WO1994000473A2 - Pentavalent synthesis of oligonucleotides containing stereospecific alkylphosphonates and arylphosphonates - Google Patents

Pentavalent synthesis of oligonucleotides containing stereospecific alkylphosphonates and arylphosphonates Download PDF

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WO1994000473A2
WO1994000473A2 PCT/US1993/006277 US9306277W WO9400473A2 WO 1994000473 A2 WO1994000473 A2 WO 1994000473A2 US 9306277 W US9306277 W US 9306277W WO 9400473 A2 WO9400473 A2 WO 9400473A2
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aryl
lower alkyl
oligonucleotide
group
alkyl
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WO1994000473A3 (en
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Eric Wickstrom
Alexander V Lebedev
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Res Corp Technologies Inc
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    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3212'-O-R Modification

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Abstract

The present invention provides a method for making R stereospecific alkyl- and aryl-phosphonate linkages between nucleotides. These methods can be used for automated synthesis of oligonucleotides having sequential R stereospecific alkyl- and aryl-phosphonate linkages. The present invention is also directed to the oligonucleotides having several sequential R phosphonate linkages which were produced by the subject methods. Moreover, the present invention provides methods for using the subject oligonucleotides, including methods for regulating the biosynthesis of a DNA, an RNA or a protein and methods for detecting and isolating complementary nucleic acid targets.

Description


  
 



   PENTAVALENT SYNTHESIS OF
 OLIGONUCLEOTIDES CONTAINING   STEREOSPECIFIC   
   ALRYlPHOSPHONATES    AND   ARYLPHOSPRONATES   
 The present invention provides methods of making R-stereospecific alkyl- or aryl-phosphonate linkages between nucleotides. Moreover, these methods are amenable to automation. The present invention is also directed to the R-stereospecific alkyl- and arylphosphonate oligonucleotides formed by such methods.



  Moreover, in another embodiment, the present invention is directed to methods of using the R-stereospecific oligonucleotides, for example, as diagnostic probes and as therapeutic agents having the capability of regulating cellular and viral DNA replication, RNA transcription, protein translation, and other processes involving nucleic acid templates. Furthermore, the present R-stereospecific oligonucleotides can be used as probes for detection or isolation of a target nucleic acid.



   Oligonucleotides have been employed diversely in utilities ranging from diagnosis and therapy of disease to discovery, cloning and synthesis of nucleic acids. For example, oligonucleotides can be used as probes to identify target nucleic acids that are present in vivo, in tissue samples or that are immobilized onto a filter or membrane. After identification by the oligonucleotide, a target nucleic acid can be cloned and an oligonucleotide can be used to prime the synthesis of that nucleic acid. Moreover, hybridization patterns of an oligonucleotide to a nucleic acid that differ from normal hybridization patterns are frequently useful in diagnosis of disease. Furthermore, there has been great  interest recently in developing oligonucleotides as therapeutic agents which can regulate the biological function of cellular or viral nucleic acids.



   Interest in oligonucleotides as therapeutic agents has arisen from observations of naturally occurring complementary, or antisense, RNA used by some cells to control protein expression. More recently, synthetic oligonucleotides have been used with success to inhibit gene expression. For example, oligonucleotides were initially utilized to inhibit growth of Rous sarcoma virus (Zamecnik et al. 1978 Proc.



  Natl. Acad. Sci. USA 75: 280-284). Since such initial studies, oligonucleotides have been used to inhibit the expression of a wide variety of target nucleic acids in both cell-free extracts and in whole cells derived from diverse organisms, including viruses, bacteria, plants and animals. For example, expression of vesicular stomatitis virus matrix protein, human   c-myc    protooncogene, and c-Ha-ras protooncogene has been inhibited by oligonucleotides (Wickstrom et al. 1986
Biophys. J. 49: 15-19; Heikkila et al. 1987 Nature 328:   445-449;    Wickstrom et al. 1988 Proc. Natl. Acad. Sci.



  USA 85: 1028-1032; and Daaka et al. 1990 Oncogene Res.



  5: 267-275). A review of such therapeutic applications for oligonucleotides is provided by Uhlmann et al. 1990,
Chemical Reviews 90: 543-584.



   However, the development of oligonucleotides for in vivo regulation of biological processes has been hampered by several long-standing problems, including the nuclease sensitivity and poor cell penetrability of oligonucleotides.  



   In contrast to normal phosphodiester (O-PO2-O) linkages present in common, naturally occuring nucleic acids, both R and S stereoisomeric aryl- or alkylsubstituted phosphonate linkages confer several desirable properties upon an oligonucleotide, including increased nuclease resistance and increased cell penetration. Moreover, oligonucleotides having racemic alkylphosphonate linkages have been shown to specifically inhibit growth of simian virus 40, vesicular stomatitis virus, herpes simplex virus type 1 and human immunodeficiency virus (Miller et al. 1985
Biochimie 67: 769-776; Agris et   al.    1986 Biochemistry 25: 6268-6275; Smith et al. 1986 Proc. Natl. Acad. Sci.



  USA 83: 2787-2791; and Sarin et al. 1988 Proc. Natl.



  Acad. Sci. USA 85: 7448-7451).



   However, relatively high concentrations of alkyl- or aryl-phosphonate oligonucleotides have been required to achieve a significant therapeutic effect.



  This requirement for high oligonucleotide concentrations is apparently due to inefficient binding by oligonucleotides which have some phosphonate linkages in the S-stereospecific configuration (Miller 1991
Biotechnology 9: 358-362). S-stereospecific linkages are generated in addition to R-stereospecific linkages using presently available non-stereospecific synthetic procedures.



   In particular, replacement of a phosphate oxygen with another group, generates a chiral phosphate which can exist in two stereo- configurations, R and S (Rp and Sp, respectively). Current synthetic procedures are non-stereospecific and typically generate a linkage having either a Rp or Sp configuration, as each  nucleotide is added, to thereby generate an oligonucleotide having a mixture of Rp and Sp linkages.



  However, the melting temperatures of pure Rp and Sp isomers differ significantly, with the Rp isomer binding much more strongly than the Sp isomer (Miller et al.



  1980 J. Biol. Chem. 235:   9659-9665;    and Lesnikowski et al. 1990 Nucleic Acids Res. 18: 2109-2115). Hence, oligonucleotides with Rp phosphonate linkages have highly desirable binding properties and consequently greater utility than oligonucleotides with Sp or racemic phosphonate linkages.



   Moreover, a procedure which efficiently produces such highly desirable Rp isomer linkages on alkyl- or aryl-phosphonate oligonucleotides presents a large improvement over available prior art procedures.



   Present methods for obtaining oligonucleotides with only Rp alkyl- or aryl-phosphonate linkages require steps that are not readily adapted to automation, are inefficient or can be used for obtaining very short oligonucleotides, i.e. oligonucleotides having only up to about 8 oligonucleotides. For example, Lesnikowski et al. (1988 Nucleic Acids Res. 16: 11675-11689) have reported stereospecific dimer, trimer and tetramer synthesis of oligonucleotides using
Grignard reagent activation of the   5'-OH    group nucleotide and purification of Rp and Sp isomers after addition of each nucleotide. However, these methods present formidable difficulties for automation. More recently, Lesnikowski et al. (1990 Nucleic Acids Res.



  18: 2109-2115) have reported synthesis of an octamer   (dT)s    with a central racemic methylphos-phonate linkage and with other linkages as either all Rp or all Sp.  



  Lebedev et al. (1990b Tetrahedron Letters 31: 855-858) provide a method for making single stereospecific phosphonothioate (i.e. P-S-C-5') linkages between two nucleotides. However, to date there is no disclosure of a method which permits efficient automated synthesis of
Rp-stereospecific alkyl- or aryl-phosphonate (i.e.   P-O-      C-5')    linkages.



   The present invention provides efficient methods for synthesis of Rp stereospecifc alkyl- and aryl-phosphonate linkages between nucleotides of an oligonucleotide. Moreover, the present methods can readily be adapted for automated oligonucleotide synthesis. The present invention is also directed to Rp isomeric oligonucleotides produced by these methods, and to methods of using the present Rp alkyl- or arylphosphonate oligonucleotides as diagnostic probes and as therapeutic agents.



   The present invention relates to a method for producing an oligonucleotide having an Rp stereoisomeric alkyl- or aryl-phosphonate linkage between a first nucleotide and a second nucleotide in the oligoncleotide, wherein the oligonucleotide is of the formula:  
EMI6.1     
 which comprises:
 (a) reacting a first nucleotide of the formula:
EMI6.2     
 with an alkyl- or aryl-phosphonothioate intermediate of the formula:
EMI6.3     

 under conditions sufficient to produce the Rp stereoisomeric alkyl- or aryl-phosphonate linkage, wherein:  
   Yl    is a hydrogen, phosphate, phosphate present in the oligonucleotide or V1;

  
 Y2 is a hydrogen, phosphate, phosphate present in the oligonucleotide or V2,
 X is hydroxy or V3,
 M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group;
 each B group is independently a purine or pyrimidine base and each B group can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl;
 V1 is a protecting group, solid support or phosphate attached to the penultimate nucleotide of the oligonucleotide;
 V2 is a protecting group; and
 V, is hydrogen or   OY3,    wherein   V3    is lower alkyl or protecting group;
 A is an activating group;

   and
 the intermediate has an Sp stereoisomeric configuration at the phosphate; and
 (b) when V1, V2 or V, is a protecting group optionally removing said   Vl,    V2 or V, protecting group.



   The present invention also relates to a method of producing a polynucleotide chain of an oligonucleotide having at least one Rp alkyl-phosphonate or one Rp aryl-phosphonate linkage.



   The present invention further relates to a method of producing an alkyl- or aryl-phosphonothioate  nucleotide intermediate having an Sp stereoisomeric phosphorus configuration.



   The present invention still further relates to such an alkyl- or aryl-phosphonothioate nucleotide intermediate, wherein the intermediate has an Sp stereoisomeric phosphorus configuration. Such an intermediate can be used to generate the present Rp stereoisomeric linkages.



   The present invention additionally relates to a compartmentalized kit for producing a polynucleotide chain of an oligonucleotide having at least five Rp alkyl-phosphonate or Rp aryl-phosphonate linkages.



   The present invention also relates to an oligonucleotide having at least five Rp alkylphosphonate or Rp aryl-phosphonate linkages produced by the subject methods.



   The present invention further relates to the present oligonucleotides which have an attached agent to facilitate cell delivery, a drug or a reporter molecule.



   The present invention still further relates to a compartmentalized kit for detection or diagnosis of a target nucleic acid.



   The present invention additionally relates to a compartmentalized kit for isolation of a template nucleic acid.



   The present invention also relates to a method of regulating biosynthesis of a DNA, an RNA or a protein using the subject Rp alkyl- or aryl-phosphonate oligonucleotides.



   The present invention further relates to a pharmaceutical composition for regulating biosynthesis of a nucleic acid or protein comprising a  pharmaceutically effective amount of one of the present oligonucleotides and a pharmaceutically acceptable carrier.



   The present invention still further relates to a method of detecting a target nucleic acid which includes contacting one of the present oligonucleotides with a sample to be tested for containing such a nucleic acid for a time and under conditions sufficient to form an oligonucleotide-target complex; and detecting such a complex.



   Fig. 1 depicts a chromatograph of Rp and Sp stereoisomers of dithymidine methylphosphonate separated by liquid chromatography on a 4.6 x250 mm   Cia    silica column with gradient elution using 10% to 15% acetonitrile in water (0.25%/min) at a flow rate of 1.0 ml/min.



   Fig. 2 depicts superimposed circular dichroism spectra of Rp and Sp dithymidine methylphosphonate stereoisomers separated as illustrated in Fig. 1. Each stereoisomer has a characteristic spectrum which can be used to identify that stereoisomer.



   Fig. 3 depicts 1H NMR spectra of Rp (top) and
Sp (bottom) stereoisomers of dithymidine methylphosphonate, illustrating several distinct peaks characteristic of a given stereoisomer which can be used for stereoisomeric identification, e.g. the H2 and   H6    peaks.



   Fig. 4 depicts   31P    NMR spectra of Rp (top) and
Sp (bottom) stereoisomers of dithymidine methylphosphonate. The Rp stereoisomer has a characteristic additional peak at 7.984 ppm which can be used to identify this stereoisomer.  



   Fig. 5 depicts a spectrograph of 5'dimethoxytrityl-tetrathymidine methylphosphonate-3'acetate (DMT-TpTpTpT-OAc) produced by fast atom bombardment mass spectroscopy (FABMS). Specific peaks corresponding to distinct molecular fragments of
DMT-TpTpTpT-OAc are identified (e.g. 5'-dimethoxytrityldithymidine, DMT-TpT, at 850   m/e).   



   The present invention provides a method for producing an oligonucleotide having an Rp stereoisomeric alkyl- or aryl-phosphonate linkage between a first nucleotide and a second nucleotide in oligoncleotide, wherein the oligonucleotide is of the formula:
EMI10.1     

 According to the present invention, Rp stereoisomeric alkyl- or aryl-phosphonate linkages between two nucleotides are formed by:
 (a) reacting a first nucleotide of the formula:  
EMI11.1     
 with an alkyl- or aryl-phosphonothioate intermediate of the formula:
EMI11.2     

 under conditions sufficient to produce the Rp stereoisomeric alkyl- or aryl-phosphonate linkage, wherein:
 Y1 is a hydrogen, phosphate, phosphate present in the oligonucleotide or   V.;   
 Y2 is a hydrogen, phosphate, phosphate present in the oligonucleotide or V2;
 X is hydroxy or V3;

  
 M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group;
 each B group is independently a purine or pyrimidine base and each B group can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl;  
   Vl    is a protecting group, solid support or phosphate attached to the penultimate nucleotide of the oligonucleotide;
   V2    is a protecting group; and
 V3 is hydrogen or OY3, wherein   V3    is lower alkyl or protecting group;
 A is an activating group; and
 the intermediate has an Sp stereoisomeric configuration at the phosphate;

   and
 (b) when   Vl,    V2 or V3 is a protecting group, optionally removing the V1, V2 or V3 protecting group.



   The present invention further relates to a method of producing a polynucleotide chain of an oligonucleotide having at least one Rp-alkyl-phosphonate or Rp-aryl-phosphonate linkage, wherein the oligonucleotide has the formula:
EMI12.1     
  which method includes the following steps:
 (a) reacting a 5'- terminal nucleotide of the formula:
EMI13.1     
 with an alkyl- or aryl-phosphonothioate nucleotide intermediate of the formula:
EMI13.2     
 under conditions sufficient to produce the Rp stereoisomeric alkyl- or aryl-phosphonate linkage and so generate a new 5'-terminal nucleotide, wherein:
   Y1,      V2,    X, M, B,   V.,      V2,    V3 and   V3    are as defined hereinabove;
 n is an integer from 0 to 200;
 the intermediate has an Sp stereoisomeric phosphorus configuration;

   and
 (b) removing the V2 protecting group from the new 5'-terminal nucleotide;
 (c) reacting the product of (b) with another alkyl- or aryl-phosphonothioate nucleotide intermediate under conditions sufficient to produce the Rp stereoisomeric linkage and so generate a new 5'-terminal nucleotide;  
 (d) repeating steps b and c to extend the polynucleotide chain n-l times; and
 (e) when V1, V2 or V3 is a protecting group, optionally removing the V1, V2 or V3 protecting group.



   If the desired product is a compound of
Formula I or II wherein X is OH and   Yl    or Y2 are hydrogen or phosphate, such groups are generated upon removal of the protecting groups by standard techniques known to one skilled in the art.



   The Rp stereoisomeric alkyl- or arylphosphonate linkages produced by the methods of the present invention have M substituents on the phosphate atom. Such an M substituent is present instead of an oxygen atom commonly found in conventional nucleic acids which have   -O-PO,-O-    linkages. According to the present invention, M is a lower alkyl, a cycloalkyl, a thioxo, a thio-lower alkyl, an aryl or an aryl lower alkyl group wherein such lower alkyl and aryl groups can be substituted with at least one hydroxy, halogen or cyano group.



   As used herein the term lower alkyl refers to alkyl groups containing one to six carbon atoms. Lower alkyl groups can be straight-chained or branched, and include such moieties as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, t-butyl, pentyl, amyl, hexyl and the like. Preferred M alkyl groups of the present invention have from one to four carbon atoms. The most preferred M alkyl group is methyl. Similarly, a lower alkenyl is a lower alkyl with 1-3 carbon-carbon double bonds.



   Moreover, an alkoxy group is a lower alkyl attached via an oxygen atom; a lower acyl is a lower  alkyl attached via a carbonyl (C=O); and a lower cyanoalkyl is a lower alkyl with a CN substituent.



   The term cycloalkyl refers to saturated cyclic structure, i.e. a ring, having 3-7 ring carbon atoms and includes such groups as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl rings.



   A thioxo group is a =S group and a thio-lower alkyl is a lower alkyl attached to the phosphate via a sulfur atom.



   The term aryl refers to an aromatic moiety containing 6-10 ring carbon atoms and includes phenyl, a-naphthyl, B-naphthyl, and the like. A preferred aryl group is phenyl.



   An aryloxy group is an aryl attached via an oxygen atom and an aroyl is an aryl attached via a carboxyl (CO). Similarly, an aryloxy acyl is an aryl linked to an acyl via an oxygen atom.



   According to the present invention a halo group is a halogen. Halo groups include fluorine, chlorine, bromine and iodine. A preferred halo group for substitution on M lower alkyl, aryl, and aryl lower alkyl groups is fluorine.



   Preferred M groups are lower alkyl or phenyl groups which can be substituted with a halo group, preferably a fluorine. More preferred M groups are unsubstituted lower alkyl groups. An especially preferred M group is an unsubstituted methyl group.



  Therefore, the preferred Rp-stereoisomeric linkages of the present invention are alkylphosphonate linkages and more preferably are methylphosphonate linkages.



   According to the present invention, the nucleotides joined by the present alkyl- or aryl  phosphonate linkages can have deoxyribose or ribose sugar moieties. Therefore, as defined herein X is either hydroxy or V3, wherein V3 is hydrogen or OY3 and   V3    is lower alkyl or a protecting group. Accordingly, when X is hydrogen a deoxyribose sugar is present but when X is hydroxy or -O-Y3 a ribose sugar, an O-alkyl ribose sugar or a protected ribose sugar, is present in the associated nucleotide. Preferred oligonucleotides of the present invention have X as hydrogen or OH.



  However, during synthesis of the present oligonucleotides such an OH is protected with a protecting group which can be removed at conclusion of synthesis by the present methods.



   The nucleotides linked according to the present invention each have a B group which represents the base moiety present on the nucleotide. Each B group is independently a purine or pyrimidine base which can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl. Preferred purine and pyrimidine B groups have 1-2 lower alkyl, amino, oxo, hydroxy or lower alkoxy substituents.



   Preferred B groups of the present invention are purines such as guanine (G) and adenine (A), pyrimidines such as thymine (T), cytosine (C) or uracil (U), and any related base analog that is capable of base pairing with a guanine, adenine, thymine, cytosine or uracil. For example, such base analogs include pseudocytosine, isopseudocytosine, 3-aminophenylimidazole, 2'-O-methyl-adenine, 7-deazadenine, 7deazaguanine, 4-acetylcytosine, 5-(carboxy  hydroxylmethyl)-uracil,   2'-O-methylcytosine,    5carboxymethylaminomethyl-2-thiouracil, 5carboxymethylamino-methyluracil, dihydrouracil, 2'-0methyluracil, 2'-O-methyl-pseudouracil,    -D-    galactosylqueonine, 2'-O-methylguanine, xanthine, hypoxanthine, N6-isopentenyladenine, l-methyladenine, 1methyl-pseudouracil, 1-methylguanine, l-methylxanthine, 2,2-dimethylguanine, 2-methyladenine,

   2-methylguanine, 3-methylcytosine, 5-methylcytosine, 5-methyluracil, N6methyl-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil,   8-D-    mannosylqueonine, 5-methoxycarbonylmethyluracil, 5methoxyuracil, 2-methyl-thio-N6-isopentenyladenine, N  (9-beta-D-ribofuranosyl-2-methylthiopurine-6-yl) -    carbamoyl)threonine, N-(9-beta-D-ribofuranosylpurine-6yl)-N-methylcarbamoyl)threonine. B groups in an aanomeric configuration can also be present in the nucleotides linked by the present methods.



   Preferred B groups are unmodified G, A, T, C and U bases. In addition, preferred B groups include pyrimidines and purines with lower alkyl, lower alkoxy, lower alkylamine, phenyl or lower alkyl substituted phenyl groups. It is more preferred that these groups are present on the 5 position of the pyrimidine and on the 7 or 8 position of the purine. Especially preferred base analogs are 5-methylcytosine, 5-methyluracil and diaminopurine. The most preferred B groups are unmodified G, A, T, C and U.



   Moreover, the selection of a B group for each nucleotide added to the growing polynucleotide chain determines the nucleotide sequence of an oligonucleotide produced by the present methods. Accordingly, the  present methods can be used to generate oligonucleotides having any desired nucleotide sequence by varying which nucleotide base B is placed at each position. The selection of a nucleotide sequence is generally determined by the intended purpose of the oligonucleotide and is described in more detail hereinbelow.



   According to the present invention n is an integer used to describe the number of Rp alkyl- or Rp aryl-phosphonate linkages sequentially synthesized by the present methods. As used herein, n is   0    to 200.



  Moreover, up to 201 Rp alkyl- or aryl-phosphonate linkages can be formed when n ranges from 0 to 200.



  However, when n is   0    a single Rp alkyl- or arylphosphonate linkage is formed. Therefore, the present invention is directed towards application of the subject methods to form isolated Rp phosphonate linkages as well as sequential chains of Rp stereoisomeric alkyl- or aryl-phosphonate linkages.



   Preferably, n is at least 5. However, a value of at least 8 for n is more preferred. Even more preferred is a value of at least 10 for n. Especially preferred values for n are at least 12 or 14.



   According to the present invention, Y1 is present on a 3'-oxygen of a nucleotide and can be a hydrogen, phosphate, phosphate present in the oligonucleotide or   Vl.    V1 is related to Y1 in that   Vl    and   Yl    are at the same position and   Yl    can have the same meaning as   Vl.    As used herein, V1 is a protecting group, a solid support or a phosphate attached to a penultimate nucleotide. Such a penultimate nucleotide is the nucleotide next to the 5'-terminal nucleotide.  



   Moreover, as used herein, Y2 is present on a 5'-oxygen of a nucleotide or an oligonucleotide and can be a hydrogen, a phosphate, a phosphate present in the oligonucleotide or V2, wherein V2 is a protecting group.



  Since Y2 and V2 are at the same position, removal of a
V2 protecting group can generate a Y2 hydrogen or phosphate.



   Similarly, X and   V3    are related not only by virtue of placement at the same position (2') but also because X can have the same meaning as   V3,    i.e. X is hydroxy or   V3.    When X is   V3,      V3    can be hydrogen or 0-Y3 wherein Y is a lower alkyl or a protecting group.



  According to the present invention, removal of a Y3 protecting group can produce a hydroxy group, i.e. X as
OH.



   As used herein, formulas I and II represent a portion of an oligonucleotide when Y1 or   y2    is defined as a phosphate present in the oligonucleotide. Hence additional nucleotides can flank the Rp phosphonate linkage being formed when   Y1    or Y2 is a phosphate present in the oligonucleotide. In particular, usage of   Yl    or Y2 as a phosphate present in the oligonucleotide is intended to indicate that the oligonucleotide can be longer than the n Rp linkages formed by the present methods. More particularly, the present invention contemplates conventional phosphodiester linkages, or an interspersing conventional phosphodiester and Rp phosphonate linkages, in the parts of the oligonucleotide attached to a Y, and Y2 phosphate.

   As used herein a conventional phosphodiester linkage is a 
O-PO2-O- linkage between 3'- and 5'-positions of two nucleoside sugars. Preferably about 1 to about 50 -0  
PO2-O-linkages can be added to or interspersed between   Rp    phosphonate linkages of the present oligonucleotides.



  Conventional oligonucleotides are added by known procedures (e.g. Uhlmann et al. 1990 Chemical Reviews 90: 544-584).



   Accordingly, the present methods can be adapted to incorporate at least one additional step directed to adding 1-50 nucleotides wherein such nucleotides are joined by O-PO2-O linkages.



   As provided by the present methods, an internal or non-terminal Rp linkage is produced when both   Yl    and Y2 are phosphates present in the oligonucleotide. However, when Y1 or   Y2    is other than a phosphate present in the oligonucleotide, a 3'-terminal or a 5'-terminal linkage, respectively, can be made.



  Accordingly, the present methods can be used to generate both internal and terminal Rp stereoisomeric alkyl- or aryl-phosphonate linkages.



   Moreover, sequential Rp linkages can also be formed by the present methods since V1 can be defined as the phosphate present on the penultimate nucleotide of the oligonucleotide at each round of synthesis. Such a penultimate nucleotide is the nucleotide next to the 5'terminal nucleotide.



   As defined, V1 can be a solid support.



  Preferably   V1    is a solid support when the present methods are performed by automation since V1 can thereby serve as an anchor for the growing polynucleotide chain.



  Such a solid support can be any known support used during synthesis of DNA or RNA. Common types of solid supports include controlled pore glass (CPG), polystyrene silica, cellulose, nylon, and the like.  



  Preferred solid supports are CPG and polystyrene. An especially preferred solid support is CPG.



   The   Vl    solid support is covalently linked to the 3'-OH of a nucleoside by known procedures   (e.g.,   
Matteucci et al. 1980 Tetrahedron Lett. 21: 719-722).



  Alternatively, nucleosides linked to solid supports can be purchased commercially, e.g. from Sigma Chemical
Company. Moreover, a solid support can also be removed from an oligonucleotide of the present invention by known procedures, e.g. by alkaline hydrolysis.



   The   Vl,      V2    and   Y3    protecting groups can be used when the present synthetic methods are employed to form the subject Rp sterospecific phosphonate linkages.



  In particular, the present invention provides such protecting groups for covalent binding to a reactive group on a nucleotide. Such binding of a protecting group renders that reactive group unreactive while the present synthetic methods are performed. Reactive groups of the present invention include 5'-OH,   3'-OH,      2'-OH    and related groups, e.g. reactive groups present on the B bases. Ideally, a protecting group is easily removed to regenerate the correct structure of the reactive group without chemically altering the remainder of the molecule.

 

   Examples of protecting groups contemplated by the present invention include any known blocking or protecting agent used during synthesis of deoxyribooligonucleotides or ribooligo-nucleotides to protect a a hydroxy group on a nucleotide, e.g. a 5'-OH,   3'-OH    or 2'-OH group. The V1, V2 and Y3 protecting groups are preferably attached via an oxygen atom. Such
O-linked protecting groups are useful for protecting the  
OH groups on nucleotides. In this regard, Greene (1981
Protecting Groups in Organic Synthesis, John Wiley  & 
Sons, Inc.) provides a comprehensive review of protecting groups which can be used for different reactive groups, including OH reactive groups.



   Preferred protecting groups of the present invention are lower alkyl, lower cyanoalkyl, lower alkanoyl, aroyl, aryloxy, aryloxy-lower akanoyl, haloaryl, fluorenylmethoxy carbonyl (FMOC), trityl, monomethoxytrityl (MMT), dimethoxytrityl (DMT), and related groups. More preferred protecting groups include isopropyl, isobutyl, 2-cyano-ethyl, acetyl, benzoyl, phenoxy-acetyl, halophenyl, MMT, DMT and the like.



   As used herein, an activating group A is a heteroaromatic ring with at least one lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl or arylalkyl substituent. It is preferred that the heteroaromatic ring is substituted with a lower alkyl or cycloalkyl.



  Moreover, the A group is attached to the sulfur atom of the alkyl- or aryl-phosphonothioate nucleotide.



  However, prior to attachment of the A group, a leaving group L is present on the activating group A at the position to which the A group will be attached to the phosphonothioate nucleotide. As used herein, an activating group A attached to a leaving group L is referred to as an activator or A-L.



   According to the present invention the activating group A includes a heteroaromatic ring containing from 1 to 4 nitrogen ring atoms, which A group is of the formula:  
EMI23.1     
 or a salt thereof, wherein:
   9    is C-R1 or N;
 D is C-R2 or N;
 E is   C-R3    or N;
 G is C-R4 or N;
 J is   C-R,    or N;
 Y is -S-, -NR6-, or   -O-;   
 R is a substituent attached to one nitrogen atom, wherein such a substituent is lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl;

  
   RI,    R2,   R3,    R4 and Rs are independently hydrogen, lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, or   Rl    and R2 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R, and
R4 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R4 and   R5    are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring;
 and R6 is lower alkyl or hydrogen.



   In a preferred embodiment the activating group
A is a salt of a positively charged heteroaromatic ring.



  In one embodiment, the activating group A is of the formula:  
EMI24.1     
 or salts thereof, wherein R,   Rl    and R2 are as defined hereinabove.



   More preferably, the positively charged A group is of the formula:
EMI24.2     
 or salts thereof, wherein R is as defined hereinabove.



   In an especially preferred embodiment the A group has the formula:
EMI24.3     
 or salts thereof, wherein R is as defined hereinabove.



   Accordingly, as used herein, heteroaromatic groups of the present invention contain from 5-14 ring atoms and 1, 2 or 3 nitrogen, oxygen or sulfur heteroatoms. Preferred heteroaromatic rings are either monocyclic or bicyclic with 1 or 2 ring nitrogen heteroatoms and 5 to 10 ring atoms. Preferred  heteroaromatic rings can also have 1 other nitrogen, sulfur or oxygen ring atom. Especially preferred heteroaromatic rings are monocyclic with 5 or 6 ring atoms and one nitrogen heteroatom.



   Heteroaromatic rings contemplated by the present invention include pyrrole, isopyrrole, pyrazole, triazole, oxazole, isoxazole, thiazole, isothiazole, oxodiazole, tetrazole, pyrazine, pyrimidine, pyridine, oxazine, isoxazine, oxadiazine, imidazole, indole, pyrindine, quinoline, isoquinoline, pyridopyridine and the like.



   Preferred heteroaromatic rings include pyridine, imidazole, triazole, tetrazole, indole and pyridopyridine rings. Moreover, preferred heteroaromatic rings are positively charged nitrogen heteroaromatic rings, e.g. nitrogen heteroaromatic rings with an N-linked lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl group. An especially preferred heteroaromatic ring is pyridine with an N-linked lower alkyl.



   In particular, a preferred A group is an Nalkyl pyridinium. The most preferred A group is 2-Nmethylpyridinium. When attached to the alkyl- or arylphosphonothioate nucleotide, such a pyridinium is preferably attached via the 2 or 4 position, and most preferably via the 2 position.



   Prior to attachment of A to the phosphonothioate, L is present on A at the position to which the phosphonothioate will be attached. As used herein, L is a leaving group. As is generally known in the art, and for the purposes of the present invention, "a leaving group" is defined as a group which is readily  broken away from a covalent linkage with a carbon atom by nucleophilic attack on that atom. Leaving groups are generally electron withdrawing groups either because of their electronegativity or because they have an inductive effect.



   The L groups contemplated by the present invention include halo, nitro, diazo, azido, lower trialkylamino, lower alkoxy, aryloxy, lower alkyl sulfonate, lower fluoroalkylsulfonate, aryl sulfonate, lower alkyl sulfinate, aryl sulfinate groups and the like.



   Sulfonates include a lower alkyl or an aryl with an attached SO, group. Similarly, sulfinates can be lower alkyl or aryl groups with an attached SO2 group. Preferred lower alkyl sulfonates include methyl sulfonate (i.e. mesylate), ethyl sulfonate, propyl sulfonate, isopropyl sulfonate, butyl sulfonate, isobutyl sulfonate, t-butyl sulfonate, pentyl sulfonates, hexyl sulfonates and the like. Moreover, aryl sulfonates include groups such as tolylsulfonates (i.e. tosylates), and ammonio-alkylsulfonate (i.e. betylates). bromophenylsulfonates (i.e. brosylates), nitrophenyl-sulfonates (i.e. nosylates) and the like.



  Preferred lower fluoroalkylsulfonates include trifluoromethyl-sulfonates (i.e. -OSO2CF3 or triflates) nonafluorobutyl-sulfonates (i.e.   -0S02-C4F9)    or nonaflates and 2,2,2-trifluoroethyl-sulfonates (i.e.   OSO2-CH2-CH2CF3    or tresylates).



   Preferred L groups include diazo and halo, i.e. F, Cl, Br and I. More preferred L groups are Cl and Br.  



   In the most preferred embodiment, A-L is positively charged. Since the subject activator A-L can be positively charged, the present invention contemplates providing A-L as a salt. Such A-L salts include the positively charged or cationic A-L moiety associated with a counteranion. The variable Z is used herein to represent the negatively charged counterion.



  Counterions which can be associated with A-L include halides, e.g. Cl, Br and I. Preferred counterions for forming salts of the present A-L activators are I- and   Br.   



   Preferably A-L is a salt of a positively charged nitrogen heteroaromatic group substituted with one leaving group and one N-linked lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl. The L leaving group is preferably at the 2 or 4 position, and more preferably at the 2 position, relative to the nitrogen heteroatom. Preferred A-L activators are 2halo-N-alkyl pyridinium bromide or 2-halo-N-alkyl pyridinium iodide, wherein the alkyl is lower alkyl, and most preferably methyl or ethyl, and the halo is preferably chloro, bromo or dodo. The most preferred A
L activators are 2-chloro-N-alkyl pyridinium bromide or 2-chloro-N-alkyl pyridinium iodide.



   The A-L activators of the present invention are either commercially available or are synthesized by availible procedures. For example the appropriate heteroaromatic group can be purchased which has the desired R1, R2, R3, R4,   R5    and   R6    groups. Alternatively the   Rl,    R2, R,, R4 and   R5    groups can be attached to the heteroaromatic group by standard alkylation or arylation procedures. An L group such as halogen is then  attached, e.g. by adding the halogen at the desired position on the heteroaromatic ring by standard procedures. After addition of the L group, the R and   R6    group can be added by standard alkylation or arylation procedures. A preferred A-L activator, 2-chloro-Nmethyl-pyridinium iodide is commercially availible.



  Moreover, conditions have been described for using this activator to form esters from acids and alcohols (Mukaiyama et al. 1975 Chem. Lett.   1045;    and Fieser 1980
Reagents for Organic Synthesis Wiley-Interscience, New
York, 8: 95-96).



   According to the present invention, Rp stereoisomeric alkyl- or aryl-phosphonate linkages between any two nucleotides are formed by reacting a first or 5'-terminal nucleotide of the formula:
EMI28.1     
 with an alkyl- or aryl-phosphonothioate nucleotide intermediate of the formula:
EMI28.2     
 wherein:
 the intermediate has an Sp stereoisomeric phosphorus configuration;  
   Vl    is a protecting group, solid support or phosphate attached to the penultimate nucleotide of the oligonucleotide;
 V2 is a protecting groups;
 V3 is hydrogen, or   OY,,    wherein Y3 is lower alkyl or protecting group;
 A is an activating group; and
 B is as defined herein.



   Moreover according to the present invention, the first (or 5') nucleotide is reacted with the depicted Sp stereoisomeric intermediate under conditions sufficient to covalently link the 5'-oxygen of the   5'-    terminal nucleotide with the phosphorus of the intermediate, and thereby lose S-A and invert the Sp stereoisomeric configuration to produce the Rp stereoisomeric alkyl- or aryl-phosphonate linkage.



   As used herein, conditions sufficient to covalently link the 5'-oxygen with the phosphorus of the intermediate include those time, temperature, solvent and reactant concentration conditions permitting nucleophilic attack by the 5'-oxygen upon the phosphorus to displace the sulfur and invert the phosphorus configuration. Such reaction conditions further permit displacement of the sulfur linked to the activating group to produce an S-A product.



   A time sufficient to covalently link the 5'oxygen with the phosphorus is about 5 min to about 10 hr, and preferably is about 10 min to about 2 hr. A more preferred reaction time is about 30 min to about 90 min. An especially preferred reaction time is about 60 min.  



   The reaction temperature preferably employed for linkage of a first or 5'-nucleotide to the intermediate methods is about   0 C    to about   45"C.    A more preferred reaction temperature is about   4"C    to about   35"C.    An especially preferred linkage temperature is about room temperature, i.e. about   20"C    to   25"C.   



   The reaction solvent conditions for linkage of the first or 5'-nucleotide with the intermediate are anhydrous conditions, wherein a nonpolar or nonpolar aprotic solvent is employed. Preferred solvents for use during linkage of a nucleotide with a nucleotide intermediate include acetonitrile, dimethylformamide, tetrahydrofuran, dimethylsulfoxide, pyridine and the like.



   According to the present invention, the molar ratio of first (or 5'-terminal) nucleotide relative to nucleotide intermediate can range from about 1:10 to about 5:1. Preferably the molar ratios are about 1:3 to about 1:1. An especially preferred molar ratio of first (or 5'-terminal) nucleotide to nucleotide intermediate is about 1:2.



   In one especially preferred embodiment, the present methods are performed automatically in a nucleic acid synthesizer. The present methods have been designed for adaptation to automation by selecting reactions which can be performed under conditions typically used in nucleic acid synthesizers. For example, room temperatures, solvents and reagents contemplated herein are compatible with procedures and common protecting groups employed during automated nucleic acid synthesis (see Uhlmann et al. for a review of such procedures and protecting groups).  



   In another embodiment, the present invention is directed to an alkyl- or aryl-phosphonothioate nucleotide intermediate which has an Sp stereoisomeric configuration at the phosphorus, and an activating group
A. This intermediate is of the formula:
EMI31.1     
 wherein;
 B and M are as defined hereinabove;
 V2 is a protecting group;
 V, is a hydrogen, or   OY,    wherein Y, is lower alkyl or protecting group; and
 A is the activating group.



   The present invention is also directed to a method of producing such an intermediate by reacting an alkyl- or aryl-phosphonothioate nucleotide of the formula:
EMI31.2     
 with an A-L activator under conditions sufficient to produce the intermediate without inversion of the Sp stereoisomeric phosphorus configuration; wherein:  
 the alkyl- or aryl-phosphonothioate nucleotide has an Sp stereoisomeric phosphorus configuration;
 V2 is a protecting group;
 V3 is a hydrogen, lower alkoxy or an O-linked protecting group; and
 M and B are as defined hereinabove.



   According to the present invention, conditions sufficient to produce the intermediate without inversion of the Sp-stereoisomeric configuration include nuclear displacement conditions wherein the L group is displaced by the sulfur atom on the phosphonothioate nucleotide.



  Such conditions include a time, a solvent, a temperature and a reactant concentration sufficent for such nucleophilic displacement of L by the sulfur.



   A time sufficient to displace the L group and so produce the intermediate without inversion of the Spstereoisomeric configuration is about 1 sec to about 30 min and preferably about 10 sec to about 10 min. A more preferred time for displacing L with the sulfur of the phosphonothioate is about 30 sec to about 2 min. An especially preferred time for forming the intermediate is about 1 min.



   The solvent for generating the intermediate is an anhydrous solvent, and preferably is a nonpolar or nonpolar aprotic solvent. Preferred solvents for use during formation of the intermediate include acetonitrile, dimethylformamide, tetrahydrofuran, dimethylsulfoxide, pyridine and related solvents.



   The temperature preferably employed to displace the L leaving group with the phosphonothioate sulfur, and thereby form the intermediate, is about   OOC    to about 600C. A more preferred displacement  temperature is about   4"C    to about   45"C.    An especially preferred temperature for forming the intermediate is about room temperature, i.e. about   20"C.   



   According to the present invention, the concentrations of the alkyl- or aryl-phosphonothioate nucleotide to the A-L activator can range from a molar ratio of about 1:10 to about 10:1. Preferably the molar ratio of phosphonothioate nucleotide to activator is about 1:5 to about 3:1. An especially preferred molar ratio of phosphonothioate nucleotide to A-L activator is about 1:2.



   One embodiment of the present invention provides a compartmentalized kit for producing a polynucleotide chain of an oligonucleotide having at least five R-alkyl-phosphonate or R-aryl-phosphonate linkages, wherein the oligonucleotide has the formula:
EMI33.1     
  wherein Y1, Y2, X, M and B are defined as hereinabove; and
 n is the number of Rp alkyl- or arylphosphonate linkages in the portion of the oligonucleotide and is an integer of from about 4 to about 200; which includes:
 (a) a first container adapted to contain A-L; and
 (b) a second container adapted to contain salts of a first alkyl- or aryl-phosphonothioate nucleotide precursor of the formula:
EMI34.1     
 wherein the first precursor has an Sp stereoisomeric phosphorus configuration.



   The kit for producing such a polynucleotide chain of an oligonucleotide can further include at least one additional container adapted to contain a salt of a second Sp stereoisomeric alkyl- or aryl-phosphonothioate nucleotide precursor which has a different B group than the first precursor.



   In a preferred embodiment, the alkyl- or arylphosphinate nucleotide precursors provided in the kit have a B group selected from the group of guanine, adenine, thymine, cytosine or uracil.  



   Moreover, when a precursor is provided in a kit the M group thereupon is preferably lower alkyl or aryl. A more preferred M group is methyl or ethyl.



   In addition, a preferred   V2    group for a precursor provided in a kit of the present invention is a protecting group, preferably dimethoxytrityl or monomethoxytrityl.



   Furthermore, the present kits preferably have salts of the preferred A-L activators described hereinabove.



   In a more preferred embodiment the kit provides a first container containing A-L, a second container containing a salt of alkyl- or arylphosphonothioate guanine, a third container containing a salt of alkyl- or aryl-phosphonothioate adenine, a fourth container containing a salt of alkyl- or arylphosphonothioate cytosine, a fifth container containing a salt of alkyl- or aryl-phosphonothioate thymine and optionally a sixth container containing a salt of alkylor aryl-phosphonothioate uracil.



   As used herein, salts of the present alkyl- or aryl-phosphonothioate nucleotide precursor are alkali metal or alkaline earth metal salts, for example Li, Na,
K, Mg, Ca, and the like. Preferred salts are alkali metal salts, e.g., Li, Na, and K. Especially preferred salts are Li salts.



   After synthesis by the present methods an oligonucleotide can be purified by polyacrylamide gel electrophoresis, or by any of a number of chromatographic methods, including gel chromatography and high pressure liquid chromatography.  



   In a preferred embodiment the present invention is directed to an oligonucleotide having at least five sequential Rp stereospecific alkyl- or arylphosphonate linkages produced by the present methods.



   While the oligonucleotides prepared by the present methods can have as little as five Rp stereospeicific alkyl- or aryl-phosphonate linkages, preferred oligonucleotides have more than five Rp stereospecific linkage. For example, in another embodiment, oligonucleotides synthesized by the methods of the present invention generally have about 8 to about 200 alkyl- or aryl-phosphonate linkages. Preferred oligonucleotides of the present invention have about 10 to about 200 alkyl- or aryl-phosphonate linkages. More preferred oligonucleotides have about 12 to about 200 alkyl- or aryl-phosphonate linkages. Especially preferred oligonucleotides of the present invention have about 14 to about 200 alkyl- or aryl-phosphonate linkages.



   According to the present invention, the subject methods produce R-stereospecific linkages at a higher frequency than S-stereospecific linkages.



  However, not all of the alkyl- or aryl-phosphonate linkages produced by the present methods may be Rstereospecific. Therefore, S-stereospecific linkages can occasionally be produced, for example, if the preparation of alkyl- or aryl-phosphonothioate nucleotide precursors employed have a small percentage of R-stereoisomeric nucleotide contaminants.



  Accordingly, the present invention is directed to methods of producing a higher percentage of R  stereospecific alkyl- and aryl-phosphonate linkages than
S-stereospecific alkyl- and aryl-phosphonate linkages.



   In particular the present methods can produce at least about 75% R-stereospecific linkages in an oligonucleotide wherein the remaining linkages can be Sstereospecific. More particularly, the oligonucleotides generated by the present methods have about 85% to about 100% R-stereospecific linkages. However, the present methods have the capability for producing oligonucleotides having about 95% to 100% R-stereospecific alkylor aryl-phosphonate linkages.



   Moreover, the oligonucleotides of the present invention need not have only alkyl- or aryl-phosphonate linkages. In some instances oligonucleotides having a mixture of phosphonate
EMI37.1     
 and conventional phosphodiester (-O-PO2-O) linkages are preferred. For example, conventional phosphodiester linkages may be incorporated into the present oligonucleotides to generate an endonuclease cleavage site or to render the oligonucleotide sensitive to normal cellular enzymes at a particular sequence within the oligonucleotide. If the subject oligonucleotides have conventional phosphodiester linkages these oligonucleotides can have about 1 to about 50 conventional phosphodiester linkages.



   Therefore, the present invention is directed to oligonucleotides which can have conventional phosphodiester linkages, as well as both Sp stereospecific and Rp stereospecific phosphonate linkages, so long as the oligonucleotide has at least  five sequential Rp stereospecific alkyl- or arylphosphonate linkages generated by the present methods.



   According to the present invention, Rp stereospecific oligonucleotide products derived from the subject synthetic methods can have an attached agent to facilitate cellular delivery or uptake. Such an agent can, for example, be any known moiety which enhances cellular membrane penetration by the oligonucleotide, any known ligand for a cell-specific receptor or any availible antibody reactive with a cell-specific antigen.



   A moiety or ligand which enhances cellular membrane penetration by the oligonucleotide can include, for example, any non-polar group, steroid, hormone, polycation, protein carrier, or viral or bacterial protein capable of cell membrane penetration. Such a non-polar group can be a phenyl, naphthyl, quinoline, anthracene, phenanthracene, fatty acid, fatty alcohol, sesquiterpene, diterpene and related groups. Steroids which can enhance cell uptake include cholesterol, progesterone, estrogen, androgen and related steroids.



  For example, covalent linkage of a cholesterol moiety to an oligonucleotide can improve cellular uptake by 5- to 10- fold which in turn improves DNA binding by about 10fold (Boutorin et al., 1989, FEBS Letters 254: 129132). Hormones such as insulin can also bind to cell membranes and facilitate entry of an oligonucleotide thereto into the cell. Polycations, e.g. polyamino acid cations, including cations of basic amino acids, such as poly-L-lysine, can also facilitate uptake of oligonucleotides into cells (Schell, 1974, Biochem.



  Biophys. Acta 340: 323, and Lemaitre et al., 1987,  
Proc. Natl. Acad. Sci. USA 84: 648). Certain protein carriers can also facilitate cellular uptake of oligonucleotides, including, for example, serum albumin, transferrin, nuclear proteins possessing signals for transport to the nucleus, and viral or bacterial proteins capable of cell membrane penetration.



  Accordingly, the present invention contemplates derivatization of the subject oligonucleotides with the above-identified groups to increase oligonucleotide cellular uptake.



   Moreover, the present invention contemplates the preparation of Rp stereospecific linkages in oligonucleotides having any nucleotide sequence. In many instances the selection of a nucleotide sequence depends upon the intended purpose of the oligonucleotide, for example the nucleotide sequence can be selected for the purpose of binding to a nucleic acid target. Such a nucleic acid target can be present within a template nucleic acid which encodes a DNA, RNA or protein. Moreover, binding of the subject oligonucleotides can be used, for example, to detect or to regulate the biosynthesis of such a template nucleic acid.



   The present invention contemplates a variety of utilities for the subject Rp stereospecific oligonucleotides. Some utilities include, but are not limited to: use of oligonucleotides of defined sequence bound to a solid support for affinity isolation of complementary nucleic acids; covalent attachment of a drug, drug analog or other therapeutic agent to the oligonucleotide to allow cell-type specific drug delivery; labeling the subject oligonucleotides with a  detectable reporter molecule for localizing, quantitating or identifying complementary target nucleic acids; and binding oligonucleotides to a cellular or viral nucleic acid template and regulating biosynthesis directed by that template.



   The subject oligonucleotides can be attached to a solid support such as silica, cellulose, nylon, polystyrene, polyethylene glycol, Sepharose   4BQ    and other natural or synthetic materials that are used to make beads, filters, and column chromatography resins.



  Attachment procedures for nucleic acids to solid supports of these types are well known; any known attachment procedure is contemplated by the present invention. An oligonucleotide attached to a solid support can then be used to isolate a complementary nucleic acid. Isolation of the complementary nucleic acid can be done by incorporating the oligonucleotide:solid support into a column for chromatographic procedures. Other isolation methods can be done without incorporation of the oligonucleotide:solid support into a column, e.g. by utilization of filtration procedures.



  Oligonucleotide:solid supports can be used, for example,    + mRNA from total cellular or viral to isolate poly(A)   
RNA by making an Rp alkyl- or aryl-phosphonate oligonucleotide with only poly(dT) or poly(U) B groups.



  The present Rp alkyl- and aryl-phosphonate oligonucleotides are ideally suited to applications of this type because they are nuclease resistant and bind strongly to target nucleic acids.



   The present invention also contemplates using the subject oligonucleotides for targeting drugs to  specific cell types. Such targeting can allow selective destruction or enhancement of particular cell types, e.g. inhibition of tumor cell growth can be attained.



  Different cell types express different genes, so that the concentration of a particular mRNA can be greater in one cell type relative to another cell type, such an mRNA is a target mRNA for cell type specific drug delivery by oligonucleotides linked to drugs or drug analogs. Cells with high concentrations of target mRNA are targeted for drug delivery by administering to the cell an oligonucleotide with a covalently linked drug that is complementary to the target mRNA.



   The present invention also contemplates labeling the subject oligonucleotides for use as probes to detect a target nucleic acid. Labelled oligonucleotide probes have utility in diagnostic and analytical hybridization procedures for localizing, guantitating or detecting a target nucleic acid in tissues, chromosomes or in mixtures of nucleic acids.



  Oligonucleotide probes of this invention represent a substantial improvement over conventional nucleic acid probes for such procedures because the present Rp stereospecific linkages provide oligonucleotides with increased binding stability.



   Labeling an oligonucleotide can be done by incorporating nucleotides linked to a "reporter molecule" into the subject oligonucleotides. A "reporter molecule", as defined herein, is a molecule or atom which, by its chemical nature, provides an identifiable signal allowing detection of the oligonucleotide. Detection can be either qualitative or quantitative. The present invention contemplates using  any commonly used reporter molecule including radionuclides, enzymes, biotins, psoralens, fluorophores, chelated heavy metals, and luciferin. The most commonly used reporter molecules are either enzymes, fluorophores or radionuclides which can be linked to nucleotides either before or after oligonucleotide synthesis.

   Preferably, the reporter molecule is added after oligonucleotide synthesis, for example, by forming a covalent linkage between a 3'- or 5'-terminal hydroxy or phosphate and a phosphate, nitrogen, sulfor or oxygen atom on the reporter molecule.



   Commonly used enzymes include horseradish peroxidase, alkaline phosphatase, glucose oxidase and    -    galactosidase, among others. The substrates to be used with the specific enzymes are generally chosen because a detectably colored product is formed by the enzyme acting upon the substrate. For example, p-nitrophenyl phosphate is suitable for use with alkaline phosphatase conjugates; for horseradish peroxidase, 1,2phenylenediamine, 5-aminosalicyclic acid or toluidine are commonly used.

 

   The probes so generated have utility in the detection of a specific DNA or RNA target in, for example, Southern analysis, Northern analysis, in situ hybridization to tissue sections or chromosomal squashes and other analytical and diagnostic procedures. Methods of using such hybridization probes are well known and examples of such methodology are provided by Sambrook et al. (1989, Molecular Cloning: A Laboratory Manual,
Vols. 1-3, Cold Spring Harbor Press, NY).  



   The present oligonucleotides can be used in conjunction with any known detection or diagnostic procedure which is based upon hybridization of a probe to a target nucleic acid. Moreover, the present oligonucleotides can be used in any hybridization procedure which quantitates a target nucleic acid, e.g., by competitive hybridization between a target nucleic acid present in a sample and a labeled tracer target for one of the present oligonucleotides. Furthermore, the reagents needed for making a oligonucleotide probe and for utilizing such a probe in a hybridization procedure can be marketed in a kit.



   The kit for detection of a hybridized oligonucleotide probe of the present invention can be compartmentalized for ease of utility and can contain at least one first container providing an oligonucleotide of the present invention. The kit can also be adapted to contain at least one other container providing reagents for labeling the oligonucleotide with a reporter molecule. Moreover, the kit can be further adapted to contain at least one other container providing reagents for detecting the reporter molecule linked to the oligonucleotide.



   Moreover the present invention provides a kit for isolation of a template nucleic acid. Such a kit has at least one first container providing one of the present oligonucleotides which is complementary to a target contained within the template. For example, the    template nucleic acid can be cellular and/or viralail.



   + mRNA and the target can be the poly(A) poly(A)
Hence oligonucleotides of the present invention which    have utility for isolation of poly(A) nucleotide sequence of poly(dT) or poly(U).  



   Furthermore, the present invention provides kits useful when diagnosis of a disease depends upon detection of a specific, known target nucleic acid.



  Such nucleic acid targets can be, for example, a viral nucleic acid, an extra or missing chromosome or gene, a mutant cellular gene or chromosome, an aberrantly expressed RNA and others. Examples of such target nucleic acids contemplated by the present invention are provided hereinbelow.



   These diagnostic kits can be compartmentalized to contain at least one first container providing a oligonucleotide linked to a reporter molecule and can contain at least one second container providing reagents for detection of the reporter molecule.



   One aspect of the present invention provides a method of regulating biosynthesis of a DNA, an RNA or a protein by contacting at least one of the subject oligonucleotides with a nucleic acid template for that
DNA, that RNA or that protein in an amount and under conditions sufficient to permit the binding of the oligonucleotide(s) to a target sequence contained in the template. The binding between the oligonucleotide(s) and the target can regulate biosynthesis of the nucleic acid or the protein, e.g. by blocking access to the template. When access to the template is blocked proteins and nucleic acids involved in the biosynthetic process are prevented from binding to the template, from moving along the template, or from recognizing signals encoded within the template.



   As used herein, biosynthesis of a nucleic acid or a protein includes cellular and viral processes such as DNA replication, DNA reverse transcription, RNA  transcription, RNA splicing, RNA polyadenylation, RNA translocation and protein translation, and related processes which can lead to production of DNA, RNA or protein, and involve a nucleic acid template at some stage of the biosynthetic process.



   As used herein, a nucleic acid template can be an RNA or a DNA template.



   As contemplated by the present invention, regulating biosynthesis includes inhibiting, stopping, increasing, accelerating or delaying biosynthesis.



  Regulation may be direct or indirect, i.e. biosynthesis of a DNA, RNA or protein may be regulated directly by binding a oligonucleotide to the template for that DNA,
RNA or protein; alternatively, biosynthesis may be regulated indirectly by oligonucleotide binding to a second template encoding a protein that plays a role in regulating the biosynthesis of the first DNA, RNA or protein.



   DNA replication from a DNA template is mediated by proteins which bind to an origin of replication where they open the DNA and initiate DNA synthesis along the DNA template. To inhibit DNA replication in accordance with the present invention, oligonucleotides are selected which bind to one or more targets in an origin of replication. Such binding blocks template access to proteins involved in DNA replication. Therefore initiation and procession of DNA replication is inhibited. As an alternative method of inhibiting DNA replication, expression of the proteins which mediate DNA replication can be inhibited at, for example, the transcriptional or translational level.  



   DNA replication from an RNA template is mediated by reverse transcriptase binding to a region of
RNA also bound by a nucleic acid primer. To inhibit DNA replication from an RNA template, reverse transcriptase or primer binding can be blocked by binding a oligonucleotide to the primer binding site, and thereby blocking access to that site. Moreover, inhibition of
DNA replication can occur by binding a oligonucleotide to a site residing in the RNA template since such binding can block access to that site and to downstream sites, i.e. sites on the 3' side of the target or binding site.



   To initiate RNA transcription, RNA polymerase recognizes and binds to specific start sequences, or promoters, on a DNA template. Binding of RNA polymerase opens the DNA template. There are also additional transcriptional regulatory elements that play a role in transcription and are located on the DNA template.



  These transcriptional regulatory elements include enhancer sequences, upstream activating sequences, repressor binding sites and others. All such promoter and transcriptional regulatory elements, singly or in combination, are targets for the subject oligonucleotides. Oligonucleotide binding to these sites can block RNA polymerase and transcription factors from gaining access to the template and thereby regulating, e.g., increasing or decreasing, the production of RNA, especially mRNA and tRNA.



  Additionally, the subject oligonucleotides can be targeted to the coding region or 3'-untranslated region of the DNA template to cause premature termination of transcription. One skilled in the art can readily  design oligonucleotides for the above target sequences from the known sequence of these regulatory elements, from coding region sequences, and from consensus sequences.



   RNA transcription can be increased by, for example, binding a oligonucleotide to a negative transcriptional regulatory element or by inhibiting biosynthesis of a protein that can repress transcription. Negative transcriptional regulatory elements include repressor sites or operator sites, wherein a repressor protein binds and blocks transcription. Oligonucleotide binding to repressor or operator sites can block access of repressor proteins to their binding sites and thereby increase transcription.



   The primary RNA transcript made in eukaryotic cells, or pre-mRNA, is subject to a number of maturation processes before being trans located into the cytoplasm for protein translation. In the nucleus, introns are removed from the pre-mRNA in splicing reactions. The 5' end of the mRNA is modified to form the 5' cap structure, thereby stabilizing the mRNA.



  Various bases are also altered. The polyadenylation of the mRNA at the 3' end is thought to be linked with export from the nucleus. The subject oligonucleotides can be used to block any of these processes.



   A pre-mRNA template is spliced in the nucleus by ribonucleoproteins which bind to splice junctions and intron branch point sequences in the pre-mRNA.



  Consensus sequences for 5' and 3' splice junctions and for the intron branch point are known. For example, inhibition of ribonucleoprotein binding to the splice junctions or inhibition of covalent linkage of the 5'  end of the intron to the intron branch point can block splicing. Maturation of a pre-mRNA template can, therefore, be blocked by preventing access to these sites, i.e. by binding oligonucleotides of this invention to a 5' splice junction, an intron branch point or a 3' splice junction. Splicing of a specific pre-mRNA template can be inhibited by using oligonucleotides with sequences that are complementary to the specific pre-mRNA splice junction(s) or intron branch point.

   In a further embodiment, a collection of related splicing of pre-mRNA templates can be inhibited by using a mixture of oligonucleotides having a variety of sequences that, taken together, are complementary to the desired group of splice junction and intron branch point sequences.



   Polyadenylation involves recognition and cleavage of a pre-mRNA by a specific RNA endonuclease at specific polyadenylation sites, followed by addition of a poly(A) tail onto the 3' end of the pre-mRNA. Hence, any of these steps can be inhibited by binding the subject oligonucleotides to the appropriate site.



   RNA trans location from the nucleus to the cytoplasm of eukaryotic cells appears to require a poly(A) tail. Thus, a oligonucleotide is designed in accordance with this invention to bind to the poly(A) tail and thereby inhibit RNA translocation. The sequence of such an oligonucleotide can consist of about 10 to about 50 thymine residues, and preferably about 20 thymine residues.



   Protein biosynthesis begins with the binding of ribosomes to an mRNA template, followed by initiation and elongation of the amino acid chain via translational   "reading" of the mRNA. Protein biosynthesis, or translation, can thus be blocked or inhibited by blocking access to the template using the subject oligonucleotides to bind to targets in the template mRNA. Such targets contemplated by this invention include the ribosome binding site the 5' mRNA cap site, an initiation codon, a site between a 5' mRNA cap site and the initiation codon and sites in the protein coding sequence. There are also classes of protein which share domains of nucleotide sequence homology. Thus, inhibition of protein biosynthesis for such a class can be accomplished by targeting the homologous protein domains (via the coding sequence) with the subject oligonucleotides.



   Regulation of biosynthesis by any of the aforementioned procedures has utility for many applications. For example, genetic disorders can be corrected by inhibiting the production of mutant or over-produced proteins, or by increasing production of under-expressed proteins; the expression of genes encoding factors that regulate cell proliferation can be inhibited to control the spread of cancer; and virally encoded functions can be inhibited to combat viral infection.



   Some types of genetic disorders that can be treated by the oligonucleotides of the present invention include Alzheimer's disease, some types of arthritis, sickle cell anemia, and types of cancer for which patients can be a genetically predisposed, as well as other genetic disorders. Many types of viral infections can be treated by utilizing the oligonucleotides of the present invention, including infections caused by  influenza, rhinovirus, human immunovirus, herpes simplex, papilloma virus, cytomegalovirus, Epstein-Barr virus, adenovirus, vesticular stomatitus virus, rotavirus and respitory synctitial virus among others.



