcag aggcagatgc 3960 agcagcaggt gcagcagcgg actctgatga tgagaggaca gggcttgaat gtgaccccaa 4020 gcatggtggc tcccgctggc ctaccagcag ccatgagcaa tccccggatc ccccaggcca 4080 atgcccagca gttcccattt cctccgaact acggaataag tcaacaacct gatcctggct 4140 ttactggggc tacgactccc cagagtcctc taatgtctcc ccggatggca catactcaga 4200 gtcccatgat gcagcagtct caagccaacc cagcctacca gcccacctca gacatgaatg 4260 gatgggcaca ggggagcatg ggtggaaaca gcatgttctc acagcagtcc ccaccacact 4320 ttgggcaaca agcaaacacc agcatgtata gtaacaacat gaacatcagt gtgtcgatgg 4380 caaccaacac gggtggcttg agcagcatga accagatgac atgccagatg agcatgacct 4440 cagtgacctc cgtgcctacg tcaggactgc cctccatggg tcccgagcag gtcaatgacc 4500 ctgctctgag gggaggcaac cttttcccaa accaactgcc tggaatggac atgatcaagc 4560 aggagggaga tgcatctcgg aaatactgct gaccctggag aaactgtctg catctttctt 4620 caacccactg ggcttacaaa catttaccag tctggagagc tgcgtctctt tgtgttgcca 4680 cctgacatgc cgccagttct cccaggacat agcagcagac agtcgggccc tgggcccgca 4740 gcatagagcg tgctggcttg gctgnnacng gaagagttgc ctctcccgac agcctgcagc 4800 tcgcctccag accaacccgc agtctgttca ctgcattcac cgtagtgcaa cttagatctc 4860 ctgcagagta actgtccc 4878 <210> SEQ ID NO 32 <211> LENGTH: 240001 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(240001) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 32 tgtgctgggt ggtgaacttg ctatgtagcc aaggatggct ttgaactcat cccgtgcctc 60 tacctcccca gtgctgcaat tagaaatatg agccatcata tcaagttgat tctgaggtct 120 caggaattga tacttcagaa acagggaaag ccttttttat aagaatgttt tatagtgtac 180 tcatgtaaat aaaataaata aaatttttaa taaaagggga gctgaagaga tggctcaatg 240 gttaagagca ctgactgctc ttacagaggt cctaagttca attcccagca gccacatggt 300 ggctcaccaa ccatccgata atgagatctt gatgccctct tctggtgtct gagacagctg 360 cagtgtactt atgtaaataa aagcaatgtt tgatgatttg gaccctggca aaagaggtat 420 gaaaggccac gaggcctcgc cagatacagt tgtccctttt ctttctgtag cttcactggt 480 ccatgctcaa ctacaatttg agaatagtaa gtgaaaaatt tcatagataa ctcacaactt 540 ttacattgct tgccactatg tcatgtaatt ttacaatgtc ttcttcagtc ccactttgta 600 ccaaatccac ccctttgtgt agtctctgct tactatctgt gctttttggc taccaagaaa 660 atctataaag tgttcccttc aagcaaaaca attcaagtac agagagatgt gcgtgggaaa 720 gcctacagat atttgtgtaa cactgattat agtatagctt tcattgtttt gtagtattag 780 ttacaacctc tcactctgct taatatataa actttatcat tggtatccag gtaaagaaaa 840 aacatgttag gaacttggta ctctatgtga tttcaagggt cactagaggg tattacattg 900 gctgaggtgg gagggtcttg ggccctagga gcttagtctg gagaatgaga agggcaaatg 960 cacaaacaag gccacacgct ctgtacaaac agaacacagt aatacttacg tgttgttgaa 1020 ctggcacagg acttaatagg caaatacaaa aatagttttc tgcaacccgg aaatcattgt 1080 tcagtatgag tcttgataca tacaggagag attgttactc aaggcagctc aaagatgatg 1140 tattgataat acggctggtt ctaagaatac aaagttaaac atataaaagc aaaataaata 1200 aataccacag ttataacatg ggtgtgacgt cttgacacta tttcagtact ccaaagtgac 1260 atgattcttc caggtcccgc tggagtgagg cagctgggca tggagttctt tacgctactg 1320 taagagctgt ttggtttgtt ttattgttta gagacagtcg tgtgtcttga gcattcagta 1380 agaaggtgca ctgagtaaca cagcatggaa gcagggatgt gtttgtctgc acgttcagca 1440 caggtagttt tttcatgtta attctgttgc cactgagcac tgatggactc tggatagctg 1500 cctctcccct caagagttgg aatagaaagc aacaagagtc tttcttaact cttaagaatt 1560 taggacagga gaagaaatct aagtggcaat ggggacattc ctgcgaggaa cccaacctcc 1620 ctgcaaaaat attatgggtt aagagtggag gaggacagat cagagggaca ctctgtatct 1680 ccttgttctg tccctaagct gctgaaggct tttgagtctt cggggaacat aatttattct 1740 agctaattaa aaaaaaaatc cttaaaattt actaacaggt ggtcaaaacc aatcattcca 1800 aacagcagac acttccctga aaaacgtgaa gtagcctatt gcagacctcc ttccgattcc 1860 actcaccaat gttaacattt gttacagctt tctaaatatt ttctagctat agccaagtag 1920 gcatatactt ttctttttct ttgtcataat aaactggagc taaaaaaaaa atacgatcaa 1980 aaagcatgtt ttgcaattaa tggacctggg ctcaaatctt gcccaccttg cttactgtgt 2040 aactctacaa aaattacttc tttaggtttc aatgttttat gaggtataaa aatagcaatt 2100 acttcgtaag gtttgaggat taaaatttgg agtgtgtgtg aatcacttaa tgcagtgcca 2160 agtcgttaca gttcaataaa cacttattgt ctatggcaag tgacctttca taagagttaa 2220 aataaggaaa cgtgttcctg tcatattttg ataacttccg ttaagcaaac aaatgttgct 2280 catttctttc aactaattat atctaaatgg aaaagaagtt gcttttccag ttaaaaacca 2340 aacaacattt aaacgtgaaa actcctccac gtctccttaa tcccaatact ccattgagga 2400 tttgataatg gattccccaa ttaaaaaaca aaacaaaact tttgttgtct cactgcgtgc 2460 ggagaacact cccctcggtc tttctaaata ctgagcagcc tttgctttgt caggcaatcc 2520 cggggtggta ccccggtaag ttcgcctccc gcggtcacgc ccctctatcc cctccagaga 2580 cctcagggac agcaattggg gaggcgtatc cacgaaaaaa ccgaggggac atggtggcca 2640 aggagtgcgc cccggaacag cgtctgggtg cagaggtgcg cccgaggggt gcaggctgcc 2700 ggctaccggg ccctgcctga gcgcgcgcgg gaggcacctc tgggactagg ttttccgcga 2760 ccttctcgcc gcagcgtccc tgccgtcgga ggcgcggcag tcccttggcc tccaccccca 2820 ggcccgggcc agtccccctt tttagctttc ttttgggcat tgccctttgc cctcgcatgg 2880 agtcctctgt tgactctccc ttcacttcca gtcacccata ggtcacggtc cctagaccac 2940 agccacccat cttgtccaac tccccgagct ctgaagtctc gccagccagg gagatgctga 3000 ggaccccgcg ggtggggtag ccccggtgtt cccgggccca cgctcggggg gcgcgggacg 3060 caagtttccg cccggtcccc tgagcggtga cagcgttcgc tcggaggcgg cggggaggcg 3120 gagggcgggc cagccccgtg cccgagcccc ctcccctgct cgcgagctcg cgcggtctgt 3180 gtctctctcc gcaagtgcag agccgcggag gaggaggggg aggaggagga gggagctggg 3240 ggaggatctc cattgaaata aacaaccagg cagcagttat taacacggga acatggcggc 3300 cgcagcctgg gctcccgcgg cggcggcgga ggtcagcgcc gacggcagcc cgcacctgac 3360 ggcgtgacgg ccacattggt aagcgcgcct cccctggggg ctcacgggcg gcgggcgggg 3420 ggcgccgcat tcccacccgg gccgctgccc ttggtgcgcg cagcccggcg gagccgcgcg 3480 ccggccggcc gggcaggctg ttgttgtgtg cgggcaccgc tgcccaggcg tgcggagccc 3540 gcgacgccnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 3600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnag aacctggaaa 3660 gtgccgaggg tgtgtgaagg tgacgcggcc ggcaggggcg gcggcggggg ctcgggcgtc 3720 tggggggcct cgggcttggg tggcttcggg gcggtagcgc tcgggccgcg caggccgggc 3780 cgcggtgggg gcggggagcc ggggtcgggc ggcggcggcg gtggcggcgc cgcgccgggc 3840 tcgcccctga cttaactttc tgggtgcggg catgtgtgcc ggaggcgcgc tggggccgcg 3900 gccgggggcg ggaggcgggc tgcgggccag gaggttccgg gttggctcgc cagcgccccc 3960 tcttccgtac cccttctgcg gcccctgcag ggacaggccc tcgggggccc cccgcgggaa 4020 gcgggagggg tcctggcggc cctcgcgccc cggtcacgcc ctgggccggg gaccctcctc 4080 tccgggcccc tggaggctcc cggggaggcg tccagggtcg gcgccgcggg ctggagtgcc 4140 cgcaccccgc ccctggggga gtcctggagg cgccgcggcc gcgctcgggg gtggctcggt 4200 ccctgcttcc atggtccctc cctttcccct cccccaagtg gcttccgggg cctgcggact 4260 gaggggcggg aatcggggac ccgagcccct tactctccgg gagtgacgtt gggcctcaag 4320 cctagagggc ctgtcactgg caggggaaac tttcccaaac ccgagcctga gctcgagcac 4380 cctcctccgc cacctcgtcc tctaatccca ctcccactcc acctcctccg actccttccc 4440 ctcccaccga cccgaatctg gctgtgcctg actgatgggg cagtgagcca atggaaggca 4500 ggaactgacc tgccgggtac cggtaagcca atggtgggag ccagaggcag gaaggaggcg 4560 gggtttcttc cgtccagtta gggctgagtt gcaggcgggg cgggggagcc ttggagacgc 4620 cgcgagccct ccactctggc gcgtcccttg gtcacccgca cctgggtttg tggaatagtg 4680 tcactcacag aatctgtgac ccggggagac ctgcataggt gcgcgaagat attgcttttc 4740 tctggtgctg cgagaggcgt tgttttagac atgacaaagt ctaaagccac ttcaggatgt 4800 ggcagtaact gcgaggcccg gttttaaaat ggcatatgtt gatagtgacc gcgttctgga 4860 tctcagcacc aggtgagatc tttgaaggtc tgcgttagtt tcactgggct tctgtccagc 4920 acccggacga tggtgaattg aaagggcacc ctgagagtaa aggcgcgggg tggcctcttg 4980 tgaggtgatt tttaggagtg ctaaagcatt cttgtttgga attggcctca ctgggatctt 5040 gtttaatcag accaacacca atttcccaag tctccttgaa agtttcgtgc ttggtctggg 5100 tgtgacattt taacaaagtt actggttatg ctgtgcatat ttttttgtct tgttcttggg 5160 taaacaaaat gaagttttga accaaagcgc cactaagata ccaagcgtgg gtacttagca 5220 aaagcagcta aagaatattt gttggcagaa aacaaaagga ataaagtata gcagtatagc 5280 tttccatatt actcccttac aaaagattcg taaaacattt tatctattta tttatttatt 5340 tatttattta tttttagttt ccttaaacac ggatgaattg tacagtatgt ggctacttct 5400 ctgatgtgta agaggtcaag agctatcttt ggttgtttgg gtccagtgaa ctgactttct 5460 tgactcctga gttttaggaa aggggggcgg gggcggttcc cttgaggatc cctggttgct 5520 cagcgggaat tgcggtctgt taaaaagacc gccgctgctg ctgcagtgct ttttgtgtgt 5580 gtacatgctc tgttctttgt tggtgaggtt agtccaaccg gagggcagca acacattcct 5640 tttcccaatt ggaatctttg ggagttcaaa ggatgagaaa tgttaaactt aaaatccatt 5700 catttttgga atctgtcacc catgaattta attttgggat ttaaaaaaat atctaatggg 5760 cacgaaccac actgggttct ccagctttta ttactattgg attattaaga aaggacttgc 5820 gagagactaa tgtaaggaaa gagtagtgtg taatatgtga ctttcaaatc tatagtgtag 5880 attcccaacc tgtgtaattt tagacgttct tgtagaagta aattgctttt tttttttttc 5940 cttcgagaca gggtttctgt gtatagccct ggctgtcctg gaactcactt tgtagaccag 6000 gctggcctcg aactcagaaa tccgcctgcc tctgcctccc aagtgctggg attaaagctg 6060 tgtgccacca ccacctggtg taaattacgt ttttctgtag cttttgaagt gttattttgg 6120 tgataaatga gtcaagtgaa agataagcac ttatttcaac tgacagaagt agggagtatt 6180 gtaaattaat gttcagaacc cagcaacatt cagagactcc cactgctggt taatttggga 6240 ggccactctg atgcaggccc tttctctttc ctgaattctt aaaagcaacc cattatttca 6300 cttcattctc cataaggatc cttcaaagcg ttcttagatt cttggtggca gagaatagca 6360 agtcgcctaa tgcctggtga ggggaaaaac ctcgcaagca tatggaggca tctagaaaaa 6420 gatgtgcatt gtcagcggcg gcgattccat tgtgtgctct cttgctggag ctgaaccttc 6480 ttcctcctgg gaatttccct cttaaaagag aggatttctt tgactttaga tgtcagggtg 6540 ctgaggccca ggtttcagga cagctcaaca atcattcatg tgagtttaat gcttttgagg 6600 acttaatatt tttaaaaata tttttaaccc ctcatcgatt aaatataatt tagatgactt 6660 tcagcatgag agacatctta ctgaaaatac atataaaaga tggagggtcc taggattgca 6720 taaagggtta atggttctcc ccttacctct caatagatgc gtcttattaa agctttccag 6780 tctccatgga atccatgatc tctgattacg tttctatttt acatgtagaa gttaaggact 6840 cagtgcctta gctgtttcag gccacagtag gttgctattt gacccatact ttgacagctt 6900 agatctctag gaaaaattgt ttttgtcgta ttgaatacaa aggcagtccg tatattgtta 6960 gaaagaaaaa gcatgaagag tggcccttta aagcattttt aatagaagac taattttctg 7020 gtatgcatgg gtgtctttga tatcttggtc attgttgtgt tgtggttgaa attatattta 7080 aaagtttaac tatttttagt tgttaatatg ataaaaccaa tgtttaagcc ctattagctt 7140 tttaatttgt ttatttttta agatttattt attatatgta agtacactat agctgtcttc 7200 agacacccca gaagaggaca tcagatctca ttatggatgg ctgtgagcca ccaagtagtt 7260 tctgagaatt gaactcagga cctctggaag agcagtcagt gctcttaacc actgagccat 7320 ctctccagcc ccatgatact gatttttgaa tgaagaaaag ccatggaatg gaaaacacaa 7380 tgttgagttc tttttcccct tttctatcac acgctccttt gcctccatgt cttctaagtg 7440 gaaagaaagg aggcactcag tgtttatgcg cttctttctt tcttttgttt ttgttttgat 7500 tgtttcctac tttttgattt agactagaga agcaagaagg ggtgccatgg cataccaccc 7560 tctgaagcct cttaaagtat cctacctggc aaagctgtaa agtgcagttc agtgtcacag 7620 gccctcactt cagagagcac gagggaaact ttacaggttc cagatgttct agatagaggc 7680 gacagtatga cttgcgtggc tgttatagca gtctatgcga cgtcctagct gctgtgaaag 7740 ggagagtaca gagttggcag cttacagtga aggtaactag gtgttctgct ggtctgcagt 7800 agagcacacg acttggcttc aagagcaaag agtctctgtg tttactaatt agcgatattc 7860 attcccattt ctagggtcag aggcagtggt ggaatgctag gatttgtttt agaccggtgt 7920 ttatttggtt ctatggttgg gaatttctag caaactcgaa tgagtacagt gcgtacggta 7980 atgtttctca cagctgcttt ggaacttctg gacatagtgt cagtcatcag gaggaggttg 8040 caaatcggga gacgttaagg ggcacttgac agatagatgg aaactgaagt ttgcggtaaa 8100 ttctggtggg acttatacct caagccagcc agttcttatt ctgtcctggg cccatgttta 8160 gcagaatctt tattttgggt tttggaggtc ttttctctgc ctttttttct tctttagcaa 8220 ttgtttcatt gatttatttc atcattattg atggaaattt gactcttcta gtcttgacag 8280 tgtatttggt aataaaatct tcaagttaca gagccaggga ctaaagggag ggccacaggc 8340 tgggggtgat gggcgatggt ctccttcctt cctccttttc ctcacacctt ggtggtaggg 8400 aaggaaatat ttgccttaat cttatcttct gtgtgagtgt aatttcaagt atgtactatc 8460 tagcaaattt tgcatggatt tgggattctg ctatttttcc tgagaaagga attatgttta 8520 gaataaagaa gttgtggggc ttggggggtg gctgagtcag tagtgtgtct gcactgcagg 8580 actggagttt aagcttctag cactcatgta gatgcctggc atggctacgt ctgtagtctc 8640 agtgcttggg agcagagaca ggctgacccc agagtgcact aaccagcctg cgtagtcagc 8700 tgtgggcttt ggggtcaggg agagtcgttg ttgttttaaa tgagatggag aacaaagtgc 8760 agggcacctt gagctctggc cttcacatgc acacactgat agacatacac ttcgtactct 8820 cacacaccat cctcaagttg tttaaatgtc acacactgat agacatacac ttcgtactct 8880 cacataccat cctcaagttg tttaaatgtt cccttgatag atgagcttaa aattaattag 8940 attcctcttt atgaaaatat ggacgcttat gattggttca gttttgtttg gcttgaagct 9000 tacgtgctgc tctaggcgcc ctgtgtggta tggtacatgg ttacatggtc agagtggtcc 9060 tatgcagctg gtaggatgtg acagggtggc ttggcaggtg ggccccatca tctctgtccc 9120 accccctctc ctatggccat ttcttgtgct gcctcctctg ggcctctgta gcctggcttt 9180 agctctgtat gcagccttgt gttctgctgt ggctatgggt cttctggaaa gagctcattc 9240 ccgtcaggcc cacagtgtct gtgtcaggga tagtgccagc cactttctag actttcttat 9300 gagtggtcca ttcttttgat tatggccaca aacacataaa tacatgctgt tatcctcatg 9360 ttccaggagg ttagaggtta aggggaagtc tgggatggct gtccatcaag agtgggatat 9420 aacaaatgac cttaggactc tgagctgttc agtctaagaa ggaacagatc tgaatagctg 9480 aggttctgcg gacgttccca gtcaggactg agaagttaac tcctgtaagt catatacaac 9540 acatacctca actattcttg aaatttcaag atccccttac ctttaaatgt caagaagcag 9600 gacaagcagt gaagtaaact tgatggagtt tactaaatgt gtctggggtg agggacattt 9660 gttatgcact tgggtttttc acttagatgt gtgaagcagt tgtagcatcc tcctttggct 9720 gctcaggaag gaaatggaca cacagggatc agataacttc caggctcaca cagttgggct 9780 actgaagcac attagaaccc caggcttctg gcctgctgag ctggggttcc tattggctga 9840 ctgttaggct cttgcgtcag cctttgttaa gacaagacaa catcaatcca tttattctgt 9900 gaaaagcata ctcttgtctg ttgttctctg tatggaaaat ttgtttgtgg gggatcagta 9960 gaaaatgtac ccagggaaca ctttccggga tacagatttg gaaaagacaa ggagttgacg 10020 tacatatgtg gcttcttatt tcttcaatat agatttaatg ttgtctgttt aactgtcgga 10080 cacaggttgt gtggtgcctt ttggtgagtg ttgtgcactc catgtagagc ggatgactct 10140 gctgagatac catagaccca aaagaaggct gataatatat tccgtcatct gacttctgct 10200 atgctatttg tggaattctt ctgtctgctc aattgtttgc agggagcagg cgcgctttca 10260 ggaaactcgc tcctgtgctc tgccaggatc tgcacgcatt gcttgtaatg ttccagctgc 10320 caggacccag ggcctgttgt cagagatgaa aatgatgcat gggatttttt gttggtcact 10380 tatgtcccca aaggcttcac ttggagagtg agtgagttcc ggaacgtgct gctcgctgcc 10440 ctctgcccat tagaggccac aactgaagga gggtaggccc ttccagcagc tccatcttgc 10500 tcataggatc tgctcgtgaa caaacttcct ctgcctctga tgtcacccct gctttcgtaa 10560 gaacatttaa taattatctt aaaatttcta attatattgt taatatgctt aagatgaaaa 10620 actttgagtt gttttgaaaa tgtaagttag aatattgaat cgtgccaggc ctggtggtgc 10680 agttctttca tgaaatcttt agggaggtaa agagaggggt gtctctgacc ctgagaccta 10740 gttcatgttc aggatagcca tgactaagta gagaggcctt gtttcgaaaa ccataaccca 10800 acacaaacaa caaatgttgg gttgtgtgta tgtatgcagt tgtgtcttga tgatgttact 10860 cagtgctgga ctgcttgctt agcatgttca aggtcctggg ttcaagctca gagagatgac 10920 ccctccccaa tgtaattgtg tatttccaag gacccttcag catgtctcca gttattttag 10980 gccatcttta gagtctgtgc aaatggagac tttagataat tacataagta atatttttta 11040 agaattagtt ttattttgtg tatgagtgtt tgcctgcatg tttgtccagg caccacatgc 11100 atgtctggtg cctacagaat ccaaaagagg gcattggatc ccttaggact gcagctgtag 11160 ctggttatga gccactgtgt gggtactggg aatcaaaccc aggcaattct taaagtgcaa 11220 ccagtgttct taaccactga gccattgttt tctagtttaa ggaacaaaat tttaatgata 11280 cttttaatgc actaagatgt gtgtgtgtgt gttattattc tctactatta tttcattcat 11340 atatttttgt ggtgttgtgc ccagggcctc cagtatgcta aacattagat caatattata 11400 tataaaatcc taacatgtat ataattagaa ttactcatag ctgtcacttt catctaacat 11460 gtaatcactt ctgagcagtt attgttggga tgtgagaagg aaattcttcc acatgcactt 11520 ggtaggtccc taagtaagga ttatagaaac tcattaaaat tcggagttac cacagtgcca 11580 tgtcctcaag ttgctgtcct gggctggggg actccctggc ccagaggtga tctttttgcc 11640 tgtccctgtt gtgtgtgctg cagaggagga cgcggagtga ggcaggcacc agagtgagat 11700 gtgagaagag ctgctctcgg gttccaccag gaatgctttg cacatctttt ccctcttttt 11760 ttccttctgt ctttcttccc tcaaccccac ctcccacccc aagtagaatt ggagatgtaa 11820 agatgaatat gggcagagga caaaccagaa ggatttcgtg tgaatgagca tggtaggcag 11880 tgtcccttct tggtaggtag gtctaacctg tttgcagcac ttagtgagag aagtagctct 11940 ctctctgtta ggaatgtgac atgtaaaatc attgctgttg ttcagtgttg tcgcagcagt 12000 aggggcactg atgtgtaatt tagttggatt gttatattcc atgccttttc atgtttctct 12060 gcttagggat attattacag acttgacaat gttaggtgat ccaagtggct cacatgttat 12120 aattgaaaat attgaagtta tttaagatgg ttcaaaagtg taaccaaatg tttaagacct 12180 taagaatgtt tgcctctaaa tttttttgcc agctgtgttg gcgcacgcct ttaatctgtg 12240 atctaagaaa gcagagccag atgggcctct gagttcgaga ccagcctgac ctctacatag 12300 tgtgtttcca ggctatccag ggcttcaaag tgagatcctt actaaaataa gcacacacat 12360 aaataagtag aaaagaatgc aaagagagag agagaaagaa tccttgcctg tgaggtcaga 12420 ggatatagct caggctgtca agtgcttgct tagtgtacag gaggctctgt gttcactagg 12480 caagcactag taacctaggg ggttcccagc agcagtaaac caagtgtccc ggcacacctg 12540 caatcctagc cctcaggagc tggagccctt gggtcagagg ttcaaggcca ttctcagcta 12600 tacagtgagt gtaaggttag tcaggaatat gtgactgttt tctgttcctt ccttttccca 12660 aaggaaaaga atgcattttt ttaaaaaaag atttatttat ttattattat atgtaagtac 12720 actgtagctg tcttcagaga ccccagaaga agacatcaga tctcattatg gatggttgta 12780 agccaccatg tggttgctgg gatttgaact caagacctgt ggaagagcag tcagtgttct 12840 taaccgctga gccatgtctc cagccccaag aatgtatttt ttataatttc cttctgagcc 12900 ttggttttct tagttgcttt cttaagttgt gttagttttt tggtttttta agacttttcc 12960 atttaagggt gatagaaaaa ttccttgaaa atgttagttt tcgtattcac cgcatcagag 13020 tcttggcaga acaaacaggt ggtggagagg agagccagca aggaagtccc aggaagtgct 13080 cgctgctctg tcgtggactt ttatcttcag caagaggcaa tgcggaagct tagtcttcaa 13140 gtttccactt cacacatgta attatgaatc atagcataat ggaagaccga gatattagct 13200 gtaatacaag aaaacaacac agtcatcact tcagacacag aactgaccat tttagtcagt 13260 attgacagct accctcttac cctcccagcc cagcattgtg cttggacatg aagtggattg 13320 gaaaacaaaa cgagagcttg gggtctcagc atagcaggaa gcacatgggg ctggtctacc 13380 tggactgggc tggccctgtt cccttcaggg tcctgacacc atcactgaga gaggactctt 13440 gtttcctgtg agggctgtgt gggtgggcta gtggggaggg aaggcgagaa tggctgacct 13500 tgctggttgg gggagtaagt cagacccctg atgatcacca gcaaagcagc tgtctgcacc 13560 tggatcttcc caggagccaa cctggactgt gctcaggtgt caggtgcaca ggattctaat 13620 gtgcacgttc atggaggaca ccagtgtaca gaggggctgt gcagagagag gaccctactg 13680 aggcagagag taaagcaaga gtgttatgtc cgtcctcttg catcttagag gatgctaaag 13740 gatgttttaa tagttttccg agttatcaaa agtgcaggtg actgatggtg ttgccagtgc 13800 atggaagaaa gaactactgc tacatgatac atcagcatca gtgtatatta agatggtttg 13860 ttctgtgtcc tgtaaataaa tatagtcttt acatctaagc aactcaggaa cttgcacttg 13920 ctctctcatt ggttcagaat acatgtgcct gtgcataaac atagcataca tacacataca 13980 tgctatacac acactatatg catgcagaca catactacat gtaattacat atcatatata 14040 tatatatata tatagtacat gtgtgtgttt attttcaccc cagacagtgt gtagaacagc 14100 tgaacagcat agaagacttt gtttttctaa actttctatt tgactgacac ttaaatcttt 14160 ctctactgca agccattaat aggttgatct tcccacggta ttcctttcct aataatgtaa 14220 tttcccactt actatagaac gatatcttta aacacttacc tctgagtctt tgatgaaccc 14280 acccttcttc tatttctgct ggcacatgtt gtggtatacc ctcttgttct cttgatttgc 14340 ctagagaaag tagatgagtt aatctaaaat ttaggaagca tgcctttgac ataagaatta 14400 ttttaggaat tcctactgct aatttaaacc tgaagtaatg aaccagaaca aaaggaggag 14460 tccaaaaata ttccaaagtc attactaagt agcttaatga atcaattatg gattaaaatt 14520 gtcctacagg aacggaagca aatctaactg tgttctcctc agaaacaata agcacagtgt 14580 gctttgtcgc tgtgatatga tcacacagtc cttcagtgcc agggtttagt ggtttttcct 14640 ctgcatagta tttgacactt tagagaaaat ggattttagt ttatagtgga gaggagaaaa 14700 aaaatgaaga aaaccatggg gatagttggt agtgctagga agttaataaa ccagacactt 14760 cagagatagt gtgccagggt ggttacttga gtacctgcat tgaagaagca gtaacaagaa 14820 cgaacggaag tgtcaactga aggactaaaa cctcaagaga tgatgaaatt ctacaatata 14880 cattaatata gactgtatta acacttataa aaatatcctg attctccaaa ttttacttac 14940 atatttttat tatttttaat tgtgtgtgca tctgtgttcc tggaggccag aggcatgaga 15000 ttcccgcagt tggtgttgcg gtgcttgtga ggcatctgac atacgtgaca tctgacatgg 15060 gtgcctcaca atagaactcc agttctctga gccatctctt catccctcac cccctaattt 15120 aattttttgt tttggacagg gtctcactgt aatcctggct agcatggaac tttctgtgta 15180 gaccaggctg ggctgctcac tcttctcttc tctctcttta tccttctatc gccatctctt 15240 tgtatctttt cattgtgaaa gattacaaac attcagaaaa attccagtga gtgcctgtgt 15300 gcagtgcatt tccatctatc tgtctgtcca tccacatacc catctatcta tccacccatc 15360 catccattat acatacattt attcactccc cctctgtctt tgcccccccg ccccccctct 15420 cgtgtgtgtg tgtgtgtgtg gggggggggg tatgtaggta ggataaatca taaataaagc 15480 ggtagatagg attcttcatc cgtaaagaac aatgtcttag gagcactgcc ctgagtccca 15540 tcacctcaga actaatctct tcttgctgag ttttgatttt tcaaaactag tccacctcat 15600 agttaaccaa gtccactccc tgcatctcct ttccaggctt ttctcctttg aatggctcta 15660 agagtccagg tcagttgtcc tgagggtttg tgcttatcct gctagctttg gggtggcttc 15720 tgttgcttgt tggtgaccat ggcgtggtcc acttgggcgg ttctccctga gtcttcctgc 15780 agtctgttta gattgggcct acacaaacca tgctgtggat cacaagggaa gacaggaagg 15840 tcaggactga cctgaaggac gctcatcacc cattaatctg aggtatactt tttaccttta 15900 agaagaggta gattttgttc aggcacagac cagaagaagg tgagtcctga ggcattaatt 15960 gtatagtcat ctggacaaac aggaagtcta taacgggctt tctctgacct gccagggata 16020 gaggtaagca ggcgcttcta gttgagttga aagcttaggc cttctgcttg ggcagtctcc 16080 agctactcta acttaagcat ccttagagcc tacggcctgc tgtgtggctg gctctatctg 16140 tccctttctc tgctctgctc cagtccatgg ttgttcctct gcctgctctc tgtagctccc 16200 tctgctcctc cttctcccag ctccccctcc tccgccctgt ctgaaagttc caccctctac 16260 ttcctgctca gctattggct gtcagctctt tattaccacc aatcagaacc tcagataatt 16320 ctaaattccc ttaggcaagt gagaaaggat gaatatttac aaaatataag gctggtggtg 16380 ggtcataaaa atgacaatac caatataatg ccagcagaga cacatcttca cacaatatga 16440 agaaaagatt accccagcag aagcctttgt ttgaaattct tcccgtttct tgttctgtgt 16500 tggagaatgg taatttacat ttcttgcacg cttgactaat ttcgttttta atgtttctga 16560 ttttcttctt tctttatagt cttcatttgt tctctcctcc aactttccca accctgaaac 16620 tcttcctagt gtctttagtt tctcaagctc cttcagaact gtctggaagg ggtggtggga 16680 gcttcactcc ccaccactct tgagggtgtg gagcttcatt ctcaccttga caaaaggact 16740 ttaaaggtga gaggcattcg cagggactgt ctgggcttct gcttttgcca cgcacctgcc 16800 taatacggtg tagagatagc aattatcagt agatatctgt ttacttttag ttgatgtgtt 16860 taatgcttag gcgaggacag aagtcaccac tgttttgttt tgttttgttt tgttttgttt 16920 tgttttgttt tgttttgctt tgctttgttt ttcgagacag ggtttctctg tatagctgtg 16980 gctgtcctgg aactcacttt gtagaccaga ctggcctcga actcagaaat ccacctgcct 17040 ctgcctctcg agtgctagga ttaaaggtgt gtgccaccac gcccagcaga agtcaccact 17100 tttaacaact atattttatg tatctataac aacaaacaaa ttacatttga ttgttaatgc 17160 aattttgcct gatttcatac ccaacaaatg aattattctc atttctgacg agaaggaaaa 17220 cagcaattct gtctttaatg tgaatctaca ttcatgtata agaattggga ggcggaaaga 17280 taccatcacc taaaatggag aggtcactga agatatcaag atttactcca gagtcaatcg 17340 gagttaccaa agacttagtt actgagactc ctgtcttttg gcacggcctg gctctgctag 17400 aggtggagtc tgatggcctg ggtcacacct gcactgcttt caaggggcac tcccacctga 17460 gacaagaaat gctgtctagg aagctggagg agtgttttat tatattaata gttaatattt 17520 aaattgagaa agaacatatt taggagacca gagaaattaa gaaaggaaag aaaaatgagt 17580 ctggtgacca gattttcaag actgtagttt tcaaggtgta gttaacaaat cagggttatt 17640 ttattaagca gagaagtaac aaagatattt aataataata aaatatttta attgatttta 17700 tagaactttc cagaagtgta tattattggt atgttacata atcttgtttt gtcattgtgt 17760 gttatatata tgcgcgcaca cacacacaca cacacacaca cacacacaca cacacacatc 17820 cctagtgccc tgggcccctc gtgataagct ttcattgagg tctcccatgc gggagcctca 17880 tgcaagagcc ttgctgcatt ttacttgata tggctgcttc tctaaatgtg gtgtcatgct 17940 tgcagatgtt gggagtaagg acatgcttct gggttccatg acagaggcag gcctgatgca 18000 ggtctgtgac aagatctaac tggggactat gggctgggat ctcggcacat atcctctccc 18060 cacagccttg gcaagctggg gttaaaacca gttgtcttac ataagacaga tttcactttg 18120 tgaagcctca gaagttgtgt agacacttta agcatgctgt aaccctcttg taatggaggc 18180 tcagcagagg gagtgtaagt gagcaggtga ggctagaagt ggagttatcc tgtttattac 18240 aggctaaggc agacaacaga agtgttagga gagaggaata ttgacataca agtgatccat 18300 tcattatgag atttaagcag ctcttccttg gttaacaaaa ccctaacact atatctatcc 18360 atgggtatag taagacattt agatggtttg gagaccctca aatgcagtag ttcgcttgct 18420 tttcaagtct gtgaaagcat tttggtcaac gccatgcact gctgtttaat aatgcatttg 18480 tatatgggtg gcctcatgtc ccgtttctgt tactgcctcc tattgttatc cttcctttaa 18540 tgctgcgatg atcagcattg acccatgttg atgccctgtc agtcttagct aggtctctgg 18600 aattttaatc taaagtaaat tgttttaatt tttaaaatga ggattttcta aagggctggc 18660 tatttaagaa gttagtcctg aagacgagaa ctgcctgtat gttgggattc tctgtggtct 18720 ggcttttgat ttagcctccc ctcttttgac agctaatgca ctgtccagga gtgcgaagtg 18780 tcactgggac tcttcagtct atgagacgct attttgaatg ctctttgtca actgtttaga 18840 gcaaatatgt tcccattttg ttacattaga gaatgttttt gataatcttt ttagcaccca 18900 gtagatttaa tgctatgatt ctcaacaggc agattatttg atgtatagtc tcattatgga 18960 gtgtctgtcc ctctgtgttc atgtggctcc acacaatggt tggtgaggct gggagtcatg 19020 ttttgtgcag aagactgaga acagggtaat ttaaatcagt aaagtgcctg acttttaagg 19080 gaaaaaaaaa agtagttatt ttaactactt ggaggtggta gaacatttaa attatattga 19140 aaatagctga agaataaagt acatagaatt cacatttcct taactcggaa gattgtctgc 19200 ttgcttgaca tatcttaagt gttggtctta gaagcagaca ctgttattct ccacagagag 19260 attatacttg gatctgtcag agaactatct aatgggaact cactgttaaa atcatttggg 19320 tgagccgggc atggtggtgc acgcctttaa tcctagcact cgggagccag aggcaggcgg 19380 atatctgagt tcgaggccag cctggtctac aaagagagtt ccaggacagc cagagctaca 19440 cagagaaacc ctgtctcaaa aaatcaaaaa aaaaaaaaaa tcatttggat ggtttgatta 19500 tagtttaaaa caaaaccacc tgtcttttgg gaatattaat gcataagact agatgctact 19560 tttgactagt tcaatctgtg gcttattctt caatactttt ctcaggggaa aaaatgcagc 19620 tcttgctatg agtggtcgga ctaattcacc agagtcaggc atctgcgatc gttttgggtt 19680 tggaagatgg tctggtacag tgggcttcgc aggtagcata agtaaacctg atcactagca 19740 acgcggaggg gaggcaggga gaagctgact cagatttgta ctgtatctcc cagttgcaga 19800 taaaagtccg tttcactgaa gatagaggat ggccgtggtc aggcgtatta gcctgtgttt 19860 acctggggaa tagaatgtgc ttaatagctt agaagtggtg ggaaagttta tataaaaatt 19920 gtttggtggg gacttggcag atctgcaggg acagatgaga tatttagata tagttagcag 19980 ataataatgc ttaggagctg gttatgaagt ttacaggaac ttctgaggct acacagtact 20040 agaaggacat ttataaatac ctatcactga aagaaatctc taaggtgatt ttggtgtgta 20100 cctcataaaa cataaaccct ttagaaactt ttggatttcc aacagttata tttaaatatg 20160 attgataact caggagcact gggtgtgtca gactgtcacc cgtgcttcac tctggacaca 20220 ccgtgacaat gtgactgtga ggaattactg gtgaggtgta gcacactcat ggacagagga 20280 tctccgcccg gtcctatcat gcttgcctgt taccctgcca cacagcatgt tcaagagcta 20340 gggtgtgcta cgggtgctgt gctggttggt gttttagggt ctacctatct agccacacat 20400 gcactgtctt ttttttgttt tcatttcctt agtatttcat atttgctttt aaatcttgaa 20460 ataggaatgc atattagtga acttttccgt cacagtcctg gggactgtag agggccatct 20520 gtgtcgttca tgatgtgcca tatcaactca gatttgagct tttagcagga aagtaaagca 20580 ttactgagac agccaatccc acagtgagtc agggtgagag gaccctgcgt tacagcggag 20640 tccagcacag tttactaagc ctgaagcatg tgataacagt taactgaaag agattagtat 20700 gttaactaag aagtgtccat gctctgactt ggatagatta aatcaaaact atagtgttca 20760 ccgggaatag gcacattgct gtcccctccc attcgtggtt cactgactag aattcctgaa 20820 cacaatgctt aacagcttca ggttgttttc tagacatgaa atgaaccgat ctcagccttt 20880 ctcaacagaa caatagtttt tatgagctct ggaggactaa gtcctatttg ttttccttca 20940 tttctttagg cataaaatgt tttagataca aacttctatg tgcttttatg attctttgtt 21000 ttagccagtt ggtttattgt taggaacatg gaaatttcat ggttgtaaaa gtttcctgga 21060 ggggctggag agatggctca gcggttaaga gcactgattg ctcttctgaa ggtcctgact 21120 tcaaatccca gcaaccacat ggtagctcac aaccatccat aatgagatct ggcgccctct 21180 tctggtgcgt ctgaagacag ctatagtgta cttacatata ataaataaat aaatcttaaa 21240 aaaaaaaatt ccctggagac tgaaggccac ctctgtcttc ccctgtcagg tgagccggtc 21300 cttgcttggg tgacatcagt tctgaatgcc ttgcttattg atggcccttt ccctctatga 21360 tcttcatggg cactcccctt ccactgcatg catgcctgtg gtgtcttctg accttataaa 21420 gctttccctc ttcctcctgc tcctcctctc cctcctcctc ctcttctctt cttcctcctc 21480 ataggtggta gttggggctt tgtatcttta atgaagaaac aaaccgcttc agtagtagaa 21540 ggaagagatg ttggagttag aggatgcctt aagttggcaa tgggcagagt attagctttt 21600 aaaggattct tttatgatat agtactcaca tgatcttgta taaaaaacaa gattacatgt 21660 tttttgtttt gtttttgttt tttaacctac aagaagccat gtgttgggac tgtgcatgaa 21720 cctttattcc aagcactcag agacagacac agaatctgtg tgttctaggc cagcctagtc 21780 cacatagtga gccccaggat agccaggatt atatagagaa cctgtctcaa aacaccaagg 21840 cgtgtgtcag gagaagacat gcatgtttgt acttaacggc tgttggccag gacttgaatg 21900 agaactgaga ttctcgagaa actgtagatt aaaatctgtt atattctcag ttggttagtt 21960 ttcatctcca tatcatcaac ttcattatgt caagttcgtc tttgcgtttg ttatcacctc 22020 tgtaagcttg aataacatga taaaattgtt ttacatttgg caattatgac ataatagctc 22080 aacgagtgtt agtctctaca gtcttcactt cgtaccttcg gaggcttcct gttctctctg 22140 atgtccttag atatttctcc tgtcagtttg gagcacttta aacaataaga agttaaagag 22200 atcgtgtcct gggatggcct cttgtttcag taccttctga aattcttcat agtttctagt 22260 tctacaggat attcattcat tcattcattc attcattctc tctctcttcc ctcccccaca 22320 gctctccccc atccccccat ctaacagagg caggtgcatg cttgtaatct taggatctgg 22380 gggtgaaggt aagaagatag gaaggtcaac acttgggtca gcctccactg cataccagtt 22440 cactgcccat ttgagctagg aggctgacta ggaggaaagg gaagcaatcc caaacagaca 22500 cccaaaacct aaagagcagc aagagtttga agcaaattcc aagtatcatt tcattttgtg 22560 ttaagaacga ggcaaaaaaa aaaaaaaaaa aggcctggtg tggtggtgca cacctttaat 22620 cccagcactc agaaggcaaa aaggcaggtg gatctctgaa ttcgaggcca gcctggctta 22680 tgtagtcagt tttgatggtt ctgaaattac aaatgcaaag agaagacaca aagccttggt 22740 ttctagccct cgcagtgctg tgctcagcga cagagcactg atgtgttgtt aggtgcagag 22800 ctgatgcttt ttcctgaagg tgtgccaatg gacagtgcag cctgggcggg gtctcagaca 22860 tttaacttag gaggcacgta aaatcccaag ccctggggtc agaaatcttg tccgtttttg 22920 cctagcatgg ggcctggaac cttgagtact aatagagaat ggaagtggat tcttgtgaag 22980 atgaatcttt cttagtgact ggtatctttt aggacttaaa gtatgggaaa tgaatgaagg 23040 gcaggagaaa cagctcagca gccgagagca ctggctgctc ctgcagaaga cctgggtttc 23100 actctcatca cccaaatgga ggctcacacc catttgtacc tccaggaggg atggggcatc 23160 tgatgccttc tgctctcttc caaggtcact agccatgcac acaatgcaca tatatacatg 23220 caggcagaac attcctacac ataaaataaa aatccctcat atacacagaa ttattagtta 23280 attaaaaaag aggagatgaa ttaagaattt gctcacagtt cctgcagaca atacctgaag 23340 tgcggggtgt ggtcagcggt gtcgcctctg tgaaatctga ttgagagaac tctgaagctt 23400 gcaggtcagt atttcctagt gcacagcagc actggttctt gtttatgttt attttctatc 23460 aagaacctgc ttgacatcgt ttctgtctta tagaagaagg caggctatgc ctcaagtagc 23520 catgtttgca tattcaaaac acttaaaata atctaccttc tcttgaacca gagtgagcta 23580 tttataaact ttgtaatcat tgacacactt ctatatcctt cactaagaca attaatgtgg 23640 gaagacagta tttcagtgca taaccagctg ttgatcatct ttgtagctat tttagttgct 23700 ctgtaagact ataacaaaac tatcttcaga gacagttgat agaatgagaa atttagttgc 23760 ccaatgtttt aagtaggaaa aaggcaaatt acttggttac tttactatat acataataaa 23820 ggttagaatg aacacaagtg tgtcccttac cccctcattg tgggtatgct gtatataacc 23880 agtacatgga ggggttttga gtcaggtctc tgctggtgtc tgttttgact ttgaatacta 23940 tgtggtagag gctatcttta aagtactgct cctgcctcca cctaccaagt tctgagatta 24000 ctgccatggg ttatctactt agctcgagtt ccttttctca gctactgtct ccagcaaact 24060 gaaattacag cagatactgt tgtcattgac agtataagct agcaggcaga cttgtgacac 24120 agctgccaag cagtgatgtg tgtgtctaga ccattcttgg aaaagggaga ctgccaggga 24180 cttagaaagg ttgtgtacag ccaaatgata attatttttc agtgatcttg agcggcttgg 24240 atctttcttc tcctgtcatg tgctaaatgc atttaattaa tatttccaag acactgaatt 24300 tctcccgtac ttctcaaaaa atgattagag gtggaagatg gtggctgtct agacagtagg 24360 tgggtagaaa gctttcaagt ttacccaaat cttttagaaa ccaggtaatt gttctaacta 24420 tttttgagaa tttagtcttg catggtatta aattctagct aaaatgtgga agaatagtgc 24480 tggcaagatg gctcaggagt tctaggcaat tgttgtccat cccgagttct atcctcagga 24540 cctacctggt ggaagaagag aatgacaaat gcagattgtc ccctgacctc cacatgtgca 24600 ttgttgcata tatgcacaca tacacacaga gaagaattac catatagtat gtattctcta 24660 aaatgcatct taaaacatta agagacctat aaaagacttc ccacatcacc tgttaactgt 24720 ttggctctat gagaggaaca tagcctgctg gttaaaggta tatagactgg aaacattgcc 24780 tgccccaatc ccagctcatc cactggggag ttctatagac cagtaagtaa tacagtaagt 24840 tggtctgact gtattaacca agccactaag aacatctgag agcattatca gactgcttct 24900 agtagagctt acttaaacag catcttgtta acttcatgtt gtcttttcag tattgttcct 24960 gtaagagctg ggcctatgta agttgttttg ttagtacttt gttgctctta ggaaaacatt 25020 ctaaatttat aaggtcttta tttttgaata gtacatcata gacttatggt aagaaatcag 25080 tgggttggtt tttttgtttg tttgtttgtt tttgtttttt taaattacaa gagtcctttg 25140 aaaagccaca caccatgttc cttacacatt tacccttgtc tctagctctg attttgcaca 25200 gttaggcctt gtagacagac atgtggattg cctagtctgt aatggcagtg gctagtgatt 25260 caacagctca cactggaggc taagttctat gatgttttag cttttagaaa taattgtaca 25320 tagcacctaa aatgctcaga atggtattta aactgtactg cactgacagg tctgactaga 25380 taactgcttg tctaattgtc acacagccta gttgggttgt attctgaccc agttgtggca 25440 gttatattca agacctggta tgtgacatga acagtgtctg ttaggctgcc tcactgaaaa 25500 gtggaaggaa tcagtccgtg ttagttgatt gcctggttcc aacttaaggc gaacctttct 25560 gcttcttaaa gatttattta tttatttatt atatgtaagt acactgtagc tgtcttcaga 25620 cactccagaa gagggagtca gatctcctta tggatgattg tgagccacca tgtggttgct 25680 gggatttgaa ctccggacct tcggaagagc agtcgggtgc tcctacccac tgagccatct 25740 caccagcccc ctttctgctt cttatcaaga gccagatgat gggacggacc ctggtgccta 25800 ggccagcttc agcctgtgga acgagaggca aacttaccag gttagttgtg agactgaagc 25860 actatcagaa ccccacactt tcctgcctgt ttagtttggg attgtgggct ccagtaatag 25920 cagctgcctc atttttagat tttgtggaag aactgtcaga tttggggttt ttaatttgtt 25980 tttctgaaaa ctttttattt aatgactcta cccgtaaact aattttcata tttctgtttg 26040 cactgctgtg gaaatgggag ccattctttt caactcagtg cctggaatgt tggactgaaa 26100 attccatttt attgtgtgtg tgtgtaaaaa tgtgtgaaag cttttgttcg tttgtttaag 26160 taattccgct tatttttcat ggaaagatgg gtggctcaaa attgccagat taattaaagg 26220 tatgagaagt gttcaaagat ttaattttgt agtgaaactg atcagtgcaa cataataaat 26280 actaaatttt gatgtgctta tttattcact attccctcta tcttatctca caggagtaga 26340 aatatgtccg atttacaggt catttctaat agaccagaac taagattttc tttggaagat 26400 ggactgatag tctttataga gttttcatca atcaagatgt taagaatacg tatctacaaa 26460 ataagaacta ttagaggact ttcatttgtg gttttgtttg cttgtttttg gtttttcatt 26520 cattgaaaga gttttgattt ctaagtatta aaaaataaat accaccgtgc ttttttgatt 26580 cctgcactgg ccattgtcac ggtgtacaga gcacaagatt gtgtgagccc atttgctgca 26640 gaaagccatc ccatcatgat cagtggaaaa atcgattgtg tagttttgaa aatttagatg 26700 gatggttgtg ctgctggtgt cagctggagc tggggtcagg agcgggccag cccagcatcc 26760 gcacggtgga ggactgaggt tagcagccct tcccagcatg agccccaagc tccctcgtgg 26820 aagatgagag atatacctga acaggaatac ctgatttgaa caggaaatca cattaaataa 26880 gtgttggact gatctgcccc ctaacatggt caccttgggc aagtgagtag actctgcctg 26940 tccactaaca ttggagctca ttgttctttt ttgttttttt gtttttagtg gaagtttagc 27000 gtaagataaa gcacccaacc acaaaccttt aaggtaatat tatatccgtg tgtgttttat 27060 aacctcacag cgttcagaga tgttccatcc attcacctct gctctcattg ctttagcagg 27120 ttgttgtttt aaactgaatt ttttaaccca ctagtaagtc ctgaaatcac tttagttagc 27180 tgtagccagt ataaaaccaa aacaaagcta atgaatataa aagaaaactt tagggtgtga 27240 tgcagagttc agtaaaggca aagctaaacg cacagttgtg tgcgcctaca gctttccctc 27300 cacaggactg acggtggtag agtgttttgc ctaccttgtt caaggccgct ctgccttcct 27360 gtgagtgttt tctctctctg actgtactct tcatctctac ttttcagatg gagagccttc 27420 tggtatagaa ggctaactat caatatttca tggctcccta agggcagagt tcctaaagga 27480 agtactgtga cttgtaggtc ccgtgatacc tgagcatgtc tgaggtgctc cttggtgggt 27540 aacatagaag gcccatcttg agctttcatt ggctctcagg tctaagcagt gtcgcagtgt 27600 gatctaagca gccgcctgtg caggtgctct gtctctcaac accattacag acggattagc 27660 agggaaccct tcgtcttcta catcgcattt tagttgtatt ttaattgttc attttgcaaa 27720 ggctttgctg aaatagcata ttctgcatcc ttctgatttt caagtatgcc tacctctact 27780 ccctgtagta aatgcacata tgtgtgcaca cattcataga ggccagaggg gcattattct 27840 ctcctccgga tgttctggac ctggagttta gtgctaggac tgtctacgct gcttggtcca 27900 tgtgctctgg ggatctttct gttagtgtct gccatgctag tgctgggtta cagttttcat 27960 gtaggtgttg caggtctgaa cttgggtctt tgcacttaaa cagagtgagc catctcccta 28020 gcctgtgaat cctttttggg tttctaaaag agctattcca ccctgcaaca taagcaaact 28080 cctaacgaag caaaaaaact tttctttaat tcaaaattca aataacagac agttggtatt 28140 tttgaaataa tggagttgga tacttatata actctatttt cctcactgag tgctttatta 28200 agaaaagaga ggagctgatg agatgaccca gtggtttaaa gcactggccg ttcttccagg 28260 agacccaggt ttgattcctg tcactacatg gtgacaccct atctggcttt cacaaggatg 28320 caagtgatgt acatgcaggc aaaacaccaa tacgcaaaat aatatatatt ttaaagaaga 28380 tagttatcta ggtcagcaag caagatccct tggccattgt tgaggacctg cggctaatgt 28440 catcacaaaa gtgggaatat gtgctgaggt gtcatatggt gagccaggaa gccagagagg 28500 ttcaggggcc acccttgcta ttttataaca tcttgctttt gtgaaaacta actcatttca 28560 agaaatgtgg ccttaaactc agagatcgaa ttgcctcttc ttccaaatgc tgggattaaa 28620 ggtgtctgtc agcatactta ggcactgtaa tggctcttcc tggttgtcaa cttgactgta 28680 tctggaatga actacaatcc agaactagaa ggctcacctg tgatcctaac ctggaggctg 28740 ggagatacaa ggttctgccc tggatctcag catggagatc tggaggcaca gtggctatga 28800 atcccatcca gaagattaag taagacaggg agatctctga gttcaagggc atctggaaca 28860 aagcaagtcc cagatccagg cttgttggca cacaccttct gctggagccc tacataagga 28920 cattggaaga aggaagatat atgctctctt cttcacctgc ttgcctgtgg ggctgagcaa 28980 ctgctagatc cttggacttc cattcacagc tgctgctgac cattgttggg agttggacta 29040 cagacctaag tcatcaacag atttccttac tatatacaga ctacccgtaa gttctgtgac 29100 tctagagagc cctgattatt acaggcacat acagatttta tttttttatt atttttttta 29160 gatacggttt ttctgtgtag ctggttgtcg tgaactcatt ctgtagatca gactagcctc 29220 aaattcagag atccacctgc ctttgcctct ggagttctgg gatcaaaggt gttcactacc 29280 actacctggc gatttgattt tagcttaaat ctacatagac agaatagtta gaattgcaca 29340 cctagtgcag gggaagagag gtgaccagat gttgccacag cttgccagct ccatagagag 29400 tgtctgtagt gcagaataca cttggcatag tgttcagctc ttctctcagg atggaagcta 29460 agcatgtgtc cacaacactg tgtgtgtgga tgtttatagt ggcctagtca tgcagccaga 29520 gataagagaa gctcaagtgt ctgtccacgg ggaaagtcac ccaacggaat cctgttaagc 29580 tgtaaaagga agcagtgaat gagaaaggtg acagtcacgt ggatggggca gacttgctgt 29640 gtaagagacc agagcatgca ctttgtcttt ttctctgaaa cttgggaact agaacaagag 29700 aaatcagacg gctgttgctt gaggctgggg tggagaaaaa gacccatcta gaatggtaag 29760 cgtagcttgt atgttgtagt gcaccacctg tttggtgtgc gtcagttgtc aggaagtgga 29820 cccaccttgt gtataagcgg tccttgtgcc cgccggtgtt ggttgcttta tgtaaagtag 29880 aaagcagcct ttcttggtgg accgcatccg tccccagctt atacacgtgg cctcagttaa 29940 atcttaaagt tacccaaatt aatatttgtg gcacttggtt tggggacatt tttgggaccc 30000 gaagggtgta ttactctgca taatctccaa ctggtctcag cagttctggg cactccatac 30060 tgtcttcccc ttttctgata acagagcttc gggacatgtt ttttatgggc agatgatttt 30120 tgagcttctg agaattttag aacagattct ggtttccaga aatactgttt gaaattgttt 30180 ggaatctttt cctttgtagg atttcaaaat gaatgcactc ctatgtctgg gttgtattgt 30240 ttgttgtttt gcttttcttg cctattaatt ccgtgtctga gtcactgagt ttttactttt 30300 ctggttaggt tgacttatag ttaatgtgac ttggcctgat atttttcaaa agacttacac 30360 agatatgtag tgtatttgtg aatatttata ttttgttaat cactggattt tacttgttta 30420 ctattaatag actctagtgt ttaccaccag ctccttagaa agctccaggg ttagactaga 30480 cttctcagag gtccctgtga tgatggccaa aaaggacagg gagtttccat ctcaggtcgg 30540 gtccggtggg agactgcagc gggttctcct tgatcgaagt gttctcacag tactcgtgat 30600 tacagggtca taaaacaaac catgctttgt atgcacactg gaagttgttg ttttgttttg 30660 tttttccttc aaaacagggt ttctctgtgt agccctggct gtcctggaac tcactttgta 30720 gaccaggctg gcctcgaact cagaaatctg cctgcctctg cctcccaagt gctgggatta 30780 aagacgtgcg ccaccactgc ccagcacact ggaagttttt acaagcctta gtactgccct 30840 tgtaaatttg atattgctgt cttaggtata ttgtgaagaa atctagattg tcctgtgctt 30900 tttactctat attttttatt gtatgatata gaatacattt caaaatttat caccttagca 30960 catggttacg cttatcttta tttttgttgc aacaacataa agaacattac ttactatgac 31020 aaaggttaca tgcatttatt tagctttttt ttaacctttt tgttttgtat ttgagtcggt 31080 gtctcactct gtaaccctag cttggcctgg aactcacaga gctccttcct ctgcctccca 31140 gccctgaggc tcctgcccgt tcttgcgtgg caggggagat gagtgagtac acgctctaaa 31200 aatctctttt ttaaaattta aatctcttct caattactct ccagtgttgc tggtcagagc 31260 ttgtgcactg tttggctctt ccatgccttt tcttgccatc acagcttctt ccagcttggg 31320 gtgggcttct gtccagtccc cctccccttt ctcctattag agcagttcta tttgcttggt 31380 ttttttgaga tagggtttca tggtttctgg ttccattccc tatgtggctg tggttggcct 31440 tgagtgcctg atgctcttgc ttctacctcc ccgttgctgg gatcacaaga gcatcccacc 31500 ttgtttgctt agcagtgaga ctcctgaagg gtgtacttag gtgtacaata aaggtgctta 31560 cttcacagtt gttatttgaa atgtaatttg ctcacacagg gagtaataaa tttggagtgt 31620 ctcaggagag aaagcctggg attttctgac aggcagtttt gctctattac tgtctccact 31680 ctgtactgtg tgaccagata tgtgtagagt cctgcaagaa caccgagtgg cttctgtctg 31740 tattttatag tttcttagtt cactccttag gcaaagcaaa cacagtaatc cagggcctga 31800 ggtccagaca gcccatggac ccagaacaga ttccctatct ggtttatgcc tccagctgtt 31860 accgttgcct ctacagcact ggctcccgtc tttccatcgc tgcgaccctc taatacggtt 31920 cctcttgctg tggtgaccct cagctgtaag attatcttca ctgctacttc atagctatga 31980 ttttgcataa gtatcagtat tttctgatgg tgttaggcaa cctctgtgaa agggctgttg 32040 gaccactgtg gaatggttgg ccctacctca gcctgataac cctatgatgg taaacgtgtt 32100 ttgttctctg ctcttgtcct gaagagccaa ccagggtgca ggatacagta gattagttgt 32160 gtatgcttct ctaacaaacc tgaactccag taaatcacac ttttctgctc caggctcata 32220 agagttgttt tggtaccatc tttctttctt tctttctttc tttctttctt tctttctttc 32280 tttctttctt tctttctttc tctctctctc tctctctctc tctctctctt tctttctttc 32340 tttcttttaa ttttaaaaaa atttttatgt ctgtgggtac actgtagctg tcttcagaca 32400 ccccagaaga gggcatcaga ccccattaca gatggttgtg agccaccatg tggttgctgg 32460 gaattgaact caggaccttt ggaagagcag ccagtgctcg caagtgctga gccatctctc 32520 cagtccggga ccatgtttct aataggcctt tttgttcact tgtctgcttt gattttgaaa 32580 tagggcctgc cctgtactct agatgtacct acgacttgcc actctcctgc ctaagcctct 32640 ggattgctag gattccagtt ctacaccacc tcacctggcc tggaaggtgg attttagaaa 32700 actgtcaaag atgaacaaac tttaaagaaa tccagagtta gaaaaccaga ttaatcaggg 32760 ctgatttatt cattttatgt tggtgtatgt tcaattttat acactcaatt acacattcaa 32820 ttctatcaaa gaaccagtta tactaatgat ttcttaaatg aatattttcc aaaccttgtt 32880 taaactcttt gagttacaaa agttgaatct gcatataatc tttcagtttg tcaaatgagc 32940 tgtgagtttt caggaaatct atccatttgc tagtgatagg aatgttacaa catgttcaaa 33000 ctgttactta agtttattat tttagcaata ctgccacata tgaagagata taagggaagt 33060 ggtaaattat aatgaggaat agttaatgtg acaggaccca aaagtgtatt tcagtccttg 33120 tccctggagg tctgtcatgg tagtttttgg aagacatcta gtgagtcact gttttattta 33180 gttcagtggc cattatagca atgatactga ttttgtttta tatggcagat ttacggggca 33240 catgaaaaat agaatttgca ggctagggat gtagctaagt tggtagagtg cttacttgtg 33300 gagaggcaag ttcgatcccc agcacctcat aaagtgggtt tagtggcttg tgcctgtaat 33360 cccagcactc aggagtgggg aggcaggtgg acccaatatt atcctgtgtt gctattaata 33420 gcaaagtcaa ggccaggttg ggttatatga gactatgaga ctctatcaga aaaaaaaaat 33480 aataattagg ggaaaaaaag aaaaagaaag cagatcctgc ctccaggaat gacaggattg 33540 cagtttgggg agggtcactg gtcaggaagg gactgactta gtaaagtgca gtctggccgt 33600 ctccttttga gggcctcagc cagtgactgc tgtcctaatt aacatatcag taaaacttat 33660 tgtgtgatac ttgaactcag tgaaagatta tagtaaactt actcacgcta gactttgcca 33720 acattgtaag aaaaatggaa ttgatgactt tcaggatatt gtaatggatt gctttagctt 33780 tagtagcaga tttttaaaag gaatgaatca ataaagccat tattctgtgt gtgtgtgtgt 33840 gtgagcatcg caagcatgtt cgtgccatcg tctgtctgtg gtgttgcaat gcatcagccc 33900 acattgagat cagaggatag cctgagagag tcaggaatgg cactcagacc caaggccact 33960 cagacccaag gtagccgctg cctttaaccc tttacctgct gagttcttcc ttgctgtcaa 34020 aggataggta atgactgtgt ttttcttcca tctggtcact tcttttgggc tcctgtttac 34080 cttcacttcc cttagagacg aagttctgta aaactacccc atttgtctga gagcttattt 34140 gtgtcctccg agttgcctgt tggaaaaagt cctggcctag aggattccac agcctcccct 34200 ctgagtgctt cctcatcaga cttgtggttg ctgagggcag aatgtagaac tctgcagaat 34260 gatgtcctgt ctcagcctcg ctcatgtctt agcgctgaag agtgacccca tggaccatcc 34320 atcagcctca catctcacat tgttgctgct gactcccttt accttgcatt cgggttgtca 34380 gactctgcac tgtcctgagc accatgaaac ccttgcagtc tcttgtactt cccagtcctc 34440 atctggagat ggagcaagca cagtggctta tagatcttcc cttgtgagtc cgtggtatgt 34500 caagtttctc ttcttaatgc gttcagaatg tggtcagtgt tgaggagcgc tgcactcaca 34560 cagacaggaa ggaagagctg gagtctgcac tctaacatcc ttagacccaa ggtcacttct 34620 gtgtctatgt tcactagacc cacctgaaga ccctcgtttc ttatcctgaa ggctcagctt 34680 agacaagctc acagctcttt tatttcagcg ggtctctctg taatagggtt tagttttttt 34740 gtttttttac ttttagaaag taggtgttaa catctttagc atttagattt ataattactg 34800 agaattttct gacattttga atagtaccac ttaatacatg gagactaata atcaaacatt 34860 tagactggag ctgtttgtgg caggagccag ttttccctca aagctggcgg actgtgatta 34920 tctgtcccta tgtacagcag ctccacaagc catgctacac tctccgcagt cccatttcta 34980 tatggtgttg gggtaactac cactctgttg gtagtctttc actgtatgtg gaaatatagt 35040 ccacctcctg aggacgagag agaggaaaca gtagcaatta atgctttatt cccgcagtgc 35100 ttcagaaatc ggcatgcaag ttctcatgct agtcttacta atgctgttat tttgaatttg 35160 tttaatttca aaacagtgtt cagtgtctcc taatgagaca tagcccctga aacaaggtca 35220 gtgtgataga agagggagcc tggtctgtca ataacaggtg gattttaaaa gcctctctcc 35280 aagctggtgg agctctgagg gctaggtgtg cagtggatgt gatgcggatg ggtgcttcca 35340 ctctcccttg ggaacactgc agaggctcct tctgtgctcc cctgggatgg atggctactg 35400 cctgtagatt tgggttatac ccactccggg caatcttcag gagtcttgcc ttcacacttg 35460 gtctttctag cagtaagact gcttctgtgt gagagtgtct gttttgacta gcttctgcaa 35520 aattggggtt gcctaggaat cctgtctttg cctaaaaatc tgaactctag attttgtaag 35580 tacaccaagc ttccacataa tactggatat tggacccagg gtctggtgcc ttcgaggtaa 35640 gccttctgcc tctgagcggc acccagctgc tggttttgtt tgttcggttt tcccgagatg 35700 ggttttgctg tgcagcctct gctgtccttg aactcactgt ttagaccagg ctggcctagt 35760 gctgagatta aatgtttgta ctaccatcac cctgctcttt ccttttgtgc ttagtcaggc 35820 ctaagttgtt cactctgtat gccaggccgc ctttgaactg gagctctgcc tgtctcagcc 35880 atccacatcc atgctgcctg caagacaagc acaggccaca ggcttggctc caagttaaaa 35940 aagaaaaggc tacagaactt tgtaggcttt tgtatttttt taacaaacac aggctatata 36000 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtatttc tgaataaagt gcttaataaa 36060 aattaagaaa aagattgcta atttattcag taccattgta tactgcagag ctttatcaag 36120 tattttcctt ctttattttt ttaaaacttc ctttggccaa cctttgtcct acctcaatcc 36180 tcaaacttgt ctccttgtgt agatacagtc cttggagcac tgcagcaaga ggcccttgta 36240 ggatcttgga gctctgtgta aattcaactt ggaagccaga aatggttctt ggcacttgag 36300 gccaggaaag ggcagtgtga gcagcggtga atggaggtgg cggtgaatgg aggcagtggg 36360 atgctgttta gtctgtttcg gttgactagc ttggtgctta cgctcgctct gttctgtctc 36420 ccattgttgt atcactaaca tgaaggaagg tacctgtggg cctcggatgg ctcacagcct 36480 acccagtcct tttacttcat ggttttgctg aacacttttt taaaaatcct ttttattgtt 36540 ttttgttggc attcctcacc ccgtccttgc ttttcatttc cattttgaag gacagcttaa 36600 agaaatgtcc atgtctcagc acccgtgtac cttctgtccc catgtggaac tcaacaaatt 36660 tggaagacat ttgcttggaa ttccaaaggg cactgtggaa actgaacttt catggtaaac 36720 attctggaaa tgacagaaaa tgggggtatt ctcttctgaa agaagacctg tggtcttgtt 36780 gaagataaag ctgagaataa cagcatgcgg taaaatctgg ctttgagtta gagatttaga 36840 tgagcggttt ctatgtcctt ggtttgttaa gcctgtctac aatattgtat ctgttcagaa 36900 atatttatta ggttgaaatg aaggtatttt tttccagttg tttggtaagc aactattata 36960 tatcgctacc aaatacaaat gtctcaagtg catgttaaat taggaaagca aagctagaaa 37020 gacttcgggc agcataaggt gtcgcagaat aaatgtacta ttcggtttct tctcatgaac 37080 cccttctaga ctcgcccaag atgggaatgg tatatccacc cagagttccc acgctgtcag 37140 cacggacaga ctggaacaca gctgttgatt tctataggac ttgcctggct gtttcagaag 37200 agttggtctc tccttcagca cattgagtag tgctcatttt gtagtgttac tgggaactag 37260 agagtagagg gctgagagac tgatgtccca catatggggt cttgagttgt acctcctaat 37320 gtggccctgt gtctgtgata atctatgtgg ttatcattag tttttagcat agagagggtg 37380 tgatgaaact agtcacactt ttatacttag gacttcaata tgcgtcattt gatttagttc 37440 tcccaagatc tagcccttca tggtggtgca tgcccataat cccagcactt gggaggcaga 37500 aggttgatat ctgtgatttt gatacaaatc aagttctggg acagccaggg atgcataaaa 37560 cagactgtct cgttaaaaaa cttaaaaaaa ggatcccttg gtgctgtttc tatttttgac 37620 ttaacatggt ttctctttga aagaataaat ttctcttaag aagtcaacat tactgttaac 37680 aaattatcag ctgattaact atttcccttg agtgtctcaa agcttttttt cttgcactgc 37740 tttttctatc atctcctctg ttttataccc tcctgccccg gcagactgtt tcctgcccac 37800 ctcccccccc cccnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 37860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnngatgcag 37920 caaacacccc tttccgtgtg ctcttggatt aacagtgctc tccctctgtc catatttttc 37980 ctggtctagg agatcggccc ttgcgccttc tgtgcttcga ctctgggttg agccatgtgt 38040 catccagcac tatctccctc attttcatgt cattcttaga gtctcctcca ctttcatttc 38100 tgttttattg ctatccccat cagcactgta cattatattc gttgtgggag aaacatttta 38160 tgtttgtttg ctttttaaaa caaagtctga atatgttgcc ttgtctggcc tgtatgtaat 38220 tccttgtgta gaccaggacg ctacacagat ctgctggcct ctgggttccc cagagtgctg 38280 gaattaggta tgtgaactac catgcctggc tccaaaacat tattttataa taagataaag 38340 aacattttgt ctctagagaa ctctaggtca taaccagtat tttatttctt ttgagcatta 38400 aaaaatacaa ttacattttt actaaatata acacgacata aaatatataa tgcaataaat 38460 aatacaatta tatgtaatat atgtgtccac acacacatac atcaactttg taagtataaa 38520 gttgcaaact ttgacaaatg tttgtaataa gctacttaga cacaagtgta tataattaga 38580 aaatttactg tacttttaag tcacccttgt tttcaccctt agactggccc cccacctggg 38640 tcctctcagg tgtaaaggtg taaaactgcg aattgatttt tacaccttta cacctnnnnn 38700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnncctgg ctgtggagtg 39840 tagacagtac tccagagtac agccacaccc cattctcttc acccgcacac caggggaagg 39900 aagttttgac tgtctctgtc acaaagctgc catgagctct tgcttgctgg ggtggcccta 39960 ctcagggcag gcatttgaga gagcacttag ttggacagtg gttgggaagg cttaaatgtg 40020 cagccttgct ggacgaggca ccgcgctctt tcccttcatg ttttcccctg aagcgtgtga 40080 gcgctcagcc tcttgcagcc ttccatgcct gcctctggct gccactctgc agtgcctaag 40140 ttgtgttagt actgaaacag aaaaaagtat tatagctact aaatgtctga caaacatttt 40200 catttcatat tgggttaata cctacgaatg ggtttgtggc aaattttcac ttgtttactg 40260 ttcttgttca ataaactaca gaagtttgga aagaaacttt ccaactaaag gctcggtgcc 40320 tttccagaga gaaagtcagt tcgactgtgg tttgattgtt gagctgatga ggagctgcct 40380 tgttgattga cagctttcct tagtttccca cttcctcatt ctcacttcct gcccacacaa 40440 tcaccctctg ccccacaaat ctgttgtgtt tattttaaat tagattcttt ttttgtaaga 40500 tagtaaatat gtgctggaaa ctcagccctc gttgtatggg tgctaatgtc tctcagccag 40560 ccacgctgtt ctcaggccgg tgctgagtga aggtgcaagc attaggtcag cccacgtggc 40620 ttgttcagtc aaactcggta tgttctgggc tttgctttga aatacttgga attttccaga 40680 agttactttg gttgttcttc tttcaagaca gagtttcttt ctctgtatag ccctggctgt 40740 cctggaactc actctagacc aggctgtcct cgaactcaga aatccacctg cctatgcctc 40800 ccaagtgctg ggattaaagg cggaacggat gccaccactg cccagctttc ctttggttct 40860 tcttaagggt gtgtttctga ttcctgctaa cttgcccgcc acatggtctc tgaatggact 40920 cactgctcct ttggatgaag gaatgcactt cccagatact ggcattctgt ttggagactg 40980 gacatttagg gatgtgttta ctcgtaatta aactgtttga gattttgtag tagtggacgg 41040 tttggtttta agatctattt aagataaatt cttttaaaat catttccttt ttaaaaaaga 41100 tttatttatt ttatgtatat gagtacactg tagctgtatt cagacacacc ggaagaggga 41160 atcaggatac cattacagat ggttgtgagc caccatgtgg atgctgggat ttgaattcag 41220 gacctctgga agagcagtca gtgctcttaa ccactgagcc atctctccag ctcctcttta 41280 agataaatta taagataaag ctagaaaata ttttttgaac atgtatatat atatgtgtgt 41340 gagcgtgtat gtatgtgtgt gtgtatatat tcattttttt tcttgagtta aaaaatgtat 41400 atacacatga tttaaagtga attaagcacc ccttgctgct actgaagatc aaatgtaagg 41460 cctcacgctt tctgttcttc cctgagctat atcactaagc ccagattagg cttttttttt 41520 ttttctttcc attttttatt aggtatttag ctcatttaca tttccgatgc tataccaaaa 41580 gtcccccata cccacccacc cccactcccc tacccaccca ctcccccttt ttggccctgg 41640 cgttcccctg ttctggggca tataaagttt gtgtgtccaa tgggcctctc tttccagtga 41700 tggccccaaa ttaggttttt ataaccacaa ctttatttag atttttgtat taaataattt 41760 tgatgaagct ccaattttca tgtatacatt tcctctatag acaaagtatt cagtgatggg 41820 ttagtgctag aagctcttaa gaacttaaga ttagattctg tgcttcaaaa ccacccagag 41880 tcgttttaga tacaattttg aatcctctta ttttttaact tgactcttaa aaaggtttat 41940 ctttagtgtt tgctttgaca atacatatat taaaattgga acaatgcaga ggtgattaga 42000 atacccccca gaaggatgac atgcaaattc gtgtcataga aagcattcca tacttttaca 42060 aatgctaatc tttattgttt aaatgatgtg tttggcctgg gcgcacactg ggatagtatt 42120 ccataagtaa taccttaact ggcagagata tttcaattct ctgatcacat ggaaaggggg 42180 ctagcaaacc tggctgtact ggcaatggct agtgccttgg ctattcttgg ttgtcactgg 42240 actatatctg gaatgaatta caatccagaa atattgggca catctgtgat tgagatggtg 42300 agacaggaag acaacatgct tttgatccag atcttgaggt ggtttggaac aggcctttaa 42360 tccagatctt taggcacacc tttcctctgg gccacacaca ccttctgctg gaggcctatg 42420 gaaggagaat ggaaggaaaa gggtttgctc attccttgtt tgcgtgtact cactctgtct 42480 gtcagcacat ctgtgggacc ctacttcttc agtggagttc caccttacac agaagaccac 42540 tgagacaccc agcctcacgg gactgagcag ctgctgggct tttggacttg gcattcacaa 42600 cccccattgt tgggttagtt ggattgctgc ctctaagtca ttcaataaat tacacacaca 42660 cacacacaca cacacacaca ctatttgtat atatttcatc ctgtaagttc tgtgactcta 42720 gagaaccctg attaatacag ctagggatgg gctggctggg atgatgagag catcaaggct 42780 tctagtggcc tcttaacaat gtgtaatgaa ctgtccttaa atgcaagggt tctgttttgt 42840 gctattaatt aaattcacag tgaatactgg taggacagct tgcaatttat gtgttttgtc 42900 ttgggacttt agtaatttgc aaggtgagat gaagggacag atagtgaatt ttcagtaaat 42960 tgtaccagga aaacgtgtaa cttcttggat tataaccaat ttgttggaag acagtggctg 43020 tgcagcacat gccaattcat tgtttctctc actgattact gcagtttaac tcaggtacca 43080 tgctttcctc attggtctaa gctgactttg gaggtattaa aaatgtacta cggtttgctt 43140 gatgattcta gatgggtcac ttgcttagtg tgggctgctg cccctgtgtt taatgtgcat 43200 taggtttttc ctacaatcct gccttaaaat ggagcatctg tttgtcatag acactcacgt 43260 atctctggtt gcttgtcatc ttctcagtgc tgccttttga taaacaagca cttttaattt 43320 tgataaattt aaagttaaat ttgttgcttt tagagccata ctcaaggtta caaagcattg 43380 tggaaatttc tgtatttggt aggagctagg taggggttca cctctattcc tttccatgtg 43440 actgttcagg catggttgga agtcatttgg ccacaggcat ccagtcttac ttttgttctg 43500 taatccagta caattgttga ttgtgctgtc ttggtgcagt tttaaggctg agtagtgaag 43560 gtctttcacc attgctccct tatactattg tttgattatt ttgaattctg gcatctctat 43620 gaatttgagg attcgttctc catttctata caaaagatca ttgtcatttt gacaggaact 43680 tcgctgactc actagttgac tttgggtgtt tgtccttttg acagtatcct ggtgtcttcc 43740 cgtgctcagt ctctggttcc tgtcagcagt gggcgtggtt ttcagtgcct agtcctcacc 43800 tccttgactg tcagtcccga gtagtgtagt ctttggattg ttccttattc ttacattgat 43860 agcatggcaa gcacacatca agcagaggga gcacactgag cacacacact gagcacactg 43920 aacacactgg cttcctagga ggaggcagat cacagcactc ctaaagtgca ggatgaactg 43980 ttttcagact gtgcacataa ccttaaggaa agcacactga tgccgagggc cccaggagaa 44040 ggtgactgga ggccagatgg cccatgatcc cggtttagtg agctcagcta gctttgcagc 44100 gactccaatg agatgtttca cagtgcagtg atgggttgtg gatcctgatg cctcagtaag 44160 ggtctaagga gggaaaagcc ctcctgcccc ctttacaggc gaaacaggca actgatagca 44220 aactttgcct tctgttctta agtgtttctg ctggtttcaa aatgttaagt aaccagaatt 44280 gatgagtgcc ttacttttga ggaagaaagg tatttactta caacaattaa acacaccttt 44340 cacactgaaa catgtaatgg ttgatatttt ctaggtacct ttctttgctc ctttactcgt 44400 ttgtctggac tgtggtctcg agacagtttt agtttgcaag tggtgttttt gtttttttgt 44460 tggggacggg aggtcctgtg atctctggtg ctgggctttt ataacatcat tggtgggaga 44520 ctgcattgct gcttcaggag tgcttggcag taaagctccg tgtgcacagg agacagggct 44580 ttcaggcctc tcctgtggtc tttgtgatca ttatggcaga tagatggtct gacctagtta 44640 ggttgcttgt gagcatgaga gagtcagtcc taagacacag tatggcagac tatttcttct 44700 gttgttgact atgtctgtgg acactgctgt cagtggtagg tttcctgttg aactttgggc 44760 atggcttggg gatatttctt agctgagggc ttcggacagt attttggagc tagagtatga 44820 caggaaacga tttagtctct agtagattaa agattctgtg ggaatagttt ttgtggagtt 44880 ggggatttag ctcagtgata gagtgcttac ctggcaagct cgaggctctg agttcagtgt 44940 tcagctgggg gagggggggt caggtaactg ggattttttt gtttttcctt tctccggtta 45000 tttttactca ttgcttggtc tctaggacca gaatagtgtt tggtgtagca gagcctcagt 45060 aaataaatag ggactgacca tgtgtcttca gaagtatcct tggaactcca tgttggttta 45120 tgtttaaagt caccccctta gaggattata tagtttgact agtgagggac aacatatgtc 45180 ttgcttagtc ttctttatat tgatcatggc tgatttggcc atgtgccata cataacagct 45240 gatgtagtaa tagagatata agtacatcag ctagctcaat cagcactcac ttcccagtat 45300 ataatagctt aattttgttg aatttgcatt tacaatatta taaacagtgt gctaattgcc 45360 acagtgtgag tatggattag acagctaaca aagctggcat ttgaagacca acatctgtgc 45420 caaacacctt taattacagc aggctttgat tgccttgatt tgccccataa ataaattcat 45480 tctattggaa ctgctaaaat ttctgataat aatcgccctc ttttccagaa tctgccacct 45540 acaatataca tcttctactc ttacgcaaac ttctgttatt ttcttttaaa gatatacatt 45600 tatttatata attttatgtg tgcttacatg tatgcatgcg tgtagacatg ccactgtaca 45660 tgtgtggtgg tcacaggaca acttatggga gtcagtacct cattctcata tcgtgatccc 45720 atgaataaaa cacaggttgc caggagcagt caaatccaac cggagacatc tcagcagcag 45780 acagaagtcc tgttagtttg agagattgct attctgcaaa cattctttat aggatacttt 45840 agttgatcaa gcttgttgtc gctgtccata tcattgaact cttcgtgagt accgaagaga 45900 ggcagagatt tccctgacgt tgcctagatt tttacttgaa taggaacaca ctgttacatt 45960 ttcttccttt ctgtttttta ttgtatttat gagacagggt ctgtgtagct caggctggcc 46020 tcaagcttgc tttgtgaggg tgaccccgaa gtcctgctcc cttctagacc tatataggtg 46080 ctgtttccta tggtgctggg gctgtgcact gggcttctgc tttgcctgct gagctacagc 46140 ccccgttctt cttttttctt tcttttaatg atgtcattga tagggggggg agttagagag 46200 agagagagag agagagagag agagagagag attgagagag agagaaaatt gtgtggttgt 46260 gtatttgtgt ttgccctcgt atgtgcgtgt gcacatgcgt gtctgtctgt cttggaaagg 46320 ctgcttctga gggaannnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46560 nnnnnnnnnn ncccgaaggt cattggagag ctggggtgta ctcccagaag tgatcagact 46620 atagtcacat actgttttta tattatagag ctcacaccac agtgaccttg gcactggggc 46680 aagggagagg ttggggctgg cggctgctgg cactgatact cagcagtggg cagcagaaag 46740 agtggactgg caggctcttc tccaggttct cccataggcg acatgcctgt ctttggacag 46800 tccgctttca ctctgcgtct tcagactgtt tttcttttgg gctatgttga gattgaacag 46860 agagccttca ggatactaag caagctttct accaccgacc cactgacctg catttcccgc 46920 cgtgtagacc atttatctct ttaatttcca aggtctctcc caccaattct gccaaagcag 46980 gttttccatt ttatttgcca acttgctttt taaaacttcc tgttaatcat cataatatta 47040 aaggtttttt tcttcaaaca ctagggtggt tggcttactt aacttggtga taaattctct 47100 gatctcaacc acaagtcaga ttgctgcagt tgtcagaata gtttgcctta ataatttgag 47160 tccaacaaca taatgtgttc taaggggaag aaatagaaac tcttaaaggt aaacacacca 47220 ttaaacagga gggtgttttc agtctagggt ggcttggatg atctgtaata ttgacattat 47280 gtgcagaagg aaacctgcct ctgcctaacc tcctgtgagt gcttcatcta cagaggatgg 47340 ccaagttcaa ttagaaacac ggtccaggtc catctggcta gcctgtttga ccagggagaa 47400 ggaactgtat gtagattgtc attttacaaa aatgtagaag agaacaggaa atatgagagt 47460 atatttgata gagcaacaat aattactttt aggggaaaac ttggatttca gttattatgt 47520 gctctggtcc attactaaga tgtctttcat tcttaactgt tcctgtcttt gctgtggaca 47580 cctcatgtac ttcacagtgc agtcacagtg ataggcagta aatagtgttt agttatacag 47640 aaactcagta cagttacatg gggaaaccca tacagctttg gatgactggg atactattta 47700 gaaaattaaa ggaattgaca tgtcataatt ggttttgtta catccctgca acctttgtgg 47760 gcatagggaa ggtgctctat gtagtttata tccgtgtgca tggtgagagc cttggttttg 47820 gggctagcaa tactggttcc agtcttgtga cccacataaa cttggggcat tggtgatttt 47880 cttttcaact aggttggact tcctcattta aaaaggaaag cagtcaggct ggagagatgg 47940 ctcagcagct gagagcactg actctgatct tccagaggtc ctgagttcaa ttcccagcaa 48000 ccacattggt agcttacaac catctgtaaa gggatctgat gccctcttct ggtgtgtctg 48060 aagacagcta cagtgtgctt gtcatatata taaaataagt aaataaaaat ctatttcttt 48120 cttttttaat ttttttaaag gaaagcaatc gtactacctt catggtgagg ggaaatcata 48180 ctgcaagtac ctagagtact ttgtaataga gtagatgttt aaaaatgttt attaaataag 48240 ttaaaaggct gttaaatcat agcaaactag tagtgattat tttaagtatt ttgttaaaaa 48300 aataaattat aaggctaatt ggatcctatg catggagaaa ttccttgtga cactctgaaa 48360 acttaaaacg aactgtagtt agagaagaag gcattcctct tgtgttccag aaatgtctgt 48420 gtacataggc agactgtatg gagaccagag gccatctctc actagcttag aactggctga 48480 agagacaggg ctggctggca agaatccctc cctccctccc tnnnnnnnnn nnnnnnnnnn 48540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnccctctc 48960 cctctcctct ctcttcgtca tggcagcagc agcatttgaa tttctttaag ggaggtttca 49020 ggttagaact ctggtcctag gagttgctta cccagcaggc agatgcttca ctcagtgagc 49080 cgtctctcta gcctacaaat cactcttttt tgataaaagg caagcattaa tcaaataaga 49140 aattataata tgcaagatag aaactagaga gtaagtagac caaaatcaaa tcactgactc 49200 acttgccaag acttcaaaga actccaaatg aatcctctga agaagcacac ccaagtgaag 49260 aagagccatg cgtaatccac ttgacctggc tgatgctcgc atggtggaga catcacatct 49320 actcaggaat gaaaaatagg agtatgctta catgagacct accttttgcc tagcttgtct 49380 tctatgctta ccagcaggaa aaaatgttaa atattctgaa tattctgcct taattagcag 49440 agccagtggc tgtccagtaa tgggctataa cagtttgctt tgctgttagt tttcagaaaa 49500 ttgaaaatca tatgctggtt aggcttgcta cattttaagg aattttgaac aaatgattga 49560 ctttggtttt ataaaagaaa accctttatg agaacatgct agctgctcag tctctgaggc 49620 tgccacactc agcagtccca tgctggtgct gaaggcatgg aggagccctg gagagctgct 49680 gctctttagt tcgtgttgga atgccaaaga tggtggcaga gaagagcata ggaacagcaa 49740 cgaagcagag gctgccaggg aggcgtgaag gcggtagaca gagccatagc ttttccttgg 49800 gatcttctcc tacggagcca cccaccacat gccgctgctt ctccttctgt taagcaaacc 49860 cataggaaat accctggccc acctaaatct agccatgttg acaaccgagt tagccgtcat 49920 agccactgca gagcagattc cccttagata tctgcttaag tcatcgatgt gctaggcatt 49980 ctgtggaggt atggaaacac ttgatcttgc cattacccaa aatcaggctt tatatgcatc 50040 tgagatagat gctatatgat atgttaaata aaagtgcctg gacatacagc agtgtactaa 50100 tatacgtatt ccttagggct gaatattaag aaaggtgcaa tcggtgtgat gctaggtgag 50160 accgagggag agttagtttt ataaaagtta gtttgggata aagaactccc tatgcatcta 50220 ctggagtggg aacttgtaga actttgtcct gccacatgtg gtgcagatgt agaatttgct 50280 cacgatggcc cattcagaat agaacatcaa agaggcagtg accaagccag gcatggtggc 50340 acaccccttt aatgccagga ctcgggaggc agaggcaggc ggatttctga gttcgaggcc 50400 agcctggtct acagagtgag ttccaggaca gccagggcta cacagagaaa ccctgtctca 50460 aaaaaaaaaa aaagcagtga ccacgtcgta tttcatttgt aagatcacat gaaggaattc 50520 ctaggcgtca gaattcagca tctgactgag tgctggcatg ggacacatag tcacttcttg 50580 aactgaaagt acagttattt ccagtggatc cacacagagt gttgggacta cctggctctt 50640 ctgttagtcc ctttctgaac ctttgctaac cattcctttt ccttcgattt gcagctatcg 50700 actttatctg ttagagactc gcagatcaat ttgtttttat ggttattaca tgttttaaat 50760 ttattattga ggcaatttca ataacatata cttttctaca atattttgtt atacatcatt 50820 ttcaactatg agttctgagt tctcttttgt tcccagtgct ctgcactgct tctgcagtac 50880 cggtaactat acttatgtcc tctgactgtt tacagctgcc ccactcctgg gtctccatct 50940 aggcaagagc tttttaattt ccctacagcc cgtttgactt ccttgatgtg atgtgtttaa 51000 cccatgttgc tgctttaccg ctattactat gatccaactt cagaccttgt gtacactaga 51060 cctaaatact ctcccatttg gataaacaca caagttggca tcatacgctt aatgtttgcc 51120 cctgcatagt gctcatagcc accagctcct gatgagttct gttagactga gagtctcgtg 51180 ccagtctccc atggctgggg ttagctttcc ttctggcttt ccttcacccc ctcagccatt 51240 tttaaatgac ttttcctctg gaatctgcca gtgtgctctt tttcaagtgg tcttatttat 51300 cttattcatc cagtatcacc acctttgagt agcttctaaa tccacagatt tcagcctgac 51360 cttgcttgaa gcgctgcttg cttgacacag tgtcacacaa ctgagtgaaa ccaagtactt 51420 cccccaccca aaccagttct tgcccaggtc tcctagtttc tgcgtgcggg cactgctgca 51480 tacctatctg ggagcaatcc tcttgcttct tttgtgcact ttgtctcttt ctgtgctcac 51540 ctgccctctt cctgcagacc acttcccagg ccctcccaga agaggactgt gatccagnnn 51600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 51660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnctc ccagaagagg actgtgatcc 51720 attgtatgcc ttcggccgcc tgcatgccca gactctccct taggatttag tactctgact 51780 acaattagag cagaaggttc ctcactttgc cagacactgg ccaggcaccc ctgtgggttt 51840 gctggccttc tatgacctca ttggtcagtg atccaccata agactttggg cctggtctgc 51900 cctccccagg ttcagctctt agggagcccc ctctgcctac atctcctctg tggaaaggag 51960 tgaagggccc tctcctacag cctttcctaa tcacacagag tatgtgtctt tggaggtctt 52020 gccattcacc taacttctgt ggtgtgcagg tggcaggcag cttggagtgt tgaggctcct 52080 actgggcgga gcctctctta ctcatccttt tcttgttgtc taagcagtta gcacagattg 52140 gaaatattga ttgagaataa ttaaactgat tgcagatggg tttagtttcc tttaatgagg 52200 ctgctaacca ttttcttcct aagaaacttg attaccctgc cttttctttt tttttttttt 52260 tttttttttt tttttttttt aaatttattt atttattata tgtaaataca ctgtagctgt 52320 cttcacacac accaaaagag ggagtcaaat cttgttacgg atggttgtga gccaccatgt 52380 ggttgctggg atttgaactc tggaccttcg gaaaaacagt cgggtgctct tacccactga 52440 gccatctcac cagccctacc ctgccttttc aaagggcagc aagcttaccc atgccaccga 52500 cacagccact tctatgcaac cctgctcctg ggtggccggc atcctgggct gttgtgactg 52560 caatggtata atgaggcttt ggcttgagtg gacattcatt gattatgcgc tagcaggcct 52620 agcttttata tattttcctc ctttaaaaat tattcttttg gtacagtatc tcaacaactc 52680 atgatagtat tataaaattt aaggtaagag ctattgtgtg tgagtagatt tgtaaacatc 52740 agaagcaaat ccccttgccc tggctttttc ttcacctgta gaaccaagga ttcaaagagc 52800 gagcagtacc ttactcacag ccaggaaagc ctttctggcc agttggccat gagtctgcca 52860 ttgcatctta tgctgatggt atctacaatt attaaagtgg tagttttgaa ggggaaatca 52920 tgattagtct gtcagcaagc tgagcctagt agaatcccac cctgttgaaa gacttgggcc 52980 tagttgggaa tggatagcca ggagatgaca gtgagtggta atcagcccca ggtctcatgt 53040 ttgtttctcc tcattcccag ctctacttct gggcacctgc aggatacgcc tggctggtga 53100 cacttctact ccctctcatg ggcctcttgt gataacacag tgtcttaatt ttgtgaaagg 53160 aaacaattgc cttattggca ttttagagaa gaggcaggca gctcaggttc agattgataa 53220 gtcatttcag gaacaatctg aaatttgaac attgcagaca aaccagtatt gtgctccttg 53280 cagacccagg cctggaccta tcaacaggga tgttgcaaga agatgtaatt atcattcagc 53340 agcaactttg atacttacac ccagtggctg taaacagtta gtaagagctg tgacacaggt 53400 cacaatggtg gagccagggc gaaggccaga aaagcaggct tctgtgcggc tttgaatcca 53460 cagggaagtg tactcctgct gaaatgttgt gtgcttaaat gggcagtgct acatttttgt 53520 ctgtacctgt gtgtggtggt atacatcttt atttccagca gaggcaggtg aatctctgtg 53580 agtttgaggc cagtctggtc tacatagcga gttccaggac agcaagagct acatagttga 53640 gactctgtct ctaaaaccaa aatcaaaacc agacacactt tgttggtttc tgcatattag 53700 gaggcatctc aggtaaccca tctctgatca ctgctaggac acatacctgg acacactagt 53760 ccctagaggc cccggaggga aggccatttg agggtaggca gtctgtgctg cttgggtttg 53820 caccccaagg cggggacttg cagtgcgctg ggagatggtt ggatctgggg ccctggttgt 53880 caggcttggt caggtctgtg ctgctcctgc agctctgtga acttggagtt gccccttgtt 53940 ggcccagcgc tgtcttgtgc tctctggcaa aagcaccttg cgatcttttt tatttgctta 54000 cttaaaagta gttgtgtgtg tgtgtgtgtg tgtgtgtgtg tgcgtgcgtg catgtgtgta 54060 gaggggttag tggatgggaa aactctcatg tgctttggag aaccttggca gagggtggta 54120 ggcacataac gttagtgaga aggcctgtgc tgcacttaag gtcttgtagc taaaacgaac 54180 ccaaattaag agtgtttctt ggtatgaata taatttcaca aggtacctga aggagggcca 54240 ggtctgggtt gcatctgact actgcagact gttttgtagc tcctgcttga gttgcttgtt 54300 tctttgtccc ttagatttgt ttgctactgt cctgcacatg gtcaccggct gtgtggctac 54360 agttacagta actctactta cttctttaca aatgctttga aattttatct gcctgaaaac 54420 tgacatttct gaattgaaga acacnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54540 nnnnagaaca ctcctggctg aagaagaaag ttatgagcca catgggacac atttacaagt 54600 tctttgatag aactttgaat gaaggccttg gaggtcatta gccctgtgtc cctgcgtgtc 54660 actgcttcca tttaactcct cgggagcaac cgtattactt tgttggtgat cctttggagc 54720 tatatgaaat gataatttaa ctttcagatg tggttaatct ttaggtctct cttctaagta 54780 ctaatgtcca tggcatgaca ggcttaaccg tttccaggag tgggtgtggc tgaggcgctt 54840 ggctgagaag tggctcgtcc attacctagc tgctgctatt ccccagccgt ttggcactgg 54900 cactgaatgg agcatgtaag cctcaacccc acttgagaca ggttttacat taaataaatg 54960 cactgccttc ttgaggtggt ttagtgtgtt tatcatcttt tataatgcag tttagaactg 55020 tgttttgtct tctgaacgct taagtttgtt aataaacaga ccttgacact tataatccca 55080 actttcccgt cagcatatga ctgtcctgat gtcttttccc acttctcttt tcctctccgt 55140 gccttgcttt gatccctccc tagaatcaaa gagaagctgt ctgtgtgggt gccggtctgt 55200 ttgcttctct gctctctagt gtgtccacca gtgctctgtt gttggtgtca ctgttgggtt 55260 gtgggtgggg acagctcttg ctgtgctcag gactgatgct ggaggctttt gtgccacctt 55320 ggaaactgtg gcggttttag aacaggccgt ctattagcaa gttttaatat ttgagtaagg 55380 atgttaaata tcacagaata aaactttagg gaaaggcata agtaggtatt ttgcaccaat 55440 ttcattagta aaaataaaca ttttatagaa atacttgagt atcttcagtt cttgtggttt 55500 tgcatcttgc aagttattcc cagtgcccag attcataggt ataggtgctc agtaatgtat 55560 agacagtcat tcttggagta actcaggctt ccttgactat ctggggatag tggttgttta 55620 cttttgctgg gtgcttgcag ggagacagtc agtatacaag gaaacagtta atgaccgagt 55680 tgctagctca tgtaatttgt ccggtgatgt cttttatatt ttgtctgtga tacacatcat 55740 cttttgaatc cacattattc ccaaggaaac ataaattctg aaagatgcat tacagctacc 55800 taggttgtgt gtaggaatct acaaaggttg gagaggatgt tgacttgtag cctatgaaga 55860 attggtttct tttaaaccca aatagaatac aacaagaata tatcattagc ataaaatgtc 55920 ttctggtacc ctagcagtat ctagtgcttt caaaaatgtc taatgttgtt gtcaggaggt 55980 tacacataag agtgtaggtt ttcaaaggat gaccaaataa aattgtgcaa agaggctggg 56040 ttagtttgca tttttcttca gcatattaaa ctagaagtgt cttaacatta ttggtcttat 56100 ttgaattgga caaatgttag gaaaaactaa aaatcttttt attctttaaa ctgagaaaat 56160 aattcatttg attatttcaa attttataaa agctgaaaaa attatcccgg aaagccagtt 56220 attaagtctg atgtgtctgg acctaaaagg cagtcttggg ttttcattgt gttttgctag 56280 tttctgttca gtcagtcttc aggatcctga agctggctgc ctaagggtgg aagagctcca 56340 ccaccaccaa aaagcagcag caacaagaac gctccagccc aggactgtga atttcaaagc 56400 tataagaagc tcagttagtg tcacagcaca gataacttag aaatggctgg tacattacgt 56460 aatctcacac aaagtgaggt tgatggattt tgtaatagtg ataacaaatt tataaaaatg 56520 ctttagagtc tggcagcagt tttcagtttt tcttaaaaga aaagaatcct aagagtttct 56580 tataaagtcc ttcacactcg gaagacagtg aggttaaagc gtgttgtgtt aaaagtcttg 56640 tgtgatagag tacaaaatgc acgtatggac aacacacttt taaaaatatc tgtatgaatt 56700 catttacaat ttggtttcat tgtaaagagc aatctgatct taacttaata ctactttgtt 56760 tacattcaaa ggtgttcccc ttcattgtgg gttgttttac atctttgaag acatggaatg 56820 ggaagagtat taattacctg gctcatattt atagcgtaca tttctataag aggttattca 56880 tgcatttgaa aacaacagga agaactcaga gcctctgcac actaattgca ttcacaaatt 56940 ttgctatcat cagagtaata ctacatctgg aacatgaaca aatgcaaaca ggaaaaaatt 57000 tctacttccc ttttcagcag tgtgaattgg taaatgtccc caataatgtt gggaaagtag 57060 ttatttatga acttatagca catttagaat gtctactcaa agtggggtgt actgcatatc 57120 ttctgattgc tttggaaaag agaaagggat gatgcttctt tcagtatccc tatgctcaca 57180 tggcttgtct ccatagtaac ctatgccatc catatcacaa gaagaataac aagtgaaaag 57240 gttccacatt acattcacac agttgacttt ttttccctca tagacatgtg gtacagggat 57300 taaggtttct ccagaaaaat cattcttgaa tcttataaac tgttcatctc tctaaattta 57360 tcaatgttgt tacaagtata tcattaagca catatttact atgtattatt tgcttattac 57420 aagtttttgg acatacactt atcacctaat caaagtgttt cccttttgca atagctaagt 57480 ggtatgagac tgaagagact tgcacttcta cagcatggct ctactgggct tgatttaagc 57540 agagacctat ctgttaagcc attccttctg tgtctttgaa cgtactggaa tgccttgcaa 57600 acaataatta catacctgcc atagacatgc atggttttgt gagatttaat aatcatccat 57660 aactgaaagc agtgcttagt gtatgctatt gattttcttt acaactttgt agcacatatt 57720 aaattttctt cttaggcatt ttttcatcag cttgcacagg aaaattacct tccatgactt 57780 ctagaacttt gaaaatggtc ttcaatagta tgttcttcct aaatgtagcc tatagctgtg 57840 agattcctat aggtctctaa catcacacct ttgtagagac tcttgtgaga aggaagcatc 57900 cagcaaagcc cactcttctc gagtgaagtt ctcaagcccg tcatcatagg tcgctctatc 57960 caagtctgca tgcacgtcat cataggtcgc tctatccatg tctgcatgca cgtcatcatg 58020 ggtcgctcta tccatgtctg catgcacgtc atcataggtc gctctatcca tgtgtgcatg 58080 cacgtcatca taggtcgctc tatccatgtc tgcatgccca tcatcatagg tcgctctatc 58140 catgtctgca tgcacgtcat catgggtcgc tctatccatg tctgcatgca cgtcatcatg 58200 ggtcgctcta tccatgtctg catgcatgtc atcataggtc gctctatcca tgtctgcatg 58260 cccatcatca taggtcgctc tatccatgtc tgcatgcacg tcatcataga tcgctctatc 58320 catgtctgca tgcccgtcat catagatcgc tctatccatg tctgcatgcc catcatcata 58380 ggtcgctcta tccatgtctg catgcatgtc atcataggtc gctctatcca tgtctgcatg 58440 cccatcatca taggtcgctc tatccatgtc tgcatgcacg tcatcatggg tcgctctatc 58500 catgtctgca tgcccgtcat catagatcgc tctatccatg tctgcatgcc cgtcatcata 58560 gatcgctcta tccatgtctg catgcccgtc atcataggtc gctctatcca tgtctgcatg 58620 cacgtcatca tagatcgctc tatccatgtc tgcatgcacg tcatcatagg tcgctctatc 58680 catgtctgca tgcacgtcat cataggtcgc tctatccatg tctgcatgca cacgtcatca 58740 taggtcgatc tatccatgtc tggaggtctg agtttgacga gctcccctca cagaacccag 58800 cagggtctct cagaacatag ctcacagaaa tcctcacagg cttgacccag aagagctgcc 58860 gccaacactc ttcattgagg tgttccaggg gctgggtacg tacgtagggc taaggtccac 58920 tgcttaccct gtaactatat ctcctgggca aagtcagaca gattatccct tgcatttcat 58980 tgaacagaag gttactaatt aataaattta agtgtgaggc cggcaagtgt gcacgtactt 59040 aaatagaaat ctttttgggg ttgtgtctgt tttatttgta ccacggaggt cattagtagt 59100 tctcaaagca gtcaaggcca ttgttgggga ggtcacacac cactgcaaga gttttactga 59160 ctactcctag ataattaaat tttgtgttat aagagtgttt atcaaggaat atgacagtga 59220 agaattgtct gagattagag tgtagctcag gttagagatc tctacctctc atacagaggc 59280 catgtatcct aattgcagct ccagaaacgg caaaacaacc ccacatttgt ttgaggcacc 59340 gagcatcatt aaattcattg atattttgcc catcctcgag cttaagttac ccctccttca 59400 gttcttctcc tcccccttcc tccctccctc ctttttggtt tttcgaaggt tttctctgtg 59460 tagatgtggt catctgcgac tcagtgtgga agtcaggctg gcctcaaact cagaggtctg 59520 tctgccctgc actaccacca ctgcctaata tttctttcat aaaaacctgc agtcctcatc 59580 acaaccagac agtgccactg ttgttgctac tggtccttgg ctgagcgtct agaagcagta 59640 ttgggacttg gatgtgactc tttgtgtctt tctttagcac aaaaaggcca ggtaccaaac 59700 ttgctgaagc tagctagcat caccggcaag tggaggccta tctttagtct cctagtcagt 59760 ttcttgcagt gggaatcctg accactttgt tgctatttag aaagattgct ctgggcaagt 59820 ggagttcaca tttttttgtg actctgaccc cttcctctca aggtttcact gaccagaact 59880 ggactgagag gcacatgttg ccagtgattt tacagtggtg gtgttctggc cacaggtcag 59940 ccatgtggtt gtggcagctt ctgagagctg accctgattg gtttccagaa aggccctgac 60000 tatcctcatc ctaaaccaga ggctgtcctg tgtccggtgg agaggcaggg taagcatctc 60060 caccttctgg caggagctca gcagagagaa tgaatggcct agcgtgagtg tctccaaagg 60120 cccagatgct gatggcttgc tcttcccttc agtgctgttt tgaggtggtg gagggactgg 60180 gtggttcaag aaaacattgt ggtcacttga gggtaggtgt agtgctttgc ctgtgccccc 60240 ctcgattgtc tcaatatctc agctgtgaag taagcaaatt tgtaccacac acatacacac 60300 acaaaataaa acatctaaaa agggtgccta gtcaactatg tagaggcaaa gagtagaatg 60360 ctggcagcca gggtttggaa gggacttgga gttgttcagt acccagtttc agttttgcaa 60420 gatgaaaact tgaattgtca gatacgtctc agcaacacca cagtggtgga gaataactag 60480 ctgggttgtg cttcctagat tccattatgg tacccagtga atgttttttt gtttttgttt 60540 ttttctccga gacagggttt ctctgtttag ccctagctgt cccggaactc actctgtaga 60600 ccaggctggc ctcgaactca gaaatccgcc tgcctctgcc tcccaagtgc tgggattaaa 60660 ggcgtgtgcc accatgcttg gctcccagtg attgttttta tatctgttta ggaagagctc 60720 atggtgcatg ctaagagaag tgagggagca gagaccatag tgacagggac agtgtccata 60780 tgtcccaggg aacatatgga agcttgtgga ttgaggcaga gatggctgac atagctccat 60840 cttccgtgac gtgctgccag tcagctttcc ctctatgtcc catctggtca gcaagcacat 60900 ctgtttggta gcctctccag aggacggaac ccgtgacccc gacttcaacg agagcactgc 60960 cgggaagtat taagattgat ttggtttttc atcctgagta tcctgtatct gacatgcttt 61020 ggcttagaac tgcgttagat tctggaatat ttgcacagac atgggattca tgtatgtttt 61080 atatgcatgt gacttatata catggcctga tggtgatttt gtccaatgtt gtaaataatt 61140 ttttgtgcat gaattgtatt ttattttttg agataaggtc tcactggcag gcctagaact 61200 tgctatttaa accaggtagg ccttcaactc atcgatatcc tcctgtctgc cttgcaagta 61260 tgcttggaat gaagtgaagt tttgtggtgt gaaattttct acttgggatc tcaaatacag 61320 gttttggtct atgccagacc ttaaagtttc aagttaagat agtcacagtg tggagttggg 61380 tagagaggat gtttagaact gatgttttaa tctatctgaa aaaggaaacc agcttatgta 61440 agtcaatgta aaggtataaa ctgtcctaag aagcaagagg tgaaaacaac aacaacaaca 61500 acaacaacaa caccagcctt accatcaaga gccaccaaaa gttgtcagtg catcagacac 61560 gacggttggc tgtgaacctg acttttaata gttgaaccat ctttccaggc aggattggca 61620 tgatggggac tacgttcata tttgatggct agcagtggat agtgcagatt gtgtagatag 61680 gaagccactg gacaggtcag gactcacaca tgagaagtga gaacactgag ctgacataga 61740 tagggtgcaa ggggggacag ggacagttag catgtgtgct gcttgtacag agcacttccc 61800 agggctgtga cccacccatc catgtccctc tataccttca ggcaagctgc cacagcctcc 61860 cttatgctgg aacatctctg ctagagcatg atggggctct gtggtgagga gacagaggtg 61920 gcaagctctg gatggtgatc accagcatgt cctggctctg ttacaagacc acagagatgc 61980 caggcctttc cagcttccat gcctctgcac acgggtgtgc actacacact cggaaggtta 62040 gagtatgtaa gctttttttg taaactgtca tctgtagttg cccagcagtt tctggaggag 62100 gctgaaatac agcaggtcga tacagtgatg ctgagccggg cagcggtagg tgttagagag 62160 gaaaaggccc acggccagca ttgctcagtg ctccattctg gagcgtcaga gtggaaagcg 62220 cctgcagctg aggctgagac tgaagctgct gtgtgctgtc tccatgtccc agcacccctc 62280 caagcacatc agtagatgtg tgagaatttc aggttattat ggacttggtt gagttctgat 62340 ttaagttaat tctttctgca aatataaagt cctttaaata tggcatgtaa gcacctgtaa 62400 aaagcattgt ccagccatca ctttgtgaaa tgatgctgct agctccgggt gagttggggg 62460 tagggtgaag tggaaacagg gttgggtctc tgctctgggc cagccgaggg ttttagagca 62520 gctattgagc tgagtctttg tgaagtgagg catgtagccc acacaagtac tctgacgact 62580 taggctaatg attaaggcac aggcactgtt ctttgtcgta aaaagaatgt gtttttcacc 62640 tccactgtgt gaggcctcag gtgtacgaaa cagctccctc cacggttgaa gaagcatgtg 62700 gctgctgaac tgtgaactcc tggagtttga gctttcaaga ttaaataggc tctgagccat 62760 caatgaagac agtaagggtg cagccacttt gagctatttc taggggaaac tttaatttga 62820 tatacatatt atatggtaaa tatgcttaaa tagtgacatg ccttgtgcac tcattcactt 62880 acacaatgtt cacctcacca gctacagaat ttgtgtctca gatagtcaca ggggttttgg 62940 cagactttgt caacgtccac agaggaagac ccaccttcat ggagttagga gttgcttggg 63000 aagaagtttc cttaagaccg ttattgtaca cagacttaga aatacatgca tcctgtaatg 63060 taatgtcctg actagtcaaa tgttggtttt cttttagtta ttaagcatag tttgaaacct 63120 gcttgtactg tagccatttg aattcacagt ggacagaact tggcacggat gccctgaaat 63180 catagtgtag ttgtcttgct gaaaacttgg acccttaact tcctagacat tgaaacgttt 63240 tgaatcacga gcactctgcc ctgcttttgc tctaagcaat tgtgttggct tctccccagc 63300 ctctgtaatt gtagttcttg tgggtggcag cttctgtttg ggaaaagctg tgggtttaca 63360 ggtccttgct gagcccctgc ttttcctaag atgagctctc tgaagtctta taggagatca 63420 ggagacattc ctttttcata aaagaatgga gctagagcaa tgcctcagtg gttagagccc 63480 tcactgctct cctcgaggac cacgtttgga tcctagcacc atggcagggg tctcataagt 63540 gcctgttgtc actccagttc aggaaatttg atgccctctc ttggacttca tgggcaccct 63600 cattcatgtg ctcattccac ccaaactccc tgtcattaaa aagaataaag tatcaaaaac 63660 aacaaaaaca aaaaacaaag actaaaggag agttgcccat gaggggcttg tagtctgttg 63720 tgtgtcttga aagacatggc ttgctgttta aaccatggtt aaccctgtct gtgagaatct 63780 caacaccttg gccaggactc cagtccatca caaggctttt attttgttca caatatttgg 63840 ttgccacttt actcaataat gagagtattg catttaaaag taaagtttaa gtcatgcaca 63900 ggcctggaag ctcagggcca gtaggagagg gattcctcgg aaagactgaa ccggaagcag 63960 aagccagaca gcccaggtaa tgctgagctg gggcttcagg ggcacgtggc caaggctgag 64020 tctactgtgg ttcttcagac agtgggcagc tcagggcctt taagtatagc tctgaatggt 64080 tggcacaaag tgccacaatg gcgacggctc tgtcacctcg gctgctctcg ctgtgtaagc 64140 cgtagacacg tgtaaaaagg agactgcctt gcataatgtc tgagctggag ttgactaacc 64200 aggtttgcaa atgactcgga ctttgttttt gtaagatttg tattctatca ggacccagag 64260 acataaaagt gggtgttaag atggagacta aaaagtcctg tcctggtcct ttgttgtgct 64320 tctctgtcgt ctcaggggct tctgaccttc taaaggctta ttattgctca gtcatgttag 64380 acgttttgtg gtttttgttg ttgttgttgt tgttgttgtt ctcttaagag atctcagtag 64440 ttttagtttg aactattatc taaagattca taaacagcat ttgtagagaa cacatagttg 64500 aaattgtgaa cccagacttt gccttctgta gctaaaagct ttccagtgtg ggcacccctg 64560 taaacccctg tttatcttaa aacttctttt ctgtgctgag ggtccttacg tcagagaacc 64620 tttcaaacag agtcactaat taagagtaga gatagagaaa aactactgta ttattttctc 64680 atcatgtagc ccagactggc ctggagcttg tgatcctcct gcctcagtct ctggagtagt 64740 ggcattcacg ggtgtttgcc acagcagctg ctagcctttt gtctgttctg cacagctgtc 64800 ttctgagtaa ctggagagaa ccccctcttc tgagtgagag tcgctcttaa aagcacttca 64860 aaggtgaggt ttgttcctaa atgtgttgtg ttcaagcctt ttaagattac acaaggtgat 64920 tttttttttc ttgtgacgtg aggaaacaca cctatggctt ttgttgctgt gttgagcatt 64980 ttgctctgag acatcagact tgtccaaagc ctgtgtttct gttcctgatt tttgctcata 65040 gttgtcagct gttgcttctt actgccggca ttcagatgtc ccgtctccac actccttgtg 65100 tggtgcaata acatcctagg aaagaacaca tacacactgt gtgctttaca gtcttactgt 65160 cagcgctgtt tcacaagtgc catccttgac atgcagagga agagagtcag gtgtagctac 65220 tgcattatcc tgctcaagtc cgaaagtcac tgagtgacga tggatgccat gcagatgact 65280 attcccatag ttactggagt aagtggacag tgctgcccat gtacactcgg ggcattgcta 65340 atgctcaaaa ttccctcttc tccctcccaa agacaaccac cacctcgaca ttcttctcta 65400 tagatttgtg tctctgcccc ccaaggatga cattttttaa atcaggcttt tagcttcata 65460 aaaatagaat cagggcgaca ctgtttttgt gtccagcttt tttcatacca ttaaatctgt 65520 gagctccatc catctttggc ttatagtgcc ttcattgatg tgggctgaat tattaatgtt 65580 tgtatgaata tttggggcct acctgttagg gaagaactta ctgtgaagat tactatatat 65640 gttgttagag gatgtgactc ctcctaaatt acttagttta ttgaactata tagtcagtgt 65700 aatccaggtt attagtcact tttatgctgc tgtaatcaag gcagtgtgta tcttgagttt 65760 ctggaataat ggagaagatg ggggcaggag ttggaggcag aaggagatgc atgctggtgc 65820 ttaccccagg cttcttttta tacagactaa gattccagcg taacaaatag aactacctac 65880 agtggctggt tgggtttccc acctcagtta acctaatcat gataaccccc agaggcacgt 65940 ctcccaggtg attcaaaagc tcatctagtt gacaattgag acatatccca gctaccattc 66000 tttctgtagt tacaggttct gccagatgcc ttgaaagtat gtgaagcaaa aagtgccctg 66060 ttgctgagta tgtgcaagtt taccacgcag acacagcatc tgtaccgtgg tgagcattgg 66120 gagtaatcta gagatgcttt tgcgtatgca ggaggagttg gggctgtgca aacagtggtt 66180 ggctttgtag aagaacctga actgctacaa cattttctgt gcacaagggt cctgaaacct 66240 acccctttct acattcaggg tcaactttgt caccagttta actgtggtga cacttgtctc 66300 atcagcagtg caagagggct ctgggagcta catcacttcc tgactaatgc cagggttggt 66360 ttccctgttc tttacattgt aattcattag caagaaattt agtttgatac aggggaaatg 66420 caaattataa gctatatttc aaaataaaaa tatttaatgt gcagttctca tgcatagaga 66480 ttaatagttc tatattatat actgatgatt cttttcctcc cagtatgttt ccattgtttt 66540 gttttggagt gtattgtagt aggtatgttc atgagtgtgt gcaaatgtgt atgtgggcca 66600 gagtgttatc ttccatcacc tctctccctt gtctcttgag atggaatctc ttactgaact 66660 cggagctcag taagtcatct agttagctgg ccagtggggt cagctccagg gtctgcagct 66720 atgattttca catgggattc aagctcaggt cctggtactt gtgcagtgtg tttaactgcc 66780 ctagcagtcc ctagtctccc aatccctact tttttttttt ttttaaaggc agccttgatt 66840 tcttctttga gcactgatgt taacacaggt ctgtgggagt agaaaccatc gctcagtatt 66900 ctagaaattt gtttagattg tgggatgggg gctggccaga ggagaggaag agcacccagc 66960 ctggccacaa gctcaccatg taagcggttt ggcctctgcc tcccatatgc tgggattaca 67020 ggtatgctac caggaatagc tattttagaa ttttagttaa gaaaattaaa tggtgactcc 67080 acacacacac acacacacac acttgtctgc agcagcagat ctcatggaac ttggagccct 67140 gcacacttaa gttccttcca ccacaataaa gatctttatc tgtgggaaca aattcaaaag 67200 atccaaggaa ggtgttggta tggttgtgag ctagctgcca tgtaagaaat caaacccagg 67260 tcttctgcaa gagcagcgtc tgatcttaac cagtgagacg tttctaagga gttaagttta 67320 aacagtacat acaaaggtgg cttggaggga ctaaaacatt atattaaaaa atgtcacaaa 67380 ttatagccaa agatgtaaaa ttgtctttaa aagaacacag taaagaactt tatagctgga 67440 aaaatgaaac gtggtttttg ttttctgttt atttatttat tttttgtttt gtttttttac 67500 agaagtctag cagttaacaa catttgggtc tttatcatct ttgttaaatg acttactagg 67560 ttcaagtgtg gtcgaattga ttagttctta ttgtcccaac tctagctact tatgttccac 67620 ttttctgtgt ctcaggtatg ctaattagtc aggcggtctc atctgaaact aggaaggtgt 67680 gatagtgcta ggttgtacaa cttgccatac cagttttaca gtgtttttgt tttgctccga 67740 ctagatgaaa ggtttaagtg tggccacact ggtactgcat tcctggtgat cttggagggt 67800 taatgacaat ctttgtcata gacatcagga aatgtgggtt gagtctctgg gatgcacaag 67860 gctagttcat tagcatgctc cttccggagc actggggatt gttggaggta tccggtggta 67920 ggtaggtgat gcagcttcag agaactttca tctgtctgtc atcagctgtc atttgtccgt 67980 ttacccttct atctttccat ctatccatcc agcctgactg tttctatagt catcttggtt 68040 tttaaaaact gtttttaacg tattggtgtt tggttaaatt accactgggt ggttgctttc 68100 tctagcaaga cccagcaggg aaaccaggta ggttttgtgc cacagtcagg cttgtttcct 68160 cggtgttgtt ggcttggttt cgaggacagg catgtgagag atcatcgctg ctgttgaact 68220 ggttgccttt tagctgagta aactatcagt cagtgctgtg gtctatgcct cagttgtttt 68280 cttttttaat tagggtagct ggaagagctg cttaaaatag gtatctgtga gactcgcaga 68340 cgcagctggt ttggacttag cacgctttca ggcaggttca ctgaacgtgg ttctggttgc 68400 tctggtttct gtaaaagcct gcgcttgtgg tgactgtgcc aatataggtg agcatttagg 68460 agagcgacac actgctgttg ccttttttct taagaggtgt acttaactta tttcagatag 68520 attccttaat aataccatga tccaaatgta actaaataca aagcagggtg cttcatttca 68580 atactcttca tgtacaagtg ctatagatgc aagcagaatg tacttagttt cctggagcat 68640 tcaaagactg tatgccacca tcggcaaagg cattggagtg ggctagtact gttgagtcac 68700 tgattgtccc atctggagcc ttagtgaagc ctggagagta agttatttat tagaacccct 68760 gaggatgtgc tgagctgata atgcactggg gtcttttctt ttaaaggtat ctctgttgtg 68820 tgagactgtt ggcagtctcc agagttcagg ctgcgaaggt taaatagtga ccaacctttt 68880 catccacctc tgcatttgga gcattgtgag ggttggagag gagctgagag gcccagccaa 68940 catgttcagg attgaatctg cacctccttc ccaagtagtg agctttgctg gagtttctac 69000 atgttcaatc tgagggtttg aggctgtgat tggccatctt catgattcat tatatacata 69060 agtaacataa aaaattaaaa tctattaaat atgctgtgat ttgagtaaaa gaatatgttt 69120 ctattaaata aataaataaa taacaagtta tctaggcatg attgtgtatg ccttgaattc 69180 caaatcatgg gagggagagg caggctggta tctataagtt ccatgccagc taagggtaca 69240 caagaccctg cctcaaataa gaatatgtaa ttacaataaa aaatttaaaa cttgttcatt 69300 ttcctcctgt agagttgcat atttaatgaa tgaagtatcc tacaacttaa gtctatgtat 69360 aagtctgaga atcaaaaccc cagggttttt ccttggcttc gtttgtattg atttattttg 69420 tgatcttgtt ttgaactaac aacagggaag tggctgtgtc atttcacatg tatgtgggag 69480 actgtaaata ggaataggga catgttttct gcatccaggt gttattcaca gactcggtta 69540 atgtggtaag tagctagcta ccttgaaaag aatatgtgga gccatagctt ggcagcagga 69600 agaactgaag tgttgctcag aacttggagt ttcggtggaa gtcagttaaa acctcagctg 69660 ggtgttttgc ttgtcttgcc agttgctggg aggtggggag tagcttcctg gtggctcctt 69720 ctgaactcac agttgctaga atggtaggct tgtcttagcc agaatagtca actgcctatg 69780 gtgatggttc tggcctcagt ttatgagccc atgaggcagt agtgtctgag ctttggccag 69840 aaagatcaga atgccagacc acattagtgg gttacctgtg tcatctgttg atgggcagag 69900 accattttag agtatataaa gaatagggtc ttaaattagc agctaacata ctattttctg 69960 ttaaattatt aaatgattga taaaataaag gggtgatttc attaagggtg tcatcaaaac 70020 aaaactttta gaaaccactc tcgtgcaaat tgattttatt tttctgaaaa atcattggtt 70080 ttgtaattca aatctttaca actcgtctct cttggcccag taatgctttg tgcagacttt 70140 gcccacatat gatggaggca tttggttctg tgaaatggaa gcactgttta ggtagcaaga 70200 gcagagccag ggaagcagca aatggtaagt gttctgtaga tttatgccca gctaagtcta 70260 ctaaagcaac cacaaagcag ccgacaaagc cagcgaacaa gacattattt aaaatattgg 70320 cagagtttcc ttcatggtgg ggaacagtgg gcatcttcct tttttccatt ttctgtaatg 70380 attgcttact tattttttaa tctttaaagt tgaaagggaa cagggtgacc taagggagac 70440 atggccagat cagcaggcca caggaaacaa ggtcacaggt tcgagggata gcagggcggt 70500 ttggggatga gtaagaaagt gggttaattt ttctaaagaa catgctatgt gggaaaggaa 70560 accatgaaca catttctata cctctggctt gataaattca taggaagagt gggtgaatga 70620 atgactgtgg cacgaattga caagatcaag ttggctatat ccacttggca gcaatcgtat 70680 gtttgaagag ctacagacaa cagagatgtt tgaggtggaa tggtgaccag cttagaatgt 70740 gatatcctga gaatatgtgt ccttgacgga tgtgtgccag gggcagcaga ggttgggatg 70800 gagccagtct gggggggctt agatgaggct agggctcaga actcaacctt cccctctgga 70860 gatcaggatt tccttggaca tagtgagcca gttcactgga tagtgttgag tgattgtatt 70920 tacacatgct tattattttt aagtattgaa ctcttttaga ggcttacttt atttaatttt 70980 taaaattttt atttatttta caacttcctc ttacccagct aaattcatgc cgtcctgttg 71040 tgtggcaaaa tttcaaaaag tagttgggtc acagtatttg agtgggacgg tgttagagct 71100 gtagctttgg caatatggca tacttgttct ttgtagggac agcgacagca acagcatcag 71160 cacaggatga gcagtgagga cctagtgcag tcaacactta ctcacaagct cctggtacat 71220 tcctcgtgag tctttcctgg tgtttattag taaccttgtt gaagttggct gtttttgtta 71280 ttttcctacc ctgataatgt tgctttttaa ctgagaaaat tatttcatgc agcactgatg 71340 tgagttctta cagttgccgc acatgctatc taaatgtagt ttgtatttat agccatctct 71400 cttctgtgag tcactcttga tagtctcccc tatttttagg tttttccttt cctaagcttg 71460 tgtgcctgtg acacacccag cttgtcctct gccactgagc tgtaccccca gccccacttg 71520 aacgaaactg ttgaagctag tagccactcc tgttttctgc taactggcat actaaaggat 71580 agcatgtttt cttaccattt cctttgtgtg catgtctttt gagagagagt acaggatttt 71640 aaggataggt ttgtgtctga ttgttggagt gcgccaggtt tccagtacac acctctgatc 71700 tccatggact ctgttcactg actaactatt gaagattgct gcatgctccc ggggtgtttg 71760 cagtagcctc agtagtttct gtgtgagtgt cctctgagtc aggagttggc agtctagctt 71820 ccacataata atgagatatc tgcgtcaagg tggcacctgc agagcctcct gccagtctat 71880 ctcatgcata acaagaggcc acttggactc tgccaacccc agaattcaac cctagtatct 71940 atcatcttta tttttctttt ttttttcttt tgctcctgga ggttgaaccc agggactccc 72000 aacatgctat gcacatgctc tgccccctag tcatatctcg gtccctacag acattttaaa 72060 aattaattct gtgaagtatc tccgaaggtc ctgtggtttt ttttggggga ggggggttaa 72120 gtagcagtaa ctgtagcaat tattgtaact ggtatcctta ctcattacag tctctatcac 72180 cgggaccctt ctcgggatgt ttccttattt gcatttttaa caactcagat tacaggtgaa 72240 gtaactcagg caatgggaga tgagctggct tacgtggggc aggtagtaga tgtcacattc 72300 ggagctgtgg tttgtcaggt cccaaaacat gtgtgaattt taagtatgct cgggggtgag 72360 ggtcctggaa gaactgtatt aagagcacag gttgctgtta cccattaacc tgctgaatac 72420 tagcaaatac ccacattgtt cttacagcta cttataacat gcagtagttg gcattttaca 72480 tagaaaccta aggttccctt acctaggcaa accctgctat ctattttttg tttgttttca 72540 gcttttcaag acggggtttc tctgggtagc ccgggctgtc ctggagttca ctctgtagac 72600 cagggcggcc ttgagctctg cctgcctctg cctcccaaga gctgggatta aggtttgtat 72660 cactgtagtc aggcaaaacc tgctatcttt atgaaaggcc actcacaagg catgtctgtg 72720 ttgtgcacac cacacggtga ctgctgttta tcttttgaca gggtttctct gagtaataga 72780 atccaggctg gcctaaactc gcaaggatcc cccagcctgt gcctcatgag tgctggaatt 72840 aaaggcacgt gccgccatgc ccagtgactg ccgtttatct ttaggcatca gtaaatcttt 72900 gtaataggaa cacattccta ttaataatgt caactaagtc ctagagacaa gtgtagcagg 72960 tctcagtaag agccacgtcg gaagtatggt ttgcatactc tcagagtccc caggtttaat 73020 ggcagcgttg ctagatctga atttaggtga gtggtgagga agtagcctcc cggcagttgg 73080 agatagtttt atatgctagg tcagtgaacc aaaaatctct attatgtagc ttagggaaga 73140 gtttctagga atcagatttc tgaggtctat tatagctgag aaaggttttg ttcttgatta 73200 aagaatcgta tatttcaaag ctcacagaaa ctggaaggtt aggaaaggct ggaacaggag 73260 ggctgcagtc tccagacctg acagggcttc atagaaaacc tgcctcagaa accaaagcat 73320 gttcatgaga aaaactgcag tgttggtcct gattagggaa gagtggcctt gctaaagcta 73380 tgaactctat gtgaaggaaa atgaatgtcc cttccctggc ccctccggca cctacttggg 73440 ttgcctgagt agtttcacat aaattatgta tgtgatatgt ctcctgtctc atgtcagata 73500 tgtctgtctg tctggtggag cttttatctt ttatgtaaga tacgtatctt cctgcagctc 73560 ataccgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgttgctg 73620 atagttgaat ccaggtttca tatgtgccat ataggggttc tccactaagc tgcaccccta 73680 gctctctctt ttttcttctt atatttttat ttttatagat aaatgataaa ctatctattt 73740 ataattgtgt cggtggggga caaatgacat tatgagtcat taaagcaatg tagaattgtt 73800 aaaataatgg agatatccgt cacctcacag ccttacctgc tttatggtga gaatacaaca 73860 tttactctta acaattttga aattgtcaac acatgtttag tagctgtgtc cctcatattg 73920 tacagttctc caaatcaacc cacaggcgtt ttcctcctaa gggatttgtc ctccgagcct 73980 gtcatcttcc tttccctaca tccgtggcct ctggaaccac tgttcacttt gagtgtcctg 74040 ggtccccttg tttctgattc tgtatatagc atttatgttc ctgtggttgg tctgtttcac 74100 ttagtttgcc ccaggctgac agaaacaata gtctggtttt aaggctgagt gtgtgctgta 74160 catgcatctg tcagttcaag gccactgtct ttcaggctga ttgtacaccg tagctttagg 74220 gcagtgctgc agtgaatatg aggatataga tatctcttaa aaatttagtt tatgtgtaga 74280 gcagtctgcc tgcgtgtaaa tctatgcatc gcacacttcc ctggtgcttt ccgaggccag 74340 aagacagtgt tagatccctt gggatcggag attatgggtg attgtgagcc accctgtggg 74400 tggtgggaac tgtacttggg ttctctagaa cagccagtat tcttaaccac aaaacctcct 74460 ctccagcctc ctgcagatat ctcttgacaa gatgatttca aatcgtttgg taaatgacta 74520 gtgttggggt tgctggggct ggagagtagg ttcgcagtga tctggaaacc aggccgcagc 74580 ttcactctta gatgtttaca gcttcgatac tgtgttggaa ggtgtctagg ttcttggagt 74640 tgtgctaagt tgtttgctgc ggcacaccca gggcttggta aagatgtgtg tatttaaaac 74700 agctcattaa acagcccgga gtccttgtaa accaagttca gtctctaaca gtctaacaag 74760 actctccttt atccttaggt gttttgactt ggagaggaca ctaggttcac atgtagactt 74820 taccgagagt cggcatgtcc ttgaagccat gtgtgaaggc gctgttctgc ctctgggtga 74880 tgccccatgg gaaggacatg cactgctagc tattgcaggt gctttctgct gaccattcaa 74940 cacgttacag ttctgagcct cactagtttt gtagcataat attcccccag tagtgacctg 75000 tttcagcagg cagggtgtgg gccagctcag tcagacccag gtctgtttgt tttcatgcag 75060 tcttggctcc tcactggagg ctctctgctg ccaactgtgg gctttggttg aggcttgtgg 75120 caagattgtg ggtttaaccc aggagtattg cagcatcact tgtcatggag gtatcacact 75180 gttcagtggc ctcctatggt ttaggtttag atcatttgtc atgtggctta ggtttgtgtg 75240 tgttcatggc tttctcctcc tttagtcctt tcctgggtca cacagacatg cgagcgggga 75300 gtaaaccctg ctgatgactt tgcccttgct tacagtttca gtttccaggc agctttcttt 75360 acaatcgctc acatacagac ccaagctaac tggacactga ccctttagat tagcccactt 75420 tcccaacagt tctcatgtga ctttgatatt aagtggaact gttaatagag ttagtagttt 75480 agtgtggaca gtaaagacca tgctcaccca tgctcagtgc atgtgctctc agcgagctga 75540 gacacatggt gtgtttggtt tgtgagtgct tttctttgga atgctgctca aaggttggga 75600 ttttaccatc ttttctttcc ctcagaggtg ctggatgcca agatgatgca caggtaaagg 75660 gtaagccaaa catggaggag gctgggcaag ttgtgtgctc actgctcatg gttggcgtgc 75720 aggccctccc tgttactggg agaccgtcag ggcttccttg gtgtttcctc accatttctc 75780 ttagggtctc ttagaacatg ggccttggac agctccacct tttccgagaa cttccagggg 75840 tggactcttt ccctacttcc tcagtgaatt cagactcaag ttcttcgccc taacccactt 75900 gtgcagtcct ccacagcgca ctgcagcctc ttcagctccc catacttgta tggaatgcat 75960 gtacttctat gcatttcaac tgtgcaaatg ccggaaaaga ctcaggttgt caaggtgact 76020 ggagctaggc atgccactgt cactcaggaa ggctctgctc tgccattgac ctgtaggaaa 76080 cggctctatt ctcagaagtt aaaaggtggg ctggtgaggt ggctccatgg ttcagagagt 76140 ttactactgc acagcagagg gctcggtgcc acgcatgaag gtgttggtat gcatttgaca 76200 tcttttaatt acattgcatt ttgtagtgga tgctgttgtg tgtcctgttt aaagattaaa 76260 gaatgttcca aaaccactta gagcagtgtt ccttgaagca agctgacagt gaagaggtgt 76320 cctccctcct ccttcttctc caccttcgtc catccgtccg tccgtccgtc cttctgtgtg 76380 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg ttccagttat aatcgtctgc 76440 agagtgcagt cttatttctt ggacattcag acatgccttt tcgatgccgt gagctttggg 76500 tagtttcatc atttagtgtg tgtggttttt ttgttttttg ttttttccaa acaatgcctt 76560 agttacatct atctcaagtg gctctggatt tgtgtcctca cttacagagc agtcatttta 76620 tagaattttc cttcatgtca ggaaacacgg taattgtgca ctggtggaat gtgccgtgca 76680 tatgcacact ctgtactgtt ttctgtgctg ttgttttcct ggggtcttgg tgggatgctg 76740 tgctttgttg agataggact tgctatgtat ttgtggagaa cactgttgct gttgaaatgt 76800 atattgtatt tccaaatgtt tgtggtctgt tgggagagtc accccctcaa ttctaaaacc 76860 gatatgatgg ggggagggcg ggagactgat atgtgcttaa ggaccaggaa gttctggagt 76920 gtctgaaatc tagccagcac agactgcagc tattgcttta aacacttgtg tatctttaga 76980 aacaaacgca tactattttg ttatagttca ttctccttta aaagcagaaa tgtgtgtatt 77040 gcataaacct taatacttgc atgtctacat ctatgtataa atgaggagga ggtttgagac 77100 tacatcacaa tctcttattg tcttcccaca gccctgtcag cctcaaggca ttacgtcacc 77160 aagtgagaag ccatgcctct atcctgaagt ggtaaagatg ctattcctga aaacagcttg 77220 aattactaag ctgcttttta ctttcaaaag cttttgaagt attttgggac ttgccaacca 77280 ctattagttg gaagtgtgtt tggtttgttc tgggagctga tagttgtctg aaagaagggt 77340 tagaaatgtc tcgtttcttt gggaattgtg ttataatttg gattaattag ctttcgcctc 77400 agagttttct cttttataaa tagggcaaac cccatatttg tcaggagttc tgggccccag 77460 ttagccagct gagtttttac acaagctttt acgcttggac ctggatgctg gctccaggtg 77520 cagacacagc accatggatg ctgaagatgg cgttacttcc ctggtgtcat cccttccacc 77580 ttctgcttga tgtgtgctaa gtgtgcccac ttctgatgaa ctgagggccc cttggttcct 77640 cagcattgct ttaatgtagc tacagaccca tggagtggag agctgcagtc tcatgttagg 77700 agtctagtgt ctatgagcat ggcaaaatgc ctaccgtccc ttgccgaatt atctgcaggg 77760 tctctggggt ttttaaccta gctcaaccag aaaccaggct gcctttaaca gtcccacata 77820 gcaaaaagca tatagtgtta aaggggaaat tgcaaagttg tgttaaaggg gaaattgtag 77880 taaagttaca tgatttttaa taaaataaaa aaagaggatt tttaggaagt ataaaccagt 77940 cattgtgtca tccatctatc catctatcca tccatccatc catccatcca tccatccatc 78000 catctatcca tccatccagg tggtggggat gaagtgtgtt tgtgtagccc agactggcct 78060 tgaactcaga gatctcttgt ctctgtcacc taagtgcttc tggggtcaaa ggcgtgtacc 78120 accatagcct accattctga tttgttattt tagaaataaa accacccccc cccccacaga 78180 gtttctctct atagccctgg aactcactct gtagaccagg ctggccttga actcagatat 78240 tcccctgcct ctgcctctgc ctcccaagtt ctgggattac attgctgctt taaaacaccc 78300 acgttcacta cagacccttt ccctcaacca agaaaggcac caattatcaa cacttgataa 78360 cttagtagcc acttgagcct ttctgtacct gaaatcttga caaaaaattg agacataaag 78420 gccccaaact gtgttatttt aggaaattta agatataaca ttttaccaga tagtggtgac 78480 aggcctttcc ccgcactcag gtagcagagg caggtgtttc tgagtttgca gggagcctcg 78540 tctacaaagt gagttccagg acatgcaagg ctacacagag aaaccctgtt tggaaagaac 78600 aagcacaaca gtaacacaca aaaccaaaag atacggcaat gtaacttcta gaaacaatca 78660 attaattaaa aatgatgcaa tgtttttctt agggctataa aatttatttt gtagctcttg 78720 tgtatttgca agggagccag aaggcctcag ctctagactt ttgtgtctga atgatttctt 78780 tttccaatag ttgaatggtg cacagcagtg tcttcccaca cgcctttgag tgcccaccct 78840 gaacccttgt ctccttcctt gctcctacac tcccatgagt cttctacttt caggtcatat 78900 gtgttcacgt gtgttgtgtg tctgtgtgca ctccatgatt tagtggcttt ggtcacatcc 78960 agtgccatca gagcatttac agggcataat taaaagctca tgatacctca caattgtagg 79020 ctgcaatgaa acagtaagag ggggtattgt tgtttagggt gtggttagag aaatagttgt 79080 atcttttaat taaacaaagg atggctaatg cctgaaaact agtctattga acaggaggga 79140 ctgtgagctt tcaaacaaat caggaacttg agaatcacgg tgtgtaggtt cttttgtcac 79200 tgatgaattt gagtcttagc gatgctcagt ggtgatctca ggagcccaga tcgttgcttg 79260 gcatctgtac ccctgnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnntagcata gactcttaag gcatctcttc 81780 cagatggcag gatttggggg agagcggggt gatagtttac taagtcttag tgtgtgtgca 81840 catgcgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtc cccatgtgca cactggagcc 81900 atggcactta tgtggaagtc agggctgcta cagagagtag tttttctcct tcctctattt 81960 gggtcccagg gatcaaactc aggtagtaag gcctggtgcc tcccatatta taatgggtga 82020 gccatctcag caggtccacg tgttactttt catacttgaa ggctattgtt ttgacttttt 82080 cagtattttt gaacaaagta ttgatgagct aatagttagc attgtgaatt ttttcttatt 82140 ttaaaaagga agttgacata gtagcaagtg ttgtgcttta agcgaaatga taagaggaag 82200 gcaaaccagc ctgagtgact tggctggcaa gaggctgtct ctttgcaggg gatttagagg 82260 gacgattagg aaaagaaaga aaagagacaa gtgtagagct ccacagccag cgatcttgga 82320 caccgtgctt acctgatgac tgttttgttc tttcacaaca tgggatcaag cagttttctt 82380 aggtttaaaa atactttgtt gaatattgac tcttatttgt gttccctttg gtatcatatg 82440 acatttgaag agagaaagct acaaatagaa gaagtttgac taattttagg acctagagaa 82500 tagtattatg aaaggttaca ttgtgcttct ttaataaaag aagcagttag aattatttta 82560 gccactggca tagtgtgttt aaactgcaca cacacctaga cagacataaa tccccgaaaa 82620 agcagcagct cactgctcgc ctgtttccca ccccatgtcc tggagtcaca gctgcagtaa 82680 agcagggcag tcctatagct ggtctagaat gcatcttaga cgtgtctctc ggccatactc 82740 agtgacgaaa acgtgaaggg gattagttac gcgtgccttg aatttccccg tctgaaacga 82800 gaacccaaac attataccat ccaggagagc taactatggc ctgggtaacc tgcagacctt 82860 ctgtggatgc cggtgctgcc ttcacctcct tctcgtggag gcactcagac tcgggtgaca 82920 ctgagactgc tctaggtttt acgacttgga caaatttggt tgatttctta attatgctcc 82980 tcatggctag ctatttttgt gagggaggaa aaattaaaat atacaggaag acatcatgaa 83040 gcattcttca aatttaagtt tcttataatc ttttggttgt gaacctagcc tttaacagtt 83100 gagccatccc tccagcccca aatttaaaat ttttaaagnn nnnnnnnnnn nnnnnnnnnn 83160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 83220 nnnnnnnnnn nnnnnnnnag gctgctgcta tgaggtgtgg ttcttctatg atctgggcag 83280 agcagtgagt tgtagcccca gacagccatt ggcagaagca gaagcagaag cagcaggcag 83340 tacacagtca ctgtgctact aagacattag acgtgtggga agtgagttgt agggtatgtg 83400 tggatacagt ctcgtgcaaa gtgataaaca cccacagatt cccagagcct gcctttggaa 83460 ataaaggaca gataagtggt cactagtcac tgtgggcctt tttgtgcttg atgccattct 83520 ggctggctcc tctctgatct tgagaaatgt ggggtttttt gtttgttcat ttgttttgtt 83580 ttgttttgtt ttgctttgtt tttaacttta aaacccttac tgaattacta tatatacagt 83640 ttgctggttg ttactcggtt gtgtctctgt taggaacttg gacagagtag accacatcga 83700 acagctgggc ctggcttggc tgttcccata gttttggaca tggcctccgt gacttactgc 83760 cttccataac ctcaacagag tgccaccggg aaccatagat aactcaggac actgacacag 83820 ggctctcaag tgaatgtgtg aggttcacca gttcctgctc tttgccaaag ctgcccagtt 83880 tcatgggagg gcatttagcc tcttgtatcc agggaagaag tggccaaggt ccttgccatc 83940 tatagtctcc aatggttcca ttcagggatc atgttcttct gtaacacttg accttgcgag 84000 tgacattacc ataactgcca cttattcagg tgaatacata cttcaatctg tagggcttaa 84060 agatagtttg ctgtcttcct tctgtggttt gtggctgcct gcccatagta cttgttgttc 84120 ttggtggatt ggagggtgtt gagcacagag gatgtttgct cattgtgaat ttgccctgga 84180 gagctagagt ctcccaaaga ggtcccggca tttgtgaagt gggtgccttt gcttgatnnn 84240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84960 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85020 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85140 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85200 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85260 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnntgcc 85920 cccacccccc gccccacaat tgtttaaact gtagcatctc tgttctttat tatgctttag 85980 ggcacagcat gaaggtacca ctttggctta aatttggtgt gtcagtaaag tttttgaaaa 86040 acacccgtac atgaatgatg ttttaaaccc cccattttat agtcatgtct attttttgtg 86100 aataatgggg acattttagc ttatagtagc ttctatgaaa agcaacagag ttctttgtgt 86160 cactctcgcc cttgattgtc agtggaacct atgatataag gccaggccac taaatccagg 86220 tccacaggga ttgaaatggg ctcttcgcag atggctctgt tgcacttttt cagtgtgcac 86280 tttttttttc ttgagagtgt cacacatgtg cggtgtactt acatcatttc caccctcttc 86340 ccaggcaccg cattagtgca tgcatgtgcc ggatttccaa tcttacttgc tttctgtact 86400 taaccttata gagacctttg tcccccagag cttgatatca agcatcaata tttagtaagg 86460 gcaaatgcaa ggctgagact gaagtgactg ttggttgttc caggtgacaa cagttctcaa 86520 cctgtaagtc acaaccatta gcagacacat atttccaacg gccttaggaa ctgttaagat 86580 atgagagact gctcatttgc aaaattacag ataagaagca gcaataaaaa caaatttatg 86640 gttgggggtc cctaaaactg tcagaaataa tgtgttttcg aatggtcatg acccacaggt 86700 tgagaaccac caccttagga cttagcagat ttacctgtgg gtcactttgc attctcatgt 86760 aaggtatggg agggaactaa catctagcca ggatatatgg gacatttatg cgcagtttgc 86820 atcccagcaa cctctggttt gaaggaagaa gagaatgatg ctaggttatt ttccagtgct 86880 tgctttctac ttcaagtttc agaatggttt cactttcttt ttaaatacca tatcctgtgt 86940 ctgataaatt ctttgtcaga gccttctccg tgttccttca cctctgttgt aatgtgatgt 87000 tatatcttct agtttccttg cttttgttgg cataagcaat tgggcagtct tgttcgggtg 87060 ataaggtgca gctccttgct aggcagctgc tggcggctgg gttaggctgc acgtggcaaa 87120 gcatctttgt ggtgctcagc tgcgctttct gagtggagaa ggaagtaggg gagagccagg 87180 gaagcaggga gggctttcgt tcttctgatt taacgtgaac accgtttact ggcactaacc 87240 tatttgtgag aagtaattaa aataattcat gtaaaagtta cagcagagcc attggtattt 87300 gttctcagca atcagtaggt cttgtttctt tatgtgtgaa tagtacagta ccgttttatc 87360 tgcttgtaca ggtgggtacc tgagttgatt ctgaatcttg gaatcagtct ttgtgtatat 87420 cgctgcagtg cacacaggtg tgcacacatc tattgtcaca ctgatttatt tttctttgga 87480 catatcacat gggactggtg tgacatggat gagcccagag gacattatgt tatgtagtca 87540 gatacagaac aaatactgta tattctcact tatatgtggg aattaagacc ttgatctcat 87600 gatctggaga atagaatagt ggctcctgga aaagagagct tagtggcaca gctgatagga 87660 ataataaatt cctatagcac tgtaagcttg ccgtgttagt cagtcctata catttcccag 87720 gggcgtagga agaagatcca gactgttcca gtacaaacag atgatacacg tttgaggggt 87780 tggatttgcc aggggccctg ttcatggaca tgcccattgt gggcctgtac tgctctccat 87840 cgctttgcat acatagctgc tctccatagc gctgatagcg tgtatcatta cctcacacca 87900 attaaaaaaa gagtgcaaaa gcagttccca taagtatgtg cttcaaatgc tagaccaatc 87960 atttccagat ctgtccagtc tctcttatac tttctattgt tagctatttc atccatgcat 88020 tttatatttc gaggcttcat gctttctttg taagcataat actcacccag gatgggaaag 88080 ttggtgaaga tagggcgttt caaccaaaga gcttagagtt cattgttcct ggactcataa 88140 aacactcagg atgagtggag aaagtatatc gcccacaggg cgacatgagc acctggactc 88200 ggaagggtgt ggggaggtgt ggggaagaga tgctttcctc ctcgtcgacg gccagcgctc 88260 tggcatgcgc gtgcagcttc tggtcatcat actgaaatga tgatctgaat gtggtgacaa 88320 tcatttgaca gaggcacctt tggtagacag atgtctgctg cctgttgagg gtgcttttgg 88380 gtgttaaaga ctgtttctga cctgtgtgga cggatcatta agtttaaata ttacttttgg 88440 tccaattgct tagctcattg tctgacgatg ttttatatat gtcttgggca gtcctaaagt 88500 gtcttacagg cttgtctacc ttaaactcaa gaatataaac ggaagggtaa aggctcattt 88560 atttttcagt gtgattgatt tcattaacaa taattaggaa ttaaaaaaca aaaacctaag 88620 agaaggtgaa tgtctgaagg gagtttgtaa tttgagattg tccactgcgt gactgaagta 88680 aggacagaaa aacttcactg tgtttgagga attttaacat agcctttaat ttgaggaact 88740 ggttggtgtg agaggccaca tgacctgttc tagtcttggt aggaaggtga agctgagcct 88800 tgtgtgtata tttcagagag cttctagcct aagtgcaggg tgccctgctc tactcagagc 88860 tggctcactc cttagccctg ctctcccaag gaccaccgtg gccttactta ctcttgccct 88920 caaagaactc ccacgaagat agcaaggtac agtttagttt aaggtaatga tagttgtcat 88980 tttcatgtgc taaacctgaa tccttatttc ctattcactt gtcagcacct cagccctttc 89040 cagcctaata tatatctttc tctctttgtg tgcttttaaa gggtccagca tttctgatta 89100 cccaatcaag taggagcctg ctcgtctcac ccgtggaatg gaatgctatg cctctcctct 89160 tgcattcctt tccccagact ttgctggcct tccacctgnn nnnnnnnnnn nnnnnnnnnn 89220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 89280 nnnnnnnnnn nnnnnnnntt tgagacatat agtggtatgt tattgtggtc cagggacttc 89340 aggaagctgg ggcaggaggg tcataaacaa attagagacc aacccaggca cctatctcaa 89400 aaggccctcc ccattacccc tcctcacacc cctgtgctgg gcaagtaggt gacatggagc 89460 tgcgttcctc gccctatgtg tgttagtaag tcttaggatg cagtactgga ttttcttatt 89520 cactgaaatt tatactactg ccgctgcatt ttaggatgta tttatgttac ttaaacagta 89580 tacacacaca gatgtgcacg cacacagacg cacgcacaca gacgcacaca cacagacaca 89640 ttctatcgtt aaggtgattt gaagcaatct tgtgatttga agcaaactgt taaaattgat 89700 tttatgttta actatgtggt aggttctgtg tttttaagca aaatattatt attattatta 89760 ttattattat caagtgctga cagtagtaca tcatgactgt ttgaccatat attataggct 89820 gttggcatcc atattcatgt atggtttaag gaatttgaag attcctttgc agctttccct 89880 atccctatat agtcctcagg gcttcccagg ctgcctgcct ggaggtgggg gtgggggtgg 89940 gggtgggggt ggctggagtg actctagcct aatggaggcc agtctctgtc agccagagca 90000 tgcgggctgg cagtggcctg gttcctttgt ctggccagtc agtcatcttt ctaacagaca 90060 cttggcttct ccagtgtatg tcagagatgc agacagctgg ttcaggatgg cctgcctggc 90120 ttcccccagc accacactct gctgtatagg acatggcttc ttttgatcgg tgacagcttg 90180 aactgagaaa atcacgtggc tcaggccttg ctctcagcct gtatgtgcca gggctcgaag 90240 gggccatgca cttctgctgt tcttattagt gtgacatcag agatcagaag gcagttttca 90300 gggggtcaca tctctgcctt cttggttagt tggcaaaaaa ttatagcatt atcaaaactg 90360 gccttccctg actgcccgga aggtatggtg accatacact gtgaatctgg tcagccttgt 90420 caacctttcc agccatgagc tctacagctg gaccttgctc cccaggcatg cctcggggac 90480 aatatggaca tgtggcagaa cacctgcctt aggtgtgtat agattgaact gggaacaccc 90540 gtgccttcta ccccatgctc acccagtaag cttccagtgg atgatagctg cttgtgcgtt 90600 ggtatttcag tttgacacta tgtacagact ttaaaagaaa aacaaaacaa aaaccaaaaa 90660 aactccttca ggcaaattaa atgccctttt ggtaggtagc aaagctgccg cttccttctt 90720 ttcccaactt tattttctct ggctctgttt ataatcactt attaacaaaa tctgagaggg 90780 tcctgagtgt gactgttcct tacctatgcc ctcaacgtac ttgttctcat gtttctcgca 90840 gagtgcacat ggagcagact tggtgctgca gggagtgacc tgctgctaac tgatgatcta 90900 ctggcaaggt gcacattgtt ttagaaagac ctttctcgtg ctgcctttat cctagaacag 90960 ggacacagaa caatcttgta gaaaccattc actcttcctg gtcggggtga gagagaggat 91020 aacttaaaaa cctgagcatt ttaaacagtt gcatgggagc tagtgagagc tcagcatctg 91080 agagcacttg ctgcatctct gtgaggacaa gagcttgact cgtgctaccc agtgttggtg 91140 gccgtgggtg gagggggctg actgtcagcc tagctgacaa acagatgagc tgctgaagtt 91200 actgcctccc ctcagaggaa taaggcagag agtgatagag ggagacgccc ttctgtggct 91260 gccttgcaca tacatgcatg tacactacat atatacatat ccatgcacac atgcagcaca 91320 cacacacaca cacacacagt agggggagat ttaaaatagc tggatcttct tagaccaaga 91380 tcctaatatt gagcaaatgt gtattttact tcttctaaga aactgcctta gtggttagag 91440 agatcgttct gtagttaaga acatctgctg cttcgcagag gcctgaagtt cacagcctgt 91500 aagacatgtg atagaggtgc taaatccctc taagggatcg atgcctctat agtcacctac 91560 atatacacgg gacacacaca cacacccagg atacctacat atacatagca tacacacata 91620 caggttacct gcatatccat tgcatgtgca tacatctttt taaagctcct tcttaatgat 91680 ttatttgtat cttatgcatg tgaatgtttt atctgagttt atgtctgtgc accatgtgta 91740 tatcagggat ctgtggaggt cagaagaggg cactgaatgg accattgtga gctgccttgt 91800 gtgtgctggg tctcaactcc tgggccatca gatctccagc cccacactat tttcaaaatt 91860 gtttttaaaa agttattttt cttattagtg agtggtagga gctcttggtt tttctagaca 91920 ctgccttttt ccagatgggt ccctcttggt ttccagtgag tttctgtaca cgatgcacta 91980 ggctgcttct ctgtgcactt gtgcagccag gcttgaccat ttctgcaaag accagccttc 92040 ccagttgaat gactttgacc tattttgttc agtgtgaacc tacacagaag tcagttccgg 92100 gactcgattt tgttctgttg cttggtttat atggatgccc cactgctctc tgattatggt 92160 gactttccag taagtcggaa atgggtcagt gcaagtttaa agtaggtggg ttcaagggta 92220 aatacatgaa gatctgctag gtggacttgg ggtggatggg cctgcccaag ctctgtgtct 92280 tctagatgct tctctcaaga ttacgtaaag aactgtgtta gtttcctttc ataatgaagt 92340 ctgtgatgga tgtgctaggt tgtggtatta gtctcatggt aatcataatc tatagatagc 92400 agtagtcttt gtgggggtga gacctagtct gtataaggaa tgtaacctcg gctgcttcac 92460 ccgtcccacc atgcttttgt agacctacca tgcctaagtg acacctggaa atgcagtgaa 92520 cccacagtgc agcccctctg ccctatgtgc ctatgtgctc ctgtcttctg acctatgtgc 92580 cctctgccct atgtgcctat gtgctcctgt cttctgtcct atgtgccctc tgccctatgt 92640 gcctatgtgc tcctgtcttc tgccctatgt gccctctgcc ctatgtgctt atgtgctcct 92700 gtcttctgtc ctgtgtgccc tctgccctat gtgcctatgt gccctctgcc ctatgtgcct 92760 ggctcctgtc ttctgtcctg tgtgcctggc tcctgtcttc tgtcctgtgt gcctggctcc 92820 tgtcttctgt cctgtgtgcc tggctcctgt cttccccagc tctccccagc cccagtcggt 92880 ggctcctccc ccaggactgg cacagcagag ctggttacta gttgcagtct taccttttat 92940 gccatgcact gttgcttttt aagtagtgtt aaacttaaaa cttgagtttg taactcttta 93000 taaattttgt tagttttctg tttggaactt gcactaagga tatctggaaa cctattggtc 93060 tcctatgtat ctgtctttaa ctggaatgaa ttgataggtg gcctcatgtt gtttttacat 93120 ctgatcaaag catactgaat aggatagagc aagcaggcag tgtcctgtcg atactgcagg 93180 ctttagctca tagttgttga ctgcttgatg gctttgagca gaggattgga tggggtttgg 93240 agtggctcac gaaggctagt gcacgtaagg catggtttaa aatctgcctg cgtctcagga 93300 aaggatggag agtgctcctt tatgggtgtt attacccctg ccactgactg ccactcactt 93360 tactaggata acttgtttgc atatacattt tctgttactt tcgtccaact gtttctgata 93420 cccatgttac attttattat atatgatgat ttcaagacta tgttctggtg taaaccaaac 93480 ttcatccttg tcagctgctc tactatatag acattatata gtcaaatgtt tccagtgttc 93540 tagaaaaagt gcagtttgaa tattaatttg gtgttagctt cttcaccttc tgttttctct 93600 tctaaaacaa aactgaaaag ctttaaatgc attagcactg ctttaggttt ggtaatgaat 93660 acaatgtcat tggcaatgtc actgatgtca catgaagaaa atacaaccct tgaagctcac 93720 ttgcaagaac atttccttga tgctaagtct gtaacgttaa tgcttttcca aaagacgatt 93780 ttagaactgt tgccagcaac gagcactcgg gcttttttct tgcatccata acatatacaa 93840 ttaatctaga taaaatagca taagcgtgca ttttaggtct tgtgtttctc agtatgcgtc 93900 ttgtatgtcc aggcagcagc ctgccagctt gcgcttgcgg cctgtgttct gagatagacc 93960 ctgagggaac ttggggctgc tttctggcct tgcacttctc tctagcaaac tatgatggct 94020 gttcctcatt gtgtgtgctt tgctccaaca gacttttctt cagagaacaa attgctctga 94080 catctttgtt cttttaaaca cttactatat agatttttgt tttattttag taattttaag 94140 catctccatt gtaattatga gaactcaaaa tcttgtacat gttctgatgt tcataaggaa 94200 atatctcgtg caccttttgt actgcgctcc acaagcagaa gccatgcctt ggccattctg 94260 cctcttgcct tgctatgcat ttcagtgcag agtggtccct ggtgactggt gctgtgcatt 94320 gggagcattg agcgggcatt agctatatag cgattacaaa aatggcatct gctcggagca 94380 gtccagcagg gctcggcatc ctcactaacg tctgggtttt gttcccattg cagattttcc 94440 tcgcatctgg cttcactgca ttggctcttc tgcactgtgt acaggcacag gtgagttaat 94500 ccttgggtct ttcatgttgc gctatgttga ctattagatt aaatatttta aattgcctaa 94560 tacattagaa acaataagca aataagagga atgtgagtaa gaacagaata aaacttacta 94620 ttttcctgca tgtttttgtt aagagagttc ttttatgaaa ttgttgaaat gacattgaag 94680 gtgacacacc agatatcttg attggtggtt attgtttcta tttggaaagt gtgtgtcttc 94740 agtgtacctg ctggacaagt tgagttaatt cattaagttt taacctcaga gcctggaaaa 94800 aaaatttttc tacttatttt catatgtcac atatttttga gtggttgtat tatttacctg 94860 ttattaaact ggtataatgt aggagaaaag aaaacttctg taggttttac cattaactct 94920 caggctgcat gtacaggtgc tgtgcaatac tgggcttggc ctctgtgcca gtggcgttcc 94980 ccactcatcc actgatgatg tccatgagat ttatgaaaca tgttagtaac atgcgataca 95040 cttttcttca tttgtaactt acccttggag aacttcagct cccttagcat tgggactgct 95100 tgtactcaaa gacatagcct tagttcttag agcacggaat gctttgcagt gaagactaaa 95160 gcctgctgag tgtgagcatc tgtaagtaca cagtagaagc gagaattatc tgtacagagt 95220 gtataaggct ttggaacatt atgagaagtc agtatgttgg acctgttcct tcagagatca 95280 gggtagagtt gaggggatgt ggcttctgac tcctcactct gtcaggtgtc tgtggtctta 95340 ggatgaagtg caaacacctt aagtttggta ttttttaccc tcttagcatc ttgggtatgt 95400 tttgtgatac caagttttga tgtctgaaga ttggatgaat taaatctttt ctactgtctg 95460 tcgctggatt taccgttttt catttagttc ccagcctggg agacttgtct gctcattttc 95520 ctgctgtgtg cactcatgtg ggcactggtc tcagtggctg ttgacctcac aggacacctg 95580 atgcccatgt gctcttgacc acgccaccct tcttcaagtg ttgagatact agccatctct 95640 cttgggtact tgtctgtttt acttaaagtt gttactgtat ttccttattt attgagtgct 95700 gcactggaca tttgtggagg tcagaagata gcctgcaccg agttggttct tttcttctac 95760 catgtgggtc ccaggactca aactccactc atcaggacta gcagtaaacc ccttagctgc 95820 ccagcctccc tcaagactcg ttttgctttt gctctgtctt catgcatatt tgtctctcgt 95880 ctttacaggg gctatttttc ctcctaggac ctttaatttg cttgtaatta aataaaacgt 95940 tagctgttgt acactatttc ccattcacac atccttacag ggttagtctg cagaagcacc 96000 attgctcttt cagcagctct gcagtgctcc tctgagtgcc cagcagccac agttgctctc 96060 tggttgtgtc tggattagca gatgaggaca cgcatctggt taagtgactc tcccaaggac 96120 atatcacctg agtggtggtt tgctgctctg aggaccgtga tcttaaccat gaagcaccat 96180 ttctgcctaa acagccctgc tggctctcat gtttgtggca gtaagtgtaa tatatgaaaa 96240 ttattttcat gtttgaagac ttcaaaccta atttgaaaaa tcagacatta tttacttgtg 96300 ttttattaac taggcctaac ttttaacctg taatcttcat ttcaaactgt ggaacacgat 96360 ggcttacttg aaaaccaatg actgcattag tgataaaagc tctgcagctt gtctcagatt 96420 gactggtgac tggagcgagg gtcgcagctc cagcctcttt tgttttcatt atttgttttt 96480 taagcatggt atgctaggaa ttggcattct ttccccctta gacattttag attataggta 96540 gcatctgtgc ttcactggat aaattgcaaa acatctgggt gtggtggcac atgcctataa 96600 ccgccagcat ctgcagggtg ggaacagagg gaggagggcc tggagtccaa agacatctgc 96660 agctgtacag tgagttcaag gccaccctca gtacttggtc ctgttcaaaa aatcccaagc 96720 acacaaaagg aatacacatg taatacacat gtctaaatac acgtgtactc acagaatagc 96780 tggatatgta gctcagtggt gattctatgt ctatgtaata taatgcatac ataattattt 96840 atatatgaaa tatagtgact atattttata tagtgaatat attatatatt tcatatatag 96900 atttttgcct taaaacatgt agtgagagag ctgccatttc aagacaggaa taaaagccta 96960 ggagagtgtg agtattgacc tgcctcatta gtgagctgcc attatctctt gcacatttat 97020 actgctcact gacaagctca caggccagag cttggaaaga ccatctttat atgcatttct 97080 tatttgtcag gacactattt aactcctatc ttctggttct gaagatatct cactacttgg 97140 cttggaggac agagtagaca caagtcttct taatattgtt agtagctttg atagcttttt 97200 aagcttaagt tcttgctatt aaagacagta agatacagtg actgcatttc aacaaagggt 97260 ccagtgcttg aggtttaatt aaagaagtca acatgcacat atacatctgt agggctctct 97320 gcactcacgt cacccagtca taggtcagtc ttgtctgctg agtgctctag agtggctttc 97380 caaagcaccg aggcatcccc ctattctgta tatgtactct gaacagaatt accgcactgt 97440 aatgcaccat gtaccttgtc agaatgcaaa tcgaagagca ggtaagggat ttcttagttt 97500 attttttaca tgactaaacc acctcttaaa ggctgctagc atggtcgcca gaaaactgat 97560 tttgaagttg cagagctcct caacaaggga ttgacagtgc acttccagag cctggagctg 97620 ccgtcccagg ctgtggcacc gtatgccagg gatggagggc tttgcctctg tagtagttag 97680 ctgctttcag gctcaaaatt aactcttgta gttgatactt cacttattga aacagacact 97740 tatttctagt aacatgtctt tgaaaaaaca aagtagatta cttaaattgt gctacagaaa 97800 gtctaatatt gtcttgaaat gtttaaatta taaataaacg atttcccctt aaggaacatg 97860 atgacatatc ttcaggaagt tttgtttatt taagaactga catggtatca ccggtgttta 97920 ggtagagcat acttagactc tctcttagcc ccttcatgct tagttgtctt caggactgaa 97980 cagttcattg tataaaggta ctttgggtct taattgcata atattggttc aatatacctt 98040 aaaattttca ttggaaaaca aacttaattg tattttcttc aactttctga aaagactgta 98100 agagaattcc tggtctgaat tatgggatgg agaattcttt agtttgaatt caaaaggcaa 98160 aggactatgt gccattaaaa aaaaagtctg tagcaagcta ctggttccag tctagatcac 98220 acttttaaca tcattaaacc taaactggct ttgtccacta aacagcagga tttaggttag 98280 ccttgacatg ccattgaatt taaatacatg actagtgctt cactactgct gtgtgtgtgt 98340 gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt ttaaggcttg tatgataagt 98400 acattctaat gttttcgtca tctcatgatg ttccttttac ttgagccact gttttgacag 98460 acatctgtgt tgatgaagcc tcttgttttc tgcaggtttc caaggactga tggtgatagt 98520 gacacacctg gtgtgtttgt tacatgtcac tgtgtagttt cctggttatc agagtcatat 98580 aaaggctaca gagaaagaca gagggaagag aaagaacaaa ctttggcaaa gcgcagctct 98640 tggacatgta ctgtgtcaag ttaaactaga tgattctttg tcagagagtg aagtgtattt 98700 ggattttacc tgatcaattt tatttggcag acttacactt tgcatcctag ccggtggctt 98760 aggtggtaaa gtatcagaac tgtgtcctgc aagctgtcat ctttagtttg atctgtaaga 98820 gtcccagaga tgctttacgc ctcaagctgc aagtgcaaga gctactctgg aggctgtgac 98880 aggacctgag ggaaagtgtg cgtgggagtt cttacatgtc tgtctcagca gtatgtgctc 98940 tgctcgctta tttatgggac attattagtg ttacagctgc ccacacgtgc atgcctaacc 99000 ttagttatgt ccttgaatag aaacttactt atccaaaata gcattattgt attataaaag 99060 acgaatactg attgaagcgc caatagtagc aaatgagtag aaattaatgc atgtatacta 99120 aagttaccta aatgtgtgtt tatttacgtg tgataacgtt tgtcagaact gaccgcactg 99180 tagtttgagt agagaggcat gaagggaagg cacgtgatgg caatagtgtg ctcgcctatc 99240 atacccacaa tggaatggaa tggagagaat cctgtgcaca ctgaggcagg taatgtccta 99300 cggccttctc ctatcagtca gataatcatc agaagaaccc agggactcac tattgtggtc 99360 ttaaggcttt gtttggttga tctgtggatt ttgggttttt tgtttgtttg tttgtttgtt 99420 tgttgagata gggtcttcct gtgttcctgg ctgtgctgga aattgatatg ggaaccagat 99480 tgacctcgaa ttctgcctgt ccctgcctcc tgaactctgg aattagttgg ccccaaagtg 99540 gagccaatga tcacatttta aaatgagaaa tgaagtaact gttgtgttaa atgaccactc 99600 agtgatgtat ccaagttcac aagctattta gaggccaaac tcaggttgat ttttgtggtg 99660 tttggctctt tagaaacgaa acagcaaatg cagacagttc ttatgagatg cagttgcttg 99720 ctgttcaggc cccatgatca gggcaatatg gaacacatgt aaaggtatac agaaagagcc 99780 agctccacag ggtgggtctc tctctctctc tctctctctc tctctctcac tctcgctctc 99840 ccccctctct ttctctcttt ctcaccacaa agttcatttc aagctgcctt cccccacagt 99900 gagatgtgca ggccctttac actggctatt tgagaagttg aaggcctgtt ttataatcag 99960 aaactatacc tgtcggtgat tagtacggga aagcacaatt caagtgatgt ttcattttca 100020 aagattgaaa aaaggacacc aactttttcc ccccattttc ttctgtttac aaacaacttt 100080 aaggctatgg agttatataa aataaagcta tacaggggct ctataatgta cttggtagat 100140 tgcttgccta gcatgctcga gcaccaggtt tggtttcccc tgttataaac tgtgtatggt 100200 ggcacaacct ttcatcctat gactcaggaa atgcaggcag gaacatcaag agttcagagt 100260 cagcctctgc ccgacagcga gttcacggcc agtctcgcta tgtgcagccc tgtctcaaaa 100320 caaaatgaga cttattttta cttgataaat attgtaaagg aatgtcttag aattcatata 100380 atcagaaatc aacacaggac tctctcacag agaagaaatc ttcagaaaag attttggctt 100440 ttagttttta aatgttaaca ttttgaggac tgatgagatg tcttggctgc tgagtctgat 100500 aactgaattc aactctccca cctctgagct ccatttaaag gaatagagaa cctcttcctt 100560 cctacaagtc gtcctatgcc cttgaccgtt tcaccctctc cctctgtttc tctgtcctac 100620 aagtattagt tggatggaga acccttctag ttagtttaaa aagcatacat ttatgttagg 100680 ttttatatta tgacgtctta acagacatta cactttaccc tggtaaaaaa tgaggctatt 100740 tttcgccatg ttgtttcttg agttgttaag gggccgtgta cagtggtagc tgaggagcgc 100800 tgaggtctaa ccactgcacc atctaaaata gacacagagg gcttccatca cttcccctaa 100860 ggttcctggc ctacacctgc catttcagct cctcttctct tttaaaacca ttttcaagga 100920 gattcataat agagctataa ttttatcagt gctgtcaaag gttttcctgg tatctcaata 100980 attcatgctg tttctcaact tactgattga ctttgaatct ttatattgtc caaatatttt 101040 tttataaatt agaatgtgaa gcttattagt aaattatatg taacataact atttgaagat 101100 gactctagtc gaggcacaat gaccgggcag gaagctgatg agatttttgg gaatgggagc 101160 tgtccagtga ggctcctctt tccagcattg ggcatcgccg cgccacatgg gaagagcagc 101220 agagttcact ttgcttgagc tgtgacactt acctccaggc ctcattcatt atctgtgaca 101280 gacgttagcc ttggctagcc tgcctgtgtt cctgttcacc taggtgtcca tttgtttttt 101340 cttatactgt gggtttttag tattgatgga actcataaag tatacagcac atagattatt 101400 acttttatat ttccctcctc cactctatcc caccctccct cctctcttcc cccccccccc 101460 atcctcctcc cttctctcct caattcttat cctacaccta ggttacatat atctcttttt 101520 ttcacccctc cctctccctc ctatttcctc ccctcccctc ccctcctccc tctgttttgg 101580 gacagggttt ctctgtgtag ccctggctgt cctggaaatc cctctgtaga ccaggctggc 101640 ctcaaactta acagagatct gcctgcctct gcctctctgc ctcctgagtg ctgagatcaa 101700 aggtgtatgc caccatgcca ggctggttat atttatgtct acaggttcag ataatgtgtc 101760 aatagtggtt cccagctcag ctctacctgt tacataagta cctatgctta gtcccaccac 101820 caccctggcc accctgcctt cactggacta tcaggactga gacaaactta ttccagaata 101880 gcaacccatg atacttagca gcagccttca ctgaccagca catcctttgc tgtcctcact 101940 tctgaaagtg cacacacatg ctagctgtgg attcgactgc agtgactttg tcagagacag 102000 cagatggctg agagactgtg gtcccttccc aacaaatctt ttctttgcaa acctcttcag 102060 aactgatgaa atgctctgag agctgcagac cttcaaagag cagttctaac ctgaaaaacc 102120 agttctgggc ttgcattctt gccactgagt atttctatgg catttttctt taacatatat 102180 ttctttgtga cctccttact gttcttcttg tccctggtca tgcctcagta tggtggaaaa 102240 caaaaatagt aaagcaacaa aggaaaacat gattttaaat gtgtacctac ctagctaggg 102300 tttatacaga tagagaggta taataacagc cacttaaggt cccttgaaga tccaacaggt 102360 ggtcatttta ttttagagtc tctttcataa gccttctgat gatcaccctg tgttgtaaga 102420 ggcaaatcag tcattggtca tctggtagag atgggtgtag cagagagctg gctatgttgt 102480 aagaggtggg tcaggcattg gtagtcatta gtagagaggg tggggataat ggagagctct 102540 atggctcctt ctcttaaaag ggataccttt gaacatcctt gtctataaat ttgtgatagt 102600 aacctcccat gagaagagta aaaatcaagc agataccaga cagatgagca tgtgcattcc 102660 cagatgcagt tgctgcgtta ccagaatgag cgtgtgtcct tacagttaac atatccccag 102720 gaggtagcat ggagcctcct aatgcctctc ttcccagttg ggtggccggc tggtctggtg 102780 tagcagaagt gcagagccca ggcttccttc catatctgtg cttcctgctg gaaaggacat 102840 gggaagccgc caaaatttca ccagctcagt ctcagactgg tggctgtgag attttaagca 102900 ggtagatttg tcttttacct caagtctcct cttgattcca ttagatgaac taagagtaag 102960 ccatcaatat tgactatgaa tcacggtatg gctggtccct caaaatgttg gtggatcccc 103020 aaatccagga cctgtcaggg aagctggtct gccttcccca gttttattct cagtgcccag 103080 cccttcttgg aagctgtcag cactcagatt taggtacact agccctataa actgtgtgca 103140 gatagtccaa atcaaaacag gagatagaag atggctcagc agttaaaaca ctcaatactt 103200 ccacagagga cctgaggttt tcccagcacc catcagggga ctctttcatt gtcagagttg 103260 tcccattgag tccctggggc atggatacac acactcaaaa agaaaaagaa agcatttaaa 103320 acacaaaaca aaagccctct aaaatctgag acattgcccc aagcatttcg aatatgggct 103380 gggaaggtgc tatactgttc tgtgcctggt ataaaggttt cttggtctta gtaacaagtt 103440 tgtgcacatt ttgtgtgcat gagccctgtg ctcagattct tacgtgcata tttactttca 103500 gttttcatgt gtatatctgt cttatatctg tgtatctgtg tatcatgtgt gttcctgggt 103560 catggcagtc acaacagggt gtcggattcc ctggaaatgg agtttcagat ggttttgggt 103620 gagcactcca tggaactggt gaattgaacc caggtcctct agaagagcag cagctcctaa 103680 cagctgagcc atttctccag ctaccccttt gtcctctgaa agaaaggaag aaagcataca 103740 gctttgtact caggcatgtt aggaggttaa ctcctaagct gcaaggcctt ccactgtcat 103800 atattagtag catatattca gaatcaggac tgtaagactc caagtcacag agagtgaaat 103860 tatctttaga atgttaaact tagcaagata ggggattatg gtaattttta atttatttta 103920 ggatagcttc aaatgataat ttaataattt aatgtggttt tgttttgttt tgtttctgta 103980 actgtgtgct gataggttac aggttctgtt gtgttgtggc aatctcagtt gaaaactcag 104040 ctctgcagca tgtgctacag agacactggc agtaggtggc cacactgtga aaggcaggcc 104100 atgaggagag agattttact tggtggcctc cggtgttaat gttgcttggc agctgtcatc 104160 tattagtact gtgaggattt cccacgtcag tgtcactgct tgtgacacta gtgttctgga 104220 tctgggatct gccagagtat ctctgtgtag ccttggctat cctggaactg agtttgtaga 104280 ccacgttggc ctcaaactga actctgagac ccatctgcct ctgccttctg agttctcagt 104340 gctgagatca aaggtatgct ccacagtgct aggctgtacc cggggtttct aagttacttt 104400 tcccaagttt taagggctga cgcaagatga cacaagaaag catctttctt ggaagtttcc 104460 agggccagga tacctgcaca taggccacct gctttcatca tgggtggctg cctttccaca 104520 agatcatgct gccttccctg cctttggaca atgagaagcc actctgtgca gatgtggatg 104580 cagatgcgga tgtgggtgcg gatgaggaag cattgtttag ggttgggtag ctgtctgtgc 104640 agaaccacta gctggaagga cattcctacc gcgcggcctg cagtgtggat gctgcacgca 104700 tgtctgattt cctaattggt gttcatctta ctgttcgtcc cactcatgtg caccagtcac 104760 cagggcacag agttttccaa catcactgtt tttctggaaa agtcatttag ctcagacaga 104820 tgcccaattt gtaacaaccc acaagcaatt tattttgtaa aactgattct gccccatttt 104880 cttcacctat aagggatgtt tttgagtttg agcgattgtt catacaactt gggaagaatt 104940 ctatacacca aacatgaccc tttaagaaat ctgattacat ttttaaaaaa gtaatcctta 105000 ttcccctaca gtttgtagga gatctttatt ttaatgtctg agctgaaggc aggctgtgcg 105060 ttttcatggc tttccagagg ctcatggtcg cagccttccc agttagaaat gctgatgcca 105120 catttattat tttccccatt acaggtgaaa tcattagagt ctcacatccc caggcctata 105180 gtgccgctct cacaatgtct gtctgtcatt atgtatgctc actgaaggaa gcaggtgtct 105240 aaacctgtta tattatagac gtatggcttc tgtgctgggg catgtggaga tggtgctgaa 105300 agacaggcat gctcacccac tgtggtgcta gctatgggtt aataagtaca tagatggctg 105360 ccagcattat aaattcaagt caaacacact gctatgggct atacgatcta gcagtgcagt 105420 ggaggttttt gtccatgttg tagagcgagt agccaaggct aaagtttatg ttttgtgtcc 105480 ttgccagcaa taattttcaa ttcaggttta ctaattccct catcagttca gacagttcca 105540 tgacatggga aggaagcatc cttgaaggta gtacctagta ggaaggagaa ggccatgtgt 105600 caatgcccag ttgtgtccat ttgtccattt gcttttattc caagtcttgt tatgtagcat 105660 aaggtattat taaactctgg actatcttcc tgtctcaggt tcttaaatgc taggattatg 105720 gtgttatggg gatggaccac catgctcaac agaatggtgt ttgtatatat cctacatgta 105780 tgttagcctg gacaggttag taggatcaag ggtcatcttc tcactaaggt attttaatgt 105840 agtcctgata agtaggggtc tgctaaaggg ctgcagaatt gtgaagctct acaacacatt 105900 cagactgaat accctacaga gttgccagag gaggatgtag ttggaggata aggcaagagt 105960 agccttctga agtgtgccag gtggtagtgg ggactaagag gacaaggtgg gggcagggca 106020 ggatgtaagt gtgtgcatgg gttgatggga gtttaattgg ggtgctcaga ctgcatgtaa 106080 tcattccatg ttctatgaaa catctgattt tgtttacctt gactgttcag tttctatgtt 106140 ctagattatc ccactttcca cagctaatta gtaatttttc tatcttgaca aagataactt 106200 ggtgattttt catagtagca tcattcataa tagctccaaa gtgaggagaa ttcagatgtc 106260 cattggctga agaacagagg aataaaatga gctacaaaca tcaatggaat gttattcaag 106320 aatgaaaata atgacgtaat gaagcatgct gtaaggtgga taagtcccag aagcattaca 106380 tgtgcaggat gctatttggg aaagcatgtt tggtgatcat tccatttatt acagaatgcc 106440 taggaagggt aaatctgtgt tagagaaagt agagtaatgg ctgcccaggg ctgggacggg 106500 gcagggaggg atggagctga tgcctgattg gtgctgatgg catggggttt cttctggcgt 106560 gtgtgttata gttcagtaaa tttctttgta ctaacaataa gaacatggaa tcaaagtcac 106620 ctacaatttt ttttagaaaa caaacaaact tgtatggtag aatcccacat atggaatatg 106680 tcagagggtc aagtgaggaa ataaggaaaa gcaatgtcag caaaaaaaag gtaaattgta 106740 atacagtcat taaaagaaaa ttaacaaagc cacagaaaag attatcactt acagatacaa 106800 cctaaaaata gcctttgtgg acagtcttgg tataaatcca ctatcttatt cagttttcta 106860 gcctgaagca ctaaaagaac gccatttgag gccaagagac caaggatttt agaacaaata 106920 ttttattata tttttcaaca tttaagcaaa attcaagatt agtttcattt aactgaacaa 106980 tttagaaaat tgcctatctt taaagaaaaa acaatgaagt tttttaattg atttttgtta 107040 aggttagata caaaagagaa agagcttatt tgttaatgga aacaataaga gaaggaagct 107100 gtgctcacat aacaaggtgt cggaagcagc tcagccagga gtccttcagc ccttacagac 107160 tctttctgca ggcacgcatt gcaaagcatt tgcttgccct gcttctcatg tgttnnnnnn 107220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 107280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnntcacac acacacacac attctcacac 107340 acacacacac acgcacgcgc acagcagacg acaaaagaga ggaaaggctt gctttgctcc 107400 cagtttcaga agttccagcc tgtgggagtc atccagaact cagcagagca gaagtgtgtg 107460 gcagaggctt ccatgtcacc aagtccattg aagcaaggac caagttatgt ggccttcaga 107520 ggtccaaccc tcctgctcgg cttcctccag ccacaggctt acaaaataat tctaccagct 107580 gggaaataac ttttcaaaac tatatgagtc tgtgaggtgg gggagggtct ttcataatca 107640 agccaccatg ttctggccct ggttgccaag acctgaccat gtcataatga aaactgcatt 107700 tagtcctcct ttaagaaaca gcctgggcag tttccagctc tgttcagaag tacaaagttt 107760 aaagtctgct gacacttgac atttgttggc ctgttaaagt cgctattctt ctaatatata 107820 gtggtaacat taccattcta ttcaaatatg gaaaaacagg aagatagcaa agaaactttg 107880 ggccaaacca aaaccatcaa gatgcacatg acattctata attctgagct atcgtgtggg 107940 cttgggcccc taccttgtag ccgtctgcag cacacagtgc ccaagatggc tttccttgtt 108000 gcctgaagct ttccttggca aacacccatg ttctggcatc ttaagttcca ggtatctccc 108060 aggtttctct ggggatgtga tcttgatgtc cattgcgtag cctctttaaa atctttgtac 108120 aagtacactg ggtacccaac aacgccacct ggatgacacc aggttctgct gtctgctttg 108180 gaagtggcca ggccacagtg gaccatagca cctgcagcca ctgaatgcct gaatgacaac 108240 acttggaaaa agactttcct agatggccgt tttccaataa ggcaccccaa tcacagttcc 108300 ttttcacgta ggtcttataa agttttacat cttgcccatt tagaggccag ctcttgctac 108360 ttcctgaagt actcacacaa taccctttct gtggtcccat ggcagggatc ctggcttcgt 108420 atgtggtgct aatctgttta gtaattgcag atgcttgccc atacctcctt tgtcagaaat 108480 tttaaatgtg ctcacattct tttcctggcc atttgtatat ctatcacatc tttatgttct 108540 tttttccttt ctgttctgac tgtaaaccta agtgcagcca acgataacca taccagaccc 108600 agaatcctat gtattctttg aaatttcctc ccaagattaa tctattcctt tggaattagg 108660 ctgcacaagt tttcaggata cgggcagaac agggacagag ctccccctac ccaccccacc 108720 cccccaatcg tgaagtgagt agcctgctgt ttaatgtctc atcaacgatc ctaagatcac 108780 agcttgtgta ggcatcctgg tcctctgaat tcctagtgat cacccatcaa actctaccct 108840 ctgcatgcta tagttttcta gcctctacct ccagagcaca gcaaatcctt cttacaaatg 108900 tgctctcaaa gccttgtcag gcttaactgt agcagccacc tagctcctgg taccaacttt 108960 ctgtattagc cttcgcatga gtcaaacaag acagctcaag agagagaaag ttgtttgggc 109020 tcacagtttg aaagttttat gttcatttct ggtgggaaag aaagatatgg cagaggtcac 109080 agtgaaagaa atatggggtg aagagccttc acatcaagcc tgaccaggaa gcaaacaggg 109140 ctaggttcca gctttcagag gtttaaccct ctgagcaatt catccctgct aggctttacc 109200 ctctcaaggt tccgaacccc ttagaatgga ctagcacagc cagttgggaa gaggcactga 109260 acatgggaac ctgggagaga atgtttcaca ttcaagctga gacatctgct aagctctgct 109320 cacgaggagc ttaagatcat taacaggtat ttgcttagac agtgttttgg ctttagttta 109380 tattttattg tttgtctcaa ttttaggagg gtttcactta caaacaaaag caaagtgtga 109440 gttaataaaa attaacagaa attaaacaga aaactacatg tagtagatat aggtgatact 109500 tctgagttta aagaagttat ttttgtagta tatattgtgt gtgtgatgta tatgtggacg 109560 ggttgggcat gccaagtatg agtgtgcttg tcagaggaca gtttggtgaa gacatttata 109620 aacaccaggt gggacgtctc acttgcctga cctctgcttt attagagttc aagaggtact 109680 caatgcctag tgagtgcctg tatttaaatg tggaagacac aggtctttgt cccattggga 109740 ctttgtgtcc taaactttga gtttgctgtt ctttagtctg atcctccgta tcccagccag 109800 tccctcatct caaagcctgg acgacgtatc tgagtttcct ttcctgtctt tttaattgca 109860 gtgctgttat gggtcctgcc ctaattccta atttaggaat ttcctaattc ctcccttcgt 109920 attcatttaa tgtaggcata cccctttcac tgcagcagaa gacgcaggta ctcaatgtga 109980 aattcttcat caaagtaact gtgtctctga caattagaca attcttctca gtcaacattt 110040 tgccctatat tttacattga tggttcacaa agttatatgg gttttttgga cagactattt 110100 cagcagtatc agtagccata caacctttaa ttttcaaaag ttttgctgct taaacacaca 110160 aatcatggtt atctacaatc tggggttttc attgtagaat atgtacactg cagttagcat 110220 ggccccatgg tgtgatccag ttcagctctg tgttggagtt ctatttaatc aggaagggaa 110280 aattttctgt aagtctaaga aaacccttgc taatttagaa acaccttttc aaatgttctt 110340 ttctttcctc tgctgacctg gtcttgggct agcctgctgt tttccttcac cgtcatggct 110400 cctgagtagg cgctgaccat ttgtattact cagggacatg cagctatcaa aaggactgtg 110460 cgtggttctc ttacataatt aaggttctct tgtacagtta tctgtagcct gtgtttaggg 110520 gaaattttgg taaatacagc tctgactggt cttagtcctg tgtaagaact atttctcccc 110580 taatgtagtc ccattaggcc actgaattta tggtggcaat ttcgttttac tggttatttc 110640 ttctgaataa ttgtttgaca actgcaaatg aaagaagtga aatagaataa gagggttttt 110700 ttaattgtca tggttacgct taggcagtct gggtgaaaag gcccttcctg gccagtggcc 110760 ctctatgtaa tagtgaagag cctgggactc tgtgtagacc aggctgacct caagctcact 110820 taaatcttct agcctgttcc ccatgagtgc ttacactaag gcttgccctg ccttatccta 110880 gcttctaaat tttatttaat ttttgttaga gacagggttt ctctgtatag ccctggctgt 110940 cctggaccat agaccagact ggtatttaac tcagagattt acccaattct gccttttaag 111000 tgccaggatt aaaggggcat accaccatgc ctagaatctc agacattata atagacagaa 111060 gttctttttt tttggtaaga tttatttatt tattatatgt aagtacacta tagctgtctt 111120 cagacacacc agaagagggc atcagatccc attacagatg gttgtgagcc accatgtggt 111180 tgctgggaat tgaactcagg acttttctct taaccgctga gccatctctc ctgcccctag 111240 acggaagttc ttattataac tgattccatc tgaggatctc agacccactc tgcagcccag 111300 atctgagtca gggcccctgg agccacagga ggaaagccca ggcagaacca ggctggaccc 111360 agagatcaca cactttcaac ctcatatagt ggattgctgg gttattaagc aaatcttaga 111420 acaattacta tattaaaata gccagtgtgg gagtgagaat tatttcgagg aatttctcaa 111480 acctttttgc taacagaaga aaaggtgtgt acacacacac acacacacac acacacacac 111540 acacacacac acacaccctg agcttctcag tgatgatgat cttacactct gcctactgga 111600 agctgttaca ctcttacact ctgcctactg gaagctctta cactctgcct actggaagct 111660 cttacactct tacactctgc ctactggaag ctgttacact cttacactct gcctactgga 111720 agctcttaca ctcttacact ctgcctactg gaagctctta cactcttaca ctctgcctac 111780 tggaagctct tacactctta cactctgcct actggaagct cttacactct tacactctgc 111840 ctactggaag ctcttacact cttacactct gcctgctgga agctcttaca ctcttacact 111900 ctgcctactg gaagctggtc tttcagtgag ggaaagttgg acctggattc ttttctaggt 111960 gatttaaaga aaagaaaaga aaagaaagaa attgttttgc aagattttat tgttgtgttt 112020 caaatgcttc ccctacatgt tgcttttggc acaaaattac aagttgcaac tcagacttct 112080 gaggtgtgtg ccaaccagtc ctcagccact cctaccttca tttaaaagct agaagtgcct 112140 ttttgtgtgt gtgtgtctat tgaaagagtc tctgatttat aaacagttta ggcaggtcac 112200 agattgactt taaaaattta agtcaccaag ataaagatgt tttaataaaa agcagaggta 112260 gtgatataca atgtggaatt tgctttgtaa tgatcagatt ttactgtttt cttaaagacg 112320 gggaagtcgt gacatttgtt tttttcagtg caattagtaa attagtaagt tattaattca 112380 tctctgaggc tttgaaaata aatagataga taaaaataaa cagctccaaa gaagatgtat 112440 ttgggaatta ctattctttt tgtaaacatt accatttatc ttcatgttct aacttagcac 112500 ccacctgtca ttttctggga ctttgatttg gacggttgta atataaccct tgtggcagat 112560 gtcaggaggt gggggaaagg gaagacctgc ctgaaggtcg gtcccagagg agactgctgt 112620 taaatctgtg gtcagggaaa aaaaatgctt tacgccttat aaaatttgcc ttatcaaagg 112680 ggggaagtga tgatgtaaac aggaaactga cagtgaagag cgaaggcacc agcagcagcg 112740 ttggcggcgg cggcagcggc agtagacttg aagatgaacc agacactgct ggggataggg 112800 tccagaggaa gggtagggtt atgtgttcaa agcatgtgct ttgctttgac agactctggc 112860 tgaattttat cctcctttca ggataaagtt tagccatgtc tgtgcctgta gaaaaatgct 112920 agctagtgtt gaaggtttag gacaatttaa agatgggagg gcagtttgag agcacaggct 112980 gcacagggaa tcacacttca aacccaggaa agtagtggct aggaagaggc ccacacggtg 113040 cagtcatgtg accacaaata ctgatttcct ggtgtctatg tgtttgtgta gtctctacaa 113100 cctcctttct tcttcagcct actaaactca tctttctctc atctccccct cccccctccc 113160 ctctccccac ccccccaccc ccttnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnaag ccttgctgct ttgtgaaggc 113340 gtatctgttt gcagaggtag cagtaaggac ctggccaccc cactgtggct gggtgtccct 113400 gaagctggag cagaggagca ttgccgtgcc tctcttcctg cactgctata gaaagctcta 113460 acttacaggt tctgagaagc agttactcac agtagttctg gaacacacgg ccaagtcctc 113520 cagcagcacc atttaataac ttaccgttct gaaaagtatt tgttccctca aactctttat 113580 tcaggtttta ctttccttat ttttgctgtg ctgcagctta tacctaggcc ttcagacatg 113640 ctatgtaaat acccttctct actcagtcct agtccttacg tataacttga ttttaaatga 113700 ggaaagaacc gctccttctt ccagtatcag gaaggaaagc aaacataatg gcagcttact 113760 tactgcccag ccctcacata agccgcaccc ataggtgcag ggtacccttt ggggattctc 113820 agctgaacca gtgccctctg ccatgcttca tgctgggctt ttcttgctcc catttctttg 113880 attttattct tttctcttag gcagaacaca tggcagatct gcagtcaggt gagaagctgt 113940 gtgtatttgg aagagctcct ccatgctttc aaagttttaa aagtattttc atgtcttgtt 114000 ttttttaatt agacaaaata tattccaaca tatatttttc ttttattgaa gatgacaagc 114060 ataaatttac agaattaggc tcttagagta cattcattag agtttcagtt gataatttaa 114120 tgtgctttga aatctcacag caattctcta ttttcaataa atatgaggta ggtaattcag 114180 cattaagtaa ttgctcacag gtatatgttc aagataaacg agtgcaagca taatttcatg 114240 ggctttttta ttaactctgg gagcatgttt gtcagagcag ataccattag tgtttgttga 114300 ttgggcagat agtaaaatag gcttgaatat gtatcataaa atcagtatag gtctcctcac 114360 aagttttgat tttgttgctt taaaaaagat tcagagaatt aggttggcca aagaaggaag 114420 actttcttag ttttagtgtt gttttgtttt agaatattgt ccatttgttt agcacagaca 114480 gggacattct gaacataatc tcgagtcagt taggatatga catccaccaa ggggtcctgt 114540 gtcccacggc taccagtgaa gggagcgaca ggcctgtagt cctgttgtgt gcagtgcttc 114600 actcatcttt gttttagagc ggggaagcac taggcatttc tgtaccaaca ctgagcgccc 114660 gggcctggga gatgactctg ctgtcgggtg atcatggaca ctgctgggac cctagtctag 114720 gttctgactt tctgcagctc cttaaacaaa tctgctgttt ccctaattgc ttttctaaat 114780 aaaatgtttt tatgcattgc tgttcataaa aatgataggt attgaatctg tcagtcagtg 114840 attgagtttc agtgaatatc tgagcatttt tttatctgag aaactataat atccataagc 114900 tattacatgc caaattacag tttttatata gacacatgat ggaacctagc ttaatttgcc 114960 attaaattgg aatgtaagtg cattatttta tatatttgtt aatattaatt attttaattt 115020 taagatagag tcttgataaa tagtacagac cggccactcc cttcctcctt ctcccaactg 115080 ttaggttaat actgtgttct cccaagcctg gggtgtggtt acaagtgttt gctgccgtgc 115140 ctgatgggaa tctttgaata ttaacattta agctgacacc ataactttat tcaatatttt 115200 atcatgtttc tattttggtt tttcaagaca gggtttctct gtatagcccg ggctgcccta 115260 gaactcattc tgtagaccat gctggactcg aactcagaaa tccgcctgcc tctgcctccc 115320 aagtgctggg attaaaggcg tgcgccaccc ggcttttttt ggtcgtgttt cttagtgcag 115380 tgctccagca ttgttttggt gattgacatg gctgtgtgat tgctgtcgac catctatctg 115440 cattccatga ttgcagatct atcatttaaa ccaagcatgt gcacaccgtg aacaaaatgg 115500 caatggcgag gttgaagtta tgagaaagtt ctgccaggtt tactttaaac tataactgcc 115560 acttagaata ttatggcagt gttaaaagtt attttgccca gcagtcatga ggcagcggca 115620 ataatatgag ttctagtctt gattgggcca catagcagta cttcactact gtcagtttgt 115680 ctgcctgtcc tagctgcttt cctgtcagtc tgcctgactg tcttctgtct atctacttct 115740 ctccttcctc tgctcacacc tttgtctttc tctttgtttc tctctctcac acacacacat 115800 ttagacaaaa ggtcaaacac tgaaataagg aaatattttt attatagtgt tacagggaaa 115860 tggtaggagt caattttata aattgatttt aaaattacct ttttgcctta aaattttcag 115920 aagtgaatat atcaacttaa atactatgtt cctacagtaa aaatatgcaa gctcggggct 115980 ggagagatgg ctcagcactt aagagcatta attgctcttc cgaaggtcct cagttcaaat 116040 tctattaacc acatagtggc tcacaaccat ccacaatgag atatgacgcc ctcttctggt 116100 gtgtctgaag acagctacag tgtacttgca tataataaat aaatcttttt taaaaatatg 116160 caagctcggg gcagtgggtg ggtaggggag tgggggggtg ggtatggggg acttttggga 116220 tagcattgga aatgtaaatg aggaaaatac ctaataaaaa attattaaaa aaatatgcaa 116280 gctctttttc tttcttttct gtattttcct tgtacatttt tatatggaaa tgataaagct 116340 acccgggcgt ggtggccgtt cactgtggag gctgaggtag gaggatcata agtttcagac 116400 cagctcagac tcccaagtga gactctgtct cacatttaca aagaagacat tggacctgag 116460 gactgctgag gtggttcaac ccactaacat tcttgccatg caagcatact gtgtcacaga 116520 gaactatagt gagaggaagg acagatagtc ggtcatagtg tacctagtag aagctcttgt 116580 atctaactga acccacagat acacagtgca caaatctgtg ctgccagtga ccagattgga 116640 ggtcattaaa tgggtgtaaa aggccaaaga atagcaagaa aaatagagtg tgtacggcct 116700 gtgtggtagt tcagcaggta gtgctgcttg ctgatgtgtg cctatctgag gtccacatca 116760 gggcccacat agtgggagca gagaactata agttgtccct gacacatgta cacacacgca 116820 tgcacacaca ttatttaagt gtaaaagaga gtgtaaggca tattgggagg tcttaaacag 116880 acttacatgg tctattttat gttagctttt gtggggtaaa actcaaggag acaattgtgg 116940 gatccccagg tcattgcagt gcgtcaggga tgaggtgaag atctgtggcc ctggaggtcc 117000 actgcactgc tgttgttttt aaaagatttg tttattgtat ataagtacac tgtagctgtc 117060 ttcggacact ccagaagagg gcgtcagatc tcattgtgga tggttgtgag ccaccatgtg 117120 gttgctcagc tccggacctt cggaagagca gtcagtgctc ttacccactg agccatctct 117180 ccagtcctct gcactagttt tgttttgttt taaatactta ctctaattag caattttatt 117240 aacttttcaa atttttcctt taaaatttta aaacattgtg tatttatata tcagatatat 117300 ttgtatgtgt ttgctggtgg tgtgtgtacg tgtctgtctg tctgtcttac tgtctcagag 117360 gggatggctg actctaccac atgggtcctt cagatagtct ggcctgggaa caagtacatt 117420 tacctgctga gccaccccac cagcctctac tctgtgtgtt actcatagaa tagagacatt 117480 ttagaagtag gattattgaa tgacattcag agaagaggcg gcccaacagt taaatgcact 117540 tgctgtcttg cagaggacct actgttcaca atcatttgtg attccagttt tagtggcctc 117600 tgtgggtgtt gtggtcaaca tggtgcttat atatacttac atgtaggtag ataaaatact 117660 caaacacgga aaataaacag tctatttttt aaataaacag tcattttttt atttctgtag 117720 tcactctgtt ttcattaggc aaaagcagcg tccctgctgg ttgccaagga ggaaatgagt 117780 cttcgtaagc aggccttgta gtaaatgagg gtcttggcat cttttgagaa cagccttgta 117840 aatgtctgtt gggtaataaa caagttctac gcagtcttct tgtatagcaa caaacatctc 117900 ttcactcatt ccacataaca gccacaaaga tcctgtcaga agatggagtg tttttcatcc 117960 tattggaatg gatcatggtc agtgatggcc catgttggag ccccagctcc acacagacct 118020 tctgactcca agttcactgt tcttctgttc agttatatat aacacaagaa aatgtgttta 118080 ttcaaaaacg ccaaggataa actttaaact gtctattacc atatgcattt attatacatt 118140 taagcagagg acatttattg aaccccaacg acttgtaaaa tagtgttgaa gaaatttatg 118200 atatgcattt aaaatcaaca tacacagcaa ggagaaaaga aaaggagccc ttagcttcat 118260 ttgtgcacct gtgagttatg tcttgtgctg gcatccagca aatgctcaga gagagaatga 118320 gtaagctgga gtttgggtga ggtggttaag ggggccttta cataaaaaga aggagacccg 118380 gatttagcaa gacagtgaaa ctgcaatctc agaggaaggc actacgagag agagacgtaa 118440 catctgaagc aagaaagagt gtgaccaaag gagggggagc gagcagagcc tacacaggac 118500 tttgagtaaa gcagcaagac tagaaggagc cattttttac agagttgaca agctgtggct 118560 ttgagctaag ctttggggcc ttttaatttg ggataaagga gttttctaca gcttgtaaat 118620 accatcaaat atttaaatcc caagagttga caagtgtcat tacccaagtg gtattttatg 118680 aagattactt tgctcctggt ttattcagga tgcagttgag aaatggaaag ggaacaagca 118740 gagaaaggga gactggcgaa aggcaatgtg tgggcttaga gcagtagagg tggccttcta 118800 aaaggaccgc gtctctggca acagggagaa ggcttgctgg agcctctcac tgattagttt 118860 ggagaatgga aatttaatgt attgtattgt ataactatgt aagtataaaa acagtaggag 118920 tcatagtgta ttaatatata cttgcttata tgtacacatc tataaagaaa acacagacag 118980 gagccaccgt cgtccgttgt ttggatcatg tagtgctgag gtggataact ctccctgcct 119040 gcatttggtg gataactctc cctgcctgca tttggtggtt ccttttttca cctcctttga 119100 catcacctct ccaaatctgc cttcaaacac catcactgag tgtcaggact ttaacttgtg 119160 caggcaggtt ggtggtcctg aaacttacag taatgttttt cactctcccg ttcggtggat 119220 tactcgtaca attctctttt ctttttatca gagacaattg ccatagtgaa ttcattgttc 119280 agtgtaccaa gatcttaaag tgttccaccc actgtgtgcc cagttattga caccatttga 119340 tttactttaa ggtgtcactt gctgggctgt tttgtaactt gctttccccc taatacttct 119400 caaggtaatg gccacgtacg tgtagaggta ggctggtgct ctgcggcctc cattgtgtga 119460 atgcattctt catttggctt tgctccttgt cagggttggt cctctgcatc ttgacaaagg 119520 gcctcattct gcctgctcct tgaacaccta tgaggatttc cttggccatc acctagagaa 119580 gaacactccg gggataggct acagaaattt tccactgtaa ccggaagtgc aggtttgcat 119640 ttggtattta agacattttt atagggactt ggcatgggaa gaatgggaaa caatatcccc 119700 ttgatgcttt acagtggatt ttggatgctg ctgagactgt ataggggcta tttttatttc 119760 ttttttggaa ctgttaacac aatttgcgta ctttttagtg tgttggcttt tctggatgtt 119820 gatacatttt agatgtgtca ggttggagtt tttaagcttt ggttaaactc tgtacctatt 119880 cttctgattt ttctaactat tccaacatga atctatggag ctgcaggaaa aatgacccta 119940 atcaactgta tctttttttt tttttttttt ttttttggtt ttttcgcaga cagggtttcc 120000 ctatagccct ggctgtcctg gaactcactt tgtagaccag gctggccttg aactcagaaa 120060 tccgcctgcc tctgcctccc gaatgctggg attaaaggta tgcgccacca cgcccggcta 120120 tcaactgtat cttgatagaa agttgaatgg aatgtaaata tctgagggga atcccagatt 120180 cagtctcctc aaaggaaata agggttttcc tcaccaggac cttgacgtgc tgccattact 120240 aaaaacttct tggaggccat agacaatcgt ggattagaag attctaactg ggcacttcct 120300 gctcctaccc acctagactt gcctgcctct gttgacatgg ctgcttgaat aggcatgagg 120360 tttagcaaaa tgcctgtctg gagtctgcca atgcatgtgt gatagctgtg agtctggttg 120420 tttagttata actaagagga taccttgcag ccatgttgcc agttaagatt gtcttagaaa 120480 tggctgtgag attgcttcga aggcctggga gatatatgag tcaccatagg cctgggagat 120540 acatgagtca ccaaaggcct ggggggatag gcaggttctt tgctatggtt tttctcgtcn 120600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 120660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnng agccgggcgc ggggcgcagc 120720 ctttagtccc agcactcggg cactcgggac gcagaggcag gcgggtttct gagttccagg 120780 acagccaagg ctacacagag aaaccctgtc tcaaaacaaa aacaaaaaga gttagcttct 120840 gggctggagg tgtcaccaga gacagagccc ttcctcatga gtaaggccca agcttctgtc 120900 accagcaggg caaacatgta aacacacacc tacctcccag tatgttggat agttcaacaa 120960 aatgttcata actttcttag agtaaattta taatacagtt tctatatcct gataaacaat 121020 cgcagtcctc agttgaggag gaggaaagtc tcctggtttg taatgtatgc ctctggcatt 121080 ccccggccat cctatgagta ttttgcttgc ttttgatctc agaggttgag gacttgggcc 121140 agtgccgctt gtttgattgc tgttggaatc tatagttctc tctcacttgg atttccagcc 121200 cagctcatca ctggctttct cctttttcat gggatcatac ttttctctga tttgacatga 121260 atatggtatt tttatatgtg gatcaattta ggagcatata cttatttggt gatatataag 121320 ggtatactat ttactatatc atatactaac gtaaatataa gtatattttt tatcttgttg 121380 taaagttaac ccctccccat ttaaaatcca ttgtgacata cattcagtgt cattaaatat 121440 attaatgttg ctgtatagct tctatctccg gccatctcta gagtttatct ctcagagctc 121500 caactttcaa gtaggtaagg tctcttccct tttctggcca ctgtttgctc gtgcctaggt 121560 acttatcttt cacccctcct agaccagtgc aaagcatgtc cccatgtggc aggaactcaa 121620 gggctcattg aggctgtccc tgctgccctg tgtctgaagc tgtcaccacc cttgacgggt 121680 tctctctcca tatgacagtg ctgttcgttc tgtatgggat gtgcttgatg atgaaggaat 121740 agtccctttc tctcctgcca tgctcctccc ttgatgataa tggactggac ctctgaacct 121800 gtaagccagt cccaattaaa tactgtcttt tgtaagagtt gccttggcca tggtgtctgt 121860 tcaaaaacta agatgccatt tttagataga aatctcattt atacccgtcc ccctcccccc 121920 ctccccctcc cttcccttcc tctctcctgt gtgtagatgt gagtgtgggt atgcctgtgt 121980 gtcatcctgt gtgtagatgt gagtgtgggt atgcctgtgt gtcatcctgt gtgtagatgt 122040 gagtgtgggt atgcctgtgt gtcatcctgg gtgtagatgt gagtgtgggt atgcctgtgt 122100 atcatcctgg gtgtagatgt gagtgtgggt atgcctgtgt gtcagttctg ggactacaca 122160 cccagggctt tatggctgat aaaccagtgc catactgaat atcatcctct ggctgcagat 122220 ctgcttctta aagaatggat tctgtctcaa aagaaacgga agtattggtt atattcttaa 122280 acaaatagac aacctttagt atctacaaaa aggatataga ttctatcgtg ctgatttgca 122340 gattcttagt taactgtgtg attgtgcttg tcagatttat ttaacactgg cagttatgct 122400 attgatgtat ttactacaat gttgactgta tgggaagaga tggccctggg ttttcattca 122460 actctgccct gccgagtcgc agtcaccact gacttgagaa tcccacttgc agtgagagca 122520 gctatacgga gagcagacat actcagcccc agcactggtg agagctgggg gagggctgag 122580 gcagagggtt atgagattcc aacagtagct gcatagctgc acagtaaaat gtctcaaaga 122640 acccaaatca ccttgcctgt tgtggccttc tgagcagttt ccatgtctct gcggtttcta 122700 agctactgca tactggccgg catttggttt tcttatagat tgctttggtg agtgaggttc 122760 tagcccctca tggtaactga gacattgggt ttaaggggag gcgtccgagg aggagttttc 122820 tgtctacttg tcatccccct gtctttgact cgtgtgtaac agcaggtcag gctcctctct 122880 tctcgttggt gtgtttttct gtgtgtgggg cctctcagct gtgaggcttt gaagcacgtt 122940 tgtactgcag tgagcagggc aagggcccag ctctgtaatg gcctcttact cagtcattgc 123000 ttcactgtgt ttctcataat ctgaagtttg ttgtcagtag ctaagactaa attctattcc 123060 tagttttgta tatttaaact atagcagaat ttatgtacaa aatctctata taattatttt 123120 tttcatttaa gaggttacag atagcccctt tctctcattt cttttacaat aggtaatcat 123180 tccttaagaa aacttgaaga ctctgtaata aaatgctgtg actgctgtca ggtttgagtc 123240 atatctcttg tgttgctgtc agaatacaaa gacgaataaa aacaagagac tctgacatca 123300 gactcaccct cactgtgctg gtcacggcca tgtctgcagt ctaccgaggg taagatacat 123360 ccgtagataa tagcaggctg atacagagaa agccacagtt tttctccttg gctgctgagg 123420 cctgaggaaa gggctgtgat ttagagagaa ctcctcagat ggtgggcatg gagatgataa 123480 gccttagaaa gactgcgggg taagctctta atcccaccag gcgagagtag gagtactacc 123540 acaatgtcga accaaatttg aagcaagctt taaacaaata ctgaccagga tgatggcccc 123600 tggcaaggtc tactcctggg ttcctagaaa atgttgatga gtcacatttt gcagaggctt 123660 aaaaacccat aaggccgtgt tttcccacca ggtccaactg ggggcaagca tgtatcctga 123720 catacttcct gcttgtgtat ctcctgcgtc catccaatca ggggcaagca tacatcttac 123780 gtacatgtga tcaagcacat tgacttcaat tggctcaaac agacttgttt agggaagtca 123840 aaacatgggg cttgttatcc tccctaaaca atagcctcta gcatttgagg aagtatctgc 123900 ccttgagcaa ggggcttaca agttagagaa atgttatttt atggaactct taggcacagt 123960 aattaagact ttggctctca cagaggtcat tatagtggaa gcagatagaa agcatgaaca 124020 gttagtgggc cagaccaggc tgatctcaga caacacagca cagggactgt ttgatggatc 124080 tggctggaaa acgaagagtg cacagcttcc tcagtgcagc ccctgtttgc tttgacagtg 124140 agaaaaagca cttgcgctcc tgcagtgtgt ggtgaactgc agggaaatta gcactgtatc 124200 ctctggccat ttctgtcctc ggttacactt gaaggatatg agacaactac aagttaaacc 124260 aaagtaacag cactggacgt gctggtccac acagaggccc aggaggggga agactgaaga 124320 tagcactgcg ttcagcgaga agaccctgct gctgtgggag gtggctttgt gagaagcatt 124380 gaagagaagg aaatctggga catccgagga gcaacagtct taaacagatc caaagttctg 124440 gaagtgggta ggcttcacag ttgaaggagg aaagggtttg taagaaattg tcagttgata 124500 gagtggggag cagcaggcac cagaaggttc catagacatg taaggagatc tattttggac 124560 acttccagtg agggagagaa atgtgggtga gaggctggaa gtgggcactg gaacttacgg 124620 tgatacccga agctacaaat gtaggggcct catttgccta gacactatca ctgaaacgtc 124680 agccatctgc gtgctgattt caaggagtgg ctttagagca ggaagaattg tgaggctcag 124740 ggtcacagag gcaaaggtga gggaggagag agcctgaaga caggctacag ttctgaccga 124800 gctggcttgg cgtgacttgg agccctgctc actctgtggt tctccaggag ccagtagaat 124860 aaattggctg ggtgagatgg gtgtgctgtg gctagaacca tgctgctggt ctggacggga 124920 gaaggcgtgc atgcacacac acacacacac acacattctc tctctctctc tctctcacac 124980 acacacacac acacacacac actctctctc acacacacac atactctctc tctcacacac 125040 acacacacac tctctctctc acacacacac actctctcac acacacacac actctcagac 125100 acacacacac actctcacac acacacactc tctctctcac acacagacac acacacacac 125160 tctctctcac acacacactc tctcacacac agacacacac acacactctc tctcacacac 125220 acacacactc agctgccttt tctgctggtg ttgaagcttg tgttcaagca tcttactatc 125280 tctagatggt catgtcagag ggccaagact tcactgtgtg caaatcctct gcagtgcaca 125340 catgcagcaa gtcttgattg atcaatacat ggaaatgatg gtatctgcac atctgtcctt 125400 tgtcactcag tgccctccaa acataatctg tagagtccag tcaaccttta taaggaagac 125460 ccgagtttgg ggttcgcttg gtgtgtgttt aacttctgtt cttgctagcc tgatcctaac 125520 tgaacttcca acatcttcaa agccccgttt tcccccgctg cagcatagaa gagagcagtc 125580 atgttgtctt ggctgttgag aggattgaag aaggacagtg gcagagcctg tgctcactcc 125640 agtctcactg gctgtgaagt gttgaatagg cctcactcac tgaggtttag ttttgtcatc 125700 tctagaattc taggggatgc ctgagctcac tttggtttca gaggaagtac cagccaccat 125760 atgcacaggg cctggctgct ttcctcttcc atgccaggca ggagtgcaag ccaccgagat 125820 ctctgtgcag cgtataagag cagttctgga tttgaaccta cgcagtgagg cttggtaatg 125880 acttcacttc tctgtaaact gggaggagtg ttgctatcca cttcacgtgg tcctatgaga 125940 acaatagagc aacacattgt gcactgttag caccctgtgt gccccactcc cacccctcac 126000 tcccgctagt tgtaacctaa tgtaaccatt atgagggaca agttaatctg taaagaagga 126060 ggcgcttttc taatgagatt ggccatgtcc aaagggggaa atgtaattca accacaataa 126120 tgctctttgg tggttcagca tgatgggtgt tgctgtggcc gggtcttcca ggtacaacag 126180 aggaaagact ccatctggcc tctgggctgg ccagtgtcct cctcagcaat ggcagtctgc 126240 agtctgactc cacacccagt ctccttgtcc tgccagctgc tctctaggaa gtgttgggaa 126300 tgtggagcat aaagattcca gagaggaata atgctgagtg gacaggtagc ctggaacagt 126360 ccaatctggt accttccctg actgggaaag gctggcttta ctagcaaacc acttttcaaa 126420 cagaactcat gccttaatcc taccaaggac aaggagcgct ggtggcttat gggaggagtg 126480 gctaaagcag taagaaaagg cagctactgc tgtctgcacg ttcaccctgc atccctgtgg 126540 caacctgcat ccctgcagca agctacccag actgtagtat cctggaggac cccccccccc 126600 actccagctc catttgatca cagagaccac ctggaatgct agcaacctag agggaagtga 126660 gaaaccacag acaggttctg ggaatgacct agcagctgag tcctctgtgg aagggagtgg 126720 tgagacttaa gcgtacagca gaaggattcc ctggggcagc acagccctga catgcaaagt 126780 cttgttttgt gtctttgaat gaatctattt tcccatgtta atctattcag ctggcttgta 126840 gaaaacctac atgcatttgt ttatttgtgg ctcacttaag aaaactctga cttttgagat 126900 aaatttgttc tctgggcttt tcatgatttt ctgttgctta gttggcatag tgttttgatc 126960 tctttctaga aagttcagca gaaaatacaa attttgagca atttcactta tgttttattt 127020 cttggggtgg gtgtatgtgt ggccttcaag tatgtgtatg tatgcatcat gtgtgtgctt 127080 gtgcccttga aggtcaccag agggcatcat gtatcctgag ttggagtact aatacctgct 127140 gctgagccgc tctggatgct ggggacctag gccctctgga agagcatcac cacctcttac 127200 ctcctcagcc atctctcctg cccattattt cagtagtgac cagtaggtta gcatcaatca 127260 ctagaaactt gggtgccggc tgtcatcgac ttttgtacag tgtgttgcct tttggcctct 127320 cagatagaac attgggggtt tctaatcact ctgaccacta agtcccaggg gatttcttct 127380 gttttgtttt ggtttggttt taggactccc tgtttttgta gctggagaga aacatttcta 127440 ctgaggcagt agtgttgaaa actaatgaag ctttaagaga acattgaaga gattattaaa 127500 tataaggccc ctgagcttca ggttctcacc atttttgagg tacagctttg aggcattctg 127560 tacacgtccc ctgccatgca gccgtgtcag gtgtctgggg tctgtgtcct ccccagctgt 127620 gagtgcatcg tgacatcccc agtcttctct ccttcgctgt gccagccagt gctctagttt 127680 ctgccattcc aggcccctca tgcccaagga atgacacggg tcttggggat tttccccatt 127740 ggcttatttc acttagcgca gtgtctttaa aggtaagtct ccattctgta ggtgactctt 127800 acatctgctc gcactctgcc ctactctctg ctgtgtttaa cctcccatcc cactcagtgc 127860 tggcctagtg tcatttgaca tagcagcagt gcagaaggga gccagcttct agatcctcat 127920 ggtcacattt tggcctctgg tcttttgata gtcattctca ggggcatgcg ctggtgtctc 127980 actttgcttc tggcttgcat ttctgtggtg attagtgatg gccaaggaga aatgtttgat 128040 caggaccctt tctcatcaat cactatagca gcacctttgt cctaatcatt tgatagatag 128100 cgtatgtgta taaacatgat tctgtgcccg attctcccct gcattactgc tgaggcctcc 128160 tgactcgcca taaccgaatt tcattttgca gataatctct ctgctatggc ctttgtggag 128220 ttttgtgggt cttgttttct gtttgtcctg gagaattggc tcttgcactg tgtgctgggc 128280 tccctgagct gggaggaagg gtttctctgc tccacagatg gcatttttct gctttgttgt 128340 gggtgttgct gggattgcag ctattcccac cttctgccta acaaagataa atagtaaata 128400 ttctagagct atttctagac aaaggagaaa gtgaggagtg tgaagggaag aagcccacgt 128460 tctcaaaaag tattatcaaa tggtgcttga agcagtcgga atcagctcag ctaataaacc 128520 acgctctgtc cactgagaga cttgcgggtc tagagacagc gcaaggcaca tccttcttag 128580 cacccctcgt tcggagtctt gctggttctt gcacaagtta ggaaaagatg aataattatc 128640 tgactctgaa taaatttagt tctcacataa agtaccttct ggtcttttat tctgtttgtg 128700 tggccaacta gtgaacaaag gaaaagtgat ctttgattaa acgggttgtc agtgaaagac 128760 ctaaggagga cgaggatgta tctctgtgga tgagagtgtt ggcctaacat gttcatagca 128820 tcccttttca ttggatggga agatcaagtg tcatcccagt gttttgcact ttacgttctg 128880 tgtggatgaa gttaatacac agaacccaag tgtgaagagc agatcctgag ccctgcattt 128940 gtcatgtaca catatacaca tgtatgtata tgtatacatg attaattaga atggtttaca 129000 ggctgtggtc cagctaatcc agcaatgtct gactgtgaat ggaaagtcca agaacgcagt 129060 agctgctcag tccacaaggc tggatagctc agctgatctt cagtgtacac tggaatccca 129120 aagtagtcaa ctccagtgcc agagaaggaa tggacgtgct agcaaggtga gagcacacag 129180 gcaaagaaca aaagctcctt ccttctctcc ttagacagca gagacctcag cctcctaact 129240 aactctgtgg cccatgaata cagcagtgac ctcagccttc ctaactctgg gacccatgaa 129300 tacactcctg caggtctggg agccaaccat agaaatattt gattgctact tcatagctgt 129360 aattttgcta ttgttataaa tcattatgta aatacttgat atgcagggta tctgatacgc 129420 aaccttcgaa aggggtcaaa cccacgcgtt gagaatcacc tttgtatggg cttctagcag 129480 gtgtattcta tattagatct ggattcgtgg tatatcttcc tacctcaaac taagcagaaa 129540 tccctctcag ccatgtcctc tattttgggg ttttagttaa ttttagatat agccatgttg 129600 acaaccaaga acagccatca cattccctga atgaccaagg attcggggga acacaggtca 129660 aagggatgtg gcaaccttgt ctctaccacg tcgattcttt atagctcaaa gactaggtat 129720 agactagtct cacctttgct tactttgtga gttctaagta acatttttgg aatattggtt 129780 ttttttagtt aatatataaa tagtttaaaa agtaaatact ggaaaagtct tggctggacc 129840 tggaactctc tgggcctggg gatttgaaat gagtgatggc ggctgtggtg ctcatctcca 129900 ctttagtcag acagtttaca gttctggtca gtcagagagc ctcgcaggca tctcagaaag 129960 tgatgagcgt tccctcatca gccctcggag ggctcagcta atccgtgaag cacactcctt 130020 tgacatagga tcatttctga acctcaggca ttcttgaaag cctatggtat aggtttaata 130080 tttcctacac cactaacatt tgtattaatt ttggctacca ggtcacttaa tttcaatttt 130140 agtcctataa ttttgaagaa tagattcatc taaaaggaag tttagattgt ttgcagctgc 130200 accagtggcg agcctggggc tgtggtttga agcttctgaa atcttaggtg aggggcagaa 130260 gctggactgg aagtgcatcg tgcaccctgt gcctgacttc aaaagtggga cttggcagtg 130320 ttgtgtttag agaaagtcgc agttcgcagc ccttctcctc agtcctctcc tgcagtggga 130380 tggactgaga cattcatgca ctgctcttta taggagcgac tgctgaaaat aacccgacaa 130440 gctagcagtc tctactcaga atactgttgg gtcttctata aggctcattt tgctctggta 130500 gaaagaatgc agtccctagt gagtgttcat agggtgataa cccagcagca gaggctgtca 130560 gaggtgagcg tctcacttgc tctctgaagg aaggatgcta gaggctcaag tggctttgtg 130620 tacttccaca tctgctatgt acaggaattc aaatgacatt cttattgcat ttcttacaat 130680 tagttgtgaa actcgttatt gcattttaaa atagatttaa ccagtagtta taccatgata 130740 actactgtaa ctagtagtta taccatgatg atttaacgat aatgatggac gaatgatggt 130800 catgagatta tgagtacaca ctgtttgtcc atccacattc tacaaagtgt tgttcatgtc 130860 accttcagag cttacctcat tcctagtcac acaaacgtgt gctcacagtt gctatggagt 130920 atttctaggt tagaactttt taactttggg atagaataaa atcaggggtc tgttcttgtt 130980 ctgtgtttgt gttttgtctc tgtgacaagg tctctgttta tgttcctggg tgtcctggaa 131040 ttccctctat tccagactaa ccttgcactc acagtgccct gcctgccttg gtctctgcac 131100 tactcccggc accagggatg aaaggtgtgc acactatgcc cagtttgggt tttggggttt 131160 tttgacatat atatcacaga agtccattaa gaagtcattg actttgtttt gtgtgcatag 131220 agcttaggat ataaagacca tagattccca gctacaattg tccaattaac tttacatatg 131280 cacttttatt tttttcttat aattcttatt attttcaaat attatttctc tcttcctttt 131340 gttaaatcag aacattcctt ttgttgaatc tttttttttt aattagttag ggttctctcc 131400 tctctaatga ctgctgttta tttcaagttg acataaaacc agggagcaca cacgtcagcc 131460 taagaaacag cagtagctgc cattgaggtg tcttactaca tcaggccgga gctacacgtt 131520 gtacctgtaa cccacagatt tatagcagtc ccaattgtta ccctttcata taggacacat 131580 gagactcaga gaattgcatg ttgcttgggc atctctgtat tcagcatgtg aacgcagtgc 131640 tctttcctgc ctgtaagtgg gcttcgtcaa tggattttcc ctgtcaggcg tgatggcgca 131700 tgccttagca cctgtaaggc agaggcagga tgatctctga gttcaaagac agccgagttt 131760 agaaagggag accaagacag ccagggctac ccagagaaac cctgtcttga taaaatccaa 131820 aacaaaacaa ataaggaaac caaaaacaaa acaaaacaga aaacnnnnnn nnnnnnnnnn 131880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131940 nnnnnnnnnn nnnnnnnnnn nnnnatttta cagaataaat actaggtcac aaatcacttt 132000 acagaatcgg tgttattcaa aactaagtaa aaaagttaca tactttagta cagaaaatcc 132060 agaaatttga cagaaactac ttaacaaaat gcctcctatc aaacacaact cctcccaggt 132120 ggggtgcagc tcaaggacgg gtcagaggtg tgattggcgc tccttgatgc ctgtgctccc 132180 agatgctctg ctcttaggag cctgattctc agataaacta gcaaagaagc ttagacccac 132240 ctgtaacccc caccttaaag ctgtggaacc acatgacata aactgatgaa tatagtaaag 132300 tcagccctaa ggtcagtgct gaggtatata tcattcagga tatgtaccca agagggagga 132360 gcgtgtctgt gaaccttttt agagttcttt gtatgacaag cttttccttg aaaatggttt 132420 gagtgcccct ctataggagt ttgggcaaac aggctgtaat atactcacat ttataggata 132480 ctcgccaatg aacaggagca caatatatgc aggaccttga atgagttgta gaaactcaag 132540 agtaattacc atgcatttgt gtttgaagtt ccacaaaaag cacaactggt ctgtagtaaa 132600 agaacatcag atgttagaac tgtctgcaga tgaggtaagg agccccttgc agcatgcgcc 132660 tgagacctgt acagggagaa agatttctag cttcatagag cctgagtcag ccacaccttt 132720 gttggtctcc actcctgatc tccgtgtaat gagctctgaa tcctatatat tgcaccgaat 132780 agaaattata tctcggttta caaactacag cagcattttg ctgagttgtt gttttattcc 132840 ttcctcatca agctcttgag ttaggacctg aacctaagct ctgtattgcc accagttata 132900 cattaccacc attatagatg ttgacaccag aaacaacttc acagattttc tcatttgatt 132960 cttttataaa cactgctgcc ttgatgaaga aaaaaagttt aaaattgcta atgataaaat 133020 ctgttgtagc cactgtctgc atccaagagt gaactcagat gattttaccg gtgtgtgcat 133080 gccagcagaa accatggcag agggatagac ttgctgacag cgatccatct tgcagtgtaa 133140 gcacagagtc tggtgaagac attctactga gatgtgtttg ataggaggca ttttgttaag 133200 tagtttctgt caaatctcag gattttctgt actaaagtat gtaacttttt tacttagttt 133260 tgaataacac cgattctgta aagtgatttg cgacctagta tttattctgt aaaatgtccg 133320 tacatgaagg gacagatatc gcacgggttc acttaccaga ggtgtctgag caagctggac 133380 tgctgggtgc tagggctggg aaacggggaa gcagggagct ttgggggacc tgaagtgtta 133440 gttttgtaaa atgcagtgtt ctacacatca gttgtgcaac agtctgaaaa cactgggcag 133500 cactgaactt aagatagtta acacactgag tctgatggca catggcttta atccatacta 133560 agtgctcaac aaactaaacc attattatac cccataaata catacaaatg tatgtcaaat 133620 aaataagagg cagagaaatg gctcagcaat taagaactgc atagtctttc tgaagacctg 133680 agttcagttc ctagagccct tgtgaaatca ctcacaacta cctactttag caccaagaga 133740 tctgatacat acacatggtc actctcatga acacacacac acttaaaaat acatttaaaa 133800 ctttttaaag agataaaagt gtaaaaacaa caacaacaaa aagaccttct ctgcagacct 133860 tgtagccaat tcctgtcacc caggtcagcc acttgtgctc attggcattg gcaagtctct 133920 ttgaagccat ttgcagacaa cgctttaaag ataacagacc gacctgctct gagcagcaga 133980 gagaaaggat tcttgttgcc cagactcatc ctaggagtca gtgctaggtg atgatgtcag 134040 gctctgtgat gaccctggca gcagctcctt ctcagagaaa atgaggatga agacttcatc 134100 ctgaagcaga tcctggtatc ttatccttgg caaatgctga actcaacatg ttctaggctt 134160 tccattggca cagccaaacc tgagtagctg atggcaagca agctgtggtt ttggggaagg 134220 ggaaagttag cgtgaacatg gtggaagcca tggggccttt tgagtttatg aacagcaagg 134280 tgagcaagat caccatgacg atcttagcca ccaggccagt ccttcagaga atcccaggca 134340 cctactgttc tcactgttcc tttagaaaac acaagtactt gatgccctca ggcacttcct 134400 gttttcctta accctccagg tctagctgga ctgtagttaa gtttatagct acacataaaa 134460 ctaaatgaag aaaaagaaag aaacaccgcc tttaatagag gaccagcagt tagcagaccc 134520 tgttgctgct gctgctgtta ttgttctcct ccctcttccc ccttcttccc tcctcctccc 134580 ccctcctcct tccttcttgg tcaaaaatag atcaaattaa ctaatgaagg gaactttctg 134640 tgttcttaat attgtgttag ccacggaagt acttttcttc ttggagtaac ttataaatta 134700 ctgaggataa ttactgtgct tatgagtatt ttgctaaaac aaggaatttg tttccagcat 134760 gtgagtagct attaaatctc caaagtgctc atcatgcgag attcgacagc tttatgtcac 134820 taggggcaaa gctctagaga ggagcaggaa ggggtgtgca tgatttcttc aaactgtccc 134880 gtcttctctg ccgaatattg tggttcctta agaagacttc agaatgctac atctagagaa 134940 gagaaaacct gaatcaaaat gcttgctctg agcagttatt tttagtaaca aatctagaaa 135000 ccatagaaga tatgtgagtg tctgccggta tatcatgcat gcacatagaa gatatatgag 135060 tgtctgccgg tatatcatgc atgcacatgt gtgttttcaa cagtgagatc ctgagttaca 135120 gactgtgtgt atggggttgg ggggaggtag ggctgtgggg gttgggggtg tgggcaagag 135180 atgacgtctg tctcttaata gcaagtgggg cagtggcttg ctcagtctgt tatcataaag 135240 ctctgttaat gtagcttttg caccatgtga ctgcaggaaa agctattatc tcaatgaaaa 135300 gaaagccagt tttagagcaa gcaatagact agaagcagga agaattttcg agtgttccac 135360 catgctggat tgtcaaaggg gtgggtatct gtgtggccag cagctgaaaa aggatccagt 135420 gatagtttgt cagctctccc cagaagggca ctcagcctgg gcttcagttc acatccagac 135480 aagctgtggg ctggggctga tggaggggat cgatctaaga tgacacttgc tcgttgctaa 135540 tctagagaga gcttgtttgg aagatggtgt gtgtgtgtat cactgaagat gcagatctga 135600 accacagagg ctgtggacaa tcaccaggtg tgtctcagaa gtgttctgac ttttatttgg 135660 taatgttcct ggaattccgt atgctctggg ctggagtgta cttgtggagc ggagggctga 135720 acatggcagc tagtgagagc acgccaagga caaatgtaca tagcatggca caaatgtatt 135780 ctagggtctt tatttatttc tgttatattt atttagtgtc taaaggttat ttgcagattt 135840 tcattctgct aattctcttg gttgtctgaa ggaagtattt tggtaagcat tttctgaaat 135900 tcagacaaat cttaaatcct taaggtacaa attaaattac taagagatga atgtctttat 135960 gcttctgtct cttttattca ttatcctttt gtaattgtaa gcacaaaaac gatctttgca 136020 gtgaatttga aatcattcca tgatttcagg agctttctaa ttttgactga ggttctcatt 136080 gcatgacttt gctatacagt acttaacttt ctctgctttg ttcttaagct gttacatgca 136140 gacaccaaat agcacccacc tagtcaagtt tcagatcgca cttgaccatt tgtaatgtta 136200 ttggttctct tgttagcatg tcccttcctc tcaacctagg aaggcatagt actcaaactc 136260 cccagatgct gtaagggaac gggcggccat ctgaggagtc agtcacctgt cacgtggcac 136320 tcagctcagg agtttcggtt tcaggggtgt gtgtgtgtgt gtgtgtgtgt gtgtccaaat 136380 cacatgtaat tctgaagcta agtggtgttt tataccattc cctttaaaaa tgatatcaaa 136440 ggaggtgagc aatcaaccaa gatatttgtg caatatgtgg cagtttaata aataattcct 136500 tgaccctttt ttaataaaag caactcccat aatttttaat tatacttagt caaggatcct 136560 tcttgcttat ccgatctata gaccagatat tgtacaacag ttggataaat cactcatctt 136620 agctttgctc ttgggaggag tggcagaggc accttggcct agtcttttct acatgaaata 136680 gtttggttca gatacttatg taaatgaagg tggatttaaa aaaaaaaaaa aactacagag 136740 ggctagagag atggctcaga ggttatgagc accaactgct tttccaaagg tcttgagttc 136800 aattcccagc aaccacatgg tggctcacaa ccttctgtaa tgggatctgc tgccttcttc 136860 tggtgtgtct gaagagagca atgatataac atataaaatt tgaagctaaa ttgtttgggc 136920 atttaatttt ttccattgtt ttgctgttta atttatagct tattgtgttt tctcatgtaa 136980 agacttcaga tgacctgagc agtttgtaaa agtaaaagat gttcccactg agtactgtta 137040 ctgtattaga ctgaaagcct gtgggacgcc aagagcaact gcagtagtta atccagtaag 137100 ataacttagt acctgtcatt gaatccatgc cttatgaaca tgaatatctt gaatctcatg 137160 tgacttttat gtgattgaag gaatttttat gcaaaatgtt tctgtctgat gacagtgcct 137220 tcctggtagc tttctgcatg actgcccact ggggtggctc tatatgagag tgtaaaatag 137280 tctgtgcctg ggcctatatt ttcttttatc acaacagaag tattcgtcat agggctgggg 137340 atagactagt gacctgggaa ctgagctgac ctggaagtca ctttgaacct aaaacggaag 137400 agtttgctgg atcgctggac ttttgcttgt tttctgtttt agttctgttt catttctgtg 137460 gcactgagtg attaaaccta agggttcaga ggcattttac gtccaatccg taagggtgct 137520 tttagataat acaatatagc aacatttttt taatgaaaat aatacaaact ggaggtagag 137580 tacccttcaa agttaggttc agtcactcgg tgccacagaa gtaaagcaag acgtcaggat 137640 aatgtccaaa caggctgaac aaccagcctg ccgatcctgc tggactccaa aacatagcca 137700 caataactaa ccacagatat tatgaccagg cctgatcgtg tcggccgagg gcttcattcc 137760 ttgcagttct gtttaatctg tgggtggagc tgacagcagc gctgtaagat gcggtggtgg 137820 ccatgggacc tctggcctct aaagtcagtt tggggctgat taagtcagaa ttcatgtacc 137880 acatatgttt taaacacagt tttactcata ggaagccaga gaaacgtaca gttcatgaag 137940 agtcatagcc agtgtgtttt ctgaaggcac aatttccagg attgggacac tgaaggcaag 138000 ggcataccta ttgctcgatg acatagcctg tccttgacac aggaggcagc ctgggcattt 138060 ctgatgtctt catttcattt gcagcagaga ctcttggcca agttcatgaa gtcccagctc 138120 atggctctta atcacaacac cataacagaa acagtgtgcc gtattttaac tgataaaaaa 138180 atagttttta tagtttgtgt ttttcagtga ttttatgtgg aacaaccaaa ttctgtactt 138240 gactttgcat gagttgtttc ttactggaac actgattcga ttgagtgggt ctctaaacct 138300 agaagctaga cgtttggttt tatcatctta gatgtctgct cagagtggta aatcagctgg 138360 ctagcgtaca gctggtcgaa gtagtccatg aggtttctat tccaataggt aaatgttaga 138420 atctagttaa aataagtgat aaatcttcca ccaagacttc agatcccaag agcttttgaa 138480 ataatgttta ttaactggcc tttaccagtt ttactttcat tttaagtatt gaaaatagat 138540 atcataccat tttttacaca tgatttttaa aaaatatgtt ttgtgggctt tctttgtccc 138600 atgtatgatg cacattgtat gagctataag tactttggcc aacactatca accatggagc 138660 tctcctggcc ttgaacttga atcacagtgt ccgtccatcc attccctcct cctgtcactg 138720 tcccatgcct ggcttacagt tgagcaaaca ctcagaggtc aggcaggcag tgcaaacata 138780 ggccatccgc ctcatgcttt gtctccagtg tctgtgctct gacgttgccg taggctggag 138840 ttcaggtagc attgatggtt tgttctacaa tgagagagca ggatggacat aggcacaggg 138900 agacgccctg tgaaggttga gtctttctgc ttctagtttt tgtgcattta atgaactttt 138960 acttctgcct taccttacat ataccaaaag taaaggattt cataaaggat gcttagtctg 139020 caatgaaaag aactgtttgc ttgtgggaaa ttcctgcaga gctcatgctg aagtattgca 139080 gaggaaagag gactgaagga ttcttgtggg gtaccagaga ttgctagaga gataagagta 139140 gcttgctatg ggactgataa gtagggaaaa gctctgaagt tgtggagtct aaaagccagt 139200 gtttgcgtgt gagctctctg ctgagtacac actgctcact tcctaggtcc cttgctcatc 139260 ccagaacagt tgctcagata gaaaaccgta gaggagccat gttaaagtgc taactttcag 139320 acaaggagaa cactctggaa tgcaaaccat ttactaagat ctgtggtaag tccttttaca 139380 tccatgcaga tcccctggag atgagttctg tccgggtagg ctttcaggtg agggtctttt 139440 gtactttgtc atacttttaa tggtctgtag ctttattatg accatgacag aatacctaag 139500 tcaagttagc tttataaaga aaagaccttt attttggctc ataatttaga agattcaagt 139560 caattgtttt aagagtcttg tggtgcggca gagcatgtgt tatgtctggt tctgtgtgtg 139620 cctgtctctc tcctttccat aaagccacaa gggttccatc aagcgttctg tcccaaagtc 139680 tttctctaag ccaggccaca ttccagagag tgtaactcac accattctca ggttctctgc 139740 ctcttattac cattggcatg tgacatgtgc agtggagact tcagacacca gcagctgtgc 139800 gttctcttgc tggtcatgtc actcttgctg gtagcccgct ttattgcctc taggttctgg 139860 ggatgatgag gagagcaaat tagatgtaac cttgccactt gtcctttctc gtggcctcca 139920 gtatgttgac ttgtttttgg caatcagaaa taaccactgc gggttcgttc tcagatcctc 139980 cagctgacct agctactgtt tgttgtaact gtggctgtgt gctccaggaa aacacaacag 140040 taacagtaac agtaactgcc tcttctggga gtgagaggag gattgatctg caagctggga 140100 cgggaaggtc tgaactgcag acagcactgc ctcgacatcc cagggattcg cagagtgtgc 140160 aggcttgcct gccccattgt ggtgataaga taagaataga tcaatttgca ttcttctaca 140220 tgatatctgc cagttctgcc agcaccattt gttgaaaatg tcttttttgc cactggatgg 140280 ttttagctcc cttgtcaaag atcaagtgac cataggtgtg tgatgcaaac cagtcactgc 140340 ttcaaagccc atggctttct ggagttgtga gttctctagc aaatggagtt ataggtagtt 140400 gtaagcctcc tgaagtaggt acaaggaact gctctgaggc cccctgccag agaagtaaat 140460 acccttaacc cctgagccat ctcttcagcc ccagatttta acagtgtcat cttttaaaaa 140520 tgtgtattgg tattttgcct acacatttgt ctgttacatg tgactgcctc gtgcctgcag 140580 aggccacatg acggtgtcag tccctgggac tggagttacc aatggctgtg agctgccatt 140640 tgggtgctgg caatcaaacc ctggtcctct agaagaatag ccagtgactt tttaactgct 140700 gagccatctc tccaccaccc ctctgcccta gattataact ttaacatgca tgacagaaaa 140760 atgtaaaagg aagtgtttac ttgagatgtc caataagaca gcagcgagca gttgtagtgt 140820 gctgactata ccttctgcct cctgccgcct agaggacttc aggtgtgtga tttcattttt 140880 ctgtgtttca gggattatgc taataattat ctcatacggt taattgtgag gtcaagttga 140940 aaaatacaga tatactacta aaagtagaca cattactatt tggaataaaa ctagaaatat 141000 tacctatttg gggttaaata gtcttgagct ctggtagttt gtgaagcgat catgagcatc 141060 aagctttttt gtatcaagca tgctgataga taagggacta agatagaaaa gaaagaacaa 141120 tatataattt tatgacttga aggcatttaa aatgcagtag tgacagggat gcaagaggaa 141180 gtaatgatgt ggtgttacag ctgttagtgg gcatatgcag gtggtctgtg gacagatggg 141240 ggtctgcagc agttctaaaa gagtggaatg agtttgaagt ggcttcatag aagataagca 141300 aatggactga gaccaggagg agcaaacaca aaagaacagg tgtgttggat agttcaggcc 141360 agcttgacac agctagtctt cagagtggag ggaggctcca ttaagaaaat acctccataa 141420 aatctggatg tagatgtgcc tgtggggtgt tttcttaatt agtgattgtt ggggaggacc 141480 cagccccttg tgggtagtgc cattcctggg ctggtagtcc tgggttttag aagaaagcag 141540 gttgagcaag ccgtggcgaa gaagccagta agcagcaccc ctctgcagcc tctgcatcag 141600 ctcctgcctc cagccttctg ttctcagtgc ttttgataat gaaccaggga ggacacagga 141660 cactcctcac attgcttttg gtcatggtgt ttcatcacag cagtagaaac cctaagaaac 141720 aaagacagag acaagggcag gccgttatgt cccctgcagt gcattccagt gacacaggga 141780 atcgatgaga accgtaaggc agatgctcag ctcaaacatc attccaggca gaggagaagg 141840 aaaggcgagt tcagagacgg aaaggtttga gaagaaagcc tgaaaggaag acttagagga 141900 aaccatagaa atagactgcc accaaagaag ctgccacacc atctgggaag cttagagaac 141960 agtagtgatg gctaaactat actgccaacc tctctgcttt gatggatcta gaagagccct 142020 tgttacaccc atttatttat ttaaatttct gttttgtctt gttttaatat ttttttgcag 142080 caagttacat gtaacataaa aatgattgtt tcacttcttc agtaacatta acacaccctc 142140 aaggttatat aatcattgct agtgtacatt tccagaacta cattatccca aacagaaact 142200 gcaaacttca aacagtcctc cctgtcctgt cccgagctct gatactttct cttctgtctt 142260 tgcgtcttta gctgtttagt gctattcttt ttagtgcctc cacacctgct ttcatttgct 142320 gtagttcact agtgtctaaa ggtgttgtca gtgttggttc ctctttaaag ttgcacaact 142380 gctctatgta tgtgtccatt ttctgtgtcc attcatttgt cctggatgtg catgttgcta 142440 ccactccttg gctactttgt cattcttagt cctgaatcac cctactttgg ttgcagtatg 142500 tatatattgt cttttaaagt cctgctttgg ttctttgggg tattgttgga tcaaggtttc 142560 cccagtgatt tacaaagaca tgtagccata gatgggaaaa ctgtgctgtg agacaagagt 142620 gcataaatct gcaaggctag aaacagtgca ctgagtttgg gacttttggg ggagattttg 142680 tcttattttg catgttttta tgcttttact ttatagcttt gattgagtag tttctcaaat 142740 ttgtttctaa acacaaacgc aacatggagt cactagggaa ttttttaaaa attaattaat 142800 gccaggcggt ggtggcgcaa gcctttaatc ccagcactgg agaggcagag gcaggtggat 142860 ttctgagttc gaggccagcc agggctacac agagtaaccc tgtctcgaaa aaaaaaaatt 142920 aattaatctt ttagtattgg tggtcaaagc caggacctca tgtgctatgt ctgtaatcat 142980 agaacactat ttttaacatg agcttatgag tccaaagtat acatcacaag agtctatgtc 143040 actagccaga tgatcagaaa gcatgctcat catccttaag tagctcggga agtttaatac 143100 accgaggtat acttccaacc caggcattga ctgtaataac taaaagcagg ggatgctggc 143160 cgtctgcaaa ggagttgaca tcagagtgcc cgccttgctg gctagaaacc caagtgcagt 143220 cgtgtggata tcagtttaat acagcatcag gaaatggaac ataggcttcc accatgacta 143280 tactaactcc tttctgaact ctacatccca gagaacttgg aaggaatagt ggaaaagtag 143340 aaacaagcca gtgttcatcc tgatagtgct actgaacctt gagaggatta taccaaagaa 143400 aataagtagt ttgcttattt taaaagattg gagacagaag gccagtcatt gaccaccagt 143460 agctggggca agtagaaagg acaagatgtc attgcatatc aagtatgagt tttctatctg 143520 aagatggaaa tactgtgaag ttaggtaaga agatatttgt atgactgaaa acacatatta 143580 aatatattaa gagtgagagg agagaaatcc aggaaggttg atgggcgcca aggggggggt 143640 gtgtttataa gtgttacata gcagtgaaag agtttgacac tgtgtgccag atgcccatga 143700 gctcggtggt tttaagcttg tttagaggtt ccagctcagc tgctcatata ccctgggctg 143760 aggactagtc atcctctatt tgtggatagt cagcatcttt gacccagtgc acttaaggaa 143820 gagtgcaccc gtctagccag cctgaccaac tagcaggtga cagatgcttt ggtcagtcca 143880 gcctcacaac caggttttac atttgaatat tccagaaaac taaaaaggga gaattgacag 143940 aagaaaggtg agctttggaa cctgctagtg ttggaggcgg ggcaccagcc cgtagaccta 144000 catcccctgt ttggatctca gagtacaaca aactctgaaa ggtttcccaa ttcatttgta 144060 gtaaactctg acctaacaag tgtgagatga cataaactca tctgtcctgc ctggtgtgag 144120 tgaccgtgta tttcattgtg gagatagcat cgaatttgat tatagaacac ttctgtagat 144180 ccctcctaga ggcactacag aataagctgt cttccaagta ttgtatcgag aggcagacag 144240 ggagaggcgt gaattctaaa gcccacgtta tttggctcca tttctttgat gcaggggatg 144300 taaactccgt gatttggaca ggggtgaaag tgaagggaaa gcgagagcct gagttggtgg 144360 tacctaaaga gggattcaga ctaatggaac ttccccccaa gaatagggga gtagtttgaa 144420 tgtgccttgc atacagttta aagaggaaca ggtagaacat gatactaccc cttcccacct 144480 cagcaacaac ttttacagta atatcttgga gaacctaggg gtgggaagga gaaatggctg 144540 gcagtggtct gtgagaataa gtcgggtatc ctctgagatg gcagaaggaa agggatcagt 144600 atcttctgag attgactcca tgaaagctgg aaacacaggc tgacctgaga ataacgacgt 144660 ttctgacagg actaggagca gtgtcataaa ccatgaggag tctgtggggc tgtctctccc 144720 gagaacatgt ggtatgctcc atcagtcccc atctgtcccc ttctacgaga aacagaagca 144780 ctgtaggtca cgggagctag ggatgatgga aagtcagtga gaaaaaggat cccagttctt 144840 cataccagtg acggtcacat gaggagacta aaagtactgg tctcttcagg ggctggggga 144900 cgaggtgaca ttcaagtggg tacacctgaa aggaggataa gagctaacca tggctgaagt 144960 aaaatggaag tctgatcaga cctttggaga cagtaattac tagctcttca cagcctttga 145020 agtcactcag ggaaacaacc agattacggc tgggaaggaa gagctattca gaagccagat 145080 cttcactgat gtaaaagact gtgtggcgac tacgggatgc tggcgaagct ccacaaaagg 145140 agaggagatg gacaggaatg ttgttattta tagtccttgt ccttcatgaa aggaattaag 145200 gaccaggaat atggaagtag gaactggagg agagaccatg ggagaatgtt tcttactcag 145260 tctctcctca tggcttgcac agactgcttt cttatacaca cccggccacc tgcctaggtg 145320 ggcagctctg ctcccagtgg tctggaccct tccacatcag gcattagcca tgataatgtc 145380 ccacaggctt gcctgcaggc caatttgatg agggcttttt ctcagttgag gttccctctt 145440 ctcctctgat agctctaact taagttgaca aaaaaacaaa acaaaacaaa caaaaaaacc 145500 taattatggt tgtgggtgga gagcatgttc cacaggagct gggtttttaa gcagtgcacc 145560 tctagttgga tagtggcttc cagctcttct gcatactctc tgtatgtgag aatccagcaa 145620 cttctagagg actgcactac aaggaagagg tagcctgtca gagagccaaa aagaaccagt 145680 agttgattga cacagcatat tatcacactg gcttcgctcc tgtcgtcttc ttgcccagta 145740 gttgtagaca ttgttaggtc tttgtgatcc caggtcatca cccacagtct ggagtggagc 145800 cagaaaaggc agtgctgtct gcagactcct ctgctgattc ctttgctgtc caagtttgag 145860 gacctctagg aatccacctg tttttatttt ttatgtgttc actgtacatg tgtatagcat 145920 gcacatgcct ggtgttgagg gccagaagag gacttcaggt cctctgtagc tggattaaga 145980 ttctctcagt cactttgtgg gtgctgagaa cccagcctgg gtcctctaca ggagcaacaa 146040 gtgctgctta ttgggaccgg ctctccaact ccagactccc attttgctct catctctaca 146100 atagcacatg gatgtgaagc atacttctgc atctacagta ttcctacagt gcggccagaa 146160 atcttgtagg gaatgcagag acacctggtt tctgctgacc agtctaaact gtaaagctga 146220 actgtgcttt aattttcaaa tgagcaaagc ctttctagag ctcagtgttg ctctcagtgt 146280 tggctgtgag gcaggaggtc ctgcaagagt gcttgctgtc aggggatgca gctggcttgg 146340 aagacagtct ggcagggcca cacatatatg tatagcatgc acagtctgtg tgctctagtc 146400 ctcacaggtt taaaggagac aggcagaagt ggattgagtt acatagaagg aattcactat 146460 gctgttaact cgaaacaaag aaactggaaa ataggaactg gttaaatatt tatggtttac 146520 tcgtatgaga aattatagag ccattaaaag ttattcttta tttgcatggt ggtgccgtgg 146580 tggcacatgc ctttaattga agcattcaag aagcagagcc aggcagatct ctgtgtttga 146640 ggccagcctg gtctacagag tgagttccac aacagccagg gctacacaga gaaattctgt 146700 ctcaaaacca aagaaaacaa atttaaacat ttttaaaatg ctcatacaga taaaacttag 146760 tggcctaata ttcttttttt tttaagattt atttatttaa tgagtacact gtagctgtct 146820 tcaggcacac cagaagggag ggtatcagat ctcattacag atggttgtga gccaccatgt 146880 ggttgctggg aactgatctc atgacctctg gaagagcagt cagtgctctt aacttctgtg 146940 caatctctcc agcctgtggc ttaatattct taattttact aattttctta atattaagaa 147000 aaaggaacaa atgtaaaatt agacgtgtgc atatgcattt taattgctta gcatgaaagt 147060 tttcaaggtt agtggtgagc atatgcagtt ttgtgtgtgt gtgtgtgtgt gtgtgtgtgt 147120 gtgtgtgtgt gtgtgctcta acccacagca ttgtgcaaga tttaacagtt tactggtgtg 147180 ctagaacggg tgcctgtggc atgttctcca ttaggacagg ctgaatcccc cccatctact 147240 cacaccccat ctctgctttc tgctccctcc tccctcctca ccttgatctc ttatcctttc 147300 tctcatacct agaatacagt catttcagtg atgttataga gcacccctgt gtaaactcta 147360 atgtattgac ctatgttgta ctaacagagc aggtacccct acctccatct gtagtccctg 147420 ctgtgaatcc cagccacctc tgagttggtg gctacttcag gacacctcac tcttctgaac 147480 ccagtgatgg tgtcttagac caaccaaaaa gccagattct tgtaaagcca gattcttgtt 147540 ttccaaccag tttattccag ttgtacttgt tactataatt gcatattgat cttgaaattt 147600 gaatttgaaa acatgtattt gttagaaata ataagatacg tcatgtggac aatttcctgt 147660 taaacgggga catgtaagac atctatagta gctgggggag tgatgttctt ttaggtaaac 147720 agtgaagaag cactcttaag ggcttagtag ggctgtgtaa agatgcatgc ctgcagtcag 147780 tgctatggag cctgaagtgc agggacctga ggtgaaggcc agtcagtatt cagtattcag 147840 gaggcagtac acccctgtcc cccaaaaaga aaaaacctta agtcttttta aataaataaa 147900 aatgggaaat catagcccct tcactgcagg tctggtttac accaggaagt gctgagagag 147960 cagtaaagat ggatattcat gcttatgtac ttatgatgaa atgcttaaag ttacaggcat 148020 cattttctat aattatcttt cacaacttta gtgttcttaa tcagccaatt actatttctg 148080 attttacaag gaaagttttc tgtttagagt gaaactgaga catcttggtg tgcctgagaa 148140 agtgcctagc aacttccttt ctttaaactc tgcggtctac aacagtaatg gagtcttatg 148200 tattgaccca ctggatagtt ctgaaggatg tgtgtttatt acacaatgaa aaaaagaaag 148260 attctatcaa atgatgaagt aagcctttaa taagttagat taagaaaata atttctataa 148320 cacattcaag tttataaatt ggtcttttca gtgatcatta tgtcctgaac agatcacttt 148380 agtgcccaca ttacagttaa aattaaaatt gagggacaat tgggtccctc ctacctctgc 148440 atttgagtgc tgggtttgaa ggtgagtgcc attgccattc ctggcaggat taacttttga 148500 gttctaaaat gtcttatgtg ccttgttcat gtttcagaac tgttctcttg gtgccttgtt 148560 ctcttcctgt gtgcagtggt ggtgagctca cacaggacgg gtgaagggca cgtatatcac 148620 tgtatgaggc actcagccag tgtcagttac tgagtcacac ctgagtttga gtccagcctg 148680 tcctttggta tctgtgagac tgaagttgct ttgcaagcag gttagagaag ttagataacc 148740 aacagggtgt atatgtgtcc atctcaagac atcaggcaga gtgaggtgtg caaagtgtct 148800 gtgtgcaacc tcctcctcct gagtgagtgc taaccaaaaa gccccaagga aagaagatgc 148860 tgtagggtga gagagagcgc catggaggtc aggaacaaag ctgattgcct caggctgaag 148920 gcctttgaca tcttagtcat tttctcacat caactgggaa ggctgttaag tctcagaaag 148980 aaattataag taacagtaaa gaaagatcat tgaatttacc tttgacaagt tatgaaagtc 149040 taacataaat cttcttcctc tgctcttggt ttgctgattt ctttacattt atacttaagc 149100 aaattggatt ttaaaatgtt agctggaagc aggcacctca cttgcagtgc ggagaaaatg 149160 gcttatgggg tgcaaggagt ggtgctcttt ctgtgttttc tcatctgatg ccttattaaa 149220 aattgtcttg ctatttctgt ctagattcaa agagccccgt gagtgcctgc actgaggaat 149280 ttagcctgag aggacgcaga aaacagaaac tggctctagc cagtgatgtc acactgatat 149340 accccaaccc taccccaccc ccacaccact tacatattct gcaatgaatt ttgccagtga 149400 ggcatttggg gcttgggggg aatttctttc tcccacttta aggaagatgt agacatgaaa 149460 atgtcacaat gtaatatttg tgtcaccagt gactatgagt caagacattc atttgattat 149520 agcagtgcac attaaagagc caccacccgc ttctgtttaa tgtgtttatt actgtcttcc 149580 caatggcatc ttgaagtgtc tttcactaaa aaattcatga gtattattgg ctttcagaca 149640 gaaaatacaa tatgtctttt agtaactgtc taatagacca ctttaaggcc attatacaaa 149700 agtaaatcta agagcaaagc attttgggga ggaagaattt ttagcttaaa catttgttta 149760 tacagtcttc ttactcttgc gtagaagagg atctggaacg cagaaggtag ttgccgacgc 149820 catctccttg gagagtagtt gtagggtgtg ttgttttctt tagtcctggc aactgctgct 149880 gttgtagtat tgaagtcatt ttcttttttt tcttttttct ttttttcttt tttccctgag 149940 acagggtttc tctgtgtagc cctggctgtc ctggaactca ctctgtagac caggctggcc 150000 tcaaactcat tttcttttct ttttttaaga tttttattta ttattataca taggcacact 150060 gtagctgact tcagatgcac cagaagaggg cgtcagatct cattatgggt ggttgtgggc 150120 caccatgtgg ttgctgggaa ttgaactcag gacttttgaa agagcagtca ctgctcataa 150180 ccgctgagcc atctcgccag cccccttgaa ctcattttct aatgaggttg ttgtgtgcct 150240 gacctgctgt ttctttataa agtcaaatat acaatatggt actgtaaagg agtcagatta 150300 aactgagact ctgcttccaa ataagatgtc tttcatcatg ctttccttag aagtgactct 150360 tgtaaacgtt tgcaagctaa caactgtcag tgtggacagt gcatgtactg gtgtgcagtt 150420 tgtgagtctg aacatgtagg taactgtggg agccatagtg ttgtttaaga tgaagttaaa 150480 aggattcctg tgttctaata aaaatttaat actccttgca ggaaagtaat accccatttt 150540 actacctcag atactttaaa ctaatatatg atgtcctctc tccatttggt ttttctgtgt 150600 actttcaccc acattaagta cgtgtctcgt tctgcttcac tttgattggt atatatcgtg 150660 ctgctttgtt tgtgtgaatc ataagtattt tttatataat ctgtatattt actacattaa 150720 gtgaatgttt atttagctgt tggggcaaaa gttggaatct tatcagagta gcgcttgcct 150780 gggatagttt tgaccagtga gcacaattgg gaaccaggtt atttccaaaa tgtttgtccc 150840 ctctctctcc tcttcccagt actcacaagc agaagatcca ctttgtccgt tcaagtatta 150900 gctactgtgt tttcttacgt gtatcagaga aggcccaaga attgtgagtt tgtataatac 150960 agagctcctt ctccctggaa agtgtaggta gatctggaga gaattgagaa tggctgttct 151020 cacatgacct gataaactgg ggaagcgcag tgagtttcta agcaatgggc tctccctcaa 151080 agagcagaga tggagggtag tcttttatgt gtgttaacgt gcaaacattt ctcggcgttc 151140 tgaaaggtgg tccccagcac ttaggcagac ggattgggag ttcaggtctg ctgtgggcta 151200 cagaggataa ccctgttcag aaaaccaagg gctggaagag ttcttgtcta gcgctctcaa 151260 ggccctgggc ttgatcccca tcactgaaaa attgtgcaga tccagctacc attgtgcacc 151320 agtttcgtgg atcttaagtg agccgagaaa gattggaaag acctgggctg tggtggtgcg 151380 cacctttcct cccagcattg gagaggcagc attgggcagg cagatctctg agattgagcc 151440 caacctctac agattgaatt ccagaacagc caggacgacg aaaaaggctg gcccccatgg 151500 aaaagctatg atcaaaggac ttgttttacc tctctgtgtg gacatgtatc atttctgtcc 151560 atctcaaagt caggaactta ctagggccca actctcaaac tatgtctttt tggagctagg 151620 aagaggcctg gtgcttggtg gagttgttac atgtggagtt aagcaagggt gttatccttt 151680 aactgaattt gtttagcata tagtaaatct gacaggttta caggccttgt ttggaagatg 151740 gcctgtgctg ataagagata aagtgcgcat ttatcacttg caagaattct ggatgattaa 151800 ctagctctaa tgtcatgagg ctgttttgca aacaacagct ttgctgcctc ctatgttaga 151860 tggattcgct ctgcaaacaa agactgcttt ctttaattga attgaaattt gacattttat 151920 attgcttttt gtcacttgct gaggacttga ctatgggtat tgttcatccc tcccagatat 151980 tgctacttat aaaagctgaa gcttgctgaa ttgtgtgtct atatctcttc cttcttctac 152040 caagtacatt caagctgata tggagggatg ggaggacaag cctcctgtcc cagggaaagc 152100 actgccattg tgtgactatt gataacaaga atggcaaaaa gaaacatctc caggcttgtc 152160 cttcacagct cccatcaact ggtaaaaact ggtttgcccc cagtcactct aattatgtca 152220 gccacctcaa gttttatttg tgtcctagtc aatttctgtg atttacagtg aagtcttaag 152280 tttgatggtg acatgttcga gagctttaat ttcctggaag tgttgaaaac atgcagagat 152340 gtagagcata cctttactct ttcccatttc atactttaac tttggaaatt aatgtacaaa 152400 aatacattaa aactcatctc tatgtagttt tattttgctg tgaggtattc ttctgtaagt 152460 ctgaagtcga tcttatccat ctcacccacc tatgtcacct cggccctgcc tcatgtttta 152520 gtggtacatt gaagtgtttt ctaagtgatc tggagaaggt acagtaaggg ttttaaactg 152580 tcattgggct acagggcaca cagtctttgt ttttaagatt tattcattta ttttatatat 152640 gtgagaacac tatagctcta cagatggttg tgagccttcg tgtggttgtt gggaattaga 152700 tttttaggac ctctgcttgc cctggtcaac cccgcttgct cctgtcatcc cctccccagt 152760 caaccccact tgctcagtcc ctgcttgctc agactcaaag atttattttt tattattata 152820 tctaagtaca ctgtagctgt cttcagacgc accagaagag ggcgccagat ctcattacga 152880 gtggtcgtga gccaccatgc ggttgccggg atttgaactc aggaccttca gaagagcagt 152940 gagtgctctt acctgctgag ccatctcacc agctccagtg cacacattct tgattgactc 153000 aatccctcga gtccagttgt tgcaatgtgc ttgttggctg cttgtgtgca ttcagttgtt 153060 attgtgtgaa tttaaaggag aatttgaagc cagtgttcaa tcccaaatta actttctgtg 153120 actagcaagc acttatttta attgttgaga ggtttctggc ctttctggca gtatgatttt 153180 aatatgcatg gtgatagtta tatagctctt atcttcaata aagaatcatc cacaccttct 153240 gctcttgagt tttggtttgg tttgcttttg tttgcgctgt cctagtgaag gctgttcttt 153300 ataactttat atttttacaa cttgctgaca gctgattcaa gggaaaagtt acctggacca 153360 cttctcggga gattcctagg tgtgaagctt tctctttcac agtcgtgaat gaaaccttgg 153420 gaaatatggc tcagaaagaa ttaggaagaa tgagtgtttg tagcgtgttg tccctggctc 153480 cccagccctc tgtaactcac ccacttcatc ccagcctgca tggccctctt ggatctcagt 153540 gtgggaatgg atcgcagcac tgtccctgta ctcatctcca tttgccttgt ttctctcttg 153600 aacagcagta ttctgtctct gcccccctgc catgtccatc tacagtgaca ggaaggcagg 153660 tgttatatac tgaagtaaca atcattttgt gcacagaagc ccttgttggt tagatcttgt 153720 gactttttcc atggcgctct gcctgtagtg aatgaagacc aactcaccca tgacaggcaa 153780 ggcaggaaga cgtatatgga tgactacctc aacagtgact tgctagtgaa gagcaagggt 153840 cctctccatc gaggtcccag accttcccct tccacctcct ctaggcagcc tgtgctacgg 153900 atgccagagg tgtgactcca gcttacagaa aatcagtagt gtgcagtagc aagttttaag 153960 gtcacatggc taaccacgca gtgaagcttg ggcctcaacg ttagcccttg gctacttagc 154020 aatacagatt tcaatgtgag gtgtgaatct gtaaattggc tttagtacat agcataaact 154080 aagtgaattc agcacttatt atcaggcaga aagtagagca ggaccttggg acttggttac 154140 attgcttcca cccacaggaa gcacaggcat cagttctcag attgtatgtg accatgtgac 154200 ctcctaaact gcatgtgcca ttgctgccac cgccctcttg ctgatgctcc ctaaaaacaa 154260 ttggttctgt aaaacacatg actcgcaaaa aaaaaagaga gagagagagg gacagagaga 154320 gaacaattgg ccctcctgct cgcttggatc agaacagtgg ccagaggagt gtgtgtggag 154380 cactgagact gagggctggg accacaccca agtcgaccgc agacagttgg actggtaggt 154440 gtccatgagg cccaggtctc tccacagctt tccttggcca attttactct tgctggtcct 154500 cctggtctgt gctgtgtttt gggggctcct gggctgctac tgacctcacc ttctcgctgg 154560 attctcctag tctatccaga gtaaaggacg gtagcagtct ttcaggatga agagtgagca 154620 taggacgcgt ttctaggaat gaagtaccac tgactctgga gcttgtgggc tgagctgttt 154680 tcctttgctg ggcatatcct aagcccttta aataactcat aagtgaattt ttctcagaac 154740 cggtgatagg gcttttgtct cttctagaac tgtcactttg tccttgcatg caagtcacat 154800 gatggcccca gtggcgtcca gcgtgaggac actgggtctc tttctgtgtg cccttttcag 154860 tttctcatgg aaaacagttc agcaagcgga agctttatca gggccttcct ctcacaacca 154920 ttctaaagac ccttggtgat tatacctgca ctgccagaaa agggaacccc agcagaacgt 154980 gagaaaggaa ggaagccacc ttgctagctt aagagcaagg tgaactgccc gggggatggg 155040 gggggggggg ggtatgaggt tgaaggagga ggcttgaggc ttgaggggga gacaggaagg 155100 atctccattt tgacaaggga gtcagatcta ccaggccaaa tttggaaccc tttataaagg 155160 tgttcctgcc cacttcccta gactgtctgt caccgagcca ttccagcaca cacagcacat 155220 tggcaaaccc aacacaagag actgggaaga gcttgcaaca cctgtcattt ctctggtgca 155280 ggagcaccct caaaaccaga gactagccag gcccaggctg acagaaagca gctcatggta 155340 ttgttgagtc tctctgtcta aagagcctgg gctcagtgag gcgggagggg ttgttcttaa 155400 tattaacctt tgctcttgct tagcctttaa gtgtgcattt atgcacaccc tgtgttcaga 155460 actgcggtcg ggcttgggtt gaagtgggca gtccttacac cttggcaggc agagtgctgt 155520 gacagtttac taggactttc ttcacgccct tttcccatgt gttctgtttt agttgctgat 155580 atgtgttcaa gatgagtggg atgggagaaa acacctctga cccgtccagg gcagagacca 155640 gaaaacgcaa ggaatgtccc gaccagctcg gacccaggtg agccgatcgt caaccaaaga 155700 aaccgccttg tctgttagtt tcctgtgtgt gtcttcgttt attgcttttg catcgattta 155760 gtataactat tgtgttcagc ttttctcttt aatgatgaat ttttatgtaa tagcttaaat 155820 tttgaatatg tggattattt gcagaatcta ttccttttaa aaaacatttt tattgccctt 155880 gtgtatttta cttttataat cagttcattg ccataatgtt ttagttttcc atatttttta 155940 attaggaaca gaacattgta acaagtagat tttgtagtga aagatttgct atttgtttga 156000 tactgagttc ttatttgtct gtttgtttgt ttttgttttg tggcatgaag tattcaattc 156060 agttgttttt ttagttaaaa ataaattgtg gttcttcagt gactaaaaca aacacttcta 156120 aaacaagttg gcaatatcat aatggcagtt ctgatttcag gaatttcctc acggtagtgt 156180 ctgtatgtgc agagcactgt aagtgtgagg ttactcattt gcatccttgc ttagattcat 156240 aaaagagcag gaaacaattt ttgcagagaa cattttaaga tggtgtgtgg cctggaacac 156300 agtgcaaata tgataaacaa taaggctagt atttttaaag gcctcctaat actgaggcac 156360 agagccagta gtggtagtgt accctaaagt ctgaggcatg aggagtttaa gaccaagctg 156420 ggctacaaag gagttggggg ccagcctagg ctacatatat agttagatac tattccaaaa 156480 gatgctgtga gagagaaagg gcaaagttca aaagatgatt ttggagtata ccgcctgtta 156540 tattgaaaaa acaatttgga gaggaggagg catgtgcatt tgtgttgtag agtaatggct 156600 gctccctgct ttggtagatt agaaccggtg caaaagggaa acaaaggtgg aaaggtttgc 156660 ttccctgttg ctgtgatgaa acatcacaac caaagctctt tcagaaagtg agggttcatt 156720 catgatagca ggcagggagg cagagcagca agctgcagcc cggctgaagg agtaggaagc 156780 aggggagcag actagttgta gcacagttgt agcccgccca atcgtgtact tctccatcaa 156840 ggccacgcct cctaagcttg tctttacagg gccaccaact ggggaccagg cattcaagtg 156900 actgaacctg tggaggacat ttctcattta aaccaccaca aagagagatt ttttttcccc 156960 cagactttta atattttcaa tcctgtaaat gttttttgtt gttgtatttg tgttgtcttt 157020 atcttcccag nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 157080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn ggctgtcctg 157140 gaactctttt tagaccaggc tggtctcaaa ctcaaataga tccacctgtc tctgcatcct 157200 gattgctgag attaaaggtg tgtgcccacc acacccagca cctagaaatt agttttaaag 157260 ttaaataaaa acagtgctct agattgtgtg attaaaaaca acaggaatgt gggttagaaa 157320 aagttaccta ggcgggcatt ggtggcgcac acctttaatc ccagctcttg ggaagcagag 157380 gcaggcagat ttctgagttt gaggccagtc tggtctacag agtgagttcc aggacagccg 157440 gggggtaggg gggggagtta cctagagaag tggagagagg ttagaaaacc catggtttag 157500 gctattcctg cagcgctgat cacaggtctg tctaactccc tctccacacc cagccctgct 157560 accttttacc ctcaggttcc caacaacttc ttggtccgct ccacctgctg ctggctccca 157620 gatttccctt catgctttag tacccctctg gggagagagg ttccagaggc cacatagtct 157680 ctggggctca gttgtggtag caaggagggc agcccttcct tgtgctgtct ccagggtctt 157740 gtgcctcagc tccttttctc actgacttgc catttatcct gtctttctca ttctaagaga 157800 gaggggtatg gggaggagcc aggtgaaccg ggctcctcta aggccctctt tcagccacct 157860 ccttcctgtg acttcagtaa agtagaacac cccagaaacg aggccaagga gacacagacc 157920 ctcttccccg cactgctgca gtgcactggc gatcttgggc aaatcgtgga gccactaaaa 157980 agggagaatc gtgttaaaaa tcttaggttt attaatttat gaaaataaaa ctaatagatt 158040 ccaatgtgag aatcctgaac ttgcaattaa tattttgtgt taattttaaa ttgatattat 158100 atatgaatac atataaaagt acagaaaatt aaatacagaa aactaaacaa ctcagcttct 158160 ttccttgttt tggggccatt taatggactt ctgcatgtac acagataact atattatttt 158220 caagaggaaa tttggagttt tgttattttg tcaaattcat atgagaagat ttttccagtt 158280 ttgatatttt tctccactca ctgaagttca gttgaactct gaccacttgg cttgcctgtc 158340 attggcacgg acagcgccca tgggtcacgt gggctttgct tagctgcttt agcacttttt 158400 accttacctg attggatcac agatattcta aggaagtctt tagaaattac agatctaaaa 158460 gaagaatcta aaggtgttat aaagatttgg tttttattac cctttatgat taccaaaata 158520 aaacaaaagc gtgattgaaa cttacgtttc caattctaat tacattaatt ataacttgtt 158580 ccttctaaac taccttaagt agacgttgac tccttactaa ctctgtccag cagtaaggtc 158640 agtgctcacc ctgtcaagct ctgttgtagg ccagggccgt gctgccctcg ctgtggtgag 158700 actggagatg agcgatgagc atgctcagga agccatccac agagaacaaa agagaagcag 158760 agataccaga tcactccctc gctcttacct gctttcctga gcaggcagcc tgttgtctgt 158820 gttcacattt aaaagagttt agcagtttct ttcaaataaa tagtaatgtc ccgttccttc 158880 ttagccccaa aaggagcact gagaaacgga accgcgagca ggagaataag tacatagagg 158940 agctggccga gctgatcttc gcaaacttta atgatattga caacttcaac ttcaaacctg 159000 acaaatgtgc catcctaaaa gaaactgtga agcagatccg ccagatcaaa gagcaaggta 159060 agaggacggg aggggttctg cgcctccgcg tgggtgaagt cccctgaatc ttatttctta 159120 cacttaaatt attgatgaaa tgatgtcata ttaccagatg aatgcaagta tcacttgcag 159180 ggtttataaa caggctttac ataaaatcca gccgttccct caagaccaag gagatgtagg 159240 tgagccactg ataggacttt gcatctgcga acgcccccat atccctagag ttttggctgg 159300 tgtcattaca agtgagggcg actcttctat gtaatccctg aagaaggaag cagggaggac 159360 ctcctgctcc atccacttag ccaattggtc tggattagaa tttcacaccc tgaatgatgg 159420 agccttcaaa ggctctaatc gccagtaaag atccctttat gaagtcacag acatccttta 159480 acagctttct ttccttggtt ttctccccct acctcccacc ccaccacccc caaaattgtt 159540 ttatacttcc ctcttgaaat ttttgcctac ctaaaaaaaa ttataatagt ttttaaaaca 159600 tagttgactt tgtagtgcca aaaataaatc taaggcatgt acgagcaagg ctcttttgct 159660 cgaggctggc gcgtgctctg aagagtccac acactgagat ccttcaggtg tgaggatggt 159720 tacctctcag aatgcttttg atgaattatg taatttatat tcttttaaac tgccttttat 159780 atattagttg aaaaaaacaa tttcaggaaa attgtatctt tgtcttttta gatcttggag 159840 cctcaaactc tttttcctcc aaggaatgat aaaactttac ctctggggtg gggggggggg 159900 ccccccccct ggactgggga ggccttaaag atggataggt tcagggtccg aaagaatcta 159960 gaccccagtg gaggaggcta aaattagagg gtggagggca gcaaaatata aaagaacaaa 160020 gatataaccc ctgaccgatg gtcgnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160140 nnnnccccca ccccgacact ttggggttta gcaggtaccg ctaatctcat cttgttaggt 160200 tctttctttg tgacattagc aaatggatca aatactatcc ctcgaacttg taggggaatt 160260 gctacctgta gtgtgcgtag tgcgtgaagt ctgtgctttt gataatagta aaaaatgtaa 160320 gcctgctgtt tcaggtctcc aaaaatcttg aatggttcca tttttgtgag catttcatgt 160380 tacaagtttg gtgtttcaga tagtcatact cgtattttca actacaatga gggtcttgca 160440 caaccttggt aaatccccct tccaaccaga aaccacatta agatgtgtcc cgctgggcct 160500 gcttctctgc agggttctct catcaagcac acaccacaac cacccagaag cagccatgta 160560 agcaccccat aggtcatagt ctcaaagcag gactgggcaa tttgaaaggc aatgggtttt 160620 gaaacaagaa gaaacgttaa atgtcaaata cacaaaagtt aaataccaag aagagaaata 160680 tacttctaag ttctcagtaa tctaatgctt taagaatatt cctgttttaa taatttttag 160740 taattgtatc agacagaagt taggtatgca ccagtgccaa agaagagtcc tttgcacccg 160800 tgcagtaggg tttttccctc tctctctctc tctctctctc tctctgcaag gcttctcaga 160860 tataattgag cagtgaccac agctggcaca cgtagctcct gaagagtgag cggtaccagc 160920 caggcagccc actcctgcca tggaaatgtg gtaggtgtgg tcttcttttc cacattaagc 160980 agacacttcc tccttccggt ggaaaacaaa gcaaaggagg ctgccagggg gtactctcct 161040 gcttccagag aggcctcgag aattaaaaag tgaagaatgt tttcctaggg tcagaactct 161100 ctgggatgga gcagttggac ccactttgat ttctgtctgc agctgacagc cagccaaggt 161160 tcaaagtacc acataagttt gggttgagct cttgcctctc ccggtgtctt ctctgttctg 161220 aactgagccc ccagcagtca gcataaataa aacccagcca ctacctctgc cccggtccta 161280 agcttacctc atatctcagt cggtcacact gtcagcctaa ataaaattat ttgagttatt 161340 gaggagaaaa tgtccatgat aatcactaaa cctgtgtgtt tggctcagag aaggtaagct 161400 gtgtctaggg tatggcacta aagaccactg aagaaggctc caggtgtgtg cgggcatcag 161460 ctgtgagtgt gcatcatggg ccttgttccc tcagctctcc atgtgccttg taaattgagg 161520 aaaatggaac gaaatgttaa aaatggcata tacttcaaga atttggaggg ggaattacca 161580 ggtgtttaaa ttaaccatcg tttcagacac aaaactttat gagatgcttt actctgacca 161640 aatgtggtaa cacttgggag gcagaggcag gaggattgcc acaagttcaa gatcaaacct 161700 gctttacatg tatcctaggc tggccagagc tacataataa aaccctgtct ggaagaaacc 161760 agcatctagg agcagacact ggaggcaggc atcctgagga gcagagcaag gctctgatag 161820 caagggttcg agactagcaa tacatcactg ttccgtttgg aattccattt gccttgatga 161880 ctttctgtgc ccacagtcat agaaccttag ctggtttgtt tggggttgtt ttgttttgtt 161940 ttgtttgttt gttttttgct tgtttgtttt ttttttaaac aaaggtagta actggttgat 162000 taagacctca tgttatgact aaattctctt tgacagtttt cagtaggagc cagttctttt 162060 tgtatgctgg atgccttgtt atatacttag gtttgcttgt ctacttaata ctccaaacat 162120 ggaaaatagc agttttactg ttttcccctc ttccaaatgg aaaatctgag atatgggaca 162180 gttaagtagc aaaatgtcat gctctagagg gaatgtcggg tggaatcctg ataacctggc 162240 ctcatagcta ccctcagatc cacacaactt gttagtacta aatatgacat ttctttgtat 162300 tctagtgtgg tgatgtttaa agtctctgcc ttcatccata acttagagtt atcttatgta 162360 acaaacacca actcgtctta actggagaac tgctgttgat atatcccaca gaatgctgag 162420 taaaggggaa atacagatct tagattttgg attactgtgt ccaatttcat tccatttagc 162480 agaaaacaaa aattctgtac aaaatatttg gggtacaaat atttaggact gtaaaaaggc 162540 taccaagtag agggaatttt aaaattaaga acatttctgc tgtcctgttt atgtctcctg 162600 ttactccaaa gtagccacac attgtatttc aaaaataatt aaagtgagtt tatcaattta 162660 aagtgagtat gaaaattata taagtctgtg ggcatggtag tataagtggg aaatcccagc 162720 acatggcaga agcgccaggt gttcagacac tgtctttaaa aaaaaaatca ttgaaacaca 162780 ttttatttca ttgcatttgg atttatcagt tagagcatca gtttcaaact tttgtttcac 162840 aaagttgaaa aaagaagagg ctgtatcaag tattcaagaa tatatttcaa aagaatatgt 162900 gttgatatac atgtcatcgc agtttttcat tacagttatt ctagagataa catacggtgt 162960 tgacatgaga atgtgggatt ctagattgct tcacacggga attttacctg ataggatagc 163020 atcactaagt gaagaaggac ctggaggagg agggcagggg cttggtggag ccggcaaagt 163080 taagccaggt agagtggtac ggcctttaat cccagcactc tggagccagc ctggtcttac 163140 atagtaattt taggacaggt aaggctctgt ctcaaaaaca tttttgttaa ttatgcaagt 163200 cagttgttaa gcatagccgt cgttactaac catgtggacg tggaagccgg tacactaagc 163260 aaaggtgaag aaaatggcag tgtttcttac ctctctgctg catgctctgg gatgcatgcg 163320 agctgtgcct ctgcctacga ggctggcgtc ctggctagtg gtgcctactg tacccctact 163380 gtgggaacac ctgaggtcag gaatgtggta tagttacatt gaagtccacc atgaggagaa 163440 tattcctgct acaggactgg gacactcaag tttgtgattt tttttttttt tttttttttt 163500 ttttggtggc tgttgctcta gactttaaca gtcagggaga ggattgatat tttgtttcca 163560 ccatcttagc tctggcagct ggcacatgaa tacacacaac ctgatagaca gcagaaagtc 163620 actcatggat ggacagttac atttatgggt atgatttaac cattagttct cttgtctact 163680 cattaattta aatggaaact agccatgagt cgctacagaa caagagttca atggaagcgt 163740 tctctgagag tcaagtgact gcatgtttac aatgacagtg tatgtgtcat tctcatttgt 163800 aagttacgaa tgcactactt accttttaca ctagagaaat atgccataaa cattgtgttg 163860 cactacacac actcaaagag ctggctttaa gcatttagca gtcgtctgtc attgagaggg 163920 caatggcggc aagacattca aacacatatc cgcctgtctg cctgcttgct ttctccccta 163980 tgattctgtg acctttactg taggtgcaga ccctgctgga caagcccagg cgatacacta 164040 gggcgagctt gcaaactggg acagaggatg gagagcacat ctccacaggg actggctgag 164100 gcagaccgtg aacctctggg tgtgttctat tctgcttctc tttgtgttcc tgaagcctgt 164160 agctgtacaa ggcacagaag ctgtttatat ctgagtgtga atacaggaga agctgccgtg 164220 tttaaggctc ttacctgctg agctgtctct ccatctctta cgatatggtt ttacttagca 164280 atattcagac tgctccagac acattcatgc agatctttat tcccttattc ttcctctagg 164340 aaacctgttg tgctctctac ctctaacctc catactcctt caggcttgct gttatcctgt 164400 gtgttgttaa tgaggcagat acccagaaac actaggctgg ctgagggcct caaactgatg 164460 agtgacaaag tagaattgac tgcagcacct gtctgatcgt ggccatgtgt gaaacttcct 164520 tgttttgttt gtttgtttgt ttgtttgttt gtttgtctga ggaaagaaaa atcatgttcc 164580 acagagtaat ttcacaaggt tcatgggcac tagttgcgca tggatggagg tagttttact 164640 tgtataattg cgagctagtt gtgcatggat ggaagtagtt ctactgtatt attgagagca 164700 gccctgatga ttgagccctc tgacttcacc catgtctgtg gctcggcccc agcacctcac 164760 agcaggacag accacctgga gctgcttcct gagagctcct cacagctgca gttttttctt 164820 ttccatttct tttccttcct tttttgtttt tataagattg ggtttctcta tgtgctgaga 164880 ttaaaggtgt gtcgtcgtcc ccccatcccc gtctgcattt tgaacaggtg cctttaattt 164940 ctggtgagca tctagtaact aagacgaggt tatttcctgt ccctgaagat gctacaatgc 165000 tgattggtgg gaagggtctc ttatgtcacc tcaccttcgg agtactgttg ctttgccttc 165060 aaagcattct gacttcacta tggtttcacg aggagcctaa aaagggggta cagtggtgtt 165120 ctgtgtaatg gtgggtcctg cttgttgtat ctcaggtggt catagtaagt tgagtggatc 165180 tcggcaagtc tggggtggag aagagtgtaa tcaccgagct ctggggaaga gggcactgcc 165240 tgtggtgggg gaggtgggac atggagtgca cgcactcatc agtgttctgc agacacacag 165300 cgcttcatgg gaccatttat attttggggg acagaaatac ctggaaattt ggcacaacac 165360 agttgatcac aaaaataaga tataggacat aaaataagag tcttccaggc aaaagagact 165420 tgcatgacat taaaagaaag aacttactgc ctctgtgcca ggaatgaagc tcaggtgtca 165480 ggtccctgct cacactggcc ttgccacatg tcagtcagga gacacctcct aaacatttca 165540 gatctctctc tgcagagact gcagacggtg tgctccagct gtccaaactc tagcacttgt 165600 gctaatgatg gcccctccct ctgttagcca gctgtgtacc ctgtgaaatg tgggttcatc 165660 tctatactat atgggaattc tgtgactacc tgtcctttat tcatcttcat caaaaggcaa 165720 aagtcagctg ccaccatgga ggtgagaggc catcctggca gagtgcttcc tctgtcctaa 165780 gttttgctct gctgtcttca tatcctttga tctgtacaat gcccctgtag agtaagtctg 165840 cttattctct cagttttaca ggggaaggcc ttgggttagg gctggctgct ctaaagctac 165900 aaggcctcag atctaaatct ctacttcgtt cccacgcctg tgtgttcagg gagcctgtca 165960 tccagcctgc cctggtggtt ttgtctgcca tttggaggaa gttgttctga gcaaattggg 166020 ttaagtgtgg actcagctgt tattcaggat gcttcgtgta ccgagaggaa tatttcttac 166080 agagctctgt tttaaaggat agtatgcatg ttcaaggcag gtcatgtttt tcagtagcac 166140 acacgcacgc acacacactt taggagaaaa aaaaaatccc aagaaagaat gttatgtgtg 166200 ggagggaaaa gaaaagaaaa aacaacaact tggtatttag ccaaaagtag tgacattcca 166260 agcttgtttt cgagtatttg ttttgttcac tgttaattat aaaagaagag tccatctgtc 166320 agtcagtcag actggtgttc tgttgtctca tcatgttgtc ttttccatct taataagagg 166380 ccatgtgctc tgatttcagg agctgatatt cactgaccat cccagtactc attgcctcat 166440 tggccaaaag taaagagctg catgtgaggg ccccaggctg gaccactgtc tagcagagcc 166500 agggagtggc actgtgaggg cccaggctgg accactgtct agcagagcca aggagtggca 166560 ctgtgagggc ccaggctgga ccactgtcta gcagagtgta gtggctattc ctggttgtca 166620 acttgacaat atttggaatg aactacaatt tggaattgga aggctcacca gtgaccctta 166680 tctggaggct tggagatcct tatctggatc ttggtttgaa gatcttgagc cactagtggc 166740 tatggattcc agaagattga atctccgagt taaggaacac acctttaatc tgggctactg 166800 cctttcactc tgggattaaa ggtgtgagtg gaacacacct ttaatctggg ctacaccttt 166860 tgctggagac aatataagga cattggaaga agggagtcta gctctagttc ttgctcttgc 166920 tccttcgcct gcttgctgcg tgagactgag taactgctag atccttggac ttccattcac 166980 agctgcgact gaaccattgt tgggaattgg gctgccgact gtaagtcatc aataaattcc 167040 tttactatct agagactatc cataagttct gtgactctag agaaccctga ctaatacaca 167100 gagccaggga gtggcgctgt gaaggcccag gctggaccac tgtctagcag agccaggggg 167160 tggcactgtg aggctttggg tccctgcgct tacactgaga gaggagggag tgactcagaa 167220 agagtctttt cctcacgact gccctttgag cactgtgggc agacttagca ctaagttcca 167280 ctggacctgt ccatcgcaca agtggcacat ttcgtcctgt gtagaaaaag agtgaaataa 167340 ataatgccaa tattggcatc agcccctcca ggccttccca gtgatggcag tagtgaactt 167400 gcacaattcc tgggtgtgtt tgtctacttc cctgtactta aaagagtttc tcagtacagc 167460 aaggatttat tatttatgcc tatctacaca gacagatgtg tgcatgccac tacattttgt 167520 aagattccaa atgttataat tagcttgtta cataggagaa gggaagtggt ggtggtgagg 167580 tctagacatg ggcgtggtca atctggacag ggagggcact gtgggtacag gctggacagt 167640 agacctcgaa gctgagccag gggtgactct tcattatctg agtctgtacc tccccttctg 167700 ctctcttcta attattcttc agttctggga agtttcttat tctttggtct gccacaaccg 167760 ccaaactcag gttttgatgg gtccttctcc ccaaccagat gcgcaactct ttttgtaaat 167820 gtctaaggat tactgcccta caaaaaggaa gggcaaattc acaaataatc agaagagaag 167880 acagacttag aggaagtctt aggcctagtt gtgagctctc tgaaatgtaa gacggtcggt 167940 cggttctgat atttgcctgc ctgctgccca gtttcttagt tctcctccct ctcccctggg 168000 gtgggggtgg gggtgggggt tggggttgag atgggtttnn nnnnnnnnnn nnnnnnnnnn 168060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168180 nnnnnnnnnn nnntaccttg gctgccctgg agctcactga gtagccgcct gctgtctgtg 168240 aaccctcagt cctgctgctt gagttcccag tggctgggat tacaggcttg caccacaggc 168300 ctagctttct ttcctttggc tctgctgaag gagaatccca gcaagtcttg gcttatataa 168360 agatctataa gaaggagcca tttccttttt ttcttttttg gttttttcga gacagggttt 168420 ttctgtgtag ctctggctgt cctggaactc actttgtaga ccaggctggc ctcgaactca 168480 gaaatccacc tgcctctgcc tcccgagtgc tgggattttc aaagtcactt caggctgatt 168540 tcctgagagt tccattgcca aaagatattc ccagtgaggg gctgggaagt atgaaggaag 168600 tctctgcagt ctatgtgtgg aggaatctcc agtcttgcca actggtgttt ggcttgtagt 168660 tctgaagtta ccttcagaac acattacctg acattgaagt ttggaatctc taggtgtgtt 168720 ttcaaagcct ggtaatttta tcaataatat agtcaatgat tcaatataat tcaataatgt 168780 gtttactgtc tcttcttggc ctataggaca tgacagcgct aattccatat attttaggta 168840 tacccattat gaacaattta ggttttttct tgatattatg ttttagatgg aggggtaggg 168900 attgtataag gattcagtgt acagctctgc agcacaagag ccatgtgcct gccatgacca 168960 cctctgttaa tttcctttct agtgagtcct tagctgcatt accaagttac tattccctaa 169020 tagatgttta gatgcccact caattttctt ccttgatcta gtcaagctga tgctaggcga 169080 ggctgcactc ttctgtaagt ccatcactta actgaattta actttaggaa tttaacaaag 169140 tattcttatc cctatagagt gtgttcttaa tctaaatttt tgagacatgt ctaatttcct 169200 cggcagttga tttatctaga gagggtaaca gaaaagatct ttattagcct acacattttc 169260 ttttccaaaa cttttttgag cggctccact tgaatggctg cttggaccca ttcacatcct 169320 gaggtgcctg cgttgctctg gcactgatgg aagcttattt tgagctcagc agtcagtctt 169380 gcgacgttcc ctcgcagatg aaagcatccc tggtcttaat cagcatctct tcattgaaca 169440 tcctagtaag tgctgtttcc tcaactcagc tggtccgaca actggctctc ccggctacat 169500 tcataaagta gtactacggc taacttaaat gttgaatttt ctatttttat acgtttatga 169560 catgttaaaa atagttcact cgttctattt ctgtgctcac cttagctgtg gcagtatgct 169620 cagactcagg agagcaaagc ccatgcagac tcctccaaaa aaatggaaaa tagtactttt 169680 tggaatgaaa attacaaaat cagattcctc agctgatttg tgtgcttggg tttaagacgg 169740 atcctctgtg aagaactctg tcctgttgtc tttcaaagtg gcagcgcctc tcccttttcc 169800 tgagtgtgtt tacctgtgag cagtgtgggg catggagtca ggtgaagagc cagggtttgg 169860 ttccgagctc tggcagtcct ctggtaacac tgatactatc cagatacaac tcgatggctt 169920 ccagaagaca tagcaaattc cctcagccac gttaggaagt gcagagggaa accaacttgg 169980 atttttttag atttcctaaa ggaaatggca gcaactgagt gaaaaatgct gagtcaccat 170040 tgagtgagga cagtggccct gtccctgcat gctgctttag tccagcctac tcagttggac 170100 atctccagtt gaacgttgac tggacttgtc cacagctcca caaaacatat tcctcttcct 170160 ttatcttttt ataaacacat caggtttccc atctcaaaag caacattatt ttaatatttt 170220 aaaaagaaat gaatggggtg gtgatacagt ttagcagata aaagctcctt ttgtacctgt 170280 gtacgcagga cgcacatggt gggagagaac ccactcccac agttatcttg tgaggtccac 170340 ctgtctcatg cgcacaatac tacaggttat tttctgttaa agtattcccg tattgccaca 170400 ggaactaaca tatgtgttct tgtctataaa gaaaagacaa gctagctatg gtgctgactt 170460 cggctttaaa tggatagaag aactgtatag cagggttata gtaagtagct tatcacaaat 170520 gtgtgtgata ctctttccct ctagaagaaa cctgtctgta gccttagagc ttagaattat 170580 aaatgtaccc attccatttt taagcctgag tagcttcaga ttttatcata aaatatcttg 170640 atgttttcaa agtctccttt tatttgtaat ttgtgagcag ctcctttaga gacttgtttt 170700 tctgaagctg tttgtagttg tgcacgcagg ataatcctgc ttggcacctg tcttccgtag 170760 aactcggtat ccacgtgcat tttttcctga agcctaatca tacccttgtg aagcagggcg 170820 ttttgcaagc gattaggggt tgctttgctg agtcagcata gccttacggc attatgataa 170880 gctcagaaaa gattgaggtc atgtactaac ttgctcctgg ggaaacccag ggtgcaacca 170940 atgtttttct tggcgactca aagctgacaa ctgccgatat tctctttcct ctgaagcaca 171000 ctgttcattg atgcgatttg aaaagacaac aaacagcaca tgtgtatctg agacaggcta 171060 tggcttgagt aacatgaact caggtgacat gaggctggtg ccatctcctg tagtcaaggc 171120 tggaaatcca tagagaaggg ctacctcctc ccctgcagag cttctgactg ggtcttccac 171180 cctgtcgtat cttcagccat attgtctgcc tcgcctgcaa gccatcacat ggtagcagca 171240 ttgcctcgcc tgcaagccgt cacatggtag cagcattgcc tcgcctgcaa gccgtcacat 171300 ggtagcagca ttgcctcgcc tgcaagccgt cacatggtag cagcattgcc tcgcatgcaa 171360 gccgtcacat ggtagcagca ttgcctcgca tgcaagccat cacatggtag cagcatttcc 171420 agagaggctt cttacttgca aactgtcaac ctttgctgag actacactgg attcaaaatg 171480 tcattaatgt actggggaca gcttcgttgc tgtgagcgtc ttcctgttca tggctactca 171540 ctgtgatgtg ttcccaaggc tcctcgcctt ctgagagatt ctcttcgtgt cttaaccact 171600 agagagccag gatactcgtg gcctataccc ctgccacagg tgtaaagatc cctggagagt 171660 ttactgaaga tgcagttgtc acactttaag tcagtccttc tgattttctg caggtggatc 171720 tgtctgcttg aacagtcttt ttaatttaga acatagaaca ttgtgagacc ctagggaatc 171780 actaaggcac ggtatctttc ctcaaacttc ccagatttgc tggagaatgg cagagatatg 171840 aaaggaaaag atttagtcat agaagagtag tcatgatcca aaattggaaa atttgtaaag 171900 ggaccttagt ttatttcatt ttgacctcag cgtgcaaatt ggccacttcc ttgcctatcg 171960 tttcacgggg ctctgaaata tgcggtgccg gcaaggtctt gtctgcctct gcacccggct 172020 gagcacggca agtccaagcc cagccgagca cgtgtctgct ctgatagttg ctgcccgagt 172080 gtcagtcgtg ggcatttgct tgatgatttg gtcactgccg ctcctgcttc agagttagaa 172140 agaaagcatc tgtgtcagaa ggaaccagtc agaaagactg ccttacacac tgctttcagt 172200 gcacactgtt gtctcgctga ggggcctcct gagtgaagac ttggtagaac ttcttcctat 172260 agcatctagg gttcaatcca gaggacacgt gtggttgtct ccatgacagt cgccatttct 172320 ctctccaccc agttgtccct gctcacccac atgtgtccca tgcccgtggt gttctcggtt 172380 gtccctgctc acccacccat gtcctgtgcc cttggtgttc ttggttgtcc ctgctcaccc 172440 acccatgtcc atggtgttct ctgccacatt ttgagtacac ttatcaaaaa tcaacagaga 172500 aaagtagggt ttcgttgagt aaaaaacaaa aaagcttgtg agatggctca ttggataaag 172560 gtgcaaggac caaggctgat tcggtcccga ctcaacagac ctgagtttga ccccagaagc 172620 ccacatgggg gaaggaaaga ggccggccac ctcttcacta ggcagctccc agcatttgca 172680 gcatttcgtt ttcatctctc catttagaaa aataaatgtg agattttttt ttctttttcc 172740 aagctgtgcc ttaatcccag cagcactcag gaggtagaga caagggaatc actgtgagtt 172800 atgactctag gccagccata gcttcatagt gagacctgtc taaaaaacca acagcagtcc 172860 ctccaccgct gccagacaac atgtaaaaac ctctctttga accaaagaaa aagtaagcat 172920 acagaggaaa gggtacccca tagaggatga ggacacccca tagactctgt gcaggagtca 172980 ctggccatga gctccacgta cagtaactgt ccacacatct ttggtgtcta gactcctgta 173040 gaaccaggtt gctagctgct agagactttc cacagagctg atgtgctggc ttgaacccgt 173100 aatgcctaca tccaggagac taaggcttct tttcctccac tgccacagga ttcctcacca 173160 gcctgagcta caatgtgtaa gatttttctg gaagaaagcc cctcctccac tatgtgacat 173220 ataaccctag gaataggttc tatgaacctt gattgaccct ctcaggagct tcaaacatgg 173280 gggcactgaa cttgccccct tcctgtcact gcctttgttc tggtagatta gactgtttag 173340 ctcagcctac cccctgcgta gccaaaccat gatctctctt gtcagtgtgt tgctctctgc 173400 ttatgtgata tgacttggca taatttgagg tttggggtct ctaaattgga tgattggtgc 173460 ttaattatca gctgttttgc actgggggca ggggttaaat tgggaatacc tgcttttcac 173520 ccactgcatc atccggttct cttgtggatt cacagaggcc agagcaagag aaccagggat 173580 agacaggagt gatcagaaaa gattgctagg acccgaggag gtaaacagaa aatgcacaca 173640 gctgcttgtg gccatctcta gaatggaatc cactctactg tggaaagaaa ctaaaataga 173700 gatgcccaga cagagaagac tgaagggtcg gctgatctta gggaagttca accaaaactc 173760 tgactcagga tgagagcaaa gaggctctga aaggactgcc catgcagtga gggtcaggag 173820 gcaggatggg ttgcaggcct ctctggagcg ctgacagtgc ggtaacagag ccagccctct 173880 cctcctcctt tcctacaccc ctgtattatt ctctgctcct ttgctggctt tcttcataga 173940 acccaacttt actgttgtct ttgggtctac caagtgagtt gaataactct tgcagggatt 174000 gcgacccttg agcagaggtt ctcaaccttc atgatgctgc agctcctcct tcagtccctc 174060 tcatggtgac ctcccaaaca taaaattatt ttgttacttt atgactggat ttcgctacta 174120 ttatgaatgt aaatagaggt tcttcgaccc ccacaggttg aaagcagctc ttgtagatag 174180 attttgagca cgacttcatc ttcactagcc aaagcttctt gtagctttgg aaaggacaca 174240 gcttgtaaca ctgtctttca cacagattcc ctccctctcc cacacggatt ctgttctggg 174300 gattaaatct ggggtttcat gtgtctcaag actggcctta aactcagatc cacctacctc 174360 tgcctcccaa gagctgagat taaaggtgtg tgcaactact gtttagctag gatttatttt 174420 cttaagagca ctgaatgact agggaaggtt ctgatctagt aaaagctcat gatgcccaaa 174480 ttgctttgtt atatattgtg gctccctaga tgaaggttga ttaaatgggt ttttggggtc 174540 ttgccctctg aaacttaggt gtagggtgac ctctggagcc ttttcttcct cagggatgct 174600 tttcacagtg gctccatagc cttctgagct atcctgggat cctggctgtg accggtctgc 174660 ctttcactcc ctacttatga tggctccaaa gatctatctt cacatacatc tccacccagc 174720 catgtaagaa cagacaagta cacaggctct gtcttagggt tttacttctg tgaacagaca 174780 ccatgaccaa ggcaactctt ataaaggaca tctcattggg gttggcttat aggttcagag 174840 gtttagtcca gtatcatcaa ggtgggagca cagaagcatc caggcaggca tggtgcagtc 174900 ggagctgaga gttctacgtc ttcatctgaa ggctgctagc agaatactgg cttccaggca 174960 gctgagtgtc ttatagccca cacccacagt gacacaccta ctctaacagg gccacacctg 175020 gaaatagtgc tggtccatgg gctaggcata tacaaaccat cacagagccc gtggatcctg 175080 gctaaactga gctcaattcc tgcttctctg ggaagcactc agtatcaaca ctgcatgacg 175140 gagcacgagt gttagtggag tacggtgtga ggacagtggg acactcttgg gaagatgaca 175200 ttcctaggga tagtttttcg tggtgatgag gacaacagct ggagcaaaat gcttattcaa 175260 ctttgccctg gctctcaaga ttttagaaat agcctctgtc gaatgtattt ccaaactgag 175320 ctattatgac catattagtt tccatagttc atgagaaact ttgagtgttt ctataatttc 175380 gtggaacttg cttttttgag ccagcacgtg taatttttct ctgtatgtat gggtgttttg 175440 cctgtgtaca ttgttttgca gtgccccaca aggacaggag agggcgtcta ctctcctggg 175500 actggggata cagcgatagt gtgtgggaat ggaacccagg ccttctggaa aagcagccag 175560 caccatgtat gttttaaaga aatgaaacgt tcataatgag ggaggtatgc agtttggtcc 175620 tttgagaggc tgtttcctct gccccttcct tcagtttcat cctgccattc catccatctg 175680 tccaaaccct gagtcttctg ccccttgttc tgagagctcc taaagcccca ctagtcacag 175740 ttttacttat tggagtgcac ctgtggggtt agatgtgtgt gcaagcatgg gccaggcaca 175800 catgtgaaag ttcggggata actggtgtga gtctgttctt ccatcatgtg gatcccaggg 175860 ttcagaccca tgtggtgagg cttggttctt ggtgctgagc cacctcacta gtcctaaatg 175920 tacttgaaac aagtattttt tattggtatt ggcctttgcc tcgcaaactc ttgctgtaga 175980 agatgaaggt gcagatccac tcacattgaa cagttgggtg atagagagag agctggaggt 176040 gcacacacca caaatttagt ggttgatgcc ctgatgaact tgtttcctct ttgttacctc 176100 ttggtttctt cccttgtgga actgctgggg cagtgtccat gagctttcac tgccagtgtg 176160 gtttagccac cttatttggt tttgtttttc tcaccctttt cctttttgct tctgtaatgt 176220 atctttacac tccttcaggc cctgaccagt gcaatcacag ggatgtaaat tatcggaaag 176280 agatactttg gctaaattgt taaacactca cattgtctta gtcaaggttt ctattcctgc 176340 acaaacatca tgaccaagaa gcaagttggg gaggaaaggg tttattcagc ttactcttcc 176400 acattgctgt tcatcaccaa aggaagtcag gactgaaact caaacaggtc aggaagcagg 176460 agctgatgca gaggccatgg agggatgttc attactggct tgcttcccct ggcttgctca 176520 gcctgctctc ttatagaacc caagattacc agcccaggga tggcaccacc cacaatgggc 176580 cctccccact tgatcactaa ttgagaaaat gccttacagc tggatctcat ggaggcattt 176640 cctcaacgga agctcctttc tctgtgataa ctccagctgt gtcaagttga cacaaagcta 176700 gccagtacac acatgacttc cagtgtccat gttacctgcc agtgaatcca acaggtagtg 176760 tgttaaataa aagttgtttg tgggcataag agagtgagta gatctcttgg acaggcaggt 176820 tctagctagt tttacctagt gacctagtct tctctagtaa ccatctctct tggaaagtgt 176880 agtctttaaa ggagtttgtg ctggctagtt ttatgacaac ttgacacaag atttaatcat 176940 cagagaggat ggagccacac ttgagaaaat gcctccataa tattggtctg taggcaagac 177000 tatagggtat tttcttaatt agtgattgat ggtggagggt ccagcccctt gtgggtggtg 177060 ctatccctgg gcttgtgctc ctgggttcta aagctgagca agccatgggc gtaagccagt 177120 aagcagcact cctccatggc ctctgcttta gctcctgcct ccaggttcct tgccagttca 177180 gttgttgtcc tagctttctt cagtgatgga ctacagtgtg ggagtgtgag ctacagaaac 177240 ccttgcttcc ctcacttgat catggcgttc cattgaagaa tagaaaccct aactaagaca 177300 gaagtgagac caaggcttag ttctctaatg atgggtgtca gtcaggggat atgtgtaggg 177360 tgggaatggc cttgaagttg attgagtttg cttgatttgt gcagaaggaa agtcatgata 177420 tgctaagtag aagctcagtg tcaaaagtga gggaggcaac tcgggtctta ggctcctccc 177480 actgctaaca aagtgcagct gcaggtttag tgtgcacgca cgcacgcagg gcaggtgatc 177540 ctgttgaaaa gatgaacccg ttggagagct caggaaggcc gtgtgttttc tgttagcaga 177600 atgcttccta atgagtagga atgtgctgcc ggtttcacgg agccatatgg caactttgct 177660 aattttagct gggtgcagtt gcctgattct ttccttttgc cttctagaac ctctgagatg 177720 ctgcacaact tttcttgtaa cttttaacct gtgctgcttg gccagacact atgtgtccct 177780 gtttccatga cttctttgtc cctcatgggt ctgtacaggt tgtactgcta ccaagtttca 177840 cagccaggta ctgcatgcaa cacagggcag gcagggcaga agcagtgcgt gtattcccgg 177900 taggatctta gagtctgcta tgcaggtgat tagacttgtg tttgacatca gcccattgaa 177960 aaatcgatag gtttctgagt gaatgctttt actcatttta aagcagtggg attaattata 178020 aaacctgtgt agtgtatctg gttcatttta gcaaaagatt ttaatgttct actctgaata 178080 acttggattc agtttttttt ttttaaaggc agtgctcttc atgcttggcc tgatgtgaaa 178140 gtcattaatt ggctttccag tcgagggtgg atctggtctc gagcacacag ggatttttat 178200 atgtataaat atctgtgcag tatcgtcatc agacaacatg tcacagagtg ggccctagtt 178260 gatgacgtct gtctttttaa agctaatgtt tgtaagcttc tacagccttt tttattgaga 178320 gagagagaga gagagtgagc gttcgcaatt gagcacacac gaaggtgtat atcatcttct 178380 cccgtgatga ttcctcacct catacctgta acgggtactc cagtggtact tgagtttctg 178440 tctgcctgac ggctgccact gctctgctgg agtagagcag tcatgtgact gcccatcaga 178500 gccaaggctg ccatccctct attctgaagg gagggaccct ctattctggc agtgttttat 178560 ggaaagacta cacttaaatg ttctcagtac acttggctaa taaacaaata cacaatacta 178620 atataaaaaa gcattagtta ccaccacaga ccaatgaata tacctcagag gaatctaaaa 178680 aaaaataaaa ctatttcata attcccaaat agctcatatg ttttctttta aaatgaattg 178740 ttttttacaa agctgtattt ttgatttatt gctgttctca ccagaatctg ggattttgct 178800 ttcagacttc tcctcgtgca tggcagtgac gaagagcaat ttaatccatc cacttcaaag 178860 aaatgttttt cctgcattaa gtcagtttta tttctagaga tcaaatgccc caccttttct 178920 tttgttctta gagaaagcac aaataataat tacttatgaa aaataggaat ttaatattaa 178980 tgatttcccc ccgtttgcag tatgactcat cttacacagt ccctgaagag acaggatttg 179040 ttctctgctt tgaaactgga aatctaatta attggtatta gatttttgga gtacaggcaa 179100 atggaagagg gagagggtgg gacatcggga acagccaccc aggaggacaa gggtgggcaa 179160 aggtagagaa agggttggtg ggagggctgt cctgccaggg cttggcgttt gtaaagcaga 179220 gctgtgacat agctgttcta tgcttttcag aaatcttctg gagagcattg tgccttcgct 179280 gtcactctct caagtcagag tctttatcta aagaacacgg ccggaatggc taagacacag 179340 cagggacatg tgaagtcaaa gcacagaggg actctggaat ttaaatgtta gcatctcttt 179400 ctctgatgtt gtgatgagat ttcataaggt tgtgatcatg gaaaatctgg taccagcctt 179460 ccactggttc ctctaccaaa gggtattttt ataacaatgt atttttatag ttaatggatg 179520 aagaaaacta aatatagttc ataaccactg agaaaattgc ctaatttaaa atattaaatg 179580 gtgtgtttta gtatagaaat gctgtactta cggaagtata aatatctaag aatcaaagct 179640 tatttttata tgctgcatac aaatggctta ctcattgctg cactgtctga gatacagcac 179700 atgtccagtt aacatacagt tagtcccaga ggagagctcc tcacccctcc cccagctccc 179760 tcctcctccc tcctctgctt tgcctcccta cctctgcagc tcttatttaa tgtcaaggcc 179820 gaactgaata ttgggcagaa gtggcaagta cttcatgaaa aagtacaaat actgaaaatt 179880 caggacaagt tttttgttta ttacaattgc tttagtaaag ctgggtttct gggtattttg 179940 tatcacttgt tattattgac tagtttttat tattttacta ctgagaagtg gcccaaacgt 180000 aaactcaatg cagaactgaa gaaccttaca acagattgtc tagaaaatgc attccaaaca 180060 gtgaggtgta caggactgcg aagctgggtt ttccctgcca gagactttct ggagacgctc 180120 tcaggctcca caccgcttgc cttgtcgtgg ttctgcacac ccgagtgatc tttaaagtta 180180 catgctccac taatacaact tcagcctaat actgaacatt gtttctttgg tcctcactac 180240 acctctagtt ttggtcattt ggggacacca gaatattggc ttttttcaca gtggggtagc 180300 agcagcgata gtgcacgcct ctgatcccac tacttggaag gcagaggcaa gtagccaagc 180360 ctggtctaca gagcaagttc caggacagtc agggtcacac agagaaactg tttctcaaaa 180420 aaacacaaaa aacaaaaaaa gagaaaagag gaatattgtt tgaaggcctg cctgagactt 180480 gtggtggtct tctgccactg gtccacaggt ctaaccccta gaatctaacc taaccaatct 180540 taacattcat gaaacacagc cacccatgcc cagccatccc tcccttctct gaactaaagt 180600 tggctcctta cggctcaagc cttcattttc ctcttctgct gaatgacacg tgttctgccc 180660 tcctggaagc attgtgaact actggccaat aaggactacc ttgacacacc acccactcac 180720 ccactccaag gccctcgggc tgtattccac tgcctatgtg ggctgtgatg ttagaatcac 180780 ctgctgcctt tttcctttta aagatttacc aggtgagtat taaaaggaga aaacagcata 180840 ttttgttatt ataaacagtt ttccagtatg gtacctattt ttatccaagt gttccaaagt 180900 ctctcctagc ccttgttccg tgttctatct gattgataag tttctaaaaa gaaacttgtg 180960 tgctgatttg ctcttggttc tttgtatctg tcttttccta aaggtgtaaa atggtctgtt 181020 tgagcatatt gctgcaacag ttagttacac acccaggcct ggagtttata agtggcaggg 181080 gtacttgcct gattgagttg tcataaggaa agttgtgtac tttacacaga actactaata 181140 gatgaattta ctgctatcag aaagctatca taccctttag atatatgtct cataaagtct 181200 aatgattgct caagggctat gacaaacatc actaagatgt gtttatttga ccctcaaaac 181260 aacaatagta ctccactgaa agaagcgatc agaatctcct ctgaccataa ccttaggttt 181320 tctagcaggt gattttaaaa actggagaag gagtctgagc accagccctc actctttgcc 181380 ccctaactct aggtcatggc cagctgcctt aggctctgcc ctcagactac agtggtcctc 181440 aacactgcct tcctgtgtgt catgagctag gtcaactttg attccttgtc aggttatttt 181500 tgttcaatga tgacaaaaat atctaataca catggtaaca tatttgagag gtattttctt 181560 tgatactagt ttttatactc ttaagttcaa gtagtagtat tttattccat tagggagaaa 181620 atgttgtttg ttttagatta aaacttttta agggctaggg agaaggatcg caggtgagag 181680 cccgggctgc tcttgtagct gtcagtaaca ggcacggagt tcccattcac agcaactgca 181740 gcttcatctc tcactggatc ccccaacatt accgtcagcc aagtgccccc ccacacacac 181800 actccttctc taacccggag cctcacattt accaccaagc tgcatgcctg acccaagtcc 181860 aaggaataag atagagattt aacagtggag gatgaactga gagaagagca gaggcgtggg 181920 aatttaccgt gtccacacaa atgtctctct gtagagcaat tctctggaaa ccctgcgccg 181980 tactcctcaa ccctgcccct cgccttgctt tctaggcttg agctgcaccc tgaagtggag 182040 ctcagagggg aataactttc cattccacca accttcgaat tcactaactc tcactgtgcc 182100 caggccaggg acagccctct ttgtcggcca aacagagtga cattcctggc ctacagtgct 182160 ggctgttgaa gatacagatg tcctgttctg gcttactaat ctgccttcag tgcagcggca 182220 ttcgttctgt tttatggact gagaagacaa gagcactcag gcatcctcta gagcgttggt 182280 tctcaccctg tgagccatgg tccctttgca ggggaatgac ccttactctg gggtcaccta 182340 agaccagtgg aaaacaaaaa tgtacattat gattcctaac cgtagcaaaa gtagagctag 182400 gaagtagcaa tgaagataat ttagagtggg ggtcgccaca ccatgagcag ctgtatcaaa 182460 ggctgacagc attaggaagg tcgagaccca ctgctctgga tgcatatcgg actgatggaa 182520 ggcaagccct ctagtctgtg cccgtgtccc ctacagtctg aaaccttggg aggacacctc 182580 ttgtgtatcc ttctgccaga ggatatatct aggaggacac accccacaga cagtgagggg 182640 cacaggaaag gacaccgtgt gctccatctg agcaagggtt gtcagcacct cgctcctcca 182700 cactgaagag taaaactaag ggtgcacggg gagggcctca aacccacaca gaacatagtg 182760 catgcttcag aatcgatgac tcgtgggagc tcagtgccaa gcatgcaggt tcccttgtaa 182820 ggcggtgacc gctctgcagt gcccagagaa gtaggtaagg gatgtggtgg cacaggtctg 182880 ggtcctgtgc ttctaggtgg aagagtgagg gtctgactaa aaaccagcgt ccctgtcttt 182940 gggatttacc agagagaagg gagtcctata cagtaacaat agcagccagt cctatgtcct 183000 atgattggag aagagggtgt ttcctgcgct ctgaggacca ctaggatgag tcagagcctg 183060 tggagaggcg acttttaggg agctcttagg gaagagagca aaccacgcca caggtaagac 183120 ggtagaggaa ccaagagaag tgggcacagt gtgtggccgg tcagctctct gaagaaaacg 183180 cagtgtgatg ctctttgaga agaccagagt gcacccagtg cttgtggtta gcagttgtcg 183240 catgaggaag gatggagagc cgaggacagc ctggggagga ggttctttcc tactttgtag 183300 tttctgaagt gtgttttaca tctgtcattg acatagccat gatgcacagg tggcagacac 183360 tgacacttgg tttgcctcgt tctgaactgt ggtgctaata atggactcaa gccggagcta 183420 caatcttctt tgtctactgg caaatagaca tcataaacac tttccattgg gagcagaaag 183480 atttggagga tctacataat tccctaatta tttttaggtt ccataaatta gactttaaca 183540 gattttttta aatactgcat aaaattgttt tttacaaaga aaatagttac tatggtcagg 183600 gaaaagcaag ttgattgtga atactaaatt gagttacagt ttcgtttgaa tctttaattt 183660 ttttacattt aattataatg aaaacatgca gcgtaaacaa ggatgtaatt tattcagttt 183720 acatgtaatt ggcacattgc ttttgtgttg ttttctaaca ggttgtggct gtgtatgtta 183780 tgctgtaaac ttacttgcca tccttgaagg agctcatttg cacatgtatt gatagctatg 183840 catcttttcc cctgtaagca actactctaa tgctgatggc acgggctgga gagatggctc 183900 aattgttaag agcactgact gctcttccag aggtcctgag ttcaattccc agcaaccaca 183960 tggtggctca caaccatctg taatgagatc tggtgccctc ttctggtgtg tctgaagata 184020 gctacaatgt attcatatat atatataaaa taaataaata aatagatttt aaaaaaaaat 184080 gctgatggca cgacttcagc gctgtctggg agtttgagtc ctggagtgct cgctgtccag 184140 ctcctctgta caaagtcaaa gctcagccat tgacatcctc tgagcgcctg atggggctgc 184200 tcaccccatc tgcgttgagt cattgagtgc tgtgagcagg ccaggtcaag gctctgaact 184260 cggagcaaga ggacctcacc ccaccccctt ataattgtgc cataggatgc tcagcttcat 184320 aatctatatt ttgaaaatgt ctgccaggaa cagcatgaac cctctaaact cattttctcc 184380 agagcctgaa aggaaatctg atacatgtat tctggaggtg agaggtgcca tctgggtcct 184440 cctcctagcc agtcccgccc tccagggcag ttggctgcac tctaattcat tcataggcac 184500 acctgacccc agcagagatt ttggtgttga tgtgcccttg gtgtgcacca ctatttaatt 184560 tgctcttgtg ttttgttgca gagaaagcag cagctgccaa catagatgaa gtgcagaagt 184620 cagatgtgtc gtccacgggg cagggtgtca tcgacaagga tgcactgggg cccatgatgc 184680 ttgaggtaac cacagcctta cctggttttg atgcttggag taccacgctc ccgtggcttt 184740 gtatcacaca tgtttcagta ttcatgtgct gcatttatgt atgttcaggt acatatgatt 184800 taaggagaat ccacattgct gtgcttactg atgcaagtgg gaatgtctat ctgtgagctc 184860 ttgccccagc aacattctct gtatgtggaa cagcatagac ttcaattaga tgaaaatacg 184920 aagtgcaggt gtgaattgtc agttgagcac ttattttctg aagctgaact tggacgtcct 184980 attgaagggt gggactcttg cctcaggctc agggttcctg tgtgccacat gcctcggcct 185040 gtgtagacgg tttaaaatgt gagagccaac aaaacgaggg ttatgctttt tagggctggt 185100 aattccaact agtatgtttt tctcatagaa gtcaaggtta aaataggaag aaggaacttt 185160 ttaaaagcat aaccgagtga ctggccttag ggccttaggg cagctactgt ctcaggctta 185220 taaaatcctc cttgtttttt taatgagtac taaacaccca gtgctttact gtccctcttt 185280 caaagttaaa attcaagatg tgggctatgg taaaatgaga gaagaaatag cagtgaatag 185340 acagagctgc ctgagacata aattatctca agtctcgtgg cgctctgctc tgctgaagac 185400 attctaagcg taaaggacca cgtggtcaga accgcggcgt tgtgcctgct ctgtgcctgc 185460 tgcagcaggc ttgtggattc aggactagga ttttttaaac aaagctagtt ggcactctct 185520 tgaccttact gtcccctttc tcatctagaa acgctaaatc tgcaggtatg tcctgtgtag 185580 ttgggagctc gcctttgcat taacaactaa cagctcatcc ctagggggca gaggggcact 185640 tcccacacac tgtaggagcg ggaaagaaag ctgtggccag gtgaccactt agaattacat 185700 aaaagagccg aggaggacag ctttctttag aaaaccttgt gaattgtaag cagagattta 185760 attggaattt ttccatataa ctgtttattc attatgcctc ggggagtggg aaatagcact 185820 gaaaccccaa ggaggacttt gaggccttta aaaagaaacg cttagagcaa ggcaggctgt 185880 ggcttagccc ttgcaacaag ttcattaatt gtagaaactg gattgcagga tggcagtggc 185940 ccttatttca taaaatcaaa ccaaaatttt tgctgtttga aaataatctt ctgagaatga 186000 gtggagtgca ttgaggaagc gcctgtgcaa gctgagtact aagtcagcgt gccagagagg 186060 aagctccggg atctagtggc ttacggctta actggagacc tttcaacagg gagagcatgt 186120 gtgtgctcgg agagctgttc ctaggcatag atgcacactc atgcttgcat catagcatag 186180 cggttgctag gcaacagaag caaatgtcag ctcttgccat cagagcatat catagtgagc 186240 tttaaaaaac acagttttat aaaacgagcc actttcattt ttcaatttta ttaggccaca 186300 aatgagcctt ctcaccatac tctaagaagc cacatgccct ttcaaagcca acactagtaa 186360 tgtagtattg aaagcctaag aactctgctg aacgaacacc cagcggtggc agtagtgaga 186420 agtaacaaga gatctgtaag tgccatgtgc tgttgctgtg cctctccagt gtacacagct 186480 tagtgcagcc tgtgttgttg gccacttagg tttctagagt cttgctttac cctgaatgtg 186540 catcatgcta tagagaaaac ctgacagact agttaaggaa agtctaaagc cagtgggttt 186600 ttttgtttgc tttggtttgg gtttcattgt tgttcgcttt tttgctgtta ttattacaag 186660 acaggtcctt gacctttagt ccagactggc cttgttcttc tactgtagcc caggtattaa 186720 gatagctgat gccatcacac ccagtttact ttttctttaa acaacttctt atttataccc 186780 cagaatcagt tttagattga tggaaatcta gtctgacaaa acagaagcct tttatataaa 186840 cagccttggg tggaccaagc attccggcca tccctcacca ccgtgtgggg actgggcatg 186900 ctttaaatgc agtagatatg tatctgaaga gcctaagtgg catcagctga ctgggaattt 186960 agctttgaag gtgtccaggt cttcttagac tgtgaaggga aactctgctc tgttctgaac 187020 aagcatcaga tgtaggagag acacggagct gccattgcca gggcagacca gaaggagtct 187080 taccaggaga agtatctgag ctcctggagt cgctagcgga ctatgtgcaa ttttccttcc 187140 ataacccctg atcccctctg tgccttggag aagagggcct tgggaggaca cagtatgccc 187200 acagcagagt gaacatgccc acagctgctg tttaccttct cttcctaaag tgtggagacc 187260 agtctctttc tggagtctag acatggtggg cacatggagt gacagtgagc ccgttatagc 187320 atgcaggcaa ccagcactga gctgttttag ccacccccaa gacacttagc ccgtagcacc 187380 gtccccattc acctacctgg ccagagagcc tacccagatc cttccctaca caccagacag 187440 taaaggccgg atgttgcttt gaaggtctgc gaccatctgt gagttcactt aaatcctggc 187500 caccttaaaa gtaaaaatta ggggatttct cctgatattt ttaaactgag gggaaaaggt 187560 agcagcagcc cctttctctc ttggcatatg ccctgactcc tgcacttagc cctgtggtac 187620 tcccccatcc tgctttgttt atttggccat agttctcttc tggcaggtta acagacttca 187680 tgtttctttt ttggttttaa cagcagaccc taatctagcc tctcttccac tataatggaa 187740 tcacttctat ttccccagag aacatgtgtt cattgtttct gaagggcatc ggagatttct 187800 ttccttgaag aatcagttcc cccatgacag ctgcatgttt ttatgttgtt gcaccctgta 187860 ggccctcgat gggttcttct tcgttgtgaa cctggaaggc agtgtggtgt tcgtgtcaga 187920 gaatgtgaca cagtatctac ggtataacca agaagagctg atgaacaaga gtgtctacag 187980 catcctgcat gtcggggacc acactgaatt tgtcaagaac ctgctgccaa agtccatggg 188040 taaatgtcag tggatcccgc tgccccccac tactccaaca gattctcttg gtgagagtga 188100 gtcagtaaag cctgttgtgt ctgtcatagg catgtcagca accgtaagca ttcaggtagt 188160 catggaaggc tgccgatgct gctccttaat gcactgttga tcttatgagt tgtggaatga 188220 tgcaggcgga aggcccccag caactagcag gagggtttgt tatattttaa aacaaattgc 188280 aaccttccct ctctgcccac caacttgatc atccattttg cttctcgcct gccatcaaaa 188340 gagtgggcca tgacatgttt gagatttgac tcccttgagt tctatgtata agaagaatat 188400 gtgtgtatgg ggcattctga aaacagacac aggcacaatg taacagacag tgactccaga 188460 ggactggttc atgttagtct cctgagcagc tctgcaggtg gcattgcagg gcacagcccc 188520 tcagcccttc atgcccgtcc atctgtccct ccgttgttcc actttcccca agtttcttga 188580 cctctatcct tctttggagg attctgttca gaggttgcct gtggtgcagg ccgccgttgg 188640 cagtgagtgc ctggcagcgt ggagctgcct tagagggttg ctgttcactc ttagtggttc 188700 cttagtgttg tcactgttag ggatattttc acaggtaaaa cacagtacat atttcagtgc 188760 ttaggaaggt cattcctgga ttgcaagtat tctttttctt gaaactgttt gtatgtgcta 188820 gtcttatagt taaccagtaa atggggaaag atccttttta tttaccatta tggctagttt 188880 tgcttcatga ggataaaaca tttgcaaacg cagccgtcct ccaagatgtg tgagcacttg 188940 tgtggaattc ttctgtttca gaagagtgga tttcatagtt gaagtaacca attttcttca 189000 gggattttct gttgctcaaa ggacttgtgc ttgttacctc ctgtctgaag acccctcccc 189060 ctggcctcac gcaccttttc tttagtttcc acttcttagt gtgggctgat aagcatgttt 189120 tcctttcttc ttggacagtt ctgtagcgtc tcattatgtt aatagatttc acaaatgctg 189180 atagactaaa ggtagaggtg taaaggtacc tggatgacca gagcagtggg caggcaagtg 189240 accttggctt cctgctctct gagtggtttt ccttccagcc tgtgagcaag ccttggcctg 189300 ggtccactgt ggcatctctg tccctgtcac ctgttaggcc aatgactgct tttcataagg 189360 ttgccatttc attgggggat ggtaaagaaa agcattaagg tggttttact tggggcactt 189420 ctgacaactc acatttctct ggaggagaaa ttaacacttg atcaattaac actctttagt 189480 aacccacatt agtcattctt ttctttcttt tgtttttttc tctaatgtgt ttcagaaggt 189540 attgatgtat ttcccttcgt taagcagctc ttctttcttt tcattactca tttcctttac 189600 atcccagtat cggcctcccc tcgcctccca ttcccccaca attgttttta attttgacac 189660 taaaacaaga cagcatcact tgacacagta tcagcacttt gtctttaaga atgttcagtc 189720 ccactaagga agtctatatg aaccctaagg tagtctatag actgtaattg ggtggctcag 189780 gaacagctcg ttagagacaa cactctaaag tttatttgag aagtttgaca gcagcgtgtg 189840 tcagaggagg cccaagaagc tgggttgtgt ccagtagagc gagcaccctg ccatgctctg 189900 ctgtgctcag aagggagaag ctcagtggaa gcagcaggag cagacatcca tgtggggctg 189960 agggtggagt gtggacagcc tggccagctg ggcaggtggc tatcagcgag gtttgcatta 190020 tatgttgagg ttgctctcag gctaactcct accgtccgag tcctctggaa aacatcagtg 190080 cttgtcacag tcagtgccat tcccaaagtt ttaagcagta tttgcacctt gaaaaccaga 190140 atgcaagcag actgaactat atttccaaga aatcaaagat agaaacccaa aaatagagtg 190200 tgcagtattt tagtactatg tagtcagggt gtggccttga atagaagtgg tcatggtgga 190260 ggctctggag tatagaagat gtctgcaaag cccaagttcc taccaaggag gtaggaagtc 190320 cttgtgctct ccctgcaccc tcttagcaat gcagcagccc tggaacctat cgctccttgt 190380 gatcaggtgt ctctttcccc cctcgcagtg aatggaggat cctggtctgg agaacctccc 190440 aggcggagca gccatacctt caactgtcgc atgctggtga agcctttgcc agattcagaa 190500 gaggaaggcc atgatagcca ggaagcccat cagaaatacg aggcgatgca gtgcttcgct 190560 gtgtctcagc ccaagtccat caaagaggaa ggcgaaggta ggacgaccct gggagagaga 190620 ggtcacgtgt ctgcacctcc ctcctgtgca cgactctggc ttagtgatca caccctggca 190680 ggcgctcaca gagaagacca ggaagccact tcctgattcc ttcccatctt tattcgtttt 190740 gagcttctgt tgtttttttt tttcctctac aacattagac gttgaactct cacatgctaa 190800 gccgtgttgt cctctgagct gttctcagtt tgaaaatgct ctgtagtgat gtaagtggcc 190860 agtgcaggcc cagcacagca gccaggattc atatctgagg ccggcatttg aagctgcagc 190920 agggttgatt tcagttaagt gcttatgtac atagcatgtg ctcctggtga ctgtggcact 190980 tctgcacccc tgacagtagc agtttaggag atcctgggtt gctttgaata tctaatgtaa 191040 atcgtatgcc acagccccca aaaaacatgc ctgggtataa gcagcatttt tctatagact 191100 ttccagggag taacagaatg catgtaatta tctgtgcaca ccaggccttc aatgtgatat 191160 aacagcagag aggacaaaca gaagagcagg ggctggtgag ctctcagcaa ctgacagggt 191220 tgctccccat aatgagatgc tgatgtcata ccattccctg ccttccagtc actaagtgtc 191280 cctctgtagt gtaagatgtt ggtagaaaaa gcactctggg agttacagag ggaaacagct 191340 tttgactagc agtgcaatga aatattctag cagataatta ggcagaccaa cccccaattc 191400 agccatcagt tccgcctctg gacaaatgcc ttcacttctc tgtgtatcaa tgtattaagt 191460 caaattacca gtgtgagcat cagaatctgg tacagaatgg gcggcgtggg actccggggt 191520 ggaatactta cctgatatac gacaccctga gttctgttct cagcttgtgt gcacacacac 191580 acaaagggct tatgacaatg gctgaactat agtagccact gaatactaat gtagtactgc 191640 ttaattaaaa tgtgtaactg ttcttaaatt ttatcagaaa ggaattccag agagctatta 191700 tagagatacg gtatttcaaa atgaaccttt gctcaggtgt gactgtcaga cagtttgctt 191760 ctgttcaccc aacaagagag agcgacactg cagaatcatc cttggtagtc cacaggaaag 191820 tgaggcacag ccgtgctacc tgactgctct gcactggaga cgaaaatgga ttctggttga 191880 gatggagcct ggttggtgaa gtgcttgcct agaacgcaca aacgcctagg ttcagcccct 191940 aaagcacata gaatcagtca ttgtacccct ctaatcctag actcgggaga tagccaggtg 192000 agttagaata gtgagcgtca gcaagtgtga cgcccagcca agacgtagca gactctgtct 192060 ataaattcat tagttagttc atgaatgaga ttggattttc cggcagagtg tggtggtgca 192120 cacctctgat cctggcactc aggtgggatc gggtgcattt atgtggtaac tacaacttca 192180 gtgatcccag cacgggataa aggtgggagt cccggtaagc gacagagacc agcccgctct 192240 acaactgagt tgcaggggag gcagaggggc atagcaagac ccttgccttt aaaaaaaaaa 192300 aaaactgtat gtttataaaa aaacaagggc ttcttttctt tttcttcttc tttcttttat 192360 tgtagctaaa atactcatgg ccttacacat ggtagaaggt tcaaccactg acccacatat 192420 cccacttccc atggtgatta cattttaacc taaagacact agccattact tgagatctac 192480 ctgctcccaa aaaaaaagac aggaagcttc ccaagtttac aggggaccga gtgcagcccg 192540 tggcgggaga tgtgtgaaga gcctgcttgc ttttagccct ttggtcggcc ttcctctttt 192600 agcttgaaag agccatacga agtgctctac atgctacaca cttgttctcc agaagtaagc 192660 cccacgcaaa acacaatgaa agtgggggct ggagagatgt cggcagttag gagcactcgc 192720 tgtccttcca caggacctct gttcagttcc cagcacccac gtggtagttc acaaccatct 192780 gtaagtccag tcccagggga tctgtcagcc tcttccggac tccacaggca ccaggcctgt 192840 aagttataca cagacacata tacaggcaaa acatctatac aaataagtaa cattttaaag 192900 cgttcacgtg gggacaaggc taacccttac cactggctgt ggaggaactg gccatgtcgg 192960 atgctggcta caacagtgac tgctgcatgg acagtacact gtatccttga tcattgttgt 193020 gcaccctcgg tccatggcat cttgccatct tcatgaacct acatggtttg ttaagtataa 193080 ccgtgaagct gagaagcaga acccttccca actgtgtctg gtcttagttc tagctttttg 193140 ttttgcttac tttattatga attaattttg cttttacacc cagtggctcc atacttttca 193200 tcattgggga ggtggtttcc agtcattaac cctggcttgg tgaatagact cttaccacga 193260 gtgctgtgta gtttcggcat ctgcccctgc tccagctcat cctaacagcc ggcttccact 193320 atactcaagc agagaatgaa gccagtgaga agctgagaac catggcaact cattgattca 193380 ccaggctgtg ctgtcataga tatttgagtt gatttgatca ctacaaatat gataaacaat 193440 tgtgtcctct taagatttgc agtcctgctt gatttgtgtg gcacgaagag tccccatgaa 193500 ggaaagacca actcttccct catcagaaag ctttaccacc cgccaggacc tccaaggtaa 193560 attcctgtca gagaagacaa aagtggtcgc ttgaaaatgc ataggtacct gaacacagtg 193620 cctgtctgga ggaccacagt gttcctcagc ggttgcagtg gtgaccttta gctgctgaga 193680 agcagcagcc ctctttcttc accatgctcc ctcctggagc tgtatttagg ctgccatctc 193740 caaacagcag ttctgtctct atgtggtcca ccaaccccag aacagaatga ctttaaaaga 193800 tcattgttct gtgtagaatg tgatattaat tagagatgac ttgcagtatt gggggtgaag 193860 ggagctaggc atgctagcac aggtctgaaa ccatgtcagg aagtaaggcc gagttccaga 193920 ccatcctgga ctctacaaga tctgtctaaa aatcagagat aattaagatg aataaaatag 193980 aaaggacaca ggacgataga gtcagctgta taaactgtgc cattttacat gaatccagtc 194040 cccacagata cagcccataa ctgtgagtaa atctatgtat tcctaagtgg taattgtttc 194100 tctggaaaat tggtgttata attgtaatgt ctgctgttat ctttcaggca agatcacttc 194160 actggacact agcaccatga gagccgccat gaagccgggc tgggaagatc tggtaagaag 194220 atgcattcag aagttccaca cacagcatga aggggagtct ctatcatatg ccaagaggca 194280 tcaccatgaa ggtaggcctc tctgcatact actctatgca gcctttacac atttgcttcc 194340 tgtggggacc gtctaccgaa gctcgcagtt cagggcttct atgtcctctg ctggtgctcc 194400 ccggcccagt acactacttg aggaaataaa gtaagaggtc ttgatatcac aaagatggag 194460 aaagaggtca ttttctgtgg tcctcatact tctggataca tgacaagata accaaggtct 194520 gtgtaattta agaaacagga ccaagttcat aagagcaatc tggaaggaag aatatataga 194580 tgggattttc aagagccagt caatcccaag ctctccttca taattcgaac agcagattcc 194640 agaagtttgc agaaggcctg gagaggcaac gggctctgct cttggtcaca gactaaaaga 194700 acagctggaa ggaaactcaa cactgccatt gcatggcctg gtcctccttt gtcttctcct 194760 caccccacac caagcctctg agagacgccc cacctacctg tgcacgttac aggtgttggg 194820 tggcacaggg tcctggccag catgtgctcc acagcccgtg agggactcag ggcagaccaa 194880 ggctctcggt ctcagcatgg accattgtct gctctgcaga agaaagtctt aagtcatctg 194940 tggcaaatgg agctgtagtt tgtcatccag ttagtgtgca tctatggcct tggctttcta 195000 accagtcagg tttgtacgtt gaagctttat gcttttgagg ccacttcatg agaaagcaca 195060 gacatagtaa atgtacaccg actaatctat ttgctcccca cacctgcatc tttttcaccc 195120 taatttcttg aaaattaaac aaataatcaa acattttgta ccttccaatg ttgtctagaa 195180 taagggcaaa tatatacagt acatttaaca gaaatcaata tttaacctgg tgtttcatta 195240 aataaaggct tggaatagaa gcagaaatta aagagatgcc cttagcaaac atgttcagtg 195300 ccgctgggtt ccaagtgccc tacatttaat tacctagacg ggggctctgt tgtgtttaga 195360 gagatgggat ccactgaaag gaaactgcac atagatgtac aaaacaggga atgcagagcc 195420 cagggtgata gctcactcag taagaggact tcctggctag tcatgaggac ctgagttcag 195480 atccccaaga gcgtacttaa agataaaggt gtgcttgctt gctcacctct aaccccatac 195540 tgtggaaggt tggggtggga ttgctagggc acatacaggt gcacacacca tatgtacaca 195600 ctcatacaca cccccacaaa agtgactatg aatagccact tttaaaagaa acttgtaatg 195660 ctaggagctg ccccctgcat ctagtagaaa tgttctagaa ggttttcctt gagttggggg 195720 gcatctccgg ctcaggaaca ggcaggtgtg ctgactcatt attgctgcat agtatgcaga 195780 ccaaatggaa cgtcttcaga gatcacagcc aagggcagag gaaaatcgaa agtcataagc 195840 ccgagtcctt tacacagctg tatttctgtt acctttccac aaatgcttat tgtacaaagc 195900 acagcataca tagaacagga agtgatcccc agagcagcca cttcagcatc cctgcaggca 195960 gcagaggaca gcagccagcc atgtcccagt accctagctc cctgaggtta tagaggaagg 196020 cgctgtttga cagagtgaag ccttacggag aaatcagaga cctctcccct acctgtaatt 196080 ctctggcctg gccaccttgg ggcgagtagt tcaacccacc aaatctgtgt gacaactacg 196140 ttagaaacat gatacttttc ttaaaatcat ttaagaagca actgagtttt aacatttttt 196200 tcctgaatcg aagtcttctt tttgtgtgaa atgtttgtta tgaaatacag ttctataaat 196260 ctcaagatta ttttaagaga aaatacatta agccagttga tttactttgt atttcttgtc 196320 ttaacaatag aagtattggg agctggagag atggctcagc ggttaagagc actgactgct 196380 ctacctaaat tcaaatccca gcaaccacat ggtggttcac aaccatctgt agtgagatct 196440 gacaccctct tctggggtgt ctgaagacag ctatggtata cttagatata ataataaata 196500 aatctttatt tttttttatt tatttattta ttttatttta ttttattttt tggtttttcg 196560 agacagggtt tccctgtgta gccctggctg tcctggaact cgctctgtag accaggctgg 196620 cctcgaactc agaaatccac ctgcctctgc ctcccgagtg ctgggattaa aggcgtacac 196680 caccacgccc agcataaatc ttaaaaaaaa aaatagaagt atctgacctt tctgaaaaca 196740 ttaaagcaat tacactggct taggtctgtg cttgggtttc aggtatgttt agcgctttcg 196800 cctgacacac aatgcttttc agttttacta ctacaccgtg agaagaagca aagcctagca 196860 aagcagtgtg aggcggtggg ccggggaggt cgcctgagga cgagcgttcc atccgacact 196920 gcaaaggaaa gcagaggcag actgtcctta gacacaccat gcttgggggt tatgttgctt 196980 tcatggtgtt tttaatatta ttaagaaatt atggaaaggc ttattttgac ctgataaact 197040 gtttatactc tctttgcccc ataataataa tttgatttaa gaaagtttat ttagggtgcg 197100 agggagctag cccagagaga ggttaagaga gcactggctg ctcttcttga ccactcaggc 197160 tcacgttcat cagcgtccta catagattgg gtttacatac atgactcgta actcccagtt 197220 accacttaac atatagtttg tggcaaaata cacaaaatta aaaataaaaa caaattttta 197280 aaaataaagg atagtttgag tttccaagct gttattcttt gtcatacaaa aaaacaaaaa 197340 caaaaaccca cctaattcac tgtttggtat ttttaaaagt aactgctttt taaatggatg 197400 ttttctgacc tgtaactttt aacatactgg tagcaaaacc agtgaggtca atcactgttg 197460 tgccttgtca cactttcctt gacacttgac tccacttttc tgattttttt cccctttctt 197520 tagctttttg ttctaatcat gctttgtttc cttttttgcc tgcagttctg agacaagggt 197580 tggcgttcag tcagatctat cgtttttctt tgtctgatgg cactctcgtt gctgcacaaa 197640 ccaagagcaa actcatccgt tctcagacta ctaatgagcc tcagcttgta atatctttac 197700 acatgcttca caggtaatca taaactcagc ctcggtttcc catcccttgt cgagagatgt 197760 gctacaaagc agtatgccac ccaaatgcct ctcgggttcc cggaatcctc cttttttgac 197820 tatggcatta taaactgtca aatgagatgg ctgttaactg tcggctagaa accactgcac 197880 ggtgccagca aagcattttc ctttaacatt aggaactaca gcatcagatt gggtgtggtg 197940 gtgcactcct tagtcccaac acttggaggc agaggcaggt gaatctctga gagttctagg 198000 ccagcctgat ctactcagca aagtccacga cagccaggac tacatagaga gatcctgtct 198060 caaacaaaca aaagcagaag aagagtgccc agggcttggc tggaccttcc tgttacagtc 198120 cagaagggaa gttcccgagc agtacagtga ggacaggaac attaaagcca gtgctaagat 198180 ctctgatcct ggatgcttaa tccttcacat gagtattctt agactagttt tgatttttgt 198240 tcttgggttt aatttctttg cattagactt taaattgagt ggttttccta tagtaaaaga 198300 aagaaacatg aatgttgatt ttaaaataaa tgtcatagag catattgttt aagatactca 198360 tttgggaaaa tgattgaatt tcaaatttta taaatgttta tggatatgct gagggaaact 198420 ttacgaggtg ctgccaagag atatctacag ttgctctgct taaagagtgc cagtttatta 198480 gatttctcat ttattttgct ttctaggaga ggaataaaac tcaggtaggc ctggttgcca 198540 gctaatagta aagctgccct cacgctgcag ccctttgaaa gtggttatga ggcgcagact 198600 tcaccctgcc ccagctcagc tgccgtttga tgaccactga acatgtttgc taactcagaa 198660 gtagctgcca agactgaggc aaaagccctg gggcctggga gacctgctta taggtgtcag 198720 ggaagtggat tcaaattttc ctggaatgac ggccagttaa aatcacaaac tctgtcaccc 198780 cagaacccta ccacaccaca tttaatcctt tggcctgcag ggagttgagg agatgggcag 198840 gaacctatga ggcaacttga tattactaat acctgcatct ggaactggcc atctctctaa 198900 cagttagggc aaggtgttcc ccactaaggc ctctgtctac cgtgaacagg tgacacctat 198960 cagcacctct aggcctacag atgtgcccac agctacagat gtgcccacag ctacagatgt 199020 gcccacagct acagatgtgc ccacagctgg gagccgaagc tgtggcaaag ggttaaatca 199080 agcagtactt atgtggtcgt ttgtgtaagg ctgtggaagt tctcagtgat catcggggag 199140 atgcatattt gagatcttcc taatgtcctc tttacttact gaaatttcaa tatgggggta 199200 gtctaattta agctccatac acacacttca gtaaaaccac agacatcttg gtacgttgcc 199260 tgaaagcatc ccttagtcca gagctgtaca tgttcagtct agcccataag atgccataag 199320 gcatctttta aatgtagtcc acttttgtaa agaaaagagt ccctgccatt tttttaatta 199380 ataagtttac tttgtatttc tcttttatct tatatatgtt tctttcctca ttgtacagag 199440 agcagaatgt atgtgtaatg aatccggatc tgactggaca agcgatgggg aagccattga 199500 atccaattag ctctagcagc cctgcccacc aggccctgtg cagtgggaac ccaggtcagg 199560 acatgaccct cggtagcaat ataaattttc ccatgaatgg cccaaaggaa caaatgggca 199620 tgcctatggg caggtttggt ggttctgggg gcatgaacca tgtgtcaggc atgcaagcaa 199680 ccactcctca gggtagtaac tatgcactca aaatgaacag tccctcgcaa agcagccccg 199740 gcatgaaccc ggggcaagcc agctccgtgc tctccccaag gcagcgcatg agccccggcg 199800 tggctggcag tcctcgcatc ccacccagtc agttttcccc tgcaggaagc ttgcattccc 199860 ctgtgggagt ttgcagcagc acaggaaata gccatagtta taccaacagt tccctcaatg 199920 cactgcaagc cctcagcgag ggccatgggg tctcactcgg gtcctcgctg gcttcaccgg 199980 acctaaaaat gggcaatttg caaaactccc cagttaatat gaatcctccc ccactcagca 200040 agatgggaag cttggactcc aaagactgtt ttggacttta tggggagccc tcagaaggta 200100 caactggaca agcagaggcc agctgccatc ctgaagaaca aaaggggccc aatgattcca 200160 gcatgcccca ggcggccagc ggggacaggg ctgagggaca cagccggctg catgacagca 200220 aagggcagac caaactcctg cagctgctga ccaccaagtc cgaccagatg gagccttcac 200280 ccttgcccag ctccttgtcg gacacaaaca aggactcaac agggagcttg cctgggcctg 200340 ggtccacgca tggcacctcg ctcaaggaga agcataagat tttgcacaga ctcttacagg 200400 acagcagttc ccctgtggac ttggccaagc tgacagcaga agccacaggc aaagagctga 200460 gccaggagtc cagcagcaca gctcctgggt cggaagtgac tgtcaaacag gagccagcga 200520 gccccaagaa gaaagagaat gcactactgc gctatttgct cgacaaagat gatactaaag 200580 atattggttt accggaaata acccccaaac tcgagcgact ggacagtaag acagatcctg 200640 ccagtaacac aaagttaatt gctatgaaaa ctgtgaagga ggaggtgagc tttgagccca 200700 gtgaccaggt gagttttcta atgtcttctc ccaggtgtgc tcatctgtgt catagatgtt 200760 ctcaaagagg acatctgtga ctccctaaaa gtagtatttg tgttggtggg ccttaccgtg 200820 taacagttac tttgcatgaa gttgtgtgtt tacactgcaa agaattacag ggcacagaca 200880 cgagcttagg aggccatgta gcttgctctc agacactgta ggccagagca gctgtggaca 200940 ctgagcaaga aagtatggct gagctctgta cagttttaca gatacttaca gaccctgggg 201000 cagacaatgg gatggacaca aagtattttt gggggggtgg ggggcagtca ttgttctttc 201060 tatgagcagg gtaaattcat ccttgggtta caggtcatgc gtaacaatgg cgagcaggag 201120 gaactgcagc gtgactgtag ctagctgaac ccagagtgct ggcaatccct tccttagacc 201180 agggcttgct cagaacagac ttgagcatct atttgttact ctctccatag gaccagagtt 201240 cagccagtaa agatcctctg cctcttccct ctctctgaac acttctgagt aatgtacagg 201300 aatctcagtg actgttggtt aaggcacacc aaaggaaatg gatagacaca tcaaagccat 201360 catgtatcga ttcaaaacca gaataccggg ttacattctc tctgcacttc tctccaaagt 201420 taataccttt ggaacaatcc aggggaccta agtaatgatt agaatcattc ttctatttaa 201480 ttaatttatt tatttttaac aaaaaacaat ccttatacaa tatgatcctc tgtagaatag 201540 cactatcaga ctagttaata tatcactgca tttgtgctgg tcatttttgt ggtacaaata 201600 cctttttaaa actcttttga gtgaccttca atatacatgt gttatggttt ccactacatt 201660 gtacaacaga cctctggaat gttttcatcc aaactgacat tttaatcctt ctccaacatt 201720 tcagccctag cccctctacc attcccagca agactgtggt ggggaaggcg ccacagtgga 201780 agcaaaccat tgatattttc actgacttac aaaaacaagt gatataagtt gttgcaactg 201840 cagtggtaga atcatgactg actgaaggtt aggacctagc ctcaccttcc ccaggctgaa 201900 caggtcctgt ctggaagact ctttcttctg tcatggttga ttaagcaggg aggaagtcac 201960 aggggcctct ctccttaaca tggctataat ttgcccttga aagctgtgtt gcaagtagga 202020 aggtagtgtc accagcttca agagagcagt gactgtgagc ccttgacccc acaaatccac 202080 ggaggctgca tttggggaca gtccctgcca gcctaactgg ttcctaagac ttaacctctt 202140 tcaatgtgat gtcaccggtt gtcgccattc ctgagaacag atacaaccat tcagacattg 202200 tgctgctcgc aggggaagca gactaagatt acatgaacat tattggtgat taatcctaaa 202260 gtccagcagc aggcttcatg cagcagctat tttataatgc tgtgaactca tgagttgggg 202320 caccgaggcc aacagaaagt taatagcaat gcctttgtga tgtgatgtga tgtgatgtga 202380 tgtgatgtga tgtgatgtga tgtgatgtga tgtgatgtga tgtgatgtga aaaccatatt 202440 gacgatgggc tttcatcttc cggggtgtac tgggttaaat gacacagagg tagtgctagt 202500 tcagaacaac aagcacagat agccagtgtc acataggtgt cttaccgtgc tagagggcag 202560 atcagtgact cgggagatga cccctgatgc tcagttacag catggctgcc ccaccctcca 202620 tagctagaat gagtttctct ctctgacctc agaccctagg gactgagagg gacagtgaaa 202680 ggtgtcactg acatgtctca ttactctgca tatatcacaa atgccaaaca agaaaaggct 202740 ttgtggggtt gggttggctt cacttttacg tctttgaatc acttggagtt ttcttatttg 202800 gaagaaataa ttttctaatc aaaattatgt gagaaacaaa gactagtatg aatcagtata 202860 aatctgttgt ttgaagatga aaaataaaac agggcacgca tgctcacata caggaagtat 202920 attgtcctta aagaaatctc accccttgct cacctcccct ccaccctctc ccagacccca 202980 tctaaaatac agtttcacag agccagttta gcatcaaaac catagcaagg ggaaaagtta 203040 ccacaggaag catgctttac ctaaatttag atccattatg aggagaagaa aactcaattg 203100 tttcacctct tgctcacctt ctgttcccta aggatggtct cctcaccttt catttcagag 203160 gaatgcagta attatttagt aaacatgcac acatagcaag cctggattgc aatggactgt 203220 cttgttattt tgactcaaaa aaaaaaaaaa aaaaaaaaaa gacctgagag cctgagtgtg 203280 tgtaatgcat tactgacttt gtaaggtcag ggagtacagt gcacttcagc agcacagtgt 203340 tactctacta aaaatgacat agttttacca ggcagagcat tcaaacaaga catttctaac 203400 gccatttcct agccaacagg aaacaaactg acagaaacat tgccagtgtg tttactgctc 203460 taagtcacgt gcttatttcc acaatggagc attgctggta ctcggccagc caatactttt 203520 ggctcctgct ttctttgagg acttggaacg gtctcccatt gcttaactcc attagaaaag 203580 ccatgttaag ctggtagtca ccagacactc cctccagata ctatagaatt ccttcacagg 203640 tctgtaccaa gcaaatggta tgatgctata gtttttattt aaaatgtttt caaaagctac 203700 tttttaattt attagattac tcatgtattt ctgtattcgg agaacaagtt gatttttgac 203760 tcatgaaaat aattataaca ctaaaaagaa aaattaaaga aatgaagtct atttttcatt 203820 ttgtagaact taaaaaaaaa caaaaaactt tctgactcat tttctgccag aaatagttga 203880 aactaactac tgaaattgat gtggctagtt tgagcattca aatagatgcc taagtgagac 203940 tctgaagtgt ctacaaggca ttttaaagaa aggcactgat ctctctgtct tgcaaagaca 204000 ctgcctaaca gagtgcaagg atcagaagaa catcagtgag atgtaagctc cagagctgta 204060 gaacacatct tccttcagaa acatctaatt atcacacttc agcccttcca gagcgtgcgc 204120 gaacactaag ggaagtatta aaatcaatct gcctgagggt tataagccat gctgaaatct 204180 atctcctata gaaatattta aacttaggcc agacatggtg gtgtgctcct gcaatcccaa 204240 cattctagag ctgagagaga attgtaaatt ccaggtcaac cttacctcag gataagaaaa 204300 gttaaactga taacaaatta atgataaatg catattccaa aaattgacaa ggaataaatt 204360 cagacaaagc aatgtctcta aaagttcctg gtgcatcttg aaatgtaacc tgagtgagtt 204420 cagatagtgc ctggagctct gagcctgtag aagcaggctg cccatagcaa agcgctgccg 204480 agctctcaga tttgctgctt ctcaagtcaa cgttgctgct gctaactttt cctccctccc 204540 tttcttcctt tcctgttctg gacattgaac ccaaggcctc ttaaaagcct catgactgaa 204600 ttacgctctc actcacatag gtagctggta aagctgtaaa tgggagtaat cagaatgtga 204660 aagtcagttt aagacatttc ttttaaagaa aaacaaaatt aagccgggcg tggtggcgca 204720 tgcctttaat cccagcactt gggaggcaga ggcaggcgga tttctgagtt cgaggccagc 204780 ctggtctaca aagtgagttc caggacagcc aaggctacac agagaaaccc tgtctcgaaa 204840 aaccaaaaaa aaaaaaaaga aaaacaaaat taggatgaga gggagaaggt aactcaggcc 204900 acatcacaca aagctggttt tgtccctagc actgcatgaa tacataaata aaaactttac 204960 attgagtaaa tatatatatg tgtatatata tatatatata tatatatata tatatatata 205020 tatatatatg cacacacaca tatatatact gattatgaaa ttttttactt agaaattatt 205080 tgagctggac attttccaca tccctgtagt cccaatgctt tgagggttag ggtaggaaga 205140 ccaagaggta aaagctggac tctgctccat agcaagtgga aaaccagcct gggtccctga 205200 ctcataattt tttctcatat aaattgattt tagttactca tatagcttaa cacatatgta 205260 ttaaacatta tatgtgcctg taatgttaaa atgtatgtca agtgtcaagt atttacatgt 205320 atatatatat acttaaatta atatgttaca cagaattaca caaacaacaa aagaagaact 205380 acggccagat gtgatttagt gccagcactc aggagtcaga agtaggcagt taggtctatg 205440 tagtgttcca gcacagccag caagagccac agagcctcta ggaagggagg gtaagaagga 205500 aaggaaagac caggcatgat acagtgtgcc tagaatccca gctcccggga ggcagacagt 205560 ataatacttc aagttcgagg ccattctggg cgacacagtg acctctgtct ccaaaatgtc 205620 tttttaaaaa accttgttag ttgtgattaa ggtggtttat aattttgata gtggactgta 205680 acggggaaag cattctgtca tggctcagat tggaggcaaa ctcaagtgca tctattaaga 205740 aaacacatag acacttctgg ctttgcttac atgagcctgt tttctataat tttcatcagg 205800 ggcaatctgc caggttttgt cagagacaga ctgtcattta cttcagctat cttcctcacc 205860 tgcacactga gctttaaatg tcctcaggct agggcatcat tgccatagga cactacttca 205920 aagaccagtg gtagctcgct gaagccctgt tcttaccaca gaagcatagg aaacactctt 205980 ctgaggactc gggaagctgt gggaatttct gttttagttt taatgatgac tgaccaccac 206040 ccacaccctt caggtctcac tgtcgatggg cctgtcagtc acagctgatc cacagtgtgc 206100 aaggcttccc ttgctcagga actttcaggg ccacgtctct tgcctgaacc tctcccatag 206160 aaagcttgtt gtcctgttgc aaataggtga cacaggaatg ttcttcttgt tttaagagta 206220 catgaagaat tttctggaaa ggagtggcta agttcactgc tgaagtagct acctctgaaa 206280 agactcaagt aaaatgtcac ttcaacaggg aacttcctaa cttgacaggc tcagttggca 206340 aaggcgtttg tcattgtcat gcctggtgat ccgagctctg tcccttagac tcgcgtgggg 206400 aagagagaat cggcacccac aggtcctcct cggatgttca cacacacgaa ggaatgagtg 206460 gacttttctt attagaaaga cacggtagac tacacagaag cacactccta taatttgcac 206520 atgagcgaat ccattagaag tcgttgccag tttcacgtgg actcagatac ttttgttcag 206580 ttttgaaacc atctccctct agcccagaat agcctacagc tcactgtagc tcaggctggc 206640 tttagcctca agtgctggga ttcaggcatg atcacacttg tttgaccact ttcctgtgta 206700 attgaaatct atgatcttaa atgctagcac cctgataggt tatacccaaa agaatgccag 206760 tgaagtcatt ctagctctta gacaaaaaaa aaaaaaaaaa gtaggcaata taatatagtg 206820 gtcatactta ggttattaat cagtattggt aattggaatt gaattcaaga aatgatttga 206880 agaaactggc gcatatgaaa tcaaatgaat acacgctatg cttggcatca gccggtggtg 206940 gcacacgcac gcctttaacc ccagcactcg ggaggcagag gcaggtgaaa ctctgagttc 207000 aaggccagcc tggtctgcag atcaagttcc aggacagaaa cctgtctcaa aaaacaaaga 207060 gggggtaggg ggagctagtt aggtcatcta agctggttaa taagaaagct actgacattc 207120 aaacctaaaa taaaagcaag caaaaagcac atttcaagtt gaaaaagcaa gacttagcta 207180 gtccatgaat atttgaagct tattttacag ccaactcaca cagacaaggg aaatagccat 207240 ggttatttgt accatattct acaccagctt tattgttatt atttcttaag aaaaaaaatg 207300 aaacctagat ccaaactgta agtcatggtc caattataag taattggata taatctttca 207360 taattaatgg ggtggttcaa ataaaataaa gggactacat aaactgctag tgagttgcaa 207420 ggtgggaaac agcttccttt ttttaagtcg gccatgccta gtttctaagg gagggagtca 207480 tggtcctcgg tggattcagt tacgagagat ggttggccca tcattaggcc ttacatttgc 207540 acatacctgc tttttttttc ctttttaaac ttggctggga tgccctgtgt gatggttggg 207600 tctgtactcg ccaatggcca gggttggggt cccctcttgc agcatggacc tggatgtaca 207660 cttctgtttg ttaactgcag cctggcagcg agctggacaa cttggaagag attttggatg 207720 atttgcagaa cagtcagtta ccacagcttt tcccagacac aaggccagga gctcctactg 207780 ggtcagttga caagcaagcc atcatcaatg acctcatgca actcacagct gacagcagtc 207840 ccgtcccacc tgccggagcc cagaaggcag cactgcgcat gtcacagagc agtaagtatg 207900 cactctaacc ccatcagaga ccaactcaag gctgccagag tcctggtctg tccggcagct 207960 taccgccata gtttcctttg gagaggaaaa ttcaaaccag gcatggttac tgcatgcctg 208020 taatcccaga catgaggctg aggcaggagg atggtgagag ttcaagggca acctgagcta 208080 catagtgaga ccctgtctca aaaagtttta attgttcaca aaaagggtgc tcacggtcaa 208140 atgccttatg ccattgactc tgatagaata ttttgcgatt tcagttttgt gtgaaaggac 208200 ggttttagtt tacagaaaga caagtcttca gtgctggtaa acaaaagcac cacttccacc 208260 tcaggagagc accaacgcca tgcctagcag cgctctcaag tctggaaaag cgaacctcag 208320 ccaagtcaca gataactacc tttagaaact acgtccttcc ttgcatggtt cctgaccatt 208380 ctggaaaggg gtaaaggaaa gtaagatgaa gttttatttg acctgggcaa atcacaaagc 208440 taaagaataa gagactagcc cggcatggtg gtgcacgcct ttaatcccag cactcgggag 208500 gcagaggcaa gcggatttct gagttcgagg tcagcctggt ctacaaagtg agttccagga 208560 cagccagggc tacacagaga aaccctgtct taaaaaaaaa aaaaaaaaaa aaatgagaga 208620 ctgaggtaag ctagtacttt ttaacccaga gaggagcaaa gaacacggtg ggggctcgca 208680 gctcgcagct acactcgctc aggagcccca gggaccctga aatggtgagc tgagccgtag 208740 gaaggcaggc ctgggagagg caagcaatgt ccattcccag cctggttttt ctgaatggtt 208800 tttctctacc ataggttttt gaaaagtctt ctttcttcta actgctagtg cagtctatgc 208860 ttataaaact aaaagaaagt aaagtcttga tatgactaat aaattagccc tgtaagttag 208920 tgtgtatagc attgagtgtt ttaataacat tgttataaaa ttacaggtca tctacttgac 208980 actagattac tgctcagtac acagtcaatt cttgtgaact aaccatcaaa accatttcaa 209040 atctaaatag tgcctggagt taaagccata ctgctagtca taggctacaa tggagttttg 209100 tttcaggtga cactcaacag ttttaacttc tagtggaagt atctacttct aacttattct 209160 aaaccttgag cccagttaag aaataatgta acatccaaac cacatgtgtg taggctgctg 209220 ctgcatgcaa gagatgttta taggctcctt actgtagaaa taagaactcc tgaagcagac 209280 aagtgcatac caaatttaag gggagatctt atcaaaagaa acaaaaaaaa aaatgggaaa 209340 cagaaaaaga ccacccacca acgtgtgaat agtataacat gaacactatc atattaatgt 209400 acgataatgg tttagttagc aaaaaacttt tcaatgctac aattcctgga gagaaaacat 209460 ggtacttttt tttacatccc ctttttgcaa ggccattgag agttatataa taccaaccag 209520 ggtgctgcat atgttttctg tagttgtctt tcatggagag agttaccaaa gatgtgcatc 209580 tttgtcatgc tacaggagac attttcccta aacactactt actgttaata ttctttttca 209640 ttgtccttta ttaaccttca atttttcatt tgttctttcc ttagctttta ataacccacg 209700 accagggcaa ctgggcaggt tattgccaaa ccagaactta ccacttgaca tcactttgca 209760 aagcccaact ggtgctggac ctttcccacc aatcagaaac agtagcccct actcagtgat 209820 acctcagcca ggaatgatgg gtaaccaagg gatgctagga agccaaggaa acttagggaa 209880 caatagcaca ggtaagggct cagcggtact gctgcttact ggcgggttgt gtaatttaac 209940 aatgtgttcg tccacatcaa aatggtagaa cttgaccatg ggcttgttag aaacctcacg 210000 gatcccctgt gagggtggcc ttgggaagcc actccatcaa gctgaccaag tcattcctca 210060 gctgctgctt tgaggaagtt cctgatctcg gtcttcttgt ctagccttgc tgcatttcca 210120 tcccaactgc tggtctgaac ttggaagaat atatgcaaaa taaaccaaaa ctggtgcttg 210180 ttagtccata gatatctgct gaaaactcca aaaacagatt gatggttttg gaatgggagt 210240 ttaaaattct accattcttc cacaattcta gatccttttt ccacttagga aaaaaaaaaa 210300 aaaaagaagt aaaagtgagg agctttttgc ctgtgttgcc acgtttccac tgtatgctca 210360 gccatgcagg acggctgctg gaggaccact tgagccacag actttgttgt gttttgtttt 210420 attggctttt gtgttctggt ttcttaacct taatgcattt taacagcttc aagtcagggc 210480 acagttaaat gagcacactg gtttgaagtc acaccaatca ggcggcttcc tggagattgg 210540 agaagctgcc tgtaatctag ctggagcttg acctgatagt tttccagtgt cctcccccat 210600 atttcctaag tggtacatct tcccgccaca gcggcataga attcagaatg agctcacagt 210660 gcgggccgtg gagtggcatt tgttacgcgt ctgggagagt gctggcttcc taaggaagag 210720 ctggctgtag ctttctttcc ttgtctcagt gatgtgttag agacttgggc accctatcaa 210780 tacattacca ttttcgttca ctgaagatca gagcactgct caaggggaag tgatggatgc 210840 tgcatttctg attgctaaga gcgaattcat gggaagtgtg agctatagtg tgtcggttta 210900 ttcattcaac agatactcac ccctgcctaa ttacacacct gtactgactc cctcattaaa 210960 ttacagatcc ctgaaaacag tgccatattc actccattac tcttaaataa aagcacgact 211020 catagatata ttggtgatga gaaactcttt aaagaaaagt agcagatgag tgactaggag 211080 tcgctcccta tcggtgaata caatgcttac actgttgaag tcttgtatag gaccttggga 211140 ccatggggac ggcctctgca tgtcccagaa cctagtagtg cccaggctgt caggatcaca 211200 tggtataaag accagcacca tagggaacag tgtccattct tgctgcactg atactgttga 211260 gtttcaggtg acttcaccct cctcctctcg tcttattatg ctatttaaat aggttgtttt 211320 gaaactaaaa tgcctttcca cttatccact tatagataaa atataaatgg ttttaaatat 211380 gtcttaatat tgcagttttt aaccctaact aatcaccctt ctccttttaa catctcagca 211440 catccctcat ttcacacatg aggaaacacc catgttccat ctacatgttc attataccaa 211500 atttgcttaa ccgaaataaa gtaatctaaa gcaagccata aatttgaaag caaatcttta 211560 tatcccctgt atcacgtttc agaacaaaga gatgtttctg aggcttcttc ttcagtatgt 211620 cttaggcagt gtttggccac tgccgtcacc tagagcctgg acactaatag aacagaccct 211680 gagtcctgcc tggtcatgtt gagttctcat tgttccgtgt gatcagatgc caagtgtaga 211740 tttccctcac gcctctgcta gcccattctg catcggtgtg gcctggaatg cagtgcttca 211800 ggagggtggg accctttgct caggcactgt gtcaggaaag tctttaactt cctgagtgct 211860 tagaggctac ccttggtaaa ttttgaaatt tactaaattt ttttttttga tggaagttgt 211920 tgctgaagta tcctgtccat gcagacgtat gcctgtggtg gggcagcttc acttgatggt 211980 cacccagcga acatgtctgc atgctccaga agtgtagcag gcgccgaccc cctgaaagga 212040 tgaggatgct cagctctctc tcgcaaaagc tttgcaggat agtctctgac tggggtcgat 212100 aattttggga ttgattatca gttcttacct tgttcctcct caccttacct catctcacct 212160 cccttttgga aagtagagct ctgacgtata cgtcagctaa tgtgattcac ttcctgagga 212220 aggaagttgg ggttatccac ttgccgcagt gcctgttcta ataagtacat atgggaacag 212280 ttttaacagc tcttctgagc agatgcatgc tgtgaaaact gtagtaatca ccaactctta 212340 gttcttagcc cagggcccac atctgccctg ggggagtgtt tgctgttgag ccaactgcag 212400 gttacagtca tggtctgagt cttgtaggta ggtctggcat gcgtgcatat gctgttttca 212460 atgtctgcgt ctctcagttt cctctgtctt ggatgcagga atgattggca gcagcacttc 212520 ccggcccagc atgccttctg gggaatgggc accacagagt ccagctgtga gagtcacttg 212580 tgctgctacc actggtgcca tgaaccgacc agtccaagga ggcatgattc ggaacccaac 212640 agccagcatc cccatgcgag ccaacagcca gcctggccaa agacagatgc ttcagtctca 212700 ggtcatgaac ataggtaagg ctccttccct gctgccctta ccccgtggtc cttcaggatg 212760 tgcagtcctc aatggcattt gctaaaaccc tgttaaatca tggactgatt acctaatttt 212820 aatttggaag caaaatacat taaaatgtca cattataaat gccacatata taaaatgtca 212880 catatatatg catgtatatg gtagtttaaa ggcaacgaaa tagtttggtt gtacagcctc 212940 tatgtggtca tcctaaacca ctaatgccct caggcaggct gtgaagtcag cgtctccctc 213000 agcctcattg atagtgcgac cactcaagaa catgacacag cacccaagca tctctagcat 213060 tctagctgga ggcagttcac atgtcacgga aatgaatttt ttgtgtacac tccacaaaac 213120 cttcatcata gctgcctata gctgaaggcc tggaaggagg caggaagtga gtcctgagac 213180 aagggcttcc tcttcaggta agtgaaagtg cctgagttga tgtggtagtg gtacactcga 213240 acacattgac acctacagga tgctgcacct gaagtcatga gttgtatgta tgatgaatga 213300 atcatcagga aacttgttac tacatattga tgtacacact tagaatcctg agccttggga 213360 ggtccaggca agagttcagc atcctcagct ccttagcaag tctgaggcct gactgagctg 213420 aacaaggccc tgtctcaagg gaaaaagatc agttgcctat acagctccta cttgatatta 213480 tttgtaaccg tagacatagg acttaaatct taaacattag ctcaattcta aaaagtctgt 213540 gtgtgtaaac ttttgtgtta gatattgccc aggaagtgct aattcattcc caggaaaatg 213600 caagattgtt ttgacagaag agcaggcctc ttgccagaac tttgaatcag gtttcttcca 213660 taggtgttga agtgctgtgt gtgtgttgac tcagtatttc tgagagtgac atttataatt 213720 aattacattt ctacatatat gctcatggta gtaggtggaa aattaagctg agacatgagt 213780 aagatgttta taaaagtgac agtaagaggt cttgcataaa tatttaattt attccccatc 213840 ttgctgatag tttggaactc ccagtacagc tctgtaagat ttagtatgta gctgaatttc 213900 tctagtggta agtacagtca ataaatcgga atttgcccaa tacaacattg cctgttatgg 213960 atgtccagtc aatggataat aaaataaaac aattagaaag ctcatgtgca ttagagccac 214020 aaaaagagaa cgctgtgtat ctgagtgtgt gtcctgtggg agagctaaga cttgtgaaag 214080 tactggtgca ggtgatctgc tccctggtgc cttgcagctt gtctctgcag ccttacatgt 214140 ttgcaccata ttgcagggaa gaagggagtt ggaggttctg ctaactcaca tgtgcatgtt 214200 tatgattttt tttaaaaaat gagttagcat tttcaatatt ttccatacaa acaaaagctt 214260 taagtaagag accagatatc ctgctgtcac tactgaccta gacgtgccct aagttgggcg 214320 gtattagcct tgtgttcatc acttgtattt gtacctcaca ccagagctgc atccaactct 214380 gcattttcta tcaaccaaca attttatttg ctattacaca gtaaacctgt gctttctaaa 214440 ttataagatt caaaaattta ggtctttctt ctcttttttt ttcctccctc tttcaggccc 214500 ttctgagtta gagatgaaca tgggaggacc tcagtataat caacagcagg cccctccgaa 214560 ccaaactgcc ccgtggcctg agagcatcct gcctatagac caggcatcgt ttgccagcca 214620 gaacaggtaa gtccaggccc ccggagagct agaagagcat tagctcatgg ctcctggctc 214680 ccagagttgt ttcacatgta cgctgggtga atcccttcgg aatggatgat acctgcccag 214740 tcatcctttc ttcagaccga gtcatctgct aggctcagcg tgaaagaaag gtgcagaact 214800 cggcatgacc tgagcacacc tttaaacacc ggcagcttag ttgggaaaat gatatgtttg 214860 aactgctaat cgctattagg cagcagtgta gatgctgtat acagtataga tgctgtaagg 214920 ggaggaatca gtagctcatc cggcaaggct gacagagaag gtttcagagt cttgggggaa 214980 gtgcacaggc atagcagcct agtgcatatg gccggccaca cagcaccatg ttccatcggg 215040 ggttacatgg tacgtgtagg gtaacaggga atgatcttat tttgaattgt gtttatttta 215100 ccacagttta caaaaaatag aaagggaggg ggggtccatg gtctagctag gtaagtcctc 215160 ctccctcgtc aaaaaagctt ctttgcaaca gagaccattg taaaaaagaa tcccagccag 215220 gcgtggtggc acacgccttt agtcccagca cttgggaggc agaggcaggc ggatttctga 215280 gttcaaggtc agcctggtct acagagtgag tcccaggaca gccagggcta cacagagaaa 215340 ccctgtcttg gaaaaaaaaa aaaaagaaaa gaaagaaaaa aatcacaaac aatcaaaatg 215400 atggttgtag agccctattt caatgataca tctgtaaaac acacccatac ctaaggctca 215460 gggaacattg tgaaggaagg gatgggcagg atataatatc cagacagcca tggagagact 215520 agtgacatct gaaggctgca cccatgaagt ctcaccgcat gacaaggata acaataaaca 215580 ctccatagtg gatggaggaa tccccacgag gcctcagtcc tacataagag ctgcgggcca 215640 ctaaggaatg ctgggaggga ggaacagtcc tcctcagaga agagcacacc aattggttat 215700 caataccaag tggtcagccc tgaacacatg cacatgcaag tgtagcatta tataggctaa 215760 gcaggtcata cttacacaca cacacacaca tacacacata tgtgcctgta acaacaacaa 215820 atgaaaaagg aagctctgaa tttgagctga gctgggagag gtatatggaa ggcttgaagg 215880 aagaaataat gtattgcagt tggagctagg aagataacac agttgatcaa gtgcttgctt 215940 cactaacatg aaaacctgag ttcaggtcca gaacatattg aaaagccagt gatggtggcc 216000 cacattgtag acctaagcac tgcagaggca gaggcaagag gatctacagg gcccaggggc 216060 cagctgctct agagtaagca gtaggcacag aggggatggg agaaagagag agggggggag 216120 gagagaggag agagagagga gagaagagga gagggagaga aagagagaga gagagagaat 216180 gagaatgaga ggagagagat ctcccaacac ttaggacagc cggggctaca cagagaaacc 216240 ctgtttcaaa aaaaaaaacc aaaactgaaa accaaaaccg ccggggccta gcaaacacag 216300 aagtggatgc tcacagtcag ctaatgaatg gatcacaagg tccccaatgg aggagctaga 216360 gaaagtaccc aaggagctaa agggaactgc agccctatag gtggaacaac attatgaact 216420 aaccagtacc ccggagctct tgactctagc tgcatatgta tcaaaagatg gcctagtcgg 216480 ccatcactgg aaagagaggc ccatataaag gcaaacttta tatgccccag tacaggggaa 216540 tgccagggcc aaaaaggggg agtaggtggg gaggggagtg ggggtgggtg ggtatggggg 216600 acttttggta tagcattgga aatgtaaatg agctaaatac ctaataaaaa atgaaaaaga 216660 aaaaagaaaa ccaaaaccaa acttgcagtc cttctgcatg ggcctccgag agctgggatc 216720 acaggtgtgt gctgcacact gggctgtagt aaatcattgt gaatgggtgt gtctagaaga 216780 ctcctgccac tgtttacaca ctgcattatg tgttttcagt tctttgttga aatatgacag 216840 tatgtcagac cttctctcta tttcatccac acattgtcgt cctgtgtgtg tgtgtgcgtg 216900 cgtgcgagcg tgcgtgcgtg cgtgcgtgcg tgcatgttgg gaagcagagt cagatggatc 216960 tctaacttca aagctacata gtgagtcctg tgcactaggc tgtagtgccc agggacttcc 217020 tccaagactc tgctggagga gcttctgaaa catgcaactg ggctgcatag tgagaccctg 217080 tctcagaaaa agcacaaaca acacaacaca aaacagtatt ttattattca gtgtacgtgt 217140 ctaacttggg catctgtttt ctgttgtaag tactgggttg ctgcagggtt aagaatttat 217200 tctcagaaaa gatgattcct tctactgtca ctgtttgaaa ttaattgttg gtttaggtgc 217260 tcagcaggac accatgttca gttctaagtc agagtaacac attagactgc ctaagaaaac 217320 acagtagact gaactgggtc agggccagac aactctgtcc cttgatacat tgattgccac 217380 ttgtttaaga atgagctttc tggggtgtga gcatgcctca cctggcacat aggatgccct 217440 gggttcaatt cccagtacca cacacaataa aacgtaagct agcttctctg taaaactgtg 217500 tgttctccac aggattccat agtaggtcta cagcacaaag ctgactttgg tgaagtgctg 217560 gcattatgtc ccctctcagg gttgcagtga ctagaagatc ctctaatctg gtaacttaat 217620 tataatgtta gataccatag aaatggcagc ttagtgtcaa gatcacatat tgccttatag 217680 caattacatt agaaggtttg agattccctt ctaattcctg agggctaaca ggtaaacttc 217740 ttcggagttt tggtaaatgc ttgcaaattc tggttctgca taaacacaca gtttcataga 217800 ccagccaagt tcacaagccc agattgtatt caagtgtgtg agtgtgctgc tctctccttt 217860 gctcatcgta gtcgcattga aaaggactgt gtatgagtca ctgcgttctg cattcacctg 217920 tcactgcaca gcagatacac acacacagac cagtgcaggt ctgtgaactt aggtaggtga 217980 gccccgaaca cacacacatc aaagtagctt ttacggcggt gcctttccga ctttgcacag 218040 atgtgagtac ctggctaagc taaccctgta ctttatggga agatggagaa acataactgg 218100 ttaactggcc tttattaaca ctaaataaaa tagatttttc agatgcatat tttcagaagt 218160 cttcattctg tccagtgctt ggctggagga agagtttggt gaagtcaact ggtatttcta 218220 ccagcccatg gtgaagtttg tctctttaca ggcagccctt cggcagctcc cctgatgacc 218280 tgctgtgtcc acatcctgca gcagagtcgc caagcgatga gggcgctctt cttgaccagc 218340 tgtatctggc cttgcggaac ttcgatggcc ttgaggagat tgatagagct ctggggatac 218400 cagaactggt cagccaggta ggccagagca tcagagcggc caagcactgc gtaggccaaa 218460 ggtctctgtt cctgcaggct tctctgggat gctttttccc tccccaccag caggcctccc 218520 tactcctcct ctttactctc atactctcac ataaactgtt gcccaagaag caaacacctg 218580 ggaaggacca ttgcacaaga caagttaagc agaaaggcag aagcaagccg agagcctctt 218640 gtccacgctt gctgaaaggg cagattagga aaacaagtta gagaagccac agggtcactg 218700 cttcctgggg gccttggtcc tcgatgctgg gatgggagac catgtgagca ggcctcagtc 218760 cggccatgcc tattcactga gacaggcagc cgctacttag aaaggactgt ttcacacaca 218820 ggtagcagaa gcatcttaag tgtgactgca gctcaccaaa cactacaacc cttatgtggg 218880 tgtcgcccgt aacaatttta ggatgccaac caccctagtg agcctagttc tctctctgct 218940 ccctcgttag tttatttgaa gaagtaacag actttgtctt tctttgattt gagaaagccc 219000 tgaggctgtg ataataaccc catggcccct cagcatctga aacaacctcc tcctggtcct 219060 ccttcctgtc cagtgccagt ctccctgtca caagcatctt ccaaggccag gctgcctggc 219120 cctgcagcat gtcactgtga ggatagtgat agtcatcgaa gactctggaa ccttaaaaac 219180 agtcataatt cccagagttt agcagacaca ggtgggagtt cagacttgtt gattcatatt 219240 gaaaacagca gaatggaaag aaatgactgg aggttgcaca gtacaccctg acttaaaacc 219300 agaaaggaaa tggggtacct atttcctgca tgactggtcg gcttcgcctt tagcttcagc 219360 tagagttcag cttttctgcg attatccttg agtttatgca ggtgacattc ttaaatgtcc 219420 ttggagttcc tcagtgactg gaatactttg agggactttg gaagcggggg ttatgtttta 219480 agagattaga tttttaagaa atttaagaga tcccagccca acctaggctc aaatttatgg 219540 cagttgacct gtcttggcat ctaaaatatt gaaatacttt ttaaaaatta aaaccagtat 219600 tacatcattt tgaatgctct cctcaggtca gtcaccgtgt cgtttaagct gaactacaga 219660 cggcattctt aggggcagcg gtggaaatgt ggtgtgnnnn nnnnnnnnnn nnnnnnnnnn 219720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 219780 nnnnnnnnnn nnnnnnttta gccagagttg catacacagt atagaaataa agttcttgtc 219840 tcacaaacat ccccagagcc caggaaaacc accaggctca gtggtacaca cgttacccca 219900 gcaatggtga gtttgtgacg gtggaaacag gaggattccc acagcaccag ccagtctagc 219960 gtaatcagtg agttctaaac agaagtgaga cctgtctcaa acagagcaaa aactaaatag 220020 atcaatatgg aaataaccta agtagatttt ctattaaata tgggcagatg taaagttctg 220080 aaatatttca acaaggagtg gtctccctgc tggtggtact ccatacacac tttttttttt 220140 aattatcaag aggagagggc agtatactga cgctgtcctg ctgaccacag accacaggca 220200 gcgttatcat cctagggcgt ctggaaggaa ggactaaggc tgccagagca gtaacctgat 220260 ggcggcttga gatgtgactt ctgctgcggc ttgccctcta aagaccttca gatgtctagt 220320 cgtggcttct agaaggacaa gggtatatta gatcttcata ttgacactag agcatcgccc 220380 tgagagagcg ctagattccc tatgcatgga aacaggacag tcagccagaa gtttccatgt 220440 tcagctcagt agcagaaatg acaagacccc ttgtctcaga aactgagtga aagggccgca 220500 tccccagaaa ccctccaggc ttcacacact cgtgtgcgct tgcttgggct ggctccctct 220560 ctccttcctt tctttctctc tctctctctc tctctgtgta tgtgtgtatc actcacatgt 220620 gcacacactt ttttaaaaac taaatagcta atgcaagatg caactggaat ttatgcagct 220680 ctctctgtaa aacacatatc agctgggcat ggtatcacat gccttcaatc cagtactcat 220740 tgagacaggc agatctttgt gagtttgaag ctaactcagt ctacatagtg ggttccagga 220800 cagcgggact acataatgag accatgtctt ggggtttaaa aaaatgcatc tttcagacaa 220860 ttaaattaac caaatatata caaactagtc ttgcagatac tctgtcagat gctggtcagg 220920 gcacagggag gacctgctac atgcccttac accaccttcc attcctttcc ctctgtaggt 220980 ctttggtagg agaaaagctg ttgaaaaatc aaatgacaaa cacattgaat atgtctagca 221040 tgtagtagtg aattatagca aagtgtacgc atgtaagaag ttccactaac catagagaac 221100 agcgtagtaa acagtacaca gtgtaaggca ggcattgtga cactgacctc gaatcccagc 221160 acttgggagg tggaggccag agactcatgg ttgaaaccca tcctgggctg catagcaagt 221220 cagaaaccaa cttgggctat gtaagaccgt atatcaaact cttttcacca aaacataata 221280 ggcagtaagt ttatcacccc actggtgagc ttaagtccca catcacagta cgcaccacag 221340 cctacccgcc cggtctttgc tagaaagtct ccctcgagtg ggcctcatgt ccccaagtct 221400 gtgggtgtct agagtggaga ctgtaggctg cttccccagc attgcttatg gtgactaagg 221460 tgaccatagg ttaaaataac tgacatgggg ctgtgtctct gtcaaaagag gaaacatttg 221520 cagctgcctg ctcactaaag gccctgccag gttctcactg gaaggaagga ggaagctctg 221580 cagggaggca gcccaaccct tgcttcttcc ctcgaggagt tgcaaagagg cattgggtag 221640 aaggaaaagt agaggcaaac taaaaaaaaa tacattggta aacttggtac agtatttcta 221700 aatcatcact tacaggaggg ggggagcgca gcctcgtgtt cagtacagta gtagtagtag 221760 tagctttact gtgtgcttat ttggggcttc ttttcagagc caagctgtgg atgcagagca 221820 gttctcaagt caggagtcca gcataatgct ggagcagaag ccccccgttt tcccacagca 221880 gtacgcatct caggcacaaa tggcccaggg tggctataat cccatgcaag atccaaactt 221940 tcacaccatg ggacagcggc caaattacac cacactccgt atgcagccac ggccaggcct 222000 caggcccaca ggcattgtgc agaaccagcc aaaccaactg agacttcagc ttcagcaccg 222060 cctccaagca cagcaggtta gtttctcatg ggactcaggc gggggccctg gctggctgag 222120 gaatgaagaa gagttaagtt tttggagagg gctgttaatt ggaaaagatg atttgaaata 222180 cacatgtcct gttgtttaaa tgtattgagc taggaatagc taccttactc tttagtctca 222240 gtactcagga ggcagagtcc tggtctacag agtgaaacac aggacagaca gggctatata 222300 gagaaaccgt gtctcaaaaa aatatggatg gattctaggt cagcctgggt tacatagtaa 222360 gaccccgtct taaagtcccc ctcccgacga gtgctaatgc ccgtgtttgt gtgtagaatc 222420 gccagccgct tatgaatcag atcagcagtg tttccaatgt gaacctgact ctgaggcctg 222480 gagtgcccac tcaggtgaga agcctctcat ttttcctccc agataggctg agtgacctgg 222540 gttttcctag ttcctctgac tccctgtgtt agttctgaat gccatccctg ttgccagggt 222600 cagctgattc ctataataca caagagttgt attacaaaaa tgtatcaacc aattctggat 222660 tcaagtactg cccactgttc ccatgagaac acgggtttag ccttcaagac tggccacaac 222720 attgctctcg gcaatagcct tgtttctatg gagtttctgt gtgaagacac tttacgtgta 222780 tgtaatttac ttattaaact caatggacag gctatctcag actcaaacaa gccttgccta 222840 acactcgtac ttttcttcgt aagcacacct atgtcttcca cttgagaaca ctggacagtc 222900 ctgcaccagc acagagcctg ttaggttctg tcggccacat cagaaggcca cacatccatc 222960 tagccctccc cttggcagga agcaggcgag tgctaagcat aggaaatccg tgctgctgtc 223020 cttacagtca taaatggctt gacagtgctg cgcacactca tgtttgcatt gcagataaac 223080 tttagagtag gcagccttgt gagtggcgag gggatgccat tccagcacca gcgtacagca 223140 cacgcccagg gcccctcctc acatcatgtc actcatcctg gcctctcagc agacatctaa 223200 agaccattct gagatcaggt gcatctgaca tgatgtagcc atagaccagg gggacacagg 223260 ggacacaggg gacacaggga cacaggggac acctgtgcag ccagccagag cagcctggag 223320 atcagtaaag taacagaaat tactgtcaga tcacccccac ctccatctct ccgaagtcac 223380 caagtcacct ttggcagtgg cttggtttct tgttaagttg gaatgttcct tcaaagagac 223440 tctaaatgct gtcctcaact tacataaagt cttctgccag gccagggtag ctgcgctgta 223500 accccagtgc tgtagtagct cccagcactt gggatactaa agcagaaaag aggtgacagt 223560 caagctagag gacccagaaa gcagcacgtg ggcacctgta actccatttc ctggtgatta 223620 gccgccctct tctggcctcc atgagcactg cacacataaa aataaatttt aaaaataaac 223680 ataaagtctt cctgtagaaa ggcctgtgct cttttgacat cttttgattg actgtaccct 223740 cgagaaatga gttggtcact atcagagggt tacagaatcg tcatcacaca ggctgaactt 223800 agagcactcg catgcgtgct cactaggtgc tctgctccga ggacccccct tcatggaact 223860 ttgtttttca aatgatttta catacagtat gccattggta tcctgtctaa cctatctatc 223920 cttgatttcc cttcatgatt gcccacaatt tcaggctcct attaatgcac agatgctggc 223980 ccagaggcag agggaaatcc tcaaccaaca tcttcggcag agacagatgc agcagcaggt 224040 gcagcagcgg actttgatga tgagaggaca gggcttgaat gtgaccccaa gcatggtggc 224100 tcccgctggc ctaccagcag ccatgagcaa tccccggatc ccccaggcca atgcccagca 224160 gttcccattt cctccgaact acggtactga cttagatccc tcccaccgtt gctgtcccgt 224220 cttggcctat ctgttctttc tcctttctcc cgaggcacct cagtcctggt cacggcttcc 224280 ttctcacggc tatgtgcctg gttagccagg aaacgatagg aggcctggag cagattaggg 224340 cctggcaagt ctcccagtcc cgcacagtgc ctacctgtta gctcgggtcc tccttttctt 224400 tgggtgcagg tctttaagaa tgaccaaagt taagtgtcat gtgtctctgg tgagcatgca 224460 tggatgttat ctgctcaggt cagggtctat gaatgtaata cacattgcta cttatccttg 224520 attgtttctg agtctgacac aaagaaatca gtagctaaat atgaaatgtc agaagacata 224580 agccaattta aatattacaa atagtctaca gcttttaaaa aataaaggct ttgtttgtta 224640 ctgacaacac ttatcaaaac aaaaaataaa aactttcaag attgtaccaa gtcttcactg 224700 gattggtcgt tcctgaagtg ttactcggag ccacgtggga ggcctctggc tttacttaat 224760 cctgatttgt tctcggatgt cattctaaca gacgagacac caagggtgat gtcatggaga 224820 ttgacatccg gttgttatct tccgctaaca gtgggagtct cggtgcttcc atagtgcgtc 224880 catgcttgca tgttccagat ggctctgctt tgccctgtct gagggatctg taaggaacca 224940 tgaacatgga agcctttgtg ttgcctaaat acaaacgtcg tgtctcctta aagagcagag 225000 atagtgcatt gtgttcttct cctcttcaga ctcttctctt gtagctactt ttaaatatta 225060 agtgttgcgc aggattaagc gaatgggtcc ttactctgtc cctgaaatgc cccctcgctg 225120 tcttcctttt ggtgcctttg ctcgctttcc gttgctagct cagggaagtc tgctgagatt 225180 ccttttcttt tgctgtgaat tcttttaccc taaactatac aagaaatgga taatcctgac 225240 agcactcaag tgccacaagc ccttttccaa aaacaaaata agccaatgtg ggcgtgcagt 225300 tgtgtatttt ctgaaataca tctcctgaac atgagatgat gtaagttaat ttagtgtaag 225360 ttattcatat gttgactgtt ggtatataga tgaatttaat gagctcagac taaatttaaa 225420 aggaacgata ctattacact gactgaccgg ctcagataaa atcaagtctc tacatagtag 225480 actcgtcctt ggtttagaga gggcttcagg aacaaatgtc atttctctga ctctagccct 225540 gatgctagtg tgcatcctcg gagccctgtg actcttggag agctttcaag tatagagagg 225600 gttttctcca tgtacttctg tctcagcttc tttcaaatat ctaataattt gcacataatc 225660 agataattga aagtaatttt tctgtgtata cttaatttgg aacattctct ctatgatata 225720 gataacaatc tcctttgggc ttctgttttg tttttgtttt taaggaataa gtcaacaacc 225780 tgatcctggc tttactgggg ctacaactcc ccagagtcct ctaatgtctc cccggatggc 225840 acatactcag agtcccatga tgcagcagtc tcaagccaac ccagcctacc agcccacctc 225900 agacatgaat ggatgggcac aggggagcat gggtggaaac aggtaacatc acattactgc 225960 gtctgatata aatgatcacc cctagccagg cggtggtggc gtttagcaag caatagcaaa 226020 tgaactgcta aaaagctagc ttattcttag caaaagtcaa caatttcaca gaagcctagc 226080 acagcacctc ttgttttaga gcaaaaacat tacctctaag cagttgccac tcctaactgt 226140 agaattcctg tggatggcgg tggcacagag ccaggcttca tcagtgcaca tgctaagaag 226200 caaacagcaa gcccccagca gctgggaaag caggagtgtg tgtgcttccc agcaatgtgt 226260 gcaagggaag aagcaagcct gatgcctggg ccagcaccca tttagataga gactgcctca 226320 gcttaccatc agactaactc tgtctcccac gctacagcat gttctcacag cagtccccac 226380 cacactttgg gcaacaagca aacaccagca tgtatagtaa caacatgaac atcagtgtgt 226440 cgatggcaac caacacgggt ggcttgagca gcatgaacca gatgacaggc cagatgagca 226500 tgacctcagt gacctccgtg cctacgtcag gactgccctc catgggtccc gagcaggtaa 226560 gagcctcaga gaagcagctc agaacgttct ccttggcttt gtgtctgttt atgccacaaa 226620 tcccatatct attttgaaaa gtgttttttc accttatttt cacctgtgcc agtgagattt 226680 aacaaaaaat acttgttaat gacgaaggaa ctattgggaa ggactcctgg ctgctaacat 226740 gttgggggtt ttttgctttg ttttggtttt tatttcctaa ttttcacatc attaaccttt 226800 tttatcattt gtgggattta gaaatggagt ggtaggtgtt aggaagtttc tgctgggcat 226860 ggtgacccac acctttagtc ccagcactgg ggaggcagag gcaggtggat ctccgagttc 226920 aagtccagcc tgctctgcag agcatattcc ggaatgggca gggctacaca cagaaatcct 226980 ctctcaaaaa acaaaacaaa actagctttt taaaacctct ggtaagcatg gccacacagc 227040 ctaccagccg gtcactctcg gggccgcttt gcttacgtga caaggctggc acactgttgc 227100 ccccttgatg ctccagtgct ggtgacttta gttccagacc agcctggact ctaagcgcat 227160 gttagaaagg gtagggagaa gatgtgtagc ccacacgggc caggagcacc ttctgctctg 227220 tcgggccagt gttgagagtg aggtacacag agacacagaa ccgagcgtaa tcatgggcca 227280 gcccactcag gaacattcat caacccagac catttgaaat gtgtgcatgg atttaaatat 227340 ttttgagttt cggagtttat atagaagccc aggtccaaac ccacaacccc agtgtgtctg 227400 ctgaaaaatc attgtcttat tagccctggt gggctagctc catgagtaaa agtgcctgcc 227460 accaagcctc accacctgag tgtagtcccc agactccccc gagagagctg gcctctacac 227520 tccggcctcg gacatacatg cagccatcac acacaagtaa atgtaatgag aagagttttt 227580 tttaaaaaca cataaatgct gatgagtagg ttttttggcc agtccattcc caaaagccag 227640 tttgggtgtt ctcacgtcat tcttgctaat taatgacttg cctgagagca gaagtggcag 227700 atggtctcag gtgcttcacg ctctcagggc tgagtcacca gcctataaat gaaaatgtgc 227760 aaataagctg tgcttttgaa ggtaagtagt gtttgcagcc tcctctgccc catgtgtgca 227820 catggaaagc tgttagctgt gggatacagc ctcttttccc tagggccaca aaacttaaaa 227880 tcggaaatgt gtcatgttgt caccacaggt caatgaccct gctctgaggg gaggcaacct 227940 tttcccaaac caactgcctg gaatggacat gatcaagcag gagggagatg catctcgggt 228000 aagcagcagg agcccagagt gcaccttagg gtggctgtgg gccttctgaa ggccaaacgc 228060 ttctctctgc cttgtcggcc tggaaagtgc tgggatcaaa agagcacact acaaaaacag 228120 caggcatgat ggtgcatgcc tgtaactctg gctctgagga ggcagagaca agagagtcag 228180 gagttcaagg tcaactacac tgtgagttta agaccagcct gggctacaca ttaccctatc 228240 ttagagcaaa caaaaaaaca acactcccac cttgaaaaaa aacaagaaaa taactattta 228300 cacgcagaaa gcagcctaca gcaaatgcaa ctgtgacgtg ctttccagct cttcctaaca 228360 cactgatgta cactgccacg tccaaccctc aggaaaggtt catcctgtca gagagacgca 228420 ggagggtggg gactcggcat cattagcaag tcttaagcca gccccggtta tgagagatcc 228480 agtctcaaaa aatgaagagg gccagggaga actgaattaa atccccgaag tcagagtgga 228540 aagagccaac tctccacatt gtcctcgtgc ctgcacacgg gtgcctgcac acgggtgcct 228600 gcacacgcca cagaaacagt aaaatgttta aagaaataac ctcttaggcc acctccgcat 228660 actcaaaacc aagcaatagc ttgatcccat tggagagagt ggagtgtaaa tgagcactga 228720 acttcctcac tccagagcct ttgtgttgtt agcagcaggg ctacagtaga cctcacccgc 228780 ccattgctca gcaatgtcct ggattggctt tcccactgtg gcttttctgg gttttgtaac 228840 cctgattgtg ggcttcagag atactactga cagcgggtag gagtcctgta gctgtttctc 228900 acacgtgtcc ttaaaacgtg ataattaggt gcacgaagct taccatatct tccttcctta 228960 ctgtatgtgt atctggtatg tatacatagc aggtaagaat gtcagacagc ggggtagatt 229020 gtacactaac catgtgttcc tttgtttggg tttatcactt cccaagggct gatacctctc 229080 ctatagccat ggttttcaca ggcagggagt gctaagagct cagaggtaac tccatgcaaa 229140 agcagaggtc caaaacctga ggcacagtga cagcaggtga cactcacaca ctcagagagg 229200 acattgtaac tgcaaagtgc caggggagcc tagccagagt gctgtaagta tgagtgagag 229260 tgagccagct agcatttgaa cagctatcta ggaaaagccc cttgccagcc aagccctctg 229320 aagcagaccc aggcttctgc tttctcctag gagcaccagg aatctccctg ctttgtttct 229380 cctgccttct tgcctcctgt aaagcacagc atggttgtca atgcatgtta tgtccttgaa 229440 tattgcaaga gcagccaagc ataaccgcgc atgcaggaaa gtcactacaa gagcagcctg 229500 gttgacatag aattctagcc agccagcact gcatagagag gcatggtctc aaaaagatgg 229560 agggagagaa ggaaaaaaag gaaagaaaat catggaagca gcattgacat agaattctag 229620 ccagccagca ctgcatagag aggcatggtc tcaaaaagat ggagggagag aaggaaaaaa 229680 aggaaagaaa atcatggaag cagccgatag gaatcaatca gttgctcact tagtaggcac 229740 catactgtct ggtctaacta cagccttacg aatgtaacga tttgtcctag gcctggggag 229800 atcagaaagc aagcaagctg acctctgaat gccttcctat tctttctttt tttttttttt 229860 aatttatttt atttatatga gtacactgta gttgtcatcc gacacaccag aagagggcat 229920 cagatcccat tacagatggt tgtgagccac catgtggttg ctgggatttg aactcaggac 229980 cactggaaga gcagtcagtg ctctcaaccg agatctctcc agaccatgcc tgcctatttt 230040 taacctgagc accactgtcc tctcccaaga gagacaagca ggctctcaca aggattttct 230100 caggggctat gtagcctcat ttaagaaggc ccagaggggc aagttgtttc tttggtgccc 230160 tcctccacct tgctactcaa gtcctgaagg aaggcagggt cagaaagaca ccacagaagt 230220 ttcaactacg tgtttaaatg tcatcggtct tcttttgttt tgttttgttt tgttttgttt 230280 tgttttgttc tgtttttttt cgagacaggg tttctctgta tagccctagc tgtcctggaa 230340 ctcactttgt agaccaggct ggcctcgaac tcaaaaatct acctgcctct gcctcccgag 230400 tgctgggatt aaaggcgtgc accaccatgc ccggctgtca tcagtctttt taagcatcca 230460 ggtgcttcat cccaggaggg gagaacctcc aatgctgaga cacagtgtcc cttttggact 230520 ctgtcaggcc tacatggatg ttaaaggctt cctggccatc ctgtggaaga atgtaggtga 230580 ggatcaaggg agctggtgac caacaccaac ccaactgagg aagaaagcct ggagcactgg 230640 gtgtcgccca gtccagagcc acctccccgc aaggactcat ctgaggaggc taatggagtc 230700 ctgttgctga tcaccagacc gcttacaggg acacagcagg cacatatacg atttcaggct 230760 ggcttcctct cttcaaatag atattcttag tggccctcta gtacctgctg ctcaatacag 230820 ccttggcata tatagtcatc tagattatga gttgagagtg gggtgggttt atcttaatga 230880 agtcagagtg agcacaccct cctaggacct gacagtgact cagagacgat ctagggaggg 230940 gagcgcttac gcgggcctct actcccagga ctcaggaagt agagacaggt gactcgatga 231000 ttagaggcca cactgtctag gtaaagaatt ctaaggccct gacttaaaaa atgaggagga 231060 gggctggaga gatgcctcag tggttaagag cactgactgc tcttccaaag gtcctgagtt 231120 caaattccag caaccacatg gtggctcaaa gccatctgta atgggatcca gtgccctatt 231180 ctggtgtctg aggccagcca tagtattctc acatacgtga aataaataaa atctttaaaa 231240 aaaaaaaagt ggggaggaaa actggagaga tggctcagtg gatagaagca cctactactc 231300 tctcagaagt tctgtgctca acagcaggcc agtggctcac agctacctgg aactctactt 231360 ccaggggctc tgacaccctt ttctgtgtgt ggaatataca catacaaatt aaaaatatat 231420 atatcaaatc atgatttttt taaatcagta gtagccaggc atgtgggtgc cacacacctt 231480 agtcccagca cttggaagaa aaagtaggag gatcttggtg aagccaaggc cagtctggtc 231540 tacataacga gttccaggat aaccaggatt acatagacac tgtctcaaaa acaagcacat 231600 tctttaaaaa gtcaaaggga tcaccctggg ctggggaggc actcggtggg taaagtgcca 231660 tgcaaacatg agagaggctc tcggatcaaa cccccagctc cccggttgtt ctgtacagac 231720 gggtggtcgt ccacagactg actacagcct gcgggagctt cacactgatg gatggagcgt 231780 gcacctgcgc cattcagtta gggacagcgc cacctgcctt cccgtgtcag aaacccacca 231840 ctcaccaaat gcggagcctt cgtactctag aataagctag tatgttgtgt tttatgatga 231900 tcactccatt gttttcattt caaacaaaaa caaacaaaca aaaaaactct tgatattgcc 231960 agtgtggtgg cgcacgcatt tgaaagacta gtgtatgggg gcacagaatc tgccaatagg 232020 ccagggtggc agcagaaaaa actatgcaaa cataaagagc cccttgtctt cacacaacct 232080 ttctgtctgt ttcccctcag aaatactgct gaccctggag aaactgtctg catctttctt 232140 caacccactg ggcttacaaa catttaccag tctggagagc tgcgtctctt tgtgttgcca 232200 cctgacatgc cgccagttct cccaggacat agcagcagac agtcgggccc tgggcccgca 232260 gcatagagcg tgctggcttg gctgccaccg gaagagttgc ctctcccgac agcctgcagc 232320 tcgcctccag accaacccgc agtctgttca ctgcattcac cgtagtgcaa cttagatctc 232380 ctgcagagta actgtcccca ggccgacttc atccccatca gattgaatgt atttaaatgt 232440 gtgtgtttga ggagagccat gcccttggcc tgttcctgct cggctccaga cactggtttc 232500 ttgctttgtt ctctgtggct cttctgtgta aaagatgaga atcttatcta caggaaagaa 232560 aggaactttt aacacagtac aacccaaggt gttctaagct taaagcctgc atttgactgg 232620 gatggagaca gggcagacac tgtgcacagc gctgtgtatg ccggcacacc tagtcagcaa 232680 cacgtaaccg aggcagagtt ctgtctccag gaaggagtgt cccgtcactg aacagatgga 232740 aggctcttga gagaggctgt tagcattaac aagtatctgt tcccacttct ctctgttaaa 232800 accaaactag tttcccctaa atcatgaatc aaaaagaaat acttgtttct aaattgtttt 232860 tagatcagat agtttgattg gcatctcttc ccttcctctc cccaccttct ctcgtccctc 232920 cctctttcat tcctttaaag taaaaacatc aacagcagca tacaccatag agaccaggga 232980 agcccttagg atctctcagt gctgtgccag ccacttacag cagcttccca gtgaccatgc 233040 atttcctatc agagaggaac aaagtcaggc tgtgacatct gcttaggtag cctgggctgc 233100 cccatcagct caggcctcca aaatgagaga acttactaat gaaatcaaca gcagacgtca 233160 cgacagatct aacctctgcc atatggggtt gttttttatt tttggttttt agcagtgctg 233220 acgaagccga agttttgtaa ggtacataaa gatccaattt atatgtaaac aagcaataat 233280 ttaagttctg aacttaagtg ttttaactgt ataattttgt gaggtataca tattgtggga 233340 ttgactcaaa atgaggtact tcagtattaa attagatatc ttcatagcaa tgtctcctaa 233400 aggtgttttg taacggctgc caatgccttg gttagacctg acttgtagac gtaagacctt 233460 ttgttttcta acccttgaga ctctcctcat gaatcctgta tctaatctat atgatatgca 233520 gccgctgtca gaaccaagtc ttgattttat atgtttatat tctttcttaa taaaccttag 233580 aaagacaaca ttactaagca gcccactttg atggttgttt tcttgcccac tgtcggggat 233640 aacctctatt aactggtgtc agtttcagac agctgcagta cccagaaccg agaccttttc 233700 aattctcccc aaccttgata cacacacttt cgtacctaaa tttcagaatg atgtcttttt 233760 gatgtctaaa aacaaagcat tttataatat ctcattatcc aagctttcta ggaacagaga 233820 agattttcct tgaagtttgt ttattcctgg cagggttaaa aacatataaa ctaccctatt 233880 tatatttatg tctccctata tatctacaga ttgtagaaat atagaaagag atgtgaccca 233940 aagacaaatg gtcagtcatc tgaaagtgtt gctgcgtgct aaggaactct ggaaatttgc 234000 atttccatac ctttttccac ttagagaaga atctcagtga gggaggtggc ccaggaacag 234060 cgcttccccg ttggccacca gttcctgtgt ctgctcgaga ctccaccaaa ccattggctt 234120 gcacatctgt cctgcaaagg gagcagatag aacccagaac tccaggccct gccccaggag 234180 tgaggctcag gtgcactact gagctcgacc tgttctcaga taagtcagaa atgtgaggta 234240 ggtaaaaatg acttcacaca gcacaagaga aaaaggaatt taaaacatac ttgttttgta 234300 ttaaatccca tctcactgta acatcaagcc acaatatctt acctttcagc cttcatccaa 234360 tctcccactg ctttctaatg ttgacccggc tgttagcgta gcccatggtc atggcaaatc 234420 ctctcacagg tcagagcagc catgaactgt gtgccatctc atcaggagga tcaatcgcat 234480 cagcaaaggc atcctgatca tgttctcaga gccagggcca gcccagcctc ccctgccatc 234540 agtattgctc acgctctgca caacacattt gtacttggtt ttgtctgaca gaacatagaa 234600 tcagtgttct cttagatgac tcaatgtgaa aagcgtaatg tgaaaagtac acacctgatc 234660 gtggttgtaa aatccattta agtgttcatg caacatggtg agttttaaaa gtgaagtgtg 234720 ctgtgatact acaaccaatt gactcaaaga ttaaagcacg cacgcacaca cacacacaca 234780 tacacacgtg tatctcttac gacctgtaat gattgaaagc aatggttttt ttgcagttta 234840 agatgcaatt tttaatctgt gtttaaaaac ggagttcata tgggtgtgac acgtgaactg 234900 ggaggcacag atccacttgc agaacccaaa gatacacaat caattttgaa atgcaactta 234960 agccattaat tgttggtgtg aatttaaaat tttctagttg tttatatggt agtatgctgc 235020 cgaagagcaa agcattctct gcacaaaaga aaacactgta gtggcttcga ttttaattag 235080 aactttctcc ctggtgtttc tttatagact aaaacaaaat cttttaagtt tctttactac 235140 aggtaaaagc tatgtgcaag aacctcaaaa tgctaaaacc tagcataatg ccttagatct 235200 gtttttaagt cttgtatatt cctacatagc tgtccaatgt attatatttg tatagtgaat 235260 tgtgtaaaat ttttgaataa gtaagtcatc gcttacccgt atgttactga acagtgatga 235320 caactcgttt cttcaaacat ttaactgtct tctctttttc ctttgtcatt tgtgggtttt 235380 atttgtacag ttcctcatga agttgcattt gagatatgtg tatatgaaaa aattatacaa 235440 gggtaaaatt aagcaatata ttaactatgg ttcttcagga gaaagcttac agtgtttcag 235500 gttgtgattt attttcaaaa cagagttgac tctgaacatc actttgttca tctgcattga 235560 tgtttgtatt tctagtgtga gcagtttatg caaaggtaga tatatacaga gaaattttaa 235620 atacatttat gcaagttact attgctttgc tgatgctatt tgcttatttg atgttaaata 235680 atgctattgt aaataaagaa tctgttgtta ctgcatcatt taataaattt taatgccttc 235740 gggttttaca tggctttaga gattttaatg tggcgatacg gtatcttctt ttgtagttta 235800 aacttaaaaa tacctgagaa ctactactgg ctgctctttc agaagaccca gattcaattt 235860 ctagcaccca cacatcatct cagaatcatc tgtaactcca gttccaggag gtccagcccc 235920 ttcttcctgc tcttacaggc attaggacca ctcctgatac agttttcaaa caaacaaagc 235980 atctatagac atacaacctt ttaaaaaaat atattaacga cattatcttt taagaatttc 236040 ttgggctggg tgggtaggga agtggggggg agggtatgga ggacttttgg gatagcattg 236100 gaaatgtaat tgaggaaaat atgtaataaa aaaaaagaat ttcttgggct aggcatgatg 236160 gtgcacacct ttgaccccag cactccagag gcagaggctg gtggatctgc cccgtctaca 236220 gagcaagctc cagggtagcc tgggctgttg ggggggaaaa aaaaaaaaaa aaaacagaag 236280 gaaaaaggga atttcttgtt tctggagcga tgactcaata tgcttattgc ttttatgcag 236340 gagcccactt ctcttcccag cactcaggtc aggaggctca caactgcctg taagtccttt 236400 tcctggggga tacactgccc tcttatggcc tctatagaca ctgcactcgg gtgcacatat 236460 ccacaaggag aaacacccat gcacataatt aaaaatacat tttaaaaatg gtagtcagtg 236520 gtcacagcac tcttaacacc ttgccctccc agagaagcca agtatatcct agttgacatc 236580 actagctctt tatggcagat gtggcctgtc tagttcctgc tacaaatatt gctgcagtat 236640 ctgtggatgt gaggagtcac ggcgtacctg tgctggtcag aggtcaactc tcaggagttg 236700 gctctctccc gccactctat gggtcctgga gatggaaccc caggtcacca gacttggcaa 236760 gtgagcacct ttaccagctg agccctcccc cagcccacac tgtttataaa gatggaaagt 236820 actgtgtcct cttcaaaagt gctggtgccc ctctcacaag cttgcgtctt acaggattcg 236880 tgaagggcat atcttctggg ccttcccagt gtggacgatt aggttttcca caatgtatcc 236940 actctaccat tgcaatttcc ctgagcctta aaatcccttc atcaacacta agccgaggga 237000 catcaggcat cttcaactcc ttttcagtag gccatctttt tttttttttt tttttttttt 237060 ttttgagaca ggggtttctc tgtatagccc tgacggtcct ggaactcact ttgtagacca 237120 ggctggcctc gaactcagaa atctgcttgc ctctgcctcc aaatgctggg attaaaggtg 237180 tgtgccaccc acgcccggct tgtaggccat cttttgataa acacttcagc caaccattca 237240 aacaaacaaa cttctgacag cttttttaac tgtgcaagct tccatattaa acctagaatc 237300 tccactcaga gggaccacat cagtaaactc agcctgctct agttttatgt tccttccacc 237360 attttcccac acccttaaaa tccattccca cacatatccc ccaggtttct gcttgaatca 237420 attagcaaac tcatgaagct cctttgtagt gaagcgcatt tcctcccctc tatggctctc 237480 ttctgccttg agtctggtta taggtctaga agaagctatt ggtgggcctt gagaaacatc 237540 agtattgtct ggcattttct tcagcgaaag tcactgctgg tttaacagac tctgagggat 237600 taattttctc atgtgaaaat ggcattattt caaggggtgg ggcactactt cctcaggtgg 237660 ggcaaaccct tgagaatctg aagattcaaa attctcagct tcaacatggt cttcccacac 237720 atccccatcc caagttttaa gatcccattc tttgccttta actgctgaca ccctctgaga 237780 cttgaatttt cgctgtaatt caaccaacct tataatgagg gcttcagttt gattttctgc 237840 aacttgagct ctatggctgc tgaagagaag attctcttca aggacacaca tagcaacttt 237900 tagatcactt ccttgcatct ggagccattt gatattatca cacaataact tcttttcctt 237960 catccttttt ccccaagatg ctaagagcaa ccagccagca aaatcatttt ccaatttttc 238020 cccatcttgt agaaagcttt gtacactgaa tcatctaata cattaagata atcaaaggca 238080 ttagcttctt taaacttgaa atacagtttc aaccacgggt cttcaatatt ctccaagctc 238140 ccaggaggga gagaatctgg agaggtttca gtcgttgaag gtgctggtga attatcaaac 238200 caactccaga atttcatcct tatacttctg ctcctctaga actcctcctg gtaccagctt 238260 ctgtaatagt cagggctctc tagagtctag aacttacggg tagtctgtat atagtaaggg 238320 aatctgttga cgtaagtctg tagtccaact cccagccatg gtcagcagca gctgtgaatg 238380 gatgtccaag gatctagcag tttctcagcc ccacaggcaa gcaggggaag gaaagagggg 238440 taaacagtgc aattacgctg ccttcaaccc aggtcctaaa tcgcatgcag tgctagaggc 238500 ccagtttggg tttttccctt ctctagcatg aagggaaaca ttggccattg caggtggtgg 238560 cccagagagg actgtgttaa gctgctgctg ctgctgctgg caagggtacc ccgtcccagg 238620 aaggtaccag aagcgagcag tcagtttcat agatctctgc agagctgttg gcctatagca 238680 ccgagccagc tgtccacttt ccctttccct ttttcttttt ggatactggc caagccaaag 238740 caatattatc tctaatattt tacagaagct accacactcc gttgtgtggt tgcttacaag 238800 aggtgtggat ttttatctct cctgtcttcc tcctccagtg acatctgaaa ctcactgtgc 238860 agcaaaacct ggccttgaac ccctcctgca tctatctcct aggtgctgaa attgcaggtg 238920 tgccccatca tcccaggcat caaccctgga ttgctctcta agaaacgctg ctagctcatt 238980 cctgcaacca caaataccag tcatgcacaa gttgtaccca ggggctggtg acaggaagaa 239040 gagaactggt ggccagtcaa agcactgcct gcctagttag ggtgtccagc agcatcacaa 239100 aatagaaatg atacatcatg attggtcctc atccggcaac acagttcagc aagtaaaggc 239160 acttgccacc aagcctgaac gtcatggtag gggattaagt gactcctgca ggttgtcgtc 239220 tgtcctagtt agggttacta gcactgctgt gatgaaacac catgaccaaa gcaacctgca 239280 gaggaaagga ttcattcagc ttctacatca cagttcatca tcaaaggaaa ttaggacaac 239340 ttaagcaggg aggaacctgg aggcaggagc tgatgcagag gccatagagg ggtgctgctt 239400 actgcttccc atggcttgtt caagcctgct ttcttagaga gcccaggacc accagcccag 239460 agtgaacccc tcctacaata ggctaggcct cctccatcaa tcacaaagaa aatgccctac 239520 agactctctc tgataactcc agcttgtgtc aaatcaacat aaaacaaacc agtacctcct 239580 ctgacctcca aacgtgtgca agtgtggcac tttcatgcca ctagcaaaca tctgacccaa 239640 gatcagcacc acatagccag ggagactcgg aaactggcta gctgacactg aaagatcctg 239700 agagagaaga gtgaaaaatt atgtaagccc ctagacttgt gtccaaaata gacctgacta 239760 atggcaggga gtaaaagttt aactcacccc attgttttag gttgtactaa ccacaaagta 239820 gaagtttaac ttccattgtt ttaggaaatg ttcatacaga atattccaac tatttcttga 239880 acccgttgtg cttgccaaat gctatagccc atgccaggtg tttacggttt ctgcctttat 239940 aagcccctta tcctttgagc tgggggcgac tcctctaccc cttcgtggga tacgagtcgt 240000 c 240001 <210> SEQ ID NO 33 <211> LENGTH: 4039 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 33 actccccaga gtcctctaat gtctccccgg atggcacata ctcagagtcc catgatgcag 60 cagtctcaag ccaacccagc ctaccagccc acctcagaca tgaatggatg ggcacagggg 120 agcatgggtg gaaacagcat gttctcacag cagtccccac cacactttgg gcaacaagca 180 aacaccagca tgtatagtaa caacatgaac atcagtgtgt cgatggcaac caacacgggt 240 ggcttgagca gcatgaacca gatgacaggc cagatgagca tgacctcagt gacctccgtg 300 cctacgtcag gactgccctc catgggtccc gagcaggtca atgaccctgc tctgagggga 360 ggcaaccttt tcccaaacca actgcctgga atggacatga tcaagcagga gggagatgca 420 tctcggaaat actgctgacc ctggagaaac tgtctgcatc tttcttcaac ccactgggct 480 tacaaacatt taccagtctg gagagctgcg tctctttgtg ttgccacctg acatgcccca 540 gttctcccag gacatagcag cagacagtcg ggccctgggc ccgcagcata gagcgtgctg 600 gcttggctgc caccggaaga gttgcctctc ccgacagcct gcagctcgcc tccagaccaa 660 cccgcagtct gttcactgca ttcaccgtag tgcaacttag atctcctgca gagtaactgt 720 ccccaggccg acttcatccc catcagattg aatgtattta aatgtgtgtg tttgaggaga 780 gccatgccct tggcctgttc ctgctcggct ccagacactg gtttcttgct ttgttctctg 840 tggctcttct gtgtaaaaga tgagaatctt atctacagga aagaaaggaa cttttaacac 900 agtacaaccc aaggtgttct aagcttaaag cctgcatttg actgggatgg agacagggca 960 gacactgtgc acagcgctgt gtatgccggc acacctagtc agcaacacgt aaccgaggca 1020 gagttctgtc tccaggaagg agtgtcccgt cactgaacag atggaaggct cttgagagag 1080 gctgttagca ttaacaagta tctgttccca cttctctctg ttaaaaccaa actagtttcc 1140 cctaaatcat gaatcaaaaa gaaatacttg tttctaaatt gtttttagat cagatagttt 1200 gattggcatc tcttcccttc ctctccccac cttctctcgt ccctccctct ttcattcctt 1260 taaagtaaaa acatcaacag cagcatacac catagagacc agggaagccc ttaggatctc 1320 tcagtgctgt gccagccact tacagcagct tcccagtgac catgcatttc ctatcagaga 1380 ggaacaaagt caggctgtga catctgctta ggtagcctgg gctgccccat cagctcaggc 1440 ctccaaaatg agagaactta ctaatgaaat caacagcaga cgtcacgaca gatctaacct 1500 ctgccatatg gggttgtttt ttatttttgg tttttagcag tgctgacgaa gccgaagttt 1560 tgtaaggtac ataaagatcc aatttatatg taaacaagca ataatttaag ttctgaactt 1620 aagtgtttta actgtataat tttgtgaggt atacatattg tgggattgac tcaaaatgag 1680 gtacttcagt attaaattag atatcttcat agcaatgtct cctaaaggtg ttttgtaacg 1740 gctgccaatg ccttggttag acctgacttg tagacgtaag accttttgtt ttctaaccct 1800 tgagactctc ctcatgaatc ctgtatctaa tctatatgat atgcagccgc tgtcagaacc 1860 aagtcttgat tttatatgtt tatattcttt cttaataaac cttagaaaga caacattact 1920 aagcagccca ctttgatggt tgttttcttg cccactgtcg gggataacct ctattaactg 1980 gtgtcagttt cagacagctg cagtacccag aaccgagacc ttttcaattc tccccaacct 2040 tgatacacac actttcgtac ctaaatttca gaatgatgtc tttttgatgt ctaaaaacaa 2100 agcattttat aatatctcat tatccaagct ttctaggaac agagaagatt ttccttgaag 2160 tttgtttatt cctggcaggg ttaaaaacat ataaactacc ctatttatat ttatgtctcc 2220 ctatatatct acagattgta gaaatataga aagagatgtg acccaaagac aaatggtcag 2280 tcatctgaaa gtgatgctgc gtgctaagga actctggaaa tttgcatttc catacctttt 2340 tccacttaga gaagaatctc agtgagggag gtggcccagg aacagcgctt ccccgttggc 2400 caccagttcc tgtgtctgct cgagactcca ccaaaccatt ggcttgcaca tctgtcctgc 2460 aaagggagca gatagaaccc agaactccag gccctgcccc aggagtgagg ctcaggtgca 2520 ctactgagct cgacctgttc tcagataagt cagaaatgtg aggtaggtaa aaatgacttc 2580 acacagcaca agagaaaaag gaatttaaaa catacttgtt ttgtattaaa tcccatctca 2640 ctgtaacatc aagccacaat atcttacctt tcagccttca tccaatctcc cactgctttc 2700 taatgttgac ccggctgtta gcgtagccca tggtcatggc aaatcctctc acaggtcaga 2760 gcagccatga actgtgtgcc atctcatcag gaggatcaat cgcatcagca aaggcatcct 2820 gatcatgttc tcagagccag ggccagccca gcctcccctg ccatcagtat tgctcacgct 2880 ctgcacaaca catttgtact tggttttgtc tgacagaaca tagaatcagt gttctcttag 2940 atgactcaat gtgaaaagcg taatgtgaaa agtacacacc tgatcgtggt tgtaaaatcc 3000 atttaagtgt tcatgcaaca tggtgagttt taaaagtgaa gtgtgctgtg atactacaac 3060 caattgactc aaagattaaa gcacgcacgc acacacacac acacatacac acgtgtatct 3120 cttacgacct gtaatgattg aaagcaatgg tttttttgca gtttaagatg caatttttaa 3180 tctgtgttta aaaacggagt tcatatgggt gtgacacgtg aactgggagg cacagatcca 3240 cttgcagaac ccaaagatac acaatcaatt ttgaaatgca acttaagcca ttaattgttg 3300 gtgtgaattt aaaattttct agttgtttat atggtagtat gctgccgaag agcaaagcat 3360 tctctgcaca aaagaaaaca ctgtagtggc ttcgatttta attagaactt tctccctggt 3420 gtttctttat agactaaaac aaaatctttt aagtttcttt actacaggta aaagctatgt 3480 gcaagaacct caaaatgcta aaacctagca taatgcctta gatctgtttt taagtcttgt 3540 atattcctac atagctgtcc aatgtattat atttgtatag tgaattgtgt aaaatttttg 3600 aataagtaag tcatcgctta cccgtatgtt actgaacagt gatgacaact cgtttcttca 3660 aacatttaac tgtcttctct ttttcctttg tcatttgtgg gttttatttg tacagttcct 3720 catgaagttg catttgagat atgtgtatat gaaaaaatta tacaagggta aaattaagca 3780 atatattaac tatggttctt caggagaaag cttacagtgt ttcaggttgt gatttatttt 3840 caaaacagag ttgactctga acatcacttt gttcatctgc attgatgttt gtatttctag 3900 tgtgagcagt ttatgcaaag gtagatatat acagagaaat tttaaataca tttatgcaag 3960 ttactattgc tttgctgatg ctatttgctt atttgatgtt aaataatgct attgtaaata 4020 aagaatctgt tgttactgc 4039 <210> SEQ ID NO 34 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 34 aaccacactt acccatgggc 20 <210> SEQ ID NO 35 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 35 atgcactcaa gaactcggta 20 <210> SEQ ID NO 36 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 36 atgtccagtt ttccgccctt 20 <210> SEQ ID NO 37 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 37 atttgcatcc atgagctcca 20 <210> SEQ ID NO 38 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 38 caggagatgt tggccgtggt 20 <210> SEQ ID NO 39 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 39 ccagggctgc ctcagacaca 20 <210> SEQ ID NO 40 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 40 cgctcgtact cgtaggccag 20 <210> SEQ ID NO 41 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 41 ctcgtgaacc agagcaccac 20 <210> SEQ ID NO 42 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 42 ctgctagcct ctggatttga 20 <210> SEQ ID NO 43 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 43 gagctttgcc ttcttgccat 20 <210> SEQ ID NO 44 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 44 gcactttgtg gtgccaaggc 20 <210> SEQ ID NO 45 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 45 gctccttcca ctgatcctgc 20 <210> SEQ ID NO 46 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 46 ggacctgtag ccatagccaa 20 <210> SEQ ID NO 47 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 47 gtgtttctga gaacttgtgg 20 <210> SEQ ID NO 48 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 48 gttcctgtca aagctcgtgc 20 <210> SEQ ID NO 49 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 49 gttggtctcc tttgcctgga 20 <210> SEQ ID NO 50 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 50 tcaaggactg ctgatcttcg 20 <210> SEQ ID NO 51 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 51 tcaagtttct ctgtgcccaa 20 <210> SEQ ID NO 52 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 52 tccatttatt agtctaggaa 20 <210> SEQ ID NO 53 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 53 tctacagtca tgctgagtaa 20 <210> SEQ ID NO 54 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 54 tgtcatcggg ttcccagcct 20 <210> SEQ ID NO 55 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 55 tgtgctattc tgtgaatt 18 <210> SEQ ID NO 56 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 56 tgttgcaaga atttctcatg 20 <210> SEQ ID NO 57 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 57 ttcatgaact gcacagaggt 20 <210> SEQ ID NO 58 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 58 ttctcatgat gaggtgtacc 20 <210> SEQ ID NO 59 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 59 ttgttgacat tgtactcggc 20 <210> SEQ ID NO 60 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 60 ttgttgacgt tgtactcagc 20 <210> SEQ ID NO 61 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 61 cctgatccct ctaatgatgc 20 <210> SEQ ID NO 62 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 62 cctgctcact ctaatgctgc 20 <210> SEQ ID NO 63 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 63 cctgctccct ctaatgctgc 20 <210> SEQ ID NO 64 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 64 ccttccctga aggttcctcc 20 <210> SEQ ID NO 65 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 65 cgttattaac ctccgttgaa 20 <210> SEQ ID NO 66 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 66 cttctagcct ctggattgga 20 <210> SEQ ID NO 67 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 67 gcgatttccc gttttcacct 20 <210> SEQ ID NO 68 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 68 gttcgtgttc tctggctcga 20 <210> SEQ ID NO 69 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 69 tacttgacct acagagtgga 20 <210> SEQ ID NO 70 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 70 tcaagtcctt ccacacccaa 20 <210> SEQ ID NO 71 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 71 ttgttaacgg tgttctcagc 20 <210> SEQ ID NO 72 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 72 tttgtaacgg tgttcactga 20 <210> SEQ ID NO 73 <400> SEQUENCE: 73 000 <210> SEQ ID NO 74 <400> SEQUENCE: 74 000 <210> SEQ ID NO 75 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(20) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 75 nnnnnnnnnn nnnnnnnnnn 20 <210> SEQ ID NO 76 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 76 attcttaaac ctgagggagc 20 <210> SEQ ID NO 77 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 77 tgatcgtctt ccaagctccc 20 <210> SEQ ID NO 78 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 78 gagagatgca gctggagcca 20 <210> SEQ ID NO 79 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 79 tgccatcatc tgatgcccgg 20 <210> SEQ ID NO 80 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 80 ttagaaggat ctgtgagttt 20 <210> SEQ ID NO 81 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 81 gcacattgac cactgttctt 20 <210> SEQ ID NO 82 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 82 agtgctttca taaggcagtc 20 <210> SEQ ID NO 83 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 83 ctctggttgc aggcccctca 20 <210> SEQ ID NO 84 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 84 aagtctgaac actgcacagc 20 <210> SEQ ID NO 85 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 85 ttacctttgt gttcgtggag 20 <210> SEQ ID NO 86 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 86 gcagcatcag tattccaatc 20 <210> SEQ ID NO 87 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 87 tcttccgagc aaagttgtgt 20 <210> SEQ ID NO 88 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 88 tgagcaggaa tttctgacag 20 <210> SEQ ID NO 89 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 89 tggaaacaat aagagttgtc 20 <210> SEQ ID NO 90 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 90 ggaaacagac tctcgcatac 20 <210> SEQ ID NO 91 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 91 gtgctgagaa ctaacaggca 20 <210> SEQ ID NO 92 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 92 tgaccatgtg gacattaggt 20 <210> SEQ ID NO 93 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 93 ctgtccacag gcagcgtggt 20 <210> SEQ ID NO 94 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 94 gaaggtgagg ctgattcgct 20 <210> SEQ ID NO 95 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 95 cacgaggcct aattttgttt 20 <210> SEQ ID NO 96 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 96 atttcccaat aatagcttga 20 <210> SEQ ID NO 97 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 97 gcaacatctc cgtgccattt 20 <210> SEQ ID NO 98 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 98 tcctgaaggc ctggaattgc 20 <210> SEQ ID NO 99 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 99 ccgtgttttg cgcagaacag 20 <210> SEQ ID NO 100 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 100 caggttgtcc tttgtcatgt 20 <210> SEQ ID NO 101 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 101 ggacatgcag gtgtttgtag 20 <210> SEQ ID NO 102 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 102 attagctgga acatctgaaa 20 <210> SEQ ID NO 103 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 103 atgcaaatag tccattccct 20 <210> SEQ ID NO 104 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 104 gaaatatatt gttggatttc 20 <210> SEQ ID NO 105 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 105 cgtgacttta ctgttgccaa 20 <210> SEQ ID NO 106 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 106 gggccatcca gaggacagag 20 <210> SEQ ID NO 107 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 107 tgaagatgat ctgatctcgg 20 <210> SEQ ID NO 108 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 108 atatagctta ctaagatctg 20 <210> SEQ ID NO 109 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 109 aatggaagac aggatctggg 20 <210> SEQ ID NO 110 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 110 cttcggtaga gagtgttgga 20 <210> SEQ ID NO 111 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 111 tatcctcagt gtgggctgcc 20 <210> SEQ ID NO 112 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 112 tgcaaagtca actagaagac 20 <210> SEQ ID NO 113 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 113 ttctgcctct ggagaaaggg 20 <210> SEQ ID NO 114 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 114 aggtccttag cagagcttct 20 <210> SEQ ID NO 115 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 115 aaatggcttc cttctcccag 20 <210> SEQ ID NO 116 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 116 tacagaaggc tgggccttga 20 <210> SEQ ID NO 117 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 117 tttttgtact accatcaaca 20 <210> SEQ ID NO 118 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 118 acttcctcta aatactcatg 20 <210> SEQ ID NO 119 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 119 tccacatcag ggctggactg 20 <210> SEQ ID NO 120 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 120 gaagctgatt tccaaaatcc 20 <210> SEQ ID NO 121 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 121 tcccgcctgt gacatgcatt 20 <210> SEQ ID NO 122 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 122 accactctct gaagaaagtc 20 <210> SEQ ID NO 123 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 123 gtgccttatg tgcaaaatgt 20 <210> SEQ ID NO 124 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 124 ggcggccaga gtctcggcag 20 <210> SEQ ID NO 125 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 125 ctaagaaaag ttccatagta 20 <210> SEQ ID NO 126 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 126 gaagctgtga aaggaggacg 20 <210> SEQ ID NO 127 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 127 gggcagctcc tggaagacaa 20 <210> SEQ ID NO 128 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 128 tgtatacaca tgatgtgact 20 <210> SEQ ID NO 129 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 129 aacatagcta tttgaagcta 20 <210> SEQ ID NO 130 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 130 aagcaataat ttcaatttct 20 <210> SEQ ID NO 131 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 131 gcccagctta acgtgtattt 20 <210> SEQ ID NO 132 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 132 tcatcaggcc cagcttaacg 20 <210> SEQ ID NO 133 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 133 ccatccatgg aaacattatc 20 <210> SEQ ID NO 134 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 134 acagcatcta acatcactgt 20 <210> SEQ ID NO 135 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 135 agtcaatctc ccgaggatag 20 <210> SEQ ID NO 136 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 136 agtgacgctt tccaagaaga 20 <210> SEQ ID NO 137 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 137 atgtaagcta acgatgaata 20 <210> SEQ ID NO 138 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 138 ttccctgggc tattctccca 20 <210> SEQ ID NO 139 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 139 aattgagaat tacactcacc 20 <210> SEQ ID NO 140 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 140 aacgcctcct aaattgagaa 20 <210> SEQ ID NO 141 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 141 tggattggct tagggaccca 20 <210> SEQ ID NO 142 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 142 actattttgc ccttatgaag 20 <210> SEQ ID NO 143 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 143 tcttaaaatc tactctgaaa 20 <210> SEQ ID NO 144 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 144 cttaactgtc ttaaaatcta 20 <210> SEQ ID NO 145 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 145 tgaaaaatgt acttttctat 20 <210> SEQ ID NO 146 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 146 aaagttttct ttaaacaatg 20 <210> SEQ ID NO 147 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 147 gcccatgttc tcagaataaa 20 <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 148 aatctaggtc tgttgaactc 20 <210> SEQ ID NO 149 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 149 aaggtaattt gctcaaggcc 20 <210> SEQ ID NO 150 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 150 agaaaactgg gactctaaga 20 <210> SEQ ID NO 151 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 151 tatttctatc tgaaaaataa 20 <210> SEQ ID NO 152 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 152 aacaaaccta tgaagtaggt 20 <210> SEQ ID NO 153 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 153 tgccacctac ctgagggagc 20 <210> SEQ ID NO 154 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 154 attcttaaac ctggtaagaa 20 <210> SEQ ID NO 155 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 155 gttcacatac cactgttctt 20 <210> SEQ ID NO 156 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 156 gcacattgac ctacaaacaa 20 <210> SEQ ID NO 157 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 157 gagctcttac cctttgtgtt 20 <210> SEQ ID NO 158 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 158 tgcaacttac aaagttgtgt 20 <210> SEQ ID NO 159 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 159 tcttccgagc ctacaacaag 20 <210> SEQ ID NO 160 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 160 aatgccttac aagagttgtc 20 <210> SEQ ID NO 161 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 161 gtgctgagaa ctaggaggag 20 <210> SEQ ID NO 162 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 162 gccctattac ctcaatcatc 20 <210> SEQ ID NO 163 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 163 gaattgcatc ctgaaacaga 20 <210> SEQ ID NO 164 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 164 ggaaaagtac ctgattcgct 20 <210> SEQ ID NO 165 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 165 gaaggtgagg cttaatagac 20 <210> SEQ ID NO 166 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 166 cacgaggcct ctgaaacaag 20 <210> SEQ ID NO 167 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 167 ccaagcttac cgtgccattt 20 <210> SEQ ID NO 168 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 168 gcaacatctc ctgcaaaatt 20 <210> SEQ ID NO 169 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 169 ttctactcac cgcagaacag 20 <210> SEQ ID NO 170 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 170 tctactcact ccattccctg 20 <210> SEQ ID NO 171 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 171 atgcaaatag ctgtgaaggg 20 <210> SEQ ID NO 172 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 172 caaaggatac tgttggattt 20 <210> SEQ ID NO 173 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 173 agaaatatat ctcaatgctt 20 <210> SEQ ID NO 174 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 174 agattctcac catccagagg 20 <210> SEQ ID NO 175 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 175 acagacttac ctgatctcgg 20 <210> SEQ ID NO 176 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 176 tgaagatgat ctaagggaaa 20 <210> SEQ ID NO 177 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 177 ggaagacagg atctgaaaca 20 <210> SEQ ID NO 178 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 178 gtgcgcgcga gcccgaaatc 20 <210> SEQ ID NO 179 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 179 tatcagcaac tgtgcctgta 20 <210> SEQ ID NO 180 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 180 cccactcatc ttgaacacat 20 <210> SEQ ID NO 181 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 181 tctgcacttc atctatgttg 20 <210> SEQ ID NO 182 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 182 cagctcttct tggttatacc 20 <210> SEQ ID NO 183 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 183 tgtctcagaa cttcatggtg 20 <210> SEQ ID NO 184 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 184 gaacggatga gtttgctctt 20 <210> SEQ ID NO 185 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 185 tcattagtag tctgagaacg 20 <210> SEQ ID NO 186 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 186 acctgggttc ccactgcaca 20 <210> SEQ ID NO 187 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 187 gggaaaattt atattgctac 20 <210> SEQ ID NO 188 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 188 atgcccattt gttcctttgg 20 <210> SEQ ID NO 189 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 189 tgcttctcct tgagcgaggt 20 <210> SEQ ID NO 190 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 190 aggatctgtc ttactgtcca 20 <210> SEQ ID NO 191 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 191 tgttactggc aggatctgtc 20 <210> SEQ ID NO 192 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 192 tgcaaatcat ccaaaatctc 20 <210> SEQ ID NO 193 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 193 atggcttgct tgtcaactga 20 <210> SEQ ID NO 194 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 194 tgatgatggc ttgcttgtca 20 <210> SEQ ID NO 195 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 195 gttgcatgag gtcattgatg 20 <210> SEQ ID NO 196 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 196 gtgggttatt aaaagtgctc 20 <210> SEQ ID NO 197 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 197 tggtcgtggg ttattaaaag 20 <210> SEQ ID NO 198 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 198 ccagttgccc tggtcgtggg 20 <210> SEQ ID NO 199 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 199 cctgcccagt tgccctggtc 20 <210> SEQ ID NO 200 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 200 ctggtttggc aataacctgc 20 <210> SEQ ID NO 201 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 201 gtccagcacc agttgggctt 20 <210> SEQ ID NO 202 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 202 gaaaggtcca gcaccagttg 20 <210> SEQ ID NO 203 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 203 tgattggtgg gaaaggtcca 20 <210> SEQ ID NO 204 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 204 ctactgtttc tgattggtgg 20 <210> SEQ ID NO 205 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 205 ggctgaggta tcactgagta 20 <210> SEQ ID NO 206 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 206 ttcctggctg aggtatcact 20 <210> SEQ ID NO 207 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 207 ttacccatca ttcctggctg 20 <210> SEQ ID NO 208 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 208 gtctttggcc aggctggctg 20 <210> SEQ ID NO 209 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 209 tggctctggc tgaccagttc 20 <210> SEQ ID NO 210 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 210 agtttggatc ttgcatggga 20 <210> SEQ ID NO 211 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 211 ttctgctgtg cttggaggcg 20 <210> SEQ ID NO 212 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 212 gtcgtagccc cagtaaagcc 20 <210> SEQ ID NO 213 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 213 agttgcacta cggtgaatgc 20 <210> SEQ ID NO 214 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 214 gcatctttac cacttcagga 20 <210> SEQ ID NO 215 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 215 gaaaactcac ctggtcactg 20 <210> SEQ ID NO 216 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 216 aacaggtcga gctcagtagt 20 <210> SEQ ID NO 217 <211> LENGTH: 40 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 217 gttggaggca atggcaagaa ggcaaagctc ttcaggagga 40 <210> SEQ ID NO 218 <211> LENGTH: 21 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 218 cucauccucu guggcaaacu u 21 <210> SEQ ID NO 219 <211> LENGTH: 21 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 219 aaguuugcca cagaggauga g 21 <210> SEQ ID NO 220 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(19) <223> OTHER INFORMATION: bases at these positions are RNA <400> SEQUENCE: 220 ggagccuugc guccugggct t 21 <210> SEQ ID NO 221 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(19) <223> OTHER INFORMATION: bases at these positions are RNA <400> SEQUENCE: 221 gcccaggacg caaggcucct t 21