  According to the present invention, animal and plant viral infections may also be treated by administering the subject oligonucleotides.



   Accordingly, template nucleic acids contemplated by the present invention include cellular oncogenes, genes having a role in Alzheimer's disease, genetic functions encoded by viruses such as those described above, and others. Such template nucleic acids include but are not limited to SEQ ID NO:1 to SEQ
ID   NO:98    which encode the following genetic functions:
 SEQ ID   NO:1    human c-abl;
 SEQ ID   NO:2    human c-bcl-2a;
 SEQ ID   NO:3    human   c-bcl-2b;   
 SEQ ID NO:4 human c-bcr-l;
 SEQ ID   NO:5    human c-bcr-2;
 SEQ ID   NO:6    human c-bcr-3;
 SEQ ID   NO:7    human c-cbl;
 SEQ ID   NO:8    human c-erbB-2;
 SEQ ID NO:9 human c-ets-l;
 SEQ ID NO:10 human c-dbl;
 SEQ ID NO:

   11 human c-fgf;
 SEQ   ID'NO:12    human c-fgr-l;
 SEQ ID NO:13 human c-fgr-2;
 SEQ ID NO:14 human c-fgr-3;
 SEQ ID   NO:15    human c-fgr-4;
 SEQ ID   NO:16    human c-fgr-5;
 SEQ ID NO:17 human c-fgr-6;
 SEQ ID NO:18 human c-fgr-7;  
SEQ ID NO:19 human c-fms;
SEQ ID NO:20 human c-fos;
SEQ ID NO:21 human c-has/bas;
SEQ ID NO:22 human   c-int-l;   
SEQ ID NO:23 human c-int-2;
SEQ ID NO:24 human c-jun;
SEQ ID NO:25 human c-kit;
SEQ ID NO:26 human c-mas;
SEQ ID NO:27 human c-met;
SEQ ID NO:28 human c-myc;
SEQ ID NO:29 human c-Ki-rasl;
SEQ ID NO:30 human N-ras-l;
SEQ ID NO:31 human N-ras-2;
SEQ ID NO:32 human N-ras-3;
SEQ ID   NO:33    human N-ras-4;
SEQ ID   NO:34    human c-ret;
SEQ ID   NO:35    human c-ros-l;

  
SEQ ID   NO:36    human c-ros-2;
SEQ ID   NO:37    human c-ros-3;
SEQ ID   NO:38    human c-ros-4;
SEQ ID   NO:39    human c-rps-5;
SEQ ID   NO:40    human c-ros-6;
SEQ ID NO:41 human c-ros-7;
SEQ ID NO:42 human c-ros-8;
SEQ ID NO:43 human c-ros-9;
SEQ ID NO:44 human c-ros-l0;
SEQ ID NO:45 human c-sec;
SEQ ID NO:46 human c-sis-l;
SEQ ID NO:47 human c-sis-2;
SEQ ID NO:48 human c-sis-3;
SEQ ID NO:49 human c-sis-4;
SEQ ID NO:50 human c-sis-5;  
SEQ ID NO:51 human c-sis-al;
SEQ ID NO:52 human c-sis-a2;
SEQ ID NO:53 human c-sis-a3;
SEQ ID NO:54 human c-sis-a4;
SEQ ID NO:55 human c-sis-a5;
SEQ ID NO:

   56 human c-sis-a6;
SEQ ID NO:57 human c-sis-a7;
SEQ ID   NO:58    human c-sis-bl;
SEQ ID   NO:59    human c-sis-b2;
SEQ ID NO:60 human c-sis-b3;
SEQ ID NO: 61 human c-sis-b4;
SEQ ID   NO:62    human c-sis-b5;
SEQ ID   NO:63    human c-snoA;
SEQ ID   NO:64    human   c-snoN;   
SEQ ID   NO:65    human c-spi-1;
SEQ ID   NO:66    human c-src-1;
SEQ ID   NO:67    human c-src-2;
SEQ ID   NO:68    human c-src-3;
SEQ ID   NO:69    human c-src-4;
SEQ ID NO:70 human c-src-5;
SEQ ID NO:71 human c-src-6:
SEQ ID NO:72 human c-src-7;
SEQ ID NO:73 human c-src-8;
SEQ ID NO:74 human c-src-9;
SEQ ID NO:75 human c-src-l0;
SEQ ID NO:76 human c-src-ll;
SEQ ID NO:

  77 human   c-syn;   
SEQ ID NO:78 human c-trk;
SEQ ID NO:79 human c-vav;
SEQ ID NO:80 human c-mos-OA;
SEQ ID NO:81 human GP5-mos;
SEQ ID NO:82 human c-yes-1;  
 SEQ ID NO:83 human c-yes-2;
 SEQ ID NO:84 human c-ski-1;
 SEQ ID NO:85 human c-ski-2;
 SEQ ID NO:86 human c-ski-3;
 SEQ ID   NO:87    human c-ski-4;
 SEQ ID   NO:88    human   c-ski-S;   
 SEQ ID NO:89 human c-myb-l;
 SEQ ID   NO:90    human c-myb-2;
 SEQ ID   NO:91    human c-myb-3;
 SEQ ID NO:92 human c-myb-4;
 SEQ ID   NO:93    human c-rel.



   Moreover, according to the present invention the subject oligonucleotides need have only sufficient complementarity to detectably bind to either strand of a target nucleic acid sequence, e.g. SEQ ID   NO:1-98.   



   Complementarity between nucleic acids is the degree to which the bases in one nucleic acid strand can hydrogen bond, or base pair, with the bases in a second nucleic acid strand. Hence, complementarity can sometimes be conveniently described by the percentage, i.e. proportion, of nucleotides which form base pairs between two strands or within a specific region or domain of two strands. For the present invention sufficient complementarity means that a sufficient number of base pairs exists between the subject oligonucleotides and a target nucleic acid to achieve detectable binding of the oligonucleotide.



   Therefore a sufficient number, but not necessarily all, nucleotides in the present oligonucleotides can hydrogen bond to a target. The number of positions which are necessary to provide sufficient complementarity for binding of the subject  oligonucleotides, can be detected by standard procedures including a melting temperature determination, standard
Southern and Northern hybridization, light absorption detection, gel shift, DNA footprinting, alkylation interference and related procedures (as provided for example in Sambrook et al.). Moreover, according to the present invention oligonucleotide binding can be detected functionally, e.g. by observing a decrease in cellular or viral proliferation or by observing a decrease or increase in the synthesis of the DNA, RNA or protein encoded within or by a template nucleic acid.



   Accordingly the degree of complementarity between an oligonucleotide of the present invention and a strand of a target nucleic acid need not be 100% so long as oligonucleotide binding can be detected.



  However, it is preferred that the present oligonucleotides have at least about 50% complementarity with their target nucleic acids. In an especially preferred embodiment sufficient complementarity is greater than 70% complementarity with the target.



   Moreover, the degree of complementarity that provides detectable binding between the subject oligonucleotides and the target is dependent upon the conditions under which that binding occurs. It is well known that binding between nucleic acid strands depends on factors besides the degree of mismatch between two sequences. Such factors include the GC content of the region, temperature, ionic strength, the presence of formamide and types of counter ions present. The effect that these conditions have upon binding is known to one skilled in the art. Furthermore, conditions are frequently determined by the circumstances of use. For  example, when an oligonucleotide is made for use in vivo, no formamide will be present and the ionic strength, types of counter ions, and temperature correspond to physiological conditions.

   Binding conditions can be manipulated in vitro to optimize the utility of the present oligonucleotides. A thorough treatment of the qualitative and quantitative considerations involved in establishing binding conditions that allow one skilled in the art to design appropriate oligonucleotides for use under the desired conditions is provided by Beltz et al., 1983, Methods
Enzymol. 100: 266-285 and by Sambrook et al.



   Thus for the present invention, one of ordinary skill in the art can readily design a nucleotide sequence for the subject oligonucleotides which exhibits sufficient complementarity to detectably bind to the target nucleic acid of interest, including nucleic acids having SEQ ID NO: 1-93. To confirm a nucleotide sequence, oligonucleotides may be subjected to DNA sequencing by any of the known procedures, including Maxam and Gilbert sequencing, Sanger sequencing, capillary electrophoresis sequencing, the wandering spot sequencing procedure or by using selective chemical degradation of oligonucleotides bound to Hybond paper. Sequences of oligonucleotides can also be analyzed by plasma desorption mass spectroscopy or by fast atom bombardment (McNeal, et al., 1982, J. Am.



  Chem. Soc. 104: 976; Viari, et al., 1987, Biomed.



  Environ. Mass Spectrom. 14: 83; Grotjahn et al., 1982,
Nuc. Acid Res. 10: 4671). Sequencing methods are also available for RNA oligonucleotides.  



   A further aspect of this invention provides pharmaceutical compositions containing the subject oligonucleotides with a pharmaceutically acceptable carrier. In particular, the present invention provides a pharmaceutical composition for regulating biosynthesis of a nucleic acid or protein comprising a pharmaceutically effective amount of the subject oligonucleotide with a pharmaceutically acceptable carrier.



   As used herein a pharmaceutically effective amount of the subject oligonucleotides is about 0.1   ug    to about 100 mg per kg of body weight per day, and preferably of about 0.1   ug    to about 10 mg per kg of body weight per day. Dosages can be readily determined by one of ordinary skill in the art and formulated into the subject pharmaceutical compositions.



   As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like.



  The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions.



   The subject oligonucleotides can be provided to a mammalian cell by topical or parenteral administration, for example, by intraveneous, intramuscular, intraperitoneal subcutaneous or intradermal route, or when suitably protected, the  subject oligonucleotides can be orally administered.



  The subject oligonucleotides may be incorporated into a cream, solution or suspension for topical administration. For oral administration, oligonucleotides may be protected by enclosure in a gelatin capsule. Oligonucleotides may be incorporated into liposomes or liposomes modified with polyethylene glycol for parenteral administration. Incorporation of additional substances into the liposome, for example, antibodies reactive against membrane proteins found on specific target cells, can help target the oligonucleotides to specific cell types.



   Topical administration and parenteral administration in a liposomal carrier is preferred.



   The following examples further illustrate the invention.  



   EXAMPLE 1
 PREPARATION OF AN   STEREOISOMERIC   
   ALKYL -    OR ARYL-PHOSPHONOTHIOATE NUCLEOTIDES
 The reactions used to produce Sp- and Rpstereospecific nucleotides are as described in (Lebedev, et al. 1990 Tetrahedron Letters 31: 855-858) and are depicted below in Reaction Scheme I. DMT is used for   dimethokytrityl    in Reaction Scheme I.



   The phosphate present on 5'  dimethoxytritylthymidyl-3' -methylphosphonoamidate (1)    was protected by cyanoethylation in the presence of 4 (N,N-diethylamino)-pyridine (DMAP) and trifluoroacetic anhydride at room temperature to produce 5'   dimethoxytritylthymidyl-3' -methylphosphono-ethylcyanate    (2). The phosphite triester present in 2 was then oxidized with sulfur   (sue)    in the presence of CH3CN to generate racemic   5' -dimethoxytrityl-thymidyl-3' -    cyanoethylphosphonothioate (3). The diastereomers of 3 were purified and separated by silica high pressure liquid chromatography (HPLC). Cyanoethyl groups were removed with concentrated ammonium hydroxide in ethanol (v/v 1:2).

   The deprotected diastereomers were then purified by silica HPLC and the ammonium cation was replaced with lithium   (Li+)    by using a Dowex 50W x 2 exchange column to yield the lithium salts of separate
Sp- and Rp-stereoisomers of 5'-dimethoxytritylthymidyl3'-methylphosphonothioate (4).



   Each reaction was was monitored by observation of distinct   3 lip    nuclear magnetic resonance (NMR) peaks which are characteristic of a given reactant or product.



  *The chemical shift frequencies (6) of the reactants,  intermediates and products generated during the foregoing synthetic procedures are provided in Reaction
Scheme I.  



   EXAMPLE 2
 METHODS FOR DETECTING AND MONITORING
THE   STEREOlSOMERIC    CONFIGURATION OF A PHOPHONATE LINKAGE
Separation of Stereoisomers:
 Rp and Sp stereoisomers of alkyl- or arylphosphonate nucleotides prepared as in Example 1, were stable and were separated by ion exchange chromatography or by high pressure liquid chromatography (HPLC) using anhydrous or aqueous solvents. Reversed phase or silica gel columns were employed when separation was by
HPLC. For example, Sp- and Rp-stereoisomers of 5'  dimethoxytritylthymidyl-3' -methylphosphonothioate    were separated by   Cia    silica gel HPLC using either acetic acid/methanol or a gradient of 10-15% acetonitrile in water.



   Similarly, racemic 5',3'-protected dithymidine methylphosphonate was resolved into Rp and Sp stereoisomers by HPLC on a 4.6 x 250 mm column of silica gel a gradient of 10-15% acetonitrile in water for elution (Fig. 1). Accordingly, Rp and Sp stereoisomers of both nucleotides and short oligonucleotides can be chromatographically separated.



  Detection by Circular Dichroism:
 Circular dichroism (CD) has been used to detect stereoisomeric differences. For example, separate Rp and Sp stereoisomers of dithymidine methylphosphonate have different CD spectra, wherein the
Rp isomer has a larger CD peak and the Sp isomer CD trough is blue-shifted (Fig. 2).



  Detection by Nuclear Magnetic Resonance:  
 Separated Rp and Sp stereoisomers have distinctive 1H and   31P    nuclear magnetic resonance (NMR) spectra. For example, Figs. 3 and 4 depict the respective   XH    and   31P    NMR spectra of both Rp and Sp stereoisomers of dithymidine methylphosphonate.



  Detection by Mass Spectroscopy:
 Fast atom bombardment mass spectrometry (FABMS) has been used extensively to examine the structures of oligonucleotides having molecular weights up to 10,000 g/mole (Stec et al. 1985 J. Org. Chem. 50: 3908; Ulrich et al. 1984 Org. Mass Spectrom. 19: 585;
Grotjahn et al. 1982 Nucleic Acids Res. 10: 4671;
Grotjahn et al. 1983 Int. J. Mass Spectrom. Ion Phys.



  46: 439; Sindona et al. 1982 J. Chem. Res. (S):184;
Eagles et al. 1984 Biomed. Mass. Spectrom. 11: 41;
Connolly et al. 1984 Biochemistry 23: 3443-3453; and
Matsuo et al. 1986 34th Annual Conference on Mass
Spectrometry and Allied Topics, 329). Therefore, FABMS has utility for structural analyses of R and S stereoisomers of alkyl- and aryl-phosphonates.



   For example, FABMS of tetrathymidine methylphosphonate (i.e. DMT-TpTpTpT-OAc) which was sputtered from thioglycerol yielded the spectrogram depicted in Fig. 5 wherein peaks corresponding to distinct molecular fragments are identified (e.g. DMT
TpT is dimethoxytrityl-dithymidine methylphosphonate).  



   EXAMPLE 3
 A METHOD FOR MAKING AN R   STERBOISOMERIC   
   ALKYLPHOPHONATE    LINKAGE
 Reactions for producing an Rp-stereospecific linkage are depicted below in Reaction Scheme II. DMT is used for dimethoxytrityl in Reaction Scheme II.



   A purified Sp stereoisomer of an 3'-Omethylphosphonate nucleotide (4) is made by the procedures provided in Example 1. In the first.step, 1 mmole of 4 is reacted with 2 mmole of an activator, 2chloro-N-methylpyridinium (5) in 10 ml of acetonitrile (CH,CN) under anhydrous conditions at room temperature for 1 min. This reaction yields a reactive intermediate (6) without altering the S configuration of the phosphate. To this reaction mixture is added 0.5 mmole of a 5'-OH unprotected nucleoside and the mixture is allowed to react at room temperature for 60 min. The 5'-oxygen atom of the nucleoside attacks the phosphorus and displaces the sulfur with the attached activating group by SN2 nucleophilic substitution. This   SH2    displacement reaction inverts the S stereoisomeric configuation of the phosphorus to an R stereoisomeric configuration.



   The displaced 2-thio-N-methylpyridinium molecule is stabilized by resonance tautomerization and does not further react with the phosphorus to cause epimerization of the R configuration. This was confirmed in a separate study, wherein the only   31P    NMR peaks characteristic of a phosphorus-sulfur linkage (at 86-88 ppm) were attributable to reactive intermediate 6.  

 

     SEQUENCE    LISTING (1) GENERAL INFORMATION:
   (j)    APPLICANT: Wickstrom, Eric and Lebedev, Alexander V.



   (ii) TITLE OF INVENTION: Pentavalent Synthesis of Oligonucleotides containing Stereospecific   Alkyiphosphonates    and Arylphosphonates
 (iii) NUMBER OF SEQUENCES: 93
 (iv) CORRESPONDENCE ADDRESS:
   (A)    ADDRESSEE: SCULLY, SCOTT, MURPHY    &     PRESSER
 (B) STREET: 400 Garden City Plaza
 (C) CITY: Garden City
 (D) STATE: NY
 (E) COUNTRY: USA
 (F) ZIP: 11530
 (v) COMPUTER READABLE FORM:
 (A) MEDIUM TYPE: Floppy disk
 (B) COMPUTER: IBM PC compatible
   (C)  
   (D)    TOPOLOGY: linear
   (li)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:1:
GATCTTGCTG CCCGAAACTG CCTGGTAGGG GAGAACCACT TGGTGAAGGT   AGCTGATTTT    60
GGCCTGAGCA GGTTGATGAC AGGGGACACC TACACAGCCC ATGCTGGAGC CAAGTTCCCC 120
ATCAAATGGA CTGCACCCGA GAGCCTGGCC TACAACAAGT TCTCCATCAA GTCCGACGTC 180
TGGGGTAAGG GC 192 (2) INFORMATION FOR   SEO    ID NO:2:
 (1) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 5086 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (11) MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:2:
GCGCCCGCCC CTCCGCGCCG CCTGCCCGCC CGCCCGCCGC GCTCCCGCCC GCCGCTCTCC 60
GTGGCCCCGC CGCGCTGCCG CCGCCGCCGC TGCCAGCGAA GGTGCCGGGG CTCCGGGCCC 120
TCCCTGCCGG   CGGCCGTCAG    CGCTCGGAGC GAACTGCGCG ACGGGAGGTC CGGGAGGCGA 180
CCGTAGTCGC GCCGCCGCGC AGGACCAGGA GGAGGAGAAA GGGTGCGCAG CCCGGAGGCG 240
GGGTGCGCCG GTGGGGTGCA GCGGAAGAGG GGGTCCAGGG GGGAGAACTT CGTAGCAGTC 300   ATCCITTTTA    GGAAAAGAGG GAAAAAATAA AACCCTCCCC CACCACCTCC TTCTCCCCAC 360
CCCTCGCCGC ACCACACACA GCGCGGGCTT CTAGCGCTCG GCACCGGCGG GCCAGGCGCG 420
TCCTGCCTTC ATTTATCCAG CAGCTTTTCG GAAAATGCAT TTGCTGTTCG   GAGTTTAATC    480
AGAAGACGAT TCCTGCCTCC GTCCCCGGCT CCTTCATCGT CCCATCTCCC CTGTCTCTCT 540  
CCTGGGGAGG CGTGAAGCGG TCCCGTGGAT AGAGATTCAT GCCTGTGTCC GCGCGTGTGT 600
GCGCGCGTAT AAATTGCCGA GAAGGGGAAA 

  ACATCACAGG   ACTTCTGCGA    ATACCGGACT 660
GAAAATTGTA ATTCATCTGC CGCCGCCGCT GCCAAAAAAA   AACTCGAGCT    CTTGAGATCT 720
CCGGTTGGGA TTCCTGCGGA TTGACATTTC TGTGAAGCAG AAGTCTGGGA ATCGATCTGG 780
AAATCCTCCT AATTTTTATC CCCTCTCCCC CCGACTCCTG ATTCATTGGG AAGTTTCAAA 840
TCAGCTATAA CTGGAGAGTG CTGAAGATTG   ATGGGATCGT    TGCCTTATGC ATTTGTTTTG 900
GTTTTACAAA AAGGAAACTT GACAGAGGAT CATGCTGTAC TTAAAAAATA CAAGTAAGTC 960
TCGCACAGGA AATTGGTTTA ATGTAACTTT CAATGGAAAC CTTTGAGATT TTTTACTAA 1020
AGTGCATTCG AGTAAATTTA ATTTCCAGGC AGCTTAATAC ATTGTTTTTA GCCGTGTTAC 1080
TTGTAGTGTG TATGCCCTGC   TTTCACTCAG    TGTGTACAGG GAAACGCACC   TGAT:

  TTTA    1140
CTTATTAGTT   TGTTTTTCT      TTAACCrrTC    AGCATCACAG AGGAAGTAGA CTGATATTAA 1200
CAATACTTAC TAATAATAAC GTGCCTCATG AAATAAAGAT CCGAAAGGAA TTGGAATAAA 1260
AATTTCCTGC GTCTCATGCC AAGAGGGAAA CACCAGAATC AAGTGTTCCG   CGTGATTGAA    1320
GACACCCCCT CGTCCAAGAA TGCAAAGCAC ATCCAATAAA ATAGCTGGAT TATAACTCCT 1380
CTTCTTTCTC TGGGGGCCGT GGGGTGGGAG CTGGGGCGAG AGGTGCCGTT GGCCCCCGTT 1440
GCTTTTCCTC TGGGAAGGAT GGCGCACGCT GGGAGAACGG GGTACGACAA CCGGGAGATA 1500
GTGATGAAGT ACATCCATTA TAAGCTGTCG CAGAGGGGCT ACGAGTGGGA TGCGGGAGAT 1560
GTGGGCGCCG CGCCCCCGGG GGCCGCCCCC GCACCGGGCA TCTTCTCCTC   CCAGCCCGGC.    1620
CACACGCCCC ATCCAGCCGC ATCCCGCGAC CCGGTCGCCA GGACCTCGCC GCTGCAGACC 1680
CCGGCTGCCC CCGGCGCCGC CGCGGGGCCT GCGCTCAGCC CGGTGCCACC TGTGGTCCAC 1740
CTGGCCCTCC GCCAAGCCGG CGACGACTTC  <RTI  

   ID=65.10> TCCCGCCGCT      ACCGCGGCGA      CTTCGCCGA(;    1800
ATGTCCAGCC AGCTGCACCT GACGCCCTTC ACCGCGCGGG GACGCTTTGC CACGGTGGTG 1860
GAGGAGCTCT TCAGGGACGG GGTGAACTGG GGGAGGATTG TGGCCTTCTT TGAGTTCGGT 1920
GGGGTCATGT GTGTGGAGAG CGTCAACCGG GAGATGTCGC CCCTGGTGGA CAACATCGCC 1980  
CTGTGGATGA CTGAGTACCT GAACCGGCAC CTGCACACCT GGATCCAGGA TAACGGAGGC 2040
TGGGATGCCT   TTGTGGAACT      GTACGGCCCC    AGCATGCGGC CTCTGTTTGA TTTCTCCTGG 2100
CTGTCTCTGA   AGACTCTGCT    CAGTTTGGCC CTGGTGGGAG CTTGCATCAC   CCTGGGTGCC    2160
TATCTGAGCC ACAAGTGAAG TCAACATGCC TGCCCCAAAC AAATATGCAA AAGGTTCACT 2220
AAAGCAGTAG AAATAATATG CATTGTCAGT GATGTACCAT GAAACAAAGC TGCAGGCTGT 2280
TTAAGAAAAA ATAACACACA TATAAACATC ACACACACAG ACAGACACAC ACACACACAA 2340
CAATTAACAG TCTTCAGGCA AAACGTCGAA 

  TCAGCTATTT ACTGCCAAAG GGAAATATCA 2400
TTTATTTTTT   ACATTATTAA    GAAAAAAGAT   TTATTTATIT    AAGACAGTCC CATCAAAACT 2460
CCGTCTTTGG AAATCCGACC ACTAATTGCC AAACACCGCT TCGTGTGGCT CCACCTGGAT 2520
GTTCTGTGCC TGTAAACATA GATTCGCTTT CCATGTTGTT GGCCGGATCA CCATCTGAAG 2580
AGCAGACGGA TGGAAAAAGG ACCTGATCAT TGGGGAAGCT GGCTTTCTGG CTGCTGGAGG 2640
CTGGGGAGAA GGTGTTCATT CACTTGCATT TCTTTGCCCT GGGGGCGTGA TATTAACAGA 2700
GGGAGGGTTC CCGTGGGGGG AAGTCCATGC CTCCCTGGCC TGAAGAAGAG ACTCTTTGCA 2760
TATGACTCAC ATGATGCATA CCTGGTGGGA GGAAAAGAGT TGGGAACTTC   AGhTGGACCT    2820
AGTACCCACT GAGATTTCCA CGCCGAAGGA CAGCGATGGG AAAAATGCCC TTAAATCATA 2880
GGAAAGTATT TTTTTAAGCT ACCAATTGTG CCGAGAAAAG   CATTTTA(;

  CA      ATTrATACAA    2940
TATCATCCAG TACCTTAAAC CCTGATTGTG TATATTCATA TATTTTGGAT ACGCACCCCC 3000
CAACTCCCAA TACTGGCTCT GTCTGAGTAA GAAACAGAAT CCTCTGGAAC TTGAGGAAGT 3060
GAACATTTCG GTGACTTCCG ATCAGGAAGG CTAGAGTTAC CCAGAGCATC AGGCCGCCAC 3120
AAGTGCCTGC   TTTTAGGAGA    CCGAAGTCCG CAGAACCTAC CTGTGTCCCA GCTTGGAGGC 3180
CTGGTCCTGG AACTGAGCCG GGCCCTCACT GGCCTCCTCC AGGGATGATC AACAGGGTAG 3240
TGTGGTCTCC GAATGTCTGG AAGCTGATGG ATGGAGCTCA   CAATTCCACT    GTCAAGAAAG 3300
AGCAGTAGAG GGGTGTGGCT GGGCCTGTCA CCCTGGGGCC CTCCAGGTAG GCCCGTTTTC 3360
ACGTGGAGCA TAGGAGCCAC GACCCTTCTT AAGACATGTA TCACTGTAGA GGGAAGGAAC 3420  
AGAGGCCCTG GGCCTTCCTA TCAGAAGGAC ATGGTGAAGG CTGGGAACGT GAGGAGAGGC 3480
AATGGCCACG GCCCATTTTG GCTGTAGCAC ATGGCACGTT GGCTGTGTGG CCTTGGCCAC 3540   CTGTGAGTTT    AAAGCAAGGC  <RTI  

   ID=67.2> TTTAAATGAC    TTTGGAGAGG GTCACAAATC CTAAAAGAAG 3600
CATTGAAGTG AGGTGTCATG GATTAATTGA CCCCTGTCTA TGGAATTACA TGTAAAACAT 3660
TATCTTGTCA CTGTAGTTTG GTTTTATTTG AAAACCTGAC AAAAAAAAAG TTCCAGGTGT 3720
GGAATATGGG GGTTATCTGT ACATCCTGGG GCATTAAAAA AAAATCAATG GTGGGGAACT 3780
ATAAAGAAGT AACAAAAGAA GTGACATCTT CAGCAAATAA ACTAGGAAAT TTTTTTTTCT 3840
TCCAGTTTAG AATCAGCCTT GAAACATTGA TGGAATAACT CTGTGGCATT ATTGCATTAT 3900
ATACCATTTA TCTGTATTAA CTTTGGAATG TACTCTGTTC AATGTTTAAT   GCTGTGGTTG    3960
ATATTTCGAA AGCTGCTTTA AAAAAATACA TGCATCTCAG CGTTTTTTTG TTTTTAATTG 4020
TATTTAGTTA TGGCCTATAC ACTATTTGTG AGCAAAGGTG ATCGTTTTCT GTTTGAGATT 4080
TTTATCTCTT   GATTCTTCAA    AAGCATTCTG AGAAGGTGAG ATAAGCCCTG AGTCTCAGCT 4140
ACCTAAGAAA AACCTGGATG TCACTGGCCA   CTGAGGAGCT      TTGTrTCAAC    CAAGTCATGT 4200
GCATTTCCAC 

  GTCAACAGAA TTGTTTATTG TGACAGTTAT ATCTGTTGTC CCTTTGACCT 4260
TGTTTCTTGA AGGTTTCCTC GTCCCTGGGC AATTCCGCAT TTAATTCATG GTATTCAGGA 4320   TTACATGCAT    GTTTGGTTAA ACCCATGAGA TTCATTCAGT   TAAAAATCCA    GATGGCGAAT 4380
GACCAGCAGA TTCAAATCTA TGGTGGTTTG ACCTTTAGAG AGTTGCTTTA CGTGGCCTGT 4440
TTCAACACAG ACCCACCCAG AGCCCTCCTG CCCTCCTTCC GCGGGGGCTT TCTCATGGCT 4500
GTCCTTCAGG GTCTTCCTGA AATGCAGTGG TCGTTACGCT CCACCAAGAA AGCAGGAAAC 4560
CTGTGGTATG AAGCCAGACC TCCCCGGCGG GCCTCAGGGA ACAGAATGAT CAGACCTTTG 4620
AATGATTCTA ATTTTTAAGC AAAATATTAT TTTATGAAAG GTTTACATTG TCAAAGTGAT 4680
GAATATGGAA TATCCAATCC TGTGCTGCTA TCCTGCCAAA ATCATTTTAA TGGAGTCAGT 4740
TTGCAGTATG   CTCCACGTGG      TAAGATCCTC    CAAGCTGCTT   TAGAAGTAAC    AATGAAGAAC 4800
GTGGACGTTT TTAATATAAA GCCTGTTTTG TCTTTTGTTG TTGTTCAAAC 

  GGGATTCACA 4860  
GAGTATTTGA AAAATGTATA TATATTAAGA GGTCACGGGG GCTAATTGCT AGCTGGCTGC 4920
CTTTTGCTGT GGGGTTTTGT TACCTGGTTT TAATAACAGT AAATGTGCCC AGCCTCTTGG   4980   
CCCCAGAACT   GTACAGTATT    GTGGCTGCAC TTGCTCTAAG AGTAGTTGAT GTTGCATTTT 5040
CCTTATTGTT AAAAACATGT TAGAAGCAAT GAATGTATAT AAAAGC 5086   12)    INFORMATION FOR SEQ ID NO:3:
 (i) SEQUENCE   CilARACTERISTICS:   
 (A) LENGTH: 911 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (il)    MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:3:
TGATTGAAGA CACCCCCTCG TCCAAGAATG CAAAGCACAT CCAATAAAAT AGCTGGATTA 60
TAACTCCTCT TCTTTCTCTG GGGGCCGTGG GGTGGGAGCT GGGGCGAGAG   GTGCCGTTGG    120
CCCCCGTTGC TTTTCCTCTG GGAAGGATGG CGCACGCTGG GAGAACGGGG TACGACAACC 180
GGGAGATAGT GATGAAGTAC ATCCATTATA AGCTGTCGCA GAGGGGCTAC GAGTGGGATG 240
CGGGAGATGT GGGCGCCGCG CCCCCGGGGG CCGCCCCCGC ACCGGGCATC TTCTCCTCCC 300
AGCCCGGGCA CACGCCCCAT CCAGCCGCAT CCCGCGACCC GGTCGCCAGG ACCTCGCCGC 360
TGCAGACCCC GGCTGCCCCC GGCGCCGCCG CGGGGCCTGC GCTCAGCCCG GTGCCACCTG 420
TGGTCCACCT GGCCCTCCGC CAAGCCGGCG ACGACTTCTC CCGCCGCTAC   CGCGGCGACT    480
TCGCCGAGAT GTCCAGCCAG CTGCACCTGA CGCCCTTCAC CGCGCGGGGA CGCTTTGCCA 540
CGGTGGTGGA GGAGCTCTTC AGGGACGGGG TGAACTGGGG GAGGATTGTG GCCTTCTTTG 600
AGTTCGGTGG GGTCATGTGT   GTGGAGAGCG    

  TCAACCGGGA GATGTCGCCC   CTGGTGGACA    660
ACATCGCCCT GTGGATGACT GAGTACCTGA ACCGGCACCT   GCACACCTGG    ATCCAGGATA 720
ACGGAGGCTG GGTAGGTGCA TCTGGTGATG TGAGTCTGGG CTGAGGCCAC AGGTCCGAGA 780  
TCGGGGGTTG GAGTGCGGGT GGGCTCCTGG   GCAATGGGAG    GCTGTGGAGC   CGGCGAAATA      840   
AAATCAGAGT   TGTTGCTTCC    CGGCGTGTCC CTACCTCCTC CTCTGGACAA AGCGTTCACT 900
CCCAACCTGA C 911 (2) INFORMATION FOR SEQ ID NO:4:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 90 base pairs
   {B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:4:
ATGATGAGTC TCCGGGGCTC TATGGGTTTC TGAATGTCAT CGTCCACTCA GCCACTGGAT 60
TTAAGCAGAG TTCAAGTAAG TACTGGTTTG 90 (2) INFORMATION FOR SEQ ID NO:5:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 204 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:5:
CCCTTTCTCT TCCAGAAGCC CTTCAGCGGC   CAGTAGCATC    TGACTTTGAG CCTCAGGGTC 60
TGAGTGAAGC CGCTCGTTGG AACTCCAAGG AAAACCTTCT CGCTGGACCC AGTGAAAATG 120
ACCCCAACCT TTTCGTTGCA CTGTATGATT   TTGTGC.CCAG    TGGAGATAAC ACTCTAAGCA 180
TAACTAAAGG TAAAAGGGTT GTGG 204 (2) INFORMATION FOR   SEO    ID NO:6:  
 (i) SEQUENCE CHARACTERISTICS:
 (A)   LENGTH:    200 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID   NO:6:      TTCCTTTCTT    CTCAGGTGAA AAGCTCCGGG TCTTAGGCTA TAATCACAAT GGGGAATGGT 60
TTGAAGCCCA AACCAAAAAT GGCCAAGGCT GGGTCCCAAG CAACTACATC ACGCCAGTCA 120
ACAGTCTGGA GAAACACTCC TGGTACCATG GGCCTGTGTC CCGCAATGCC GCTGAGTATC 180
TGCTGAGCAG   CGGGATCAAT    200   {2)    INFORMATION FOR SEQ ID   NO:7:   
   (i)    SEQUENCE CHARACTERISTICS:
 (A)   LENGTH:    3090 base pairs
   (fl)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID   NO:7:   
GAATTCCGGG CCCGGATAGC CGGCGGCGGC GGCGGCGGCG GCGGCGGCGG CGGCCGGGAG 60
AGGCCCCTCC TTCACGCCCT GCTTCTCTCC CTCGCTCGCA   GTCGAGCCGA    GCCGGCGGAC 120
CCGCCTGGGC TCCGACCCTG CCCAGGCCAT GGCCGGCAAC GTGAAGAAGA GCTCTGGGGC 180
CGGGGGCGGC ACGGGCTCCG GGGGCTCGGG TTCGGGTGGC CTGATTGGGC TCATGAAGGA 240
CGCCTTCCAG CCGCACCACC ACCACCACCA CCACCTCAGC CCCCACCCGC CGGGGACGGT 300
GGACAAGAAG ATGGTGGAGA AGTGCTGGAA GCTCATGGAC AAGGTGGTGC GGTTGTGTCA 360
GAACCCAAAG CTGGCGCTAA AGAATAGCCC ACCTTATATC TTAGACCTGC TACCAGATAC 420  
CTACCAGCAT CTCCGTACTA TCTTGTCAAG ATATGAGGGG AAGATGGAGA CACTTGGAGA 480
AAATGAGTAT TTTAGGGTGT TTATGGAGAA TTTGATGAAG AAAACTAAGC AAACCATAAG 540
CCTCTTCAAG GAGGGAAAAG AAAGAATGTA TGAGGAGAAT   TCTCAGCCTA      GGCGAAACCT    600
AACCAAACTG TCCCTCATCT TCAGCCACAT   GCTGGCAGAA    

  CTAAAAGGAA TCTTTCCAAG 660   TSGACTCTTT    CAGGGAGACA CATTTCGGAT TACTAAAGCA GATGCTGCGG AATTTTGGAG   720   
AAAAGCTTTT   GGGGAAAAGA    CAATAGTCCC TTGGAAGAGC TTTCGACAGG CTCTACATGA   780   
AGTGCATCCC ATCAGTTCTG GGCTGGAGGC CATGGCTCTG AAATCCACTA TTGATCTGAC   840   
CTGCAATGAT TATATTTCGG   TTTrrTGAATT    TGACATCTTT ACCCGACTCT TTCAGCCCTG 900
GTCCTCTTTG CTCAGGAATT GGAACAGCCT TGCTGTAACT CATCCTGGCT ACATGGCTTT 960
TTTGACGTAT GACGAAGTGA AAGCTCGGCT CCAGAAATTC ATTCACAAAC CTGGCAGTTA 1020
TATCTTCCGG CTGAGCTGTA CTCGTCTGGG   TCAGTGGGCT      ATTGGGTATG    TTACTGCTGA 1080
TGGGAACATT CTCCAGACAA TCCCTCACAA TAAACCTCTC TTCCAAGCAC TGATTGATGG 1140   CTTCAGGGAA    GGCTTCTATT TGTTTCCTGA TGGACGAAAT CAGAATCCTG ATCTGACTGG 

  1200
CTTATGTGAA CCAACTCCCC AAGACCATAT CAAAGTGACC CAGGAACAAT ATGAATTATA 1260
CTGTGAGATG GGCTCCACAT TCCAACTATG TAAAATATGT GCTGAAAATG   ATAAGGATGT    1320
AAAGATTGAG CCCTGTGGAC ACCTCATGTG CACATCCTGT CTTACATCCT GGCAGGAATC 1380
AGAAGGTCAG GGCTGTCCTT TCTGCCGATG TGAAATTAAA GGTACTGAAC   CCATCGTGGT    1440
AGATCCGTTT GATCCTAGAG GGAGTGGCAG CCTGTTGAGG CAAGGAGCAG AGGGAGCTCC 1500
CTCCCCAAAT TATGATGATG ATGATGATGA ACGAGCTGAT GATACTCTCT TCATGATGAA 1560
GGAATTGGCT GGTGCCAAGG TGGAACGGCC GCCTTCTCCA TTCTCCATGG CCCCACAAGC 1620
TTCCCTTCCC CCGGTGCCAC CACGACTTGA CCTTCTGCCG CAGCGAGTAT GTGTTCCCTC 1680
AAGTGCTTCT GCTCTTGGAA CTGCTTCTAA GGCTGCTTCT GGCTCCCTTC ATAAAGACAA 1740
ACCATTGCCA GTACCTCCCA CACTTCGAGA TCTTCCACCA CCACCGCCTC CAGACCGGCC 1800
ATATTCTGTT GGAGCAGAAT CCCGACCTCA AAGACGCCCC   TTGCCTTGTA    CACCAGGCGA 1860  
CTGTCCCTCC AGAGACAAAC 

  TGCCCCCTGT CCCCTCTAGC CGCCTTGGAG   ACTCATGGCT      l920   
GCCCCGGCCA ATCCCCAAAG TACCAGTATC TTGCCCCAAGT TCCAGTGATC CCTGGACAGG 1980
AAGAGAATTA ACCAACCGGC ACTCACTTCC ATTTTCATTG CCCTCACAAA TGGAGCCCAG 2040
ACCAGATGTG CCTAGGCTCG GAAGCACGTT CAGTCTGGAT ACCTCCATGA   GTATGAATAG    2100
CAGCCCATTA GTAGGTCCAG   AGTGTGACCA    CCCCAAAATC AAACCTTCCT CATCTGCCAA 2160
TGCCATTTAT TCTCTGGCTG CCAGACCTCT TCCTGTGCCA AAACTGCCAC   CTGGGGAGCA    2220
ATGTGAGGGT GAAGAGGACA   CAGAGTACAT    GACTCCCTCT TCCAGGCCTC TACGGCCTTT 2280
GGATACATCC CAGAGTTCAC GAGCATGTGA   .rTGCGACCAG    CAGATTGATA   GCTGTACGTA    2340
TGAAGCAATG TATAATATTC AGTCCCAGGC GCCATCTATC ACCGAGAGCA GCACCTTTGG 2400
TGAAGGGAAT TTGGCCGCAG CCCATGCCAA CACTGGTCCC GAGGAGTCAG  <RTI  

   ID=72.9> AAAATGAGGA    2460
TGATGGGTAT GATGTCCCAA AGCCACCTGT GCCGGCCGTG CTGGCCCGCC GAACTCTCTC 2520
AGATATCTCT AATGCCAGCT CCTCCTTTGG CTGGTTGTCT CTGGATGGTG ATCCTACAAC 2580
AAATGTCACT GAAGGTTCCC AAGTTCCCGA GAGGCCTCCA AAACCATTCC CGCGGAGAAT 2640
CAACTCTGAA CGGAAAGCTG GCAGCTGTCA GCAAGGTAGT GGTCCTGCCG CCTCTGCTGC 2700
CACCGCCTCA CCTCAGCTCT CCAGTGAGAT CGAGAACCTC   ATGAGTCAGG    GGTACTCCTA 2760
CCAGGACATC CAGAAAGCTT TGGTCATTGC CCAGAACAAC ATCGAGATGG CCAAAAACAT 2820
CCTCCGGGAA TTTGTTTCCA TTTCTTCTCC TGCCCATGTA GCTACCTAGC ACACCATCTC 2880
CCTGCTGCAG GTTTAGAGGA CCAGTGAGTT GGGAGTTATT ACTCAAGTGG CACCTAGAAG 2940
GGCAGGAGTT   CCTTTGGTGA    CTTCACAGTG   AAGTCTTGCC    CTCTCTGTGG GATATCACAT 3000
CAGTGGTTCC AAGATTTCAA   AGTG(;TGAAA    TGAAAATGGA GCAGCTAGTA TGTTTTATTA 3060  
 (D) TOPOLOGY:

   linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:
CCCGGGGGTC CTGGAAGCCA CAAGGTAAAC ACAACACATC CCCCTCCTTG ACTATCAATT 60
TTACTAGAGG ATGTGGTGGG AAAACCATTA TTTGATATTA AAACAAATAG GCTTGGGATG 120
GAGTAGGATG CAAGCTCCCA GGAAAGTTTA AGATAAAACC TGAGACTTAA   AAGGGTGTTA    180
AGAGTGGCAG CCTAGGGAAT TTATCCCGGA CTCCGGGGGA GGGGGCAGAG TCACCAGCCT 240
CTGCATTTAG GGATTCTCCG AGGAAAAGTG TGAGAACGGC TGCAGGCAAC   CCAGCTTCCC    300
GGCGCTAGGA GGGACGCACC CAGGCCTGCG CGAAGAGAGG GAGAAAGTGA   AGCTGGGAGT    360
TGCCACTCCC AGACTTGTTG GAATGCAGTT   GGAGGC,GGCG    AGCTGGGAGC GCGCTTGCTC 420
CCAATCACAG GAGMGGAGG AGGTGGAGGA GGAGGGCTGC TTGAGGAAGT ATAAGAATGA 480   
AGTTGTGAAG CTGAGATTCC CCTCCATTGG GACCGGAGAA ACCAGGGAGC CCCCCCGGG 39    (2) INFORMATION FOR SEQ ID NO:9:

  
   (i)    SEQUENCE CHARACTERISTICS:
 (A)   LENGTH:    1604 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

     SEO    ID NO:9:
GAATTCCGGG CGAGGGCCGG GCAGGAGGAG CGGGCGCGCG GCGGGCGAGG CTGGGACCCG 60
AGCGCGCTCA   CTTCGCCGCA    AAGTGCCAAC TTCCCCTGGA GTGCCGGGCG CGCACCGTCC 120
GGGCGCGGGG GAAAGAAAGG CAGCGGGAAT   TTGAGATTTT    TGGGAAGAAA GTCGGATTTC 180
CCCCGTCCCC TTCCCCCTGT TACTAATCCT CATTAAAAAG AAAAACAACA ATAACTGCAA 240  
ACTTGCTACC ATCCCGTACG TCCCCCACTC CTGGCACCAT GAAGGCGGCC   GTCGAT TCA    300
AGCCGACTCT CACCATCATC AAGACGGAAA AAGTCGATCT GGAGCTTTTC CCCTCCCCGG 360
ATATGGAATG   TGCAGATGTC      CCACTATTAA    CTCCAAGCAG CAAAGAAATG ATGTCTCAAG 420
CATTAAAAGC   TACTTTCAGT    GGTTTCACTA AAGAACAGCA ACGACTGGGG ATCCCAAAAG 480
ACCCCCGGCA GTGGACAGAA ACCCATGTTC GGGACTGGGT GATGTGGGCT GTGAATGAAT 540
TCAGCCTGAA AGGTGTAGAC TTCCAGAAGT TCTGTATGAA TGGAGCAGCC 

  CTCTGCGCCC 600
TGGGTAAAGA CTGCTTTCTC GAGCTGGCCC   CAGACTITGT      TGGGGACATC    TTATGGGAAC 660
ATCTAGAGAT CCTGCAGAAA GAGGATGTGA AACCATATCA AGTTAATGGA GTCAACCCAG 720
CCTATCCAGA ATCCCGCTAT ACCTCGGATT ACTTCATTAG CTATGGTATT GAGCATGCCC 780
AGTGTGTTCC ACCATCGGAG TTCTCAGAGC CCAGCTTCAT CACAGAGTCC TATCAGACGC 840
TCCATCCCAT CAGCTCGGAA GAGCTCCTCT CCCTCAAGTA   TGAGAATGAC    TACCCCTCGG 900
TCATTCTCCG AGACCCTCTC CAGACAGACA CCTTGCAGAA TGACTACTTT GCTATCAAAC 960
AAGAAGTCGT CACCCCAGAC AACATGTGCA TGGGGAGGAC CAGTCGTGGT   AAACTCGGGG    1020
GCCAGGACTC TTTTGAAAGC ATAGAGAGCT ACGATAGTTG TGATCGCCTC   ACCCAGTCCT    1080
GGAGCAGCCA   GTCATCTTTC    AACAGCCTGC AGCGTGTTCC CTCCTATGAC   AGCTTCGACT    1140
CAGAGGACTA TCCGGCTGCC CTGCCCAACC ACAAGCCCAA GGGCACCTTC 

  AAGGACTATG 1200
TGCGGGACCG TGCTGACCTC AATAAGGACA AGCCTGTCAT TCCTGCTGCT GCCCTAGCTG 1260
GCTACACAGG CAGTGGACCA ATCCAGCTAT   GGCAGTTTCT    TCTGGAATTA CTCACTGATA 1320
AATCCTGTCA GTCTTTTATC AGCTGGACAG GAGATGGCTG GGAATTCAAA CTTTCTGACC 1380
CAGATGAGGT GGCCAGGAGA TGGGGAAAGA GGAAAAACAA ACCTAAGATG AATTATGAGA 1440
AACTGAGCCG TGGCCTACGC TACTATTACG ACAAAAACAT CATCCACAAG   AC GCGGGGA    1500
AACGCTACGT   GTACCGCTTT    GTGTGTGACC TGCAGAGCCT GCTGGGGTAC ACCCCTGAGG 1560
AGCTGCACGC CATGCTGGAC GTCAAGCCAG ATGCCGACGA GTGA   1604    12) INFORMATION FOR SEQ ID $NO:10:  
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH:   2S34    base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:10:
GAACTTGTTT GAGCCGTAAG CCCGAGCCTA GCGTCGCACG   CTGGGCGACT    CCCCTCAGGC 60
TCTCAGGCCG GCGCCTTCGG GGGACCACGT AGCGCCCCAG CGGTGGCGGC TGCGCCCGGC 120
TCAGGGCGGT GCCGCGGCCA CTGGCTCCTC CTCGGGGTGG GGCGGGCCGC GCCGGGCGAG 180
GGCGGGAGGA GGAGCAGCGC AGCGGCGTGA GGAGCTGCCG CGCGAGGAGC GCGTCGCGTC 240
CGCACTTCTC CTGCCCGAGA GACTGAGCCG CGCTGGCAGC TCGCGTCGAG TCGGACTGCC 300
CTAGCCGCAT CCCGCGGCGC CCGGTCGGGT CCCGGGCACC AGGCAACACC TAGGCCGTTC 360
CCTTCAGACA GCCCCGGGCC AGCGGCCCCC TCGGGAAATG TCCAGCGGCC GCAGAAGGGG 420
CAGCGCCCCC TGGCACAGCT   TCTCCCGGTT    CTTCGCTCCC CGAAGTCCTT CCCGGGACAA 480
GGAAGAGGAA GAGGAGGAGA GGCCGGGGAC GAGCCCGCCT CCAGCTCCAG GCCGGTCCGC 540
TGCCAGCCAC GTACTAAATG AACTGATACA   GACTGAGAGA    GTTTATGTTC GAGAACTGTA 600   TACTGTTTTG    TTGGGTTATA GAGCGGAGAT GGATAATCCA  <RTI  

   ID=75.7> GAGATGTITG    ATCTTATGCC 660
ACCTCTCCTG AGAAATAAAA AGGACATTCT CTTTGGAAAC   ATGGCAGAAA    TATATGAATT 720
CCATAACGAC ATTTTCTTGA GCAGCCTGGA AAATTGTGCT CATGCTCCAG AAAGAGTGGG 780
ACCTTGTTTC CTGGAAAGGA   AGGATGATTT    TCAGATGTAT GCAAAATATT GTCAGAATAA   840   
GCCCAGATCA GAAACAATTT GGAGGAAGTA TTCAGAATGC   GCATTTTTCC    AGGAATGTCA 900
AAGAAAGTTA AAACACAGAC TTAGACTGGA TTCCTATTTA CTCAAACCAG   TGCAACGAAT    960   CACTAAATAT    CAGTTATTGT TGAAGGAGCT ATTAAAATAT AGCAAAGACT GTGAAGGATC 1020
TGCTCTGTTG AAGAAGGCAC TCGATGCAAT GCTGGATTTA CTGAAGTCAG TTAATGATTC 1080  
TATGCATCAG ATTGCAATAA ATGGCTATAT TGGAAACTTA AATGMCTGG GCAAGATGAT 1140
AATGCAAGGT GGATTCAGCG TTTGGATAGG GCACAAGAAA GGTGCTACAA AAATGAAGGA 1200
TTTGGCTAGA TTCAAACCAA TGCAGCGACA CCTTTTCTTG TATGAAAAAG 

  CCATTGTTTT 1260
TTGCAAAAGG CGTGTTGAAA GTGGAGAAGG CTCTGACAGA TACCCGTCAT ACAGTTTTAA 1320
ACACTGTTGG AAAATGGATG AAGTTGGAAT CACTGAATAT GTAAAAGGTG ATAACCGCAA 1380
GTTTGAAATC TGGTATGGTG AAAAGGAAGA AGTTTATATT GTCCAGGCTT CTAATGTAGA 1440
TGTGAAGATG ACGTGGCTAA AAGAAATAAG AAATATTTTG TTGAAGCAGC AGGAACTTTT 1500
GACAGTTAAA AAAAGAAAGC AACAGGATCA ATTAACAGAA CGGGATAAGT TTCAGATTTC 1560
TCTTCAGCAG AATGATGAAA AGCAACAGGG AGCTTTTATA AGTACTGAGG AAACTGAATT 1620
GGAACACACC AGCACTGTGG TGGAGGTCTG TGAGGCAATT GCGTCAGTTC AGGCAGAAGC 1680
AAATACAGTT TGGACTGAGG CATCACAATC TGTAGAAATC TCTGAAGAAC CTGCGGAATG 1740
GTCAAGCAAC   TATTTCTACC    CCACTTATGA TGAAAATGAA   GAAGAAAATA    GGCCCCTCAT 1800
GAGACCTGTG TCGGAGATGG CTCTCCTATA TTGATGAAGC TACTATGTCA AATGGCAAGT 1860   AGCTCTTTCC    TGCCTGCTTC TCAGCTCATT TGGAAAAATA CTGCGCAAAA GACATTGAGC 1920
TCAAATGATG 

  CAGATGTTGT TTTCAGGTTA ATGGACACGC AAAGAAACCA CAGCACATAC 1980
TTCTTTTCTT TCATTTAATA AAGCTTTTAA TTATGGTACG CTGTCTTTTT AAAATCATGT 2040
ATTTAATGTG TCAGATATTG TGCTTGAAAG ATTCTCATCT CAGAATACTT TTGGACTTGA 2100
AAATTATTTC TTCTCTACTT TGTAACCAAA TGCAATCGGT GTGCCTTGGA TTATTTAGTT 2160
TATTAATGAA TTAAGTCAAA ATTACGGCTG CAAAATGGCT AAGGTCAAGT AAAGCACAAC 2220
ATTATGATTT AATATGCTTT TGTTGAAACC ACAGCTTTTG TGCCCATTGT TTTAACTTGT 2280
GTGAAACAAT ACAAAGCCCA GAAATTCTTT TCGGGGCATG   AGTAAATTTT    GTTCAGGGCT 2340
ACTGTCTGTA TGTGCCCAGA TAAAATTTTC ATGAGAGTAG TTTACAAAAG CCGTATTTAA 2400
AAGTTAATAT TTTCACACTT   TTTTTCTGGA      TTTCTGCTTA    TAATTAATGT AACTTAAATT 2460
AGTTGTGCTC TGCTATTTTC TGTATATTTC   ATGTTGTAAT      TCTTTTTTTC    AAATAAAAAT 2520    TAATTCTTCA    GGTT  <RTI  

   ID=77.2> 2534    (2) INFORMATION FOR SEQ ID   NO:11:   
 (i) SEQUENCE   CflARACTERISTICS:   
 (A) LENGTH: 1219 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xl)    SEQUENCE DESCRIPTION:

   SEQ ID NO:ll:
GGGAGCGGGC GAGTAGGAGG GGGCGCCGGG CTATATATAT AGCGGCCTCG GCCTCGGGCG 60   GGCCTGGCGC    TCAGGGAGGC GCGCACTGCT CCTCAGAGTC CCAGCTCCAG   CCGCGCGCTT    120
TCCGCCCGGC TCGCCGCTCC ATGCAGCCGG GGTAGAGCCC GGCGCCCGGG GGCCCCGTCG 180
CTTGCCTCCC GCACCTCCTC GGTTGCGCAC TCCCGCCCGA GGTCGGCCGT GCGCTCCCGC 240
GGGACGCCAC AGGCGCAGCT   CTGCCCCCCA    GCTTCCCGGG CGCACTGACC GCCTGACCGA 300
CGCACGCCCT CGGGCCGGGA TGTCGGGGCC CGGGACGGCC GCGGTAGCGC TGCTCCCGGC 360
GGTCCTGCTG GCCTTGCTGG CGCCCTGGGC GGGCCGAGGG GGCGCCGCCG CACCCACTGC 420
ACCCAACGGC   ACGCTGGAGG    CCGAGCTGGA GCGCCGCTGG GAGAGCCTGG TGGCGCTCTC 480
GTTGGCGCGC CTGCCGGTGG CAGCGCAGCC CAAGGAGGCG GCCGTCCAGA GCGGCGCCGG 540
CGACTACCTG CTGGGCATCA AGCGGCTGCG GCGGCTCTAC TGCAACGTGG GCATCGGCTT 600
CCACCTCCAG GCGCTCCCCG ACGGCCGCAT CGGCGGCGCG CACGCGGACA CCCGCGACAG 

  660
CCTGCTGGAG CTCTCGCCCG TGGAGCGGGG CGTGGTGAGC ATCTTCGGCG TGGCCAGCCG 720
GTTCTTCGTG GCCATGAGCA GCAAGGGCAA GCTCTATGGC TCGCCCTTCT TCACCGATGA 780
GTGCACGTTC AAGGAGATTC TCCTTCCCAA CAACTACAAC GCCTACGAGT CCTACAAGTA 840
CCCCGGCATG TTCATCGCCC TGAGCAAGAA TGGGAAGACC AAGAAGGGGA ACCGAGTGTC 900
GCCCACCATG AAGGTCACCC ACTTCCTCCC   CAGGCTGTGA    CCCTCCAGAG GACCCTTGCC   960     
TCAGCCTCGG GAAGCCCCTG GGAGGGCAGT GCGAGGGTCA CCTTGGTGCA CTTTCTTCGG 1020   ATGAAGAGTT    TAATGCAAGA GTAGGTGTAA   GATATTTAAA    TTAATTATTT AAATGTGTAT 1080
ATATTGCCAC CAAATTATTT ATAGTTCTGC GGGTGTGTTT TTTAATTTTC TGGGGGGAAA 1140
AAAAGACAAA ACAAAAAACC AACTCTGACT TTTCTGGTGC AACAGTGGAG AATCTTACCA 1200
TTGGATTTCT   TTAACTTGT    1219 (2) INFORMATION FOR SEQ ID NO:12:
 (i) SEQUENCE CHARACTERISTICS:

  
   (A)      LENGTH:    139 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA Igenomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:12:
GTTCTGTTCT GTGCCTACAG TGAAGGTGAC TGGTGGGAGG CTCGGTCTCT CAGCTCCGGA 60
AAAACTGGCT GCATTCCCAG CAACTACGTG GCCCCTGTTG   ACTCAATCCA    AGCTGAAGAG 120
TAAGTAGGGA TTGGGGCAA 139 (2) INFORMATION FOR SE0 ID NO:13:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGHT: 144 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 Ixi) SEQUENCE DESCRIPTION:

   SEQ ID NO:13:
TTGCCTGCCT TTCCCAACAG GTGGTACTTT GGAAAGATTG GGAGAAAGGA TGCAGAGAGG 60
CAGCTGCTTT   CACCAGGCM    CCCCCAGGGG GCCTTTCTCA TTCGGGAAAG CGAGACCACC 120  
AAAGGTAGGG   GTGGTGCCAC    CCCC 144 (2) INFORMATION FOR SEQ ID   NO:14:   
 (i) SEQUENCE   CllARACTERISTICS:   
 (A) LENGTH: 190 base   pairs:   
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:14:
AAAAGTGATC CTCTCCACAG GTGCCTACTC CCTGTCCATC CGGGACTGGG ATCAGACCAG 60
AGGCGATCAT GTGAAGCATT ACAAGATCCG CAAACTGGAC ATGGGCGGTT ACTACATCAC 120
CACACGGGTT CAGTTCAACT CGGTGCAGGA GCTGGTGCAG CACTACATGG GTGAGGGCAG 180
GGGCCTCAGA 190 (2) INFORMATION FOR   SEO    ID NO:15:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 196 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (il)    MOLECULE TYPE:

   DNA (genomic)
 Ixi) SEQUENCE DESCRIPTION:   SEO    ID   NO:15:   
CTTCATGACC CCTCCCCTAG AGGTGAATGA CGGGCTGTGC AACCTGCTCA TCGCGCCCTG 60
CACCATCATG AAGCCGCAGA CGCTGGGCCT GGCCAAGGAC GCCTGGGAGA TCAGCCGCAG 120
CTCCATCACG CTGGAGCGCC GGCTGGGCAC CGGCTGCTTC GGGGATGTGT GGCTGGGTAC 180
GGAGCTCCCG GGGGCC 196 (2) INFORMATION FOR SEQ ID NO:16:  
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 212 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:16:
ACAAGACAGC CTCCGAGCAG GCACGTGGAA CGGCAGCACT AAGGTGGCGG   TGAAGACGCT    60
GAAGCCGGGC ACCATGTCCC   CGAAGGCCTT    CCTGGAGGAG GCGCAGGTCA TGAAGCTGCT 120
GCGGCACGAC AAGCTGGTGC AGCTGTACGC CGTGGTGTCG GAGGAGCCCA TCTACATCGT 180
GACCGAGTTC ATGTGTCACG GTCAGGAGGC GG 212   (2)    INFORMATION FOR SEQ ID NO:17:
 (i) SEQUENCE CRARACTERISTICS:
 (A) LENGTH: 117 base pairs
   tB)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
   ID)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:17:
ACTTTCTGGC TTCTTCCCAG GCAGCTTGCT GGATITTCTC AAGAACCCAG AGGGCCAGGA 60
TTTGAGGCTG CCCCAATTGG TGGACATGGC AGCCCAGGTA ACTGGGCCAG CAGCCTT 117 (2) INFORMATION FOR SEQ ID   NO:18:   
 (i) SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 219 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (11) MOLECULE TYPE: DNA (genomic)  
 (xi) SEQUENCE DESCRIPTION: 