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 221 <210> SEQ ID NO 1 <211> LENGTH: 12 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 1 cgcgaauucg cg 12 <210> SEQ ID NO 2 <211> LENGTH: 12 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 2 gcgcuuaagc gc 12 <210> SEQ ID NO 3 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 3 cgagaggcgg acgggaccg 19 <210> SEQ ID NO 4 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 4 cgagaggcgg acgggaccgt t 21 <210> SEQ ID NO 5 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 5 ttgctctccg cctgccctgg c 21 <210> SEQ ID NO 6 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 6 gctctccgcc tgccctggc 19 <210> SEQ ID NO 7 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 7 tccgtcatcg ctcctcaggg 20 <210> SEQ ID NO 8 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 8 gtgcgcgcga gcccgaaatc 20 <210> SEQ ID NO 9 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 9 atgcattctg cccccaagga 20 <210> SEQ ID NO 10 <211> LENGTH: 1115 <212> TYPE: DNA <213> ORGANISM: M. spretus <400> SEQUENCE: 10 aagagtggct cctgtaggca gcacggactt gaacaaccag actcctgtag acgtgttcca 60 gaacttacgg aagcacccac gatggacccc agatgcacca tgggcttggc aatccttatc 120 tttgtgacag tcttgctgat ctcagatgct gtttccgtgg agacgcaagc ttatttcaat 180 gggactgcat atctgccgtg cccatttaca aaggctcaaa acataagcct gagtgagctg 240 gtagtatttt ggcaggacca gcaaaagttg gttctgtacg agcactattt gggcacagag 300 aaacttgata gtgtgaatgc caagtacctg ggccgcacga gctttgacag gaacaactgg 360 actctacgac ttcacaatgt tcagatcaag gacatgggct cgtatgattg ttttatacaa 420 aaaaagccac ccacaggatc aattatcctc caacagacat taacagaact gtcagtgatc 480 gccaacttca gtgaacctga aataaaactg gctcagaatg taacaggaaa ttctggcata 540 aatttgacct gcacgtctaa gcaaggtcac ccgaaaccta agaagatgta ttttctgata 600 actaattcaa ctaatgagta tggtgataac atgcagatat cacaagataa tgtcacagaa 660 ctgttcagta tctccaacag cctctctctt tcattcccgg atggtgtgtg gcatatgacc 720 gttgtgtgtg ttctggaaac ggagtcaatg aagatttcct ccaaacctct caatttcact 780 caagagtttc catctcctca aacgtattgg aaggagatta cagcttcagt tactgtggcc 840 ctcctccttg tgatgctgct catcattgta tgtcacaaga agccgaatca gcctagcagg 900 cccagcaaca cagcctctaa gttagagcgg gatagtaacg ctgacagaga gactatcaac 960 ctgaaggaac ttgaacccca aattgcttca gcaaaaccaa atgcagagtg aaggcagtga 1020 gagcctgagg aaagagttaa aaattgcttt gcctgaaata agaagtgcag agtttctcag 1080 aattcaaaaa tgttctcagc tgattggaat tctac 1115 <210> SEQ ID NO 11 <211> LENGTH: 2262 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 11 ggtggccgcg cttcgctggc tttctgctca tctagggtgg cagcggctac ctacctcagc 60 tctcgccctg ctgccgccac ggcctgggcg ctgtccctca gctcccggag ctcagcgcga 120 agccctggcc ccggcggccg gggcatgggt caggggcgcg gcgtgaggcg gctttctgca 180 cggccgtgac gtgcattggc ttcagcatga agaccctcat cgccgcctac tccggggtcc 240 tgcggggtga gcgtcgggcg gaagctgccc gcagcgaaaa caagaataaa ggatctgccc 300 tgtcacgcga ggggtctggg cgatggggca ctggctccag catcctctca gccctccaag 360 acatcttctc tgtcacctgg ctcaacagat ctaaggtgga aaaacagctg caggtcatct 420 cagtactaca atgggtccta tccttcctgg tgctaggagt ggcctgcagt gtcatcctca 480 tgtacacctt ctgcacagac tgctggctga tagctgtgct ctacttcacc tggctggcat 540 ttgactggaa cacgcccaag aaaggtggca ggagatcgca gtgggtgcga aactgggccg 600 tgtggcgcta cttccgagac tactttccca tccagctggt gaagacacac aacctgctga 660 ccaccaggaa ctatatcttt ggataccacc cccatggcat catgggcctg ggtgccttct 720 gtaacttcag cacagaggct actgaagtca gcaagaagtt tcctggcata aggccctatt 780 tggctacgtt ggctggtaac ttccggatgc ctgtgcttcg cgagtacctg atgtctggag 840 gcatctgccc tgtcaaccga gacaccatag actacttgct ctccaagaat gggagtggca 900 atgctatcat catcgtggtg ggaggtgcag ctgagtccct gagctccatg cctggcaaga 960 acgcagtcac cctgaagaac cgcaaaggct ttgtgaagct ggccctgcgc catggagctg 1020 atctggttcc cacttattcc tttggagaga atgaggtata caagcaggtg atctttgagg 1080 agggttcctg gggccgatgg gtccagaaga agttccagaa gtatattggt ttcgccccct 1140 gcatcttcca tggccgaggc ctcttctcct ctgacacctg ggggctggtg ccctactcca 1200 agcccatcac caccgtcgtg ggggagccca tcactgtccc caagctggag cacccgaccc 1260 agaaagacat cgacctgtac catgccatgt acatggaggc cctggtgaag ctctttgaca 1320 atcacaagac caaatttggc cttccagaga ctgaggtgct ggaggtgaac tgacccagcc 1380 ctcgcgtgcc agctcctggg agggacgact gcagatcctt ttctaccgag ttcttgagtg 1440 cattttgttc tgtaaatttg gaagcgtcat gggtgtctgt gggttattta aaagaaatta 1500 taatgtgtta aaccattgca atgttagatg tttttttaag aagggaagag tcagtatttt 1560 aagctcactt ctagtgtgtc ctgctcaagg tggaggctga tatttatggg ccttggtggt 1620 ttcttaccca ccccttctag cgttccccag acgacagaca cttggccctg gctagctggg 1680 caagggcagt ccttagtgac tccagggatt cttgagaggc agaggccatg tcccacccgt 1740 ggctgcaggt cgggttcctc gtaccaaggg gaggctgagg gcacagctgg ccccacttgg 1800 ggagggtaga taacatctgg actgcccggc ttgggtctct gctcctcacc ctagccctct 1860 tctccaatct gagcctaccc tggcctcctg tctcctggct agggacacgg ctgtcccaca 1920 ggtgccgtct tgggttatct cgctgctgtt ggctggtttc actctggagg ttggcaccat 1980 ggacacagct cagcgttgct ctggcgcata tcctcctgag ccacacccca agtctggtgt 2040 gaggaagggc ttctcttctc ttcacagagg tgcctggctt cctgtgcagc acactgggtc 2100 caggacagga ggcccccccc ccaaaccaag cctcacgtgt gtgcctttat gaggcgttgg 2160 gagaaagcta ccctcctgtg tattctgttt tctccatgag attgttgtgc catgtcacac 2220 ttttgtatat tcctagacta ataaatggaa acaagaacag cc 2262 <210> SEQ ID NO 12 <211> LENGTH: 8363 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 12

tcctcgcttg tcgtctgcct ccagagccca gacagagaag agccatggag gaggtggtga 60 tagccggtat gtcggggaag ttgcccgagt cagagaacct acaggagttc tgggccaacc 120 tcattggtgg tgtggacatg gtcacagatg atgacaggag atggaaggct gggctctatg 180 gattacccaa gcggtctgga aagctgaagg atctctccaa gttcgacgcc tccttttttg 240 gggtccaccc caagcaggca cacacaatgg acccccagct tcggctgctg ttggaagtca 300 gctatgaagc aattgtggat ggaggtatca acccagcctc actccgagga acgaacactg 360 gcgtctgggt gggtgtgagt ggttcagagg catccgaggc ccttagcaga gatcccgaga 420 cgcttctggg ctacagcatg gtgggctgcc agcgtgcaat gatggccaac cggctctctt 480 tcttcttcga cttcaaagga ccaagcattg ccctggacac agcctgctcc tccagcttgc 540 tggcactaca gaatgcctac caggccatcc gtagtgggga atgccccgcg gcccttgtgg 600 gtgggatcaa cctgctcctg aagccgaaca cctctgtgca gttcatgaag ctgggcatgc 660 tcagcccgga cggcacctgc agatcctttg atgattcagg gagtggatat tgtcgctctg 720 aggctgttgt agcagttctg ctgactaaga agtccctggc tcggcgggtc tatgccacga 780 ttctgaatgc cggcaccaat acagatggca gcaaggagca aggtgtaaca ttcccctctg 840 gagaagtcca agaacaactc atctgctctc tgtatcagcc agctggtctg gccccggagt 900 cgcttgagta tattgaagcc catggcacgg gcaccaaggt gggtgacccc caggaactga 960 atggcattac tcggtccctg tgcgccttcc gccaggcccc tctgttaatt ggctccacca 1020 aatccaacat gggacaccct gagcctgcct ctgggcttgc agccctgacc aaggtgctgt 1080 tatccctgga gcatggggtc tgggccccta acctgcactt ccacaacccc aaccctgaga 1140 tcccagcact tcttgatggg cggctgcagg tggtcgatag gcccctgcct gttcgtggtg 1200 gcaacgtggg catcaactca tttggcttcg gaggctccaa tgttcatgtc atcctccagc 1260 ccaacacacg gcaggcccct gcgcccactg cacacgctgc ccttccccat ttgctgcacg 1320 ccagtggacg caccttagag gcagtgcagg acctgctgga acagggccgc cagcacagcc 1380 aggacctggc ctttgtgagc atgctcaatg acattgcggc aacccctaca gcagccatgc 1440 ccttcagggg ttacactgtg ctaggtgttg agggccgtgt ccaagaagtg cagcaagtgt 1500 ccaccaacaa gcgcccactc tggttcatct gctcagggat gggcacgcag tggcgcggga 1560 tggggctgag cctcatgcgc ctggacagct tccgtgagtc tatcctgcgc tccgatgagg 1620 ctgtgaagcc gttgggagtg aaagtgtcag atctgctgtt gagcacagat gagcgcacct 1680 ttgatgacat cgtgcatgcc tttgtgagcc tcactgccat ccagattgcc ctcatcgacc 1740 tactgacttc tgtgggactg aaacctgacg gcatcattgg gcactccttg ggagaggttg 1800 cctgtggcta tgcagatggc tgtctctccc agagagaggc tgtgcttgca gcttactggc 1860 gaggccagtg catcaaagat gcccacctcc cgcctggatc catggcagct gttggtttgt 1920 cctgggagga atgtaaacag cgctgccccg ctggcgtggt gcctgcctgc cacaactctg 1980 aggacaccgt gaccatctct ggacctcagg ctgcagtgaa tgaatttgtg gagcagctaa 2040 agcaagaagg tgtgtttgcc aaggaggtac gaacaggagg cctggctttc cactcctact 2100 tcatggaagg aattgccccc acattgctgc aggctctcaa gaaggtgatc cgggaaccac 2160 ggccgcgctc ggctcgatgg ctcagcacct ctatccctga ggcccagtgg cagagcagcc 2220 tggcccgcac atcttctgcc gagtacaatg tcaacaacct ggtgagccct gtgctcttcc 2280 aggaagcact gtggcacatc cctgagcatg ccgtggtgct ggagattgcg ccccacgcac 2340 tgttgcaggc tgtcctgaag cgaggcgtga agtccagctg caccatcatt cccttgatga 2400 agagggatca taaagataac ttggagttct ttctcaccaa ccttggcaag gtgcacctca 2460 caggcatcaa tgtcaaccct aacgccttgt tcccacctgt ggagttcccg gctccccgag 2520 ggactcctct catctcccct cacatcaagt gggaccacag tcagacttgg gatgtcccgg 2580 ttgctgagga cttcccaaac ggctccagct cctcctctgc tacagtctac agcatcgacg 2640 ccagtcctga gtcgcccgac cactacctgg tagaccactg cattgacggc cgggtcatct 2700 tccctggcac tggctacctg tgcctggtgt ggaagacact ggctcgcagc ctgggcttgt 2760 ccctagaaga gacccctgtg gtatttgaga atgtgtcgtt tcatcaggcc actatactac 2820 ccaagacagg aaccgtggcg ctggaggtga ggctgctaga ggcctcccat gcctttgagg 2880 tgtctgacac tggcaatctg attgtgagcg gaaaagtgta cctgtgggaa gacccgaact 2940 ccaagttatt cgaccaccca gaagtcccaa caccccctga gtctgcatcg gtctcccgcc 3000 tgacccaggg agaagtatac aaggagctgc ggctgcgtgg ctatgattat ggccctcagt 3060 tccagggcat ctgtgaggcc acccttgaag gtgaacaagg caagctgctc tggaaagata 3120 actgggtgac cttcatggac acaatgctgc aggtatccat tctgggttct agccagcaga 3180 gtctacagct acctacccgt gtgaccgcca tctatatcga ccctgccacc caccgtcaga 3240 aggtgtacag gctgaaggag gacactcaag tggctgatgt gacaacgagc cgctgtctgg 3300 gcataacggt ctctggtggt atccacatct caagactaca gacgacagca acctcacggc 3360 ggcagcaaga acagctggtc cccaccttgg aaaagttcgt tttcacaccg cacatggagg 3420 ctgagtgcct gtctgagagc actgccctgc agaaggagct gcaactgtgc aagggtctgg 3480 cacgggctct gcagaccaag gccacccagc aagggctgaa ggcggcaatg cttgggcaag 3540 aggaccctcc acagcacggg ctgcctcgac tcctggcagc tgcttgccag ttgcagctca 3600 acgggaacct gcagctggag ctgggagaag cgctggctca agagaggctc ctgctgccag 3660 aagaccctct gatcagtggc ctcctcaact cccaggccct caaggcctgc gtagacacag 3720 ccctggagaa cttgtctact ctcaagatga aggtggcaga ggtgctggct ggagaaggcc 3780 acttgtattc ccgaatcccg gcactgctca acacccagcc catgctacaa ctggaataca 3840 cagccaccga ccggcacccc caggccctga aggatgttca gaccaaactg cagcagcatg 3900 atgtggcgca gggccagtgg aacccttccg accctgcgcc cagcagcctg ggtgcccttg 3960 accttctggt gtgcaactgt gcattagcca ccctggggga tccagccttg gccctggaca 4020 acatggtagc tgccctcaag gaaggtggtt tcctgctagt gcacacagtg ctcaaaggac 4080 atgcccttgg ggagaccctg gcctgcctac cctctgaggt gcagcctgcg cccagcctcc 4140 taagccagga ggagtgggag agcctgttct cgaggaaggc actacacctg gtgggcctta 4200 aaaggtcctt ctacggtact gcgctgttcc tgtgccggcg agccatccca caggagaaac 4260 ctatcttcct gtctgtggag gataccagct tccagtgggt ggactctctg aagagcactc 4320 tggccacgtc ctcctcccag cctgtgtggc taacggccat ggactgcccc acctcgggtg 4380 tggtgggttt ggtgaattgt ctccgaaaag agccgggtgg acaccggatt cggtgtatcc 4440 tgctgtccaa cctcagcaac acatctcacg cccccaagtt ggaccctggc tctccagagc 4500 tacagcaggt gctaaagcat gacctcgtga tgaacgtgta ccgggacggg gcctggggtg 4560 ccttccgtca cttccagtta gagcaggaca agcccaagga gcagacagcg catgcctttg 4620 taaacgtcct cacccgaggg gacctcgcct ccatccgctg ggtctcctcc cccctgaagc 4680 acacgcagcc ctcgagctca ggagcacagc tctgcactgt ctactacgcc tcactgaact 4740 tccgagacat catgctggcc acgggcaagc tgtcccctga tgccattcca ggtaaatggg 4800 ccagccgaga ctgcatgctc ggcatggagt tctcaggccg ggataggtgt ggccggcgtg 4860 tgatggggct ggttcctgca gaaggcctgg ccacctcagt cctgctatca tctgacttcc 4920 tctgggatgt accctccagc tggaccctgg aggaggcggc ctctgtgccc gtcgtctata 4980 ccactgctta ctactcgtta gtggttcgcg ggcgcatcca gcgtggggag accgtgctca 5040 tccactcagg ttcaggtggt gtgggccaag cggccatttc cattgccctc agtctgggct 5100 gccgcgtctt caccactgtg ggctctgcag agaagcgagc atacctccag gccaggttcc 5160 ctcagcttga tgacaccagc tttgccaact cgagggacac atcatttgag cagcacgtgt 5220 tactgcacac aggtggcaaa ggggtcgacc tggtcctcaa ctcactggca gaagagaagc 5280 tgcaggccag tgtgcggtgc ttggctcagc atggtcgctt cttagagatt ggcaaatttg 5340 atctttctaa caaccaccct ctgggcatgg ctatcttctt gaagaacgtc actttccatg 5400 ggatcctgct ggacgccctt tttgaggagg ccaatgacag ctggcgggag gtggcggcac 5460 tcctgaaggc tggcattcgt gatggagtcg tgaagcccct caagtgcaca gtgtttccca 5520 aggcccaggt ggaagatgcc ttccgctaca tggctcaggg gaaacacatt ggcaaagtcc 5580 ttgtccaggt acgggaggag gagcctgagg ctgtgctgcc aggggctcag cccaccctga 5640 tttctgccat ctccaagacc ttctgcccag cccataagag ttacatcatc actggtggcc 5700 taggtggctt tggcctggag ctggcccggt ggctcgtgct tcgcggagcc cagaggcttg 5760 tgctgacttc ccgatctgga atccgcaccg gctaccaagc caagcacatt cgggagtgga 5820 gacgccaggg catccaagtg ctcgtgtcaa caagcaacgt gagctcactg gagggggccc 5880 gtgctctcat cgccgaagcc acaaagctgg ggcccgttgg gggtgtcttc aacctggcca 5940 tggttttgag ggatgccatg ctggagaacc agaccccaga gctcttccag gatgtcaaca 6000 agcccaaata caatggcacc ctgaaccttg acagggcaac ccgggaagcc tgccctgagc 6060 tggactactt tgtggccttc tcctctgtaa gctgcgggcg tggtaatgct ggccaaacta 6120 actacggctt cgccaactct accatggagc gtatatgtga acagcgcagg cacgatggcc 6180 tcccaggcct tgccgtgcag tggggtgcca ttggtgacgt gggcattgtc ctggaagcga 6240 tgggcaccaa tgacacagtc atcggaggta cgctgcctca gcgcatctcc tcctgcatgg 6300 aggtactgga cctcttcctg aatcagcccc acgcagtcct gagcagcttt gtgctggcag 6360 agaagaaagc tgtggcccat ggggacgggg acacccagag ggatctggtg aaagctgtag 6420 cacacatcct aggcatccga gacctcgcag gtattaacct ggacagcacg ctggcagacc 6480 tcggcctgga ctcgctcatg ggtgtggaag ttcgtcagat cctggaacga gaacacgatc 6540 tggtgctgcc catgcgtgag gtgcggcagc tcacgctgcg gaaacttcag gaaatgtcct 6600 ccaagactga ctcggctact gacacgacag cccccaagtc caggagtgac acgtctctga 6660 agcagaacca actgaacctg agcacactgc tggtgaaccc tgagggtcct accctaaccc 6720 agctcaactc ggtgcagagc tctgagcggc ctctgttcct tgtgcacccc attgagggtt 6780 ccaccaccgt gttccacagt ctggctgcca agctcagtgt gcccacctac ggcctgcagt 6840 gcacccaagc tgcccccctg gatagcattc cgaacctggc tgcctactac atagattgca 6900 tcaagcaagt gcagcctgag ggaccctacc gcatagctgg gtactcattt ggagcctgtg 6960 tagccttcga gatgtgctcc cagctgcagg cccagcaggg cccagccccg acccacaaca 7020 acctcttcct gtttgacggc tcacacacct acgtgttggc ctacacccag agctaccggg 7080 caaagatgac cccaggctgt gaagccgagg ccgaggctga ggccttatgc ttcttcataa 7140 agcagtttct tgatgtggaa cacagcaagg tgctggaggc cctgctgcca ctgaagagcc 7200 tggaagatcg ggtggctgcc tccgtggacc ttatcactaa gagtcaccac agcctggacc 7260 gccgagagct gagctttgct gccgtgtcct tctaccacaa gctccgggca gctgatcagt 7320 ataagcccaa ggccaagtac catggcaacg tgacactgct gcgtgccaag acaggcggca 7380 cctatggcga ggacttgggt gctgactaca acctctccca ggtgtgtgac gggaaggtgt 7440 ctgtgcacat cattgagggt gaccaccgca cactgctgga gggcagtggc ctggaatcca 7500