   SEQ ID   NO:18:   
GAGCTCCCAT CTCTCCACAC TATGGTCCCC CAGGTAGCTG AGGGCATGGC CTACATGGAA 60
CGCATGAACT ACATTCACCG CGACCTGAGG GCAGCCAACA TCCTGGTTGG GGAGCGGCTG 120
GCGTGCAAGA TCGCAGACTT TGGCTTGGCG CGTCTCATCA AGGACGATGA GTACAACCCC 180
TGCCAAGGTG   CCCTGCTTCA      CCCCACCTTC      CAAGAGCTC    219 (2) INFORMATION FOR SEQ ID NO:19:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 35100 base pairs
 (B) TYPE: nucleic Acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:19:
AA 
TATATATTTT AAGAATTATG CAGAACAATT AGATTCTTTG TAAAAATAAA TAAACAATGT 780
AAGTAACGCA CAAAAGATAG TTTTATAACC AGACTGCTGG GATCCAAATC CTATCTCCAC 840
CATTTGGTAG CTGTTTGACT ATGGACAAGC TTAAGGCACT TGATCTCTCT   GAGCTITAGT    900
TTTCCCATCT GTGAAATGAG AATGACAATA GTACTTACCT ACATAAAGTT TTGCAGTACT 960
AAAGGAGACA GTGAATGTAA AAGGTTTGGC TAGTAAATGT CCTGTAAAAG GAAGCTTATT 1020
GCCAATATTA TCAGGCTCTC CCAGACCAAC CTGTATACAG GAAGAAAACA AACTCCGTTT 1080
CTCCTATAGT CTCACAACAC AAAATACTTC TGACCCCAGA TGTAGAGGAT GGGGCATATT 1140
TCCCCATACA CCAAGCAATC AACCAATTGT TCAGATTCTG CAGCAGACAC GAATCTGGTG 1200
CCCTCCGATT CAATTTGAAC ACTATATTTA CCTAGAGATA ACGTCAGATC   TCACAGCTTG    1260
AAGGCTTGAG   CCAGGAGTTT    GAGGCTGCAG TGAGCTATGA   TCGAGCCACA    GAGCTCCAGC 1320   CTGGGCAACA    GAGTGAAACT GCGTCTCTAA 

  AATAATAATA ATAAATTTTT   AAAAGATATG    1380
CATTACTTTG GAGATTCCAA GGATTTTAGG AGTTGTAAGC CAGGACATCA GGGTAAAGAA 1440
AAAATATATA TGTCACAATA TCATGCAACC TAACTTCTCT TTGGGATCTG CCAGAGCCAC 1500
CTGATCACTC TGAAGACCCT CATTTGTGCT ACTGACTAAC   GGTCTGGCTG    CTCTTGGACA 1560
TGTCTCTTCT CCCAAGACCC CTTGAAGATG   GCTTTAGAAG      GGCCCCAAAC    TTAGCTAGCT 1620
CCCCCCAAGC TCAGGCTGGC CCTGCCCCAG ACTGCGACCC CTCCCTCTTG   GGITCAAGGC    1680
TTTGTTTTCT TCTTAAAGAC CCAAGATTTC CAAACTCTGT GGTTGCCTTG CCTAGCTAAA 1740
AGGGGAAGAA GAGGATCAGC CCAAGGAGGA GGAAGAGGAA AACAAGACAA ACAGCCAGTG 1800
CAGAGGAGAG GAACGTGTGT CCAGTGTCCC GATCCCTGCG   GAGCTAGTAG    CTGAGAGCTC 1860
TGTGCCCTGG GCACCTTGCA GCCCTGCACC TGCCTGCCAC TTCCCCACCG AGGCCATGGG 1920
CCCAGGAGTT CTGCTGCTCC TGCTGGTGGC CACAGCTTGG CATGGTAAGA 

  GCAGAACGGG 1980
GGGTGGGGGA CTTTGTTGGG GTGTGATGGA GAAGACCCCT GTGAAAGGAT TCAGTCCTTG 2040
CCCCTCACTG GGTGTCCTCA GGCTGTTTTA GTCTCCCCAA CACTGGACTG CAGGCTTGTG 2100
GGTATCTGCT TTGGAGAGGT AGTGGGGTGA AAAGAGATGG GTGTGGTGGA ACTGGTCCAC 2160  
CTGGTGCTGT GGATCTGTCC   CAGCTCTGCC    AGCGACTCAC TGTGTGTCCT GAGCAAGCCT 2220
CTGATACTCT TGAGGCTTCA GTGTCCACTT CTATTCAATT GCAGGTGTTG GGGGCAGGGG 2280
GACAGTGATA GACTAGACCA GAGCAGTGCT TTTCATACTT TCCTGTGCAT ACAAGTTACC 2340   TGAGGATTTT    GTTACAATGC AGATTCAGAC   TCAGTCC.CTC    TCAGGTGCGA CCTGAGATTC 2400
TGTATATCCA ACACACTCCT GGGAGATGTG AGATGCCGGC ACTGCTGGTC CAGACCTACA 2460   CTGAGTTGGG    AGGACCTGGA GAGCTCCTGA TGGCTCTGGC AGCTCTGCCA GCCTGTGATT 2520
CGATGATTCT ATGCAAGATC   TGATTTGGAA    GGGCCTGATA GGGGTGGTGG   TTCTTCCTTG    

  2580
GGTGGCTTGT GTAAGGGGTC AGAGGGGAGA GACAAGAGGT TGGCCTCTCT GGCCCAGGGC 2640
TCAGGAGAGG GGAATTCGGG GTGAAATAGG TATAGGGCTA GAGGAGGGAT TGGGAAGAGG 2700
CCAGTGAGGG TCTCCTGGAC CAGAGCCCTC CCAGACACAG GCTGCCAAGT CTCAGGAGGT 2760
CCCCAGGCTG TAGCAGTTCT GCAGAATTTC CATCTGGGAG GGAACATGAC TAGAGGTGAG 2820
GGGCTGCTGT GCTTGGCTTG TTGGCCCAAC AAACACATTT CTATTGCCTG CTTATTCAAA 2880
GGGACCTTGG GGGAGGATGG GGATTGAAGG GGAGAAAGGA CAGCCTCATA CTGGCCTCTT 2940
CACAGAAGGA   CCCTAAGGCC    GTGGCGCTTC TGGTCCCTGA TGAGGAGGAG   ATGGCCCACT    3000
GACCATCCTT CTCTGGCCCA GGCAATCACA CTGAGCTTGA GTATTTGGGT   TTITIITaTT    3060
TTTTTCCTGA GACAGAGTCT CTCTCTGTCA CCAGGCTGGA GTACAGTGGC ACAATCTCGG 3120
CTCACTGCAA CCTCCACCTC CCGGGTTCAA GTGTTTCTCC TGTCTCAGCC TCCCAAGCTG 3180
GGATTACAGG CATACACCAT CATGACTGGC TAATTTTTGT   ATTTTAGTA    GAGATGGGAT 

  3240
TTCACCATGT TGGCCAAGCT GGTCTCGAAC TCCTGACCTC AGGTGATCCA CCTGCCTTGG 3300
CCTCCCAAAG TGTTGGGATT ACTGGTGTGA GTCACGGCGC CCGGCCTGGA CTTCTTATTT 3360
TGCAATGTAA CTTACATGCA GTAGAAAGCA CAGGTTCTTA AGTTCAATGA GGTCTGACAA 3420
ATGCACACAC AGTGTACCCG CCACCCCCTT CATCTCAGAG AGTCCCACAG   GTTTGATTTC    3480
ACTGCCTTGT CCTATCCTTA CACCCACAAC CTGCCTGTGG GGCAAAAACG GAAAAGTATC 3540
TGAGCCAGGT   CTCAATTTAA    TTTTATTTTT   TTTATTGAGA    TGGAGTCTTG TGGCCAGGCA 3600  
TGGTGGCTCA CACCTGTAAT CCCAGCACTC TGGGAGGCCG AGGCGGGTGG ATCACAAGAT 3660
CAGGAGTTTC AGACCAGCCT CGCCAATATG GTGAAGCCCC CTCTCTACTA   AAAAATACAA    3720
AAATTAGCCG GGTGTGGTGG TGGGTTCCTG TAGTTCCAGC TACTCAGGAG GCTGAGGTGG 3780   GAGAATCACT    TGAACCCGGG   AGGCAGAGGT    TGCAGTGAGC TGAGATCATG CCACTGCACT 3840
CCAGCCTAGG 

  CGACAGAGCA AGACTCCATC TCCTTCCTTT CTTTCTTCCT TCCTTCCTTC 3900
CTTCCTTCCT TCCTTCCTTC CTTCCTTCCT TCCTTCCTTC CTTCCTTCTT TCTTTCTTTC 3960
TTTCTTTCTT TCTTTCTTTC TTTCTTTCTT TCTTTTTTCT ATCTTTTTGA GACCGAGTCT 4020
TGCTCTGTTG CCCAGGCTGG AGTGCAATGG CATGGATCTC   GGCTCACTGC    AACCTCCGCC 4080
TCCGGGGTTC AAGCAATTCT GCCACTCCTG AGTAGCTGTG ATTACTGGTG CCTGCCACCA 4140
CACCCAGCTA ATTTTTTTAT TTTTGGTAGA   GACAGGGTIT    TATCATGCTG GCCATGCTGG 4200
TCTCGAACTC   CTGAACTCAA    GCGATCCCCC TGCCTTGGCG TCCCAAAGTG CTGGGATTAC 4260
AGGCATGAGC CACTGTGCCT GGCTTCAATC AATTTAGAAG TTTATTTTGC CAAGGTTAAG 4320
GACATGCTGG CGAGAAAAAA ACATGGAGTC ACAAAAACAT TCTGTGGTCT GTGCCATTCT 4380
GGATGAATTC GAGGGCTTTA ATATTTAAAG GGGAAAGTGG GCTGGAGGGG AAAAGGGGAG 4440
GTTGTGGTAA TCCACATGTT   GCAAAAGAAA    AGCAGCAGGT AGGGGAACAG TCAATTATCT 4500  <RTI  

   ID=84.8> CGGTTCAGTA    AATTGGCTCT TTACATAGGG AAAGTGAACA TAGAGGAGCT GCCTGTGGGA 4560
TATTTTACCT TTTATCTGTC GCTATCTGCT TAGGAATAAA AGGCAAGGCA GCTTCTTGCA 4620
TGACTCAGTT TCCAGCTTGA TTTTTCCTTT TGGCAGAGTG AATTAGGGTC CCAAGTTTTT   4680   
ATTTTCCCTT CACAGGGGCA TGGTGTGTGG GAGGGGGGCC AGATGGTTTT CCAGGGTCCA 4740
GTCCCAAGAG AAAGAAGAGA TGGGGAGGCT GGAAACCTAA   GTTTTCAGCC    CAACAGACCA 4800
ATGATGAGTG GATGAGGGGC CACTGTGAGG AGACTGGGGA TGGTATTGGA GGACCCTAGA 4860
GAGAGAGGGG GGCTCTCTCT TCATTACTGC GATGAGATCC   TGGGCTGAAG    AGGGGCTGTG 4920
TCCAGCCTTA GTGTGCAGTG TGTGTGTGTG TGTGTGTGTG TGTGTGTGTG TGTGTGTGTG 4980
TGTGTGTGTT GGGAGAGAAG AGTAGAGATT GGGGCACATT CTGGAAGTGA   TGAGGGAGGG    5040  
GCTTCCAGGC AAGTGGGAGC TAGTGGAGAG   GTGTGC,

  GGCA    TGGGGAGAAT TGGGGAGTGG 5100
AGATGAGAGG GGGGAAGAAT GGACAGGCAC AGAAGGGGAC CTCAGTTAAT GTTCATAAGC 5160
CCATGCCCCC ACCCCGAGGA GGATGGGGGC CAAGCCGGCT TCCTTCCCTG CTAGCCAAGC 5220
CAGCAGGGGA AGTTGGCTGC GGAAGTTGCG GGTATCAGCC TTATCCTGCG TGAATACCTG 5280
GGACAATAGG ATAGGACAAA ATAGGGCAGA CACCGCTCCC TGACCACATT TCCTGGAGGC 5340
CAAGGCAGGG TCTAGAGAGA CAGGCTGGGG GAAGGGATGG GAGAAGCCCA CTGTAAGGTG 5400
TGAGGCAGGT GTAAAAAAGG AACAAATGGA   ATCACAGAAT    CCAAGGTTAA AATCTTGAGC 5460
GATCAGAGTT GGCCCAGAAG GGACATTAGA AATGTAGCAA TTAAAGCAGG TGCCCAGGGC 5520
AGGAGTAGTT CTATACATCA TCTCACTCAA   CCTTCAGCTG      AAGTTTTTGG    GGTGGGAGCT 5580
GGGATTATTC CCATCAGACA   GAAC.AATAGC    CTGAGGCTCA AAGAGGTTAA GAAACTAACC   5640   
CAGCTGGTAA GGGAAGAACC AAGATCCAAA   CCCAAGTTGG    TGTGAGCCCA 

  CACTCCAAGC 5700
TGTTTCCTGC TATAAAACCC CGGCCTGGGG GCCCTAGATT GCTGCAGCAG TGATAGGGCA 5760
GCCCCAGCTC   TGTTGAGATT    TGCTAAAAAG GCTGCTAGAA ATGACACTTG   TCCCTCTTCC    5820   TGGCAGTTGC    ACTGCATAGG AGGGCTACAA CCCCAGGTGG   CAGGCTTGGC      AGTATTCACA    5880   ATTCACTCAA      TCCCGTTTGC    TGATCAGAGT CTTGGGGAGA AGGGATGCAC ATTCTGATGA 5940
ATACAAAATC AAAACGTGAA TTAAGCCATC CTGAAAGGAC TTGAGAGAGG   AAACCTTTCC    6000
AATTCTGGGC TCTATGGTGG GGCAGGGGGA ATTTCCATTT CAAGGGGGTT TGCAGAGAAC 6060
AATGGAGATA CCCTGAATTC ACCGAAAGCC CTCGGGGTGG CCTGTCATTG TGCCCCCATC 6120
ACTGGGAAGA GGAAGGGCCA GAGCTGAGGA GTTGGATGGC CAGGGTCAGC CAGTGGGTCA 6180
GCGTCAGAGC CCAGCCTCAC AGCTGCCCCG CAAGTGGCAC TCCCTCTCCC TGCCTGGAGA 6240
GAGGAGAGTG GCTAGGAGGC 

  TGGGGAAGCA GAAGTGAGAA CATCCCTGTA GAAGGGCCAC 6300
AGGCTGAGCG GAAACCGGGG GCTGAGCCTG ACGCCAACAA TGTGTTTCCG CCCACACAGG 6360
CTGGGGGGCG CCTGGCAGCC CCTCGGAGGC TTGAATCAGC TCTCACTTCC   CTCcTTrGCC    6420
CCTATTTTAG GCCCTGGAAA AATGCTGACG CTGCAGAGGC AACGGGCCTT CTTCCCGGAC 6480  
AGCCTGATAG GGGTTTCAAG   TTCTCTTTTC      TCCTTCAAC.A    AAATTTTCCT TAAAAGAGAT   6540   
TGGCTTCCCA GTAAACACAG ATGTGTGGGG GTGCCGGGGT GAGCTGCTGG GTGTAGACTA 6600
GGTAATAAAC ATAGTGACTA ACTCTTACTG   AGCCATTTAT    TTGGTGACAG GTGATGTTCT 6660
AAAGTCTTCC CATGCATTTA AAATGCCTAA CATACCAATG AGTGGGTACG ATGATTGTCC 6720
CTGTTTTATA GGTGGGGAAA CTGAGGCATG GCACCTCCCC ATCCCACTGT GCTGCAGACC 6780
AGATGTCCAT TGGTGGGAGC GGGCACACCA GGAGATTCTT GGGACCTCTC TAACTCTGCT 6840
GGGCTAAGAT CCTACATCTC   TTTTTTTTC    TTTCCCATAT 

  GAATTAAGCT GAGGACTTGG 6900
CCGTGAACAT TCCATTCATT TGTTTCTTCA TTCGGTGGTA GAAATACATC CACTTTGTAC 6960
ACAGGGTTAA AAGAGTCCAT TCCTGGGGAG TAGAAAGATG GCATCACAGC AGGGAAGACT 7020
GAGGCAGGAG GCTGAGGACC CCAGGGGGAC   AGAGGCCTGG    GTGAGAGGCT GAGCAAGCTG 7080
CAAGCCCCCT TTCTCAGAGG AGGGACCTCC TGGACATCAG AGACATCAGT CTGTCCCTGA 7140
GCAGGTTGAG GGTTAGGAGC TGAGCAAATG ACCAGGGGGC AGGGGCTCGT TCAAGGTGGT 7200
CCCTTGATGG CACAGCACCA TCCCTGCCAA GCTACCACCC   ATCTCAGAGT      CAGGACGGCC    7260
CAAGGGGCGC ATCCTAGACC TCACTTCTGT   CTGCTGTCCC    TCTCTCCCAC CAGGTCAGGG 7320
AATCCCAGTG ATAGAGCCCA GTGTCCCCGA GCTGGTCGTG AAGCCAGGAG CAACGGTGAC 7380
CTTGCGATGT GTGGGCAATG GCAGCGTGGA ATGGGATGGC CCCCCATCAC CTCACTGGAC 7440
CCTGTACTCT GATGGCTCCA GCAGCATCCT CAGCACCAAC AACGCTACCT TCCAAAACAC 7500
GGGGACCTAT CGCTGCACTG AGCCTGGAGA CCCCCTGGGA 

  GGCAGCGCCG CCATCCACCT 7560
CTATGTCAAA GGTGAGGAGT CTGAGCCTCC TCCCAAGAGG CCTGACCCGG CAGGCCCCAC 7620
TACAATGGGC CCTAAAATTA ACAATCGTAA CAATTCAGCT CTGCATTTAC TGAGTGCTGG 7680
CTATGAGCAA GGACCTGGAA GAGCTGCTAA   TGTAATGCAG    TCCTCACAAC AACCCTGCAA 7740
GTCGGGTCTA TGATGATGCA   TTTTCTAGAA    GTGCAGGGAG GTTATCCAAG   GTCACACAGC    7800   CTCACATAGT    GGGACTAGAC TGGAGCCCAG GTGCGCCTGA CTCTGGAGCC ACCACGCTGA 7860
AGCATCCGCT GAACTGTCCT GGCGTGGTGT GACCTCAGAT GAATGATCAG CCTCTCTGAG 7920  
CTTCCTTGTC ACCTATGTCC AGGTACTCCT TGGCCCAGTG   GAGGGAGGGC    AGTTGTAACC 7980
CTGTGCCCTC CTCTACTCTA GACCCTGCCC GGCCCTGGAA CGTGCTAGCA CAGGAGGTGG 8040
TCGTGTTCGA GGACCAGGAC GCACTACTGC CCTGTCTGCT CACAGACCCG GTGCTGGAAG 8100
CAGGCGTCTC GCTGGTGCGT GTGCGTGGCC GGCCCCTCAT   GCGCCACACC    AACTACTCCT 

  8160
TCTCGCCCTG GCATGGCTTC ACCATCCACA GGGCCAAGTT CATTCAGAGC CAGGACTATC 8220
AATGCAGTGC CCTGATGGGT GGCAGGAAGG TGATGTCCAT CAGCATCCGG CTGAAAGTGC 8280
AGAAAGGTGC GTGGGGCATG GGGACCGGCA GCCAGGCCTG AAGAGTGGGG ACAGAGAGCC 8340
GGCGGCCACA TGGGTGGTGA CTGGGGACTG GGTGTGATGG GGGGCAGTGG GATGTCCTCT 8400
TTCTTTCACT TCTTCCCCTC AATGGTTCCA CGATCATCTA TGGGGCAGGA CTGACAAGGT 8460
GTCGGGGCAG GGAGACAAAC CACATGTGAG CAAATAACTC AGTGGGCAAG GTCATCTCAG 8520
GTCATTGGAC ATGCTACAAA AATAAACATT   CACATG(;

  TA    GCTGAATAAG GAGTGTGTAG 8580
GGCGGGGAGC CTCACTGAGA AGGAAACACT   TTATTAGAGC    GGAAATCTGA ATGACAT20
GAGGCAGGAG GCTGAGGACC CCAGGGGGAC AGAGGCCTGG GTGAGAGGCT GAGCAAGCTG 7080
CAAGCCCCCT TTCTCAGAGG AGGGACCTCC TGGACATCAG AGACATCAGT CTGTCCCTGA 7140
GCAGGTTGAG GGTTAGGAGC TGAGCAAATG ACCAGGGGGC AGGGGCTCGT TCAAGGTGGT 7200
CCCTTGATGG CACAGCACCA TCCCTGCCAA GCTACCACCC ATCTCAGAGT CAGGACGGCC 7260
CAAGGGGCGC ATCCTAGACC TCACTTCTGT CTGCTGTCCC TCTCTCCCAC CAGGTCAGGG 7320
AATCCCAGTG ATAGAGCCCA GTGTCCCCGA GCTGGTCGTG AAGCCAGGAG   CAACGGTGAC    7380
CTTGCGATGT GTGGGCAATG GCAGCGTGGA ATGGGATGGC CCCCCATCAC CTCACTGGAC 7440   CCTGTACTCT    GATGGCTCCA GCAGCATCCT CAGCACCAAC   AACGCTACCT    TCCAAAACAC 7500
GGGGACCTAT CGCTGCACTG AGCCTGGAGA CCCCCTGGGA GGCAGCGCCG CCATCCACCT 7560
CTATGTCAAA   GGTGAGGAGT    

  CTGAGCCTCC TCCCAAGAGG   CCTC;ACCCGG    CAGGCCCCAC 7620
TACAATGGGC CCTAAAATTA ACAATCGTAA CAATTCAGCT CTGCATTTAC TGAGTGCTGG 7680
CTATGAGCAA GGACCTGGAA GAGCTGCTAA   TGTAtTGCAG    TCCTCACAAC AACCCTGCAA 7740  
GTCGGGTCTA TGATGATGCA TTTTCTAGAA GTGCAGGGAG GTTATCCAAG GTCACACAGC 7800
CTCACATAGT GGGACTAGAC TGGAGCCCAG GTGCGCCTGA CTCTGGAGCC ACCACGCTGA 7860
AGCATCCGCT GAACTGTCCT GGCGTGGTGT GACCTCAGAT GAATGATCAG CCTCTCTGAG 7920
CTTCCTTGTC ACCTATGTCC AGGTACTCCT   TGGCCCAGTG    GAGGGAGGGC AGTTGTAACC 7980
CTGTGCCCTC CTCTACTCTA GACCCTGCCC GGCCCTGGAA CGTGCTAGCA   CAGGAGGTGG    8040
TCGTGTTCGA GGACCAGGAC GCACTACTGC CCTGTCTGCT CACAGACCCG GTGCTGGAAG 8100
CAGGCGTCTC GCTGGTGCGT GTGCGTGGCC GGCCCCTCAT GCGCCACACC AACTACTCCT   8160   
TCTCGCCCTG   GCATGGCTTC    ACCATCCACA GGGCCAAGTT 

  CATTCAGAGC CAGGACTATC 8220
AATGCAGTGC CCTGATGGGT GGCAGGAAGG TGATGTCCAT CAGCATCCGG CTGAAAGTGC 8280
AGAAAGGTGC GTGGGGCATG GGGACCGGCA   GCCAGGCCTG    AAGAGTGGGG ACAGAGAGCC 8340
GGCGGCCACA TGGGTGGTGA CTGGGGACTG GGTGTGATGG GGGGCAGTGG GATGTCCTCT 8400   TTCTITCACT    TCTTCCCCTC AATGGTTCCA CGATCATCTA TGGGGCAGGA CTGACAAGGT 8460
GTCGGGGCAG GGAGACAAAC CACATGTGAG CAAATAACTC AGTGGGCAAG GTCATCTCAG 8520
GTCATTGGAC ATGCTACAAA AATAAACATT CAACATGGTA GCTGAATAAG   GAGTGTGTAG    8580
GGCGGGGAGC CTCACTGAGA AGGAAACACT TTATTAGAGC GGAAATCTGA ATGACATGAA 8640   GAAGGTGGCT    GTGCAAAGAT CTGCTTCAGC AGGGGGACAG TGAGTACCAA GTGGTGAGGT 8700
GGGGACAGGC TCTGAATGTT CTAGGTATGG AAAGAGGACG GAAGCTCAGC CTCAGACATG 8760
GATTTCCCAC TGGGGGCCTG CCTAAGGCCA   AGTGCTGG(;

  C    ATGTGTAGGA   GGGATGCTGA    8820
GCCAAGAGGC AGGGAGGAGA TGGTGGGTGC GTGTGATGGC TCTCGCGGTG GCCAGGTAAC 8880
AGTGGAGGTG GAGTCTCACC CTGCTGGGAT GGCAGGCAGG ATTCTGGTTT CTGGGAGGAC 8940
TGGTGAGAGC AAGCAGGACC   CCAGCCTGAG    GACCTGGGCT TGAGACAGCA ATCAGTCCCT 9000
GTAACAAGGG CCAGGGTCAG AGTGAAGCAG CTAGCCCAAT GCCACTGGGA TCTGAAGCCA 9060
CTAAACCTGC CTAGGGGGTC AAAGGACCCC AGCTGTGTGG GCAGAGGAGG CCATTAGGGC   912.0   
TCTTTCCTGG   CATTTCATCC    TGCAGAGCCC TGGGCTGGCC AAGAGCCAAA GGTCCTGGGC 9180  
CCTAGTTCTG CCTTGACCCC CCCTCAGGGA CCTTGGGTGA   GTCCTTTCAT    GTCCCTGGGC 9240
CTTAGGAATC TGGATTAGAT   TATC m CAA    CAGCAGCAAT GGGCATAAAT ATGAATTCAA 9300
GGCCTACTGT GCATCAGGCA TCTTGCTGGC TGCTGGAATA TTCCTGTCAC GGATITGACA 9360
TTCGACTAGA GTCTAACTAT TAAATAGAAA GTAAATACAA ATGTGATGAG 

  CAAGAAACCA 9420
AGCTGGGGAG TGGCGGGCAT GGAGGTGCTG GGGAGGCTAA TTCATATCAG CTGGTCACAG 9480
AAGCCTTGCT GAGGAATTTT TGAGCTAAAG ATCTGAAGGA TGAGAACAGC   CTCCCATITG    9540
AAGTGTGGGA   GGAAGGCAT    TCCAGGAGGG AAAGGTGGGT GCAAAGGCCC TGTGGTAGGA 9600
AAGAGGTCCA GCGGGCTGCA GTGCAGTGAA CAAGGGGTGG GGTTATCAGG GCGGTCAGAA 9660
ACAGGTTGGG CTGTGGAAGG   ACTTTGACTT    CTTTTCTGAG AGTAATGGGA AGCCCCAAAT 9720
GTTTACAGAG GAGAGAGGCA TGGTCCCATT   TATATTTGTA    AGAGGTCACT   TTGGTGAAC.A    9780
ATCTAGGTGT GGGGGGCTTG GAGGGAGGCA GGGAGGTCTC TGAGGAGGCT GGTGCAGAAG 9840
TCCAGAGTGG AGAATGGTGA CGGGACTGGG GAGGGGTAGA GGTGATGGAG AAAGTAGACT 9900
TTCCAAGGTC   TCTTTAGGAC    AGGCCTTGCA GTGGGGGGAC TGGGAGCATC AAGGCTGCCT 9960
CCCAGGATTT GGGATGGGGC AGTGATGGGG ACCCTGGCCT GTGTGTCCTG GCCCATGGCA 10020
GGGAGGAGAG 

  CAATATCTCT ATCATATTCA GGGAGCCTGG GTGTTCAGGG GTCTCTCCCC 10080
CGGTCTCAGT CATCCCAGGG CCCCCAGCCT TGACACTGGT GCCTGCAGAG CTGGTGCGGA 10140
TTCGAGGGGA GGCTGCCCAG ATCGTGTGCT CAGCCAGCAG   CGTTGATGTT    AACTTTGATG 10200
TCTTCCTCCA ACACAACAAC ACCAAGGTCA GTCCCTGCAG ATCACAAGGT GAAGTCTGGC 10260
CATCCTCCCA GCACACCAGG   TTTCCCATGG    TGGAGTCCTG GGCCCCCAAC TCCAAACTGG 10320
CTGTCTTAGC TGAAGGCACA GCTCAGACTC CAGAGAGGGG TGCAGACTCA CCCGAGATCT 10380
CACTCCCAGT CAGTAGCTGA CACAGAATCA GGACTCATGC TTGTGCCGCT   GAACTTTGTG    10440
GGGGTGGGTG GGGGGAGGTG GTTCTCTGTC ACCTTGACAC   ATGGCCTTTG    CCCCAGCCTT 10500
TAGACAAAAG CCAGAGGTGA GCTCACTTCT   GATTTAGCAA    GGGTTTCCTA GGCCACCATT 10560
GAAGCCCAGG AATATAACAG CTATTTCAGA AAGACATTGG GAGAGAGGGA GGAGGAGGGA 10620  
GGATTCCAGG AGGGACTCAC GTTGGGCTGC CTCTAAGAGC 

  CCCCTCCCTT CCCACTGCAC 10680
CTGCCGTGTT CCAGACACAG CCCTAAGCCA CTTGCATGCA TATCTCATTT ACTCCTCACT 10740
ACAGTCTTGG GGCAGGGAGC CAGTATTAGC   CCCATTTTAC      AAGTGAAGCA    ACAGGCTCAG 10800
AGGAAAGGCA GATAGTAATC CTTAAAGGCT   GAGGATTGGA    ACCCAGATCT TTCTAATCCC 10860
TAAACTACCT TGGTATAACA TCTCCATTCC   TTCTGGCTGC    AGCTCGCAAT CCCTCAACAA 10920
TCTGACTTTC ATAATAACCG TTACCAAAAA GTCCTGACCC TCAACCTCGA TCAAGTAGAT 10980
TTCCAACATG CCGGCAACTA CTCCTGCGTG GCCAGCAACG TGCAGGGCAA GCACTCCACC 11040
TCCATGTTCT TCCGGGTGGT AGGTAAGCAT CAGGGTGGTG GTGGACAGTC GGTAGGGATC 11100
CTGCAGGAGT GTGAGCAGAA   GGGTTTTGTT    GAGGAAGCTG ATGTCAGGGA AGGAGACCTG 11160
CTGAGGATAT CTCTGCTGGA   GTTTGTTTAT    CCAAGGCCTG GCTAAGGAGC CACTCTCCAG 11220
GAGCTTTCCC TTACCCTCTC CTGGGATCTC TCTCCCATCT TGGAGCTCTT 

  ACAGTGCATG 11280
GCTGCATTGG GTGCACCTTA   GTGCCATTTT    TTGTTTATTT   GGGGATTGGG    GTCCAGTAGC 11340
TCCCTACTGG ACTTCATTTG TTCATTCTTT CATGCATTCC TTTATGGAAA CATGAAAAGA 11400
CAATGATCAC CCAGTGATTA TGGGGGAAGC ACAAGGTGTC CTGGGAACAC TGAAGAGTCC 11460
CCCCAACCCA GGCTTCGAGA AGGTGGCCTC TAAACTGGGA TGGGAAGAAT GAAGGTGAGT 11520
TGGCCGGGCA GAAGGGTGGG AAAGGAAGGG GAACAGCGCT TCTGGCAGAG GGAGGAACAT 11580
ATGCAAGGCT CAAAGGCAAA GAGAACATAG   ATCATTTGGA    ACACTGAAAG AACTTGACAA 11640
CAGCTGGGAT GTGGAGTGGT GTGAGGAGTG GCCACAGGGG AGCAGAGGAG GTGGCAGAAG 11700
CCGGAGGTAA AGGTGTCTTA AAGTGAGAAA GAATAACTGC   ATCTTMCCT    ATTGGGAGGT 11760
CATTGTAAAG AGGAGAGTGA TGGGGTCAGA TTGTACAGAG GAGGCACTTC GTGGTGGTCA 11820
GGAGCACACA CTCCAGGGCA GTGTTCCAAC CTGAGTCTGC CAAGGACTAG CAGGTTGCTA 11880
ACCACCCTGT GTCTCAGTTT TCCTACCTGT  <RTI  

   ID=90.11> AAAATGAAC;A    TATTAACAGT   AACTGCCTTC    11940
ATAGATAGAA GATAGATAGA TTAGATAGAT AGATAGATAG ATAGATAGAT AGATAGATAG 12000
ATAGATAGAT AGGAAGTACT TAGAACAGGG TCTGACACAG GAAATGCTC;T CCAAGTGTGC 12060  
ACCAGGAGAT AGTATCTGAG AAGGCTCAGT CTGGCACCAT GTGGGTTGGG TGGGAACCTG 12120
GAGGCTGGAG AATGGGCTGA AGATGGCCAG TGGTGTGTGG AAGAGTCTGA GATGCAGGGA 12180
TGAGGAAGAG AAAGGAGATA AGGATGACCT   CCAGTCTCT    GGCTATGGTG ATTGGGTGCA 12240
GGCAGTGGCA GTCACTGGAC TCAGACCCTG AAGCAAGGCA   GCAGCTCATC    GGAGTGTGAG 12300
CAGGCTCTGA   GACATTTAGG    TCTGGCCGTG CCTCATGTGT TGAATGTTAT GGGAGATGGA 12360
GGTGGCGAGG AGCATGAGAA TCATGAGCAT CACTGCCCCT AGAGTATGTG CAAGGCACTG 12420
GACTTGCAGC AGATTGTGAG CTCTGCTGTG GACCCCAATC TGCACTGGGA GCTTTGGCAG 12480
GGTAAAGGGG AAGAAGAGCA AAAGCACAAG AATTCAGTTA   CGGCTTCTAA   

   TCCTGTCTGC 12540   TTTCTAGTAC    AGGCATACAG TCATCACTCA   AGAAATGTTT    ATGTTCATTC   ACAC m GGG    12600
CCAGACACTG TTCTAGACAT CGAGGATACA GCTGCAAGTG AAACAGATAC AACAACCCCC 12660   GACTCATGAA    GTGTGTGCTC TAGCTGGGAG TGGGCAAGCA ATGAGCCAAG TAAATTATTA 12720
AAAAAACAAA TTATATAGCA   TTTGCAGCTT    CAGATAGGGT GTTCACCAAG GAAGATCTCA 12780
CTAGAAAGCT   GATATTTGAG    CAAAGGCTTA AATTGCTGAA GGAGCAAGCC ATGCGGCCAT 12840   TTTGGAGAAG    GGAGCTCCAT CCTGCAGCGG GACTGTGCTT GCCATGTTCA GGGGACAAGT 12900
GGGCCAGTGT GGCTGCGGGG AGAGAGTGAG AAAAAAAGTG GTCTCAGATG AGGTCAGAGA 12960
GCTAAAGTGG GAAGGTGAGA TGAAAGGAGG CTACCGCAGT GGTCCAGGCT GGAGCTGATG 13020
GTGGGTGGAC TAGAGTGGTA ATGGTGAAGG CAGCAGGAAG TTGTTGGTGT TTGGATGGAT 13080
GAATGGACTA ATGGATGGAT GAATAATAGA TAGATGGATT 

  GTTGAGAGAG ACAGAGAAGA 13140
GAAAAGCCTT GCCCCCAAAA GCTCACAGAC TACTTGGAGA GAGAAGAAAG CTACCTGGAG 13200
GGAGAACCAG ATGCATGAAG CAGTGCAGAT GTGGTGCCTA ATGAGTGTGT AGTCTGGAAG 13260
GGCAGCAAAA GTCGAGTGGA GTGAGAGGTT CCTGTGTCCT GGAGCACTGA GTAGAGACTC 13320
CCTCATGGGG GTGAATCTTA AAGGATAAAG GGGCCTCTAT AATGAAAAGG AGGAGGATGG 13380
GATTTCTGGT AGAGGAAATT GCTTGAGCAA AACCTCCAAG GTTGGAATGA CTATGGTGTG 13440
TTCAGGGATG TTAGCAGACC CAGATGGGTG GAGCGTTGAG TGTGTGTGTG   TAGGMGGAA    13500  
GAGGGGAGGT GGCTGGATGA GCACAGTGAG ACCTGATTTG ATTGAGAGCC   TTGAACGCCA    13560
CGCTGAATAA TGGAGGCAAT GGGACGCCAT AGAGGGCTTT TGAGTAGACA TATATCAGTG 13620
TAGAAGGGTG AATTTCAGAT   TTTTAGACAG    AATAGAGTAA GGAGAGGAGC TCTTAGAAAT 13680
CATCTAGTCC AGGGCTTGTG GCAGAGCCCT GAGGTTTTAA GAAGGCATGT CAGGGGCTAC 13740
CATGACAGGC ACGGAGAGGC TGAGTGAATT GGGGTTCTTG CCACAATTCC CTTGCCTGAG 

  13800
ATTCAACAAG AGCAGCTGTA TTACAATCTG TGCAAAATGT CATTAGGAGA AACTAGTTAG 13860
TAGCTGGGCG TGGTGGCATG CAACTGTTGT CCCAGCTACT CGGGAGGCTG AGGCCGGAGA 13920
ATCGCTTGAA   GCTGGGAGGC    GGAGGTTGCA GTGAGCAGAG ACTGTGCCAC TGCACTCCAG 13980
CCTGGATGAC AGAGCAAGAC   TCTGTTTCAA    AAAAAAAAAA   AAAAAMACT    AGTCAGGACT 14040   CTTTCAGATA    CAAGTAATAG AAACCAACTC AAACTGGCCT   AATTMAAGG    ATTTTTTTCC 14100
TTATAGCTAA AAAGCTCATG GATATCAGCT TCAGGAACAC TTGGATCCAG GTGTTCAGCT 14160
GATGCTGGAA AGAATCTATG ACTCCCCAAC TCTCAGCCCT GCCAGGAAGG   CTTTCCCCTT    14220
GTAGGACTCC GACTATCCGC CTTGTAGTAT CTGATCCAGC AACACCAGTA AAATGAGGGC 14280
TTCTCTTTTC CCAGAGTCTT AACAAAAATC ATGGAATTGA GTGTTATGGA CTCATGGATT 14340
CATGGTAACC   CAAACCAATC    ACCGGGCCAG  <RTI  

   ID=92.10> AGGGGACAGA    GTACCCTCAC TGGTTGGCCT 14400
GGGTTACACA CCTACTCCAG AGCTATATTT   GGAAGCCGCA    TTGACTGATT TATGACCAGA 14460
AGAAAGGGAA ATGGATGAGG ACACGTGAAA   TTGTGTGTGT    ATGTGTGTGT GTGTTTTCTT 14520
GCTGCCAAAA ATTTTTCAAA AACTTGGAAA ATCACAGATA TATTCAATCT CTTCATTACA 14580
CAAATAAGGA GATGGAGGCA CAAATGGGGA TAGAGGGATT TGCCCAGGTT CTCCTAGGGC 14640
TTCAGTGAGA AAAGTTTTGA TCCAGGGATT CTGAAGGGGG TGGTGAGAAG AGGGGTGTCA 14700
GAGGACCTGT CTTGGGTGGT GGGGACTATG TACCTGTGAC ATAGCTGCTC   AGGGACTGGA    14760
TCAATGGGTG GATGACAAAA TGGACAAATA AACAAGGACA TCTTCCCACT AATGCCAGAT 14820
GCTTGTGTGT TCTGCTTTCC AGAGAGTGCC TACTTGAACT TGAGCTCTGA GCAGAACCTC 14880
ATCCAGGAGG TGACCGTGGG GGAGGGGCTC AACCTCAAAG   TCATGGTGC;

  A    GGCCTACCCA 14940  
GGCCTGCAAG GTTTTAACTG GACCTACCTG GGACCCTTTT CTGACCACCA GCCTGAGCCC 15000   AAGCTTGCTA    ATGCTACCAC CAAGGACACA TACAGGTACC ACTTATCAGC TCCCGTCTAC 15060
ACAGCCCGAC AACCAGATGG GGTATGCTTC AGCAAGCATC   AGGACGCTTG    GCTCATGTCC 15120
CAACCTTGGT GTATGACCTT GAGCAAGTCC   CTGCCCCTTT    CTGGGCTTCG CTTTCCCTGA 15180
CTTCATGGAA TCCCAATATT   GGTCATCTGT    GTTTGAGATC TAGATGAAAT TGACCTACCT 15240
CTCCATCCCA CATCCTTGGG ATAGTCAATG CCCCACCCAA GGATTCTACC ATTTCTTGGG 15300
AGTGTGCATT   CTCATTGGTC    CCTCAAGAAC CCTCAGCCTC ATTCATTTTC   CTCTcTTGGG    15360
GCCAATCCAA ATGCAGAAAA CAGCCCCACT CATAGACACA CTCCTGATAA TGACTGCACA 15420
AGTTATCTGC TACATACAAA   AGCTTGGAGG    GAGGGGAAGA GGGAATTAAG ATCACACAAT 15480
CACAGATACA TGAAATGTTC TTTAAAGGAT 

  TGTGATCACC CAGCCCCAAG AATTTCTCAC 15540
TGGCTGCTCT TCTCTGTAAG CTCAAAACTC TTCCCATGAA GTGCAATCTA TAATAACTCC 15600
ACACCCCTCT TCTTCCGTCT CTCCACTCCC ACAATCCTGT GTATTCCACA   CACATTTTAG    15660
AAATCTTTTT CCTGTCTGCT TGTGAACTGT GTTCTTGGGG   TCTTGCTTTC    TCATCCAAAG 15720
TGGCTTAAGC   AGGTAGGTTC    TAAATAAGAA   AGCTTTGTGC    CTAAGAGGAA CACTCATACC 15780
AGGTATATCA GGTATTAACT CAGGTATTAA AATAGTTCCT TCTTTTCTTT CTTTTTATTA 15840
TTTTTTTTAG ATGGAGTTTT GCTCTTGTTG CTGGAGTGCA ATGGCACAAT CTCGGCTCAC 15900
TGCAAACTCG GCCTCCCGGG TTCAAGTGAT TCTCCTGCCT CAGCCTCCCG AGTAGCTGGG 15960
ATTACAGATG CCCACCACCA CACCCAGCTA ATTTTTGTAT   TTTTAGTAGA    GACAGAGTTT 16020
CACCATGTTG GCCAGGCTGG TCTCGAACTC CTGACCTCAG GTGATCTGCC TGCCTCGGCC 16080
TCCCAAGGTG CTAGGATTAC AGGTGTGAGC CATCGTGCCT GGCCTGAAAT AATCATTCAT 

  16140
ACCCTGCCCT TTCAGAGGGA GACAGTACAG CTTAAGGGCA GCGAATACGT GGTGTGCATG 16200
CCACACTCAC TCTCATTCTT GTTTCTGCAA CTCTGTTCTG CAGAGTGTAG ATGCGGCCTC 16260
AGAGTCCTCC TCAACACAGG TCCCAGGCAG TATTTCCAGC ATAGTTGGCT CATGAGAGAT 16320   CTGTTTGTCA TCCCTGTGTG GATCCCTTAG ACAACTTCAA AACTCTTTGG GATTCTCGTT 1 380     
CTAGCTCTGG AAGCCCAAAC CTCATTGATT CCCACAATCT TGCTTGTCAA TTGTCAGAAG 16440
CAACAAGGAT   GTTITCTTGT    CCTCATCTTC CTCCTCTCAG TTCCCTTCTG GTCCTTTCTG 16500
GCCAGGTCTC TGTCTTCCTC   TCATTTAAAG    CAGAAGTTCT   GAATCTGGAA    TGTGTAGGCC 16560
CTTTGGAGGG GGCTGGTCCA TGGATCGGTT TAATGGGTCC ATAAGCCACA GAGACATTGA 16620
GGAAAGGAAC ACGAGATCCC CTAAAACACA GTAGTCTGGG CCCATTCAGC ACAAGGCAGA 16680
CAAGCCTGGA CACCAAACAG CCACAGAATT TTAGTTCATG   TCATGGGTTG    TTCATAATGG 16740
TGACTTTCAA TTATCCAAAA AAGTCAAATT 

  ATTTTTAGTT AAAGGGGTTA GTTATCTCAA 16800
GAAGTGACCT GGGCAGAGGC CTTGTATATG CCCAGGGTCT GGCTGGATGA GACTGCTCTC 16860
TGAATACCAT   AGATTTTAGT    CTAGTAGTAG CTGCAGACAT TTCCCAAGCA AGAACTGGCC 16920
ATTTGCTATA ATTTTTAAAA TTTTATTTAT TTTGACAGTG AACTGGGGGA CTTTTTAAAA 16980   AATGTATTTA    TTACCTAAAA CAACACATGT TCATTATGGA CAAATTGTAA AATAGAGATT 17040   AAAGAAAGAA    TAAAACAAAA AATTTCCCAG AATCAGCCAA AGATGATTTT TATTGTTAGT 17100
TTTTGCTCCA GGGCCTTTTC TGTAATAAAG GGTACCATTG AATTGAGTGC CCACAAAGAT 17160
TCAACTTCTG TGTCAAGCAC CCTAAAAAGG TCCTTTAATC CTCAAGCCAA   GCCTGTGAAT    17220
TAATAACCAT CGATATCACT CTCACAGCAA AGGAAGTGAG GGATCAGAGA   GGTTMGTAC    17280
TTGTCTAAGA TCACACAGCC AAGAAACAGC AGCACCAGGA CTTGAACCCC AGTCTCTGCA 17340
GCAACATGGC TCAGAACCCA   GGGCCCTACA    TCCTGCCTCT  <RTI  

   ID=94.11> TGTCTCTTTC    TCAGTCCCTC 17400
TTGGCAAGGT TGGCACTTCA GGGATTTGTA GCAGGGATTG CAGCTTTCAT GAAAGCTTAG 17460
TCCAGTGACA GTGGTCAACG TAGGCGACCT GTGATAGGCC TCCCAGCACC   TTGAAGACAT    17520
CACCTCTATT AAACCTCGGG AAAAAAACAC   TTTCAGATAA    GAAAACCAAC TAAGGAAATG 17580
GGATTGGTGG   TTTTTGCATG    TCTCAATGGC ACCCTGTCTG AGTATCTGGC TTACCCAAGG 17640
CCGTTGGGCC   CTGAATATTT    TACCAAAAAT AAAATAAACC CCTTTAAGGC   TGTTATCTGA    17700
CTGCAATCCT GGCAGGGGCC ATACTAGGCT GGGGCTCACC AACACCACCT GATTCTCTCC 17760
TGCAGGCACA CCTTCACCCT CTCTCTGCCC CGCCTGAAGC CCTCTGAGGC TGGCCGCTAC 17820  
TCCTTCCTGG CCAGAAACCC   AGGAGGCTGG    AGAGCTCTGA   CGTTTGAGCT    CACCCTTCGA 17880
TGTGAGTGCT GGGGCCGAGC GCCACCTGGG GCGGAGGCCC TGGGACTGCC TGGAGGGATG 

  17940
GGGTTGACTG GGGCAGGGCA CAGGGAAGTA   GGTACTGG(;A    GATTGGGAGG TGGCGGGGAA 18000
AGTGTGACTT GGGGCCTCCT CCTTTCTTCC TCAGACCCCC CAGAGGTAAG CGTCATATGG 18060
ACATTCATCA ACGGCTCTGG   CACCCTITTG    TGTGCTGCCT CTGGGTACCC CCAGCCCAAC 18120
GTGACATGGC TGCAGTGCAG TGGCCACACT GATAGGTAAG TGGGCTCCAC TCACCTCCCT   18180   
CACCTGGGCT CAGGGGCTGG GCACCCTGTG   AGTGGGAGGG    ACATGCTGGC   GCTGGGAACC    18240
CTGAAGCTCT GAGCCACATT   CTGCTTTTGC      CAGGTGTGAT    GAGGCCCAAG TGCTGCAGGT 18300
CTGGGATGAC CCATACCCTG AGGTCCTGAG CCAGGAGCCC TTCCACAAGG TGACGGTGCA 18360
GAGCCTGCTG ACTGTTGAGA CCTTAGAGCA CAACCAAACC TACGAGTGCA GGGCCCACAA 18420
CAGCGTGGGG AGTGGCTCCT GGGCCTTCAT ACCCATCTCT GCAGGTGAGA   GGGAGCCTTC    18480
GCACCCGCAC CGCCCCCCCG 

  CCCGCCCCCC GCCCCTGCTC CTTTAGGCGG CTCCTCCCCC 18540
ACCCCCCACC GAGGGAGCTG GGGTTGGCTC CACCTTTGGA GCAGATCCTA GCAGTACCAA 18600
GGTCCACCTC TCTGGGCCAG TCCAAGCCCC TCCTGCCTGG CAGGTCCCCC   GAAGCAGTAC;    18660
GACGGGGTAG TCTCTGAGAA AGCAGAGAGA AAGCAGCCTG AAGAAACTGG CCCCCACTCT 18720
TGTCCCTGCA CTCTAACTCA TGCATCTATT CACAAGTATG   TGCAGGCATT      ATGCACCGTC;

      18780
TGCCAGGGAC GTGCCCTATG CAGGGAAGCA GTGCCTCCCC AGAGCTCAGA GGCTGATGAG 18840
GGAGGCAGGC AATGAGCAAG GAAACAGTCC ATCTCCAGCT CGGGGCCAGC TAAGGACGGC   1890n   
CTTCTCCAAC TCTCCCCTCT TGCTCCAGAC ACAGTCTATC   CATTTGAGGT    TGCTGTGCAA 18960
GAGGCTGCCC CGGGGGATGA TGCCCGGCCC TGTGCACAAC ACAGGCTGCC TCTCTGCTTT 19020
ACACAAAGGC TCCTTACCAG CTAGTTCTGT GATTCTCAGA GGCCCACAGC ATCCTCAGGC 19080
TTTTGACAAC CAGGCTCTGG CACCCACTGT GTGCCAGACC CTGGCATCTG CCTGGCTCAG 19140
GGGTGGTCAC TCACGTCCCC AGCTGCTGGC CTTGGAGCAA CTGCTACCAG GGTCCAGCTG 19200
CAAGCAGGAG CCTGCGGCCG CGCTGGGCCT CACTGCTGGA GGTTGTATAT TATAATAAAG 19260    CCAACATTTT    GTTGAAGGCT TCTGCTGCGC   CAGGCACTGT      GTTAAGCTCT      TTGTGC; 

  GGAT    19320
TATCTCGATT AACTCCTACA AACCTAGAGAA ATAAATAGAA TTTTCCCTAG GCTCAATCTC 19380
ACACAGCTCC CAAGTGGCAC AGGTGAAACT TGACTGCAGA TCTAAGTTAC TGATCTGAGC 19440
AAGGAAGTGG AAATTATGTT CTCCAAAACA TCGCTAGAAC TAGTAGTATA GATTCTGGGA 19500
AGAGGAGACT CAGGGGCCAC AAGCCTGGCT TGCTAGACCC TCAGAAGGGC TGTATGATTC 19560
CAAAGGCATG TGGAGAAGCT GCAGGGGAAA TGCAGGAGAG GAAGGTTGCA  <RT 
CATCCTCTTC ATTATTTCAT GTTACTGTCC TATTAGCCAA   AGCCACAATT    TAGTGCATGT 20760
TGCGTATAGT GTGCTTCCTG TGTCTGCTCA GTATATCACA GTGATTTGAG GGGCATTTTT 20820
CTATAGCATG TTACCTACAT CATCTCATTT AATGCCCTCA GCAACCACTG TATGCAGCTA 20880
GCATTAGTCT ATTTTACAGA GTTGTAAACT GAGGTTCTGA GAGGTTGGGA CAGTTGCCCT 20940
TGTCTACAGC   TGGTCAAAGG    CAGAGTCTGG TTTTTAACCC TGAAGGAGGA CTCACTCCAA 21000
AGCATGTCCC AATCATTATG TGAAACATTG ACTCATCTTA TTTTACCCTC ACAAGAAGCT 21060
GGAGGCAGGA AGTATACTAG TCAGTATCTT 

  ACCCATCAGG   AAGCTGAGGC    TCAGCAAGGT 21120
TAAAAAAAAA ACCCCAAGGG   GCTGAGGC;AT      AGGGTTGGCA    CTGGGCCCCA GGGGCTTCTG 21180
TCCCTAGAGC CCATGGCCTC CACTGCCTGC CTGCCCACAC AAAGACCATG TGCAATGTGA 21240
TCAGAAGCTG   AGAC.GACCAG    GCCAGAGGGC   TGTGGGAGTT    CAGAGGTGGA CGGACTTTTC 21300
AGGCTGGTGG   GTAAGGGAGA    CTGCCTGGAG   GAGGTGGCTT    GGCATTGGTG GGACGGGCTT 21360
TGGAGGATGA GGATGCAGCA GGGGAGATGA CACTAAGGGA AAGGGTATCT CTGGGGGAGA 21420
GGGCAGAGTG TGCAGAGGTG CAGGTGAGGG   AAGGACCAGG    GTGGGGCTGG   GGGTCTGAAG    21480
GGTTGGACCC CACCCTGTCG GTCCAAGGCC ATCAGTGGGT TTGAACAAGG GAGTGGTGTG 21540
ATCAAGGACT GAATGACCCA TCTTGTGTCC CCTTGGCTAC CTTTTCTTCC CCACACCCCT 21600
TGGGGCTTTT GTGAGAAGAG  <RTI  

   ID=97.12> GGCTTGAAGT    GGGCAGGGTG GGAAGGATGT TGGGGGAGCC 21660
CCAGGGGCAC ATGGATCGGG ATCTCTACTC CTGCCAGCAC TCAGCATGAG AAGGCTGCTC 21720
TGAGGGCAGC CCCGGTCAAT ACCTCCGGAT CTAGGTCCAG CTCTGACACT   GTTITGCCAT    21780
GTAACCTCAG CTGACTCGCT   GTCCTCTCTG    GGCCTTAGTT   TCCCCTCTTA      TACCATGGC,

  T    21840
CTGGGTGTTC TCTAACAGCC CCTCCTCCTC TGACATGCCA AGAGCCCACT GGTGGTCTAG 21900
TTTAAGCACC AGAAACTTGG ACTTCAGTGA ATCTGGGTCC AAATCCTGCC TCTGCCAAGC 21960
TCTGGCTATG GGGTGATGAG AAAGTTGGTG TGTCTGAGTC TCTTCTCCAT TTGTAAAATG 22020
GGATCATTAA CAGCCTGTTG TGAGGGATTC CGTACCACAA CGCACATAGA GGACTGAGCG 22080
GGGTGCTGGA CGAGACAGTC TCTGTGATGG GAGCTGCACA CTCTTGTCCC AGGAGGAAGT 22140  
TCGTTGGGGA ACCAGAGTTA GCTCATGCCT CTTGGGATGG TGGAAGGAGG   GGGACGTCTG    22200   AGGTCGGGCA    TCATCTCCTT GACTACACAC CCAAAGCC.GT TGTTTGGCCC AGCCCACCCA 22260
CCTCCAGGGA CAGGACCTTA CTCACTCTCG GGGCCACCCG TTCCTTCTCT GAGCAGCTCC 22320
AATGTTTGCA   AAGTTCTTCC    TTACATGGAA CTGAAAACTG CCTCGCAGTG CCCACAGAGC 22380
TGCCAGGACA GTCATGCAGA GATTCCAGAG   AAGGGCCTAG    GGCCCCCTGC GGCCCTTTCT   22440   
GCCTTGGGCT GGCCAGCCCC 

  CTTGGCTGTG GTTTAGGAAC TCTGTATCCC   CTCTCCACGG    22500
GACCATTTTT GGAACATGTC ACCTCCACAC TTCCTGTCCA   GGAAATTCAG    CTGCCCCTGG 22560
AGCCCATGCA AGGCTGCGAG AAGACTTGCA GCTACCCTCC   TCCCCTACAC    CCATTCACAG 22620
ACCCTTTAGC TCCAGGCCGA GGTGTCCACC CATGGGAGCG GAGGGGGCAG GATGGTCATG   22680   
CCCGTGCTAA GTGCCTGCCC   TCCCATCCTC    CTCTGCCTTG CCCCATGAGG TTCGGAGCCT 22740
TGCCCCTTCA CTGGGGACTC AGCCCAGCCT CTCCTCATTG CCCAGGCCTG GGGAAAGAAG 22800
TGGCCTGTCT GTGGGGAGTG   TTTGTTCTGC    CTCAGGGCTG AATCATCACC TTTCTGTCCC 22860
CCAGAGTGAC CACAAGGGGG GCCGTGGGGG AAGAGAAAAG GGCAGGAGTC AGCAGGCTCC 22920
CCTGGAGGAG GAGGCGCACA GGGAAATGGC TGAGGCAGCA GGGAAGGGAG GGTCCAGGGA 22980
GGCTGCTGGA AAGACTACGA   TTCTGGGGGC    TGGAACTGAG CTCTGAGGAG CAACAGGAGG 23040
GTCCCCAAAG 

  ATTCCACTGG GAATTGTTCA GATCTCCACC TTCCTGTGAG AACATCCACT 23100
CACCCAGAAC CAGCAGGCCT AGATGGGGAG   GGGACCGGGA      CTTTGTCTCC    ATGCCCCCTT 23160
TGGTGGGGAG   GATGGGAGGA    AGGGAAGAAG TCAGGGGGTG GGCCTGGGGC TTAGGCCCAT 23220
TGCAAGGAAT   GAATGGGGTG    ATGTGCTTCA AGCATCTAGC CCAGCGCCCC ACTCCCAGGA 23280
AGAGCTCAGG AAGAACCCGC TGCCATCATG   ACMTTACGT    CCACCCTTCT CAGGGAGCCT 23340
CGCCCATCCC CACCTCTTGA TCTCTCACTC ATAGTTCTTT GGAAGAGAGG CTGCCTCTGG 23400
GTAGACGCCC   ATGAGCCCTT    TCCAGGGATG GCACAGGTGC CCTGGGAGGT TTACATGCCC 23460
AGCAGGGGCA GGGGAGGGTT CCTGAGGCAG GCAGAAGGCA GCTTGGTCCG   CTTCCAGAAA    23520
TTAGGAGCCT AGGATTCAGA AATCTGAGAA TCCAGCCAAA CCTCCATCCT CCTTGATCCC 23580  
CTCCCTTTCA ACAGTGCCCC CTGCCCAGCT GGGGGCAGGG AGGGGCTGAC TCAGCCCAGC 

  23640
TGCAGAGGGA CAGAGGAACA AGAAGTGGTA AGAAAAAACA GTCTTAGCCA CAGAGGCTCC 23700
TAGAGATGGA AGTGGCCAGG AGAGGCTGAA GAATCCCCTC CTCGCCTTGT TGCTGTCTTT 23760
TGGGCTGGGA AGGCACCCAC GGGCAGGATT TGGATCCTCA GAGGCTTGGG AAGCTCTTCT 23820
CCCTGGGTCC CGTTTCAGAC TCTCTCCCAA GCTATAACGC AGAGGCTCTG AAGTTCACCT 23880
GCAGTCCGCC CTTCCAAATC AGAGCCTGGA AGTTAGTTCC   TTCTCATITC    TAATTGCAGT 23940
CTTTTCTCTC TAACTACCAG CTAGAAGTTC TTCCTGATGG TTAGCTGGAA GCTTTCTCCC 24000
TGTCTCTCTC TTTAAAAATG   TCCACATTTT    ATTTTTGATT   CAGGGGATAG    ACGTACAGGT 24060
TTGTTGCATG   CGTATGTTTC    GTGATGCTGA   GCTTTGGAAT    ATGGATCCCA TCACCTGCTA 24120
CTGAGCATAG   CTCCCATAGT      TTTTCAACCC      TCGCCCGCTT    CCACCCTCCC TGCTCTAGTA 24180
GCCCCCAGTG TCTGTTGGTG CCATCTTTAT 