tcatcaacat catccatagc tccctggctg agccacgagt gagtgtacgg gagggctaga 7560 cctgccgacc accatgaagc cacgctccac acctgccacc agagatgctc cgatccccac 7620 cacaccctga gtgcaggaac tggggagggt cctgctggtg ggacccctcc ccccagtggc 7680 ccagcaccac ccgctcccct ggtggctgct acaaacagac catcacgcgt gtgtttccca 7740 gccgcgtagt ggggttccca gagccactga cttggagaca ccctggtctg tgaagagtca 7800 gtggaggcag gagccaaact gagccttttc taccgtgtgg catttgccac gctggtcgtt 7860 tctccattaa attctcatat ttattgcatt gctgggaaag acccccaggg gtgactcatt 7920 ccagaacccc ctaaaatggg agaagccatg tggggaagat ttctgggaaa gtttctagac 7980 tcaatacaca ggctgctggc tggagcccct ttttgtcttg tcctgtccct gctcactgca 8040 gggcaggata tggagagggc tggttcccag ggaacaagga ccccagcaga cactgtagcc 8100 cgtggccctt ggtccccagc atccccggct gccccatgat gcagggccat cctgactctg 8160 cggaccgcac cgggcactga ctgtctgttt tccaagacga aaatgatgct tgggttttga 8220 cttttctgca gctgtcagtg tgaagaagtg tctggactgt gtcattttta caccaacctg 8280 gtaaaaatgc tgctcttgat gctctcctga tcccacaatt aaactgcacg tgagcgaaaa 8340 aaaaaaaaaa aaaaaaaaaa aaa 8363 <210> SEQ ID NO 13 <211> LENGTH: 23713 <212> TYPE: DNA <213> ORGANISM: R. norvegicus <400> SEQUENCE: 13 ggtacctcct tcccccacac agggaggact gtctaaagag aggccaccaa gaagagtgtc 60 ctgttcttcc tttaactaga cctacttagg aacagctcaa gtaagtgtgt ctagctcttg 120 gtgccagtta gaagctactt gtctgacact ggcctgagtc atgaacagct ccactgtgac 180 cactggttag atcaggctag ttccttcctt ggcctttgct cctacctggc tgggccaggt 240 cggcagcaag aggacctagc atggagccct tctatgattc ctgccctcca tgatgccttc 300 tggaagactt agaggagaag agccatgtga tatggttagc tggtgctggg aggaacatgt 360 gtataagagg agggtggtct aggtttggag aaccaggcat agctagcagg tgtcctcagg 420 atcctgagtc agcacagcct tgtcctgcag gagctagggc agaaatgacc ctaatgaggt 480 tgctgcttct aaatgtttca aaaagttcct tcctcagaaa gctgggcatg gtatcacata 540 ctgcgttctc acaagcctga agcaagagga ttgccatgac tccagcctgc attacaaagc 600 aagaccctga tttaaaagaa accaaagaaa aagagaccca cacagtctca ggacagggag 660 gagggcagct cacttctctg gagcctatgc aagcactcag gctccatgcc cacagcacat 720 tagattctgc caggcactct gtggctctac tgactcttac cctacctacc ctgtgcccat 780 gcggcatgtt ccaggtccac gggagtcaca gagataggct cctcagctct ggacagacat 840 gcacataaga cagctgagct aagactggca agcagtgggc tgtgtcccca agacaccaga 900 ctctgctgta agatatagtg catggtgttg tgttgcatgc tcttaatccc tccacttggg 960 aggcagaggc aggtgtgtcc ctaatgtcta ggccaagcag tttacatagt gagttccagg 1020 taaaccagaa ctgcatagta gttcctgtct aaaaaggagg gaaaaaaaag tataaaaatg 1080 caaaagcccc agaagcttcc tgtctgctgg gccaggttgc cagggaggaa ggataggtct 1140 gtctgtgtgc ctgagggagg tgaaatagtt ttagaaaaga tagacattgg ggttggggat 1200 ttagctcagt ggtagagcgc ttgcctagga agcgcaaggc cctgggttcg gtccccagct 1260 ccgaaaaaaa gaaccaaaaa aaaaaaaaaa aaagataaga catttttagt atcaaagatt 1320 caaagtacac aaaagatcaa aagataaaga tgatcatcta caaaagctag tgggacttac 1380 tagtgggcta actagtgggg cttactaact agtggggctt actaactagt ggggcttact 1440 aactagtggg gcttactagc aggcccttac ccatgaagtc tgggttctag cagcagccgc 1500 agcagcggca ataaagtgac cactttgact acggctcaag tggactctgg cagagctgct 1560 ctaggcttta acctgtgcct gtgtgtgtgg tacagcttac cagacagtcc ttggcctgtc 1620 tgtgtcagaa gtgttcacga acactccctg tacacgcaag ccccaagcac aggacaactc 1680 actgaactct cgatgaggtg gcttggcttg aatgggaggt ggggccacct gcccccatgc 1740 ccttaggaaa tggttataac agctcagggt gttttgttca gtgctttctt ttgtttccag 1800 agcccagatt tctgtgcggt agggaagagg caggcccagg atcagttgaa gatatgtgaa 1860 gcctgtgccc acacagacct cctacaccct agtcaggacc caataccgtt gctgccactg 1920 gccagggcta gggcactccg gaggcctgct ggcctgtata ggctcctgca gagaaaagca 1980 gactgagtcc ttacaggctg ctgattatga tatgaccaac tctgggcaca tacccacctc 2040 cgtttcctgt gatcctaacc tacatctttt tctacttctt gcctgtagag tgtcccgcac 2100 ctctgggacc cagctgtttc caaaaggtca gccggagccc tgtccccaca caaagggtca 2160 gccggagccc tgtccccaca caaagggcct ttgctgtcaa agggctaaag atggaagctc 2220 agccaaaagc ctcacacccc agacccagca agtcgcatcc agcaaagcct gcaaactgcc 2280 agccacagcg gcacccaagg atccgcaact acaacctcaa ggactagatc tcagcctcct 2340 gcagggcact gcacaggggc ctccaccttg gtccacgggg cctgtgcatg tacaagttgg 2400 gagtgagtac acacataata cacaggtgga ctgtgacaca ggacagactc ccaaatgctg 2460 gcctgcctga tactaaagag aaattaaaac cctcctccat ctgcttggcc tgtgaagttg 2520 tctgtcttgt cctacttggg aaatgaagta tcaacatgca ggctagatcc tgggctggtc 2580 tctgccacct gcctgtgtca ccacccacag ccactgtgca ctgaccctgt cagtgacact 2640 attcttctct agaatctggt gggcagaata gagtggccac ctgcaaagta tgtccccaag 2700 gaacattgtg agagaggtcc tcccaggagc atgagcctgg ccgaggccct atctcagaaa 2760 tatactcatc tgccgactga aaacctcatc aagggacctg cctgaccatt cctgcccaca 2820 gtagatctta aagagggtca tggccttagc cttgctgggc ataagacaca cagggctgca 2880 ggggtggaag cagctcccag gtccaggttg ctgtgtgtcc ctgattaatc atgtgactct 2940 tacagcttca ttttgcatct gtgtaaaatc ctgatagtgg ttcccgctgg ctggctcaca 3000 tgtgtgggcc acacaaacat cacaagaaag cccacgctca gtaatgtggt cttgggacgc 3060 tagctgaaac cctcaggcct aggtatcaca caactgcaga tcactcttgc tgtgtctgta 3120 gtaggctgct ctcgaggtgc atacgccaag agacatagga tgatgtcttc acaacagccc 3180 acctaggcac actgtgcttt caagaccagc aagggcaatg gcaggccatc ttgatgtggc 3240 tctcccacat ccacatctgg cagtccactc tctttgctga gatgtagcct gcaacctcta 3300 tgggtaaaaa gatgagcaga gaagtctgct gaccccagca tcctcctctg cacaggccca 3360 tactctgcat tccagcctgc tctccttggt tacaacccct ccactgaaga ccccagtagc 3420 tgcagagggc agagctctgc tgaccaagta tggttagcca gcagcctggc cagcgagaag 3480 gcaaacacag ggcacctgga ggtggggtgg gacagctctg gctggcacat gcacaagcca 3540 tttataaaac tctcctaggc tgaccctgaa acccaaagac acaacaaagt gaagaccctc 3600 caatagagag agtgcaggac ctgggtcctg cactcctcac ctccatagaa tacacattac 3660 aacaagagat gccatcagta ggccatggaa caggccctaa agacacaggg gcactaatag 3720 gagaacttgg gggcaagccg gcatgtgggc agaatacacc tgccagtcct acaggctgcc 3780 cttcagggtc cccacttagc ctccttccac agagagcctg tggacagcca agctggagaa 3840 gctagaagcc agggttgaca agcaaggctc tgaggctctg gcttttgcta tagacatgca 3900 gtcaaggacc actgacacta ctccctcctt agcgcccccc ccccccaaag ccactgccca 3960 taaggttggt cttagtggcc tgggcctgta gtggaagggc agaaggaaag ggatcaactc 4020 tgagcagtct gtgtcttttt ggtcggtgag ttttcatcat ctcccgtccc caaattcgat 4080 aaccctttca aaagaggaat ttaaagggag ggagggtgag ggtcccggaa accagcaact 4140 cagggaggcg cgcagacgct cctttgttcc caccaggcgg gggaggggtg gtatcccgct 4200 cgccagatgg ccgcgcctgg acactgaacg gactcaggag accgcggcac gcgcccgtca 4260 gtgttcccta tcctgcctac tgctctcgtc cctgcccgca tcctggtctc caaggcggcc 4320 acagaaaggg tgggtgtctg agaaagctgg gccacgatga ccggtagtaa ccccgcctga 4380 ggcgccctcc gccagggtca acgaccgcgc ttgcgcgggg gcccgagaag cgctttgccg 4440 cttttgccgg cccatcaccc tattgcctag caacgcccac ccgcgcgcca ccattgggcc 4500 accgagaacg gcctcggtgt ccaattggtc tcgatgtgga gcaggccacg cccctcggct 4560 ctgcgcgcgc tacgatcacg gcgtggaatc gcagcgacac ggacctgttc tgttcccccg 4620 cgtggcccca gtgtcctcag tgcagttccc agtgtgacca agcacgcccg acccacactg 4680 cgcgcgcaca gtgcacacct ggccccggcc gcgggggtgg gggggtgaga gaaaggacag 4740 agatgagggc gtcgggatga gccccgcgtg gcccgcggga ggccgggggc ggggacggaa 4800 gcgggcgggg gctgcgcgtt ccttgtgctc cagcgcgcgc ctgtgcaggg tcccggctgg 4860 gggcggcgcg cgcgggcatc accccaccga cggcggcgcg ccgggtcccg gggcgcagcc 4920 ccgacgctca ttggcctggg cggcgcagcc aagctgtcag cccatgtggc gtggccgcgc 4980 ggggatggcc gcggtttaaa tagcgccggc gcggcctaga gggagccaga gagacggcag 5040 cagcgtcccg tccagttcgc ctgccgcgct cctcgcttgt cgtctgcctc cagatcccag 5100 acaggtacgc cgctgcgttc ggggttccgg gatggcaggc cggtgtcggg gtgccgcggc 5160 tccagtggga ggacaggcgg gcgcccatcc tcaacagccc tgcgctcaca aaagcgccgc 5220 cgcgcccctc cgacagccaa ccacccggct gtgcgccgcg gtccggccga gaggggcgcg 5280 ggaggggtgt gcggagagcc agcgcggcgg gccgctgtca cgtgggcgcc gcgccagccg 5340 ggtgcaggag gctgggtgcc tcgtggatgg ggccggggcc tccactctca tccggaggct 5400 ttggcagggc acaggaggcc gcggtggtac ccgggctcca gtttggagag gccagttgtg 5460 ggtctgggag cgcacgaggc cccaggggcc tcagcggaag tcatcagacc atccaggcct 5520 caccggctgg gtggcgcgga agccttctcc ttggactacg gctgcaaggc ctgaactgcc 5580 ctgggcaagt gccttaggga ccagaggatc tatcaaaccc ttcagctggc tcagccaggt 5640 tacaaggtgt tcgaccaaat ggcgagaggc ttctcctgtc ccggatccgc acctagttag 5700 gagtggtact ctaggtcgga tcttgctgaa aggatccgtt ggcaggggat cggtttgcct 5760 cagccctgct aggcctgagc actaagtagt cgggcctgtt ctctctgggt ccttaccatg 5820 cctggcgttc tggctggccc tgcagggcag tcagtctcca ccctcatcat gaaagggaag 5880 cgttggcttc cccgtggctt gaggtgagag tgtcccagac cctgcttctt gaagccccac 5940 ttctgtttgc aagttcctta tgattgggat ggagcaccca gtaggcaact ggagatcata 6000 tggtcccagg taactagcaa ggcatggtag ggtcaggcca ggtcatgtgt ctggaaggga 6060 ttaaaaacct cagaagtagc tatcccgtgc aagggaaccc gagcacccgg gctcatccat 6120 tgattatagc tgggtcctgc tagtttccac cactgggggg ctttctgagc cctttgctct 6180 cagaaagtca gggcctggct gtgaggtgtg ctacctgtgg attcaggtgg ctgtagctgg 6240 gaatgactct atgagggagg cccaccaggc tacctacctt cccccacaga gaagagccat 6300 ggaggaggtg gtgatagccg gtatgtccgg gaaattgccc gagtcagaga acctgcagga 6360 gttctgggcc aacctcattg gcggtgtgga catggtcaca gacgatgaca ggaggtggaa 6420

ggctggtgag tgtcccctcg ggatcaggca gcaggacaga ctgagagtct cacccaagat 6480 gcttctagag acagtgaact ccctgtagag ctgtgaggtt gagaaccggt tagaatgaga 6540 agggacaggt gtcttggttg gttccgcatg caagacaccc aaggtgggcc gtagaagagg 6600 actggccctt tggatctccc atctgtaacc tctgccctga gctggcggat agtgtctaag 6660 atgacgctca cacccagtgg attctaacag tgccatagag cagctagctc tacctgatgg 6720 gcaggtgtga gtcagcactg ggctggcctg gccagcctcg gagtaggcag agggtctccc 6780 agtcaggtcg gggttaccag ggggtgatcg ccagcctcac ttcctgctcc tacaggtttt 6840 gctttgggtc acccacatgt ggcggttttg gggctcctca ttagcagtga ggctgggtca 6900 ctctctggga accttcctcc aggagaggtt ggttccctgg cctcagactg tgatgttcca 6960 cagggctcta tgggttgcct aagcggtctg gaaagctgaa ggatctgtcc aagttcgacg 7020 cctccttttt tggggtccac cccaagcagg cacacacaat ggacccgcag ctccggctgc 7080 tgctggaagt cagctatgaa gctattgtgg acggaggtgg gtcattgggg tattattatt 7140 gcccttttta ggacttactg tcatgagggc tggggacgta gtccagtggg agagcacttg 7200 cctagtatgc acaaggacct gggaacatca tcatccccag tccaggaaaa ggaaacacaa 7260 caatgatacc ttcttggctc tgagatgtca agagctcaga gacaggcatg gatggcatgg 7320 gtccctctag ctatgtcccc aaccctgatg tagggccagt ggctcaggag gcgggggccc 7380 tgagcagggc acgggtttca caaccacaca cttagtgtcc caggcgcgcc ctgttacccc 7440 agttacttca ctccccgacg tctggttgtt cttggactga gggcggggct tacagcaggt 7500 agcactgcag gggctcagcc tcagctttgg caacaaccca gtcccactgg ctgtctctca 7560 ctctggatcc tgctgcttgg gtcatggacg tgtccccagg gatagaaggc cccatagtgg 7620 gcagccagtg tgggttagta tggcgggggt gagcttcagg ttggtagatg ctaattaacc 7680 ctgtacttga taaacagctt gatgtataac tgccctgggg tagagtagaa gaccagagga 7740 tgcaggatcc tggtaacctc ggtggtgaaa atgaaggtcc tcaccttggg cctgtctggc 7800 tgcccaggct ctatcaatgg ctgggcacag ctcccagggg gttacccact gtcctctgct 7860 ttcccagctt ggacacttgg tctttgtctt cttgtatctc cttatcacag cctgtcccag 7920 ggcaggctgc ccttggcact agagaactca ttggccagcg gcctctcgag acccaccagt 7980 aacaccagag cccgagggag ttgccctcag acaatgctgt cctctgtctt aactatagcc 8040 tcctatggtt gcagctctga cccagacctt agaggtccac tgtggcccct atggtacccc 8100 tctgacccaa acccatgtgg ttattgctgc ccccggcagg tatcaacccg gcctcactcc 8160 gaggaacaaa cactggtgtc tgggtgggtg tgagtggttc cgaggcgtcg gaggccctga 8220 gcagagatcc tgagactctt ctgggctaca gcatggtggg ctgccagaga gcaatgatgg 8280 ccaaccggct ctctttcttc ttcgacttca aaggtgggtg ggcagcccag ctctgggcac 8340 gacccagctg tatgtgcatt cacctacaca acccttttgg actcagactt ccttattcct 8400 ggggaaggca ctgagtgggg tactcacagc ccgggaggcg gggggtgtgg gacagcatct 8460 gcccaagggt acccacaccc actttatgac cttgtccaca ggacccagca ttgccctgga 8520 cacagcctgc tcctctagcc tactggcact acagaatgcc tatcaggcta tccgcagtgg 8580 ggagtgccct gctgccattg tgggcgggat caacctgctg ctaaagccta acacctctgt 8640 gcagttcatg aagctaggca tgctcagccc cgatggcacc tgcagatcct ttgatgattc 8700 aggtaaggtt ggcctgggta gggatcgtta ggctctactt tgcagggctc cagcctgtac 8760 cctgagtggc atctgggctc ctggtggtgt ggggaaggga ggacgtgtgc atgtatagac 8820 tcatagcaca caccccatca caccagagca cctagctgag gtgttgatct actctaggga 8880 acgggtattg ccgtgctgag gctgtcgtgg cagttctgct gactaagaag tccttggctc 8940 ggcgagtcta tgccactatt ctgaatgccg ggacgaacac agatggctgc aaggagcaag 9000 gtgggcatgg agggaaagag catggggaat ggggacgtgg agcacacaag gcttgacacc 9060 gtactgtacc attacccatc tccgtaggcg tgacattccc ctctggagaa gcccaggaac 9120 aactcatccg ttctctgtat cagccgggcg gtgtggcccc cgagtctctt gaatatattg 9180 aagcccatgg cacgggcacc aaggtgaaag ccctttccag cccatacctg ccactcctct 9240 atcctcacta gagggacctg gctgcagcct taacctactc tgtcccctgc aggtggggga 9300 cccccaggaa ctgaacggca ttactcggtc cctgtgtgct ttccgccaga gccctttgtt 9360 aattggctcc accaaatcca acatgggaca ccctgagcct gcctcggggc ttgcagccct 9420 gaccaaggtg agcaggctgg gggctctgag tcaagaatga tgtggatagg tctgtactgt 9480 gaccaccact tgacctaccc cggggctcct gcctgctcac caaccagccc tttggctgta 9540 ccgttgctga agtggcaggg agactgggta cactccctgt ggttgctgtg ctgacttaca 9600 tagcttctgg ctgaaggaaa cacttggctg cataaaggac aggtgcagtt ctgaggaagt 9660 atctaggcag ccaggtctag cagaatgccc cattctgaga tgaggagaga ggagcgagcc 9720 agtgtctgat ctggtgtgtt ctttccctgg gtgaccctgc acgtgtaggc accttcagct 9780 tgtttctatg ctgggaggtg tgcggttgtc tggatgacct atctgttggg gcttctgggc 9840 ctggcttcag agtttgtgcg ctcaggccta ctgccccttg acttgggcac catgcaccct 9900 ggaccactgg tggcaaggcc agagaagaca agggtcttgg tgcccagtac catacacagc 9960 tcatgggccc tggggaggta ggtggccacg cttggtgggg acagctgccc agtaaccatg 10020 tgttttgtct acaggtgctg ttatccctag aaaatggggt ttgggccccc aacctgcatt 10080 tccacaaccc caaccctgaa atcccagcac ttcttgatgg gcggctgcag gtggtcgata 10140 ggcccctgcc tgttcgtggt ggcatcgtgg gcatcaactc gtttggcttc ggaggtgcca 10200 atgttcacgt catcctccag cccaacacac agcaggcccc agcacctgcc ccacatgctg 10260 ccctaccgca tttgctgcat gccagtggac ggaccatgga ggcagtgcag ggcctgctgg 10320 aacagggccg ccagcacagt caggacttgg cctttgtgag catgctcaat gacattgcag 10380 caacccctac agcagccatg cccttcagag gttacactgt gttaggtgtt gagggccatg 10440 tccaggaagt gcagcaagtg cctgccagcc agcgcccact ctggttcatc tgctcaggtg 10500 agcctgctcc catgttccca ggctggcccc aaaggaggag gggagtcggt cccttttctt 10560 gagggtgagg ctggaggttg gccatgctat ggccctgata agctttctgg tacagggatg 10620 ggcacacagt ggcgtggaat ggggctgagc cttatgcgcc tggacagttt ccgtgagtcc 10680 atcctgcgct ctgatgaggc tctgaagccc ttgggagtca aagtgtcaga cctgctgctg 10740 agcactgatg agcacacctt tgatgacatc gtgcattcct ttgtgagcct caccgccatc 10800 caggtatgcc accttcgtgg tactcggacc ccgggacact ccacaccaga gtcacgtagt 10860 cctggccctg actggtatgt aggcagagcc ttaaataggt acacctgagg aggagcaggg 10920 tcttctcaga ggaccctaag agaggcttgg cgtgcttggt gtgctcagct ttactgtgag 10980 ggatggtcag gctagtgatc tagggtctac gtgacatggc ttatatcccc acttcgcaga 11040 ttgccctcat cgacctgctg acgtctatgg ggctgaaacc tgatggcatc attgggcact 11100 ccttgggaga ggttgcctgt ggctatgcag atggctgtct ctcccagaga gaggctgtgc 11160 ttgcagccta ctggagaggc cagtgcatta aggatgccaa ccttccggct ggatccatgg 11220 cagctgttgg taggtatcct ctcaagggcc cccgacctca ttaggcacca ggatcttctt 11280 ggaaggggtt tctgtcctgg gtcctccaaa agaatcagtt gctttgttgt gagacatggg 11340 gttgcaaagg gagaagtcac tctgctcaga ttatctttat aggaggcttc agttctgacc 11400 ccacaggccc gagcaaggta tgaaacacca tacacatcag atgagggttc caggagctga 11460 ggagagccac ttaccaaccc taggtgttca tcgcccagct tctcagctgc ttacccccta 11520 caccacttag gtgtcatttc tgaggtccgg ctcctttcct acactccctc cataatgaca 11580 cctctcttga gatcagaaac agcagggagg gagtaaaggt gccctggaag gtcgactctt 11640 agcatcccaa caccattggc tctaagtagt gctcatggtc caggaggatg ggctgagttc 11700 gggccagctc tgaggccagc ctctctgctt ataggtttgt cctgggaaga atgtaaacaa 11760 cgctgccctc ctggtgtggt gcctgcctgc cacaactctg aggacactgt gaccatctct 11820 ggacctcagg taggccctgc aatcatagca ggacttctgt tccctgcaat tttgccctgg 11880 ccctgcctag gaggcaaggc ctcctcagtc tgtgtccacc aagttctgaa gggcccagct 11940 ggtgagctac acttgtcgca ggccctctgg gtggactgtg tccctgacca gggaaagcca 12000 gtccaggccc cctgaccact ggccttgatg cctgcaggct gcagtgaatg aatttgtgga 12060 gcagctaaag caagagggcg tgtttgccaa ggaggtgcga acaggtggcc tggccttcca 12120 ctcctacttc atggaaggaa ttgcccccac gctgctgcag gctctcaaga aggtgagtac 12180 ctggccatgt gcttggaccc cagggcacgg tgacttgacc tcactcgcta accaagcgtc 12240 tgtgtgcagg tgatccggga gccacggcca cgctcagcac gctggctcag cacctctatc 12300 cctgaggccc agtggcagag cagcctggcc cgcacatctt ctgctgagta caacgtcaac 12360 aacctggtga gccctgtgct cttccaggaa gcactgtggc acgtccccga gcacgccgtg 12420 gtgctggaga ttgcacccca tgcactgttg caggtgagca ctggtccgcc tgggatgggg 12480 cacatcagcc tgccagtcac tggcgaaggc gagtggcacg gaaggggtcg gagcctagct 12540 ctcctttgct atgtgtaggc tgtcctgaag cgaggcgtga agcctagctg caccatcatc 12600 cccttgatga agagggacca taaagataac ttggagttct tcctcaccaa cctcggcaag 12660 gtgcacctca cagggtaggt ctcccttctg tctgctgctc gtgtgcaggc ccacaccaac 12720 ccccatgaga ggggttgctg tggcctagct cagtgctggc cctcggtcct catcttggcc 12780 atcttggggt cttagagcaa aactagggcc acagactctc agggacaggt gtgtcactta 12840 acttgtttgt caccagcatc gacatcaacc ctaatgcctt gttcccacct gtggaattcc 12900 cggttccccg agggactcct ctcatctccc ctcacatcaa gtgggaccac agtcagactt 12960 gggatatccc agttgctgaa gacttcccca acggttccag ctcctcctca gctacagtct 13020 acaacattgg tgagccaggc tccgtggtca gtgggttcct cccaggcctg tgggcccgtg 13080 ctgaggcatt gtccttacag acgccagttc cgagtcatct gaccactacc tggtcgacca 13140 ctgcattgac ggccgtgtcc tcttccctgg cactggctac ctgtacctgg tgtggaagac 13200 actggctcga agcctgagct tgtccctaga agagacccct gtggtgtttg agaacgtgac 13260 atttcatcag gccaccatcc tgcccaggac aggtaagagg cccttcagtg ggggctggtg 13320 aggtggttgt gactactccg ctctgacctt ctttttttct ctgcaggaac cgtgcctctg 13380 gaggtgcggc tgctagaggc ctcacatgca tttgaggtgt ctgacagtgg caacctgata 13440 gtgagcggtg agtagtacct ggctgggcct gtgtggctga ggacctcagc tcctagcctg 13500 ccccatgctc agaccctcct gttgccctgc ctcctacagg gaaagtgtac cagtgggaag 13560 accctgactc caagttattc gaccacccag aagtcccgat ccccgccgag tccgagtctg 13620 tctcccgctt gacgcaggga gaagtataca aggagctgcg gctacgtggc tatgactatg 13680 gccctcattt ccagggcgtc tatgaggcca ccctcgaagg tgggcaggag caatccccga 13740 gtcagtgagc atgatgacca ggagccattg tcactcctgg gccatgtctt gctgggggtc 13800 agggaagacg gaggaagggt agtagaggcc ctggagcagg tgaggcctcg tgtgctgagc 13860 agccccccta ctgcaggtga gcaaggcaag ctgctctgga aagacaactg ggtgaccttc 13920

atggacacaa tgctgcagat atccatcctg ggcttcagca agcagagtct gcagctaccc 13980 acccgtgtga ctgccatcta tattgaccct gcaacccacc tgcagaaggt gtacatgctg 14040 gagggagaca ctcaaggtag ctctggccct cgctctgtcc acttgtcctg gactgagcat 14100 tgcctacact gaccagtgtg tctcatagtg gctgacgtga ccacgagccg ctgtctgggc 14160 gtgaccgtct ctggtggtgt ctacatttcg agactacaga caacagcaac ctcacggcgg 14220 cagcaggaac agctggtccc caccctggag aagtttgtct tcacacccca tgtggagcct 14280 gagtgcctgt ctgagagtgc tatcctgcag aaagagctgc agctgtgcaa gggttgagga 14340 tccaaacctt ccctcttctt cctcagtctt tgcctttgaa actcctgagg caaggcctgg 14400 atggcgggga gctcagggtt ggtgagagca cagcctacct tccatgggta gcacggcact 14460 gctgcatcct tcctattgag tttccgctct tcccattgct gtgggcttgt cctgtggaca 14520 cgctagaagc aggccctggc agtaggctgg aggccgtaga gagagaacgt aggcctttct 14580 ttgtccctcc caggtctggc aaaggctctg cagaccaagg ccacccagca agggctgaag 14640 atgacagtgc ctgggctaga ggaccttccc cagcatggac tgcctcgact cttggctgct 14700 gcctgccagc tgcagctcaa cgggaacctg caactggagt taggtgaggt actggctcga 14760 gagaggctcc tgctgccaga agaccctctg atcagtggcc tccttaactc ccaggccctc 14820 aaggcctgca tagacacagc cctggagaac ttgtctactc tcaagatgaa ggtggtggag 14880 gtgagtgctg ggaaggtaga caggccatgt gcgtggatcc agggcaatct cagacccgag 14940 cccaaggcag gcagccatga tgtagcagct ttctatggcc tttgtgcttt ggtttgttcc 15000 accctaaaag attgtgggga acttttcact gctaccagtc caggggatga gatatcagaa 15060 ggaaggcttc tgggaaagaa tcctgggatg ctctgagctc tagcctggga tgtcgcagac 15120 agtctccaca ggagagtaga ggagaacact ggaagagcct cccggccagc attgccacaa 15180 aactgagcat gagcagcacg gagaggctca cccaggcccc agggttttct gcctcctaga 15240 aacaacagat ctaagatgct ctcccacacc aggtgctggc tggagaaggc cacttgtatt 15300 cccacatctc agcactgctc aacacccagc ctatgctgca actggagtat acagccaccg 15360 accggcaccc ccaggccctg aaggatgttc agaccaagct gcagcagcat gatgtagcac 15420 agggccagtg ggacccttct ggtcctgctc ctaccaacct gggtgctctt gaccttgtgg 15480 tgtgcaactg tgcgttagcc accctggggg atccagccct ggccctggac aacatggtag 15540 ctgccctcaa ggatggtggt ttcctgctaa tgcacacagt gctcaaagga catgcccttg 15600 gggagaccct ggcctgcctc ccttctgagg tgcagcctgg gcccagcttc ttaagccagg 15660 tactgctcct gggcatgcag ggcaggtaag ggctgggtat ggttccgcca gttcagtact 15720 tacaagactt catacacata ggaagagtgg gagagcctgt tctcaaggaa ggcactgcac 15780 ctggtgggcc ttaaaaagtc attctacggt actgcgctgt tcctgtgccg ccgtctcagc 15840 ccacaggaca agcccatctt cctgcctgtg gaggatacta gtttccagtg ggtggactct 15900 ctgaaggtca ggctctgggg ctgggtacct tggcttcccc tgacgtatga tcaccctaga 15960 ggctgaccct actttatcct gcagagcatt ctggccacat cctcctccca gcctgtgtgg 16020 ctaacagcca tgaactgccc cacctcaggt gtggtaggct tggtgaactg tctccgaaaa 16080 gagccgggtg gacaccggat tcggtaggaa aggccctgag aggtgcctac ccttcctccc 16140 tcaccccctc cattcttggt atccttaccc actttgcccc cacaggtgta tcctgctgtc 16200 caacctcagc agcacatctc acgtccccaa gctggaccct ggctcttcag agctacagaa 16260 ggtgctagag agtgatctgg tgatgaacgt gtacagggac ggtgcctggg gtgccttccg 16320 tcacttccag ttagagcagg gtaagcctgt ccatgcccta tatacttaat aggcttgtga 16380 ggtggcaggg gaacaaggag ctggccaggt aggcccctgt ggcatccttg ctttctttcc 16440 cctcagacaa gcccgaggag cagacagcac atgcctttgt aaacgtcctt acccgagggg 16500 accttgcctc catccgctgg gtctcttctc ccctgaaaca catgcagccg ccctcgagct 16560 caggagcaca gctctgcact gtctactatg cctcactgaa cttccgagat atcatgctgg 16620 ccacgggcaa gctgtcccct gatgccattc caggtgccaa ccaggatggg ggcttatgat 16680 tgggttgctg ggagtagaga aggtgcctgt actgtagcag cccagtgagg aggagtcctg 16740 cccggctcct ggggaagaga gggttcccag caccagaggc tgcacttgca tcctgctccc 16800 ctgacaacct gtcctagggt ctgggctaac aggagcctcc ctctgtctac acacaggtaa 16860 atgggccagc cgggactgca tgcttggcat ggagttctca ggccgtgata agtgcggccg 16920 gcgtgtgatg gggctggtac ccgcagaagg cctggccacc tcagtcctgt tatcacccga 16980 cttcctctgg gatgtaccct ctagctggtg agtggctggc tgcagttggg ggttatgtga 17040 tcttagttgg tggccaggct gaattgatcc tgtgctccgt tccctcagga ccctggagga 17100 ggcggcttct gtgcctgttg tctacaccac cgcctactac tccttagtag tgcgtggtcg 17160 tattcagcac ggggaaactg tgctcattca ctcgggctcc ggtggtgtgg gccaagcggc 17220 catttccatt gcccttagcc tgggctgccg agtcttcacc actgtgggta aggccctcac 17280 cccctcccga tcccaatcaa ggagcttctt gaaccctgtg ggccaaactt actggggtct 17340 cccttgactg acaggctccg ctgagaagcg agcttacctc caggccagat tccctcagct 17400 ggatgacacc agctttgcta actctcgaga cacatcgttt gagcagcatg tgttactgca 17460 cacaggtggc aaaggtaaat accccctggg ccattgcctg agagtgagtg ggtcacatag 17520 tcagtccagc gctgaggact gaggtacagg tgagcccagt atgaccgact gacatgtttg 17580 ccaccgtagg ggtggacctg gtcctcaact ccctggcaga agagaagctg caggccagtg 17640 tgcggtgctt ggctcagcat ggccgcttcc tagagatcgg caaatttgat ctttctaaca 17700 accaccctct gggtatgact cgtagtcagg agcaggggtg ggcgctggtg ttggggccag 17760 gggcatccca cagtgaacag gattctcgaa tacaggcatg gccatcttct tgaagaacgt 17820 cactttccat gggatcctgc tggatgcact ttttgagggg gccaacgaca gctggcggga 17880 ggtggcagag ctgctgaagg ccggcatccg tgatggggtt gtgaagcctc tcaagtgtac 17940 agtgtttccc aaggcccagg tggaggacgc cttccgatac atggctcaag gaaaacatat 18000 tggcaaagtc cttgtccagg tgaagtgagg ccctcgggca ccaagcctgg tttcgccttt 18060 tgtagtgcat tttttttcta attatattta cttacttttg atggttgtga gtggcatgtg 18120 tgggtaccag aggacaactt gcaggagttg gttctcctcc atgggtcatc aggttttttt 18180 ttattttttt ggttcttttt tttcggagct ggggaccgaa cccagggcct tgcgcttctt 18240 aggtaagcgc tctaccactg agctaaatcc ccagcccggg tcatcaggtt tgatagaagc 18300 actgttaact acccagctgt ctcgctggtc ctgggacagc ttctgaacca ctgctacttg 18360 tatgcaggta cgggaggagg agcccgaggc tatgctgcca ggggctcagc ccaccctgat 18420 ttccgccatc tccaagacct tctgcccaga gcataagagt tacatcatca ctggtggcct 18480 aggtggcttt ggcctggaac tggcccggtg gcttgtgctt cgtggggccc aaaggcttgt 18540 actaacttcc cgatctggaa tccgcacagg taggcaagta gaagcagttg gtagtgtagg 18600 cttcccttca gtggaaagtg tcctgggagg gctgtaggcc actgctttcc tctggtgcag 18660 ccccatttcc ctgtgtccca taggctacca agccaagcac gttcgggagt ggaggcgcca 18720 gggcatccat gtgctagtgt cgacaagcaa tgtcagttca ctggaggggg cccgtgctct 18780 catcgctgaa gccacaaagc ttgggcccgt tggaggtgtc ttcaacctgg ccatggtgag 18840 aaaagcatgc agggctctgc gtacctccag agcctgagac ccaggctgct gctaagtggg 18900 gttagaacct cagagctgca gcagacacta aaaccccttc ttctaggttt taagggatgc 18960 catgctggag aaccagactc cagaactctt ccaggatgtc aacaagccca agtacaatgg 19020 caccctgaac cttgacaggt aggcagttgg tccctctgct gagtttcatg tatgcttgca 19080 atgtatactg gtccctgctg gacttgaggg tctggggaag tgaaactgtg ccacccgtgg 19140 ccttctgggc ctgccctggg gaggtacgga catgaaagtt atcagactga catgagtacc 19200 cacagggcga cccgggaagc ctgtcctgag ctggactact ttgtggcctt ctcctctgta 19260 agctgcgggc gtggtaatgc tggccaatcc aactatggct tcgccaactc taccatggag 19320 cgtatttgcg aacagcgccg gcacgatggc ctcccaggtg ggcctctttg tctagcccac 19380 ccctgcttgt ggtctcactc cccaaagcac ctcaccggct gcctcccttg ctctcaggtc 19440 ttgccgtgca atggggtgcc attggtgacg tgggcattat cttggaagcg atgggtacca 19500 atgacacagt cgttggcggc acactgccac agcgcatctc ctcctgcatg gaggtgctgg 19560 acctcttcct gaatcagccc cacgcagtcc tgagcagttt tgtgctggct gagaagaaag 19620 ctgtggccca tggtgatggt gaagcccaga gggatctggt gaaagcagtg gcacacatcc 19680 taggtaagcc agcttccggg accttcccgg cttaggtgac ttggagcctt agttttccca 19740 tctgtagaag cagacgacag agttctgtgg tctgaatgct ggccaggcca ggtgattggc 19800 agtgatgctg gagagccaca gtatgtacct ggttcccacg tccccttctc agtaatgacc 19860 agttacccat cccctttgtt aggcatccgc gacctcgcag ggattaacct ggacagctcg 19920 ctggcagacc tcggcctgga ctcgctcatg ggtgtggaag tgcgccagat cctggaacgt 19980 gaacatgatc tggtgctacc cattcgtgaa gtacggcaac tcacactgcg gaagcttcag 20040 gaaatgtcct ccaaggctgg ctcagacact ggtgcgtacc aggcagcagg ctgtgagaga 20100 cacaagtgca tcctagtatt gtaggcagca gcgctgccct tttgcaaaga acacatgggc 20160 ctgtgcttaa tctgtgtgtg tatgacctca caaggggatg tgtaccagag cccatgtgcc 20220 aaggctaccc tacaccctct gtctttacag agttggcagc ccccaagtcc aagaatgata 20280 catccctgaa gcaggcccag ctgaatctga gtatcctgct ggtgaaccct gagggcccta 20340 ccttaacacg actcaactca gtgcagagct ctgagcggcc tctgttcctg gtgcacccca 20400 ttgaaggttc catcactgtg ttccacagcc tggctgccaa gctcagtgtg cccacctacg 20460 gtctgcagtg cacccaaggt actgtgcaca tggcgaagca gtacatgctg ccttgggcct 20520 ccgttcctca ctgactgctg gctgagtcct ctgtttgtcc ttacagcggc ccccctggac 20580 agcattccaa acctggctgc ctactacatt gattgcatca agcaggtgca gcctgagggg 20640 ccctaccgag tggctgggta ttcttttgga gcttgtgtag ccttcgagat gtgctcccag 20700 ctgcaggccc agcagggccc agcccccgcc cacaacaacc tcttcttgtt tgatggctca 20760 cacacctacg tattggcgta cacccaggtg agagccgggc caactggtcc taagcattgc 20820 cgcctatgtc ttggctctga acacacttct gggagggtcc tggttacttt agcccttgca 20880 gcatcaatct ctccttccct gacagagcta ccgggcaaag ctgaccccag gctgtgaggc 20940 tgaggctgaa gctgaagcca tatgcttctt cattaagcag tttgttgatg cagagcatag 21000 caaggtgggc ctggacacac cctagagagg gcaggaaagg caaggctggg agggttgggg 21060 tctctgtgcc tttaaaatgg agcagggaaa tccaagcgct tcttcagaaa cccgtctgcc 21120 cagagaaggc agggcagacc gtgtagcccc ccatcccacc ccacatgctc agagctgttg 21180 cttttaggtg ctagaggccc tgctaccact gaagagcctg gaggaccggg ttgctgctgc 21240 tgtggacctc atcactagaa gccaccagag cctggaccgc cgtgacctga gctttgctgc 21300 cgtgtccttc tactacaagc ttcgagccgc cgaccagtat aaacccaagg ccaagtacca 21360 cggcaatgtg atcctgctgc gggccaagac aggtggcacc tacggcgagg acttgggtgc 21420 cgattacaac ctgtcccagg taagcgagtg agtggggcag acgaggcggt gtgggacgga 21480

cgcctgctgg tggtcacaga atgacacctg aatgtttaca ggtgtgtgat gggaaggtgt 21540 ctgtgcacat cattgagggt gaccaccgta cgctgctgga gggcaggggc ctggagtcta 21600 tcatcaacat catccacagc tccctggctg agcctcgagt gagtgtacgg gagggctaga 21660 cctgcctacc atgaagccac gacccacacc ggccaccaga gatgctccga tccccaccac 21720 accctgagtg cagggactgg ggagggtcct gctggtggga ccccctcacc ccagtggccc 21780 agcaccaccc cctcccctgg tggctgctac aaacaggacc atcacatgtg tcccagccac 21840 ttagtggggt tcccagagcc actgacttgg aggcaccctg gtctgtgaag agtcagtgga 21900 ggccagcaag agccaaactg agccttttct gccaagtgac atttgtcaca ctggttgttt 21960 ctccattaaa ttctcatatt tattgcattg ctgggaaaga ccgcccaccc cagggttaac 22020 tcattccaga acccctaaag tgggaaaagc catgtgggga aggctgctgg ctggagcccc 22080 tttttgtctt agccctgtac ccgctcactg cagggcaggg tatggagagg gctggttcgc 22140 ggggaacgag gaccccagca gacactgtag cccatggccc ttggtcccca gcactcccgg 22200 ctgcacccat gatgcagggc ctaccagact ctgcggaccg caccgggcac tcactgtatt 22260 tgttttccaa gattcaaatt gctgcttggg ttttgaattt actgcagctg tcagtgtaaa 22320 gaaacatgtc tgaactgtgt cctttttaca ccaacctggt aaaaatgctc ttgatgctgt 22380 cccgttgcca caattaaact gcacgtgagc tctggcttcc gttcagtctc tttccagtcc 22440 cagacctgag tccccagagc ctccacagct cttacagtga gaatcaaatt ggcccactcc 22500 ttggaaggcg tggcattctg tcagagtaaa aggaaagtag agtgtgctga ttcacgttca 22560 gcgtgtgggg ctggctagag accttggcac tgtagtgaac agaatgtgtc cacctttaag 22620 tcaccctgaa ggcatcacca tagctacagc ctcacccagg ggtagagaat agtactgtct 22680 acttgttgac tacctggcag ttggtgccag cccctataga ggaaaacagc agtgtgtggc 22740 cactgtgaga agcatatccc tggaaacagg tgaccagagc agagggctaa cgcctacctg 22800 agtcacacaa aactgaccag gcttgagtgt ccagaagagt ctatcagaag gccacagcat 22860 tcagtcctat ccacagagag cagcagacta agttgtctcc ttgccagctt agaaaactgc 22920 agtgctgggg tacaggtagg gtgttcagga ggtccgggcc ccagtgatta gtctaagact 22980 gaagcatctg gttggctgtg gtcccaccta gaaaattctt aaagctcttg tcatgtactt 23040 cctgggaagg acctaccctg tctcaataat gtctctagct cgttggagtc tactgactca 23100 aacatttata aagtgtccta gaaaggcctg actcccctac aaggctgtgt gatccttcaa 23160 actcacatat gtgagccaat aaaaccttga gactctagtc ttatggccac cttgctcctt 23220 cctgctcttc gtgctcatgt aacaagactt ccactgcgtc tgatgagatt gctctgggta 23280 gagtcggagt ttgatcactg gaacccacgt aaaggttgtc atctgacttc cacacgtgtt 23340 gagtggagca atactaaaat gaaaatttaa aagagcagtt gctgttcatg gggatcttaa 23400 aatacaggta gaggaccaaa tttagcatct ggcttgttgg tacgacactg agttcttaca 23460 tcagtcagga ataggagtgc tcctaggaac ttcagcaata aaaatgacta agagggtaga 23520 gaagcgactc tacagttaaa ggacccagat taggttccca gcaaccatag caactccagc 23580 cccaagggac ctgacaccct gtgcaggaac cactgagagt actcagacat gcatgcaagc 23640 aaaatgttca cacacataaa actaattaaa cttttaaaca aaagctcaaa gagcttaaag 23700 gtcaaagttt ctg 23713 <210> SEQ ID NO 14 <211> LENGTH: 2848 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 14 ggtggattgc agtgacagcc gcctgtggag cagcccgggc agcggaggag aattctgcat 60 agagaaccac caacccagaa ccatggaagt ccatgaattg ttccggtatt ttcgaatgcc 120 agagctgatt gacattcggc agtacgtgcg cacccttcca accaacaccc tcatggggtt 180 tggggctttt gcagcgctca ccaccttctg gtatgccacc aggcctaagg ccctgaagcc 240 accatgtgac ctctccatgc agtcagtgga aatagcgggt accactgatg gtattcgaag 300 atcagcagtc cttgaagatg acaagctctt ggtgtactac tacgacgatg tcagaaccat 360 gtacgatggc ttccagaggg ggattcaggt gtcaaataat ggtccttgtt taggttctcg 420 gaagccaaac cagccctatg agtggatttc ctacaaagag gtggcagaac tggctgagtg 480 cataggctcc gggctgatcc agaaggggtt caagccttgc tccgagcagt tcatcggcct 540 cttctctcaa aacagacccg agtgggtgat cgtcgagcaa ggatgcttct cttactcaat 600 ggtggtcgtc ccgctctatg acacccttgg agctgacgcc atcacctaca tagtgaacaa 660 agctgaactc tctgtgattt ttgctgacaa gccagaaaaa gccaaactct tattagaagg 720 tgtagaaaac aagttaacac catgccttaa aatcatagtc atcatggact cctacggcag 780 tgatctggtg gaacgaggca agaagtgtgg ggtggaaatc atcagcctca aagctctgga 840 ggaccttgga agagtgaaca gagtgaagcc caagcctcca gaacccgaag atcttgcgat 900 aatttgtttc acaagtggaa ctacaggcaa ccccaaagga gcaatgatca ctcaccaaaa 960 cattataaac gactgctcag gttttataaa agcaacagag agtgcattca tcgcttccac 1020 agatgatgtg ctgatatctt tcttgcctct cgcccatatg tttgagaccg ttgtagagtg 1080 tgtaatgctg tgtcatggag ctaagatagg atttttccaa ggagatatca ggctgcttat 1140 ggacgacctc aaggtgcttc agcccaccat cttccctgtg gttcccaggc tgctgaaccg 1200 gatgttcgac agaatttttg gacaagcaaa cacttccttg aagcgatggc tgttggactt 1260 tgcctccaaa aggaaagagg cggagcttcg cagtggcatc gtcagaaaca acagcctgtg 1320 ggataaactc atcttccaca agatacagtc gagcctgggt gggaaagtcc ggctgatgat 1380 cacaggagca gccccggtgt ctgccacagt gctgacgttt ctgaggacag cgctcggctg 1440 ccagttctat gaaggctacg gacagaccga gtgcactgct ggttgctgcc tgagcttgcc 1500 cggagactgg acggcaggcc atgttggagc ccccatgcct tgcaattatg taaagcttgt 1560 ggatgtggaa gaaatgaatt acctggcatc caagggcgag ggtgaggtgt gtgtgaaagg 1620 ggcaaatgtg ttcaaaggct acttgaaaga cccagcaaga acagctgaag ccctggataa 1680 agatggctgg ttacacacgg gggacattgg aaaatggctg ccaaatggca ccttgaagat 1740 tatcgacagg aaaaagcaca tatttaaact agcccaagga gagtacatag caccagaaaa 1800 gattgaaaat atctacctgc ggagtgaagc cgtggcccag gtgtttgtcc acggagaaag 1860 cttgcaggcc tttctcatag cagttgtggt acccgacgtt gagagcctac cgtcctgggc 1920 acagaagaga ggcttacaag ggtccttcga agaactgtgc aggaacaagg atatcaataa 1980 agctatcctg gacgacttgt tgaaacttgg gaaggaagcc ggtctgaagc catttgaaca 2040 ggtcaaaggc attgctgtgc acccggaatt attttctatt gacaacggcc ttctgactcc 2100 aacactgaag gcgaagaggc cagagctacg gaactatttc aggtcgcaga tagatgaact 2160 gtacgccacc atcaagatct aacgtgagga aggatactta gaagaaatgg cgcatctcca 2220 caatcctcct cgtaccaatg gccttcgagt tggtaacttt gcctgcagcg agtgtgggaa 2280 aggaaatgcc ctgccgccgg acttgtccac ggggtcttac catagggata gtcgagggca 2340 cggaacactg ccttacttac agtcacctgt gttgcagccc atgatcccgg ggacacacaa 2400 tttccaaaac gagccttaaa cattgtaaag gggaacccat aaaagtgcta agttatttaa 2460 gacttcttca accaataagg tggatgctac aagttctgtc tcctgttttt ctaactgagg 2520 ggttaggact tattctttct gatatgtctg ctgcttgctg cgcgttttgc agctgtctgc 2580 tgctctgaag agcaccgtac actggaggaa agctgtccct ttaagaacaa ctgtccaggc 2640 tgaagaaagt cacagtggac cagaggtttt ccttttgaac ccctcctccc ccttgcccct 2700 ttccctcacc acctcacata cagtacactc acatgacctt tctggtttgt aagggttcca 2760 cacggtccct gtttgcgcct gctggaacat gaggttttca gtaaactaaa gagcagaccc 2820 tcttcagaac atgtgggtgt ccagtctc 2848 <210> SEQ ID NO 15 <211> LENGTH: 2034 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 15 ggatctggca gcgccgcgaa gacgagcggt caccggcgcc cgacccgagc gcgcccagag 60 gacggcgggg agccaagccg acccccgagc agcgccgcgc gggccctgag gctcaaaggg 120 gcagcttcag gggaggacac cccactggcc aggacgcccc aggctctgct gctctgccac 180 tcagctgccc tcggaggagc gtacacacac accaggactg cattgcccca gtgtgcagcc 240 cctgccagat gtgggaggca gctagctgcc cagaggcatg cccccctgcc agccacagcg 300 acccctgctg ctgttgctgc tgctgctggc ctgccagcca caggtcccct ccgctcaggt 360 gatggacttc ctgtttgaga agtggaagct ctacggtgac cagtgtcacc acaacctgag 420 cctgctgccc cctcccacgg agctggtgtg caacagaacc ttcgacaagt attcctgctg 480 gccggacacc cccgccaata ccacggccaa catctcctgc ccctggtacc tgccttggca 540 ccacaaagtg caacaccgct tcgtgttcaa gagatgcggg cccgacggtc agtgggtgcg 600 tggaccccgg gggcagcctt ggcgtgatgc ctcccagtgc cagatggatg gcgaggagat 660 tgaggtccag aaggaggtgg ccaagatgta cagcagcttc caggtgatgt acacagtggg 720 ctacagcctg tccctggggg ccctgctcct cgccttggcc atcctggggg gcctcagcaa 780 gctgcactgc acccgcaatg ccatccacgc gaatctgttt gcgtccttcg tgctgaaagc 840 cagctccgtg ctggtcattg atgggctgct caggacccgc tacagccaga aaattggcga 900 cgacctcagt gtcagcacct ggctcagtga tggagcggtg gctggctgcc gtgtggccgc 960 ggtgttcatg caatatggca tcgtggccaa ctactgctgg ctgctggtgg agggcctgta 1020 cctgcacaac ctgctgggcc tggccaccct ccccgagagg agcttcttca gcctctacct 1080 gggcatcggc tggggtgccc ccatgctgtt cgtcgtcccc tgggcagtgg tcaagtgtct 1140 gttcgagaac gtccagtgct ggaccagcaa tgacaacatg ggcttctggt ggatcctgcg 1200 gttccccgtc ttcctggcca tcctgatcaa cttcttcatc ttcgtccgca tcgttcagct 1260 gctcgtggcc aagctgcggg cacggcagat gcaccacaca gactacaagt tccggctggc 1320 caagtccacg ctgaccctca tccctctgct gggcgtccac gaagtggtct ttgccttcgt 1380 gacggacgag cacgcccagg gcaccctgcg ctccgccaag ctcttcttcg acctcttcct 1440 cagctccttc cagggcctgc tggtggctgt cctctactgc ttcctcaaca aggaggtgca 1500 gtcggagctg cggcggcgtt ggcaccgctg gcgcctgggc aaagtgctat gggaggagcg 1560 gaacaccagc aaccacaggg cctcatcttc gcccggccac ggccctccca gcaaggagct 1620 gcagtttggg aggggtggtg gcagccagga ttcatctgcg gagaccccct tggctggtgg 1680 cctccctaga ttggctgaga gccccttctg aaccctgctg ggaccccagc tagggctgga 1740 ctctggcacc cagaggcgtc gctggacaac ccagaactgg acgcccagct gaggctgggg 1800 gcgggggagc caacagcagc ccccacctac cccccacccc cagtgtggct gtctgcgaga 1860

ttgggcctcc tctccctgca cctgccttgt ccctggtgca gaggtgagca gaggagtcca 1920 gggcgggagt gggggctgtg ccgtgaactg cgtgccagtg tccccacgta tgtcggcacg 1980 tcccatgtgc atggaaatgt cctccaacaa taaagagctc aagtggtcac cgtg 2034 <210> SEQ ID NO 16 <211> LENGTH: 1944 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 16 cagggtctcc cttgcaacct gaggagaggt gcacacactc tgaggaccta ggtgtgcaac 60 ctctgccaga tgtggggcgt ggctacccag aggcatgccc ctcacccagc tccactgtcc 120 ccacctgctg ctgctgctgt tggtgctgtc atgtctgcca gaggcaccct ctgcccaggt 180 aatggacttt ttgtttgaga agtggaagct ctatagtgac caatgtcacc acaacctaag 240 cctgctgccc ccacctactg agctggtctg taacagaacc ttcgacaact actcctgctg 300 gcctgacacc cctcccaaca ccactgccaa catttcctgc ccctggtacc taccttggtg 360 ccacaaagtg cagcaccgcc tagtgttcaa gaggtgtggg cccgatgggc agtgggttcg 420 agggccacgg gggcagccgt ggcgcaacgc ctcccaatgt cagttggatg atgaagagat 480 cgaggtccag aagggggtgg ccaagatgta tagcagccag caggtgatgt acaccgtggg 540 ctacagtctg tccctggggg ccttgctcct tgcgctggtc atcctgctgg gcctcaggaa 600 gctgcactgc acccgaaact acatccatgg gaacctgttt gcgtcctttg tgctcaaggc 660 tggctctgtg ttggtcatcg attggctgct gaagacacgg tacagccaga agattggcga 720 tgacctcagt gtgagcgtct ggctcagtga cggggcgatg gccggctgca gagtggccac 780 agtgatcatg cagtacggca tcatacccaa ctattgctgg ttgctggtag agggcgtgta 840 cctgtacagc ctgctgagcc ttgccacctt ctctgagagg agcttctttt ccctctacct 900 gggcattggc tggggtgcgc ccctgctgtt tgtcatcccc tgggtggtgg tcaagtgtct 960 gtttgagaat gttcagtgct ggaccagcaa tgacaacatg ggattctggt ggatcctgcg 1020 tattcctgtc ttcctggcct tactgatcaa ttttttcatc tttgtccaca tcattcaact 1080 tcttgtggcc aagctgcgtg cccatcagat gcactatgct gattacaagt tccggctggc 1140 caggtccacg ctgaccctca tccctctgct gggggtccac gaggtggtct ttgcctttgt 1200 gactgacgag catgcccaag gcaccctgcg ctccaccaag ctcttttttg acctgttcct 1260 cagctccttc cagggtctgc tggtggctgt tctctactgt ttcctcaaca aggaggtgca 1320 ggcagagctg atgcggcgtt ggaggcaatg gcaagaaggc aaagctcttc aggaggaaag 1380 gttggccagc agccatggca gccacatggc cccagcaggg ccttgtcatg gtgatccctg 1440 tgagaaactt cagcttatga gtgcaggcag cagcagtggg actggctgtg tgccctctat 1500 ggagacctcg ctggccagta gtctcccaag gttggctgac agccccacct gaatctccac 1560 ttggagccta ggcaggttgt gttcaagaaa gggcctcaga ggacaaccca gagccagatg 1620 cccggccaag gttgaagagc caaagcagca agacagcagc ttgtactgtg cacactcccc 1680 taacctgtcc tagcctggca caggccacag tgacagagta ggggttggat atgatggaga 1740 agccatgtta tctatgaact ctgagtgttc ccatgtgtgt tgacatggtc cctgtaccca 1800 gatatgtcct tcagtaaaaa gctcgagtgg agctgctgca cagctcgtgg acagcaggct 1860 tgaagccccc agggacgggg tttgggaggc cggggatgag cagcacactc agcaggtgga 1920 gcgctagtgc aacccaggaa agaa 1944 <210> SEQ ID NO 17 <211> LENGTH: 3172 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 17 ctgagaagga aacttggagt gggacttgaa tgcgtgggtc ttcagaagga gaaccgctaa 60 gcatcccgat ttcccagaac aagaaggaca agtccaaaga cagtaaacaa agataggagt 120 tcacccttga atacctggaa ggaagaagga agagggtggg cccgcctctg gaatagaggg 180 ctcaggagat tggactccta gatccaggaa gaaggccaaa agacctggtc agtgggtttc 240 taattctgaa gaggagctag tcagggtctg ctcagtctga gggcttcgac tcccagctgc 300 tagaaagagg atgaggatgc agccgcaggc ttctagaaga caaggagata aattcctagg 360 tgtgagagag aagataatag gaaggcccct gcgtctccag gaggattggg acagacctga 420 ggaaggagag ggctcggctt tggactcctg catctcagca aggacggtcc taggtttgaa 480 tacttggttg gcctagggaa agagaggaag ggcatggact cctgggcctg acagagcaaa 540 gggtaaccac agaccttccc atcttctcac agcctcagcg ttctcacaca gcatggattt 600 acgcacgatg acacagtcgc tggtgacact cgcagaagac aatatggcct tcttctcaag 660 ccagggccca ggagagacag cacggcggct gtctaatgtc tttgcaggtg ttcgggaaca 720 ggcactgggg ctggaaccaa ccctaggcca actgttgggt gtggcacacc attttgacct 780 ggacacagag acaccagcca acggataccg tagtttggtg cacacagccc gatgctgcct 840 ggcacaccta ctacacaaat cccgctatgt ggcttctaac cgcaaaagta tcttcttccg 900 tgccagccac aacctagcag agctggaggc ctacctggcc gccctcaccc agctccgtgc 960 tatggcctac tatgcccagc gcctgctgac catcaaccga ccaggagtgc tcttcttcga 1020 gggtgatgaa ggactcaccg ctgacttcct gcaagagtat gtcacgctac acaaaggctg 1080 cttctacggc cgctgcctgg gcttccagtt cacacctgcc atccggccgt tcctgcagac 1140 tctctccatc gggctggtgt ccttcgggga gcactacaaa cgcaacgaga caggcctcag 1200 tgtgaccgcc agttccctct ttaccggtgg ccgattcgcc atagacccag agttgcgtgg 1260 ggctgaattt gaacgcatca tacagaacct ggatgtgcac ttctggaaag ccttctggaa 1320 catcactgag attgaggtgc tgtcgtctct ggccaacatg gcatcaacca ctgtgagggt 1380 aagccgcctg ctcagcttgc cacctgaggc ctttgagatg ccactcacct ctgatcccag 1440 gctcacagtt accatctcac ctcccttggc acacacggga ccagctcctg tgctagccag 1500 gctcatctcc tatgacctac gggaaggaca ggacagcaag gtactcaaca gcctggcaaa 1560 atctgagggc ccacgcctgg acgtgcgccc acggcctcac caagcacccc gttcacgggc 1620 cctggttgtt cacatccacg gaggcggctt tgtggcacag acctctaaat cccacgagcc 1680 ctacctcaag aactgggccc aggagctagg agtccctatc ttctccatcg actactccct 1740 ggcccccgag gctccctttc cccgagcgct ggaggagtgt ttttttgcct actgctgggc 1800 tgtcaagcac tgtgacctgc ttggttcaac tggagagcgg atatgccttg caggggacag 1860 tgcaggtggg aatctctgca tcactgtgtc ccttcgggca gcagcctatg gagtgagggt 1920 gccagatggc atcatggcag cctacccagt taccaccctg cagtcctctg cttctccctc 1980 tcgtctgctg agcctcatgg accctcttct accactgagc gtactctcta agtgtgtcag 2040 tgcctattca gggacagagg cagaggacca ttttgactca gaccagaagg cactaggcgt 2100 gatggggctg gtgcagagag acacttcgct gttcctcaga gacctccgac tgggtgcctc 2160 ctcatggctc aactccttcc cggaactaag tggacgcaag ccccaaaaga ccacatcgcc 2220 cacagcagag tctgtgcgcc ccacggagtc tatgcgcagg agtgtgtctg aggcagccct 2280 ggcccagcct gagggcttac tgggcacaga taccttgaag aagctgacaa taaaggactt 2340 gagcaactca gagccttcag acagccccga gatgtcacag tcaatggaga cacttggccc 2400 ctccacaccc tctgatgtca acttttttct gcggcctggg aattcccagg aagaggctga 2460 agccaaagat gaagtgagac ccatggacgg agtcccccgc gtgcgcgctg ctttccctga 2520 ggggtttcac ccccggcgct caagccaagg tgtcctccac atgcccctct acacgtcacc 2580 catagtcaag aaccccttca tgtctcctct gctggcccct gacagcatgc tgaagacctt 2640 gccgcctgtg caccttgtgg cttgcgctct ggaccccatg ctagatgact cggtcatgtt 2700 cgcgcggcga ctgcgcgacc tgggccagcc ggtgacgctg aaagtggtag aagatctgcc 2760 gcatggcttc ctgagcctgg cggcactgtg tcgcgagacc cggcaggcca cggagttctg 2820 cgtgcagcgc atccggctga tcctcacccc gcctgctgca ccactgaact gagctgggga 2880 cggcgggggg cggcactaaa agacctcttg ctcccatctg cgcgggcttc cgttatgagt 2940 gcgctccgag atgggctcca ggccccctca gtcgggctgg gcgggcggga gtgggctgtg 3000 cttaacttga gacagtaagt ggggcgggac aggggccaaa agctgaacct gggggaggga 3060 cacacacaca cctgtcactg agacagctgg atctgcactc taccactgcc ttctgctgct 3120 gtgaccgacc cggctagtcg gttttgcctt tttgtaaata aaagttattt aa 3172 <210> SEQ ID NO 18 <211> LENGTH: 1350 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 18 ggatgagaca gaaggataga gaggaggaga gagagagaga gaagagaagc aaccagaaat 60 aggcagccaa taaaaaggag ccgcacttat ctgaagcctc aaggggcctg agccaggtcc 120 ctgtttgatg gcagttatga aaaattacct cctcccgatc ctggtgctct ccctggccta 180 ctactactat tctacaaatg aagagttcag accagaaatg ctccagggaa agaaagtgat 240 tgtcactggg gccagcaaag ggattggaag agaaatggca tatcatctgt caaaaatggg 300 agcccatgtg gtattgactg ccaggtcgga ggaaggtctc cagaaggtag tgtctcgctg 360 ccttgaactc ggagcagcct ctgctcacta cattgctggc actatggaag acatgacatt 420 tgcggagcaa tttattgtca aggcgggaaa gctcatgggc ggactggaca tgcttattct 480 aaaccacatc actcagacct cgctgtctct cttccatgac gacatccact ctgtgcgaag 540 agtcatggag gtcaacttcc tcagctacgt ggtcatgagc acagccgcct tgcccatgct 600 gaagcagagc aatggcagca ttgccgtcat ctcctccttg gctgggaaaa tgacccagcc 660 tatgattgct ccctactctg caagcaagtt tgctctggat gggttctttt ccaccattag 720 aacagaactc tacataacca aggtcaacgt gtccatcact ctctgtgtcc ttggcctcat 780 agacacagaa acagctatga aggaaatctc tgggataatt gacgccctag cttctcccaa 840 ggaggagtgc gccctggaga tcatcaaagg cacagctcta cgcaaaagcg aggtgtacta 900 tgacaaattg cctttgactc caatcctgct tgggaaccca ggaaggaaga tcatggaatt 960 tttttcatta cgatattata ataaggacat gtttgtaagt aactaggaac tcctgagccc 1020 tggtgagtgg tcttagaaca gtcctgcctc atacttcagt aagccctacc cacaaaagta 1080 tctttccaga gatacacaaa ttttggggta cacctcatca tgagaaattc ttgcaacact 1140 tgcacagtga aaatgtaatt gtaataaatg tcacaaacca ctttgggcct gcagttgtga 1200 acttgattgt aactatggat ataaacacat agtggttgta tcggctttac ctcacactga 1260 atgaaacaat gataactaat gtaacattaa atataataaa ggtaatatca acttcgtaaa 1320 tgcaaaaaaa aaaaaaaaaa aaaaaaaaaa 1350 <210> SEQ ID NO 19 <211> LENGTH: 1418

<212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 19 cattaattgc ttgccatcat gagcagaagc aagcgtgaca acaattttta tagtgtagag 60 attggagatt ctacattcac agtcctgaaa cgatatcaga atttaaaacc tataggctca 120 ggagctcaag gaatagtatg cgcagcttat gatgccattc ttgaaagaaa tgttgcaatc 180 aagaagctaa gccgaccatt tcagaatcag actcatgcca agcgggccta cagagagcta 240 gttcttatga aatgtgttaa tcacaaaaat ataattggcc ttttgaatgt tttcacacca 300 cagaaatccc tagaagaatt tcaagatgtt tacatagtca tggagctcat ggatgcaaat 360 ctttgccaag tgattcagat ggagctagat catgaaagaa tgtcctacct tctctatcag 420 atgctgtgtg gaatcaagca ccttcattct gctggaatta ttcatcggga cttaaagccc 480 agtaatatag tagtaaaatc tgattgcact ttgaagattc ttgacttcgg tctggccagg 540 actgcaggaa cgagttttat gatgacgcct tatgtagtga ctcgctacta cagagcaccc 600 gaggtcatcc ttggcatggg ctacaaggaa aacgtggatt tatggtctgt ggggtgcatt 660 atgggagaaa tggtttgcca caaaatcctc tttccaggaa gggactatat tgatcagtgg 720 aataaagtta ttgaacagct tggaacacca tgtcctgaat tcatgaagaa actgcaacca 780 acagtaagga cttacgttga aaacagacct aaatatgctg gatatagctt tgagaaactc 840 ttccctgatg tccttttccc agctgactca gaacacaaca aacttaaagc cagtcaggca 900 agggatttgt tatccaaaat gctggtaata gatgcatcta aaaggatctc tgtagatgaa 960 gctctccaac acccgtacat caatgtctgg tatgatcctt ctgaagcaga agctccacca 1020 ccaaagatcc ctgacaagca gttagatgaa agggaacaca caatagaaga gtggaaagaa 1080 ttgatatata aggaagttat ggacttggag gagagaacca agaatggagt tatacggggg 1140 cagccctctc ctttagcaca ggtgcagcag tgatcaatgg ctctcagcat ccatcatcat 1200 cgtcgtctgt caatgatgtg tcttcaatgt caacagatcc gactttggcc tctgatacag 1260 acagcagtct agaagcagca gctgggcctc tgggctgctg tagatgacta cttgggccat 1320 cggggggtgg gagggatggg gagtcggtta gtcattgata gaactacttt gaaaacaatt 1380 cagtggtctt atttttgggt gatttttcaa aaaatgta 1418 <210> SEQ ID NO 20 <211> LENGTH: 2181 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 20 agagagccga gctctggagc ctcagcgagc ggaggaggag gcgcagggcc gacggccgag 60 tactgcggtg agagccagcg ggccagcgcc agcctcaaca gccgccagaa gtacacgagg 120 aaccggcggc ggcgtgtgcg tgtaggcccg tgtgcgggcg gcggcgcggg aggagcgcgg 180 agcggcagcc ggctggggcg ggtggcatca tggacgagaa ggtgttcacc aaggagctgg 240 accagtggat cgagcagctg aacgagtgca agcagctgtc cgagtcccag gtcaagagcc 300 tctgcgagaa ggctaaagaa atcctgacaa aagaatccaa cgtgcaagag gttcgatgtc 360 cagttactgt ctgtggagat gtgcatgggc aatttcatga tctcatggaa ctgtttagaa 420 ttggtggcaa atcaccagat acaaattact tgtttatggg agattatgtt gacagaggat 480 attattcagt tgaaacagtt acactgcttg tagctcttaa ggttcgttac cgtgaacgca 540 tcaccattct tcgagggaat catgagagca gacagatcac acaagtttat ggtttctatg 600 atgaatgttt aagaaaatat ggaaatgcaa atgtttggaa atattttaca gatctttttg 660 actatcttcc tctcactgcc ttggtggatg ggcagatctt ctgtctacat ggtggtctct 720 cgccatctat agatacactg gatcatatca gagcacttga tcgcctacaa gaagttcccc 780 atgagggtcc aatgtgtgac ttgctgtggt cagatccaga tgaccgtggt ggttggggta 840 tatctcctcg aggagctggt tacacctttg ggcaagatat ttctgagaca tttaatcatg 900 ccaatggcct cacgttggtg tctagagctc accagctagt gatggaggga tataactggt 960 gccatgaccg gaatgtagta acgattttca gtgctccaaa ctattgttat cgttgtggta 1020 accaagctgc aatcatggaa cttgacgata ctctaaaata ctctttcttg cagtttgacc 1080 cagcacctcg tagaggcgag ccacatgtta ctcgtcgtac cccagactac ttcctgtaat 1140 gaaattttaa acttgtacag tattgccatg aaccatatat cgacctaatg gaaatgggaa 1200 gagcaacagt aactccaaag tgtcagaaaa tagttaacat tcaaaaaact tgttttcaca 1260 tggaccaaaa gatgtgccat ataaaaatac aaagcctctt gtcatcaaca gccgtgacca 1320 ctttagaatg aaccagttca ttgcatgctg aagcgacatt gttggtcaag aaaccagttt 1380 ctggcatagc gctatttgta gttacttttg ctttctctga gagactgcag ataataagat 1440 gtaaacatta acacctcgtg aatacaattt aacttccatt tagctatagc tttactcagc 1500 atgactgtag ataaggatag cagcaaacaa tcattggagc ttaatgaaca tttttaaaaa 1560 taattaccaa ggcctccctt ctacttgtga gttttgaaat tgttcttttt attttcaggg 1620 ataccgttta atttaattat atgatttgtc tgcactcagt ttattcccta ctcaaatctc 1680 agccccatgt tgttctttgt tattgtcaga acctggtgag ttgttttgaa cagaactgtt 1740 ttttcccctt cctgtaagac gatgtgactg cacaagagca ctgcagtgtt tttcataata 1800 aacttgtgaa ctaagaactg agaaggtcaa attttaattg tatcaatggg caagactggt 1860 gctgtttatt aaaaaagtta aatcaattga gtaaatttta gaatttgtag acttgtaggt 1920 aaaataaaaa tcaagggcac tacataacct ctctggtaac tccttgacat tcttcagatt 1980 aacttcagga tttatttgta tttcacatat tacaatttgt cacattgttg gtgtgcactt 2040 tgtgggttct tcctgcatat taacttgttt gtaagaaagg aaatctgtgc tgcttcagta 2100 agacttaatt gtaaaaccat ataacttgag atttaagtct ttgggttgtg ttttaataaa 2160 acagcatgtt ttcaggtaga g 2181 <210> SEQ ID NO 21 <211> LENGTH: 3160 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 21 cctcccctcg cccggcgcgg tcccgtccgc ctctcgctcg cctcccgcct cccctcggtc 60 ttccgaggcg cccgggctcc cggcgcggcg gcggaggggg cgggcaggcc ggcgggcggt 120 gatgtggcag gactctttat gcgctgcggc aggatacgcg ctcggcgctg ggacgcgact 180 gcgctcagtt ctctcctctc ggaagctgca gccatgatgg aagtttgaga gttgagccgc 240 tgtgaggcga ggccgggctc aggcgaggga gatgagagac ggcggcggcc gcggcccgga 300 gcccctctca gcgcctgtga gcagccgcgg gggcagcgcc ctcggggagc cggccggcct 360 gcggcggcgg cagcggcggc gtttctcgcc tcctcttcgt cttttctaac cgtgcagcct 420 cttcctcggc ttctcctgaa agggaaggtg gaagccgtgg gctcgggcgg gagccggctg 480 aggcgcggcg gcggcggcgg cggcacctcc cgctcctgga gcggggggga gaagcggcgg 540 cggcggcggc cgcggcggct gcagctccag ggagggggtc tgagtcgcct gtcaccattt 600 ccagggctgg gaacgccgga gagttggtct ctccccttct actgcctcca acacggcggc 660 ggcggcggcg gcacatccag ggacccgggc cggttttaaa cctcccgtcc gccgccgccg 720 caccccccgt ggcccgggct ccggaggccg ccggcggagg cagccgttcg gaggattatt 780 cgtcttctcc ccattccgct gccgccgctg ccaggcctct ggctgctgag gagaagcagg 840 cccagtcgct gcaaccatcc agcagccgcc gcagcagcca ttacccggct gcggtccaga 900 gccaagcggc ggcagagcga ggggcatcag ctaccgccaa gtccagagcc atttccatcc 960 tgcagaagaa gccccgccac cagcagcttc tgccatctct ctcctccttt ttcttcagcc 1020 acaggctccc agacatgaca gccatcatca aagagatcgt tagcagaaac aaaaggagat 1080 atcaagagga tggattcgac ttagacttga cctatattta tccaaacatt attgctatgg 1140 gatttcctgc agaaagactt gaaggcgtat acaggaacaa tattgatgat gtagtaaggt 1200 ttttggattc aaagcataaa aaccattaca agatatacaa tctttgtgct gaaagacatt 1260 atgacaccgc caaatttaat tgcagagttg cacaatatcc ttttgaagac cataacccac 1320 cacagctaga acttatcaaa cccttttgtg aagatcttga ccaatggcta agtgaagatg 1380 acaatcatgt tgcagcaatt cactgtaaag ctggaaaggg acgaactggt gtaatgatat 1440 gtgcatattt attacatcgg ggcaaatttt taaaggcaca agaggcccta gatttctatg 1500 gggaagtaag gaccagagac aaaaagggag taactattcc cagtcagagg cgctatgtgt 1560 attattatag ctacctgtta aagaatcatc tggattatag accagtggca ctgttgtttc 1620 acaagatgat gtttgaaact attccaatgt tcagtggcgg aacttgcaat cctcagtttg 1680 tggtctgcca gctaaaggtg aagatatatt cctccaattc aggacccaca cgacgggaag 1740 acaagttcat gtactttgag ttccctcagc cgttacctgt gtgtggtgat atcaaagtag 1800 agttcttcca caaacagaac aagatgctaa aaaaggacaa aatgtttcac ttttgggtaa 1860 atacattctt cataccagga ccagaggaaa cctcagaaaa agtagaaaat ggaagtctat 1920 gtgatcaaga aatcgatagc atttgcagta tagagcgtgc agataatgac aaggaatatc 1980 tagtacttac tttaacaaaa aatgatcttg acaaagcaaa taaagacaaa gccaaccgat 2040 acttttctcc aaattttaag gtgaagctgt acttcacaaa aacagtagag gagccgtcaa 2100 atccagaggc tagcagttca acttctgtaa caccagatgt tagtgacaat gaacctgatc 2160 attatagata ttctgacacc actgactctg atccagagaa tgaacctttt gatgaagatc 2220 agcatacaca aattacaaaa gtctgaattt ttttttatca agagggataa aacaccatga 2280 aaataaactt gaataaactg aaaatggacc tttttttttt taatggcaat aggacattgt 2340 gtcagattac cagttatagg aacaattctc ttttcctgac caatcttgtt ttaccctata 2400 catccacagg gttttgacac ttgttgtcca gttgaaaaaa ggttgtgtag ctgtgtcatg 2460 tatatacctt tttgtgtcaa aaggacattt aaaattcaat taggattaat aaagatggca 2520 ctttcccgtt ttattccagt tttataaaaa gtggagacag actgatgtgt atacgtagga 2580 attttttcct tttgtgttct gtcaccaact gaagtggcta aagagctttg tgatatactg 2640 gttcacatcc tacccctttg cacttgtggc aacagataag tttgcagttg gctaagagag 2700 gtttccgaaa ggttttgcta ccattctaat gcatgtattc gggttagggc aatggagggg 2760 aatgctcaga aaggaaataa ttttatgctg gactctggac catataccat ctccagctat 2820 ttacacacac ctttctttag catgctacag ttattaatct ggacattcga ggaattggcc 2880 gctgtcactg cttgttgttt gcgcattttt ttttaaagca tattggtgct agaaaaggca 2940 gctaaaggaa gtgaatctgt attggggtac aggaatgaac cttctgcaac atcttaagat 3000 ccacaaatga agggatataa aaataatgtc ataggtaaga aacacagcaa caatgactta 3060 accatataaa tgtggaggct atcaacaaag aatgggcttg aaacattata aaaattgaca 3120 atgatttatt aaatatgttt tctcaattgt aaaaaaaaaa 3160 <210> SEQ ID NO 22

<211> LENGTH: 4127 <212> TYPE: DNA <213> ORGANISM: R. norvegicus <400> SEQUENCE: 22 agccgctgct ggggaggttg gggctgaggt ggtggcgggc gacgggcctc gagacgcgga 60 gcgacgcggc ctagcgcggc ggacggccga gggaactcgg gcagtcgtcc cgtcccgcca 120 tggaaatgga gaaggaattc gagcagatcg ataaggctgg gaactgggcg gctatttacc 180 aggatattcg acatgaagcc agtgacttcc catgcagaat agcgaaactt cctaagaaca 240 aaaaccggaa caggtaccga gatgtcagcc cttttgacca cagtcggatt aaattgcatc 300 aggaagataa tgactatatc aatgccagct tgataaaaat ggaggaagcc cagaggagct 360 atatcctcac ccagggccct ttaccaaaca cgtgcgggca cttctgggag atggtgtggg 420 agcagaagag caggggcgtg gtcatgctca accgcatcat ggagaaaggc tcgttaaaat 480 gtgcccagta ttggccacag aaagaagaaa aagagatggt cttcgatgac accaatttga 540 agctgacact gatctctgaa gatgtcaagt catattacac agtacggcag ttggagttgg 600 agaacctggc tacccaggag gctcgagaga tcctgcattt ccactacacc acctggcctg 660 actttggagt ccctgagtca cctgcctctt tcctcaattt cctattcaaa gtccgagagt 720 caggctcact cagcccagag cacggcccca ttgtggtcca ctgcagtgct ggcattggca 780 ggtcagggac cttctgcctg gctgacacct gcctcttact gatggacaag aggaaagacc 840 cgtcctctgt ggacatcaag aaagtgctgt tggagatgcg caggttccgc atggggctca 900 tccagacggc cgaccaactg cgcttctcct acctggctgt gatcgagggt gcaaagttca 960 tcatgggcga ctcgtcagtg caggatcagt ggaaggagct ttcccatgaa gacctggagc 1020 ctccccctga gcacgtgccc ccacctcccc ggccacccaa acgcacattg gagcctcaca 1080 atggcaagtg caaggagctc ttctccaacc accagtgggt gagcgaggag agctgtgagg 1140 atgaggacat cctggccaga gaggaaagca gagccccctc aattgctgtg cacagcatga 1200 gcagtatgag tcaagacact gaagttagga aacggatggt gggtggaggt cttcaaagtg 1260 ctcaggcatc tgtccccact gaggaagagc tgtccccaac cgaggaggaa caaaaggcac 1320 acaggccagt tcactggaag cccttcctgg tcaacgtgtg catggccacg gccctggcga 1380 ctggcgcgta cctctgttac cgggtatgtt ttcactgaca gactgctgtg aggcatgagc 1440 gtggtgggcg ctgccactgc ccaggttagg atttggtctg cggcgtctaa cctggtgtag 1500 aagaaacaac agcttacaag cctgtggtgg aactggaagg gccagcccca ggaggggcat 1560 ctgtgcactg ggctttgaag gagcccctgg tcccaagaac agagtctaat ctcagggcct 1620 taacctgttc aggagaagta gaggaaatgc caaatactct tcttgctctc acctcactcc 1680 tcccctttct ctggttcgtt tgtttttgga aaaaaaaaaa aaagaattac aacacattgt 1740 tgtttttaac atttataaag gcaggttttt gttattttta gagaaaacaa aagatgctag 1800 gcactggtga gattctcttg tgccctttgg catgtgatca gattcacgat ttacgtttat 1860 ttccggggga gggtcccacc tgtcaggact gtaaagttcc tgctggcttg gtcagccccc 1920 ccaccccccc accccgagct tgcaggtgcc ctgctgtgag gagagcagca gcagaggctg 1980 cccctggaca gaagcccagc tctgcttccc tcaggtgtcc ctgcgtttcc atcctccttc 2040 tttgtgaccg ccatcttgca gatgacccag tcctcagcac cccacccctg cagatgggtt 2100 tctccgaggg cctgcctcag ggtcatcaga ggttggctgc cagcttagag ctggggcttc 2160 catttgattg gaaagtcatt actattctat gtagaagcca ctccactgag gtgtaaagca 2220 agactcataa aggaggagcc ttggtgtcat ggaagtcact ccgcgcgcag gacctgtaac 2280 aacctctgaa acactcagtc ctgctgcagt gacgtccttg aaggcatcag acagatgatt 2340 tgcagactgc caagacttgt cctgagccgt gatttttaga gtctggactc atgaaacacc 2400 gccgagcgct tactgtgcag cctctgatgc tggttggctg aggctgcggg gaggtggaca 2460 ctgtgggtgc atccagtgca gttgcttttg tgcagttggg tccagcagca cagcccgcac 2520 tccagcctca gctgcaggcc acagtggcca tggaggccgc cagagcgagc tggggtggat 2580 gcttgttcac ttggagcagc cttcccagga cgtgcagctc ccttcctgct ttgtccttct 2640 gcttccttcc ctggagtagc aagcccacga gcaatcgtga ggggtgtgag ggagctgcag 2700 aggcatcaga gtggcctgca gcggcgtgag gccccttccc ctccgacacc cccctccaga 2760 ggagccgctc cactgttatt tattcacttt gcccacagac acccctgagt gagcacaccc 2820 tgaaactgac cgtgtaaggt gtcagcctgc acccaggacc gtcaggtgca gcaccgggtc 2880 agtcctaggg ttgaggtagg actgacacag ccactgtgtg gctggtgctg gggcaggggc 2940 aggagctgag ggtcttagaa gcaatcttca ggaacagaca acagtggtga catgtaaagt 3000 ccctgtggct actgatgaca tgtgtaggat gaaggctggc ctttctccca tgactttcta 3060 gatcccgttc cccgtctgct ttccctgtga gttagaaaac acacaggctc ctgtcctggt 3120 ggtgccgtgt gcttgacatg ggaaacttag atgcctgctc actggcgggc acctcggcat 3180 cgccaccact cagagtgaga gcagtgctgt ccagtgccga ggccgcctga ctcccggcag 3240 gactcttcag gctctggcct gccccagcac accccgctgg atctcagaca ttccacaccc 3300 acacctcatt ccctggacac ttgggcaagc aggcccgccc ttccacctct ggggtcagcc 3360 cctccattcc gagttcacac tgctctggag caggccagga ccggaagcaa ggcagctggt 3420 gaggagcacc ctcctgggaa cagtgtaggt gacagtcctg agagtcagct tgctagcgct 3480 gctggcacca gtcaccttgc tcagaagtgt gtggctcttg aggctgaaga gactgatgat 3540 ggtgctcatg actcttctgt gaggggaact tgaccttcac attgggtggc tttttttaaa 3600 ataagcgaag gcagctggaa ctccagtctg cctcttgcca gcacttcaca ttttgccttt 3660 cacccagaga agccagcaca gagccactgg ggaaggcgat ggccttgcct gcacaggctg 3720 aggagatggc tcagccggcg tccaggctgt gtctggagca gggggtgcac agcagcctca 3780 caggtggggg cctcagagca ggcgctgccc tgtcccctgc cccgctggag gcagcaaagc 3840 tgctgcatgc cttaagtcaa tacttactca gcagggcgct ctcgttctct ctctctctct 3900 ctctctctct ctctctctct ctctctctct ctctaaatgg ccatagaata aaccatttta 3960 caaaaataaa agccaacaac aaagtgctct ggaatagcac ctttgcagga gcggggggtg 4020 tctcagggtc ttctgtgacc tcaccgaact gtccgactgc accgtttcca acttgtgtct 4080 cactaatggg tctgcattag ttgcaacaat aaatgttttt aaagaac 4127 <210> SEQ ID NO 23 <211> LENGTH: 2194 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 23 gacaggctgg tcctcaccat ggccacctgc tggcaggcac tatgggccta tcgctcctac 60 ctgattgtgc tatgtctgcc cattttcctg ttgcctctgc cactcattgt ccaaactaag 120 gaagcctact gtgcttactc catcatcctc atggcgctgc tgtggtgtac agaggccctg 180 cccttggctg tcaccgccct cttccccatc atcctcttcc ctttgatggg tatcatggaa 240 gcctccaagg tctgcttaga gtacttcaag gacaccaaca tattgttcgt cgggggtctg 300 atggtggcca tcgccgtgga gcactggaac ctgcacaagc gcattgccct tggagtgctc 360 cttatcatag gagtgcggcc cgccctgctg cttctgggct tcatgttggt cacagccttc 420 ctctccatgt ggatcagcaa cacagccacc acagccatga tgctgcccat cgggtatgca 480 gtcctggagc agctgcaggg ctcacaaaag gatgtggagg aaggcaatag taacccttcc 540 tttgagctcc aggaagcaag tccccagaag gaggagacca agcttgataa cggtcaggct 600 gtatctgttt cttcggagcc aagagctcag aagaccaaag agcatcaccg cttcagccag 660 ggcctgagtc tctgcatctg ctactcagcc agcattgggg gcattgccac cctgacgggt 720 accacaccca acctggtgct ccaaggccag gtcaactcga tcttccctga aaatagtaac 780 gtggtgaact ttgcttcatg gtttggtttt gccttcccca ccatggtgat cttgctgcta 840 ctggcttggc tatggctaca ggtcctcttc ctgggtgtca acttccggaa gaactttggc 900 tttggggaag gggaagagga acggaagcag gctgccttcc aggtcatcaa gacccagcac 960 aggctgctgg gccccatgag ttttgcagag aaggctgtca ctttcctgtt tgtcctgcta 1020 gtggtgctct ggttcacgag ggagccgggc ttcttcccag gctggggtga cacagctttc 1080 gccaataaaa aagggcaaag catggtatca gatgggacag tggccatctt tatcagcctg 1140 attatgttca tcataccctc caagattcca ggactaaccg aggacccaaa aaaaccaggg 1200 aagctgaagg ctcctcctgc catcctcacc tggaagacag tgaacgataa gatgccctgg 1260 aatatcctga tcttgctggg tgggggcttt gccctggcca aaggcagtga ggaatcaggt 1320 ttgtctaagt ggctgggaga caaactgacc ccgctgcagc acgtaccgcc atcagccacc 1380 gtgctcatcc tctctctatt ggtggccatc ttcactgagt gcaccagcaa cgtggccacc 1440 actacactat ttctgcccat cctggcctcc atggcacagg ccatctgcct tcacccgctt 1500 tatgtcatgc ttccctgcac cctggctgcc tccctagctt tcatgctacc cgtggccact 1560 ccacccaacg ccattgtctt ctcttttgga ggcctcaaag tgtctgatat ggcccgtgca 1620 ggattcctgc tcaatatcat cggagtgctg actatcacat tatccataaa cagctggagt 1680 atccctatct tcaagctgga cacatttccc acctgggcct actccaacac aagccagtgc 1740 cttctcaatc cgcctaattc cactgtacca ggccactaga ctatggtaca acctagctct 1800 gctaggggaa aagccgctgg tgccactcct cggagccagg agagggcgct ccaaactcca 1860 agtcccggga cagaggtgca gaatcggctg gcgcatgcga aatcatgtat tcgtgtgttt 1920 gcctacatcc tgtatgtgtg ctctccggtg aagaggaaga tgctcgtgtc tccgtgtggt 1980 gtgcgtggac gcttgcgtgt ggtgtggcct gagggctcct cagtagttgt atgcatggca 2040 accgcgcccg ccctctgact cccagctagg cctccagatc tctttgccct gtatttattg 2100 aaactctggg caggaggccc ctgggagcag gaactccaaa gttcattaaa ggctttttca 2160 gtagagtccg ggtgtgtttc ccggtgttca gaag 2194 <210> SEQ ID NO 24 <211> LENGTH: 5383 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 24 tcccagtctc ccggggtttc tctttgctgg tgcctggaag tgggggtaga tgtgaagtta 60 gaccgagttg tgagtggcgg tagccagtgt cttcctcact tctttcgatg cgatttcccc 120 agtgaaccat ttgctaagcg ccagaccaaa gtcctaggct tgcacacaat tcctacttgg 180 aatcacgtta tcctgctctt aaagaaaagt cacccatcag cccacagcaa agaggataag 240 gagaaaaaga ggggaggaga gacggagaag ctagaggcag agggaacagc agattgcgcc 300 tagccaatgg aaaaggcagg acaaggtggc accaaattct ctttggccaa tgacaagacg 360 ggcttcacag gaggcacatt agcatttatc cccaggcagg gggttggagc agcgcgccct 420 gttgatgcct tcagcatccc ggcgcctcca aggtctactc tggaatctac ttggctttct 480 ttcccgttct tggtcccgcc ctctctctct ccctccctcc ctccctccct tcctccctcc 540

ctccctccct ccctccctcc ctcacctcca cgcctggctt ccttggctag ctatctctgc 600 gctctttacc ctttgctggc agccgataaa agggggctga ggaaatactg aacacggtca 660 tcccatcgcc tgctctaccc tttaaaatcc cagcccagga gatctgtgca cagccagacc 720 gggctgaaca cccatcccga gagtcaggag ggcaggtttc caagcgcagt tccgccactc 780 gcctacacca acgggctccg gaaccgaagt ccacgctcga tctcagcact gggaaagtga 840 ggcgagcaac tgactatcat catgccggcc cacatgctcc aagagatctc cagttcttac 900 acgaccacca ccaccatcac tgcacctccc tccggaaatg aacgagagaa ggtgaagaca 960 gtgcccctcc acctggaaga agacatccgt cctgaaatga aagaagatat tcacgacccc 1020 acctatcagg atgaggaggg acccccgccc aagctggagt acgtctggag gaacatcatt 1080 ctcatggtcc tgctgcactt gggaggcctg tacgggatca tactggttcc ctcctgcaag 1140 ctctacactg ccctcttcgg gattttctac tacatgacca gcgctctggg catcacagcc 1200 ggggctcatc gcctctggag ccacagaact tacaaggctc ggctgcccct gcggatcttc 1260 ctaatcattg ccaacaccat ggcgttccaa aatgacgtgt acgactgggc ccgagatcac 1320 cgcgcccacc acaagttctc agaaacacac gccgaccctc acaattcccg ccgtggcttc 1380 ttcttctctc acgtgggttg gctgcttgtg cgcaaacacc cggctgtcaa agagaagggc 1440 ggaaaactgg acatgtctga cctgaaagcc gagaagctgg tgatgttcca gaggaggtac 1500 tacaagcccg gcctcctgct gatgtgcttc atcctgccca cgctggtgcc ctggtactgc 1560 tggggcgaga cttttgtaaa cagcctgttc gttagcacct tcttgcgata cactctggtg 1620 ctcaacgcca cctggctggt gaacagtgcc gcgcatctct atggatatcg cccctacgac 1680 aagaacattc aatcccggga gaatatcctg gtttccctgg gtgccgtggg cgagggcttc 1740 cacaactacc accacacctt ccccttcgac tactctgcca gtgagtaccg ctggcacatc 1800 aacttcacca cgttcttcat cgactgcatg gctgccctgg gcctggctta cgaccggaag 1860 aaagtttcta aggctactgt cttagccagg attaagagaa ctggagacgg gagtcacaag 1920 agtagctgag ctttgggctt ctgagttcct gtttcaaacg ttttctggca gagatttaat 1980 attctgttga ttaactaaca actggatatt gctatcgggg tgttaatgat gcatttaacc 2040 tattccggta cagtattctt ataaaatgag aaagctttga tcacgttttg aggtaataaa 2100 tattttattt agctaggatt aaccatgcca caagacatta tatatttcta agcacacatg 2160 ataaatgcat atacaatttt gcacaacagc tttaaataat aacaataaat ttgaacattc 2220 tatacagaga ggatcaaagc caaggaacat gctgttttga tgctagggtg agcatggtgc 2280 tcagtccctg tttgtttgca tggtgtccag ctttgtttct tctctgtcat caccaccttc 2340 aggcaaatag ttgaccaacc actggcctgt gtctgtccac cctccaaagc ccaggccacc 2400 tttctgtttt ctgaaatact gatccttcct cctgaataca tccctccttg ttcctagctt 2460 caagactgct gcctcaaata gggatagagc aagtccccgc tgcaggttgt gctagatggg 2520 atggagaaat tatcttcatt tgatacagag caagtagatt gtctcgagag aaaagttagc 2580 atgcgtggta tgatttgtaa gtaaagatgg aagagagaga gagagagaga gagagagaga 2640 gagagagaga gagagaggta gccatatcta acagcctact taccaaagac cccaggcctc 2700 tctgcttggc atgcctcctt tctgtccatc ctctgaaccc cagagattag tgagatttga 2760 ataattaaat cattttcaga gtgaaggggg ttaatgcagg gtctgtgcta ggggagggtt 2820 ttagcttttg gtaactgaag attttttcat ggaaaaagtc ttcgtgttca atgtgcctag 2880 aactgataac taaacagctg acatttgtcg gggacagata tggtgtgaaa ctatgaaaat 2940 ataagcaaaa tcttcacttg gaacatgaaa ctatttcact tagaaaataa tcgaaggacc 3000 cgaggtgttg cctgggttgc cagtttcttt cgtggctggg caggaactag tgaggttgag 3060 gggcagtgtc tgtaagtagc tgctaagagg tgcatttcca gatgaagccc ttggggaaca 3120 tctgccaggg atccgcatgg tgttggctcc atccattgct ttagtttcct ccttggattg 3180 tgtagaaact tggcttccca tggttttgaa ccttccatgc cttctttgct ttgtggccac 3240 ccagcctgcc tagtgctgcc taggaagctc ttacccacct gatttcttct gacatttctt 3300 tctttggcct ttttttcttt ctccggacat gcagctagtt gcctgagtgt atcaagagca 3360 cccaggactt gctgctgtcc aggcctgttc ctcccccagt atccgtgggt gtggaagagc 3420 tgtgtagctt caggaagcag agccaggtgc cacctttctg tggcttccag atcctcccta 3480 cctccaactc atgtgcctct gtcacagtga tttcaggaaa gcttggtaga ccctctagca 3540 acatctcggt tcagaaagtc tctctggttt gtgagttaac agctcagcta agtgctgttt 3600 tgtctcagtg agttaaccac tgaatgcgag ggttggttgt tgatctgtct cggtgtgtgt 3660 cggagtagac agcatatgca cttctccctg tgcgctttgc aaggtaatgt ggctttggct 3720 gatccatgca ggcaggtagt ggtacagtgc tgctgaaagg aagaagttcc ccattttatc 3780 tgttaaaaca ccagagacat gggcaagtgc taatggacct cacttcagga agagggtctg 3840 cttcctgaag ccagtgtgtg atgaaaagtg actgagacct gatatctaag gtgagacctg 3900 atacctaaca ctctgtcaca cagtccaggg ccaacagtgc tataggaaag tctagaagaa 3960 aacatcacat cagtatttta gaaccatcaa ccatctcttg tccctatagc ccaatccaga 4020 ggcctggttt ttagaactgg ctgtgtaagg tgccaaacac tcagttcact tgtagaatca 4080 gagccttttt tcccccctat gttaattgaa cacgcgctct gagctgtttt gttgaagtag 4140 aaaatctcat agaaaaatca ctgtagatct actgacctat agccctctgg aaatgccttt 4200 gagatggttt tacttttcta ggtcatagat gcctgattat aaagatgaac aataaaatca 4260 gctttctttc tttctcttct gatcttattc cccagatctg attcaggcca tgttccaaag 4320 caaggctaca ttgaggtcct ggtgtcttta agtaaaggac atctttcaga tcctctcaaa 4380 gaaggattta taacagtttc cagatgaatg tactaatagc tttgggtgcc ttatctcttt 4440 cctaatctgt agtgcctgtg agctcagtct cactccttcc cttagcccgg agacccctta 4500 gatcgagtgg gaatagtcaa gaggctggct ggagagtcat cagtacattg gtttgcagaa 4560 atcttttaca ggctacattt tggaattttt ttttttttag taagtgatca aatttggtgg 4620 gaagtaattc gagtgtattc gattgtattg tcgtcctcgt tatcattgtc aaacatgtta 4680 tagacggcag ttggcactgg ggctgctaat ctctgggtgt agtctctgaa actgtagctc 4740 cagtgaggtg gtgtgaaagg ttagcaaagc caccatctgc tggtgctcca gccaaggtgc 4800 ctcttagcca ctgaattgct atgttatcct ttctcttgta acaaacccac cccagagata 4860 aagcctttaa tcaacccaag aaactcctgg gctaagtatc tgacagtctc acatctcaac 4920 agtgtgaatt aagtgtccat agcatcagct caggaggaca ctctgggaga gtgctgacaa 4980 aaaagggtta ttaatactga cctactactt caagggcagt tctgaggtga ttagagcttt 5040 ttttaaaaac caagtatttg gggatcctca gcagaggtat tcatacagac tcccaaagaa 5100 ctatatatgt tcctgagacc atcgtttagt ctacattgct cttcccagag actgacagat 5160 atgaccagtc aaagtgcaag actacctacc cactgccatg aaaaccattg caggaaacct 5220 ttcccttcct gaatgagatt ttttttttcc ctttttatgt ggggtaatta tttgtgaccc 5280 aagtgtaatt tggatgattt ccattaatat caactcttga agcctacttg tactgattga 5340 gattgtattt gttcctaata aaagtggatc tggttgtact gtc 5383 <210> SEQ ID NO 25 <211> LENGTH: 14796 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 25 tctagacatg cggatatatt caagctgggc acagcacagc agccccaccc caggcagctt 60 gaaatcagag ctggggtcca aagggaccac accccgaggg actgtgtggg ggtcggggca 120 cacaggccac tgcttccccc cgtctttctc agccattcct gaagtcagcc tcactctgct 180 tctcagggat ttcaaatgtg cagagactct ggcacttttg tagaagcccc ttctggtcct 240 aacttacacc tggatgctgt ggggctgcag ctgctgctcg ggctcgggag gatgctgggg 300 gcccggtgcc catgagcttt tgaagctcct ggaactcggt tttgagggtg ttcaggtcca 360 ggtggacacc tgggctgtcc ttgtccatgc atttgatgac attgtgtgca gaagtgaaaa 420 ggagttaggc cgggcatgct ggcttatgcc tgtaatccca gcactttggg aggctgaggc 480 gggtggatca cgaggtcagg agttcaatac cagcctggcc aagatggtga aaccccgtct 540 ctactaaaaa tacaaaaaaa ttagccgggc atggtggcgg gcgcatgtaa tcccagctac 600 tgggggggct gaggcagaga attgctggaa cccaggagat ggaggttgca gtgagccaag 660 attgtgccac tgcactgcac tccagcctgg cgacagagca agactctgtc tcaaaaaaaa 720 aaaaaaaaag tgaaaaggag ttgttccttt cctccctcct gagggcaggc aactgctgcg 780 gttgccagtg gaggtggtgc gtccttggtc tgtgcctggg ggccacccca gcagaggcca 840 tggtggtgcc agggcccggt tagcgagcca atcagcagga cccaggggcg acctgccaaa 900 gtcaactgga tttgataact gcagcgaagt taagtttcct gattttgatg attgtgttgt 960 ggttgtgtaa gagaatgaag tatttcgggg tagtatggta atgccttcaa cttacaaacg 1020 gttcaggtaa accacccata tacatacata tacatgcatg tgatatatac acatacaggg 1080 atgtgtgtgt gttcacatat atgaggggag agagactagg ggagagaaag taggttgggg 1140 agagggagag agaaaggaaa acaggagaca gagagagagc ggggagtaga gagagggaag 1200 gggtaagaga gggagaggag gagagaaagg gaggaagaag cagagagtga atgttaaagg 1260 aaacaggcaa aacataaaca gaaaatctgg gtgaagggta tatgagtatt ctttgtacta 1320 ttcttgcaat tatcttttat ttaaattgac atcgggccgg gcgcagtggc tcacatctgt 1380 aatcccagca ctttgggagg ccgaggcagg cagatcactt gaggtcagga gtttgagacc 1440 agcctggcaa acatggtgaa accccatctc tactaaaaat acaaaaatta gcctggtgtg 1500 gtggtgcatg cctttaatct cagctactcg ggaggctgag gcaggagaat cgcttgaacc 1560 cgtggcgggg aggaggttgc agtgagctga gatcatgcca ctgcactcca gcctgggcga 1620 tagagcgaga ctcagtttca aataaataaa taaacatcaa aataaaaagt tactgtatta 1680 aagaatgggg gcggggtggg aggggtgggg agaggttgca aaaataaata aataaataaa 1740 taaaccccaa aatgaaaaag acagtggagg caccaggcct gcgtggggct ggagggctaa 1800 taaggccagg cctcttatct ctggccatag aaccagagaa gtgagtggat gtgatgccca 1860 gctccagaag tgactccaga acaccctgtt ccaaagcaga ggacacactg attttttttt 1920 taataggctg caggacttac tgttggtggg acgccctgct ttgcgaaggg aaaggaggag 1980 tttgccctga gcacaggccc ccaccctcca ctgggctttc cccagctccc ttgtcttctt 2040 atcacggtag tggcccagtc cctggcccct gactccagaa ggtggccctc ctggaaaccc 2100 aggtcgtgca gtcaacgatg tactcgccgg gacagcgatg tctgctgcac tccatccctc 2160 ccctgttcat ttgtccttca tgcccgtctg gagtagatgc tttttgcaga ggtggcaccc 2220 tgtaaagctc tcctgtctga cttttttttt ttttttagac tgagttttgc tcttgttgcc 2280 taggctggag tgcaatggca caatctcagc tcactgcacc ctctgcctcc cgggttcaag 2340 cgattctcct gcctcagcct cccgagtagt tgggattaca ggcatgcacc accacgccca 2400

gctaattttt gtatttttag tagagacaag gtttcaccgt gatggccagg ctggtcttga 2460 actccaggac tcaagtgatg ctcctgccta ggcctctcaa agtgttggga ttacaggcgt 2520 gagccactgc acccggcctg cacgcgttct ttgaaagcag tcgagggggc gctaggtgtg 2580 ggcagggacg agctggcgcg gcgtcgctgg gtgcaccgcg accacgggca gagccacgcg 2640 gcgggaggac tacaactccc ggcacacccc gcgccgcccc gcctctactc ccagaaggcc 2700 gcggggggtg gaccgcctaa gagggcgtgc gctcccgaca tgccccgcgg cgcgccatta 2760 accgccagat ttgaatcgcg ggacccgttg gcagaggtgg cggcggcggc atgggtgccc 2820 cgacgttgcc ccctgcctgg cagccctttc tcaaggacca ccgcatctct acattcaaga 2880 actggccctt cttggagggc tgcgcctgca ccccggagcg ggtgagactg cccggcctcc 2940 tggggtcccc cacgcccgcc ttgccctgtc cctagcgagg ccactgtgac tgggcctcgg 3000 gggtacaagc cgccctcccc tccccgtcct gtccccagcg aggccactgt ggctgggccc 3060 cttgggtcca ggccggcctc ccctccctgc tttgtcccca tcgaggcctt tgtggctggg 3120 cctcggggtt ccgggctgcc acgtccactc acgagctgtg ctgtcccttg cagatggccg 3180 aggctggctt catccactgc cccactgaga acgagccaga cttggcccag tgtttcttct 3240 gcttcaagga gctggaaggc tgggagccag atgacgaccc catgtaagtc ttctctggcc 3300 agcctcgatg ggctttgttt tgaactgagt tgtcaaaaga tttgagttgc aaagacactt 3360 agtatgggag ggttgctttc caccctcatt gcttcttaaa cagctgttgt gaacggatac 3420 ctctctatat gctggtgcct tggtgatgct tacaacctaa ttaaatctca tttgaccaaa 3480 atgccttggg gtggacgtaa gatgcctgat gcctttcatg ttcaacagaa tacatcagca 3540 gaccctgttg ttgtgaactc ccaggaatgt ccaagtgctt tttttgagat tttttaaaaa 3600 acagtttaat tgaaatataa cctacacagc acaaaaatta ccctttgaaa gtgtgcactt 3660 cacactttcg gaggctgagg cgggcggatc acctgaggtc aggagttcaa gacctgcctg 3720 gccaacttgg cgaaaccccg tctctactaa aaatacaaaa attagccggg catggtagcg 3780 cacgcccgta atcccagcta ctcgggaggc taaggcagga gaatcgcttg aacctgggag 3840 gcggaggttg cagtgagccg agattgtgcc aatgcactcc agcctcggcg acagagcgag 3900 actccgtcat aaaaataaaa aattgaaaaa aaaaaaagaa agaaagcata tacttcagtg 3960 ttgttctgga tttttttctt caagatgcct agttaatgac aatgaaattc tgtactcgga 4020 tggtatctgt ctttccacac tgtaatgcca tattcttttc tcaccttttt ttctgtcgga 4080 ttcagttgct tccacagctt taattttttt cccctggaga atcaccccag ttgtttttct 4140 ttttggccag aagagagtag ctgttttttt tcttagtatg tttgctatgg tggttatact 4200 gcatccccgt aatcactggg aaaagatcag tggtattctt cttgaaaatg aataagtgtt 4260 atgatatttt cagattagag ttacaactgg ctgtcttttt ggactttgtg tggccatgtt 4320 ttcattgtaa tgcagttctg gtaacggtga tagtcagtta tacagggaga ctcccctagc 4380 agaaaatgag agtgtgagct agggggtccc ttggggaacc cggggcaata atgcccttct 4440 ctgcccttaa tccttacagt gggccgggca cggtggctta cgcctgtaat accagcactt 4500 tgggaggccg aggcgggcgg atcacgaggt caggagatcg agaccatctt ggctaatacg 4560 gtgaaacccc gtctccacta aaaatacaaa aaattagccg ggcgtggtgg tgggcgcctg 4620 tagtcccagc tactcgggag gctgaggcag gagaatggcg tgaacccagg aggcggagct 4680 tgcagtgagc cgagattgca ccactgcact ccagcctggg cgacagaatg agactccgtc 4740 tcaaaaaaaa aaaaaaaaga aaaaaatctt tacagtggat tacataacaa ttccagtgaa 4800 atgaaattac ttcaaacagt tccttgagaa tgttggaggg atttgacatg taattccttt 4860 ggacatatac catgtaacac ttttccaact aattgctaag gaagtccaga taaaatagat 4920 acattagcca cacagatgtg gggggagatg tccacaggga gagagaaggt gctaagaggt 4980 gccatatggg aatgtggctt gggcaaagca ctgatgccat caacttcaga cttgacgtct 5040 tactcctgag gcagagcagg gtgtgcctgt ggagggcgtg gggaggtggc ccgtggggag 5100 tggactgccg ctttaatccc ttcagctgcc tttccgctgt tgttttgatt tttctagaga 5160 ggaacataaa aagcattcgt ccggttgcgc tttcctttct gtcaagaagc agtttgaaga 5220 attaaccctt ggtgaatttt tgaaactgga cagagaaaga gccaagaaca aaattgtatg 5280 tattgggaat aagaactgct caaaccctgt tcaatgtctt tagcactaaa ctacctagtc 5340 cctcaaaggg actctgtgtt ttcctcagga agcatttttt ttttttttct gagatagagt 5400 ttcactcttg ttgcccaggc tggagtgcaa tggtgcaatc ttggctcact gcaacctctg 5460 cctctcgggt tcaagtgatt ctcctgcctc agcctcccaa gtaactggga ttacagggaa 5520 gtgccaccac acccagctaa tttttgtatt tttagtagag atggggtttc accacattgc 5580 ccaggctggt cttgaactcc tgacctcgtg attcgcccac cttggcctcc caaagtgctg 5640 ggattacagg cgtgaaccac cacgcctggc tttttttttt ttgttctgag acacagtttc 5700 actctgttac ccaggctgga gtagggtggc ctgatctcgg atcactgcaa cctccgcctc 5760 ctgggctcaa gtgatttgcc tgcttcagcc tcccaagtag ccgagattac aggcatgtgc 5820 caccacaccc aggtaatttt tgtatttttg gtagagacga ggtttcacca tgttggccag 5880 gctggttttg aactcctgac ctcaggtgat ccacccgcct cagcctccca aagtgctgag 5940 attataggtg tgagccacca cacctggcct caggaagtat ttttattttt aaatttattt 6000 atttatttga gatggagtct tgctctgtcg cccaggctag agtgcagcga cgggatctcg 6060 gctcactgca agctccgccc cccaggttca agccattctc ctgcctcagc ctcccgagta 6120 gctgggacta caggcgcccg ccaccacacc cggctaattt ttttgtattt ttagtagaga 6180 cgggttttca ccgtgttagc caggagggtc ttgatctcct gacctcgtga tctgcctgcc 6240 tcggcctccc aaagtgctgg gattacaggt gtgagccacc acacccggct atttttattt 6300 ttttgagaca gggactcact ctgtcacctg ggctgcagtg cagtggtaca ccatagctca 6360 ctgcagcctc gaactcctga gctcaagtga tcctcccacc tcatcctcac aagtaattgg 6420 gactacaggt gcaccccacc atgcccacct aatttattta tttatttatt tatttatttt 6480 catagagatg agggttccct gtgttgtcca ggctggtctt gaactcctga gctcacggga 6540 tccttttgcc tgggcctccc aaagtgctga gattacaggc atgagccacc gtgcccagct 6600 aggaatcatt tttaaagccc ctaggatgtc tgtgtgattt taaagctcct ggagtgtggc 6660 cggtataagt atataccggt ataagtaaat cccacatttt gtgtcagtat ttactagaaa 6720 cttagtcatt tatctgaagt tgaaatgtaa ctgggcttta tttatttatt tatttattta 6780 tttattttta attttttttt ttgagacgag tctcactttg tcacccaggc tggagtgcag 6840 tggcacgatc tcggctcact gcaacctctg cctcccgggg tcaagcgatt ctcctgcctt 6900 agcctcccga gtagctggga ctacaggcac gcaccaccat gcctggctaa tttttgtatt 6960 tttagtagac ggggtttcac catgctggcc aagctggtct caaactcctg accttgtgat 7020 ctgcccgctt tagcctccca gagtgctggg attacaggca tgagccacca tgcgtggtct 7080 ttttaaaatt ttttgatttt tttttttttt gagacagagc cttgctctgt cgcccaggct 7140 ggagtgcagt ggcacgatct cagctcacta caagctccgc ctcccgggtt cacgccattc 7200 ttctgcctca gcctcctgag tagctgggac tacaggtgcc caccaccacg cctggctaat 7260 tttttttggt atttttatta gagacaaggt ttcatcatgt tggccaggct ggtctcaaac 7320 tcctgacctc aagtgatctg cctgcctcgg cctcccaaag cgctgagatt acaggtgtga 7380 tctactgcgc caggcctggg cgtcatatat tcttatttgc taagtctggc agccccacac 7440 agaataagta ctgggggatt ccatatcctt gtagcaaagc cctgggtgga gagtcaggag 7500 atgttgtagt tctgtctctg ccacttgcag actttgagtt taagccagtc gtgctcatgc 7560 tttccttgct aaatagaggt tagaccccct atcccatggt ttctcaggtt gcttttcagc 7620 ttgaaaattg tattcctttg tagagatcag cgtaaaataa ttctgtcctt atatgtggct 7680 ttattttaat ttgagacaga gtgtcactca gtcgcccagg ctggagtgtg gtggtgcgat 7740 cttggctcac tgcgacctcc acctcccagg ttcaagcgat tctcgtgcct caggctccca 7800 agtagctgag attataggtg tgtgccacca ggcccagcta acttttgtat ttttagtaga 7860 gacagggttt tgccatgttg gctaagctgg tctcgaactc ctggcctcaa gtgatctgcc 7920 cgccttggca tcccaaagtg ctgggattac aggtgtgaac caccacacct ggcctcaata 7980 tagtggcttt taagtgctaa ggactgagat tgtgttttgt caggaagagg ccagttgtgg 8040 gtgaagcatg ctgtgagaga gcttgtcacc tggttgaggt tgtgggagct gcagcgtggg 8100 aactggaaag tgggctgggg atcatctttt tccaggtcag gggtcagcca gcttttctgc 8160 agcgtgccat agaccatctc ttagccctcg tgggtcagag tctctgttgc atattgtctt 8220 ttgttgtttt tcacaacctt ttagaaacat aaaaagcatt cttagcccgt gggctggaca 8280 aaaaaaggcc atgacgggct gtatggattt ggcccagcag gcccttgctt gccaagccct 8340 gttttagaca aggagcagct tgtgtgcctg gaaccatcat gggcacaggg gaggagcaga 8400 gtggatgtgg aggtgtgagc tggaaaccag gtcccagagc gctgagaaag acagagggtt 8460 tttgcccttg caagtagagc aactgaaatc tgacaccatc cagttccaga aagccctgaa 8520 gtgctggtgg acgctgcggg gtgctccgct ctagggttac agggatgaag atgcagtctg 8580 gtagggggag tccactcacc tgttggaaga tgtgattaag aaaagtagac tttcagggcc 8640 gggcatggtg gctcacgcct gtaatcccag cactttggga ggccgaggcg ggtggatcac 8700 gaggtcagga gatcgagacc atcctggcta acatggtgaa accccgtctt tactaaaaat 8760 acaaaaaatt agctgggcgt ggtggcgggc gcctgtagtc ccagctactc gggaggctga 8820 ggcaggagaa tggcgtgaac ctgggaggtg gagcttgctg tgagccgaga tcgcgccact 8880 gcactccagc ctgggcgaca gagcgagact ccgtctcaaa aaaaaaaaaa aaagtaggct 8940 ttcatgatgt gtgagctgaa ggcgcagtag gcagaagtag aggcctcagt ccctgcagga 9000 gacccctcgg tctctatctc ctgatagtca gacccagcca cactggaaag aggggagaca 9060 ttacagcctg cgagaaaagt agggagattt aaaaactgct tggcttttat tttgaactgt 9120 tttttttgtt tgtttgtttt ccccaattca gaatacagaa tacttttatg gatttgtttt 9180 tattacttta attttgaaac aatataatct tttttttgtt gtttttttga gacagggtct 9240 tactctgtca cccaggctga gtgcagtggt gtgatcttgg ctcacctcag cctcgacccc 9300 ctgggctcaa atgattctcc cacctcagct tcccaagtag ctgggaccac aggtgcgtgt 9360 gttgcgctat acaaatcctg aagacaagga tgctgttgct ggtgatgctg gggattccca 9420 agatcccaga tttgatggca ggatgcccct gtctgctgcc ttgccagggt gccaggaggg 9480 cgctgctgtg gaagctgagg cccggccatc cagggcgatg cattgggcgc tgattcttgt 9540 tcctgctgct gcctcggtgc ttagcttttg aaacaatgaa ataaattaga accagtgtga 9600 aaatcgatca gggaataaat ttaatgtgga aataaactga acaacttagt tcttcataag 9660 agtttacttg gtaaatactt gtgatgagga caaaacgaag cactagaagg agaggcgagt 9720 tgtagacctg ggtggcagga gtgttttgtt tgttttcttt ggcagggtct tgctctgttg 9780 ctcaggctgg agtacagtgg cacaatcaca gctcactata gcctcgacct cctggactca 9840 agcaatcctc ctgcctcagc ctcccagtag ctgggactac aggcgcatgc caccatgcct 9900 ggctaatttt aaattttttt ttttctcttt tttgagatgg aatctcactc tgtcgcccag 9960

gctggagtgc agtggcgtga tctcggctga cggcaagctc cgcctcccag gttcactcca 10020 ttcgcctgcc tcagcctccc aagtagctgg gactacaggc gctgggatta caaacccaaa 10080 cccaaagtgc tgggattaca ggcgtgagcc actgcacccg gcctgttttg tctttcaata 10140 gcaagagttg tgtttgcttc gcccctacct ttagtggaaa aatgtataaa atggagatat 10200 tgacctccac attggggtgg ttaaattata gcatgtatgc aaaggagctt cgctaattta 10260 aggctttttt gaaagagaag aaactgaata atccatgtgt gtatatatat tttaaaagcc 10320 atggtcatct ttccatatca gtaaagctga ggctccctgg gactgcagag ttgtccatca 10380 cagtccatta taagtgcgct gctgggccag gtgcagtggc ttgtgcctga atcccagcac 10440 tttgggaggc caaggcagga ggattcattg agcccaggag ttttgaggcg agcctgggca 10500 atgtggccag acctcatctc ttcaaaaaat acacaaaaaa ttagccaggc atggtggcac 10560 gtgcctgtag tctcagctac tcaggaggct gaggtgggag gatcactttg agccttgcag 10620 gtcaaagctg cagtaagcca tgatcttgcc actgcattcc agcctggatg acagagcgag 10680 accctgtctc taaaaaaaaa aaaaaccaaa cggtgcactg ttttcttttt tcttatcaat 10740 ttattatttt taaattaaat tttcttttaa taatttataa attataaatt tatattaaaa 10800 aatgacaaat ttttattact tatacatgag gtaaaactta ggatatataa agtacatatt 10860 gaaaagtaat tttttggctg gcacagtggc tcacacctgt aatcccagca ctttgggagg 10920 ccgtggcggg cagatcacat gagatcatga gttcgagacc aacctgacca acatggagag 10980 accccatctc tactaaaaat acaaaattag ccggggtggt ggcgcatgcc tgtaatccca 11040 gctactcggg aggctgaggc aggagaatct cttgaacccg ggaggcagag gttgcggtga 11100 gccaagatcg tgcctttgca caccagccta ggcaacaaga gcgaaagtcc gtctcaaaaa 11160 aaaagtaatt ttttttaagt taacctctgt cagcaaacaa atttaaccca ataaaggtct 11220 ttgtttttta atgtagtaga ggagttaggg tttataaaaa atatggtagg gaagggggtc 11280 cctggatttg ctaatgtgat tgtcatttgc cccttaggag agagctctgt tagcagaatg 11340 aaaaaattgg aagccagatt cagggaggga ctggaagcaa aagaatttct gttcgaggaa 11400 gagcctgatg tttgccaggg tctgtttaac tggacatgaa gaggaaggct ctggactttc 11460 ctccaggagt ttcaggagaa aggtagggca gtggttaaga gcagagctct gcctagacta 11520 gctggggtgc ctagactagc tggggtgccc agactagctg gggtgcctag actagctggg 11580 tactttgagt ggctccttca gcctggacct cggtttcctc acctgtatag tagagatatg 11640 ggagcaccca gcgcaggatc actgtgaaca taaatcagtt aatggaggaa gcaggtagag 11700 tggtgctggg tgcataccaa gcactccgtc agtgtttcct gttattcgat gattaggagg 11760 cagcttaaac tagagggagt tgagctgaat caggatgttt gtcccaggta gctgggaatc 11820 tgcctagccc agtgcccagt ttatttaggt gctctctcag tgttccctga ttgttttttc 11880 ctttgtcatc ttatctacag gatgtgactg ggaagctctg gtttcagtgt catgtgtcta 11940 ttctttattt ccaggcaaag gaaaccaaca ataagaagaa agaatttgag gaaactgcga 12000 agaaagtgcg ccgtgccatc gagcagctgg ctgccatgga ttgaggcctc tggccggagc 12060 tgcctggtcc cagagtggct gcaccacttc cagggtttat tccctggtgc caccagcctt 12120 cctgtgggcc ccttagcaat gtcttaggaa aggagatcaa cattttcaaa ttagatgttt 12180 caactgtgct cctgttttgt cttgaaagtg gcaccagagg tgcttctgcc tgtgcagcgg 12240 gtgctgctgg taacagtggc tgcttctctc tctctctctc ttttttgggg gctcattttt 12300 gctgttttga ttcccgggct taccaggtga gaagtgaggg aggaagaagg cagtgtccct 12360 tttgctagag ctgacagctt tgttcgcgtg ggcagagcct tccacagtga atgtgtctgg 12420 acctcatgtt gttgaggctg tcacagtcct gagtgtggac ttggcaggtg cctgttgaat 12480 ctgagctgca ggttccttat ctgtcacacc tgtgcctcct cagaggacag tttttttgtt 12540 gttgtgtttt tttgtttttt ttttttggta gatgcatgac ttgtgtgtga tgagagaatg 12600 gagacagagt ccctggctcc tctactgttt aacaacatgg ctttcttatt ttgtttgaat 12660 tgttaattca cagaatagca caaactacaa ttaaaactaa gcacaaagcc attctaagtc 12720 attggggaaa cggggtgaac ttcaggtgga tgaggagaca gaatagagtg ataggaagcg 12780 tctggcagat actccttttg ccactgctgt gtgattagac aggcccagtg agccgcgggg 12840 cacatgctgg ccgctcctcc ctcagaaaaa ggcagtggcc taaatccttt ttaaatgact 12900 tggctcgatg ctgtggggga ctggctgggc tgctgcaggc cgtgtgtctg tcagcccaac 12960 cttcacatct gtcacgttct ccacacgggg gagagacgca gtccgcccag gtccccgctt 13020 tctttggagg cagcagctcc cgcagggctg aagtctggcg taagatgatg gatttgattc 13080 gccctcctcc ctgtcataga gctgcagggt ggattgttac agcttcgctg gaaacctctg 13140 gaggtcatct cggctgttcc tgagaaataa aaagcctgtc atttcaaaca ctgctgtgga 13200 ccctactggg tttttaaaat attgtcagtt tttcatcgtc gtccctagcc tgccaacagc 13260 catctgccca gacagccgca gtgaggatga gcgtcctggc agagacgcag ttgtctctgg 13320 gcgcttgcca gagccacgaa ccccagacct gtttgtatca tccgggctcc ttccgggcag 13380 aaacaactga aaatgcactt cagacccact tatttatgcc acatctgagt cggcctgaga 13440 tagacttttc cctctaaact gggagaatat cacagtggtt tttgttagca gaaaatgcac 13500 tccagcctct gtactcatct aagctgctta tttttgatat ttgtgtcagt ctgtaaatgg 13560 atacttcact ttaataactg ttgcttagta attggctttg tagagaagct ggaaaaaaat 13620 ggttttgtct tcaactcctt tgcatgccag gcggtgatgt ggatctcggc ttctgtgagc 13680 ctgtgctgtg ggcagggctg agctggagcc gcccctctca gcccgcctgc cacggccttt 13740 ccttaaaggc catccttaaa accagaccct catggctgcc agcacctgaa agcttcctcg 13800 acatctgtta ataaagccgt aggcccttgt ctaagcgcaa ccgcctagac tttctttcag 13860 atacatgtcc acatgtccat ttttcaggtt ctctaagttg gagtggagtc tgggaagggt 13920 tgtgaatgag gcttctgggc tatgggtgag gttccaatgg caggttagag cccctcgggc 13980 caactgccat cctggaaagt agagacagca gtgcccgctg cccagaagag accagcaagc 14040 caaactggag cccccattgc aggctgtcgc catgtggaaa gagtaactca caattgccaa 14100 taaagtctca tgtggtttta tctacttttt ttttcttttt cttttttttt gagacaaggc 14160 cttgccctcc caggctggag tgcagtggaa tgaccacagc tcaccgcaac ctcaaattct 14220 tgcgttcaag tgaacctccc actttagcct cccaagtagc tgggactaca ggcgcacgcc 14280 atcacacccg gctaattgaa aaattttttt ttttgtttag atggaatctc actttgttgc 14340 ccaggctggt ctcaaactcc tgggctcaag tgatcatcct gcttcagcgt ccgacttgtt 14400 ggtattatag gcgtgagcca ctgggcctga cctagctacc attttttaat gcagaaatga 14460 agacttgtag aaatgaaata acttgtccag gatagtcgaa taagtaactt ttagagctgg 14520 gatttgaacc caggcaatct ggctccagag ctgggccctc actgctgaag gacactgtca 14580 gcttgggagg gtggctatgg tcggctgtct gattctaggg agtgagggct gtctttaaag 14640 caccccattc cattttcaga cagctttgtc agaaaggctg tcatatggag ctgacacctg 14700 cctccccaag gcttccatag atcctctctg tacattgtaa ccttttattt tgaaatgaaa 14760 attcacagga agttgtaagg ctagtacagg ggatcc 14796 <210> SEQ ID NO 26 <211> LENGTH: 515 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (266)..(266) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 26 ttcggatcct tggctgggat taaaggtgtg agccaccacg cccggcttga aaaaacatgt 60 ttatatatat atatgtatat atataaaaaa tcaaggaagg aaaattccag tttgtagctc 120 agtaagtatt tgcttattac tattgaggcc ctaggttcaa ttcccagcaa tacaaaaata 180 ataactttcc ttttaatgat ttatcttgcc acgatggtga tgacactagc atctcaccct 240 ggacaggcaa gcctggccct ctggcnaccc cagccccttc gtgtctgttc atcattccag 300 gcaaaggaga ccaacaacaa gcaaaaagag tttgaagaga ctgcaaagac tacccgtcag 360 tcaattgagc agctggctgc ctaatgctga gcctttgctg agataacttg gacctgagtg 420 acatgccaca tctaagccac gcatcccagc ttttccagcc agggcctcct agcaggatct 480 tagagcagga gacagtggta ttttgaaact ggata 515 <210> SEQ ID NO 27 <211> LENGTH: 955 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 27 ggcacgaggg ggccggggct ctcccggcat gctctgcggc gcgcctccgc ccgcgcgatt 60 tgaatcctgc gtttgagtcg tcttggcgga ggttgtggtg acgccatcat gggagctccg 120 gcgctgcccc agatctggca gctgtacctc aagaactacc gcatcgccac cttcaagaac 180 tggcccttcc tggaggactg cgcctgcacc ccagagcgaa tggcggaggc tggcttcatc 240 cactgcccta ccgagaacga gcctgatttg gcccagtgtt ttttctgctt taaggaattg 300 gaaggctggg aacccgatga caacccgata gaggagcata gaaagcactc ccctggctgc 360 gccttcctca ctgtcaagaa gcagatggaa gaactaaccg tcagtgaatt cttgaaactg 420 gacagacaga gagccaagaa caaaattgca aaggagacca acaacaagca aaaagagttt 480 gaagagactg caaagactac ccgtcagtca attgagcagc tggctgccta atgctgagcc 540 tttgctgaga taacttggac ctgagtgaca tgccacatct aagccacgca tcccagcttt 600 tccagccagg gcctcctagc aggatcttag agaaggagac agtggtattt tgaaactgga 660 tatcaaatat ttttggtttt gctttaaagt ggctacctct ctttggtttt gtggctttgc 720 tctattgtga cgtggactta agcaataagg aagtgatgaa gggacagtgt tctctgacag 780 gacctgtggg ggtcggggtg cctgtgcaag gtcttggttc tgattgtgat atttccatac 840 agggctgcta atgcagccca tgggtaagtg tggttatatg tgtttgtgct gataattttg 900 tcctgatgag ttttcctacc acggggtaac ggaataaaat cacttgaaaa agtgg 955 <210> SEQ ID NO 28 <211> LENGTH: 1435 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 28 ctggcgggcg tgggaaccca ggccccgccg aggcggccag gaggtgagat ggcagctggg 60 caaaatgggc acgaagagtg ggtgggcagc gcatacctgt ttgtggagtc ctcgctggac 120 aaggtggtcc tgtcggatgc ctacgcgcac ccccagcaga aggtggcagt gtacagggct 180 ctgcaggctg ccttggcaga gagcggcggg agcccggacg tgctgcagat gctgaagatc 240 caccgcagcg acccgcagct gatcgtgcag ctgcgattct gcgggcggca gccctgtggc 300

cgcttcctcc gcgcctaccg cgagggggcg ctgcgcgccg cgctgcagag gagcctggcg 360 gccgcgctcg cccagcactc ggtgccgctg caactggagc tgcgcgccgg cgccgagcgg 420 ctggacgctt tgctggcgga cgaggagcgc tgtttgagtt gcatcctagc ccagcagccc 480 gaccggctcc gggatgaaga actggctgag ctggaggatg cgctgcgaaa tctgaagtgc 540 ggctcggggg cccggggtgg cgacggggag gtcgcttcgg cccccttgca gcccccggtg 600 ccctctctgt cggaggtgaa gccgccgccg ccgccgccac ctgcccagac ttttctgttc 660 cagggtcagc ctgtagtgaa tcggccgctg agcctgaagg accaacagac gttcgcgcgc 720 tctgtgggtc tcaaatggcg caaggtgggg cgctcactgc agcgaggctg ccgggcgctg 780 cgggacccgg cgctggactc gctggcctac gagtacgagc gcgagggact gtacgagcag 840 gccttccagc tgctgcggcg cttcgtgcag gccgagggcc gccgcgccac gctgcagcgc 900 ctggtggagg cactcgagga gaacgagctc accagcctgg cagaggactt gctgggcctg 960 accgatccca atggcggcct ggcctagacc aggggtgcag ccagcttttg gagaacctgg 1020 atggccttag ggttccttct gcggctattg ctgaacccct gtccatccac gggaccctga 1080 aactccactt ggcctatctg ctggacctgc tggggcagag ttgattgcct tccccaggag 1140 ccagaccact gggggtgcat cattggggat tctgcctcag gtactttgat agagtgtggg 1200 gtggggggga cttgctttgg agatcagcct caccttctcc catcccagaa gcggggctta 1260 cagccagccc ttacagtttc actcatgaag caccttgatc tttggtgtcc tggacttcat 1320 cctgggtgct gcagatactg cagtgaagta aaacaggaat caatcttgcc tgcccccagc 1380 tcacactcag cgtgggaccc cgaatgttaa gcaatgataa taaagtataa cacgg 1435 <210> SEQ ID NO 29 <211> LENGTH: 2977 <212> TYPE: DNA <213> ORGANISM: H. sapiens <400> SEQUENCE: 29 ccgaatgtga ccgcctcccg ctccctcacc cgccgcgggg aggaggagcg ggcgagaagc 60 tgccgccgaa cgacaggacg ttggggcggc ctggctccct caggtttaag aattgtttaa 120 gctgcatcaa tggagcacat acagggagct tggaagacga tcagcaatgg ttttggattc 180 aaagatgccg tgtttgatgg ctccagctgc atctctccta caatagttca gcagtttggc 240 tatcagcgcc gggcatcaga tgatggcaaa ctcacagatc cttctaagac aagcaacact 300 atccgtgttt tcttgccgaa caagcaaaga acagtggtca atgtgcgaaa tggaatgagc 360 ttgcatgact gccttatgaa agcactcaag gtgaggggcc tgcaaccaga gtgctgtgca 420 gtgttcagac ttctccacga acacaaaggt aaaaaagcac gcttagattg gaatactgat 480 gctgcgtctt tgattggaga agaacttcaa gtagatttcc tggatcatgt tcccctcaca 540 acacacaact ttgctcggaa gacgttcctg aagcttgcct tctgtgacat ctgtcagaaa 600 ttcctgctca atggatttcg atgtcagact tgtggctaca aatttcatga gcactgtagc 660 accaaagtac ctactatgtg tgtggactgg agtaacatca gacaactctt attgtttcca 720 aattccacta ttggtgatag tggagtccca gcactacctt ctttgactat gcgtcgtatg 780 cgagagtctg tttccaggat gcctgttagt tctcagcaca gatattctac acctcacgcc 840 ttcaccttta acacctccag tccctcatct gaaggttccc tctcccagag gcagaggtcg 900 acatccacac ctaatgtcca catggtcagc accacgctgc ctgtggacag caggatgatt 960 gaggatgcaa ttcgaagtca cagcgaatca gcctcacctt cagccctgtc cagtagcccc 1020 aacaatctga gcccaacagg ctggtcacag ccgaaaaccc ccgtgccagc acaaagagag 1080 cgggcaccag tatctgggac ccaggagaaa aacaaaatta ggcctcgtgg acagagagat 1140 tcaagctatt attgggaaat agaagccagt gaagtgatgc tgtccactcg gattgggtca 1200 ggctcttttg gaactgttta taagggtaaa tggcacggag atgttgcagt aaagatccta 1260 aaggttgtcg acccaacccc agagcaattc caggccttca ggaatgaggt ggctgttctg 1320 cgcaaaacac ggcatgtgaa cattctgctt ttcatggggt acatgacaaa ggacaacctg 1380 gcaattgtga cccagtggtg cgagggcagc agcctctaca aacacctgca tgtccaggag 1440 accaagtttc agatgttcca gctaattgac attgcccggc agacggctca gggaatggac 1500 tatttgcatg caaagaacat catccataga gacatgaaat ccaacaatat atttctccat 1560 gaaggcttaa cagtgaaaat tggagatttt ggtttggcaa cagtaaagtc acgctggagt 1620 ggttctcagc aggttgaaca acctactggc tctgtcctct ggatggcccc agaggtgatc 1680 cgaatgcagg ataacaaccc attcagtttc cagtcggatg tctactccta tggcatcgta 1740 ttgtatgaac tgatgacggg ggagcttcct tattctcaca tcaacaaccg agatcagatc 1800 atcttcatgg tgggccgagg atatgcctcc ccagatctta gtaagctata taagaactgc 1860 cccaaagcaa tgaagaggct ggtagctgac tgtgtgaaga aagtaaagga agagaggcct 1920 ctttttcccc agatcctgtc ttccattgag ctgctccaac actctctacc gaagatcaac 1980 cggagcgctt ccgagccatc cttgcatcgg gcagcccaca ctgaggatat caatgcttgc 2040 acgctgacca cgtccccgag gctgcctgtc ttctagttga ctttgcacct gtcttcaggc 2100 tgccagggga ggaggagaag ccagcaggca ccacttttct gctccctttc tccagaggca 2160 gaacacatgt tttcagagaa gctctgctaa ggaccttcta gactgctcac agggccttaa 2220 cttcatgttg ccttcttttc tatccctttg ggccctggga gaaggaagcc atttgcagtg 2280 ctggtgtgtc ctgctccctc cccacattcc ccatgctcaa ggcccagcct tctgtagatg 2340 cgcaagtgga tgttgatggt agtacaaaaa gcaggggccc agccccagct gttggctaca 2400 tgagtattta gaggaagtaa ggtagcaggc agtccagccc tgatgtggag acacatggga 2460 ttttggaaat cagcttctgg aggaatgcat gtcacaggcg ggactttctt cagagagtgg 2520 tgcagcgcca gacattttgc acataaggca ccaaacagcc caggactgcc gagactctgg 2580 ccgcccgaag gagcctgctt tggtactatg gaacttttct taggggacac gtcctccttt 2640 cacagcttct aaggtgtcca gtgcattggg atggttttcc aggcaaggca ctcggccaat 2700 ccgcatctca gccctctcag gagcagtctt ccatcatgct gaattttgtc ttccaggagc 2760 tgcccctatg gggcgggccg cagggccagc ctgtttctct aacaaacaaa caaacaaaca 2820 gccttgtttc tctagtcaca tcatgtgtat acaaggaagc caggaataca ggttttcttg 2880 atgatttggg ttttaatttt gtttttattg cacctgacaa aatacagtta tctgatggtc 2940 cctcaattat gttattttaa taaaataaat taaattt 2977 <210> SEQ ID NO 30 <211> LENGTH: 76698 <212> TYPE: DNA <213> ORGANISM: H. sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15311)..(15410) <223> OTHER INFORMATION: n = A,T,C or G <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (15414)..(15414) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 30 cgcggaattc cagacctcag gtgatccacc cacctcggcc tcccaaggtg ctgggattac 60 aggcgtgagc caccatgcct ggccgattgt tccaatgtat atgcacccca gtaatttatg 120 agagagccca ggtcttaatt tttaattgtt ttccaagatg gctgtactag gctttcctgc 180 aaatgacacc atagcatata ttgtggttgc caccccagca accaggccct caccctccat 240 catgggctgc ccattatggc atgaggggga ttgacactgg gccaggtatc ttttgcccct 300 ctaggattcc ccttcatcat tctctccatg ccgtctgccc caggaaggcg atctccaacc 360 tcagagacct gcttgctgtt tcccaaactt atgctaatca cacctctatg cctttgccca 420 tactgttccc acctcttgcc ctgcactcct tcccttctca gtctggaaca ttctgaagtt 480 gtcctcacag gattaacaag aattttggac aaaaatatat taatagttat aattaagcat 540 tacttaggct gcactttgac ccactttctt gtaactgaaa attacagggc actagatact 600 gaccatttgc atccccattg ttcctacaga taggtttttt tttttttttt tgacaaggtc 660 tcactctgtc acccaggctg gagtgcagtg gtacaatcat ggctcactgc agtcttgacc 720 tcccacactc aagcaatcct cccgcctcaa cttcctgagt agcccagtct acaggtgtag 780 gctaccacac ctcgctaatt tttaaatttt tttgtagaga caggggtctc cctatgttgc 840 ccagaatggt cttgaactct tgggctaaga ggtcctccca cctcagcctc ccaaagtgct 900 aggattacaa gtgtgagccg ccaccacacc tggcctatag atcagctttc tgatgctaga 960 ataataagcc ttttatttaa gataggtaga atctctgaca ttagaatcat aaggtttttg 1020 tttaagaatt tcttaagatg ttttttagat cctgaattcc agcaagacag ctgacctcaa 1080 atagtctgaa gacccactga cccctacaga ggaatggaat cagcatgaga atacagtttc 1140 ttcatctccc tgttccatga ctttgccctg tgccctttga gcaatcaagg atctccacac 1200 tttggctgat tcccaaaccc ctgaaaaccc tagccccaaa ctctgtggag acggatttga 1260 ggtttcctcc catctcctgg ttcagcatcc ctagaaataa acctctttca ctgctgcaat 1320 gtggtgaatt gacttgccac gtgcaccgga taaaggacct attatggtta caattccact 1380 catcctttaa gatagcttat atgttgtctc tggtcactgc ctccctcctc ttggtgcccc 1440 tcgcacagtt atccatgaga gcacatttgc gtcacctgct ggggcaactg tttgtttaca 1500 tggctctgtc tctcccagca cccagcccag gccagcccca cacttcaaag tccctgcagg 1560 gcaggatggc atggaaaggt cacaggtttg ggagtcagac tgaatatgac tccaccctct 1620 gtcctcagcc tcatctgctc ccccagtttt ctgtgctcta accacactgg cctgcactcc 1680 tgtctcactt catggccctt atacatgctg ttccaactgc ttagaatgct cttcctctgg 1740 ctctttttca tcctttcgtg cccagcttaa ctatcacctc ctgagacagg ccttccttga 1800 ctactgaatc taaaggcaca ccctcttccc attctgtcat tctccagcaa ttcccttcat 1860 tgatttgcca caaccctaat tatcatatta ttcatttact tgtttgctgc ttgtctcccc 1920 tgctagagct taaagtcctt gagtacatac agggactttg ccttgtttac tgctataggc 1980 ccagctctaa cacagggcct ggcatatatt aagtattaaa aaaatttaat tttagctttt 2040 tttttttttt tgtgaacgga gtttcgctct tgttgcccag gctggagtgc aatggcacga 2100 tctcgactca ccgcaacctc tgcctcccgg gttcaagcga ttctcctgcc tcagcctccc 2160 tagtagctgg gattacaggc atgtgcctcc atatctggat aattttgtac ttttagcaga 2220 gatggggttt ctccatgttg gtcaggctag tctcgaactc ccgaactcag gtgatccacc 2280 cgcctcggcc tcccaaagtc ctgggattac aggcatgagc cactgcaagc ggccaatttt 2340 agcttttttc agacaagctg gagtgcagtg gcatgatcat agctgactgc agcctctaat 2400 tcctgggctc agctgatcct cctgcctcag cctcccagga agctagaact acaggaatgt 2460 gccaccaccc ctggctaatt ttaaaaattt ttgatagaaa tggagtctca cgatgtagtc 2520 caggctggtc tcaaactcct ggtctcaagt ggttctctca ctttggcctc ctgaattgct 2580 gggattacag gtgtgagcca ccagtccacc aagaaatttt tattaactga atgaggaatg 2640 aacaaacaaa atagatccaa atccttgctc cactacttac caccagattt gtgtcttagg 2700

acaaattact taccctctcc tcatgtgaag atgaggcctc tcatgggttg tgtattggaa 2760 actgtaaaaa tgcctgatac gtgaagacat tccataaatg gccgttattt tttctttcct 2820 tcatctgaaa aatgtaccct ttttgccaag cataaagacc ttactgtaca tctttacttt 2880 ttcttttctt ttttgttttt tgagatggag tctcgctctg tagcccaggc tggagtacag 2940 tggtgtgatc ttggctcact gcaagccccg cctcctgggt tcacgccatt ctcctgcctc 3000 agcctccgga gtagctggga ctacaggcat ccgccaccac gcccagctaa ttttttgtat 3060 tttgtttagt agagacgggg tttcactgtg ttagccagga tggtctcgat ctcctgacct 3120 catgatccac ccgcctcggc ctcccaaagt gctgggatta caggcgtgag ccaccatgcc 3180 tggccaacgg tacatctttt tttttttttt ttttttttga gacagggtct ccctctgtcg 3240 cccaggctgg agtgcagtgg cacaatcttg gctcactgca acctccaact ccccggttca 3300 agcaattctt gtgcctcagc ctacagagta gctgggacta caagcatgcg ccaccatgcc 3360 cagctaattt ttgtattttt agtagagatg ggattttgtc atgttggcca ggctggtctt 3420 aaactcctga cctcagatga tctgcctgcc tcagcctccc aaagtgttgg gattacaagc 3480 gtgagccact gcgcccggcc tattttcctc ctctgatctg acatcatggg catgtctatt 3540 cttccttcaa accatttcag actcattcct tcctcctatt actcttctga gacctttcct 3600 aataacttta gcacacttga cctctcctac caccaaacca gaggtatcta aagtagggga 3660 tatgcaaccc agcatgtaac acacatgttt tagcacacac gatgcccaaa aaatggaaac 3720 agcccaaatg tccaccaaca gatgaatgga taaacaaaat gtggcataaa cttacaatgg 3780 gatattattc agccatgaaa atgaataaag tactgacaca tgctaccatg tggatgaacc 3840 ttgaaaacat tatgccaggt gaaagaagtc agtcacaaaa ggccacatat tgtgtgagtc 3900 catttttatg taatatccag aatagaaaaa tccatagtga cagaatgcat attggtgatt 3960 gccagacgtt caggggatgg ggaagaaact gcttgatggg taaggggttt tactttggag 4020 taatggaaat gttttggaac taggggtggt ggctgtaaaa gactgaatgt actaaatgcc 4080 actaaatgtt cagtttaaaa tggttcattt cacctcaata aattttttaa aaaatgaagt 4140 agccattctt ccaggtgagc tgaaaagttt gaatgaggca caggctcctt aaatttcttt 4200 tttttttttt tttttttttt tgagacggag tctcgctctg tcgcccaggc tggagtgcag 4260 tggcgcgatc tcggctcact gcaagctccg cctcccgggt tcacgccatt ctcctgcctc 4320 agcctcccga gtagctggga ctacaggcgc ccgccactac gcccggctaa ttttttgtat 4380 ttttagtaga gacggggttt caccgtgtta gccgggatgg tctcgatctc ctgacctcgt 4440 gatccgcccg cctcggcctc ccaaagtgct gggattacag gcgtgagcca ccttaaattt 4500 ctaagatgta aagtgctggg caaatatcag ctggggatgc tgaaggaagg aataatcaga 4560 aggtcagcaa gtgtggcttc gaaactctgc ctcaagtaat aatgataatg ataattagag 4620 atagttataa tattgacttc tttggtttcc ttgtaaacca gtgttatttt agaaaaagag 4680 ggagatagct ctagtaatta cagctaacac ttctacaatg cttaatatga ggaaggcact 4740 gttccaagta ctttacgtct aaaacttact aaatccttac aactctaaga ggtagtatca 4800 tcacatttcc attatagatg agggaatgga agaattgaga agtttaaatg agttctccaa 4860 gtcacagata aggaaatggc agagtccaaa tttgaaccca ggcaagtcag actctaggca 4920 ctgaagtctc aaccaccagg ctctgcacta agtgctctcc aggttttatc tcatttaatc 4980 ctgcaaggaa agtgttatta ttcccatttt attttattta ttatttattt atttatttat 5040 tgagacggag tttcaccctt gttgcccaag ccaaagtgca atggcacaat ctccgctcgc 5100 tgcaacttct gcctcccagg ttcaagcagt tctcctgcct cagcctcccg agtagctgag 5160 attacaggcc accatgcccg gctaattttg tatttttagt agacatgggg tttctccatg 5220 ttggtcaggc tggtctcgaa ctcccaacct caggtgatct gcctgcctca gcttcccaaa 5280 gtgctgggat tacaggcatg agccaccgtg cctggcctat tattcccatt ttaaaaatcc 5340 ccctcatgct atccacattc cacaccttct agtctttctt tttttttttt ttttttttga 5400 gacggagttt cgctctgtcg cccaggcaga cggagtgcag tggcgccatc ttggctcact 5460 gtaagctctg cctcctgggt tcacgccatt ctcctgcctc agccttccga gtagccggga 5520 ctacaggcac ccgccaccac acccggctaa ttttttgtat ttttagtaga gatgggattt 5580 caccgtgtta gccaggatgg tctcgatctc ctgacctcgt gatccgcctg ccttggcctc 5640 ccaaagtgct gggattacag gcgtgagcca ccgcgcccgg cttttttaaa aattttttta 5700 ttttttttat ttttagtaga gaccgggttt caccgtgtta gccaggaggg tctctatttc 5760 ttgaccttgt gatctgcctg cctcggcctc ccaaagggct gggattacaa gcgtgagcga 5820 ccgcgcctgg ccagtctttc tcctacattt atttttacgt tggtccacat actcctgtca 5880 ttctcacttt gcttcacttt tcctttcttc ttctttttta agagacgggg gcttgctatg 5940 ttgtccaggc tggagtgcag tgaggcaatc atagcttatg ccatccccaa ctccaagtga 6000 tcctccagcc tcagcctcct ccctagctgg attacaggag catgtcacca tgcacactaa 6060 ttttcttttc tttttttttt ttggtagaga tggggtctca tgttgctcag gctggtcttc 6120 aacatctggg ctgaagtgac cccccttcct tggcctctca aagtgctggg attagaggct 6180 ttggccacca catccaacct gaattttatt atttatattt tcttttaatc tcccattact 6240 agatggcagg gattttgatt actgttaatt ttccaatatc caaaataatg tgtggtacct 6300 aataggctct caatatcgaa aagtaatagt gcacatggca ttctgtagta ttaggtaggt 6360 atcttgtgtt cctgtgtttg cgtaaataag atcatacatt atgttctgct tttttaactt 6420 aatggctttt tttttccttt ttttgcgaca gagtctggct ctgtcaccta ggctggagtg 6480 cagtggcgct atctcggctc actgcaacct ctgcctactg ggttcaagtg attctcctgc 6540 ctcagcctcc tgagtagctg ggattacaga cgcgcaccac cacacctggc caattttttt 6600 tttttttttt ttaggcggag tctcactctg ttgtccaggc tggagtgcag tggcgcgatc 6660 tcagctcact gcaagctccg cctcccgggt tcatgccatt ctcctgcctc agcctcctga 6720 gtagctggga ctacaggggc ccgccaccac acccggctaa tcttttgtat ttttagtaga 6780 gacggggttt tactgtgtta gccaggatgg tctcgatctc ctgacttcgt gatctgcccg 6840 cctcggcctc ccaaagtgct gggattacat gtgtgagcca ccgcacccgg cctatttgtt 6900 ttgtattttt tagcagagac aggtttcacc atgttggcca ggctggtctc aaactcatga 6960 cctcaagtga tctgcccgcc tcggcctccc aaagtgctgg gattacaggc atgagccacc 7020 acgcccagcc atgtcttttt tttttttttt tttgagacaa gagtttcgct cttgttgccc 7080 aggctggagt gcaatgacgc gatttcggct caccgcaatc tccgcctcct gggtacaagc 7140 aattctcctg ccttagcctc ccgagtagat gggatgacag gcatgcacca ccatgcccag 7200 ctaatttggt atttttattt ttttatattt atttattttt tcgagacgga gtctcgctct 7260 gtcgcccagg ctggagtgta atggtgcgat ctgggctcac tgcaacctct gcctcccggg 7320 ttcaagcgat tctcctgtct cagcctcctg agtagctggg attacaggcg cccgccacca 7380 cgcccggcta atttttgtat ttttagtaga gacggggttt ctccatgttg gtcaggctgg 7440 tctcgaactc ccgacctcag gtgatccgcc tgcctcggcc ttccaaagtg ctgggattac 7500 aggagtaatc ccaaaaaaag cgccgggccc tttttttgtt gttttttaaa ttcagtaact 7560 atctagttca ttcttggatg gatgacaacc cagattggat gtgtagcagc gttctcttaa 7620 ccagtttcct attaatcttc atttcatccc cagtgtttct ccagaatgca aataatatgg 7680 cattaaatat cttcacacat agctttttgt gtatgtgtat acttatttct ctagaattag 7740 tgtctagaag tgaaactgcc gggaggaagg atatatactt ttaacatgtc caagttccac 7800 tgtgatagcg ctgcgagggc acacaacagg tttcaatata ccttggacca aaccggatat 7860 tatcagtttt tttaacttgt tgctaatgtg atgggggaaa aatgaactcg gaatttacac 7920 acaaggaaaa gaccgtttaa ggttcaggga ctgtccacat agctgtcaag tggcggagcc 7980 gtgatttggt attaaagtgc ccggagagga cgcgtcaaag ttggacactg tgccctgtgt 8040 cctgaggcac gtctggtgat cgctgggcct tgcaatgctg ggcaggcagg ccttcctctc 8100 cccttctagg cctctggcca ctcctggctg gccgaaagcc ggttcttctc gattaccgag 8160 tgcctctcct gaaagcaagt cagcgtcgcc taacctcttc agcttcgaaa tggcggccac 8220 cagatcgcta ggccacgccc cgggggcggg gcctgagttc aggccagagc gatggatgcc 8280 cgagccaagt tagaagtcga ctgccagtag ggctcgcgca gaatcggaga gccggtggcg 8340 tcgcaggtcg ggaggacgag caccgagtcg agggctcgct cgtctgggcc gcccgagagt 8400 cttaatcgcg ggcgcttggg ccgccatctt agatggcggg agtaagagga aaacgattgt 8460 gaggcgggaa cggctttctg ctgccttttt tgggccccga aaagggtcag ctggccgggc 8520 tttggggcgc gtgccctgag gcgcggagcg cgtttgctac gatgcggggg ctgctcgggg 8580 ctccgtcccc tgggctgggg acgcgccgaa tgtgaccgcc tcccgctccc tcacccgccg 8640 cggggaggag gagcgggcga gaagctgccg ccgaacgaca ggacgttggg gcggcctggc 8700 tccctcaggt aggtggcagg accgggtcgt ggatgccggg ggagccgggc ggcggggctg 8760 agggatcggc ttccagggcg accgggcctg ggtggcgctg atggagcggc cccgcggctg 8820 ccgggcagag ggcttgggcc aggccgttgt caccctgggg tagcgttggg cgggggcccc 8880 ggagtccggt gtcatggccg gcgagccgag ttcccacatc ccactcaaat ttccttgtgt 8940 ttggcggaaa cgtgccaacg ccacccttat gccatgcgca ttcctcatat ttggcagtgg 9000 gaaaatccgc ccagagctgc cccatatctg ttgtcacttg gatgggccaa ttccttttct 9060 cttgggccgc cgaatgtggg acccgggctt gcaccctttc tcagggtact tcagtcaagt 9120 gacacccttt tagagacgac gtgaggaatc gggtaagaga ggaggaaact ggccagtgcc 9180 ctaccacaaa ggcacagggg cctcttcttg ggtatcagga ctagccttgg gtatcaggac 9240 tctgggttat taatgaaagg tttgggatac ttatagagga ttggcctcag gacgctttgg 9300 aatgaagagc cagggctgtc ttttgtgtga cgcgagagcc gccgggacgc ttcagctctg 9360 cagctgctga ggctctgcga gcgagtcgat gcccaagaga gaggggtttg gacgtcgtga 9420 gaggcgaggc ggccgtgttc attcattgtt ctcgttctag ggctctgggt gtgcccctgg 9480 tattcattct gtggtgggaa gaaggaatgg aacttagtgt atccttgaga tgtgaacggg 9540 ttctaggggg tcacttaatc taagtggaaa atgaattcaa ggcacgttca ttgagcgttt 9600 ctgcttgcct ggtcctctgt gggctgagtg gagagactct gccctccctg cgctcctaag 9660 gcgtgaaaac aatgcagtgt gataagaatt ggcttatcaa gtgttatggg gatttagaac 9720 agttagtttt gcttggggag gagttgagga agcttctaca ctcgaggaga cttctgagtc 9780 gagttttgaa acacctgtga gtaagtgctc atcgggtgag gaggagctca gggaacagct 9840 ggtacaaagg cttagagcca tgtgggagtt gggatgagtt tggggagcag caaattgcct 9900 ggggtgcagg aaggaaatgg tgagagatga gagtaaaata aaagttgcta gaattgtgag 9960 ggggctgtct ttgttgtaga tagtgaacta gttgaatttg gattattgta catgggttgc 10020 cgagtcttca ttcttgctga taattttctc cctttgttga tgttgaagct gatagtgatt 10080 gaacatattt agtttaactt agttaatgac ttttaaattt ttttttattt tttcagaaca 10140 atgcaaactt tttttttttt tttttttttt tttttttttt taaaggaaca ggatctcact 10200

ctgtcgccca ggctagagtg cagtggcatg atcatagctc ggttgcagcc tctaactcct 10260 gggcttaagc agttctcctg cctttgcctc ctgagtagct gggactacag acaggtgcca 10320 ccacacatgg ctaattaaaa aaaaaatagt agagatggag tctggcagtg ttgcctaggc 10380 tggtctcaaa ctcctgggct caggcgatcc tcctgcttcc acctctccct cccaacgtgc 10440 ttgctgggat tacaggggtg agccactggc caggcagaac tttttttttt tttaaataat 10500 agagaggggg tcacactatg ttggccaggc tggtcttgaa ctcttgggct caagtgatcc 10560 tccagcttca gcctcttaaa gtgctgaaat tacaggtgtg atccactgtg cctggctagc 10620 agaacatttt tgataagtgt tttatatcaa atgttttgac ttacacagtg gtgaatgaat 10680 tgaactcata tattcctggg gattcttgca aaaaattctc ttaaagttat acttgctcac 10740 aaaaatgtta actttataaa tgtagaacac tctcctacta atttttattt tattattcta 10800 ttgtttttta tttttttgcg acggagtctc actctgttgc ccaggctggc gtgcaatgat 10860 gcgatctcgg ctcactgcaa cctctgcctc cttggttcaa gcagttctcc tgcctcaccc 10920 tcctgagtag ctgggtaggc acactccacc acgcccggct gatttttgta tttttagtag 10980 agatggggtt ttgtcgtgtt ggccaggctg gtctcgaact cctgaccgca agagatctgc 11040 ccacctcggc ctcccacggc ctcgctggga ttacaggcat gagccactgt gcctggccta 11100 aattttaaat ataagtaatg tactccccag tcttacagaa attggacgac tatagaaaac 11160 aaacatcaaa aaaagtgtag aatgtgagta tttttagttt aataagtgta ttttataaac 11220 tatttatttg tattgacttc tcggataaca acctgttata aaatctttat ccccataaac 11280 ataattttcc taaaatagct ataatattgt gattaatgtt tatgctaaag tgactattat 11340 ggaattaaca gacttcagtt gcagtttcta aatcttgctt tggttgtgat gattatatac 11400 cactgaagaa cattcaggat tattttggct tgtttttacc cttatcactc aagggctaag 11460 ctgtttaaaa tgcaacataa acatttgacc cagttgaatg ctgggatact tggaaaaata 11520 aacctgttac tgtttctgta ctaaaggctt atcttttaaa gatatgtggt gtttttttag 11580 cgcagtggtg cgatcttggc tcactgcgac ctctgcctcc tgggtttaag cattctcctg 11640 cctcagcctc ctgagtagct gggactacag gcgcctgcca ccacgcctag ccaactttta 11700 tgtttttagt agagacggga tttcaccata ttagccaggc tggtcttgaa ctcctgacct 11760 tgtgatctac ccgccttggc cttgcaaagt gctgggatta caggcgtgag ccactgtgcc 11820 tggctgatat gtggtgtttt gtgattataa attgtagtgg agttccttag ttttgttaaa 11880 gtcttgtcag tagttgtaaa aacatcagcc agttgtggtg gctcaggcct gtaagcccag 11940 cactttggga ggccgaggct ggtgaattgc tagagctcag gagtttgaga ccagcctggg 12000 caacatggtg aaaacctgtc cctacaaaaa atacacacac acaaaaagaa aaaaatcagc 12060 agggtatggt gtagtatgcc tgtagtccca gctgcttggg aggctgaggt gaaaggctca 12120 cctgagccca gggagattga ggctgcagtg agccatgttc atgccactgt actccagtgt 12180 tggtgatgga gtgagaccct gtctcaaaaa aaaaaagtgt gccttcaata gaaggcttga 12240 acgtatttta tgggatttgg tttagctgaa aaaaacagtg agaagcagat taagctggta 12300 atttctgaca aaaagtatct aaaagatgaa gtgaagaatg ttaaacatca agtattatat 12360 tacagttgct cttagactag tagcttttag tttataacat gtcatttgtt tgctctgaag 12420 attaagcaag ttcatacttc ttggaagtta aatttgactt ttccagaagc actggattat 12480 ttacgaaata aaaaatataa ttgataactt taaactacta tttcaggtag tctattacta 12540 gtaaatgtat gattctacat ttaaatttca ggtaaatctt tgttagtaac ctactgccta 12600 aaaaaatgtt acatgaggga gtacttttgt ttgcatgtta ggatcataat aggccataca 12660 taataatctt gagcttggga ggagcttgtt agccaaacag catgccttaa tgttgacttg 12720 cagaagacaa ttttaaatat tgcctttgaa aggcagtgga taatgtgaca gtgagggggt 12780 ttatgaaacc ataaaattga gctttttgac ttagtttttg tttttaagtt gttcagatct 12840 tgggagtcat ttcttcaaaa caaatgacta tgaggtggaa aattacttac cttgaataaa 12900 ttaattggaa aatcagagaa cactgggttt atttaggatg aggttgtttg gtatgtgtat 12960 gggagggtag aattcctaat tgctcatctg actgggttca aaatgtaata ctagatattt 13020 gtgttgcaat tcagttggta cttttggtat agggctaact tatcttgcgt gtaatttttt 13080 tttttttttt ttgagatgaa atctggtgct gttgcccagg ctggagtgca gtggtgtgat 13140 cttggctcac tacaacctcc gtctcccagg ttcaagggat tctcatgcct cagcctcccg 13200 agtagctggg attacaggcg ccggccacct tgcctggcta atttttgtat ttttagtaga 13260 gacgaggttt caccatgttg gccaggctgg tcttgaactc ctgacctcaa gtgatccacc 13320 tgcctcggct tcccaaagtg ctggcattac aggctcgctc aggcatcttg ccttgtaatt 13380 ctcatgatag taatggctat ttttttcttg ccttagagtt gtaagtaaaa attccttaat 13440 tacacattaa ggtttgatct ttaattttac aatgtttgag tcattttgtt acttcttttc 13500 tcccagaatg acttgcgtag ctctaaatga ttttagttaa tttcacatct gtttgccttt 13560 cttctaaaat gacccctaga atctcagctt aactaaggaa aatgtcaagt gggtgttgtt 13620 tctttgttag tggttttggc ctagactatc taaagtttgg caaattactc acaaagtatg 13680 ttaattggca tcacattcca atcagtgtac atagcatttt ttgaggaaca cttgacacac 13740 ggttttattt ttagaccaga ttctaagggg ttttactggg tggggcttaa caatcctaaa 13800 gctagtttac ggttttaaaa tctttatgat ttagaggttg tttacatttt ttgttaataa 13860 atgggaagca gcaggcagtg gcagtcaatt ttgtttgttt ctttttttgt tttttttgag 13920 acggagtttc gttcttgttg cccaggctgg agtgcagtgg catgatcttt cctcaccaca 13980 gcctctgcct cctgggttca agcgattctc ctgcctcagc ctcctgagta gctgggatta 14040 caggcatgcg ccaccacacc tggctaattt tgtattttta gtagagacag ggtttcactg 14100 tgttggtcat gctggtcttg aactccctaa ctcaggtgat ctgcctgcct cagcctccca 14160 aagtgctggg attacaggcg tgagccacca cgcccagccc tcacataact tttatgatat 14220 tatgttctta taattgttcc attattaatt ataattaatc tctcactgtg cctaatttat 14280 atgttaaact tgatcatggg tatgtatgta caggaaaaaa catagtgtat acagtatagt 14340 atactgttct tgctttcagg cattcattgg tagtcttgga acatattcca agtggatatg 14400 gaagcactac tatgtgatgg aatgttactc agtaataaaa agaaggatgt actggtgtat 14460 actacaacat tggaaacata ttaagtaaaa gaaaccatgc aggaaagacc acatattgaa 14520 ttattccatt tatatgtaat gtccagaata ggaaaatcct tagtgacaga aagtagatca 14580 ggggctgagg gatgtaggga atggtcagtg actgtgatag ggttttcttt ttgcttttga 14640 cagcggtctg cattcataat tgctaatact tggaagcaac caagatgtcc ctcagcaggc 14700 gaatggaaaa actggtacat ccagacaagg gactattgtt cagtgccaaa aagaagcaag 14760 ataccaagcc atgaaagaca tggaggaaac ttaaatgcat atcactgagt ggaagaagcc 14820 aatctaaaaa ggctgtatac ggtatgactc ccaactatat gaaactgtgg aaaaggcaaa 14880 actgctgaga caggaaaaag atcagtggtt gacggaaggg agggatacat aggcagagta 14940 cagagaattt ttagggcggt gaaactactg taatatgtca ttatacattt gtcaaaaccc 15000 atagagtaag cctgggcaaa atagcaagac cccatctcta ccaaaaattt ttaaacctag 15060 ccaggcactt gtcctccaaa agcccacttg gccctcttca agtatatttt actttctttt 15120 ccttcctgct ctgaagcttt ttataacctt tcatgctgct ggaaaacttg cctcagtttc 15180 tttatcttgc ctatgcccct catccaattc cttcttctga ggaggcaaaa atgagggtcg 15240 tgcagcctgc acggatcact tgccggaaac tcgacacccg cacgcaaaat aattcggggt 15300 gcgctcacta nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 15360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn aagnaaaagg 15420 ttaggaaaca ttaacttagc ctgcctcttt tttttttttt tttttttttg agacagagtc 15480 tcgctctgtc gcccaggctg gttggagtgc agtggcatga tctcggctca ctgcaagctc 15540 cgcctcctgg gttcatgcca ttctcctgcc tcagcctcct gagtagctgg gactacaggt 15600 gcccaccacc acgcccggct aattttttgt atttttagta gaggggtttc accctgttag 15660 ccaggatggt ctccatctcc tgacctcgtg atccatctgc ctcggcctcc ctaagtgctg 15720 ggattacagg cgtgagcccc cgcacccaac ccttagcctg cctcttaagc tgtaagtggt 15780 cttgatatgg agatagaaaa taaaatacta tgaatgacaa ataatctaaa acttgaatta 15840 aataaagtag gtgtattttt attttgtcac tttttattaa aagttattgc agtatattct 15900 ctactgagta ccagcactat attttgagtg cctgcaagac ttagaattca ttgtaaaatt 15960 actgttcttg gactgaggtt acattttagt cttatcagtg gattcttcac caatcgattg 16020 gaatcagtca attccaatac agtcttcccc cacagttgaa tatagaataa aatctattgc 16080 aagctgggtg caggggcaca agtgtggcag gagtgcttga gcctaggagt tcaagaccag 16140 cctgggcaac atagtgagac ctcatctcaa ttgaaaatat atatctatat aaaaaataaa 16200 atttattaca gttcatcttg ctggaaaaca aaatactgtt tttgtaatta aaattttttt 16260 tttaaattta gaaatggggt cttgctgtgt tgaccaggct ggtcttgaac tcttggcctc 16320 aagctgtcct cccatctggg cctcccaaag tgctgggatt acaggtgtga acaactgcgc 16380 ccggctgaca aagtattttt taaagatgta ccactaaatg gagatttgat tcacatttga 16440 tagtttttga caggtctttt ctatttaaaa acattactgt ttttgtagca ttattctggc 16500 ttttccctta atttagtaaa tatttgagtg cctttgtatt ccagatactg agcaagattg 16560 gcagggttct gcccttatgg agcagaagga aggtaggggg actgactaaa acttgaaaac 16620 tgtctaacat aagtaccatg cagaaaatga aacagtatta attggcagaa ggagagcagg 16680 ctattttggc tagtgtggtt agggaaagcc tctctaaaga gatgtctctt gggtggagac 16740 aagatgtgaa aaaaccagct tgcctgtttt tggggtttca gccttgcagg tgaagagaaa 16800 cacgaagttc agaagtcttg aggcacaaag tctggcatgt tacgaaagaa ggcctttaga 16860 cgccttgtca gggagtttag attttattct gagttttaaa acgggagtga cacaatgagt 16920 tgcattttaa gcctgttcag gctgttacat ggattattag gagctgtatc atttcaggct 16980 agtgagatgc tcagatgagt ctgccttctg tctcttccgt catctatttc tctcttatct 17040 ggtcttaagc tcctccatct tttccttttt agttggaaaa aaactcaaag atctagaaaa 17100 aagaggagct gtatgtactc ctaaaaaggg acctcatagt aacctgggga tagagttatg 17160 taggagtgag tcagggctca ggttgaggct ttagaggcag gaggcagcga gatcttgttc 17220 tgtcatcccc tcttacagaa ataaaatatg ccgataaaag tttatagtgt aatagtaaaa 17280 tataaaaaca aaaagtaagt aatgtagaaa ataaaaaccc ttcacagtcc tgctgaaatg 17340 attactgtta acactttaat tctagagttc cccatccatt tatttatttc tagatttccc 17400 tctttgtaga ttaatattaa agggttcaga cttgttcatt ttttgttgtc ttggatatct 17460 tttcccacct ctgtatatat ggatctactt tatttatcac gtggatatta acatggttta 17520 tttaattccc tattgttagg tatttggtct ttaccacagt ttttcaaggg tatgaatagt 17580 gctgcaagga atatgcttac acatgttttt atacacttgt cttaggcttc tgtaggacaa 17640 atttctggag tagaatacta ggtcattctt taagaacatt tcaaactttt aatagatatt 17700 accgtattct ttcccaaaaa gaatgtacaa agactgtatg agaataactc catgttgtga 17760

tcttaagttg tctctaaacc tctttggttt tcttagctgt catctaagaa tactaagtat 17820 ctaacctccc tcttgatttg ggcatgtgat gtgatttagc atatagtgga tattcagtta 17880 gaaacttttg gttgaaaaca aggtttggat tctgtggtct ttaattctag gccatttcag 17940 ctctgactaa aatgatttga gtgttagtgt tatatatggg aaggtaaggg ctatggagtc 18000 agtgcagccc agttcagaat cccagtttgc cacttacaag ctgtgtgtgt gagaattttc 18060 tcaactgtaa aatggggaca taattcctac ctagagtaat actgtaagta ttaaggtgga 18120 taatgattgg aatgtatgct gtgtatcctg cctcataata gtaagctttt agtaaatggt 18180 agctactgtt aataataaaa caagtttctg aaggaggaag gcttgaaaag atgggattcc 18240 ttatcaacct caaagttttc taaaggagga aaccctaccc cccttacttc tgcatggttt 18300 ctgaccatga actgaactct gaactctgaa tgaactgaac tctgaactct gaatgaactg 18360 aactctgaac tctgaatgtt atggtagaaa attcatggac tttaaattta aacagataaa 18420 gaatctggtt attttaccca ctgctggggt gttcttgggc aagtagcatg acttctgtgt 18480 ccaaaaaaga aagggtttgc agtgactgaa cctgtaatcc cagtactttg ggaggctaag 18540 gagagtggat tgcctgagct caggagttca agaccagcct gggcaacata gtgagagcct 18600 ttctcaacaa aaaaaactgt tcttaaaaat tagctgggca tggtgatgca cgtctgtggt 18660 cccagctatg tgggaagctg aggtaggaga atcatttgag cctggaaaat tgaagctgca 18720 gtgagctgtg atcatgtcac tgcaccccag cctgggcaac agagcaagac cctgtctcag 18780 aaaataaatt aattaaaaag aaagtgtgga tggaggaagg gattaaaaat ctggctgggc 18840 acggtggctc atgcctgtaa tcccaggcgt gatttgggag gccgaggcgg acagatcacg 18900 aggtcaagag attgagacca tcctggccaa catggccaac cccatctcta ctaaaaatac 18960 aaaaatcagt cgggcgtggt ggtgcatgcc tgtaatcccg gctactcggg aggctgaggc 19020 aggagaatcg cttgaacctg ggaggttcag tgagccaaga tcgcgccact acactccagc 19080 ctggcaatag agtgagactc tgtctcaaaa gaaaagaaaa gaaaagaaaa tctttggggt 19140 tcttacacaa attaaatgag ataatttatt attattattt tttttgagat ggagtcttgc 19200 tctgtccccc aggctggagt gcagtggtgc gatctcagct caccgcaagc tctgcctccc 19260 gggttcacgc cattcccctg cctcagcctc ctgagtagct gggactacag gcgcccgcca 19320 ccatgcctgg ctaatttttt gtatttttag tagagacagg gtatccctgt gttagctagg 19380 atggtctcga tctcctgacc ttgtgatccg cccatctcgg cctcccaaag tgctgggatt 19440 acaggtatga gccaccatgc ccggcttgag ataatttata aagtgcctaa aatacatcct 19500 agaaatatta gtttttcttc cttgaagtca taaattatgg cttacacttt ttttcaggta 19560 tttctcatag tactaatgtg ttgctcacac tcaagggtag tagttgctta ggaagaagag 19620 aaatgtagtt gaaaaagtaa tagactagaa gtcttgagac ctgggctcat gttccaagtt 19680 ggcttttttt tttttttttg ggagatggag tctcgctctt gtcccccagc ctggagtgca 19740 atgacacgat atcgactcac tgcaacctcc acctcctggg ttcaagtgat ttctcctgcc 19800 tcagcctccc tagtagctgg gatgacagac acccaccacc atgcctggct aatttttgta 19860 ttttaagtag tgacagcatt ttaccatgtt agccaggctg gtcttgaact cctggcctca 19920 agtgatgcgc tggcctcggc ctcccaaagt gctgggatta caggcatgag ccactgtgcc 19980 tggtcccttg ctaaatgttt tgttttgttt tgttttgttt ttgaggtgga gtcttgctct 20040 gtcacccagg ctggagtgcg gtggcatgat ctccgctcac tgcaagctcc gcctcccagg 20100 ttcccgccat tctcctgcct cagcctcccg agtagctggg actacaggcg cccgccacca 20160 cgcccggcta attttttgta tttttagtag agatggggtt tcaccgtgtt agccaggatg 20220 gtctccatct cctgacctcg tgatgcaccc acctcggcct cccaaagtgc tgggattaca 20280 ggcgtgagcc accgtgcccc gcagttgctt gctaaatctt ttaactgctg gtcccatttt 20340 cctcatctat gaaatattta atggaagtgt actattaaag aaacttttct ttgctgatga 20400 atgcaggagg tatcattaaa aacccacata gtgctatttt cataattact ctttatgtat 20460 tgtgttcttg ggttgaatac ttttgttcta gagttacaat tatttgtgtt tcttaccagg 20520 tttaagaatt gtttaagctg catcaatgga gcacatacag ggagcttgga agacgatcag 20580 caatggtttt ggattcaaag atgccgtgtt tgatggctcc agctgcatct ctcctacaat 20640 agttcagcag tttggctatc agcgccgggc atcagatgat ggcaaactca cagatccttc 20700 taagacaagc aacactatcc gtgttttctt gccgaacaag caaagaacag tggtatgtga 20760 acattctact taggaaattt agctatttat ctgcctgtgg agcacattaa ggatcatgtt 20820 caacttaaag acaggcaaaa tattcattgt catttagggt ctttattttt ttttttctaa 20880 ctgcagattt atttttttat attgctgttc cttccacacc ccctattttt tcctacctct 20940 tggccttcct tctgttactc ttgcctggaa tgtcttcctt tgtgccactt catccaaaca 21000 aatagtacat tcttatgggt atatttcaaa gacttttctt tgagaagtct ctaggccttt 21060 ccaactactt attttagaag acattttatt tcttctatta aaatattcac ctaaagcttt 21120 ttgactatta caatcaagta taaagaagaa agtaaagtta catagaaaag attatttttg 21180 tatatttcat aggcccagga ccagtctgga ggcagcttag aaatcataga atcttctttt 21240 tcagggcact gacaccagcc acttagttct gcgtagttta ttttttcagt gccagtgaca 21300 ggttcatatt ggcatcatgg caggacactg ccactaggtt ttctgataga aaatttcttt 21360 ttctttttct tttctttttt ttttttttga gacggattct cactctgtca cccaggctgg 21420 agtgcagctc actgcaacct ctgcctcctg ggttgaagtg attctcctgc ctcagcctcc 21480 caaatagctg ggactacagg cacacaccgc cacgcctggc tgatttttgt tttttgtatt 21540 tttagtagag acggggtttc accatgttaa ccaggctggt ctcaaactcc tgacctcagg 21600 taatccacct gcctcggcct cccaaactgc tgggattacc aacatgagac accacgccca 21660 gcctgataac aaaacttcaa tttttctaag aatttagctc tcaaaaagtt ttctggctgg 21720 gtgtggtgat ttatacctgt aatcccagca ctttgggaga ccgaggtggg cagattgctt 21780 gagctcagga gttcgagacc agtcgggcaa cgtggcaaac cccatctcta caaaaaaaaa 21840 ttcaaaaaag taggcctggt gcagtggctt acgcctgtaa tcctagcact ttgggaggct 21900 gaggccagct cattacttga ggtcaggagt tcgagacaag cctggccaac atggtgaaac 21960 cccatctcta ctaaaattgc aaaaattaca gccaggcatg gtgttgcacg tttgtaatcc 22020 cagctacttg ggaggctgag gcaggagaat cactcgaacc cgggaggcag aggttgcagt 22080 gggccaggat tgcgccactg cactccagcc tgggcgaaag ggtgagacta tattaaaaaa 22140 agaaataaca acaaaaatgt agccgggcgt ggtggcacac gtctgtagtc ccagctactc 22200 ggtactcggg aggctgaggt gggaggatgg cttgagccca ggaggcaaag gttgcagtga 22260 gctgagattg caccacttca ccccagcctg ggtgacagag agccagaccc cttctcaaag 22320 aaaagaaaaa caaaaaaagt tttctactat tatggataaa acaaacaaaa ccaaccacct 22380 ggccaaaaca gaaaagtgaa attgcattgg ttttgcttgg tggaactttt gagaaaactt 22440 gggttcaaaa cttccatgcc tcttcctttc ccatcctctg ttctttgtgt aaaatcaatg 22500 cattgtgttt attccatata gtcaggtgaa gcaaggttct gaggtgggga accccagtcc 22560 agagttttct gtttgcttct aacagttcca ctcttcccaa tttgttaata aattgtttat 22620 actttttttg tgaacctaag gagcctccca agtgtagtgt tgaatactta ggtgcatttt 22680 gaactgaagg caaaactcaa aagtctaact ttaattaaag tttgagtaag tttatctttg 22740 tctctcttcc taaaaatgaa aattttatgg ctggcaaaat aagcagtaat aatcccctat 22800 atctgaacaa tggtcttcca tttgcaaagt aattttgcct actgtttctc attaattttc 22860 tttgtgacct taaattgaga agtcagatag gaagtgtgtg ttatgagaag ctgaagacca 22920 tttggtgctt cttcaaagtg ttattgagac tatcttctcc atccccatct gctaccagtt 22980 tgcccagaag gctgggaaac ttaatttggc atagtgatta agtgtatgaa cctttaaaac 23040 aagaaaatcc caatttaaat cctcattgcc ttttattagc tgtatcattt agacaagttc 23100 tgtacttttt tgatcctctt tcctgacctt tatgaaatga ggcttgtact tagcacagtg 23160 gctgattcat aagtgaagtg gtagctatta ttattattat tatatgtatt ttttttagat 23220 ggaggctctc actgtcaccc aggctggagt gcagtggccc aatctcggct cactgcaacc 23280 tctacctccc aggttcaagc gattctcctt gcctcagcct cccaagtagc tgggattgca 23340 ggcacccgcc accacgcctg gctaatttgt ttgtattttt agtagagaca gggtttacca 23400 tgttggcaag gctggtctca aactcctgac cttctgatcc gcctgcctcg tcttcccaaa 23460 gtgctgggat tacagacatg agccactgca cccggctgct atgattattt cttagctttt 23520 tatacatcta tgtagtcctt gatcccctcc atttgagcac agctggtggt tggaagccaa 23580 gcttgacttc tcctacagct tatgagaagg ttgtagccta ggttagtttt gcctgtttct 23640 ttgggtaaag atgaactaac tgtggaagaa ctagctgctt tcaccaggca cgcagcttga 23700 ggaaagcggt agaagaggga agagttgctt agctaggcca gcaccatcag tcagctcttt 23760 ttactcctcc ccaggttgct ttacttcctg aacccagaat gactctcata atcactcagt 23820 gggttctaga aattatttaa ctgatttcag catgtatcca tggagggctg taaagaggag 23880 aatgagacag aggacgcgta tctgatttaa ataattttag atgtgataat taggtttttg 23940 aatgtttctt ggaattttta ttttctaaat gtgtgcctct ttgacttcct cctgctgctg 24000 ttgctgctat tgctgctgct gctactgctt ctaattatta ttagataagt gattgactgg 24060 agccgaggac cactactatt agagtcagct gaccagcagg ttaaaataca gattcattct 24120 gtatgaatgg gctttattcc atactaactg aatcagaatc cttggatgtg ttggacaggt 24180 agatggaatc tatattttct caagcttctc tgaggattct aatgccagct acatttggga 24240 atctgactgg attagatgat atttaaagaa ctgtccagct tgcagtatga tttagtgaag 24300 actgataatg taacagatat cactttatag cttagaaaac attgctatac agtatttgat 24360 gcaggtcatg attccgttag gtatgtttat tactctttgt tttcctcatt cttagtgtct 24420 tagtagttca catcagtata gcttacttgt tttgtttctg aaaagctgga agttggtggg 24480 tatcactgcg tcaagaaact tttaaaataa acttattttg gaacattaaa aaatatatac 24540 aggctgggtg cagaggctct tccctgtaat cccagcactt tgggaggctg aggtggaagg 24600 attgcttgag cccaggagtt tgagaccagc ctgggcaata tagtgagatc ttgtctctac 24660 aaaaaaaaaa aacattagct agaagtggtg ctgcccacct gtggtcccag ccgaggctga 24720 ggcaggggga tcacttaaac tggggtggta aagggtacat gtgtcatgat catgccattg 24780 tattccagcc tagatgacag agcaagattc tgtctcagta tatataatat agattttaca 24840 cacacacaca cacgcacgca cgtagagaaa ataacaaatc tgatgtaccc cttacccact 24900 ttcaacactt agctaaccat ggcaggcctg cttaatctgt tttcatccac tcctttccca 24960 gtgttttgac acaaatccca ggtatcattt gtctgaacta ttttggtatg tacaagaaac 25020 ttttaaagaa tgctaatttt atttattttt aaataggtaa agcattcata tgagccaaaa 25080 gtcttgggtg acccctgccc ctgtatcccc atttcttttc ctcagaggtt tcttatgatc 25140 aatctttatc tattcgaaga atcagttggt ttccccttac cctgttgttc acgacctttc 25200 ctttcttcca catctctgaa ggagaggaaa aaccatcggt agctaaggag gctatcacaa 25260

actccaaagg aacttttttc gtttggagaa tcttttcctt ctcccagatg attgatcctc 25320 ctggagaata ttccttcccc actcccatca ccttctcgac taatctgtta caagttcaaa 25380 ttcttctata ctgtactctc aatgtggagt ccatctttgg gcttcaaaga atgattactg 25440 ggcagataag tccccttcag tccctggtga tagcaaaata aagccttgtg aaaaacttct 25500 tacgttgccc ctctctgatg ttttcaaatt ccttatgctt acatgcattc ccttctttcc 25560 tagattgttt tctctgcttt gcatccacat actatgccct agtttggagc ctggtaacta 25620 gaagggccca gataactatg tcctctttct taagactttt ttctgttgta aaccagctag 25680 agaaggttgg ctggattggc attgaggtgg ctggagtaag agccaagatt aagaacactt 25740 tgggcctttt gcagccctgc tttacttcct tccccctccc cgtgtaccca cataggtaga 25800 tatatgcata cactcaccac cttctggggg cggggtgtgg ggggggatgg cggggtgggg 25860 gagcggttgg ctggctgctg tcagctgtta gcactttcaa tcagaggagg aacctggtag 25920 gcagttcaca agcactgcaa atctctgttt tgccctcctt gctggccata ctgactctag 25980 ttaccttact tttgattaat tcttggcttt gaagttaaac atggagggct tttatcaaaa 26040 ctctgaaatt ttcattcaaa tttttttaca gctgccatta attgtgagta tcctgggcac 26100 tcacacttcc cagtagggtt ctgagtacct gcctagcttt ttgaggattg agtacagggg 26160 aatatagaga agtatgtgcc actaaggctg cttggtatgg tgtgcacata tatttaaact 26220 aagattggtg tttgtcccta cagcagggct ggagttctat atcttccact tcctgctttg 26280 ccttcactag tgttaagtac ttgtgagatg gaatttttgt tagaatcatc agtcattttt 26340 gttgaaagag gttgaagtac aaattttgat cataaaaact cgtttgttta tagatcagat 26400 tggcttattt cctctctaat gaatctagtg aacatatatg tgtatacatt ctaatcacac 26460 aaaattagag acgtataaag gaaaagttta tcattttatc tttcttaacc actttctaac 26520 cactttctta actgtctctt gatgtgaaca gctaggtgta aatctttcca cttgtataac 26580 atatacagat ttcttcactt tttttttttt tttttttgag acggagtctc gttcttgtca 26640 cccaggctgg agtgcaatgg tgcgatctca gctcactgca acctctccct cctgggttcc 26700 agcaattctc ctacctcagc ctcccaagta gctgagatta caggcgtcca ccaccatgcc 26760 cggctaattt ttgtattttt agtagagacg gggtttcacc atgttggcca ggctggtctc 26820 gtactcctga cctcaggtga tccacccgcc tcggcttccc aaagtgctga gattacaggc 26880 gtgagccacc gtgcctggcc tcttcacctt taaaataatc ttactctatt attctgaagg 26940 atattttccc ccaattaata tatcatggac tcctctccat ccaggtcatt ataagtaata 27000 taatagctgc ataatgtgac ataatacaga tgtctcacac tccattcaag tactttccta 27060 ttgctggaca ttcaggttgt ttcgtatatg tgtgtgtgcg tgggccatca caagcaatac 27120 agactggtgc atttatttct gtgcccacct ttccaagggg tgctgcagcc tgtgttggtc 27180 ctaaaggtgg tcctttgttt gtaggtcaat gtgcgaaatg gaatgagctt gcatgactgc 27240 cttatgaaag cactcaaggt gaggggcctg caaccagagt gctgtgcagt gttcagactt 27300 ctccacgaac acaaagggta agagctcaaa agtcaattga cttcttcaga ctagtaagga 27360 tcttctagct tcaaatagct atgtttgtat taaattgtac tagcttccta tagaatattg 27420 tatatttcta tacctttctt tataaagaga taattcagaa aaataggtat taagaaattg 27480 aaattattgc ttggacattc tcttgaaaag ttaaatacac gttaagctgg gcctgatgac 27540 caatacctgt aatttttttt tctttttgag gtggagtctt gctctgtcgc ccaggctgga 27600 gtgcagtggc gcgatctcgg ctcaccgcaa gctccgcctc ccgggttcac gccattttcc 27660 tgcctcagcc tccggagtag ctgggactac aggcgcccac caccgcgccc ggctaatttt 27720 ttgtattttt agtagagacg gggtttcacc gtgttagcca ggatggtaat acccgtaatt 27780 ttaacactgg gaaactgagg caagagggtt gcttgaggcc aagagttcaa gaccagcctg 27840 ggcacatagc gaaggcccat ctctacaaaa gatttttaaa aattagccag gcatggtggt 27900 gcggccctgt agtcctagct gttcgaaagg ctgacgtgag aatattgcat gaccccaggg 27960 gcttgaggct gcagtgagtc atgattgtgc tactggactc cagcctgggc tggagcaaga 28020 tcctgtctat taaaaaaagc caaaaaacaa aaaaacaaaa acaaacacat gttaggtatt 28080 gataatgttt ccatggatgg aaacagtgat gttagatgct gtgttttttt gagacaaaga 28140 tttttctttg tgtttactct aatgcattat atagactggg cactcagaaa gtgcattatt 28200 ttatataaag aatgctatcc tcgggagatt gacttttctc attcactaat tttttttttt 28260 attcagttaa atgtgtacta atccctgctg tttgatagat tgtttaaaga tgcagaagca 28320 tttctgcttc agggaagatt catggtttat cctattccta atggtggtgg caagatagag 28380 gcatcccctc aaaggctagg agtaatacct caaagcagca gagctgtcca taattatcca 28440 ttatccatta ttccctccac cccgaaaata tagggaaacc tttaaagggt tcttttttac 28500 cctcttcttg gaaagcgtca cttatgttat tcatcgttag cttacatttt ttcatgtttc 28560 aaagagttct gcagtttggg agaatagccc agggaatgaa tctactcgaa ggggtgagtg 28620 taattctcaa tttaggaggc gtttgttgaa gtgcaaatct ttgaagcaga cgttaacttt 28680 tgctgaaggt agcccaggtt gggtccctaa gccaatccat agtgttcctt aaggactaga 28740 gagattctga gacagggagg gcttggtcta ctctcatcca aggctgcact ggtttggagc 28800 tactctggag tctctaggac agacagcaga ttgtcactag gatcagtctg cagattgatg 28860 agaaaataag gcttgtcctc cttctcttca taagggcaaa atagtccttt ggagttatag 28920 gaagttttcc aggtgctgta taggtaatta tattaaggaa tgtattgttt actgttggat 28980 agtgagaaaa atggcttgac taggcttctg gtagataatg gagaggcttg aatggtgcta 29040 tacatgttat tttctcttta cctgagaata ttcttccttt ggaaaatggg ccagattaac 29100 tggataaaac ataagaaagg aattgggcat tactttttac ttatgtatct attttttgtc 29160 ttatttatac tgtaggcaca gaaagtgtgg tttcagagta gattttaaga cagttaagtt 29220 tctcattgac ttatagaccc tacaactaca gatttgagtc tgttattaat taatagaaaa 29280 gtacattttt catttgtggt tcctttctat ttatctagat tgaaataggc tactgaagac 29340 taaattttgt actgcagcaa tatttataat ccattttaca ggatttgggg atttttgtaa 29400 gattttagtg ttacaaattc caatttaacg tatattgact ttattgtgag attttatata 29460 tcattgttta aagaaaactt tattctggcc agacatggtg gttcacacct gtaatcccag 29520 cactttggga ggctgaggca ggaggaccgc ttgaggccag ggattcaaga ccagcctggg 29580 caacacagca agactctctc tctaccaaaa aacatttttt taagtaaata aagagaaaac 29640 tttattctga gaacatgggc tttggagttc aacagaccta gattccaaca taggccctta 29700 aacttgctgt gtggccttga gcaaattacc ttcttagagt cccagttttc ttatttttca 29760 gatagaaata atacctactt cataggtttg ttgtatgaat taaataaatt attgttgtat 29820 ggattaaata aagttgtgtt tatatggcat gtgataaatg gtagctgttg ttatttctat 29880 tgaactttga tcttgtttaa acatttcatg ttttttttaa atcctttcta gtaaaaaagc 29940 acgcttagat tggaatactg atgctgcgtc tttgattgga gaagaacttc aagtagattt 30000 cctggatcat gttcccctca caacacacaa ctttgtaagt tgcagatctc ttctctttct 30060 ggcatgttga gggctttgcc aggcataaca gagatttctc aggtaatatg cgtatgtata 30120 tatatatata gttggattgt ttaaagttct ttatgctgtt gtttacagta aggcaattta 30180 gatttcatta gtcagagata tactctaatt tgtgattatg aattctgtac atgctggaag 30240 tatgattcat tttgtaaaaa cttttttgga ggccaagaaa tgatgttgtc ttttgtcatc 30300 ttttatttat tcagcataat ttacacctgt gttcttgttg taggctcgga agacgttcct 30360 gaagcttgcc ttctgtgaca tctgtcagaa attcctgctc aatggatttc gatgtcagac 30420 ttgtggctac aaatttcatg agcactgtag caccaaagta cctactatgt gtgtggactg 30480 gagtaacatc agacaactct tgtaaggcat tgttctttta tccaaggaag atagggatga 30540 ggagtataca tactttaaag ggtatttgtt gtagattttg actgacaggt ctggattcta 30600 gactcattta atgaattgtg atccagaaac tactttagaa acagtgataa ttctgaaact 30660 agctaggttt ggtggcattc atactccaga atgagcaggt aggagtagga cttgttatct 30720 gtcaaattga gattgacata ctgtgactgt gattcagtaa ggaaaggagc aaaaggatat 30780 gaaaacaaga agattttttg cttttcgctc ttaatagtat tatctactag ggttgctagt 30840 agacactgct ctgtattttg ttgaatatgc tgaatgagcc tttgacattg agaaggagca 30900 gaaagcacgg ttgatgctat tttcttcact tcaaactgga gaaaacttag ttgtttggac 30960 ttaaaattgt ttgaatataa aatcttgaaa gattcttgtt tctttcagga gacaatatat 31020 ttcatataga taaaatgtta ttaaagaatt taaagtttac attaaaagta catggtccaa 31080 actgcctttt aaaaactgta actaggtata tgaaaagttt aaaagttttg tccttttttg 31140 acagtactag agaaaccaag ggagtgttat tattagacca tgatgaaaac gtttttgctt 31200 tcatggtcac ttacgtattg attttgtgat gagagcttga gtagcacaaa tggcacaagc 31260 ttttaaaatt tatcttattt ttgtccccca cccttttttt tttttttttt ttttggagac 31320 aagtctcttt ctgtcattag gctggagtac agtggcatga tctcggctca ctgcaacctc 31380 tgcctcccag gttcaagtga ttctcctgcc tcagcctccc gagtagctca gactacaggc 31440 acacaccacc acgcccagct aatttttgta gttttagtag agatgaggtt tcaccatctt 31500 ggccaggatg gtctcgatct cttgacctca tgatctgccc acctcggcct cccaaagtgc 31560 tgggattaca ggcatgagcc accacgccca gccttttttt ttattattat tttttaaaga 31620 cagggtctcg ctctgtctcc cacagtggag tgcagtggca tgatcacagc tcactgtagc 31680 ctcgacctct cgggttcaag taatcctcct acctcagcct cctgagtagc tgggactaca 31740 agtgtatgcc atcatgccta gctaattttt gtattttttc tagagacggg gtttcagcat 31800 gttgcccagg ctggtctcga actcctgagc tcaagcaatc tgtccgcctt ggccttccaa 31860 agtgttgtgg ttacaggtgt gagccaccgc atccggcggc acaagctttt gagtctaaca 31920 gacatatgtc aaaatctcag tgttgtcatt aaccataacc acatctgagt tttcgttcat 31980 gcatctgaat aaaggggata ttaccttcct tgcattgttc ttatgaggct tgctgacata 32040 acctgtgaaa ttactaagca caagtgccca cctcatggaa aaaaggtgcc taattactca 32100 cttttctgtg atttattcct tctattttag tcttttatct atgcattttc aagatggaat 32160 gtttccagag aagctgtgtg tgacatagtt tgtgaaatgt tatactgtag tttgaaaaat 32220 attattttga tatagctaga cacaggacca gtatttccta gaaatgcaca ctgggccggg 32280 cgcggtggct cacgcctgta atcccagcac tttgggaggc caaggcaggt gaatcacctg 32340 aggtcaggag ttcgagacca gcctggccaa catagtgaaa ccccgtctct gctaaaaata 32400 caaaaattgg gggaagggat agcattagga gagacaccta atgttaaatg acaagttact 32460 gggtgcagca caccaacatg gcacatgtat acctatgtaa caaacctgca tgttgtgcac 32520 atgtacccta aaacttaaag tataattaaa aaaaaaatac gaaaattagc tgggcatggt 32580 ggtgtgtgcc tgtaatccca gctactcggg aggctgaggc aggagaaccc gggaggtgga 32640 ggttgcagtg agccgccatt acacctctgc actccagcct gggcaacaga gtgagactcc 32700 atcttaaaaa aaaagaaaaa gaaaaagcac acaggagcct gtatgtttat tggcaggtca 32760 gtattattca cattcaataa tcattcaaat ccagttattt ggaatattgt tccctttatt 32820

ctaggtaatg taaaacagtt gaggaaaatg tgactgggaa aagttcagtt ttagtagctc 32880 tgagtttgca aaagcaaggc atgctgattg tctctgtaag attactgcaa gcctaaaaac 32940 cagtctttcc ctgcttttgt ttagattgtt tccaaattcc actattggtg atagtggagt 33000 cccagcacta ccttctttga ctatgcgtcg tatgcgagag tctgtttcca ggatgcctgt 33060 taggtaattt tttacctata gcttttcttt tagaaagtta tttggggtgg tggggttgga 33120 agcttgaaga caaaaaataa gagtttcttc gcattccctc ctctctacgt ggaaacccct 33180 tgctgcttct gtggaacttg atactggtgg tacagcaaaa ggtagaaatt tctgtttatg 33240 gacctgtagg tcttacattc tggaaagtga ctttgactgt agcttcttct gttatcatag 33300 catatttctt aatatgtcat tacattttaa agagcttgag attctgcttt cctcagtatg 33360 tactgagttc aacctcaatg gaaagggtcc taaaacttaa tacagtgatt tgataaaaat 33420 aaaaccctta actttgaaat gcatgttgtg gccgatgcat ttgctaaaac catgtattta 33480 aatagactag tgtctttaaa aacatttaat tagattttca gcataaatat tgtttctcat 33540 gtgtctctga gtttgcatat aacttgtctt tctttactct gttttccagc tttataatca 33600 gttttgttgc gtttatctac tgctcagtgt taacacacat gaatttgaaa cctaaagtaa 33660 aatctacatc caaaatatct tactttaggc caggcacggt agctcacacc tgtaatccca 33720 gcactttggg aggccgaggc agatggacca cttgaggtca ggagttccag actagcctgg 33780 ccaacatggt gaaaccccat ctctactaaa aatacaaaaa actgggtggg tgtggtgata 33840 tgtgcctttt ggcccaggta cttgggaggc tgaagcagga gaatcttgaa cgtggtaggc 33900 agtgagctga gatggcacca ctgcactcca gccttggtga cagagcaaga ctctgtctcc 33960 aaaaaaaaat atattatgta tacacacaca cacacacaca cacacacaca cacacacaca 34020 cacacacaca taatgtgtaa tcagataatg tttaatgtga aaatactatg gaaatattaa 34080 acgcagcata tcttagaata aggaatttgc atatatctgg atatatattt ctgtatggct 34140 tttatttttc ttgataattt gaaaagcaaa tctgaccaag aatttgtagt tacctctgaa 34200 gattagaaga aaccaggcct ctgaagccat aaaacagagg attatgtggg aaggcatttt 34260 tttcaagaca atagaacaat ttcccttaga aaagctggcc tttttccctt taattcatac 34320 atgggtgtta cctgaatctg aacaaacctc gaacgaatct ttagagcaaa taatgaaaat 34380 gttatacctc ttaatgcatg ttcccagttt ggttggtggg gttggtggtg actggaagag 34440 gccagtggtt aatttcacat ttaggtattt ccatctaaaa actgaattcc catttattta 34500 ctttgtttgc tggttgtagc aggtaaggac aaacagaggg taaaatcctg gcctttttac 34560 agacatgctc agcacgtcta cttatctgtt taaataaatt ctcaaattta gtctctaaac 34620 tgggcgtgtt ccaactagct taataggtgg tagcgtggtt gtcaaatgtt aatctgttct 34680 ttcctggaga tgttgtaaaa atttggagta gagtggtgct ttatttaaaa aaagaaaact 34740 tataatgcac tctccttttc attgaattcc caatacatgt attatttcct gttccaaatt 34800 ttgtatgcaa aagcacctag acttaagata atttttagat gtcacacatt tgaaagaatc 34860 aaacattttg tcaaaggttg tacaggtaga gtttgccctt aagcatctta cttagtcaaa 34920 tatgtacttg aaagacttca ccagtatgaa agcctaagtg ccaatcatgg aattttcttt 34980 ctcctcctag ttctcagcac agatattcta cacctcacgc cttcaccttt aacacctcca 35040 gtccctcatc tgaaggttcc ctctcccaga ggcagaggtc gacatccaca cctaatgtcc 35100 acatggtcag caccaccctg cctgtggaca gcaggatgat tgaggtaata gggcaccttg 35160 ggggtggtaa tgtcagtcaa ttaatggggt gaggttgata cttatttcag agttttgggt 35220 ttcaaatctg atcaaggaat gttgcaacac tttctcaggt ctctggactt ttacagttta 35280 ttttatatcc ataatatctt cagactggct gaatagtctg gttagtatat cattcaactg 35340 gagaactaaa acttcctgaa aaaatgttaa catttgaact cttcccatta tcagatttga 35400 ataggctatt aatgaacaag tgtctaagat atttaaagag cagtttagtt ttggtgtggg 35460 acagaaatta acagtgatgg agaactacag attctctgga agacttttgt gattttattt 35520 agaaataaaa gggtggagtc ctaggacttt aataagcagg tgtttgggga gatgtcaaag 35580 tgcccaaagc tagtgttttt gaactgcttt ttcttctctt ggctttttgg ttatgtccta 35640 ttggtttaat ttgctttctg cttcatcttt aataacaact gaatacactt aaatacttcc 35700 tttgttcttt attcttcttt atttctcatt gctttggact agaataacaa cctgagtgct 35760 tctcccaggg catggtccag acgattttgt ttgaggggaa gagtaggtat ttttcttcat 35820 gcctttgctt tcttgtaatt aacaggattg ctaaaactgt cagacagcag actaccaaaa 35880 atgaaatagt tgctaagtta aatttatatt tcttgtcact tgtttccatg ttttcttttt 35940 ctttctttct ttttaaaatt ttttttggca gtagagtata tagaagtaaa aaaaatgttg 36000 tatgtggtat tgatgatagg tgaaatgaat ttctgaagtt aggccaggca tgacggtgta 36060 tgtctgttgt cccagctact ccagaggcta aggcaggagg atcactggag cccagaagtt 36120 ctaggctgta gggagctaca attgtgcctg tgaatagcca ttgcactcca actggggcaa 36180 cataataaga atccacctta aaaacaaaca aaaaatgtta agttagattt tgaggccaag 36240 ggcattaaaa agtttttttt ttaaatcaat tccaaccaaa ggctaatgtt agacttactt 36300 agttggtgct cacagcattg gtattctgtt tatacattag taaccaaatg tgtttttggt 36360 tgataaaccc tagaataaat attctttatt gaaagcttat cagagacaac tatgctctct 36420 ctcatcatgt agacacctgc tgcgttaggc acagtttatc tcattcagac ctcaaatcac 36480 tttcaacata attgtcctgc cactattgtg aggagatcat gtataagcta taaattttat 36540 tattttgact ttatcattat gattagtcct gataatacaa taatatacca gttactgcta 36600 cttctattaa atggtttgtt cctgtatgaa cactgtaata cttacaggga acagtaaagg 36660 tcagaattgg ctgggtggga agatcacttg cgaccaggag ttcaagacct acctgggcta 36720 tatgtagcaa aaccccacct ctacaaaaaa aaatgtaaaa attagctggg cttggtggtg 36780 tgcacctgca gtcctagtta ctcaggaggc ttgggcagga ggattacttg agcccaggag 36840 tttgaggttg tagtgagctg tgtatgattg tgtcaagtaa gaatttttga gtttttatta 36900 taaaagaatt agcacaattg ttgtgcctaa tcatttttta ctttagaagc agggtaaatt 36960 ttgattcctg ttaatttaat cacatataag tcagcatttt taaagtagac taattgttgc 37020 tttattcaaa ttatttgtgg gtctcaaatt attcatagtt ctcttgagta tttagactcc 37080 aggaacaata ggaaaattct ttctagaata aattgatcca actatagaaa ttagcacaga 37140 ataaaatatg ggatatttaa ttgatacagg gaagaaaatt accataacat taaggaaaat 37200 attctgctac ataggaatat aattgtggtt aataaaaata aattgtgctt tgctttaaaa 37260 acaaagaaca gcttagttgg ataatgaaat tacagctgcc gatttctatt gaaatccaca 37320 ttattttttg ccagtgtttt gcccacctgg cagttatcct gctgtactta aaaacacaca 37380 ttcctggact tctcacattc ccctccaaaa catgctcagt caatcgtggg tcggggatta 37440 ggggtggatc ttcattcttc tttccagagt cagaatcact ctccaggtaa ttctgaagac 37500 tagctagttt tgggaaccag aactaggctt tcttgttaaa ttccgaatta tgttttggga 37560 gcaggggaac agcttggttt gattcttttt atctaattat ataattagat atataatttt 37620 atctttttat ataattgagt gggagcattc tagtaatagt tgtgtggaac aagtatcttg 37680 tctatactgt agttacacaa agagaatata gtaggacttc cccccaaaaa atgtcctttt 37740 ttaggatatg ggggccaagt ggtttcatat tattctatta tactgttcta ttccaagcga 37800 tgaattttag attggggttt aggtctcatg gagccctctg caatttaaac tattttccaa 37860 acagtttcta ataaattcta aagatagcct ttgctttctc ccatgaggag aatgtaaccg 37920 atttccaaat ttacccataa ggcagtgttt tgtggtgaaa gagctgaggg ctgagatcca 37980 tatatgatgg tttctggttc tatttctgcc acctactggt tctgccaagt gaccctgcca 38040 agtctctcta cctgttcaga tgtgttttct tatatgtaaa atgtaggttt tgaacttgga 38100 tttgtggtct ttccagcttt ctgtgatttt aggcttggat aaagtatata ggctgcttac 38160 ctttttcaaa tccaacttct agtcaattta gcctaactcc ttgtggagta agagtgagct 38220 tcccccagaa tccacctccc caccctggct ttttaaaaaa agttttgagc ctcagtggaa 38280 caagaatccc aatctttgga agggtctcag ctgagagtaa ctttgctagc ttcccttgaa 38340 agagtatgtt tgttgtgtac attgctttct tttgagaaaa agaatgtggt tttcattata 38400 tatgaaaaac taataccagg cttggcacgg tggctcacgc ctgtaatccc agcactttgg 38460 gaggccgagg cgagaggatc acctcaggtc aggagttcaa gacgagcctg gccaacatgg 38520 cgaagccctg tctctactaa aaatgcaaaa attagccggg cgtgctggtg cacacctgta 38580 atcccagcta ctcgggagac tgaggcagga gaattgcttg aacctgggag gtggaatatt 38640 aaatccttct aatatttaat gaaaaatcag ccttggagat actggccact gatatttgct 38700 gaatttaatc aaggaacgtt gattagagta tgtttaggat ttctatggtt tttagaggtt 38760 tttataatct attttgttct tgcacatcct cctcctcttt tttccctccc ccagagaaaa 38820 tcttttgtgt gtaggagttg accagctttc cttttctgtt tcaggatgca attcgaagtc 38880 acagcgaatc aggtactttt ccatagtcat ttagccaaca ataatgggct ttttttcttt 38940 atgcggtgta tcttctgttg gcttatcctt gtgtggcttc tgtttgtctt gtctattaag 39000 cctcaccttc agccctgtcc agtagcccca acaatctgag cccaacaggc tggtcacagc 39060 cgaaaacccc cgtgccagca caaagagagc gggcaccagt atctgggacc caggagaaaa 39120 acaaaattgt gagtatagac aacagtacct cctgccaatt agggttcagt aagaaaaacc 39180 tcgttggaaa ttagaatact taaacttatt ttgggagaag attctaataa aatacattca 39240 atgaaggaga ttataaatgt cactgtcatt tttggcacac ttgcatcaga cagtttgcca 39300 gtgctataac taaaatggta tttctcaaaa gacaaaaatt ggaagtatgg ttaatatgtt 39360 tatctttaaa agatatggaa acagatgaca tgggttgatc ctttgatgcc ctcattatca 39420 aaagattatt accattgcat ggagtataat aatgatctct acttgtttca gaggcctcgt 39480 ggacagagag attcaagcta ttattgggaa atagaagcca gtgaagtgat gctgtccact 39540 cggattgggt caggctcttt tggaactgtt tataagggta aatggcacgg taagcttggg 39600 gccctccctt tactaactgc agggctttgg tgtgaagtca agtttcagcc cagggggcca 39660 ggaggaggag aggactgagt gctcctgggc ttatagcagt actctccctt acatacttga 39720 ttatacctga agattgaact taattctttt tagactaagt tcttataaag ctcccaggat 39780 aattagaaat tagtgaataa gacttgagcc ctataatcaa atgtcaggag tacttctcct 39840 ttaaactgat taaatacagt ctgcacatgg gtcatgcttg gaagctcctt aagtgagcaa 39900 gagtctgctg ctatggaggg agcatgggtt ctagaaactt taagctggaa aggaccttag 39960 agattgaaat ggggactgat ttgcccatgg tcatgcagtt aggcatagga aagctggaaa 40020 tctcctgaag taacttctct ttgtcctgcc ctaggattag ctgtgggtgt ccctatcaaa 40080 cagggaaggc attgacttaa ttcttgaatc tatgtggaat attaatgttc tgattttaat 40140 ggaaacactt tgtcacttgg aagaaaggta ctatttaact tatgtagtta cagcttgtgt 40200 attttggcaa cactgaacat tttggcaaca tacttagcat ttctctgtta ggtttttaat 40260 gcctctggct ttaggacttt gggaaataat aggtatttcc ttgaaaatgc tgcatgttcc 40320

caaaaagtca tctcttctaa attcagatta taataaagca aaaatcacag agtcccttgg 40380 tgcctatact actttggatg acactggaat tatctttaga gataaatgtg caaagattga 40440 gagaagttaa aagcatcaaa tgaatggagt attaaaattc aaggtactga aaatatcaaa 40500 ccccccccat ttttaggacc tgggggtttt tttttttttt tttttttttt tttttttttt 40560 tttgagatag attcttgctc tgttgcccag gctggagtac agtggcacaa tcacagctca 40620 ctgcagcctc caactcttgg gctcaaacag tcctcctgcc taagcctccc aagtagctgg 40680 gaccacaggt gaatgcccag ctaatttgtt ttaccttttg tagagacaag gtctcactat 40740 gttgcccagg ctggtctcca actcctggac tcaagcagtc ctcttgggtc tctcaaaatg 40800 ctgggattac aggcatgagc cactgtgccc agccttacca tgtgctcgtt aatgcatggt 40860 ttttaccact tgtaattaat catctgacca atttctagtt ccttaagagg attggcaccc 40920 gactgaacat ttgtaaagta catgtggaat gattcctttt cctttgaaaa ttgcatctgg 40980 ctgggcaggg tggctcacgc ctgtcatccc agcactttgg gaggctgagg caggcagaac 41040 acttgagcct aggagttcaa gaacagcttg ggcaacatcg tgaaacccca tctctaccaa 41100 aaattaggta gatgtgatgg cactcgcctg tagtcccagc tacttggaag gctgaggcag 41160 gaagattgct tgagctcagg aggcgaatgt tgtagtgagc tcaatacagt gagtacacac 41220 tactgtactc cagcctgggt gaaagggcaa gaccctgtct cagaaaaaaa aaaaaaaaga 41280 aaagaaaatt gcatctagta tgtactactg ggctgtctcc tgggtcccag agaaatgata 41340 ctgttgtaga atatttattt atatgtattt agagacaaga tctggctctg ttgcccaggc 41400 tggagtagtg gcacaatctt ggcttactgc agtctctgcc tcctgggctc aagctagcca 41460 tcctcctgcc tcagcctccc aagtagctag gactacaggc acatgccacc acacccagct 41520 aatttttgta ttttttgtag agatggggtt tcgccatgtt tcctagactg gtctcgaaat 41580 catgagctca agcgatccgc ctgcctcggc ctcccaaagt actgggattg caggtgtgag 41640 ccactgtgct cagccagttg cagaatattt tagatggcat aaatatctcc aggatttctt 41700 aggaaagaac acaagcactt tgtgggatag agcacttgtg tctgagataa caaggctgct 41760 agtagttgta ggaggcagag caatggatat tgcatttatt gcttctgtta gcattagaac 41820 atttttatat cacattttaa aagccccagc taaaagccag cggatgaagt tttaagttgt 41880 acccaagttt aattttcctc tggttgcgca ctttcatttg gggattcata atttttcaag 41940 gcattggtac gtggtactgc ttctgagctt tgtcttctct caatagagtg agctttcaaa 42000 ctgtgataaa gattatttgt tacagtgtta cttccataaa gactgctatt agaatgtaga 42060 taacttgttt ttaagattct aggtttttta ggccaggtgc ggtggctcac gcctgtaatc 42120 ccagcacttt gggaggccga ggtgggtgga tcacgaggtc agtagattga gaccatcctg 42180 gctaacacgg tgaaacccca tctctactaa aaatacaaca aattagccgg gcgtgggggt 42240 gggcgcctgt agtcccagct actttggagg ctgaggcagg agaatggcgt gaacccggga 42300 ggcagaactt acagtgagcc gagatcgtgc cactccactt cagcctgggt gacagagcga 42360 gactccgtct caaaaaaaaa aaaagattct aggtttttta agtcagaaag tctcaaaagt 42420 cagaggagtg aggagcagtg gacttttatg ccatgctttc agaaagcaag ctctggtcta 42480 tgaatgaaga agaaaaatga gtggtccagg aaacataact tctagattgt tttgtgcaat 42540 acttttttcc gccatattct ggttcctgta tacagtatat ctgttcagta tcttaaaaat 42600 tacaactgtt ttcatgattt tgattgaaga tttttttaac tcagcccacc cacttatgga 42660 agtaaagcag aaagggtctc aaagcaactc agaagcctca ggtgcatgat ttaaaactca 42720 acatatttat ttaaagcagc atctgtcagg cccaaagctc acaacctcct tttgggcatt 42780 aaatttggca tcaaggctgg gtgcggtggc tcatgcctgt aatcccagca ctttgggagg 42840 ccaaggcagg gagatcattt gaggtcagga gttcaagacc agcctgaccg acatggtgaa 42900 accctgtctc cactaaaaat aaaaaaatta gccgggtgtg atggcatgcg cctgtaatcc 42960 cagctactta ggaggctaag gcaggagaat tgcttgaacc caggaggcga ggttgcagtg 43020 agccaagatc ataccacagc actccagcct gggcgacaga acgagactct atctcaaaaa 43080 aaaaaaaaaa agaaagaaaa attctttctc taggccaggt gtggtggttc acacctgtaa 43140 tccctagcac tttgggaggc tgagttggga ggatcacttt agcccaggag atcgagacca 43200 gcctggacaa catagtgaga ccctgtctct acttaaaaca caattagctg accatggtgc 43260 tgtgtgtctg ttgtccccgc tactcgagaa actgaggcag gaggatcact tgagcctggg 43320 agatagaggc tgcagtgagc cgtgataaca ccactgcact ccagcctggg caacagaaca 43380 agaccctgtg tccaaaaaaa aaaaaaagaa acttaaggag tttatattct agtggagaca 43440 gtaaacagga aaagtagaat atatagtatg ctgtaattgc taaggagaaa aatggaggaa 43500 aggagatatg gagtggcagt cccagttcaa tgtttttaat aggttggtca gggaggaatc 43560 tgccaagaaa gtggcatttg catggagggc gagggtgggt ggtgcagata tctagggaag 43620 cagtaacatc aagtgcaaag tggaccactc acctggcctg ctccgagaac tcaaggagat 43680 cttatggctt catttagagt gagtgagagg tatactaata ggagtgaggt ccagtggtag 43740 ggtgttttag ggtcctgtaa agactatcat ttgggttaaa tgggatctgg ggttgtacga 43800 gacctttagg aggtttggca agcctttgtt tgaaaatgag tgtgatgaga gagctcatta 43860 tctgtctgag agcccattct aactccaggt agttcctact agtagaaaat agtttgattg 43920 ggtgcagtgg cccacatcta taaccccaac actttaggag gctgaggtgg gagaatcact 43980 tgaagtcagg aatttgagac cagcctgggc aacatgagac ccttgtctct acaaaaaatt 44040 ttaaaaatta ggtgggcgtg gtgatgcaca cctgtattgt agtcccagtt acttgggagg 44100 ctgaggtggg aggatccctt gagcccagga gtttgaggct gcagtgagcc gtgatggtgc 44160 tgctgcactc cagcctcggt gacagagcaa gagccagagt ggggcgaggg gagggcatgg 44220 aatagttctt tattagagtt gaaatccgtt ttcctataat gtttgctcat tgatcctagc 44280 agactgaatg aatccctttc atggcagtcc ttgggttatt tatatgtaaa tgaggggaat 44340 gctgcagtat agaacattcc ttctggattt cataagaaat tgcaaataat ctgttaccat 44400 aactgtgtta acgagagctg gctggcagat ggatccctgc aagtaccatg ggcactgtct 44460 ttggttgacc ctgttcagtc ttcccatcag tgacttaatc agaggtgtga tatgtatttg 44520 catagtagtg cggatttaga aaagcgagaa gagttcaact ggctaggatg atggaaaaaa 44580 gaaaagatca ccttttaaca gagataagtc atattcattg ttccaaaaag tagaactgga 44640 gggggaagat gtggcttaat gataacgtgt gtggaaactg ccaaggaagt tcagccgact 44700 gcaaggtcag agtaagtcac tgcgtgggct tggctctgaa ttctgaggtt atattactga 44760 ttagggccag aacaggtgac accaaagggt gggttcagtg acaactagag catgcccaga 44820 ggagagctat aagaaaggga atggactaca aaacgaggtc catgaaatag gaaggtcctt 44880 agaagcagtt ccccctgagc gatcatccag catctcccaa gccacatgcc tgaaccccta 44940 gccctgtcct gtcccctccc gttaaaggct ctgccctttt ctgggtcctg gagcctgggt 45000 catagcgttg gccattttcc cagcacttcc actcagttga ctgcctcatt gggtcagttt 45060 accttcacag gatttcttat cttcatccct tctttctgag tccccacagt caaccattct 45120 tcttgtacct ttcctgagct attgcagcag attcctctct ggtctccctc tttctctcct 45180 acaggtgtcc aaatcctacc ctagagttta ctaaacacag ctcaggtttc tctcatcccc 45240 ctcacctcac ctttatttct gatgtgccca gtctgaaaca ttctctgtcc tatttactaa 45300 aatccttccc ttggtttata gcccatttcc ttcagaaaac ctttctgtat tctctttgaa 45360 aagagattta cttaggcacc tgtagtccca gctgcttgga aggctgaggt tggaagattg 45420 cttgagccca ggagtttgag gccagcctgg gcaacatagt gaggccccat ctctaaaaaa 45480 gaaaaaaaaa aaaaaaaagg atttactccc ccatcttggg gaactcccct tctgttccag 45540 cactcctgtc ttggctccaa ctgtaccaga atggacactt atgcaaatga ttgttgtcct 45600 cctactcagg gctggttata cacgtttccc atatggtgtc ccatatggat ccatttttct 45660 agatagaagg tagctccaaa catagtgtgg atctctccca tccagtcaac agcaccttca 45720 ccggcagccc atggcaaaca catgtgcagg ttaactggat gagagccact ttggaggctg 45780 ctgttaaaac atggggactc gttgaaactt tagatgataa aaccagagat cacagggaga 45840 cagtttgggc ctatcgtgag gaccatctct ctaccaattt tcttcccaaa aatgaaatgg 45900 ggagggctgg gtggggtggc ttacgcttgt aatcccagca ctccaggagg ccgaggcagg 45960 cagatcattt gaggtcagga gtttgagacc agcctgggca acatggtgaa accccatctc 46020 cacccaaaaa tacaaaaatt agttgggcat ggtggagcat gcctgtaatc ccagctactc 46080 gggaggctga ggcaggagaa tcgcttgcgg aggttgcagt gagccaagat tgtgccactg 46140 cattccagcc taggtaacag agcgagtctc catctcaaaa aaaaaaaagg aaggaggaag 46200 gctccaacag agaggctcca gaaacacttt taaaagtggc ttttggccag gcacggtggc 46260 tcatgcctgt aatcccagca ctttgggagg ccgaggtggg aggcctcaca aggtcaggag 46320 atcgagacca tcctggctaa catggtgaaa ccccgtctct actaaaaaca cacacaaaaa 46380 attagccaga cgtggtggcg ggtgcctgta gtcccagcta ctcgggaggc tgaggcagga 46440 gaatggcgtg aacctgggag gtggagcttg cagtgagccc agatcacacc actgcactcc 46500 agcctgggtg actgagcgag actctgtctc aaaaaaaaaa aaaaaaaaaa agtggctttt 46560 aaatttatag cactctaaag tggaatggat ccctggatgt gtctaaagtt atatcaagag 46620 gctggtttta cagtgcttga caatcagttg tcagtgttat aggtagaata gcaattggag 46680 tcagactggg gttttgatcc tggctgcagc gttctttgtt ttttggctgt atgaccttgg 46740 gcaagtgact aaacttctca gcttgttgtc tgtgaagata aattatttac gtcagagggc 46800 agctgtgagg attaacagag ataaaagtat acacagtgcc aggattcagt attattagaa 46860 ttacttttta atggtattga aggcagagaa gcttaatttc aatatatatc tctgaatttt 46920 tactagggac catcttaggt ctcactgaaa tgtggattca gagttcagcc tcaatagttg 46980 ctaaatggcc tgcttcctta caccagcaac cagccccagt cattctgtat ttgccaggcc 47040 attcatatgt atgcactgat ttcatcccca caggacaagg ttttgacctg tcacacatga 47100 cctcacctct gtggcttgcc agggttggtg tgaatagttt aaccaaggct atcgaaggcc 47160 taactgtagc gatagcagtt aacctatgta acttttttga gtcatttgaa ttatgtagag 47220 attggacctg taatcccagc actttgggag gccaaggtgg gaggattgct taagccctgg 47280 aggtcaaggc tgcaatgtgc cactgcactc tagcctagac aacagagtga gaccctgtct 47340 caaaaaaaaa aaaaaaaatt ggaaatttgc cgtatctgtg taggtatgtg attctttgga 47400 taaatgattc actgtatctt cctcaaaact aggttatttg aaagactgag atcattcaac 47460 tgattgcact gactgccaac taattttgca ggagatgttg cagtaaagat cctaaaggtt 47520 gtcgacccaa ccccagagca attccaggcc ttcaggaatg aggtggctgt tctgcggtga 47580 gtagaaagct ggcggtccag tccctctgga gtgctggagt ggggagtaca aggactgtag 47640 agttagtgga ctgtgccgca ggttgggacg ggcaggcagt taggactcac tgtggagttt 47700 ctgtggttgg atgctcctcc cttgagagca aagggatgtt tcctttagtt tatgtggttg 47760 tcaagccttt cgaagagccc ctttttagga gaataccctc ctctgggcac agtaaactca 47820 atagcccaat ttctgtctct gggttttggt ttgaggtggg cagaaatagg ccctattttt 47880

acctttattt cccagaaccc ttttttttat agctgagttg ccttatttta gacttcagaa 47940 cagtcagctt tccaatcttt cagtcactat ttagacttgt aggaataagt catataatgg 48000 agacttctac aaggagtcct tgtgacctcc acaggagggt catggagtgt acattgatga 48060 aagagaatgt cctctctgta agcaaggctg gcactgaact gatggcccag tgaactaatg 48120 gtgggcttct gtttgctcag aatgccaccc gggttatcag ccgtgccatg tgtttgtttt 48180 tgggactggg ggtggtgttg ggactggggg tggtgtcgac agcacagaac ccactgtcca 48240 cgggaaagca cagtagacct ccctgagcac tttcctcctc cctctcctct cttcccctcc 48300 cctccccagc aaaacacggc atgtgaacat tctgcttttc atggggtaca tgacaaagga 48360 caacctggca attgtgaccc agtggtgcga gggcagcagc ctctacaaac acctgcatgt 48420 ccaggagacc aagtttcaga tgttccagct aattgacatt gcccggcaga cggctcaggg 48480 aatggagtga gtagatggtc tgatgcctct ctgggaccca ggcatcaaat ttgtccctaa 48540 attggaacca ggatcaggaa aagccttcta gtccattaag cgattctgtg atatctttgc 48600 acaagcctct ggcctgggct ggaggggcca attatcagga atgagttgtt caggttccag 48660 ctgggtgggg tggctcacac ctgtaatccc agcactttgg gaggccaagg ccagtggatc 48720 acttgaggcc agtagttttg agaccagcct tgccaatatg gcaaaaccct gtttctactg 48780 aaaatacaag aatgaaccag gcctggtggc acatgcctat aatcccagct actcaggagc 48840 tgggacagga gaatcgcttg aacatggaag gcagaggttg cggtgagcta agatcacgtt 48900 actgcactcc agcctgggct gcagagcgag actctgtctc aaaaaaaaaa aagagaagtt 48960 caggttcctc cttgggactg aacttccccc ttggggctca gatttgggct ctgcctgcta 49020 ccctggcttt atcagaaacc tgagaatata gtggggtgca tgtaccttct gcttggacag 49080 ctgtggcaat gccttctgct cagctgtctg aggcatggct gtcccacatg agggtttaag 49140 cagatgttgt ttttgggata attttttttt tttaattaaa aactttttcc tggccaggca 49200 cggtggctca tgcccataat cccagcactt tgggaggctg aggcgggtgg atgacgaggc 49260 caggagttcg aaaccagcct ggccaatgtg gtgaaatctc atctctacta aaaatacaaa 49320 aattagctgg ttgtggtggc aggcgcttgt aatcccagct actcgggagg ctgaggcaga 49380 agaatcactt caacccggga ggcggaggtt gcagtgagtg gagattgtgc cattgcactc 49440 tagcctgggt gacagagcca gactccatct gaaaaaaaaa aaaaaaccca aaaaaaccac 49500 acttttttcc ttagagacac aggttctcac tctgtcacct atgctagagt gcagcggcgc 49560 aatcatagct cactgcatcc ttgaactcct gggctccagc tatcctcttg gctcagtctc 49620 ataggttgct gggactgcag gcacatgcta ccgtgcccag ctaattttcg tgtattttgt 49680 agagtcggag gtctcactat gttgcccagg ctggtctcaa actggactca agtgatcctc 49740 ccacctttcc tggctagcct agggtagtgc ttctcaaact tctcctctga agtagaggag 49800 ctcctcgtac ccctagacat ctgggagtta ctaagctata gctgtgcttg caagtcctac 49860 ataaattctc acactgtctt taaaattcat atggaagttg ccttctgtgt attttaagaa 49920 atggaatgac ttttcagaaa aattgagata taattcatac atcataaaat tccccctttt 49980 aaaatgtaca cctacctcag tgtttttctg gtattgagtt gtgcagccac caccactatc 50040 taattttaga acattttcat tatcccggaa agaaacacat gcccattgta ttagtctgtt 50100 tgggttgctc taaaggaaga cctaagggtg ggtaatttat aaagaaaaga ggtttatttg 50160 actcggggtt ctgcagactg tacaaaaagc atgacaccag catctgtgtc tggtgaggcc 50220 ctcaggaagc tttcactcat ggcagaaggc aaggggagcc acgtgtgatg tggtgagaga 50280 aaggagcaag agagagagca tggagggagg tcccagactc tttaataacc aggtttcatg 50340 tgagctaata gtgtgtgaac tcactcgtta ctgcagggag gccaccgagc cgtttgtgag 50400 gaatccatcc ccatgaccca aacacctgcc acttaggtcc cacctccaac actggggatc 50460 acatttcaac ttgagatttg gagtggacag atatccaaac aatataccca ttagaggtta 50520 cccaatacct cccacccact tgcagtctac tttctgtttc tatggatttt gcctacttta 50580 tagttcaata taaatggaat catgtaagat ataatatagt caggtaacat ataatgatgt 50640 ttcggtcaat gaccacatat aggaaggtgg tcccacaaga ttataatact gtatttttac 50700 tgtgcctttt ctatgtttgg ctatgtttag agacacaaat actcaccatg ttacaaccag 50760 ctacagtatt cagtacactg agggccatac agttttgtag cctaagtgca acacgttata 50820 ccatttagcc agggtgtgta gaaggctgta ccttcttggt ttgtgtgaat acactttatg 50880 atgtgtgcat gatgacaagt tggctaacaa cacatttctc agaaggtatc cctgccgtta 50940 agtgatgctt ggctgtatat aatacataag atatggtatt gtgtgcctgg gctcttagac 51000 ctagcatagt attttcaagg ttaatgtgta gcatgagtca ctacttcatt cctttctgtg 51060 tctgagtaac attccattgt atggatatgc cacattattc attcatcatt tatggacatt 51120 gggttatcag aattacttta gagtaaaact gatgcttgaa gaagtgtcag caatggtcag 51180 gcgccagggg cccatgcctg taatccaagc attttggagg ccaacatggg aggatcactt 51240 gagcccagga gtcaagacca gcttgggcaa cagtgcaaga ccctgtatct acccaaaaaa 51300 aaaaaaaaaa aaaaaaaggc ggcatggtgg cacatgcctg tggtcccggc tactgggagg 51360 tgggaggatc acttgagccc aggaggttaa ggctgcagta agctattgac tgcactccag 51420 tctccaaaaa aaaaaaaaaa aaggtgtaag catgtttgtg ctgtggcctc accttcaggt 51480 aagcagtgat gtgaaccagg ctgaacagca cagggtctat ccctgtgtgt aacactcctt 51540 ggagccaggc cttcagtggc tttacttctt agctgtagtt taaaactgct ttctactcat 51600 gcccctcaaa cttattttta ataatttctt ttcccttcac agctatttgc atgcaaagaa 51660 catcatccat agagacatga aatccaacag tatcctttgg ttgttgagtt catttgactg 51720 ctcggttcta aatttaggga aacagaaggg aggctttcta tcacaagtgg ctctcggtgc 51780 caggggatat ctttttaagg aaagaggcag aggacaggaa aacagaaaag tcagaaaatt 51840 agtaggcttg gcctgtccct cagcagctta tgcctcacct ggactgatga gagcgatgtt 51900 taggttaggt tcctttctga gtttatctca gcaaaagtga tttggagaga tttccgtaag 51960 cttgaaatag gcataatttt atcacactat tagtaaatgt aacctgacgg ggattgggct 52020 tttgtcttaa gtttatttct agtttgtggc cagcgtgtgt atgtctatct gcttgttatg 52080 tggatagcaa gtagctacaa gccaaatgtt gaaaggtttc caaaatcact aattaaaata 52140 gtctttcttg actgggcgtg atggctcaca cctataatcc cagcactttg ggaggctgag 52200 gcaggtggat cacttgaggc taggagtttg agacttgcct ggccaatgtg gtgaaacccc 52260 atctctaaat ttaaaaatta gctgagtgtg gtggcacgta cctataatcc cagctactca 52320 ggaggctgag gcacgagaat tgcttgaacc tgggaggcag aggttgcagt gagctgagat 52380 cacgccactg cactccagcc ttggggacag agcaaggctg tgtctcaaaa aaataaataa 52440 ataaaatggt ctttctcaaa ggtacataag tgggttcttc agaagtcact attagaagag 52500 gagaggggtt gtttttatag aagagtaaat gaagaaaggt atttttaatg ctgtgaggcg 52560 tgaaatttaa caattttgaa tctgccaccc tccacgagcc tttccttgtg aaagaaagat 52620 ggcattacaa cccacgtttt gcctcttgag cagtgagagg catgatagtt gtgttggatt 52680 atgggacatg gcctatttta ggtacatgtc tgaggtgtgg aacacctttc agtggtgggg 52740 tttttagcag ccaaacatta taccatgaaa gcagacacca cagatttaag gaggtgtgaa 52800 ttcctgggca ccaacatcac aagttacttt gtgtgtgttt tgttttttaa ttttttgttc 52860 ttttttaatt tttttttcct cacaagtttg acttaaactg tatgacttct ttacccagaa 52920 gcgagccgac ttcagttctc attttgaagt cactgagtgg taccgattct agtgaggaat 52980 ttcttactac aacattgaac actcagtaag ggatttgcta ttttgttaac cactcaagtt 53040 tcagatggtg atttgagggc agaatacagg cagaaacgac tgtaagctgt caggccatcc 53100 ttggccctct ggggagcact ggagtgtggc ctctgctcat cctgttaggg tttcaagtac 53160 ctgtattatg tggaaaggtc acaaggccag agacccagca cctagatgtg caaatgggga 53220 gaagaagcag ggaagaaacg ctggcttgct tttggctagg gccaaataat ctggcacatt 53280 gaccaatccc tgcctgtctt ctggaagaag gtgcatttca aaagcacttt aaagaacttc 53340 agaaacctta ggaagttcag tgcagagagg ctgtgacaga ggtaaggtgg agagattacc 53400 gtgttataaa gaactttggg atatttttca aaattaacct gaccattctt ttgaaaccag 53460 agtccttaac aagcattgag atatatttct ccatgaaggc ttaacagtga aaattggaga 53520 ttttggtttg gcaacagtaa agtcacgctg gagtggttct cagcaggttg aacaacctac 53580 tggctctgtc ctctggatgg tgagaatctg ggctcccacc agcagtctct ggtatagggc 53640 aaaaggaatg ccttggagat ttatgtgcaa acttaaagcg tttctgtaca tttccccgaa 53700 atccacatga cccctagtga cagccagcct cagggcaatt gtagattttc ttgaggaagc 53760 tgttgatcag aaccactgtg aagcttagtg tggagaggag ttaataagct gggtgacaga 53820 aatgctgggt cttggtcctt taaagacaag gattcctgag ctgttttaac cagtgcctga 53880 gttggagtcc tttgggggaa aagctatgtg gggactgaag aatggactca ttcataacta 53940 atgaaaggga cagcctggcc cctagatgtc tgtgaggcct gtcatatggt gataaatgca 54000 cttttgtcat atggtgatac atgtaggccc cagaggtgat ccgaatgcag gataacaacc 54060 cattcagttt ccagtcggat gtctactcct atggcatcgt attgtatgaa ctgatgacgg 54120 gggagcttcc ttattctcac atcaacaacc gagatcaggt aagtctgtgc tggtgcgaaa 54180 ggacccaact cgtgggagcc cctgggcctc cgccagccta agcagctaga gggttaggac 54240 ttgttattat ctgttgttca ttcacccccc attagctcag ctgttttctt tcccttagat 54300 catcttcatg gtgggccgag gatatgcctc cccagatctt agtaagctat ataagaactg 54360 ccccaaagca atgaagaggc tggtagctga ctgtgtgaag aaagtaaagg aagagaggcc 54420 tctttttccc caggtaaggc tcagggctgc tagaatgtga ttaaagcatg ggttggttcg 54480 taaagatggc aatataaggt gggagtgttt tgttttgttt tatagggagg ggacccaggt 54540 cctctacaag atggtggggg gcagggtaca tcctgtgtct ttgagacaca gctaatgaga 54600 gcattcttgg gctttgtttc agatcctgtc ttccattgag ctgctccaac actctctacc 54660 gaagatcaac cggagcgctt ccgagccatc cttgcatcgg gcagcccaca ctgaggatat 54720 caatgcttgc acgctgacca cgtccccgag gctgcctgtc ttctagttga ctttgcacct 54780 gtcttcaggc tgccagggga ggaggagaag ccagcaggca ccacttttct gctccctttc 54840 tccagaggca gaacacatgt tttcagagaa gctgctgcta aggaccttct agactgctca 54900 cagggcctta acttcatgtt gccttctttt ctatcccttt gggccctggg agaaggaagc 54960 catttgcagt gctggtgtgt cctgctccct ccccacattc cccatgctca aggcccagcc 55020 ttctgtagat gcgcaagtgg atgttgatgg tagtacaaaa agcaggggcc cagccccagc 55080 tgttggctac atgagtattt agaggaagta aggtagcagg cagtccagcc ctgatgtgga 55140 gacacatggg attttggaaa tcagcttctg gaggaatgca tgtcacaggc gggactttct 55200 tcagagagtg gtgcagcgcc agacattttg cacataaggc accaaacagc ccaggactgc 55260 cgagactctg gccgcccgaa ggagcctgct ttggtactat ggaacttttc ttaggggaca 55320 cgtcctcctt tcacagcttc taaggtgtcc agtgcattgg gatggttttc caggcaaggc 55380

actcggccaa tccgcatctc agccctctca gggagcagtc ttccatcatg ctgaattttg 55440 tcttccagga gctgccccta tggggcgggg ccgcagggcc agccttgttt ctctaacaaa 55500 caaacaaaca aacagccttg tttctctagt cacatcatgt gtatacaagg aagccaggaa 55560 tacaggtttt cttgatgatt tgggttttaa ttttgttttt attgcacctg acaaaataca 55620 gttatctgat ggtccctcaa ttatgttatt ttaataaaat aaattaaatt taggtgtaat 55680 ggctggctgt tacctccttt taaagtaatt ctgagctcac aacttgaatg ccccatttgt 55740 tcaccctctt caggagcaga attcaagaac aggaaatgtg cccagagcct aggctgggaa 55800 tgaatttgta atttaacctt tgtactcttt gtaaacctct actgaagagt taagtataaa 55860 aattaattaa gcagaaagta ctctaaactc agctaatacc ttaagtaata cattttataa 55920 actatttatt tatttggtag gtacagcttt tttaaacaca aaaatagatt agataaattc 55980 cagcttggaa caagctagtg ctggttcaca aggttatgct cacccttcaa ttaaaatcaa 56040 aatgactaca agacttgcca tcagctctct tcaggaccac tgctgggtca gaatcagaaa 56100 ccttgggtgc catgaaattt ttacaaaatt tcaaatcaaa gccaggcttt gcagctagat 56160 aatagatcac ttgagtacga accacacatg taagtgcacg tatatttgag ttctcaatac 56220 aattaccctg atgggcaaga acccacaggt gagagcagag gcttggttcc cctagagggc 56280 cctggctgga ggccccaaca ccaaccagac gacaggaggg ccagactgct acccagtact 56340 gtacctcctg ctccttcaag agcctcccta agggagaaga agatctatac ttccactttg 56400 tttgctgcac atgtggcaac aagattgcta ccctgatttg ggacacttga gagaacttga 56460 aaaaaatgac cacccttaaa gccctagaaa aaagttgtat gtttgttaac agctatgctg 56520 cgctcacttt gcattgtgtg ttcttgaaag ctctgtataa atcaaaattt tgacgacaca 56580 ctaaatacac tagagaaata cactatagag gaatcctttt atagggctga agactccttt 56640 ggtaagaaaa atatgctgca ttaggggcag ctgcaagttt actatttctg gggaagaaaa 56700 gatcaaaggt aagagccagg tttgtttttt aaagcaatca atccaaacag tttgggtgtt 56760 tgttagttgt tacccctgag gggcttgagg tgtaactata tcagctataa aaatagcaat 56820 tccatacatt taattaggtt actttatatc tttcactctt ccccatggct gtaataatgg 56880 agattgaatg agactaaggc taagcccaac tccactcaaa tccaagtcac acgtcacctt 56940 ggctgcagta cagggaagct ccgcacaccc tggcttggga aagtttcggc cgatggagcc 57000 caagatgcag ggcaaccatc tactctttag ggttctgatg attccactcc agaaaggtgc 57060 atgaagaggt ccccgagctc tgtcatgtcg acatcttcat tgttggggac atgccggctt 57120 tctcggttct cgatgaaatc ccagagccgc actgaattaa agaactgcaa aaacagccag 57180 tggacatgcc tggttactgc taagagcaac aggaaggctg cgttccttga tcgttctttt 57240 gcctacccca tttctctgcc aggaacggta cctggaaatg cccacagctg ctaagtgtcc 57300 ccaactagag atggctaaag tccttaccct cacagtgcct tgagaactga gctgtttccg 57360 aggtttctca ggctctgcta gccgcccatc ggggtaagca tggcgataaa gacatttgct 57420 tccaaatggg caggtcccct tgccttgctc aaagtattta caggcttttt tcctgaaaag 57480 cagaaagaaa aagtcaagag gctggtggga aaatgagggg tccaaactgg gccactgcct 57540 gcctccatcc ttaccaccct tacgccagag gtaggtcagc ctcacattct aggtggggca 57600 gctgaggctg ggagaggttg agtgatttgt ctcaggtcac acacagctgg gattctgatt 57660 tccaagcagg ataggaagta tccccactta cctgcagcct tgcaaaggat attaacctgc 57720 ctggggactt gctgtgtgga gactgcagtg ctccacaggc cctccggcag ctccagagca 57780 cctcctgggt caccacagag ctaagccagg cctggtcact cctctgggca ctaagctctg 57840 aagctgggcc acttgtctct gctcaaagtt ccctaggtac cccaccaagc caactctccc 57900 cttcctcctg gccgcagtgc tgtcaaggtg gctacaggga aagcagaggg ttttagcaac 57960 tgcctaaagc cataggtctc cttccagttt tcctgtctcc aacctcggca ccagggaggg 58020 cttcttcacg ccttatgtgc tttggacccc ttctctgaac agtgtttttc aatgcataaa 58080 acatgggtct acagcataca gtgaccaaac agttcaaaat gttttccctc tctcttaatt 58140 ctaccattct ccccacagac ctctatgtta agaaccctgc ccaaggaaac tcaatcaaat 58200 gaattcccat tttgctcaaa tgaactctgg tttatccaat cataaaggat cccaaactga 58260 agttaaaaaa aaaaagatac ccaagaatcc agagggccat ctcggagtac agaggaaggg 58320 gaaagtcaca gaaataaagc caaacaacag aaagggcacg ctgctgtcag gggcagctgg 58380 ggtgtgtgac agcgggagac aagaacaggg aaaggaggct cctgaatcca gtggttttcc 58440 gtcttgtcag atgggatggc cgcaggccgg tggtgaagtt ctctgaggac ggcttcatag 58500 cagcataaag aaaagccctc tggccgggtg tggtggctca cacctgtaat tccagcattt 58560 tgggaggcca aggtgggtgg atcacttgag gtcaggagtt tgagaccagc ctggccaaca 58620 cagcgaaacc ccatctctac taaaaataca caaatgagct gggtgtggtg gctggcacct 58680 gtaatcccag ctactcggga ggctgaggct gaggcaggag aattgcttga acccaggagg 58740 tggaggctgc agtgagccaa gattgtgcca ctgcactcca gcctgggaga cagagtgaga 58800 cttcgtctca ctgggggtgg tggcgggggg gtagggtggg gggagagaga acaagctccc 58860 tggccagctg atctgatttg agcacaggtg gctggagagc aggtgtgtgg acgacacatc 58920 ctccaggccc ctgcttgcct ggagttctga gcggacttca aatgaccgtg agcagtttgc 58980 tctcaccaga gcctgctgga caactccaga gcatcctagc acactggcta tgaactcgat 59040 caggtcaaac acattatata ctggtccccc actctcacaa gaatattact ctttttcctc 59100 ccccaggctt atctggtcac caaggccaaa agcctccagt tcactctgac tcactctgtg 59160 tcctcggctc tcacacccaa ctgtgttcat tctgtttaca aatcacttcc caatctcccc 59220 ttcctttggg ttcccacact tgtggaagcc tctggggcct gcctgccagg gccacttcct 59280 cactggcctc cctcccactc ccaccagttt ccaccttcag agcagcacgg aggagcttcc 59340 caaccttttt tttttcttta aagagatgag gtctccctat gtctcccctg gacttaagca 59400 atctgccctc ctcagcctcc caaagtgctg ggattacagg cataagccac tgcgcctggc 59460 cccaacctgt tcttaaagac catggtcaca ctgggattca agtgtccctt agattccagt 59520 ctgtaggtcc caccacatcc ttctacacac ctgtttcaat gccaggagcc actcccagtg 59580 tcccccagac acaaaaccta cacccttctg tgcccatgtc cttccatcac ttccccctac 59640 agacaggtgc ttcctgcttc atggttcagg ctcccatgct gcttcccctg gcagcccccg 59700 gtggatccaa gtgctttctc tgttgtgata gatggtccct catgaagaac tggtcaccag 59760 caaacctgta tcataattgc ccttttgcag tttcccatga agttgtctta cttggcgggg 59820 cacagtggct cacacctata atcctagcac tttgggaagc tgaggtgggt agatcatctg 59880 aggccaggag ttcaagacca gcctggccaa catggcgaaa ccccatccct actaaaaaaa 59940 tacaaaaatt agctgggtgt cgtggcgcac acctgtaatc ccagctactc gggaggctga 60000 ggcagaagaa tcacttgaac cctggaggcg gaggttgcag tgagctgaaa tcatgccact 60060 gccagcctgg gtgacagagc gagactcgaa agaaaaaaga aattgtctta ctaatctcta 60120 catcccccag tggtgcttag ctagaaggta cctgacccat agtgagtact cagtaaatgt 60180 ttgtggattg caaaaaacac agtcattaaa ggaaagcaaa gcaaggaaag atccaaatag 60240 caataacaat ctccagactg cttttcagca gagccccttt ctacaggctg ggaccctttt 60300 ctacaggctg gggccctttt ctacaagctg ggacccctct gcttgccacg ccttgccctc 60360 ttgtggacac acaggaagat tgtatgagga aaaaatggta aaaaaaaaaa aaaaaaaaaa 60420 atcaagcttt agtaaactaa tatgcaacat aaaggaacca ttaaaaaagg taatgcatag 60480 tttcactttt agtatgacaa gtaaacgcct gccataccca accctcctgc agataagtct 60540 taacacaaat atttcaagaa gacctgaagg caccagagaa tgaacaaacg cagttagatt 60600 ctttggagga gtaaacacaa agaagaatag caatggcaaa ggctaagtta ccttttttaa 60660 aaaaggtagc ttttgtggct cacatctgta atcccagcat tttgggaggc cgaggcaggt 60720 ggattgcctg agctcaggag ttcaagacca gcctgggaaa cacagtgaaa ccctgtctct 60780 actaaaatac aaaaattagc caggcgtggc ggcatgcgcc tgtagtccca ccttcttggg 60840 aggctgaggc agaagtgctt gaacctggaa ggcggaggtg gcagtgagct gagactgtgc 60900 cactgcactc cagcctgggc tacaaagcaa gactccatct ccaaaaaaaa aaaaaaaaaa 60960 aaaaaaagaa gtagctctta tcctggagca ggccaaaatc ataaccacat ggggtggcta 61020 aaactccaag gggaaatcca atctttctgg cctgaagaac taaaagacaa gagttcaagg 61080 aaatcacagc cattggaaag tgaggaagca atcccacaaa gtaaggggcc tgtgaaaaag 61140 tgctcaaagg ctgtgtataa actctgccca aatctgacta actcccaaac cacacaggaa 61200 tgcgacaaag tcagctacga atgcaaaacc agaactgaga tctgaactgc tacctgggtt 61260 tgagttcaaa caatttacct gcctgttaaa aacagcaaca cttggccagg cgcagtggct 61320 catgcctgta atcccagcac tttgggaggc cgaggtgggc ggatcacctg aggtcaggag 61380 tttgagacca gccaggctaa catggtgaaa ccccgtttct actaaaaata caaaaaattg 61440 gccaggtgca gtggtgcatg cctgtaatcc ctgctactcg ggaggctgag gcaggagaat 61500 cgcttgaacc cgagaggcag aggttgcagt gagccgagat tgtgccactg cactccagct 61560 tgggcaacaa gagtgaaact ccgtctcaaa aaaaaaaaaa tcatcacttt acagataaac 61620 cataacagaa tcctaagtct ctctacaatg taatatttac aatgtcaagg ataaaatcta 61680 aaattactag acatacgaag aatcaggaaa atgtgatcca ttcttaaaag acaacagagg 61740 tcaacttcaa gataacaagg atttcaaagt agctgctaca actatgttca aggagatgaa 61800 aagaaaaaaa gattgaaaaa gaatgaatat ccccagagat ctatgaacaa tataaaaaaa 61860 ctatcataaa cggaagtaga gtcccagcag gaaaagaaaa aaacaagaca gaaaaaaagt 61920 taatgaaaca atagctaaaa tttcgctcat cttggggagt gacataagcg tagagaaaaa 61980 ccactccact cctaggcaaa atatcaacat gctgacaacc aggataaaga ggaacatttg 62040 aggccgggca cggtggctca tgcctgtaat cccagcactt tgggaggccg aggcaggagg 62100 atcacttgag cctaggagtt caagaccagc ctgggctaca tggcgaaacc ttgtctctac 62160 caaaaaaaat tagccaatta gctgggcatg gtggcgcaca ctactggtgg ccccagctac 62220 tcaagaggct cctgcttgag cccaggaggc tgaggctgca gtgagctgag attgcaccac 62280 tgcactccag cctgggcaac agagtgagac cctatctcac cgaaaaaaaa aaaaaaaaaa 62340 aaaaaacacc aaaactaaac aggtccacat caccatgtcc ttgctcattg ctgcatccca 62400 gagcccagca tggtgcctga gagaaggaag agaggaagag gcccctaaga ccacactcct 62460 gggaaggaga acgaggacac gggctgacag cagagccagg caggcagcag gggcacgtcg 62520 aaactcaaaa gcacttaccc catcccctgt ttgaaagctt caatcaactc gttcttttta 62580 ttctgatctt ccacccaata cacacttgga attacaaact ctgatatcac acggcattct 62640 ggacaagacc tgaaataaga attagattac taagggagaa gtcatgttac gaagcctggg 62700 cacactctct gctaaacctc ttgctcaact gcctcaccac tacaggcatt tccttcacca 62760 gaaattccaa aagatgaaat cacaatcatc caagaacctt atttactatt aacaaaatag 62820 ggtttcccaa tgagaacaca tggacacatg tgggggaaca tcacacaccg gggcctgtcg 62880 gtgcaggggc aaggggaggg agaacatcag cacaaacagc taatgcatgc atggctgaaa 62940

acctaggtga tgggttgaga ggtgcagaaa accaccgtgg cacatggata cccatgtaac 63000 aaagctacac attctgcaca tgtaccccag aacttaaagc aaaaaaaata cacacacaca 63060 cacacacaca cacacacaca cacacacaca tatatggttt cctcaacaaa aaagacagat 63120 gaaataaccc tcatacattg ctggtgagaa tgtaaaaggg tgcagccact ttgaacagag 63180 tctggcagat tctccaacag tttaatgtag agttattata ccataaaacc tagcaatccc 63240 acgcccaggt gtatacccaa gagaaatgaa aacacatgcc cacatgctgt gttcacaaat 63300 gttgacagca gcattattca taatagttgc aaagttaaaa cagcctaaat gtccactagc 63360 tgaggaatgg ataagggaaa tgtgctgcgt ccatacaatg gaacatattc cgccaggaga 63420 aggggactct ggcacatgct acagtcggga tgaactctga caacactatg ctcagtgaaa 63480 ggggccaggc acaaaaggcc ccaaattcta tgattccatt tataagaagt gtccagaata 63540 ggcaactctg tagagacaga aagcggatga gtggtgagtt aaattgtggg cttttatctc 63600 aatagagcag ttgtttcacc acacgatttt aggcaaatta cttgaccccc gcaccccagg 63660 cctgtttcct aatctgtaac tgaggagggt ctttgaggga atgagatgag cggacagatg 63720 tggagttctg aacagtagaa cgcgtgcagt aacctctcca catgccagct cttcccctgt 63780 cctgctggag aatttgagac tcctatgttg gccacattga gcacatccca tgtgccaggc 63840 atcatgcaga atgttttaca tgcattattc cacttcatcc tcaaataacc ctattttcgt 63900 ttttggtggg gggaaaaaac gaagctcaaa atgattaaca ggcaactggg ctacaggcag 63960 gtactactgg atttcaaaca caaggctagg agatgaaaac aggtcagtgc catttaacac 64020 ctttttacac agatcatctt tgctgagttc ctccccaaca cccagaaagc ttggtaggaa 64080 ttgttgccca tcttttatag gaacaggcac ttaggctcag gaagagtaaa tgacttgctg 64140 aagttcatgc agccaggggc cagaactcac cagttactct tgagggtaac ggagggctta 64200 aaagtggacg gaataaagtc tcaaatcaaa cattctccta gctcccacag ctaagacccc 64260 tggctgtact tacttaatga ttgggttttc aaactgtttg gcacaccgcc actgccggat 64320 gcaggacaaa cagtacgtgt gattgcaatt ggagagaatc ccaaatctcc tctcagaagc 64380 agaggccttc tccaggatca cttccatgca gatactgcac actttgtcct ggcttgcctg 64440 gaaggcaaag gccttttcca tctcgtgttc gaacgtcaac atgcagatct gaagcacaga 64500 caggaaggaa ggctttggtt gtgggccact gaggagtggc aggagcccta ggagtagctg 64560 cagccacact gccacagctg agatcaggaa ggaacactga cagcgactgc tgtgagcaaa 64620 ggcccaggct cccccaagtc aggacactga catctccctc agaccacaca aaggacttca 64680 aaccatcact ggtccagccc cttgctttcc taggaggtga catggtcacc acccatttag 64740 gactgagaac acggagatcc aaaaaggtta aactgcagtg gagtcagagt ccgtaaggac 64800 tgcggcccta gtcccccagc tcctctgggc actgtttccc ccgactctga gccatgtcta 64860 catcagagat gctgactcgt ccttaccatg aggcttgagg ctggcagcct agtcctatgt 64920 aagaagcacc acttctcccc aagaaaatga ttcaatgaat tcattcattc actaggcatg 64980 ccctgaattc cttctatgtg ctggcatttg agcaagagtg agaagaccta ggcccagccc 65040 ttgtaagctc agtctgtcca gatctgagac aagccaacac tcaccgcaga gacctcacac 65100 acttgcataa agaagacagc tctaaccctc tgcttccctg gaagacaatg gagagtgtct 65160 ccttgtccgc tgccacatgg agtcagtact aatttacctc ttgattatct aggaatacgc 65220 tgtccattta aacatgcctt aggccaggtg cagtggctca cacctgtaat cccattactc 65280 tgggaggcca tggtaagagg actgcttgat ctcaggagtt caagaccagc ctaagcaaca 65340 tagcaagacc tcacctctga aaaataaaat aatttttttt tttttttgag acagagtctc 65400 tctctgtcgt ccaggctgga gtgcggtggt gcaatctcag ctcgctgcaa gctccacctc 65460 ctgggttcag actattctcc tgcctcagcc tcccaagtag ctgggactac aggcgcccgc 65520 caccacaccc agttaacttt ttgtattttt agtagagacg gggtttcacc atgttagcca 65580 ggatggtctc aatctcctga ccttgtgatc cgcctgcctc gtcctcccaa agtgctggga 65640 ttacaggcgt gagccactgt gcccagccaa aataaaataa aattttaaaa gttagccaag 65700 ccaccacacc tggcattttt aaattttttt attattattt ttcttgagac agggtctcac 65760 tcttattgcc caggctgtag tgcagtggca caatcttggc tcactgcaac cttctgcttc 65820 ccaggctagg gtgatcctcc cacctcagtc cttgctgagt agctgggact acaggtgtgc 65880 accaccacac ctggataatg tttgtatttt tttttttttg tagagacggg gatcttacca 65940 tgttgcccag gctggtctca aactcctggg gtcaagcaat ctgcctgcct tggcctgcca 66000 aagtgctggg attacaggtg tgagtcacca tgcctggccc tcccccgcct cttatccagc 66060 ttcgtaccct ctgcatcatg catagggcct agcataaggc aaagcctccc aaaacactgc 66120 agacattaat gactttaaaa ggcccttcca acaagtggct cctcagattc tatgatttgg 66180 gctcaaatct tccaaaactt cacctagctg gatcccaacc atgaggaagt gtgaacccag 66240 ggagggagga tgctgtatct gcatgtgata gagacataca cacagacgac ataccatggt 66300 cctgagctag atctgttctt tgaacttagc atgattttat atttcagata cgacttcttt 66360 ttctctttat tctgagtaat taaaaattgg caaaataggc cgggcatggt ggctcatgcc 66420 tgtaatccca gcactttggg aggccaaggc aggcggacaa cttgaggtca ggagttcgag 66480 accagcctgg ccaacgtggt gaaaccccat ctttcctaaa aatacaaaaa gtagccgggt 66540 gtggtggtgg gcgcctgtaa tcccagctac tcggtggggc tgaggcagga ggatcacctg 66600 agccagggaa gcagaggttg cagtgagccg agattgcacc actgtactcc agcctgggtg 66660 agagggagac tccattaaaa aaaaaaaatg gcaaaatgac tgcaggaaaa agaacctgaa 66720 aacaggatgt aaatatacca gatacataat atgggtatta ctggcagggg gatgcctgtg 66780 gaaataccaa caattctgtc acttagtaca tttcagattt cttgagtgta tatggatggc 66840 cttccgtgtc ctgttcagta catttcagat ttcttaacat gagttcatgc aaaggtttgt 66900 gactttacct tttcatgagc cttcctctgc tctgggtcga atgggtgcaa gacttgcagc 66960 ctacagattt cacacacctc cccgtgcagg tagacacagg catccccaaa ccggcactcc 67020 ccagcagctg cgtaggggca cagctgctgc tcgttgctgt aggagctgct ggcctccacg 67080 tcatcaaggc cactcctgat ggcatccagg taggaatgcg gcttcatctc ggggctgggc 67140 tgggggtcgc tgcagctgcc tggattactc accatgctcg gctgggtctt cctttcagcc 67200 atgccagaga gatctgaaaa caacacacag cacacatgca catgaaaatg gccccatttt 67260 tctggtatgc cgttagccaa agcctaacat attaagctac tctgacctaa gaattccact 67320 cttgagaaca tatggcaaaa aaaacacacc gaaggggaaa aataaaagga atagtataaa 67380 atgttcatag tgacattact tataattact taaaaaaaca aaaaacaaaa aacaaaaatg 67440 gcaagacagg gaaatagcaa aacaatagga tatacttata caaaagaaca ctaaagccgt 67500 ttaaaatggc aaatatggaa atgttaacac atggaccagt taacactaaa acaaacaaaa 67560 aaacagtgag agcactagaa cacagtgttt ccttcatacc agcaaaggta aaatcatttt 67620 aagtgaacta gaatagatgt ctagagcaaa tctgtgggtc ctgaggccag tgtaaactgc 67680 cccatggtca ccccttctca cgccaggagc tgctgccttc ccactgcaca cctccgagct 67740 tgtttagagg tcacgtattc tcacaggatt actcatttgc tgaggacaga atctgcctac 67800 ctcatggtag ccaattccaa gaactagaaa tctcttcacc tggtgaggac cagccaataa 67860 aaacaacttt tatggccagg tgcagtggct cttgcctgta atcccagcac tttgggaggc 67920 cgaggcgggc ggatcatgag accaagagtt tgagaccagc ctggccaaca tagtgaaaca 67980 ctgtctctac taaaaataca aaaattagct gggcatggtg gtgggcacct gtattcccag 68040 ctactcagaa ggctgaggca agagaatccc ttgaacccgg gaggtggaga tcatgccact 68100 gcactgcagc ctaggcgaca gagcgagtct ccatctccaa aaaaaaaaca aaaacaaaac 68160 aaacaaaaaa cacaacaaaa aaacttttac aatttgtagc tttcttcctc atcaaaccct 68220 gttttaaggc acagaccatg ccccaaaccc tagtgtgcta ttcttttccc aaaggtgcaa 68280 tctaaactgt caaacactgt cagcataaaa actaagacca ttcactggcc taaaagtcaa 68340 acagtgaaac atgctcttta gcaaaatatt tagttttctt tttttttttt ttttttttga 68400 gagggagtct cactcttgtc atccaggctg gagtgcagtg gcgtgatctc agctcactac 68460 aatctttgcc tcccgggttc aagaaattct cctgcctcag cctcccaagt agctgggatt 68520 acagacacct gccactacac ccggctaatt tttgtatttt tagtagagac agggtttcta 68580 ctaaaccatg ttggccaggc tggtctcgaa ctcctgacct caggtgatcc acccgcctca 68640 gcctcccaaa gtgttggggt tataggtgtg agccacttta cccagacaaa atatttacgt 68700 ttgaaatgaa gagcttgatg cttctcacca gctggacaac caccatatga agatggaagt 68760 tacatgttga caaaaagatt gtgtttttat gttttaccag gccagtcttg gagctcaacc 68820 cagccttggg cacgagggcg aatgtatcat ttgaatgatc tgcagccaca tggagcctct 68880 tcagaacagt tctgaagtct ctccgcgcag acaatctgga ggtgtattag gttaggagtc 68940 ctcttgacaa gaggaggcta gaaaggagca ccaagcatta acaagagtgc tatgcaaaaa 69000 gacgcaacaa aaggcttccg cttactcact tcggtctcta agaaccaatg ttctcttttc 69060 acgctttccg ggttcatgtg agttagtttt cacaatggat gcagtgacct cggaaggagg 69120 gtgaggactg tggaaagctg gggagggcac actgtgggcc atggtgccca cagcacctcc 69180 agctgcagca gagggcctcg tgtggtcata tctaaacaaa acacacagca gatgcattac 69240 agacatgcca cccacacaca tctcccacac tccccagatg ccaatggccc tccttctgct 69300 gcacttgttg aggtgaagaa ggcggccatc ttttccaata tttaaactct aacaggatta 69360 tcgattatta acagatgctt ggcaattcat tgtgaggggg acatttgcta tctatcacct 69420 atgcttaagt gtctctgtgg gacttgagtg ggacagacac acagcaccag accacacaga 69480 gaacctgaaa gttccaaaca gatgttgagc taaaatctcc tgatgcctga ctgacccagt 69540 attcttttga gcaggagtcc ccaaaatgct gacaagggcc aatgatctct ccctgactgt 69600 ctctcttggc actcattgac aggggaagac caacgtgggc ctacttccat catctcccac 69660 tgcactgcag agaaaaagga gggaaggaag ctttgcagtc tagaaagaaa agatcggctc 69720 tttgctacaa aagcatgaac aagtttccgg aattgtgtac aattttataa ctatatattc 69780 ataagaataa ggctgaaaag tagttttaaa aaatgaaaat taggccaggc acggtggctc 69840 acgcctgtaa ttccagcact ttgggaagct gaggcgggag gatcacgagg tcaggagtta 69900 gagaccagcc tgaccaacat ggtgaaaccc catctctact aaaaatacaa aaaaaaaaaa 69960 aatcagccag gcgtagtggc agatgcctgt aatctcagct acttgggagg ctgaggcagg 70020 agaaccctgg aggcggaggt tgcagagaac tgagatcgca ccactgccct ccagcctggg 70080 caacagtgag agactctatc tcaaaaaaaa aaagaaaaga aaattagttt tagggtactg 70140 aaactgaggt tttaaactta tttgccatac tttttgtgat gttgccatat tacttttaca 70200 ttaaaatttc ccccttatca agacccattc tccaaatgaa atcagtgtca cagctggaat 70260 ctgttgcaga gtccttgcct gcaccgagtt ccataggcac agtagccctt ctggtagtac 70320 ttgcagatgg tggacggttt gctgtttgcc aagtcatgtg agaataggca ctgacttcct 70380 tcccgacaca caccatgcat aaaatacctg cagagacaag cacaggcata caacttttag 70440

aagcacattt tgctttataa aatcagctta ttcttgaact tagcatacaa acatttacca 70500 ggcatatatt atgtataaag gctctattag gcactggaga gagatctata tatttccttg 70560 attctacaac agtgatttca gaggcactac aactgattca atgacagctt ttctgaaaga 70620 aaaacaaatg atcccatata tttctatgtg aagatatatc ttcctgattt gagatatgtt 70680 caatgtgagc cacataattg agaaaacact ctgtgaaaaa ctgttctctc tgttctcaag 70740 gagcttaaag ggcatgacta acgaaaccag aagatctggg ctcaagaccc agctctgcca 70800 cttaagaaca tgtcacaaaa ccaacttccc tgggccttgc tacctttccc tataaaatga 70860 agattatact acccacttaa ctggtcgtgg tgaggatcaa ataccatagt gtggtatcaa 70920 aagatataca cagatgctcc ttgactaatg atggagttac atcccaataa agccactgtt 70980 ttttgttttt tgttttgaga tggagtctct ctgtcaccca ggctgaagtg caatggcaca 71040 gtctcagctc actgcaacct ctgccttccg ggttcaagcg attctcctag ctcagcctgg 71100 gctaccttac ttatgcttag aacacttaca tcagcctaca gttgggccaa atcatctaac 71160 acaaaatcta ttttacaata aagtgtagaa taatctcatg caatttattg aacaccgtac 71220 tgaaagtgag aaacagaaag gttgtatggg tacttgtagt ttttaatgaa agctgtttct 71280 catacattgt ttcagatgtt tcagaatatc agatgtatca catgttctgt atcagaatat 71340 tccactgaga tatcagatcc tggccttgaa gaataagtgg tacaggaata cctgggaggc 71400 taactctgtc cagacagggt agagagacct gagtgaatac tcaaacagta gagaccctag 71460 atgaacatgt cttgatatta aagataaact aggctgggtg tggtggctca cacctgtaat 71520 cctagtactt tgggaggcca aggcgggcgc atcacctgag gtcgggggtt ccagaccagt 71580 ctgaccaaca tggagaaacc ccgtctctac taaaaaaaat acaaaattag tcaggagtgg 71640 aggtgcatgc ctgtaatccc agctacttgg gaggctgagg caggagaatc gcttgaactc 71700 aggaggtgga ggttgcggtg agccgagatt gcgccattgc actccagcct gggtgacaag 71760 agcaaaaact ctgtctcaaa aaaaaaaaaa aaaaaaaaaa gataaactag ccagggcaac 71820 aaagggagac cctaaaattt aaaaattagc ctagcatggt ggtatgcacc tgtggttcag 71880 ctactcagga gagtgagaca ggaggattgc ttaaacccag gagttcaagg ctgcagtagc 71940 catgattgtg ccactgcact ctagcctggg tgacagcaag atcctgtctc acaaaagaaa 72000 aaaaaaaagt aaactagtgt tagagtagaa gtattttaga cacaccctaa taaggcttaa 72060 aaaaaaaaaa cacaagctga tagcaagtat ataacttact gtcagccaaa acaaacttta 72120 aaggaagaca atacaatcca aatgctcaga aactcacaat gcttggcatc caatcataaa 72180 ttactagata tgccaaaaag cagaaaataa tgtgacctat aaccaggaga aaaataaaga 72240 acaggaatta cagagatgat ggaatcagca aaataagacc ttaagaacag ctattataca 72300 tatgctcaat atgctgaaag atttaaagaa aaacataaac ataatgtgga gagaaatgga 72360 tgatttaaat aagaccaaat actaggtgtg gtggctcacg cctataatcc cagcgctttg 72420 ggagactgag gtgggtggat gaccagaggt caggagttcg aaaccagcct ggtcaacatg 72480 gtgaaacacc atctctatta aaaatacaaa aattagccag gtgtggtggc aggtgcctgt 72540 aatcccagct acttgggagg ctgaggcagg agaatcacct gaaccctgga ggcggaggtt 72600 gcagtgagcc aagatcgcgc cattgcactc cagcctgggc aataagagcg aaactccacc 72660 tcaaaacaaa acaaaacaaa aaacaaatga aacttctaga agtgaaaaat acaatgtctg 72720 aaatgagaat tacattagat gagtttagta gatgggatac tacaaaggaa aatatcagaa 72780 tacttgaaga cacagaatag aaaccatctg agagagagag agagagaaac aaacttgctt 72840 ctgactacca aggagcatgg atcttggctt ctcactgtaa aaaaacaaaa caaaacaaaa 72900 caaacccaac tgaaaaatga aacaaaatat gtgaaacaac tgctttcaga caatagaaaa 72960 aaggactggt ccttaagaga agggaaacac aggaagtaag ccccacattt agtctgactt 73020 cctacctgga ggcatattct aggtcttggt actgggagta gaacctcagg caaatcacag 73080 agattgagtt tagggaggct gcagggattc tttaaagatc cataaatagt ctgggctcag 73140 aggctcatgc ccgtaatccc accacttcag gaggccaagg tgtgaggact gcttgaaccc 73200 aggagtttga ggtcagcctg ggcaacatgg caaaacccaa tctgtataaa aaatacaaaa 73260 atcagccgtg catgatggct acttgggggc ctgaggtggg aggactgctt gagcccagaa 73320 ggagagagcc tgcagtgagc tctgtttgca ccactgtact ccagcctggg tgacaaagca 73380 agaccctgtc tcaaaacaaa caaaaaaaca aacaaaaaac cctgtaaata gaaccacaca 73440 taggccgcat gcagtggctc atgcctgtaa tcccagcact ttgggaggcc aaggtgagtg 73500 gattgcttga gctcaggagt ttgagatgag actgggcaac atggtgaaac ctcgtctcta 73560 ccaaaaaata tacaaaaaat tagccaggca cggtagcgtg cacctgtgct cccagctact 73620 tgggaagatg aggtaggagg atcgattgag cccaggaggc agtggttgca ataagccaag 73680 atcatgctgc tgcactctag cctgggtgac agagtgagac cctgtctccc aaaaaaaaaa 73740 aaaaaaaaaa aaaaaaaggt aagttgggga aagaatcttt tcaacaaatg atgctggacc 73800 caaaatcgac ttggaaaaaa cttaaatatg tacctgctga tatgacccaa aatgaagtat 73860 aaaacaacct atgacgtatt ctagccagaa acaattaatt tgaatccaca aaactccaga 73920 tctaacatcc agttcataga aaatacagga gactggggac aacctatgaa agacatctcg 73980 agaaaacaac caaataaata caaaagaggc tgtacgtggg acctaggcct actgtcttta 74040 taagtgccat gtaactaaag gaggctgagt ttggaagaca gtttgacagt ttcttaaaaa 74100 atgtaaacat aaatctacca tatgacccaa caattctacg cctaggtatg tacccaagaa 74160 aatgaaaatc tatgtccaca caaatacttg tacatgaatg tccaaagcag cactatgcat 74220 aacagccaaa aagtggaaac aatccaaatg tccatcaact gatgaacaga cagagaaaat 74280 gtgatttatc catacaatgg gctcttatcc agccataaaa aggaaagaag tactggcaca 74340 cactacaaca tgggtgaacc ttgaaaacat tacgcagagt gaaagaagct ggacacaaaa 74400 gaccacatgt tgcatgattc catttatatg caatgtcaga aaaggcaaat ctacagagac 74460 aaaaagtaga ttaagtggtt gcctagggtt gggaggagag aagtgagggt gactgttaat 74520 gggcacaagg gatcttttgg gggtgataga aatgtcctaa aatttaactg tggtgatggt 74580 tgtacaactt tgtaaattca ttaaaaagtt ttgcactgta cacttcaaac aggtaaattt 74640 tatggtatat aagttatacc tcagaaaaag ctgttaaaaa agagaaaaaa gggaagggac 74700 aatgctaggt tagcagacag aacacaaggg acataaccag atgcaatact tacctctgga 74760 ctagaatctg gtttcaacaa accagataca aaagacattt ttgaaaccag atattttgaa 74820 agatattttg aaataaatgt gagtatggac taggtataaa atgaaaattt attaatatgg 74880 aaagttaaac acaattaact gagaagagta gattataaaa cagctaatgg tgcagcttct 74940 atagaaaaac agtacggaag ttccttaaaa aattaaaaat atatttacca tatgatccgg 75000 caattccact tctgggtata gacacaaaat aattcaggcc aggcccagtg gctcacgcct 75060 gtaatcccag aactgtggga ggccgaggtg ggtggatcac ctgaggtcag gaatttgaga 75120 ccagccggat caacatggtg aaaccccatc tctactaaaa atacaaaaat tagccgggcg 75180 tggtggtggg cgcctgtaat cccagctact ttgggggccg aggcaggaga atcacttgaa 75240 cctgggaggg agaggttgca gtgagccaag atcacgccac tgcactccag cctgggcaac 75300 agagtgaatc tgtttcaaaa aaaatagaag acttcaaagt agggactcaa acaaacattt 75360 gcacacccgt gttcatacca gcattattca caatagccaa aaggtggaag caactcaagc 75420 gtgcgctaat ggacgaatgc ataaacaaga tgtggtctat ccatacaatc agccttaaaa 75480 agaaaggtga ttctggccgg gtgtggtggc tcatgcctgt aatcccagca cttagggagg 75540 ccgaggcagg cggatcatga ggtcaggaga tagagaccat cccggctaac acggtgaaac 75600 cccgtctcta tgaaaaatac aaaaaaatta gccgggcgtg gtggcaggcg cctgtagtcc 75660 cagctactcg ggaggctgag gcaggagaat ggcatgaacc cgggaggtgg agcttgcagt 75720 gggccacgat tgcgccactg cactacaacc tgggcgacag agcgagactc cgtctcaaaa 75780 aaaaaaaaaa agaaaggtga ttctgacaca cgctgcaaca tgcatgaacc ttgaggacat 75840 gacgctaagt aaaataaacc agtcacgact ccacttctgt gaggtcccta gagtagtcaa 75900 attcataggg acagacagtc gaatgccagg tgtcagaggc tggggatggg agaaatggaa 75960 gttttttaat gggtagtaca gagtttcagt tatgcaagat aaagagctct ggagattggt 76020 tacacaacaa tgtgaatgca cgtgacagaa ctataactta aaaatggtta agatggtaaa 76080 ttttatggaa attttacaat gatttttttt ttttttttga gatggagtct tgctctgtca 76140 cccaggctgg agtgtagtga catgatcttg gctcactgca acctccgcct gccaagttca 76200 agcgatcacc tgcctcagac tccgcagtag catggaaggc acactccccc aacaccgtac 76260 cagtaaaata atctcctctc tcctcccagc gcatattctc atacatacca gccaccagat 76320 tctgatactt ggaatccata ttaacccccg ccccctccgc gaacgatcgc tctccctacc 76380 cttccgcaca ccaccaccgg tgaccatccc tctacacccc cgttacccaa aactctcatc 76440 attcacggct tctgcccagt acgatgcata cctcactccc tacccaacac gagcccttca 76500 gcctccgagc atcgcctaca tcggcacttc catgcattgt ggaccaatgc tctctaattc 76560 cctccaccaa caccgaacat tctcacctct cctgtataac ccttccttcc gctatcccca 76620 tcataaaccc cgcgttgccc tctgaacggc ctctcacttt aacgagaact cttgctctcc 76680 ccatcgtcct atctcgcc 76698 <210> SEQ ID NO 31 <211> LENGTH: 4878 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4765)..(4766) <223> OTHER INFORMATION: n is a, c, g, or t <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (4769)..(4769) <223> OTHER INFORMATION: n is a, c, g, or t <400> SEQUENCE: 31 attgaaataa acaaccaggc agcagttatt aacacgggaa catggcggcc gcagcctggg 60 ctcccgcggc ggcggcggag gtcagcgccg acggcagccc gcacctgacg gcgtgacggc 120 cacattgatt ttcctcgcat ctggcttcac tgcattggct cttctgcact gtgtacaggc 180 acagttgctg atatgtgttc aagatgagtg ggatgggaga aaacacctct gacccgtcca 240 gggcagagac cagaaaacgc aaggaatgtc ccgaccagct cggacccagc cccaaaagga 300 gcactgagaa acggaaccgc gagcaggaga ataagtacat agaggagctg gccgatctga 360 tcttcgcaaa ctttaatgat attgacaact tcaacttcaa acctgacaaa tgtgccatcc 420 taaaagaaac tgtgaagcag atccgccaga tcaaagagca agagaaagca gcagctgcca 480 acatagatga agtgcagaag tcagatgtgt cgtccacggg gcagggtgtc atcgacaagg 540 atgcactggg gcccatgatg cttgaggccc tcgatgggtt cttcttcgtt gtgaacctgg 600 aaggcagtgt ggtgttcgtg tcagagaatg tgacacagta tctacggtat aaccaagaag 660 agctgatgaa caagagtgtc tacagcatcc tgcatgtcgg ggaccacact gaatttgtca 720 agaacctgct gccaaagtcc atggtgaatg gaggatcctg gtctggagaa cctcccaggc 780