  GCCCATGCAC ACTCAATATT TAGCTCCCAC 24240   TTATAAGTGA    GAACATGCGG TATGTAGGTT TTCTGTTTCG GTGTTAATTT GCTTAGGATA 24300
ATGGCCTTCA GCTGCACCAC GTTGCTGCAA AGGACATGAC TGGAATCTTC   TCTCTCAACC    24360   AGGACTTGCA    GCTAAAGGCC AGCCTCCTCC CTAGCACCGG TCCACACTTC CTTTAAGTTT 24420   CTAGCTCGGG    TGCCCAGGGA AGGAGCCCAG CTGCAGGCAC AGCCAAGCTT GTCCCATCCC 24480
CAAGGCCTGG CCGGAAAGAG TTGCTCTGCT   GACCCAGGGC    CTCAGTGTCC TCCACCGCCC 24540
CAGCCCAGCT   TCCACTTTCC    CCCTCAACTT GGTCTTCCAT CAGCATTTCT TATGGGCAAC 24600
CCTTAGCATG GTACTCCCCC TCAGCAGCTG ACCCCTGGGC AAGAAACAGG GGCAGCCATT 24660
CCTCCTCCCC ACATCCCAGG GCTTGCCTCC CCTGGCTGGG TGGTAACAGC ATGGAGAGCC 24720
TAAGGAAGGA AATCAGGTCT TTCCAAAGGT GCTGGTCCTC   CAGAATCTAT    CTAGTGGGCA  <RTI  

   ID=99.16> 24780   
GCGTCTCTCT TTCTCTCTCA AAAAGGTAAA   GTCAAGGCTG    GGTGCGATGG CTCACGCCTA 24840
TAATCCCAGC ACTTTGAGAG GCCAAGGCAG AAGGATTGCT TGAGCCCAGG AGTTTGAGCC 24900
TAGTGAGCTA TGATCGTGCC ACTGCACTCC GGCATGAGTG AAGGAGCAAG ACTCTGTCTC 24960
AAAAAAAAAA AGTCAGATGG CGACTCACCT GTGTCAAACT CTCAGGGTCT   CTCACTGCCC    25020  
GGCCAGGCAT GGTAGCTCAT GCCTGTAATC   CCAGCAv r    GAGAGACCGA GGCAGGCAAA 25080
CTGCTTGAGC TCACGAGTTC AAGACCAGCC TAGGCTGCGA CAAAGCCCCG TCTCTACAAA 25140
AATTAGCCAG GTGTGGTGCC   ACATGCTTGT    AGTCCCGGCT GCTTGGGAGA CTGAGGTGGG 25200
AGGATTGCTT GAACCTCGGG GGTCGAGGCT   GTAGTGAGCC      AAGACTGCCC    CCACTGCATG 25260
CCAGTCTGGG GGACAGAGAT CCTGTCTTGG AAAAAAAAAA ATCCCAAAAG GGAACCCACT 25320
CACCTTATCA TAGCCCTCAA GGCCTTCCTG TTTCTGGAAT CTGCCCCCCA 

  CTTCCCTCAA 25380
GCCATGATGG CTGCCTTCCT ATAGCTCAAA CTTGCCAGGA TCATTCCCAT GTCAACCATA 25440   CAGCATTTCC    ATGCACTGTT CCTGGAAAAT TCTTCCTCTG ATGGTCACAT GGTGGGCTCT 25500
TTAGGGGCCT TCCCTGACTT ATCTTACTTT   ATTTTCTTCA    TAGCACCACT TGAGAATCTC 25560
CTAGATACAT   GTTTATTTGC      GTTTAATGCC    TCTCTCAGCC   ACTAC.AATGC      AAACTCCATG    25620
GAGGGGCAGG GACTTTGTCC TGTTCAACTC TGAATCAGCG GTGCCTGACA   CAAATAGATC;

      25680
TTCAAGAAAG TATGTGGATG GGCTACTATT ATTCAGCCTT AAAAAGGAAG GGAATTCTGA 25740
CCTGTGCTGC AGCATGAATG AACCTTGAAG ACATTATGCT GGGTGAAATA AGGCAATCTC 25800
AATAGACACA TGCTGTGTGA GTCCACTGAG GTGCAGTGCC TAGAGCAGTG   CAATTCACAG    25860
AGACAGCAGA ATCATGGTTG CCAGGGGCTG GAGGAGGGAA AGGGGAGTTG CTTTTTAACA 25920
GGAACAGAAT TTCAGTTTTG CAAGATGAAA AGAGCTCTGG AAACTGGTTG CACAAGGTAG 25980
AATGTAATTT ACTTAATACT ACTGAACCAT ACACTTAAAA ATGGTTGAAA TGGTAAATTT 26040
CATGTATGTT TTATCACAAT TAAAATATAT   ATATATATIT    GGATGGGAGG TTGGGTGGGT 26100
GGATGGATGG GTAGATGGAT GGACAGATGA ACGGATGGAT AAGATCTCAA GTTCCACCCT 26160
CCCTCCTGGC TCAGGAATTA CCAGATTATC AGAGATATCA GGGCCCTCAG AGGTTGTCTT 26220
GTCCAAGGTC TTCAATACAC AAATAGTGAA ACAGGCTTGG AGAAGGGAAG GTCACACAAC 26280
AAGGCAGAGT CAAGCAGGAA CATGCTCTCA GTGCTATGTT CATGAGACGA CCTCTCTCAG 26340
CCCAGAGCAG GCCTTGCCCT 

  GCCTTCTCCC ACTGGGCGCC TTGGGACTGC CCACACCCCT 26400
GCTCTTGGGG GTCAGAAACA AGGTCCAGGA   ACTGCCTGCC    AGCCCCGACT GCCACGTGCT 26460  
CCCTTCCTCT TCTGCAGAAG CCCAAGTACC AGGTCCGCTG GAAGATCATC   GAGAGCTATG    26520
AGGGCAACAG   TTATACTTTC    ATCGACCCCA CGCAGCTGCC TTACAACGAG AAGTGGGAGT 26580
TCCCCCGGAA CAACCTGCAG   TTTGGTGAGA    TGGCAGCTCA TCACTCCACA GCTTCCTATC 26640
ACAGGGCCTG TGGGGGTTGC AGGGAGCCCA TGGGCCCTTG GACAGAGGCC CTTTGGTGCC 26700
CAGGGACTTA AGGGACCTGT GTGCGTGGCA GGTAAGACCC TCGGAGCTGG AGCCTTTGGG 26760
AAGGTGGTGG AGGCCACGGC   CTTTGGTCTG    GGCAAGGAGG ATGCTGTCCT GAAGGTGGCT 26820
GTGAAGATGC TGAAGTGTGA GTGAGGGGAG GGGATGAGGG AAGGGATGGG GGTGGTAGAT 26880
GCTGGGGGTG GGCTGGCCCT GGTGTCACAA GAGGCATCAC   ACACA m CA    ACCTGTTGAA 26940
GCCTGGGGGA CAGAGCTCAG 

  GGGTGAGGAC   TTGGGTTTC    TTGTGAGCTC CAGGCACCCT 27000
CTGACTCCCG GCTCCAAGAA GGTCTAGGTC   ACCCTTTAGT    TGTGAAGGGG CTCCTGACTG 27060
AGCTCCAAAA AGTCTGGGGG   TGCAGAAAGG    CCACCTATGG CCATGGCCTG GCCACAGTTT 27120
GGCTTCCTGT CACCTGAAGA CCAGCTCAGT GACAGGCTCA   TCCCTTCTCT    CTCTCTCTCT 27180
GCCATCTGTG TGTCTGCATT   TTTCCTTCTC      CTTCTTTTGG    CTTCTGGTCA CTCCGGGTCT 27240
TGGGATATGC CCTGCTTTCT CCCCTGGGTC   TCTGCATrTG    GTCCCCATGT ATCTGTGTGG 27300
TGCTCTCTGT CCTGCCCTCT CCCTGTCTTT GGGACTGTGG TTCTTCCTCC CAGCCACGGC 27360
CCATGCTGAT   GAGAAGGAGG    CCCTCATGTC CGAGCTGAAG ATCATGAGCC ACCTGGGCCA 27420
GCACGAGAAC ATCGTCAACC TTCTGGGAGC CTGTACCCAT GGAGGTAAGG GCCTTGGGGT 27480
TCCTGGGGCC AAGGTCTTGG GGCCTCTGGG GAATCTCAGG 

  GCCCCAGGGC TACCTTGTTC 27540
CGTCTTCTCC TTCTCAGGAT CCTACTGCTC CAAGTGTCAG GGGGATCCCG GTCACAGCAT 27600
CCCTTAAACT CCTGGGCCCA TCTCCTGGAA TAGTCAGGAG CTGCACGGGC AGCTTGAGGT 27660
ATAAAGAGAG ACTGATAGGG AGCATCGGAG CCCTTGGAGG AGGAGATGAA TGTGCAAGCT 27720
CCTAGGCCCT GCTTCCAGGG   AGCCGGATCC      TCTGGGTCTG    GAGTGAAGCC CCCCGCCTAC 27780
CTCTTATGAA GCTTCCATTC   AAGGATGCTr    GGACACTCTC CCCAGGGCCC CCAAAGGTGC 27840
CCCGGGCTTT GCTGGGACTC CAAGTGCCCC ACATCCTCTT CACTGATAGC AGCTCTGACC 27900  
TACAGTGAGC CGCCATAGCT TTCCTTTGAA GAAATAATTC TTGGGCTACA TTTTTTTTAA 27960
GGTTGTCTTT TTTTTTTCAT TTTTTGTTTT TTTTTTCTTG AGACGGAGCC TCACTCTGTC 28020
ACCCAGGCTG GAGTGCAGTG GTGCGATCTC GGCTCACTGC AACCTCTGCC   TCCCAGGTTC    28080
AAGCAATTCT CCTGCCTCAA CCTCCTGAGT AGTTGGAACT ACAGGCACAT GCCACCATGC 28140
CCGGCTGATT TTTTTGTATT TTTGTAGAGA 

  TGGGGTTTCA CCATGTTAGC CAGGATGGTC 28200
TCGATCTCCT GACCTCGTGA TCCACCCACC TTGGCCTCCC AAAGTGCTGA GATTACAGGC 28260
ATGAGCCACC GTGCCCCGCC AAAGCCATCT GTTTTAAACA AATGGAACTA CTGAGGCACA 28320
AGGAAACTTG CTCACAGAGC CGAGGTTAGA ACTCAGCTAT GCTGAGTCCA   AGTCCAGTGG    28380
CCTCACTGCC CCCAGTCTCA TGCTCCTGTT CATGGAGGGG AGCACTCAGC ACCTCCCTCA   28440   
CCCCACACCC TTGGCTGCTC TAGGCCCTGT ACTGGTCATC ACGGAGTACT GTTGCTATGG   28500   
CGACCTGCTC AACTTTCTGC GAAGGAAGGC TGAGGCCATG CTGGGACCCA GCCTGAGCCC 28560
CGGCCAGGAC CCCGAGGGAG GCGTCGACTA TAAGAACATC CACCTCGAGA AGAAATATGT 28620
CCGCAGGTAG CCCCTGGCAA AGGACAAGAA AAAGGCCAGG TCTGGGAGGC AGGATCCGAG 28680
TCTGTCTTCA AAGCCAGCTC AGGGTTGGAT   GGCTCATC,AA      TG(;

  GTGGCTA    TGCAGCCCTC 28740
ACCTGCCACC TGTGTCATGG GAAGTAGCCA CCACAGGTTT TATGGCCATC TCTTGTTTCT 28800
CTACTCCTTT TCCCCTTCAT TCAACAAATA   TrTGAACACC    TACCGTGTTC TGGGAGTGTG 28860
GAGGGCAAAG ATGGGCAGCT CATAATCTGG TGGAGATATG CATCAATGAA ATCACCACCC 28920
AGTGTGTGTA AAAGATCAAC CAAGATCTGT   GCCTGGAGCC    CTAGTAAGAG ATGGGCAGAT 28980
GTGGCCGGGT GCAGTGGCTC ATGCCTGTAA TCCCAGCACT TTGGGAGGCT GAGGCGGGCA 29040
GATCACCTGA GGATGGGAGT TCGAGACCAG CCTTACCAAC AAGGTGAAAC CCCGTCTCTA 29100
TTAAATATAC AAAATTAGCC GGGCGTGGTG GCGCATGCCT ATAATCCCAG   CT CTCGGGA    29160
GGCTGAGGCG GGAGAATTGC TTGAACCCAG   GAGGCAGAGG    TTGCTGTGAG   CTGAGATCAC    29220
ACCATTGCAC TCCAGCCTGG   GCAACAA(;

  AA    TGAAACTCCG   TCTCAAAAAA    AAAGAGAGAT 29280
GGCTCTGTTG   TCCTGTTGCT    GTGATTCCTG GAAGCCATCC AGAACAGAGC CATCCAACAG 29340  
ACAGAGCCAC ATGGGGAACC AAAGAGAGGA AGTGGGGAGA TTCATGTCAC ACATGAGTCA 29400   GGGTTAGAGG    TGGAGCCTGG ACTAGAATCC TGCTCTCTTG ACTTCCAGTC   CAGGAGTCAC    29460
CCAAGCCACA CTGCTGTCCT GGAGGTCTCT GTCTCAGGGG CTTGTGGGGT CAGGACAGGA 29520
TCAGAACAAG AAGGGTGTAC ACTGCGCCCT   CATCCTAGAT      ACTGTCAGCT    GCCACGCCTG 29580
GGGAGGCAAA AGAGAAGGAG GCCATCTCTT CACCCAGGGC CTTAAAAATG GGGGCCTGGC 29640   AGCATCACTI    CCTCTTCTGA TTCCCTGACA CTTCTATGAG GGTGGCACAC ACTAGGCCTC 29700
TGAAGATCAG ATCAAAATGA GCACCAAAGG AAAGTATTAG CTTCCATCTT CAAATACGCA 29760
GATGGGGAAA GTATTCCCAG AGTGGGTAAT TTCGAGGGCA  <RTI  

   ID=103.6> AATGGCCTGT    AAACCAACTC 29820
TGTCAAAGGA TTCCAGGCTG TTAACGGAAG CATAGTTTCT   AChAGGGAGC    GGAAGGTTTT 29880
TTCGGTTTCT CCTTCTGGGA ACACTAGAAT ATGGACATTG TCAAGGTACA CATCTCTAGC 29940
GCAGAGGGGA CAGGAGGGAG AGAGAAATCC TATCTGGCTG GAACGTTAGG AGCAGTAGTG 30000
CTTCAGTCTA CAGTAGTGCT TCTCAAATTC TCTACCCCAA GTGTGCTCTC ATAGGCATCT 30060
CTTGAGGACT   GTTGGAAGTG    CACCACCTCA GGCCCATCCA CCCAGGCCTG CTGATTCAAA 30120
ATCTGCATTG CAGAGATTCC CGGGGTGATT TATCTGCACA TGAGTTGCAG CGTAAGCAGC 30180
ACTGCTCTAG   ACCAGTGGGC    CTCAGCTTAG GCTGTACTTT GTGATCACCT   GGGGAGATIT    30240
AAATCTGTGA   ATGACTGTTT    TGTCCCTAGA GTTTCTGAAG TATTAGTAAT TAGCCTGATC 30300
CTAAAAGCTC CCGAAGTGAT   TTTMTGTGA    AGCCAGGGGT GTGAGGCACT GTCCAGAGAA 30360
GAGAGGGCAC AAGGGGCCCT AGAATATGCC 

    CCAATTCTAG    TAGGGCTGTT ATGGGGAAGA 30420
GGACTCCAAC TTCTCTGTGG CCCTTGAGGG TAGAGCAGGG GCTAGGAGGA AAATCTCAGG 30480
GGTAGATTGG CATTAGGAAC   AGTGAAGAAC    TTTCTCACAG GCAGAGCTGC CCAAAACCAG 30540
AATGGGTTGT AAGCTCCCTC ACCGGGGACA GCCGAGCAGA GACCAATGCT CACTCAGATG 30600
GAGTGTGGCA GGAGGGTTTC TTATCAGAAA GGGAGGTTCC AGTTGACCAT   GGGGTGGTGG    30660
GTGGTCAAGG CCTGAGCTGA GCAGTGCAGT GATGATGACT GACCTCTGCC CCCCAACCCT 30720
CTCTCCTATG TAGGGACAGT GGCTTCTCCA GCCAGGGTGT GGACACCTAT GTGGAGATGA 30780  
GGCCTGTCTC CACTTCTTCA AATGACTCCT TCTCTGAGCA AGGTGAGGAG GTCCCAGGGC 30840
CAGGCCCCAT TTGCTTGATA ACAAGGGAAA AGGAGAAGGG GCTGCTGGGG TGAGGGGTGG 30900
GGAGTGTGGC AGGGCTGCCC TGACGCCTCT TCCCACCCTA GACCTGGACA AGGAGGATGG 30960
ACGGCCCCTG GAGCTCCGGG   ACCTGCTTCA    CTTCTCCAGC CAAGTAGCCC AGGGCATGGC 31020  <RTI  

   ID=104.2> CTTCCTCGCT    TCCAAGAATG TGAGTAGGAA CCTGGCCCTG GCTCATAGCC ACCCAGGTCT 31080
GTGCTCCGGG GAGGCTGGAT GAGTGACGAT GGGGAGGAGG AAACGGGAGC CTGTGAGGGG 31140
GTAGGGGAGG AGACAGAGTA TGAGAGAGTC ATTTGGGCAG CAGCTGCAAG GATGAGTGGG 31200
AGAAAGCTGT GCCCAGGGCT GGAGCTCTGG GGCTGGGCAC   CTGTGTCCCC    AGCGTGAAGA 31260
TGAGGAAGGG TACCAGGCTT TCTTCATTCG   TTTTACTAA    ATAGTGTATG AGAGACAACA 31320
GTTGTCTCTG CTCATAAAGC ACGTGGTCTG GTGGGGATGA   TAACGGAAGC    TTCCTCAGAA 31380
TTTTGGGGAT ATTAGATAAC GTATAAAGTG CGCTCGGCCT AGGAAGAAGT GCCAGGGAAT 31440
GGGAGCTCTT GCCATCTTCC TTAGAACAGA TTCGGGAGTC AGTGGTTTGA TTGTTGGCTC 31500
TGCCACCTGC TCCGTGACTT TAAGCAACTA TTTAAATTCT GTGCCTCAGT TTCTACACCT 31560
ATAAAAATGG   GCATAACGAT    TGTTGAAAAG AAAAAGGGTT CAATGTGTGC   AGAGTTTAGG    31620  <RTI  

   ID=104.8> GAAGGGCCTG    GCAGATAGCA   GCTGCTATGA      TCAGAAGTAA      CGGTAGGGTT    TGGAGACTGC   3t680   
TCTCTGCACG GAAGCCCTTC GCTTCTGGGC; CCTGAGCAGA   CCAGTCAGAG    GACAAAGGGT 31740
GAGAAGGGCC ATGGCTGCTC AGGGTAATGG GGGTTTCTAA GCATTAAATG ATCAGATCAC 31800
GATACACATT CTCAGATCCT   GGGCCCTGGT    AGAAGGTATA GACAAGGGTT TGTGGTAAAG 31860
GACCAAAACT GTTGTTCACT CCAGCAGGGA   CTCCAAAGCC    ATGTGGGGCC CTCCCTGCCA 31920
TCCTCCTCAC CTCAGGCTCA GGTAGGAGAA GGCCCAAGAC TAACCCTGCA   GTGCTITCCC    31980
TCAGTGCATC   CACCGGGACG    TGGCAGCGCG TAACGTGCTG TTGACCAATG GTCATC;

  TGGC 32040
CAAGATTGGG GACTTCGGGC TGGCTAGGGA CATCATGAAT GACTCCAACT ACATTGTCAA 32100
GGGCAATGTA AGTGCTGGGA GGGCTTGGGT CAGGCTGGGG AGGGGGTGAA GAGTCGGGGC 32160
CCAAAATAAC TGGGGACTGT CATCCCAGGC CCGCCTGCCT GTGAAGTGGA TGGCCCCAGA 32220  
GAGCATCTTT GACTGTGTCT ACACGGTTCA GAGCGACGTC TGGTCCTATG GCATCCTCCT 32280
CTGGGAGATC TTCTCACTTG GTGAGCCACT GGGCCCACTC CAGGCAGAGC   CTGGGGCTG      32340      CTCCTCTGGT    TGCCCCACTG GTGGACAAAG CTGTTTGGTG CCCAGGACAC AGCGAGGGTT 32400
GGTGAGAGTG CAGGAATGGG CAAGGGCTCT CGAAACCCAG CATCGTGGCT CCTGCGGGAC 32460
TCGGCAGACC CTCTGCCCCT GACAGGCGCT CCTTTCTGGC TCTTCCCTCG   TTTGTCTCTG    32520
CTCAGTTGCT GTTACCTGTT   ACCCTCCTTT    GTCACTGTIT CCCTCCTTTG TCTGAAATCT 32580
ACAGACCCTT GAAGATGCAG CTCTCTACTA CTAGGCTCTA GTAGAAAGAA CTGCTATTTC 32640
CCGAGGACTA GGCACAAGGA 

  CTTGTACTCA GTTCTTAAAT ACGCTGCTCC TATACCCTCA 32700
TAACCACCTG ACTGTCCACA   CTTTAACGAT      ACACAGCTGA      AGCTTTGGTC    TGATTCCAAA 32760
GCCTGTGCAA GAATGTTTGG TGTGATAAGG CCTGGATAGA GGCTCACACC TTCCTAAAGC 32820   CTAAGCCTGC    CACACACTGG CTGGCACACA GGAAGCACCG GGTAAGAGTA GCTGCTGTTG 32880   CAGATGTTGT    CAAGTGGGAC CCTTTAAACC CAGTCTAAGA TGTGTGTGGG TGTGCGGGAA 32940
TGGGGAGAAG ACAATGGGCA   TGGCCTCTTA    CCTGATCTTG   GCCTTTGCAG    GGCTGAATCC 33000
CTACCCTGGC ATCCTGGTGA   ACAGCAAGTT    CTATAAACTG GTGAAGGATG GATACCAAAT 33060
GGCCCAGCCT GCATTTGCCC CAAAGAATAT GTAAGCGAAG GGATCCCAGG   GAGGGAAAAC.    33120
GACACCCCAG GCTITCGCTG GAAAGGGATG GAAGGCCGTG TGGCCCTGAT CTTTCCCTGT 33180
CCAAAATGTT 

  CCAGGGTCAG ACTTTATCTC TCCCATAGTG GACACAACAA GCCCCTTTTG 33240
AGTTCAAGCT ATGGGGGATG TTCTCAGAGA AGCAGCTGTT CACTAGGGCT GGTCCTAACC 33300
GACCACTTTT CCTTTTTTTT TTTTTTTTTT TTTGAGACAG CATCTTGCTC TGTAGCCCGG 33360
GCTGGAGCGC AGTGATGTGT GCAATCATAG CTCACTGCAG CCTCAATCTT CAGGGCTCAA 33420
GCAATCCTTT GGCCTCAGCC TCCCAAACAG   CTGGGACTAC    AGGTGTGCAC CACCAAGCCC 33480
AGCTATTTTT AAAAAATTTT TTAGTAGAGA TGGGATCTCA CTATGTTGTC CAGGCTGGTC 33540
TGGAACTCCT GGCCTTATGC AATCCTCCTG CATCAACCTC CCAAAGTGTT   GGGATTACAG    33600
GAATGAGCCA CTGCACCTGT CCCTAAACAG ACTTTTAAGA GATCGTTATT ACAGTTACCC 33660  
TGAGGATACC AAAATGGCCT CATCTGTCAG AATGAGGGTG ATGAGAGTAC CCTTCTGCAA 33720
GGGTTACTGT GAGGATTAAA TGGTAAAGCA TGCCAAGGAC TTGGCATAGG   TTTTATACTA    33780
AACTTACTTT GACTGGGTTT GGGGACCTCT GCTGGGTAGG TCTCTCTAGG GGTGTGTGTT 33840
AATGGCCCCT GGACCCTAGG 

  GAGCTGCCCA TGGGCATCCT   CTGTCCTATC    TCCCAGATAC 33900
AGCATCATGC   AGGCCTGCTG      GGCCTTGc,AG    CCCACCCACA GACCCACCTT CCAGCAGATC 33960   TGCTCCTTCC    TTCAGGAGCA GGCCCAAGAG GACAGGAGAG AGCGGGTGAG TGGGGTGAGG 34020
CTTGGGGTGG GTGGCCGGTA   AAGCACGTTG    GGCTGGGCCT GATGGATCTG GACTGACAGT 34080
TTCTGGTCCC TCCCACCCTC AGGACTATAC CAATCTGCCG AGCAGCAGCA GAAGCGGTGG 34140
CAGCGGCAGC AGCAGCAGTG AGCTGGAGGA GGAGAGCTCT AGTGAGCACC TGACCTGCTG 34200
CGAGCAAGGG GATATCGCCC AGCCCTTGCT GCAGCCCAAC AACTATCAGT TCTGCTGAGG 34260
AGTTGACGAC AGGGAGTACC ACTCTCCCCT CCTCCAAACT   TCAACTCCTC    CATGGATGG 34320
GCGACACGGG GAGAACATAC AAACTCTGCC TTCGGTCATT TCACTCAACA   GCTCGGCCCA    34380
GCTCTGAAAC TTGGGAAGGT GAGGGATTCA GGGGAGGTCA GAGGATCCCA CTTCCTGAGC 

  34440
ATGGGCCATC ACTGCCAGTC AGGGGCTGGG GGCTGAGCCC TCACCCCCCG CCTCCCCTAC 34500   TGTTCTCATG    GTGTTGGCCT   CGTGTTTGCT    ATGCCAACTA GTAGAACCTT   CTITCCTAAT    34560
CCCCTTATCT TCATGGAAAT GGACTGACTT TATGCCTATG AAGTCCCCAG GAGCTACACT 34620
GATACTGAGA AAACCAGGCT CTTTGGGGCT AGACAGACTG GCAGAGAGTG AGATCTCCCT 34680   CTCTGAGAGG      AGCAGCAGAT    GCTCACAGAC CACACTCAGC TCAGGCCCCT TGGAGCAGGA 34740
TGGCTCCTCT AAGAATCTCA   CAGGACCTCT    TAGTCTCTGC CCTATACGCC GCCTTCACTC 34800
CACAGCCTCA CCCCTCCCAC CCCCATACTG GTACTGCTGT AATGAGCCAA GTGGCAGCTA 34860
AAAGTTGGGG GTGTTCTGCC CAGTCCCGTC ATTCTGGGCT AGAAGGCAGG GGACCTTGGC 34920   ATGTGGCTGG    CCACACCAAG CAGGAAGCAC AAACTCCCCC AAGCTGACTC ATCCTAACTA 34980
ACAGTCACGC CGTGGGATGT CTCTGTCCAC ATTAAACTAA 

  CAGCATTAAT GCAGTCAGCC 35040
TCTGGTTCTT TGTGCCACAT GAGTACCTGC AAATTCCCTG GAACGTCTTT CTTTCCTTCC 35100   (2) INFORMATION FOR SEQ ID   NO:20:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 3565 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID   NO:20:   
GCAGCCGGGC GGCCGCAGAA GCGCCCAGGC CCGCGCGCCA CCCCTCTGGC GCCACCGTGG 60
TTGAGCCCGT GACGTTTACA   CTCATTCATA    AAACGCTTGT TATAAAAGCA GTGGCTGCGG 120
CGCCTCGTAC TCCAACCGCA TCTGCAGCGA GCAACTGAGA AGCCAAGACT GAGCCGGCGG 180
CCGCGGCGCA GCGAACGAGC   AGTGACCGTG    CTCCTACCCA GCTCTGCTTC ACAGCGCCCA 240
CCTGTCTCCG CCCCTCGGCC CCTCGCCCGG   CTTTGCCTAA    CCGCCACGAT GATGTTCTCG 300
GGCTTCAACG CAGACTACGA GGCGTCATCC TCCCGCTGCA   GCAGCGCGTC    CCCGGCCGGG 360
GATAGCCTCT CTTACTACCA CTCACCCGCA GACTCCTTCT CCAGCATGGG CTCGCCTGTC 420
AACGCGCAGG TAAGGCTGGC TTCCCGTCGC CGCGGGGCCG   GGGGCTTGGG    GTCGCGGAGG 480
AGGAGACACC GGGCGGGACG CTCCAGTAGA TGAGTAGGGG GCTCCCTTGT GCCTGGAGGG 540
AGGCTGCCGT GGCCGGAGCG GTGCCGGCTC   GGGGGCTCGG    GACTTGCTCT 

  GAGCGCACGC 600   ACGCTTGCCA    TAGTAAGAAT TGGTTCCCCC   TTCGGGAGGC    AGGTTCGTTC TGAGCAACCT 660
CTGGTCTGCA   CTCCAGGACG      GATCTCTGAC    ATTAGCTGGA   GCAGACGTGT    CCCAAGCACA 720
AACTCGCTAA CTAGAGCCTG GCTTCTTCGG GGAGGTGGCA GAAAGCGGCA ATCCCCCCTC 780
CCCCGGCAGC CTGGAGCACG GAGGAGGGAT GAGGGAGGAG   GGTGCAGCGG    GCGGGTGTGT 840
AAGGCAGTTT CATTGATAAA AAGCGAGTTC ATTCTGGAGA CTCCGGAGCG GCGCCTGCGT 900
CAGCGCAGAC GTCAGGGATA TTTATAACAA ACCCCCTTTC AAGCAAGTGA TGCTGAAGGG 960
ATAACGGGAA   CGCAGCGGCA    GGATGGAAGA GACAGGCACT GCGCTGCGGA ATGCCTGGGA 1020  
GGAAAAGGGG GAGACCTTTC ATCCAGGATG AGGGACATTT AAGATGAAAT GTCCGTGGCA 1080
GGATCGTTTC TCTTCACTGC TGCATGCGGC ACTGGGAACT CGCCCCACCT GTGTCCGGAA 1140
CCTGCTCGCT CACGTCGGCT TTCCCCTTCT GTTTTGTTCT 

  AGGACTTCTG CACGGACCTG 1200   GCCGTCTCCA    GTGCCAACTT CATTCCCACG GTCACTGCCA TCTCGACCAG TCCGGACCTG 1260
CAGTGGCTGG TGCAGCCCGC CCTCGTCTCC TCTGTGGCCC   CATCGCAGAC    CAGAGCCCCT 1320
CACCCTTTCG GAGTCCCCGC CCCCTCCGCT GGGGCTTACT CCAGGGCTGG CGTTGTGAAG 1380
ACCATGACAG GAGGCCGAGC GCAGAGCATT GGCAGGAGGG GCAAGGTGGA ACAGGTGAGG 1440
AACTCTAGCG TACTCTTCCT GGGAATGTGG   GGGCTGGGTG    GGAAGCAGCC   CCGGAGATGC    1500
AGGAGCCCAG TACAGAGGAT GAAGCCACTG ATGGGGCTGG CTGCACATCC GTAACTGGGA 1560
GCCCTGGCTC   CAAGCCC TT    CCATCCCAAC TCAGACTCTG AGTCTCACCC   TAAGAAGTAC    1620   TCTCATAGTT    TCTTCCCTAA GTTTCTTACC GCATGCTTTC AGACTGGGCT   CTTuTTTGTT    1680   CTCTrGCTGA    GGATCTTATT TTAAATGCAA GTCACACCTA TTCTGCAACT 

  GCAGGTCAGA 1740
AATGGTTTCA CAGTGGGGTG CCAGGAAGCA GGGAAGCTGC AGGAGCCAGT TCTACTGGGG 1800
TGGGTGAATG GAGGTGATGG   CAGACACTTT    TACTGAATGT   CGGTCTTTTT    TTGTGATTAT 1860
TCTAGTTATC TCCAGAAGAA GAAGAGAAAA GGAGAATCCG AAGGGAAAGG AATAAGATGG 1920
CTGCAGCCAA ATGCCGCAAC   CGGAGGAGG    AGCTGACTGA TACACTCCAA GCGGTAGGTA 1980
CTCTGTGGGT TGCTCCTTTT   TAAAACTTAA    GGGAAAGTTG GAGATTGAGC ATAAGGGCCC 2040
TTGAGTAAGA CTGTGTCTTA TGCTTTCCTT TATCCCTCTG TATACAGGAG ACAGACCAAC 2100
TAGAAGATGA GAAGTCTGCT TTGCAGACCG AGATTGCCAA   CCTGCTGAAC,

      GAGAAGGAAA 2160
AACTAGAGTT CATCCTGGCA GCTCACCGAC CTGCCTGCAA GATCCCTGAT GACCTGGGCT 2220
TCCCAGAAGA GATGTCTGTG GCTTCCCTTG ATCTGACTGG GGGCCTGCCA GAGGTTGCCA 2280
CCCCGGAGTC TGAGGAGGCC TTCACCCTGC CTCTCCTCAA TGACCCTGAG CCCAAGCCCT 2340
CAGTGGAACC TGTCAAGAGC ATCAGCAGCA TGGAGCTGAA GACCGAGCCC TTTGATGACT 2400
TCCTGTTCCC AGCATCATCC AGGCCCAGTG GCTCTGAGAC AGCCCGCTCC GTGCCAGACA 2460  
TGGACCTATC TGGGTCCTTC TATGCAGCAG ACTGGGAGCC TCTGCACAGT GGCTCCCTGG 2520
GGATGGGGCC CATGGCCACA GAGCTGGAGC CCCTGTGCAC TCCGGTGGTC   ACCTGTACTC    2580
CCAGCTGCAC TGCTTACACG TCTTCCTTCG TCTTCACCTA CCCCGAGGCT GACTCCTTCC 2640
CCAGCTGTGC AGCTGCCCAC CGCAAGGGCA GCAGCAGCAA TGAGCCTTCC TCTGACTCGC 2700
TCAGCTCACC CACGCTGCTG GCCCTGTGAG GGGGCAGGGA AGGGGAGGCA GCCGGCACCC 2760
ACAAGTGCCA CTGCCCGAGC TGGTGCATTA CAGAGAGGAG AAACACATCT TCCCTAGAGG 2820
GTTCCTGTAG ACCTAGGGAG GACCTTATCT  <RTI  

   ID=109.2> GTGCGTGAAA    CACACCAGGC TGTGGGCCTC 2880
AAGGACTTGA AAGCATCCAT GTGTGGACTC AAGTCCTTAC CTCTTCCGGA GATGTAGCAA 2940
AACGCATGGA GTGTGTATTG TTCCCAGTGA CACTTCAGAG AGCTGGTAGT   TAGTAGCATG    3000
TTGAGCCAGG CCTGGGTCTG TGTCTCTTTT CTCTTTCTCC TTAGTCTTCT CATAGCATTA 3060
ACTAATCTAT TGGGTTCATT ATTGGAATTA ACCTGGTGCT GGATATTTTC AAATTGTATC 3120
TAGTGCAGCT GATTTTAACA ATAACTACTG TGTTCCTGGC AATAGTGTGT TCTGATTAGA 3180
AATGACCAAT ATTATACTAA GAAAAGATAC   GACTTTATTT    TCTGGTAGAT AGAAATAAAT 3240   AGCTATATCC    ATGTACTGTA GTTTTTCTTC AACATCAATG   TTCATTGTAA    TGTTACTGAT 3300
CATGCATTGT TGAGGTGGTC TGAATGTTCT GACATTAACA GTTTTCCATG AAAACGTTTT 3360
ATTGTGTTTT TAATTTATTT ATTAAGATGG ATTCTCAGAT   ATTTATATTT    TTATTTTATT 3420   TTTTTCTACC    TTGAGGTCTT  <RTI  

   ID=109.9> TTGACATGTG    GAAAGTGAAT TTGAATGAAA AATTTAAGCA 3480   TTGTTTGCTT    ATTGTTCCAA GACATTGTCA ATAAAAGCAT TTAAGTTGAA   TGCGACCAAC    3540
CTTGTGCTCT TTTCATTCTG GAAGT 3565 (2) INFORMATION FOR SEQ ID NO:21:
 (i) SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 695 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)  
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:21:
GGTAACCTCA GCCCTCGGGC GCCTCCCTTT   AGCCTTTCTG    CCGACCCAGC AGCTTCTAAT 60
TTGGGTGCGT GGTTGAGAGC GCTCAGCTGT CAGCCCTGCC   TITGAGGGCT      GGGTCCCTTT    120
TCCCATCACT GGGTCATTAA GAGCAAGTGG GGGCGAGGCG ACAGCCCTCC CGCACGCTGG 180
GTTGCAGCTG CACAGGTAGG CACGCTGCAG TCCTTGCTGC CTGGCGTTGG GGCCCAGGGA 240
CCGCTGTGGG   TTTGCCCTTC      AGATGGCCCT      GCCAGCAGCT    GCCCTGTGGG GCCTGGGGCT 300
GGGCCTGGGC   CTGGCTGAGC    AGGGCCCTCC TTGGCAGGTG GGGCAGGAGA CCCTGTAGGA 360
GGACCCCGGG CCGCAGGCCC TTGAGGAGCG ATGACGGAAT ATAAGCTGGT GGTGGTGGGC 420
GCCGACGGTG TGGGCAAGAG TGCGCTGACC ATCCAGCTGA TCCAGAACCA TTTTGTGGAC 480
GAATACGACC CCACTATAGA GGTGAGCCTG GCGCCGCCGT CCAGGTGCCA GCAGCTGCTG 540
CGGGCGAGCC CAGGACACAG CCAGGATAGG GCTGGCTGCA GCCCCTGGTC 

  CCCTGCATGG 600
TGCTGTGGCC CTGTCTCCTG CTTCCTCTAG AGGAGGGGAG TCCCTCGTCT CAGCACCCCA 660
GGAGAGGAGG GGGCATGAGG GGCATGAGAG GTACC 695 12) INFORMATION FOR   SEO    ID NO:22:
 (i) SEQUENCE   CllARACTERISTlCS:   
 (A) LENGTH: 4522 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:22:   CAGCTGAGTG    AGGCGGGCGC GCGTGGGAGG GTGTCCCAAG GGGAGGGGTC CGCGGCCAGT 60
GCAGGCCCGG   AGGCGGGGGC    CACCGGGCAG GGGGCGGGGG TGAGCCCCGA CGGCCAACCC 120
GTCAGCTCTC GGCTCAGACG GGCGGGAACC   ACAGCCCCGC    TCGCTGCCCA TTGTCTGCGC
CCCTAACCGG TGCGCCCTGG TGCCACAGTG CGGCCCGGAG GGGCAGCCTC CTCCCGTCAC 240  
TTCAGCCAGC GCCGCAACTA   TAAGAGGCGG      TGCCC;CCCC; 

  C      CGTGGCCGCC    TCAGCCCACC 300
AGCCGGGACC   GCGAGCCATG    CTGTCCGCCG CCCGCCCCCA   GGGTTGTTAA    AGCCAGACTG 360
CGAACTCTCG CCACTGCCGC CACCGCCGCG TCCCGTCCCA CCGTCGCGGG CAACAACCAA 420
AGTCGCCGCA ACTGCAGCAC AGAGCGGGCA AAGCCAGGCA GGCCATGGGG CTCTGGGCGC 480
TGTTGCCTGG CTGGGTTTCT GCTACGCTGC TGCTGGCGCT GGCCGCTCTG CCCGCAGCCC 540
TGGCTGCCAA CAGCAGTGGC CGATGGTGGT AAGTGAGCTG GTG 
AGCTCGGGGC CAGACTTCTA CCAGGCGTTT   TCCAGCCGTG    CACCCTGGAA ACGAAGCTTA 1740
ACTTTTCTGA   GCTACTGCCC    CAGATAAAGA AAGTTTCGGG TCGCGGACGC CGGCTGACCG   1800   
CCGCTTTCCC CCAGCCTCTC TCAAAAGCGC   CTGGGAAGCT    GCTCTCTGCA GGCGTGTGTC 1860
TGGCCTCTCG CCCAGCAAGG CTTGCACCGC CAAAATGGGC CGAAAGTTTT   GGGCTGCGAA    1920
GAAGTCTTGG GGATGTATGG 

  TTCTTCCGCT CCCCTCTCTT   CGGTTTGTCT    CTCTGGGGCT 1980
GCTCCACTTC CGCTATCGAG CCAAAATGCG CCCTAGAATC TCCCAGTAAG GTGTGATTAC 2040
GCCCGTGGAC GTGGCTGCGT GCCCACGCAC CTGCTTTCTC TACTAGCCCT   AGAC.ACCAGC    2100
TTTCCAGCAC TGCCGGCCCT GGTCCTCAGG   ACTCAAAGTG    CGGAGTCGGG GGTGGGATTC 2160
CGGTCCCAAG CCCTTCATGA GGGTGCTGGC CGCGCCCCGC GTACCCCCTC GCTGATCCCC 2220
GCTCCCTTCT CCCACAGGCT GTCGAGAAAC   GGCGTTTATC    TTCGCTATCA CCTCCGCCGG 2280
GGTCACCCAT TCGGTGGCGC GCTCCTGCTC AGAAGGTTCC   ATCGMTCCT    GCACGTGTGA 2340
CTACCGGCGG CGCGGCCCCG GGGGCCCCGA   CTGGCACTGG    GGGGGCTGCA GCGACAACAT 2400
TGACTTCGGC CGCCTCTTCG GCCGGGAGTT CGTGGACTCC GGGGAGAAGG GGCGGGACCT 2460
GCGCTTCCTC ATGAACCTTC ACAACAACGA GGCAGGCCGT ACGGTGAGCT TTGAGAGGCT   2520   
CCGCACCCTA 

  AGCGGAGCGG CAGGGGCCAA   CCTCGGGCTG      GGGAAGTGAC    GGTCGGTGAG 2580
ATAAGGCAAG GGGCACCAGG AGAGGGCGTC   CTGGGAGAC;C    CGGAGGCTTG GAACGAAGAC 2640
GGAGAATAGA GGAGACAGTG GCTGAGGGCA AAGGTATGTC TGGCCCGCGG ACAGGTAGAA 2700
GAGGTTGCAA ATCAAGCACA GTCTCTTCGC TGTACAGATT CGAAAAATAA GCCTGAGAGG 2760
CCGAGACTGA CTCGCCGCGG CGGAGCAGGG TTGGGCAGGG TTTCCAAATC TCAGCGGAAC 2820
ATTTCGCGCC TCCCTTCCCC TGGGCTCAGC TAGGCCTGGG   CCTTTGCTGA    GGTCCGGCCC 2880
CCGTGGCGTC CGGGAGAGGG CAGTGTCTGG GAGGGTGACT CTGGCCCGGT GCCCTGGGAC 2940
ACTCTTTCTT CCCCTATCCC CGCAGACCGT ATTCTCCGAG ATGCGCCAGG AGTGCAAGTG 3000
CCACGGGATG TCCGGCTCAT GCACGGTGCG CACGTGCTGG ATGCGGCTGC CCACGCTGCG 3060
CGCCGTGGGC GATGTGCTGC GCGACCGCTT CGACGGCGCC TCGCGCGTCC TGTACGGCAA 3120  
CCGCGGCAGC AACCGCGCTT CGCGAGCGGA GCTGCTGCGC CTGGAGCCGG AAGACCCGGC 

  3180
CCACAAACCG   CCCTCCCCCC    ACGACCTCGT CTACTTCGAG AAATCGCCCA ACTTCTGCAC 3240
GTACAGCGGA CGCCTGGGCA CAGCAGGCAC GGCAGGGCGC GCCTGTAACA GCTCGTCGCC 3300
CGCGCTGGAC GGCTGCGAGC TGCTCTGCTG CGGCAGGGGC CACCGCACGC GCACGCAGCG 3360
CGTCACCGAG CGCTGCAACT GCACCTTCCA CTGGTGCTGC CACGTCAGCT GCCGCAACTG 3420
CACGCACACG CGCGTACTGC ACGAGTGTCT GTGAGGCGCT GCGCGGACTC GCCCCCAGGA 3480
ACGCTCTCCT CGAGCCCTCC CCCAAACAGA CTCGCTAGCA CTCAAGACCC GGTTATTCGC 3540
CCACCCGAGT ACCTCCAGTC ACACTCCCCG CGGTTCATAC GCATCCCATC   TCTCCCACTT    3600
CCTCCTACCT GGGGACTCCT CAAACCACTT GCCTGGGGCG GCATGAACCC TCTTGCCATC 3660
CTGATGGACC TGCCCCGGAC CTAACCTCCC TCCCTCTCCG CGGGAGACCC CTTGTTGCAC 3720
TGCCCCCTGC TTGGCCAGGA GGTGAGAGAA GGATGGGTCC CCTCCGCCAT GGGGTCGGCT 3780
CCTGATGGTG TCATTCTGCC TGCTCCATCG CGCCAGCGAC CTCTCTGCCT CTCTTCTTCC 3840
CCTTTGTCCT GCGTTTTCTC CGGGTCCTCC TAAGTCCCTT CCTATTCTCC 

  TGCCATGGGT 3900
GCAGACCCTG AACCCACACC TGGGCATCAG GGCCTTTCTC CTCCCCACCT GTAGCTGAAG 3960
CAGGAGGTTA CAGGGCAAAA GGGCAGCTGT GATGATGTGG GAATGAGGTT   GGGGGAACCA    4020
GCAGAAATGC CCCCATTCTC CCAGTCTCTG TCGTGGAGCC   ATTGMCAGC    TGTGAGCCAT 4080
GCCTCCCTGG GCCACCTCCT ACCCCTTCCT   GTCCTGCCTC    CTCATCAGTG TGTAAATAAT 4140
TTGCACTGAA ACGTGGATAC AGAGCCACGA GTTTGGATGT TGTAAATAAA   ACTATTTATr    4200
GTGCTGGGTC CCAGCCTGGT TTGCAAAGAC CACCTCCAAC CCAACCCAAT CCCTCTCCAC 4260
TCTTCTCTCC TTTCTCCCTG   CAGCCTTITC    TGGTCCCTCT TCTCTCCTCA GTTTCTCAAA 4320   GATGCGTTTG    CCTCCTGGAA   TCAGTATTTC    CTTCCACTGT   AGCTATTAGC    GGCTCCTCGC 4380
CCCCACCAGT GTAGCATCTT CCTCTGCAGA ATAAAATCTC TATTTTTATC GATGACTTGG 4440
TGGCTTTTCC TTGAATCCAG 

  AACACAACCT TGTTTGTGGT GTCCCCTATC CTCCCCTTTT 4500
ACCACTCCCA GCTTGGAAGC TT 4522   (2) INFORMATION FOR SEQ ID   NO:23:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 11558 base pairs
   (R)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA {genomic)
   lxi)    SEQUENCE DESCRIPTION:

   SEQ ID   NO:23:   
GGATCCTCCG AGGCCTGCCA GACGAGAGCT AACCCCACCA CTCCGGGTGC CCAGTTGGTG 60
TGCGCAAAAG GAGATAGCAT CTCCAGACCC GGCCTGCCCC   GCGCCTTGCA    AGGCTGAGGA 120
CAGCGCCACT GCTCCTGCAG GAAGCGCCGG GCGCAGACAC AAACCCGGAG CTCCCCACGC 180
GTGCCCGCGC CCCGGAGCCT CCCCGCCGCC GCCCTCCGCG GTCCCCTTCA TTATGCGCCG 240
CCTTTAATGG GCGTTTGTCA GCTCGACTTC CCCGCAAGTT GTTTTCACGG ACATCAGTCA 300
TCGGCGGCGG CCCCATTGTG CAGGGGGATT GATGGGGAGC GGGAGGGGGT GACAGGGCCT 360
GGGGCGGCCT CCTCAAGGCC TCGGTCTATA ATTTTCGGAG GCATAATTGG TCTGGGGGAG 420
GGGGCGGGGG AGGGGCGGGT AGGGGACCTT TCAGAGCCAG GAGGGCTTTC GGGGGCGTGG   480   
GGCGCGCTGC GGAGCGGAGC CGCGGCTCGA CGGCGGTGCG CTGGCGGCGA GTGTATGCAG 540
ACGGCGCCCG GCCCGAACCC CGAGCCCCGC GGGGCTCCCC ACCCGCCGGC CTCCCGCCCC 600
TCCCGCGCCT CCGCCTGGGG ACCACGTCGG   CCTTTTGTTG    GCGAACCGTC CTTTCTTTCA 

  660
GCGCTTTGCG CAGCAACGGA   AATTTCATTG    CTCCTGGGTG GAAATTAAAG GGACTCGCGT 720
TCCCTCTCTC CCTCTCCCTC TCCCACTCTC CCTCTCTTTC TCTCTCTCGC CCACCCTTCC 780
CCCTTCTTCC CCCACCTTTC CCGCGAAGCC GGAGTCAGCA TCTCCAGGCG CGGGATCCCG 840
CTCCGAGCAC CTCGCAGCTG TCCGGCTGCC   GCCCCTTCCh    TGGGCGCCGC GCTCGCCTGC 900
AGCCGCCGCC GCCGCGGGGC GGGCGCGATG CCACGATGGG   CCTAATCTr,G    CTGCTACTGC 960
TCAGCCTGCT GGAGCCCGGC TGGCCCGCAG CGGGCCCTGG GGCGCGGTTG CGGCGCGATG 1020  
CGGGCGGCCG TGGCGGCGTC TACGAGCACC TTGGCGGGGC   GCCCCGGCGC      CGCAAGCTCT    1080
ACTGCGCCAC GAAGTACCAC CTCCAGCTGC   ACCCGAC;

  CCG    CCGCGTCAAC GGCAGCCTGG 1140
AGAACAGCGC CTACAGTGAG TGCCGGACGC TGCGGGGCCC CGGGGGAAGC GGCGCCGGGA 1200
GGGGTCGGGC   CCGGGAGAAG    GCGCGCTGCG GGGCCCCGCG GGGGAGGCGG CGCCGGGGAG 1260
GGGTCTGGCC CGGGAGAAGG CATGGTGCGC CCGGGGTGTC CGGAAAAGA CCGTCTGCCT 1320
CCCGCTGCCA   GAAGGGGAAT    GCCAGGGTGC CCTCCTCAAC CTACACGTCC GGGAGAAGAG 1380
CGCGCGCTGG GGTTCGAGCA GAACTCGGGG GCATGGGCGT TCACGTCCGA AGAGGGCGCC 1440
GGCGGCTGTC AGAGTCCGTC CCCGGTCCGG   CCCGCTGC;

  TC    TGAGGGGACG CGAGCTAGGC 1500
GACCCCGGGG CTCCAGGCTC TGCTGCTTTG GGCAGCTCTG   ACAAGTTTAA    GCCCTTTGAA 1560
TGTGTCGGAG   AAAAGGAGCC    GGACAAGGCA   TTTATCATCT      TCTTTATTAT    TTTGACGACT 1620
TCTCCTCCTC CTGCCGACCC CTGGACGCCC CGCCGTCCCC TCCGCCCTCC   CCGCTCGCGG    1680   CTGCCCAGGT    GGCCGCCCCC GCTGCTGCCT CTGCGCGGAG GACTCTTGCC CTGCGGAGCT 1740
CGGTTCCCTG GCCGCGGCCG CCACCGACAG TTTTCCCCGC GCTGGAATCT GCACCTCCCC 1800
CGCCTCCGCC CTGGCCGCAC AGCGACAGGA GGGTGGAGGC CCTCGCCGTC GGGACGTGCG 1860
GATCACGAGC GCGGAACGGT GTCCGCCCGG GCCTGGGGGT GCAGACACAC ACACTCCGGC 1920
CCCCGCACGC AGGACCCGCG GCCCGGGCTG CGCTCACCGC GGGAGTCTGC CGGACTACAC 1980
GGTTGGGCTC CTCTGGTCAC AGGGACCTGA   GGCCCGCGCC    GAGCCCTTTG AGGAGCAGGA 2040
TAGCGGAGCT CAGGGCCCGG 

  GAGGACCGCG TGGGGAGCGT GGGAGGGCAG TCAAGACCAC 2100
AGCTGTCCTC GGGTGCTCCG CGCGGCGCTC GGCTCCGGCC CCGGGCGCAG GAAGCGGTTC 2160
CGCCGCTTGA AGGTGGCGGC GGCGGCCTCA GCAAACCGCG GCTTCCTCCA GGAAAGCCGC 2220
AGCCCTGAGA GGGCGTCCTG GGGACATGCG CCTCCGGAGC   CGCACGGTGG    GCACCAGCTG 2280
TCACCAGGGG GTCCGAGTGC GCGGAATTCG TCTCACTAAG ACACTCCGGT TCTCTCCAAA 2340
GCCAGGCTCC CCCTCGGAGT CTCACAGCAT CCAAACTTCT   TGGTGTTGGC    TGCTCACGGG 2400
GAGGGGAGGG CGCGCGCCCG CAGCCGCCCC TGTCCTGCGT CGAGACTCGT GCTTCGCTGG 2460  
TCCCCGGTCA GGCACCGCCG ATGCCGCCCA   GCCTGCGCAC      TGGGAAGGCG      GAGGCTCGC    2520
AGCCTGCACC ACAGCACCCC TGGGCTGGAG   CAAAAGCCCG    GTGGTGACCG CGTCTGTGCT 2580
CGGACCGCGT GCCAGGAGGG CGCTCCTGAG AGGCATGCCT TGGAGAGGGT GCAGGCAGTC 2640
GCCCCAATCC CCTCGCAGCC TCTATTGGGA 

  GACAATGACC CCAACCCGTC CTTTGATGTA 2700
GTCCCCCGCC CCCAGCCCCC ACCACAGCAC TCGTGTATCC AGAAGGAAAG GCGGGAGGGG 2760
AGATTTAAAC TTTCTTATCC CTGGGGAGTG   GGTGAGACCC    GTCCAGCTTC CCTCTGCGGG 2820
CTCCAGGGTC TAAACTGGCT TCCTGCCCTT CCAGGTCCCC CGGCGAGTAC AATGATCTCC   2680   
CGCCAGGTCT ATTGCCAGCA TGATTTGGGT GGCAGGCACC CTGGCTGTGT TATTGCCAGT 2940   GGTTTATATT    ATCAGCCTGG CTCATCAGGG CCCAGCTTTC CCGCTGGCAG   GCACAGGCAT    3000
TGGGGACCGT GCAGTCCCAG AGCTCAGACT CCCATGGCTG CCGCCAGGGC   TTGATTTCCC    3060
GCTCAAGCAC ATGTGCAGGG GCCTGACAGT CACCCAGCCA TAGTGGTCCC CACTTGCTTG 3120
TCTGTCGGAT GATGATGGCA GCTGGCAAGG TGTTGTGAGG CTCGAATGAA AGCCAGGGTG 3180
CAGGCAGCGT CAGCAGGTGG GAATGTTAAT TTCATTGTTA CCCTCCCAAG TTTGAATGAA 3240
GAGAAGCCTT CCCTGATGTT CCCTTCTCTA CCTCCTGTCC GGTGACTTCT CCCTTCCTGA 3300
ACTTCCACTC 

  ACTCCCCGAC CTGTGGGGTG TGTGCTACCC TCCCCAGCCC TGAGCCCGGG 3360
GTGTGGCTTT GGGCAGGGCC AGCTGGGCCT CAGCCGCCCC CTCCGTGGGG GCGGCGGGAG 3420
TGAGGCACCT CTCATTTCTT   CTAGGTATTT    TGGAGATAAC GGCAGTGGAG GTGGGCATTG 3480
TGGCCATCAG GGGTCTCTTC TCCGGGCGGT ACCTGGCCAT GAACAAGAGG GGACGACTCT 3540
ATGCTTCGGT GAGTCCAGGC TGTCACGTGG GTGGGCGCTG ACGGAGTAGC GGTCTGGCCT 3600
GCACATCAAG CCAGGGGACG GGGGATGTGG GCAGTAGAAT GCTTTGCCAA GGGTACATGG 3660
GATCCAAGCT AGGACCAGAC CCTGGCCCAG GGCTCCACGC CCAGTGATCT   TTGGCTGTGT    3720
CTGTTAGAGG CTGCTCCGCG AGTGACCTGG AGCCTGGCCC TGGGGGACCT GGGATCTGGA 3780
GAATGCCAGG TTAGCAAAGG TTTCCCCCAT CCTTGTCATC ACTACCACCC TCCCTTGAGA 3840
GTAGCTGAGA GCAGGGAAGT GATTGTTCTC CAAATTTCCA CCAAAATAAA   TGGACCCAAG    3900  
ACAACCTGGG AGTGTTCCTT GGGGCAGCCA GAGCTCTCCT GGGAGCATGG AGAGGAGGGC 3960
GCTGGCCCAG CTCCACCGGC TCTCTCCAAG 

    GGTGGAAAGG    CGAGAGCTGA AGCCTAGGAG 4020
GGGAAGGGGG ATGGCGCCCA TGTCCCGGGC   ACACAGGAGC    CTTGGAGCCC TGGCTTGGGA 4080
CCCAGTCTAT CTACTGCCTG GGCCTCCGTG TAACCAAAAA GGGTCTGTGGG 4140
TATGGCAGCG CCCCTCTTCA TAAGGGGTAG GGGTGGGGAA   TACACAGAGT    AAAATACATG 4200
TCACAGGGAA ATTTGCTACC TCCAACTAGT CATTACATGC AATTTGGCTG ATACTTCCTT 4260
GGGCAATGAG   AGGTITTCCA    TCCATGAGTA GCCTGGCTGA CGCGGCCCAA GGACAATCTC 4320
CCTGCAGTGA   GCTCTCTGCT    CAGTCCTGCT CACAGAGGAC ACATCCCGCA   GCTCCCTCTC    4380
GCAGAAGCTG ATGATTTCAT CACAGATTTT TAGCCGTTTT GCTAAAGGAA GGTCCAGAAA 4440
GCCGGGATGC GCCCCTTCAT   TTTCTCTGGT    CCAGAGGCTA CTCCCTCCTT CCTCCCATCC 4500
ACTCACCCAT CCACCCATCC ACCCATTCAC   CCATCChCTC    ATCCACCCAT CCACCCATCC 4560
ATCCATCCAC 

  TCATCCACCC ATCCACCCAT CCATCCATCC ACCTATCCAT CCATCCATCC 4620
ACCCATCCAC CCATCCTTCC ATTTACCCAT CCACCATCCA CCTATCCATC CATCCATCCA 4680
CCCATCCACC CATCCACCCA TTTACCCATC CACCCATCCA CCCATCCACC TATCCATCCA 4740
TCCATCCATC CACCTATCCA CCCATCCACT CATCCACTCA CCCATCCACC TATCCACCCA   4900   
CCCACTCACC CATCCATCCA CCCACCCACT CACCCATCCA TCCATACACC TATCCATCTG 4860
ACATTCAGTC CATTCATCAG TCAGTGTCCT GGAAGCTGTG TCTGGGAGCA GGGGCCCTCA 4920
TGGTGCCAGC TTCTGCCATA GGGGAGCCAG GATTTGGAGA GACAGAATAA AGCATGACAT 4980
GAGGGGGTCC CAGTGGTTCA GAGCCCACCT GGGGCTTCCG TGCCTGAGAA CTCACAGCCT   5040      GGCTTTGAGA    AGGGTGGACA GAGGCTCCTA GCCCCACCAG   GC.ATGCTTAG    CCAAGCAGTC 5100
TGGCTGGAGG GTGTGGAACT TTCCAGAGTG   CCCAGTG(;

  AG    AAGTTCCCAT TGCCCTGCAG 5160
ACAACCTGGG AGGCATAGTA GCCTGGATGC CAACTCCGTC ACCTGCCACC TGCCACCTGA 5220
TACCACAGTC CTGCGTGTGG CCAGCTTGCC TAGGAGTGCT GTCCCACCAC   GGGGCTCCCT    5280   GGACTTTGCC    GGCAGCATGC TTGCCCTCAG GCCAGCTCAT   CTCACTGTGG    GCCAGTGAGC 5340  
ACTGCACCCT GACACTCCTG GTCTGGCCCT GACCTCCCTT CTGAGGTATA GACCACCCTC 5400
CCCCAACATC CTGCTGACTC AGACACTCCA ACCGAACTCA GCAGCTCCCC GACTCCCCAT 5460
CTTAATCATT GCCCCACCAG CCACTCACTC TCACCCAGAG TGGACTGGGA GTCATGGTAG 5520
ACCCCTCCTG CTATTCAGTC CATCCCTAGT CCTCAGACCA CGCCCCTGCA TCTCTTCAGC 5580
CCACACACCT CACCTCCCTC TGCCTCATCC CCGAGAGCAC GCCTTAAAAG GCAGGCTCAT   560   
CACTTCCCAC CTGGATCACT GCTCCAGCCT CTCCTACCTC CAGTCCATCT GTTTGTCAAG 5700
CCATCCATCC   ATClTCCTTC      CTTCTTTCCC     <RTI  

   ID=118.4> CTTCCZTTAT    TCTCTTCACC CATCTGTCCA 5760
TACACCTCTC   CTTCCTTCCT      TCTITCCTTT    CTCTCATCCT TCTTTCCATC CATCCTTCCA 5820
ACCGTTCATC TGTCCATCTG CCCATTCACA TGTCCATCCG TCCATGCTCC CTCCTTCCTT 5880
CCATCCTTTC ACCCATCCAC CCATCCACCC ATCCACCCAT CCACCAATCC ATCCAGCAAT 5940
CCACCCATCC ATCCAGCCAT CCACCCATCC ATCCGTCCAC CTATCCATCC ATCCACCCAT 6000
CCATCCAACC AGCCATCCAC CCATCCATCC ATCCATCCAT CCATCCATCC ATCCACCCAC 6060
CCACCCATCC ACCCATCCAT CCATCCAGCC AACCAGCCAT CCACCCATCC ACCCATCCAC 6120
CCATCCATCC ATCCATCCAT CCATCCATCC ATCCATCCAT CCACCCATCC ACCCATCCAT 6180
CCATCCAGCC ATCCACCCAT CCATCCATCC ACCTATCCAT CCATCCACCT ATCCATCCAT 6240
CCACCCATCC ATCCATCCAG CCATCCACCC ATCCATCCAT CCACCCATCC ACCCATCCAT 6300
CCATCCATCC ATCAATCCAT CCATCCATCC ACCCATCCAT CCATCCATCC ACCCACCCAT 6360
CTGACATTCA GTCCTTCGTT CACCAGTCAG TGTCCTGGGC ACTTACCATG  <RTI  

   ID=118.7> TGTTGCACTC    6420
TGCTAGTGCA TGTTAAAGGG GCTTCCTAAA AAAGCAAATC AGCCCAGTTC ATGGCTTCTG 6480
AGGACTCCCA TGATGCGCAG GCATCCCCCA GGCACCTTAG CTCCACCCAC AGAGCAGCAG 6540
CCCAGGTGCC ATCTGCTCCC AGGGGGGCCG TCATCCAGAG GTTGAGCCTC   CTCCAGCTTC    6600
CGGAAGCCCC CTCAACTCTC CAAGCCATCT GTACTGCTCA   GGCCACACCT    TCACTGCCTG 6660
GAACGCCCTC   CTCCAGAAAA    TGCCCATGAG AAAGTGCCCG   CCCCGCCCTT      ACAGCTCCCT    6720
TTAGAAGTCA CCTCCTCAAC AAAGCAGCTT CGGAGTCGGC TTCCTCCCCA CCCTTCATGG 6780  
GGTGGAAGCG GCCCTGGGGG AGGGGCCTGT GGAACCAGGT CTGGTGGGGC GGCAGTGTCA 6840
GGACACACAT TGGAAAGTGT TGTCACAGCG AGTCCCAACT GCAGTAGCTC   TGGAGTCTAT    6900
GGCCCCGGCC CCTGAGCCAA CACCTTCTGC CCTGGTCATC   TTGGCCACCC    CAGGTGCCCT 6960
ACCACGTGTC AGCAATTGAT 

  CTACACTGCC CCCAATCTCC CACCTCGGGA GAGCCTGAGC 7020
CCCCTGCCAC CTGAGGCTCA CAGGCACCTG   TCCTTCAGTG    ACCCACCCCT CAAGTGGCCC 7080
CCCAAAGAGA   AAGCCTATTT    CCTGGCCTCT CTGGCCCTGA GAGGACTCAC CTGCTGCAGG   71.40   
ATCGAGGGAC CTGGGAGAAG CTTGGGTCCT GCCCTGAGCT TCTCACAGTC   TGCCATGGGA    7200
GCCAGACACT AACATGTTGT ACCCAGTGTG TGGGGTGGGG AAGTCGGCCC TGAGCCCACC 7260
CGCTCATTCC CAGATAGTCG CTGAGCCCCA GGCTATGTGG GGGTCAGGCA CAGATCAGAC 7320   ACTGTTCTAT    CCCCTGTAAT   GTAGGGCCTG    GCACCACCCC   TGGGCCTCAG    TTTCCCCATC 7380
TATAAACATG GAGACCGGTC TTGGATAGTA ACATCCAGAC TGTGGCCCAG GGGGCACTGG 7440
GCCTCCAAGA GGGCTGGAGA GCAGGGGGGC TTGGGGTTAT GGGGAGAGGC AGCCCCTACC 7500
ACCAGGTCAA GCCTTCCACC CTTCCCTGCT CTGGGCTTTC ATGTCGCTGA AAAACAGGAT 7560
GGGGTGCTTG 

  AAGCATCTTG TTCCCTGAGG TCCTGCGAGG TCAGATGCTG CTCGGTCCAG 7620
TCTGGGAGCC TCTGGAGGCC ATTTCCACTC TCCCTCTCTC   CCACGGGACA    CCACACCCCA 7680
GATGGGGACA GACCATGAGG GCCTCCGACT CCTCCTGCGG CCAGTCCCCA GGAGGAAAGA 7740
GAGATCCTAC TGTCTGCCTT GCACCTGCTG CTTCCACCTC CCACCACCCT TTCTGGTTTG 7800
GAGGGAGCAG CTCCTGTCAG TCATCCCCTG AGGGAGGTGG   CCCTAGGCAT    TACCACTTGC 7860
CTGTAGCTGG GACTGAAGCC TAGTGGGTCT GCATAAGGCA TACCCACCTC TTCCCTACGC 7920
CACAGACTAA GAAGACCCCA TGAGGCAGCC CTTGAGGGAA ACTCCCACGG CCAGGCCTTG 7980
GGGATGTTGG TGTAAGCTCC TTCAGTTCAG AGCTTCACTG   TGCCTTTGAG    AGGGCAGGGT 8040
CCCTTCTGCC CTTCCCCCAC TGCACCCTGG GCCTGACAAG GGTCCCATTA ATCTCTGATG 8100
ACAAAGAGGT GTCCTCTCTG   TCCTGCTTGT    GGTGGGACAC CCCAGCTTCT GCTCTCATCC 8160
TAAGAACAGC AGTATCTGTG GCACTGATTG ATCACGTGCC TCATGCCAGG CCCCAGCCCC 8220  
TGCTCTGTGT 

  TGTAACCTCT TCAACCTGCA AGGCGAGATC CTCCAGCTTA AGAGAGTGTT 8280
GCTCAGGGGT CAATGACCCC AGCTGGGGCC CCTGAGCGCA GCGTTTAATG GAGAGTCTGG 8340
GCTCATCAAA CCTGGCTGTG TCCCCTTCCC TTCCTGCTTT TTGTGTTCTT TCTTCTTTTT 8400
ACTTTTCTGC AATTTCTTTT TTTTTCTTTT CTTTTTTTTT TTTTTTGAGT CAGAGTTTTG 8460
CTCTTGTCGC CCAGACTGGA GTGCAGTGGC ACAATCTCTG CTCACTGCAA CCTCTGCCTC 8520
CCGGGTTCAA GTGATTCTCC TGCCTAAGCC TCCCAAGTAG CTGGGATTGT   GGGCGCACGC    8580
CACCACACCC GGCTAATTTT TTTGTATTTT TAGTAGAGAC GGGGTTTTGC CATGTTGCCC 8640
AGGCTGGTCT CGAACTCCTG ACCTCAGGTG ATTCACCTGC CTCGGCCTCC CAAACTGCTG 8700
GGATTACAGG CATGAGCCAC CGTGCCCAGC CTCTGCAATT TCTTTAAAAG AGATCTGGGT 8760
GTTGTCATCT TCCTTTGTCC AAATGCCCAG TCCTTGCTGA CCTCCACACT   GCCAGCAGAC    8820
TGCCAGGGCA CCTGGGTTGG CCGGCCTGGT CTCTGCTCCA CAGACAACCC   TACACATCCC    8880
TTTGCTGTGT CAGCGCCCTC AGATGGGGGA CAGAGGCTGG 

  TGGAACCCAG AGAGTAGGAG 8940
CTGGGAGTTG TCTGGCACAG CTTTGAGTGA AGGTGACCTT TAGGCAGAAG GCCAAGTTCA 9000
CCAGGCACAC AGGGGAGGAA GGACATGCTG GGCAGAGGGC AGGGCCTAGG CAAAGGTGTG 9060
ACTGGCTGAG AGTGCGCTGG GGTTTGGCAC TGGACCGAAC AGCCTCACAG   GAGGGGAGGC    9120
AGGCATCAGG CAACCCTGGG CCCTGACGCT GCCGCAGTCT CCCCGGGGCA CTGACCATGA 9180
TATCTCATCC CCGCAGGAGC ACTACAGCGC CGAGTGCGAG TTTGTGGAGC GGATCCACGA 9240
GCTGGGCTAT AATACGTATG CCTCCCGGCT GTACCGGACG GTGTCTAGTA CGCCTGGGGC 9300
CCGCCGGCAG CCCAGCGCCG AGAGACTGTG   GTACGTGTCT    GTGAACGGCA AGGGCCGGCC 9360
CCGCAGGGGC TTCAAGACCC GCCGCACACA GAAGTCCTCC CTGTTCCTGC CCCGCGTGCT 9420
GGACCACAGG GACCACGAGA TGGTGCGGCA GGCGGCGGCA GAAGCAGAGC   CCGGATAACC    9480
TGGAGCCCTC   TCACGTTCAG    GCTTCGAGAC   TGGGCTCCCA    GCTGGAGGCC AGTGCGCACT 9540
AGCTGGGCCT GGTGGCCACC 

  GCCAGAGCTC CTGGCGACAT CTTGGCGTGG CAGCCTCTTG 9600   ACTCTGACTC    TCCTCCTTGA   GCCCTTGCCC    CTGCGTCCCG CGTCTGGGTT CTCAGCTATT 9660  
TCCAGAGCCA GCTCAAATCA GGGTCCAGTG GGAACTGAAG   AGGGCCCAAG    TCGGAGCTCG 9720   GAGGGGGCTG    CCTGCAATGC AGGGCATTTG TGGGTCTGTG TGGCAGGAAG CCGGCAGGGA 9780
AGGGCCTGAG TGCCAGCCCT GGCAGACTGA   GGAGCCTCCC    AGGAGCAGCG GGGCAGTGTG 9840
GGGCTTTGTG TCATCACAAC ATTAAAGTAT TTTATTCTAC TCTGTCGTTT GGTAGACCGT 9900
GATGCAGGCT GAGGAGCGCT   TGCCGCCITT      ACTSGhACGT    GCTTGCTTCC AGCACAGCAG 9960
AATCCGCGCT GGCATCAGCC TGCGTCAGCT GCTGCTTTAA GAGGAAGACG GCATTCCCAG 10020
AAATCGGGCT AAAGGTGCAT TTCAGTTCCC   TGGTTTTAGA    AAGTTACGTT TTTTTGGATG 10080
GTTGGAAACA AGCAAAGGCA TGTTTGTGCA TGTGTGTGCA TCGTGTGTGT 

  GTGCGTGGAG 10140
AGAAGGATCG TGTATTTCTG AAAGCGTGAG TGTGCATGTG GGTATGTGTG   ATCITGTGTT    10200
AGTGGTACCT GTGTGAGGAC ATGTATGTGT GTGTGTGTTT CTGGGTGTGT CTGAATGTGT 10260
GATGTGTGTG   TQTCTGTGTG    TGTGTGTGTG TGTGTGTGTG TGTGTGGAGA GAGAGAGAGA 10320
GAGTTTACTT TCTTTGAAAA CTCTAAAAAG CCTCTCCCTC TGGAAGCTGT GTGCTTCTCC 10380
AGGGACCCTT TAGAGCAACT GTGTCAGGTC AGGCAGCACA   GAMCTTCCT      TTATCCTTAC    10440   AACCTGCTCT    TGGGGCCCGT GCACCCTGTC TTTACCTAGA AGGTGAGGCT CAGAGAAGCA 10500
ATTACTCAGT GGCCGGCCCC TGCCTTGGAC TAGGTGCCTC CTCACACCTG TTCCCCAACA 10560
ATGGCATGGG TGGAATCACC TGGGCCGGCC CAGGTGAGAG CCAGCATGGG CAGTGTACTA 10620
ACCTCTCCTG GCACTTGGCA GGATGGGCAG GGTCCAGGTG AGGAGGCTCT CCTGAGCCTG 10680
GGACTGTGAG GACCATCGCT CTCTGTTCCC ATGCCCTCCC   AGGGGTCAGA    GAGCCCAGAC 

  10740
TCAGAGAGCC CAGGGTCAGA GAACTTAGGG TCAGAGAGGC CAGAGTCAGA GAGCTGAGAC 10800
TCAGAGAGCC CAGGGTCAGA GTGTCCAGGG CCAGAGAGCT TGTGGTCACA GAGCCCAGAC 10860
TCAGAGAGCC CAGACTCAGA GCCACCTGAT TGGTTAGTGC AGACTCGCCA   AACCCACAGG    10920
GAGGCTGGGC TCCTCCCTGG CACGTGTGCA ACACAAGTGA AAATCTCGGT GCCTCCTTCA 10980
GCCCCCAGCG CATGTCAGAT TTCCCGGAAT   C.GCTCCCCTG    CAGCTGCGAA CATTCCTGGC 11040
AGTCAACAGG AGCAGCACGC AGCTGAGCTC TGCTGTGGGT TTTGTTGTTT CTCTAGAGTG 11100  
AGATGGGGCA GGGGCTGCCA TCACTCCCTC   CTTGCAGATG      ATGACCCTGA    GTCCTGGCAA 11160
GGGGAACTTG CCCGGGGCTG TGTCAACACA GGGGAAGCAG CAGTACTCAG TGCTGCAGGA 11220
TCAACAGATG GTCCCTGATG AAGGCGTAGG AGACACTGGG GGCTCTTGTT TAACATGTAA 11280
AACAGCTTTG ACAAGAGAAT   GTGGATTTTT    CGCAGCTGAT GGCTGTGCCA TGGTCACCTT 11340
CTTCCCCACA CCAGAGTCCA 

  AGGGACTTCA TTTTGTGTGT GTGTTTGGGG GGTCATGGGC 11400
TGAATTATGT   cTCCTCCCCA    GAGTTCATCT GTTGAAGTCC TAACCCCTAG TAACTCAGCA 11460
TGTGACCTTA TTTGGAATAG GGTCATTACA GATGCAACTG GTGAAGATGA GGTAACATAG 11520   GAGTAGAATG    ACCCCTGAAT CCATTGTGAC CAGGATCC 11558 (2) INFORMATION FOR SEQ ID NO:24:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 3622 base pairs
 (B) TYPE: nucleic acid
   IC)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
   (11)    MOLECULE TYPE:

   DNA Igenomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:24:
CCCGGGGAGG GGACCGGGGA ACAGAGGGCC GAGAGGCGTG CGGCAGGGGG   GAGGGTAGGA    60
GAAAGAAGGG CCCGACTGTA GGAGGGCAGC GGAGCATTAC CTCATCCCGT GAGCCTCCGC   120   
GGGCCCAGAG AAGAATCTTC TAGGGTGGAG TCTCCATGGT GACGGGCGGG CCCGCCCCCC 180
TGAGAGCGAC GCGAGCCAAT GGGAAGGCCT TGGGGTGACA TCATGGGCTA TTTTTAGGGG 240
TTGACTGGTA GCAGATAAGT GTTGAGCTCG   GGCTGGATAA    GGGCTCAGAG TTGCACTGAG 300
TGTGGCTGAA GCAGCGAGGC GGGAGTGGAG GTGCGCGGAG TCAGGCAGAC AGACAGACAC 360
AGCCAGCCAG CCAGGTCGGC AGTATAGTCC GAACTGCAAA TCTTATTTTC TTTTCACCTT 420
CTCTCTAACT   GCCCAGAGCT    AGCGCCTGTG GCTCCCGGGC TGGTGGTTCG GGAGTGTCCA 480
GAGAGCCTTG TCTCCAGCCG GCCCCGGGAG GAGAGCCCTG CTGCCCAGGC GCTGTTGACA 540  
GCGGCGGAAA GCAGCGGTAC   CCCACGCGCC    

  CGCCGGGGGA CGTCGGCGAG CGGCTGCAGC 600
AGCAAAGAAC   m CCCGGCG    GGGAGGACCG GAGACAAGTG GCAGAGTCCC GGAGCGAACT 660
TTTGCAAGCC TTTCCTGCGT CTTAGGCTTC TCCACGGCGG TAAAGACCAG AAGGCGGCGG 720
AGAGCCACGC AAGAGAAGAA GGACGTGCGC TCAGCTTCGC TCGCACCGGT TGTTGAACTT 780
GGGCGAGCGC GAGCCGCGGC TGCCGGGCGC CCCCTCCCCC TAGCAGCGGA GGAGGGGACA 840
AGTCGTCGGA GTCCGGGCGG CCAAGACCCG CCGCCGGCCG GCCACTGCAG GGTCCGCACT 900
GATCCGCTCC GCGGGGAGAG CCGCTGCTCT GGGAAGTGAG TTCGCCTGCG GACTCCGAGG 960
AACCGCTGCG CCCGAAGAGC GCTCAGTGAG TGACCGCGAC TTTTCAAAGC CGGGTAGCGC 1020
GCGCGAGTCG ACAAGTAAGA GTGCGGGAGG   CATCTTAATT    AACCCTGCGC TCCCTGGAGC 1080
GAGCTGGTGA GGAGGGCGCA GCGGGGACGA CAGCCAGCGG GTGCGTGCGC TCTTAGAGAA 1140
ACTTTCCCTG TCAAAGGCTC CGGGGGGCGC GGGTGTCCCC CGCTTGCCAG AGCCCTGTTG 1200
CGGCCCCGAA   ACTTGTGCGC    GCACGCCAAA   CTAACCTCAC    

  GTGAAGTGAC GGACTGTTCT 1260
ATGACTGCAA AGATGGAAAC GACCTTCTAT GACGATGCCC TCAACGCCTC GTTCCTCCCG 1320
TCCGAGAGCG GACCTTATGG CTACAGTAAC CCCAAGATCC TGAAACAGAG CATGACCCTG   L380   
AACCTGGCCG ACCCAGTGGG GAGCCTGAAG CCGCACCTCC GCGCCAAGAA CTCGGACCTC 1440
CTCACCTCGC CCGACGTGGG GCTGCTCAAG CTGGCGTCGC CCGAGCTGGA GCGCCTGATA 1500
ATCCAGTCCA GCAACGGGCA CATCACCACC ACGCCGACCC CCACCCAGTT CCTGTGCCCC 1560
AAGAACGTGA CAGATGAGCA GGAGGGGTTC GCCGAGGGCT TCGTGCGCGC CCTGGCCGAA 1620
CTGCACAGCC AGAACACGCT GCCCAGCGTC ACGTCGGCGG CGCAGCCGGT CAACGGGGCA 1680
GGCATGGTGG CTCCCGCGGT AGCCTCGGTG GCAGGGGGCA GCGGCAGCGG CGGCTTCAGC 1740
GCCAGCCTGC ACAGCGAGCC GCCGGTCTAC GCAAACCTCA GCAACTTCAA CCCAGGCGCG 1800
CTGAGCAGCG GCGGCGGGGC GCCCTCCTAC GGCGCGGCCG GCCTGGCCTT TCCCGCGCAA 1860
CCCCAGCAGC AGCAGCAGCC GCCGCACCAC CTGCCCCAGC AGATGCCCGT GCAGCACCCG 1920
CGGCTGCAGG CCCTGAAGGA GGAGCCTCAG ACAGTGCCCG AGATGCCCGG 

  CGAGACACCG 1980  
CCCCTGTCCC CCATCGACAT GGAGTCCCAG GAGCGGATCA AGGCGGAGAG GAAGCGCATG 2040
AGGAACCGCA TCGCTGCCTC CAAGTGCCGA AAAAGGAAGC TGGAGAGAAT CGCCCGGCTG 2100
GAGGAAAAAG TGAAAACCTT GAAAGCTCAG AACTCGGAGC TGGCGTCCAC GGCCAACATG 2160
CTCAGGGAAC AGGTGGCACA GCTTAAACAG AAAGTCATGA ACCACGTTAA CAGTGGGTGC 2220
CAACTCATGC TAACGCAGCA GTTGCAAACA   TTTTGAAGAG    AGACCGTCGG GGGCTGAGGG 2280
GCAACGAAGA AAAAAAATAA CACAGAGAGA   CAGACTTGAG      AACTTGACM    GTTGCGACGG 2340
AGAGAAAAAA GAAGTGTCCG AGAACTAAAG CCAAGGGTAT CCAAGTTGGA CTGGGTTCGG 2400
TCTGACGGCG CCCCCAGTGT GCACGAGTGG GAAGGACTTG GTCGCGCCCT CCCTTGGCGT 2460
GGAGCCAGGG AGCGGCCGCC TGCGGGCTGC CCCGCTTTGC GGACGGGCTG TCCCCGCGCG 2520
AACGGAACGT TGGACTTTCG TTAACATTGA CCAAGAACTG CATGGACCTA ACATTCGATC 2580
TCATTCAGTA TTAAAGGGGG GAGGGGGAGG GGGTTACAAA CTGCAATAGA GACTGTAGAT 2640
TGCTTCTGTA 

    GTAcTCCTTA    AGAACACAAA GCGGGGGGAG GGTTGGGGAG GGGCGGCAGG 2700
AGGGAGGTTT GTGAGAGCGA GGCTGAGCCT ACAGATGAAC TCTTTCTGGC CTGCTTTCGT 2760
TAACTGTGTA TGTACATATA   TATATTTTTT      AATTTGATTA    AAGCTGATTA CTGTCAATAA 2820
ACAGCTTCAT GCCTTTGTAA   GTTATTTCTT    GTTTGTTTGT TTGGGTATCC   TGCCCAGTGT    2880
TGTTTGTAAA TAAGAGATTT GGAGCACTCT GAGTTTACCA TTTGTAATAA AGTATATAAT 2940
TTTTTTATGT TTTGTTTCTG AAAATTCCAG AAAGGATATT TAAGAAAATA   C AATAAACTA    3000   
TTGGAAAGTA CTCCCCTAAC CT CTTTTCTG CATC ATCTGT AGATCCTAGT CTATCTAGGT 3060   
GGAGTTGAAA GAGTTAAGAA TGCTCGATAA AATCACTCTC AGTGCTTCTT ACTATTAAGC 3120
AGTAAAAACT   GTTCTCTATT    AGACTTAGAA   ATAAATGTAC    CTGATGTACC TGATGCTATG 3180
TCAGGCTTCA 

  TACTCCACGC TCCCCCAGCG   TATCTATATG    GAATTGCTTA CCAAAGGCTA 3240
GTGCGATGTT TCAGGAGGCT GGAGGAAGGG GGGTTGCAGT GGAGAGGGAC AGCCCACTGA 3300
GAAGTCAAAC ATTTCAAAGT TTGGATTGCA   TCAAGTGGCA    TGTGCTGTGA CCATTTATAA 3360
TGTTAGAAAT TTTACAATAG GTGCTTATTC TCAAAGCAGG AATTGGTGGC AGATTTTACA 3420  
AAAGATGTAT CCTTCCAATT TGGAATCTTC   TCTTTGACAA    TTCCTAGATA AAAAGATGGC 3480
CTTTGTCTTA   TGAATATTTA    TAACAGCATT   CTGTCACAAT    AAATGTATTC AAATACCAAT 3540
AACAGATCTT GAATTGCTTC CCTTTACTAC   TTTTTGTTC    CCAAGTTATA TACTGAAGTT 3600   TITATTTTA    GTTGCTGAGG TT 3622 (2) INFORMATION FOR SEQ ID   NO:25:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 5084 base pairs
   IB)    TYPE:

   nucleic acid
   (C)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID   NO:25:   
GATCCCATCG CAGCTACCGC GATGAGAGGC GCTCGCGGCG   CCTGGGATTT    TCTCTGCGTT 60
CTGCTCCTAC TGCTTCGCGT CCAGACAGGC TCTTCTCAAC CATCTGTGAG TCCAGGGGAA 120
CCGTCTCCAC CATCCATCCA TCCAGGAAAA TCAGACTTAA TAGTCCGCGT GGGCGACGAG 180
ATTAGGCTGT TATGCACTGA TCCGGGCTTT GTCAAATGGA CTTTTGAGAT CCTGGATGAA 240
ACGAATGAGA ATAAGCAGAA   TGAATGGATC    ACGGAAAAGG CAGAAGCCAC CAACACCGGC 300
AAATACACGT GCACCAACAA ACACGGCTTA AGCAATTCCA TTTATGTGTT TGTTAGAGAT 360   CCTGCCAAGC    TTTTCCTTGT TGACCGCTCC TTGTATGGGA AAGAAGACAA CGACACGCTG 420
GTCCGCTGTC CTCTCACAGA CCCAGAAGTG ACCAATTATT CCCTCAAGGG GTGCCAGGGG 480
AAGCCTCTTC CCAAGGACTT GAGGTITATT CCTGACCCCA AGGCGGGCAT 

  CATGATCAAA 540
AGTGTGAAAC GCGCCTACCA TCGGCTCTGT CTGCATTGTT CTGTGGACCA GGAGGGCAAG 600
TCAGTGCTGT CGGAAAAATT CATCCTGAAA   GTGAGGCC G    CCTTCAAAGC TGTGCCTGTT 660
GTGTCTGTGT CCAAAGCAAG CTATCTTCTT AGGGAAGGGG AAGAATTCAC AGTGACGTGC 720
ACAATAAAAG ATGTGTCTAG TTCTGTGTAC TCAACGTGGA AAAGAGAAAA CAGTCAGACT 780  
AAACTACAGG AGAAATATAA TAGCTGGCAT CACGGTGACT TCAATTATGA ACGTCAGGCA 840
ACGTTGACTA TCAGTTCAGC GAGAGTTAAT GATTCTGGAG TGTTCATGTG TTATGCCAAT 900   AATACTTTTG    GATCAGCAAA TGTCACAACA ACCTTGGAAG TAGTAGATAA AGGATTCATT 960   AATATCTTCC    CCATGATAAA CACTACAGTA TTTGTAAACG ATGGAGAAAA TGTAGATTTG 1020
ATTGTTGAAT ATGAAGCATT CCCCAAACCT GAACACCAGC AGTGGATCTA TATGAACAGA 1080
ACCTTCACTG ATAAATGGGA AGATTATCCC AAGTCTGAGA ATGAAAGTAA TATCAGATAC 1140
GTAAGTGAAC TTCATCTAAC GAGATTAAAA GGCACCGAAG GAGGCACTTA CACATTCCTA 1200
GTGTCCAATT CTGACGTCAA 

  TGCTGCCATA GCATTTAATG TTTATGTGAA TACAAAACCA 1260
GAAATCCTGA CTTACGACAG GCTCGTGAAT GGCATGCTCC AATGTGTGGC AGCAGGATTC 1320
CCAGAGCCCA CAATAGATTG   GTATTTTTGT    CCAGGAACTG AGCAGAGATG   CTCTGCITCT    1380
GTACTGCCAG TGGATGTGCA GACACTAAAC TCATCTGGGC   CACCGTTTGG    AAAGCTAGTG 1440
GTTCAGAGTT CTATAGATTC TAGTGCATTC AAGCACAATG GCACGGTTGA ATGTAAGGCT 1500
TACAACGATG TGGGCAAGAC TTCTGCCTAT   TTTAACTTTG      CATTTAAAGG    TAACAACAAA 1560
GAGCAAATCC ATCCCCACAC CCTGTTCACT CCTTTGCTGA   TTGGTTTCGT    AATCGTAGCT 1620
GGCATGATGT GCATTATTGT GATGATTCTG ACCTACAAAT ATTTACAGAA ACCCATGTAT 1680
GAAGTACAGT   GGAAGGTTGT    TGAGGAGATA AATGGAAACA ATTATGTITA CATAGACCCA 1740
ACACAACTTC   CTTATGATCA    CAAATGGGAG  <RTI   

   ID=126.11> TTTCCCAGAA    ACAGGCTGAG   TTTTGGGAAA    1800
ACCCTGGGTG   CTGGAGCTTT    CGGGAAGGTT GTTGAGGCAA CTGCTTATGG CTTAATTAAG 1860
TCAGATGCGG CCATGACTGT CGCTGTAAAG ATGCTCAAGC CGAGTGCCCA TTTGACAGAA 1920
CGGGAAGCCC TCATGTCTGA ACTCAAAGTC CTGAGTTACC TTGGTAATCA CATGAATATT 1980
GTGAATCTAC TTGGAGCCTG CACCATTGGA GGGCCCACCC TGGTCATTAC AGAATATTGT 2 
ACCAAGGCCG ACAAAAGGAG ATCTGTGAGA ATAGGCTCAT ACATAGAAAG AGATGTGACT 2280
CCCGCCATCA TGGAGGATGA CGAGTTGGCC CTAGACTTAG AAGACTTGCT   GAGCTTTTCT    2340
TACCAGGTGG CAAAGGGCAT GGCTTTCCTC GCCTCCAAGA ATTGTATTCA   CAGAGAOTTG    2400
GCAGCCAGAA ATATCCTCCT TACTCATGGT CGGATCACAA AGATTTGTGA   TTTTGGTCTA    2460
GCCAGAGACA TCAAGAATGA TTCTAATTAT GTGGTTAAAG GAAACGCTCG ACTACCTGTG 2520
AAGTGGATGG CACCTGAAAG   CATTTTCAAC    

  TGTGTATACA   CGTTTGAAAG    TGACGTCTGG 2580
TCCTATGGGA TTTTTCTTTG GGAGCTGTTC   TCTTTAGGAA    GCAGCCCCTA TCCTGGAATG 2640
CCGGTCGATT CTAAGTTCTA CAAGATGATC AAGGAAGGCT TCCGGATGCT CAGCCCTGAA 2700
CACGCACCTG CTGAAATGTA TGACATAATG AAGACTTGCT GGGATGCAGA TCCCCTAAAA 2760
AGACCAACAT TCAAGCAAAT TGTTCAGCTA ATTGAGAAGC AGATTTCAGA GAGCACCAAT 2820   CATATTTACT    CCAACTTAGC AAACTGCAGC CCCAACCGAC AGAAGCCCGT GGTAGACCAT 2880
TCTGTGCGGA TCAATTCTGT CGGCAGCACC GCTTCCTCCT CCCAGCCTCT GCTTGTGCAC 2940
GACGATGTCT GAGCAGAATC AGTGTTTGGG TCACCCCTCC AGGAATGATC   TCTTCTTTTG    3000   GCTTCCATGA    TGGTTATTTT   CrTTcTTTC      AACTTGCATC    CAACTCCAGG ATAGTGGGCA 3060
CCCCACTGCA   ATCCTGTCTT    TCTGAGCACA CTTTAGTGGC CGATGATTTT TGTCATCAGC 

  3120
CACCATCCTA TTGCAAAGGT TCCAACTGTA TATATTCCCA ATAGCAACGT AGCTTCTACC 3180
ATGAACAGAA AACATTCTGA   TTTGGAAAAA    GAGAGGGAGG TATGGACTGG GGGCCAGAGT 3240
CCTTTCCAAG GCTTCTCCAA TTCTGCCCAA AAATATGGTT GATAGTTTAC CTGAATAAAT 3300
GGTAGTAATC ACAGTTGGCC TTCAGAACCA TCCATAGTAG TATGATGATA CAAGATTAGA 3360
AGCTGAAAAC CTAAGTCCTT TATGTGGAAA ACAGAACATC ATTAGAACAA AGGACAGAGT 3420
ATGAACACCT GGGCTTAAGA AATCTAGTAT TTCATGCTGG GAATGAGACA TAGGCCATGA 3480
AAAAAATGAT CCCCAAGTGT GAACAAAAGA TGCTCTTCTG TGGACCACTG   CATGAGCTTT    3540
TATACTACCG ACCTGGTTTT TAAATAGAGT TTGCTATTAG AGCATTGAAT TGGAGAGAAG 3600
GCCTCCCTAG CCAGCACTTG TATATACGCA TCTATAAATT GTCCGTGTTC ATACATTTGA 3660  
GGGGAAAACA CCATAAGGTT   TCGTTTCTGT    ATACAACCCT GGCATTATGT CCACTGTGTA 3720
TAGAAGTAGA TTAAGAGCCA TATAAGTTTG AAGGAAACAG TTAATACCAT   TTTITAAGGA    

  3780
AACAATATAA CCACAAAGCA CAGTTTGAAC AAAATCTCCT CTTTTAGCTG ATGAACTTAT 3840
TCTGTAGATT CTGTGGAACA AGCCTATCAG CTTCAGAATG GCATTGTACT   CAATGGATTT    3900
GATGCTGTTT GACAAAGTTA CTGATTCACT GCATGGCTCC CACAGGAGTG GGAAAACACT 3960
GCCATCTTAG   TTTGGATTCT    TATGTAGCAG GAAATAAAGT   ATAGG m AG    CCTCCTTCGC 4020
AGGCATGTCC TGGACACCGG GCCAGTATCT ATATATGTGT   ATGTACGTTT    GTATGTGTGT 4080
AGACAAATAT TTGGAGGGGT ATTTTTGCCC TGAGTCCAAG AGGGTCCTTT AGTACCTGAA 4140
AAGTAACTTG GCTTTCATTA TTAGTACTGC TCTTGTTTCT TTTCACATAG CTGTCCTAGAG 4200
TAGCTTACCA GAAGCTTCCA TAGTGGTGCA GAGGAAGTGG AAGGCATCAG TCCCTATGTA 4260   TTTGCAGTTC    ACCTGCACTT AAGGCACTCT   GTTATTTAGA    CTCATCTTAC TGTACCTGTT 4320
CCTTAGACCT TCCATAATGC TACTGTCTCA CTGAAACATT TAAATTTTAC CCTTTAGACT 4380
GTAGCCTGGA 

  TATTATTCTT GTAGTTTACC   TCTITAAAAA    CAAAACAAAA CAAAACAAAA 4440
AACTCCCCTT CCTCACTGCC CAATATAAAA GGCAAATGTG TACATGGCAG AGTTTGTGTG 4500   TTGTCTTGAA    AGATTCAGGT   ATGTTGCCTT    TATGGTTTCC CCCTTCTACA   TTTCTTAGAC    4560   TACA=AGA      GAACTGTGC;

  C    CGTTATCTGG AAGTAACCAT TTGCACTGGA GTTCTATGCT 4620
CTCGCACCTT TCCAAAGTTA ACAGATTTTG GGGTTGTGTT GTCACCCAAG AGATTGTTGT 4680
TTGCCATACT TTGTCTGAAA AATTCCTTTG TGTTTCTATT GACTTCAATG ATAGTAAGAA 4740
AAGTGGTTGT TAGTTATAGA TGTCTAGGTA CTTCAGGGGC ACTTCATTGA GAGTTTTGTC 4800
TIGCCATACT TTGTCTGAAA AATTCCTTTG TGTTTCTATT GACTTCAATG ATAGTAAGAA 4860
AAGTGGTTGT TAGTTATAGA TGTCTAGGTA CTTCAGGGGC ACTTCATTGA GAGTTTTGTC 4920
AATGCTTTT GAATATTCCC AAGCCCATGA GTCCTTGAAA ATATTTTTTA TATATACAGT 4980
AACTTTATGT GTAAATACAT AAGCGGCGTA AGTTTAAAGG ATGTTGGTGT TCCACGTGTT 5040
TTATTCCTGT   ATGTTGTCCA    ATTGTTGACA GTTCTGAAGA ATTC 5084   (2) INFORMATION FOR SEQ ID   NO:26:   
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 1388   btse    pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY:

   linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:
GGATCCAGAA GGGTCATTCA ATCAGTTCTC AGTCTTATCA GGTCTAAGTT CCTTTCTTAT 60
CAGGTCCTAA AGGCCTAATC   TTATCATTGT    GACAAAGATA ACTGTAGAGT CTGTTAAACT 120   TlTTTTTTAA    TAACATGAAG   ATTATGATIT    ATAGCTGAAT   TTCTCCCTTT    TATTCCAATT 180
CAACAATTTT CATGGCTTTT TGTGTTTGTT TTGTTCTGGA CATATTTACA GAAAATTACC 240
TGAAGAGTTC CAACCTGAGG CCTCCTCATG GATGGGTCAA ACGTGACATC   ATTTGTTGTT    300
GAGGAACCCA CGAACATCTC AACTGGCAGG AACGCCTCAG TCGGGAATGC ACATCGGCAA 360
ATCCCCATCG TGCACTGGGT CATTATGAGC ATCTCCCCAG TGGGGTTTGT TGAGAATGGG 420
ATTCTCCTCT   GGTTCCTGTG    CTTCCGGATG AGAAGAAATC CCTTCACTGT CTACATCACC 480
CACCTGTCTA TCGCAGACAT CTCACTGCTC TTCTGTATTT TCATCTTGTC TATCGACTAT 540
GCTTTAGATT  <RTI  

   ID=129.10> ATGAGCTTTC    TTCTGGCCAT TACTACACAA TTGTCACATT ATCAGTGACT 600   TTTCTGTTTG    GCTACAACAC GGGCCTCTAT    GCTGACGG    CCATTAGTGT GGAGAGGTGC 660
CTGTCAGTCC TTTACCCCAT CTGGTACCGA TGCCATCGCC CCAAGTACCA GTCGGCATTG 720   GTCTGTGCCC    TTCTGTGGGC TCTTTCTTGC TTGGTGACCA CCATGGAGTA TGTCATGTGC 780
ATCGACAGAG AAGAAGAGAG TCACTCTCGG AATGACTGCC GAGCAGTCAT CATCTTTATA 840
GCCATCCTGA GCTTCCTGGT CTTCACGCCC CTCATGCTGG TGTCCAGCAC CATCTTGGTC 900
GTGAAGATCC GGAAGAACAC GTGGGCTTCC CATTCCTCCA AGCTTTACAT AGTCATCATG 960
GTCACCATCA TTATATTCCT CATCTTCGCT ATGCCCATGA   GACTCCTTA    CCTGCTGTAC 1020  
TATGAGTATT GGTCGACCTT TGGGAACCTA CACCACATTT CCCTGCTCTT CTCCACAATC 1080
AACAGTAGCG CCAACCCTTT   CATTTACTTC    TTTGTGGGAA GCAGTAAGAA GAAGAGATTC 1140
AAGGAGTCCT TAAAAGTTGT  <RTI  

   ID=130.2> TCTGACCAGG    GCTTTCAAAG ATGAAATGCA ACCTCGGCGC 1200
CAGAAAGACA   ATTTTAATAC    GGTCACAGTT GAGACTGTCG TCTAAGAACT GTGAGGGAAG 1260
TTGTGGATAA AAATGGTGGA ACACAGGTCA TTTTTAGTTT GTGCTTGGAA TATGACTTAA 1320
GTATCTCCTA AATGTGATAC AGAAGAACAT CTCATCCCAT ATGCATGAGA TACTAATTAA 1380
TGATGAAA 1388 (2) INFORMATION FOR SEQ ID   NO:27:   
   li)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 4626 base pairs
   (B)    TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:27:
GAATTCCGCC CTCGCCGCCC GCGGCGCCCC GAGCGCTTTG TGAGCAGATG CGGAGCCGAG 60
TGGAGGGCGC GAGCCAGATG CGGGGCGACA GCTGACTTGC   TGAGAGGAGG    CGGGGAGGCG 120
CGGAGCGCGC GTGTGGTCCT TGCGCCGCTG ACTTCTCCAC TGGTTCCTGG GCACCGAAAG 180
ATAAACCTCT CATAATGAAG GCCCCCGCTG TGCTTGCACC TGGCATCCTC GTGCTCCTGT 240
TTACCTTGGT GCAGAGGAGC AATGGGGAGT GTAAAGAGGC ACTAGCAAAG TCCGAGATGA 300
ATGTGAATAT GAAGTATCAG CTTCCCAACT TCACCGCGGA AACACCCATC CAGAATGTCA 360
TTCTACATGA GCATCACATT TTCCTTGGTG CCACTAACTA CATTTATGTT TTAAATGAGG 420
AAGACCTTCA GAAGGTTGCT GAGTACAAGA CTGGGCCTGT GCTGGAACAC CCAGATTGTT 480
TCCCATGTCA GGACTGCAGC AGCAAAGCCA ATTTATCAGG AGGTGTTTGG AAAGATAACA   540      TCAACATGGC      TCTAGTTGTC    GACACCTACT ATGATGATCA ACTCATTAGC TGTGGCAGCG 600  
TCAACAGAGG GACCTGCCAG CGACATGTCT TTCCCCACAA TCATACTGCT GACATACAGT 

  660
CGGAGGTTCA CTGCATATTC TCCCCACAGA TAGAAGAGCC CAGCCAGTGT CCTGACTGTG 720
TGGTGAGCGC CCTGGGAGCC AAAGTCCTIT CATCTGTAAA GGACCGGTTC ATCAACTTCT 780
TTGTAGGCAA TACCATAAAT TCTTCTTATT TCCCAGATCA   TCCATTGCAT    TCGATATCAG 840
TGAGAAGGCT   AAAGGAAACG    AAAGATGGTT   TTATGTTTTT    GACGGACCAG TCCTACATTG 900
ATGTTTTACC TGAGTTCAGA GATTCTTACC CCATTAAGTA TGTCCATGCC TTTGAAAGCA 960
ACAATTTTAT TTACTTCTTG ACGGTCCAAA GGGAAACTCT AGATGCTCAG   ACTITTCACA    1020
CAAGAATAAT CAGGTTCTGT TCCATAAACT CTGGATTGCA TTCCTACATG GAAATGCCTC 1080
TGGAGTGTAT TCTCACAGAA AAGAGAAAAA AGAGATCCAC AAAGAAGGAA   GTGTTTAATA    1140
TACTTCAGGC TGCGTATGTC AGCAAGCCTG GGGCCCAGCT TGCTAGACAA ATAGGAGCCA 1200
GCCTGAATGA TGACATTCTT TTCGGGGTGT   TCC;

  CACAAAG    CAAGCCAGAT TCTGCCGAAC 1260
CAATGGATCG ATCTGCCATG TGTGCATTCC CTATCAAATA TGTCAACGAC   TTCTTCAACA    1320
AGATCGTCAA CAAAAACAAT GTGAGATGTC TCCAGCATTT TTACGGACCC AATCATGAGC 1380
ACTGCTTTAA TAGGACACTT CTGAGAAATT CATCAGGCTG TGAAGCGCGC CGTGATGAAT 1440
ATCGAACAGA GTTTACCACA GCTTTGCAGC GCGTTGACTT ATTCATGGGT CAATTCAGCG 1500
AAGTCCTCTT AACATCTATA TCCACCTTCA TTAAAGGAGA CCTCACCATA GCTAATCTTG 1560
GGACATCAGA GGGTCGCTTC ATGCAGGTTG TGGTTTCTCG ATCAGGACCA TCAACCCCTC 1620
ATGTGAATTT TCTCCTGGAC TCCCATCCAG TGTCTCCAGA   AGTGATTGTG    GAGCATACAT 1680
TAAACCAAAA TGGCTACACA CTGGTTATCA   CTGGGAAGAA    GATCACGAAG ATCCCATTGA 1740
ATGGCTTGGG CTGCAGACAT TTCCAGTCCT GCAGTCAATG   CCTCTCTGCC    CCACCCTTTG 1800
TTCAGTGTGG CTGGTGCCAC GACAAATGTG TGCGATCGGA GGAATGCCTG AGCGGGACAT 1860
GGACTCAACA GATCTGTCTG 

  CCTGCAATCT ACAAGGTTTT CCCAAATAGT GCACCCCTTG 1920
AAGGAGGGAC AAGGCTGACC ATATGTGGCT GGGACTTTGG   ATTTCGGAGG    AATAATAAAT 1980
TTGATTTAAA GAAAACTAGA GTTCTCCTTG GAAATGAGAG CTGCACCTTG ACTTTAAGTG 2040  
AGAGCACGAT GAATACATTG AAATGCACAG TTGGTCCTGC CATGAATAAG CATTTCAATA 2100
TGTCCATAAT   TATTTCAAAT    GGCCACGGGA CAACACAATA CAGTACATTC TCCTATGTGG 2160
ATCCTGTAAT AACAAGTATT TCGCCGAAAT ACGGTCCTAT GGCTGGTGGC ACTTTACTTA 2220
CITTAACTGG AAATTACCTA AACAGTGGGA ATTCTAGACA   CATTTCAATT    GGTGGAAAAA 2280
CATGTACTTT AAAAAGTGTG TCAAACAGTA TTCTTGAATG TTATACCCCA GCCCAAACCA 2340   TTTCAACTGA      GTTTGCTGTT    AAATTGAAAA TTGACTTAGC CAACCGAGAG ACAAGCATCT 2400
TCAGTTACCG TGAAGATCCC ATTGTCTATG AAATTCATCC AACCAAATCT   TTTATTAGTA    2460
CTTGGTGGAA AGAACCTCTC AACATTGTCA 

  GTTTTCTATT   TTGCTTTGCC    AGTGGTGGGA 2520
GCACAATAAC AGGTGTTGGG AAAAACCTGA ATTCAGTTAG TGTCCCGAGA ATGGTCATAA 2580
ATGTGCATGA AGCAGGAAGG AACTTTACAG TGGCATGTCA ACATCGCTCT AATTCAGAGA 2640
TAATCTGTTG TACCACTCCT TCCCTGCAAC AGCTGAATCT GCAACTCCCC CTGAAAACCA 2700   AAGCCT,

  fITT    CATGTTAGAT   GGGATCCTTT    CCAAATACTT TGATCTCATT TATGTACATA 2760
ATCCTGTGTT   TAAGCCTTT    GAAAAGCCAG TGATGATCTC AATGGGCAAT GAAAATGTAC 2820
TGGAAATTAA GGGAAATGAT ATTGACCCTG AAGCAGTTAA AGGTGAAGTG TTAAAAGTTG 2880
GAAATAAGAG CTGTGAGAAT ATACACTTAC ATTCTGAAGC CGTTTTATGC ACGGTCCCCA 2940
ATGACCTGCT GAAATTGAAC AGCGAGCTAA   ATATAGAGTG    GAAGCAAGCA   A m CTTCAA    3000
CCGTCCTTGG AAAAGTAATA GTTCAACCAG   ATCAGAATTT    CACAGGATTG ATTGCTGGTG 3060
TTGTCTCAAT ATCAACAGCA CTGTTATTAC TACTTGGGTT TTTCCTGTGG CTGAAAAAGA 3120
GAAAGCAAAT TAAAGATCTG GGCAGTGAAT TAGTTCGCTA CGATGCAAGA GTACACACTC 3180
CTCATTTGGA TAGGCTTGTA AGTGCCCGAA GTGTAAGCCC AACTACAGAA ATGGTTTCAA 3240
ATGAATCTGT AGACTACCGA GCTACTTTTC CAGAAGATCA GTTTCCTAAT TCATCTCAGA 3300
ACGGTTCATG CCGACAAGTG CAGTATCCTC TGACAGACAT 

  GTCCCCCATC CTAACTAGTG 3360
GGGACTCTGA TATATCCAGT   CCATTACTGC    AAAATACTGT CCACATTGAC CTCAGTGCTC 3420
TAAATCCAGA GCTGGTCCAG GCAGTGCAGC ATGTAGTGAT TGGGCCCAGT AGCCTGATTG 3480    TGCATTTCAA    TGAAGTCATA GGAAGAGGGC ATTTTGGTTG TGTATATCAT   GGGACTTTGT    3540
TGGACAATGA TGGCAAGAAA ATTCACTGTG CTGTGAAATC CTTGAACAGA ATCACTGACA 3600
TAGGAGAAGT TTCCCAATTT CTGACCGAGG GAATCATCAT GAAAGATTTT AGTCATCCCA 3660
ATGTCCTCTC   GCTCCTGGGA    ATCTGCCTGC GAAGTGAAGG GTCTCCGCTG GTGGTCCTAC 3720
CATACATGAA ACATGGAGAT CTTCGAAATT TCATTCGAAA TGAGACTCAT AATCCAACTG 3780
TAAAAGATCT TATTGGCTTT GGTCTTCAAG TAGCCAAAGC GATGAAATAT CTTGCAAGCA 3840   AAAAG=GT    CCACAGAGAC TTGGCTGCAA GAAACTGTAT GCTGGATGAA AAATTCACAG 3900   TCAAGGTTGC    TGATTTTGGT CTTGCCAGAG  <RTI  

   ID=133.6> ACATGTATGA    TAAAGAATAC TATAGTGTAC 3960
ACAACAAAAC AGGTGCAAAG CTGCCAGTGA AGTGGATGGC TTTGGAAAGT CTGCAAACTC 4020
AAAAGTTTAC CACCAAGTCA GATGTGTGGT   CCTrTGGCGT    CGTCCTCTGG GAGCTGATGA 4080
CAAGAGGAGC CCCACCTTAT CCTGACGTAA   ACACCTTTGA    TATAACTGTT TACTTGTTGC 4140
AAGGGAGAAG ACTCCTACAA CCCGAATACT GCCCAGACCC CTTATATGAA GTAATGCTAA 4200   AATGCTGGCA    CCCTAAAGCC GAAATGCGCC CATCCTTTTC TGAACTGGTG TCCCGGATAT 4260   CAGCGbTCTT      CTCTACTTTC    ATTGGGGAGC   ACTATGTCCA    TGTGAACGCT ACTTATGTGA 4320
ACGTAAAATG TGTCGCTCCG   TATCCTTCTC    TGTTGTCATC AGAAGATAAC GCTGATGATG 4380
AGGTGGACAC ACGACCAGCC TCCTTCTGGG AGACATCATA GTGCTAGTAC TATGTCAAAG 4440
CAACAGTCCA CACTTTGTCC AATGGTTTTT TCACTGCCTG ACCTTTAAAA GGCCATCGAT 

  4500
ATTCTTTGCT CCTTGCCATA GGACTTGTAT TGTTATTTAA ATTACTGGAT TCTAAGGAAT 4560
TTCTTATCTG ACAGAGCATC AGAACCAGAG GCTTGGTCCC ACAGGCCAGG GACCAATGCG 4620
CTGCAG 4626 (2) INFORMATION FOR SEQ ID NO:28:
   li)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 8082 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear  
   Iii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:28:
AGCTTGTTTG   GCCGTTTTAG    GGTTTGTTGG   AA=TTTT    TCGTCTATGT ACTTGTGAAT 60
TATTTCACGT TTGCCATTAC CGGTTCTCCA TAGGGTGATG TTCATTAGCA GTGGTGATAG 120
GTTAATTTTC ACCATCTCTT ATGCGGTTGA ATAGTCACCT CTGAACCACT TTTTCCTCCA 180
GTAACTCCTC   TTTCTTCGGA    CCTTCTGCAG CCAACCTGAA AGAATAACAA GGAGGTGGCT 240   GGAAACTTGT      TTTAAGGAAC    CGCCTGTCCT TCCCCCGCTG GAAACCTTGC ACCTCGGACG 300   CTCCTGCTCC    TGCCCCCACC TGACCCCCGC CCTCGTTGAC ATCCAGGCGC GATGATCTCT 360
GCTGCCAGTA GAGGGCACAC TTACTTTACT TTCGCAAACC TGAACGCGGG TGCTGCCCAG 420   AGAGGGGGCG    GAGGGAAAGA CGCTTTGCAG CAAAATCCAG CATAGCGATT GGTTGCTCCC 480   CGCGTTTGCG    GCAAAGGCCT GGAGGCAGGA   GTAATTTGCA    ATCCTTAAAG CTGAATTGTG 

  540
CAGTGCATCG GATTTGGAAG CTACTATATT CACTTAACAC TTGAACGCTG AGCTGCAAAC 600
TCAACGGGTA ATAACCCATC TTGAACAGCG TACATGCTAT ACACACACCC CTTCCCCCG 660
AATTGTTTTC TCTTTTGGAG GTGGTGGAGG GAGAGAAAAG TTTACTTAAA ATGCCTTTGG 720
GTGAGGGACC AAGGATGAGA   AGAATGTTT      TTGTTTTTCA    TGCCGTGGAA TAACACAAAA 780
TAAAAAATCC CGAGGGAATA TACATTATAT ATTAAATATA GATCATTTCA GGGAGCAAAC 840
AAATCATGTG TGGGGCTGGG CAACTAGCTG AGTCGAAGCG TAAATAAAAT GTGAATACAC 900
GTTTGCGGGT TACATACAGT GCACTTTCAC   TAGTATTCAG    AAAAAATTGT GAGTCAGTGA 960
ACTAGGAAAT TAATGCCTGG AAGGCAGCCA AATTTTAATT AGCTCAAGAC TCCCCCCCCC 1020
CCCCAAAAAA AGGCACGGAA   GTAATACTCC    TCTCCTCTTC TTTGATCAGA ATCGATGCAT 1080
TTTTTGTGCA TGACCGCATT TCCAATAATA AAAGGGGAAA GAGGACCTGG AAAGGAATTA 1140
AACGTCCGGT TTGTCCGGGG AGGAAAGAGT   TAACGGTTTT    

  TTTCACAAGG GTCTCTGCTG 1200
ACTCCCCCGG CTCGGTCCAC AAGCTCTCCA CTTGCCCCTT TTAGGAAGTC CGGTCCCGCG 1260  
GTTCGGGTAC CCCCTGCCCC TCCCATATTC TCCCGTCTAG   CACCTTTGAT    TTCTCCCAAA 1320
CCCGGCAGCC CGAGACTGTT GCAAACCGGC GCCACAGGGC GCAAAGGGGA TTTGTCTCTT 1380
CTGAAACCTG GCTGAGAAAT TGGGAACTCC GTGTGGGAGG CGTGGGGGTG GGACGGTGGG 1440
GTACAGACTG GCAGAGAGCA GGCAACCTCC CTCTCGCCCT AGCCCAGCTC TGGAACAGGC 1500
AGACACATCT CAGGGCTAAA CAGACGCCTC CCGCACGGGG CCCCACGGAA GCCTGAGCAG 1560
GCGGGGCAGG AGGGGCGGTA TCTGCTGCTT TGGCAGCAAA TTGGGGGACT CAGTCTGGGT 1620
GGAAGGTATC CAATCCAGAT AGCTGTGCAT ACATAATGCA TAATACATGA CTCCCCCCAA 1680
CAAATGCAAT GGGAGTTTAT TCATAACGCG CTCTCCAAGT ATACGTGGCA ATGCGTTGCT 1740
GGGTTATTTT AATCATTCTA GGCATCGTTT TCCTCCTTAT GCCTCTATCA TTCCTCCCTA 1800
TCTACACTAA CATCCCACGC TCTGAACGCG CGCCCATTAA TACCCTTCTT TCCTCCACTC 1860
TCCCTGGGAC TCTTGATCAA  <RTI  

   ID=135.2> AGCGCGGCCC    TTTCCCCAGC CTTAGCGAGG CGCCCTGCAG 1920
CCTGGTACGC GCGTGGCGTG GCGGTGGGCG CGCAGTGCGT TCTCTGTGTG GAGGGCAGCT 1980
GTTCCGCCTG CGATGATTTA TACTCACAGG ACAAGGATGC   GGTITGTCAA    ACAGTACTGC 2040
TACGGAGGAG CAGCAGAGAA   AGGGAGAGGG    TTTGAGAGGG AGCAAAAGAA AATGGTAGGC 2100
GCGCGTAGTT AATTCATGCG GCTCTCTTAC TCTGTTTACA TCCTAGAGCT AGAGTGCTCG 2160
GCTGCCCGGC TGAGTCTCCT CCCCACCTTC CCCACCCTCC CCACCCTCCC CATAAGCGCC 2220
CCTCCCGGGT TCCCAAAGCA GAGGGCGTGG GGGAAAAGAA AAAAGATCCT CTCTCGCTAA 2280
TCTCCGCCCA CCGGCCCTTT ATAATGCGAG GGTCTGGACG GCTGAGGACC CCCGAGCTGT 2340
GCTGCTCGCG GCCGCCACCG CCGGGCCCCG GCCGTCCCTG GCTCCCCTCC TGCCTCGAGA 2400
AGGGCAGGGC TTCTCAGAGG CTTGGCGGGA AAAAGAACGG AGGGAGGGAT CGCGCTGAGT 2460
ATAAAAGCCG GTTTTCGGGG CTTTATCTAA CTCGCTGTAG TAATTCCAGC GAGAGGCAGA 2520
GGGAGCGAGC GGGCGGCCGG CTAGGGTGGA AGAGCCGGGC GAGCAGAGCT 

  GCGCTGCGGG 2580
CGTCCTGGGA AGGGAGATCC GGAGCGAATA GGGGGCTTCG CCTCTGGCCC AGCCCTCCCG 2640
CTGATCCCCC AGCCAGCGGT CCGCAACCCT TGCCGCATCC   ACGAAACTTT    GCCCATAGCA 2700  
GCGGGCGGGC   Aulw GCACT    GGAACTTACA ACACCCGAGC AAGGACGCGA CTCTCCCGAC 2760
GCGGGGAGGC TATTCTGCCC   ATTTGGGGAC    ACTTCCCCGC CGCTGCCAGG ACCCGCTTCT 2820   CTGAAAGGCT    CTCCTTGCAG CTGCTTAGAC GCTGGATTTT TTTCGGGTAG TGGAAAACCA 2880
GGTAAGCACC   GAAGTCCACT    TGCCTTTTAA TTTATTTTTT TATCACTTTA ATGCTGAGAT 2940
GAGTCGAATG CCTAAATAGG GTGTCTTTTC TCCCATTCCT GCGCTATTGA CACTTTTCTC 3000
AGAGTAGTTA TGGTAACTGG GGCTGGGGTG   GGGGGTAATC    CAGAACTGGA TCGGGGTAAA 3060
GTGACTTGTC AAGATGGGAG AGGAGAAGGC AGAGGGAAAA CGGGAATGGT   TTTTAAGACT    3120   ACCCTTTCGA    GATTTCTGCC 

  TTATGAATAT ATTCACGCTG ACTCCCGGCC GGTCGGACAT 3180
TCCTGCTTTA TTGTGTTAAT TGCTCTCTGG GTTTTGGGGG GCTGGGGGTT GCTTTGCGGT 3240
GGGCAGAAAG   CCCCTTGCAT    CCTGAGCTCC TTGGAGTAGG GACCGCATAT CGCCTGTGTG 3300
AGCCAGATCG CTCCGCAGCC GCTGACTTGT CCCCGTCTCC GGGAGGGCAT   TTAAATTTCG    3360
GCTCACCGCA TTTCTGACAG CCGGAGACGG ACACTGCGGC GCGTCCCGCC CGCCTGTCCC 3420
CGCGGCGATT CCAACCCGCC CTGATCCTTT TAAGAAGTTG GCATTTGGCT TTTTAAAAAG 3480
CAATAATACA   ATTTAAAACC      TGGGTCTCTA    GAGGTGTTAG GACGTGGTGT TGGGTAGGCG 3540
CAGGCAGGGG   AAAAGGGAGG    CGAGGATGTG TCCGATTCTC CTGGAATCGT TGACTTGGAA 3600
AAACCAGGGC GAATCTCCGC ACCCAGCCCT GACTCCCCTG CCGCGGCCGC CCTCGGGTGT 3660
CCTCGCGCCC GAGATGCGGA GGAACTGCGA GGAGCGGGGC   TCTGGGCGGT    TCCAGAACAG 3720   CTGCTACCCT    