ggacgagcca taccttcaac tgtcgcatgc tggtgaagcc tttgccagat tcagaagagg 840 aaggccatga tagccaggaa gcccatcaga aatacgaggc gatgcagtgc ttcgctgtgt 900 ctcagcccaa gtccatcaaa gaggaaggcg aagatttgca gtcctgcttg atttgtgtgg 960 cacgaagagt ccccatgaag gaaagaccaa ctcttccctc atcagaaagc tttaccaccc 1020 gccaggacct ccaaggcaag atcacttcac tggacactag caccatgaga gccgccatga 1080 agccgggctg ggaagatctg gtaagaagat gcattcagaa gttccacaca cagcatgaag 1140 gggagtctct atcatatgcc aagaggcatc accatgaagt tctgagacaa gggttggcgt 1200 tcagtcagat ctatcgtttt tctttgtctg atggcactct cgttgctgca caaaccaaga 1260 gcaaactcat ccgttctcag actactaatg agcctcagct tgtaatatct ttacacatgc 1320 ttcacagaga gcagaatgta tgtgtaatga atccggatct gactggacaa gcgatgggga 1380 agccattgaa tccaattagc tctagcagcc ctgcccacca ggccctgtgc agtgggaacc 1440 caggtcagga catgaccctc ggtagcaata taaattttcc catgaatggc ccaaaggaac 1500 aaatgggcat gcctatgggc aggtttggtg gttctggggg catgaaccat gtgtcaggca 1560 tgcaggcaac cactcctcag ggtagtaact atgcactcaa aatgaacagt ccctcgcaaa 1620 gcagccccgg catgaacccg gggcaagcca gctccgtgct ctccccaagg cagcgcatga 1680 gccccggcgt ggctggcagt cctcgcatcc cacccagtca gttttcccct gcaggaagct 1740 tgcattcccc tgtgggagtt tgcagcagca caggaaatag ccatagttat accaacagtt 1800 ccctcaatgc actgcaagcc ctcagcgagg gccatggggt ctcactcggg tcctcgctgg 1860 cttcaccgga cctaaaaatg ggcaatttgc aaaactcccc agttaatatg aatcctcccc 1920 cactcagcaa gatgggaagc ttggactcca aagactgttt tggactttat ggggagccct 1980 cagaaggtac aactggacaa gcagaggcca gctgccatcc tgaagaacaa aaggggccca 2040 atgattccag catgccccag gcggccagcg gggacagggc tgagggacac agccggctgc 2100 atgacagcaa agggcagacc aaactcctgc agctgctgac caccaagtcc gaccagatgg 2160 agccttcacc cttgcccagc tccttgtcgg acacaaacaa ggactcaaca gggagcttgc 2220 ctgggcctgg gtccacgcat ggcacctcgc tcaaggagaa gcataagatt ttgcacagac 2280 tcttacagga cagcagttcc cctgtggact tggccaagct gacagcagaa gccacaggca 2340 aagagctgag ccaggagtcc agcagcacag ctcctgggtc ggaagtgact gtcaaacagg 2400 agccagcgag ccccaagaag aaagagaatg cactactgcg ctatttgctc gacaaagatg 2460 atactaaaga tattggttta ccggaaataa cccccaaact cgagcgactg gacagtaaga 2520 cagatcctgc cagtaacaca aagttaattg ctatgaaaac tgtgaaggag gaggtgagct 2580 ttgagcccag tgaccagcct ggcagcgagc tggacaactt ggaagagatt ttggatgatt 2640 tgcagaacag tcagttacca cagcttttcc cagacacaag gccaggagct cctactgggt 2700 cagttgacaa gcaagccatc atcaatgacc tcatgcaact cacagctgac agcagtcccg 2760 tcccacctgc cggagcccag aaggcagcac tgcgcatgtc acagagcact tttaataacc 2820 cacgaccagg gcaactgggc aggttattgc caaaccagaa cttaccactt gacatcactt 2880 tgcaaagccc aactggtgct ggacctttcc caccaatcag aaacagtagc ccctactcag 2940 tgatacctca gccaggaatg atgggtaacc aagggatgct aggaagccaa ggaaacttag 3000 ggaacaatag cacaggaatg attggcagca gcacttcccg gcccagcatg ccttctgggg 3060 aatgggcacc acagagtcca gctgtgagag tcacttgtgc tgctaccact ggtgccatga 3120 accgaccagt ccaaggaggc atgattcgga acccaacagc cagcatcccc atgcgagcca 3180 acagccagcc tggccaaaga cagatgcttc agtctcaggt catgaacata ggcccttctg 3240 agttagagat gaacatggga ggacctcagt ataatcaaca gcaggcccct ccgaaccaaa 3300 ctgccccgtg gcctgagagc atcctgccta tagaccaggc atcgtttgcc agccagaaca 3360 ggcagccctt cggcagctcc cctgatgacc tgctgtgtcc acatcctgca gcagagtcgc 3420 caagcgatga gggcgctctt cttgaccagc tgtatctggc cttgcggaac ttcgatggcc 3480 ttgaggagat tgatagagct ctggggatac cagaactggt cagccagagc caagctgtgg 3540 atgcagagca gttctcaagt caggagtcca gcataatgct ggagcagaag ccccccgttt 3600 tcccacagca gtacgcatct caggcacaaa tggcccaggg tggctataat cccatgcaag 3660 atccaaactt tcacaccatg ggacagcggc caaattacac cacactccgt atgcagccac 3720 ggccaggcct caggcccaca ggcattgtac agaaccagcc aaaccaactg agacttcagc 3780 ttcagcaccg cctccaagca cagcagaatc gccagccgct tatgaatcag atcagcagtg 3840 tttccaatgt gaacctgact ctgaggcctg gagtgcccac tcaggctcct attaatgcac 3900 agatgctggc ccagaggcag agggaaatcc tcaaccaaca ccttcggcag aggcagatgc 3960 agcagcaggt gcagcagcgg actctgatga tgagaggaca gggcttgaat gtgaccccaa 4020 gcatggtggc tcccgctggc ctaccagcag ccatgagcaa tccccggatc ccccaggcca 4080 atgcccagca gttcccattt cctccgaact acggaataag tcaacaacct gatcctggct 4140 ttactggggc tacgactccc cagagtcctc taatgtctcc ccggatggca catactcaga 4200 gtcccatgat gcagcagtct caagccaacc cagcctacca gcccacctca gacatgaatg 4260 gatgggcaca ggggagcatg ggtggaaaca gcatgttctc acagcagtcc ccaccacact 4320 ttgggcaaca agcaaacacc agcatgtata gtaacaacat gaacatcagt gtgtcgatgg 4380 caaccaacac gggtggcttg agcagcatga accagatgac atgccagatg agcatgacct 4440 cagtgacctc cgtgcctacg tcaggactgc cctccatggg tcccgagcag gtcaatgacc 4500 ctgctctgag gggaggcaac cttttcccaa accaactgcc tggaatggac atgatcaagc 4560 aggagggaga tgcatctcgg aaatactgct gaccctggag aaactgtctg catctttctt 4620 caacccactg ggcttacaaa catttaccag tctggagagc tgcgtctctt tgtgttgcca 4680 cctgacatgc cgccagttct cccaggacat agcagcagac agtcgggccc tgggcccgca 4740 gcatagagcg tgctggcttg gctgnnacng gaagagttgc ctctcccgac agcctgcagc 4800 tcgcctccag accaacccgc agtctgttca ctgcattcac cgtagtgcaa cttagatctc 4860 ctgcagagta actgtccc 4878 <210> SEQ ID NO 32 <211> LENGTH: 240001 <212> TYPE: DNA <213> ORGANISM: M. musculus <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(240001) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 32 tgtgctgggt ggtgaacttg ctatgtagcc aaggatggct ttgaactcat cccgtgcctc 60 tacctcccca gtgctgcaat tagaaatatg agccatcata tcaagttgat tctgaggtct 120 caggaattga tacttcagaa acagggaaag ccttttttat aagaatgttt tatagtgtac 180 tcatgtaaat aaaataaata aaatttttaa taaaagggga gctgaagaga tggctcaatg 240 gttaagagca ctgactgctc ttacagaggt cctaagttca attcccagca gccacatggt 300 ggctcaccaa ccatccgata atgagatctt gatgccctct tctggtgtct gagacagctg 360 cagtgtactt atgtaaataa aagcaatgtt tgatgatttg gaccctggca aaagaggtat 420 gaaaggccac gaggcctcgc cagatacagt tgtccctttt ctttctgtag cttcactggt 480 ccatgctcaa ctacaatttg agaatagtaa gtgaaaaatt tcatagataa ctcacaactt 540 ttacattgct tgccactatg tcatgtaatt ttacaatgtc ttcttcagtc ccactttgta 600 ccaaatccac ccctttgtgt agtctctgct tactatctgt gctttttggc taccaagaaa 660 atctataaag tgttcccttc aagcaaaaca attcaagtac agagagatgt gcgtgggaaa 720 gcctacagat atttgtgtaa cactgattat agtatagctt tcattgtttt gtagtattag 780 ttacaacctc tcactctgct taatatataa actttatcat tggtatccag gtaaagaaaa 840 aacatgttag gaacttggta ctctatgtga tttcaagggt cactagaggg tattacattg 900 gctgaggtgg gagggtcttg ggccctagga gcttagtctg gagaatgaga agggcaaatg 960 cacaaacaag gccacacgct ctgtacaaac agaacacagt aatacttacg tgttgttgaa 1020 ctggcacagg acttaatagg caaatacaaa aatagttttc tgcaacccgg aaatcattgt 1080 tcagtatgag tcttgataca tacaggagag attgttactc aaggcagctc aaagatgatg 1140 tattgataat acggctggtt ctaagaatac aaagttaaac atataaaagc aaaataaata 1200 aataccacag ttataacatg ggtgtgacgt cttgacacta tttcagtact ccaaagtgac 1260 atgattcttc caggtcccgc tggagtgagg cagctgggca tggagttctt tacgctactg 1320 taagagctgt ttggtttgtt ttattgttta gagacagtcg tgtgtcttga gcattcagta 1380 agaaggtgca ctgagtaaca cagcatggaa gcagggatgt gtttgtctgc acgttcagca 1440 caggtagttt tttcatgtta attctgttgc cactgagcac tgatggactc tggatagctg 1500 cctctcccct caagagttgg aatagaaagc aacaagagtc tttcttaact cttaagaatt 1560 taggacagga gaagaaatct aagtggcaat ggggacattc ctgcgaggaa cccaacctcc 1620 ctgcaaaaat attatgggtt aagagtggag gaggacagat cagagggaca ctctgtatct 1680 ccttgttctg tccctaagct gctgaaggct tttgagtctt cggggaacat aatttattct 1740 agctaattaa aaaaaaaatc cttaaaattt actaacaggt ggtcaaaacc aatcattcca 1800 aacagcagac acttccctga aaaacgtgaa gtagcctatt gcagacctcc ttccgattcc 1860 actcaccaat gttaacattt gttacagctt tctaaatatt ttctagctat agccaagtag 1920 gcatatactt ttctttttct ttgtcataat aaactggagc taaaaaaaaa atacgatcaa 1980 aaagcatgtt ttgcaattaa tggacctggg ctcaaatctt gcccaccttg cttactgtgt 2040 aactctacaa aaattacttc tttaggtttc aatgttttat gaggtataaa aatagcaatt 2100 acttcgtaag gtttgaggat taaaatttgg agtgtgtgtg aatcacttaa tgcagtgcca 2160 agtcgttaca gttcaataaa cacttattgt ctatggcaag tgacctttca taagagttaa 2220 aataaggaaa cgtgttcctg tcatattttg ataacttccg ttaagcaaac aaatgttgct 2280 catttctttc aactaattat atctaaatgg aaaagaagtt gcttttccag ttaaaaacca 2340 aacaacattt aaacgtgaaa actcctccac gtctccttaa tcccaatact ccattgagga 2400 tttgataatg gattccccaa ttaaaaaaca aaacaaaact tttgttgtct cactgcgtgc 2460 ggagaacact cccctcggtc tttctaaata ctgagcagcc tttgctttgt caggcaatcc 2520 cggggtggta ccccggtaag ttcgcctccc gcggtcacgc ccctctatcc cctccagaga 2580 cctcagggac agcaattggg gaggcgtatc cacgaaaaaa ccgaggggac atggtggcca 2640 aggagtgcgc cccggaacag cgtctgggtg cagaggtgcg cccgaggggt gcaggctgcc 2700 ggctaccggg ccctgcctga gcgcgcgcgg gaggcacctc tgggactagg ttttccgcga 2760 ccttctcgcc gcagcgtccc tgccgtcgga ggcgcggcag tcccttggcc tccaccccca 2820 ggcccgggcc agtccccctt tttagctttc ttttgggcat tgccctttgc cctcgcatgg 2880 agtcctctgt tgactctccc ttcacttcca gtcacccata ggtcacggtc cctagaccac 2940 agccacccat cttgtccaac tccccgagct ctgaagtctc gccagccagg gagatgctga 3000

ggaccccgcg ggtggggtag ccccggtgtt cccgggccca cgctcggggg gcgcgggacg 3060 caagtttccg cccggtcccc tgagcggtga cagcgttcgc tcggaggcgg cggggaggcg 3120 gagggcgggc cagccccgtg cccgagcccc ctcccctgct cgcgagctcg cgcggtctgt 3180 gtctctctcc gcaagtgcag agccgcggag gaggaggggg aggaggagga gggagctggg 3240 ggaggatctc cattgaaata aacaaccagg cagcagttat taacacggga acatggcggc 3300 cgcagcctgg gctcccgcgg cggcggcgga ggtcagcgcc gacggcagcc cgcacctgac 3360 ggcgtgacgg ccacattggt aagcgcgcct cccctggggg ctcacgggcg gcgggcgggg 3420 ggcgccgcat tcccacccgg gccgctgccc ttggtgcgcg cagcccggcg gagccgcgcg 3480 ccggccggcc gggcaggctg ttgttgtgtg cgggcaccgc tgcccaggcg tgcggagccc 3540 gcgacgccnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 3600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnag aacctggaaa 3660 gtgccgaggg tgtgtgaagg tgacgcggcc ggcaggggcg gcggcggggg ctcgggcgtc 3720 tggggggcct cgggcttggg tggcttcggg gcggtagcgc tcgggccgcg caggccgggc 3780 cgcggtgggg gcggggagcc ggggtcgggc ggcggcggcg gtggcggcgc cgcgccgggc 3840 tcgcccctga cttaactttc tgggtgcggg catgtgtgcc ggaggcgcgc tggggccgcg 3900 gccgggggcg ggaggcgggc tgcgggccag gaggttccgg gttggctcgc cagcgccccc 3960 tcttccgtac cccttctgcg gcccctgcag ggacaggccc tcgggggccc cccgcgggaa 4020 gcgggagggg tcctggcggc cctcgcgccc cggtcacgcc ctgggccggg gaccctcctc 4080 tccgggcccc tggaggctcc cggggaggcg tccagggtcg gcgccgcggg ctggagtgcc 4140 cgcaccccgc ccctggggga gtcctggagg cgccgcggcc gcgctcgggg gtggctcggt 4200 ccctgcttcc atggtccctc cctttcccct cccccaagtg gcttccgggg cctgcggact 4260 gaggggcggg aatcggggac ccgagcccct tactctccgg gagtgacgtt gggcctcaag 4320 cctagagggc ctgtcactgg caggggaaac tttcccaaac ccgagcctga gctcgagcac 4380 cctcctccgc cacctcgtcc tctaatccca ctcccactcc acctcctccg actccttccc 4440 ctcccaccga cccgaatctg gctgtgcctg actgatgggg cagtgagcca atggaaggca 4500 ggaactgacc tgccgggtac cggtaagcca atggtgggag ccagaggcag gaaggaggcg 4560 gggtttcttc cgtccagtta gggctgagtt gcaggcgggg cgggggagcc ttggagacgc 4620 cgcgagccct ccactctggc gcgtcccttg gtcacccgca cctgggtttg tggaatagtg 4680 tcactcacag aatctgtgac ccggggagac ctgcataggt gcgcgaagat attgcttttc 4740 tctggtgctg cgagaggcgt tgttttagac atgacaaagt ctaaagccac ttcaggatgt 4800 ggcagtaact gcgaggcccg gttttaaaat ggcatatgtt gatagtgacc gcgttctgga 4860 tctcagcacc aggtgagatc tttgaaggtc tgcgttagtt tcactgggct tctgtccagc 4920 acccggacga tggtgaattg aaagggcacc ctgagagtaa aggcgcgggg tggcctcttg 4980 tgaggtgatt tttaggagtg ctaaagcatt cttgtttgga attggcctca ctgggatctt 5040 gtttaatcag accaacacca atttcccaag tctccttgaa agtttcgtgc ttggtctggg 5100 tgtgacattt taacaaagtt actggttatg ctgtgcatat ttttttgtct tgttcttggg 5160 taaacaaaat gaagttttga accaaagcgc cactaagata ccaagcgtgg gtacttagca 5220 aaagcagcta aagaatattt gttggcagaa aacaaaagga ataaagtata gcagtatagc 5280 tttccatatt actcccttac aaaagattcg taaaacattt tatctattta tttatttatt 5340 tatttattta tttttagttt ccttaaacac ggatgaattg tacagtatgt ggctacttct 5400 ctgatgtgta agaggtcaag agctatcttt ggttgtttgg gtccagtgaa ctgactttct 5460 tgactcctga gttttaggaa aggggggcgg gggcggttcc cttgaggatc cctggttgct 5520 cagcgggaat tgcggtctgt taaaaagacc gccgctgctg ctgcagtgct ttttgtgtgt 5580 gtacatgctc tgttctttgt tggtgaggtt agtccaaccg gagggcagca acacattcct 5640 tttcccaatt ggaatctttg ggagttcaaa ggatgagaaa tgttaaactt aaaatccatt 5700 catttttgga atctgtcacc catgaattta attttgggat ttaaaaaaat atctaatggg 5760 cacgaaccac actgggttct ccagctttta ttactattgg attattaaga aaggacttgc 5820 gagagactaa tgtaaggaaa gagtagtgtg taatatgtga ctttcaaatc tatagtgtag 5880 attcccaacc tgtgtaattt tagacgttct tgtagaagta aattgctttt tttttttttc 5940 cttcgagaca gggtttctgt gtatagccct ggctgtcctg gaactcactt tgtagaccag 6000 gctggcctcg aactcagaaa tccgcctgcc tctgcctccc aagtgctggg attaaagctg 6060 tgtgccacca ccacctggtg taaattacgt ttttctgtag cttttgaagt gttattttgg 6120 tgataaatga gtcaagtgaa agataagcac ttatttcaac tgacagaagt agggagtatt 6180 gtaaattaat gttcagaacc cagcaacatt cagagactcc cactgctggt taatttggga 6240 ggccactctg atgcaggccc tttctctttc ctgaattctt aaaagcaacc cattatttca 6300 cttcattctc cataaggatc cttcaaagcg ttcttagatt cttggtggca gagaatagca 6360 agtcgcctaa tgcctggtga ggggaaaaac ctcgcaagca tatggaggca tctagaaaaa 6420 gatgtgcatt gtcagcggcg gcgattccat tgtgtgctct cttgctggag ctgaaccttc 6480 ttcctcctgg gaatttccct cttaaaagag aggatttctt tgactttaga tgtcagggtg 6540 ctgaggccca ggtttcagga cagctcaaca atcattcatg tgagtttaat gcttttgagg 6600 acttaatatt tttaaaaata tttttaaccc ctcatcgatt aaatataatt tagatgactt 6660 tcagcatgag agacatctta ctgaaaatac atataaaaga tggagggtcc taggattgca 6720 taaagggtta atggttctcc ccttacctct caatagatgc gtcttattaa agctttccag 6780 tctccatgga atccatgatc tctgattacg tttctatttt acatgtagaa gttaaggact 6840 cagtgcctta gctgtttcag gccacagtag gttgctattt gacccatact ttgacagctt 6900 agatctctag gaaaaattgt ttttgtcgta ttgaatacaa aggcagtccg tatattgtta 6960 gaaagaaaaa gcatgaagag tggcccttta aagcattttt aatagaagac taattttctg 7020 gtatgcatgg gtgtctttga tatcttggtc attgttgtgt tgtggttgaa attatattta 7080 aaagtttaac tatttttagt tgttaatatg ataaaaccaa tgtttaagcc ctattagctt 7140 tttaatttgt ttatttttta agatttattt attatatgta agtacactat agctgtcttc 7200 agacacccca gaagaggaca tcagatctca ttatggatgg ctgtgagcca ccaagtagtt 7260 tctgagaatt gaactcagga cctctggaag agcagtcagt gctcttaacc actgagccat 7320 ctctccagcc ccatgatact gatttttgaa tgaagaaaag ccatggaatg gaaaacacaa 7380 tgttgagttc tttttcccct tttctatcac acgctccttt gcctccatgt cttctaagtg 7440 gaaagaaagg aggcactcag tgtttatgcg cttctttctt tcttttgttt ttgttttgat 7500 tgtttcctac tttttgattt agactagaga agcaagaagg ggtgccatgg cataccaccc 7560 tctgaagcct cttaaagtat cctacctggc aaagctgtaa agtgcagttc agtgtcacag 7620 gccctcactt cagagagcac gagggaaact ttacaggttc cagatgttct agatagaggc 7680 gacagtatga cttgcgtggc tgttatagca gtctatgcga cgtcctagct gctgtgaaag 7740 ggagagtaca gagttggcag cttacagtga aggtaactag gtgttctgct ggtctgcagt 7800 agagcacacg acttggcttc aagagcaaag agtctctgtg tttactaatt agcgatattc 7860 attcccattt ctagggtcag aggcagtggt ggaatgctag gatttgtttt agaccggtgt 7920 ttatttggtt ctatggttgg gaatttctag caaactcgaa tgagtacagt gcgtacggta 7980 atgtttctca cagctgcttt ggaacttctg gacatagtgt cagtcatcag gaggaggttg 8040 caaatcggga gacgttaagg ggcacttgac agatagatgg aaactgaagt ttgcggtaaa 8100 ttctggtggg acttatacct caagccagcc agttcttatt ctgtcctggg cccatgttta 8160 gcagaatctt tattttgggt tttggaggtc ttttctctgc ctttttttct tctttagcaa 8220 ttgtttcatt gatttatttc atcattattg atggaaattt gactcttcta gtcttgacag 8280 tgtatttggt aataaaatct tcaagttaca gagccaggga ctaaagggag ggccacaggc 8340 tgggggtgat gggcgatggt ctccttcctt cctccttttc ctcacacctt ggtggtaggg 8400 aaggaaatat ttgccttaat cttatcttct gtgtgagtgt aatttcaagt atgtactatc 8460 tagcaaattt tgcatggatt tgggattctg ctatttttcc tgagaaagga attatgttta 8520 gaataaagaa gttgtggggc ttggggggtg gctgagtcag tagtgtgtct gcactgcagg 8580 actggagttt aagcttctag cactcatgta gatgcctggc atggctacgt ctgtagtctc 8640 agtgcttggg agcagagaca ggctgacccc agagtgcact aaccagcctg cgtagtcagc 8700 tgtgggcttt ggggtcaggg agagtcgttg ttgttttaaa tgagatggag aacaaagtgc 8760 agggcacctt gagctctggc cttcacatgc acacactgat agacatacac ttcgtactct 8820 cacacaccat cctcaagttg tttaaatgtc acacactgat agacatacac ttcgtactct 8880 cacataccat cctcaagttg tttaaatgtt cccttgatag atgagcttaa aattaattag 8940 attcctcttt atgaaaatat ggacgcttat gattggttca gttttgtttg gcttgaagct 9000 tacgtgctgc tctaggcgcc ctgtgtggta tggtacatgg ttacatggtc agagtggtcc 9060 tatgcagctg gtaggatgtg acagggtggc ttggcaggtg ggccccatca tctctgtccc 9120 accccctctc ctatggccat ttcttgtgct gcctcctctg ggcctctgta gcctggcttt 9180 agctctgtat gcagccttgt gttctgctgt ggctatgggt cttctggaaa gagctcattc 9240 ccgtcaggcc cacagtgtct gtgtcaggga tagtgccagc cactttctag actttcttat 9300 gagtggtcca ttcttttgat tatggccaca aacacataaa tacatgctgt tatcctcatg 9360 ttccaggagg ttagaggtta aggggaagtc tgggatggct gtccatcaag agtgggatat 9420 aacaaatgac cttaggactc tgagctgttc agtctaagaa ggaacagatc tgaatagctg 9480 aggttctgcg gacgttccca gtcaggactg agaagttaac tcctgtaagt catatacaac 9540 acatacctca actattcttg aaatttcaag atccccttac ctttaaatgt caagaagcag 9600 gacaagcagt gaagtaaact tgatggagtt tactaaatgt gtctggggtg agggacattt 9660 gttatgcact tgggtttttc acttagatgt gtgaagcagt tgtagcatcc tcctttggct 9720 gctcaggaag gaaatggaca cacagggatc agataacttc caggctcaca cagttgggct 9780 actgaagcac attagaaccc caggcttctg gcctgctgag ctggggttcc tattggctga 9840 ctgttaggct cttgcgtcag cctttgttaa gacaagacaa catcaatcca tttattctgt 9900 gaaaagcata ctcttgtctg ttgttctctg tatggaaaat ttgtttgtgg gggatcagta 9960 gaaaatgtac ccagggaaca ctttccggga tacagatttg gaaaagacaa ggagttgacg 10020 tacatatgtg gcttcttatt tcttcaatat agatttaatg ttgtctgttt aactgtcgga 10080 cacaggttgt gtggtgcctt ttggtgagtg ttgtgcactc catgtagagc ggatgactct 10140 gctgagatac catagaccca aaagaaggct gataatatat tccgtcatct gacttctgct 10200 atgctatttg tggaattctt ctgtctgctc aattgtttgc agggagcagg cgcgctttca 10260 ggaaactcgc tcctgtgctc tgccaggatc tgcacgcatt gcttgtaatg ttccagctgc 10320 caggacccag ggcctgttgt cagagatgaa aatgatgcat gggatttttt gttggtcact 10380 tatgtcccca aaggcttcac ttggagagtg agtgagttcc ggaacgtgct gctcgctgcc 10440 ctctgcccat tagaggccac aactgaagga gggtaggccc ttccagcagc tccatcttgc 10500 tcataggatc tgctcgtgaa caaacttcct ctgcctctga tgtcacccct gctttcgtaa 10560

gaacatttaa taattatctt aaaatttcta attatattgt taatatgctt aagatgaaaa 10620 actttgagtt gttttgaaaa tgtaagttag aatattgaat cgtgccaggc ctggtggtgc 10680 agttctttca tgaaatcttt agggaggtaa agagaggggt gtctctgacc ctgagaccta 10740 gttcatgttc aggatagcca tgactaagta gagaggcctt gtttcgaaaa ccataaccca 10800 acacaaacaa caaatgttgg gttgtgtgta tgtatgcagt tgtgtcttga tgatgttact 10860 cagtgctgga ctgcttgctt agcatgttca aggtcctggg ttcaagctca gagagatgac 10920 ccctccccaa tgtaattgtg tatttccaag gacccttcag catgtctcca gttattttag 10980 gccatcttta gagtctgtgc aaatggagac tttagataat tacataagta atatttttta 11040 agaattagtt ttattttgtg tatgagtgtt tgcctgcatg tttgtccagg caccacatgc 11100 atgtctggtg cctacagaat ccaaaagagg gcattggatc ccttaggact gcagctgtag 11160 ctggttatga gccactgtgt gggtactggg aatcaaaccc aggcaattct taaagtgcaa 11220 ccagtgttct taaccactga gccattgttt tctagtttaa ggaacaaaat tttaatgata 11280 cttttaatgc actaagatgt gtgtgtgtgt gttattattc tctactatta tttcattcat 11340 atatttttgt ggtgttgtgc ccagggcctc cagtatgcta aacattagat caatattata 11400 tataaaatcc taacatgtat ataattagaa ttactcatag ctgtcacttt catctaacat 11460 gtaatcactt ctgagcagtt attgttggga tgtgagaagg aaattcttcc acatgcactt 11520 ggtaggtccc taagtaagga ttatagaaac tcattaaaat tcggagttac cacagtgcca 11580 tgtcctcaag ttgctgtcct gggctggggg actccctggc ccagaggtga tctttttgcc 11640 tgtccctgtt gtgtgtgctg cagaggagga cgcggagtga ggcaggcacc agagtgagat 11700 gtgagaagag ctgctctcgg gttccaccag gaatgctttg cacatctttt ccctcttttt 11760 ttccttctgt ctttcttccc tcaaccccac ctcccacccc aagtagaatt ggagatgtaa 11820 agatgaatat gggcagagga caaaccagaa ggatttcgtg tgaatgagca tggtaggcag 11880 tgtcccttct tggtaggtag gtctaacctg tttgcagcac ttagtgagag aagtagctct 11940 ctctctgtta ggaatgtgac atgtaaaatc attgctgttg ttcagtgttg tcgcagcagt 12000 aggggcactg atgtgtaatt tagttggatt gttatattcc atgccttttc atgtttctct 12060 gcttagggat attattacag acttgacaat gttaggtgat ccaagtggct cacatgttat 12120 aattgaaaat attgaagtta tttaagatgg ttcaaaagtg taaccaaatg tttaagacct 12180 taagaatgtt tgcctctaaa tttttttgcc agctgtgttg gcgcacgcct ttaatctgtg 12240 atctaagaaa gcagagccag atgggcctct gagttcgaga ccagcctgac ctctacatag 12300 tgtgtttcca ggctatccag ggcttcaaag tgagatcctt actaaaataa gcacacacat 12360 aaataagtag aaaagaatgc aaagagagag agagaaagaa tccttgcctg tgaggtcaga 12420 ggatatagct caggctgtca agtgcttgct tagtgtacag gaggctctgt gttcactagg 12480 caagcactag taacctaggg ggttcccagc agcagtaaac caagtgtccc ggcacacctg 12540 caatcctagc cctcaggagc tggagccctt gggtcagagg ttcaaggcca ttctcagcta 12600 tacagtgagt gtaaggttag tcaggaatat gtgactgttt tctgttcctt ccttttccca 12660 aaggaaaaga atgcattttt ttaaaaaaag atttatttat ttattattat atgtaagtac 12720 actgtagctg tcttcagaga ccccagaaga agacatcaga tctcattatg gatggttgta 12780 agccaccatg tggttgctgg gatttgaact caagacctgt ggaagagcag tcagtgttct 12840 taaccgctga gccatgtctc cagccccaag aatgtatttt ttataatttc cttctgagcc 12900 ttggttttct tagttgcttt cttaagttgt gttagttttt tggtttttta agacttttcc 12960 atttaagggt gatagaaaaa ttccttgaaa atgttagttt tcgtattcac cgcatcagag 13020 tcttggcaga acaaacaggt ggtggagagg agagccagca aggaagtccc aggaagtgct 13080 cgctgctctg tcgtggactt ttatcttcag caagaggcaa tgcggaagct tagtcttcaa 13140 gtttccactt cacacatgta attatgaatc atagcataat ggaagaccga gatattagct 13200 gtaatacaag aaaacaacac agtcatcact tcagacacag aactgaccat tttagtcagt 13260 attgacagct accctcttac cctcccagcc cagcattgtg cttggacatg aagtggattg 13320 gaaaacaaaa cgagagcttg gggtctcagc atagcaggaa gcacatgggg ctggtctacc 13380 tggactgggc tggccctgtt cccttcaggg tcctgacacc atcactgaga gaggactctt 13440 gtttcctgtg agggctgtgt gggtgggcta gtggggaggg aaggcgagaa tggctgacct 13500 tgctggttgg gggagtaagt cagacccctg atgatcacca gcaaagcagc tgtctgcacc 13560 tggatcttcc caggagccaa cctggactgt gctcaggtgt caggtgcaca ggattctaat 13620 gtgcacgttc atggaggaca ccagtgtaca gaggggctgt gcagagagag gaccctactg 13680 aggcagagag taaagcaaga gtgttatgtc cgtcctcttg catcttagag gatgctaaag 13740 gatgttttaa tagttttccg agttatcaaa agtgcaggtg actgatggtg ttgccagtgc 13800 atggaagaaa gaactactgc tacatgatac atcagcatca gtgtatatta agatggtttg 13860 ttctgtgtcc tgtaaataaa tatagtcttt acatctaagc aactcaggaa cttgcacttg 13920 ctctctcatt ggttcagaat acatgtgcct gtgcataaac atagcataca tacacataca 13980 tgctatacac acactatatg catgcagaca catactacat gtaattacat atcatatata 14040 tatatatata tatagtacat gtgtgtgttt attttcaccc cagacagtgt gtagaacagc 14100 tgaacagcat agaagacttt gtttttctaa actttctatt tgactgacac ttaaatcttt 14160 ctctactgca agccattaat aggttgatct tcccacggta ttcctttcct aataatgtaa 14220 tttcccactt actatagaac gatatcttta aacacttacc tctgagtctt tgatgaaccc 14280 acccttcttc tatttctgct ggcacatgtt gtggtatacc ctcttgttct cttgatttgc 14340 ctagagaaag tagatgagtt aatctaaaat ttaggaagca tgcctttgac ataagaatta 14400 ttttaggaat tcctactgct aatttaaacc tgaagtaatg aaccagaaca aaaggaggag 14460 tccaaaaata ttccaaagtc attactaagt agcttaatga atcaattatg gattaaaatt 14520 gtcctacagg aacggaagca aatctaactg tgttctcctc agaaacaata agcacagtgt 14580 gctttgtcgc tgtgatatga tcacacagtc cttcagtgcc agggtttagt ggtttttcct 14640 ctgcatagta tttgacactt tagagaaaat ggattttagt ttatagtgga gaggagaaaa 14700 aaaatgaaga aaaccatggg gatagttggt agtgctagga agttaataaa ccagacactt 14760 cagagatagt gtgccagggt ggttacttga gtacctgcat tgaagaagca gtaacaagaa 14820 cgaacggaag tgtcaactga aggactaaaa cctcaagaga tgatgaaatt ctacaatata 14880 cattaatata gactgtatta acacttataa aaatatcctg attctccaaa ttttacttac 14940 atatttttat tatttttaat tgtgtgtgca tctgtgttcc tggaggccag aggcatgaga 15000 ttcccgcagt tggtgttgcg gtgcttgtga ggcatctgac atacgtgaca tctgacatgg 15060 gtgcctcaca atagaactcc agttctctga gccatctctt catccctcac cccctaattt 15120 aattttttgt tttggacagg gtctcactgt aatcctggct agcatggaac tttctgtgta 15180 gaccaggctg ggctgctcac tcttctcttc tctctcttta tccttctatc gccatctctt 15240 tgtatctttt cattgtgaaa gattacaaac attcagaaaa attccagtga gtgcctgtgt 15300 gcagtgcatt tccatctatc tgtctgtcca tccacatacc catctatcta tccacccatc 15360 catccattat acatacattt attcactccc cctctgtctt tgcccccccg ccccccctct 15420 cgtgtgtgtg tgtgtgtgtg gggggggggg tatgtaggta ggataaatca taaataaagc 15480 ggtagatagg attcttcatc cgtaaagaac aatgtcttag gagcactgcc ctgagtccca 15540 tcacctcaga actaatctct tcttgctgag ttttgatttt tcaaaactag tccacctcat 15600 agttaaccaa gtccactccc tgcatctcct ttccaggctt ttctcctttg aatggctcta 15660 agagtccagg tcagttgtcc tgagggtttg tgcttatcct gctagctttg gggtggcttc 15720 tgttgcttgt tggtgaccat ggcgtggtcc acttgggcgg ttctccctga gtcttcctgc 15780 agtctgttta gattgggcct acacaaacca tgctgtggat cacaagggaa gacaggaagg 15840 tcaggactga cctgaaggac gctcatcacc cattaatctg aggtatactt tttaccttta 15900 agaagaggta gattttgttc aggcacagac cagaagaagg tgagtcctga ggcattaatt 15960 gtatagtcat ctggacaaac aggaagtcta taacgggctt tctctgacct gccagggata 16020 gaggtaagca ggcgcttcta gttgagttga aagcttaggc cttctgcttg ggcagtctcc 16080 agctactcta acttaagcat ccttagagcc tacggcctgc tgtgtggctg gctctatctg 16140 tccctttctc tgctctgctc cagtccatgg ttgttcctct gcctgctctc tgtagctccc 16200 tctgctcctc cttctcccag ctccccctcc tccgccctgt ctgaaagttc caccctctac 16260 ttcctgctca gctattggct gtcagctctt tattaccacc aatcagaacc tcagataatt 16320 ctaaattccc ttaggcaagt gagaaaggat gaatatttac aaaatataag gctggtggtg 16380 ggtcataaaa atgacaatac caatataatg ccagcagaga cacatcttca cacaatatga 16440 agaaaagatt accccagcag aagcctttgt ttgaaattct tcccgtttct tgttctgtgt 16500 tggagaatgg taatttacat ttcttgcacg cttgactaat ttcgttttta atgtttctga 16560 ttttcttctt tctttatagt cttcatttgt tctctcctcc aactttccca accctgaaac 16620 tcttcctagt gtctttagtt tctcaagctc cttcagaact gtctggaagg ggtggtggga 16680 gcttcactcc ccaccactct tgagggtgtg gagcttcatt ctcaccttga caaaaggact 16740 ttaaaggtga gaggcattcg cagggactgt ctgggcttct gcttttgcca cgcacctgcc 16800 taatacggtg tagagatagc aattatcagt agatatctgt ttacttttag ttgatgtgtt 16860 taatgcttag gcgaggacag aagtcaccac tgttttgttt tgttttgttt tgttttgttt 16920 tgttttgttt tgttttgctt tgctttgttt ttcgagacag ggtttctctg tatagctgtg 16980 gctgtcctgg aactcacttt gtagaccaga ctggcctcga actcagaaat ccacctgcct 17040 ctgcctctcg agtgctagga ttaaaggtgt gtgccaccac gcccagcaga agtcaccact 17100 tttaacaact atattttatg tatctataac aacaaacaaa ttacatttga ttgttaatgc 17160 aattttgcct gatttcatac ccaacaaatg aattattctc atttctgacg agaaggaaaa 17220 cagcaattct gtctttaatg tgaatctaca ttcatgtata agaattggga ggcggaaaga 17280 taccatcacc taaaatggag aggtcactga agatatcaag atttactcca gagtcaatcg 17340 gagttaccaa agacttagtt actgagactc ctgtcttttg gcacggcctg gctctgctag 17400 aggtggagtc tgatggcctg ggtcacacct gcactgcttt caaggggcac tcccacctga 17460 gacaagaaat gctgtctagg aagctggagg agtgttttat tatattaata gttaatattt 17520 aaattgagaa agaacatatt taggagacca gagaaattaa gaaaggaaag aaaaatgagt 17580 ctggtgacca gattttcaag actgtagttt tcaaggtgta gttaacaaat cagggttatt 17640 ttattaagca gagaagtaac aaagatattt aataataata aaatatttta attgatttta 17700 tagaactttc cagaagtgta tattattggt atgttacata atcttgtttt gtcattgtgt 17760 gttatatata tgcgcgcaca cacacacaca cacacacaca cacacacaca cacacacatc 17820 cctagtgccc tgggcccctc gtgataagct ttcattgagg tctcccatgc gggagcctca 17880 tgcaagagcc ttgctgcatt ttacttgata tggctgcttc tctaaatgtg gtgtcatgct 17940 tgcagatgtt gggagtaagg acatgcttct gggttccatg acagaggcag gcctgatgca 18000 ggtctgtgac aagatctaac tggggactat gggctgggat ctcggcacat atcctctccc 18060

cacagccttg gcaagctggg gttaaaacca gttgtcttac ataagacaga tttcactttg 18120 tgaagcctca gaagttgtgt agacacttta agcatgctgt aaccctcttg taatggaggc 18180 tcagcagagg gagtgtaagt gagcaggtga ggctagaagt ggagttatcc tgtttattac 18240 aggctaaggc agacaacaga agtgttagga gagaggaata ttgacataca agtgatccat 18300 tcattatgag atttaagcag ctcttccttg gttaacaaaa ccctaacact atatctatcc 18360 atgggtatag taagacattt agatggtttg gagaccctca aatgcagtag ttcgcttgct 18420 tttcaagtct gtgaaagcat tttggtcaac gccatgcact gctgtttaat aatgcatttg 18480 tatatgggtg gcctcatgtc ccgtttctgt tactgcctcc tattgttatc cttcctttaa 18540 tgctgcgatg atcagcattg acccatgttg atgccctgtc agtcttagct aggtctctgg 18600 aattttaatc taaagtaaat tgttttaatt tttaaaatga ggattttcta aagggctggc 18660 tatttaagaa gttagtcctg aagacgagaa ctgcctgtat gttgggattc tctgtggtct 18720 ggcttttgat ttagcctccc ctcttttgac agctaatgca ctgtccagga gtgcgaagtg 18780 tcactgggac tcttcagtct atgagacgct attttgaatg ctctttgtca actgtttaga 18840 gcaaatatgt tcccattttg ttacattaga gaatgttttt gataatcttt ttagcaccca 18900 gtagatttaa tgctatgatt ctcaacaggc agattatttg atgtatagtc tcattatgga 18960 gtgtctgtcc ctctgtgttc atgtggctcc acacaatggt tggtgaggct gggagtcatg 19020 ttttgtgcag aagactgaga acagggtaat ttaaatcagt aaagtgcctg acttttaagg 19080 gaaaaaaaaa agtagttatt ttaactactt ggaggtggta gaacatttaa attatattga 19140 aaatagctga agaataaagt acatagaatt cacatttcct taactcggaa gattgtctgc 19200 ttgcttgaca tatcttaagt gttggtctta gaagcagaca ctgttattct ccacagagag 19260 attatacttg gatctgtcag agaactatct aatgggaact cactgttaaa atcatttggg 19320 tgagccgggc atggtggtgc acgcctttaa tcctagcact cgggagccag aggcaggcgg 19380 atatctgagt tcgaggccag cctggtctac aaagagagtt ccaggacagc cagagctaca 19440 cagagaaacc ctgtctcaaa aaatcaaaaa aaaaaaaaaa tcatttggat ggtttgatta 19500 tagtttaaaa caaaaccacc tgtcttttgg gaatattaat gcataagact agatgctact 19560 tttgactagt tcaatctgtg gcttattctt caatactttt ctcaggggaa aaaatgcagc 19620 tcttgctatg agtggtcgga ctaattcacc agagtcaggc atctgcgatc gttttgggtt 19680 tggaagatgg tctggtacag tgggcttcgc aggtagcata agtaaacctg atcactagca 19740 acgcggaggg gaggcaggga gaagctgact cagatttgta ctgtatctcc cagttgcaga 19800 taaaagtccg tttcactgaa gatagaggat ggccgtggtc aggcgtatta gcctgtgttt 19860 acctggggaa tagaatgtgc ttaatagctt agaagtggtg ggaaagttta tataaaaatt 19920 gtttggtggg gacttggcag atctgcaggg acagatgaga tatttagata tagttagcag 19980 ataataatgc ttaggagctg gttatgaagt ttacaggaac ttctgaggct acacagtact 20040 agaaggacat ttataaatac ctatcactga aagaaatctc taaggtgatt ttggtgtgta 20100 cctcataaaa cataaaccct ttagaaactt ttggatttcc aacagttata tttaaatatg 20160 attgataact caggagcact gggtgtgtca gactgtcacc cgtgcttcac tctggacaca 20220 ccgtgacaat gtgactgtga ggaattactg gtgaggtgta gcacactcat ggacagagga 20280 tctccgcccg gtcctatcat gcttgcctgt taccctgcca cacagcatgt tcaagagcta 20340 gggtgtgcta cgggtgctgt gctggttggt gttttagggt ctacctatct agccacacat 20400 gcactgtctt ttttttgttt tcatttcctt agtatttcat atttgctttt aaatcttgaa 20460 ataggaatgc atattagtga acttttccgt cacagtcctg gggactgtag agggccatct 20520 gtgtcgttca tgatgtgcca tatcaactca gatttgagct tttagcagga aagtaaagca 20580 ttactgagac agccaatccc acagtgagtc agggtgagag gaccctgcgt tacagcggag 20640 tccagcacag tttactaagc ctgaagcatg tgataacagt taactgaaag agattagtat 20700 gttaactaag aagtgtccat gctctgactt ggatagatta aatcaaaact atagtgttca 20760 ccgggaatag gcacattgct gtcccctccc attcgtggtt cactgactag aattcctgaa 20820 cacaatgctt aacagcttca ggttgttttc tagacatgaa atgaaccgat ctcagccttt 20880 ctcaacagaa caatagtttt tatgagctct ggaggactaa gtcctatttg ttttccttca 20940 tttctttagg cataaaatgt tttagataca aacttctatg tgcttttatg attctttgtt 21000 ttagccagtt ggtttattgt taggaacatg gaaatttcat ggttgtaaaa gtttcctgga 21060 ggggctggag agatggctca gcggttaaga gcactgattg ctcttctgaa ggtcctgact 21120 tcaaatccca gcaaccacat ggtagctcac aaccatccat aatgagatct ggcgccctct 21180 tctggtgcgt ctgaagacag ctatagtgta cttacatata ataaataaat aaatcttaaa 21240 aaaaaaaatt ccctggagac tgaaggccac ctctgtcttc ccctgtcagg tgagccggtc 21300 cttgcttggg tgacatcagt tctgaatgcc ttgcttattg atggcccttt ccctctatga 21360 tcttcatggg cactcccctt ccactgcatg catgcctgtg gtgtcttctg accttataaa 21420 gctttccctc ttcctcctgc tcctcctctc cctcctcctc ctcttctctt cttcctcctc 21480 ataggtggta gttggggctt tgtatcttta atgaagaaac aaaccgcttc agtagtagaa 21540 ggaagagatg ttggagttag aggatgcctt aagttggcaa tgggcagagt attagctttt 21600 aaaggattct tttatgatat agtactcaca tgatcttgta taaaaaacaa gattacatgt 21660 tttttgtttt gtttttgttt tttaacctac aagaagccat gtgttgggac tgtgcatgaa 21720 cctttattcc aagcactcag agacagacac agaatctgtg tgttctaggc cagcctagtc 21780 cacatagtga gccccaggat agccaggatt atatagagaa cctgtctcaa aacaccaagg 21840 cgtgtgtcag gagaagacat gcatgtttgt acttaacggc tgttggccag gacttgaatg 21900 agaactgaga ttctcgagaa actgtagatt aaaatctgtt atattctcag ttggttagtt 21960 ttcatctcca tatcatcaac ttcattatgt caagttcgtc tttgcgtttg ttatcacctc 22020 tgtaagcttg aataacatga taaaattgtt ttacatttgg caattatgac ataatagctc 22080 aacgagtgtt agtctctaca gtcttcactt cgtaccttcg gaggcttcct gttctctctg 22140 atgtccttag atatttctcc tgtcagtttg gagcacttta aacaataaga agttaaagag 22200 atcgtgtcct gggatggcct cttgtttcag taccttctga aattcttcat agtttctagt 22260 tctacaggat attcattcat tcattcattc attcattctc tctctcttcc ctcccccaca 22320 gctctccccc atccccccat ctaacagagg caggtgcatg cttgtaatct taggatctgg 22380 gggtgaaggt aagaagatag gaaggtcaac acttgggtca gcctccactg cataccagtt 22440 cactgcccat ttgagctagg aggctgacta ggaggaaagg gaagcaatcc caaacagaca 22500 cccaaaacct aaagagcagc aagagtttga agcaaattcc aagtatcatt tcattttgtg 22560 ttaagaacga ggcaaaaaaa aaaaaaaaaa aggcctggtg tggtggtgca cacctttaat 22620 cccagcactc agaaggcaaa aaggcaggtg gatctctgaa ttcgaggcca gcctggctta 22680 tgtagtcagt tttgatggtt ctgaaattac aaatgcaaag agaagacaca aagccttggt 22740 ttctagccct cgcagtgctg tgctcagcga cagagcactg atgtgttgtt aggtgcagag 22800 ctgatgcttt ttcctgaagg tgtgccaatg gacagtgcag cctgggcggg gtctcagaca 22860 tttaacttag gaggcacgta aaatcccaag ccctggggtc agaaatcttg tccgtttttg 22920 cctagcatgg ggcctggaac cttgagtact aatagagaat ggaagtggat tcttgtgaag 22980 atgaatcttt cttagtgact ggtatctttt aggacttaaa gtatgggaaa tgaatgaagg 23040 gcaggagaaa cagctcagca gccgagagca ctggctgctc ctgcagaaga cctgggtttc 23100 actctcatca cccaaatgga ggctcacacc catttgtacc tccaggaggg atggggcatc 23160 tgatgccttc tgctctcttc caaggtcact agccatgcac acaatgcaca tatatacatg 23220 caggcagaac attcctacac ataaaataaa aatccctcat atacacagaa ttattagtta 23280 attaaaaaag aggagatgaa ttaagaattt gctcacagtt cctgcagaca atacctgaag 23340 tgcggggtgt ggtcagcggt gtcgcctctg tgaaatctga ttgagagaac tctgaagctt 23400 gcaggtcagt atttcctagt gcacagcagc actggttctt gtttatgttt attttctatc 23460 aagaacctgc ttgacatcgt ttctgtctta tagaagaagg caggctatgc ctcaagtagc 23520 catgtttgca tattcaaaac acttaaaata atctaccttc tcttgaacca gagtgagcta 23580 tttataaact ttgtaatcat tgacacactt ctatatcctt cactaagaca attaatgtgg 23640 gaagacagta tttcagtgca taaccagctg ttgatcatct ttgtagctat tttagttgct 23700 ctgtaagact ataacaaaac tatcttcaga gacagttgat agaatgagaa atttagttgc 23760 ccaatgtttt aagtaggaaa aaggcaaatt acttggttac tttactatat acataataaa 23820 ggttagaatg aacacaagtg tgtcccttac cccctcattg tgggtatgct gtatataacc 23880 agtacatgga ggggttttga gtcaggtctc tgctggtgtc tgttttgact ttgaatacta 23940 tgtggtagag gctatcttta aagtactgct cctgcctcca cctaccaagt tctgagatta 24000 ctgccatggg ttatctactt agctcgagtt ccttttctca gctactgtct ccagcaaact 24060 gaaattacag cagatactgt tgtcattgac agtataagct agcaggcaga cttgtgacac 24120 agctgccaag cagtgatgtg tgtgtctaga ccattcttgg aaaagggaga ctgccaggga 24180 cttagaaagg ttgtgtacag ccaaatgata attatttttc agtgatcttg agcggcttgg 24240 atctttcttc tcctgtcatg tgctaaatgc atttaattaa tatttccaag acactgaatt 24300 tctcccgtac ttctcaaaaa atgattagag gtggaagatg gtggctgtct agacagtagg 24360 tgggtagaaa gctttcaagt ttacccaaat cttttagaaa ccaggtaatt gttctaacta 24420 tttttgagaa tttagtcttg catggtatta aattctagct aaaatgtgga agaatagtgc 24480 tggcaagatg gctcaggagt tctaggcaat tgttgtccat cccgagttct atcctcagga 24540 cctacctggt ggaagaagag aatgacaaat gcagattgtc ccctgacctc cacatgtgca 24600 ttgttgcata tatgcacaca tacacacaga gaagaattac catatagtat gtattctcta 24660 aaatgcatct taaaacatta agagacctat aaaagacttc ccacatcacc tgttaactgt 24720 ttggctctat gagaggaaca tagcctgctg gttaaaggta tatagactgg aaacattgcc 24780 tgccccaatc ccagctcatc cactggggag ttctatagac cagtaagtaa tacagtaagt 24840 tggtctgact gtattaacca agccactaag aacatctgag agcattatca gactgcttct 24900 agtagagctt acttaaacag catcttgtta acttcatgtt gtcttttcag tattgttcct 24960 gtaagagctg ggcctatgta agttgttttg ttagtacttt gttgctctta ggaaaacatt 25020 ctaaatttat aaggtcttta tttttgaata gtacatcata gacttatggt aagaaatcag 25080 tgggttggtt tttttgtttg tttgtttgtt tttgtttttt taaattacaa gagtcctttg 25140 aaaagccaca caccatgttc cttacacatt tacccttgtc tctagctctg attttgcaca 25200 gttaggcctt gtagacagac atgtggattg cctagtctgt aatggcagtg gctagtgatt 25260 caacagctca cactggaggc taagttctat gatgttttag cttttagaaa taattgtaca 25320 tagcacctaa aatgctcaga atggtattta aactgtactg cactgacagg tctgactaga 25380 taactgcttg tctaattgtc acacagccta gttgggttgt attctgaccc agttgtggca 25440 gttatattca agacctggta tgtgacatga acagtgtctg ttaggctgcc tcactgaaaa 25500 gtggaaggaa tcagtccgtg ttagttgatt gcctggttcc aacttaaggc gaacctttct 25560 gcttcttaaa gatttattta tttatttatt atatgtaagt acactgtagc tgtcttcaga 25620

cactccagaa gagggagtca gatctcctta tggatgattg tgagccacca tgtggttgct 25680 gggatttgaa ctccggacct tcggaagagc agtcgggtgc tcctacccac tgagccatct 25740 caccagcccc ctttctgctt cttatcaaga gccagatgat gggacggacc ctggtgccta 25800 ggccagcttc agcctgtgga acgagaggca aacttaccag gttagttgtg agactgaagc 25860 actatcagaa ccccacactt tcctgcctgt ttagtttggg attgtgggct ccagtaatag 25920 cagctgcctc atttttagat tttgtggaag aactgtcaga tttggggttt ttaatttgtt 25980 tttctgaaaa ctttttattt aatgactcta cccgtaaact aattttcata tttctgtttg 26040 cactgctgtg gaaatgggag ccattctttt caactcagtg cctggaatgt tggactgaaa 26100 attccatttt attgtgtgtg tgtgtaaaaa tgtgtgaaag cttttgttcg tttgtttaag 26160 taattccgct tatttttcat ggaaagatgg gtggctcaaa attgccagat taattaaagg 26220 tatgagaagt gttcaaagat ttaattttgt agtgaaactg atcagtgcaa cataataaat 26280 actaaatttt gatgtgctta tttattcact attccctcta tcttatctca caggagtaga 26340 aatatgtccg atttacaggt catttctaat agaccagaac taagattttc tttggaagat 26400 ggactgatag tctttataga gttttcatca atcaagatgt taagaatacg tatctacaaa 26460 ataagaacta ttagaggact ttcatttgtg gttttgtttg cttgtttttg gtttttcatt 26520 cattgaaaga gttttgattt ctaagtatta aaaaataaat accaccgtgc ttttttgatt 26580 cctgcactgg ccattgtcac ggtgtacaga gcacaagatt gtgtgagccc atttgctgca 26640 gaaagccatc ccatcatgat cagtggaaaa atcgattgtg tagttttgaa aatttagatg 26700 gatggttgtg ctgctggtgt cagctggagc tggggtcagg agcgggccag cccagcatcc 26760 gcacggtgga ggactgaggt tagcagccct tcccagcatg agccccaagc tccctcgtgg 26820 aagatgagag atatacctga acaggaatac ctgatttgaa caggaaatca cattaaataa 26880 gtgttggact gatctgcccc ctaacatggt caccttgggc aagtgagtag actctgcctg 26940 tccactaaca ttggagctca ttgttctttt ttgttttttt gtttttagtg gaagtttagc 27000 gtaagataaa gcacccaacc acaaaccttt aaggtaatat tatatccgtg tgtgttttat 27060 aacctcacag cgttcagaga tgttccatcc attcacctct gctctcattg ctttagcagg 27120 ttgttgtttt aaactgaatt ttttaaccca ctagtaagtc ctgaaatcac tttagttagc 27180 tgtagccagt ataaaaccaa aacaaagcta atgaatataa aagaaaactt tagggtgtga 27240 tgcagagttc agtaaaggca aagctaaacg cacagttgtg tgcgcctaca gctttccctc 27300 cacaggactg acggtggtag agtgttttgc ctaccttgtt caaggccgct ctgccttcct 27360 gtgagtgttt tctctctctg actgtactct tcatctctac ttttcagatg gagagccttc 27420 tggtatagaa ggctaactat caatatttca tggctcccta agggcagagt tcctaaagga 27480 agtactgtga cttgtaggtc ccgtgatacc tgagcatgtc tgaggtgctc cttggtgggt 27540 aacatagaag gcccatcttg agctttcatt ggctctcagg tctaagcagt gtcgcagtgt 27600 gatctaagca gccgcctgtg caggtgctct gtctctcaac accattacag acggattagc 27660 agggaaccct tcgtcttcta catcgcattt tagttgtatt ttaattgttc attttgcaaa 27720 ggctttgctg aaatagcata ttctgcatcc ttctgatttt caagtatgcc tacctctact 27780 ccctgtagta aatgcacata tgtgtgcaca cattcataga ggccagaggg gcattattct 27840 ctcctccgga tgttctggac ctggagttta gtgctaggac tgtctacgct gcttggtcca 27900 tgtgctctgg ggatctttct gttagtgtct gccatgctag tgctgggtta cagttttcat 27960 gtaggtgttg caggtctgaa cttgggtctt tgcacttaaa cagagtgagc catctcccta 28020 gcctgtgaat cctttttggg tttctaaaag agctattcca ccctgcaaca taagcaaact 28080 cctaacgaag caaaaaaact tttctttaat tcaaaattca aataacagac agttggtatt 28140 tttgaaataa tggagttgga tacttatata actctatttt cctcactgag tgctttatta 28200 agaaaagaga ggagctgatg agatgaccca gtggtttaaa gcactggccg ttcttccagg 28260 agacccaggt ttgattcctg tcactacatg gtgacaccct atctggcttt cacaaggatg 28320 caagtgatgt acatgcaggc aaaacaccaa tacgcaaaat aatatatatt ttaaagaaga 28380 tagttatcta ggtcagcaag caagatccct tggccattgt tgaggacctg cggctaatgt 28440 catcacaaaa gtgggaatat gtgctgaggt gtcatatggt gagccaggaa gccagagagg 28500 ttcaggggcc acccttgcta ttttataaca tcttgctttt gtgaaaacta actcatttca 28560 agaaatgtgg ccttaaactc agagatcgaa ttgcctcttc ttccaaatgc tgggattaaa 28620 ggtgtctgtc agcatactta ggcactgtaa tggctcttcc tggttgtcaa cttgactgta 28680 tctggaatga actacaatcc agaactagaa ggctcacctg tgatcctaac ctggaggctg 28740 ggagatacaa ggttctgccc tggatctcag catggagatc tggaggcaca gtggctatga 28800 atcccatcca gaagattaag taagacaggg agatctctga gttcaagggc atctggaaca 28860 aagcaagtcc cagatccagg cttgttggca cacaccttct gctggagccc tacataagga 28920 cattggaaga aggaagatat atgctctctt cttcacctgc ttgcctgtgg ggctgagcaa 28980 ctgctagatc cttggacttc cattcacagc tgctgctgac cattgttggg agttggacta 29040 cagacctaag tcatcaacag atttccttac tatatacaga ctacccgtaa gttctgtgac 29100 tctagagagc cctgattatt acaggcacat acagatttta tttttttatt atttttttta 29160 gatacggttt ttctgtgtag ctggttgtcg tgaactcatt ctgtagatca gactagcctc 29220 aaattcagag atccacctgc ctttgcctct ggagttctgg gatcaaaggt gttcactacc 29280 actacctggc gatttgattt tagcttaaat ctacatagac agaatagtta gaattgcaca 29340 cctagtgcag gggaagagag gtgaccagat gttgccacag cttgccagct ccatagagag 29400 tgtctgtagt gcagaataca cttggcatag tgttcagctc ttctctcagg atggaagcta 29460 agcatgtgtc cacaacactg tgtgtgtgga tgtttatagt ggcctagtca tgcagccaga 29520 gataagagaa gctcaagtgt ctgtccacgg ggaaagtcac ccaacggaat cctgttaagc 29580 tgtaaaagga agcagtgaat gagaaaggtg acagtcacgt ggatggggca gacttgctgt 29640 gtaagagacc agagcatgca ctttgtcttt ttctctgaaa cttgggaact agaacaagag 29700 aaatcagacg gctgttgctt gaggctgggg tggagaaaaa gacccatcta gaatggtaag 29760 cgtagcttgt atgttgtagt gcaccacctg tttggtgtgc gtcagttgtc aggaagtgga 29820 cccaccttgt gtataagcgg tccttgtgcc cgccggtgtt ggttgcttta tgtaaagtag 29880 aaagcagcct ttcttggtgg accgcatccg tccccagctt atacacgtgg cctcagttaa 29940 atcttaaagt tacccaaatt aatatttgtg gcacttggtt tggggacatt tttgggaccc 30000 gaagggtgta ttactctgca taatctccaa ctggtctcag cagttctggg cactccatac 30060 tgtcttcccc ttttctgata acagagcttc gggacatgtt ttttatgggc agatgatttt 30120 tgagcttctg agaattttag aacagattct ggtttccaga aatactgttt gaaattgttt 30180 ggaatctttt cctttgtagg atttcaaaat gaatgcactc ctatgtctgg gttgtattgt 30240 ttgttgtttt gcttttcttg cctattaatt ccgtgtctga gtcactgagt ttttactttt 30300 ctggttaggt tgacttatag ttaatgtgac ttggcctgat atttttcaaa agacttacac 30360 agatatgtag tgtatttgtg aatatttata ttttgttaat cactggattt tacttgttta 30420 ctattaatag actctagtgt ttaccaccag ctccttagaa agctccaggg ttagactaga 30480 cttctcagag gtccctgtga tgatggccaa aaaggacagg gagtttccat ctcaggtcgg 30540 gtccggtggg agactgcagc gggttctcct tgatcgaagt gttctcacag tactcgtgat 30600 tacagggtca taaaacaaac catgctttgt atgcacactg gaagttgttg ttttgttttg 30660 tttttccttc aaaacagggt ttctctgtgt agccctggct gtcctggaac tcactttgta 30720 gaccaggctg gcctcgaact cagaaatctg cctgcctctg cctcccaagt gctgggatta 30780 aagacgtgcg ccaccactgc ccagcacact ggaagttttt acaagcctta gtactgccct 30840 tgtaaatttg atattgctgt cttaggtata ttgtgaagaa atctagattg tcctgtgctt 30900 tttactctat attttttatt gtatgatata gaatacattt caaaatttat caccttagca 30960 catggttacg cttatcttta tttttgttgc aacaacataa agaacattac ttactatgac 31020 aaaggttaca tgcatttatt tagctttttt ttaacctttt tgttttgtat ttgagtcggt 31080 gtctcactct gtaaccctag cttggcctgg aactcacaga gctccttcct ctgcctccca 31140 gccctgaggc tcctgcccgt tcttgcgtgg caggggagat gagtgagtac acgctctaaa 31200 aatctctttt ttaaaattta aatctcttct caattactct ccagtgttgc tggtcagagc 31260 ttgtgcactg tttggctctt ccatgccttt tcttgccatc acagcttctt ccagcttggg 31320 gtgggcttct gtccagtccc cctccccttt ctcctattag agcagttcta tttgcttggt 31380 ttttttgaga tagggtttca tggtttctgg ttccattccc tatgtggctg tggttggcct 31440 tgagtgcctg atgctcttgc ttctacctcc ccgttgctgg gatcacaaga gcatcccacc 31500 ttgtttgctt agcagtgaga ctcctgaagg gtgtacttag gtgtacaata aaggtgctta 31560 cttcacagtt gttatttgaa atgtaatttg ctcacacagg gagtaataaa tttggagtgt 31620 ctcaggagag aaagcctggg attttctgac aggcagtttt gctctattac tgtctccact 31680 ctgtactgtg tgaccagata tgtgtagagt cctgcaagaa caccgagtgg cttctgtctg 31740 tattttatag tttcttagtt cactccttag gcaaagcaaa cacagtaatc cagggcctga 31800 ggtccagaca gcccatggac ccagaacaga ttccctatct ggtttatgcc tccagctgtt 31860 accgttgcct ctacagcact ggctcccgtc tttccatcgc tgcgaccctc taatacggtt 31920 cctcttgctg tggtgaccct cagctgtaag attatcttca ctgctacttc atagctatga 31980 ttttgcataa gtatcagtat tttctgatgg tgttaggcaa cctctgtgaa agggctgttg 32040 gaccactgtg gaatggttgg ccctacctca gcctgataac cctatgatgg taaacgtgtt 32100 ttgttctctg ctcttgtcct gaagagccaa ccagggtgca ggatacagta gattagttgt 32160 gtatgcttct ctaacaaacc tgaactccag taaatcacac ttttctgctc caggctcata 32220 agagttgttt tggtaccatc tttctttctt tctttctttc tttctttctt tctttctttc 32280 tttctttctt tctttctttc tctctctctc tctctctctc tctctctctt tctttctttc 32340 tttcttttaa ttttaaaaaa atttttatgt ctgtgggtac actgtagctg tcttcagaca 32400 ccccagaaga gggcatcaga ccccattaca gatggttgtg agccaccatg tggttgctgg 32460 gaattgaact caggaccttt ggaagagcag ccagtgctcg caagtgctga gccatctctc 32520 cagtccggga ccatgtttct aataggcctt tttgttcact tgtctgcttt gattttgaaa 32580 tagggcctgc cctgtactct agatgtacct acgacttgcc actctcctgc ctaagcctct 32640 ggattgctag gattccagtt ctacaccacc tcacctggcc tggaaggtgg attttagaaa 32700 actgtcaaag atgaacaaac tttaaagaaa tccagagtta gaaaaccaga ttaatcaggg 32760 ctgatttatt cattttatgt tggtgtatgt tcaattttat acactcaatt acacattcaa 32820 ttctatcaaa gaaccagtta tactaatgat ttcttaaatg aatattttcc aaaccttgtt 32880 taaactcttt gagttacaaa agttgaatct gcatataatc tttcagtttg tcaaatgagc 32940 tgtgagtttt caggaaatct atccatttgc tagtgatagg aatgttacaa catgttcaaa 33000 ctgttactta agtttattat tttagcaata ctgccacata tgaagagata taagggaagt 33060 ggtaaattat aatgaggaat agttaatgtg acaggaccca aaagtgtatt tcagtccttg 33120

tccctggagg tctgtcatgg tagtttttgg aagacatcta gtgagtcact gttttattta 33180 gttcagtggc cattatagca atgatactga ttttgtttta tatggcagat ttacggggca 33240 catgaaaaat agaatttgca ggctagggat gtagctaagt tggtagagtg cttacttgtg 33300 gagaggcaag ttcgatcccc agcacctcat aaagtgggtt tagtggcttg tgcctgtaat 33360 cccagcactc aggagtgggg aggcaggtgg acccaatatt atcctgtgtt gctattaata 33420 gcaaagtcaa ggccaggttg ggttatatga gactatgaga ctctatcaga aaaaaaaaat 33480 aataattagg ggaaaaaaag aaaaagaaag cagatcctgc ctccaggaat gacaggattg 33540 cagtttgggg agggtcactg gtcaggaagg gactgactta gtaaagtgca gtctggccgt 33600 ctccttttga gggcctcagc cagtgactgc tgtcctaatt aacatatcag taaaacttat 33660 tgtgtgatac ttgaactcag tgaaagatta tagtaaactt actcacgcta gactttgcca 33720 acattgtaag aaaaatggaa ttgatgactt tcaggatatt gtaatggatt gctttagctt 33780 tagtagcaga tttttaaaag gaatgaatca ataaagccat tattctgtgt gtgtgtgtgt 33840 gtgagcatcg caagcatgtt cgtgccatcg tctgtctgtg gtgttgcaat gcatcagccc 33900 acattgagat cagaggatag cctgagagag tcaggaatgg cactcagacc caaggccact 33960 cagacccaag gtagccgctg cctttaaccc tttacctgct gagttcttcc ttgctgtcaa 34020 aggataggta atgactgtgt ttttcttcca tctggtcact tcttttgggc tcctgtttac 34080 cttcacttcc cttagagacg aagttctgta aaactacccc atttgtctga gagcttattt 34140 gtgtcctccg agttgcctgt tggaaaaagt cctggcctag aggattccac agcctcccct 34200 ctgagtgctt cctcatcaga cttgtggttg ctgagggcag aatgtagaac tctgcagaat 34260 gatgtcctgt ctcagcctcg ctcatgtctt agcgctgaag agtgacccca tggaccatcc 34320 atcagcctca catctcacat tgttgctgct gactcccttt accttgcatt cgggttgtca 34380 gactctgcac tgtcctgagc accatgaaac ccttgcagtc tcttgtactt cccagtcctc 34440 atctggagat ggagcaagca cagtggctta tagatcttcc cttgtgagtc cgtggtatgt 34500 caagtttctc ttcttaatgc gttcagaatg tggtcagtgt tgaggagcgc tgcactcaca 34560 cagacaggaa ggaagagctg gagtctgcac tctaacatcc ttagacccaa ggtcacttct 34620 gtgtctatgt tcactagacc cacctgaaga ccctcgtttc ttatcctgaa ggctcagctt 34680 agacaagctc acagctcttt tatttcagcg ggtctctctg taatagggtt tagttttttt 34740 gtttttttac ttttagaaag taggtgttaa catctttagc atttagattt ataattactg 34800 agaattttct gacattttga atagtaccac ttaatacatg gagactaata atcaaacatt 34860 tagactggag ctgtttgtgg caggagccag ttttccctca aagctggcgg actgtgatta 34920 tctgtcccta tgtacagcag ctccacaagc catgctacac tctccgcagt cccatttcta 34980 tatggtgttg gggtaactac cactctgttg gtagtctttc actgtatgtg gaaatatagt 35040 ccacctcctg aggacgagag agaggaaaca gtagcaatta atgctttatt cccgcagtgc 35100 ttcagaaatc ggcatgcaag ttctcatgct agtcttacta atgctgttat tttgaatttg 35160 tttaatttca aaacagtgtt cagtgtctcc taatgagaca tagcccctga aacaaggtca 35220 gtgtgataga agagggagcc tggtctgtca ataacaggtg gattttaaaa gcctctctcc 35280 aagctggtgg agctctgagg gctaggtgtg cagtggatgt gatgcggatg ggtgcttcca 35340 ctctcccttg ggaacactgc agaggctcct tctgtgctcc cctgggatgg atggctactg 35400 cctgtagatt tgggttatac ccactccggg caatcttcag gagtcttgcc ttcacacttg 35460 gtctttctag cagtaagact gcttctgtgt gagagtgtct gttttgacta gcttctgcaa 35520 aattggggtt gcctaggaat cctgtctttg cctaaaaatc tgaactctag attttgtaag 35580 tacaccaagc ttccacataa tactggatat tggacccagg gtctggtgcc ttcgaggtaa 35640 gccttctgcc tctgagcggc acccagctgc tggttttgtt tgttcggttt tcccgagatg 35700 ggttttgctg tgcagcctct gctgtccttg aactcactgt ttagaccagg ctggcctagt 35760 gctgagatta aatgtttgta ctaccatcac cctgctcttt ccttttgtgc ttagtcaggc 35820 ctaagttgtt cactctgtat gccaggccgc ctttgaactg gagctctgcc tgtctcagcc 35880 atccacatcc atgctgcctg caagacaagc acaggccaca ggcttggctc caagttaaaa 35940 aagaaaaggc tacagaactt tgtaggcttt tgtatttttt taacaaacac aggctatata 36000 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtatttc tgaataaagt gcttaataaa 36060 aattaagaaa aagattgcta atttattcag taccattgta tactgcagag ctttatcaag 36120 tattttcctt ctttattttt ttaaaacttc ctttggccaa cctttgtcct acctcaatcc 36180 tcaaacttgt ctccttgtgt agatacagtc cttggagcac tgcagcaaga ggcccttgta 36240 ggatcttgga gctctgtgta aattcaactt ggaagccaga aatggttctt ggcacttgag 36300 gccaggaaag ggcagtgtga gcagcggtga atggaggtgg cggtgaatgg aggcagtggg 36360 atgctgttta gtctgtttcg gttgactagc ttggtgctta cgctcgctct gttctgtctc 36420 ccattgttgt atcactaaca tgaaggaagg tacctgtggg cctcggatgg ctcacagcct 36480 acccagtcct tttacttcat ggttttgctg aacacttttt taaaaatcct ttttattgtt 36540 ttttgttggc attcctcacc ccgtccttgc ttttcatttc cattttgaag gacagcttaa 36600 agaaatgtcc atgtctcagc acccgtgtac cttctgtccc catgtggaac tcaacaaatt 36660 tggaagacat ttgcttggaa ttccaaaggg cactgtggaa actgaacttt catggtaaac 36720 attctggaaa tgacagaaaa tgggggtatt ctcttctgaa agaagacctg tggtcttgtt 36780 gaagataaag ctgagaataa cagcatgcgg taaaatctgg ctttgagtta gagatttaga 36840 tgagcggttt ctatgtcctt ggtttgttaa gcctgtctac aatattgtat ctgttcagaa 36900 atatttatta ggttgaaatg aaggtatttt tttccagttg tttggtaagc aactattata 36960 tatcgctacc aaatacaaat gtctcaagtg catgttaaat taggaaagca aagctagaaa 37020 gacttcgggc agcataaggt gtcgcagaat aaatgtacta ttcggtttct tctcatgaac 37080 cccttctaga ctcgcccaag atgggaatgg tatatccacc cagagttccc acgctgtcag 37140 cacggacaga ctggaacaca gctgttgatt tctataggac ttgcctggct gtttcagaag 37200 agttggtctc tccttcagca cattgagtag tgctcatttt gtagtgttac tgggaactag 37260 agagtagagg gctgagagac tgatgtccca catatggggt cttgagttgt acctcctaat 37320 gtggccctgt gtctgtgata atctatgtgg ttatcattag tttttagcat agagagggtg 37380 tgatgaaact agtcacactt ttatacttag gacttcaata tgcgtcattt gatttagttc 37440 tcccaagatc tagcccttca tggtggtgca tgcccataat cccagcactt gggaggcaga 37500 aggttgatat ctgtgatttt gatacaaatc aagttctggg acagccaggg atgcataaaa 37560 cagactgtct cgttaaaaaa cttaaaaaaa ggatcccttg gtgctgtttc tatttttgac 37620 ttaacatggt ttctctttga aagaataaat ttctcttaag aagtcaacat tactgttaac 37680 aaattatcag ctgattaact atttcccttg agtgtctcaa agcttttttt cttgcactgc 37740 tttttctatc atctcctctg ttttataccc tcctgccccg gcagactgtt tcctgcccac 37800 ctcccccccc cccnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 37860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnngatgcag 37920 caaacacccc tttccgtgtg ctcttggatt aacagtgctc tccctctgtc catatttttc 37980 ctggtctagg agatcggccc ttgcgccttc tgtgcttcga ctctgggttg agccatgtgt 38040 catccagcac tatctccctc attttcatgt cattcttaga gtctcctcca ctttcatttc 38100 tgttttattg ctatccccat cagcactgta cattatattc gttgtgggag aaacatttta 38160 tgtttgtttg ctttttaaaa caaagtctga atatgttgcc ttgtctggcc tgtatgtaat 38220 tccttgtgta gaccaggacg ctacacagat ctgctggcct ctgggttccc cagagtgctg 38280 gaattaggta tgtgaactac catgcctggc tccaaaacat tattttataa taagataaag 38340 aacattttgt ctctagagaa ctctaggtca taaccagtat tttatttctt ttgagcatta 38400 aaaaatacaa ttacattttt actaaatata acacgacata aaatatataa tgcaataaat 38460 aatacaatta tatgtaatat atgtgtccac acacacatac atcaactttg taagtataaa 38520 gttgcaaact ttgacaaatg tttgtaataa gctacttaga cacaagtgta tataattaga 38580 aaatttactg tacttttaag tcacccttgt tttcaccctt agactggccc cccacctggg 38640 tcctctcagg tgtaaaggtg taaaactgcg aattgatttt tacaccttta cacctnnnnn 38700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 38940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 39780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnncctgg ctgtggagtg 39840 tagacagtac tccagagtac agccacaccc cattctcttc acccgcacac caggggaagg 39900 aagttttgac tgtctctgtc acaaagctgc catgagctct tgcttgctgg ggtggcccta 39960 ctcagggcag gcatttgaga gagcacttag ttggacagtg gttgggaagg cttaaatgtg 40020 cagccttgct ggacgaggca ccgcgctctt tcccttcatg ttttcccctg aagcgtgtga 40080 gcgctcagcc tcttgcagcc ttccatgcct gcctctggct gccactctgc agtgcctaag 40140 ttgtgttagt actgaaacag aaaaaagtat tatagctact aaatgtctga caaacatttt 40200 catttcatat tgggttaata cctacgaatg ggtttgtggc aaattttcac ttgtttactg 40260 ttcttgttca ataaactaca gaagtttgga aagaaacttt ccaactaaag gctcggtgcc 40320 tttccagaga gaaagtcagt tcgactgtgg tttgattgtt gagctgatga ggagctgcct 40380 tgttgattga cagctttcct tagtttccca cttcctcatt ctcacttcct gcccacacaa 40440 tcaccctctg ccccacaaat ctgttgtgtt tattttaaat tagattcttt ttttgtaaga 40500 tagtaaatat gtgctggaaa ctcagccctc gttgtatggg tgctaatgtc tctcagccag 40560 ccacgctgtt ctcaggccgg tgctgagtga aggtgcaagc attaggtcag cccacgtggc 40620 ttgttcagtc aaactcggta tgttctgggc tttgctttga aatacttgga attttccaga 40680

agttactttg gttgttcttc tttcaagaca gagtttcttt ctctgtatag ccctggctgt 40740 cctggaactc actctagacc aggctgtcct cgaactcaga aatccacctg cctatgcctc 40800 ccaagtgctg ggattaaagg cggaacggat gccaccactg cccagctttc ctttggttct 40860 tcttaagggt gtgtttctga ttcctgctaa cttgcccgcc acatggtctc tgaatggact 40920 cactgctcct ttggatgaag gaatgcactt cccagatact ggcattctgt ttggagactg 40980 gacatttagg gatgtgttta ctcgtaatta aactgtttga gattttgtag tagtggacgg 41040 tttggtttta agatctattt aagataaatt cttttaaaat catttccttt ttaaaaaaga 41100 tttatttatt ttatgtatat gagtacactg tagctgtatt cagacacacc ggaagaggga 41160 atcaggatac cattacagat ggttgtgagc caccatgtgg atgctgggat ttgaattcag 41220 gacctctgga agagcagtca gtgctcttaa ccactgagcc atctctccag ctcctcttta 41280 agataaatta taagataaag ctagaaaata ttttttgaac atgtatatat atatgtgtgt 41340 gagcgtgtat gtatgtgtgt gtgtatatat tcattttttt tcttgagtta aaaaatgtat 41400 atacacatga tttaaagtga attaagcacc ccttgctgct actgaagatc aaatgtaagg 41460 cctcacgctt tctgttcttc cctgagctat atcactaagc ccagattagg cttttttttt 41520 ttttctttcc attttttatt aggtatttag ctcatttaca tttccgatgc tataccaaaa 41580 gtcccccata cccacccacc cccactcccc tacccaccca ctcccccttt ttggccctgg 41640 cgttcccctg ttctggggca tataaagttt gtgtgtccaa tgggcctctc tttccagtga 41700 tggccccaaa ttaggttttt ataaccacaa ctttatttag atttttgtat taaataattt 41760 tgatgaagct ccaattttca tgtatacatt tcctctatag acaaagtatt cagtgatggg 41820 ttagtgctag aagctcttaa gaacttaaga ttagattctg tgcttcaaaa ccacccagag 41880 tcgttttaga tacaattttg aatcctctta ttttttaact tgactcttaa aaaggtttat 41940 ctttagtgtt tgctttgaca atacatatat taaaattgga acaatgcaga ggtgattaga 42000 atacccccca gaaggatgac atgcaaattc gtgtcataga aagcattcca tacttttaca 42060 aatgctaatc tttattgttt aaatgatgtg tttggcctgg gcgcacactg ggatagtatt 42120 ccataagtaa taccttaact ggcagagata tttcaattct ctgatcacat ggaaaggggg 42180 ctagcaaacc tggctgtact ggcaatggct agtgccttgg ctattcttgg ttgtcactgg 42240 actatatctg gaatgaatta caatccagaa atattgggca catctgtgat tgagatggtg 42300 agacaggaag acaacatgct tttgatccag atcttgaggt ggtttggaac aggcctttaa 42360 tccagatctt taggcacacc tttcctctgg gccacacaca ccttctgctg gaggcctatg 42420 gaaggagaat ggaaggaaaa gggtttgctc attccttgtt tgcgtgtact cactctgtct 42480 gtcagcacat ctgtgggacc ctacttcttc agtggagttc caccttacac agaagaccac 42540 tgagacaccc agcctcacgg gactgagcag ctgctgggct tttggacttg gcattcacaa 42600 cccccattgt tgggttagtt ggattgctgc ctctaagtca ttcaataaat tacacacaca 42660 cacacacaca cacacacaca ctatttgtat atatttcatc ctgtaagttc tgtgactcta 42720 gagaaccctg attaatacag ctagggatgg gctggctggg atgatgagag catcaaggct 42780 tctagtggcc tcttaacaat gtgtaatgaa ctgtccttaa atgcaagggt tctgttttgt 42840 gctattaatt aaattcacag tgaatactgg taggacagct tgcaatttat gtgttttgtc 42900 ttgggacttt agtaatttgc aaggtgagat gaagggacag atagtgaatt ttcagtaaat 42960 tgtaccagga aaacgtgtaa cttcttggat tataaccaat ttgttggaag acagtggctg 43020 tgcagcacat gccaattcat tgtttctctc actgattact gcagtttaac tcaggtacca 43080 tgctttcctc attggtctaa gctgactttg gaggtattaa aaatgtacta cggtttgctt 43140 gatgattcta gatgggtcac ttgcttagtg tgggctgctg cccctgtgtt taatgtgcat 43200 taggtttttc ctacaatcct gccttaaaat ggagcatctg tttgtcatag acactcacgt 43260 atctctggtt gcttgtcatc ttctcagtgc tgccttttga taaacaagca cttttaattt 43320 tgataaattt aaagttaaat ttgttgcttt tagagccata ctcaaggtta caaagcattg 43380 tggaaatttc tgtatttggt aggagctagg taggggttca cctctattcc tttccatgtg 43440 actgttcagg catggttgga agtcatttgg ccacaggcat ccagtcttac ttttgttctg 43500 taatccagta caattgttga ttgtgctgtc ttggtgcagt tttaaggctg agtagtgaag 43560 gtctttcacc attgctccct tatactattg tttgattatt ttgaattctg gcatctctat 43620 gaatttgagg attcgttctc catttctata caaaagatca ttgtcatttt gacaggaact 43680 tcgctgactc actagttgac tttgggtgtt tgtccttttg acagtatcct ggtgtcttcc 43740 cgtgctcagt ctctggttcc tgtcagcagt gggcgtggtt ttcagtgcct agtcctcacc 43800 tccttgactg tcagtcccga gtagtgtagt ctttggattg ttccttattc ttacattgat 43860 agcatggcaa gcacacatca agcagaggga gcacactgag cacacacact gagcacactg 43920 aacacactgg cttcctagga ggaggcagat cacagcactc ctaaagtgca ggatgaactg 43980 ttttcagact gtgcacataa ccttaaggaa agcacactga tgccgagggc cccaggagaa 44040 ggtgactgga ggccagatgg cccatgatcc cggtttagtg agctcagcta gctttgcagc 44100 gactccaatg agatgtttca cagtgcagtg atgggttgtg gatcctgatg cctcagtaag 44160 ggtctaagga gggaaaagcc ctcctgcccc ctttacaggc gaaacaggca actgatagca 44220 aactttgcct tctgttctta agtgtttctg ctggtttcaa aatgttaagt aaccagaatt 44280 gatgagtgcc ttacttttga ggaagaaagg tatttactta caacaattaa acacaccttt 44340 cacactgaaa catgtaatgg ttgatatttt ctaggtacct ttctttgctc ctttactcgt 44400 ttgtctggac tgtggtctcg agacagtttt agtttgcaag tggtgttttt gtttttttgt 44460 tggggacggg aggtcctgtg atctctggtg ctgggctttt ataacatcat tggtgggaga 44520 ctgcattgct gcttcaggag tgcttggcag taaagctccg tgtgcacagg agacagggct 44580 ttcaggcctc tcctgtggtc tttgtgatca ttatggcaga tagatggtct gacctagtta 44640 ggttgcttgt gagcatgaga gagtcagtcc taagacacag tatggcagac tatttcttct 44700 gttgttgact atgtctgtgg acactgctgt cagtggtagg tttcctgttg aactttgggc 44760 atggcttggg gatatttctt agctgagggc ttcggacagt attttggagc tagagtatga 44820 caggaaacga tttagtctct agtagattaa agattctgtg ggaatagttt ttgtggagtt 44880 ggggatttag ctcagtgata gagtgcttac ctggcaagct cgaggctctg agttcagtgt 44940 tcagctgggg gagggggggt caggtaactg ggattttttt gtttttcctt tctccggtta 45000 tttttactca ttgcttggtc tctaggacca gaatagtgtt tggtgtagca gagcctcagt 45060 aaataaatag ggactgacca tgtgtcttca gaagtatcct tggaactcca tgttggttta 45120 tgtttaaagt caccccctta gaggattata tagtttgact agtgagggac aacatatgtc 45180 ttgcttagtc ttctttatat tgatcatggc tgatttggcc atgtgccata cataacagct 45240 gatgtagtaa tagagatata agtacatcag ctagctcaat cagcactcac ttcccagtat 45300 ataatagctt aattttgttg aatttgcatt tacaatatta taaacagtgt gctaattgcc 45360 acagtgtgag tatggattag acagctaaca aagctggcat ttgaagacca acatctgtgc 45420 caaacacctt taattacagc aggctttgat tgccttgatt tgccccataa ataaattcat 45480 tctattggaa ctgctaaaat ttctgataat aatcgccctc ttttccagaa tctgccacct 45540 acaatataca tcttctactc ttacgcaaac ttctgttatt ttcttttaaa gatatacatt 45600 tatttatata attttatgtg tgcttacatg tatgcatgcg tgtagacatg ccactgtaca 45660 tgtgtggtgg tcacaggaca acttatggga gtcagtacct cattctcata tcgtgatccc 45720 atgaataaaa cacaggttgc caggagcagt caaatccaac cggagacatc tcagcagcag 45780 acagaagtcc tgttagtttg agagattgct attctgcaaa cattctttat aggatacttt 45840 agttgatcaa gcttgttgtc gctgtccata tcattgaact cttcgtgagt accgaagaga 45900 ggcagagatt tccctgacgt tgcctagatt tttacttgaa taggaacaca ctgttacatt 45960 ttcttccttt ctgtttttta ttgtatttat gagacagggt ctgtgtagct caggctggcc 46020 tcaagcttgc tttgtgaggg tgaccccgaa gtcctgctcc cttctagacc tatataggtg 46080 ctgtttccta tggtgctggg gctgtgcact gggcttctgc tttgcctgct gagctacagc 46140 ccccgttctt cttttttctt tcttttaatg atgtcattga tagggggggg agttagagag 46200 agagagagag agagagagag agagagagag attgagagag agagaaaatt gtgtggttgt 46260 gtatttgtgt ttgccctcgt atgtgcgtgt gcacatgcgt gtctgtctgt cttggaaagg 46320 ctgcttctga gggaannnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 46560 nnnnnnnnnn ncccgaaggt cattggagag ctggggtgta ctcccagaag tgatcagact 46620 atagtcacat actgttttta tattatagag ctcacaccac agtgaccttg gcactggggc 46680 aagggagagg ttggggctgg cggctgctgg cactgatact cagcagtggg cagcagaaag 46740 agtggactgg caggctcttc tccaggttct cccataggcg acatgcctgt ctttggacag 46800 tccgctttca ctctgcgtct tcagactgtt tttcttttgg gctatgttga gattgaacag 46860 agagccttca ggatactaag caagctttct accaccgacc cactgacctg catttcccgc 46920 cgtgtagacc atttatctct ttaatttcca aggtctctcc caccaattct gccaaagcag 46980 gttttccatt ttatttgcca acttgctttt taaaacttcc tgttaatcat cataatatta 47040 aaggtttttt tcttcaaaca ctagggtggt tggcttactt aacttggtga taaattctct 47100 gatctcaacc acaagtcaga ttgctgcagt tgtcagaata gtttgcctta ataatttgag 47160 tccaacaaca taatgtgttc taaggggaag aaatagaaac tcttaaaggt aaacacacca 47220 ttaaacagga gggtgttttc agtctagggt ggcttggatg atctgtaata ttgacattat 47280 gtgcagaagg aaacctgcct ctgcctaacc tcctgtgagt gcttcatcta cagaggatgg 47340 ccaagttcaa ttagaaacac ggtccaggtc catctggcta gcctgtttga ccagggagaa 47400 ggaactgtat gtagattgtc attttacaaa aatgtagaag agaacaggaa atatgagagt 47460 atatttgata gagcaacaat aattactttt aggggaaaac ttggatttca gttattatgt 47520 gctctggtcc attactaaga tgtctttcat tcttaactgt tcctgtcttt gctgtggaca 47580 cctcatgtac ttcacagtgc agtcacagtg ataggcagta aatagtgttt agttatacag 47640 aaactcagta cagttacatg gggaaaccca tacagctttg gatgactggg atactattta 47700 gaaaattaaa ggaattgaca tgtcataatt ggttttgtta catccctgca acctttgtgg 47760 gcatagggaa ggtgctctat gtagtttata tccgtgtgca tggtgagagc cttggttttg 47820 gggctagcaa tactggttcc agtcttgtga cccacataaa cttggggcat tggtgatttt 47880 cttttcaact aggttggact tcctcattta aaaaggaaag cagtcaggct ggagagatgg 47940 ctcagcagct gagagcactg actctgatct tccagaggtc ctgagttcaa ttcccagcaa 48000 ccacattggt agcttacaac catctgtaaa gggatctgat gccctcttct ggtgtgtctg 48060 aagacagcta cagtgtgctt gtcatatata taaaataagt aaataaaaat ctatttcttt 48120 cttttttaat ttttttaaag gaaagcaatc gtactacctt catggtgagg ggaaatcata 48180

ctgcaagtac ctagagtact ttgtaataga gtagatgttt aaaaatgttt attaaataag 48240 ttaaaaggct gttaaatcat agcaaactag tagtgattat tttaagtatt ttgttaaaaa 48300 aataaattat aaggctaatt ggatcctatg catggagaaa ttccttgtga cactctgaaa 48360 acttaaaacg aactgtagtt agagaagaag gcattcctct tgtgttccag aaatgtctgt 48420 gtacataggc agactgtatg gagaccagag gccatctctc actagcttag aactggctga 48480 agagacaggg ctggctggca agaatccctc cctccctccc tnnnnnnnnn nnnnnnnnnn 48540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 48900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnccctctc 48960 cctctcctct ctcttcgtca tggcagcagc agcatttgaa tttctttaag ggaggtttca 49020 ggttagaact ctggtcctag gagttgctta cccagcaggc agatgcttca ctcagtgagc 49080 cgtctctcta gcctacaaat cactcttttt tgataaaagg caagcattaa tcaaataaga 49140 aattataata tgcaagatag aaactagaga gtaagtagac caaaatcaaa tcactgactc 49200 acttgccaag acttcaaaga actccaaatg aatcctctga agaagcacac ccaagtgaag 49260 aagagccatg cgtaatccac ttgacctggc tgatgctcgc atggtggaga catcacatct 49320 actcaggaat gaaaaatagg agtatgctta catgagacct accttttgcc tagcttgtct 49380 tctatgctta ccagcaggaa aaaatgttaa atattctgaa tattctgcct taattagcag 49440 agccagtggc tgtccagtaa tgggctataa cagtttgctt tgctgttagt tttcagaaaa 49500 ttgaaaatca tatgctggtt aggcttgcta cattttaagg aattttgaac aaatgattga 49560 ctttggtttt ataaaagaaa accctttatg agaacatgct agctgctcag tctctgaggc 49620 tgccacactc agcagtccca tgctggtgct gaaggcatgg aggagccctg gagagctgct 49680 gctctttagt tcgtgttgga atgccaaaga tggtggcaga gaagagcata ggaacagcaa 49740 cgaagcagag gctgccaggg aggcgtgaag gcggtagaca gagccatagc ttttccttgg 49800 gatcttctcc tacggagcca cccaccacat gccgctgctt ctccttctgt taagcaaacc 49860 cataggaaat accctggccc acctaaatct agccatgttg acaaccgagt tagccgtcat 49920 agccactgca gagcagattc cccttagata tctgcttaag tcatcgatgt gctaggcatt 49980 ctgtggaggt atggaaacac ttgatcttgc cattacccaa aatcaggctt tatatgcatc 50040 tgagatagat gctatatgat atgttaaata aaagtgcctg gacatacagc agtgtactaa 50100 tatacgtatt ccttagggct gaatattaag aaaggtgcaa tcggtgtgat gctaggtgag 50160 accgagggag agttagtttt ataaaagtta gtttgggata aagaactccc tatgcatcta 50220 ctggagtggg aacttgtaga actttgtcct gccacatgtg gtgcagatgt agaatttgct 50280 cacgatggcc cattcagaat agaacatcaa agaggcagtg accaagccag gcatggtggc 50340 acaccccttt aatgccagga ctcgggaggc agaggcaggc ggatttctga gttcgaggcc 50400 agcctggtct acagagtgag ttccaggaca gccagggcta cacagagaaa ccctgtctca 50460 aaaaaaaaaa aaagcagtga ccacgtcgta tttcatttgt aagatcacat gaaggaattc 50520 ctaggcgtca gaattcagca tctgactgag tgctggcatg ggacacatag tcacttcttg 50580 aactgaaagt acagttattt ccagtggatc cacacagagt gttgggacta cctggctctt 50640 ctgttagtcc ctttctgaac ctttgctaac cattcctttt ccttcgattt gcagctatcg 50700 actttatctg ttagagactc gcagatcaat ttgtttttat ggttattaca tgttttaaat 50760 ttattattga ggcaatttca ataacatata cttttctaca atattttgtt atacatcatt 50820 ttcaactatg agttctgagt tctcttttgt tcccagtgct ctgcactgct tctgcagtac 50880 cggtaactat acttatgtcc tctgactgtt tacagctgcc ccactcctgg gtctccatct 50940 aggcaagagc tttttaattt ccctacagcc cgtttgactt ccttgatgtg atgtgtttaa 51000 cccatgttgc tgctttaccg ctattactat gatccaactt cagaccttgt gtacactaga 51060 cctaaatact ctcccatttg gataaacaca caagttggca tcatacgctt aatgtttgcc 51120 cctgcatagt gctcatagcc accagctcct gatgagttct gttagactga gagtctcgtg 51180 ccagtctccc atggctgggg ttagctttcc ttctggcttt ccttcacccc ctcagccatt 51240 tttaaatgac ttttcctctg gaatctgcca gtgtgctctt tttcaagtgg tcttatttat 51300 cttattcatc cagtatcacc acctttgagt agcttctaaa tccacagatt tcagcctgac 51360 cttgcttgaa gcgctgcttg cttgacacag tgtcacacaa ctgagtgaaa ccaagtactt 51420 cccccaccca aaccagttct tgcccaggtc tcctagtttc tgcgtgcggg cactgctgca 51480 tacctatctg ggagcaatcc tcttgcttct tttgtgcact ttgtctcttt ctgtgctcac 51540 ctgccctctt cctgcagacc acttcccagg ccctcccaga agaggactgt gatccagnnn 51600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 51660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnctc ccagaagagg actgtgatcc 51720 attgtatgcc ttcggccgcc tgcatgccca gactctccct taggatttag tactctgact 51780 acaattagag cagaaggttc ctcactttgc cagacactgg ccaggcaccc ctgtgggttt 51840 gctggccttc tatgacctca ttggtcagtg atccaccata agactttggg cctggtctgc 51900 cctccccagg ttcagctctt agggagcccc ctctgcctac atctcctctg tggaaaggag 51960 tgaagggccc tctcctacag cctttcctaa tcacacagag tatgtgtctt tggaggtctt 52020 gccattcacc taacttctgt ggtgtgcagg tggcaggcag cttggagtgt tgaggctcct 52080 actgggcgga gcctctctta ctcatccttt tcttgttgtc taagcagtta gcacagattg 52140 gaaatattga ttgagaataa ttaaactgat tgcagatggg tttagtttcc tttaatgagg 52200 ctgctaacca ttttcttcct aagaaacttg attaccctgc cttttctttt tttttttttt 52260 tttttttttt tttttttttt aaatttattt atttattata tgtaaataca ctgtagctgt 52320 cttcacacac accaaaagag ggagtcaaat cttgttacgg atggttgtga gccaccatgt 52380 ggttgctggg atttgaactc tggaccttcg gaaaaacagt cgggtgctct tacccactga 52440 gccatctcac cagccctacc ctgccttttc aaagggcagc aagcttaccc atgccaccga 52500 cacagccact tctatgcaac cctgctcctg ggtggccggc atcctgggct gttgtgactg 52560 caatggtata atgaggcttt ggcttgagtg gacattcatt gattatgcgc tagcaggcct 52620 agcttttata tattttcctc ctttaaaaat tattcttttg gtacagtatc tcaacaactc 52680 atgatagtat tataaaattt aaggtaagag ctattgtgtg tgagtagatt tgtaaacatc 52740 agaagcaaat ccccttgccc tggctttttc ttcacctgta gaaccaagga ttcaaagagc 52800 gagcagtacc ttactcacag ccaggaaagc ctttctggcc agttggccat gagtctgcca 52860 ttgcatctta tgctgatggt atctacaatt attaaagtgg tagttttgaa ggggaaatca 52920 tgattagtct gtcagcaagc tgagcctagt agaatcccac cctgttgaaa gacttgggcc 52980 tagttgggaa tggatagcca ggagatgaca gtgagtggta atcagcccca ggtctcatgt 53040 ttgtttctcc tcattcccag ctctacttct gggcacctgc aggatacgcc tggctggtga 53100 cacttctact ccctctcatg ggcctcttgt gataacacag tgtcttaatt ttgtgaaagg 53160 aaacaattgc cttattggca ttttagagaa gaggcaggca gctcaggttc agattgataa 53220 gtcatttcag gaacaatctg aaatttgaac attgcagaca aaccagtatt gtgctccttg 53280 cagacccagg cctggaccta tcaacaggga tgttgcaaga agatgtaatt atcattcagc 53340 agcaactttg atacttacac ccagtggctg taaacagtta gtaagagctg tgacacaggt 53400 cacaatggtg gagccagggc gaaggccaga aaagcaggct tctgtgcggc tttgaatcca 53460 cagggaagtg tactcctgct gaaatgttgt gtgcttaaat gggcagtgct acatttttgt 53520 ctgtacctgt gtgtggtggt atacatcttt atttccagca gaggcaggtg aatctctgtg 53580 agtttgaggc cagtctggtc tacatagcga gttccaggac agcaagagct acatagttga 53640 gactctgtct ctaaaaccaa aatcaaaacc agacacactt tgttggtttc tgcatattag 53700 gaggcatctc aggtaaccca tctctgatca ctgctaggac acatacctgg acacactagt 53760 ccctagaggc cccggaggga aggccatttg agggtaggca gtctgtgctg cttgggtttg 53820 caccccaagg cggggacttg cagtgcgctg ggagatggtt ggatctgggg ccctggttgt 53880 caggcttggt caggtctgtg ctgctcctgc agctctgtga acttggagtt gccccttgtt 53940 ggcccagcgc tgtcttgtgc tctctggcaa aagcaccttg cgatcttttt tatttgctta 54000 cttaaaagta gttgtgtgtg tgtgtgtgtg tgtgtgtgtg tgcgtgcgtg catgtgtgta 54060 gaggggttag tggatgggaa aactctcatg tgctttggag aaccttggca gagggtggta 54120 ggcacataac gttagtgaga aggcctgtgc tgcacttaag gtcttgtagc taaaacgaac 54180 ccaaattaag agtgtttctt ggtatgaata taatttcaca aggtacctga aggagggcca 54240 ggtctgggtt gcatctgact actgcagact gttttgtagc tcctgcttga gttgcttgtt 54300 tctttgtccc ttagatttgt ttgctactgt cctgcacatg gtcaccggct gtgtggctac 54360 agttacagta actctactta cttctttaca aatgctttga aattttatct gcctgaaaac 54420 tgacatttct gaattgaaga acacnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 54540 nnnnagaaca ctcctggctg aagaagaaag ttatgagcca catgggacac atttacaagt 54600 tctttgatag aactttgaat gaaggccttg gaggtcatta gccctgtgtc cctgcgtgtc 54660 actgcttcca tttaactcct cgggagcaac cgtattactt tgttggtgat cctttggagc 54720 tatatgaaat gataatttaa ctttcagatg tggttaatct ttaggtctct cttctaagta 54780 ctaatgtcca tggcatgaca ggcttaaccg tttccaggag tgggtgtggc tgaggcgctt 54840 ggctgagaag tggctcgtcc attacctagc tgctgctatt ccccagccgt ttggcactgg 54900 cactgaatgg agcatgtaag cctcaacccc acttgagaca ggttttacat taaataaatg 54960 cactgccttc ttgaggtggt ttagtgtgtt tatcatcttt tataatgcag tttagaactg 55020 tgttttgtct tctgaacgct taagtttgtt aataaacaga ccttgacact tataatccca 55080 actttcccgt cagcatatga ctgtcctgat gtcttttccc acttctcttt tcctctccgt 55140 gccttgcttt gatccctccc tagaatcaaa gagaagctgt ctgtgtgggt gccggtctgt 55200 ttgcttctct gctctctagt gtgtccacca gtgctctgtt gttggtgtca ctgttgggtt 55260 gtgggtgggg acagctcttg ctgtgctcag gactgatgct ggaggctttt gtgccacctt 55320 ggaaactgtg gcggttttag aacaggccgt ctattagcaa gttttaatat ttgagtaagg 55380 atgttaaata tcacagaata aaactttagg gaaaggcata agtaggtatt ttgcaccaat 55440 ttcattagta aaaataaaca ttttatagaa atacttgagt atcttcagtt cttgtggttt 55500 tgcatcttgc aagttattcc cagtgcccag attcataggt ataggtgctc agtaatgtat 55560 agacagtcat tcttggagta actcaggctt ccttgactat ctggggatag tggttgttta 55620 cttttgctgg gtgcttgcag ggagacagtc agtatacaag gaaacagtta atgaccgagt 55680 tgctagctca tgtaatttgt ccggtgatgt cttttatatt ttgtctgtga tacacatcat 55740

cttttgaatc cacattattc ccaaggaaac ataaattctg aaagatgcat tacagctacc 55800 taggttgtgt gtaggaatct acaaaggttg gagaggatgt tgacttgtag cctatgaaga 55860 attggtttct tttaaaccca aatagaatac aacaagaata tatcattagc ataaaatgtc 55920 ttctggtacc ctagcagtat ctagtgcttt caaaaatgtc taatgttgtt gtcaggaggt 55980 tacacataag agtgtaggtt ttcaaaggat gaccaaataa aattgtgcaa agaggctggg 56040 ttagtttgca tttttcttca gcatattaaa ctagaagtgt cttaacatta ttggtcttat 56100 ttgaattgga caaatgttag gaaaaactaa aaatcttttt attctttaaa ctgagaaaat 56160 aattcatttg attatttcaa attttataaa agctgaaaaa attatcccgg aaagccagtt 56220 attaagtctg atgtgtctgg acctaaaagg cagtcttggg ttttcattgt gttttgctag 56280 tttctgttca gtcagtcttc aggatcctga agctggctgc ctaagggtgg aagagctcca 56340 ccaccaccaa aaagcagcag caacaagaac gctccagccc aggactgtga atttcaaagc 56400 tataagaagc tcagttagtg tcacagcaca gataacttag aaatggctgg tacattacgt 56460 aatctcacac aaagtgaggt tgatggattt tgtaatagtg ataacaaatt tataaaaatg 56520 ctttagagtc tggcagcagt tttcagtttt tcttaaaaga aaagaatcct aagagtttct 56580 tataaagtcc ttcacactcg gaagacagtg aggttaaagc gtgttgtgtt aaaagtcttg 56640 tgtgatagag tacaaaatgc acgtatggac aacacacttt taaaaatatc tgtatgaatt 56700 catttacaat ttggtttcat tgtaaagagc aatctgatct taacttaata ctactttgtt 56760 tacattcaaa ggtgttcccc ttcattgtgg gttgttttac atctttgaag acatggaatg 56820 ggaagagtat taattacctg gctcatattt atagcgtaca tttctataag aggttattca 56880 tgcatttgaa aacaacagga agaactcaga gcctctgcac actaattgca ttcacaaatt 56940 ttgctatcat cagagtaata ctacatctgg aacatgaaca aatgcaaaca ggaaaaaatt 57000 tctacttccc ttttcagcag tgtgaattgg taaatgtccc caataatgtt gggaaagtag 57060 ttatttatga acttatagca catttagaat gtctactcaa agtggggtgt actgcatatc 57120 ttctgattgc tttggaaaag agaaagggat gatgcttctt tcagtatccc tatgctcaca 57180 tggcttgtct ccatagtaac ctatgccatc catatcacaa gaagaataac aagtgaaaag 57240 gttccacatt acattcacac agttgacttt ttttccctca tagacatgtg gtacagggat 57300 taaggtttct ccagaaaaat cattcttgaa tcttataaac tgttcatctc tctaaattta 57360 tcaatgttgt tacaagtata tcattaagca catatttact atgtattatt tgcttattac 57420 aagtttttgg acatacactt atcacctaat caaagtgttt cccttttgca atagctaagt 57480 ggtatgagac tgaagagact tgcacttcta cagcatggct ctactgggct tgatttaagc 57540 agagacctat ctgttaagcc attccttctg tgtctttgaa cgtactggaa tgccttgcaa 57600 acaataatta catacctgcc atagacatgc atggttttgt gagatttaat aatcatccat 57660 aactgaaagc agtgcttagt gtatgctatt gattttcttt acaactttgt agcacatatt 57720 aaattttctt cttaggcatt ttttcatcag cttgcacagg aaaattacct tccatgactt 57780 ctagaacttt gaaaatggtc ttcaatagta tgttcttcct aaatgtagcc tatagctgtg 57840 agattcctat aggtctctaa catcacacct ttgtagagac tcttgtgaga aggaagcatc 57900 cagcaaagcc cactcttctc gagtgaagtt ctcaagcccg tcatcatagg tcgctctatc 57960 caagtctgca tgcacgtcat cataggtcgc tctatccatg tctgcatgca cgtcatcatg 58020 ggtcgctcta tccatgtctg catgcacgtc atcataggtc gctctatcca tgtgtgcatg 58080 cacgtcatca taggtcgctc tatccatgtc tgcatgccca tcatcatagg tcgctctatc 58140 catgtctgca tgcacgtcat catgggtcgc tctatccatg tctgcatgca cgtcatcatg 58200 ggtcgctcta tccatgtctg catgcatgtc atcataggtc gctctatcca tgtctgcatg 58260 cccatcatca taggtcgctc tatccatgtc tgcatgcacg tcatcataga tcgctctatc 58320 catgtctgca tgcccgtcat catagatcgc tctatccatg tctgcatgcc catcatcata 58380 ggtcgctcta tccatgtctg catgcatgtc atcataggtc gctctatcca tgtctgcatg 58440 cccatcatca taggtcgctc tatccatgtc tgcatgcacg tcatcatggg tcgctctatc 58500 catgtctgca tgcccgtcat catagatcgc tctatccatg tctgcatgcc cgtcatcata 58560 gatcgctcta tccatgtctg catgcccgtc atcataggtc gctctatcca tgtctgcatg 58620 cacgtcatca tagatcgctc tatccatgtc tgcatgcacg tcatcatagg tcgctctatc 58680 catgtctgca tgcacgtcat cataggtcgc tctatccatg tctgcatgca cacgtcatca 58740 taggtcgatc tatccatgtc tggaggtctg agtttgacga gctcccctca cagaacccag 58800 cagggtctct cagaacatag ctcacagaaa tcctcacagg cttgacccag aagagctgcc 58860 gccaacactc ttcattgagg tgttccaggg gctgggtacg tacgtagggc taaggtccac 58920 tgcttaccct gtaactatat ctcctgggca aagtcagaca gattatccct tgcatttcat 58980 tgaacagaag gttactaatt aataaattta agtgtgaggc cggcaagtgt gcacgtactt 59040 aaatagaaat ctttttgggg ttgtgtctgt tttatttgta ccacggaggt cattagtagt 59100 tctcaaagca gtcaaggcca ttgttgggga ggtcacacac cactgcaaga gttttactga 59160 ctactcctag ataattaaat tttgtgttat aagagtgttt atcaaggaat atgacagtga 59220 agaattgtct gagattagag tgtagctcag gttagagatc tctacctctc atacagaggc 59280 catgtatcct aattgcagct ccagaaacgg caaaacaacc ccacatttgt ttgaggcacc 59340 gagcatcatt aaattcattg atattttgcc catcctcgag cttaagttac ccctccttca 59400 gttcttctcc tcccccttcc tccctccctc ctttttggtt tttcgaaggt tttctctgtg 59460 tagatgtggt catctgcgac tcagtgtgga agtcaggctg gcctcaaact cagaggtctg 59520 tctgccctgc actaccacca ctgcctaata tttctttcat aaaaacctgc agtcctcatc 59580 acaaccagac agtgccactg ttgttgctac tggtccttgg ctgagcgtct agaagcagta 59640 ttgggacttg gatgtgactc tttgtgtctt tctttagcac aaaaaggcca ggtaccaaac 59700 ttgctgaagc tagctagcat caccggcaag tggaggccta tctttagtct cctagtcagt 59760 ttcttgcagt gggaatcctg accactttgt tgctatttag aaagattgct ctgggcaagt 59820 ggagttcaca tttttttgtg actctgaccc cttcctctca aggtttcact gaccagaact 59880 ggactgagag gcacatgttg ccagtgattt tacagtggtg gtgttctggc cacaggtcag 59940 ccatgtggtt gtggcagctt ctgagagctg accctgattg gtttccagaa aggccctgac 60000 tatcctcatc ctaaaccaga ggctgtcctg tgtccggtgg agaggcaggg taagcatctc 60060 caccttctgg caggagctca gcagagagaa tgaatggcct agcgtgagtg tctccaaagg 60120 cccagatgct gatggcttgc tcttcccttc agtgctgttt tgaggtggtg gagggactgg 60180 gtggttcaag aaaacattgt ggtcacttga gggtaggtgt agtgctttgc ctgtgccccc 60240 ctcgattgtc tcaatatctc agctgtgaag taagcaaatt tgtaccacac acatacacac 60300 acaaaataaa acatctaaaa agggtgccta gtcaactatg tagaggcaaa gagtagaatg 60360 ctggcagcca gggtttggaa gggacttgga gttgttcagt acccagtttc agttttgcaa 60420 gatgaaaact tgaattgtca gatacgtctc agcaacacca cagtggtgga gaataactag 60480 ctgggttgtg cttcctagat tccattatgg tacccagtga atgttttttt gtttttgttt 60540 ttttctccga gacagggttt ctctgtttag ccctagctgt cccggaactc actctgtaga 60600 ccaggctggc ctcgaactca gaaatccgcc tgcctctgcc tcccaagtgc tgggattaaa 60660 ggcgtgtgcc accatgcttg gctcccagtg attgttttta tatctgttta ggaagagctc 60720 atggtgcatg ctaagagaag tgagggagca gagaccatag tgacagggac agtgtccata 60780 tgtcccaggg aacatatgga agcttgtgga ttgaggcaga gatggctgac atagctccat 60840 cttccgtgac gtgctgccag tcagctttcc ctctatgtcc catctggtca gcaagcacat 60900 ctgtttggta gcctctccag aggacggaac ccgtgacccc gacttcaacg agagcactgc 60960 cgggaagtat taagattgat ttggtttttc atcctgagta tcctgtatct gacatgcttt 61020 ggcttagaac tgcgttagat tctggaatat ttgcacagac atgggattca tgtatgtttt 61080 atatgcatgt gacttatata catggcctga tggtgatttt gtccaatgtt gtaaataatt 61140 ttttgtgcat gaattgtatt ttattttttg agataaggtc tcactggcag gcctagaact 61200 tgctatttaa accaggtagg ccttcaactc atcgatatcc tcctgtctgc cttgcaagta 61260 tgcttggaat gaagtgaagt tttgtggtgt gaaattttct acttgggatc tcaaatacag 61320 gttttggtct atgccagacc ttaaagtttc aagttaagat agtcacagtg tggagttggg 61380 tagagaggat gtttagaact gatgttttaa tctatctgaa aaaggaaacc agcttatgta 61440 agtcaatgta aaggtataaa ctgtcctaag aagcaagagg tgaaaacaac aacaacaaca 61500 acaacaacaa caccagcctt accatcaaga gccaccaaaa gttgtcagtg catcagacac 61560 gacggttggc tgtgaacctg acttttaata gttgaaccat ctttccaggc aggattggca 61620 tgatggggac tacgttcata tttgatggct agcagtggat agtgcagatt gtgtagatag 61680 gaagccactg gacaggtcag gactcacaca tgagaagtga gaacactgag ctgacataga 61740 tagggtgcaa ggggggacag ggacagttag catgtgtgct gcttgtacag agcacttccc 61800 agggctgtga cccacccatc catgtccctc tataccttca ggcaagctgc cacagcctcc 61860 cttatgctgg aacatctctg ctagagcatg atggggctct gtggtgagga gacagaggtg 61920 gcaagctctg gatggtgatc accagcatgt cctggctctg ttacaagacc acagagatgc 61980 caggcctttc cagcttccat gcctctgcac acgggtgtgc actacacact cggaaggtta 62040 gagtatgtaa gctttttttg taaactgtca tctgtagttg cccagcagtt tctggaggag 62100 gctgaaatac agcaggtcga tacagtgatg ctgagccggg cagcggtagg tgttagagag 62160 gaaaaggccc acggccagca ttgctcagtg ctccattctg gagcgtcaga gtggaaagcg 62220 cctgcagctg aggctgagac tgaagctgct gtgtgctgtc tccatgtccc agcacccctc 62280 caagcacatc agtagatgtg tgagaatttc aggttattat ggacttggtt gagttctgat 62340 ttaagttaat tctttctgca aatataaagt cctttaaata tggcatgtaa gcacctgtaa 62400 aaagcattgt ccagccatca ctttgtgaaa tgatgctgct agctccgggt gagttggggg 62460 tagggtgaag tggaaacagg gttgggtctc tgctctgggc cagccgaggg ttttagagca 62520 gctattgagc tgagtctttg tgaagtgagg catgtagccc acacaagtac tctgacgact 62580 taggctaatg attaaggcac aggcactgtt ctttgtcgta aaaagaatgt gtttttcacc 62640 tccactgtgt gaggcctcag gtgtacgaaa cagctccctc cacggttgaa gaagcatgtg 62700 gctgctgaac tgtgaactcc tggagtttga gctttcaaga ttaaataggc tctgagccat 62760 caatgaagac agtaagggtg cagccacttt gagctatttc taggggaaac tttaatttga 62820 tatacatatt atatggtaaa tatgcttaaa tagtgacatg ccttgtgcac tcattcactt 62880 acacaatgtt cacctcacca gctacagaat ttgtgtctca gatagtcaca ggggttttgg 62940 cagactttgt caacgtccac agaggaagac ccaccttcat ggagttagga gttgcttggg 63000 aagaagtttc cttaagaccg ttattgtaca cagacttaga aatacatgca tcctgtaatg 63060 taatgtcctg actagtcaaa tgttggtttt cttttagtta ttaagcatag tttgaaacct 63120 gcttgtactg tagccatttg aattcacagt ggacagaact tggcacggat gccctgaaat 63180 catagtgtag ttgtcttgct gaaaacttgg acccttaact tcctagacat tgaaacgttt 63240

tgaatcacga gcactctgcc ctgcttttgc tctaagcaat tgtgttggct tctccccagc 63300 ctctgtaatt gtagttcttg tgggtggcag cttctgtttg ggaaaagctg tgggtttaca 63360 ggtccttgct gagcccctgc ttttcctaag atgagctctc tgaagtctta taggagatca 63420 ggagacattc ctttttcata aaagaatgga gctagagcaa tgcctcagtg gttagagccc 63480 tcactgctct cctcgaggac cacgtttgga tcctagcacc atggcagggg tctcataagt 63540 gcctgttgtc actccagttc aggaaatttg atgccctctc ttggacttca tgggcaccct 63600 cattcatgtg ctcattccac ccaaactccc tgtcattaaa aagaataaag tatcaaaaac 63660 aacaaaaaca aaaaacaaag actaaaggag agttgcccat gaggggcttg tagtctgttg 63720 tgtgtcttga aagacatggc ttgctgttta aaccatggtt aaccctgtct gtgagaatct 63780 caacaccttg gccaggactc cagtccatca caaggctttt attttgttca caatatttgg 63840 ttgccacttt actcaataat gagagtattg catttaaaag taaagtttaa gtcatgcaca 63900 ggcctggaag ctcagggcca gtaggagagg gattcctcgg aaagactgaa ccggaagcag 63960 aagccagaca gcccaggtaa tgctgagctg gggcttcagg ggcacgtggc caaggctgag 64020 tctactgtgg ttcttcagac agtgggcagc tcagggcctt taagtatagc tctgaatggt 64080 tggcacaaag tgccacaatg gcgacggctc tgtcacctcg gctgctctcg ctgtgtaagc 64140 cgtagacacg tgtaaaaagg agactgcctt gcataatgtc tgagctggag ttgactaacc 64200 aggtttgcaa atgactcgga ctttgttttt gtaagatttg tattctatca ggacccagag 64260 acataaaagt gggtgttaag atggagacta aaaagtcctg tcctggtcct ttgttgtgct 64320 tctctgtcgt ctcaggggct tctgaccttc taaaggctta ttattgctca gtcatgttag 64380 acgttttgtg gtttttgttg ttgttgttgt tgttgttgtt ctcttaagag atctcagtag 64440 ttttagtttg aactattatc taaagattca taaacagcat ttgtagagaa cacatagttg 64500 aaattgtgaa cccagacttt gccttctgta gctaaaagct ttccagtgtg ggcacccctg 64560 taaacccctg tttatcttaa aacttctttt ctgtgctgag ggtccttacg tcagagaacc 64620 tttcaaacag agtcactaat taagagtaga gatagagaaa aactactgta ttattttctc 64680 atcatgtagc ccagactggc ctggagcttg tgatcctcct gcctcagtct ctggagtagt 64740 ggcattcacg ggtgtttgcc acagcagctg ctagcctttt gtctgttctg cacagctgtc 64800 ttctgagtaa ctggagagaa ccccctcttc tgagtgagag tcgctcttaa aagcacttca 64860 aaggtgaggt ttgttcctaa atgtgttgtg ttcaagcctt ttaagattac acaaggtgat 64920 tttttttttc ttgtgacgtg aggaaacaca cctatggctt ttgttgctgt gttgagcatt 64980 ttgctctgag acatcagact tgtccaaagc ctgtgtttct gttcctgatt tttgctcata 65040 gttgtcagct gttgcttctt actgccggca ttcagatgtc ccgtctccac actccttgtg 65100 tggtgcaata acatcctagg aaagaacaca tacacactgt gtgctttaca gtcttactgt 65160 cagcgctgtt tcacaagtgc catccttgac atgcagagga agagagtcag gtgtagctac 65220 tgcattatcc tgctcaagtc cgaaagtcac tgagtgacga tggatgccat gcagatgact 65280 attcccatag ttactggagt aagtggacag tgctgcccat gtacactcgg ggcattgcta 65340 atgctcaaaa ttccctcttc tccctcccaa agacaaccac cacctcgaca ttcttctcta 65400 tagatttgtg tctctgcccc ccaaggatga cattttttaa atcaggcttt tagcttcata 65460 aaaatagaat cagggcgaca ctgtttttgt gtccagcttt tttcatacca ttaaatctgt 65520 gagctccatc catctttggc ttatagtgcc ttcattgatg tgggctgaat tattaatgtt 65580 tgtatgaata tttggggcct acctgttagg gaagaactta ctgtgaagat tactatatat 65640 gttgttagag gatgtgactc ctcctaaatt acttagttta ttgaactata tagtcagtgt 65700 aatccaggtt attagtcact tttatgctgc tgtaatcaag gcagtgtgta tcttgagttt 65760 ctggaataat ggagaagatg ggggcaggag ttggaggcag aaggagatgc atgctggtgc 65820 ttaccccagg cttcttttta tacagactaa gattccagcg taacaaatag aactacctac 65880 agtggctggt tgggtttccc acctcagtta acctaatcat gataaccccc agaggcacgt 65940 ctcccaggtg attcaaaagc tcatctagtt gacaattgag acatatccca gctaccattc 66000 tttctgtagt tacaggttct gccagatgcc ttgaaagtat gtgaagcaaa aagtgccctg 66060 ttgctgagta tgtgcaagtt taccacgcag acacagcatc tgtaccgtgg tgagcattgg 66120 gagtaatcta gagatgcttt tgcgtatgca ggaggagttg gggctgtgca aacagtggtt 66180 ggctttgtag aagaacctga actgctacaa cattttctgt gcacaagggt cctgaaacct 66240 acccctttct acattcaggg tcaactttgt caccagttta actgtggtga cacttgtctc 66300 atcagcagtg caagagggct ctgggagcta catcacttcc tgactaatgc cagggttggt 66360 ttccctgttc tttacattgt aattcattag caagaaattt agtttgatac aggggaaatg 66420 caaattataa gctatatttc aaaataaaaa tatttaatgt gcagttctca tgcatagaga 66480 ttaatagttc tatattatat actgatgatt cttttcctcc cagtatgttt ccattgtttt 66540 gttttggagt gtattgtagt aggtatgttc atgagtgtgt gcaaatgtgt atgtgggcca 66600 gagtgttatc ttccatcacc tctctccctt gtctcttgag atggaatctc ttactgaact 66660 cggagctcag taagtcatct agttagctgg ccagtggggt cagctccagg gtctgcagct 66720 atgattttca catgggattc aagctcaggt cctggtactt gtgcagtgtg tttaactgcc 66780 ctagcagtcc ctagtctccc aatccctact tttttttttt ttttaaaggc agccttgatt 66840 tcttctttga gcactgatgt taacacaggt ctgtgggagt agaaaccatc gctcagtatt 66900 ctagaaattt gtttagattg tgggatgggg gctggccaga ggagaggaag agcacccagc 66960 ctggccacaa gctcaccatg taagcggttt ggcctctgcc tcccatatgc tgggattaca 67020 ggtatgctac caggaatagc tattttagaa ttttagttaa gaaaattaaa tggtgactcc 67080 acacacacac acacacacac acttgtctgc agcagcagat ctcatggaac ttggagccct 67140 gcacacttaa gttccttcca ccacaataaa gatctttatc tgtgggaaca aattcaaaag 67200 atccaaggaa ggtgttggta tggttgtgag ctagctgcca tgtaagaaat caaacccagg 67260 tcttctgcaa gagcagcgtc tgatcttaac cagtgagacg tttctaagga gttaagttta 67320 aacagtacat acaaaggtgg cttggaggga ctaaaacatt atattaaaaa atgtcacaaa 67380 ttatagccaa agatgtaaaa ttgtctttaa aagaacacag taaagaactt tatagctgga 67440 aaaatgaaac gtggtttttg ttttctgttt atttatttat tttttgtttt gtttttttac 67500 agaagtctag cagttaacaa catttgggtc tttatcatct ttgttaaatg acttactagg 67560 ttcaagtgtg gtcgaattga ttagttctta ttgtcccaac tctagctact tatgttccac 67620 ttttctgtgt ctcaggtatg ctaattagtc aggcggtctc atctgaaact aggaaggtgt 67680 gatagtgcta ggttgtacaa cttgccatac cagttttaca gtgtttttgt tttgctccga 67740 ctagatgaaa ggtttaagtg tggccacact ggtactgcat tcctggtgat cttggagggt 67800 taatgacaat ctttgtcata gacatcagga aatgtgggtt gagtctctgg gatgcacaag 67860 gctagttcat tagcatgctc cttccggagc actggggatt gttggaggta tccggtggta 67920 ggtaggtgat gcagcttcag agaactttca tctgtctgtc atcagctgtc atttgtccgt 67980 ttacccttct atctttccat ctatccatcc agcctgactg tttctatagt catcttggtt 68040 tttaaaaact gtttttaacg tattggtgtt tggttaaatt accactgggt ggttgctttc 68100 tctagcaaga cccagcaggg aaaccaggta ggttttgtgc cacagtcagg cttgtttcct 68160 cggtgttgtt ggcttggttt cgaggacagg catgtgagag atcatcgctg ctgttgaact 68220 ggttgccttt tagctgagta aactatcagt cagtgctgtg gtctatgcct cagttgtttt 68280 cttttttaat tagggtagct ggaagagctg cttaaaatag gtatctgtga gactcgcaga 68340 cgcagctggt ttggacttag cacgctttca ggcaggttca ctgaacgtgg ttctggttgc 68400 tctggtttct gtaaaagcct gcgcttgtgg tgactgtgcc aatataggtg agcatttagg 68460 agagcgacac actgctgttg ccttttttct taagaggtgt acttaactta tttcagatag 68520 attccttaat aataccatga tccaaatgta actaaataca aagcagggtg cttcatttca 68580 atactcttca tgtacaagtg ctatagatgc aagcagaatg tacttagttt cctggagcat 68640 tcaaagactg tatgccacca tcggcaaagg cattggagtg ggctagtact gttgagtcac 68700 tgattgtccc atctggagcc ttagtgaagc ctggagagta agttatttat tagaacccct 68760 gaggatgtgc tgagctgata atgcactggg gtcttttctt ttaaaggtat ctctgttgtg 68820 tgagactgtt ggcagtctcc agagttcagg ctgcgaaggt taaatagtga ccaacctttt 68880 catccacctc tgcatttgga gcattgtgag ggttggagag gagctgagag gcccagccaa 68940 catgttcagg attgaatctg cacctccttc ccaagtagtg agctttgctg gagtttctac 69000 atgttcaatc tgagggtttg aggctgtgat tggccatctt catgattcat tatatacata 69060 agtaacataa aaaattaaaa tctattaaat atgctgtgat ttgagtaaaa gaatatgttt 69120 ctattaaata aataaataaa taacaagtta tctaggcatg attgtgtatg ccttgaattc 69180 caaatcatgg gagggagagg caggctggta tctataagtt ccatgccagc taagggtaca 69240 caagaccctg cctcaaataa gaatatgtaa ttacaataaa aaatttaaaa cttgttcatt 69300 ttcctcctgt agagttgcat atttaatgaa tgaagtatcc tacaacttaa gtctatgtat 69360 aagtctgaga atcaaaaccc cagggttttt ccttggcttc gtttgtattg atttattttg 69420 tgatcttgtt ttgaactaac aacagggaag tggctgtgtc atttcacatg tatgtgggag 69480 actgtaaata ggaataggga catgttttct gcatccaggt gttattcaca gactcggtta 69540 atgtggtaag tagctagcta ccttgaaaag aatatgtgga gccatagctt ggcagcagga 69600 agaactgaag tgttgctcag aacttggagt ttcggtggaa gtcagttaaa acctcagctg 69660 ggtgttttgc ttgtcttgcc agttgctggg aggtggggag tagcttcctg gtggctcctt 69720 ctgaactcac agttgctaga atggtaggct tgtcttagcc agaatagtca actgcctatg 69780 gtgatggttc tggcctcagt ttatgagccc atgaggcagt agtgtctgag ctttggccag 69840 aaagatcaga atgccagacc acattagtgg gttacctgtg tcatctgttg atgggcagag 69900 accattttag agtatataaa gaatagggtc ttaaattagc agctaacata ctattttctg 69960 ttaaattatt aaatgattga taaaataaag gggtgatttc attaagggtg tcatcaaaac 70020 aaaactttta gaaaccactc tcgtgcaaat tgattttatt tttctgaaaa atcattggtt 70080 ttgtaattca aatctttaca actcgtctct cttggcccag taatgctttg tgcagacttt 70140 gcccacatat gatggaggca tttggttctg tgaaatggaa gcactgttta ggtagcaaga 70200 gcagagccag ggaagcagca aatggtaagt gttctgtaga tttatgccca gctaagtcta 70260 ctaaagcaac cacaaagcag ccgacaaagc cagcgaacaa gacattattt aaaatattgg 70320 cagagtttcc ttcatggtgg ggaacagtgg gcatcttcct tttttccatt ttctgtaatg 70380 attgcttact tattttttaa tctttaaagt tgaaagggaa cagggtgacc taagggagac 70440 atggccagat cagcaggcca caggaaacaa ggtcacaggt tcgagggata gcagggcggt 70500 ttggggatga gtaagaaagt gggttaattt ttctaaagaa catgctatgt gggaaaggaa 70560 accatgaaca catttctata cctctggctt gataaattca taggaagagt gggtgaatga 70620 atgactgtgg cacgaattga caagatcaag ttggctatat ccacttggca gcaatcgtat 70680 gtttgaagag ctacagacaa cagagatgtt tgaggtggaa tggtgaccag cttagaatgt 70740 gatatcctga gaatatgtgt ccttgacgga tgtgtgccag gggcagcaga ggttgggatg 70800

gagccagtct gggggggctt agatgaggct agggctcaga actcaacctt cccctctgga 70860 gatcaggatt tccttggaca tagtgagcca gttcactgga tagtgttgag tgattgtatt 70920 tacacatgct tattattttt aagtattgaa ctcttttaga ggcttacttt atttaatttt 70980 taaaattttt atttatttta caacttcctc ttacccagct aaattcatgc cgtcctgttg 71040 tgtggcaaaa tttcaaaaag tagttgggtc acagtatttg agtgggacgg tgttagagct 71100 gtagctttgg caatatggca tacttgttct ttgtagggac agcgacagca acagcatcag 71160 cacaggatga gcagtgagga cctagtgcag tcaacactta ctcacaagct cctggtacat 71220 tcctcgtgag tctttcctgg tgtttattag taaccttgtt gaagttggct gtttttgtta 71280 ttttcctacc ctgataatgt tgctttttaa ctgagaaaat tatttcatgc agcactgatg 71340 tgagttctta cagttgccgc acatgctatc taaatgtagt ttgtatttat agccatctct 71400 cttctgtgag tcactcttga tagtctcccc tatttttagg tttttccttt cctaagcttg 71460 tgtgcctgtg acacacccag cttgtcctct gccactgagc tgtaccccca gccccacttg 71520 aacgaaactg ttgaagctag tagccactcc tgttttctgc taactggcat actaaaggat 71580 agcatgtttt cttaccattt cctttgtgtg catgtctttt gagagagagt acaggatttt 71640 aaggataggt ttgtgtctga ttgttggagt gcgccaggtt tccagtacac acctctgatc 71700 tccatggact ctgttcactg actaactatt gaagattgct gcatgctccc ggggtgtttg 71760 cagtagcctc agtagtttct gtgtgagtgt cctctgagtc aggagttggc agtctagctt 71820 ccacataata atgagatatc tgcgtcaagg tggcacctgc agagcctcct gccagtctat 71880 ctcatgcata acaagaggcc acttggactc tgccaacccc agaattcaac cctagtatct 71940 atcatcttta tttttctttt ttttttcttt tgctcctgga ggttgaaccc agggactccc 72000 aacatgctat gcacatgctc tgccccctag tcatatctcg gtccctacag acattttaaa 72060 aattaattct gtgaagtatc tccgaaggtc ctgtggtttt ttttggggga ggggggttaa 72120 gtagcagtaa ctgtagcaat tattgtaact ggtatcctta ctcattacag tctctatcac 72180 cgggaccctt ctcgggatgt ttccttattt gcatttttaa caactcagat tacaggtgaa 72240 gtaactcagg caatgggaga tgagctggct tacgtggggc aggtagtaga tgtcacattc 72300 ggagctgtgg tttgtcaggt cccaaaacat gtgtgaattt taagtatgct cgggggtgag 72360 ggtcctggaa gaactgtatt aagagcacag gttgctgtta cccattaacc tgctgaatac 72420 tagcaaatac ccacattgtt cttacagcta cttataacat gcagtagttg gcattttaca 72480 tagaaaccta aggttccctt acctaggcaa accctgctat ctattttttg tttgttttca 72540 gcttttcaag acggggtttc tctgggtagc ccgggctgtc ctggagttca ctctgtagac 72600 cagggcggcc ttgagctctg cctgcctctg cctcccaaga gctgggatta aggtttgtat 72660 cactgtagtc aggcaaaacc tgctatcttt atgaaaggcc actcacaagg catgtctgtg 72720 ttgtgcacac cacacggtga ctgctgttta tcttttgaca gggtttctct gagtaataga 72780 atccaggctg gcctaaactc gcaaggatcc cccagcctgt gcctcatgag tgctggaatt 72840 aaaggcacgt gccgccatgc ccagtgactg ccgtttatct ttaggcatca gtaaatcttt 72900 gtaataggaa cacattccta ttaataatgt caactaagtc ctagagacaa gtgtagcagg 72960 tctcagtaag agccacgtcg gaagtatggt ttgcatactc tcagagtccc caggtttaat 73020 ggcagcgttg ctagatctga atttaggtga gtggtgagga agtagcctcc cggcagttgg 73080 agatagtttt atatgctagg tcagtgaacc aaaaatctct attatgtagc ttagggaaga 73140 gtttctagga atcagatttc tgaggtctat tatagctgag aaaggttttg ttcttgatta 73200 aagaatcgta tatttcaaag ctcacagaaa ctggaaggtt aggaaaggct ggaacaggag 73260 ggctgcagtc tccagacctg acagggcttc atagaaaacc tgcctcagaa accaaagcat 73320 gttcatgaga aaaactgcag tgttggtcct gattagggaa gagtggcctt gctaaagcta 73380 tgaactctat gtgaaggaaa atgaatgtcc cttccctggc ccctccggca cctacttggg 73440 ttgcctgagt agtttcacat aaattatgta tgtgatatgt ctcctgtctc atgtcagata 73500 tgtctgtctg tctggtggag cttttatctt ttatgtaaga tacgtatctt cctgcagctc 73560 ataccgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgttgctg 73620 atagttgaat ccaggtttca tatgtgccat ataggggttc tccactaagc tgcaccccta 73680 gctctctctt ttttcttctt atatttttat ttttatagat aaatgataaa ctatctattt 73740 ataattgtgt cggtggggga caaatgacat tatgagtcat taaagcaatg tagaattgtt 73800 aaaataatgg agatatccgt cacctcacag ccttacctgc tttatggtga gaatacaaca 73860 tttactctta acaattttga aattgtcaac acatgtttag tagctgtgtc cctcatattg 73920 tacagttctc caaatcaacc cacaggcgtt ttcctcctaa gggatttgtc ctccgagcct 73980 gtcatcttcc tttccctaca tccgtggcct ctggaaccac tgttcacttt gagtgtcctg 74040 ggtccccttg tttctgattc tgtatatagc atttatgttc ctgtggttgg tctgtttcac 74100 ttagtttgcc ccaggctgac agaaacaata gtctggtttt aaggctgagt gtgtgctgta 74160 catgcatctg tcagttcaag gccactgtct ttcaggctga ttgtacaccg tagctttagg 74220 gcagtgctgc agtgaatatg aggatataga tatctcttaa aaatttagtt tatgtgtaga 74280 gcagtctgcc tgcgtgtaaa tctatgcatc gcacacttcc ctggtgcttt ccgaggccag 74340 aagacagtgt tagatccctt gggatcggag attatgggtg attgtgagcc accctgtggg 74400 tggtgggaac tgtacttggg ttctctagaa cagccagtat tcttaaccac aaaacctcct 74460 ctccagcctc ctgcagatat ctcttgacaa gatgatttca aatcgtttgg taaatgacta 74520 gtgttggggt tgctggggct ggagagtagg ttcgcagtga tctggaaacc aggccgcagc 74580 ttcactctta gatgtttaca gcttcgatac tgtgttggaa ggtgtctagg ttcttggagt 74640 tgtgctaagt tgtttgctgc ggcacaccca gggcttggta aagatgtgtg tatttaaaac 74700 agctcattaa acagcccgga gtccttgtaa accaagttca gtctctaaca gtctaacaag 74760 actctccttt atccttaggt gttttgactt ggagaggaca ctaggttcac atgtagactt 74820 taccgagagt cggcatgtcc ttgaagccat gtgtgaaggc gctgttctgc ctctgggtga 74880 tgccccatgg gaaggacatg cactgctagc tattgcaggt gctttctgct gaccattcaa 74940 cacgttacag ttctgagcct cactagtttt gtagcataat attcccccag tagtgacctg 75000 tttcagcagg cagggtgtgg gccagctcag tcagacccag gtctgtttgt tttcatgcag 75060 tcttggctcc tcactggagg ctctctgctg ccaactgtgg gctttggttg aggcttgtgg 75120 caagattgtg ggtttaaccc aggagtattg cagcatcact tgtcatggag gtatcacact 75180 gttcagtggc ctcctatggt ttaggtttag atcatttgtc atgtggctta ggtttgtgtg 75240 tgttcatggc tttctcctcc tttagtcctt tcctgggtca cacagacatg cgagcgggga 75300 gtaaaccctg ctgatgactt tgcccttgct tacagtttca gtttccaggc agctttcttt 75360 acaatcgctc acatacagac ccaagctaac tggacactga ccctttagat tagcccactt 75420 tcccaacagt tctcatgtga ctttgatatt aagtggaact gttaatagag ttagtagttt 75480 agtgtggaca gtaaagacca tgctcaccca tgctcagtgc atgtgctctc agcgagctga 75540 gacacatggt gtgtttggtt tgtgagtgct tttctttgga atgctgctca aaggttggga 75600 ttttaccatc ttttctttcc ctcagaggtg ctggatgcca agatgatgca caggtaaagg 75660 gtaagccaaa catggaggag gctgggcaag ttgtgtgctc actgctcatg gttggcgtgc 75720 aggccctccc tgttactggg agaccgtcag ggcttccttg gtgtttcctc accatttctc 75780 ttagggtctc ttagaacatg ggccttggac agctccacct tttccgagaa cttccagggg 75840 tggactcttt ccctacttcc tcagtgaatt cagactcaag ttcttcgccc taacccactt 75900 gtgcagtcct ccacagcgca ctgcagcctc ttcagctccc catacttgta tggaatgcat 75960 gtacttctat gcatttcaac tgtgcaaatg ccggaaaaga ctcaggttgt caaggtgact 76020 ggagctaggc atgccactgt cactcaggaa ggctctgctc tgccattgac ctgtaggaaa 76080 cggctctatt ctcagaagtt aaaaggtggg ctggtgaggt ggctccatgg ttcagagagt 76140 ttactactgc acagcagagg gctcggtgcc acgcatgaag gtgttggtat gcatttgaca 76200 tcttttaatt acattgcatt ttgtagtgga tgctgttgtg tgtcctgttt aaagattaaa 76260 gaatgttcca aaaccactta gagcagtgtt ccttgaagca agctgacagt gaagaggtgt 76320 cctccctcct ccttcttctc caccttcgtc catccgtccg tccgtccgtc cttctgtgtg 76380 tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg ttccagttat aatcgtctgc 76440 agagtgcagt cttatttctt ggacattcag acatgccttt tcgatgccgt gagctttggg 76500 tagtttcatc atttagtgtg tgtggttttt ttgttttttg ttttttccaa acaatgcctt 76560 agttacatct atctcaagtg gctctggatt tgtgtcctca cttacagagc agtcatttta 76620 tagaattttc cttcatgtca ggaaacacgg taattgtgca ctggtggaat gtgccgtgca 76680 tatgcacact ctgtactgtt ttctgtgctg ttgttttcct ggggtcttgg tgggatgctg 76740 tgctttgttg agataggact tgctatgtat ttgtggagaa cactgttgct gttgaaatgt 76800 atattgtatt tccaaatgtt tgtggtctgt tgggagagtc accccctcaa ttctaaaacc 76860 gatatgatgg ggggagggcg ggagactgat atgtgcttaa ggaccaggaa gttctggagt 76920 gtctgaaatc tagccagcac agactgcagc tattgcttta aacacttgtg tatctttaga 76980 aacaaacgca tactattttg ttatagttca ttctccttta aaagcagaaa tgtgtgtatt 77040 gcataaacct taatacttgc atgtctacat ctatgtataa atgaggagga ggtttgagac 77100 tacatcacaa tctcttattg tcttcccaca gccctgtcag cctcaaggca ttacgtcacc 77160 aagtgagaag ccatgcctct atcctgaagt ggtaaagatg ctattcctga aaacagcttg 77220 aattactaag ctgcttttta ctttcaaaag cttttgaagt attttgggac ttgccaacca 77280 ctattagttg gaagtgtgtt tggtttgttc tgggagctga tagttgtctg aaagaagggt 77340 tagaaatgtc tcgtttcttt gggaattgtg ttataatttg gattaattag ctttcgcctc 77400 agagttttct cttttataaa tagggcaaac cccatatttg tcaggagttc tgggccccag 77460 ttagccagct gagtttttac acaagctttt acgcttggac ctggatgctg gctccaggtg 77520 cagacacagc accatggatg ctgaagatgg cgttacttcc ctggtgtcat cccttccacc 77580 ttctgcttga tgtgtgctaa gtgtgcccac ttctgatgaa ctgagggccc cttggttcct 77640 cagcattgct ttaatgtagc tacagaccca tggagtggag agctgcagtc tcatgttagg 77700 agtctagtgt ctatgagcat ggcaaaatgc ctaccgtccc ttgccgaatt atctgcaggg 77760 tctctggggt ttttaaccta gctcaaccag aaaccaggct gcctttaaca gtcccacata 77820 gcaaaaagca tatagtgtta aaggggaaat tgcaaagttg tgttaaaggg gaaattgtag 77880 taaagttaca tgatttttaa taaaataaaa aaagaggatt tttaggaagt ataaaccagt 77940 cattgtgtca tccatctatc catctatcca tccatccatc catccatcca tccatccatc 78000 catctatcca tccatccagg tggtggggat gaagtgtgtt tgtgtagccc agactggcct 78060 tgaactcaga gatctcttgt ctctgtcacc taagtgcttc tggggtcaaa ggcgtgtacc 78120 accatagcct accattctga tttgttattt tagaaataaa accacccccc cccccacaga 78180 gtttctctct atagccctgg aactcactct gtagaccagg ctggccttga actcagatat 78240 tcccctgcct ctgcctctgc ctcccaagtt ctgggattac attgctgctt taaaacaccc 78300

acgttcacta cagacccttt ccctcaacca agaaaggcac caattatcaa cacttgataa 78360 cttagtagcc acttgagcct ttctgtacct gaaatcttga caaaaaattg agacataaag 78420 gccccaaact gtgttatttt aggaaattta agatataaca ttttaccaga tagtggtgac 78480 aggcctttcc ccgcactcag gtagcagagg caggtgtttc tgagtttgca gggagcctcg 78540 tctacaaagt gagttccagg acatgcaagg ctacacagag aaaccctgtt tggaaagaac 78600 aagcacaaca gtaacacaca aaaccaaaag atacggcaat gtaacttcta gaaacaatca 78660 attaattaaa aatgatgcaa tgtttttctt agggctataa aatttatttt gtagctcttg 78720 tgtatttgca agggagccag aaggcctcag ctctagactt ttgtgtctga atgatttctt 78780 tttccaatag ttgaatggtg cacagcagtg tcttcccaca cgcctttgag tgcccaccct 78840 gaacccttgt ctccttcctt gctcctacac tcccatgagt cttctacttt caggtcatat 78900 gtgttcacgt gtgttgtgtg tctgtgtgca ctccatgatt tagtggcttt ggtcacatcc 78960 agtgccatca gagcatttac agggcataat taaaagctca tgatacctca caattgtagg 79020 ctgcaatgaa acagtaagag ggggtattgt tgtttagggt gtggttagag aaatagttgt 79080 atcttttaat taaacaaagg atggctaatg cctgaaaact agtctattga acaggaggga 79140 ctgtgagctt tcaaacaaat caggaacttg agaatcacgg tgtgtaggtt cttttgtcac 79200 tgatgaattt gagtcttagc gatgctcagt ggtgatctca ggagcccaga tcgttgcttg 79260 gcatctgtac ccctgnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79860 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79920 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 79980 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80040 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80100 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80340 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80400 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80460 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80520 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80580 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80640 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80700 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80760 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80820 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 80940 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81000 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81180 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 81720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnntagcata gactcttaag gcatctcttc 81780 cagatggcag gatttggggg agagcggggt gatagtttac taagtcttag tgtgtgtgca 81840 catgcgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtc cccatgtgca cactggagcc 81900 atggcactta tgtggaagtc agggctgcta cagagagtag tttttctcct tcctctattt 81960 gggtcccagg gatcaaactc aggtagtaag gcctggtgcc tcccatatta taatgggtga 82020 gccatctcag caggtccacg tgttactttt catacttgaa ggctattgtt ttgacttttt 82080 cagtattttt gaacaaagta ttgatgagct aatagttagc attgtgaatt ttttcttatt 82140 ttaaaaagga agttgacata gtagcaagtg ttgtgcttta agcgaaatga taagaggaag 82200 gcaaaccagc ctgagtgact tggctggcaa gaggctgtct ctttgcaggg gatttagagg 82260 gacgattagg aaaagaaaga aaagagacaa gtgtagagct ccacagccag cgatcttgga 82320 caccgtgctt acctgatgac tgttttgttc tttcacaaca tgggatcaag cagttttctt 82380 aggtttaaaa atactttgtt gaatattgac tcttatttgt gttccctttg gtatcatatg 82440 acatttgaag agagaaagct acaaatagaa gaagtttgac taattttagg acctagagaa 82500 tagtattatg aaaggttaca ttgtgcttct ttaataaaag aagcagttag aattatttta 82560 gccactggca tagtgtgttt aaactgcaca cacacctaga cagacataaa tccccgaaaa 82620 agcagcagct cactgctcgc ctgtttccca ccccatgtcc tggagtcaca gctgcagtaa 82680 agcagggcag tcctatagct ggtctagaat gcatcttaga cgtgtctctc ggccatactc 82740 agtgacgaaa acgtgaaggg gattagttac gcgtgccttg aatttccccg tctgaaacga 82800 gaacccaaac attataccat ccaggagagc taactatggc ctgggtaacc tgcagacctt 82860 ctgtggatgc cggtgctgcc ttcacctcct tctcgtggag gcactcagac tcgggtgaca 82920 ctgagactgc tctaggtttt acgacttgga caaatttggt tgatttctta attatgctcc 82980 tcatggctag ctatttttgt gagggaggaa aaattaaaat atacaggaag acatcatgaa 83040 gcattcttca aatttaagtt tcttataatc ttttggttgt gaacctagcc tttaacagtt 83100 gagccatccc tccagcccca aatttaaaat ttttaaagnn nnnnnnnnnn nnnnnnnnnn 83160 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 83220 nnnnnnnnnn nnnnnnnnag gctgctgcta tgaggtgtgg ttcttctatg atctgggcag 83280 agcagtgagt tgtagcccca gacagccatt ggcagaagca gaagcagaag cagcaggcag 83340 tacacagtca ctgtgctact aagacattag acgtgtggga agtgagttgt agggtatgtg 83400 tggatacagt ctcgtgcaaa gtgataaaca cccacagatt cccagagcct gcctttggaa 83460 ataaaggaca gataagtggt cactagtcac tgtgggcctt tttgtgcttg atgccattct 83520 ggctggctcc tctctgatct tgagaaatgt ggggtttttt gtttgttcat ttgttttgtt 83580 ttgttttgtt ttgctttgtt tttaacttta aaacccttac tgaattacta tatatacagt 83640 ttgctggttg ttactcggtt gtgtctctgt taggaacttg gacagagtag accacatcga 83700 acagctgggc ctggcttggc tgttcccata gttttggaca tggcctccgt gacttactgc 83760 cttccataac ctcaacagag tgccaccggg aaccatagat aactcaggac actgacacag 83820 ggctctcaag tgaatgtgtg aggttcacca gttcctgctc tttgccaaag ctgcccagtt 83880 tcatgggagg gcatttagcc tcttgtatcc agggaagaag tggccaaggt ccttgccatc 83940 tatagtctcc aatggttcca ttcagggatc atgttcttct gtaacacttg accttgcgag 84000 tgacattacc ataactgcca cttattcagg tgaatacata cttcaatctg tagggcttaa 84060 agatagtttg ctgtcttcct tctgtggttt gtggctgcct gcccatagta cttgttgttc 84120 ttggtggatt ggagggtgtt gagcacagag gatgtttgct cattgtgaat ttgccctgga 84180 gagctagagt ctcccaaaga ggtcccggca tttgtgaagt gggtgccttt gcttgatnnn 84240 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84300 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84360 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84420 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84480 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84540 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84780 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84840 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84900 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 84960 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85020 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85140 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85200 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85260 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85320 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85380 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85440 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85500 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85560 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85620 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85680 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85740 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85800 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 85860

nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnntgcc 85920 cccacccccc gccccacaat tgtttaaact gtagcatctc tgttctttat tatgctttag 85980 ggcacagcat gaaggtacca ctttggctta aatttggtgt gtcagtaaag tttttgaaaa 86040 acacccgtac atgaatgatg ttttaaaccc cccattttat agtcatgtct attttttgtg 86100 aataatgggg acattttagc ttatagtagc ttctatgaaa agcaacagag ttctttgtgt 86160 cactctcgcc cttgattgtc agtggaacct atgatataag gccaggccac taaatccagg 86220 tccacaggga ttgaaatggg ctcttcgcag atggctctgt tgcacttttt cagtgtgcac 86280 tttttttttc ttgagagtgt cacacatgtg cggtgtactt acatcatttc caccctcttc 86340 ccaggcaccg cattagtgca tgcatgtgcc ggatttccaa tcttacttgc tttctgtact 86400 taaccttata gagacctttg tcccccagag cttgatatca agcatcaata tttagtaagg 86460 gcaaatgcaa ggctgagact gaagtgactg ttggttgttc caggtgacaa cagttctcaa 86520 cctgtaagtc acaaccatta gcagacacat atttccaacg gccttaggaa ctgttaagat 86580 atgagagact gctcatttgc aaaattacag ataagaagca gcaataaaaa caaatttatg 86640 gttgggggtc cctaaaactg tcagaaataa tgtgttttcg aatggtcatg acccacaggt 86700 tgagaaccac caccttagga cttagcagat ttacctgtgg gtcactttgc attctcatgt 86760 aaggtatggg agggaactaa catctagcca ggatatatgg gacatttatg cgcagtttgc 86820 atcccagcaa cctctggttt gaaggaagaa gagaatgatg ctaggttatt ttccagtgct 86880 tgctttctac ttcaagtttc agaatggttt cactttcttt ttaaatacca tatcctgtgt 86940 ctgataaatt ctttgtcaga gccttctccg tgttccttca cctctgttgt aatgtgatgt 87000 tatatcttct agtttccttg cttttgttgg cataagcaat tgggcagtct tgttcgggtg 87060 ataaggtgca gctccttgct aggcagctgc tggcggctgg gttaggctgc acgtggcaaa 87120 gcatctttgt ggtgctcagc tgcgctttct gagtggagaa ggaagtaggg gagagccagg 87180 gaagcaggga gggctttcgt tcttctgatt taacgtgaac accgtttact ggcactaacc 87240 tatttgtgag aagtaattaa aataattcat gtaaaagtta cagcagagcc attggtattt 87300 gttctcagca atcagtaggt cttgtttctt tatgtgtgaa tagtacagta ccgttttatc 87360 tgcttgtaca ggtgggtacc tgagttgatt ctgaatcttg gaatcagtct ttgtgtatat 87420 cgctgcagtg cacacaggtg tgcacacatc tattgtcaca ctgatttatt tttctttgga 87480 catatcacat gggactggtg tgacatggat gagcccagag gacattatgt tatgtagtca 87540 gatacagaac aaatactgta tattctcact tatatgtggg aattaagacc ttgatctcat 87600 gatctggaga atagaatagt ggctcctgga aaagagagct tagtggcaca gctgatagga 87660 ataataaatt cctatagcac tgtaagcttg ccgtgttagt cagtcctata catttcccag 87720 gggcgtagga agaagatcca gactgttcca gtacaaacag atgatacacg tttgaggggt 87780 tggatttgcc aggggccctg ttcatggaca tgcccattgt gggcctgtac tgctctccat 87840 cgctttgcat acatagctgc tctccatagc gctgatagcg tgtatcatta cctcacacca 87900 attaaaaaaa gagtgcaaaa gcagttccca taagtatgtg cttcaaatgc tagaccaatc 87960 atttccagat ctgtccagtc tctcttatac tttctattgt tagctatttc atccatgcat 88020 tttatatttc gaggcttcat gctttctttg taagcataat actcacccag gatgggaaag 88080 ttggtgaaga tagggcgttt caaccaaaga gcttagagtt cattgttcct ggactcataa 88140 aacactcagg atgagtggag aaagtatatc gcccacaggg cgacatgagc acctggactc 88200 ggaagggtgt ggggaggtgt ggggaagaga tgctttcctc ctcgtcgacg gccagcgctc 88260 tggcatgcgc gtgcagcttc tggtcatcat actgaaatga tgatctgaat gtggtgacaa 88320 tcatttgaca gaggcacctt tggtagacag atgtctgctg cctgttgagg gtgcttttgg 88380 gtgttaaaga ctgtttctga cctgtgtgga cggatcatta agtttaaata ttacttttgg 88440 tccaattgct tagctcattg tctgacgatg ttttatatat gtcttgggca gtcctaaagt 88500 gtcttacagg cttgtctacc ttaaactcaa gaatataaac ggaagggtaa aggctcattt 88560 atttttcagt gtgattgatt tcattaacaa taattaggaa ttaaaaaaca aaaacctaag 88620 agaaggtgaa tgtctgaagg gagtttgtaa tttgagattg tccactgcgt gactgaagta 88680 aggacagaaa aacttcactg tgtttgagga attttaacat agcctttaat ttgaggaact 88740 ggttggtgtg agaggccaca tgacctgttc tagtcttggt aggaaggtga agctgagcct 88800 tgtgtgtata tttcagagag cttctagcct aagtgcaggg tgccctgctc tactcagagc 88860 tggctcactc cttagccctg ctctcccaag gaccaccgtg gccttactta ctcttgccct 88920 caaagaactc ccacgaagat agcaaggtac agtttagttt aaggtaatga tagttgtcat 88980 tttcatgtgc taaacctgaa tccttatttc ctattcactt gtcagcacct cagccctttc 89040 cagcctaata tatatctttc tctctttgtg tgcttttaaa gggtccagca tttctgatta 89100 cccaatcaag taggagcctg ctcgtctcac ccgtggaatg gaatgctatg cctctcctct 89160 tgcattcctt tccccagact ttgctggcct tccacctgnn nnnnnnnnnn nnnnnnnnnn 89220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 89280 nnnnnnnnnn nnnnnnnntt tgagacatat agtggtatgt tattgtggtc cagggacttc 89340 aggaagctgg ggcaggaggg tcataaacaa attagagacc aacccaggca cctatctcaa 89400 aaggccctcc ccattacccc tcctcacacc cctgtgctgg gcaagtaggt gacatggagc 89460 tgcgttcctc gccctatgtg tgttagtaag tcttaggatg cagtactgga ttttcttatt 89520 cactgaaatt tatactactg ccgctgcatt ttaggatgta tttatgttac ttaaacagta 89580 tacacacaca gatgtgcacg cacacagacg cacgcacaca gacgcacaca cacagacaca 89640 ttctatcgtt aaggtgattt gaagcaatct tgtgatttga agcaaactgt taaaattgat 89700 tttatgttta actatgtggt aggttctgtg tttttaagca aaatattatt attattatta 89760 ttattattat caagtgctga cagtagtaca tcatgactgt ttgaccatat attataggct 89820 gttggcatcc atattcatgt atggtttaag gaatttgaag attcctttgc agctttccct 89880 atccctatat agtcctcagg gcttcccagg ctgcctgcct ggaggtgggg gtgggggtgg 89940 gggtgggggt ggctggagtg actctagcct aatggaggcc agtctctgtc agccagagca 90000 tgcgggctgg cagtggcctg gttcctttgt ctggccagtc agtcatcttt ctaacagaca 90060 cttggcttct ccagtgtatg tcagagatgc agacagctgg ttcaggatgg cctgcctggc 90120 ttcccccagc accacactct gctgtatagg acatggcttc ttttgatcgg tgacagcttg 90180 aactgagaaa atcacgtggc tcaggccttg ctctcagcct gtatgtgcca gggctcgaag 90240 gggccatgca cttctgctgt tcttattagt gtgacatcag agatcagaag gcagttttca 90300 gggggtcaca tctctgcctt cttggttagt tggcaaaaaa ttatagcatt atcaaaactg 90360 gccttccctg actgcccgga aggtatggtg accatacact gtgaatctgg tcagccttgt 90420 caacctttcc agccatgagc tctacagctg gaccttgctc cccaggcatg cctcggggac 90480 aatatggaca tgtggcagaa cacctgcctt aggtgtgtat agattgaact gggaacaccc 90540 gtgccttcta ccccatgctc acccagtaag cttccagtgg atgatagctg cttgtgcgtt 90600 ggtatttcag tttgacacta tgtacagact ttaaaagaaa aacaaaacaa aaaccaaaaa 90660 aactccttca ggcaaattaa atgccctttt ggtaggtagc aaagctgccg cttccttctt 90720 ttcccaactt tattttctct ggctctgttt ataatcactt attaacaaaa tctgagaggg 90780 tcctgagtgt gactgttcct tacctatgcc ctcaacgtac ttgttctcat gtttctcgca 90840 gagtgcacat ggagcagact tggtgctgca gggagtgacc tgctgctaac tgatgatcta 90900 ctggcaaggt gcacattgtt ttagaaagac ctttctcgtg ctgcctttat cctagaacag 90960 ggacacagaa caatcttgta gaaaccattc actcttcctg gtcggggtga gagagaggat 91020 aacttaaaaa cctgagcatt ttaaacagtt gcatgggagc tagtgagagc tcagcatctg 91080 agagcacttg ctgcatctct gtgaggacaa gagcttgact cgtgctaccc agtgttggtg 91140 gccgtgggtg gagggggctg actgtcagcc tagctgacaa acagatgagc tgctgaagtt 91200 actgcctccc ctcagaggaa taaggcagag agtgatagag ggagacgccc ttctgtggct 91260 gccttgcaca tacatgcatg tacactacat atatacatat ccatgcacac atgcagcaca 91320 cacacacaca cacacacagt agggggagat ttaaaatagc tggatcttct tagaccaaga 91380 tcctaatatt gagcaaatgt gtattttact tcttctaaga aactgcctta gtggttagag 91440 agatcgttct gtagttaaga acatctgctg cttcgcagag gcctgaagtt cacagcctgt 91500 aagacatgtg atagaggtgc taaatccctc taagggatcg atgcctctat agtcacctac 91560 atatacacgg gacacacaca cacacccagg atacctacat atacatagca tacacacata 91620 caggttacct gcatatccat tgcatgtgca tacatctttt taaagctcct tcttaatgat 91680 ttatttgtat cttatgcatg tgaatgtttt atctgagttt atgtctgtgc accatgtgta 91740 tatcagggat ctgtggaggt cagaagaggg cactgaatgg accattgtga gctgccttgt 91800 gtgtgctggg tctcaactcc tgggccatca gatctccagc cccacactat tttcaaaatt 91860 gtttttaaaa agttattttt cttattagtg agtggtagga gctcttggtt tttctagaca 91920 ctgccttttt ccagatgggt ccctcttggt ttccagtgag tttctgtaca cgatgcacta 91980 ggctgcttct ctgtgcactt gtgcagccag gcttgaccat ttctgcaaag accagccttc 92040 ccagttgaat gactttgacc tattttgttc agtgtgaacc tacacagaag tcagttccgg 92100 gactcgattt tgttctgttg cttggtttat atggatgccc cactgctctc tgattatggt 92160 gactttccag taagtcggaa atgggtcagt gcaagtttaa agtaggtggg ttcaagggta 92220 aatacatgaa gatctgctag gtggacttgg ggtggatggg cctgcccaag ctctgtgtct 92280 tctagatgct tctctcaaga ttacgtaaag aactgtgtta gtttcctttc ataatgaagt 92340 ctgtgatgga tgtgctaggt tgtggtatta gtctcatggt aatcataatc tatagatagc 92400 agtagtcttt gtgggggtga gacctagtct gtataaggaa tgtaacctcg gctgcttcac 92460 ccgtcccacc atgcttttgt agacctacca tgcctaagtg acacctggaa atgcagtgaa 92520 cccacagtgc agcccctctg ccctatgtgc ctatgtgctc ctgtcttctg acctatgtgc 92580 cctctgccct atgtgcctat gtgctcctgt cttctgtcct atgtgccctc tgccctatgt 92640 gcctatgtgc tcctgtcttc tgccctatgt gccctctgcc ctatgtgctt atgtgctcct 92700 gtcttctgtc ctgtgtgccc tctgccctat gtgcctatgt gccctctgcc ctatgtgcct 92760 ggctcctgtc ttctgtcctg tgtgcctggc tcctgtcttc tgtcctgtgt gcctggctcc 92820 tgtcttctgt cctgtgtgcc tggctcctgt cttccccagc tctccccagc cccagtcggt 92880 ggctcctccc ccaggactgg cacagcagag ctggttacta gttgcagtct taccttttat 92940 gccatgcact gttgcttttt aagtagtgtt aaacttaaaa cttgagtttg taactcttta 93000 taaattttgt tagttttctg tttggaactt gcactaagga tatctggaaa cctattggtc 93060 tcctatgtat ctgtctttaa ctggaatgaa ttgataggtg gcctcatgtt gtttttacat 93120 ctgatcaaag catactgaat aggatagagc aagcaggcag tgtcctgtcg atactgcagg 93180 ctttagctca tagttgttga ctgcttgatg gctttgagca gaggattgga tggggtttgg 93240 agtggctcac gaaggctagt gcacgtaagg catggtttaa aatctgcctg cgtctcagga 93300 aaggatggag agtgctcctt tatgggtgtt attacccctg ccactgactg ccactcactt 93360

tactaggata acttgtttgc atatacattt tctgttactt tcgtccaact gtttctgata 93420 cccatgttac attttattat atatgatgat ttcaagacta tgttctggtg taaaccaaac 93480 ttcatccttg tcagctgctc tactatatag acattatata gtcaaatgtt tccagtgttc 93540 tagaaaaagt gcagtttgaa tattaatttg gtgttagctt cttcaccttc tgttttctct 93600 tctaaaacaa aactgaaaag ctttaaatgc attagcactg ctttaggttt ggtaatgaat 93660 acaatgtcat tggcaatgtc actgatgtca catgaagaaa atacaaccct tgaagctcac 93720 ttgcaagaac atttccttga tgctaagtct gtaacgttaa tgcttttcca aaagacgatt 93780 ttagaactgt tgccagcaac gagcactcgg gcttttttct tgcatccata acatatacaa 93840 ttaatctaga taaaatagca taagcgtgca ttttaggtct tgtgtttctc agtatgcgtc 93900 ttgtatgtcc aggcagcagc ctgccagctt gcgcttgcgg cctgtgttct gagatagacc 93960 ctgagggaac ttggggctgc tttctggcct tgcacttctc tctagcaaac tatgatggct 94020 gttcctcatt gtgtgtgctt tgctccaaca gacttttctt cagagaacaa attgctctga 94080 catctttgtt cttttaaaca cttactatat agatttttgt tttattttag taattttaag 94140 catctccatt gtaattatga gaactcaaaa tcttgtacat gttctgatgt tcataaggaa 94200 atatctcgtg caccttttgt actgcgctcc acaagcagaa gccatgcctt ggccattctg 94260 cctcttgcct tgctatgcat ttcagtgcag agtggtccct ggtgactggt gctgtgcatt 94320 gggagcattg agcgggcatt agctatatag cgattacaaa aatggcatct gctcggagca 94380 gtccagcagg gctcggcatc ctcactaacg tctgggtttt gttcccattg cagattttcc 94440 tcgcatctgg cttcactgca ttggctcttc tgcactgtgt acaggcacag gtgagttaat 94500 ccttgggtct ttcatgttgc gctatgttga ctattagatt aaatatttta aattgcctaa 94560 tacattagaa acaataagca aataagagga atgtgagtaa gaacagaata aaacttacta 94620 ttttcctgca tgtttttgtt aagagagttc ttttatgaaa ttgttgaaat gacattgaag 94680 gtgacacacc agatatcttg attggtggtt attgtttcta tttggaaagt gtgtgtcttc 94740 agtgtacctg ctggacaagt tgagttaatt cattaagttt taacctcaga gcctggaaaa 94800 aaaatttttc tacttatttt catatgtcac atatttttga gtggttgtat tatttacctg 94860 ttattaaact ggtataatgt aggagaaaag aaaacttctg taggttttac cattaactct 94920 caggctgcat gtacaggtgc tgtgcaatac tgggcttggc ctctgtgcca gtggcgttcc 94980 ccactcatcc actgatgatg tccatgagat ttatgaaaca tgttagtaac atgcgataca 95040 cttttcttca tttgtaactt acccttggag aacttcagct cccttagcat tgggactgct 95100 tgtactcaaa gacatagcct tagttcttag agcacggaat gctttgcagt gaagactaaa 95160 gcctgctgag tgtgagcatc tgtaagtaca cagtagaagc gagaattatc tgtacagagt 95220 gtataaggct ttggaacatt atgagaagtc agtatgttgg acctgttcct tcagagatca 95280 gggtagagtt gaggggatgt ggcttctgac tcctcactct gtcaggtgtc tgtggtctta 95340 ggatgaagtg caaacacctt aagtttggta ttttttaccc tcttagcatc ttgggtatgt 95400 tttgtgatac caagttttga tgtctgaaga ttggatgaat taaatctttt ctactgtctg 95460 tcgctggatt taccgttttt catttagttc ccagcctggg agacttgtct gctcattttc 95520 ctgctgtgtg cactcatgtg ggcactggtc tcagtggctg ttgacctcac aggacacctg 95580 atgcccatgt gctcttgacc acgccaccct tcttcaagtg ttgagatact agccatctct 95640 cttgggtact tgtctgtttt acttaaagtt gttactgtat ttccttattt attgagtgct 95700 gcactggaca tttgtggagg tcagaagata gcctgcaccg agttggttct tttcttctac 95760 catgtgggtc ccaggactca aactccactc atcaggacta gcagtaaacc ccttagctgc 95820 ccagcctccc tcaagactcg ttttgctttt gctctgtctt catgcatatt tgtctctcgt 95880 ctttacaggg gctatttttc ctcctaggac ctttaatttg cttgtaatta aataaaacgt 95940 tagctgttgt acactatttc ccattcacac atccttacag ggttagtctg cagaagcacc 96000 attgctcttt cagcagctct gcagtgctcc tctgagtgcc cagcagccac agttgctctc 96060 tggttgtgtc tggattagca gatgaggaca cgcatctggt taagtgactc tcccaaggac 96120 atatcacctg agtggtggtt tgctgctctg aggaccgtga tcttaaccat gaagcaccat 96180 ttctgcctaa acagccctgc tggctctcat gtttgtggca gtaagtgtaa tatatgaaaa 96240 ttattttcat gtttgaagac ttcaaaccta atttgaaaaa tcagacatta tttacttgtg 96300 ttttattaac taggcctaac ttttaacctg taatcttcat ttcaaactgt ggaacacgat 96360 ggcttacttg aaaaccaatg actgcattag tgataaaagc tctgcagctt gtctcagatt 96420 gactggtgac tggagcgagg gtcgcagctc cagcctcttt tgttttcatt atttgttttt 96480 taagcatggt atgctaggaa ttggcattct ttccccctta gacattttag attataggta 96540 gcatctgtgc ttcactggat aaattgcaaa acatctgggt gtggtggcac atgcctataa 96600 ccgccagcat ctgcagggtg ggaacagagg gaggagggcc tggagtccaa agacatctgc 96660 agctgtacag tgagttcaag gccaccctca gtacttggtc ctgttcaaaa aatcccaagc 96720 acacaaaagg aatacacatg taatacacat gtctaaatac acgtgtactc acagaatagc 96780 tggatatgta gctcagtggt gattctatgt ctatgtaata taatgcatac ataattattt 96840 atatatgaaa tatagtgact atattttata tagtgaatat attatatatt tcatatatag 96900 atttttgcct taaaacatgt agtgagagag ctgccatttc aagacaggaa taaaagccta 96960 ggagagtgtg agtattgacc tgcctcatta gtgagctgcc attatctctt gcacatttat 97020 actgctcact gacaagctca caggccagag cttggaaaga ccatctttat atgcatttct 97080 tatttgtcag gacactattt aactcctatc ttctggttct gaagatatct cactacttgg 97140 cttggaggac agagtagaca caagtcttct taatattgtt agtagctttg atagcttttt 97200 aagcttaagt tcttgctatt aaagacagta agatacagtg actgcatttc aacaaagggt 97260 ccagtgcttg aggtttaatt aaagaagtca acatgcacat atacatctgt agggctctct 97320 gcactcacgt cacccagtca taggtcagtc ttgtctgctg agtgctctag agtggctttc 97380 caaagcaccg aggcatcccc ctattctgta tatgtactct gaacagaatt accgcactgt 97440 aatgcaccat gtaccttgtc agaatgcaaa tcgaagagca ggtaagggat ttcttagttt 97500 attttttaca tgactaaacc acctcttaaa ggctgctagc atggtcgcca gaaaactgat 97560 tttgaagttg cagagctcct caacaaggga ttgacagtgc acttccagag cctggagctg 97620 ccgtcccagg ctgtggcacc gtatgccagg gatggagggc tttgcctctg tagtagttag 97680 ctgctttcag gctcaaaatt aactcttgta gttgatactt cacttattga aacagacact 97740 tatttctagt aacatgtctt tgaaaaaaca aagtagatta cttaaattgt gctacagaaa 97800 gtctaatatt gtcttgaaat gtttaaatta taaataaacg atttcccctt aaggaacatg 97860 atgacatatc ttcaggaagt tttgtttatt taagaactga catggtatca ccggtgttta 97920 ggtagagcat acttagactc tctcttagcc ccttcatgct tagttgtctt caggactgaa 97980 cagttcattg tataaaggta ctttgggtct taattgcata atattggttc aatatacctt 98040 aaaattttca ttggaaaaca aacttaattg tattttcttc aactttctga aaagactgta 98100 agagaattcc tggtctgaat tatgggatgg agaattcttt agtttgaatt caaaaggcaa 98160 aggactatgt gccattaaaa aaaaagtctg tagcaagcta ctggttccag tctagatcac 98220 acttttaaca tcattaaacc taaactggct ttgtccacta aacagcagga tttaggttag 98280 ccttgacatg ccattgaatt taaatacatg actagtgctt cactactgct gtgtgtgtgt 98340 gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt ttaaggcttg tatgataagt 98400 acattctaat gttttcgtca tctcatgatg ttccttttac ttgagccact gttttgacag 98460 acatctgtgt tgatgaagcc tcttgttttc tgcaggtttc caaggactga tggtgatagt 98520 gacacacctg gtgtgtttgt tacatgtcac tgtgtagttt cctggttatc agagtcatat 98580 aaaggctaca gagaaagaca gagggaagag aaagaacaaa ctttggcaaa gcgcagctct 98640 tggacatgta ctgtgtcaag ttaaactaga tgattctttg tcagagagtg aagtgtattt 98700 ggattttacc tgatcaattt tatttggcag acttacactt tgcatcctag ccggtggctt 98760 aggtggtaaa gtatcagaac tgtgtcctgc aagctgtcat ctttagtttg atctgtaaga 98820 gtcccagaga tgctttacgc ctcaagctgc aagtgcaaga gctactctgg aggctgtgac 98880 aggacctgag ggaaagtgtg cgtgggagtt cttacatgtc tgtctcagca gtatgtgctc 98940 tgctcgctta tttatgggac attattagtg ttacagctgc ccacacgtgc atgcctaacc 99000 ttagttatgt ccttgaatag aaacttactt atccaaaata gcattattgt attataaaag 99060 acgaatactg attgaagcgc caatagtagc aaatgagtag aaattaatgc atgtatacta 99120 aagttaccta aatgtgtgtt tatttacgtg tgataacgtt tgtcagaact gaccgcactg 99180 tagtttgagt agagaggcat gaagggaagg cacgtgatgg caatagtgtg ctcgcctatc 99240 atacccacaa tggaatggaa tggagagaat cctgtgcaca ctgaggcagg taatgtccta 99300 cggccttctc ctatcagtca gataatcatc agaagaaccc agggactcac tattgtggtc 99360 ttaaggcttt gtttggttga tctgtggatt ttgggttttt tgtttgtttg tttgtttgtt 99420 tgttgagata gggtcttcct gtgttcctgg ctgtgctgga aattgatatg ggaaccagat 99480 tgacctcgaa ttctgcctgt ccctgcctcc tgaactctgg aattagttgg ccccaaagtg 99540 gagccaatga tcacatttta aaatgagaaa tgaagtaact gttgtgttaa atgaccactc 99600 agtgatgtat ccaagttcac aagctattta gaggccaaac tcaggttgat ttttgtggtg 99660 tttggctctt tagaaacgaa acagcaaatg cagacagttc ttatgagatg cagttgcttg 99720 ctgttcaggc cccatgatca gggcaatatg gaacacatgt aaaggtatac agaaagagcc 99780 agctccacag ggtgggtctc tctctctctc tctctctctc tctctctcac tctcgctctc 99840 ccccctctct ttctctcttt ctcaccacaa agttcatttc aagctgcctt cccccacagt 99900 gagatgtgca ggccctttac actggctatt tgagaagttg aaggcctgtt ttataatcag 99960 aaactatacc tgtcggtgat tagtacggga aagcacaatt caagtgatgt ttcattttca 100020 aagattgaaa aaaggacacc aactttttcc ccccattttc ttctgtttac aaacaacttt 100080 aaggctatgg agttatataa aataaagcta tacaggggct ctataatgta cttggtagat 100140 tgcttgccta gcatgctcga gcaccaggtt tggtttcccc tgttataaac tgtgtatggt 100200 ggcacaacct ttcatcctat gactcaggaa atgcaggcag gaacatcaag agttcagagt 100260 cagcctctgc ccgacagcga gttcacggcc agtctcgcta tgtgcagccc tgtctcaaaa 100320 caaaatgaga cttattttta cttgataaat attgtaaagg aatgtcttag aattcatata 100380 atcagaaatc aacacaggac tctctcacag agaagaaatc ttcagaaaag attttggctt 100440 ttagttttta aatgttaaca ttttgaggac tgatgagatg tcttggctgc tgagtctgat 100500 aactgaattc aactctccca cctctgagct ccatttaaag gaatagagaa cctcttcctt 100560 cctacaagtc gtcctatgcc cttgaccgtt tcaccctctc cctctgtttc tctgtcctac 100620 aagtattagt tggatggaga acccttctag ttagtttaaa aagcatacat ttatgttagg 100680 ttttatatta tgacgtctta acagacatta cactttaccc tggtaaaaaa tgaggctatt 100740 tttcgccatg ttgtttcttg agttgttaag gggccgtgta cagtggtagc tgaggagcgc 100800 tgaggtctaa ccactgcacc atctaaaata gacacagagg gcttccatca cttcccctaa 100860 ggttcctggc ctacacctgc catttcagct cctcttctct tttaaaacca ttttcaagga 100920

gattcataat agagctataa ttttatcagt gctgtcaaag gttttcctgg tatctcaata 100980 attcatgctg tttctcaact tactgattga ctttgaatct ttatattgtc caaatatttt 101040 tttataaatt agaatgtgaa gcttattagt aaattatatg taacataact atttgaagat 101100 gactctagtc gaggcacaat gaccgggcag gaagctgatg agatttttgg gaatgggagc 101160 tgtccagtga ggctcctctt tccagcattg ggcatcgccg cgccacatgg gaagagcagc 101220 agagttcact ttgcttgagc tgtgacactt acctccaggc ctcattcatt atctgtgaca 101280 gacgttagcc ttggctagcc tgcctgtgtt cctgttcacc taggtgtcca tttgtttttt 101340 cttatactgt gggtttttag tattgatgga actcataaag tatacagcac atagattatt 101400 acttttatat ttccctcctc cactctatcc caccctccct cctctcttcc cccccccccc 101460 atcctcctcc cttctctcct caattcttat cctacaccta ggttacatat atctcttttt 101520 ttcacccctc cctctccctc ctatttcctc ccctcccctc ccctcctccc tctgttttgg 101580 gacagggttt ctctgtgtag ccctggctgt cctggaaatc cctctgtaga ccaggctggc 101640 ctcaaactta acagagatct gcctgcctct gcctctctgc ctcctgagtg ctgagatcaa 101700 aggtgtatgc caccatgcca ggctggttat atttatgtct acaggttcag ataatgtgtc 101760 aatagtggtt cccagctcag ctctacctgt tacataagta cctatgctta gtcccaccac 101820 caccctggcc accctgcctt cactggacta tcaggactga gacaaactta ttccagaata 101880 gcaacccatg atacttagca gcagccttca ctgaccagca catcctttgc tgtcctcact 101940 tctgaaagtg cacacacatg ctagctgtgg attcgactgc agtgactttg tcagagacag 102000 cagatggctg agagactgtg gtcccttccc aacaaatctt ttctttgcaa acctcttcag 102060 aactgatgaa atgctctgag agctgcagac cttcaaagag cagttctaac ctgaaaaacc 102120 agttctgggc ttgcattctt gccactgagt atttctatgg catttttctt taacatatat 102180 ttctttgtga cctccttact gttcttcttg tccctggtca tgcctcagta tggtggaaaa 102240 caaaaatagt aaagcaacaa aggaaaacat gattttaaat gtgtacctac ctagctaggg 102300 tttatacaga tagagaggta taataacagc cacttaaggt cccttgaaga tccaacaggt 102360 ggtcatttta ttttagagtc tctttcataa gccttctgat gatcaccctg tgttgtaaga 102420 ggcaaatcag tcattggtca tctggtagag atgggtgtag cagagagctg gctatgttgt 102480 aagaggtggg tcaggcattg gtagtcatta gtagagaggg tggggataat ggagagctct 102540 atggctcctt ctcttaaaag ggataccttt gaacatcctt gtctataaat ttgtgatagt 102600 aacctcccat gagaagagta aaaatcaagc agataccaga cagatgagca tgtgcattcc 102660 cagatgcagt tgctgcgtta ccagaatgag cgtgtgtcct tacagttaac atatccccag 102720 gaggtagcat ggagcctcct aatgcctctc ttcccagttg ggtggccggc tggtctggtg 102780 tagcagaagt gcagagccca ggcttccttc catatctgtg cttcctgctg gaaaggacat 102840 gggaagccgc caaaatttca ccagctcagt ctcagactgg tggctgtgag attttaagca 102900 ggtagatttg tcttttacct caagtctcct cttgattcca ttagatgaac taagagtaag 102960 ccatcaatat tgactatgaa tcacggtatg gctggtccct caaaatgttg gtggatcccc 103020 aaatccagga cctgtcaggg aagctggtct gccttcccca gttttattct cagtgcccag 103080 cccttcttgg aagctgtcag cactcagatt taggtacact agccctataa actgtgtgca 103140 gatagtccaa atcaaaacag gagatagaag atggctcagc agttaaaaca ctcaatactt 103200 ccacagagga cctgaggttt tcccagcacc catcagggga ctctttcatt gtcagagttg 103260 tcccattgag tccctggggc atggatacac acactcaaaa agaaaaagaa agcatttaaa 103320 acacaaaaca aaagccctct aaaatctgag acattgcccc aagcatttcg aatatgggct 103380 gggaaggtgc tatactgttc tgtgcctggt ataaaggttt cttggtctta gtaacaagtt 103440 tgtgcacatt ttgtgtgcat gagccctgtg ctcagattct tacgtgcata tttactttca 103500 gttttcatgt gtatatctgt cttatatctg tgtatctgtg tatcatgtgt gttcctgggt 103560 catggcagtc acaacagggt gtcggattcc ctggaaatgg agtttcagat ggttttgggt 103620 gagcactcca tggaactggt gaattgaacc caggtcctct agaagagcag cagctcctaa 103680 cagctgagcc atttctccag ctaccccttt gtcctctgaa agaaaggaag aaagcataca 103740 gctttgtact caggcatgtt aggaggttaa ctcctaagct gcaaggcctt ccactgtcat 103800 atattagtag catatattca gaatcaggac tgtaagactc caagtcacag agagtgaaat 103860 tatctttaga atgttaaact tagcaagata ggggattatg gtaattttta atttatttta 103920 ggatagcttc aaatgataat ttaataattt aatgtggttt tgttttgttt tgtttctgta 103980 actgtgtgct gataggttac aggttctgtt gtgttgtggc aatctcagtt gaaaactcag 104040 ctctgcagca tgtgctacag agacactggc agtaggtggc cacactgtga aaggcaggcc 104100 atgaggagag agattttact tggtggcctc cggtgttaat gttgcttggc agctgtcatc 104160 tattagtact gtgaggattt cccacgtcag tgtcactgct tgtgacacta gtgttctgga 104220 tctgggatct gccagagtat ctctgtgtag ccttggctat cctggaactg agtttgtaga 104280 ccacgttggc ctcaaactga actctgagac ccatctgcct ctgccttctg agttctcagt 104340 gctgagatca aaggtatgct ccacagtgct aggctgtacc cggggtttct aagttacttt 104400 tcccaagttt taagggctga cgcaagatga cacaagaaag catctttctt ggaagtttcc 104460 agggccagga tacctgcaca taggccacct gctttcatca tgggtggctg cctttccaca 104520 agatcatgct gccttccctg cctttggaca atgagaagcc actctgtgca gatgtggatg 104580 cagatgcgga tgtgggtgcg gatgaggaag cattgtttag ggttgggtag ctgtctgtgc 104640 agaaccacta gctggaagga cattcctacc gcgcggcctg cagtgtggat gctgcacgca 104700 tgtctgattt cctaattggt gttcatctta ctgttcgtcc cactcatgtg caccagtcac 104760 cagggcacag agttttccaa catcactgtt tttctggaaa agtcatttag ctcagacaga 104820 tgcccaattt gtaacaaccc acaagcaatt tattttgtaa aactgattct gccccatttt 104880 cttcacctat aagggatgtt tttgagtttg agcgattgtt catacaactt gggaagaatt 104940 ctatacacca aacatgaccc tttaagaaat ctgattacat ttttaaaaaa gtaatcctta 105000 ttcccctaca gtttgtagga gatctttatt ttaatgtctg agctgaaggc aggctgtgcg 105060 ttttcatggc tttccagagg ctcatggtcg cagccttccc agttagaaat gctgatgcca 105120 catttattat tttccccatt acaggtgaaa tcattagagt ctcacatccc caggcctata 105180 gtgccgctct cacaatgtct gtctgtcatt atgtatgctc actgaaggaa gcaggtgtct 105240 aaacctgtta tattatagac gtatggcttc tgtgctgggg catgtggaga tggtgctgaa 105300 agacaggcat gctcacccac tgtggtgcta gctatgggtt aataagtaca tagatggctg 105360 ccagcattat aaattcaagt caaacacact gctatgggct atacgatcta gcagtgcagt 105420 ggaggttttt gtccatgttg tagagcgagt agccaaggct aaagtttatg ttttgtgtcc 105480 ttgccagcaa taattttcaa ttcaggttta ctaattccct catcagttca gacagttcca 105540 tgacatggga aggaagcatc cttgaaggta gtacctagta ggaaggagaa ggccatgtgt 105600 caatgcccag ttgtgtccat ttgtccattt gcttttattc caagtcttgt tatgtagcat 105660 aaggtattat taaactctgg actatcttcc tgtctcaggt tcttaaatgc taggattatg 105720 gtgttatggg gatggaccac catgctcaac agaatggtgt ttgtatatat cctacatgta 105780 tgttagcctg gacaggttag taggatcaag ggtcatcttc tcactaaggt attttaatgt 105840 agtcctgata agtaggggtc tgctaaaggg ctgcagaatt gtgaagctct acaacacatt 105900 cagactgaat accctacaga gttgccagag gaggatgtag ttggaggata aggcaagagt 105960 agccttctga agtgtgccag gtggtagtgg ggactaagag gacaaggtgg gggcagggca 106020 ggatgtaagt gtgtgcatgg gttgatggga gtttaattgg ggtgctcaga ctgcatgtaa 106080 tcattccatg ttctatgaaa catctgattt tgtttacctt gactgttcag tttctatgtt 106140 ctagattatc ccactttcca cagctaatta gtaatttttc tatcttgaca aagataactt 106200 ggtgattttt catagtagca tcattcataa tagctccaaa gtgaggagaa ttcagatgtc 106260 cattggctga agaacagagg aataaaatga gctacaaaca tcaatggaat gttattcaag 106320 aatgaaaata atgacgtaat gaagcatgct gtaaggtgga taagtcccag aagcattaca 106380 tgtgcaggat gctatttggg aaagcatgtt tggtgatcat tccatttatt acagaatgcc 106440 taggaagggt aaatctgtgt tagagaaagt agagtaatgg ctgcccaggg ctgggacggg 106500 gcagggaggg atggagctga tgcctgattg gtgctgatgg catggggttt cttctggcgt 106560 gtgtgttata gttcagtaaa tttctttgta ctaacaataa gaacatggaa tcaaagtcac 106620 ctacaatttt ttttagaaaa caaacaaact tgtatggtag aatcccacat atggaatatg 106680 tcagagggtc aagtgaggaa ataaggaaaa gcaatgtcag caaaaaaaag gtaaattgta 106740 atacagtcat taaaagaaaa ttaacaaagc cacagaaaag attatcactt acagatacaa 106800 cctaaaaata gcctttgtgg acagtcttgg tataaatcca ctatcttatt cagttttcta 106860 gcctgaagca ctaaaagaac gccatttgag gccaagagac caaggatttt agaacaaata 106920 ttttattata tttttcaaca tttaagcaaa attcaagatt agtttcattt aactgaacaa 106980 tttagaaaat tgcctatctt taaagaaaaa acaatgaagt tttttaattg atttttgtta 107040 aggttagata caaaagagaa agagcttatt tgttaatgga aacaataaga gaaggaagct 107100 gtgctcacat aacaaggtgt cggaagcagc tcagccagga gtccttcagc ccttacagac 107160 tctttctgca ggcacgcatt gcaaagcatt tgcttgccct gcttctcatg tgttnnnnnn 107220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 107280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnntcacac acacacacac attctcacac 107340 acacacacac acgcacgcgc acagcagacg acaaaagaga ggaaaggctt gctttgctcc 107400 cagtttcaga agttccagcc tgtgggagtc atccagaact cagcagagca gaagtgtgtg 107460 gcagaggctt ccatgtcacc aagtccattg aagcaaggac caagttatgt ggccttcaga 107520 ggtccaaccc tcctgctcgg cttcctccag ccacaggctt acaaaataat tctaccagct 107580 gggaaataac ttttcaaaac tatatgagtc tgtgaggtgg gggagggtct ttcataatca 107640 agccaccatg ttctggccct ggttgccaag acctgaccat gtcataatga aaactgcatt 107700 tagtcctcct ttaagaaaca gcctgggcag tttccagctc tgttcagaag tacaaagttt 107760 aaagtctgct gacacttgac atttgttggc ctgttaaagt cgctattctt ctaatatata 107820 gtggtaacat taccattcta ttcaaatatg gaaaaacagg aagatagcaa agaaactttg 107880 ggccaaacca aaaccatcaa gatgcacatg acattctata attctgagct atcgtgtggg 107940 cttgggcccc taccttgtag ccgtctgcag cacacagtgc ccaagatggc tttccttgtt 108000 gcctgaagct ttccttggca aacacccatg ttctggcatc ttaagttcca ggtatctccc 108060 aggtttctct ggggatgtga tcttgatgtc cattgcgtag cctctttaaa atctttgtac 108120 aagtacactg ggtacccaac aacgccacct ggatgacacc aggttctgct gtctgctttg 108180 gaagtggcca ggccacagtg gaccatagca cctgcagcca ctgaatgcct gaatgacaac 108240 acttggaaaa agactttcct agatggccgt tttccaataa ggcaccccaa tcacagttcc 108300 ttttcacgta ggtcttataa agttttacat cttgcccatt tagaggccag ctcttgctac 108360 ttcctgaagt actcacacaa taccctttct gtggtcccat ggcagggatc ctggcttcgt 108420

atgtggtgct aatctgttta gtaattgcag atgcttgccc atacctcctt tgtcagaaat 108480 tttaaatgtg ctcacattct tttcctggcc atttgtatat ctatcacatc tttatgttct 108540 tttttccttt ctgttctgac tgtaaaccta agtgcagcca acgataacca taccagaccc 108600 agaatcctat gtattctttg aaatttcctc ccaagattaa tctattcctt tggaattagg 108660 ctgcacaagt tttcaggata cgggcagaac agggacagag ctccccctac ccaccccacc 108720 cccccaatcg tgaagtgagt agcctgctgt ttaatgtctc atcaacgatc ctaagatcac 108780 agcttgtgta ggcatcctgg tcctctgaat tcctagtgat cacccatcaa actctaccct 108840 ctgcatgcta tagttttcta gcctctacct ccagagcaca gcaaatcctt cttacaaatg 108900 tgctctcaaa gccttgtcag gcttaactgt agcagccacc tagctcctgg taccaacttt 108960 ctgtattagc cttcgcatga gtcaaacaag acagctcaag agagagaaag ttgtttgggc 109020 tcacagtttg aaagttttat gttcatttct ggtgggaaag aaagatatgg cagaggtcac 109080 agtgaaagaa atatggggtg aagagccttc acatcaagcc tgaccaggaa gcaaacaggg 109140 ctaggttcca gctttcagag gtttaaccct ctgagcaatt catccctgct aggctttacc 109200 ctctcaaggt tccgaacccc ttagaatgga ctagcacagc cagttgggaa gaggcactga 109260 acatgggaac ctgggagaga atgtttcaca ttcaagctga gacatctgct aagctctgct 109320 cacgaggagc ttaagatcat taacaggtat ttgcttagac agtgttttgg ctttagttta 109380 tattttattg tttgtctcaa ttttaggagg gtttcactta caaacaaaag caaagtgtga 109440 gttaataaaa attaacagaa attaaacaga aaactacatg tagtagatat aggtgatact 109500 tctgagttta aagaagttat ttttgtagta tatattgtgt gtgtgatgta tatgtggacg 109560 ggttgggcat gccaagtatg agtgtgcttg tcagaggaca gtttggtgaa gacatttata 109620 aacaccaggt gggacgtctc acttgcctga cctctgcttt attagagttc aagaggtact 109680 caatgcctag tgagtgcctg tatttaaatg tggaagacac aggtctttgt cccattggga 109740 ctttgtgtcc taaactttga gtttgctgtt ctttagtctg atcctccgta tcccagccag 109800 tccctcatct caaagcctgg acgacgtatc tgagtttcct ttcctgtctt tttaattgca 109860 gtgctgttat gggtcctgcc ctaattccta atttaggaat ttcctaattc ctcccttcgt 109920 attcatttaa tgtaggcata cccctttcac tgcagcagaa gacgcaggta ctcaatgtga 109980 aattcttcat caaagtaact gtgtctctga caattagaca attcttctca gtcaacattt 110040 tgccctatat tttacattga tggttcacaa agttatatgg gttttttgga cagactattt 110100 cagcagtatc agtagccata caacctttaa ttttcaaaag ttttgctgct taaacacaca 110160 aatcatggtt atctacaatc tggggttttc attgtagaat atgtacactg cagttagcat 110220 ggccccatgg tgtgatccag ttcagctctg tgttggagtt ctatttaatc aggaagggaa 110280 aattttctgt aagtctaaga aaacccttgc taatttagaa acaccttttc aaatgttctt 110340 ttctttcctc tgctgacctg gtcttgggct agcctgctgt tttccttcac cgtcatggct 110400 cctgagtagg cgctgaccat ttgtattact cagggacatg cagctatcaa aaggactgtg 110460 cgtggttctc ttacataatt aaggttctct tgtacagtta tctgtagcct gtgtttaggg 110520 gaaattttgg taaatacagc tctgactggt cttagtcctg tgtaagaact atttctcccc 110580 taatgtagtc ccattaggcc actgaattta tggtggcaat ttcgttttac tggttatttc 110640 ttctgaataa ttgtttgaca actgcaaatg aaagaagtga aatagaataa gagggttttt 110700 ttaattgtca tggttacgct taggcagtct gggtgaaaag gcccttcctg gccagtggcc 110760 ctctatgtaa tagtgaagag cctgggactc tgtgtagacc aggctgacct caagctcact 110820 taaatcttct agcctgttcc ccatgagtgc ttacactaag gcttgccctg ccttatccta 110880 gcttctaaat tttatttaat ttttgttaga gacagggttt ctctgtatag ccctggctgt 110940 cctggaccat agaccagact ggtatttaac tcagagattt acccaattct gccttttaag 111000 tgccaggatt aaaggggcat accaccatgc ctagaatctc agacattata atagacagaa 111060 gttctttttt tttggtaaga tttatttatt tattatatgt aagtacacta tagctgtctt 111120 cagacacacc agaagagggc atcagatccc attacagatg gttgtgagcc accatgtggt 111180 tgctgggaat tgaactcagg acttttctct taaccgctga gccatctctc ctgcccctag 111240 acggaagttc ttattataac tgattccatc tgaggatctc agacccactc tgcagcccag 111300 atctgagtca gggcccctgg agccacagga ggaaagccca ggcagaacca ggctggaccc 111360 agagatcaca cactttcaac ctcatatagt ggattgctgg gttattaagc aaatcttaga 111420 acaattacta tattaaaata gccagtgtgg gagtgagaat tatttcgagg aatttctcaa 111480 acctttttgc taacagaaga aaaggtgtgt acacacacac acacacacac acacacacac 111540 acacacacac acacaccctg agcttctcag tgatgatgat cttacactct gcctactgga 111600 agctgttaca ctcttacact ctgcctactg gaagctctta cactctgcct actggaagct 111660 cttacactct tacactctgc ctactggaag ctgttacact cttacactct gcctactgga 111720 agctcttaca ctcttacact ctgcctactg gaagctctta cactcttaca ctctgcctac 111780 tggaagctct tacactctta cactctgcct actggaagct cttacactct tacactctgc 111840 ctactggaag ctcttacact cttacactct gcctgctgga agctcttaca ctcttacact 111900 ctgcctactg gaagctggtc tttcagtgag ggaaagttgg acctggattc ttttctaggt 111960 gatttaaaga aaagaaaaga aaagaaagaa attgttttgc aagattttat tgttgtgttt 112020 caaatgcttc ccctacatgt tgcttttggc acaaaattac aagttgcaac tcagacttct 112080 gaggtgtgtg ccaaccagtc ctcagccact cctaccttca tttaaaagct agaagtgcct 112140 ttttgtgtgt gtgtgtctat tgaaagagtc tctgatttat aaacagttta ggcaggtcac 112200 agattgactt taaaaattta agtcaccaag ataaagatgt tttaataaaa agcagaggta 112260 gtgatataca atgtggaatt tgctttgtaa tgatcagatt ttactgtttt cttaaagacg 112320 gggaagtcgt gacatttgtt tttttcagtg caattagtaa attagtaagt tattaattca 112380 tctctgaggc tttgaaaata aatagataga taaaaataaa cagctccaaa gaagatgtat 112440 ttgggaatta ctattctttt tgtaaacatt accatttatc ttcatgttct aacttagcac 112500 ccacctgtca ttttctggga ctttgatttg gacggttgta atataaccct tgtggcagat 112560 gtcaggaggt gggggaaagg gaagacctgc ctgaaggtcg gtcccagagg agactgctgt 112620 taaatctgtg gtcagggaaa aaaaatgctt tacgccttat aaaatttgcc ttatcaaagg 112680 ggggaagtga tgatgtaaac aggaaactga cagtgaagag cgaaggcacc agcagcagcg 112740 ttggcggcgg cggcagcggc agtagacttg aagatgaacc agacactgct ggggataggg 112800 tccagaggaa gggtagggtt atgtgttcaa agcatgtgct ttgctttgac agactctggc 112860 tgaattttat cctcctttca ggataaagtt tagccatgtc tgtgcctgta gaaaaatgct 112920 agctagtgtt gaaggtttag gacaatttaa agatgggagg gcagtttgag agcacaggct 112980 gcacagggaa tcacacttca aacccaggaa agtagtggct aggaagaggc ccacacggtg 113040 cagtcatgtg accacaaata ctgatttcct ggtgtctatg tgtttgtgta gtctctacaa 113100 cctcctttct tcttcagcct actaaactca tctttctctc atctccccct cccccctccc 113160 ctctccccac ccccccaccc ccttnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113220 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 113280 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnaag ccttgctgct ttgtgaaggc 113340 gtatctgttt gcagaggtag cagtaaggac ctggccaccc cactgtggct gggtgtccct 113400 gaagctggag cagaggagca ttgccgtgcc tctcttcctg cactgctata gaaagctcta 113460 acttacaggt tctgagaagc agttactcac agtagttctg gaacacacgg ccaagtcctc 113520 cagcagcacc atttaataac ttaccgttct gaaaagtatt tgttccctca aactctttat 113580 tcaggtttta ctttccttat ttttgctgtg ctgcagctta tacctaggcc ttcagacatg 113640 ctatgtaaat acccttctct actcagtcct agtccttacg tataacttga ttttaaatga 113700 ggaaagaacc gctccttctt ccagtatcag gaaggaaagc aaacataatg gcagcttact 113760 tactgcccag ccctcacata agccgcaccc ataggtgcag ggtacccttt ggggattctc 113820 agctgaacca gtgccctctg ccatgcttca tgctgggctt ttcttgctcc catttctttg 113880 attttattct tttctcttag gcagaacaca tggcagatct gcagtcaggt gagaagctgt 113940 gtgtatttgg aagagctcct ccatgctttc aaagttttaa aagtattttc atgtcttgtt 114000 ttttttaatt agacaaaata tattccaaca tatatttttc ttttattgaa gatgacaagc 114060 ataaatttac agaattaggc tcttagagta cattcattag agtttcagtt gataatttaa 114120 tgtgctttga aatctcacag caattctcta ttttcaataa atatgaggta ggtaattcag 114180 cattaagtaa ttgctcacag gtatatgttc aagataaacg agtgcaagca taatttcatg 114240 ggctttttta ttaactctgg gagcatgttt gtcagagcag ataccattag tgtttgttga 114300 ttgggcagat agtaaaatag gcttgaatat gtatcataaa atcagtatag gtctcctcac 114360 aagttttgat tttgttgctt taaaaaagat tcagagaatt aggttggcca aagaaggaag 114420 actttcttag ttttagtgtt gttttgtttt agaatattgt ccatttgttt agcacagaca 114480 gggacattct gaacataatc tcgagtcagt taggatatga catccaccaa ggggtcctgt 114540 gtcccacggc taccagtgaa gggagcgaca ggcctgtagt cctgttgtgt gcagtgcttc 114600 actcatcttt gttttagagc ggggaagcac taggcatttc tgtaccaaca ctgagcgccc 114660 gggcctggga gatgactctg ctgtcgggtg atcatggaca ctgctgggac cctagtctag 114720 gttctgactt tctgcagctc cttaaacaaa tctgctgttt ccctaattgc ttttctaaat 114780 aaaatgtttt tatgcattgc tgttcataaa aatgataggt attgaatctg tcagtcagtg 114840 attgagtttc agtgaatatc tgagcatttt tttatctgag aaactataat atccataagc 114900 tattacatgc caaattacag tttttatata gacacatgat ggaacctagc ttaatttgcc 114960 attaaattgg aatgtaagtg cattatttta tatatttgtt aatattaatt attttaattt 115020 taagatagag tcttgataaa tagtacagac cggccactcc cttcctcctt ctcccaactg 115080 ttaggttaat actgtgttct cccaagcctg gggtgtggtt acaagtgttt gctgccgtgc 115140 ctgatgggaa tctttgaata ttaacattta agctgacacc ataactttat tcaatatttt 115200 atcatgtttc tattttggtt tttcaagaca gggtttctct gtatagcccg ggctgcccta 115260 gaactcattc tgtagaccat gctggactcg aactcagaaa tccgcctgcc tctgcctccc 115320 aagtgctggg attaaaggcg tgcgccaccc ggcttttttt ggtcgtgttt cttagtgcag 115380 tgctccagca ttgttttggt gattgacatg gctgtgtgat tgctgtcgac catctatctg 115440 cattccatga ttgcagatct atcatttaaa ccaagcatgt gcacaccgtg aacaaaatgg 115500 caatggcgag gttgaagtta tgagaaagtt ctgccaggtt tactttaaac tataactgcc 115560 acttagaata ttatggcagt gttaaaagtt attttgccca gcagtcatga ggcagcggca 115620 ataatatgag ttctagtctt gattgggcca catagcagta cttcactact gtcagtttgt 115680 ctgcctgtcc tagctgcttt cctgtcagtc tgcctgactg tcttctgtct atctacttct 115740 ctccttcctc tgctcacacc tttgtctttc tctttgtttc tctctctcac acacacacat 115800 ttagacaaaa ggtcaaacac tgaaataagg aaatattttt attatagtgt tacagggaaa 115860 tggtaggagt caattttata aattgatttt aaaattacct ttttgcctta aaattttcag 115920 aagtgaatat atcaacttaa atactatgtt cctacagtaa aaatatgcaa gctcggggct 115980

ggagagatgg ctcagcactt aagagcatta attgctcttc cgaaggtcct cagttcaaat 116040 tctattaacc acatagtggc tcacaaccat ccacaatgag atatgacgcc ctcttctggt 116100 gtgtctgaag acagctacag tgtacttgca tataataaat aaatcttttt taaaaatatg 116160 caagctcggg gcagtgggtg ggtaggggag tgggggggtg ggtatggggg acttttggga 116220 tagcattgga aatgtaaatg aggaaaatac ctaataaaaa attattaaaa aaatatgcaa 116280 gctctttttc tttcttttct gtattttcct tgtacatttt tatatggaaa tgataaagct 116340 acccgggcgt ggtggccgtt cactgtggag gctgaggtag gaggatcata agtttcagac 116400 cagctcagac tcccaagtga gactctgtct cacatttaca aagaagacat tggacctgag 116460 gactgctgag gtggttcaac ccactaacat tcttgccatg caagcatact gtgtcacaga 116520 gaactatagt gagaggaagg acagatagtc ggtcatagtg tacctagtag aagctcttgt 116580 atctaactga acccacagat acacagtgca caaatctgtg ctgccagtga ccagattgga 116640 ggtcattaaa tgggtgtaaa aggccaaaga atagcaagaa aaatagagtg tgtacggcct 116700 gtgtggtagt tcagcaggta gtgctgcttg ctgatgtgtg cctatctgag gtccacatca 116760 gggcccacat agtgggagca gagaactata agttgtccct gacacatgta cacacacgca 116820 tgcacacaca ttatttaagt gtaaaagaga gtgtaaggca tattgggagg tcttaaacag 116880 acttacatgg tctattttat gttagctttt gtggggtaaa actcaaggag acaattgtgg 116940 gatccccagg tcattgcagt gcgtcaggga tgaggtgaag atctgtggcc ctggaggtcc 117000 actgcactgc tgttgttttt aaaagatttg tttattgtat ataagtacac tgtagctgtc 117060 ttcggacact ccagaagagg gcgtcagatc tcattgtgga tggttgtgag ccaccatgtg 117120 gttgctcagc tccggacctt cggaagagca gtcagtgctc ttacccactg agccatctct 117180 ccagtcctct gcactagttt tgttttgttt taaatactta ctctaattag caattttatt 117240 aacttttcaa atttttcctt taaaatttta aaacattgtg tatttatata tcagatatat 117300 ttgtatgtgt ttgctggtgg tgtgtgtacg tgtctgtctg tctgtcttac tgtctcagag 117360 gggatggctg actctaccac atgggtcctt cagatagtct ggcctgggaa caagtacatt 117420 tacctgctga gccaccccac cagcctctac tctgtgtgtt actcatagaa tagagacatt 117480 ttagaagtag gattattgaa tgacattcag agaagaggcg gcccaacagt taaatgcact 117540 tgctgtcttg cagaggacct actgttcaca atcatttgtg attccagttt tagtggcctc 117600 tgtgggtgtt gtggtcaaca tggtgcttat atatacttac atgtaggtag ataaaatact 117660 caaacacgga aaataaacag tctatttttt aaataaacag tcattttttt atttctgtag 117720 tcactctgtt ttcattaggc aaaagcagcg tccctgctgg ttgccaagga ggaaatgagt 117780 cttcgtaagc aggccttgta gtaaatgagg gtcttggcat cttttgagaa cagccttgta 117840 aatgtctgtt gggtaataaa caagttctac gcagtcttct tgtatagcaa caaacatctc 117900 ttcactcatt ccacataaca gccacaaaga tcctgtcaga agatggagtg tttttcatcc 117960 tattggaatg gatcatggtc agtgatggcc catgttggag ccccagctcc acacagacct 118020 tctgactcca agttcactgt tcttctgttc agttatatat aacacaagaa aatgtgttta 118080 ttcaaaaacg ccaaggataa actttaaact gtctattacc atatgcattt attatacatt 118140 taagcagagg acatttattg aaccccaacg acttgtaaaa tagtgttgaa gaaatttatg 118200 atatgcattt aaaatcaaca tacacagcaa ggagaaaaga aaaggagccc ttagcttcat 118260 ttgtgcacct gtgagttatg tcttgtgctg gcatccagca aatgctcaga gagagaatga 118320 gtaagctgga gtttgggtga ggtggttaag ggggccttta cataaaaaga aggagacccg 118380 gatttagcaa gacagtgaaa ctgcaatctc agaggaaggc actacgagag agagacgtaa 118440 catctgaagc aagaaagagt gtgaccaaag gagggggagc gagcagagcc tacacaggac 118500 tttgagtaaa gcagcaagac tagaaggagc cattttttac agagttgaca agctgtggct 118560 ttgagctaag ctttggggcc ttttaatttg ggataaagga gttttctaca gcttgtaaat 118620 accatcaaat atttaaatcc caagagttga caagtgtcat tacccaagtg gtattttatg 118680 aagattactt tgctcctggt ttattcagga tgcagttgag aaatggaaag ggaacaagca 118740 gagaaaggga gactggcgaa aggcaatgtg tgggcttaga gcagtagagg tggccttcta 118800 aaaggaccgc gtctctggca acagggagaa ggcttgctgg agcctctcac tgattagttt 118860 ggagaatgga aatttaatgt attgtattgt ataactatgt aagtataaaa acagtaggag 118920 tcatagtgta ttaatatata cttgcttata tgtacacatc tataaagaaa acacagacag 118980 gagccaccgt cgtccgttgt ttggatcatg tagtgctgag gtggataact ctccctgcct 119040 gcatttggtg gataactctc cctgcctgca tttggtggtt ccttttttca cctcctttga 119100 catcacctct ccaaatctgc cttcaaacac catcactgag tgtcaggact ttaacttgtg 119160 caggcaggtt ggtggtcctg aaacttacag taatgttttt cactctcccg ttcggtggat 119220 tactcgtaca attctctttt ctttttatca gagacaattg ccatagtgaa ttcattgttc 119280 agtgtaccaa gatcttaaag tgttccaccc actgtgtgcc cagttattga caccatttga 119340 tttactttaa ggtgtcactt gctgggctgt tttgtaactt gctttccccc taatacttct 119400 caaggtaatg gccacgtacg tgtagaggta ggctggtgct ctgcggcctc cattgtgtga 119460 atgcattctt catttggctt tgctccttgt cagggttggt cctctgcatc ttgacaaagg 119520 gcctcattct gcctgctcct tgaacaccta tgaggatttc cttggccatc acctagagaa 119580 gaacactccg gggataggct acagaaattt tccactgtaa ccggaagtgc aggtttgcat 119640 ttggtattta agacattttt atagggactt ggcatgggaa gaatgggaaa caatatcccc 119700 ttgatgcttt acagtggatt ttggatgctg ctgagactgt ataggggcta tttttatttc 119760 ttttttggaa ctgttaacac aatttgcgta ctttttagtg tgttggcttt tctggatgtt 119820 gatacatttt agatgtgtca ggttggagtt tttaagcttt ggttaaactc tgtacctatt 119880 cttctgattt ttctaactat tccaacatga atctatggag ctgcaggaaa aatgacccta 119940 atcaactgta tctttttttt tttttttttt ttttttggtt ttttcgcaga cagggtttcc 120000 ctatagccct ggctgtcctg gaactcactt tgtagaccag gctggccttg aactcagaaa 120060 tccgcctgcc tctgcctccc gaatgctggg attaaaggta tgcgccacca cgcccggcta 120120 tcaactgtat cttgatagaa agttgaatgg aatgtaaata tctgagggga atcccagatt 120180 cagtctcctc aaaggaaata agggttttcc tcaccaggac cttgacgtgc tgccattact 120240 aaaaacttct tggaggccat agacaatcgt ggattagaag attctaactg ggcacttcct 120300 gctcctaccc acctagactt gcctgcctct gttgacatgg ctgcttgaat aggcatgagg 120360 tttagcaaaa tgcctgtctg gagtctgcca atgcatgtgt gatagctgtg agtctggttg 120420 tttagttata actaagagga taccttgcag ccatgttgcc agttaagatt gtcttagaaa 120480 tggctgtgag attgcttcga aggcctggga gatatatgag tcaccatagg cctgggagat 120540 acatgagtca ccaaaggcct ggggggatag gcaggttctt tgctatggtt tttctcgtcn 120600 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 120660 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnng agccgggcgc ggggcgcagc 120720 ctttagtccc agcactcggg cactcgggac gcagaggcag gcgggtttct gagttccagg 120780 acagccaagg ctacacagag aaaccctgtc tcaaaacaaa aacaaaaaga gttagcttct 120840 gggctggagg tgtcaccaga gacagagccc ttcctcatga gtaaggccca agcttctgtc 120900 accagcaggg caaacatgta aacacacacc tacctcccag tatgttggat agttcaacaa 120960 aatgttcata actttcttag agtaaattta taatacagtt tctatatcct gataaacaat 121020 cgcagtcctc agttgaggag gaggaaagtc tcctggtttg taatgtatgc ctctggcatt 121080 ccccggccat cctatgagta ttttgcttgc ttttgatctc agaggttgag gacttgggcc 121140 agtgccgctt gtttgattgc tgttggaatc tatagttctc tctcacttgg atttccagcc 121200 cagctcatca ctggctttct cctttttcat gggatcatac ttttctctga tttgacatga 121260 atatggtatt tttatatgtg gatcaattta ggagcatata cttatttggt gatatataag 121320 ggtatactat ttactatatc atatactaac gtaaatataa gtatattttt tatcttgttg 121380 taaagttaac ccctccccat ttaaaatcca ttgtgacata cattcagtgt cattaaatat 121440 attaatgttg ctgtatagct tctatctccg gccatctcta gagtttatct ctcagagctc 121500 caactttcaa gtaggtaagg tctcttccct tttctggcca ctgtttgctc gtgcctaggt 121560 acttatcttt cacccctcct agaccagtgc aaagcatgtc cccatgtggc aggaactcaa 121620 gggctcattg aggctgtccc tgctgccctg tgtctgaagc tgtcaccacc cttgacgggt 121680 tctctctcca tatgacagtg ctgttcgttc tgtatgggat gtgcttgatg atgaaggaat 121740 agtccctttc tctcctgcca tgctcctccc ttgatgataa tggactggac ctctgaacct 121800 gtaagccagt cccaattaaa tactgtcttt tgtaagagtt gccttggcca tggtgtctgt 121860 tcaaaaacta agatgccatt tttagataga aatctcattt atacccgtcc ccctcccccc 121920 ctccccctcc cttcccttcc tctctcctgt gtgtagatgt gagtgtgggt atgcctgtgt 121980 gtcatcctgt gtgtagatgt gagtgtgggt atgcctgtgt gtcatcctgt gtgtagatgt 122040 gagtgtgggt atgcctgtgt gtcatcctgg gtgtagatgt gagtgtgggt atgcctgtgt 122100 atcatcctgg gtgtagatgt gagtgtgggt atgcctgtgt gtcagttctg ggactacaca 122160 cccagggctt tatggctgat aaaccagtgc catactgaat atcatcctct ggctgcagat 122220 ctgcttctta aagaatggat tctgtctcaa aagaaacgga agtattggtt atattcttaa 122280 acaaatagac aacctttagt atctacaaaa aggatataga ttctatcgtg ctgatttgca 122340 gattcttagt taactgtgtg attgtgcttg tcagatttat ttaacactgg cagttatgct 122400 attgatgtat ttactacaat gttgactgta tgggaagaga tggccctggg ttttcattca 122460 actctgccct gccgagtcgc agtcaccact gacttgagaa tcccacttgc agtgagagca 122520 gctatacgga gagcagacat actcagcccc agcactggtg agagctgggg gagggctgag 122580 gcagagggtt atgagattcc aacagtagct gcatagctgc acagtaaaat gtctcaaaga 122640 acccaaatca ccttgcctgt tgtggccttc tgagcagttt ccatgtctct gcggtttcta 122700 agctactgca tactggccgg catttggttt tcttatagat tgctttggtg agtgaggttc 122760 tagcccctca tggtaactga gacattgggt ttaaggggag gcgtccgagg aggagttttc 122820 tgtctacttg tcatccccct gtctttgact cgtgtgtaac agcaggtcag gctcctctct 122880 tctcgttggt gtgtttttct gtgtgtgggg cctctcagct gtgaggcttt gaagcacgtt 122940 tgtactgcag tgagcagggc aagggcccag ctctgtaatg gcctcttact cagtcattgc 123000 ttcactgtgt ttctcataat ctgaagtttg ttgtcagtag ctaagactaa attctattcc 123060 tagttttgta tatttaaact atagcagaat ttatgtacaa aatctctata taattatttt 123120 tttcatttaa gaggttacag atagcccctt tctctcattt cttttacaat aggtaatcat 123180 tccttaagaa aacttgaaga ctctgtaata aaatgctgtg actgctgtca ggtttgagtc 123240 atatctcttg tgttgctgtc agaatacaaa gacgaataaa aacaagagac tctgacatca 123300 gactcaccct cactgtgctg gtcacggcca tgtctgcagt ctaccgaggg taagatacat 123360 ccgtagataa tagcaggctg atacagagaa agccacagtt tttctccttg gctgctgagg 123420 cctgaggaaa gggctgtgat ttagagagaa ctcctcagat ggtgggcatg gagatgataa 123480

gccttagaaa gactgcgggg taagctctta atcccaccag gcgagagtag gagtactacc 123540 acaatgtcga accaaatttg aagcaagctt taaacaaata ctgaccagga tgatggcccc 123600 tggcaaggtc tactcctggg ttcctagaaa atgttgatga gtcacatttt gcagaggctt 123660 aaaaacccat aaggccgtgt tttcccacca ggtccaactg ggggcaagca tgtatcctga 123720 catacttcct gcttgtgtat ctcctgcgtc catccaatca ggggcaagca tacatcttac 123780 gtacatgtga tcaagcacat tgacttcaat tggctcaaac agacttgttt agggaagtca 123840 aaacatgggg cttgttatcc tccctaaaca atagcctcta gcatttgagg aagtatctgc 123900 ccttgagcaa ggggcttaca agttagagaa atgttatttt atggaactct taggcacagt 123960 aattaagact ttggctctca cagaggtcat tatagtggaa gcagatagaa agcatgaaca 124020 gttagtgggc cagaccaggc tgatctcaga caacacagca cagggactgt ttgatggatc 124080 tggctggaaa acgaagagtg cacagcttcc tcagtgcagc ccctgtttgc tttgacagtg 124140 agaaaaagca cttgcgctcc tgcagtgtgt ggtgaactgc agggaaatta gcactgtatc 124200 ctctggccat ttctgtcctc ggttacactt gaaggatatg agacaactac aagttaaacc 124260 aaagtaacag cactggacgt gctggtccac acagaggccc aggaggggga agactgaaga 124320 tagcactgcg ttcagcgaga agaccctgct gctgtgggag gtggctttgt gagaagcatt 124380 gaagagaagg aaatctggga catccgagga gcaacagtct taaacagatc caaagttctg 124440 gaagtgggta ggcttcacag ttgaaggagg aaagggtttg taagaaattg tcagttgata 124500 gagtggggag cagcaggcac cagaaggttc catagacatg taaggagatc tattttggac 124560 acttccagtg agggagagaa atgtgggtga gaggctggaa gtgggcactg gaacttacgg 124620 tgatacccga agctacaaat gtaggggcct catttgccta gacactatca ctgaaacgtc 124680 agccatctgc gtgctgattt caaggagtgg ctttagagca ggaagaattg tgaggctcag 124740 ggtcacagag gcaaaggtga gggaggagag agcctgaaga caggctacag ttctgaccga 124800 gctggcttgg cgtgacttgg agccctgctc actctgtggt tctccaggag ccagtagaat 124860 aaattggctg ggtgagatgg gtgtgctgtg gctagaacca tgctgctggt ctggacggga 124920 gaaggcgtgc atgcacacac acacacacac acacattctc tctctctctc tctctcacac 124980 acacacacac acacacacac actctctctc acacacacac atactctctc tctcacacac 125040 acacacacac tctctctctc acacacacac actctctcac acacacacac actctcagac 125100 acacacacac actctcacac acacacactc tctctctcac acacagacac acacacacac 125160 tctctctcac acacacactc tctcacacac agacacacac acacactctc tctcacacac 125220 acacacactc agctgccttt tctgctggtg ttgaagcttg tgttcaagca tcttactatc 125280 tctagatggt catgtcagag ggccaagact tcactgtgtg caaatcctct gcagtgcaca 125340 catgcagcaa gtcttgattg atcaatacat ggaaatgatg gtatctgcac atctgtcctt 125400 tgtcactcag tgccctccaa acataatctg tagagtccag tcaaccttta taaggaagac 125460 ccgagtttgg ggttcgcttg gtgtgtgttt aacttctgtt cttgctagcc tgatcctaac 125520 tgaacttcca acatcttcaa agccccgttt tcccccgctg cagcatagaa gagagcagtc 125580 atgttgtctt ggctgttgag aggattgaag aaggacagtg gcagagcctg tgctcactcc 125640 agtctcactg gctgtgaagt gttgaatagg cctcactcac tgaggtttag ttttgtcatc 125700 tctagaattc taggggatgc ctgagctcac tttggtttca gaggaagtac cagccaccat 125760 atgcacaggg cctggctgct ttcctcttcc atgccaggca ggagtgcaag ccaccgagat 125820 ctctgtgcag cgtataagag cagttctgga tttgaaccta cgcagtgagg cttggtaatg 125880 acttcacttc tctgtaaact gggaggagtg ttgctatcca cttcacgtgg tcctatgaga 125940 acaatagagc aacacattgt gcactgttag caccctgtgt gccccactcc cacccctcac 126000 tcccgctagt tgtaacctaa tgtaaccatt atgagggaca agttaatctg taaagaagga 126060 ggcgcttttc taatgagatt ggccatgtcc aaagggggaa atgtaattca accacaataa 126120 tgctctttgg tggttcagca tgatgggtgt tgctgtggcc gggtcttcca ggtacaacag 126180 aggaaagact ccatctggcc tctgggctgg ccagtgtcct cctcagcaat ggcagtctgc 126240 agtctgactc cacacccagt ctccttgtcc tgccagctgc tctctaggaa gtgttgggaa 126300 tgtggagcat aaagattcca gagaggaata atgctgagtg gacaggtagc ctggaacagt 126360 ccaatctggt accttccctg actgggaaag gctggcttta ctagcaaacc acttttcaaa 126420 cagaactcat gccttaatcc taccaaggac aaggagcgct ggtggcttat gggaggagtg 126480 gctaaagcag taagaaaagg cagctactgc tgtctgcacg ttcaccctgc atccctgtgg 126540 caacctgcat ccctgcagca agctacccag actgtagtat cctggaggac cccccccccc 126600 actccagctc catttgatca cagagaccac ctggaatgct agcaacctag agggaagtga 126660 gaaaccacag acaggttctg ggaatgacct agcagctgag tcctctgtgg aagggagtgg 126720 tgagacttaa gcgtacagca gaaggattcc ctggggcagc acagccctga catgcaaagt 126780 cttgttttgt gtctttgaat gaatctattt tcccatgtta atctattcag ctggcttgta 126840 gaaaacctac atgcatttgt ttatttgtgg ctcacttaag aaaactctga cttttgagat 126900 aaatttgttc tctgggcttt tcatgatttt ctgttgctta gttggcatag tgttttgatc 126960 tctttctaga aagttcagca gaaaatacaa attttgagca atttcactta tgttttattt 127020 cttggggtgg gtgtatgtgt ggccttcaag tatgtgtatg tatgcatcat gtgtgtgctt 127080 gtgcccttga aggtcaccag agggcatcat gtatcctgag ttggagtact aatacctgct 127140 gctgagccgc tctggatgct ggggacctag gccctctgga agagcatcac cacctcttac 127200 ctcctcagcc atctctcctg cccattattt cagtagtgac cagtaggtta gcatcaatca 127260 ctagaaactt gggtgccggc tgtcatcgac ttttgtacag tgtgttgcct tttggcctct 127320 cagatagaac attgggggtt tctaatcact ctgaccacta agtcccaggg gatttcttct 127380 gttttgtttt ggtttggttt taggactccc tgtttttgta gctggagaga aacatttcta 127440 ctgaggcagt agtgttgaaa actaatgaag ctttaagaga acattgaaga gattattaaa 127500 tataaggccc ctgagcttca ggttctcacc atttttgagg tacagctttg aggcattctg 127560 tacacgtccc ctgccatgca gccgtgtcag gtgtctgggg tctgtgtcct ccccagctgt 127620 gagtgcatcg tgacatcccc agtcttctct ccttcgctgt gccagccagt gctctagttt 127680 ctgccattcc aggcccctca tgcccaagga atgacacggg tcttggggat tttccccatt 127740 ggcttatttc acttagcgca gtgtctttaa aggtaagtct ccattctgta ggtgactctt 127800 acatctgctc gcactctgcc ctactctctg ctgtgtttaa cctcccatcc cactcagtgc 127860 tggcctagtg tcatttgaca tagcagcagt gcagaaggga gccagcttct agatcctcat 127920 ggtcacattt tggcctctgg tcttttgata gtcattctca ggggcatgcg ctggtgtctc 127980 actttgcttc tggcttgcat ttctgtggtg attagtgatg gccaaggaga aatgtttgat 128040 caggaccctt tctcatcaat cactatagca gcacctttgt cctaatcatt tgatagatag 128100 cgtatgtgta taaacatgat tctgtgcccg attctcccct gcattactgc tgaggcctcc 128160 tgactcgcca taaccgaatt tcattttgca gataatctct ctgctatggc ctttgtggag 128220 ttttgtgggt cttgttttct gtttgtcctg gagaattggc tcttgcactg tgtgctgggc 128280 tccctgagct gggaggaagg gtttctctgc tccacagatg gcatttttct gctttgttgt 128340 gggtgttgct gggattgcag ctattcccac cttctgccta acaaagataa atagtaaata 128400 ttctagagct atttctagac aaaggagaaa gtgaggagtg tgaagggaag aagcccacgt 128460 tctcaaaaag tattatcaaa tggtgcttga agcagtcgga atcagctcag ctaataaacc 128520 acgctctgtc cactgagaga cttgcgggtc tagagacagc gcaaggcaca tccttcttag 128580 cacccctcgt tcggagtctt gctggttctt gcacaagtta ggaaaagatg aataattatc 128640 tgactctgaa taaatttagt tctcacataa agtaccttct ggtcttttat tctgtttgtg 128700 tggccaacta gtgaacaaag gaaaagtgat ctttgattaa acgggttgtc agtgaaagac 128760 ctaaggagga cgaggatgta tctctgtgga tgagagtgtt ggcctaacat gttcatagca 128820 tcccttttca ttggatggga agatcaagtg tcatcccagt gttttgcact ttacgttctg 128880 tgtggatgaa gttaatacac agaacccaag tgtgaagagc agatcctgag ccctgcattt 128940 gtcatgtaca catatacaca tgtatgtata tgtatacatg attaattaga atggtttaca 129000 ggctgtggtc cagctaatcc agcaatgtct gactgtgaat ggaaagtcca agaacgcagt 129060 agctgctcag tccacaaggc tggatagctc agctgatctt cagtgtacac tggaatccca 129120 aagtagtcaa ctccagtgcc agagaaggaa tggacgtgct agcaaggtga gagcacacag 129180 gcaaagaaca aaagctcctt ccttctctcc ttagacagca gagacctcag cctcctaact 129240 aactctgtgg cccatgaata cagcagtgac ctcagccttc ctaactctgg gacccatgaa 129300 tacactcctg caggtctggg agccaaccat agaaatattt gattgctact tcatagctgt 129360 aattttgcta ttgttataaa tcattatgta aatacttgat atgcagggta tctgatacgc 129420 aaccttcgaa aggggtcaaa cccacgcgtt gagaatcacc tttgtatggg cttctagcag 129480 gtgtattcta tattagatct ggattcgtgg tatatcttcc tacctcaaac taagcagaaa 129540 tccctctcag ccatgtcctc tattttgggg ttttagttaa ttttagatat agccatgttg 129600 acaaccaaga acagccatca cattccctga atgaccaagg attcggggga acacaggtca 129660 aagggatgtg gcaaccttgt ctctaccacg tcgattcttt atagctcaaa gactaggtat 129720 agactagtct cacctttgct tactttgtga gttctaagta acatttttgg aatattggtt 129780 ttttttagtt aatatataaa tagtttaaaa agtaaatact ggaaaagtct tggctggacc 129840 tggaactctc tgggcctggg gatttgaaat gagtgatggc ggctgtggtg ctcatctcca 129900 ctttagtcag acagtttaca gttctggtca gtcagagagc ctcgcaggca tctcagaaag 129960 tgatgagcgt tccctcatca gccctcggag ggctcagcta atccgtgaag cacactcctt 130020 tgacatagga tcatttctga acctcaggca ttcttgaaag cctatggtat aggtttaata 130080 tttcctacac cactaacatt tgtattaatt ttggctacca ggtcacttaa tttcaatttt 130140 agtcctataa ttttgaagaa tagattcatc taaaaggaag tttagattgt ttgcagctgc 130200 accagtggcg agcctggggc tgtggtttga agcttctgaa atcttaggtg aggggcagaa 130260 gctggactgg aagtgcatcg tgcaccctgt gcctgacttc aaaagtggga cttggcagtg 130320 ttgtgtttag agaaagtcgc agttcgcagc ccttctcctc agtcctctcc tgcagtggga 130380 tggactgaga cattcatgca ctgctcttta taggagcgac tgctgaaaat aacccgacaa 130440 gctagcagtc tctactcaga atactgttgg gtcttctata aggctcattt tgctctggta 130500 gaaagaatgc agtccctagt gagtgttcat agggtgataa cccagcagca gaggctgtca 130560 gaggtgagcg tctcacttgc tctctgaagg aaggatgcta gaggctcaag tggctttgtg 130620 tacttccaca tctgctatgt acaggaattc aaatgacatt cttattgcat ttcttacaat 130680 tagttgtgaa actcgttatt gcattttaaa atagatttaa ccagtagtta taccatgata 130740 actactgtaa ctagtagtta taccatgatg atttaacgat aatgatggac gaatgatggt 130800 catgagatta tgagtacaca ctgtttgtcc atccacattc tacaaagtgt tgttcatgtc 130860 accttcagag cttacctcat tcctagtcac acaaacgtgt gctcacagtt gctatggagt 130920 atttctaggt tagaactttt taactttggg atagaataaa atcaggggtc tgttcttgtt 130980 ctgtgtttgt gttttgtctc tgtgacaagg tctctgttta tgttcctggg tgtcctggaa 131040

ttccctctat tccagactaa ccttgcactc acagtgccct gcctgccttg gtctctgcac 131100 tactcccggc accagggatg aaaggtgtgc acactatgcc cagtttgggt tttggggttt 131160 tttgacatat atatcacaga agtccattaa gaagtcattg actttgtttt gtgtgcatag 131220 agcttaggat ataaagacca tagattccca gctacaattg tccaattaac tttacatatg 131280 cacttttatt tttttcttat aattcttatt attttcaaat attatttctc tcttcctttt 131340 gttaaatcag aacattcctt ttgttgaatc tttttttttt aattagttag ggttctctcc 131400 tctctaatga ctgctgttta tttcaagttg acataaaacc agggagcaca cacgtcagcc 131460 taagaaacag cagtagctgc cattgaggtg tcttactaca tcaggccgga gctacacgtt 131520 gtacctgtaa cccacagatt tatagcagtc ccaattgtta ccctttcata taggacacat 131580 gagactcaga gaattgcatg ttgcttgggc atctctgtat tcagcatgtg aacgcagtgc 131640 tctttcctgc ctgtaagtgg gcttcgtcaa tggattttcc ctgtcaggcg tgatggcgca 131700 tgccttagca cctgtaaggc agaggcagga tgatctctga gttcaaagac agccgagttt 131760 agaaagggag accaagacag ccagggctac ccagagaaac cctgtcttga taaaatccaa 131820 aacaaaacaa ataaggaaac caaaaacaaa acaaaacaga aaacnnnnnn nnnnnnnnnn 131880 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 131940 nnnnnnnnnn nnnnnnnnnn nnnnatttta cagaataaat actaggtcac aaatcacttt 132000 acagaatcgg tgttattcaa aactaagtaa aaaagttaca tactttagta cagaaaatcc 132060 agaaatttga cagaaactac ttaacaaaat gcctcctatc aaacacaact cctcccaggt 132120 ggggtgcagc tcaaggacgg gtcagaggtg tgattggcgc tccttgatgc ctgtgctccc 132180 agatgctctg ctcttaggag cctgattctc agataaacta gcaaagaagc ttagacccac 132240 ctgtaacccc caccttaaag ctgtggaacc acatgacata aactgatgaa tatagtaaag 132300 tcagccctaa ggtcagtgct gaggtatata tcattcagga tatgtaccca agagggagga 132360 gcgtgtctgt gaaccttttt agagttcttt gtatgacaag cttttccttg aaaatggttt 132420 gagtgcccct ctataggagt ttgggcaaac aggctgtaat atactcacat ttataggata 132480 ctcgccaatg aacaggagca caatatatgc aggaccttga atgagttgta gaaactcaag 132540 agtaattacc atgcatttgt gtttgaagtt ccacaaaaag cacaactggt ctgtagtaaa 132600 agaacatcag atgttagaac tgtctgcaga tgaggtaagg agccccttgc agcatgcgcc 132660 tgagacctgt acagggagaa agatttctag cttcatagag cctgagtcag ccacaccttt 132720 gttggtctcc actcctgatc tccgtgtaat gagctctgaa tcctatatat tgcaccgaat 132780 agaaattata tctcggttta caaactacag cagcattttg ctgagttgtt gttttattcc 132840 ttcctcatca agctcttgag ttaggacctg aacctaagct ctgtattgcc accagttata 132900 cattaccacc attatagatg ttgacaccag aaacaacttc acagattttc tcatttgatt 132960 cttttataaa cactgctgcc ttgatgaaga aaaaaagttt aaaattgcta atgataaaat 133020 ctgttgtagc cactgtctgc atccaagagt gaactcagat gattttaccg gtgtgtgcat 133080 gccagcagaa accatggcag agggatagac ttgctgacag cgatccatct tgcagtgtaa 133140 gcacagagtc tggtgaagac attctactga gatgtgtttg ataggaggca ttttgttaag 133200 tagtttctgt caaatctcag gattttctgt actaaagtat gtaacttttt tacttagttt 133260 tgaataacac cgattctgta aagtgatttg cgacctagta tttattctgt aaaatgtccg 133320 tacatgaagg gacagatatc gcacgggttc acttaccaga ggtgtctgag caagctggac 133380 tgctgggtgc tagggctggg aaacggggaa gcagggagct ttgggggacc tgaagtgtta 133440 gttttgtaaa atgcagtgtt ctacacatca gttgtgcaac agtctgaaaa cactgggcag 133500 cactgaactt aagatagtta acacactgag tctgatggca catggcttta atccatacta 133560 agtgctcaac aaactaaacc attattatac cccataaata catacaaatg tatgtcaaat 133620 aaataagagg cagagaaatg gctcagcaat taagaactgc atagtctttc tgaagacctg 133680 agttcagttc ctagagccct tgtgaaatca ctcacaacta cctactttag caccaagaga 133740 tctgatacat acacatggtc actctcatga acacacacac acttaaaaat acatttaaaa 133800 ctttttaaag agataaaagt gtaaaaacaa caacaacaaa aagaccttct ctgcagacct 133860 tgtagccaat tcctgtcacc caggtcagcc acttgtgctc attggcattg gcaagtctct 133920 ttgaagccat ttgcagacaa cgctttaaag ataacagacc gacctgctct gagcagcaga 133980 gagaaaggat tcttgttgcc cagactcatc ctaggagtca gtgctaggtg atgatgtcag 134040 gctctgtgat gaccctggca gcagctcctt ctcagagaaa atgaggatga agacttcatc 134100 ctgaagcaga tcctggtatc ttatccttgg caaatgctga actcaacatg ttctaggctt 134160 tccattggca cagccaaacc tgagtagctg atggcaagca agctgtggtt ttggggaagg 134220 ggaaagttag cgtgaacatg gtggaagcca tggggccttt tgagtttatg aacagcaagg 134280 tgagcaagat caccatgacg atcttagcca ccaggccagt ccttcagaga atcccaggca 134340 cctactgttc tcactgttcc tttagaaaac acaagtactt gatgccctca ggcacttcct 134400 gttttcctta accctccagg tctagctgga ctgtagttaa gtttatagct acacataaaa 134460 ctaaatgaag aaaaagaaag aaacaccgcc tttaatagag gaccagcagt tagcagaccc 134520 tgttgctgct gctgctgtta ttgttctcct ccctcttccc ccttcttccc tcctcctccc 134580 ccctcctcct tccttcttgg tcaaaaatag atcaaattaa ctaatgaagg gaactttctg 134640 tgttcttaat attgtgttag ccacggaagt acttttcttc ttggagtaac ttataaatta 134700 ctgaggataa ttactgtgct tatgagtatt ttgctaaaac aaggaatttg tttccagcat 134760 gtgagtagct attaaatctc caaagtgctc atcatgcgag attcgacagc tttatgtcac 134820 taggggcaaa gctctagaga ggagcaggaa ggggtgtgca tgatttcttc aaactgtccc 134880 gtcttctctg ccgaatattg tggttcctta agaagacttc agaatgctac atctagagaa 134940 gagaaaacct gaatcaaaat gcttgctctg agcagttatt tttagtaaca aatctagaaa 135000 ccatagaaga tatgtgagtg tctgccggta tatcatgcat gcacatagaa gatatatgag 135060 tgtctgccgg tatatcatgc atgcacatgt gtgttttcaa cagtgagatc ctgagttaca 135120 gactgtgtgt atggggttgg ggggaggtag ggctgtgggg gttgggggtg tgggcaagag 135180 atgacgtctg tctcttaata gcaagtgggg cagtggcttg ctcagtctgt tatcataaag 135240 ctctgttaat gtagcttttg caccatgtga ctgcaggaaa agctattatc tcaatgaaaa 135300 gaaagccagt tttagagcaa gcaatagact agaagcagga agaattttcg agtgttccac 135360 catgctggat tgtcaaaggg gtgggtatct gtgtggccag cagctgaaaa aggatccagt 135420 gatagtttgt cagctctccc cagaagggca ctcagcctgg gcttcagttc acatccagac 135480 aagctgtggg ctggggctga tggaggggat cgatctaaga tgacacttgc tcgttgctaa 135540 tctagagaga gcttgtttgg aagatggtgt gtgtgtgtat cactgaagat gcagatctga 135600 accacagagg ctgtggacaa tcaccaggtg tgtctcagaa gtgttctgac ttttatttgg 135660 taatgttcct ggaattccgt atgctctggg ctggagtgta cttgtggagc ggagggctga 135720 acatggcagc tagtgagagc acgccaagga caaatgtaca tagcatggca caaatgtatt 135780 ctagggtctt tatttatttc tgttatattt atttagtgtc taaaggttat ttgcagattt 135840 tcattctgct aattctcttg gttgtctgaa ggaagtattt tggtaagcat tttctgaaat 135900 tcagacaaat cttaaatcct taaggtacaa attaaattac taagagatga atgtctttat 135960 gcttctgtct cttttattca ttatcctttt gtaattgtaa gcacaaaaac gatctttgca 136020 gtgaatttga aatcattcca tgatttcagg agctttctaa ttttgactga ggttctcatt 136080 gcatgacttt gctatacagt acttaacttt ctctgctttg ttcttaagct gttacatgca 136140 gacaccaaat agcacccacc tagtcaagtt tcagatcgca cttgaccatt tgtaatgtta 136200 ttggttctct tgttagcatg tcccttcctc tcaacctagg aaggcatagt actcaaactc 136260 cccagatgct gtaagggaac gggcggccat ctgaggagtc agtcacctgt cacgtggcac 136320 tcagctcagg agtttcggtt tcaggggtgt gtgtgtgtgt gtgtgtgtgt gtgtccaaat 136380 cacatgtaat tctgaagcta agtggtgttt tataccattc cctttaaaaa tgatatcaaa 136440 ggaggtgagc aatcaaccaa gatatttgtg caatatgtgg cagtttaata aataattcct 136500 tgaccctttt ttaataaaag caactcccat aatttttaat tatacttagt caaggatcct 136560 tcttgcttat ccgatctata gaccagatat tgtacaacag ttggataaat cactcatctt 136620 agctttgctc ttgggaggag tggcagaggc accttggcct agtcttttct acatgaaata 136680 gtttggttca gatacttatg taaatgaagg tggatttaaa aaaaaaaaaa aactacagag 136740 ggctagagag atggctcaga ggttatgagc accaactgct tttccaaagg tcttgagttc 136800 aattcccagc aaccacatgg tggctcacaa ccttctgtaa tgggatctgc tgccttcttc 136860 tggtgtgtct gaagagagca atgatataac atataaaatt tgaagctaaa ttgtttgggc 136920 atttaatttt ttccattgtt ttgctgttta atttatagct tattgtgttt tctcatgtaa 136980 agacttcaga tgacctgagc agtttgtaaa agtaaaagat gttcccactg agtactgtta 137040 ctgtattaga ctgaaagcct gtgggacgcc aagagcaact gcagtagtta atccagtaag 137100 ataacttagt acctgtcatt gaatccatgc cttatgaaca tgaatatctt gaatctcatg 137160 tgacttttat gtgattgaag gaatttttat gcaaaatgtt tctgtctgat gacagtgcct 137220 tcctggtagc tttctgcatg actgcccact ggggtggctc tatatgagag tgtaaaatag 137280 tctgtgcctg ggcctatatt ttcttttatc acaacagaag tattcgtcat agggctgggg 137340 atagactagt gacctgggaa ctgagctgac ctggaagtca ctttgaacct aaaacggaag 137400 agtttgctgg atcgctggac ttttgcttgt tttctgtttt agttctgttt catttctgtg 137460 gcactgagtg attaaaccta agggttcaga ggcattttac gtccaatccg taagggtgct 137520 tttagataat acaatatagc aacatttttt taatgaaaat aatacaaact ggaggtagag 137580 tacccttcaa agttaggttc agtcactcgg tgccacagaa gtaaagcaag acgtcaggat 137640 aatgtccaaa caggctgaac aaccagcctg ccgatcctgc tggactccaa aacatagcca 137700 caataactaa ccacagatat tatgaccagg cctgatcgtg tcggccgagg gcttcattcc 137760 ttgcagttct gtttaatctg tgggtggagc tgacagcagc gctgtaagat gcggtggtgg 137820 ccatgggacc tctggcctct aaagtcagtt tggggctgat taagtcagaa ttcatgtacc 137880 acatatgttt taaacacagt tttactcata ggaagccaga gaaacgtaca gttcatgaag 137940 agtcatagcc agtgtgtttt ctgaaggcac aatttccagg attgggacac tgaaggcaag 138000 ggcataccta ttgctcgatg acatagcctg tccttgacac aggaggcagc ctgggcattt 138060 ctgatgtctt catttcattt gcagcagaga ctcttggcca agttcatgaa gtcccagctc 138120 atggctctta atcacaacac cataacagaa acagtgtgcc gtattttaac tgataaaaaa 138180 atagttttta tagtttgtgt ttttcagtga ttttatgtgg aacaaccaaa ttctgtactt 138240 gactttgcat gagttgtttc ttactggaac actgattcga ttgagtgggt ctctaaacct 138300 agaagctaga cgtttggttt tatcatctta gatgtctgct cagagtggta aatcagctgg 138360 ctagcgtaca gctggtcgaa gtagtccatg aggtttctat tccaataggt aaatgttaga 138420 atctagttaa aataagtgat aaatcttcca ccaagacttc agatcccaag agcttttgaa 138480 ataatgttta ttaactggcc tttaccagtt ttactttcat tttaagtatt gaaaatagat 138540

atcataccat tttttacaca tgatttttaa aaaatatgtt ttgtgggctt tctttgtccc 138600 atgtatgatg cacattgtat gagctataag tactttggcc aacactatca accatggagc 138660 tctcctggcc ttgaacttga atcacagtgt ccgtccatcc attccctcct cctgtcactg 138720 tcccatgcct ggcttacagt tgagcaaaca ctcagaggtc aggcaggcag tgcaaacata 138780 ggccatccgc ctcatgcttt gtctccagtg tctgtgctct gacgttgccg taggctggag 138840 ttcaggtagc attgatggtt tgttctacaa tgagagagca ggatggacat aggcacaggg 138900 agacgccctg tgaaggttga gtctttctgc ttctagtttt tgtgcattta atgaactttt 138960 acttctgcct taccttacat ataccaaaag taaaggattt cataaaggat gcttagtctg 139020 caatgaaaag aactgtttgc ttgtgggaaa ttcctgcaga gctcatgctg aagtattgca 139080 gaggaaagag gactgaagga ttcttgtggg gtaccagaga ttgctagaga gataagagta 139140 gcttgctatg ggactgataa gtagggaaaa gctctgaagt tgtggagtct aaaagccagt 139200 gtttgcgtgt gagctctctg ctgagtacac actgctcact tcctaggtcc cttgctcatc 139260 ccagaacagt tgctcagata gaaaaccgta gaggagccat gttaaagtgc taactttcag 139320 acaaggagaa cactctggaa tgcaaaccat ttactaagat ctgtggtaag tccttttaca 139380 tccatgcaga tcccctggag atgagttctg tccgggtagg ctttcaggtg agggtctttt 139440 gtactttgtc atacttttaa tggtctgtag ctttattatg accatgacag aatacctaag 139500 tcaagttagc tttataaaga aaagaccttt attttggctc ataatttaga agattcaagt 139560 caattgtttt aagagtcttg tggtgcggca gagcatgtgt tatgtctggt tctgtgtgtg 139620 cctgtctctc tcctttccat aaagccacaa gggttccatc aagcgttctg tcccaaagtc 139680 tttctctaag ccaggccaca ttccagagag tgtaactcac accattctca ggttctctgc 139740 ctcttattac cattggcatg tgacatgtgc agtggagact tcagacacca gcagctgtgc 139800 gttctcttgc tggtcatgtc actcttgctg gtagcccgct ttattgcctc taggttctgg 139860 ggatgatgag gagagcaaat tagatgtaac cttgccactt gtcctttctc gtggcctcca 139920 gtatgttgac ttgtttttgg caatcagaaa taaccactgc gggttcgttc tcagatcctc 139980 cagctgacct agctactgtt tgttgtaact gtggctgtgt gctccaggaa aacacaacag 140040 taacagtaac agtaactgcc tcttctggga gtgagaggag gattgatctg caagctggga 140100 cgggaaggtc tgaactgcag acagcactgc ctcgacatcc cagggattcg cagagtgtgc 140160 aggcttgcct gccccattgt ggtgataaga taagaataga tcaatttgca ttcttctaca 140220 tgatatctgc cagttctgcc agcaccattt gttgaaaatg tcttttttgc cactggatgg 140280 ttttagctcc cttgtcaaag atcaagtgac cataggtgtg tgatgcaaac cagtcactgc 140340 ttcaaagccc atggctttct ggagttgtga gttctctagc aaatggagtt ataggtagtt 140400 gtaagcctcc tgaagtaggt acaaggaact gctctgaggc cccctgccag agaagtaaat 140460 acccttaacc cctgagccat ctcttcagcc ccagatttta acagtgtcat cttttaaaaa 140520 tgtgtattgg tattttgcct acacatttgt ctgttacatg tgactgcctc gtgcctgcag 140580 aggccacatg acggtgtcag tccctgggac tggagttacc aatggctgtg agctgccatt 140640 tgggtgctgg caatcaaacc ctggtcctct agaagaatag ccagtgactt tttaactgct 140700 gagccatctc tccaccaccc ctctgcccta gattataact ttaacatgca tgacagaaaa 140760 atgtaaaagg aagtgtttac ttgagatgtc caataagaca gcagcgagca gttgtagtgt 140820 gctgactata ccttctgcct cctgccgcct agaggacttc aggtgtgtga tttcattttt 140880 ctgtgtttca gggattatgc taataattat ctcatacggt taattgtgag gtcaagttga 140940 aaaatacaga tatactacta aaagtagaca cattactatt tggaataaaa ctagaaatat 141000 tacctatttg gggttaaata gtcttgagct ctggtagttt gtgaagcgat catgagcatc 141060 aagctttttt gtatcaagca tgctgataga taagggacta agatagaaaa gaaagaacaa 141120 tatataattt tatgacttga aggcatttaa aatgcagtag tgacagggat gcaagaggaa 141180 gtaatgatgt ggtgttacag ctgttagtgg gcatatgcag gtggtctgtg gacagatggg 141240 ggtctgcagc agttctaaaa gagtggaatg agtttgaagt ggcttcatag aagataagca 141300 aatggactga gaccaggagg agcaaacaca aaagaacagg tgtgttggat agttcaggcc 141360 agcttgacac agctagtctt cagagtggag ggaggctcca ttaagaaaat acctccataa 141420 aatctggatg tagatgtgcc tgtggggtgt tttcttaatt agtgattgtt ggggaggacc 141480 cagccccttg tgggtagtgc cattcctggg ctggtagtcc tgggttttag aagaaagcag 141540 gttgagcaag ccgtggcgaa gaagccagta agcagcaccc ctctgcagcc tctgcatcag 141600 ctcctgcctc cagccttctg ttctcagtgc ttttgataat gaaccaggga ggacacagga 141660 cactcctcac attgcttttg gtcatggtgt ttcatcacag cagtagaaac cctaagaaac 141720 aaagacagag acaagggcag gccgttatgt cccctgcagt gcattccagt gacacaggga 141780 atcgatgaga accgtaaggc agatgctcag ctcaaacatc attccaggca gaggagaagg 141840 aaaggcgagt tcagagacgg aaaggtttga gaagaaagcc tgaaaggaag acttagagga 141900 aaccatagaa atagactgcc accaaagaag ctgccacacc atctgggaag cttagagaac 141960 agtagtgatg gctaaactat actgccaacc tctctgcttt gatggatcta gaagagccct 142020 tgttacaccc atttatttat ttaaatttct gttttgtctt gttttaatat ttttttgcag 142080 caagttacat gtaacataaa aatgattgtt tcacttcttc agtaacatta acacaccctc 142140 aaggttatat aatcattgct agtgtacatt tccagaacta cattatccca aacagaaact 142200 gcaaacttca aacagtcctc cctgtcctgt cccgagctct gatactttct cttctgtctt 142260 tgcgtcttta gctgtttagt gctattcttt ttagtgcctc cacacctgct ttcatttgct 142320 gtagttcact agtgtctaaa ggtgttgtca gtgttggttc ctctttaaag ttgcacaact 142380 gctctatgta tgtgtccatt ttctgtgtcc attcatttgt cctggatgtg catgttgcta 142440 ccactccttg gctactttgt cattcttagt cctgaatcac cctactttgg ttgcagtatg 142500 tatatattgt cttttaaagt cctgctttgg ttctttgggg tattgttgga tcaaggtttc 142560 cccagtgatt tacaaagaca tgtagccata gatgggaaaa ctgtgctgtg agacaagagt 142620 gcataaatct gcaaggctag aaacagtgca ctgagtttgg gacttttggg ggagattttg 142680 tcttattttg catgttttta tgcttttact ttatagcttt gattgagtag tttctcaaat 142740 ttgtttctaa acacaaacgc aacatggagt cactagggaa ttttttaaaa attaattaat 142800 gccaggcggt ggtggcgcaa gcctttaatc ccagcactgg agaggcagag gcaggtggat 142860 ttctgagttc gaggccagcc agggctacac agagtaaccc tgtctcgaaa aaaaaaaatt 142920 aattaatctt ttagtattgg tggtcaaagc caggacctca tgtgctatgt ctgtaatcat 142980 agaacactat ttttaacatg agcttatgag tccaaagtat acatcacaag agtctatgtc 143040 actagccaga tgatcagaaa gcatgctcat catccttaag tagctcggga agtttaatac 143100 accgaggtat acttccaacc caggcattga ctgtaataac taaaagcagg ggatgctggc 143160 cgtctgcaaa ggagttgaca tcagagtgcc cgccttgctg gctagaaacc caagtgcagt 143220 cgtgtggata tcagtttaat acagcatcag gaaatggaac ataggcttcc accatgacta 143280 tactaactcc tttctgaact ctacatccca gagaacttgg aaggaatagt ggaaaagtag 143340 aaacaagcca gtgttcatcc tgatagtgct actgaacctt gagaggatta taccaaagaa 143400 aataagtagt ttgcttattt taaaagattg gagacagaag gccagtcatt gaccaccagt 143460 agctggggca agtagaaagg acaagatgtc attgcatatc aagtatgagt tttctatctg 143520 aagatggaaa tactgtgaag ttaggtaaga agatatttgt atgactgaaa acacatatta 143580 aatatattaa gagtgagagg agagaaatcc aggaaggttg atgggcgcca aggggggggt 143640 gtgtttataa gtgttacata gcagtgaaag agtttgacac tgtgtgccag atgcccatga 143700 gctcggtggt tttaagcttg tttagaggtt ccagctcagc tgctcatata ccctgggctg 143760 aggactagtc atcctctatt tgtggatagt cagcatcttt gacccagtgc acttaaggaa 143820 gagtgcaccc gtctagccag cctgaccaac tagcaggtga cagatgcttt ggtcagtcca 143880 gcctcacaac caggttttac atttgaatat tccagaaaac taaaaaggga gaattgacag 143940 aagaaaggtg agctttggaa cctgctagtg ttggaggcgg ggcaccagcc cgtagaccta 144000 catcccctgt ttggatctca gagtacaaca aactctgaaa ggtttcccaa ttcatttgta 144060 gtaaactctg acctaacaag tgtgagatga cataaactca tctgtcctgc ctggtgtgag 144120 tgaccgtgta tttcattgtg gagatagcat cgaatttgat tatagaacac ttctgtagat 144180 ccctcctaga ggcactacag aataagctgt cttccaagta ttgtatcgag aggcagacag 144240 ggagaggcgt gaattctaaa gcccacgtta tttggctcca tttctttgat gcaggggatg 144300 taaactccgt gatttggaca ggggtgaaag tgaagggaaa gcgagagcct gagttggtgg 144360 tacctaaaga gggattcaga ctaatggaac ttccccccaa gaatagggga gtagtttgaa 144420 tgtgccttgc atacagttta aagaggaaca ggtagaacat gatactaccc cttcccacct 144480 cagcaacaac ttttacagta atatcttgga gaacctaggg gtgggaagga gaaatggctg 144540 gcagtggtct gtgagaataa gtcgggtatc ctctgagatg gcagaaggaa agggatcagt 144600 atcttctgag attgactcca tgaaagctgg aaacacaggc tgacctgaga ataacgacgt 144660 ttctgacagg actaggagca gtgtcataaa ccatgaggag tctgtggggc tgtctctccc 144720 gagaacatgt ggtatgctcc atcagtcccc atctgtcccc ttctacgaga aacagaagca 144780 ctgtaggtca cgggagctag ggatgatgga aagtcagtga gaaaaaggat cccagttctt 144840 cataccagtg acggtcacat gaggagacta aaagtactgg tctcttcagg ggctggggga 144900 cgaggtgaca ttcaagtggg tacacctgaa aggaggataa gagctaacca tggctgaagt 144960 aaaatggaag tctgatcaga cctttggaga cagtaattac tagctcttca cagcctttga 145020 agtcactcag ggaaacaacc agattacggc tgggaaggaa gagctattca gaagccagat 145080 cttcactgat gtaaaagact gtgtggcgac tacgggatgc tggcgaagct ccacaaaagg 145140 agaggagatg gacaggaatg ttgttattta tagtccttgt ccttcatgaa aggaattaag 145200 gaccaggaat atggaagtag gaactggagg agagaccatg ggagaatgtt tcttactcag 145260 tctctcctca tggcttgcac agactgcttt cttatacaca cccggccacc tgcctaggtg 145320 ggcagctctg ctcccagtgg tctggaccct tccacatcag gcattagcca tgataatgtc 145380 ccacaggctt gcctgcaggc caatttgatg agggcttttt ctcagttgag gttccctctt 145440 ctcctctgat agctctaact taagttgaca aaaaaacaaa acaaaacaaa caaaaaaacc 145500 taattatggt tgtgggtgga gagcatgttc cacaggagct gggtttttaa gcagtgcacc 145560 tctagttgga tagtggcttc cagctcttct gcatactctc tgtatgtgag aatccagcaa 145620 cttctagagg actgcactac aaggaagagg tagcctgtca gagagccaaa aagaaccagt 145680 agttgattga cacagcatat tatcacactg gcttcgctcc tgtcgtcttc ttgcccagta 145740 gttgtagaca ttgttaggtc tttgtgatcc caggtcatca cccacagtct ggagtggagc 145800 cagaaaaggc agtgctgtct gcagactcct ctgctgattc ctttgctgtc caagtttgag 145860 gacctctagg aatccacctg tttttatttt ttatgtgttc actgtacatg tgtatagcat 145920 gcacatgcct ggtgttgagg gccagaagag gacttcaggt cctctgtagc tggattaaga 145980 ttctctcagt cactttgtgg gtgctgagaa cccagcctgg gtcctctaca ggagcaacaa 146040 gtgctgctta ttgggaccgg ctctccaact ccagactccc attttgctct catctctaca 146100

atagcacatg gatgtgaagc atacttctgc atctacagta ttcctacagt gcggccagaa 146160 atcttgtagg gaatgcagag acacctggtt tctgctgacc agtctaaact gtaaagctga 146220 actgtgcttt aattttcaaa tgagcaaagc ctttctagag ctcagtgttg ctctcagtgt 146280 tggctgtgag gcaggaggtc ctgcaagagt gcttgctgtc aggggatgca gctggcttgg 146340 aagacagtct ggcagggcca cacatatatg tatagcatgc acagtctgtg tgctctagtc 146400 ctcacaggtt taaaggagac aggcagaagt ggattgagtt acatagaagg aattcactat 146460 gctgttaact cgaaacaaag aaactggaaa ataggaactg gttaaatatt tatggtttac 146520 tcgtatgaga aattatagag ccattaaaag ttattcttta tttgcatggt ggtgccgtgg 146580 tggcacatgc ctttaattga agcattcaag aagcagagcc aggcagatct ctgtgtttga 146640 ggccagcctg gtctacagag tgagttccac aacagccagg gctacacaga gaaattctgt 146700 ctcaaaacca aagaaaacaa atttaaacat ttttaaaatg ctcatacaga taaaacttag 146760 tggcctaata ttcttttttt tttaagattt atttatttaa tgagtacact gtagctgtct 146820 tcaggcacac cagaagggag ggtatcagat ctcattacag atggttgtga gccaccatgt 146880 ggttgctggg aactgatctc atgacctctg gaagagcagt cagtgctctt aacttctgtg 146940 caatctctcc agcctgtggc ttaatattct taattttact aattttctta atattaagaa 147000 aaaggaacaa atgtaaaatt agacgtgtgc atatgcattt taattgctta gcatgaaagt 147060 tttcaaggtt agtggtgagc atatgcagtt ttgtgtgtgt gtgtgtgtgt gtgtgtgtgt 147120 gtgtgtgtgt gtgtgctcta acccacagca ttgtgcaaga tttaacagtt tactggtgtg 147180 ctagaacggg tgcctgtggc atgttctcca ttaggacagg ctgaatcccc cccatctact 147240 cacaccccat ctctgctttc tgctccctcc tccctcctca ccttgatctc ttatcctttc 147300 tctcatacct agaatacagt catttcagtg atgttataga gcacccctgt gtaaactcta 147360 atgtattgac ctatgttgta ctaacagagc aggtacccct acctccatct gtagtccctg 147420 ctgtgaatcc cagccacctc tgagttggtg gctacttcag gacacctcac tcttctgaac 147480 ccagtgatgg tgtcttagac caaccaaaaa gccagattct tgtaaagcca gattcttgtt 147540 ttccaaccag tttattccag ttgtacttgt tactataatt gcatattgat cttgaaattt 147600 gaatttgaaa acatgtattt gttagaaata ataagatacg tcatgtggac aatttcctgt 147660 taaacgggga catgtaagac atctatagta gctgggggag tgatgttctt ttaggtaaac 147720 agtgaagaag cactcttaag ggcttagtag ggctgtgtaa agatgcatgc ctgcagtcag 147780 tgctatggag cctgaagtgc agggacctga ggtgaaggcc agtcagtatt cagtattcag 147840 gaggcagtac acccctgtcc cccaaaaaga aaaaacctta agtcttttta aataaataaa 147900 aatgggaaat catagcccct tcactgcagg tctggtttac accaggaagt gctgagagag 147960 cagtaaagat ggatattcat gcttatgtac ttatgatgaa atgcttaaag ttacaggcat 148020 cattttctat aattatcttt cacaacttta gtgttcttaa tcagccaatt actatttctg 148080 attttacaag gaaagttttc tgtttagagt gaaactgaga catcttggtg tgcctgagaa 148140 agtgcctagc aacttccttt ctttaaactc tgcggtctac aacagtaatg gagtcttatg 148200 tattgaccca ctggatagtt ctgaaggatg tgtgtttatt acacaatgaa aaaaagaaag 148260 attctatcaa atgatgaagt aagcctttaa taagttagat taagaaaata atttctataa 148320 cacattcaag tttataaatt ggtcttttca gtgatcatta tgtcctgaac agatcacttt 148380 agtgcccaca ttacagttaa aattaaaatt gagggacaat tgggtccctc ctacctctgc 148440 atttgagtgc tgggtttgaa ggtgagtgcc attgccattc ctggcaggat taacttttga 148500 gttctaaaat gtcttatgtg ccttgttcat gtttcagaac tgttctcttg gtgccttgtt 148560 ctcttcctgt gtgcagtggt ggtgagctca cacaggacgg gtgaagggca cgtatatcac 148620 tgtatgaggc actcagccag tgtcagttac tgagtcacac ctgagtttga gtccagcctg 148680 tcctttggta tctgtgagac tgaagttgct ttgcaagcag gttagagaag ttagataacc 148740 aacagggtgt atatgtgtcc atctcaagac atcaggcaga gtgaggtgtg caaagtgtct 148800 gtgtgcaacc tcctcctcct gagtgagtgc taaccaaaaa gccccaagga aagaagatgc 148860 tgtagggtga gagagagcgc catggaggtc aggaacaaag ctgattgcct caggctgaag 148920 gcctttgaca tcttagtcat tttctcacat caactgggaa ggctgttaag tctcagaaag 148980 aaattataag taacagtaaa gaaagatcat tgaatttacc tttgacaagt tatgaaagtc 149040 taacataaat cttcttcctc tgctcttggt ttgctgattt ctttacattt atacttaagc 149100 aaattggatt ttaaaatgtt agctggaagc aggcacctca cttgcagtgc ggagaaaatg 149160 gcttatgggg tgcaaggagt ggtgctcttt ctgtgttttc tcatctgatg ccttattaaa 149220 aattgtcttg ctatttctgt ctagattcaa agagccccgt gagtgcctgc actgaggaat 149280 ttagcctgag aggacgcaga aaacagaaac tggctctagc cagtgatgtc acactgatat 149340 accccaaccc taccccaccc ccacaccact tacatattct gcaatgaatt ttgccagtga 149400 ggcatttggg gcttgggggg aatttctttc tcccacttta aggaagatgt agacatgaaa 149460 atgtcacaat gtaatatttg tgtcaccagt gactatgagt caagacattc atttgattat 149520 agcagtgcac attaaagagc caccacccgc ttctgtttaa tgtgtttatt actgtcttcc 149580 caatggcatc ttgaagtgtc tttcactaaa aaattcatga gtattattgg ctttcagaca 149640 gaaaatacaa tatgtctttt agtaactgtc taatagacca ctttaaggcc attatacaaa 149700 agtaaatcta agagcaaagc attttgggga ggaagaattt ttagcttaaa catttgttta 149760 tacagtcttc ttactcttgc gtagaagagg atctggaacg cagaaggtag ttgccgacgc 149820 catctccttg gagagtagtt gtagggtgtg ttgttttctt tagtcctggc aactgctgct 149880 gttgtagtat tgaagtcatt ttcttttttt tcttttttct ttttttcttt tttccctgag 149940 acagggtttc tctgtgtagc cctggctgtc ctggaactca ctctgtagac caggctggcc 150000 tcaaactcat tttcttttct ttttttaaga tttttattta ttattataca taggcacact 150060 gtagctgact tcagatgcac cagaagaggg cgtcagatct cattatgggt ggttgtgggc 150120 caccatgtgg ttgctgggaa ttgaactcag gacttttgaa agagcagtca ctgctcataa 150180 ccgctgagcc atctcgccag cccccttgaa ctcattttct aatgaggttg ttgtgtgcct 150240 gacctgctgt ttctttataa agtcaaatat acaatatggt actgtaaagg agtcagatta 150300 aactgagact ctgcttccaa ataagatgtc tttcatcatg ctttccttag aagtgactct 150360 tgtaaacgtt tgcaagctaa caactgtcag tgtggacagt gcatgtactg gtgtgcagtt 150420 tgtgagtctg aacatgtagg taactgtggg agccatagtg ttgtttaaga tgaagttaaa 150480 aggattcctg tgttctaata aaaatttaat actccttgca ggaaagtaat accccatttt 150540 actacctcag atactttaaa ctaatatatg atgtcctctc tccatttggt ttttctgtgt 150600 actttcaccc acattaagta cgtgtctcgt tctgcttcac tttgattggt atatatcgtg 150660 ctgctttgtt tgtgtgaatc ataagtattt tttatataat ctgtatattt actacattaa 150720 gtgaatgttt atttagctgt tggggcaaaa gttggaatct tatcagagta gcgcttgcct 150780 gggatagttt tgaccagtga gcacaattgg gaaccaggtt atttccaaaa tgtttgtccc 150840 ctctctctcc tcttcccagt actcacaagc agaagatcca ctttgtccgt tcaagtatta 150900 gctactgtgt tttcttacgt gtatcagaga aggcccaaga attgtgagtt tgtataatac 150960 agagctcctt ctccctggaa agtgtaggta gatctggaga gaattgagaa tggctgttct 151020 cacatgacct gataaactgg ggaagcgcag tgagtttcta agcaatgggc tctccctcaa 151080 agagcagaga tggagggtag tcttttatgt gtgttaacgt gcaaacattt ctcggcgttc 151140 tgaaaggtgg tccccagcac ttaggcagac ggattgggag ttcaggtctg ctgtgggcta 151200 cagaggataa ccctgttcag aaaaccaagg gctggaagag ttcttgtcta gcgctctcaa 151260 ggccctgggc ttgatcccca tcactgaaaa attgtgcaga tccagctacc attgtgcacc 151320 agtttcgtgg atcttaagtg agccgagaaa gattggaaag acctgggctg tggtggtgcg 151380 cacctttcct cccagcattg gagaggcagc attgggcagg cagatctctg agattgagcc 151440 caacctctac agattgaatt ccagaacagc caggacgacg aaaaaggctg gcccccatgg 151500 aaaagctatg atcaaaggac ttgttttacc tctctgtgtg gacatgtatc atttctgtcc 151560 atctcaaagt caggaactta ctagggccca actctcaaac tatgtctttt tggagctagg 151620 aagaggcctg gtgcttggtg gagttgttac atgtggagtt aagcaagggt gttatccttt 151680 aactgaattt gtttagcata tagtaaatct gacaggttta caggccttgt ttggaagatg 151740 gcctgtgctg ataagagata aagtgcgcat ttatcacttg caagaattct ggatgattaa 151800 ctagctctaa tgtcatgagg ctgttttgca aacaacagct ttgctgcctc ctatgttaga 151860 tggattcgct ctgcaaacaa agactgcttt ctttaattga attgaaattt gacattttat 151920 attgcttttt gtcacttgct gaggacttga ctatgggtat tgttcatccc tcccagatat 151980 tgctacttat aaaagctgaa gcttgctgaa ttgtgtgtct atatctcttc cttcttctac 152040 caagtacatt caagctgata tggagggatg ggaggacaag cctcctgtcc cagggaaagc 152100 actgccattg tgtgactatt gataacaaga atggcaaaaa gaaacatctc caggcttgtc 152160 cttcacagct cccatcaact ggtaaaaact ggtttgcccc cagtcactct aattatgtca 152220 gccacctcaa gttttatttg tgtcctagtc aatttctgtg atttacagtg aagtcttaag 152280 tttgatggtg acatgttcga gagctttaat ttcctggaag tgttgaaaac atgcagagat 152340 gtagagcata cctttactct ttcccatttc atactttaac tttggaaatt aatgtacaaa 152400 aatacattaa aactcatctc tatgtagttt tattttgctg tgaggtattc ttctgtaagt 152460 ctgaagtcga tcttatccat ctcacccacc tatgtcacct cggccctgcc tcatgtttta 152520 gtggtacatt gaagtgtttt ctaagtgatc tggagaaggt acagtaaggg ttttaaactg 152580 tcattgggct acagggcaca cagtctttgt ttttaagatt tattcattta ttttatatat 152640 gtgagaacac tatagctcta cagatggttg tgagccttcg tgtggttgtt gggaattaga 152700 tttttaggac ctctgcttgc cctggtcaac cccgcttgct cctgtcatcc cctccccagt 152760 caaccccact tgctcagtcc ctgcttgctc agactcaaag atttattttt tattattata 152820 tctaagtaca ctgtagctgt cttcagacgc accagaagag ggcgccagat ctcattacga 152880 gtggtcgtga gccaccatgc ggttgccggg atttgaactc aggaccttca gaagagcagt 152940 gagtgctctt acctgctgag ccatctcacc agctccagtg cacacattct tgattgactc 153000 aatccctcga gtccagttgt tgcaatgtgc ttgttggctg cttgtgtgca ttcagttgtt 153060 attgtgtgaa tttaaaggag aatttgaagc cagtgttcaa tcccaaatta actttctgtg 153120 actagcaagc acttatttta attgttgaga ggtttctggc ctttctggca gtatgatttt 153180 aatatgcatg gtgatagtta tatagctctt atcttcaata aagaatcatc cacaccttct 153240 gctcttgagt tttggtttgg tttgcttttg tttgcgctgt cctagtgaag gctgttcttt 153300 ataactttat atttttacaa cttgctgaca gctgattcaa gggaaaagtt acctggacca 153360 cttctcggga gattcctagg tgtgaagctt tctctttcac agtcgtgaat gaaaccttgg 153420 gaaatatggc tcagaaagaa ttaggaagaa tgagtgtttg tagcgtgttg tccctggctc 153480 cccagccctc tgtaactcac ccacttcatc ccagcctgca tggccctctt ggatctcagt 153540 gtgggaatgg atcgcagcac tgtccctgta ctcatctcca tttgccttgt ttctctcttg 153600

aacagcagta ttctgtctct gcccccctgc catgtccatc tacagtgaca ggaaggcagg 153660 tgttatatac tgaagtaaca atcattttgt gcacagaagc ccttgttggt tagatcttgt 153720 gactttttcc atggcgctct gcctgtagtg aatgaagacc aactcaccca tgacaggcaa 153780 ggcaggaaga cgtatatgga tgactacctc aacagtgact tgctagtgaa gagcaagggt 153840 cctctccatc gaggtcccag accttcccct tccacctcct ctaggcagcc tgtgctacgg 153900 atgccagagg tgtgactcca gcttacagaa aatcagtagt gtgcagtagc aagttttaag 153960 gtcacatggc taaccacgca gtgaagcttg ggcctcaacg ttagcccttg gctacttagc 154020 aatacagatt tcaatgtgag gtgtgaatct gtaaattggc tttagtacat agcataaact 154080 aagtgaattc agcacttatt atcaggcaga aagtagagca ggaccttggg acttggttac 154140 attgcttcca cccacaggaa gcacaggcat cagttctcag attgtatgtg accatgtgac 154200 ctcctaaact gcatgtgcca ttgctgccac cgccctcttg ctgatgctcc ctaaaaacaa 154260 ttggttctgt aaaacacatg actcgcaaaa aaaaaagaga gagagagagg gacagagaga 154320 gaacaattgg ccctcctgct cgcttggatc agaacagtgg ccagaggagt gtgtgtggag 154380 cactgagact gagggctggg accacaccca agtcgaccgc agacagttgg actggtaggt 154440 gtccatgagg cccaggtctc tccacagctt tccttggcca attttactct tgctggtcct 154500 cctggtctgt gctgtgtttt gggggctcct gggctgctac tgacctcacc ttctcgctgg 154560 attctcctag tctatccaga gtaaaggacg gtagcagtct ttcaggatga agagtgagca 154620 taggacgcgt ttctaggaat gaagtaccac tgactctgga gcttgtgggc tgagctgttt 154680 tcctttgctg ggcatatcct aagcccttta aataactcat aagtgaattt ttctcagaac 154740 cggtgatagg gcttttgtct cttctagaac tgtcactttg tccttgcatg caagtcacat 154800 gatggcccca gtggcgtcca gcgtgaggac actgggtctc tttctgtgtg cccttttcag 154860 tttctcatgg aaaacagttc agcaagcgga agctttatca gggccttcct ctcacaacca 154920 ttctaaagac ccttggtgat tatacctgca ctgccagaaa agggaacccc agcagaacgt 154980 gagaaaggaa ggaagccacc ttgctagctt aagagcaagg tgaactgccc gggggatggg 155040 gggggggggg ggtatgaggt tgaaggagga ggcttgaggc ttgaggggga gacaggaagg 155100 atctccattt tgacaaggga gtcagatcta ccaggccaaa tttggaaccc tttataaagg 155160 tgttcctgcc cacttcccta gactgtctgt caccgagcca ttccagcaca cacagcacat 155220 tggcaaaccc aacacaagag actgggaaga gcttgcaaca cctgtcattt ctctggtgca 155280 ggagcaccct caaaaccaga gactagccag gcccaggctg acagaaagca gctcatggta 155340 ttgttgagtc tctctgtcta aagagcctgg gctcagtgag gcgggagggg ttgttcttaa 155400 tattaacctt tgctcttgct tagcctttaa gtgtgcattt atgcacaccc tgtgttcaga 155460 actgcggtcg ggcttgggtt gaagtgggca gtccttacac cttggcaggc agagtgctgt 155520 gacagtttac taggactttc ttcacgccct tttcccatgt gttctgtttt agttgctgat 155580 atgtgttcaa gatgagtggg atgggagaaa acacctctga cccgtccagg gcagagacca 155640 gaaaacgcaa ggaatgtccc gaccagctcg gacccaggtg agccgatcgt caaccaaaga 155700 aaccgccttg tctgttagtt tcctgtgtgt gtcttcgttt attgcttttg catcgattta 155760 gtataactat tgtgttcagc ttttctcttt aatgatgaat ttttatgtaa tagcttaaat 155820 tttgaatatg tggattattt gcagaatcta ttccttttaa aaaacatttt tattgccctt 155880 gtgtatttta cttttataat cagttcattg ccataatgtt ttagttttcc atatttttta 155940 attaggaaca gaacattgta acaagtagat tttgtagtga aagatttgct atttgtttga 156000 tactgagttc ttatttgtct gtttgtttgt ttttgttttg tggcatgaag tattcaattc 156060 agttgttttt ttagttaaaa ataaattgtg gttcttcagt gactaaaaca aacacttcta 156120 aaacaagttg gcaatatcat aatggcagtt ctgatttcag gaatttcctc acggtagtgt 156180 ctgtatgtgc agagcactgt aagtgtgagg ttactcattt gcatccttgc ttagattcat 156240 aaaagagcag gaaacaattt ttgcagagaa cattttaaga tggtgtgtgg cctggaacac 156300 agtgcaaata tgataaacaa taaggctagt atttttaaag gcctcctaat actgaggcac 156360 agagccagta gtggtagtgt accctaaagt ctgaggcatg aggagtttaa gaccaagctg 156420 ggctacaaag gagttggggg ccagcctagg ctacatatat agttagatac tattccaaaa 156480 gatgctgtga gagagaaagg gcaaagttca aaagatgatt ttggagtata ccgcctgtta 156540 tattgaaaaa acaatttgga gaggaggagg catgtgcatt tgtgttgtag agtaatggct 156600 gctccctgct ttggtagatt agaaccggtg caaaagggaa acaaaggtgg aaaggtttgc 156660 ttccctgttg ctgtgatgaa acatcacaac caaagctctt tcagaaagtg agggttcatt 156720 catgatagca ggcagggagg cagagcagca agctgcagcc cggctgaagg agtaggaagc 156780 aggggagcag actagttgta gcacagttgt agcccgccca atcgtgtact tctccatcaa 156840 ggccacgcct cctaagcttg tctttacagg gccaccaact ggggaccagg cattcaagtg 156900 actgaacctg tggaggacat ttctcattta aaccaccaca aagagagatt ttttttcccc 156960 cagactttta atattttcaa tcctgtaaat gttttttgtt gttgtatttg tgttgtcttt 157020 atcttcccag nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 157080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn ggctgtcctg 157140 gaactctttt tagaccaggc tggtctcaaa ctcaaataga tccacctgtc tctgcatcct 157200 gattgctgag attaaaggtg tgtgcccacc acacccagca cctagaaatt agttttaaag 157260 ttaaataaaa acagtgctct agattgtgtg attaaaaaca acaggaatgt gggttagaaa 157320 aagttaccta ggcgggcatt ggtggcgcac acctttaatc ccagctcttg ggaagcagag 157380 gcaggcagat ttctgagttt gaggccagtc tggtctacag agtgagttcc aggacagccg 157440 gggggtaggg gggggagtta cctagagaag tggagagagg ttagaaaacc catggtttag 157500 gctattcctg cagcgctgat cacaggtctg tctaactccc tctccacacc cagccctgct 157560 accttttacc ctcaggttcc caacaacttc ttggtccgct ccacctgctg ctggctccca 157620 gatttccctt catgctttag tacccctctg gggagagagg ttccagaggc cacatagtct 157680 ctggggctca gttgtggtag caaggagggc agcccttcct tgtgctgtct ccagggtctt 157740 gtgcctcagc tccttttctc actgacttgc catttatcct gtctttctca ttctaagaga 157800 gaggggtatg gggaggagcc aggtgaaccg ggctcctcta aggccctctt tcagccacct 157860 ccttcctgtg acttcagtaa agtagaacac cccagaaacg aggccaagga gacacagacc 157920 ctcttccccg cactgctgca gtgcactggc gatcttgggc aaatcgtgga gccactaaaa 157980 agggagaatc gtgttaaaaa tcttaggttt attaatttat gaaaataaaa ctaatagatt 158040 ccaatgtgag aatcctgaac ttgcaattaa tattttgtgt taattttaaa ttgatattat 158100 atatgaatac atataaaagt acagaaaatt aaatacagaa aactaaacaa ctcagcttct 158160 ttccttgttt tggggccatt taatggactt ctgcatgtac acagataact atattatttt 158220 caagaggaaa tttggagttt tgttattttg tcaaattcat atgagaagat ttttccagtt 158280 ttgatatttt tctccactca ctgaagttca gttgaactct gaccacttgg cttgcctgtc 158340 attggcacgg acagcgccca tgggtcacgt gggctttgct tagctgcttt agcacttttt 158400 accttacctg attggatcac agatattcta aggaagtctt tagaaattac agatctaaaa 158460 gaagaatcta aaggtgttat aaagatttgg tttttattac cctttatgat taccaaaata 158520 aaacaaaagc gtgattgaaa cttacgtttc caattctaat tacattaatt ataacttgtt 158580 ccttctaaac taccttaagt agacgttgac tccttactaa ctctgtccag cagtaaggtc 158640 agtgctcacc ctgtcaagct ctgttgtagg ccagggccgt gctgccctcg ctgtggtgag 158700 actggagatg agcgatgagc atgctcagga agccatccac agagaacaaa agagaagcag 158760 agataccaga tcactccctc gctcttacct gctttcctga gcaggcagcc tgttgtctgt 158820 gttcacattt aaaagagttt agcagtttct ttcaaataaa tagtaatgtc ccgttccttc 158880 ttagccccaa aaggagcact gagaaacgga accgcgagca ggagaataag tacatagagg 158940 agctggccga gctgatcttc gcaaacttta atgatattga caacttcaac ttcaaacctg 159000 acaaatgtgc catcctaaaa gaaactgtga agcagatccg ccagatcaaa gagcaaggta 159060 agaggacggg aggggttctg cgcctccgcg tgggtgaagt cccctgaatc ttatttctta 159120 cacttaaatt attgatgaaa tgatgtcata ttaccagatg aatgcaagta tcacttgcag 159180 ggtttataaa caggctttac ataaaatcca gccgttccct caagaccaag gagatgtagg 159240 tgagccactg ataggacttt gcatctgcga acgcccccat atccctagag ttttggctgg 159300 tgtcattaca agtgagggcg actcttctat gtaatccctg aagaaggaag cagggaggac 159360 ctcctgctcc atccacttag ccaattggtc tggattagaa tttcacaccc tgaatgatgg 159420 agccttcaaa ggctctaatc gccagtaaag atccctttat gaagtcacag acatccttta 159480 acagctttct ttccttggtt ttctccccct acctcccacc ccaccacccc caaaattgtt 159540 ttatacttcc ctcttgaaat ttttgcctac ctaaaaaaaa ttataatagt ttttaaaaca 159600 tagttgactt tgtagtgcca aaaataaatc taaggcatgt acgagcaagg ctcttttgct 159660 cgaggctggc gcgtgctctg aagagtccac acactgagat ccttcaggtg tgaggatggt 159720 tacctctcag aatgcttttg atgaattatg taatttatat tcttttaaac tgccttttat 159780 atattagttg aaaaaaacaa tttcaggaaa attgtatctt tgtcttttta gatcttggag 159840 cctcaaactc tttttcctcc aaggaatgat aaaactttac ctctggggtg gggggggggg 159900 ccccccccct ggactgggga ggccttaaag atggataggt tcagggtccg aaagaatcta 159960 gaccccagtg gaggaggcta aaattagagg gtggagggca gcaaaatata aaagaacaaa 160020 gatataaccc ctgaccgatg gtcgnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160080 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 160140 nnnnccccca ccccgacact ttggggttta gcaggtaccg ctaatctcat cttgttaggt 160200 tctttctttg tgacattagc aaatggatca aatactatcc ctcgaacttg taggggaatt 160260 gctacctgta gtgtgcgtag tgcgtgaagt ctgtgctttt gataatagta aaaaatgtaa 160320 gcctgctgtt tcaggtctcc aaaaatcttg aatggttcca tttttgtgag catttcatgt 160380 tacaagtttg gtgtttcaga tagtcatact cgtattttca actacaatga gggtcttgca 160440 caaccttggt aaatccccct tccaaccaga aaccacatta agatgtgtcc cgctgggcct 160500 gcttctctgc agggttctct catcaagcac acaccacaac cacccagaag cagccatgta 160560 agcaccccat aggtcatagt ctcaaagcag gactgggcaa tttgaaaggc aatgggtttt 160620 gaaacaagaa gaaacgttaa atgtcaaata cacaaaagtt aaataccaag aagagaaata 160680 tacttctaag ttctcagtaa tctaatgctt taagaatatt cctgttttaa taatttttag 160740 taattgtatc agacagaagt taggtatgca ccagtgccaa agaagagtcc tttgcacccg 160800 tgcagtaggg tttttccctc tctctctctc tctctctctc tctctgcaag gcttctcaga 160860 tataattgag cagtgaccac agctggcaca cgtagctcct gaagagtgag cggtaccagc 160920 caggcagccc actcctgcca tggaaatgtg gtaggtgtgg tcttcttttc cacattaagc 160980 agacacttcc tccttccggt ggaaaacaaa gcaaaggagg ctgccagggg gtactctcct 161040 gcttccagag aggcctcgag aattaaaaag tgaagaatgt tttcctaggg tcagaactct 161100 ctgggatgga gcagttggac ccactttgat ttctgtctgc agctgacagc cagccaaggt 161160

tcaaagtacc acataagttt gggttgagct cttgcctctc ccggtgtctt ctctgttctg 161220 aactgagccc ccagcagtca gcataaataa aacccagcca ctacctctgc cccggtccta 161280 agcttacctc atatctcagt cggtcacact gtcagcctaa ataaaattat ttgagttatt 161340 gaggagaaaa tgtccatgat aatcactaaa cctgtgtgtt tggctcagag aaggtaagct 161400 gtgtctaggg tatggcacta aagaccactg aagaaggctc caggtgtgtg cgggcatcag 161460 ctgtgagtgt gcatcatggg ccttgttccc tcagctctcc atgtgccttg taaattgagg 161520 aaaatggaac gaaatgttaa aaatggcata tacttcaaga atttggaggg ggaattacca 161580 ggtgtttaaa ttaaccatcg tttcagacac aaaactttat gagatgcttt actctgacca 161640 aatgtggtaa cacttgggag gcagaggcag gaggattgcc acaagttcaa gatcaaacct 161700 gctttacatg tatcctaggc tggccagagc tacataataa aaccctgtct ggaagaaacc 161760 agcatctagg agcagacact ggaggcaggc atcctgagga gcagagcaag gctctgatag 161820 caagggttcg agactagcaa tacatcactg ttccgtttgg aattccattt gccttgatga 161880 ctttctgtgc ccacagtcat agaaccttag ctggtttgtt tggggttgtt ttgttttgtt 161940 ttgtttgttt gttttttgct tgtttgtttt ttttttaaac aaaggtagta actggttgat 162000 taagacctca tgttatgact aaattctctt tgacagtttt cagtaggagc cagttctttt 162060 tgtatgctgg atgccttgtt atatacttag gtttgcttgt ctacttaata ctccaaacat 162120 ggaaaatagc agttttactg ttttcccctc ttccaaatgg aaaatctgag atatgggaca 162180 gttaagtagc aaaatgtcat gctctagagg gaatgtcggg tggaatcctg ataacctggc 162240 ctcatagcta ccctcagatc cacacaactt gttagtacta aatatgacat ttctttgtat 162300 tctagtgtgg tgatgtttaa agtctctgcc ttcatccata acttagagtt atcttatgta 162360 acaaacacca actcgtctta actggagaac tgctgttgat atatcccaca gaatgctgag 162420 taaaggggaa atacagatct tagattttgg attactgtgt ccaatttcat tccatttagc 162480 agaaaacaaa aattctgtac aaaatatttg gggtacaaat atttaggact gtaaaaaggc 162540 taccaagtag agggaatttt aaaattaaga acatttctgc tgtcctgttt atgtctcctg 162600 ttactccaaa gtagccacac attgtatttc aaaaataatt aaagtgagtt tatcaattta 162660 aagtgagtat gaaaattata taagtctgtg ggcatggtag tataagtggg aaatcccagc 162720 acatggcaga agcgccaggt gttcagacac tgtctttaaa aaaaaaatca ttgaaacaca 162780 ttttatttca ttgcatttgg atttatcagt tagagcatca gtttcaaact tttgtttcac 162840 aaagttgaaa aaagaagagg ctgtatcaag tattcaagaa tatatttcaa aagaatatgt 162900 gttgatatac atgtcatcgc agtttttcat tacagttatt ctagagataa catacggtgt 162960 tgacatgaga atgtgggatt ctagattgct tcacacggga attttacctg ataggatagc 163020 atcactaagt gaagaaggac ctggaggagg agggcagggg cttggtggag ccggcaaagt 163080 taagccaggt agagtggtac ggcctttaat cccagcactc tggagccagc ctggtcttac 163140 atagtaattt taggacaggt aaggctctgt ctcaaaaaca tttttgttaa ttatgcaagt 163200 cagttgttaa gcatagccgt cgttactaac catgtggacg tggaagccgg tacactaagc 163260 aaaggtgaag aaaatggcag tgtttcttac ctctctgctg catgctctgg gatgcatgcg 163320 agctgtgcct ctgcctacga ggctggcgtc ctggctagtg gtgcctactg tacccctact 163380 gtgggaacac ctgaggtcag gaatgtggta tagttacatt gaagtccacc atgaggagaa 163440 tattcctgct acaggactgg gacactcaag tttgtgattt tttttttttt tttttttttt 163500 ttttggtggc tgttgctcta gactttaaca gtcagggaga ggattgatat tttgtttcca 163560 ccatcttagc tctggcagct ggcacatgaa tacacacaac ctgatagaca gcagaaagtc 163620 actcatggat ggacagttac atttatgggt atgatttaac cattagttct cttgtctact 163680 cattaattta aatggaaact agccatgagt cgctacagaa caagagttca atggaagcgt 163740 tctctgagag tcaagtgact gcatgtttac aatgacagtg tatgtgtcat tctcatttgt 163800 aagttacgaa tgcactactt accttttaca ctagagaaat atgccataaa cattgtgttg 163860 cactacacac actcaaagag ctggctttaa gcatttagca gtcgtctgtc attgagaggg 163920 caatggcggc aagacattca aacacatatc cgcctgtctg cctgcttgct ttctccccta 163980 tgattctgtg acctttactg taggtgcaga ccctgctgga caagcccagg cgatacacta 164040 gggcgagctt gcaaactggg acagaggatg gagagcacat ctccacaggg actggctgag 164100 gcagaccgtg aacctctggg tgtgttctat tctgcttctc tttgtgttcc tgaagcctgt 164160 agctgtacaa ggcacagaag ctgtttatat ctgagtgtga atacaggaga agctgccgtg 164220 tttaaggctc ttacctgctg agctgtctct ccatctctta cgatatggtt ttacttagca 164280 atattcagac tgctccagac acattcatgc agatctttat tcccttattc ttcctctagg 164340 aaacctgttg tgctctctac ctctaacctc catactcctt caggcttgct gttatcctgt 164400 gtgttgttaa tgaggcagat acccagaaac actaggctgg ctgagggcct caaactgatg 164460 agtgacaaag tagaattgac tgcagcacct gtctgatcgt ggccatgtgt gaaacttcct 164520 tgttttgttt gtttgtttgt ttgtttgttt gtttgtctga ggaaagaaaa atcatgttcc 164580 acagagtaat ttcacaaggt tcatgggcac tagttgcgca tggatggagg tagttttact 164640 tgtataattg cgagctagtt gtgcatggat ggaagtagtt ctactgtatt attgagagca 164700 gccctgatga ttgagccctc tgacttcacc catgtctgtg gctcggcccc agcacctcac 164760 agcaggacag accacctgga gctgcttcct gagagctcct cacagctgca gttttttctt 164820 ttccatttct tttccttcct tttttgtttt tataagattg ggtttctcta tgtgctgaga 164880 ttaaaggtgt gtcgtcgtcc ccccatcccc gtctgcattt tgaacaggtg cctttaattt 164940 ctggtgagca tctagtaact aagacgaggt tatttcctgt ccctgaagat gctacaatgc 165000 tgattggtgg gaagggtctc ttatgtcacc tcaccttcgg agtactgttg ctttgccttc 165060 aaagcattct gacttcacta tggtttcacg aggagcctaa aaagggggta cagtggtgtt 165120 ctgtgtaatg gtgggtcctg cttgttgtat ctcaggtggt catagtaagt tgagtggatc 165180 tcggcaagtc tggggtggag aagagtgtaa tcaccgagct ctggggaaga gggcactgcc 165240 tgtggtgggg gaggtgggac atggagtgca cgcactcatc agtgttctgc agacacacag 165300 cgcttcatgg gaccatttat attttggggg acagaaatac ctggaaattt ggcacaacac 165360 agttgatcac aaaaataaga tataggacat aaaataagag tcttccaggc aaaagagact 165420 tgcatgacat taaaagaaag aacttactgc ctctgtgcca ggaatgaagc tcaggtgtca 165480 ggtccctgct cacactggcc ttgccacatg tcagtcagga gacacctcct aaacatttca 165540 gatctctctc tgcagagact gcagacggtg tgctccagct gtccaaactc tagcacttgt 165600 gctaatgatg gcccctccct ctgttagcca gctgtgtacc ctgtgaaatg tgggttcatc 165660 tctatactat atgggaattc tgtgactacc tgtcctttat tcatcttcat caaaaggcaa 165720 aagtcagctg ccaccatgga ggtgagaggc catcctggca gagtgcttcc tctgtcctaa 165780 gttttgctct gctgtcttca tatcctttga tctgtacaat gcccctgtag agtaagtctg 165840 cttattctct cagttttaca ggggaaggcc ttgggttagg gctggctgct ctaaagctac 165900 aaggcctcag atctaaatct ctacttcgtt cccacgcctg tgtgttcagg gagcctgtca 165960 tccagcctgc cctggtggtt ttgtctgcca tttggaggaa gttgttctga gcaaattggg 166020 ttaagtgtgg actcagctgt tattcaggat gcttcgtgta ccgagaggaa tatttcttac 166080 agagctctgt tttaaaggat agtatgcatg ttcaaggcag gtcatgtttt tcagtagcac 166140 acacgcacgc acacacactt taggagaaaa aaaaaatccc aagaaagaat gttatgtgtg 166200 ggagggaaaa gaaaagaaaa aacaacaact tggtatttag ccaaaagtag tgacattcca 166260 agcttgtttt cgagtatttg ttttgttcac tgttaattat aaaagaagag tccatctgtc 166320 agtcagtcag actggtgttc tgttgtctca tcatgttgtc ttttccatct taataagagg 166380 ccatgtgctc tgatttcagg agctgatatt cactgaccat cccagtactc attgcctcat 166440 tggccaaaag taaagagctg catgtgaggg ccccaggctg gaccactgtc tagcagagcc 166500 agggagtggc actgtgaggg cccaggctgg accactgtct agcagagcca aggagtggca 166560 ctgtgagggc ccaggctgga ccactgtcta gcagagtgta gtggctattc ctggttgtca 166620 acttgacaat atttggaatg aactacaatt tggaattgga aggctcacca gtgaccctta 166680 tctggaggct tggagatcct tatctggatc ttggtttgaa gatcttgagc cactagtggc 166740 tatggattcc agaagattga atctccgagt taaggaacac acctttaatc tgggctactg 166800 cctttcactc tgggattaaa ggtgtgagtg gaacacacct ttaatctggg ctacaccttt 166860 tgctggagac aatataagga cattggaaga agggagtcta gctctagttc ttgctcttgc 166920 tccttcgcct gcttgctgcg tgagactgag taactgctag atccttggac ttccattcac 166980 agctgcgact gaaccattgt tgggaattgg gctgccgact gtaagtcatc aataaattcc 167040 tttactatct agagactatc cataagttct gtgactctag agaaccctga ctaatacaca 167100 gagccaggga gtggcgctgt gaaggcccag gctggaccac tgtctagcag agccaggggg 167160 tggcactgtg aggctttggg tccctgcgct tacactgaga gaggagggag tgactcagaa 167220 agagtctttt cctcacgact gccctttgag cactgtgggc agacttagca ctaagttcca 167280 ctggacctgt ccatcgcaca agtggcacat ttcgtcctgt gtagaaaaag agtgaaataa 167340 ataatgccaa tattggcatc agcccctcca ggccttccca gtgatggcag tagtgaactt 167400 gcacaattcc tgggtgtgtt tgtctacttc cctgtactta aaagagtttc tcagtacagc 167460 aaggatttat tatttatgcc tatctacaca gacagatgtg tgcatgccac tacattttgt 167520 aagattccaa atgttataat tagcttgtta cataggagaa gggaagtggt ggtggtgagg 167580 tctagacatg ggcgtggtca atctggacag ggagggcact gtgggtacag gctggacagt 167640 agacctcgaa gctgagccag gggtgactct tcattatctg agtctgtacc tccccttctg 167700 ctctcttcta attattcttc agttctggga agtttcttat tctttggtct gccacaaccg 167760 ccaaactcag gttttgatgg gtccttctcc ccaaccagat gcgcaactct ttttgtaaat 167820 gtctaaggat tactgcccta caaaaaggaa gggcaaattc acaaataatc agaagagaag 167880 acagacttag aggaagtctt aggcctagtt gtgagctctc tgaaatgtaa gacggtcggt 167940 cggttctgat atttgcctgc ctgctgccca gtttcttagt tctcctccct ctcccctggg 168000 gtgggggtgg gggtgggggt tggggttgag atgggtttnn nnnnnnnnnn nnnnnnnnnn 168060 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 168180 nnnnnnnnnn nnntaccttg gctgccctgg agctcactga gtagccgcct gctgtctgtg 168240 aaccctcagt cctgctgctt gagttcccag tggctgggat tacaggcttg caccacaggc 168300 ctagctttct ttcctttggc tctgctgaag gagaatccca gcaagtcttg gcttatataa 168360 agatctataa gaaggagcca tttccttttt ttcttttttg gttttttcga gacagggttt 168420 ttctgtgtag ctctggctgt cctggaactc actttgtaga ccaggctggc ctcgaactca 168480 gaaatccacc tgcctctgcc tcccgagtgc tgggattttc aaagtcactt caggctgatt 168540 tcctgagagt tccattgcca aaagatattc ccagtgaggg gctgggaagt atgaaggaag 168600 tctctgcagt ctatgtgtgg aggaatctcc agtcttgcca actggtgttt ggcttgtagt 168660