  TGGTGGGGTG GCTCCGGGGG AGGTATCGCA GCGGGGTCTC TGGCGCAGTT 3780
GCATCTCCGT ATTGAGTGCG   AAGGGAGGTG    CCCCTATTAT TATTTGACAC CCCCCTTGTA 3840
TTTATGGAGG GGTGGTAAAG CCCGCGGCTG AGCTCGCCAC TCCAGCCGGC GAGAGAAAGA 3900
AGAAAAGCTG GCAAAAGGAG TGTTGGACGG GGGCGGTACT GGGGGTGGGG ACGGGGGCGG 3960
TGGAGAGGGA AGGTTGGGAG GGGCTGCGGT GCCGGCGGGG GTAGGAGAGC GGCTAGGGCG 4020
CGAGTGGGAA CAGCCGCAGC GGAGGGGCCC CGGCGCGGAG CGGGGTTCAC GCAGCCGCTA 4080
GCGCCCAGGC GCCTCTCGCC TTCTCCTTCA GGTGGCGCAA AACTTTGTGC CTTGGATTTT 4140  
GGCAAATTGT TTTCCTCACC GCCACCTCCC GCGGCTTCTT AAGGGCGCCA GGGCCGATTT 4200
CGATTCCTCT GCCGCTGCGG GGCCGACTCC CGGGCTTTGC GCTCCGGGCT CCCGGGGGAG 4260
CGGGGGCTCG GCGGGCACCA AGCCGCTGGT TCACTAAGTG CGTCTCCGAG ATAGCAGGGG 4320
ACTGTCCAAA GGGGGTGAAA GGGTGCTCCC TTTATTCCCC CACCAAGACC ACCCAGCCGC 4380
TTTAGGGGAT AGCTCTGCAA GGGGAGAGGT TCGGGACTGT GGCGCGCACT GCGCGCTGCG 4440
CCAGGTTTCC GCACCAAGAC 

  CCCTTTAACT CAAGACTGCC   TCCCGCTTTG    TGTGCCCCGC 4500
TCCAGCAGCC   TCCCGCGACG    ATGCCCCTCA ACGTTAGCTT CACCAACAGG   AACTATGACC    4560
TCGACTACGA   CTCGGTGCAG    CCGTATTTCT ACTGCGACGA GGAGGAGAAC TTCTACCAGC 4620
AGCAGCAGCA GAGCGAGCTG CAGCCCCCGG CGCCCAGCGA GGATATCTGG AAGAAATTCG 4680
AGCTGCTGCC CACCCCGCCC CTGTCCCCTA GCCGCCGCTC CGGGCTCTGC TCGCCCTCCT 4740
ACGTTGCGGT CACACCCTTC TCCCTTCGGG GAGACAACGA CGGCGGTGGC GGGAGCTTCT 4800
CCACGGCCGA   CCAGCTGGAG    ATGGTGACCG   AGCTGCTGGG    AGGAGACATG GTGAACCAGA   4860   
GTTTCATCTG CGACCCGGAC GACGAGACCT TCATCAAAAA CATCATCATC   CAGGACTGTA    4920
TGTGGAGCGG CTTCTCGGCC GCCGCCAAGC TCGTCTCAGA GAAGCTGGCC TCCTACCAGG 4980
CTGCGCGCAA AGACAGCGGC AGCCCGAACC CCGCCCGCGG CCACAGCGTC 

  TGCTCCACCT 5040   CCAGCTTGTA    CCTGCAGGAT CTGAGCGCCG CCGCCTCAGA GTGCATCGAC CCCTCGGTGG 5100
TCTTCCCCTA CCCTCTCAAC GACAGCAGCT CGCCCAAGTC   CTGCGCCTCG    CAAGACTCCA 5160
GCGCCTTCTC TCCGTCCTCG GATTCTCTGC TCTCCTCGAC GGAGTCCTCC CCGCAGGGCA 5220
GCCCCGAGCC CCTGGTGCTC CATGAGGAGA CACCGCCCAC CACCAGCAGC GACTCTGGTA 5280
AGCGAAGCCC GCCCAGGCCT   GTCAAAAGTG      GGCGGCTGGA    TACCTTTCCC ATTTTCATTG 5340   GCAGCTTATT    TAACGGGCCA CTCTTATTAG GAAGGAGAGA TAGCAGATCT GGAGAGATTT 5400
GGGAGCTCAT CACCTCTGAA ACCTTGGGCT   TTAGCGIITC    CTCCCATCCC TTCCCCTTAG 5460
ACTGCCCATG   TTTGCAGCCC    CCCTCCCCGT TTGTCTCCCA CCCCTCAGGA ATTTCATTTA 5520   GGTTTTTAAA      CCTTCTGGCT    TATCTTACAA CTCAATCCAC TTCTTCTTAC 

    CTCCCGTTAA    5580  
CATTTTAATT GCCCTGGGGC GGGGTGGCAG GGAGTGTATG AATGAGGATA   AGAGAGGATT    5640
GATCTCTGAG   AGTGAATGAA    TTGCTTCCCT   CTTAACTTCC      GAGAAGTGGT      GGGATTTAAT    5700
GAACTATCTA CAAAAATGAG GGGCTGTGTT   TAGAGGCTAG    GCAGGGCCTG CCTGAGTGCG 5760
GGAGCCAGTG AACTGCCTCA AGAGTGGGTG GGCTGAGGAG CTGGGATCTT CTCAGCCTAT 5820
TTTGAACACT GAAAAGCAAA TCCTTGCCAA AGTTGGACTT   mTrTTTCT    TTTATTCCTT 5880
CCCCCGCCCT CTTGGACTTT TGGCAAAACT GCAATTTTTT TTTTTTTATT TTTCATTTCC 5940
AGTAAAATAG GGAGTTGCTA AAGTCATACC   AAGCAATTTG    CAGCTATCAT TTGCAACACC 6000
TGAAGTGTTC TTGGTAAAGT CCCTCAAAAA TAGGAGGTGC   TTGGGAATGT    GCTTTGCTTT 6060
GGGTGTGTCC AAAGCCTCAT TAAGTCTTAG 

  GTAAGAATTG GCATCAATGT CCTATCCTGG 6120
GAAGTTGCAC TTTTCTTGTC CATGCCATAA CCCAGCTGTC   TTTCCCTTTA    TGAGACTCTT 6180
ACCTTCATGG TGAGAGGAGT AAGGGTGGCT GGCTAGATTG GTTCTTTTTT TTTTTTTTTC 6240
CTTTTTTAAG ACGGAGTCTC ACTCTGTCAC TAGGCTGGAG TGCAGTGGCG CAATCAACCT 6300
CCAACCCCCT   GGTTCAAGAG    ATTCTCCTGC CTCAGCCTCC CAAGTAGCTG GGACTACAGG 6360
TGCACACCAC CATGCCAGGC TAATTTTTGT   AATTTTAGTA    GAGATGGGGT TTCATCGTGT 6420
TGGCCAGGAT GGTCTCTCCT GACCTCACGA TCCGCCCACC TCGGCCTCCC AAAGTGCTGG 6480
GATTACAGGT GTGAGCCAGG GCACCAGGCT TAGATGTGGC TCTTTGGGGA GATAATTTTG 6540
TCCAGAGACC TTTCTAACGT ATTCATGCCT TGTATTTGTA CAGCATTAAT   CTGGTAATTG    6600   ATTATITTM      TGTAACCTTG    CTAAAGGAGT GATTTCTATT   TCCTTTCTTA    AAGAGGAGGA 6660
ACAAGAAGAT GAGGAAGAAA 

  TCGATGTTGT TTCTGTGGAA AAGAGGCAGG CTCCTGGCAA 6720
AAGGTCAGAG TCTGGATCAC CTTCTGCTGG AGGCCACAGC AAACCTCCTC ACAGCCCACT 6780
GGTCCTCAAG AGGTGCCACG TCTCCACACA TCAGCACAAC TACGCAGCGC CTCCCTCCAC 6840
TCGGAAGGAC TATCCTGCTG CCAAGAGGGT CAAGTTGGAC AGTGTCAGAG TCCTGAGACA 6900
GATCAGCAAC   AACCGAAAAT    GCACCAGCCC CAGGTCCTCG GACACCGAGG AGAATGTCAA 6960
GAGGCGAACA CACAACGTCT TGGAGCGCCA GAGGAGGAAC GAGCTAAAAC GGAGCTTTTT 7020  
TGCCCTGCGT GACCAGATCC CGGAGTTGGA   AAACAATGAA    AAGGCCCCCA AGGTAGTTAT 7080
CCTTAAAAAA GCCACAGCAT ACATCCTGTC CGTCCAAGCA GAGGAGCAAA AGCTCATTTC 7140
TGAAGAGGAC TTGTTGCGGA AACGACGAGA ACAGTTGAAA CACAAACTTG AACAGCTACG 7200
GAACTCTTGT GCGTAAGGAA AAGTAAGGAA AACGATTCCT TCTAACAGAA ATGTCCTGAG 7260
CAATCACCTA TGAACTTGTT TCAAATGCAT GATCAAATGC AACCTCACAA CCTTGGCTGA 7320
GTCTTGAGAC TGAAAGATTT AGCCATAATG TAAACTGCCT CAAATTGGAC  <RTI  

   ID=139.2> TTTGGGCATA    7380
AAAGAACTTT TTTATGCTTA CCATCTTTTT   TTTTTCTTTA    ACAGATTTGT ATTTAAGAAT 7440
TGTTTTTAAA AAATTTTAAG ATTTACACAA TGTTTCTCTG TAAATATTGC CATTAAATGT 7500   AAATAACTTT    AATAAAACGT TTATAGCAGT TACACAGAAT TTCAATCCTA GTATATAGTA 7560
CCTAGTATTA TAGGTACTAT AAACCCTAAT TTTTTTTATT   TAAGTACATT      TTGCTTTTA    7620
AAGTTGATTT TTTTCTATTG TTTTTAGAAA AAATAAAATA ACTGGCAAAT ATATCATTGA 7680
GCCAAATCTT AAGTTGTGAA   TSTTTTGTTT      CGTTTCTTCC    CCCTCCCAAC CACCACCATC 7740   CCTGTTTGTT    TTCATCAATT GCCCCTTCAG AGGGCGGTCT TAAGAAAGGC AAGAGTTTTC 7800
CTCTGTTGAA ATGGGTCTGG GGGCCTTAAG GTCTITAAGT   TCTTGGAGGT    TCTAAGATGC 7860
TTCCTGGAGA CTATGATAAC AGCCAGAGTT GACAGTTAGA AGGAATGGCA GAAGGCAGGT 

  7920
GAGAAGGTGA GAGGTAGGCA AAGGAGATAC AAGAGGTCAA AGGTAGCAGT TAAGTACACA 7980
AAGAGGCATA AGGACTGGGG AGTTGGGAGG AAGGTGAGGA AGAAACTCCT   GTTACnTAG    8040
TTAACCAGTG CCAGTCCCCT GCTCACTCCA AACCCAGGAA TT 8082 (2) INFORMATION FOR SEQ ID NO:29:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 5775 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA   Igenomic)     
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:29:
TCCTAGGCGG CGGCCGCGGC GGCGGAGGCA GCAGCGGCGG CGGCAGTGGC GGCGGCGAAG 60
GTGGCGGCGG CTCGGCCAGT ACTCCCGGCC   CCCGCCATTT    CGGACTGGGA GCGAGCGCGG 120
CGCAGGCACT GAAGGCGGCG GCGGGGCCAG AGGCTCAGCG GCTCCCAGGT GCGGGAGAGA 180
GGCCTGCTGA AAATGACTGA ATATAAACTT GTGGTAGTTG   GAGCTTGTGG    CGTAGGCAAG 240   AGTGCCTTGA    CGATACAGCT AATTCAGAAT   CATTTGTGG    ACGAATATGA TCCAACAATA 300
GAGGATTCCT ACAGGAAGCA AGTAGTAATT GATGGAGAAA CCTGTCTCTT GGATATTCTC 360
GACACAGCAG GTCAAGAGGA GTACAGTGCA ATGAGGGACC AGTACATGAG GACTGGGGAG 420
GGCTTTCTTT GTGTATTTGC CATAAATAAT ACTAAATCAT TTGAAGATAT TCACCATTAT 480
AGAGAACAAA TTAAAAGAGT TAAGGACTCT GAAGATGTAC CTATGGTCCT AGTAGGAAAT 540
AAATGTGATT TGCCTTCTAG AACAGTAGAC ACAAAACAGG CTCAGGACTT AGCAAGAAGT 600
TATGGAATTC   CTTTTATTGA    AACATCAGCA AAGACAAGAC 

  AGGGTGTTGA TGATGCCTTC 660
TATACATTAG TTCGAGAAAT TCGAAAACAT AAAGAAAAGA TGAGCAAAGA TGGTAAAAAG 720
AAGAAAAAGA   AGTCAAAGAC    AAAGTGTGTA ATTATGTAAA TACAATTTGT ACTTTTTTCT 780
TAAGGCATAC TAGTACAAGT GGTAATTTTT GTACATTACA CTAAATTATT   AGCATTTGrT    840
TTAGCATTAC CTAATTTTTT TCCTGCTCCA TGCAGACTGT   TAGCT1=TAC    CTTAAATGCT 900
TATTTTAAAA TGACAGTGGA   AGrTTTrTT    TCCTCGAAGT GCCAGTATTC   CCAGAGTTTT    960
GGTTTTTGAA CTAGCAATGC CTGTGAAAAA GAAACTGAAT ACCTAAGATT TCTGTCTTGG 1020   GGTTTTTGGT    GCATGCAGTT   GATTACTTcT    TATTTTTCTT ACCAAGTGTG AATGTTGGTG 1080
TGAAACAAAT TAATGAAGCT TTTGAATCAT CCCTATTCTG TGTTTTATCT AGTCACATAA 1140
ATGGATTAAT   TACTAATTTC    AGTTGAGACC TTCTAATTGG   TITITACTGA    

  AACATTGAGG 1200
GACACAAATT TATGGGCTTC CTGATGATGA TTCTTCTAGG CATCATGTCC TATAGTTTGT 1260
CATCCCTGAT GAATGTAAAG TTACACTGTT CACAAAGGTT TTGTCTCCTT TCCACTGCTA 1320
TTAGTCATGG TCACTCTCCC CAAAATATTA TATTTTTTCT ATAAAAAGAA AAAAATGGAA 1380  
AAAAATTACA AGGCAATGGA   AACTATTATA    AGGCCATTTC CTTTTCACAT TAGATAAATT 1440
ACTATAAAGA CTCCTAATAG   CTTTTCCTG    TTAAGGCAGA CCCAGTATGA   ATGGGATTAT    1500
TATAGCAACC ATTTTGGGGC TATATTTACA TGCTACTAAA TTTTTATAAT AATTGAAAAG 1560
ATTTTAACAA   GTATAAAAAA    ATTCTCATAG GAATTAAATG TAGTCTCCCT GTGTCAGACT 1620   GCTCT=CAT    AGTATAACTT   TAAATCTTTT    CTTCAACTTG AGTCTTTGAA GATAGTTTTA 1680
ATTCTGCTTG TGACATTAAA AGATTATTTG GGCCAGTTAT AGCTTATTAG GTGTTGAAGA 1740
GACCAAGGTT GCAAGCCAGG CCCTGTGTGA ACCTTGAGCT TTCATAGAGA GTTTCACAGC 

  1800
ATGGACTGTG TGCCCCACGG TCATCCGAGT GGTTGTACGA TGCATTGGTT AGTCAAAAAT 1860
GGGGAGGGAC TAGGGCAGTT TGGATAGCTC AACAAGATAC AATCTCACTC TGTGGTGGTC 1920
CTGCTGACAA ATCAAGAGCA TTGCTTTTGT TTCTTAAGAA AACAAACTCT TTTTTAAAAA 1980
TTACTTTTAA ATATTAACTC AAAAGTTGAG ATTTTGGGGT GGTGGTGTGC CAAGACATTA 2040   ATTTTTTTTT    TAAACAATGA AGTGAAAAAG TTTTACAATC TCTAGGTTTG GCTAGTTCTC 2100
TTAACACTGG TTAAATTAAC ATTGCATAAA CACTTTTCAA GTCTGATCCA TATTTAATAA 2160
TGCTTTAAAA TAAAAATAAA AACAATCCTT TTGATAAATT TAAAATGTTA CTTATTTTAA 2220
AATAAATGAA GTGAGATGGC ATGGTGAGGT GAAAGTATCA CTGGACTAGG TTGTTGGTGA 2280
CTTAGGTTCT AGATAGGTGT CTTTTAGGAC TCTGATTTTG AGGACATCAC TTACTATCCA 2340   TTTCITCATG    TTAAAAGAAG TCATCTCAAA CTCTTAGTTT TTTTTTTTTA CACTATGTGA 2400
TTTATATTCC ATTTACATAA GGATACACTT ATTTGTCAAG CTCAGCACAA TCTGTAAATT 2460
TTTAACCTAT GTTACACCAT CTTCAGTGCC  <RTI   

   ID=141.9> AGTCTTGGGC    AAAATTGTGC AAGAGGTGAA 2520   GTTTATATTT    GAATATCCAT   TCTCGTTTTA    GGACTCTTCT TCCATATTAG TGTCATCTTG 258 
CCAATCCATT AGCGACAGTA   GGATTTTTCA    ACCCTGGTAT GAATAGACAG AACCCTATCC 2880
AGTGGAAGGA   GAATTTAATA    AAGATAGTGC AGAAAGAATT CCTTAGGTAA TCTATAACTA 2940
GGACTACTCC TGGTAACAGT AATACATTCC   ATTGTTTTAG    TAACCAGAAA TCTTCATGCA 3000
ATGAAAAATA CTTTAATTCA TGAAGCTTAC TTTTTTTTTT TTGGTGTCAG AGTCTCGCTC 306
TTGTCACCCA GGCTGGAATG CAGTGGCGCC ATCTCAGCTC ACTGCAACCT TCCATCTTCC 3120
CAGGTTCAAG CGATTCTCGT GCCTCGGCCT CCTGAGTAGC TGGGATTACA GGCGTGTGCA 3180
CTACACTCAA CTAATTTTTG   TATTTTTAGG    AGAGACGGGG TTTCACCTGT TGGCCAGGCT 3240
GGTCTCGAAC TCCTGACCTC AAGTGATTCA CCCACCTTGG CCTCATAAAC   CTGTTTTGCA    

  3300
GAACTCATTT ATTCAGCAAA TATTTATTGA GTGCCTACCA GATGCCAGTC ACCGCACAAG 3360
GCACTGGGTA TATGGTATCC CCAAACAAGA GACATAATCC CGGTCCTTAG GTACTGCTAG 3420
TGTGGTCTGT AATATCTTAC TAAGGCCTTT GGTATACGAC CCAGAGATAA CACGATGCGT 3480
ATTTTAGTTT TGCAAAGAAG   GGGTTTGGTC    TCTGTGCCAG CTCTATAATT GTTTTGCTAC 3540
GATTCCACTG AAACTCTTCG ATCAAGCTAC TTTATGTAAA TCACTTCATT GTTTTAAAGG 3600
AATAAACTTG ATTATATTGT   TTrrTTATIT    GGCATAACTG TGATTCTTTT AGGACAATTA 3660
CTGTACACAT TAAGGTGTAT GTCAGATATT CATATTGACC CAAATGTGTA ATATTCCAGT 3720
TTTCTCTGCA TAAGTAATTA AAATATACTT AAAAATTAAT AGTTTTATCT GGGTACAAAT 3780
AAACAGTGCC TGAACTAGTT CACAGACAAG GGAAACTTCT ATGTAAAAAT CACTATGATT 3840
TCTGAATTGC TATGTGAAAC TACAGATCTT TGGAACACTG   TTTAGGTAGG      GTGTTAAGAC    3900
TTGACACAGT ACCTCGTTTC TACACAGAGA AAGAAATGGC CATACTTCAG GAACTGCAGT 

  3960
GCTTATGAGG   GGATATTTAG    GCCTCTTGAA   TTTTTGATGT    AGATGGGCAT TTTTTTAAGG 4020
TAGTGGTTAA TTACCTTTAT GTGAACTTTG AATGGTTTAA CAAAAGATTT GTTTTTGTAG 4080
AGATTTTAAA GGGGGAGAAT TCTAGAAATA AATGTTACCT AATTATTACA GCCTTAAAGA 4140
CAAAAATCCT TGTTGAAGTT   TTTTAAAAA    AAGACTAAAT TACATAGACT TAGGCATTAA 4200
CATGTTTGTG GAAGAATATA GCAGACGTAT ATTGTATCAT TTGAGTGAAT GTTCCCAAGT 4260  
AGGCATTCTA GGCTCTATTT AACTGAGTCA CACTGCATAG GAATTTAGAA CCTAACTTTT 4320
ATAGGTTATC AAAACTGTTG TCACCATTGC ACAATTTTGT CCTAATATAT ACATAGAAAC 4380   TTTGTGGGGC    ATGTTAAGTT   ACAGTTTGCA    CAAGTTCATC   TCATTTGTAT    TCCATTGATT 4440
TTTTTTTTTC TTCTAAACAT TTTTTCTTCA AAACAGTATA   TATAACTTT      TrTAGGGGAT    4500
TTTTTTTAGA CAGCAAAAAA 

  CTATCTGAAG ATTTCCATTT GTCAAAAAGT AATGATTTCT 4560
TGATAATTGT GTAGTGAATG   TTTTTTAGAA    CCCAGCAGTT ACCTTGAAAG CTGAATTTAT 4620
ATTTAGTAAC TTCTGTGTTA ATACTGGATA GCATGAATTC TGCATTGAGA AACTGAATAG 4680
CTGTCATAAA ATGCTTTCTT TCCTAAAGAA AGATACTCAC   ATGAGTTCTT    GAAGAATAGT 4740
CATAACTAGA TTAAGATCTG TGTTTTAGTT   TAATAGTTTG    AAGTGCCTGT TTGGGATAAT 4800
GATAGGTAAT TTAGATGAAT TTAGGGGAAA AAAAAGTTAT CTGCAGTTAT GTTGAGGGCC 4860
CATCTCTCCC CCCACACCCC CACAGAGCTA ACTGGGTTAC AGTGTTTTAT CCGAAAGTTT 4920
CCAATTCCAC TGTCTTGTGT   TTTCATGTTG    AAAATACTTT TGCATTTTTC   C=GAGTGC    4980   CAATTTCTTA    CTAGTACTAT TTCTTAATGT AACATGTTTA CCTGGCCTGT CTTTTAACTA 5040
TTTTTGTATA GTGTAAACTG AAACATGCAC ATTTTGTACA   TTGTGCTTTC    TTTTGTGGGT 5100
CATATGCAGT 

  GTGATCCAGT TGTTTTCCAT CATTTGGTTG CGCTGACCTA GGAATGTTGG 5160
TCATATCAAA CATTAAAAAT GACCACTCTT TTAATGAAAT TAACTTTTAA ATGTTTATAG 5220
GAGTATGTGC TGTGAAGTGA   TCTAAAATTT    GTAATATTTT TGTCATGAAC TGTACTACTC 5280
CTAATTATTG TAATGTAATA AAAATAGTTA CAGTGACTAT GAGTGTGTAT   TTATTCATGC    5340   AAATTTGAAC    TGTTTGCCCC GAAATGGATA TGGATACTTT ATAAGCCATA GACACTATAG 5400
TATACCAGTG AATCTTTTAT GCAGCTTGTT AGAAGTATCC TTTTATTTTC TAAAAGGTGC 5460
TGTGGATATT ATGTAAAGGC   GTGTTTGCTT    AAACAATTTT CCATATTTAG AAGTAGATGC 5520
AAAACAAATC TGCCTTTATG ACAAAAAAAT AGGATAACAT TATTTATTTA TTTCCTTTTA 5580
TCAATAAGGT AATTGATACA CAACAGGTGA CTTGGTTTTA GGCCCAAAGG TAGCAGCAGC 5640
AACATTAATA ATGGAAATAA TTGAATAGTT AGTTATGTAT GTTAATGCCA GTCACCAGCA 5700    GGCTATTTCA    AGGTCAGAAG TAATGACTCC ATACATATTA TTTATTTCTA 

  TAACTACATT 5760
TAAATCATTA CCAGG 5775 (2) INFORMATION FOR SEQ ID   NO:30:   
 (i) SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 151 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (XI) SEQUENCE DESCRIPTION: SEQ ID NO:30:
CAGGTTCTTG CTGGTGTGAA ATGACTGAGT ACAAACTGGT GGTGGTTGGA GCAGGTGGTG 60
TTGGGAAAAG CGCACTGACA ATCCAGCTAA TCCAGAACCA   CTTTGTAGAT    GAATATGATC 120
CCACCATAGA   GGTGAGGCCC      AGTGGTAGCC    C 151 (2) INFORMATION FOR SEQ ID NO:31:
   li)    SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 199 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:31:
GATTCTTACA GAAAACAAGT GGTTATAGAT GGTGAAACCT   GTTTGTTGGA    CATACTGGAT 60
ACAGCTGGAC AAGAAGAGTA CAGTGCCATG AGAGACCAAT ACATGAGGAC AGGCGAAGGC 120
TTCCTCTGTG TATTTGCCAT CAATAATAGC AAGTCATTTG CGGATATTAA CCTCTACAGG 180
TACTAGGAGT CATTATTTT 199 (2) INFORMATION FOR SEQ ID NO:32:  
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 160 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:32:
GGAGCAGATT AAGCGAGTAA AAGACTCGGA TGATGTACCT ATGGTGCTAG TGGGAAACAA 60
GTGTGATTTG CCAACAAGGA CAGTTGATAC   AAAACAAGCC    CACGAACTGG   CCAAGAGTTA    120
CGGGATTCCA TTCATTGAAA CCTCAGCCAA GACCAGACAG 160 (2) INFORMATION FOR SEQ ID NO:33:
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 120 base pairs
 (B) TYPE: nucleic acid
 (C) SRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:33:
GGTGTTGAAG   ATGCTTTTTA    CACACTGGTA AGAGAAATAC GCCAGTACCG AATGAAAAAA 60
CTCAACAGCA GTGATGATGG GACTCAGGGT TGTATGGGAT TGCCATGTGT GGTGATGTAA 120 12) INFORMATION FOR   SEO    ID NO:34:
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 4508 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   Iii)    MOLECULE TYPE: DNA   (gnomic)     
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:34:
CAGATCCAGT TGTTCTCATG CAGCCGTGTG CGGTACGTGC CGTAGAGATG CTGGCCCAGG 60
CGGAAGCTGG GCACCTCCTT ACTGTACTTC CATACCCTAT GGAAGTACAG TAAGGAGGTG 120   CCCAGCTTCC    GCCTGGGCCA GCATCTCTAC GGCACGTACC GCACACGGCT GCATGAGAAC 180
AACTGGATCT GCATCCAGGA GGACACCGGC CTCCTCTACC TTAACCGGAG   CCTGGACCAT    240
AGCTCCTGGG AGAAGCTCAG TGTCCGCAAC CGCGGCTTTC CCCTGCTCAC CGTCTACCTC 300
AAGGTCTTCC TGTCACCCAC ATCCCTTCGT GAGGGCGAGT GCCAGTGGCC AGGCTGTGCC 360
CGCGTATACT TCTCCTTCTT CAACACCTCC   TTTCCAGCCT    GCAGCTCCCT CAAGCCCCGG 420
GAGCTCTGCT TCCCAGAGAC AAGGCCCTCC TTCCGCATTC GGGAGAACCG ACCCCCAGGC 480
ACCTTCCACC AGTTCCGCCT GCTGCCTGTG   CAGTTCSTGT    GCCCCAACAT CAGCGTGGCC 540
TACAGGCTCC TGGAGGGTGA GGGTCTGCCC TTCCGCTGCG CCCCGGACAG CCTGGAGGTG 600
AGCACGCGCT GGGCCCTGGA CCGCGAGCAG CGGGAGAAGT ACGAGCTGGT GGCCGTGTGC 

  660
ACCGTGCACG CCGGCGCGCG CGAGGAGGTG GTGATGGTGC CCTTCCCGGT GACCGTGTAC 720
GACGAGGACG ACTCGGCGCC CACCTTCCCC GCGGGCGTCG ACACCGCCAG   CGCCGTGGTG    780
GAGTTCAAGC GGAAGGAGGA CACCGTGGTG   GCCACGCTGC    GTGTCTTCGA TGCAGACGTG 840
GTACCTGCAT CAGGGGAGCT GGTGAGGCGG TACACAAGCA CGCTGCTCCC CGGGGACACC 900
TGGGCCCAGC AGACCTTCCG GGTGGAACAC TGGCCCAACG AGACCTCGGT CCAGGCCAAC 960
GGCAGCTTCG TGCGGGCGAC CGTACATGAC TATAGGCTGG TTCTCAACCG GAACCTCTCC 1020
ATCTCGGAGA ACCGCACCAT GCAGCTGGCG GTGCTGGTCA ATGACTCAGA CTTCCAGGGC 1080
CCAGGAGCGG GCGTCCTCTT GCTCCACTTC AACGTGTCGG TGCTGCCGGT CAGCCTGCAC 1140
CTGCCCAGTA CCTACTCCCT CTCCGTGAGC   AGGAGGGCTC      GCCGATTTGC    CCAGATCGGG 1200
AAAGTCTGTG TGGAAAACTG CCAGGCGTTC AGTGGCATCA ACGTCCAGTA CAAGCTGCAT 1260
TCCTCTGGTG CCAACTGCAG CACGCTAGGG GTGGTCACCT CAGCCGAGGA CACCTCGGGG 

  1320
ATCCTGTTTG TGAATGACAC CAAGGCCCTG CGGCGGCCCA AGTGTGCCGA ACTTCACTAC 1380  
ATGGTGGTGG CCACCGACCA GCAGACCTCT AGGCAGGCCC AGGCCCAGCT GCTTGTAACA 1440
GTGGAGGGGT CATATGTGGC CGAGGAGGCG GGCTGCCCCC TGTCCTGTGC AGTCAGCAAG 1500
AGACGGCTGG AGTGTGAGGA GTGTGGCGGC CTGGGCTCCC CAACAGGCAG GTGTGAGTGG 1560
AGGCAAGGAG ATGGCAAAGG GATCACCAGG AACTTCTCCA CCTGCTCTCC CAGCACCAAG 1620
ACCTGCCCCG ACGGCCACTG CGATGTTGTG GAGACCCAAG ACATCAACAT TTGCCCTCAG 1680
GACTGCCTCC GGGGCAGCAT TGTTGGGGGA CACGAGCCTG GGGAGCCCCG GGGGATTAAA 1740
GCTGGCTATG GCACCTGCAA CTGCTTCCCT GAGGAGGAGA   AGTGCTTCTG    CGAGCCCGAA 1800
GACATCCAGG ATCCACTGTG CGACGAGCTG TGCCGCACGG TGATCGCAGC CGCTGTCCTC 1860   TTCTCCTTCA    TCGTCTCGGT GCTGCTGTCT GCCTTCTGCA TCCACTGCTA   CCACAAGTrr    1920
GCCCACAAGC CACCCATCTC CTCAGCTGAG ATGACCTTCC GGAGGCCCGC CCAGGCCTTC 1980
CCGGTCAGCT ACTCCTCTTC 

  CGGTGCCCGC CGGCCCTCGC TGGACTCCAT GGAGAACCAG 2040
GTCTCCGTGG ATGCCTTCAA GATCCTGGAG GATCCAAAGT GGGAATTCCC TCGGAAGAAC 2100
TTGGTTCTTG GAAAAACTCT AGGAGAAGGC   GAATTTGGAA    AAGTGGTCAA GGCAACGGCC 2160
TTCCATCTGA AAGGCAGAGC AGGGTACACC ACGGTGGCCG TGAAGATGCT GAAAGAGAAC 2220
GCCTCCCCGA GTGAGCTTCG AGACCTGCTG TCAGAGTTCA ACGTCCTGAA GCAGGTCAAC 2280
CACCCACATG TCATCAAATT GTATGGGGCC TGCAGCCAGG ATGGCCCGCT CCTCCTCATC 2340
GTGGAGTACG CCAAATACGG CTCCCTGCGG GGCTTCCTCC GCGAGAGCCG CAAAGTGGGG 2400
CCTGGCTACC TGGGCAGTGG AGGCAGCCGC AACTCCAGCT CCCTGGACCA CCCGGATGAG 2460
CGGGCCCTCA CCATGGGCGA CCTCATCTCA   TTTGCCTGGC    AGATCTCACA GGGGATGCAG 2520
TATCTGGCCG AGATGAAGCT CGTTCATCGG GACTTGGCAG CCAGAAACAT CCTGGTAGCT 2580
GAGGGGCGGA AGATGAAGAT   TTCGGATTTC      GGCTTGTCCC    GAGATGTTTA TGAAGAGGAT 2640
TCCTACGTGA AGAGGAGCCA 

  GGGTCGGATT CCAGTTAAAT GGATGGCAAT TGAATCCCTT 2700
TTTGATCATA TCTACACCAC GCAAAGTGAT GTATGGTCTT TTGGTGTCCT GCTGTGGGAG 2760
ATCGTGACCC TAGGGGGAAA CCCCTATCCT GGGATTCCTC   CTGAGCGGCT    CTTCAACCTT 2820  
CTGAAGACCG GCCACCGGAT GGAGAGGCCA GACAACTGCA GCGAGGAGAT GTACCGCCTG 2880
ATGCTGCAAT GCTGGAAGCA GGAGCCGGAC AAAAGGCCGG   TGTITGCGGA    CATCAGCAAA 2940
GACCTGGAGA AGATGATGGT TAAGAGGAGA GACTACTTGG ACCTTGCGGC GTCCACTCCA 3000
TCTGACTCCC TGATTTATGA CGACGGCCTC TCAGAGGAGG AGACACCGCT GGTGGACTGT 3060
AATAATGCCC CCCTCCCTCG AGCCCTCCCT TCCACATGGA TTGAAAACAA ACTCTATGGC 3120
ATGTCAGACC CGAACTGGCC TGGAGAGAGT CCTGTACCAC TCACGAGAGC TGATGGCACT 3180
AACACTGGGT TTCCAAGATA TCCAAATGAT AGTGTATATG CTAACTGGAT GCTTTCACCC 3240
TCAGCGGCAA AATTAATGGA CACGTTTGAT AGTTAACATT TCTTTGTGAA AGGTAATGGA 3300
CTCACAAGGG GAAGAAACAT GCTGAGAATG GAAAGTCTAC CGGCCCTTTC TTTGTGAACG 

  3360
TCACATTGGC CGAGCCGTGT TCAGTTCCCA GGTGGCAGAC   TCGTTTTTGG      TAGTTTGTTT    3420
TAACTTCCAA GGTGGTTTTA CTTCTGATAG   CCGGTGATTT    TCCCTCCTAG CAGACATGCC 3480
ACACCGGGTA AGAGCTCTGA GTCTTAGTGG TTAAGCATTC   CTTTCTCTTC    AGTGCCCAGC 3540
AGCACCCAGT GTTGGTCTGT GTCCATCAGT GACCACCAAC ATTCTGTGTT CACATGTGTG 3600
GGTCCAACAC TTACTACCTG GTGTATGAAA   TTGGACCTGA    ACTGTTGGAT   TTrTCTAGTT    3660
GCCGCCAAAC AAGGCAAAAA AATTTAAACA TGAAGCACAC ACACAAAAAA GGCAGTAGGA 3720
AAAATGCTGG CCCTGATGAC   cTGTCcTTAT    TCAGAATGAG AGACTGCGGG GGGGGCCTGG 3780   GGGTAGTGTC    AATGCCCCTC CAGGGCTGGA   GGGGAAGAGG    GGCCCCGAGG ATGGGCCTGG 3840
GCTCAGCATT   CGAGATCTTG     <RTI  

   ID=148.12> AGAATGATTT    TTTTTTAATC ATGCAACCTT TCCTTAGGAA 3900
GACATTTGGT   TTTCATCATG    ATTAAGATGA TTCCTAGATT TAGCACAATG GAGAGATTCC 3960
ATGCCATCIT   TACTATGTGG      ATGGTGGTAT    CAGGGAAGAG GGCTCACAAG ACACATTTGT 4020
CCCCCGGGCC CACCACATCA TCCTCACGTG   TTCGGTACTG    AGCAGCCACT ACCCCTGATG 4080
AGAACAGTAT GAAGAAAGGG GGCTGTTGGA GTCCCAGAAT TGCTGACAGC AGAGGCTTTG 4140
CTGCTGTGAA TCCCACCTGC CACCAGCCTG   CAGCACACCC CACAGCCAAG    TAGAGGCGAA 4200   AGCAGTGGCT    CATCCTACCT GTTAGGAGCA GGTAGGGCTT GTACTCACTT TAATTTGAAT 4260  
CTTATCAACT TACTCATAAA GGGACAGGCT AGCTAGCTGT GTTAGAAGTA GCAATGACAA 4320
TGACCAAGGA CTGCTACACC TCTGATTACA ATTCTGATGT GAAAAAGATG   GTGTTTGGCT    4380
CTTATAGAGC CTGTGTGAAA GGCCCATGGA TCAGCTCTTC  <RTI  

   ID=149.2> CTGTGITTGT    AATTTAATGC 4440
TGCTACAAGG TGTTTCTGTT TCTTAGATTC TGACCATGAC   TCATAAGCTT    CTTGTCATTC 4500
TTCATTGC 4508 12) INFORMATION FOR SEQ ID NO:35:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 218 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
 ID) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA   Igenomic)   
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:35:   ATTTATTATT    TTTTGCAGAA AGAGCACTTC AAATAATTTA CAGAACCAGA   ATTTAAGGTG    60
GAAGATGACA   TTTAATGGAT    CCTGCAGTAG   TGTTTGCACA    TGGAAGTCCA AAAACCTGAA 120
AGGAATATTT CAGTTCAGAG TAGTAGCTGC   AAATAATCTA    GGGTITGGTG AATATAGTGG 180
AATCAGTGAG AATATTATAT TAGTTGGAGG TATGTTAC 218 (2) INFORMATION FOR SEQ ID NO:36:
   Ii)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 111 base pairs
 IB) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:36:   TCTGATTTAT    ATTATTAGAT GATTTTTGGA TACCAGAAAC AAGTTTCATA CTTACTATTA 60    TAGTTGGAAT      ATTTCTGGTT    GTTACAATCC CACTGACCTT TGGTAAGTAT A 111 12) INFORMATION FOR SEQ ID NO:37:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 163 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:37:
TCATTTTTTC   CTITATAGTC    TGGCATAGAA GATTAAAGAA TCAAAAAAGT GCCAAGGAAG 60
GGGTGACAGT GCTTATAAAC GAAGACAAAG AGTTGGCTGA GCTGCGAGGT CTGGCAGCCG 120
GAGTAGGCCT GGCTAATGCC TGCTATGCAA TACAGTATGT AGC 163 (2) INFORMATION FOR SEQ ID NO:38:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 190 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   tD)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:38:
AATGTTGCTA TTTTACAGTA CTCTTCCAAC CCAAGAGGAG ATTGAAAATC TTCCTGCCTT 60
CCCTCGGGAA AAACTGACTC TGCGTCTCTT GCTGGGAAGT GGAGCCTTTG GAGAAGTGTA 120
TGAAGGAACA GCAGTGGACA TCTTAGGAGT TGGAAGTGGA GAAATCAAAG TAGCAGTGAA 180
GGTAATGTGA 190 (2) INFORMATION FOR SEQ ID NO:39:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 92 base pairs  
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID   NO:39:      TGTTTTTATG    TTGTATAGAC TTTGAAGAAG GGTTCCACAG ACCAGGAGAA GATTGAATTC 60
CTGAAGGAGG CACATCTGAT GAGGTAGCTC TG 92 (2) INFORMATION FOR   SEO    ID NO:40:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 157 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID   NO:40:   
TGTCTTTCCA   CCTTTCAGCA    AATTTAATCA TCCCAACATT CTGAAGCAGC TTGGAGTITG 60
TCTGCTGAAT GAACCCCAAT ACATTATCCT GGAACTGATG GAGGGAGGAG ACCTTCTTAC 120
TTATTTGCGT AAAGCCCGGA TGGCAACGGT AGGCAGT 157 (2) INFORMATION FOR SEQ ID   NO:41:   
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 125 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:41:  
TTCTTTCATT TCTTACAGTT TTATGGTCCT TTACTCACCT TGGTTGACCT TGTAGACCTG 60
TGTGTAGATA TTTCAAAAGG CTGTGTCTAC TTGGAACGGA TGCATTTCAT TCACAGGTAC 120
AATTC 125 (2) INFORMATION FOR SEQ ID NO:42:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 228 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:42:
ATATAACTTC TGCCACAGGG ATCTGGCAGC TAGAAATTGC CTTGTTTCCG TGAAAGACTA 60
TACCAGTCCA CGGATAGTGA   AGATYGGAGA    CTTTGGACTC GCCAGAGACA TCTATAAAAA 120
TGATTACTAT AGAAAGAGAG GGGAAGGCCT GCTCCCAGTT CGGTGGATGG CTCCAGAAAG 180
TTTGATGGAT GGAATCTTCA CTACTCAATC TGATGTATGG TAAGTTTA 228 (2) INFORMATION FOR SEQ ID   NO:43:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 162 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID   NO:43:   
ACCCTCTACT ATTCTTAGGT   CTITTGGAAT    TCTGATTTGG GAGATTTTAA CTCTTGGTCA 60
TCAGCCTTAT CCAGCTCATT   CCAACCTTGA    TGTGTTAAAC TATGTGCAAA CAGGAGGGAG 120
ACTGGAGCCA CCAAGAAATT GTCCTGATGA TCTGTAAGTT AA 162   (2) INFORMATION FOR SEQ ID NO:44:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 232 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:44:
CTTTCCCCAT   ATATTTAGGT    GGAATTTAAT GACCCAGTGC TGGGCTCAAG AACCCGACCA 60
AAGACCTACT TTTCATAGAA TTCAGGACCA ACTTCAGTTA TTCAGAAATT   T = CTTAAA    120
TAGCATTTAT AAGTCCAGAG ATGAAGCAAA CAACAGTGGA GTCATAAATG AAAGCTTTGA 180
AGGTAAGTTT GATTCTTCAG AATTTTCTAG   TTTTCGCTGC    ACTGTGAACT GA 232 (2) INFORMATION FOR SEQ ID NO:45:
   (i)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 540 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   [ii)    MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID   NO:45:   
CCTTTTGGTC ACAGCAGGAG ATGCGGGCTC AGGACCGGCA GCTGGCAGGG CAGCCTGTCA 60
GGCTGCGGGC CCGGCTGCAC AGACTGAAAG TGGACCAAGT CTGTCACCTG CACCAGGAGC 120
TTCTGGATGA GGCTGAGCTG GAGATGGAGT TAGAGTCTGG GACTGGCTTG CCTCTGGCCC 180
CACCGCTGCG GCATCTGGGA CTCACGCGCA TGAACATCAG TGCCAGACGC TTCACCTCTG 240
CTGACAGCAG ACTTGGGTGT CTCTTGCAGT ATCTGGGAGA AAGAAGGAAG GAAGAGGTCC 300
CCGACCCCGG AGGCTCTGGC TACCTGCTGG GGAAGGTGGG CAACACTTAG GTTTCCAAAA 360    GCTGAATTTA    GAGAGCACAG GATGGAGGGG AGGAGGAGAG GAAACTCGGT GGGCCCCAAA 420
TGTCTTAATA AAAAATGCAT TGAATCCCAT   CAAGGTTTCT    GTAGACTGTC ACAGAGCCTA 480
AATAAATGTT GTTGTATATT CATCCTGTGT CACTGGGACT TTAGGGATTC   CACAACAGGA    540 (2) INFORMATION FOR SEQ ID NO:46:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 275 base pairs
 (B) TYPE:

   nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:
GGATCCTGCC TGTCCGTCTC CCTGTGACCT TGGAGCTTTC CACAGGAGAA   AGCGAGAAAG    60
CGTGTGGTGG GGGAGACAGC CATGCTGGAA AGCCCCCACT   CCCAGCTCAC      TCAGCCTITT    120
GGTGTCTGCC CGGCAGGGGG ACCCCATTCC CGAGGAGCTT TATGAGATGC TGAGTGACCA 180
CTCGATCCGC TCCTTTGATG ATCTCCAACG CCTGCTGCAC GGAGACCCCG   GAGGTAAATG    240
GAATCCCGCC CCGCGCTCCG GCCCTCCGAG GAGAC 275   2)    INFORMATION FOR SEQ ID   NO:47:   
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 180 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY:

   linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:
CTGCAGAGGA AGATGGGGCC GAGTTGGACC TGAACATGAC CCGCTCCCAC TCTGGAGGCG 60
AGCTGGAGAG CTTGGCTCGT GGAAGAAGGA GCCTGGGTAA GACTGAGACA CCCAACAAGG 120  
GTCCTTCAAA TTAGCATGGG GGCCAGGGAA AGAGAACGGG GGCGGGCAGC CAGTCGGAGG 180 (2) INFORMATION FOR SEQ ID NO:48:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 234 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:48:
AGGTTTCGTC TCCTCCCAGG TTCCCTGACC ATTGCTGAGC CGGCCATGAT CGCCGAGTGC 60
AAGACGCGCA CCGAGGTGTT CGAGATCTCC CGGCGCCTCA TAGACCGCAC CAACGCCAAC 120
TTCCTAGTGT GGCCGCCCTG TGTGGAGGTG CAGCGCTGCT CCGGCTGCTG CAACAACCGC 180
AACGTGCAGT GCCGCCCCAC CCAAGTGCAG CTGCGACCTG TTCAAGTGCG TAGG 234 (2) INFORMATION FOR SEQ ID   NO:49:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 203 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
   lD)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:49:
GTGGTCTCTA CAGAGGCATT TTGTGGCTCT GTCCTCCAGG TGAGAAAGAT CGAGATTGTG 60
CGGAAGAAGC   CAATCTTTAA    GAAGGCCACG GTGACGCTGG AAGACCACCT GGCATGCAAG 120
TGTGAGACAG TGGCAGCTGC ACGGCCTGTG ACCCGAAGCC CGGGGGGTTC CCAGGAGCAG 180
CGAGGTAACC ACCTTTCTAG GCT 203 (2) INFORMATION FOR SEQ ID NO:50:  
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 239 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:50:
GGCAGGCCTT GGTCAGTGGG GAGAGACCTC CCCAATGGTC CACATGCTGA   CGAGGTCTTT    60
CTTTTTCTTG TGCAGCCAAA   ACGCCCCAAA    CTCGGGTGAC CATTCGGACG GTGCGAGTCC 120
GCCGGCCCCC CAAGGGCAAG CACCGGAAAT TCAAGCACAC GCATGACAAG ACGGCACTGA 180
AGGAGACCCT TGGAGCCTAG GGGCATCGGC AGGAGAGTGT GTGGGCAGGT GAGGGTCAG 239   t2)    INFORMATION FOR   SEO    ID NO:51:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 1192 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
   tD)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:51:
GAATTCATGC CGGGCCCAGC CGAGCGCGCA GCGGGCACGC CGCGCGCGCG GAGCAGCCGT 60
GCCCGCCGCC CGGGCCCGCC GCCAGGGCGC ACACGCTCCC GCCCCCCTAC CCGGCCCGGG 120
CGGGAGTTTG CACCTCTCCC TGCCCGGGTG CTCGAGCTGC CGTTGCAAAG CCAACTTTGG 180   AAAAAGTTTT    TTGGGGGAGA CTTGGGCCTT GAGGTGCCCA GCTCCGCGCT   TTCCGATTTT    240
GGGGGCCTTT CCAGAAAATG TTGCAAAAAA GCTAAGCCGG CGGGCAGAGG AAAACGCCTG 300
TAGCCGGCGA GTGAAGACGA ACCATCGACT GCCGTGTTCC TTTTCCTCTT GGAGGTTGGA 360
GTCCCCTGGG CGCCCCCACA CGGCTAGACG CCTCGGCTGG TTCGCGACGC AGCCCCCCGG 420  
CCGTGGATGC TGCACTCGGG CTCGGGATCC GCCCAGGTAG CCGGCCTCGG ACCCAGGTCC 480
TGCGCCCAGG TCCTCCCCTG CCCCCCAGCG ACGGAGCCGG GGCCGGGGGC GGCGGCGCCG 540
GGGGCATGCG GGTGAGCCGC GGCTGCAGAG GCCTGAGCGC CTGATCGCCG CGGACCCGAG 600
CCGAGCCCAC CCCCCTCCCC AGCCCCCCAC CCTGGCCGCG GGGGCGGCGC   GCTCGATCTA    660
CGCGTTCGGG GCCCCGCGGG 

  GCCGGGCCCG GAGTCGGCAT GAATCGCTGC TGGGCGCTCT 720
TCCTGTCTCT CTGCTGCTAC CTGCGTCTGG TCAGCGCCGA GGTGAGTGCC ACGGCGGCTG 780
GGGCTGGTTC TTCATTCATT ACCTTCGCCC CCCCCTTCTG ACCGCCCCCT CCTCTCCCTG 840
CAGTGAACTT TGGACCCTTG CACCCGCGAG CCTGACGCCG GGCGCTGGGT GACCTCTTCG 900
GGCTGGGAGC GAGGTCCGGG GGTGACAGGC TCTAAGGGAA GGCAACAGCG GTGGCTTTCT 960
TTCCAACCGG CGGGCGAATC TGGCTCCCTA AGCCGTTCCG TGTCGGGGGA GGGTGTGTGT 1020
GGCCCTGTCC   CCCACCCTTT    GGGAACCCGA GAACAAGCCC CTCCCGGCCG GGGGAGAGGG 1080
GGTGGGGTGG TGCCCAGGGT GCAGAAGGCA GCGCGTCCTC CCGAGCCCAC TTCGGCGCCA 1140
GCCTCGGCTT AGGCTCTGTC CTGCCATCGG CTTGCCCAGG AGGTGCAAGC TT 1192 12) INFORMATION FOR SEQ ID NO:52:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 596 base pairs
   IB)    TYPE: nucleic acid
   {C)    STRANDEDNESS: double
 (D) TOPOLOGY:

   linear
 Iii) MOLECULE TYPE: DNA (genomic)
   lxi)    SEQUENCE DESCRIPTION: SEQ ID   NO:52:   
TGGGGGAGAC AGACATAGAG ACAAGCAGGT CCAACTCAAA GCAAGCTGGG GTTCCTGTTG 60
GGGGTTGAGG GTACAGGGAC TGAGCTGGGC CTCAGAGGCT TCGGCAGGTC CAGACCCCGA 120   GGCCTTTGTG    CTCCTGATCA TCAGGCCTGG ATCCTGTCTG TCCGTCTCCC   TGTGACCTTG    180
GAGCTTTCCA CAGGAGAAAG CGAGAAAGCC CCCACTCCCA GCTCACTCAG   CCTTTTGGTG    240  
TCTGCCCGGC AGGGGGACCC CATTCCCGAG   GAGCTTTATG    AGATGCTGAG TGACCACTCG 300
ATCCGCTCCT TTGATGATCT CCAACGCCTG CTGCACGGAG ACCCCGGAGG TAAATGGAAT 360
CCCGCCCCGC GCTCCGGCCC TCCGAGGAGA CTTTAAGAGA TCTGGGAGGG GCAGGACAGG 420
AGGCATCCCT   CCTTCTTGAC    GTCTGGAGAA CTAGAGGCCC ATGGGCGCCC AGAGAGAGCG 480
TGGCCACACC CATCCAGGGC AGGGCCGAGT CAGCAGGCGG GTTGGTACTG 

  GGACTTGGGG 540
TGTGGCAGGA GAAGCACCCA CGTGTGACTC CGGGTTGGTA CCGGGGTGGG GTACAA 596 (2) INFORMATION FOR SEQ ID   NO:53:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 120 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:
TGACTTCTCC TGCAGAGGAA GATGGGGCCG AGTTGGACCT GAACATGACC CGCTCCCACT 60
CTGGAGGCGA GCTGGAGAGC TTGGCTCGTG GAAGAAGGAG CCTGGGTAAG ACTGAGACAC 120 (2) INFORMATION FOR SEQ ID NO:54:
 Ii) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 236 base pairs
   (B)    TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:54:
TTCATCTCCT CCCAGGTTCC CTGACCATTG   CTGAGCCGGC    CATGATCGCC GAGTGCAAGA 60
CGCGCACCGA GGTGTTCGAG ATCTCCCGGC GCCTCATAGA CCGCACCAAC GCCAACTTCC 120  
TGGTGTGGCC GCCCTGTGTG GAGGTGCAGC GCTGCTCCGG CTGCTGCAAC AACCGCAACG 180
TGCAGTGCCG CCCCACCCAG GTGCAGCTGC GACCTGTCCA GGTGCGTAGG CTCCGG 236 (2) INFORMATION FOR SEQ ID NO:55:
 (i) SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 175 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA   tgenomic)   
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID   NO:55:   
CCTCTCCAGC TCCAGGTGAG AAAGATCGAG ATTGTGCGGA AGAAGCCAAT CTITAAGAAG 60
GCCACGGTGA CGCTGGAAGA CCACCTGGCA TGCAAGTGTG AGACAGTGGC AGCTGCACGG 120
CCTGTGACCC GAAGCCCGGG GGGTTCCCAG GAGCAGCGAG GTAACCACCT TTCCA 175 12) INFORMATION FOR SEQ ID NO:56:
   1i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 183 base pairs
 IB) TYPE: nucleic acid
   1C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:56:   CTTTTTCTTG    TGCAGCCAAA ACGCCCCAAA CTCGGGTGAC CATTCGGACG GTGCGAGTCC 60
GCCGGCCCCC CAAGGGCAAG CACCGGAAAT TCAAGCACAC GCATGACAAG ACGGCACTGA 120
AGGAGACCCT TGGAGCCTAG GGGCATCGGC AGGAGAGTGT GTGGGCAGGT GAGGGCCAGG 180
CGG 183 (2) INFORMATION FOR SEQ ID NO:57:  
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 464 base pairs
   (B)    TYPE: nucleic acid
 IC) STRANDEDNESS: double
 ID) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)
   lxi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:57:
GGTTATTTAA TATGGTATTT GCTGTATTGC CCCCATGGGG   CCTTCGGAGC    GATAATATTG 60
TTTCCCTCGT CCGTCTGTCT CGATGCCTGA TTCGGACGGC CAATGGTGCT TCCCCCACCC 120
CTCCACGTGT CCGTCCACCC TTCCATCAGC GGGTCTCCTC CCAGCGGCCT CCGGTCTTGC 180
CCAGCAGCTC AAGAAGAAAA AGAAGGACTG AACTCCATCG CCATCTTCTT CCCTTAACTC 240
CAAGAACTTG GGATAAGAGT GTGAGAGAGA CTGATGGGGT CGCTCTTTGG GGGAAACGGG 300
TTCCTTCCCC TGCACCTGGC CTGGGCCACA CCTGAGCGCT   GTGGACTGTC    CTGAGGAGCC 360
CTGAGGACCT CTCAGCATAG CCTGCCTGAT CCCTGAACCC CTAGCCAGCT CTGAGGGGAG 420
GCACCTCCAG GCAGGCCAGG CTGCCTCGGA CTCCATGGCT AGGA 464 (2) INFORMATION FOR SEQ ID NO:58:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 139 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: 

   DNA (genomic)
   lxi)    SEQUENCE DESCRIPTION: SEQ ID NO:58:
CCCAGCTCAC TCAGCCTTTT GGTGTCTGCC CGGCAGGGGG ACCCCATTCC CGAGGAGCTT 60
TATGAGATGC TGAGTGACCA CTCGATCCGC TCCTITGATG ATCTCCAACG CCTGCTGCAC 120
GGAGACCCCG GAGGTAAAT 139   (2) INFORMATION FOR SEQ ID NO:59:
   li)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 102 base pairs
   (B)    TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA   Igenomic)   
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:59:
CTGCAGAGGA AGATGGGGCC GAGTTGGACC TGAACATGAC CCGCTCCCAC TCTGGAGGCG 60
AGCTGGAGAG CTTGGCTCGT GGAAGAAGGA GCCTGGGTAA GA 102 (2) INFORMATION FOR SEQ ID NO:60:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 218 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:60:
TCCCAGGTTC CCTGACCATT   GCTGAGCCGG    CCATGATCGC CGAGTGCAAG ACGCGCACCG 60
AGGTGTTCGA GATCTCCCGG CGCCTCATAG ACCGCACCAA CGCCAACTTC CTGGTGTGGC 120
CGCCCTGTGT GGAGGTGCAG CGCTGCTCCG GCTGCTGCAA CAACCGCAAC GTGCAGTGCC 180
GCCCCACCCA GGTGCAGCTG CGACCTGTCC AGGTGCGT 218 (2) INFORMATION FOR SEQ ID NO:61:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 157 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear  
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:61:
CTCCAGGTGA GAAAGATCGA GATTGTGCGG AAGAAGCCAA   TCTITAAGAA    GGCCACGGTG 60
ACGCTGGAAG ACCACCTGGC ATGCAAGTGT GAGACAGTGG CAGCTGCACG GCCTGTGACC 120
CGAAGCCCGG GGGGTTCCCA GGAGCAGCGA GGTAACC 157 (2) INFORMATION FOR SEQ ID NO:62:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 171 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:62:
GTGCAGCCAA AACGCCCCAA ACTCGGGTGA CCATTCGGAC GGTGCGAGTC CGCCGGCCCC 60
CCAAGGGCAA GCACCGGAAA TTCAAGCACA CGCATGACAA GACGGCACTG AAGGAGACCC 120
TTGGAGCCTA GGGGCATCGG CAGGAGAGTG TGTGGGCAGG TGAGGGCCAG G 171 (2) INFORMATION FOR SEQ ID NO:63:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 2875 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lli)    MOLECULE TYPE: DNA   Igenomic)   
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:63:   GGTTTCAAAT    TGGCCCTTTG GCCTCTGGAG CAAATTCAAA TGTAACTCTT CCCCAATCCC 60  
CCTTCTCTTC TTCCAGATTA ATTAAAAGAA GAATGAACTA TAATCCTTGA AGATAACTGG 120
GCAATTTTTT AAGTCGGAGG CTGTTCTTAC TGGTGTGAGG ATTTACACAC GTCTTCAGTT 180   TTTCAGCACA    GACCAGCAGA   CCATCATTTT    TAGAGGAAAT ACTCCCTCTG CCCTCCTTIT 240
TGGTTTCCTT GGTGGTAAAG ATTAAATTTG GTTGCATCAT   TTTGACTTGT    GTTTGAGTCT 300
AGATTTTATG GCACAAGGAA TGGCATAAAC TTTTCATGTG   TTlTGGTTAA    AACAAACCAG 360
ACCATTGCAT TGACCCTGGA   CATCTTTAAT    TGAGAAATTG GTAACTTTAT TTTAATATGT 420
ATATCTGAAG AATTCAAGAA AACAAAGGCA TCCTCAGAGG TGTGCCTCTT   TTCTTTATTA    480
TTAGAGGCAA AACGAACAAT TTTATAGGAT TTGTAGTGAA ATTATACCAG ATTATAAGGA 540
GAACCAAAAC TAAGTCGCAA AATTTATTAA TTTAAGGGGC TCTCGCTTTG 

  AAAGTTTGAG 600
AGTAAGTTAC GATAGGCATT TGTATCCATT CATTACTTTC CTCTTTTCAA ATAAGCAACT 660
AAATAGAAAT GCTAATCTCA GACTTAATTA   TITAACAGAA    GAGTGTACCA TGGAAAACCT 720
CCAGACAAAT TTCTCCTTGG TTCAGGGCTC AACTAAAAAA CTGAATGGGA TGGGAGATGA 780
TGGCAGCCCC CCAGCGAAAA AAATGATAAC GGACATTCAT GTAAATGGAA   AAACGATAAA    840
CAAGGTGCCA ACAGTTAAGA AGGAACACTT GGATGACTAT GGAGAAGCAC CAGTGGAAAC 900
TGATGGAGAG CATGTTAAGC GAACCTGTAC TTCTGTTCCT GAAACTTTGC ATTTAAATCC 960
CAGTTTGAAA CACACATTGG CACAATTCCA TTTAAGTAGT CAGAGCTCGC TGGGTGGACC 1020   AGCAGCATTT    TCTGCTCGGC ATTCCCAAGA AAGCATGTCG CCTACTGTAT TTCTGCCTCT 1080
TCCATCACCT CAGGTTCTTC CTGGCCCATT GCTCATCCCT TCAGATAGCT CCACAGAACT 1140
CACTCAGACT GTGTTGGAAG GGGAATCTAT TTCTTGTTTT CAAGTTGGAG GAGAAAAGAG 1200
ACTCTGTTTG CCCCAAGTCT TAAATTCTGT TCTCCGAGAA TTTACACTCC AGCAAATAAA 1260
TACAGTGTGT GATGAACTGT 

  ACATATATTG TTCAAGGTGT ACTTCAGACC AGCTTCATAT 1320
CTTAAAGGTA CTGGGCATAC TTCCATTCAA TGCCCCATCC TGTGGGCTGA TTACATTAAC 1380
TGATGCACAA AGATTATGTA ATGCTTTATT GCGGCCACGA   ACTTTTCCTC    AAAATGGTAG 1440
CGTACTTCCT GCTAAAAGCT CATTGGCCCA GTTAAAGGAA ACTGGCAGTG CCTTTGAAGT 1500  
GGAGCATGAA TGCCTAGGCA AATGTCAGGG TTTATTTGCA   CCCCAGTTTT    ATGTTCAGCC 1560
TGATGCTCCG TGTATTCAAT GTCTGGAGTG TTGTGGAATG TTTGCACCCC AGACGTITGT 1620
GATGCATTCT CACAGATCAC CTGACAAAAG AACTTGCCAC TGGGGCTTTG AATCAGCTAA 1680
ATGGCATTGC TATCTTCATG TGAACCAAAA ATACTTAGGA ACACCTGAAG AAAAGAAACT 1740
GAAGATAATT TTAGAAGAAA TGAAGGAGAA GTTTAGCATG AGAAGTGGAA AGAGAAATCA 1800
ATCCAAGGCA   AGTTTTTAT      ATCAATTTTT    AATAATGGTA   ATGGTTTACT    TTGAAATGAA 1860
AATTCTATGT TTAGTGTGTA ACTTAACCTG TATGTTGAAC ATTGCTCATG CAACAACAAC 

  1920
AAAATACCGA TTGATATATT TGTATTGCAG   TTTTAGGCC    ATAAAGTGCT TTGCAGTATG 1980
TTTCCTCATT TGACTTTCCA AACATCCTGT GAGAGAAGTA AGACTATTAT   TCCGTITTAC    2040
AGATAAAGTG AATGAAGCTC AGAGAGATAA AATGACTTTC CCAAAATTAT GTAGCCAGGG 2100
AGTGGAGGAG TTAGGGCTTC   mTrTTT      TTTTGTGCT    TTTAGTAGAG GCCAGGTTTC 2160
AGCATGTTGG CCAGGCTGGT CTTGAACTCC TGACCGCGTG ATCCGCCCAC CTTGGCCTCC 2220
CAAAGGGCTG GGATTACATC CTTGAGCCCC TGTGTCCAGC CAGGGCTTCT TTTTCTTATC 2280
CTCTTTGGCA CACATCTTGC TTCTTGACCA CTACATCTGT   TGTTTTTCTA    GGACTCGATA 2340
ATTTGCGCTT TGGTGTTATC TCCATTTGCA AATGGTACAA TGGCCACAAT TCCCGTGGGC 2400
TCAAAACAGC ATTTTTCAGA GATACACCTA TGATTTCTGA TGTTTCTATG TTTGGATATT 2460
CAGGCTTGCT CAATATTTGA AACAAATGGA   AAAGACATGT    ATCTGAAGAA TTTGTGATTT 2520
GAAAGGAATA ACAAAAAAAA 

  TGACAGCTAG AGTAAGGAAA AGTTATTTTA AACTAATAAA 2580
ATATTAATAT AAAAACCTGC CGGGCTCAGT GGCTCACACC TGTAATCCCA ACACTTTGGG 2640
GGGCTGAAGT AGGTGGATCA CCTGAGGTCA   GGAGTTTGAG    ACCAGCCTGG CCAACATGGT 2700
GAAATCCCAT CTCTGCTGAA AATACAAAAA TTAGACGGAT GTGGTGTCGC ACACTTGTAA 2760
TCCCAGCTAC TCAGGAGCTG AGGCAGGAGA ATCGCTTGAA CCCCGGAGGC GGAGGTTGTA 2820
GTGAGCCGAG ATTGTGCCAT TGCGCTCCAG CGTAGGCGTC GAGGGAAACT CCATC 2875 (2) INFORMATION FOR SEQ ID NO:64:  
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 2840 base pairs
   (B)    TYPE: nucleic acid
 IC) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:64:
GGTTTCAAAT TGGCCCTTTG GCCTCTGGAG CAAATTCAAA TGTAACTCTT CCCCAATCCC 60
CCTTCTCTTC TTCCAGATTA   ATTMAAGAA    GAATGAACTA TAATCCTTGA AGATAACTGG 120
GCAATTTTTT AAGTCGGAGG   CTGTTCTTAC    TGGTGTGAGG ATTTACACAC GTCTTCAGTT   180   
TTTCAGCACA GACCAGCAGA CCATCATTTT TAGAGGAAAT ACTCCCTCTG CCCTCCTTTT 240
TGGTTTCCTT GGTGGTAAAG ATTAAATTTG GTTGCATCAT TTTGACTTGT GTTTGAGTCT 300
AGATTTTATG GCACAAGGAA TGGCATAAAC   TITTCATGTG      TTTTGGTTAA    AACAAACCAG 360
ACCATTGCAT TGACCCTGGA CATCTTTAAT TGAGAAATTG GTAACTTTAT TTTAATATGT 420
ATATCTGAAG AATTCAAGAA AACAAAGGCA TCCTCAGAGG TGTGCCTCTT   TTCTTTATTA    480
TTAGAGGCAA AACGAACAAT TTTATAGGAT TTGTAGTGAA ATTATACCAG ATTATAAGGA 540
GAACCAAAAC TAAGTCGCAA AATTTATTAA TTTAAGGGGC TCTCGCTTTG AAAGTTTGAG 600
AGTAAGTTAC 

  GATAGGCATT TGTATCCATT CATTACTTTC CTCTTTTCAA ATAAGCAACT 660
AAATAGAAAT GCTAATCTCA GACTTAATTA TTTAACAGAA GAGTGTACCA TGGAAAACCT 720
CCAGACAAAT TTCTCCTTGG TTCAGGGCTC AACTAAAAAA CTGAATGGGA TGGGAGATGA 780
TGGCAGCCCC CCAGCGAAAA AAATGATAAC GGACATTCAT GTAAATGGAA AAACGATAAA 840
CAAGGTGCCA ACAGTTAAGA   AGGAACACTT    GGATGACTAT GGAGAAGCAC   CAGTGGAAAC    900
TGATGGAGAG CATGTTAAGC GAACCTGTAC TTCTGTTCCT GAAACTTTGC ATTTAAATCC 960
CAGTTTGAAA CACACATTGG CACAATTCCA TTTAAGTAGT CAGAGCTCGC TGGGTGGACC 1020
AGCAGCATTT TCTGCTCGGC ATTCCCAAGA AAGCATGTCG CCTACTGTAT TTCTGCCTCT 1080  
TCCATCACCT CAGGTTCTTC CTGGCCCATT GCTCATCCCT TCAGATAGCT CCACAGAACT 1140
CACTCAGACT   GTGTTGGAAG    GGGAATCTAT TTCTTGTTTT   CAAGTTGGAG    GAGAAAAGAG 1200
ACTCTGTTTG CCCCAAGTCT TAAATTCTGT TCTCCGAGAA TTTACACTCC  <RTI  

   ID=166.3> AGCAAATAAA    1260
TACAGTGTGT GATGAACTGT ACATATATTG   TTCAAGGTGT    ACTTCAGACC AGCTTCATAT 1320
CTTAAAGGTA CTGGGCATAC TTCCATTCAA TGCCCCATCC TGTGGGCTGA   TTACATTAAC    1380   TGATGCACAA    AGATTATGTA   ATGerrrATT    GCGGCCACGA ACTTTTCCTC AAAATGGTAG 1440
CGTACTTCCT GCTAAAAGCT CATTGGCCCA GTTAAAGGAA ACTGGCAGTG CCTTTGAAGT 1500   GGAGCATGAA    TGCCTAGGCA AATGTCAGGG   TTTATTTGCA      CCCCAGTTT    ATGTTCAGCC 1560
TGATGCTCCG TGTATTCAAT GTCTGGAGTG TTGTGGAATG   TTTGCACCCC    AGACGTTTGT 1620
GATGCATTCT CACAGATCAC CTGACAAAAG   AACTTGCCAC    TGGGGCTTTG AATCAGCTAA 1680
ATGGCATTGC TATCTTCATG TGAACCAAAA ATACTTAGGA ACACCTGAAG AAAAGAAACT 1740
GAAGATAATT TTAGAAGAAA TGAAGGAGAA GTTTAGCATG 

  AGAAGTGGAA AGAGAAATCA 1800
ATCCAAGACA GATGCACCAT CAGGAATGGA ATTACAGTCA TGGTATCCTG TTATAAAGCA 1860
GGAAGGTGAC CATGTTTCTC AGACACATTC   ATTITTACAC    CCCAGCTACT ACTTATACAT 1920
GTGTGATAAA GTGGTTGCCC CAAATGTGTC   ACTTACTTCT    GCTGTATCCC AGTCTAAAGA 1980
GCTCACAAAG ACAGAGGCAA GTAAGTCCAT ATCAAGACAG TCAGAGAAGG CTCACAGTAG 2040
TGGTAAACTT CAAAAAACAG TGTCTTATCC AGATGTCTCA CTTGAGGAAC AGGAGAAAAT 2100
GGATTTAAAA ACAAGTAGAG AATTATGTAG CCGTTTAGAT GCATCAATCT   CAAATAATTC    2160   TACAAGTAAA    AGGAAATCTG AGTCTGCCAC TTGCAACTTA GTCAGAGACA TAAACAAAGT 2220
GGGAATTGGC CTTGTTGCTG CCGCTTCATC TCCGCTTCTT GTGAAAGATG TCATTTGTGA 2280
GGATGATAAG GGAAAAATCA   TGGAAGAAGT    AATGAGAACT TATTTAAAAC   AACAGGAAAA    2340
ACTAAACTTG ATTTTGCAAA AGAAGCAACA ACTTCAGATG GAAGTAAAAA 

  TGTTGAGTAG 2400   TTCAAAATCT    ATGAAGGAAC TCACTGAAGA ACAGCAGAAT TTACAGAAAG AGCTTGAATC 2460
TTTGCAGAAT GAACATGCTC AAAGAATGGA AGAATTTTAT GTTGAACAGA AAGACTTAGA 2520    GAAAAAATTG    GAGCAGATAA TGAAGCAAAA ATGTACCTGT GACTCAAATT TAGAAAAAGA 2580   CAAAGAGGCT    GAATATGCAG GACAGTTGGC AGAACTGAGG CAGAGATTGG ACCATGCTGA 2640
GGCCGATAGG CAAGAACTCC AAGATGAACT CAGACAGGAA CGGGAAGCAA GACAGAAGTT 2700 .AGAGATGATG   ATAAAAGAGC      TAAAGCTGCA      AATTCTGAAA      TCATCAAAGA    CTGCTAAAGA 2760
ATAGAAACTG TTAAAGAGAT TCATCTGTGT ATTACTGACA AGGTTTTTTT TGTTTGTTGT 2820   TTG CTTTGGT    AATTGAATTC 2840 (2) INFORMATION FOR SEQ ID   NO:65:   
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH:

  *  1364 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:
AAAATCAGGA ACTTGTGCTG GCCCTGCAAT GTCAAGGGAG   GGGGCTCACC    CAGGGCTCCT 60
GTAGCTCAGG GGGCAGGCCT GAGCCCTGCA CCCGCCCCAC GACCGTCCAG CCCCTGACGG 120
GCACCCCATC CTGAGGGGCT CTGCATTGGC CCCCACCGAG GCAGGGGATC TGACCGACTC 180
GGAGCCCGGC TGGATGTTAC   AGGCGTGCAA    AATGGAAGGG TTTCCCCTCG TCCCCCCTCC 240   ATCAGAAGAC    CTGGTGCCCT ATGACACGGA TCTATACCAA   CGCCAAACGC    ACGAGTATTA 300
CCCCTATCTC AGCAGTGATG GGGAGAGCCA TAGCGACCAT TACTGGGACT TCCACCCCCA 360
CCACGTGCAC AGCGAGTTCG AGAGCTTCGC CGAGAACAAC TTCACGGAGC TCCAGAGCGT 420
GCAGCCCCCG CAGCTGCAGC AGCTCTACCG CCACATGGAG CTGGAGCAGA TGCACGTCCT 

  480
CGATACCCCC ATGGTGCCAC CCCATCCCAG TCTTGGCCAC CAGGTCTCCT ACCTGCCCCG 540
GATGTGCCTC CAGTACCCAT CCCTGTCCCC AGCCCAGCCC AGCTCAGATG AGGAGGAGGG 600
CGAGCGGCAG AGCCCCCCAC TGGAGGTGTC TGACGGCGAG GCGGATGGCC TGGAGCCCGG 660  
GCCTGGGCTC CTGCCTGGGG AGACAGGCAG CAAGAAGAAG ATCCGCCTGT ACCAGTTCCT 720
GTTGGACCTG CTCCGCAGCG GCGACATGAA GGACAGCATC TGGTGGGTGG ACAAGGACAA 780
GGGCACCTTC CAGTTCTCGT CCAAGCACAA GGAGGCGCTG GCGCACCGCT GGGGCATCCA 840
GAAGGGCAAC CGCAAGAAGA TGACCTACCA GAAGATGGCG CGCGCGCTGC GCAACTACGG 900
CAAGACGGGC GAGGTCAAGA AGGTGAAGAA GAAGCTCACC TACCAGTTCA   GCGGCGAAGT    960
GCTGGGCCGC GGGGGCCTGG CCGAGCGGCG CCACCCGCCC CACTGAGCCC GCAGCCCCCG 1020
CCGGCCCCGC CAGGCCTCCC CGCTGGCCAT AGCATTAAGC CCTCGCCCGG CCCGGACACA 1080
GGGAGGACGC TCCCGGGGCC CAGAGGCAGG ACTGTGGCGG GCCGGGCTCC GTCACCCGCC 1140
CCTCCCCCCA CTCCAGGCCC CCTCCACATC CCGCTTCGCC TCCCTCCAGG ACTCCACCCC 1200
GGCTCCCGAC 

  GCCAGCTGGG CGTCAGACCC ACCGGCAACC TTGCAGAGGA CGACCCGGGG 1260
TACTGCCTTG GGAGTCTCAA GTCCGTATGT AAATCAGATC TCCCCTCTCA CCCCTCCCAC 1320
CCATTAACCT CCTCCCAAAA   AACAAGTAAA    GTTATTCTCA ATCC 1364 (2) INFORMATION FOR SEQ ID   NO:66:   
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 271 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:66:
CTGCCAGGAC CATGGGTAGC AACAAGAGCA AGCCCAAGGA TGCCAGCCAG CGGCGCCGCA 60
GCCTGGAGCC   CGCCGAGAAC    GTGCACGGCG CTGGCGGGGG CGCTTTCCCC GCCTCGCAGA 120
CCCCCAGCAA GCCAGCCTCG GCCGACGGCC ACCGCGGCCC CAGCGCGGCC TTCGCCCCCG 180
CGGCCGCCGA GCCCAAGCTG TTCGGAGGCT TCAACTCCTC GGACACCGTC ACCTCCCCGC 240
AGAGGGCGGG CCCGCTGGCC GGTCAGTGCG C 271   (2) INFORMATION FOR SEQ ID NO:67:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 118 base pairs
   (B)    TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:67:
CTCTCTGCAG GTGGAGTGAC CACCTTTGTG GCCCTCTATG ACTATGAGTC TAGGACGGAG 60
ACAGACCTGT CCTTCAAGAA AGGCGAGCGG CTCCAGATTG TCAACAACAC GTGAGTGC 118 (2) INFORMATION FOR SEQ ID NO:68:
   (i)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 113 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   tii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:68:
CCTGCTCAGA GAGGGAGACT GGTGGCTGGC CCACTCGCTC AGCACAGGAC AGACAGGCTA 60
CATCCCCAGC AACTACGTGG CGCCCTCCGA CTCCATCCAG GCTGAGGAGT TAG 113 (2) INFORMATION FOR SEQ ID NO:69:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 115 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 (D) TOPOLOGY: linear
   (ii)    MOLECULE TYPE:

   DNA (genomic)  
   lxi)    SEQUENCE DESCRIPTION: SEQ ID   NO:69:   
CCCCCAGGTG GTATTTTGGC AAGATCACCA GACGGGAGTC AGAGCGGTTA CTGCTCAATG 60
CAGAGAACCC GAGAGGGACC TTCCTCGTGC GAGAAAGTGA GACCACGAAA GGTAC 115   12) INFORMATION    FOR SEQ ID NO:70:
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 164 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:   SEO    ID NO:70:
GCCCCGCAGG TGCCTACTGC CTCTCAGTGT   CTGACTTCGA    CAACGCCAAG GGCCTCAACG 60
TGAAGCACTA CAAGATCCGC AAGCTGGACA GCGGCGGCTT CTACATCACC TCCCGCACCC 120
AGTTCAACAG CCTGCAGCAG CTGGTGGCCT ACTACTCCAG TGAG 164 (2) INFORMATION FOR SEQ ID NO:71:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 170 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:71:
CCTCCTCAGA ACACGCCGAT GGCCTGTGCC ACCGCCTCAC CACCGTGTGC CCCACGTCCA 60
AGCCGCAGAC TCAGGGCCTG GCCAAGGATG CCTGGGAGAT CCCTCGGGAG TCGCTGCGGC 120
TGGAGGTCAA GCTGGGCCAG GGCTGCTTTG GCGAGGTGTG GATGGGTAAG 170 (2) INFORMATION FOR SEQ ID NO:72:  
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 194 base pairs
 (B) TYPE: nucleic acid
   C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:72:
CCTCAACAGG GACCTGGAAC GGTACCACCA GGGTGGCCAT CAAAACCCTG AAGCCTGGCA 60
CGATGTCTCC AGAGGCCTTC CTGCAGGAGG CCCAGGTCAT GAAGAAGCTG AGGCATGAGA 120
AGCTGGTGCA   GTTGTATGCT    GTGGTTTCAG AGGAGCCCAT TTACATCGTC ACGGAGTACA 180
TGAGCAAGGG TGAG 194 (2) INFORMATION FOR SEQ ID NO:73:
   li)    SEQUENCE   CHARACTERISTICS:   
 (A) LENGTH: 91 base pairs
 (8) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:73:
TCTGCCCAGG GAGTTTGCTG GACTTTCTCA AGGGGGAGAC AGGCAAGTAC CTGCGGCTGC 60
CTCAGCTGGT GGACATGGCT GCTCAGGTGA G 91 (2) INFORMATION FOR   SEO    ID NO:74:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 165 base pairs
   (B)    TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)  
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:
CTGCAGATCG CCTCAGGCAT GGCGTACGTG GAGCGGATGA ACTACGTCCA CCGGGACCTT 60
CGTGCAGCCA ACATCCTGGT GGGAGAGAAC CTGGTGTGCA AAGTGGCCGA CTTTGGGCTG 120
GCTCGGCTCA TTGAAGACAA TGAGTACACG GCGCGGCAAG GTGGG 165 (2) INFORMATION FOR SEQ ID NO:75:
   Ii)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 146 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:
TTCCTGCAGG TGCCAAATTC CCCATCAAGT GGACGGCTCC AGAAGCTGCC CTCTATGGCC 60
GCTTCACCAT CAAGTCGGAC GTGTGGTCCT TCGGGATCCT GCTGACTGAG CTCACCACAA 120
AGGGACGGGT GCCCTACCCT GGTAAG 146 (2) INFORMATION FOR SEQ ID NO:76:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 255 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
 ID) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:76:
CTGCCACAGG GATGGTGAAC CGCGAGGTGC TGGACCAGGT GGAGCGGGGC TACCGGATGC 60
CCTGCCCGCC   GGAGTGTCCC    GAGTCCCTGC ACGACCTCAT GTGCCAGTGC TGGCGGAAGG 120
AGCCTGAGGA GCGGCCCACC TTCGAGTACC TGCAGGCCTT CCTGGAGGAC TACTTCACGT 180  
CCACCGAGCC CCAGTACCAG CCCGGGGAGA ACCTCTAGGC ACAGGCGGGC CCAGACCGGC 240
TTCTCGGCTT GGATC 255 (2) INFORMATION FOR SEQ ID NO:77:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 2647 base pairs
 (B) TYPE: nucleic acid
 IC) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:77:
GCCGCGCTGG TGGCGGCGGC GCGTCGTTGC AGTTGCGCCA TCTGTCAGGA GCGGAGCCGG 60
CGAGGAGGGG GCTGCCGCGG GCGAGGAGGA GGGGTCGCCG CGAGCCGAAG GCCTTCGAGA 120
CCCGCCCGCC GCCCGGCGGC GAGAGTAGAG GCGAGGTTGT TGTGCGAGCG GCGCGTCCTC 180
TCCCGCCCGG GCGCGCCGCG CTTCTCCCAG CGCACCGAGG ACCGCCCGGG   CGCACACAAA    240
GCCGCCGCCC GCGCCGCACC GCCCGGCGGC CGCCGCCCGC GCCAGGGAGG GATTCGGCCG 300
CCGGGCCGGG GACACCCCGG CGCCGCCCCC TCGGTGCTCT CGGAAGGCCC ACCGGCTCCC 360
GGGCCCGCCG GGGACCCCCC GGAGCCGCCT CGGCCGCGCC GGAGGAGGGC GGGGAGAGGA 420
CCATGTGAGT GGGCTCCGGA GCCTCAGCGC CGCGCAGTTT TTTTGAAGAA GCAGGATGCT 480
GATCTAAACG TGGAAAAAGA CCAGTCCTGC CTCTGTTGTA GAAGACATGT GGTGTATATA 540
AAGTTTGTGA TCGTTGGCGG   AAATTTTGGA    ATTTAGATAA TGGGCTGTGT GCAATGTAAG 600
GATAAAGAAG CAACAAAACT GACGGAGGAG AGGGACGGCA GCCTGAACCA GAGCTCTGGG 660
TACCGCTATG GCACAGACCC CACCCCTCAG CACTACCCCA GCTTCGGTGT 

  GACCTCCATC 720
CCCAACTACA ACAACTTCCA CGCAGCCGGG GGCCAAGGAC TCACCGTCTT TGGAGGTGTG 780
AACTCTTCGT CTCATACGGG GACCTTGCGT ACGAGAGGAG GAACAGGAGT GACACTCTTT 840
GTGGCCCTTT ATGACTATGA AGCACGGACA GAAGATGACC TGAGTTTTCA CAAAGGAGAA 900  
AAATTTCAAA TATTGAACAG CTCGGAAGGA GATTGGTGGG AAGCCCGCTC CTTGACAACT 960
GGAGAGACAG GTTACATTCC CAGCAATTAT GTGGCTCCAG TTGACTCTAT CCAGGCAGAA 1020
GAGTGGTACT TTGGAAAACT TGGCCGAAAA GATGCTGAGC GACAGCTATT GTCCTTTGGA 1080
AACCCAAGAG GTACCTTTCT TATCCGCGAG AGTGAAACCA CCAAAGGTGC CTATTCACTT 1140
TCTATCCGTG ATTGGGATGA TATGAAAGGA GACCATGTCA AACATTATAA AATTCGCAAA 1200
CTTGACAATG GTGGATACTA CATTACCACC CGGGCCCAGT   TTGAAACACT    TCAGCAGCTT 1260
GTACAACATT ACTCAGAGAG AGCTGCAGGT CTCTGCTGCC GCCTAGTAGT TCCCTGTCAC 1320
AAAGGGATGC CAAGGCTTAC CGATCTGTCT GTCAAAACCA AAGATGTCTG GGAAATCCCT 1380
CGAGAATCCC TGCAGTTGAT CAAGAGACTG GGAAATGGGC AGTTTGGGGA AGTATGGATG 

  1440
GGTACCTGGA ATGGAAACAC AAAAGTAGCC ATAAAGACTC TTAAACCAGG CACAATGTCC 1500
CCCGAATCAT TCCTTGAGGA AGCGCAGATC ATGAAGAAGC TGAAGCACGA CAAGCTGGTC 1560
CAGCTCTATG CAGTGGTGTC TGAGGAGCCC ATCTACATCG TCACCGAGTA TATGAACAAA 1620
GGAAGTTTAC TGGATTTCTT AAAAGATGGA GAAGGAAGAG CTCTGAAATT ACCAAATCTT 1680
GTGGACATGG CAGCACAGGT GGCTGCAGGA ATGGCTTACA TCGAGCGCAT GAATTATATC 1740
CATAGAGATC TGCGATCAGC AAACATTCTA GTGGGGAATG GACTCATATG CAAGATTGCT 1800
GACTTCGGAT TGGCCCGATT GATAGAAGAC AATGAGTACA CAGCAAGACA AGGTGCAAAG 1860
TTCCCCATCA AGTGGACGGC CCCCGAGGCA GCCCTGTACG GGAGGTTCAC AATCAAGTCT 1920
GACGTGTGGT CTTTTGGAAT CTTACTCACA GAGCTGGTCA CCAAAGGAAG AGTGCCATAC 1980
CCAGGCATGA ACAACCGGGA GGTGCTGGAG CAGGTGGAGC GAGGCTACAG GATGCCCTGC 2040
CCGCAGGACT GCCCCATCTC TCTGCATGAG CTCATGATCC ACTGCTGGAA AAAGGACCCT 2100
GAAGAACGCC CCACTTTTGA GTACTTGCAG AGCTTCCTGG AAGACTACTT TACCGCGACA 2160
GAGCCCCAGT ACCAACCTGG TGAAAACCTG 

  TAAGGCCCGG GTCTGCGGAG AGAGGCCTTG 2220
TCCCAGAGGC TGCCCCACCC CTCCCCATTA GCTTTCAATT CCGTAGCCAG CTGCTCCCCA 2280
GCAGCGGAAC CGCCCAGGAT CAGATTGCAT GTGACTCTGA AGCTGACGAA CTTCCATGGC 2340  
CCTCATTAAT GACACTTGTC CCCAAATCCG   AACCTCCTCT    GTGAAGCATT CGAGACAGAA 2400
CCTTGTTATT TCTCAGACTT TGGAAAATGC ATTGTATCGA TGTTATGTAA AAGGCCAAAC 2460
CTCTGTTCAG TGTAAATAGT TACTCCAGTG CCAACAATCC TAGTGCTTTC   CT1TRTTAAA    2520
AATGCAAATC CTATGTGATT   TTAACTCTGT    CTTCACCTGA TTCAACTAAA AAAAAAAAGT 2580
ATTATTTTCC AAAAGTGGCC TCTTTGTCTA AAACAATAAA   ATTTTTTTTC      ATGl"rrrAAC    2640
AAAAACC 2647 (2) INFORMATION FOR SEQ ID NO:78:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 2301 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS:

   double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID   NO:78:   
GTCGACCGGA GGGCAGGAGG AGCAGGAGGA GCAGGAGCAG GAGGAGCAGG AGGAGCAGGA 60
GGAGCAGGAG GAGCAGGAGG AGCAGGAACA GGAGGAGGAG GAGGAGGAGA AGGAGGAGCA 120
GGAAGAGCAG GAGGAGGAGG AGCAGGAGCA GGAGGAGCAG GAGGGAGAGG AGGCTGCAAC 180
GCCGAGCGGA GGAGGCAGGA ACCGGAGCGC GAGCAGTAGC TGGGTGGGCA CCATGGCTGG 240
GATCACCACC ATCGAGGCGG TGAAGCGCAA GATCCAGGTT CTGCAGCAGC AGGCAGATGA 300
TGCAGAGGAG CGAGCTGAGC GCCTCCAGCG AGAAGTTGAG GGAGAAAGGC GGGCCCGGGA 360
ACAGGCTGAG GCTGAGGTGG CCTCCTTGAA CCGTAGGATC CAGCTGGTTG AAGAAGAGCT 420
GGACCGTGCT CAGGAGCGCC TGGCCACTGC CCTGCAAAAG CTGGAAGAAG CTGAAAAAGC 480
TGCTGATGAG AGTGAGAGAG GTATGAAGGT TATTGAAAAC CGGGCCTTAA AAGATGAAGA 540
AAAGATGGAA CTCCAGGAAA TCCAACTCGA AGAAGCTAAG CACATTGCAG AAGAGGCAGA 600
TAGGAAGTAT GAAGAGGTGG CTCGTAAGTT 

  GGTGATCATT GAAGGAGACT TGGAACGCAC 660
AGAGGAACGA GCTGAGCTGG CAGAGTCGCG TTGCCGAGAG ATGGATGAGC AGATTAGACT 720  
GATGGACCAG AACCTGAAGT GTCTGAGTGC TGCCGAAGAA AAGTACTCTC AAAAAGAAGA 780
TAAATATGAG GAAGAAATCA AGATTCTTAC   TGATAAACTC    AAGGAGGCAG AGACCCGTGC 840
TGAGTTTGCT GAGAGATCGG TAGCCAAGCT GGAAAAGACA ATTGATGACC TGGAAGACAC 900
TAACAGCACA TCTGGAGACC CGGTGGAGAA GAAGGACGAA ACACCTTTTG GGGTCTCGGT 960
GGCTGTGGGC CTGGCCGTCT TTGCCTGCCT CTTCCTTTCT ACGCTGCTCC TTGTGCTCAA 1020
CAAATGTGGA CGGAGAAACA AGTTTGGGAT CAACCGCCCG GCTGTGCTGG CTCCAGAGGA 1080
TGGGCTGGCC ATGTCCCTGC ATTTCATGAC ATTGGGTGGC AGCTCCCTGT CCCCCACCGA 1140
GGGCAAAGGC TCTGGGCTCC AAGGCCACAT CATCGAGAAC CCACAATACT TCAGTGATGC 1200
CTGTGTTCAC CACATCAAGC GCCGGGACAT CGTGCTCAAG TGGGAGCTGG GGGAGGGCGC 1260
CTTTGGGAAG GTCTTCCTTG CTGAGTGCCA CAACCTCCTG CCTGAGCAGG ACAAGATGCT 1320
GGTGGCTGTC AAGGCACTGA AGGAGGCGTC CGAGAGTGCT 

  CGGCAGGACT TCCAACGTGA 1380
GGCTGAGCTG CTCACCATGC TGCAGCACCA GCACATCGTG CGCTTCTTCG GCGTCTGCAC 1440
CGAGGGCCGC CCCCTGCTCA TGGTCTTCGA GTATATGCGG CACGGGGACC TCAACCGCTT 1500
CCTCCGATCC CATGGACCCG ATGCCAAGCT GCTGGCTGGT GGGGAGGATG TGGCTCCAGG 1560
CCCCCTGGGT CTGGGGCAGC TGCTGGCCGT GGCTAGCCAG GTCGCTGCGG GGATGGTGTA 1620
CCTGGCGGGT CTGCATTTTG TGCACCGGGA CCTGGCCACA CGCAACTGTC TAGTGGGCCA 1680
GGGACTGGTG GTCAAGATTG GTGATTTTGG CATGAGCAGG GATATCTACA GCACCGACTA 1740
TTACCGTGTG GGAGGCCGCA CCATGCTGCC CATTCGCTGG ATGCCGCCCG AGAGCATCCT 1800
GTACCGTAAG TTCACCACCG AGAGCGACGT GTGGAGCTTC GGCGTGGTGC TCTGGGAGAT 1860
CTTCACCTAC GGCAAGCAGC CCTGGTACCA GCTCTCCAAC ACGGAGGCAA TCGACTGCAT 1920
CACGCAGGGA CGTGAGTTGG AGCGGCCACG TGCCTGCCCA CCAGAGGTCT ACGCCATCAT 1980
GCGGGGCTGC TGGCAGCGGG AGCCCAGCAA CGCCACAGCA TCAAGGATGT GCACGCCCGG 2040
CTGCAAGCCC TGGCCTAGGC ACCTCCTGTC TACCTGGATG TCCTGGGCTA GGGGGCCGGC 2100
CCAGGGGCTG 

  GGAGTGGTTA GCCGGAATAC TGGGGCCTGC CCTCAGCATC CCCCATAGCT 2160  
CCCAGCAGCC CCAGGGTGAT CTCGAAGTAT CTAATTCGCC CTCAGCATGT GGGAAGGGAC 2220
AGGTGGGGGC TGGGAGTAGA GGATGTTCCT   GCTTCTCTAG    GCAAGGTCCC GTCGTAGCAA 2280
TTATATTTAT TATGGGAATT C 2301 (2) INFORMATION FOR SEQ ID NO:79:
   li)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 2757 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lil)    MOLECULE TYPE: DNA (genomic)
   lxi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:79:
CTAGGCTTTT GCAAAAAGCT TCACGCTGCC GCAAGCACTC AGGGCGCAAG GGCTGCTAAA 60
GGAAGCGGAA CACGTAGAAA GCCAGTCCGC AGAAACGGTG CTGACCCCGG ATGAATGTCA 120
GCTACTGGGC TATCTGGACA AGGGAAAACG CAAGCGCAAA GAGAAAGCAG TTCCTGTGCC 180
TTAAGAACAT TAGAACCTTC CTGTCCACCT GCTGTGAGAA GTTCGGCCTC AAGCGGAGCG 240
AGCTCTTCGA AGCCTTTGAC CTCTTCGATG TGCAGGATTT TGGCAAGGTC ATCTACACCC 300
TGTCTGCTCT GTCCTGGACC CCGATCGCCC AGAACAGGGG GATCATGCCC TTCCCCACCG 360
AGGAGGAGAG TGTAGGTGAT GAAGACATCT ACAGTGGCCT GTCCGACCAG ATCGACGACA 420
CGGTGGAGGA GGATGAGGAC CTGTATGACT GCGTGGAGAA TGAGGAGGCG GAAGGCGACG 480
AGATCTATGA GGACCTCATG CGCTCGGAGC CCGTGTCCAT GCCGCCCAAG ATGACAGAGT 540
ATGACAAGCG CTGCTGCTGC CTGCGGGAGA TCCAGCAGAC GGAGGAGAAG TACACTGACA 600
CGCTGGGCTC CATCCAGCAG CATTTCTTGA AGCCCCTGCA ACGGTTCCTG AAACCTCAAG 660
ACATTGAGAT CATCTTTATC AACATTGAGG ACCTGCTTCG TGTTCATACT CACTTCCTAA 720
AGGAGATGAA GGAAGCCCTG GGCACCCCTG 

  GCGCACCGAA TCTCTACCAG GTCTTCATCA 780
AATACAAGGA GAGGTTCCTC GTCTATGGCC GCTACTGCAG CCAGGTGGAG TCAGCCAGCA 840  
AACACCTGGA CCGTGTGGCC GCAGCCCGGG AGGACGTGCA GATGAAGCTG GAGGAATGTT 900
CTCAGAGAGC CAACAACGGG AGGTTCACTG CGCGACCTGC TGATGGTGCC TATGCAGCGA 960
GTTCTCAAAT ATCACCTCCT TCTCCAGGAG CTGGTGAAAC ACACGCAGGA GGCGATGGAG 1020
CAAGGAAACT GCGGCTGGCC CTGGATGCCA TGAGGGACCT GGCTCAGTGC GTGAACGAGG 1080
TCAAGCGAGA CAACGAGACA CTGCGACAGA TCACCAATTT CCAGCTGTCC ATTGAGAACC 1140
TGGACCAGTC TCTGGCTCAC TATGGCCGGC CCAAGATCGA CGGGGAACTC AAGATCACCT 1200
CGGTGGAACG GCGCTCCAAG ATGGACAGGT ATGCCTTCCT GCTCGACAAA GCTCTACTCA 1260
TCTGTAAGCG CAGGGGAGAC TCCTATGACC TCAAGGACTT TGTAAACCTG CACAGCTTCC 1320
AGGTTCGGGA TGACTCTTCA GGAGACCGAG ACAACAAGAA GTGGAGCCAC ATGTTCCTCC 1380
TGATCGAGGA CCAAGGTGCC CAGGGCTATG   AGCTOTTCTT    CAAGACAAGA   GAATTGAAGA    1440
AGAAGTGGAT  <RTI  

   ID=178.3> GGAGCAGTTT    GAGATGGCCA TCTCCAACAT CTATCCGGAG AATGCCACCG 1500
CCAACGGGCA TGACTTCCAG ATGTTCTCCT TTGAGGAGAC CACATCCTGC AAGGCCTGTC 1560
AGATGCTGCT TAGAGGTACC TTCTATCAGG GCTACCGCTG CCATCGGTGC CGGGCATCTG 1620
CACACAAGGA GTGTCTGGGG AGGGTCCCTC CATGTGGCCG ACATGGGCAA   GATTTCCCAG    1680
GAACTATGAA GAAGGACAAA CTACATCGCA GGGCTCAGGA CAAAAAGAGG AATGAGCTGG 1740
GTCTGCCCAA GATGGAGGTG   TTTCAGGAAT    ACTACGGGCT TCCTCCACCC CCTGGAGCCA 1800
TTGGACCCTT TCTACGGCTC AACCCTGGAG ACATTGTGGA GCTCACGAAG GCTGAGGCTG 1860
AACAGAACTG GTGGGAGGGC AGAAATACAT CTACTAATGA AATTGGCTGG   TITCCTTCTA    1920
ACAGGGTGAA GCCCTATGTC CATGGCCCTC CTCAGGACCT GTCTGTTCAT CTCTGGTACG 1980
CAGGCCCCAT GGAGCGGGCA GGGGCAGAGA GCATCCTGGC CAACCGCTCG GACGGGACTT 2040
TCTTGGTGCG GCAGAGGGTG AAGGATGCAG CAGAATTTGC CATCAGCATT AAATATAACG 2100
TCGAGGTCAA GCACACGGTT 

  AAAATCATGA CAGCAGAAGG ACTGTACCGG ATCACAGAGA 2160
AAAAGGCTTT CCGGGGGCTT ACGGAGCTGG TGGAGTTTTA CCAGCAGAAC TCTCTAAAGG 2220
ATTGCTTCAA GTCTCTGGAC ACCACCTTGC AGTTCCCCTT CAAGGAGCCT GAAAAGAGAA 2280  
CCATCAGCAG GCCAGCAGTG GGAAGCACAA   AGTATfTTGG    CACAGCCAAA GCCCGCTATG 2340
ACTTCTGCGC CCGTGACCGT TCAGAGCTGT CGCTCAAGGA GGGTGACATC ATCAAGATCC 2400
TTAACAAGAA   GGGACAGCAA    GGCTGGTGGC GAGGGGAGAT CTATGGCCGG GTTGGCTGGT 2460
TCCCTGCCAA CTACGTGGAG GAAGATTATT CTGAATACTG CTGAGCCCTG GTGCCTTGGC 2520
AGAGAGACGA GAAACTCCAG GCTCTGAGCC CGGCGTGGCG AGGCAGCGGA CCAGGGGCTG 2580
TGACAGCTCC GGCGGGTGGA GACTTTGGGA TGGACTGGAG GAGGCCAGCG TCCAGCTGGC 2640
GGTGCTCCCG GGATGTGCCC TGACATGGTT   AATTTATAAC    ACCCCGATTT TCCTCTTGGG 2700
TCCCCTCAAG CAGACGGGGG CTCAAGGGGG TTACATTTAA TAAAAGGATG AAGATGG 2757 (2) INFORMATION FOR SEQ ID NO:80: 

  
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 841 base pairs
 (B) TYPE: nucleic acid
   {C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: 
CCTGACCAAC ATGGTGAAAC CCCATCTCTA CTAAAAATAC AAAAATTATC CAGGCGTGGT 600
GGCGGGTGCC TGTAATCCCA GCTATTTGGG AGGCTGAGGC AGGAGAATCG TTTGAACCCA 660
GGAGACAGAG GTTGCAGTGA ACCAAGACCG TGTCACTGCA CTCCAGCCTG GACAACAGAG 720
CAAGACTCTG TCTCCAAAAA AAAAAAAAGA AAAAAAAAAA AGGAATGTGT CTGTCTGGAA 780
GGAAGAGCTG GAACACATAA CCCTTAGCTG TGTCTGCCTC CCGCACCAGT GTCCAGTTGA 840
C 841 (2) INFORMATION FOR SEQ ID NO:81:
   li)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 841 base pairs
   (B)    TYPE: nucleic acid
 IC) STRANDEDNESS: double
   (D)    TOPOLOGY:

   linear
   li1)    MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION: SEQ ID NO:81:
AATGAGGAAA CTGAGTTCCA ATTTAGTTGA CCTGGTAAGA TCACAAAAAC AGCAGGCAGG 60
CCGGGTGCGG TGGCTCACAC CTGTAATCCC AACACTTTGG GAGGCCAAGG CGGGCAGATC 120
ACCTGAGGTC GGGAGTTCGA GACCAGCCTG ACCAACATGG TGAAACCCCA TCTTTACTAA 180
AAATACAAAA TTAGCCGGGT GTGGTGGCGC ATGCCTGTAA TCCCAGCTAC TCGGGAGGCT 240
GAGGCAGGAG   AATCACTTGA    ACTTGGGAGA GGGAGGTTGC AGTGAGCCGA GATTGCACCA 300
TTGCACTCCA GCCAAGAGGT   CTCAAAAAAA    AAAAAAAAAG CAGGCAGCAG AGTCAGATTC 360
CAAGTCTGGC AGCTCTCACC CCCCGAGGGG TGAAAAGTAA GCACTAACCA ACCACATGAG 420
CACTAGGGGA AGTAGATTTA AAAAGGAACA TGGGCCAGGT GTGGTGGCCT ACACATGTAA 480
TCCCAGCACT TTGGGAGGCC GAGGCAGATG GATCACCTGA GGTCAGGAGA TCGAGACCAG 540
CCTGACCAAC ATGGTGAAAC CCCATCTCTA   CTAAAAATAC    

  AAAAATTATC CAGGCGTGGT 600
GGCGGGTGCC TGTAATCCCA GCTATTTGGG AGGCTGAGGC AGGAGAATCG   TTTGAACCCA    660  
GGAGACAGAG GTTGCAGTGA ACCAAGACCG TGTCACTGCA CTCCAGCCTG GACAACAGAG 720
CAAGACTCTG TCTCCAAAAA AAAAAAAAGA AAAAAAAAAA AGGAATGTGT CTGTCTGGAA 780
GGAAGAGCTG GAACACATAA CCCTTAGCTG TGTCTGCCTC CCGCACCAGT GTCCAGTTGA 840
C 841 (2) INFORMATION FOR SEQ ID NO:82:
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 1804 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
   (xi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:82:
GGATCCTCAG GGGTAACACC TTTTGGAGGT GGGCATCTTC CTCATTCTCA GTGGTGCCAA 60
GTTCATATCC TGCTGGCTTA ACACGTGGTG TTACTATATT TGTGGCCTTA TATGATTATG 120
AAGCTAGAAC TACAGAAGAC CTTTCATTTA AGAAGGGTGA AAAATTTCAA ATAATTAACA 180
ATACAGAAGG AGACTGGTGG GAAGCAAGAT CAATCACTAC AGGAAAGAAT GGTTATATCC 240
TGAGCAGTTA TGTAGCGCCT GCAGATTCCA TTCAGGCAGA AGAATGGTAT   TTTGGCAAAA    300
TGGGGAGAAA AGATGCTGAA AGATTACTTC TGAATCCTGG AAATTAATGA GGTATTTTCT 360
TAGGAAGAGA GAGTGAAATG GCTGGGTGCA GTGGCTCATG CCTGTAATCC CAGCACTTTG 420
GGAGGCCGAG TTGGGCGGAT CACCTGAGGT CAGGAGTTCG AGACTAGCCT GGCCAACATG 480
GTGAAACCCC ATCTCTACTA AAAAAAAAAG TACAAAATTA GCTGGACGTG GTGGTGAGTG 540
CCTGTAATCC CAGCTACTCA GGAGGCTGAG GCAGCAGAAT CACTTGAACC TGGGAGGCGG 600
AGGTTGCAGT GAGCTGAGAT CGCGCCACTG   CACTCCAGCC    TCGGCGACAA GAGCAAAAAC 660
TCCGTCTAAA AAACAAATAA GCAAACAGAA CAAAACAAAA CAAAAACGAG 

  AGAGCGAAAC 720
TACTAAAGGT GCTTATTCCC TCTCTATTCG TGATTGGGAT GAGGTAAGGG GTGACAATGT 780  
GAAACACCAC AAAATTAGGA AACTTGACAA TGGTAGATAC TATATCACAA CCAGAGAACA 840
ACTTGATACT CTGCAGAAAT TGGCAAAACA CTACACAGAA CATGCTGATG GTITATGCCA 900
CAAGTTAACA ACTGTGTGTC CAACTGTGAA ACCTCAGATT CAAGGTCTAG CAAAAGATGC 960
TTGGGAAATC CCTTGATAAT   CTITGCGACT    AGAGGTTAAA CTAGGACAAG   GATGTTTTGG    1020
CAAAGTGTGG ATGGGAATAT GGAATGGAAC CACAAAAGTA GCAATCAAAA CACTAAAACC 1080
AGGTACAATG ATGCCAGAAG   CTTTTCTTCA    AGAAGCTCAG GTAATGAAAA AAATAAGACA 1140
TGGTAAACTT GTTCCACTAT ATGCTGTTGT TTCTGAAGAG   CCAATTTACA    TTGTCACTGA 1200
ATTGATGTCA AAAGGAAGCT TATTCAATTT CCTTAAGGAA GGAGATGGAA AGTATTTGAA 1260
GCTTCCACAA ATGGTTGATA TGCCTGCTCA GATTGCTGAT GGTATGGCAT ATATTAAAAG 1320
AATGAACTAT ATTCACCGAG ATCTCTGGGC TGCTAATATT CTTGTAGGAG 

  AAAATCTTCT 1380
GTGCAAAATA GCAGATTTTG GTTTAGCAAG GTTAATTGAA GACAATGAAT ACACATCAAG 1440
ACAAGGTGCA GAATTTCCAA TCAAATGGAC AGCTCCTGAA GTTGCACTGT ATGGTGGGTT 1500
TACAATAAAG TCTGGTGTCT GCTCATTTGG AATTCTACAG ACAGAACTGG TAACAAAGGG 1560
CAGAGTGCCA TATCCAGGTA TGGTGAACCA TGAAATACTG GAACAGGTGG AGCGAGGATA 1620
CAGGATGCCT TGCCCTCAGG GCTGTCCAGA ATCCCTCCAT GAATTGATGA ATCTGTGTTG 1680
GAAGAAGGAC CCTGATGAAA GACCAACATT TGAATATGTT CAGTCCTTCT TGGGAGACTA 1740
CTTCACTGCT ACAGAGCCAT AGTACCAGCC AGGAGAAAAC TTCTAATTCA AGTAGCCTAT 1800
TTTA 1804 (2) INFORMATION FOR SEQ ID NO:83:
   (i)    SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 4517 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA (genomic)  
   lxi)    SEQUENCE DESCRIPTION:

   SEQ ID NO:83:
GCGGAGCCAA GGCACACGGG TCTGACCCTT GGGCCGGCCC GGAGCAAGTG ACACGGACCG 60
GTCGCCTATC CTGACCACAG CAAAGCGGCC CGGAGCCCGC GGAGGGGACC TGACGGGGGC 120
GTAGGCGCCG GAAGGCTGGG GGCCCCGGAG CCGGGCCGGC GTGGCCCGAG TTCCGGTGAG 180
CGGACGGCGG CGCGCGCAGA   UGATAATG    GGCTGCATTA AAAGTAAAGA AAACAAAAGT 240
CCAGCCATTA AATACAGACC TGAAAATACT CCAGAGCCTG TCAGTACAAG TGTGAGCCAT 300
TATGGAGCAG AACCCACTAC AGTGTCACCA TGTCCGTCAT CTTCAGCAAA GGGAACAGCA 360
GTTAATTTCA   GCAGTCTTTC    CATGACACCA TTTGGAGGAT CCTCAGGGGT AACGCCTTTT 420
GGAGGTGCAT CTTCCTCATT TTCAGTGGTG CCAAGTTCAT ATCCTGCTGG   TITAACAGGT    480
GGTGTTACTA TATTTGTGGC CTTATATGAT TATGAAGCTA GAACTACAGA   AGACCTTTCA    540   TTTAAGAAGG    GTGAAAGATT TCAAATAATT AACAATACGG AAGGAGATTG GTGGGAAGCA 600
AGATCAATCG CTACAGGAAA GAATGGTTAT ATCCCGAGCA 

  ATTATGTAGC GCCTGCAGAT 660
TCCATTCAGG CAGAAGAATG   GTATTTTGGC    AAAATGGGGA GAAAAGATGC TGAAAGATTA 720
CTTTTGAATC CTGGAAATCA ACGAGGTATT TTCTTAGTAA GAGAGAGTGA AACAACTAAA 780
GGTGCTTATT CCCTTTCTAT TCGTGATTGG GATGAGATAA GGGGTGACAA TGTGAAACAC 840
TACAAAATTA GGAAACTTGA CAATGGTGGA TACTATATCA CAACCAGAGC   ACAATITGAT    900
ACTCTGCAGA AATTGGTGAA ACACTACACA GAACATGCTG ATGGTTTATG CCACAAGTTG 960
ACAACTGTGT GTCCAACTGT GAAACCTCAG ACTCAAGGTC TAGCAAAAGA TGCTTGGGAA 1020
ATCCCTCGAG AATCTTTGCG ACTAGAGGTT AAACTAGGAC   AAGGATGTTT    CGGCGAAGTG 1080
TGGATGGGAA CATGGAATGG AACCACGAAA GTAGCAATCA AAACACTAAA ACCAGGTACA 1140
ATGATGCCAG AAGCTTTCCT TCAAGAAGCT CAGATAATGA AAAAATTAAG ACATGATAAA 1200
CTTGTTCCAC TATATGCTGT   TGTTTCTGAA    GAACCAATTT ACATTGTCAC TGAATTTATG 1260
TCAAAAGGAA GCTTATTAGA  <RTI  

   ID=183.11> TTTCCTTAAG    GAAGGAGATG GAAAGTATTT GAAGCTTCCA 1320
CAGCTGGTTG ATATGGCTGC TCAGATTGCT GATGGTATGG CATATATTGA AAGAATGAAC 1380  
TATATTCACC GAGATCTTCG GGCTGCTAAT ATTCTTGTAG GAGAAAATCT TGTGTGCAAA 1440
ATAGCAGACT TTGGTTTAGC AAGGTTAATT GAAGACAATG AATACACAGC AAGACAAGGT 1500
GCAAAATTTC CAATCAAATG GACAGCTCCT GAAGCTGCAC TGTATGGTCG GTTTACAATA 1560
AAGTCTGATG TCTGGTCATT TGGAATTCTG CAAACAGAAC TAGTAACAAA GGGCCGAGTG 1620
CCATATCCAG GTATGGTGAA CCGTGAAGTA CTAGAACAAG TGGAGCGAGG ATACAGGATG 1680
CCGTGCCCTC AGGGCTGTCC AGAATCCCTC CATGAATTGA TGAATCTGTG TTGGAAGAAG 1740
GACCCTGATG AAAGACCAAC   ATTTGAATAT    ATTCAGTCCT TCTTGGAAGA CTACTTCACT 1800
GCTACAGAGC CACAGTACCA GCCAGGAGAA AATTTATAAT TCAAGTAGCC TATTTTATAT 1860
GCACAAATCT GCCAAAATAT AAAGAACTTG TGTAGATTTT CTACAGGAAT CAAAAGAAGA 1920
AAATCTTCTT TACTCTGCAT GTTTTTAATG GTAAACTGGA ATCCCAGATA TGGTTGCACA 1980  <RTI  

   ID=184.2> AAACCACTTT    TTTTTCCCCA AGTATTAAAC TCTAATGTAC CAATGATGAA TTTATCAGCG 2040
TATTTCAGGG TCCAAACAAA ATAGAGCTAA GATACTGATG ACAGTGTGGG TGACAGCATG 2100
GTAATGAAGG ACAGTGAGGC TCCTGCTTAT TTATAAATCA   TTTCCTTTCT    TTTTTTCCCC 2160
AAAGTCAGAA TTGCTCAAAG AAAATTATTT ATTGTTACAG ATAAAACTTG AGAGATAAAA 2220
AGCTATACCA TAATAAAATC TAAAATTAAG GAATATCATG GGACCAAATA ATTCCATTCC 2280   AGTTTTTAA      AGTTTCTTGC      ATTTATTATT    CTCAAAAGTT TTTTCTAAGT TAAACAGTCA 2340
GTATGCAATC TTAATATATG   CTTTCTTTTG    CATGGACATG   GGCCAGGTTT    TTCAAAAGGA 2400
ATATAAACAG GATCTCAAAC TTGATTAAAT GTTAGACCAC AGAAGTGGAA   TTTGAAAGTA    2460
TAATGCAGTA CATTAATATT CATGTTCATG GAACTGAAAG AATAAGAACT TTTTCACTTC 2520
AGTCCTTTTC  <RTI  

   ID=184.10> TGAAGAGTTT    GACTTAGAAT   AATGAAGGTA    ACTAGAAAGT   GAGTTAATCT    2580
TGTATGAGGT TGCATTGATT TTTTAAGGCA ATATATAATT GAAACTACTG TCCAATCAAA 2640
GGGGAAATGT   mGATCTTT    AGATAGCATG CAAAGTAAGA   CCCAGCATTT    TAAAAGCCCT 2700
TTTTTAAAAA CTAGACTTCG TACTGTGAGT ATTGCTTATA TGTCCTTATG GGGATGGGTG 2760   CCACAAATAG      AAAATATGAC    CAGATCAGGG ACTTGAATGC ACTTTTGCTC ATGGTGAATA 2820  
TAGATGAACA GAGAGGAAAA   TGTATTTAAA    AGAAATACGA GAAAAGAAAA TGTGAAAGTT 2880
TTACAAGTTA GAGGGATGGA AGGTAATGTT TAATGTTGAT GTCATGGAGT GACAGAATGG 2940
CTTTGCTGGC ACTCAGAGCT CCTCACTTAG CTATATTCTG   AGACTTTGAA    GAGTTATAAA 3000
GTATAACTAT AAAACTAATT TTTCTTACAC ACTAAATGGG   TATITGTTCA    AAATAATGAA 

  3060
GTTATGGCTT CACATTCATT GCAGTGGGAT ATGGTTTTTA TGTAAAACAT TTTTAGAACT 3120
CCAGTTTTCA   AATCATGTTT    GAATCTACAT TCACTTTTTT TTGTTTTCTT TTTTGAGACG 3180
GAGTCTCGCT CTGCCGCCCA GGCTGGAGTG CAGTGGCGCG ATCTCGGCTC ACTGCAAGCT 3240
CTGCCTCCCA GGTTCACACC ATTCTCCTGC CTCAGCCTCC CGAGTAGCTG GGACTACAGG 3300
TGCCCACCAC CACGCCTGGC   TAGTTTTTG    TATTTTTAGT AGAGACGCAG   TTTCACCGTG    3360
TTAGCCAGGA TGGTCTCGAT CTCCTGACCT TGTGATCTGC CCGCCTCGGC CTCCCAAAGT 3420
GCTGGGATTA CAGGTGTGAG CCACCGCGCC CAGCCTACAT TCACTTCTAA AGTCTATGTA 3480
ATGGTGGTCA TTTTTTCCCT   TTTAGAATAC    ATTAAATGGT TGATTTGGGG AGGAAAACTT 3540
ATTCTGAATA TTAACGGTGG   TGAAAAGGGG    ACAGTTTTTA CCCTAAAGTG CAAAAGTGAA 3600
ACATACAAAA   TAAGACTAAT    TTTTAAGAGT AACTCAGTAA   TTTCAAAATA    

  CAGATTTGAA 3660
TAGCAGCATT AGTGGTTTGA GTGTCTAGCA AAGGAAAAAT TGATGAATAA AATGAAGGTC 3720
TGGTGTATAT   GTTTTAAAAT    ACTCTCATAT AGTCACACTT   TAAATTAAGC    CTTATATTAG 3780
GCCCCTCTAT TTTCAGGATA TAATTCTTAA CTATCATTAT TTACCTGATT   TTAATCATCA    3840
GATTCGAAAT TCTGTGCCAT GGCGTATATG TTCAAATTCA AACCATTTTT   AAAATGTGAA    3900
GATGGACTTC ATGCAAGTTG GCAGTGGTTC TGGTACTAAA AATTGTGGTT GTTTTTTCTG 3960
TTTACGTAAC CTGCTTAGTA TTGACACTCT CTACCAAGAG GGTCTTCCTA AGAAGAGTGC 4020
TGTCATTATT TCCTCTTATC AACAACTTGT GACATGAGAT TTTTTAAGGG   CTITATGTGA    4080
ACTATGATAT TGTAATTTTT CTAAGCATAT TCAAAAGGGT GACAAAATTA   CGTTTATGTA    4140
CTAAATCTAA TCAGGAAAGT AAGGCAGGAA AAGTTGATGG TATTCATTAG   GTTTTAACTG    4200
AATGGAGCAG TTCCTTATAT AATAACAATT GTATAGTAGG 

    GATAAAACAC    TAACAATGTG 4260  
TATTCATTTT AAATTGTTCT   GTATTTTTAA    ATTGCCAAGA AAAACAACTT TGTAAATTTG 4320
GAGATATTTT CCAACAGCTT TTCGTCTTCA GTGTCTTAAT GTGGAAGTTA ACCCTTACCA 4380
AAAAAGGAAG TTGGCAAAAA CAGCCTTCTA GCACACTTTT TTAAATGAAT AATGGTAGCC 4440
TAAACTTAAT ATTTTTATAA AGTATTGTAA TATTGTTTTG   TGG ATAATTG    AAATAAAAAG 4500
TTCTCATTGA ATGCACC 4517 (2) INFORMATION FOR SEQ ID NO:84:
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 4175 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:84:
TCCTCGTCGT CTGTGGATTG CTAAACCTGA GTGGGAAGGG GGGGGAAAAA AAAAAGGGTG 60
GGTTGTTGTT TTGTTTAAAA AAAGAAAAAA TCCCTTAAGT GGATTTGTAC CAGCGTGGAA 120
GATAACTGGG   GATTTTTGTT    GTTTGTTTTG GGAATAGAAA CTAAAAAATG GAGACTGTAA 180
GTAGAAGCAG CTTCCAGCCT CATCCAGGAC TGCAGAAGAC CTTGGAACAG TTTCATCTGA 240
GCTCTATGAG CTCCCTGGGT GGCCCTGCTG   CITTCTCAGC    GCGATGGGCA CAGGAGATGT 300
ACAAGAAAGA CAATGGCAAA GACCCAGCGG AACCTGTACT GCATCTGCCC CCTATCCAGC 360
CCCCCCCGGT GATGCCTGGT CCCTTCITCA TGCCCTCGGA CAGATCCACT GAGAGGTGCG 420
AGACCATCCT GGAAGGGGAA ACCATCTCCT GCTTCGTGGT GGGTGGGGAA AAGCGCCTTT 480
GCTTGCCCCA GATCCTGAAC TCGGTGCTCA GGGACTTCTC CCTGCAGCAG ATCAATTCGG 540
TGTGCGATGA GCTACACATT TACTGCTCCA GATGCACCGC TGACCAGCTG GAGATCCTCA 600
AAGTCATGGG CATCTTGCCC TTCTCTGCCC CCTCCTGCGG GCTGATCACT AAAACTGATG 660
CTGAGAGGCT TTGCAATGCC TTGCTTTATG GTGGCACCTA TCCTCCCCAC 

  TGCAAGAAGG 720  
AATTCTCTAG CACGATTGAG CTGGAGCTTA CAGAGAAGAG CTTCAAGGTG TACCACGAGT 780
GCTTTGGGAA GTGTAAGGGA CTCCTGGTAC CAGAGCTTTA CAGTAACCCC AGCGCAGCCT 840
GCATCCAGTG CTTGGACTGC AGGCTCATGT ACCCGCCTCA   CAAATTTGTG    GTCCACTCTC 900
ACAAATCCCT GGAAAACAGG ACTTGCCACT GGGGCTTTGA CTCTGCAAAC TGGAGGTCCT 960
ACATCCTCCT TAGCCAGGAT TACACTGGGA AAGAGGAGAA AGCTAGGCTG GGCCAGCTCT 1020
TAGATGAAAT GAAAGAAAAA   TTTGACTATA    ACAACAAATA CAAGAGGAAA GCCCCCAGGA 1080
ACCGTGAGTC TCCTAGAGTT CAGCTCCGCC GGACCAAAAT GTTCAAGACA ATGCTGTGGG 1140
ATCCAGCTGG AGGTTCAGCG GTACTGCAGC GTCAGCCAGA TGGAAATGAG   GTCCCTTCAG    1200
ATCCTCCTGC TTCCAAGAAA ACCAAAATAG ACGACTCCGC TTCCCAATCT CCAGCTTCTA 1260
CTGAGAAGGA AAAGCAGTCC AGTTGGTTAC GGTCCTTATC CAGTTCATCT AATAAGAGCA 1320
TTGGCTGTGT CCATCCCCGT CAGCGTCTCT CAGCTTTCCG GCCCTGGTCC CCTGCTGTAT 1380
CAGCAAATGA 