tctgaagtta ccttcagaac acattacctg acattgaagt ttggaatctc taggtgtgtt 168720 ttcaaagcct ggtaatttta tcaataatat agtcaatgat tcaatataat tcaataatgt 168780 gtttactgtc tcttcttggc ctataggaca tgacagcgct aattccatat attttaggta 168840 tacccattat gaacaattta ggttttttct tgatattatg ttttagatgg aggggtaggg 168900 attgtataag gattcagtgt acagctctgc agcacaagag ccatgtgcct gccatgacca 168960 cctctgttaa tttcctttct agtgagtcct tagctgcatt accaagttac tattccctaa 169020 tagatgttta gatgcccact caattttctt ccttgatcta gtcaagctga tgctaggcga 169080 ggctgcactc ttctgtaagt ccatcactta actgaattta actttaggaa tttaacaaag 169140 tattcttatc cctatagagt gtgttcttaa tctaaatttt tgagacatgt ctaatttcct 169200 cggcagttga tttatctaga gagggtaaca gaaaagatct ttattagcct acacattttc 169260 ttttccaaaa cttttttgag cggctccact tgaatggctg cttggaccca ttcacatcct 169320 gaggtgcctg cgttgctctg gcactgatgg aagcttattt tgagctcagc agtcagtctt 169380 gcgacgttcc ctcgcagatg aaagcatccc tggtcttaat cagcatctct tcattgaaca 169440 tcctagtaag tgctgtttcc tcaactcagc tggtccgaca actggctctc ccggctacat 169500 tcataaagta gtactacggc taacttaaat gttgaatttt ctatttttat acgtttatga 169560 catgttaaaa atagttcact cgttctattt ctgtgctcac cttagctgtg gcagtatgct 169620 cagactcagg agagcaaagc ccatgcagac tcctccaaaa aaatggaaaa tagtactttt 169680 tggaatgaaa attacaaaat cagattcctc agctgatttg tgtgcttggg tttaagacgg 169740 atcctctgtg aagaactctg tcctgttgtc tttcaaagtg gcagcgcctc tcccttttcc 169800 tgagtgtgtt tacctgtgag cagtgtgggg catggagtca ggtgaagagc cagggtttgg 169860 ttccgagctc tggcagtcct ctggtaacac tgatactatc cagatacaac tcgatggctt 169920 ccagaagaca tagcaaattc cctcagccac gttaggaagt gcagagggaa accaacttgg 169980 atttttttag atttcctaaa ggaaatggca gcaactgagt gaaaaatgct gagtcaccat 170040 tgagtgagga cagtggccct gtccctgcat gctgctttag tccagcctac tcagttggac 170100 atctccagtt gaacgttgac tggacttgtc cacagctcca caaaacatat tcctcttcct 170160 ttatcttttt ataaacacat caggtttccc atctcaaaag caacattatt ttaatatttt 170220 aaaaagaaat gaatggggtg gtgatacagt ttagcagata aaagctcctt ttgtacctgt 170280 gtacgcagga cgcacatggt gggagagaac ccactcccac agttatcttg tgaggtccac 170340 ctgtctcatg cgcacaatac tacaggttat tttctgttaa agtattcccg tattgccaca 170400 ggaactaaca tatgtgttct tgtctataaa gaaaagacaa gctagctatg gtgctgactt 170460 cggctttaaa tggatagaag aactgtatag cagggttata gtaagtagct tatcacaaat 170520 gtgtgtgata ctctttccct ctagaagaaa cctgtctgta gccttagagc ttagaattat 170580 aaatgtaccc attccatttt taagcctgag tagcttcaga ttttatcata aaatatcttg 170640 atgttttcaa agtctccttt tatttgtaat ttgtgagcag ctcctttaga gacttgtttt 170700 tctgaagctg tttgtagttg tgcacgcagg ataatcctgc ttggcacctg tcttccgtag 170760 aactcggtat ccacgtgcat tttttcctga agcctaatca tacccttgtg aagcagggcg 170820 ttttgcaagc gattaggggt tgctttgctg agtcagcata gccttacggc attatgataa 170880 gctcagaaaa gattgaggtc atgtactaac ttgctcctgg ggaaacccag ggtgcaacca 170940 atgtttttct tggcgactca aagctgacaa ctgccgatat tctctttcct ctgaagcaca 171000 ctgttcattg atgcgatttg aaaagacaac aaacagcaca tgtgtatctg agacaggcta 171060 tggcttgagt aacatgaact caggtgacat gaggctggtg ccatctcctg tagtcaaggc 171120 tggaaatcca tagagaaggg ctacctcctc ccctgcagag cttctgactg ggtcttccac 171180 cctgtcgtat cttcagccat attgtctgcc tcgcctgcaa gccatcacat ggtagcagca 171240 ttgcctcgcc tgcaagccgt cacatggtag cagcattgcc tcgcctgcaa gccgtcacat 171300 ggtagcagca ttgcctcgcc tgcaagccgt cacatggtag cagcattgcc tcgcatgcaa 171360 gccgtcacat ggtagcagca ttgcctcgca tgcaagccat cacatggtag cagcatttcc 171420 agagaggctt cttacttgca aactgtcaac ctttgctgag actacactgg attcaaaatg 171480 tcattaatgt actggggaca gcttcgttgc tgtgagcgtc ttcctgttca tggctactca 171540 ctgtgatgtg ttcccaaggc tcctcgcctt ctgagagatt ctcttcgtgt cttaaccact 171600 agagagccag gatactcgtg gcctataccc ctgccacagg tgtaaagatc cctggagagt 171660 ttactgaaga tgcagttgtc acactttaag tcagtccttc tgattttctg caggtggatc 171720 tgtctgcttg aacagtcttt ttaatttaga acatagaaca ttgtgagacc ctagggaatc 171780 actaaggcac ggtatctttc ctcaaacttc ccagatttgc tggagaatgg cagagatatg 171840 aaaggaaaag atttagtcat agaagagtag tcatgatcca aaattggaaa atttgtaaag 171900 ggaccttagt ttatttcatt ttgacctcag cgtgcaaatt ggccacttcc ttgcctatcg 171960 tttcacgggg ctctgaaata tgcggtgccg gcaaggtctt gtctgcctct gcacccggct 172020 gagcacggca agtccaagcc cagccgagca cgtgtctgct ctgatagttg ctgcccgagt 172080 gtcagtcgtg ggcatttgct tgatgatttg gtcactgccg ctcctgcttc agagttagaa 172140 agaaagcatc tgtgtcagaa ggaaccagtc agaaagactg ccttacacac tgctttcagt 172200 gcacactgtt gtctcgctga ggggcctcct gagtgaagac ttggtagaac ttcttcctat 172260 agcatctagg gttcaatcca gaggacacgt gtggttgtct ccatgacagt cgccatttct 172320 ctctccaccc agttgtccct gctcacccac atgtgtccca tgcccgtggt gttctcggtt 172380 gtccctgctc acccacccat gtcctgtgcc cttggtgttc ttggttgtcc ctgctcaccc 172440 acccatgtcc atggtgttct ctgccacatt ttgagtacac ttatcaaaaa tcaacagaga 172500 aaagtagggt ttcgttgagt aaaaaacaaa aaagcttgtg agatggctca ttggataaag 172560 gtgcaaggac caaggctgat tcggtcccga ctcaacagac ctgagtttga ccccagaagc 172620 ccacatgggg gaaggaaaga ggccggccac ctcttcacta ggcagctccc agcatttgca 172680 gcatttcgtt ttcatctctc catttagaaa aataaatgtg agattttttt ttctttttcc 172740 aagctgtgcc ttaatcccag cagcactcag gaggtagaga caagggaatc actgtgagtt 172800 atgactctag gccagccata gcttcatagt gagacctgtc taaaaaacca acagcagtcc 172860 ctccaccgct gccagacaac atgtaaaaac ctctctttga accaaagaaa aagtaagcat 172920 acagaggaaa gggtacccca tagaggatga ggacacccca tagactctgt gcaggagtca 172980 ctggccatga gctccacgta cagtaactgt ccacacatct ttggtgtcta gactcctgta 173040 gaaccaggtt gctagctgct agagactttc cacagagctg atgtgctggc ttgaacccgt 173100 aatgcctaca tccaggagac taaggcttct tttcctccac tgccacagga ttcctcacca 173160 gcctgagcta caatgtgtaa gatttttctg gaagaaagcc cctcctccac tatgtgacat 173220 ataaccctag gaataggttc tatgaacctt gattgaccct ctcaggagct tcaaacatgg 173280 gggcactgaa cttgccccct tcctgtcact gcctttgttc tggtagatta gactgtttag 173340 ctcagcctac cccctgcgta gccaaaccat gatctctctt gtcagtgtgt tgctctctgc 173400 ttatgtgata tgacttggca taatttgagg tttggggtct ctaaattgga tgattggtgc 173460 ttaattatca gctgttttgc actgggggca ggggttaaat tgggaatacc tgcttttcac 173520 ccactgcatc atccggttct cttgtggatt cacagaggcc agagcaagag aaccagggat 173580 agacaggagt gatcagaaaa gattgctagg acccgaggag gtaaacagaa aatgcacaca 173640 gctgcttgtg gccatctcta gaatggaatc cactctactg tggaaagaaa ctaaaataga 173700 gatgcccaga cagagaagac tgaagggtcg gctgatctta gggaagttca accaaaactc 173760 tgactcagga tgagagcaaa gaggctctga aaggactgcc catgcagtga gggtcaggag 173820 gcaggatggg ttgcaggcct ctctggagcg ctgacagtgc ggtaacagag ccagccctct 173880 cctcctcctt tcctacaccc ctgtattatt ctctgctcct ttgctggctt tcttcataga 173940 acccaacttt actgttgtct ttgggtctac caagtgagtt gaataactct tgcagggatt 174000 gcgacccttg agcagaggtt ctcaaccttc atgatgctgc agctcctcct tcagtccctc 174060 tcatggtgac ctcccaaaca taaaattatt ttgttacttt atgactggat ttcgctacta 174120 ttatgaatgt aaatagaggt tcttcgaccc ccacaggttg aaagcagctc ttgtagatag 174180 attttgagca cgacttcatc ttcactagcc aaagcttctt gtagctttgg aaaggacaca 174240 gcttgtaaca ctgtctttca cacagattcc ctccctctcc cacacggatt ctgttctggg 174300 gattaaatct ggggtttcat gtgtctcaag actggcctta aactcagatc cacctacctc 174360 tgcctcccaa gagctgagat taaaggtgtg tgcaactact gtttagctag gatttatttt 174420 cttaagagca ctgaatgact agggaaggtt ctgatctagt aaaagctcat gatgcccaaa 174480 ttgctttgtt atatattgtg gctccctaga tgaaggttga ttaaatgggt ttttggggtc 174540 ttgccctctg aaacttaggt gtagggtgac ctctggagcc ttttcttcct cagggatgct 174600 tttcacagtg gctccatagc cttctgagct atcctgggat cctggctgtg accggtctgc 174660 ctttcactcc ctacttatga tggctccaaa gatctatctt cacatacatc tccacccagc 174720 catgtaagaa cagacaagta cacaggctct gtcttagggt tttacttctg tgaacagaca 174780 ccatgaccaa ggcaactctt ataaaggaca tctcattggg gttggcttat aggttcagag 174840 gtttagtcca gtatcatcaa ggtgggagca cagaagcatc caggcaggca tggtgcagtc 174900 ggagctgaga gttctacgtc ttcatctgaa ggctgctagc agaatactgg cttccaggca 174960 gctgagtgtc ttatagccca cacccacagt gacacaccta ctctaacagg gccacacctg 175020 gaaatagtgc tggtccatgg gctaggcata tacaaaccat cacagagccc gtggatcctg 175080 gctaaactga gctcaattcc tgcttctctg ggaagcactc agtatcaaca ctgcatgacg 175140 gagcacgagt gttagtggag tacggtgtga ggacagtggg acactcttgg gaagatgaca 175200 ttcctaggga tagtttttcg tggtgatgag gacaacagct ggagcaaaat gcttattcaa 175260 ctttgccctg gctctcaaga ttttagaaat agcctctgtc gaatgtattt ccaaactgag 175320 ctattatgac catattagtt tccatagttc atgagaaact ttgagtgttt ctataatttc 175380 gtggaacttg cttttttgag ccagcacgtg taatttttct ctgtatgtat gggtgttttg 175440 cctgtgtaca ttgttttgca gtgccccaca aggacaggag agggcgtcta ctctcctggg 175500 actggggata cagcgatagt gtgtgggaat ggaacccagg ccttctggaa aagcagccag 175560 caccatgtat gttttaaaga aatgaaacgt tcataatgag ggaggtatgc agtttggtcc 175620 tttgagaggc tgtttcctct gccccttcct tcagtttcat cctgccattc catccatctg 175680 tccaaaccct gagtcttctg ccccttgttc tgagagctcc taaagcccca ctagtcacag 175740 ttttacttat tggagtgcac ctgtggggtt agatgtgtgt gcaagcatgg gccaggcaca 175800 catgtgaaag ttcggggata actggtgtga gtctgttctt ccatcatgtg gatcccaggg 175860 ttcagaccca tgtggtgagg cttggttctt ggtgctgagc cacctcacta gtcctaaatg 175920 tacttgaaac aagtattttt tattggtatt ggcctttgcc tcgcaaactc ttgctgtaga 175980 agatgaaggt gcagatccac tcacattgaa cagttgggtg atagagagag agctggaggt 176040 gcacacacca caaatttagt ggttgatgcc ctgatgaact tgtttcctct ttgttacctc 176100 ttggtttctt cccttgtgga actgctgggg cagtgtccat gagctttcac tgccagtgtg 176160 gtttagccac cttatttggt tttgtttttc tcaccctttt cctttttgct tctgtaatgt 176220

atctttacac tccttcaggc cctgaccagt gcaatcacag ggatgtaaat tatcggaaag 176280 agatactttg gctaaattgt taaacactca cattgtctta gtcaaggttt ctattcctgc 176340 acaaacatca tgaccaagaa gcaagttggg gaggaaaggg tttattcagc ttactcttcc 176400 acattgctgt tcatcaccaa aggaagtcag gactgaaact caaacaggtc aggaagcagg 176460 agctgatgca gaggccatgg agggatgttc attactggct tgcttcccct ggcttgctca 176520 gcctgctctc ttatagaacc caagattacc agcccaggga tggcaccacc cacaatgggc 176580 cctccccact tgatcactaa ttgagaaaat gccttacagc tggatctcat ggaggcattt 176640 cctcaacgga agctcctttc tctgtgataa ctccagctgt gtcaagttga cacaaagcta 176700 gccagtacac acatgacttc cagtgtccat gttacctgcc agtgaatcca acaggtagtg 176760 tgttaaataa aagttgtttg tgggcataag agagtgagta gatctcttgg acaggcaggt 176820 tctagctagt tttacctagt gacctagtct tctctagtaa ccatctctct tggaaagtgt 176880 agtctttaaa ggagtttgtg ctggctagtt ttatgacaac ttgacacaag atttaatcat 176940 cagagaggat ggagccacac ttgagaaaat gcctccataa tattggtctg taggcaagac 177000 tatagggtat tttcttaatt agtgattgat ggtggagggt ccagcccctt gtgggtggtg 177060 ctatccctgg gcttgtgctc ctgggttcta aagctgagca agccatgggc gtaagccagt 177120 aagcagcact cctccatggc ctctgcttta gctcctgcct ccaggttcct tgccagttca 177180 gttgttgtcc tagctttctt cagtgatgga ctacagtgtg ggagtgtgag ctacagaaac 177240 ccttgcttcc ctcacttgat catggcgttc cattgaagaa tagaaaccct aactaagaca 177300 gaagtgagac caaggcttag ttctctaatg atgggtgtca gtcaggggat atgtgtaggg 177360 tgggaatggc cttgaagttg attgagtttg cttgatttgt gcagaaggaa agtcatgata 177420 tgctaagtag aagctcagtg tcaaaagtga gggaggcaac tcgggtctta ggctcctccc 177480 actgctaaca aagtgcagct gcaggtttag tgtgcacgca cgcacgcagg gcaggtgatc 177540 ctgttgaaaa gatgaacccg ttggagagct caggaaggcc gtgtgttttc tgttagcaga 177600 atgcttccta atgagtagga atgtgctgcc ggtttcacgg agccatatgg caactttgct 177660 aattttagct gggtgcagtt gcctgattct ttccttttgc cttctagaac ctctgagatg 177720 ctgcacaact tttcttgtaa cttttaacct gtgctgcttg gccagacact atgtgtccct 177780 gtttccatga cttctttgtc cctcatgggt ctgtacaggt tgtactgcta ccaagtttca 177840 cagccaggta ctgcatgcaa cacagggcag gcagggcaga agcagtgcgt gtattcccgg 177900 taggatctta gagtctgcta tgcaggtgat tagacttgtg tttgacatca gcccattgaa 177960 aaatcgatag gtttctgagt gaatgctttt actcatttta aagcagtggg attaattata 178020 aaacctgtgt agtgtatctg gttcatttta gcaaaagatt ttaatgttct actctgaata 178080 acttggattc agtttttttt ttttaaaggc agtgctcttc atgcttggcc tgatgtgaaa 178140 gtcattaatt ggctttccag tcgagggtgg atctggtctc gagcacacag ggatttttat 178200 atgtataaat atctgtgcag tatcgtcatc agacaacatg tcacagagtg ggccctagtt 178260 gatgacgtct gtctttttaa agctaatgtt tgtaagcttc tacagccttt tttattgaga 178320 gagagagaga gagagtgagc gttcgcaatt gagcacacac gaaggtgtat atcatcttct 178380 cccgtgatga ttcctcacct catacctgta acgggtactc cagtggtact tgagtttctg 178440 tctgcctgac ggctgccact gctctgctgg agtagagcag tcatgtgact gcccatcaga 178500 gccaaggctg ccatccctct attctgaagg gagggaccct ctattctggc agtgttttat 178560 ggaaagacta cacttaaatg ttctcagtac acttggctaa taaacaaata cacaatacta 178620 atataaaaaa gcattagtta ccaccacaga ccaatgaata tacctcagag gaatctaaaa 178680 aaaaataaaa ctatttcata attcccaaat agctcatatg ttttctttta aaatgaattg 178740 ttttttacaa agctgtattt ttgatttatt gctgttctca ccagaatctg ggattttgct 178800 ttcagacttc tcctcgtgca tggcagtgac gaagagcaat ttaatccatc cacttcaaag 178860 aaatgttttt cctgcattaa gtcagtttta tttctagaga tcaaatgccc caccttttct 178920 tttgttctta gagaaagcac aaataataat tacttatgaa aaataggaat ttaatattaa 178980 tgatttcccc ccgtttgcag tatgactcat cttacacagt ccctgaagag acaggatttg 179040 ttctctgctt tgaaactgga aatctaatta attggtatta gatttttgga gtacaggcaa 179100 atggaagagg gagagggtgg gacatcggga acagccaccc aggaggacaa gggtgggcaa 179160 aggtagagaa agggttggtg ggagggctgt cctgccaggg cttggcgttt gtaaagcaga 179220 gctgtgacat agctgttcta tgcttttcag aaatcttctg gagagcattg tgccttcgct 179280 gtcactctct caagtcagag tctttatcta aagaacacgg ccggaatggc taagacacag 179340 cagggacatg tgaagtcaaa gcacagaggg actctggaat ttaaatgtta gcatctcttt 179400 ctctgatgtt gtgatgagat ttcataaggt tgtgatcatg gaaaatctgg taccagcctt 179460 ccactggttc ctctaccaaa gggtattttt ataacaatgt atttttatag ttaatggatg 179520 aagaaaacta aatatagttc ataaccactg agaaaattgc ctaatttaaa atattaaatg 179580 gtgtgtttta gtatagaaat gctgtactta cggaagtata aatatctaag aatcaaagct 179640 tatttttata tgctgcatac aaatggctta ctcattgctg cactgtctga gatacagcac 179700 atgtccagtt aacatacagt tagtcccaga ggagagctcc tcacccctcc cccagctccc 179760 tcctcctccc tcctctgctt tgcctcccta cctctgcagc tcttatttaa tgtcaaggcc 179820 gaactgaata ttgggcagaa gtggcaagta cttcatgaaa aagtacaaat actgaaaatt 179880 caggacaagt tttttgttta ttacaattgc tttagtaaag ctgggtttct gggtattttg 179940 tatcacttgt tattattgac tagtttttat tattttacta ctgagaagtg gcccaaacgt 180000 aaactcaatg cagaactgaa gaaccttaca acagattgtc tagaaaatgc attccaaaca 180060 gtgaggtgta caggactgcg aagctgggtt ttccctgcca gagactttct ggagacgctc 180120 tcaggctcca caccgcttgc cttgtcgtgg ttctgcacac ccgagtgatc tttaaagtta 180180 catgctccac taatacaact tcagcctaat actgaacatt gtttctttgg tcctcactac 180240 acctctagtt ttggtcattt ggggacacca gaatattggc ttttttcaca gtggggtagc 180300 agcagcgata gtgcacgcct ctgatcccac tacttggaag gcagaggcaa gtagccaagc 180360 ctggtctaca gagcaagttc caggacagtc agggtcacac agagaaactg tttctcaaaa 180420 aaacacaaaa aacaaaaaaa gagaaaagag gaatattgtt tgaaggcctg cctgagactt 180480 gtggtggtct tctgccactg gtccacaggt ctaaccccta gaatctaacc taaccaatct 180540 taacattcat gaaacacagc cacccatgcc cagccatccc tcccttctct gaactaaagt 180600 tggctcctta cggctcaagc cttcattttc ctcttctgct gaatgacacg tgttctgccc 180660 tcctggaagc attgtgaact actggccaat aaggactacc ttgacacacc acccactcac 180720 ccactccaag gccctcgggc tgtattccac tgcctatgtg ggctgtgatg ttagaatcac 180780 ctgctgcctt tttcctttta aagatttacc aggtgagtat taaaaggaga aaacagcata 180840 ttttgttatt ataaacagtt ttccagtatg gtacctattt ttatccaagt gttccaaagt 180900 ctctcctagc ccttgttccg tgttctatct gattgataag tttctaaaaa gaaacttgtg 180960 tgctgatttg ctcttggttc tttgtatctg tcttttccta aaggtgtaaa atggtctgtt 181020 tgagcatatt gctgcaacag ttagttacac acccaggcct ggagtttata agtggcaggg 181080 gtacttgcct gattgagttg tcataaggaa agttgtgtac tttacacaga actactaata 181140 gatgaattta ctgctatcag aaagctatca taccctttag atatatgtct cataaagtct 181200 aatgattgct caagggctat gacaaacatc actaagatgt gtttatttga ccctcaaaac 181260 aacaatagta ctccactgaa agaagcgatc agaatctcct ctgaccataa ccttaggttt 181320 tctagcaggt gattttaaaa actggagaag gagtctgagc accagccctc actctttgcc 181380 ccctaactct aggtcatggc cagctgcctt aggctctgcc ctcagactac agtggtcctc 181440 aacactgcct tcctgtgtgt catgagctag gtcaactttg attccttgtc aggttatttt 181500 tgttcaatga tgacaaaaat atctaataca catggtaaca tatttgagag gtattttctt 181560 tgatactagt ttttatactc ttaagttcaa gtagtagtat tttattccat tagggagaaa 181620 atgttgtttg ttttagatta aaacttttta agggctaggg agaaggatcg caggtgagag 181680 cccgggctgc tcttgtagct gtcagtaaca ggcacggagt tcccattcac agcaactgca 181740 gcttcatctc tcactggatc ccccaacatt accgtcagcc aagtgccccc ccacacacac 181800 actccttctc taacccggag cctcacattt accaccaagc tgcatgcctg acccaagtcc 181860 aaggaataag atagagattt aacagtggag gatgaactga gagaagagca gaggcgtggg 181920 aatttaccgt gtccacacaa atgtctctct gtagagcaat tctctggaaa ccctgcgccg 181980 tactcctcaa ccctgcccct cgccttgctt tctaggcttg agctgcaccc tgaagtggag 182040 ctcagagggg aataactttc cattccacca accttcgaat tcactaactc tcactgtgcc 182100 caggccaggg acagccctct ttgtcggcca aacagagtga cattcctggc ctacagtgct 182160 ggctgttgaa gatacagatg tcctgttctg gcttactaat ctgccttcag tgcagcggca 182220 ttcgttctgt tttatggact gagaagacaa gagcactcag gcatcctcta gagcgttggt 182280 tctcaccctg tgagccatgg tccctttgca ggggaatgac ccttactctg gggtcaccta 182340 agaccagtgg aaaacaaaaa tgtacattat gattcctaac cgtagcaaaa gtagagctag 182400 gaagtagcaa tgaagataat ttagagtggg ggtcgccaca ccatgagcag ctgtatcaaa 182460 ggctgacagc attaggaagg tcgagaccca ctgctctgga tgcatatcgg actgatggaa 182520 ggcaagccct ctagtctgtg cccgtgtccc ctacagtctg aaaccttggg aggacacctc 182580 ttgtgtatcc ttctgccaga ggatatatct aggaggacac accccacaga cagtgagggg 182640 cacaggaaag gacaccgtgt gctccatctg agcaagggtt gtcagcacct cgctcctcca 182700 cactgaagag taaaactaag ggtgcacggg gagggcctca aacccacaca gaacatagtg 182760 catgcttcag aatcgatgac tcgtgggagc tcagtgccaa gcatgcaggt tcccttgtaa 182820 ggcggtgacc gctctgcagt gcccagagaa gtaggtaagg gatgtggtgg cacaggtctg 182880 ggtcctgtgc ttctaggtgg aagagtgagg gtctgactaa aaaccagcgt ccctgtcttt 182940 gggatttacc agagagaagg gagtcctata cagtaacaat agcagccagt cctatgtcct 183000 atgattggag aagagggtgt ttcctgcgct ctgaggacca ctaggatgag tcagagcctg 183060 tggagaggcg acttttaggg agctcttagg gaagagagca aaccacgcca caggtaagac 183120 ggtagaggaa ccaagagaag tgggcacagt gtgtggccgg tcagctctct gaagaaaacg 183180 cagtgtgatg ctctttgaga agaccagagt gcacccagtg cttgtggtta gcagttgtcg 183240 catgaggaag gatggagagc cgaggacagc ctggggagga ggttctttcc tactttgtag 183300 tttctgaagt gtgttttaca tctgtcattg acatagccat gatgcacagg tggcagacac 183360 tgacacttgg tttgcctcgt tctgaactgt ggtgctaata atggactcaa gccggagcta 183420 caatcttctt tgtctactgg caaatagaca tcataaacac tttccattgg gagcagaaag 183480 atttggagga tctacataat tccctaatta tttttaggtt ccataaatta gactttaaca 183540 gattttttta aatactgcat aaaattgttt tttacaaaga aaatagttac tatggtcagg 183600 gaaaagcaag ttgattgtga atactaaatt gagttacagt ttcgtttgaa tctttaattt 183660 ttttacattt aattataatg aaaacatgca gcgtaaacaa ggatgtaatt tattcagttt 183720

acatgtaatt ggcacattgc ttttgtgttg ttttctaaca ggttgtggct gtgtatgtta 183780 tgctgtaaac ttacttgcca tccttgaagg agctcatttg cacatgtatt gatagctatg 183840 catcttttcc cctgtaagca actactctaa tgctgatggc acgggctgga gagatggctc 183900 aattgttaag agcactgact gctcttccag aggtcctgag ttcaattccc agcaaccaca 183960 tggtggctca caaccatctg taatgagatc tggtgccctc ttctggtgtg tctgaagata 184020 gctacaatgt attcatatat atatataaaa taaataaata aatagatttt aaaaaaaaat 184080 gctgatggca cgacttcagc gctgtctggg agtttgagtc ctggagtgct cgctgtccag 184140 ctcctctgta caaagtcaaa gctcagccat tgacatcctc tgagcgcctg atggggctgc 184200 tcaccccatc tgcgttgagt cattgagtgc tgtgagcagg ccaggtcaag gctctgaact 184260 cggagcaaga ggacctcacc ccaccccctt ataattgtgc cataggatgc tcagcttcat 184320 aatctatatt ttgaaaatgt ctgccaggaa cagcatgaac cctctaaact cattttctcc 184380 agagcctgaa aggaaatctg atacatgtat tctggaggtg agaggtgcca tctgggtcct 184440 cctcctagcc agtcccgccc tccagggcag ttggctgcac tctaattcat tcataggcac 184500 acctgacccc agcagagatt ttggtgttga tgtgcccttg gtgtgcacca ctatttaatt 184560 tgctcttgtg ttttgttgca gagaaagcag cagctgccaa catagatgaa gtgcagaagt 184620 cagatgtgtc gtccacgggg cagggtgtca tcgacaagga tgcactgggg cccatgatgc 184680 ttgaggtaac cacagcctta cctggttttg atgcttggag taccacgctc ccgtggcttt 184740 gtatcacaca tgtttcagta ttcatgtgct gcatttatgt atgttcaggt acatatgatt 184800 taaggagaat ccacattgct gtgcttactg atgcaagtgg gaatgtctat ctgtgagctc 184860 ttgccccagc aacattctct gtatgtggaa cagcatagac ttcaattaga tgaaaatacg 184920 aagtgcaggt gtgaattgtc agttgagcac ttattttctg aagctgaact tggacgtcct 184980 attgaagggt gggactcttg cctcaggctc agggttcctg tgtgccacat gcctcggcct 185040 gtgtagacgg tttaaaatgt gagagccaac aaaacgaggg ttatgctttt tagggctggt 185100 aattccaact agtatgtttt tctcatagaa gtcaaggtta aaataggaag aaggaacttt 185160 ttaaaagcat aaccgagtga ctggccttag ggccttaggg cagctactgt ctcaggctta 185220 taaaatcctc cttgtttttt taatgagtac taaacaccca gtgctttact gtccctcttt 185280 caaagttaaa attcaagatg tgggctatgg taaaatgaga gaagaaatag cagtgaatag 185340 acagagctgc ctgagacata aattatctca agtctcgtgg cgctctgctc tgctgaagac 185400 attctaagcg taaaggacca cgtggtcaga accgcggcgt tgtgcctgct ctgtgcctgc 185460 tgcagcaggc ttgtggattc aggactagga ttttttaaac aaagctagtt ggcactctct 185520 tgaccttact gtcccctttc tcatctagaa acgctaaatc tgcaggtatg tcctgtgtag 185580 ttgggagctc gcctttgcat taacaactaa cagctcatcc ctagggggca gaggggcact 185640 tcccacacac tgtaggagcg ggaaagaaag ctgtggccag gtgaccactt agaattacat 185700 aaaagagccg aggaggacag ctttctttag aaaaccttgt gaattgtaag cagagattta 185760 attggaattt ttccatataa ctgtttattc attatgcctc ggggagtggg aaatagcact 185820 gaaaccccaa ggaggacttt gaggccttta aaaagaaacg cttagagcaa ggcaggctgt 185880 ggcttagccc ttgcaacaag ttcattaatt gtagaaactg gattgcagga tggcagtggc 185940 ccttatttca taaaatcaaa ccaaaatttt tgctgtttga aaataatctt ctgagaatga 186000 gtggagtgca ttgaggaagc gcctgtgcaa gctgagtact aagtcagcgt gccagagagg 186060 aagctccggg atctagtggc ttacggctta actggagacc tttcaacagg gagagcatgt 186120 gtgtgctcgg agagctgttc ctaggcatag atgcacactc atgcttgcat catagcatag 186180 cggttgctag gcaacagaag caaatgtcag ctcttgccat cagagcatat catagtgagc 186240 tttaaaaaac acagttttat aaaacgagcc actttcattt ttcaatttta ttaggccaca 186300 aatgagcctt ctcaccatac tctaagaagc cacatgccct ttcaaagcca acactagtaa 186360 tgtagtattg aaagcctaag aactctgctg aacgaacacc cagcggtggc agtagtgaga 186420 agtaacaaga gatctgtaag tgccatgtgc tgttgctgtg cctctccagt gtacacagct 186480 tagtgcagcc tgtgttgttg gccacttagg tttctagagt cttgctttac cctgaatgtg 186540 catcatgcta tagagaaaac ctgacagact agttaaggaa agtctaaagc cagtgggttt 186600 ttttgtttgc tttggtttgg gtttcattgt tgttcgcttt tttgctgtta ttattacaag 186660 acaggtcctt gacctttagt ccagactggc cttgttcttc tactgtagcc caggtattaa 186720 gatagctgat gccatcacac ccagtttact ttttctttaa acaacttctt atttataccc 186780 cagaatcagt tttagattga tggaaatcta gtctgacaaa acagaagcct tttatataaa 186840 cagccttggg tggaccaagc attccggcca tccctcacca ccgtgtgggg actgggcatg 186900 ctttaaatgc agtagatatg tatctgaaga gcctaagtgg catcagctga ctgggaattt 186960 agctttgaag gtgtccaggt cttcttagac tgtgaaggga aactctgctc tgttctgaac 187020 aagcatcaga tgtaggagag acacggagct gccattgcca gggcagacca gaaggagtct 187080 taccaggaga agtatctgag ctcctggagt cgctagcgga ctatgtgcaa ttttccttcc 187140 ataacccctg atcccctctg tgccttggag aagagggcct tgggaggaca cagtatgccc 187200 acagcagagt gaacatgccc acagctgctg tttaccttct cttcctaaag tgtggagacc 187260 agtctctttc tggagtctag acatggtggg cacatggagt gacagtgagc ccgttatagc 187320 atgcaggcaa ccagcactga gctgttttag ccacccccaa gacacttagc ccgtagcacc 187380 gtccccattc acctacctgg ccagagagcc tacccagatc cttccctaca caccagacag 187440 taaaggccgg atgttgcttt gaaggtctgc gaccatctgt gagttcactt aaatcctggc 187500 caccttaaaa gtaaaaatta ggggatttct cctgatattt ttaaactgag gggaaaaggt 187560 agcagcagcc cctttctctc ttggcatatg ccctgactcc tgcacttagc cctgtggtac 187620 tcccccatcc tgctttgttt atttggccat agttctcttc tggcaggtta acagacttca 187680 tgtttctttt ttggttttaa cagcagaccc taatctagcc tctcttccac tataatggaa 187740 tcacttctat ttccccagag aacatgtgtt cattgtttct gaagggcatc ggagatttct 187800 ttccttgaag aatcagttcc cccatgacag ctgcatgttt ttatgttgtt gcaccctgta 187860 ggccctcgat gggttcttct tcgttgtgaa cctggaaggc agtgtggtgt tcgtgtcaga 187920 gaatgtgaca cagtatctac ggtataacca agaagagctg atgaacaaga gtgtctacag 187980 catcctgcat gtcggggacc acactgaatt tgtcaagaac ctgctgccaa agtccatggg 188040 taaatgtcag tggatcccgc tgccccccac tactccaaca gattctcttg gtgagagtga 188100 gtcagtaaag cctgttgtgt ctgtcatagg catgtcagca accgtaagca ttcaggtagt 188160 catggaaggc tgccgatgct gctccttaat gcactgttga tcttatgagt tgtggaatga 188220 tgcaggcgga aggcccccag caactagcag gagggtttgt tatattttaa aacaaattgc 188280 aaccttccct ctctgcccac caacttgatc atccattttg cttctcgcct gccatcaaaa 188340 gagtgggcca tgacatgttt gagatttgac tcccttgagt tctatgtata agaagaatat 188400 gtgtgtatgg ggcattctga aaacagacac aggcacaatg taacagacag tgactccaga 188460 ggactggttc atgttagtct cctgagcagc tctgcaggtg gcattgcagg gcacagcccc 188520 tcagcccttc atgcccgtcc atctgtccct ccgttgttcc actttcccca agtttcttga 188580 cctctatcct tctttggagg attctgttca gaggttgcct gtggtgcagg ccgccgttgg 188640 cagtgagtgc ctggcagcgt ggagctgcct tagagggttg ctgttcactc ttagtggttc 188700 cttagtgttg tcactgttag ggatattttc acaggtaaaa cacagtacat atttcagtgc 188760 ttaggaaggt cattcctgga ttgcaagtat tctttttctt gaaactgttt gtatgtgcta 188820 gtcttatagt taaccagtaa atggggaaag atccttttta tttaccatta tggctagttt 188880 tgcttcatga ggataaaaca tttgcaaacg cagccgtcct ccaagatgtg tgagcacttg 188940 tgtggaattc ttctgtttca gaagagtgga tttcatagtt gaagtaacca attttcttca 189000 gggattttct gttgctcaaa ggacttgtgc ttgttacctc ctgtctgaag acccctcccc 189060 ctggcctcac gcaccttttc tttagtttcc acttcttagt gtgggctgat aagcatgttt 189120 tcctttcttc ttggacagtt ctgtagcgtc tcattatgtt aatagatttc acaaatgctg 189180 atagactaaa ggtagaggtg taaaggtacc tggatgacca gagcagtggg caggcaagtg 189240 accttggctt cctgctctct gagtggtttt ccttccagcc tgtgagcaag ccttggcctg 189300 ggtccactgt ggcatctctg tccctgtcac ctgttaggcc aatgactgct tttcataagg 189360 ttgccatttc attgggggat ggtaaagaaa agcattaagg tggttttact tggggcactt 189420 ctgacaactc acatttctct ggaggagaaa ttaacacttg atcaattaac actctttagt 189480 aacccacatt agtcattctt ttctttcttt tgtttttttc tctaatgtgt ttcagaaggt 189540 attgatgtat ttcccttcgt taagcagctc ttctttcttt tcattactca tttcctttac 189600 atcccagtat cggcctcccc tcgcctccca ttcccccaca attgttttta attttgacac 189660 taaaacaaga cagcatcact tgacacagta tcagcacttt gtctttaaga atgttcagtc 189720 ccactaagga agtctatatg aaccctaagg tagtctatag actgtaattg ggtggctcag 189780 gaacagctcg ttagagacaa cactctaaag tttatttgag aagtttgaca gcagcgtgtg 189840 tcagaggagg cccaagaagc tgggttgtgt ccagtagagc gagcaccctg ccatgctctg 189900 ctgtgctcag aagggagaag ctcagtggaa gcagcaggag cagacatcca tgtggggctg 189960 agggtggagt gtggacagcc tggccagctg ggcaggtggc tatcagcgag gtttgcatta 190020 tatgttgagg ttgctctcag gctaactcct accgtccgag tcctctggaa aacatcagtg 190080 cttgtcacag tcagtgccat tcccaaagtt ttaagcagta tttgcacctt gaaaaccaga 190140 atgcaagcag actgaactat atttccaaga aatcaaagat agaaacccaa aaatagagtg 190200 tgcagtattt tagtactatg tagtcagggt gtggccttga atagaagtgg tcatggtgga 190260 ggctctggag tatagaagat gtctgcaaag cccaagttcc taccaaggag gtaggaagtc 190320 cttgtgctct ccctgcaccc tcttagcaat gcagcagccc tggaacctat cgctccttgt 190380 gatcaggtgt ctctttcccc cctcgcagtg aatggaggat cctggtctgg agaacctccc 190440 aggcggagca gccatacctt caactgtcgc atgctggtga agcctttgcc agattcagaa 190500 gaggaaggcc atgatagcca ggaagcccat cagaaatacg aggcgatgca gtgcttcgct 190560 gtgtctcagc ccaagtccat caaagaggaa ggcgaaggta ggacgaccct gggagagaga 190620 ggtcacgtgt ctgcacctcc ctcctgtgca cgactctggc ttagtgatca caccctggca 190680 ggcgctcaca gagaagacca ggaagccact tcctgattcc ttcccatctt tattcgtttt 190740 gagcttctgt tgtttttttt tttcctctac aacattagac gttgaactct cacatgctaa 190800 gccgtgttgt cctctgagct gttctcagtt tgaaaatgct ctgtagtgat gtaagtggcc 190860 agtgcaggcc cagcacagca gccaggattc atatctgagg ccggcatttg aagctgcagc 190920 agggttgatt tcagttaagt gcttatgtac atagcatgtg ctcctggtga ctgtggcact 190980 tctgcacccc tgacagtagc agtttaggag atcctgggtt gctttgaata tctaatgtaa 191040 atcgtatgcc acagccccca aaaaacatgc ctgggtataa gcagcatttt tctatagact 191100 ttccagggag taacagaatg catgtaatta tctgtgcaca ccaggccttc aatgtgatat 191160 aacagcagag aggacaaaca gaagagcagg ggctggtgag ctctcagcaa ctgacagggt 191220 tgctccccat aatgagatgc tgatgtcata ccattccctg ccttccagtc actaagtgtc 191280

cctctgtagt gtaagatgtt ggtagaaaaa gcactctggg agttacagag ggaaacagct 191340 tttgactagc agtgcaatga aatattctag cagataatta ggcagaccaa cccccaattc 191400 agccatcagt tccgcctctg gacaaatgcc ttcacttctc tgtgtatcaa tgtattaagt 191460 caaattacca gtgtgagcat cagaatctgg tacagaatgg gcggcgtggg actccggggt 191520 ggaatactta cctgatatac gacaccctga gttctgttct cagcttgtgt gcacacacac 191580 acaaagggct tatgacaatg gctgaactat agtagccact gaatactaat gtagtactgc 191640 ttaattaaaa tgtgtaactg ttcttaaatt ttatcagaaa ggaattccag agagctatta 191700 tagagatacg gtatttcaaa atgaaccttt gctcaggtgt gactgtcaga cagtttgctt 191760 ctgttcaccc aacaagagag agcgacactg cagaatcatc cttggtagtc cacaggaaag 191820 tgaggcacag ccgtgctacc tgactgctct gcactggaga cgaaaatgga ttctggttga 191880 gatggagcct ggttggtgaa gtgcttgcct agaacgcaca aacgcctagg ttcagcccct 191940 aaagcacata gaatcagtca ttgtacccct ctaatcctag actcgggaga tagccaggtg 192000 agttagaata gtgagcgtca gcaagtgtga cgcccagcca agacgtagca gactctgtct 192060 ataaattcat tagttagttc atgaatgaga ttggattttc cggcagagtg tggtggtgca 192120 cacctctgat cctggcactc aggtgggatc gggtgcattt atgtggtaac tacaacttca 192180 gtgatcccag cacgggataa aggtgggagt cccggtaagc gacagagacc agcccgctct 192240 acaactgagt tgcaggggag gcagaggggc atagcaagac ccttgccttt aaaaaaaaaa 192300 aaaactgtat gtttataaaa aaacaagggc ttcttttctt tttcttcttc tttcttttat 192360 tgtagctaaa atactcatgg ccttacacat ggtagaaggt tcaaccactg acccacatat 192420 cccacttccc atggtgatta cattttaacc taaagacact agccattact tgagatctac 192480 ctgctcccaa aaaaaaagac aggaagcttc ccaagtttac aggggaccga gtgcagcccg 192540 tggcgggaga tgtgtgaaga gcctgcttgc ttttagccct ttggtcggcc ttcctctttt 192600 agcttgaaag agccatacga agtgctctac atgctacaca cttgttctcc agaagtaagc 192660 cccacgcaaa acacaatgaa agtgggggct ggagagatgt cggcagttag gagcactcgc 192720 tgtccttcca caggacctct gttcagttcc cagcacccac gtggtagttc acaaccatct 192780 gtaagtccag tcccagggga tctgtcagcc tcttccggac tccacaggca ccaggcctgt 192840 aagttataca cagacacata tacaggcaaa acatctatac aaataagtaa cattttaaag 192900 cgttcacgtg gggacaaggc taacccttac cactggctgt ggaggaactg gccatgtcgg 192960 atgctggcta caacagtgac tgctgcatgg acagtacact gtatccttga tcattgttgt 193020 gcaccctcgg tccatggcat cttgccatct tcatgaacct acatggtttg ttaagtataa 193080 ccgtgaagct gagaagcaga acccttccca actgtgtctg gtcttagttc tagctttttg 193140 ttttgcttac tttattatga attaattttg cttttacacc cagtggctcc atacttttca 193200 tcattgggga ggtggtttcc agtcattaac cctggcttgg tgaatagact cttaccacga 193260 gtgctgtgta gtttcggcat ctgcccctgc tccagctcat cctaacagcc ggcttccact 193320 atactcaagc agagaatgaa gccagtgaga agctgagaac catggcaact cattgattca 193380 ccaggctgtg ctgtcataga tatttgagtt gatttgatca ctacaaatat gataaacaat 193440 tgtgtcctct taagatttgc agtcctgctt gatttgtgtg gcacgaagag tccccatgaa 193500 ggaaagacca actcttccct catcagaaag ctttaccacc cgccaggacc tccaaggtaa 193560 attcctgtca gagaagacaa aagtggtcgc ttgaaaatgc ataggtacct gaacacagtg 193620 cctgtctgga ggaccacagt gttcctcagc ggttgcagtg gtgaccttta gctgctgaga 193680 agcagcagcc ctctttcttc accatgctcc ctcctggagc tgtatttagg ctgccatctc 193740 caaacagcag ttctgtctct atgtggtcca ccaaccccag aacagaatga ctttaaaaga 193800 tcattgttct gtgtagaatg tgatattaat tagagatgac ttgcagtatt gggggtgaag 193860 ggagctaggc atgctagcac aggtctgaaa ccatgtcagg aagtaaggcc gagttccaga 193920 ccatcctgga ctctacaaga tctgtctaaa aatcagagat aattaagatg aataaaatag 193980 aaaggacaca ggacgataga gtcagctgta taaactgtgc cattttacat gaatccagtc 194040 cccacagata cagcccataa ctgtgagtaa atctatgtat tcctaagtgg taattgtttc 194100 tctggaaaat tggtgttata attgtaatgt ctgctgttat ctttcaggca agatcacttc 194160 actggacact agcaccatga gagccgccat gaagccgggc tgggaagatc tggtaagaag 194220 atgcattcag aagttccaca cacagcatga aggggagtct ctatcatatg ccaagaggca 194280 tcaccatgaa ggtaggcctc tctgcatact actctatgca gcctttacac atttgcttcc 194340 tgtggggacc gtctaccgaa gctcgcagtt cagggcttct atgtcctctg ctggtgctcc 194400 ccggcccagt acactacttg aggaaataaa gtaagaggtc ttgatatcac aaagatggag 194460 aaagaggtca ttttctgtgg tcctcatact tctggataca tgacaagata accaaggtct 194520 gtgtaattta agaaacagga ccaagttcat aagagcaatc tggaaggaag aatatataga 194580 tgggattttc aagagccagt caatcccaag ctctccttca taattcgaac agcagattcc 194640 agaagtttgc agaaggcctg gagaggcaac gggctctgct cttggtcaca gactaaaaga 194700 acagctggaa ggaaactcaa cactgccatt gcatggcctg gtcctccttt gtcttctcct 194760 caccccacac caagcctctg agagacgccc cacctacctg tgcacgttac aggtgttggg 194820 tggcacaggg tcctggccag catgtgctcc acagcccgtg agggactcag ggcagaccaa 194880 ggctctcggt ctcagcatgg accattgtct gctctgcaga agaaagtctt aagtcatctg 194940 tggcaaatgg agctgtagtt tgtcatccag ttagtgtgca tctatggcct tggctttcta 195000 accagtcagg tttgtacgtt gaagctttat gcttttgagg ccacttcatg agaaagcaca 195060 gacatagtaa atgtacaccg actaatctat ttgctcccca cacctgcatc tttttcaccc 195120 taatttcttg aaaattaaac aaataatcaa acattttgta ccttccaatg ttgtctagaa 195180 taagggcaaa tatatacagt acatttaaca gaaatcaata tttaacctgg tgtttcatta 195240 aataaaggct tggaatagaa gcagaaatta aagagatgcc cttagcaaac atgttcagtg 195300 ccgctgggtt ccaagtgccc tacatttaat tacctagacg ggggctctgt tgtgtttaga 195360 gagatgggat ccactgaaag gaaactgcac atagatgtac aaaacaggga atgcagagcc 195420 cagggtgata gctcactcag taagaggact tcctggctag tcatgaggac ctgagttcag 195480 atccccaaga gcgtacttaa agataaaggt gtgcttgctt gctcacctct aaccccatac 195540 tgtggaaggt tggggtggga ttgctagggc acatacaggt gcacacacca tatgtacaca 195600 ctcatacaca cccccacaaa agtgactatg aatagccact tttaaaagaa acttgtaatg 195660 ctaggagctg ccccctgcat ctagtagaaa tgttctagaa ggttttcctt gagttggggg 195720 gcatctccgg ctcaggaaca ggcaggtgtg ctgactcatt attgctgcat agtatgcaga 195780 ccaaatggaa cgtcttcaga gatcacagcc aagggcagag gaaaatcgaa agtcataagc 195840 ccgagtcctt tacacagctg tatttctgtt acctttccac aaatgcttat tgtacaaagc 195900 acagcataca tagaacagga agtgatcccc agagcagcca cttcagcatc cctgcaggca 195960 gcagaggaca gcagccagcc atgtcccagt accctagctc cctgaggtta tagaggaagg 196020 cgctgtttga cagagtgaag ccttacggag aaatcagaga cctctcccct acctgtaatt 196080 ctctggcctg gccaccttgg ggcgagtagt tcaacccacc aaatctgtgt gacaactacg 196140 ttagaaacat gatacttttc ttaaaatcat ttaagaagca actgagtttt aacatttttt 196200 tcctgaatcg aagtcttctt tttgtgtgaa atgtttgtta tgaaatacag ttctataaat 196260 ctcaagatta ttttaagaga aaatacatta agccagttga tttactttgt atttcttgtc 196320 ttaacaatag aagtattggg agctggagag atggctcagc ggttaagagc actgactgct 196380 ctacctaaat tcaaatccca gcaaccacat ggtggttcac aaccatctgt agtgagatct 196440 gacaccctct tctggggtgt ctgaagacag ctatggtata cttagatata ataataaata 196500 aatctttatt tttttttatt tatttattta ttttatttta ttttattttt tggtttttcg 196560 agacagggtt tccctgtgta gccctggctg tcctggaact cgctctgtag accaggctgg 196620 cctcgaactc agaaatccac ctgcctctgc ctcccgagtg ctgggattaa aggcgtacac 196680 caccacgccc agcataaatc ttaaaaaaaa aaatagaagt atctgacctt tctgaaaaca 196740 ttaaagcaat tacactggct taggtctgtg cttgggtttc aggtatgttt agcgctttcg 196800 cctgacacac aatgcttttc agttttacta ctacaccgtg agaagaagca aagcctagca 196860 aagcagtgtg aggcggtggg ccggggaggt cgcctgagga cgagcgttcc atccgacact 196920 gcaaaggaaa gcagaggcag actgtcctta gacacaccat gcttgggggt tatgttgctt 196980 tcatggtgtt tttaatatta ttaagaaatt atggaaaggc ttattttgac ctgataaact 197040 gtttatactc tctttgcccc ataataataa tttgatttaa gaaagtttat ttagggtgcg 197100 agggagctag cccagagaga ggttaagaga gcactggctg ctcttcttga ccactcaggc 197160 tcacgttcat cagcgtccta catagattgg gtttacatac atgactcgta actcccagtt 197220 accacttaac atatagtttg tggcaaaata cacaaaatta aaaataaaaa caaattttta 197280 aaaataaagg atagtttgag tttccaagct gttattcttt gtcatacaaa aaaacaaaaa 197340 caaaaaccca cctaattcac tgtttggtat ttttaaaagt aactgctttt taaatggatg 197400 ttttctgacc tgtaactttt aacatactgg tagcaaaacc agtgaggtca atcactgttg 197460 tgccttgtca cactttcctt gacacttgac tccacttttc tgattttttt cccctttctt 197520 tagctttttg ttctaatcat gctttgtttc cttttttgcc tgcagttctg agacaagggt 197580 tggcgttcag tcagatctat cgtttttctt tgtctgatgg cactctcgtt gctgcacaaa 197640 ccaagagcaa actcatccgt tctcagacta ctaatgagcc tcagcttgta atatctttac 197700 acatgcttca caggtaatca taaactcagc ctcggtttcc catcccttgt cgagagatgt 197760 gctacaaagc agtatgccac ccaaatgcct ctcgggttcc cggaatcctc cttttttgac 197820 tatggcatta taaactgtca aatgagatgg ctgttaactg tcggctagaa accactgcac 197880 ggtgccagca aagcattttc ctttaacatt aggaactaca gcatcagatt gggtgtggtg 197940 gtgcactcct tagtcccaac acttggaggc agaggcaggt gaatctctga gagttctagg 198000 ccagcctgat ctactcagca aagtccacga cagccaggac tacatagaga gatcctgtct 198060 caaacaaaca aaagcagaag aagagtgccc agggcttggc tggaccttcc tgttacagtc 198120 cagaagggaa gttcccgagc agtacagtga ggacaggaac attaaagcca gtgctaagat 198180 ctctgatcct ggatgcttaa tccttcacat gagtattctt agactagttt tgatttttgt 198240 tcttgggttt aatttctttg cattagactt taaattgagt ggttttccta tagtaaaaga 198300 aagaaacatg aatgttgatt ttaaaataaa tgtcatagag catattgttt aagatactca 198360 tttgggaaaa tgattgaatt tcaaatttta taaatgttta tggatatgct gagggaaact 198420 ttacgaggtg ctgccaagag atatctacag ttgctctgct taaagagtgc cagtttatta 198480 gatttctcat ttattttgct ttctaggaga ggaataaaac tcaggtaggc ctggttgcca 198540 gctaatagta aagctgccct cacgctgcag ccctttgaaa gtggttatga ggcgcagact 198600 tcaccctgcc ccagctcagc tgccgtttga tgaccactga acatgtttgc taactcagaa 198660 gtagctgcca agactgaggc aaaagccctg gggcctggga gacctgctta taggtgtcag 198720 ggaagtggat tcaaattttc ctggaatgac ggccagttaa aatcacaaac tctgtcaccc 198780

cagaacccta ccacaccaca tttaatcctt tggcctgcag ggagttgagg agatgggcag 198840 gaacctatga ggcaacttga tattactaat acctgcatct ggaactggcc atctctctaa 198900 cagttagggc aaggtgttcc ccactaaggc ctctgtctac cgtgaacagg tgacacctat 198960 cagcacctct aggcctacag atgtgcccac agctacagat gtgcccacag ctacagatgt 199020 gcccacagct acagatgtgc ccacagctgg gagccgaagc tgtggcaaag ggttaaatca 199080 agcagtactt atgtggtcgt ttgtgtaagg ctgtggaagt tctcagtgat catcggggag 199140 atgcatattt gagatcttcc taatgtcctc tttacttact gaaatttcaa tatgggggta 199200 gtctaattta agctccatac acacacttca gtaaaaccac agacatcttg gtacgttgcc 199260 tgaaagcatc ccttagtcca gagctgtaca tgttcagtct agcccataag atgccataag 199320 gcatctttta aatgtagtcc acttttgtaa agaaaagagt ccctgccatt tttttaatta 199380 ataagtttac tttgtatttc tcttttatct tatatatgtt tctttcctca ttgtacagag 199440 agcagaatgt atgtgtaatg aatccggatc tgactggaca agcgatgggg aagccattga 199500 atccaattag ctctagcagc cctgcccacc aggccctgtg cagtgggaac ccaggtcagg 199560 acatgaccct cggtagcaat ataaattttc ccatgaatgg cccaaaggaa caaatgggca 199620 tgcctatggg caggtttggt ggttctgggg gcatgaacca tgtgtcaggc atgcaagcaa 199680 ccactcctca gggtagtaac tatgcactca aaatgaacag tccctcgcaa agcagccccg 199740 gcatgaaccc ggggcaagcc agctccgtgc tctccccaag gcagcgcatg agccccggcg 199800 tggctggcag tcctcgcatc ccacccagtc agttttcccc tgcaggaagc ttgcattccc 199860 ctgtgggagt ttgcagcagc acaggaaata gccatagtta taccaacagt tccctcaatg 199920 cactgcaagc cctcagcgag ggccatgggg tctcactcgg gtcctcgctg gcttcaccgg 199980 acctaaaaat gggcaatttg caaaactccc cagttaatat gaatcctccc ccactcagca 200040 agatgggaag cttggactcc aaagactgtt ttggacttta tggggagccc tcagaaggta 200100 caactggaca agcagaggcc agctgccatc ctgaagaaca aaaggggccc aatgattcca 200160 gcatgcccca ggcggccagc ggggacaggg ctgagggaca cagccggctg catgacagca 200220 aagggcagac caaactcctg cagctgctga ccaccaagtc cgaccagatg gagccttcac 200280 ccttgcccag ctccttgtcg gacacaaaca aggactcaac agggagcttg cctgggcctg 200340 ggtccacgca tggcacctcg ctcaaggaga agcataagat tttgcacaga ctcttacagg 200400 acagcagttc ccctgtggac ttggccaagc tgacagcaga agccacaggc aaagagctga 200460 gccaggagtc cagcagcaca gctcctgggt cggaagtgac tgtcaaacag gagccagcga 200520 gccccaagaa gaaagagaat gcactactgc gctatttgct cgacaaagat gatactaaag 200580 atattggttt accggaaata acccccaaac tcgagcgact ggacagtaag acagatcctg 200640 ccagtaacac aaagttaatt gctatgaaaa ctgtgaagga ggaggtgagc tttgagccca 200700 gtgaccaggt gagttttcta atgtcttctc ccaggtgtgc tcatctgtgt catagatgtt 200760 ctcaaagagg acatctgtga ctccctaaaa gtagtatttg tgttggtggg ccttaccgtg 200820 taacagttac tttgcatgaa gttgtgtgtt tacactgcaa agaattacag ggcacagaca 200880 cgagcttagg aggccatgta gcttgctctc agacactgta ggccagagca gctgtggaca 200940 ctgagcaaga aagtatggct gagctctgta cagttttaca gatacttaca gaccctgggg 201000 cagacaatgg gatggacaca aagtattttt gggggggtgg ggggcagtca ttgttctttc 201060 tatgagcagg gtaaattcat ccttgggtta caggtcatgc gtaacaatgg cgagcaggag 201120 gaactgcagc gtgactgtag ctagctgaac ccagagtgct ggcaatccct tccttagacc 201180 agggcttgct cagaacagac ttgagcatct atttgttact ctctccatag gaccagagtt 201240 cagccagtaa agatcctctg cctcttccct ctctctgaac acttctgagt aatgtacagg 201300 aatctcagtg actgttggtt aaggcacacc aaaggaaatg gatagacaca tcaaagccat 201360 catgtatcga ttcaaaacca gaataccggg ttacattctc tctgcacttc tctccaaagt 201420 taataccttt ggaacaatcc aggggaccta agtaatgatt agaatcattc ttctatttaa 201480 ttaatttatt tatttttaac aaaaaacaat ccttatacaa tatgatcctc tgtagaatag 201540 cactatcaga ctagttaata tatcactgca tttgtgctgg tcatttttgt ggtacaaata 201600 cctttttaaa actcttttga gtgaccttca atatacatgt gttatggttt ccactacatt 201660 gtacaacaga cctctggaat gttttcatcc aaactgacat tttaatcctt ctccaacatt 201720 tcagccctag cccctctacc attcccagca agactgtggt ggggaaggcg ccacagtgga 201780 agcaaaccat tgatattttc actgacttac aaaaacaagt gatataagtt gttgcaactg 201840 cagtggtaga atcatgactg actgaaggtt aggacctagc ctcaccttcc ccaggctgaa 201900 caggtcctgt ctggaagact ctttcttctg tcatggttga ttaagcaggg aggaagtcac 201960 aggggcctct ctccttaaca tggctataat ttgcccttga aagctgtgtt gcaagtagga 202020 aggtagtgtc accagcttca agagagcagt gactgtgagc ccttgacccc acaaatccac 202080 ggaggctgca tttggggaca gtccctgcca gcctaactgg ttcctaagac ttaacctctt 202140 tcaatgtgat gtcaccggtt gtcgccattc ctgagaacag atacaaccat tcagacattg 202200 tgctgctcgc aggggaagca gactaagatt acatgaacat tattggtgat taatcctaaa 202260 gtccagcagc aggcttcatg cagcagctat tttataatgc tgtgaactca tgagttgggg 202320 caccgaggcc aacagaaagt taatagcaat gcctttgtga tgtgatgtga tgtgatgtga 202380 tgtgatgtga tgtgatgtga tgtgatgtga tgtgatgtga tgtgatgtga aaaccatatt 202440 gacgatgggc tttcatcttc cggggtgtac tgggttaaat gacacagagg tagtgctagt 202500 tcagaacaac aagcacagat agccagtgtc acataggtgt cttaccgtgc tagagggcag 202560 atcagtgact cgggagatga cccctgatgc tcagttacag catggctgcc ccaccctcca 202620 tagctagaat gagtttctct ctctgacctc agaccctagg gactgagagg gacagtgaaa 202680 ggtgtcactg acatgtctca ttactctgca tatatcacaa atgccaaaca agaaaaggct 202740 ttgtggggtt gggttggctt cacttttacg tctttgaatc acttggagtt ttcttatttg 202800 gaagaaataa ttttctaatc aaaattatgt gagaaacaaa gactagtatg aatcagtata 202860 aatctgttgt ttgaagatga aaaataaaac agggcacgca tgctcacata caggaagtat 202920 attgtcctta aagaaatctc accccttgct cacctcccct ccaccctctc ccagacccca 202980 tctaaaatac agtttcacag agccagttta gcatcaaaac catagcaagg ggaaaagtta 203040 ccacaggaag catgctttac ctaaatttag atccattatg aggagaagaa aactcaattg 203100 tttcacctct tgctcacctt ctgttcccta aggatggtct cctcaccttt catttcagag 203160 gaatgcagta attatttagt aaacatgcac acatagcaag cctggattgc aatggactgt 203220 cttgttattt tgactcaaaa aaaaaaaaaa aaaaaaaaaa gacctgagag cctgagtgtg 203280 tgtaatgcat tactgacttt gtaaggtcag ggagtacagt gcacttcagc agcacagtgt 203340 tactctacta aaaatgacat agttttacca ggcagagcat tcaaacaaga catttctaac 203400 gccatttcct agccaacagg aaacaaactg acagaaacat tgccagtgtg tttactgctc 203460 taagtcacgt gcttatttcc acaatggagc attgctggta ctcggccagc caatactttt 203520 ggctcctgct ttctttgagg acttggaacg gtctcccatt gcttaactcc attagaaaag 203580 ccatgttaag ctggtagtca ccagacactc cctccagata ctatagaatt ccttcacagg 203640 tctgtaccaa gcaaatggta tgatgctata gtttttattt aaaatgtttt caaaagctac 203700 tttttaattt attagattac tcatgtattt ctgtattcgg agaacaagtt gatttttgac 203760 tcatgaaaat aattataaca ctaaaaagaa aaattaaaga aatgaagtct atttttcatt 203820 ttgtagaact taaaaaaaaa caaaaaactt tctgactcat tttctgccag aaatagttga 203880 aactaactac tgaaattgat gtggctagtt tgagcattca aatagatgcc taagtgagac 203940 tctgaagtgt ctacaaggca ttttaaagaa aggcactgat ctctctgtct tgcaaagaca 204000 ctgcctaaca gagtgcaagg atcagaagaa catcagtgag atgtaagctc cagagctgta 204060 gaacacatct tccttcagaa acatctaatt atcacacttc agcccttcca gagcgtgcgc 204120 gaacactaag ggaagtatta aaatcaatct gcctgagggt tataagccat gctgaaatct 204180 atctcctata gaaatattta aacttaggcc agacatggtg gtgtgctcct gcaatcccaa 204240 cattctagag ctgagagaga attgtaaatt ccaggtcaac cttacctcag gataagaaaa 204300 gttaaactga taacaaatta atgataaatg catattccaa aaattgacaa ggaataaatt 204360 cagacaaagc aatgtctcta aaagttcctg gtgcatcttg aaatgtaacc tgagtgagtt 204420 cagatagtgc ctggagctct gagcctgtag aagcaggctg cccatagcaa agcgctgccg 204480 agctctcaga tttgctgctt ctcaagtcaa cgttgctgct gctaactttt cctccctccc 204540 tttcttcctt tcctgttctg gacattgaac ccaaggcctc ttaaaagcct catgactgaa 204600 ttacgctctc actcacatag gtagctggta aagctgtaaa tgggagtaat cagaatgtga 204660 aagtcagttt aagacatttc ttttaaagaa aaacaaaatt aagccgggcg tggtggcgca 204720 tgcctttaat cccagcactt gggaggcaga ggcaggcgga tttctgagtt cgaggccagc 204780 ctggtctaca aagtgagttc caggacagcc aaggctacac agagaaaccc tgtctcgaaa 204840 aaccaaaaaa aaaaaaaaga aaaacaaaat taggatgaga gggagaaggt aactcaggcc 204900 acatcacaca aagctggttt tgtccctagc actgcatgaa tacataaata aaaactttac 204960 attgagtaaa tatatatatg tgtatatata tatatatata tatatatata tatatatata 205020 tatatatatg cacacacaca tatatatact gattatgaaa ttttttactt agaaattatt 205080 tgagctggac attttccaca tccctgtagt cccaatgctt tgagggttag ggtaggaaga 205140 ccaagaggta aaagctggac tctgctccat agcaagtgga aaaccagcct gggtccctga 205200 ctcataattt tttctcatat aaattgattt tagttactca tatagcttaa cacatatgta 205260 ttaaacatta tatgtgcctg taatgttaaa atgtatgtca agtgtcaagt atttacatgt 205320 atatatatat acttaaatta atatgttaca cagaattaca caaacaacaa aagaagaact 205380 acggccagat gtgatttagt gccagcactc aggagtcaga agtaggcagt taggtctatg 205440 tagtgttcca gcacagccag caagagccac agagcctcta ggaagggagg gtaagaagga 205500 aaggaaagac caggcatgat acagtgtgcc tagaatccca gctcccggga ggcagacagt 205560 ataatacttc aagttcgagg ccattctggg cgacacagtg acctctgtct ccaaaatgtc 205620 tttttaaaaa accttgttag ttgtgattaa ggtggtttat aattttgata gtggactgta 205680 acggggaaag cattctgtca tggctcagat tggaggcaaa ctcaagtgca tctattaaga 205740 aaacacatag acacttctgg ctttgcttac atgagcctgt tttctataat tttcatcagg 205800 ggcaatctgc caggttttgt cagagacaga ctgtcattta cttcagctat cttcctcacc 205860 tgcacactga gctttaaatg tcctcaggct agggcatcat tgccatagga cactacttca 205920 aagaccagtg gtagctcgct gaagccctgt tcttaccaca gaagcatagg aaacactctt 205980 ctgaggactc gggaagctgt gggaatttct gttttagttt taatgatgac tgaccaccac 206040 ccacaccctt caggtctcac tgtcgatggg cctgtcagtc acagctgatc cacagtgtgc 206100 aaggcttccc ttgctcagga actttcaggg ccacgtctct tgcctgaacc tctcccatag 206160 aaagcttgtt gtcctgttgc aaataggtga cacaggaatg ttcttcttgt tttaagagta 206220 catgaagaat tttctggaaa ggagtggcta agttcactgc tgaagtagct acctctgaaa 206280 agactcaagt aaaatgtcac ttcaacaggg aacttcctaa cttgacaggc tcagttggca 206340

aaggcgtttg tcattgtcat gcctggtgat ccgagctctg tcccttagac tcgcgtgggg 206400 aagagagaat cggcacccac aggtcctcct cggatgttca cacacacgaa ggaatgagtg 206460 gacttttctt attagaaaga cacggtagac tacacagaag cacactccta taatttgcac 206520 atgagcgaat ccattagaag tcgttgccag tttcacgtgg actcagatac ttttgttcag 206580 ttttgaaacc atctccctct agcccagaat agcctacagc tcactgtagc tcaggctggc 206640 tttagcctca agtgctggga ttcaggcatg atcacacttg tttgaccact ttcctgtgta 206700 attgaaatct atgatcttaa atgctagcac cctgataggt tatacccaaa agaatgccag 206760 tgaagtcatt ctagctctta gacaaaaaaa aaaaaaaaaa gtaggcaata taatatagtg 206820 gtcatactta ggttattaat cagtattggt aattggaatt gaattcaaga aatgatttga 206880 agaaactggc gcatatgaaa tcaaatgaat acacgctatg cttggcatca gccggtggtg 206940 gcacacgcac gcctttaacc ccagcactcg ggaggcagag gcaggtgaaa ctctgagttc 207000 aaggccagcc tggtctgcag atcaagttcc aggacagaaa cctgtctcaa aaaacaaaga 207060 gggggtaggg ggagctagtt aggtcatcta agctggttaa taagaaagct actgacattc 207120 aaacctaaaa taaaagcaag caaaaagcac atttcaagtt gaaaaagcaa gacttagcta 207180 gtccatgaat atttgaagct tattttacag ccaactcaca cagacaaggg aaatagccat 207240 ggttatttgt accatattct acaccagctt tattgttatt atttcttaag aaaaaaaatg 207300 aaacctagat ccaaactgta agtcatggtc caattataag taattggata taatctttca 207360 taattaatgg ggtggttcaa ataaaataaa gggactacat aaactgctag tgagttgcaa 207420 ggtgggaaac agcttccttt ttttaagtcg gccatgccta gtttctaagg gagggagtca 207480 tggtcctcgg tggattcagt tacgagagat ggttggccca tcattaggcc ttacatttgc 207540 acatacctgc tttttttttc ctttttaaac ttggctggga tgccctgtgt gatggttggg 207600 tctgtactcg ccaatggcca gggttggggt cccctcttgc agcatggacc tggatgtaca 207660 cttctgtttg ttaactgcag cctggcagcg agctggacaa cttggaagag attttggatg 207720 atttgcagaa cagtcagtta ccacagcttt tcccagacac aaggccagga gctcctactg 207780 ggtcagttga caagcaagcc atcatcaatg acctcatgca actcacagct gacagcagtc 207840 ccgtcccacc tgccggagcc cagaaggcag cactgcgcat gtcacagagc agtaagtatg 207900 cactctaacc ccatcagaga ccaactcaag gctgccagag tcctggtctg tccggcagct 207960 taccgccata gtttcctttg gagaggaaaa ttcaaaccag gcatggttac tgcatgcctg 208020 taatcccaga catgaggctg aggcaggagg atggtgagag ttcaagggca acctgagcta 208080 catagtgaga ccctgtctca aaaagtttta attgttcaca aaaagggtgc tcacggtcaa 208140 atgccttatg ccattgactc tgatagaata ttttgcgatt tcagttttgt gtgaaaggac 208200 ggttttagtt tacagaaaga caagtcttca gtgctggtaa acaaaagcac cacttccacc 208260 tcaggagagc accaacgcca tgcctagcag cgctctcaag tctggaaaag cgaacctcag 208320 ccaagtcaca gataactacc tttagaaact acgtccttcc ttgcatggtt cctgaccatt 208380 ctggaaaggg gtaaaggaaa gtaagatgaa gttttatttg acctgggcaa atcacaaagc 208440 taaagaataa gagactagcc cggcatggtg gtgcacgcct ttaatcccag cactcgggag 208500 gcagaggcaa gcggatttct gagttcgagg tcagcctggt ctacaaagtg agttccagga 208560 cagccagggc tacacagaga aaccctgtct taaaaaaaaa aaaaaaaaaa aaatgagaga 208620 ctgaggtaag ctagtacttt ttaacccaga gaggagcaaa gaacacggtg ggggctcgca 208680 gctcgcagct acactcgctc aggagcccca gggaccctga aatggtgagc tgagccgtag 208740 gaaggcaggc ctgggagagg caagcaatgt ccattcccag cctggttttt ctgaatggtt 208800 tttctctacc ataggttttt gaaaagtctt ctttcttcta actgctagtg cagtctatgc 208860 ttataaaact aaaagaaagt aaagtcttga tatgactaat aaattagccc tgtaagttag 208920 tgtgtatagc attgagtgtt ttaataacat tgttataaaa ttacaggtca tctacttgac 208980 actagattac tgctcagtac acagtcaatt cttgtgaact aaccatcaaa accatttcaa 209040 atctaaatag tgcctggagt taaagccata ctgctagtca taggctacaa tggagttttg 209100 tttcaggtga cactcaacag ttttaacttc tagtggaagt atctacttct aacttattct 209160 aaaccttgag cccagttaag aaataatgta acatccaaac cacatgtgtg taggctgctg 209220 ctgcatgcaa gagatgttta taggctcctt actgtagaaa taagaactcc tgaagcagac 209280 aagtgcatac caaatttaag gggagatctt atcaaaagaa acaaaaaaaa aaatgggaaa 209340 cagaaaaaga ccacccacca acgtgtgaat agtataacat gaacactatc atattaatgt 209400 acgataatgg tttagttagc aaaaaacttt tcaatgctac aattcctgga gagaaaacat 209460 ggtacttttt tttacatccc ctttttgcaa ggccattgag agttatataa taccaaccag 209520 ggtgctgcat atgttttctg tagttgtctt tcatggagag agttaccaaa gatgtgcatc 209580 tttgtcatgc tacaggagac attttcccta aacactactt actgttaata ttctttttca 209640 ttgtccttta ttaaccttca atttttcatt tgttctttcc ttagctttta ataacccacg 209700 accagggcaa ctgggcaggt tattgccaaa ccagaactta ccacttgaca tcactttgca 209760 aagcccaact ggtgctggac ctttcccacc aatcagaaac agtagcccct actcagtgat 209820 acctcagcca ggaatgatgg gtaaccaagg gatgctagga agccaaggaa acttagggaa 209880 caatagcaca ggtaagggct cagcggtact gctgcttact ggcgggttgt gtaatttaac 209940 aatgtgttcg tccacatcaa aatggtagaa cttgaccatg ggcttgttag aaacctcacg 210000 gatcccctgt gagggtggcc ttgggaagcc actccatcaa gctgaccaag tcattcctca 210060 gctgctgctt tgaggaagtt cctgatctcg gtcttcttgt ctagccttgc tgcatttcca 210120 tcccaactgc tggtctgaac ttggaagaat atatgcaaaa taaaccaaaa ctggtgcttg 210180 ttagtccata gatatctgct gaaaactcca aaaacagatt gatggttttg gaatgggagt 210240 ttaaaattct accattcttc cacaattcta gatccttttt ccacttagga aaaaaaaaaa 210300 aaaaagaagt aaaagtgagg agctttttgc ctgtgttgcc acgtttccac tgtatgctca 210360 gccatgcagg acggctgctg gaggaccact tgagccacag actttgttgt gttttgtttt 210420 attggctttt gtgttctggt ttcttaacct taatgcattt taacagcttc aagtcagggc 210480 acagttaaat gagcacactg gtttgaagtc acaccaatca ggcggcttcc tggagattgg 210540 agaagctgcc tgtaatctag ctggagcttg acctgatagt tttccagtgt cctcccccat 210600 atttcctaag tggtacatct tcccgccaca gcggcataga attcagaatg agctcacagt 210660 gcgggccgtg gagtggcatt tgttacgcgt ctgggagagt gctggcttcc taaggaagag 210720 ctggctgtag ctttctttcc ttgtctcagt gatgtgttag agacttgggc accctatcaa 210780 tacattacca ttttcgttca ctgaagatca gagcactgct caaggggaag tgatggatgc 210840 tgcatttctg attgctaaga gcgaattcat gggaagtgtg agctatagtg tgtcggttta 210900 ttcattcaac agatactcac ccctgcctaa ttacacacct gtactgactc cctcattaaa 210960 ttacagatcc ctgaaaacag tgccatattc actccattac tcttaaataa aagcacgact 211020 catagatata ttggtgatga gaaactcttt aaagaaaagt agcagatgag tgactaggag 211080 tcgctcccta tcggtgaata caatgcttac actgttgaag tcttgtatag gaccttggga 211140 ccatggggac ggcctctgca tgtcccagaa cctagtagtg cccaggctgt caggatcaca 211200 tggtataaag accagcacca tagggaacag tgtccattct tgctgcactg atactgttga 211260 gtttcaggtg acttcaccct cctcctctcg tcttattatg ctatttaaat aggttgtttt 211320 gaaactaaaa tgcctttcca cttatccact tatagataaa atataaatgg ttttaaatat 211380 gtcttaatat tgcagttttt aaccctaact aatcaccctt ctccttttaa catctcagca 211440 catccctcat ttcacacatg aggaaacacc catgttccat ctacatgttc attataccaa 211500 atttgcttaa ccgaaataaa gtaatctaaa gcaagccata aatttgaaag caaatcttta 211560 tatcccctgt atcacgtttc agaacaaaga gatgtttctg aggcttcttc ttcagtatgt 211620 cttaggcagt gtttggccac tgccgtcacc tagagcctgg acactaatag aacagaccct 211680 gagtcctgcc tggtcatgtt gagttctcat tgttccgtgt gatcagatgc caagtgtaga 211740 tttccctcac gcctctgcta gcccattctg catcggtgtg gcctggaatg cagtgcttca 211800 ggagggtggg accctttgct caggcactgt gtcaggaaag tctttaactt cctgagtgct 211860 tagaggctac ccttggtaaa ttttgaaatt tactaaattt ttttttttga tggaagttgt 211920 tgctgaagta tcctgtccat gcagacgtat gcctgtggtg gggcagcttc acttgatggt 211980 cacccagcga acatgtctgc atgctccaga agtgtagcag gcgccgaccc cctgaaagga 212040 tgaggatgct cagctctctc tcgcaaaagc tttgcaggat agtctctgac tggggtcgat 212100 aattttggga ttgattatca gttcttacct tgttcctcct caccttacct catctcacct 212160 cccttttgga aagtagagct ctgacgtata cgtcagctaa tgtgattcac ttcctgagga 212220 aggaagttgg ggttatccac ttgccgcagt gcctgttcta ataagtacat atgggaacag 212280 ttttaacagc tcttctgagc agatgcatgc tgtgaaaact gtagtaatca ccaactctta 212340 gttcttagcc cagggcccac atctgccctg ggggagtgtt tgctgttgag ccaactgcag 212400 gttacagtca tggtctgagt cttgtaggta ggtctggcat gcgtgcatat gctgttttca 212460 atgtctgcgt ctctcagttt cctctgtctt ggatgcagga atgattggca gcagcacttc 212520 ccggcccagc atgccttctg gggaatgggc accacagagt ccagctgtga gagtcacttg 212580 tgctgctacc actggtgcca tgaaccgacc agtccaagga ggcatgattc ggaacccaac 212640 agccagcatc cccatgcgag ccaacagcca gcctggccaa agacagatgc ttcagtctca 212700 ggtcatgaac ataggtaagg ctccttccct gctgccctta ccccgtggtc cttcaggatg 212760 tgcagtcctc aatggcattt gctaaaaccc tgttaaatca tggactgatt acctaatttt 212820 aatttggaag caaaatacat taaaatgtca cattataaat gccacatata taaaatgtca 212880 catatatatg catgtatatg gtagtttaaa ggcaacgaaa tagtttggtt gtacagcctc 212940 tatgtggtca tcctaaacca ctaatgccct caggcaggct gtgaagtcag cgtctccctc 213000 agcctcattg atagtgcgac cactcaagaa catgacacag cacccaagca tctctagcat 213060 tctagctgga ggcagttcac atgtcacgga aatgaatttt ttgtgtacac tccacaaaac 213120 cttcatcata gctgcctata gctgaaggcc tggaaggagg caggaagtga gtcctgagac 213180 aagggcttcc tcttcaggta agtgaaagtg cctgagttga tgtggtagtg gtacactcga 213240 acacattgac acctacagga tgctgcacct gaagtcatga gttgtatgta tgatgaatga 213300 atcatcagga aacttgttac tacatattga tgtacacact tagaatcctg agccttggga 213360 ggtccaggca agagttcagc atcctcagct ccttagcaag tctgaggcct gactgagctg 213420 aacaaggccc tgtctcaagg gaaaaagatc agttgcctat acagctccta cttgatatta 213480 tttgtaaccg tagacatagg acttaaatct taaacattag ctcaattcta aaaagtctgt 213540 gtgtgtaaac ttttgtgtta gatattgccc aggaagtgct aattcattcc caggaaaatg 213600 caagattgtt ttgacagaag agcaggcctc ttgccagaac tttgaatcag gtttcttcca 213660 taggtgttga agtgctgtgt gtgtgttgac tcagtatttc tgagagtgac atttataatt 213720 aattacattt ctacatatat gctcatggta gtaggtggaa aattaagctg agacatgagt 213780 aagatgttta taaaagtgac agtaagaggt cttgcataaa tatttaattt attccccatc 213840

ttgctgatag tttggaactc ccagtacagc tctgtaagat ttagtatgta gctgaatttc 213900 tctagtggta agtacagtca ataaatcgga atttgcccaa tacaacattg cctgttatgg 213960 atgtccagtc aatggataat aaaataaaac aattagaaag ctcatgtgca ttagagccac 214020 aaaaagagaa cgctgtgtat ctgagtgtgt gtcctgtggg agagctaaga cttgtgaaag 214080 tactggtgca ggtgatctgc tccctggtgc cttgcagctt gtctctgcag ccttacatgt 214140 ttgcaccata ttgcagggaa gaagggagtt ggaggttctg ctaactcaca tgtgcatgtt 214200 tatgattttt tttaaaaaat gagttagcat tttcaatatt ttccatacaa acaaaagctt 214260 taagtaagag accagatatc ctgctgtcac tactgaccta gacgtgccct aagttgggcg 214320 gtattagcct tgtgttcatc acttgtattt gtacctcaca ccagagctgc atccaactct 214380 gcattttcta tcaaccaaca attttatttg ctattacaca gtaaacctgt gctttctaaa 214440 ttataagatt caaaaattta ggtctttctt ctcttttttt ttcctccctc tttcaggccc 214500 ttctgagtta gagatgaaca tgggaggacc tcagtataat caacagcagg cccctccgaa 214560 ccaaactgcc ccgtggcctg agagcatcct gcctatagac caggcatcgt ttgccagcca 214620 gaacaggtaa gtccaggccc ccggagagct agaagagcat tagctcatgg ctcctggctc 214680 ccagagttgt ttcacatgta cgctgggtga atcccttcgg aatggatgat acctgcccag 214740 tcatcctttc ttcagaccga gtcatctgct aggctcagcg tgaaagaaag gtgcagaact 214800 cggcatgacc tgagcacacc tttaaacacc ggcagcttag ttgggaaaat gatatgtttg 214860 aactgctaat cgctattagg cagcagtgta gatgctgtat acagtataga tgctgtaagg 214920 ggaggaatca gtagctcatc cggcaaggct gacagagaag gtttcagagt cttgggggaa 214980 gtgcacaggc atagcagcct agtgcatatg gccggccaca cagcaccatg ttccatcggg 215040 ggttacatgg tacgtgtagg gtaacaggga atgatcttat tttgaattgt gtttatttta 215100 ccacagttta caaaaaatag aaagggaggg ggggtccatg gtctagctag gtaagtcctc 215160 ctccctcgtc aaaaaagctt ctttgcaaca gagaccattg taaaaaagaa tcccagccag 215220 gcgtggtggc acacgccttt agtcccagca cttgggaggc agaggcaggc ggatttctga 215280 gttcaaggtc agcctggtct acagagtgag tcccaggaca gccagggcta cacagagaaa 215340 ccctgtcttg gaaaaaaaaa aaaaagaaaa gaaagaaaaa aatcacaaac aatcaaaatg 215400 atggttgtag agccctattt caatgataca tctgtaaaac acacccatac ctaaggctca 215460 gggaacattg tgaaggaagg gatgggcagg atataatatc cagacagcca tggagagact 215520 agtgacatct gaaggctgca cccatgaagt ctcaccgcat gacaaggata acaataaaca 215580 ctccatagtg gatggaggaa tccccacgag gcctcagtcc tacataagag ctgcgggcca 215640 ctaaggaatg ctgggaggga ggaacagtcc tcctcagaga agagcacacc aattggttat 215700 caataccaag tggtcagccc tgaacacatg cacatgcaag tgtagcatta tataggctaa 215760 gcaggtcata cttacacaca cacacacaca tacacacata tgtgcctgta acaacaacaa 215820 atgaaaaagg aagctctgaa tttgagctga gctgggagag gtatatggaa ggcttgaagg 215880 aagaaataat gtattgcagt tggagctagg aagataacac agttgatcaa gtgcttgctt 215940 cactaacatg aaaacctgag ttcaggtcca gaacatattg aaaagccagt gatggtggcc 216000 cacattgtag acctaagcac tgcagaggca gaggcaagag gatctacagg gcccaggggc 216060 cagctgctct agagtaagca gtaggcacag aggggatggg agaaagagag agggggggag 216120 gagagaggag agagagagga gagaagagga gagggagaga aagagagaga gagagagaat 216180 gagaatgaga ggagagagat ctcccaacac ttaggacagc cggggctaca cagagaaacc 216240 ctgtttcaaa aaaaaaaacc aaaactgaaa accaaaaccg ccggggccta gcaaacacag 216300 aagtggatgc tcacagtcag ctaatgaatg gatcacaagg tccccaatgg aggagctaga 216360 gaaagtaccc aaggagctaa agggaactgc agccctatag gtggaacaac attatgaact 216420 aaccagtacc ccggagctct tgactctagc tgcatatgta tcaaaagatg gcctagtcgg 216480 ccatcactgg aaagagaggc ccatataaag gcaaacttta tatgccccag tacaggggaa 216540 tgccagggcc aaaaaggggg agtaggtggg gaggggagtg ggggtgggtg ggtatggggg 216600 acttttggta tagcattgga aatgtaaatg agctaaatac ctaataaaaa atgaaaaaga 216660 aaaaagaaaa ccaaaaccaa acttgcagtc cttctgcatg ggcctccgag agctgggatc 216720 acaggtgtgt gctgcacact gggctgtagt aaatcattgt gaatgggtgt gtctagaaga 216780 ctcctgccac tgtttacaca ctgcattatg tgttttcagt tctttgttga aatatgacag 216840 tatgtcagac cttctctcta tttcatccac acattgtcgt cctgtgtgtg tgtgtgcgtg 216900 cgtgcgagcg tgcgtgcgtg cgtgcgtgcg tgcatgttgg gaagcagagt cagatggatc 216960 tctaacttca aagctacata gtgagtcctg tgcactaggc tgtagtgccc agggacttcc 217020 tccaagactc tgctggagga gcttctgaaa catgcaactg ggctgcatag tgagaccctg 217080 tctcagaaaa agcacaaaca acacaacaca aaacagtatt ttattattca gtgtacgtgt 217140 ctaacttggg catctgtttt ctgttgtaag tactgggttg ctgcagggtt aagaatttat 217200 tctcagaaaa gatgattcct tctactgtca ctgtttgaaa ttaattgttg gtttaggtgc 217260 tcagcaggac accatgttca gttctaagtc agagtaacac attagactgc ctaagaaaac 217320 acagtagact gaactgggtc agggccagac aactctgtcc cttgatacat tgattgccac 217380 ttgtttaaga atgagctttc tggggtgtga gcatgcctca cctggcacat aggatgccct 217440 gggttcaatt cccagtacca cacacaataa aacgtaagct agcttctctg taaaactgtg 217500 tgttctccac aggattccat agtaggtcta cagcacaaag ctgactttgg tgaagtgctg 217560 gcattatgtc ccctctcagg gttgcagtga ctagaagatc ctctaatctg gtaacttaat 217620 tataatgtta gataccatag aaatggcagc ttagtgtcaa gatcacatat tgccttatag 217680 caattacatt agaaggtttg agattccctt ctaattcctg agggctaaca ggtaaacttc 217740 ttcggagttt tggtaaatgc ttgcaaattc tggttctgca taaacacaca gtttcataga 217800 ccagccaagt tcacaagccc agattgtatt caagtgtgtg agtgtgctgc tctctccttt 217860 gctcatcgta gtcgcattga aaaggactgt gtatgagtca ctgcgttctg cattcacctg 217920 tcactgcaca gcagatacac acacacagac cagtgcaggt ctgtgaactt aggtaggtga 217980 gccccgaaca cacacacatc aaagtagctt ttacggcggt gcctttccga ctttgcacag 218040 atgtgagtac ctggctaagc taaccctgta ctttatggga agatggagaa acataactgg 218100 ttaactggcc tttattaaca ctaaataaaa tagatttttc agatgcatat tttcagaagt 218160 cttcattctg tccagtgctt ggctggagga agagtttggt gaagtcaact ggtatttcta 218220 ccagcccatg gtgaagtttg tctctttaca ggcagccctt cggcagctcc cctgatgacc 218280 tgctgtgtcc acatcctgca gcagagtcgc caagcgatga gggcgctctt cttgaccagc 218340 tgtatctggc cttgcggaac ttcgatggcc ttgaggagat tgatagagct ctggggatac 218400 cagaactggt cagccaggta ggccagagca tcagagcggc caagcactgc gtaggccaaa 218460 ggtctctgtt cctgcaggct tctctgggat gctttttccc tccccaccag caggcctccc 218520 tactcctcct ctttactctc atactctcac ataaactgtt gcccaagaag caaacacctg 218580 ggaaggacca ttgcacaaga caagttaagc agaaaggcag aagcaagccg agagcctctt 218640 gtccacgctt gctgaaaggg cagattagga aaacaagtta gagaagccac agggtcactg 218700 cttcctgggg gccttggtcc tcgatgctgg gatgggagac catgtgagca ggcctcagtc 218760 cggccatgcc tattcactga gacaggcagc cgctacttag aaaggactgt ttcacacaca 218820 ggtagcagaa gcatcttaag tgtgactgca gctcaccaaa cactacaacc cttatgtggg 218880 tgtcgcccgt aacaatttta ggatgccaac caccctagtg agcctagttc tctctctgct 218940 ccctcgttag tttatttgaa gaagtaacag actttgtctt tctttgattt gagaaagccc 219000 tgaggctgtg ataataaccc catggcccct cagcatctga aacaacctcc tcctggtcct 219060 ccttcctgtc cagtgccagt ctccctgtca caagcatctt ccaaggccag gctgcctggc 219120 cctgcagcat gtcactgtga ggatagtgat agtcatcgaa gactctggaa ccttaaaaac 219180 agtcataatt cccagagttt agcagacaca ggtgggagtt cagacttgtt gattcatatt 219240 gaaaacagca gaatggaaag aaatgactgg aggttgcaca gtacaccctg acttaaaacc 219300 agaaaggaaa tggggtacct atttcctgca tgactggtcg gcttcgcctt tagcttcagc 219360 tagagttcag cttttctgcg attatccttg agtttatgca ggtgacattc ttaaatgtcc 219420 ttggagttcc tcagtgactg gaatactttg agggactttg gaagcggggg ttatgtttta 219480 agagattaga tttttaagaa atttaagaga tcccagccca acctaggctc aaatttatgg 219540 cagttgacct gtcttggcat ctaaaatatt gaaatacttt ttaaaaatta aaaccagtat 219600 tacatcattt tgaatgctct cctcaggtca gtcaccgtgt cgtttaagct gaactacaga 219660 cggcattctt aggggcagcg gtggaaatgt ggtgtgnnnn nnnnnnnnnn nnnnnnnnnn 219720 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 219780 nnnnnnnnnn nnnnnnttta gccagagttg catacacagt atagaaataa agttcttgtc 219840 tcacaaacat ccccagagcc caggaaaacc accaggctca gtggtacaca cgttacccca 219900 gcaatggtga gtttgtgacg gtggaaacag gaggattccc acagcaccag ccagtctagc 219960 gtaatcagtg agttctaaac agaagtgaga cctgtctcaa acagagcaaa aactaaatag 220020 atcaatatgg aaataaccta agtagatttt ctattaaata tgggcagatg taaagttctg 220080 aaatatttca acaaggagtg gtctccctgc tggtggtact ccatacacac tttttttttt 220140 aattatcaag aggagagggc agtatactga cgctgtcctg ctgaccacag accacaggca 220200 gcgttatcat cctagggcgt ctggaaggaa ggactaaggc tgccagagca gtaacctgat 220260 ggcggcttga gatgtgactt ctgctgcggc ttgccctcta aagaccttca gatgtctagt 220320 cgtggcttct agaaggacaa gggtatatta gatcttcata ttgacactag agcatcgccc 220380 tgagagagcg ctagattccc tatgcatgga aacaggacag tcagccagaa gtttccatgt 220440 tcagctcagt agcagaaatg acaagacccc ttgtctcaga aactgagtga aagggccgca 220500 tccccagaaa ccctccaggc ttcacacact cgtgtgcgct tgcttgggct ggctccctct 220560 ctccttcctt tctttctctc tctctctctc tctctgtgta tgtgtgtatc actcacatgt 220620 gcacacactt ttttaaaaac taaatagcta atgcaagatg caactggaat ttatgcagct 220680 ctctctgtaa aacacatatc agctgggcat ggtatcacat gccttcaatc cagtactcat 220740 tgagacaggc agatctttgt gagtttgaag ctaactcagt ctacatagtg ggttccagga 220800 cagcgggact acataatgag accatgtctt ggggtttaaa aaaatgcatc tttcagacaa 220860 ttaaattaac caaatatata caaactagtc ttgcagatac tctgtcagat gctggtcagg 220920 gcacagggag gacctgctac atgcccttac accaccttcc attcctttcc ctctgtaggt 220980 ctttggtagg agaaaagctg ttgaaaaatc aaatgacaaa cacattgaat atgtctagca 221040 tgtagtagtg aattatagca aagtgtacgc atgtaagaag ttccactaac catagagaac 221100 agcgtagtaa acagtacaca gtgtaaggca ggcattgtga cactgacctc gaatcccagc 221160 acttgggagg tggaggccag agactcatgg ttgaaaccca tcctgggctg catagcaagt 221220 cagaaaccaa cttgggctat gtaagaccgt atatcaaact cttttcacca aaacataata 221280 ggcagtaagt ttatcacccc actggtgagc ttaagtccca catcacagta cgcaccacag 221340 cctacccgcc cggtctttgc tagaaagtct ccctcgagtg ggcctcatgt ccccaagtct 221400

gtgggtgtct agagtggaga ctgtaggctg cttccccagc attgcttatg gtgactaagg 221460 tgaccatagg ttaaaataac tgacatgggg ctgtgtctct gtcaaaagag gaaacatttg 221520 cagctgcctg ctcactaaag gccctgccag gttctcactg gaaggaagga ggaagctctg 221580 cagggaggca gcccaaccct tgcttcttcc ctcgaggagt tgcaaagagg cattgggtag 221640 aaggaaaagt agaggcaaac taaaaaaaaa tacattggta aacttggtac agtatttcta 221700 aatcatcact tacaggaggg ggggagcgca gcctcgtgtt cagtacagta gtagtagtag 221760 tagctttact gtgtgcttat ttggggcttc ttttcagagc caagctgtgg atgcagagca 221820 gttctcaagt caggagtcca gcataatgct ggagcagaag ccccccgttt tcccacagca 221880 gtacgcatct caggcacaaa tggcccaggg tggctataat cccatgcaag atccaaactt 221940 tcacaccatg ggacagcggc caaattacac cacactccgt atgcagccac ggccaggcct 222000 caggcccaca ggcattgtgc agaaccagcc aaaccaactg agacttcagc ttcagcaccg 222060 cctccaagca cagcaggtta gtttctcatg ggactcaggc gggggccctg gctggctgag 222120 gaatgaagaa gagttaagtt tttggagagg gctgttaatt ggaaaagatg atttgaaata 222180 cacatgtcct gttgtttaaa tgtattgagc taggaatagc taccttactc tttagtctca 222240 gtactcagga ggcagagtcc tggtctacag agtgaaacac aggacagaca gggctatata 222300 gagaaaccgt gtctcaaaaa aatatggatg gattctaggt cagcctgggt tacatagtaa 222360 gaccccgtct taaagtcccc ctcccgacga gtgctaatgc ccgtgtttgt gtgtagaatc 222420 gccagccgct tatgaatcag atcagcagtg tttccaatgt gaacctgact ctgaggcctg 222480 gagtgcccac tcaggtgaga agcctctcat ttttcctccc agataggctg agtgacctgg 222540 gttttcctag ttcctctgac tccctgtgtt agttctgaat gccatccctg ttgccagggt 222600 cagctgattc ctataataca caagagttgt attacaaaaa tgtatcaacc aattctggat 222660 tcaagtactg cccactgttc ccatgagaac acgggtttag ccttcaagac tggccacaac 222720 attgctctcg gcaatagcct tgtttctatg gagtttctgt gtgaagacac tttacgtgta 222780 tgtaatttac ttattaaact caatggacag gctatctcag actcaaacaa gccttgccta 222840 acactcgtac ttttcttcgt aagcacacct atgtcttcca cttgagaaca ctggacagtc 222900 ctgcaccagc acagagcctg ttaggttctg tcggccacat cagaaggcca cacatccatc 222960 tagccctccc cttggcagga agcaggcgag tgctaagcat aggaaatccg tgctgctgtc 223020 cttacagtca taaatggctt gacagtgctg cgcacactca tgtttgcatt gcagataaac 223080 tttagagtag gcagccttgt gagtggcgag gggatgccat tccagcacca gcgtacagca 223140 cacgcccagg gcccctcctc acatcatgtc actcatcctg gcctctcagc agacatctaa 223200 agaccattct gagatcaggt gcatctgaca tgatgtagcc atagaccagg gggacacagg 223260 ggacacaggg gacacaggga cacaggggac acctgtgcag ccagccagag cagcctggag 223320 atcagtaaag taacagaaat tactgtcaga tcacccccac ctccatctct ccgaagtcac 223380 caagtcacct ttggcagtgg cttggtttct tgttaagttg gaatgttcct tcaaagagac 223440 tctaaatgct gtcctcaact tacataaagt cttctgccag gccagggtag ctgcgctgta 223500 accccagtgc tgtagtagct cccagcactt gggatactaa agcagaaaag aggtgacagt 223560 caagctagag gacccagaaa gcagcacgtg ggcacctgta actccatttc ctggtgatta 223620 gccgccctct tctggcctcc atgagcactg cacacataaa aataaatttt aaaaataaac 223680 ataaagtctt cctgtagaaa ggcctgtgct cttttgacat cttttgattg actgtaccct 223740 cgagaaatga gttggtcact atcagagggt tacagaatcg tcatcacaca ggctgaactt 223800 agagcactcg catgcgtgct cactaggtgc tctgctccga ggacccccct tcatggaact 223860 ttgtttttca aatgatttta catacagtat gccattggta tcctgtctaa cctatctatc 223920 cttgatttcc cttcatgatt gcccacaatt tcaggctcct attaatgcac agatgctggc 223980 ccagaggcag agggaaatcc tcaaccaaca tcttcggcag agacagatgc agcagcaggt 224040 gcagcagcgg actttgatga tgagaggaca gggcttgaat gtgaccccaa gcatggtggc 224100 tcccgctggc ctaccagcag ccatgagcaa tccccggatc ccccaggcca atgcccagca 224160 gttcccattt cctccgaact acggtactga cttagatccc tcccaccgtt gctgtcccgt 224220 cttggcctat ctgttctttc tcctttctcc cgaggcacct cagtcctggt cacggcttcc 224280 ttctcacggc tatgtgcctg gttagccagg aaacgatagg aggcctggag cagattaggg 224340 cctggcaagt ctcccagtcc cgcacagtgc ctacctgtta gctcgggtcc tccttttctt 224400 tgggtgcagg tctttaagaa tgaccaaagt taagtgtcat gtgtctctgg tgagcatgca 224460 tggatgttat ctgctcaggt cagggtctat gaatgtaata cacattgcta cttatccttg 224520 attgtttctg agtctgacac aaagaaatca gtagctaaat atgaaatgtc agaagacata 224580 agccaattta aatattacaa atagtctaca gcttttaaaa aataaaggct ttgtttgtta 224640 ctgacaacac ttatcaaaac aaaaaataaa aactttcaag attgtaccaa gtcttcactg 224700 gattggtcgt tcctgaagtg ttactcggag ccacgtggga ggcctctggc tttacttaat 224760 cctgatttgt tctcggatgt cattctaaca gacgagacac caagggtgat gtcatggaga 224820 ttgacatccg gttgttatct tccgctaaca gtgggagtct cggtgcttcc atagtgcgtc 224880 catgcttgca tgttccagat ggctctgctt tgccctgtct gagggatctg taaggaacca 224940 tgaacatgga agcctttgtg ttgcctaaat acaaacgtcg tgtctcctta aagagcagag 225000 atagtgcatt gtgttcttct cctcttcaga ctcttctctt gtagctactt ttaaatatta 225060 agtgttgcgc aggattaagc gaatgggtcc ttactctgtc cctgaaatgc cccctcgctg 225120 tcttcctttt ggtgcctttg ctcgctttcc gttgctagct cagggaagtc tgctgagatt 225180 ccttttcttt tgctgtgaat tcttttaccc taaactatac aagaaatgga taatcctgac 225240 agcactcaag tgccacaagc ccttttccaa aaacaaaata agccaatgtg ggcgtgcagt 225300 tgtgtatttt ctgaaataca tctcctgaac atgagatgat gtaagttaat ttagtgtaag 225360 ttattcatat gttgactgtt ggtatataga tgaatttaat gagctcagac taaatttaaa 225420 aggaacgata ctattacact gactgaccgg ctcagataaa atcaagtctc tacatagtag 225480 actcgtcctt ggtttagaga gggcttcagg aacaaatgtc atttctctga ctctagccct 225540 gatgctagtg tgcatcctcg gagccctgtg actcttggag agctttcaag tatagagagg 225600 gttttctcca tgtacttctg tctcagcttc tttcaaatat ctaataattt gcacataatc 225660 agataattga aagtaatttt tctgtgtata cttaatttgg aacattctct ctatgatata 225720 gataacaatc tcctttgggc ttctgttttg tttttgtttt taaggaataa gtcaacaacc 225780 tgatcctggc tttactgggg ctacaactcc ccagagtcct ctaatgtctc cccggatggc 225840 acatactcag agtcccatga tgcagcagtc tcaagccaac ccagcctacc agcccacctc 225900 agacatgaat ggatgggcac aggggagcat gggtggaaac aggtaacatc acattactgc 225960 gtctgatata aatgatcacc cctagccagg cggtggtggc gtttagcaag caatagcaaa 226020 tgaactgcta aaaagctagc ttattcttag caaaagtcaa caatttcaca gaagcctagc 226080 acagcacctc ttgttttaga gcaaaaacat tacctctaag cagttgccac tcctaactgt 226140 agaattcctg tggatggcgg tggcacagag ccaggcttca tcagtgcaca tgctaagaag 226200 caaacagcaa gcccccagca gctgggaaag caggagtgtg tgtgcttccc agcaatgtgt 226260 gcaagggaag aagcaagcct gatgcctggg ccagcaccca tttagataga gactgcctca 226320 gcttaccatc agactaactc tgtctcccac gctacagcat gttctcacag cagtccccac 226380 cacactttgg gcaacaagca aacaccagca tgtatagtaa caacatgaac atcagtgtgt 226440 cgatggcaac caacacgggt ggcttgagca gcatgaacca gatgacaggc cagatgagca 226500 tgacctcagt gacctccgtg cctacgtcag gactgccctc catgggtccc gagcaggtaa 226560 gagcctcaga gaagcagctc agaacgttct ccttggcttt gtgtctgttt atgccacaaa 226620 tcccatatct attttgaaaa gtgttttttc accttatttt cacctgtgcc agtgagattt 226680 aacaaaaaat acttgttaat gacgaaggaa ctattgggaa ggactcctgg ctgctaacat 226740 gttgggggtt ttttgctttg ttttggtttt tatttcctaa ttttcacatc attaaccttt 226800 tttatcattt gtgggattta gaaatggagt ggtaggtgtt aggaagtttc tgctgggcat 226860 ggtgacccac acctttagtc ccagcactgg ggaggcagag gcaggtggat ctccgagttc 226920 aagtccagcc tgctctgcag agcatattcc ggaatgggca gggctacaca cagaaatcct 226980 ctctcaaaaa acaaaacaaa actagctttt taaaacctct ggtaagcatg gccacacagc 227040 ctaccagccg gtcactctcg gggccgcttt gcttacgtga caaggctggc acactgttgc 227100 ccccttgatg ctccagtgct ggtgacttta gttccagacc agcctggact ctaagcgcat 227160 gttagaaagg gtagggagaa gatgtgtagc ccacacgggc caggagcacc ttctgctctg 227220 tcgggccagt gttgagagtg aggtacacag agacacagaa ccgagcgtaa tcatgggcca 227280 gcccactcag gaacattcat caacccagac catttgaaat gtgtgcatgg atttaaatat 227340 ttttgagttt cggagtttat atagaagccc aggtccaaac ccacaacccc agtgtgtctg 227400 ctgaaaaatc attgtcttat tagccctggt gggctagctc catgagtaaa agtgcctgcc 227460 accaagcctc accacctgag tgtagtcccc agactccccc gagagagctg gcctctacac 227520 tccggcctcg gacatacatg cagccatcac acacaagtaa atgtaatgag aagagttttt 227580 tttaaaaaca cataaatgct gatgagtagg ttttttggcc agtccattcc caaaagccag 227640 tttgggtgtt ctcacgtcat tcttgctaat taatgacttg cctgagagca gaagtggcag 227700 atggtctcag gtgcttcacg ctctcagggc tgagtcacca gcctataaat gaaaatgtgc 227760 aaataagctg tgcttttgaa ggtaagtagt gtttgcagcc tcctctgccc catgtgtgca 227820 catggaaagc tgttagctgt gggatacagc ctcttttccc tagggccaca aaacttaaaa 227880 tcggaaatgt gtcatgttgt caccacaggt caatgaccct gctctgaggg gaggcaacct 227940 tttcccaaac caactgcctg gaatggacat gatcaagcag gagggagatg catctcgggt 228000 aagcagcagg agcccagagt gcaccttagg gtggctgtgg gccttctgaa ggccaaacgc 228060 ttctctctgc cttgtcggcc tggaaagtgc tgggatcaaa agagcacact acaaaaacag 228120 caggcatgat ggtgcatgcc tgtaactctg gctctgagga ggcagagaca agagagtcag 228180 gagttcaagg tcaactacac tgtgagttta agaccagcct gggctacaca ttaccctatc 228240 ttagagcaaa caaaaaaaca acactcccac cttgaaaaaa aacaagaaaa taactattta 228300 cacgcagaaa gcagcctaca gcaaatgcaa ctgtgacgtg ctttccagct cttcctaaca 228360 cactgatgta cactgccacg tccaaccctc aggaaaggtt catcctgtca gagagacgca 228420 ggagggtggg gactcggcat cattagcaag tcttaagcca gccccggtta tgagagatcc 228480 agtctcaaaa aatgaagagg gccagggaga actgaattaa atccccgaag tcagagtgga 228540 aagagccaac tctccacatt gtcctcgtgc ctgcacacgg gtgcctgcac acgggtgcct 228600 gcacacgcca cagaaacagt aaaatgttta aagaaataac ctcttaggcc acctccgcat 228660 actcaaaacc aagcaatagc ttgatcccat tggagagagt ggagtgtaaa tgagcactga 228720 acttcctcac tccagagcct ttgtgttgtt agcagcaggg ctacagtaga cctcacccgc 228780 ccattgctca gcaatgtcct ggattggctt tcccactgtg gcttttctgg gttttgtaac 228840 cctgattgtg ggcttcagag atactactga cagcgggtag gagtcctgta gctgtttctc 228900

acacgtgtcc ttaaaacgtg ataattaggt gcacgaagct taccatatct tccttcctta 228960 ctgtatgtgt atctggtatg tatacatagc aggtaagaat gtcagacagc ggggtagatt 229020 gtacactaac catgtgttcc tttgtttggg tttatcactt cccaagggct gatacctctc 229080 ctatagccat ggttttcaca ggcagggagt gctaagagct cagaggtaac tccatgcaaa 229140 agcagaggtc caaaacctga ggcacagtga cagcaggtga cactcacaca ctcagagagg 229200 acattgtaac tgcaaagtgc caggggagcc tagccagagt gctgtaagta tgagtgagag 229260 tgagccagct agcatttgaa cagctatcta ggaaaagccc cttgccagcc aagccctctg 229320 aagcagaccc aggcttctgc tttctcctag gagcaccagg aatctccctg ctttgtttct 229380 cctgccttct tgcctcctgt aaagcacagc atggttgtca atgcatgtta tgtccttgaa 229440 tattgcaaga gcagccaagc ataaccgcgc atgcaggaaa gtcactacaa gagcagcctg 229500 gttgacatag aattctagcc agccagcact gcatagagag gcatggtctc aaaaagatgg 229560 agggagagaa ggaaaaaaag gaaagaaaat catggaagca gcattgacat agaattctag 229620 ccagccagca ctgcatagag aggcatggtc tcaaaaagat ggagggagag aaggaaaaaa 229680 aggaaagaaa atcatggaag cagccgatag gaatcaatca gttgctcact tagtaggcac 229740 catactgtct ggtctaacta cagccttacg aatgtaacga tttgtcctag gcctggggag 229800 atcagaaagc aagcaagctg acctctgaat gccttcctat tctttctttt tttttttttt 229860 aatttatttt atttatatga gtacactgta gttgtcatcc gacacaccag aagagggcat 229920 cagatcccat tacagatggt tgtgagccac catgtggttg ctgggatttg aactcaggac 229980 cactggaaga gcagtcagtg ctctcaaccg agatctctcc agaccatgcc tgcctatttt 230040 taacctgagc accactgtcc tctcccaaga gagacaagca ggctctcaca aggattttct 230100 caggggctat gtagcctcat ttaagaaggc ccagaggggc aagttgtttc tttggtgccc 230160 tcctccacct tgctactcaa gtcctgaagg aaggcagggt cagaaagaca ccacagaagt 230220 ttcaactacg tgtttaaatg tcatcggtct tcttttgttt tgttttgttt tgttttgttt 230280 tgttttgttc tgtttttttt cgagacaggg tttctctgta tagccctagc tgtcctggaa 230340 ctcactttgt agaccaggct ggcctcgaac tcaaaaatct acctgcctct gcctcccgag 230400 tgctgggatt aaaggcgtgc accaccatgc ccggctgtca tcagtctttt taagcatcca 230460 ggtgcttcat cccaggaggg gagaacctcc aatgctgaga cacagtgtcc cttttggact 230520 ctgtcaggcc tacatggatg ttaaaggctt cctggccatc ctgtggaaga atgtaggtga 230580 ggatcaaggg agctggtgac caacaccaac ccaactgagg aagaaagcct ggagcactgg 230640 gtgtcgccca gtccagagcc acctccccgc aaggactcat ctgaggaggc taatggagtc 230700 ctgttgctga tcaccagacc gcttacaggg acacagcagg cacatatacg atttcaggct 230760 ggcttcctct cttcaaatag atattcttag tggccctcta gtacctgctg ctcaatacag 230820 ccttggcata tatagtcatc tagattatga gttgagagtg gggtgggttt atcttaatga 230880 agtcagagtg agcacaccct cctaggacct gacagtgact cagagacgat ctagggaggg 230940 gagcgcttac gcgggcctct actcccagga ctcaggaagt agagacaggt gactcgatga 231000 ttagaggcca cactgtctag gtaaagaatt ctaaggccct gacttaaaaa atgaggagga 231060 gggctggaga gatgcctcag tggttaagag cactgactgc tcttccaaag gtcctgagtt 231120 caaattccag caaccacatg gtggctcaaa gccatctgta atgggatcca gtgccctatt 231180 ctggtgtctg aggccagcca tagtattctc acatacgtga aataaataaa atctttaaaa 231240 aaaaaaaagt ggggaggaaa actggagaga tggctcagtg gatagaagca cctactactc 231300 tctcagaagt tctgtgctca acagcaggcc agtggctcac agctacctgg aactctactt 231360 ccaggggctc tgacaccctt ttctgtgtgt ggaatataca catacaaatt aaaaatatat 231420 atatcaaatc atgatttttt taaatcagta gtagccaggc atgtgggtgc cacacacctt 231480 agtcccagca cttggaagaa aaagtaggag gatcttggtg aagccaaggc cagtctggtc 231540 tacataacga gttccaggat aaccaggatt acatagacac tgtctcaaaa acaagcacat 231600 tctttaaaaa gtcaaaggga tcaccctggg ctggggaggc actcggtggg taaagtgcca 231660 tgcaaacatg agagaggctc tcggatcaaa cccccagctc cccggttgtt ctgtacagac 231720 gggtggtcgt ccacagactg actacagcct gcgggagctt cacactgatg gatggagcgt 231780 gcacctgcgc cattcagtta gggacagcgc cacctgcctt cccgtgtcag aaacccacca 231840 ctcaccaaat gcggagcctt cgtactctag aataagctag tatgttgtgt tttatgatga 231900 tcactccatt gttttcattt caaacaaaaa caaacaaaca aaaaaactct tgatattgcc 231960 agtgtggtgg cgcacgcatt tgaaagacta gtgtatgggg gcacagaatc tgccaatagg 232020 ccagggtggc agcagaaaaa actatgcaaa cataaagagc cccttgtctt cacacaacct 232080 ttctgtctgt ttcccctcag aaatactgct gaccctggag aaactgtctg catctttctt 232140 caacccactg ggcttacaaa catttaccag tctggagagc tgcgtctctt tgtgttgcca 232200 cctgacatgc cgccagttct cccaggacat agcagcagac agtcgggccc tgggcccgca 232260 gcatagagcg tgctggcttg gctgccaccg gaagagttgc ctctcccgac agcctgcagc 232320 tcgcctccag accaacccgc agtctgttca ctgcattcac cgtagtgcaa cttagatctc 232380 ctgcagagta actgtcccca ggccgacttc atccccatca gattgaatgt atttaaatgt 232440 gtgtgtttga ggagagccat gcccttggcc tgttcctgct cggctccaga cactggtttc 232500 ttgctttgtt ctctgtggct cttctgtgta aaagatgaga atcttatcta caggaaagaa 232560 aggaactttt aacacagtac aacccaaggt gttctaagct taaagcctgc atttgactgg 232620 gatggagaca gggcagacac tgtgcacagc gctgtgtatg ccggcacacc tagtcagcaa 232680 cacgtaaccg aggcagagtt ctgtctccag gaaggagtgt cccgtcactg aacagatgga 232740 aggctcttga gagaggctgt tagcattaac aagtatctgt tcccacttct ctctgttaaa 232800 accaaactag tttcccctaa atcatgaatc aaaaagaaat acttgtttct aaattgtttt 232860 tagatcagat agtttgattg gcatctcttc ccttcctctc cccaccttct ctcgtccctc 232920 cctctttcat tcctttaaag taaaaacatc aacagcagca tacaccatag agaccaggga 232980 agcccttagg atctctcagt gctgtgccag ccacttacag cagcttccca gtgaccatgc 233040 atttcctatc agagaggaac aaagtcaggc tgtgacatct gcttaggtag cctgggctgc 233100 cccatcagct caggcctcca aaatgagaga acttactaat gaaatcaaca gcagacgtca 233160 cgacagatct aacctctgcc atatggggtt gttttttatt tttggttttt agcagtgctg 233220 acgaagccga agttttgtaa ggtacataaa gatccaattt atatgtaaac aagcaataat 233280 ttaagttctg aacttaagtg ttttaactgt ataattttgt gaggtataca tattgtggga 233340 ttgactcaaa atgaggtact tcagtattaa attagatatc ttcatagcaa tgtctcctaa 233400 aggtgttttg taacggctgc caatgccttg gttagacctg acttgtagac gtaagacctt 233460 ttgttttcta acccttgaga ctctcctcat gaatcctgta tctaatctat atgatatgca 233520 gccgctgtca gaaccaagtc ttgattttat atgtttatat tctttcttaa taaaccttag 233580 aaagacaaca ttactaagca gcccactttg atggttgttt tcttgcccac tgtcggggat 233640 aacctctatt aactggtgtc agtttcagac agctgcagta cccagaaccg agaccttttc 233700 aattctcccc aaccttgata cacacacttt cgtacctaaa tttcagaatg atgtcttttt 233760 gatgtctaaa aacaaagcat tttataatat ctcattatcc aagctttcta ggaacagaga 233820 agattttcct tgaagtttgt ttattcctgg cagggttaaa aacatataaa ctaccctatt 233880 tatatttatg tctccctata tatctacaga ttgtagaaat atagaaagag atgtgaccca 233940 aagacaaatg gtcagtcatc tgaaagtgtt gctgcgtgct aaggaactct ggaaatttgc 234000 atttccatac ctttttccac ttagagaaga atctcagtga gggaggtggc ccaggaacag 234060 cgcttccccg ttggccacca gttcctgtgt ctgctcgaga ctccaccaaa ccattggctt 234120 gcacatctgt cctgcaaagg gagcagatag aacccagaac tccaggccct gccccaggag 234180 tgaggctcag gtgcactact gagctcgacc tgttctcaga taagtcagaa atgtgaggta 234240 ggtaaaaatg acttcacaca gcacaagaga aaaaggaatt taaaacatac ttgttttgta 234300 ttaaatccca tctcactgta acatcaagcc acaatatctt acctttcagc cttcatccaa 234360 tctcccactg ctttctaatg ttgacccggc tgttagcgta gcccatggtc atggcaaatc 234420 ctctcacagg tcagagcagc catgaactgt gtgccatctc atcaggagga tcaatcgcat 234480 cagcaaaggc atcctgatca tgttctcaga gccagggcca gcccagcctc ccctgccatc 234540 agtattgctc acgctctgca caacacattt gtacttggtt ttgtctgaca gaacatagaa 234600 tcagtgttct cttagatgac tcaatgtgaa aagcgtaatg tgaaaagtac acacctgatc 234660 gtggttgtaa aatccattta agtgttcatg caacatggtg agttttaaaa gtgaagtgtg 234720 ctgtgatact acaaccaatt gactcaaaga ttaaagcacg cacgcacaca cacacacaca 234780 tacacacgtg tatctcttac gacctgtaat gattgaaagc aatggttttt ttgcagttta 234840 agatgcaatt tttaatctgt gtttaaaaac ggagttcata tgggtgtgac acgtgaactg 234900 ggaggcacag atccacttgc agaacccaaa gatacacaat caattttgaa atgcaactta 234960 agccattaat tgttggtgtg aatttaaaat tttctagttg tttatatggt agtatgctgc 235020 cgaagagcaa agcattctct gcacaaaaga aaacactgta gtggcttcga ttttaattag 235080 aactttctcc ctggtgtttc tttatagact aaaacaaaat cttttaagtt tctttactac 235140 aggtaaaagc tatgtgcaag aacctcaaaa tgctaaaacc tagcataatg ccttagatct 235200 gtttttaagt cttgtatatt cctacatagc tgtccaatgt attatatttg tatagtgaat 235260 tgtgtaaaat ttttgaataa gtaagtcatc gcttacccgt atgttactga acagtgatga 235320 caactcgttt cttcaaacat ttaactgtct tctctttttc ctttgtcatt tgtgggtttt 235380 atttgtacag ttcctcatga agttgcattt gagatatgtg tatatgaaaa aattatacaa 235440 gggtaaaatt aagcaatata ttaactatgg ttcttcagga gaaagcttac agtgtttcag 235500 gttgtgattt attttcaaaa cagagttgac tctgaacatc actttgttca tctgcattga 235560 tgtttgtatt tctagtgtga gcagtttatg caaaggtaga tatatacaga gaaattttaa 235620 atacatttat gcaagttact attgctttgc tgatgctatt tgcttatttg atgttaaata 235680 atgctattgt aaataaagaa tctgttgtta ctgcatcatt taataaattt taatgccttc 235740 gggttttaca tggctttaga gattttaatg tggcgatacg gtatcttctt ttgtagttta 235800 aacttaaaaa tacctgagaa ctactactgg ctgctctttc agaagaccca gattcaattt 235860 ctagcaccca cacatcatct cagaatcatc tgtaactcca gttccaggag gtccagcccc 235920 ttcttcctgc tcttacaggc attaggacca ctcctgatac agttttcaaa caaacaaagc 235980 atctatagac atacaacctt ttaaaaaaat atattaacga cattatcttt taagaatttc 236040 ttgggctggg tgggtaggga agtggggggg agggtatgga ggacttttgg gatagcattg 236100 gaaatgtaat tgaggaaaat atgtaataaa aaaaaagaat ttcttgggct aggcatgatg 236160 gtgcacacct ttgaccccag cactccagag gcagaggctg gtggatctgc cccgtctaca 236220 gagcaagctc cagggtagcc tgggctgttg ggggggaaaa aaaaaaaaaa aaaacagaag 236280 gaaaaaggga atttcttgtt tctggagcga tgactcaata tgcttattgc ttttatgcag 236340 gagcccactt ctcttcccag cactcaggtc aggaggctca caactgcctg taagtccttt 236400 tcctggggga tacactgccc tcttatggcc tctatagaca ctgcactcgg gtgcacatat 236460

ccacaaggag aaacacccat gcacataatt aaaaatacat tttaaaaatg gtagtcagtg 236520 gtcacagcac tcttaacacc ttgccctccc agagaagcca agtatatcct agttgacatc 236580 actagctctt tatggcagat gtggcctgtc tagttcctgc tacaaatatt gctgcagtat 236640 ctgtggatgt gaggagtcac ggcgtacctg tgctggtcag aggtcaactc tcaggagttg 236700 gctctctccc gccactctat gggtcctgga gatggaaccc caggtcacca gacttggcaa 236760 gtgagcacct ttaccagctg agccctcccc cagcccacac tgtttataaa gatggaaagt 236820 actgtgtcct cttcaaaagt gctggtgccc ctctcacaag cttgcgtctt acaggattcg 236880 tgaagggcat atcttctggg ccttcccagt gtggacgatt aggttttcca caatgtatcc 236940 actctaccat tgcaatttcc ctgagcctta aaatcccttc atcaacacta agccgaggga 237000 catcaggcat cttcaactcc ttttcagtag gccatctttt tttttttttt tttttttttt 237060 ttttgagaca ggggtttctc tgtatagccc tgacggtcct ggaactcact ttgtagacca 237120 ggctggcctc gaactcagaa atctgcttgc ctctgcctcc aaatgctggg attaaaggtg 237180 tgtgccaccc acgcccggct tgtaggccat cttttgataa acacttcagc caaccattca 237240 aacaaacaaa cttctgacag cttttttaac tgtgcaagct tccatattaa acctagaatc 237300 tccactcaga gggaccacat cagtaaactc agcctgctct agttttatgt tccttccacc 237360 attttcccac acccttaaaa tccattccca cacatatccc ccaggtttct gcttgaatca 237420 attagcaaac tcatgaagct cctttgtagt gaagcgcatt tcctcccctc tatggctctc 237480 ttctgccttg agtctggtta taggtctaga agaagctatt ggtgggcctt gagaaacatc 237540 agtattgtct ggcattttct tcagcgaaag tcactgctgg tttaacagac tctgagggat 237600 taattttctc atgtgaaaat ggcattattt caaggggtgg ggcactactt cctcaggtgg 237660 ggcaaaccct tgagaatctg aagattcaaa attctcagct tcaacatggt cttcccacac 237720 atccccatcc caagttttaa gatcccattc tttgccttta actgctgaca ccctctgaga 237780 cttgaatttt cgctgtaatt caaccaacct tataatgagg gcttcagttt gattttctgc 237840 aacttgagct ctatggctgc tgaagagaag attctcttca aggacacaca tagcaacttt 237900 tagatcactt ccttgcatct ggagccattt gatattatca cacaataact tcttttcctt 237960 catccttttt ccccaagatg ctaagagcaa ccagccagca aaatcatttt ccaatttttc 238020 cccatcttgt agaaagcttt gtacactgaa tcatctaata cattaagata atcaaaggca 238080 ttagcttctt taaacttgaa atacagtttc aaccacgggt cttcaatatt ctccaagctc 238140 ccaggaggga gagaatctgg agaggtttca gtcgttgaag gtgctggtga attatcaaac 238200 caactccaga atttcatcct tatacttctg ctcctctaga actcctcctg gtaccagctt 238260 ctgtaatagt cagggctctc tagagtctag aacttacggg tagtctgtat atagtaaggg 238320 aatctgttga cgtaagtctg tagtccaact cccagccatg gtcagcagca gctgtgaatg 238380 gatgtccaag gatctagcag tttctcagcc ccacaggcaa gcaggggaag gaaagagggg 238440 taaacagtgc aattacgctg ccttcaaccc aggtcctaaa tcgcatgcag tgctagaggc 238500 ccagtttggg tttttccctt ctctagcatg aagggaaaca ttggccattg caggtggtgg 238560 cccagagagg actgtgttaa gctgctgctg ctgctgctgg caagggtacc ccgtcccagg 238620 aaggtaccag aagcgagcag tcagtttcat agatctctgc agagctgttg gcctatagca 238680 ccgagccagc tgtccacttt ccctttccct ttttcttttt ggatactggc caagccaaag 238740 caatattatc tctaatattt tacagaagct accacactcc gttgtgtggt tgcttacaag 238800 aggtgtggat ttttatctct cctgtcttcc tcctccagtg acatctgaaa ctcactgtgc 238860 agcaaaacct ggccttgaac ccctcctgca tctatctcct aggtgctgaa attgcaggtg 238920 tgccccatca tcccaggcat caaccctgga ttgctctcta agaaacgctg ctagctcatt 238980 cctgcaacca caaataccag tcatgcacaa gttgtaccca ggggctggtg acaggaagaa 239040 gagaactggt ggccagtcaa agcactgcct gcctagttag ggtgtccagc agcatcacaa 239100 aatagaaatg atacatcatg attggtcctc atccggcaac acagttcagc aagtaaaggc 239160 acttgccacc aagcctgaac gtcatggtag gggattaagt gactcctgca ggttgtcgtc 239220 tgtcctagtt agggttacta gcactgctgt gatgaaacac catgaccaaa gcaacctgca 239280 gaggaaagga ttcattcagc ttctacatca cagttcatca tcaaaggaaa ttaggacaac 239340 ttaagcaggg aggaacctgg aggcaggagc tgatgcagag gccatagagg ggtgctgctt 239400 actgcttccc atggcttgtt caagcctgct ttcttagaga gcccaggacc accagcccag 239460 agtgaacccc tcctacaata ggctaggcct cctccatcaa tcacaaagaa aatgccctac 239520 agactctctc tgataactcc agcttgtgtc aaatcaacat aaaacaaacc agtacctcct 239580 ctgacctcca aacgtgtgca agtgtggcac tttcatgcca ctagcaaaca tctgacccaa 239640 gatcagcacc acatagccag ggagactcgg aaactggcta gctgacactg aaagatcctg 239700 agagagaaga gtgaaaaatt atgtaagccc ctagacttgt gtccaaaata gacctgacta 239760 atggcaggga gtaaaagttt aactcacccc attgttttag gttgtactaa ccacaaagta 239820 gaagtttaac ttccattgtt ttaggaaatg ttcatacaga atattccaac tatttcttga 239880 acccgttgtg cttgccaaat gctatagccc atgccaggtg tttacggttt ctgcctttat 239940 aagcccctta tcctttgagc tgggggcgac tcctctaccc cttcgtggga tacgagtcgt 240000 c 240001 <210> SEQ ID NO 33 <211> LENGTH: 4039 <212> TYPE: DNA <213> ORGANISM: M. musculus <400> SEQUENCE: 33 actccccaga gtcctctaat gtctccccgg atggcacata ctcagagtcc catgatgcag 60 cagtctcaag ccaacccagc ctaccagccc acctcagaca tgaatggatg ggcacagggg 120 agcatgggtg gaaacagcat gttctcacag cagtccccac cacactttgg gcaacaagca 180 aacaccagca tgtatagtaa caacatgaac atcagtgtgt cgatggcaac caacacgggt 240 ggcttgagca gcatgaacca gatgacaggc cagatgagca tgacctcagt gacctccgtg 300 cctacgtcag gactgccctc catgggtccc gagcaggtca atgaccctgc tctgagggga 360 ggcaaccttt tcccaaacca actgcctgga atggacatga tcaagcagga gggagatgca 420 tctcggaaat actgctgacc ctggagaaac tgtctgcatc tttcttcaac ccactgggct 480 tacaaacatt taccagtctg gagagctgcg tctctttgtg ttgccacctg acatgcccca 540 gttctcccag gacatagcag cagacagtcg ggccctgggc ccgcagcata gagcgtgctg 600 gcttggctgc caccggaaga gttgcctctc ccgacagcct gcagctcgcc tccagaccaa 660 cccgcagtct gttcactgca ttcaccgtag tgcaacttag atctcctgca gagtaactgt 720 ccccaggccg acttcatccc catcagattg aatgtattta aatgtgtgtg tttgaggaga 780 gccatgccct tggcctgttc ctgctcggct ccagacactg gtttcttgct ttgttctctg 840 tggctcttct gtgtaaaaga tgagaatctt atctacagga aagaaaggaa cttttaacac 900 agtacaaccc aaggtgttct aagcttaaag cctgcatttg actgggatgg agacagggca 960 gacactgtgc acagcgctgt gtatgccggc acacctagtc agcaacacgt aaccgaggca 1020 gagttctgtc tccaggaagg agtgtcccgt cactgaacag atggaaggct cttgagagag 1080 gctgttagca ttaacaagta tctgttccca cttctctctg ttaaaaccaa actagtttcc 1140 cctaaatcat gaatcaaaaa gaaatacttg tttctaaatt gtttttagat cagatagttt 1200 gattggcatc tcttcccttc ctctccccac cttctctcgt ccctccctct ttcattcctt 1260 taaagtaaaa acatcaacag cagcatacac catagagacc agggaagccc ttaggatctc 1320 tcagtgctgt gccagccact tacagcagct tcccagtgac catgcatttc ctatcagaga 1380 ggaacaaagt caggctgtga catctgctta ggtagcctgg gctgccccat cagctcaggc 1440 ctccaaaatg agagaactta ctaatgaaat caacagcaga cgtcacgaca gatctaacct 1500 ctgccatatg gggttgtttt ttatttttgg tttttagcag tgctgacgaa gccgaagttt 1560 tgtaaggtac ataaagatcc aatttatatg taaacaagca ataatttaag ttctgaactt 1620 aagtgtttta actgtataat tttgtgaggt atacatattg tgggattgac tcaaaatgag 1680 gtacttcagt attaaattag atatcttcat agcaatgtct cctaaaggtg ttttgtaacg 1740 gctgccaatg ccttggttag acctgacttg tagacgtaag accttttgtt ttctaaccct 1800 tgagactctc ctcatgaatc ctgtatctaa tctatatgat atgcagccgc tgtcagaacc 1860 aagtcttgat tttatatgtt tatattcttt cttaataaac cttagaaaga caacattact 1920 aagcagccca ctttgatggt tgttttcttg cccactgtcg gggataacct ctattaactg 1980 gtgtcagttt cagacagctg cagtacccag aaccgagacc ttttcaattc tccccaacct 2040 tgatacacac actttcgtac ctaaatttca gaatgatgtc tttttgatgt ctaaaaacaa 2100 agcattttat aatatctcat tatccaagct ttctaggaac agagaagatt ttccttgaag 2160 tttgtttatt cctggcaggg ttaaaaacat ataaactacc ctatttatat ttatgtctcc 2220 ctatatatct acagattgta gaaatataga aagagatgtg acccaaagac aaatggtcag 2280 tcatctgaaa gtgatgctgc gtgctaagga actctggaaa tttgcatttc catacctttt 2340 tccacttaga gaagaatctc agtgagggag gtggcccagg aacagcgctt ccccgttggc 2400 caccagttcc tgtgtctgct cgagactcca ccaaaccatt ggcttgcaca tctgtcctgc 2460 aaagggagca gatagaaccc agaactccag gccctgcccc aggagtgagg ctcaggtgca 2520 ctactgagct cgacctgttc tcagataagt cagaaatgtg aggtaggtaa aaatgacttc 2580 acacagcaca agagaaaaag gaatttaaaa catacttgtt ttgtattaaa tcccatctca 2640 ctgtaacatc aagccacaat atcttacctt tcagccttca tccaatctcc cactgctttc 2700 taatgttgac ccggctgtta gcgtagccca tggtcatggc aaatcctctc acaggtcaga 2760 gcagccatga actgtgtgcc atctcatcag gaggatcaat cgcatcagca aaggcatcct 2820 gatcatgttc tcagagccag ggccagccca gcctcccctg ccatcagtat tgctcacgct 2880 ctgcacaaca catttgtact tggttttgtc tgacagaaca tagaatcagt gttctcttag 2940 atgactcaat gtgaaaagcg taatgtgaaa agtacacacc tgatcgtggt tgtaaaatcc 3000 atttaagtgt tcatgcaaca tggtgagttt taaaagtgaa gtgtgctgtg atactacaac 3060 caattgactc aaagattaaa gcacgcacgc acacacacac acacatacac acgtgtatct 3120 cttacgacct gtaatgattg aaagcaatgg tttttttgca gtttaagatg caatttttaa 3180 tctgtgttta aaaacggagt tcatatgggt gtgacacgtg aactgggagg cacagatcca 3240 cttgcagaac ccaaagatac acaatcaatt ttgaaatgca acttaagcca ttaattgttg 3300 gtgtgaattt aaaattttct agttgtttat atggtagtat gctgccgaag agcaaagcat 3360 tctctgcaca aaagaaaaca ctgtagtggc ttcgatttta attagaactt tctccctggt 3420 gtttctttat agactaaaac aaaatctttt aagtttcttt actacaggta aaagctatgt 3480 gcaagaacct caaaatgcta aaacctagca taatgcctta gatctgtttt taagtcttgt 3540 atattcctac atagctgtcc aatgtattat atttgtatag tgaattgtgt aaaatttttg 3600 aataagtaag tcatcgctta cccgtatgtt actgaacagt gatgacaact cgtttcttca 3660

aacatttaac tgtcttctct ttttcctttg tcatttgtgg gttttatttg tacagttcct 3720 catgaagttg catttgagat atgtgtatat gaaaaaatta tacaagggta aaattaagca 3780 atatattaac tatggttctt caggagaaag cttacagtgt ttcaggttgt gatttatttt 3840 caaaacagag ttgactctga acatcacttt gttcatctgc attgatgttt gtatttctag 3900 tgtgagcagt ttatgcaaag gtagatatat acagagaaat tttaaataca tttatgcaag 3960 ttactattgc tttgctgatg ctatttgctt atttgatgtt aaataatgct attgtaaata 4020 aagaatctgt tgttactgc 4039 <210> SEQ ID NO 34 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 34 aaccacactt acccatgggc 20 <210> SEQ ID NO 35 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 35 atgcactcaa gaactcggta 20 <210> SEQ ID NO 36 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 36 atgtccagtt ttccgccctt 20 <210> SEQ ID NO 37 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 37 atttgcatcc atgagctcca 20 <210> SEQ ID NO 38 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 38 caggagatgt tggccgtggt 20 <210> SEQ ID NO 39 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 39 ccagggctgc ctcagacaca 20 <210> SEQ ID NO 40 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 40 cgctcgtact cgtaggccag 20 <210> SEQ ID NO 41 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 41 ctcgtgaacc agagcaccac 20 <210> SEQ ID NO 42 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 42 ctgctagcct ctggatttga 20 <210> SEQ ID NO 43 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 43 gagctttgcc ttcttgccat 20 <210> SEQ ID NO 44 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 44 gcactttgtg gtgccaaggc 20 <210> SEQ ID NO 45 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 45 gctccttcca ctgatcctgc 20 <210> SEQ ID NO 46 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 46 ggacctgtag ccatagccaa 20 <210> SEQ ID NO 47 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 47 gtgtttctga gaacttgtgg 20 <210> SEQ ID NO 48 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 48 gttcctgtca aagctcgtgc 20 <210> SEQ ID NO 49 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 49 gttggtctcc tttgcctgga 20 <210> SEQ ID NO 50 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 50 tcaaggactg ctgatcttcg 20 <210> SEQ ID NO 51 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 51 tcaagtttct ctgtgcccaa 20 <210> SEQ ID NO 52 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 52 tccatttatt agtctaggaa 20 <210> SEQ ID NO 53 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 53

tctacagtca tgctgagtaa 20 <210> SEQ ID NO 54 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 54 tgtcatcggg ttcccagcct 20 <210> SEQ ID NO 55 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 55 tgtgctattc tgtgaatt 18 <210> SEQ ID NO 56 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 56 tgttgcaaga atttctcatg 20 <210> SEQ ID NO 57 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 57 ttcatgaact gcacagaggt 20 <210> SEQ ID NO 58 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 58 ttctcatgat gaggtgtacc 20 <210> SEQ ID NO 59 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 59 ttgttgacat tgtactcggc 20 <210> SEQ ID NO 60 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 60 ttgttgacgt tgtactcagc 20 <210> SEQ ID NO 61 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 61 cctgatccct ctaatgatgc 20 <210> SEQ ID NO 62 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 62 cctgctcact ctaatgctgc 20 <210> SEQ ID NO 63 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 63 cctgctccct ctaatgctgc 20 <210> SEQ ID NO 64 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 64 ccttccctga aggttcctcc 20 <210> SEQ ID NO 65 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 65 cgttattaac ctccgttgaa 20 <210> SEQ ID NO 66 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 66 cttctagcct ctggattgga 20 <210> SEQ ID NO 67 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 67 gcgatttccc gttttcacct 20 <210> SEQ ID NO 68 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 68 gttcgtgttc tctggctcga 20 <210> SEQ ID NO 69 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 69 tacttgacct acagagtgga 20 <210> SEQ ID NO 70 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 70 tcaagtcctt ccacacccaa 20 <210> SEQ ID NO 71 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 71 ttgttaacgg tgttctcagc 20 <210> SEQ ID NO 72 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 72 tttgtaacgg tgttcactga 20 <210> SEQ ID NO 73 <400> SEQUENCE: 73 000 <210> SEQ ID NO 74 <400> SEQUENCE: 74 000 <210> SEQ ID NO 75 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(20) <223> OTHER INFORMATION: n = A,T,C or G <400> SEQUENCE: 75 nnnnnnnnnn nnnnnnnnnn 20 <210> SEQ ID NO 76 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 76 attcttaaac ctgagggagc 20 <210> SEQ ID NO 77 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 77 tgatcgtctt ccaagctccc 20 <210> SEQ ID NO 78 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 78 gagagatgca gctggagcca 20 <210> SEQ ID NO 79 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 79 tgccatcatc tgatgcccgg 20 <210> SEQ ID NO 80 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 80 ttagaaggat ctgtgagttt 20 <210> SEQ ID NO 81 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 81 gcacattgac cactgttctt 20 <210> SEQ ID NO 82 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 82 agtgctttca taaggcagtc 20 <210> SEQ ID NO 83 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 83 ctctggttgc aggcccctca 20 <210> SEQ ID NO 84 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 84 aagtctgaac actgcacagc 20 <210> SEQ ID NO 85 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 85 ttacctttgt gttcgtggag 20 <210> SEQ ID NO 86 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 86 gcagcatcag tattccaatc 20 <210> SEQ ID NO 87 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 87 tcttccgagc aaagttgtgt 20 <210> SEQ ID NO 88 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 88 tgagcaggaa tttctgacag 20 <210> SEQ ID NO 89 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 89 tggaaacaat aagagttgtc 20 <210> SEQ ID NO 90 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 90 ggaaacagac tctcgcatac 20 <210> SEQ ID NO 91 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 91 gtgctgagaa ctaacaggca 20 <210> SEQ ID NO 92 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 92 tgaccatgtg gacattaggt 20 <210> SEQ ID NO 93 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 93 ctgtccacag gcagcgtggt 20 <210> SEQ ID NO 94 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 94 gaaggtgagg ctgattcgct 20 <210> SEQ ID NO 95 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 95 cacgaggcct aattttgttt 20

<210> SEQ ID NO 96 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 96 atttcccaat aatagcttga 20 <210> SEQ ID NO 97 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 97 gcaacatctc cgtgccattt 20 <210> SEQ ID NO 98 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 98 tcctgaaggc ctggaattgc 20 <210> SEQ ID NO 99 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 99 ccgtgttttg cgcagaacag 20 <210> SEQ ID NO 100 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 100 caggttgtcc tttgtcatgt 20 <210> SEQ ID NO 101 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 101 ggacatgcag gtgtttgtag 20 <210> SEQ ID NO 102 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 102 attagctgga acatctgaaa 20 <210> SEQ ID NO 103 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 103 atgcaaatag tccattccct 20 <210> SEQ ID NO 104 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 104 gaaatatatt gttggatttc 20 <210> SEQ ID NO 105 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 105 cgtgacttta ctgttgccaa 20 <210> SEQ ID NO 106 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 106 gggccatcca gaggacagag 20 <210> SEQ ID NO 107 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 107 tgaagatgat ctgatctcgg 20 <210> SEQ ID NO 108 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 108 atatagctta ctaagatctg 20 <210> SEQ ID NO 109 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 109 aatggaagac aggatctggg 20 <210> SEQ ID NO 110 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 110 cttcggtaga gagtgttgga 20 <210> SEQ ID NO 111 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 111 tatcctcagt gtgggctgcc 20 <210> SEQ ID NO 112 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 112 tgcaaagtca actagaagac 20 <210> SEQ ID NO 113 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 113 ttctgcctct ggagaaaggg 20 <210> SEQ ID NO 114 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 114 aggtccttag cagagcttct 20 <210> SEQ ID NO 115 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 115 aaatggcttc cttctcccag 20 <210> SEQ ID NO 116 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 116 tacagaaggc tgggccttga 20

<210> SEQ ID NO 117 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 117 tttttgtact accatcaaca 20 <210> SEQ ID NO 118 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 118 acttcctcta aatactcatg 20 <210> SEQ ID NO 119 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 119 tccacatcag ggctggactg 20 <210> SEQ ID NO 120 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 120 gaagctgatt tccaaaatcc 20 <210> SEQ ID NO 121 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 121 tcccgcctgt gacatgcatt 20 <210> SEQ ID NO 122 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 122 accactctct gaagaaagtc 20 <210> SEQ ID NO 123 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 123 gtgccttatg tgcaaaatgt 20 <210> SEQ ID NO 124 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 124 ggcggccaga gtctcggcag 20 <210> SEQ ID NO 125 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 125 ctaagaaaag ttccatagta 20 <210> SEQ ID NO 126 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 126 gaagctgtga aaggaggacg 20 <210> SEQ ID NO 127 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 127 gggcagctcc tggaagacaa 20 <210> SEQ ID NO 128 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 128 tgtatacaca tgatgtgact 20 <210> SEQ ID NO 129 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 129 aacatagcta tttgaagcta 20 <210> SEQ ID NO 130 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 130 aagcaataat ttcaatttct 20 <210> SEQ ID NO 131 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 131 gcccagctta acgtgtattt 20 <210> SEQ ID NO 132 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 132 tcatcaggcc cagcttaacg 20 <210> SEQ ID NO 133 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 133 ccatccatgg aaacattatc 20 <210> SEQ ID NO 134 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 134 acagcatcta acatcactgt 20 <210> SEQ ID NO 135 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 135 agtcaatctc ccgaggatag 20 <210> SEQ ID NO 136 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 136 agtgacgctt tccaagaaga 20 <210> SEQ ID NO 137 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 137 atgtaagcta acgatgaata 20

<210> SEQ ID NO 138 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 138 ttccctgggc tattctccca 20 <210> SEQ ID NO 139 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 139 aattgagaat tacactcacc 20 <210> SEQ ID NO 140 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 140 aacgcctcct aaattgagaa 20 <210> SEQ ID NO 141 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 141 tggattggct tagggaccca 20 <210> SEQ ID NO 142 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 142 actattttgc ccttatgaag 20 <210> SEQ ID NO 143 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 143 tcttaaaatc tactctgaaa 20 <210> SEQ ID NO 144 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 144 cttaactgtc ttaaaatcta 20 <210> SEQ ID NO 145 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 145 tgaaaaatgt acttttctat 20 <210> SEQ ID NO 146 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 146 aaagttttct ttaaacaatg 20 <210> SEQ ID NO 147 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 147 gcccatgttc tcagaataaa 20 <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 148 aatctaggtc tgttgaactc 20 <210> SEQ ID NO 149 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 149 aaggtaattt gctcaaggcc 20 <210> SEQ ID NO 150 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 150 agaaaactgg gactctaaga 20 <210> SEQ ID NO 151 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 151 tatttctatc tgaaaaataa 20 <210> SEQ ID NO 152 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 152 aacaaaccta tgaagtaggt 20 <210> SEQ ID NO 153 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 153 tgccacctac ctgagggagc 20 <210> SEQ ID NO 154 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 154 attcttaaac ctggtaagaa 20 <210> SEQ ID NO 155 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 155 gttcacatac cactgttctt 20 <210> SEQ ID NO 156 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 156 gcacattgac ctacaaacaa 20 <210> SEQ ID NO 157 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 157 gagctcttac cctttgtgtt 20 <210> SEQ ID NO 158 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 158

tgcaacttac aaagttgtgt 20 <210> SEQ ID NO 159 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 159 tcttccgagc ctacaacaag 20 <210> SEQ ID NO 160 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 160 aatgccttac aagagttgtc 20 <210> SEQ ID NO 161 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 161 gtgctgagaa ctaggaggag 20 <210> SEQ ID NO 162 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 162 gccctattac ctcaatcatc 20 <210> SEQ ID NO 163 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 163 gaattgcatc ctgaaacaga 20 <210> SEQ ID NO 164 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 164 ggaaaagtac ctgattcgct 20 <210> SEQ ID NO 165 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 165 gaaggtgagg cttaatagac 20 <210> SEQ ID NO 166 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 166 cacgaggcct ctgaaacaag 20 <210> SEQ ID NO 167 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 167 ccaagcttac cgtgccattt 20 <210> SEQ ID NO 168 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 168 gcaacatctc ctgcaaaatt 20 <210> SEQ ID NO 169 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 169 ttctactcac cgcagaacag 20 <210> SEQ ID NO 170 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 170 tctactcact ccattccctg 20 <210> SEQ ID NO 171 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 171 atgcaaatag ctgtgaaggg 20 <210> SEQ ID NO 172 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 172 caaaggatac tgttggattt 20 <210> SEQ ID NO 173 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 173 agaaatatat ctcaatgctt 20 <210> SEQ ID NO 174 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 174 agattctcac catccagagg 20 <210> SEQ ID NO 175 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 175 acagacttac ctgatctcgg 20 <210> SEQ ID NO 176 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 176 tgaagatgat ctaagggaaa 20 <210> SEQ ID NO 177 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 177 ggaagacagg atctgaaaca 20 <210> SEQ ID NO 178 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 178 gtgcgcgcga gcccgaaatc 20 <210> SEQ ID NO 179 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 179

tatcagcaac tgtgcctgta 20 <210> SEQ ID NO 180 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 180 cccactcatc ttgaacacat 20 <210> SEQ ID NO 181 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 181 tctgcacttc atctatgttg 20 <210> SEQ ID NO 182 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 182 cagctcttct tggttatacc 20 <210> SEQ ID NO 183 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 183 tgtctcagaa cttcatggtg 20 <210> SEQ ID NO 184 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 184 gaacggatga gtttgctctt 20 <210> SEQ ID NO 185 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 185 tcattagtag tctgagaacg 20 <210> SEQ ID NO 186 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 186 acctgggttc ccactgcaca 20 <210> SEQ ID NO 187 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 187 gggaaaattt atattgctac 20 <210> SEQ ID NO 188 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 188 atgcccattt gttcctttgg 20 <210> SEQ ID NO 189 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 189 tgcttctcct tgagcgaggt 20 <210> SEQ ID NO 190 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 190 aggatctgtc ttactgtcca 20 <210> SEQ ID NO 191 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 191 tgttactggc aggatctgtc 20 <210> SEQ ID NO 192 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 192 tgcaaatcat ccaaaatctc 20 <210> SEQ ID NO 193 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 193 atggcttgct tgtcaactga 20 <210> SEQ ID NO 194 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 194 tgatgatggc ttgcttgtca 20 <210> SEQ ID NO 195 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 195 gttgcatgag gtcattgatg 20 <210> SEQ ID NO 196 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 196 gtgggttatt aaaagtgctc 20 <210> SEQ ID NO 197 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 197 tggtcgtggg ttattaaaag 20 <210> SEQ ID NO 198 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 198 ccagttgccc tggtcgtggg 20 <210> SEQ ID NO 199 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 199 cctgcccagt tgccctggtc 20 <210> SEQ ID NO 200 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound

<400> SEQUENCE: 200 ctggtttggc aataacctgc 20 <210> SEQ ID NO 201 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 201 gtccagcacc agttgggctt 20 <210> SEQ ID NO 202 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 202 gaaaggtcca gcaccagttg 20 <210> SEQ ID NO 203 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 203 tgattggtgg gaaaggtcca 20 <210> SEQ ID NO 204 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 204 ctactgtttc tgattggtgg 20 <210> SEQ ID NO 205 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 205 ggctgaggta tcactgagta 20 <210> SEQ ID NO 206 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 206 ttcctggctg aggtatcact 20 <210> SEQ ID NO 207 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 207 ttacccatca ttcctggctg 20 <210> SEQ ID NO 208 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 208 gtctttggcc aggctggctg 20 <210> SEQ ID NO 209 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 209 tggctctggc tgaccagttc 20 <210> SEQ ID NO 210 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 210 agtttggatc ttgcatggga 20 <210> SEQ ID NO 211 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 211 ttctgctgtg cttggaggcg 20 <210> SEQ ID NO 212 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 212 gtcgtagccc cagtaaagcc 20 <210> SEQ ID NO 213 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 213 agttgcacta cggtgaatgc 20 <210> SEQ ID NO 214 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 214 gcatctttac cacttcagga 20 <210> SEQ ID NO 215 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 215 gaaaactcac ctggtcactg 20 <210> SEQ ID NO 216 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 216 aacaggtcga gctcagtagt 20 <210> SEQ ID NO 217 <211> LENGTH: 40 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 217 gttggaggca atggcaagaa ggcaaagctc ttcaggagga 40 <210> SEQ ID NO 218 <211> LENGTH: 21 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 218 cucauccucu guggcaaacu u 21 <210> SEQ ID NO 219 <211> LENGTH: 21 <212> TYPE: RNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <400> SEQUENCE: 219 aaguuugcca cagaggauga g 21 <210> SEQ ID NO 220 <211> LENGTH: 21 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(19) <223> OTHER INFORMATION: bases at these positions are RNA <400> SEQUENCE: 220 ggagccuugc guccugggct t 21 <210> SEQ ID NO 221 <211> LENGTH: 21

<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Oligomeric Compound <220> FEATURE: <221> NAME/KEY: misc_feature <222> LOCATION: (1)..(19) <223> OTHER INFORMATION: bases at these positions are RNA <400> SEQUENCE: 221 gcccaggacg caaggcucct t 21

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