  GAAAGAGCTC TCAACCCATC TTCCTGCATT GATCCGAGAC AGCAGTTTTT 1440
ACTCCTACAA   AAGCTTTGAG    AATGCTGTGG CCCCCAACGT GGCACTCGCA CCTCCTGCCC 1500
AACAGAAAGT TGTGAGCAAC CCACCCTGTG CCACAGTGGT GTCCCGGAGC AGCGAACCGC 1560
CGAGCAGCGC TGCGCAGCCA CGGAAAAGAA AACATGCTGC AGAAACCCCG GCTGTCCCAG 1620
AGCCAGTGGC CACGGTTACT GCCCCTGAAG AGGATAAGGA ATCAGAAGCA GAAATTGAAG 1680
TAGAGACCAG GGAGGAATTC ACCTCCTCCT TATCCTCGCT CTCCTCCCCA TCCTTTACTT 1740
CATCCAGCTC TGCAAAGGAC ATGAGCTCAC CTGGGATGCA AGCCCCAGTC CCAGTCAACA 1800
GTTCATATGA GGTTGCAGCA CATTCTGACT CTCACAGCAG TGGGTTGGAA GCTGAGCTGG 1860
AGCACCTAAG GCAGGCCCTG GACAGTGGCC TAGATACAAA AGAAGCCAAA GAAAAATTCC 1920
TCCATGAAGT TGTTAAAATG AGAGTGAAGC AGGAAGAGAA GCTAAATGCT GCCTTGCAAG 1980
CCAAACGCAG CCTACATCAG GAGCTGGAGT TCCTCAGAGT GGCAAAGAAG GAGAAACTGA 2040
GAGAAGCAAC GGAGGCAAAA CGCAACTTAA GGAAAGAGAT TGAGCGTCTG AGAGCTGAGA 2100
ATGAGAAGAA AATGAAGGAA 

  GCAAACGAGT CTCGGATACG GCTAAAGAGG GAACTGGAAC 2160  
AAGCCAGGCA GATCCGGGTT TGCGACAAGG GTTGTGAAGC TGGCAGGCTT CGGGCCAAGT 2220
ACTCTGCCCA GATTGAGGAC CTACAGGTTA AGCTTCAGCA TGCAGAGGCT GACAGGGAGC 2280
AGCTCCGAGC TGACCTGATG CATGAGAGGG AGGCTCGAGA ACACTTGGAA AAAGTAGTCA 2340
AGGAACTTCA GGAACAGCTG TGGCCTAAAT CAAGCAGTCA ATCCAGCAGT GAAAACACAA 2400
CGAGCAACAT GGAGAATTAA ACCACGTCGT CTAATACAAC AGAATGACAT ATATGCACAG 2460
TAAGGGAGGA TGGGTGGGGT ACGTGTGTAA GTGCATGTGT GAGTAGTTGT GTCTTAACAC 2520
ACAGATCTAG GAATATGGAT TCTTATTAGT TGGAAGGCAA ATGTTACTCT TTATAACAGA 2580
AGCACTGAAT TACGCCTCTT   TTTTTTTCCA    ATCCATATAG CACAACATCT TACTGTGCCT 2640
ATAAAACACA   AATGTGTTTA    TAAACAAAAT   ACTTTTAAGT    CCACAGCAAA   TTTTCTACTG    2700
GCAAACTCCA AGCAAGCAGC ATCCTCCAAC TAGAATCAGA GTAAAAGGCA AGCATGGCAG 2760
TGTTTTCATG TTGCCCTTCT 

  GCCTGTCGGA ACATTTTGGA   ATTTAAAAAC    AAACTTTTCT 2820
TATAAGCTAT TTAAAGTAAT TCATTACACA GACTTGGTAT TAAAAAAAAT TAACAAGATT 2880
TTTTATAACG AACCTTTAAA AGCAAAACAA AAACCTTCGA TGCACAATTT TTACGACTTG 2940
TTAAAGGCTT TGGGATTCTT ACTGCAGAAG CCCTTTGGTG ATGATGCCAT TTCATTAGCA 3000   GTTTTTTTTA    ATCCTGTCCT GTGGTTGTAT   GAGAATTTCA      GAGTGCTTTT    CAAAGTTGAT 3060
TTTTTTCCTT AGAAACAATC   ACCTTCATTT    CCTGTCCTGA ACACAAGAAG AAAGGAAGAT 3120
GCAGGACTGT AAGGGCGTGG GGGAGGGCAG GAAGAGAAGA TGGACGCTTT GGAATTATAA 3180
ACCCAGCCTT ACAGACTTCA GTGTTTCAAA TCACGCCATG TTTTCTAAAG ACGTCTTCAT 3240
TAATCGATGT GTTCAAAAGA CTCACTTCAT CCAAGAGCAC TTCAGCTTTA GGAAAAGAAA 3300
GAAGGAAGTA AAGGAAGGAA ATGGATGACC TGTTAAGTTG GTTGAGAAAT AAAGCAGAAG 3360
ATGTGTTTTG AAGTCATTCT GAAATCTTCG CGTCAGCTTT CAGTTCTCTG GAAAACTCAT 

  3420
CTTTGTTGCA CCATCTTACC ATAGAATTCA   GTATTTACCT    ACTTCTATTC TGAACTGTTT 3480
GTCAGGATTT CTGTGCCCAA GGAGAGTGCA ACACCGCATT ATTGGATACT ACAGAAAAGA 3540
AAAACCACGT TTTTGCTGCT GTGAATAAGC CTACATCTTT   TTTAAAAGAA    AAACTTCTGT 3600  
TTTTAAGAAT AGAAATTACT TTAATTTTGG GATCCGAGCC GCAGCCCTGG AATAGAAATG 3660
CAGCCTACCA TCACTCTGTC TTACTACCAT TGTTAGCGTC GTCGTTCATT   TTTTTTTAAA    3720
CTGCACTTTG TCAGAACCTC ACTCTGCATT TTATTCCATA TTTTGGAAGT TTACAAGTTC 3780
AGCATTCTCG ATTCTGCTCT GCAGATGTTA AAATCATCAC CACCATTTTC CACCACGCGA 3840
CACCTCGGCC   GTCATTTCCA    TGTATGCAAA AGAAGAACTC AGTGGGTACA   GAATGCTACC    3900
AAATACAAAG GCAGCAGAGC AGCGTGCTGC TGGTTGGGTT TCACAGCTGC GCTGCACGGC 3960
TGTGGCTGTC GAGGCTGGGA AGTGCTCAAA TACAGTTGGT GCTTTACTGA ATGAGAGAGG 4020
AGTTATTTTC ACCCACACAC ACTCACCTCT 

  GATACACTCA AGCTCAGTGA AAAGTTGATC 4080
TGGGGCTGCA GTTGTGCCTT CCAGCTCATT TTTCCTCTCA GCATCTTCTA TAGGCAATGC 4140
TGACACTTTT TTTTTAAACC TTAAAGAATA AAAAG 4175 (2) INFORMATION FOR SEQ ID NO:85:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 1838 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:85:
GAGGAGTTAG GGAGGCTGAG CCAGCCCGCA TTAGCTCAGC TCTCAGGCAC TCTCAGTCTC 60
TGCTGGAAAA GGAGCTGGGA GGATGTGCGC GCTGTTACCG CGGCTCCCCA CGGCACGCTG 120
AGAGCGAAGG GAAGAAAGGA AGAAAGGGGA GCGCGGCGCC AGGGAGCCCG CCCGGATCGA 180
GCGAAGGGAC CGCTCGGGGA AGGCAGCCCG CCCGCAGCCC CGCACCGCCT TGGAAGCGCC 240
GGAGATTGGG GCCTTTTAAT TCTATTCCGC GTTGCTCCCT TCCCCGCACC GAGCCGTCTT 300
CCTCCTCCCG CTTTTTACTT TCCCTCCCCG CTCCTTCCTC CTGGTGGATA TGGACACAAG 360
CGGGATGCGT GCAGAGAAGC AGCAGCCGCC AGCGCGTATT TAACCCGCGG GTGCCCGGAG 420  
CGTGGCTCGG ACCGGCGTTC CGGGGCTGGC AGTGCGCGCT GCCTGGCGCC GGGCTCGGAT 480
GAGGACCTCG CTTCGGCGAG ACTCTGCGCT CCGGCCGGGC GGCGTCGGGG CCGGGCACGC 540
GAGAGATTGT GACGGAGCGA GAGAACGGAA AGGAGAGAGA GCCGCGTACG AAAAGGATTT 600   ATTTCCTCGT    CGTCTGTGGA TTGCTAAACC TGAGTGGGAA GGGGGGGGAA AAAAAAAAGG 660
GTGGGTTGTT   GTTTTGTTTA    AAAAAAGAAA AAATCCCTTA  <RTI  

   ID=190.3> AGTGGATTTG    TACCAGCGTG 720
GAAGATAACT GGGGATTTTT   GTTGTlTGTT    TTGGGAATAG AAACTAAAAA ATGGAGACTG 780
TAAGTAGAAG CAGCTTCCAG CCTCATCCAG GACTGCAGAA GACCTTGGAA CAGTITCATC 840
TGAGCTCTAT GAGCTCCCTG GGTGGCCCTG CTGCTTTCTC AGCGCGATGG GCACAGGAGA 900
TGTACAAGAA AGACAATGGC AAAGACCCAG CGGAACCTGT ACTGCATCTG CCCCCTATCC 960
AGCCCCCCCC GGTGATGCCT GGTCCCTTCT TCATGCCCTC GGACAGATCC ACTGAGAGGT 1020
GCGAGACCAT CCTGGAAGGG GAAACCATCT CCTGCTTCGT GGTGGGTGGG GAAAAGCGCC 1080
TITGCTTGCC CCAGATCCTG AACTCGGTGC TCAGGGACTT CTCCCTGCAG CAGATCAATT 1140
CGGTGTGCGA TGAGCTACAC   ATTTACTGCT    CCAGATGCAC CGCTGACCAG CTGGAGATCC 1200
TCAAAGTCAT GGGCATCTTG CCCTTCTCTG CCCCCTCCTG CGGGCTGATC ACTAAAACTG 1260
ATGCTGAGAG GCTTTGCAAT   GCCTTGCTTT    ATGGTGGCAC CTATCCTCCC CACTGCAAGA 1320
AGGAATTCTC TAGCACGATT GAGCTGGAGC TTACAGAGAA GAGCTTCAAG 

  GTGTACCACG 1380
AGTGCTTTGG GAAGTGTAAG GGACTCCTGG TACCAGAGCT TTACAGTAAC CCCAGCGCAG 1440
CCTGCATCCA GTGCTTGGAC TGCAGGCTCA TGTACCCGCC TCACAAATTT GTGGTCCACT 1500
CTCACAAATC CCTGGAAAAC AGGACTTGCC ACTGGGGCTT TGACTCTGCA AACTGGAGGT 1560
CCTACATTCT CCTTAGCCAG GATTACACTG GGAAAGAGGA GAAAGCTAGG CTGGGCCAGC 1620
TCTTAGATGA AATGAAAGAA   AAATTTGACT    ATAACAACAA ATACAAGAGG AAAGCCCCCA 1680
GGGTAAGTGA TGCCTTAAAT   TCTTACTTTA    AGAAGGAGTA GGGTGATAAG AAGGAGAAAA 1740
GATTTTCGAT GACGACCATC GATGTACTCA ATTTGTTACC   AACTGTTTTC    CTTTTAGAGT 1800   CGTTTAGCAA    TCTAATCGCA TTCTTMTTC TCACCACG 1838   (2) INFORMATION FOR SEQ ID NO:86:
   (i)    SEQUENCE CHARACTERISTICS:
 IA) LENGTH: 402 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 ID) TOPOLOGY:

   linear
   lii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID   NO:86:   
AAAAGCAGCA GTGTCCGAGA ACCAAAACAA AAAACCCCAC AGCACAACAA CTGGCCTCCT 60
TCCATGAGCC   GACCCTATTT    TCAGCCTGTC CGCCACGGTA CCAGGGGCAC GGGCTGTTAT 120
TGAGAGGCTG   CTCTTGTACA    TAAAGCCTTG TGATTTTTGT TTAGAACCGT GAGTCTCCTA 180
GAGTTCAGCT CCGCCGGAAC AAAATGTTCA AGACAATGCT GTGGGATCCA GCTGGAGGTT 240
CAGCGGTACT GCAGCGTCAG CCAGATGGAA ATGAGGTGCA GAGGGTTGCA GGGGTGGGTG 300
TGGGGAGTTC   CTTCCCTTTA    AACCAAAAGG AAAACAATAG TGATTCTGAA ATACATGCAT 360
TCAGTGTATC TATAGCATTA AATGCTAACT ATGGTAGGCA TG 402   {2)    INFORMATION FOR SEQ ID NO:87:
   li)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 576 base pairs
 (B) TYPE:

   nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA   Igenomic)   
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:
CGTGTGTAAG TGCATGTGTG AGTAGTTGTG   TCTTAACACA    CAGATCTAGG AATATGGATT 60
CTTATTAGTT GGAAGGCAAA TGTTACTCTT TATAACAGAA GCACTGAATT ACCCCTCTTT 120
TTTTTTCCAA TCCATATAGC ACAACATCTT ACTGTGCCTA TAAAACACAA AGTGTCTATA 180  
AACAAAATAC TTTTAAGTCC ACAGCAAATT TTCTACTGGC AAACTCCAAG CAAGCAGCAT 240
CCTCCAACTA GAATCAGAGT AAAAGGCAAG CATGGCAGTG   TTTTCATGTT    GCCCTTCTGC 300
CTGTCGGAAC ATTTTGGAAT TTAAAAACAA ACTTTTCTTA   TAAGCTATIT    AAAGTAATTC 360
ATTACACAGA   CTTGGTATTA    AAAAAAATTA ACAAGATITT TTATAACGAA   C CTrTAAAAG    420
CAAAACAAAA ACCTTCGATG CACAATTTIT ACGACTTGTT AAAGGCTTTG GGATTCTTAC 480
TGCAGAAGCC CTTTGGTGAT 

  GATGCCATTT CATTAGCAGT   TTTCCAGCCG    TCTCGGAAGC 540
CATCACAGTT TTAATCCTGT CCTGTGGTTG TATGAG 576 (2) INFORMATION FOR SEQ ID NO:88:
   (i)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 1483 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:88:
AATGGAACCC GCTAGCCAGT AGGCCTTAGC CTGTGGGGGA GCAGTTTTAG AGATAAGAGA 60
ACATGTACTT AACAGAATTA TTAGTGCTCT GTTGGGATTA ATGCTTTTTA AAGATTGTTT 120   GCACTTATTT    TTCGTTCTCC TCCTTCCCAG AGCATTGGCT GTGTCCATCC CCGTCAGCGT 180
CTCTCAGCTT TCCGGCCCTG GTCCCCTGCT GTATCAGCAA ATGAGAAAGA GCTCTCAACC 240
CATCTTCCTG CATTGATCCG AGACAGGTAA GGCGGCCAGA GCTGAGGGAG GAATGGGGCT 300
GGCAACTGTG GAGAGTATCT GGAGAGCAAG TTGCTTTATG CTTGCCGTCT TGCATTGTTT 360
GTTAGTTGAT CAGTTCACTA GTAGTGGAAT   AAAAAGTATT    TGCTGGTGCA GTGTTCTAGT 420
TAGCAGAAAG GAAACAAAAA AGGTCTAAGA GTAGGCCTTT GGGCACCTAA TTCTGGGGAA   480   
AAAATACCTA AAACTTCAGC AAGTTCTCAA GTTTTAATAG ACAACTTdAA   GATACTTTGC    540
ATTATACATG CTGAGTTGAA GTTGCAGGCA GTTTTTGATA CCTTTTCTGC   TAAATTCTTT    600  
CTATGTGATG TTACAGTATT ACTGTTCTTT 

  AACATAGTTA   CTTTTAAGG      CATTTTATGT    660
ACAAGTATTC AGATGTCCTG TGTCAAGAAA GTAAAGTTGC ACAAGGATAC   ATTITGTACT    720
CCTGTGGCCT TTGTAGGGAA GCTGTTTCCA AGCTTACAAA ACATTCGTGG ATAGACAGAA 780
TTAAAGTCCA ATTAGGAAAA TCGATAATGC ACAAAGACTG TGGGGAAGCA GCATCATTTT 840
TAGACTGGGA GAGCTTGGTA CTCAGAATAT ATGGTCCATC ACATATATCC CTCCTGACCT 900
GACGGAGATT AGCAGTATAA ATTACCTCCA CATTTAAATG AGTACTTAAC AAATATATAG 960
CCAGATTCTT AGCTGGTGTG TATTGGTGGA CCTTCACCGT CACTCCAGTA AGAGCCTTGC 1020
AGTTTCAGTG TAACACACAG ATTGGGAAGC GTTTTAAAGT CAAGAATATG   ACTGTTrTCT    1080
CCTTCCTTTT GTCTCCCCCT CTCCAGCAGT   TTTTACTCCT    ACAAAAGCTT TGAGAATGCT 1140
GTGGCCCCCA ACGTGGCACT CGCACCTCCT GCCCAACAGA AAGTTGTGAG CAACCCACCC 1200
TGTGCCACAG TGGTGTCCCG GAGCAGCGAA CCGCCGAGCA GCGCTGCGCA GCCACGGAAA 1260
AGAAAACATG 

  CTGCAGAAAC CCCGGCTGTC CCAGAGCCAG TGGCCACGGT TACTGCCCCT 1320
GAAGAGGATA AGGAATCAGA AGCAGAAATT GAAGTAGAGA CCAGGGAGGA ATGTAAGTGT 1380
ATATCTGCCT TTACTTTGTT   TTATTTGTGC      TCTGTTTTCC    TCTGGTTAAC CTCCAGCAGT 1440
TAGCTACTGA ACTCTGTTGC GTTCAAACAT AATTCTGGAG GCC 1483 (2) INFORMATION FOR SEQ ID NO:89:
 (i) SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 3230 base pairs
   (B)    TYPE: nucleic acid
   (C)    STRANDEDNESS: double
 ID) TOPOLOGY: linear
   (ii)    MOLECULE TYPE: DNA (genomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:89:
ACGTCTACCC   ATTCTTATTT    CTGCAGCATA TATAGCAGTG ACGAGGATGA TGAGGACTTT 60
GAGATGTGTG ACCATGACTA TGATGGGCTG CTTCCCAAGT CTGGAAAGCG TCACTTGGGG 120  
AAAACAAGGT GGACCCGGGA AGAGGATGAA AAACTGAAGA AGCTGGTGGA ACAGAATGGA 180
ACAGATGACT GGAAAGTTAT TGCCAATTAT CTCCCGAATC GAACAGATGT GCAGTGCCAG 240
CACCGATGGC AGAAAGTACT AAACCCTGAG CTCATCAAGG GTCCTTGGAC CAAAGAAGAA 300
GATCAGAGAG TGATAGAGCT TGTACAGAAA TACGGTCCGA AACGTTGGTC TGTTATTGCC 360
AAGCACTTAA AGGGGAGAAT TGGAAAACAA TGTAGGGAGA GGTGGCATAA CCACTTGAAT 420
CCAGAAGTTA AGAAAACCTC CTGGACAGAA GAGGAAGACA   GAATTATTTA    CCAGGCACAC 480
AAGAGACTGG GGAACAGATG GGCAGAAATC GCAAAGCTAC TGCCTGGACG AACTGATAAT 540
GCTATCAAGA ACCACTGGAA TTCTACAATG CGTCGGAAGG TCGAACAGGA AGGTTATCTG 600
CAGGAGTCTT CAAAAGCCAG CCAGCCAGCA GTGGCCACAA GCTTCCAGAA GAACAGTCAT 660
TTGATGGGTT TTGCTCAGGC TCCGCCTACA GCTCAACTCC 

  CTGCCACTGG CCAGCCCACT 720
GTTAACAACG ACTATTCCTA TTACCACATT TCTGAAGCAC AAAATGTCTC CAGTCATGTT 780
CCATACCCTG TAGCGTTACA TGTAAATATA GTCAATGTCC CTCAGCCAGC TGCCGCAGCC 840
ATTCAGAGAC ACTATAATGA TGAAGACCCT GAGAAGGAAA AGCGAATAAA GGAATTAGAA 900
TTGCTCCTAA TGTCAACTGA GAATGAGCTA AAAGGACAGC AGTTATGTGG GCCATTACTG 960
AATTCTGACA TCTTTAGCGA    GGGCAGCC    AACTGGGATG   GCTCCTTGTG    CTTTGCAACA 1020
TACATAGTTA ACCAACAAAG ACAATAAAAG AGAAGTGATG   CCCAACACAG    AACCACACAT 1080
GCAGCTACCC CGGGTGGCAC AGCACCACCA TTGCCGACCA CACCAGACCT CATGGAGACA 1140
GTGCACCTGT   TTCCTGTTTG    GGAGAACACC ACTCCACTCC ATCTCTGCCA GCGGATCCTG 1200
GCTCCCTACC   TGAAGAAAGC    GCCTCGCCAG CAAGGTGCAT GATCGTCCAC CAGGGCACCA 1260
TTCTGGATAA TGTTAAGAAC CTCTTAGAAT TTGCAGAAAC ACTCCAATTT ATAGATTCTT 1320
TCTTAAACAC TTCCAGTAAC 

  CATGAAAACT CAGACTTGGA AATGCCTTCT TTAACTTCCA 1380
CCCCCCTCAT TGGTCACAAA   TTGACTGTTA    CAACACCATT TCATAGAGAC CAGACTGTGA 1440
AAACTCAAAA GGAAAATACT   GTTTTAGAA    CCCCAGCTAT CAAAAGGTCA ATCTTAGAAA 1500
GCTCTCCAAG AACTCCTACA CCATTCAAAC ATGCACTTGC AGCTCAAGAA ATTAAATACG 1560  
GTCCCCTGAA GATGCTACCT CAGACACCCT CTCATCTAGT AGAAGATCTG CAGGATGTGA 1620
TCAAACAGGA ATCTGATGAA TCTGGAATTG TTGCTGAGTT TCAAGAAAAT GGACCACCCT 1680
TACTGAAGAA AATCAAACAA GAGGTGGAAT CTCCAACTGA TAAATCAGGA AACTTCTTCT 1740
GCTCACACCA CTGGGAAGGG GACAGTCTGA   ATACCAACT    GTTCACGCAG ACCTCGCCTG 1800
TGGCAGATGC ACCGAATATT CTTACAAGCT CCGTTTTAAT GGCACCAGCA TCAGAAGATG 1860
AAGACAATGT TCTCAAAGCA TTTACAGTAC CTAAAAACAG GTCCCTGGCG AGCCCCTTGC 1920
AGCCTTGTAG CAGTACCTGG GAACCTGCAT CCTGTGGAAA GATGGAGGAG CAGATGACAT 1980
CTTCCAGTCA AGCTCGTAAA TACGTGAATG CATTCTCAGC CCGGACGCTG 

  GTCATGTGAG 2040
ACATTTCCAG AAAAGCATTA TGGTTTTCAG AACACTTCAA GTTGACTTGG GATATATCAT 2100
TCCTCAACAT   GAAACTTTC    ATGAATGGGA GAAGAACCTA   TTTTGTTGT    GGTACAACAG 2160
TTGAGAGCAG CACCAAGTGC ATTTAGTTGA ATGAAGTCTT   CTTGGATTTC    ACCCAACTAA 2220
AAGGATTTTT AAAAATAAAT AACAGTCTTA CCTAAATTAT TAGGTAATGA ATTGTAGCCA 2280
GTTGTTAATA TCTTAATGCA GATTTTTTTA AAAAAAACAT AAAATGATTT ATCTGTATTT 2340
TAAAGGATCC AACAGATCAG   TATTTTTTCC    TGTGATGGGT TTTTTGAAAT TTGACACATT 2400   AAAAGGTACT    CCAGTATTTC   ACTITCTCG    ATCACTAAAC ATATGCATAT ATTTTTAAAA 2460
ATCAGTAAAA   GCATTACTCT    AAGTGTAGAC TTAATACCAT   GTGACATTTA    ATCCAGATTG 2520
TAAATGCTCA TTTATGGTTA ATGACATTGA AGGTACATTT ATTGTACCAA ACCATTTTAT 2580
GAGTTTTCTG  <RTI  

   ID=195.10> TTAGCTTGCT    TTAAAAATTA   TTACTGTAAG    AAATAGTTTT ATAAAAAATT 2640
ATATTTTTAT TCAGTAATTT AATTTGTAA ATGCCAAATG AAAAACGTTT TTTGCTGCTA 2700
TGGTCTTAGC CTGTAGACAT GCTGCTAGTA TCAGAGGGGC AGTAGAGCTT GGACAGAAAG 2760
AAAAGAAACT TGGTGTTAGG TAATTGACTA TGCACTAGTA   TITCAGACIT    TTTAATTTTA 2820
TATATATATA CATTTTTTTT CCTTCTGCAA   TACATTTGAA    AACTTGTTTG GGAGACTCTG 2880
CATTTTTTAT TGTGGTTTTT TTGTTATTGT TGGTTTATAC AAGCATGCGT TGCACTTCTT 2940   TTTTGGGAGA    TGTGTGTTGT TGATGTTCTA TGTTTTGTTT TGAGTGTAGC CTGACTGTTT 3000  
TATAATTTGG GAGTTCTGCA TTTGATCCGC ATCCCCTGTG GTCTCTAAGT GTATGGTCTC 3060
AGAACTGTTG CATGGATCCT   GTGTTTGCAA      CTGGGGAGAC    AGAAACTGTG GTTGATAGCC 3120
AGTCACTGCC TTAAGAACAT TTGATGCAAG ATGGCCAGCA CTGAACTTTT GAGATATGAC  

  3180
GGTGTACTTA CTGCCTTGTA GCAAAATAAA GATGTGCCCT TATTTTACCT 3230 12) INFORMATION FOR SEQ ID NO:90:
   li)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 1035 base pairs
 IB) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   lii)    MOLECULE TYPE: DNA Igenomic)
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:90:
GAGGATGAAA AACTGAAGAA GCTGGTGGAA CAGAATGGAA CAGATGACTG GAAAGTTATT 60
GCCAATTATC TCCCGAATCG AACAGATGTG CAGTGCCAGC ACCGATGGCA GAAAGTACTA 120
AACCCTGAGC TCATCAAGGG TCCTTGGACC AAAGAAGAAG ATCAGAGAGT   G 
AATGAGCTAA AAGGACAGCA GGTGCTACCA GTAAGACTGT CATCATGTGC TTGAATGAGG 840
GGATAGCAGC   TTTGCCTCAG      TTTACCTAAG    CGCTCTTCTC TTCTAAATAT TACACTTAGC 900
AAGGCTCCAT ATATCCATTC AGAATGTCTC AACACAAGAA GTTGCTTGTA GTAAAATGTA 960
GTTGGTATCA GATTATATGC TGATTAAATT GGAAGCAGTC   TTTTTGTAAT    TGCAATAAAA 1020
ATGCAATATC CACTT 1035 (2) INFORMATION FOR SEQ ID NO:91:
   (i)    SEQUENCE CHARACTERISTICS:
   (A)    LENGTH: 3225 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
   (D)    TOPOLOGY:

   linear
   (ii)    MOLECULE TYPE: DNA   Igenomic)   
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:
GGCGGCAGCG CCCTGCCGAC GCCGGGGAGG GACGCAGGCA GGCGGCGGGC AGCGGGAGGC 60
GGCACCCCGG TGCTCCCCGC GGCTCTCGGC GGAGCCCCGC CGCCCGCCGC   GCCATGGCCC    120
GAAGACCCCG GCACAGCATA TATAGCAGTG ACGAGGATGA TGAGGACTTT GAGATGTGTG 180
ACCATGACTA   TGATGGGCTG    CTTCCCAAGT CTGGAAAGCG TCACTTGGGG AAAACAAGGT 240
GGACCCGGGA AGAGGATGAA AAACTGAAGA AGCTGGTGGA ACAGAATGGA ACAGATGACT 300
GGAAAGTTAT TGCCAATTAT CTCCCGAATC GAACAGATGT GCAGTGCCAG CACCGATGGC 360
AGAAAGTACT AAACCCTGAG CTCATCAAGG GTCCTTGGAC CAAAGAAGAA GATCAGAGAG 420
TGATAGAGCT TGTACAGAAA TACGGTCCGA AACGTTGGTC TGTTATTGCC AAGCACTTAA 480
AGGGGAGAAT TGGAAAACAA TGTAGGGAGA GGTGGCATAA CCACTTGAAT CCAGAAGTTA 540
AGAAAACCTC CTGGACAGAA GAGGAAGACA   GAATTATTTA    

  CCAGGCACAC AAGAGACTGG 600
GGAACAGATG GGCAGAAATC GCAAAGCTAC TGCCTGGACG AACTGATAAT GCTATCAAGA 660
ACCACTGGAA TTCTACAATG CGTCGGAAGG TCGAACAGGA AGGTTATCTG   CAGGAGTCTT    720  
CAAAAGCCAG CCAGCCAGCA GTGGCCACAA GCTTCCAGAA GAACAGTCAT TTGATGGGTT 780
TTGCTCAGGC TCCGCCTACA   GCTCAACTCC    CTGCCACTGG CCAGCCCACT GTTAACAACG 840
ACTATTCCTA TTACCACATT TCTGAAGCAC   AAAATGTCTC    CAGTCATGTT CCATACCCTG 900
TAGCGTTACA TGTAAATATA GTCAATGTCC CTCAGCCAGC TGCCGCAGCC ATTCAGAGAC 960
ACTATAATGA TGAAGACCCT GAGAAGGAAA AGCGAATAAA GGAATTAGAA TTGCTCCTAA 1020
TGTCAACCGA   GAATGAGCTA    AAAGGACAGC AGGTGCTACC AACACAGAAC CACACATGCA 1080
GCTACCCCGG GTGGCACAGC ACCACCATTG CCGACCACAC CAGACCTCAT GGAGACAGTG 1140
CACCTGTTTC   CTGTTTGGGA    GAACACCACT CCACTCCATC TCTGCCAGCG GATCCTGGCT 1200
CCCTACCTGA AGAAAGCGCC 

  TCGCCAGCAA GGTGCATGAT CGTCCACCAG GGCACCATTC 1260
TGGATAATGT TAAGAACCTC TTAGAATTTG CAGAAACACT CCAATTTATA   GATTCTTTCT    1320
TAAACACTTC CAGTAACCAT GAAAACTCAG ACTTGGAAAT   GCCTTCTITA    ACTTCCACCC 1380
CCCTCATTGG TCACAAATTG ACTGTTACAA   CACCATTTCA    TAGAGACCAG ACTGTGAAAA 1440
CTCAAAAGGA   AAATACTGTT      TTTAGAACCC    CAGCTATCAA AAGGTCAATC TTAGAAAGCT 1500
CTCCAAGAAC TCCTACACCA TTCAAACATG CACTTGCAGC TCAAGAAATT AAATACGGTC 1560
CCCTGAAGAT GCTACCTCAG ACACCCTCTC ATCTAGTAGA AGATCTGCAG GATGTGATCA 1620
AACAGGAATC TGATGAATCT GGATTTGTTG   CTGAGTTTCA    AGAAAATGGA CCACCCTTAC 1680
TGAAGAAAAT CAAACAAGAG GTGGAATCTC CAACTGATAA ATCAGGAAAC   TTCTTCTGCT    1740
CACACCACTG GGAAGGGGAC AGTCTGAATA CCCAACTGTT CACGCAGACC TCGCCTGTGC 1800
GAGATGCACC 

  GAATATTCTT ACAAGCTCCG TTTTAATGGC ACCAGCATCA GAAGATGAAG 1860
ACAATGTTCT   CAAAGCATTT    ACAGTACCTA AAAACAGGTC CCTGGCGAGC CCCTTGCAGC 1920
CTTGTAGCAG TACCTGGGAA CCTGCATCCT GTGGAAAGAT GGAGGAGCAG ATGACATCTT 1980
CCAGTCAAGC TCGTAAATAC GTGAATGCAT TCTCAGCCCG GACGCTGGTC ATGTGAGACA 2040   m CCAGAAA    AGCATTATGG TTTTCAGAAC AGTTCAAGTT GACTTGGGAT ATATCATTCC 2100
TCAACATGAA ACTTTTCATG AATGGGAGAA   GAACCTATTT    TTGTTGTGGT ACAACAGTTG 2160  
AGAGCACGAC CAAGTGCATT TAGTTGAATG AAGTCTTCTT   GGATTTCACC    CAACTAAAAG 2220
GATTTTTAAA AATAAATAAC AGTCTTACCT AAATTATTAG GTAATGAATT GTAGCCAGTT 2280
GTTAATATCT TAATGCAGAT   TTTTTTAAAA    AAAAACATAA AATGATTTAT CTGGTATTTT 2340
AAAGGATCCA ACAGATCAGT   ATTTTTTCCT    GTGATGGGTT TTTTGAAATT TGACACATTA 2400
AAAGGTACTC CAGTATTTCA 

  CTTTTCTCGA TCACTAAACA TATGCATATA   TTITTAAAAA    2460
TCAGTAAAAG CATTACTCTA AGTGTAGACT TAATACCATG   TGACATTTAA    TCCAGATTGT 2520
AAATGCTCAT TTATGGTTAA TGACATTGAA GGTACATTTA TTGTACCAAA CCATTTTATG 2580
AGTTTTCTGT TAGCTTGCTT TAAAAATTAT TACTGTAAGA AATAGTTTTA TAAAAAATTA 2640
TATTTTTATT   CAGTAATTTA      ATTTTGTAAA    TGCCAAATGA AAAACGTTTT TTGCTGCTAT 2700
GGTCTTAGCC TGTAGACATG CTGCTAGTAT CAGAGGGGCA GTAGAGCTTG GACAGAAAGA 2760
AAAGAAACTT GGTGTTAGGT AATTGACTAT GCACTAGTAT TTCAGACTTT TTAATTTTAT 2820
ATATATATAC ATTTTTTTTC CTTCTGCAAT ACATTTGAAA ACTTGTTTGG GAGACTCTGC 2880
ATTTTTTATT   GTGGTTTTIT    TGTTATTGTT   GGTTTATACA    AGCATGCGTT GCACTTCTTT 2940   TTTGGGAGAT      GTGTGTTGTT    CATGTTCTAT GTTTTGTTTT GTGTGTAGCC 

  TGACTGTTTT 3000
ATAATTTGGG AGTTCTCGAT TTGATCCGCA TCCCCTGTGG TTTCTAAGTG TATGGTCTCA 3060
GAACTGTTGC ATGGATCCTG TGTTTGCAAC TGGGGAGACA GAAACTGTGG TTGATAGCCA 3120
GTCACTGCCT TAAGAACATT TGATGCAAGA TGGCCAGCAC TGAACTTTTG AGATATGACG 3180
GTGTACTTAC   TGCCTTGTAG    CAAAATAAAG ATGTGCCCTT   ATTIT    3225 12) INFORMATION FOR SEQ ID NO:92:
   li)    SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 420 base pairs
 (B) TYPE: nucleic acid
 (C) STRANDEDNESS: double
 (D) TOPOLOGY: linear
 (ii) MOLECULE TYPE: DNA (genomic)  
 (xi) SEQUENCE DESCRIPTION:

   SEQ ID NO:92:   TTTATAGATT    CTGATTCTTC ATCATGGTGT GATCTCAGCA GTTTTGAATT CTTTGAAGAA 60   GCAGATTTTT    CACCTAGCCA ACATCACACA GGCAAAGCCC TACAGTTTCA GCAAAGAGAG 120
GGCAATGGGA CTAAACCTGC AGGAGAACCT AGCCCAAGGG TGAACAAACG TATGTTGAGT 180
GAGAGTTCAC TTGACCCACC CAAGGTCTTA CCTCCTGCAA GGCACAGCAC AATTCCACTG 240
GTCATCCTTC GAAAAAAACG GGGCCAGGCC AGCCCCTTAG CCACTGGAGA CTGTAGCTCC 300
TTCATATTTG CTGACGTCAG CAGTTCAACT CCCAAGCGTT   CCCCTGTCAA    AAGCCTACCC 360
TTCTCTCCCT CGCAGTTCTT AAACACTTCC AGTAACCATG AAAACTCAGA CTTGGAAATG 420 (2) INFORMATION FOR SEQ ID   NO:93:   
 (i) SEQUENCE CHARACTERISTICS:
 (A) LENGTH: 790 base pairs
 (B) TYPE: nucleic acid
   (C)    STRANDEDNESS: double
   (D)    TOPOLOGY: linear
   (ii)    MOLECULE TYPE:

   DNA (genomic)
 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:
AGAATTTAGA AGCAGGGAGA TGTAATTAGA GAATATGTCA TTACCTAGAA ATGAAGCCAC 60
AAAGTCTAAA GTAAAGCAGT TAGAAAGGAA GTGGACAGAT AAATAGATGA TTAATGTATT 120
TAGTGTCATT TATCTATACA CTAAAACTTT TATTCTGTGA ATGCTTTTCC TCAAATTCTT 180
CCCTGCAAAA AGAAATAAAA TATTACTAAG GTAGCAACTC   ATTI:

  TTITGA    AAATCCTTTA 240
TATTTAGGTG CTCCAAATAC TGCAGAATTA   AGGATTTGTC    GTGTAAACAA   GAATTGTGGA    300
AGTGTCAGAG GAGGAGATGA AATATTTCTA CTTTGTGACA AAGTTCAGAA AGGTATTTAT 360
TTATTTCATT GAATTTAGAA TAAATTTTAG ATTAATAGAT GCAGTTACTT TGTTTTCCCA 420
TTTTTTTTTT TTTGGTTTCT TATTGACTAG ATGACATAGA AGTTCGTTTT GTGTTGAACG 480
ATTGGGAAGC AAAAGGCATC TTTTCACAAG CTGATGTACA CCGTCAAGTA   GCCATTGTTT    540  
TCAAAACTCC ACCATATTGC AAAGCTATCA CAGAACCCGT AACAGTAAAA ATGCAGTTGC 600
GGAGACCTTC TGACCAGGAA GTTAGTGAAT CTATGGATTT TAGATATCTG CCAGATGAAA 660
AAGGTATGAC   ATTTTGCTGG    TAATAATTTA   TATATTTCTT    GAAGTGGTCC TGCTAATAAC 720
ATCTTCTTGT AATATTCATT TGAGTACAGT TATGTATATT CATAATTTAT   GTTTCTTTTC    780
CTGGAAGCTT 790
  

Claims

WHAT IS CLAIMED: 1. A method for producing an oligonucleotide having an Rp stereoisomeric alkyl- or aryl-phosphonate linkage between a first nucleotide and a second nucleotide in the oligoncleotide, wherein said oligonucleotide has the formula: EMI202.1 which compriseS: (a) reacting a first nucleotide of the formula: EMI202.2 with an alkyl- or aryl-phosphonothioate intermediate of the formula: EMI203.1 under conditions sufficient to produce said Rp stereoisomeric alkyl- or aryl-phosphonate linkage, wherein: Y1 is a hydrogen, phosphate, phosphate present in said oligonucleotide, or Vl,; Y2 is a hydrogen, phosphate, phosphate present in said oligonucleotide or V2; X is hydroxy or V,;
M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group; each B group is independently a purine or pyrimidine base and each B group can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl; V1 is a protecting group, solid support or phosphate attached to the penultimate nucleotide of said oligonucleotide; V2 is a protecting group; V3 is hydrogen or O-Y3 wherein Y3 is a lower alkyl or protecting group; A is an activating group; and said intermediate has an Sp stereoisomeric configuration at the phosphate;
and (b) when V1, V2 or V, is a protecting group, optionally removing V1, V2 or V3 protecting groups.
2. A method of producing a polynucleotide chain of an oligonucleotide comprising at least one Rpalkyl-phosphonate or Rp-aryl-phosphonate linkage, wherein said oligonucleotide has the formula: EMI204.1 which compriSes: (a) reacting a 5'- terminal nucleotide of the formula: EMI204.2 with an alkyl- or aryl-phosphonothioate nucleotide intermediate of the formula: EMI205.1 under conditions sufficient to produce said Rp stereoisomeric alkyl- or aryl-phosphonate linkage and so generate a new 5'-terminal nucleotide, wherein: Y1 is a hydrogen, phosphate, phosphate present in said oligonucleotide or V1; Y2 is a hydrogen, phosphate, phosphate present in said oligonucleotide or V2; X is either hydroxy or V,;
M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group; n is an integer from 0 to 200; each B group is independently a purine or pyrimidine base which can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl; Vl is a protecting group, solid support or phosphate present on the penultimate nucleotide of said oligonucleotide; V2 is a protecting group; V, is hydroxy or OY3 wherein Y, is lower alkyl or protecting group; A is an activating group;
and said intermediate has an Sp stereoisomeric phosphorus configuration; (b) removing said v2 protecting group from said new 5'-terminal nucleotide; (c) reacting the product of (b) with another alkyl- or aryl-phosphonthioate nucleotide intermediate under conditions sufficient to produce the Rp stereoisomeric linkage and so generate a new 5'-terminal nucleotide; (d) repeating steps b and c to extend said polynucleotide chain n-l times; and (e) when V1, V2 or V, is a protecting group optionally removing said Vl, V2 or V3 protecting group.
3. A method of producing an alkyl- or arylphosphonothioate nucleotide intermediate, having an Sp stereoisomeric configuration at the phosphorus, which intermediate is of the formula: EMI206.1 which comprises: a) reacting an alkyl- or aryl-phosphonothioate nucleotide of the formula: EMI207.1 with an A-L activator under conditions sufficient to produce said intermediate without inversion of said Sp stereoisomeric phosphorus configuration, wherein: A is an activating group; V2 is a protecting group; V, is either hydrogen, or OY, wherein Y, is lower alkyl or protecting group; M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group;
B is a purine or pyrimidine base which can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl; L is a leaving group which can be attached to A; and said alkyl- or aryl-phosphonothioate nucleotide has an Sp stereoisomeric phosphorus configuration.
4. The method of any one of Claims 1 or 2 which further comprises performing said method by automation.
5. The method of Claim 4 wherein V1 is a solid support or a phosphate present on the penultimate nucleotide of said oligonucleotide.
6. The method of any one of Claims 1 or 2 which further comprises removing the V1 solid support.
7. The method of Claim 1 or 2 wherein Y1 or Y2 is a phosphate present in said oligonucleotide.
8. The method of Claim 7 wherein said method further comprises adding 1-50 nucleotides joined by O- PO2-O linkages.
9. The method of any one of Claims 1-3 wherein M is lower alkyl or aryl.
10. The method of Claim 9 wherein M is lower alkyl.
11. The method of Claim 10 wherein M is methyl.
12. The method of any one of Claims 1-3 wherein each B is independently a purine or a pyrimidine which can have 1-2 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy or lower alkylamino.
13. The method of Claim 12 wherein each B is independently a guanine, adenine, thymine, cytosine or uracil.
14. The method of Claim 1 or 2 wherein said conditions sufficient to produce said RD stereoisomeric linkage comprise a time, a temperature, a solvent.or a reactant concentration sufficient for nucleophilic attack by the 5'-oxygen of said first nucleotide or said 5'-terminal nucleotide upon the phosphorus of said intermediate to displace the sulfur and invert the phosphorus configuration.
15. The method of Claim 14 wherein said time is about 5 min to about 10 hr.
16. The method of Claim 14 wherein said time is about 30 min to about 90 min.
17. The method of Claim 14 wherein said temperature is about 20"C to about 25"C.
18. The method of Claim 14 wherein said solvent is anhydrous.
19. The method of Claim 14 wherein said reactant concentration is a molar ratio of said first nucleotide or said 5'-terminal nucleotide to intermediate which ranges from about 1:10 to about 5:1.
20. The method of Claim 19 wherein said molar ratio is about 1:2.
21. The method of Claim 3 wherein said conditions sufficient to displace the L group comprise a time, a solvent, a temperature or a reactant concentration sufficent for nucleophilic displacement of L by the sulfur present on the alkyl- or arylphosphonothioate nucleotide.
22. The method of Claim 21 wherein said time is about 1 sec to about 30 min.
23. The method of Claim 22 wherein said time is about 1 min.
24. The method of Claim 21 wherein said solvent is an anhydrous solvent.
25. The method of Claim 24 wherein said solvent is acetonitrile or dimethylformamide.
26. The method of Claim 21 wherein said temperature is about 0 C to about 60"C.
27. The method of Claim 26 wherein said temperature is about 40C to about 45"C.
28. The method of Claim 27 wherein said temperature is about 20"C to about 25"C.
29. The method of Claim 21 wherein said reactant concentration comprises a molar ratio of alkylor aryl-phosphonothioate nucleotide to A-L activator of about 1:10 to about 10:1.
30. The method of Claim 29 wherein said molar ratio is about 1:5 to about 3:1.
31. The method of Claim 30 wherein said molar ratio is about 1:2.
32. The method of Claim 2 wherein n is 5 to 200.
33. The method of Claim 2 wherein n is 8 to 200.
34. The method of Claim 2 wherein n is 10 to 200.
35. The method of Claim 2 wherein n is 14 to 200.
36. The method of Claim 1, 2 or 3 wherein said A group comprises an heteroaromatic ring containing 1 to 4 nitrogen atoms, wherein said A group is of the formula: EMI210.1 wherein: Q is C-R1 or N; D is C-R2 or N; E is C-R, or N; G is C-R4 or N; J is C-Rs or N; Y is -S-, -NRe or -O-; R is a substituent attached to one nitrogen atom, wherein said substituent is lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl;
R1, R2, R3, R4 and R5 are independently hydrogen, lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, or Ri and R2 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R3 and R4 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R4 and Rs are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring; and R6 is H or lower alkyl.
37. The method of Claim 36 wherein said R is lower alkyl.
38. The method of Claim 37 wherein said activating group A is of the formula: EMI211.1 39. The method of Claim 38 wherein said activating group A is of the formula: EMI212.1 40. The method of Claim 39 wherein said A group is of the formula: EMI212.2 41. The method of Claim 40 wherein said A activating group is 2-N-methylpyridinium.
42. The method of Claim 3 wherein said A-L group comprises a heteroaromatic ring containing 1-4 nitrogen atoms of the formula: EMI212.3 Q is C-R1 or N; D is C-R2 or N; E is C-R, or N; G is C-R4 or N; J is C-Rs or N; Y is -S-, -NR- or -O-; R is a substituent attached to one nitrogen atom, wherein said substituent is lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl;
R1, R2, R,, R4 and R5 are independently hydrogen, lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, or R1 and Rz are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R, and R4 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R4 and Rs are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring; R6 is H or lower alkyl; and L is a leaving group comprising a halo, nitro, diazo, azido, trialkylamino, alkoxy, aryloxy, alkyl sulfonate, lower fluoroalkylsulfonate, aryl sulfonate, alkyl sulfinate or aryl sulfinate group.
43. The method of Claim 42 wherein A-L is a salt of the formula: EMI213.1 and Z is a counter ion.
44. The method of Claim 43 wherein A-L is a salt of the formula: EMI214.1 wherein Z is a counter ion.
45. The method of Claim 44 wherein A-L is a salt of the formula: EMI214.2 46. The method of Claim 42 wherein A-L is a salt of 2-N-lower alkyl pyridinium.
47. The method of Claim 46 wherein said salt of A-L is 2-bromo-N-methylpyridine bromide, 2-bromo-Nmethylpyridine iodide, 2-chloro-N-methylpyridine bromide or 2-chloro-N-methylpyridine iodide.
48. A compartmentalized kit for producing a polynucleotide chain of an oligonucleotide having at least five sequential R-alkyl-phosphonate or R-arylphosphonate linkages, wherein the oligonucleotide has the formula: EMI215.1 which comprises: (a) a first container adapted to contain an A L salt;
and (b) a second container adapted to contain a salt of a first alkyl- or aryl-phosphonothioate nucleotide precursor of the formula: EMI215.2 wherein: Yi is a hydrogen, phosphate, phosphate present in said oligonucleotide, or Vl; Y2 is a hydrogen, phosphate, phosphate present in said oligonucleotide or V2; X is either hydroxy or V3; M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group; n is an integer from 4 to 200; each B group is independently a purine or pyrimidine base which can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl;
Vl is a protecting group, a solid support or a phosphate attached to the penultimate nucleotide of said oligonucleotide; V2 is a protecting group; V3 is a hydrogen, or OY, wherein Y3 is lower alkyl or protecting group; and said precursor has an Sp stereoisomeric phosphorus configuration.
49. The kit of Claim 48 which is further adapted to contain at least one additional container containing a salt of a second alkyl- or arylphosphonothioate nucleotide precursor, wherein second precursor has an Sp stereoisomeric phosphorus configuration and a different B group than said first precursor.
50. The kit of Claim 48 wherein said first alkyl- or aryl-phosphonothioate nucleotide precursor has a B group selected from the group of guanine, adenine, thymine, cytosine or uracil.
51. The kit of Claim 49 wherein said second alkyl- or aryl-phosphonothioate nucleotide precursor has a B group selected from the group of guanine, adenine, thymine, cytosine or uracil.
52. The kit of Claim 48 wherein A-L comprises a heteroaromatic ring containing 1-4 nitrogen atoms of the formula: EMI217.1 or salts thereof, wherein: Q is C-R1 or N; D is C-R2 or N; E is C-R, or N; G is C-R4 or N; J is C-Rs or N; Y is -S-, -NR6- or -O-; R is lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl;
Rl, R2, R,, R4 and Rs are independently hydrogen, lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, or R1 and R2 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R3 and R4 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R4 and R3 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring; Rs is H or lower alkyl; and L is a leaving group comprising a halo, nitro, diazo, azido, trialkylamino, alkoxy, aryloxy, alkyl sulfonate, lower fluoroalkylsulfonate, aryl sulfonate, alkyl sulfinate or aryl sulfinate group.
53. The kit of Claim 52 wherein A-L is 2bromo-N-methylpyridinium bromide, 2-bromo-Nmethylpyridinium iodide, 2-chloro-N-methylpyridinium bromide or 2-chloro-N-methylpyridinium iodide.
54. An alkyl- or aryl-phosphonothioate nucleotide intermediate, having an Sp stereoisomeric configuration at the phosphorus, said intermediate having the formula: EMI218.1 wherein: V2 is a protecting group; V3 is hydroxy or 0-Y,, wherein Y, is a lower alkyl or protecting group; M is a lower alkyl, cycloalkyl, thioxo, a thio-lower alkyl, aryl or aryl-lower alkyl group which can be substituted with at least one hydroxy, halogen or cyano group; B is a purine or pyrimidine base which can have 1-3 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy, amino-lower alkyl, lower alkylamino, hydroxy-lower alkyl, aryl and aryl lower alkyl; and A is an activating group.
55. The intermediate of Claim 54 wherein M is lower alkyl or aryl.
56. The intermediate of Claim 55 wherein M is lower alkyl.
57. The intermediate of Claim 56 wherein M is methyl.
58. The intermediate of Claim 54 wherein B is a purine or a pyrimidine which can have 1-2 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy or lower alkylamino.
59. The intermediate of Claim 58 wherein B is a guanine, adenine, thymine, cytosine or uracil.
60. The intermediate of Claim 54 wherein said V2 or V, protecting group is lower alkyl, lower cyanaolkyl, lower alkanoyl, aroyl, aryloxy, aryloxy to lower alkanoyl, haloaryl, fluorenyl methoxy carbonyl, trityl, monomethoxytrityl or dimethoxytrityl.
61. The intermediate of Claim 60 wherein said protecting group is isopropyl, isobutyl, 2-cyanoethyl, acetyl, benzoyl, phenoxyacetyl, halophenyl, dimethoxytrityl or monomethoxytrityl 62. The intermediate of Claim 54 wherein said A group comprises a heteroaromatic ring containing 1 to 4 nitrogen atoms of the formula: EMI220.1 wherein: Q is C-R1 or N; D is C-R2 or N; E is C-R3 or N; G is C-R4 or N; J is C-R or N; Y is -S-, -NRe or -O-; R is a substituent attached to one nitrogen atom, wherein said substituent is lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl or arylalkyl;
R,, R2, R3, R4 and R3 are independently hydrogen, lower alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, or R1 and R2 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R3 and R4 are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring, or R4 and R, are taken together with the carbon atoms to which they are attached to form a 5 or 6 membered aromatic or heteroaromatic ring; and R6 is H or lower alkyl.
63. The intermediate of Claim 62 wherein said R group is lower alkyl.
64. The intermediate of Claim 62 wherein A is of the formula: EMI221.1 65. The intermediate of Claim 64 wherein A is of the formula: EMI221.2 66. The intermediate of Claim 65 wherein A is of the formula: EMI221.3 67. The intermediate of Claim 66 wherein said A group is of the formula: EMI221.4 68. The intermediate of Claim 67 wherein A is 2-N-methylpyridinium.
69. An oligonucleotide comprising at least 5 sequential Rp alkyl- or aryl-phosphonate linkages produced by the method of Claim 2.
70. The oligonucleotide of Claim 69 which comprises 8-200 sequential Rp alkyl- or aryl-phosphonate linkages.
71. The oligonucleotide of Claim 69 which comprises 10-200 sequential Rp alkyl- or arylphosphonate linkages.
72. The oligonucleotide of Claim 69 which comprises 12-200 sequential Rp alkyl- or arylphosphonate linkages.
73. The oligonucleotide of Claim 71 or 72 wherein 85% to 100% of said linkages are Rp alkyl- or aryl-phosphonate linkages.
74. The oligonucleotide of Claim 69 which further comprises 1-50 nucleotides joined by -O-PO2-Olinkages.
75. The oligonucleotide of Claim 69 wherein M is lower alkyl or aryl.
76. The oligonucleotide of Claim 75 wherein M is lower alkyl.
77. The oligonucleotide of Claim 76 wherein M is methyl.
78. The oligonucleotide of Claim 69 wherein each B is independently a purine or a pyrimidine which can have 1-2 substituents selected from the group consisting of lower alkyl, amino, oxo, hydroxy, lower alkoxy or lower alkylamino.
79. The oligonucleotide of Claim 78 wherein each B is independently a guanine, adenine, thymine, cytosine or uracil.
80. The oligonucleotide of Claim 69 wherein Y1 or Y2 are independently hydroqen or phosphate.
81. The oligonucleotide of Claim 69 wherein X is hydroxy or V, and V3 is hydrogen or O-Y3 wherein Y, is lower alkyl.
82. The oligonucleotide of Claim 69 which further comprises an agent to facilitate cellular delivery.
83. The oligonucleotide of Claim 82 wherein said agent is a non-polar group, steroid, hormone, polycation, protein carrier, or viral or bacterial protein capable of cell membrane penetration.
84. The oligonucleotide of Claim 69 wherein said oligonucleotide further comprises a drug or a drug analog.
85. The oligonucleotide of Claim 69 wherein said oligonucleotide further comprises a reporter molecule.
86. A compartmentalized kit for detection or diagnosis of a target nucleic acid, comprising at least one first container adapted to contain any one of the oligonucleotides of Claim 69 or 85.
87. A compartmentalized kit for isolation of a template nucleic acid, comprising at least one first Container adapted to contain the oligonucleotide of Claim 69, wherein said oligonucleotide is complementary to a target contained within said template.
88. The kit of Claim 87 wherein said template is poly (A)' mRNA.
89. The kit of Claim 88 wherein said each B group on said oligonucleotide is thymine or uracil.
90. A method of regulating biosynthesis of a DNA, an RNA or a protein which comprises administering to a patient a pharmaceutically effective amount of at least one oligonucleotide of Claim 69 with a nucleic acid template for said DNA, said RNA or said protein.
91. The method of Claim 90 wherein said biosynthesis comprises at least one of DNA replication, DNA reverse transcription, RNA transcription, RNA splicing, RNA polyadenylation, RNA translocation and protein translation.
92. The method of Claim 91 wherein said template for said DNA replication is an RNA template or a DNA template.
93. The method of Claim 92 wherein said target of said oligonucleotide for regulating said DNA replication is an origin of replication or a primer binding site.
94. The method of Claim 91 wherein said target of said oligonucleotide for regulating said DNA reverse transcription is a primer binding site, a site in a retroviral genome, or a site in an mRNA.
95. The method of Claim 91 wherein said target of said oligonucleotide for regulating said RNA transcription is a promoter, a repressor binding site, an operator, an enhancer, a transcription regulatory element or a site in a mRNA encoding region.
96. The method of Claim 91 wherein said target of said oligonucleotide for regulating said RNA splicing is at least one of a 5' splice junction, an intron branch point or a 3' splice junction.
97. The method of Claim 91 wherein said target of said oligonucleotide for regulating said RNA polyadenylation is a polyadenylation site.
98. The method of Claim 91 wherein said target of said oligonucleotide for regulating said RNA translocation is a poly(A) tail.
99. The method of Claim 91 wherein said template for said protein translation is an mRNA template.
100. The method of Claim 99 wherein said target of said template is a ribosome binding site, a 5' mRNA cap an initiation codon, a site between a 5' mRNA cap site and an initiation codon, or a site in a protein coding region.
101. The method of Claim 90 wherein said template is a viral DNA or RNA template.
102. The method of Claim 90 wherein said template has a nucleotide sequence comprising any one of SEQ ID NO:1 to SEQ ID NO:93.
103. A pharmaceutical composition for regulating biosynthesis of a nucleic acid or protein comprising a pharmaceutically effective amount of the oligonucleotide of Claim 69 and a pharmaceutically acceptable carrier.
104. A complex formed between the oligonucleotide of Claim 69 and a target nucleic acid.
PCT/US1993/006277 1992-06-30 1993-06-30 Pentavalent synthesis of oligonucleotides containing stereospecific alkylphosphonates and arylphosphonates WO1994000473A2 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0653438A2 (en) * 1993-08-06 1995-05-17 Takeda Chemical Industries, Ltd. Oligonucleotide compounds, their production and use
US5703223A (en) * 1994-09-02 1997-12-30 Thomas Jefferson University Solid phase synthesis of oligonucleotides with stereospecific substituted phosphonate linkages by pentavalent grignard coupling
US6486313B1 (en) 1999-02-18 2002-11-26 Isis Pharmaceuticals, Inc. Oligonucleotides having alkylphosphonate linkages and methods for their preparation
US7256179B2 (en) 2001-05-16 2007-08-14 Migenix, Inc. Nucleic acid-based compounds and methods of use thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1337639C (en) * 1989-08-01 1995-11-28 Joseph Eugene Celebuski Dna probe assay using neutrally charged probe strands
US5212295A (en) * 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US5512668A (en) * 1991-03-06 1996-04-30 Polish Academy Of Sciences Solid phase oligonucleotide synthesis using phospholane intermediates

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0653438A2 (en) * 1993-08-06 1995-05-17 Takeda Chemical Industries, Ltd. Oligonucleotide compounds, their production and use
EP0653438A3 (en) * 1993-08-06 1995-10-18 Takeda Chemical Industries Ltd Oligonucleotide compounds, their production and use.
US5703223A (en) * 1994-09-02 1997-12-30 Thomas Jefferson University Solid phase synthesis of oligonucleotides with stereospecific substituted phosphonate linkages by pentavalent grignard coupling
US6486313B1 (en) 1999-02-18 2002-11-26 Isis Pharmaceuticals, Inc. Oligonucleotides having alkylphosphonate linkages and methods for their preparation
US7256179B2 (en) 2001-05-16 2007-08-14 Migenix, Inc. Nucleic acid-based compounds and methods of use thereof
US7709449B2 (en) 2001-05-16 2010-05-04 Migenix, Inc. Nucleic acid-based compounds and methods of use thereof

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