Antisense oligonucleotides targeting cooperating oncogenes

Therapeutic combinations of two or more antisense oligonucleotides are provided. At least one first antisense oligonucleotide specific for a cytoplasmic oncogene or proto-oncogene and at least one second antisense oligonucleotide specific for a nuclear oncogene or proto-oncogene are combined for treatment of a neoplastic disease. The first antisense oligonucleotide may be specific for, e.g., a ras or raf gene, or an oncogene which codes for a protein tyrosine kinase. The nuclear gene-targeting antisense oligonucleotide preferably may be specific for a nuclear oncogene or proto-oncogene which encodes a transcriptional factor. The combined oligonucleotides have enhanced activity against neoplastic disease.

FIELD OF THE INVENTION 
The invention relates to antisense oligonucleotides, in particular to 
antisense oligonucleotides to oncogenes, and the use of such 
oligonucleotides to inhibit proliferation of neoplastic cells. 
BACKGROUND OF THE INVENTION 
Proto-oncogenes are normal cellular genes the alteration of which engenders 
a transforming allele or "oncogene" Damage to one or more proto-oncogenes 
has with some consistency been found in a variety of human malignancies, 
causing changes in gene expression or in the gene product itself. Some of 
the more consistent correlations between disease occurrence and 
alterations in proto-oncogene expression or gene product include the 
following. The list is representative, not exhaustive. 
______________________________________ 
Proto-Oncogenes and Human Tumors 
Proto- 
Oncogene Neoplasm(s) Lesion 
______________________________________ 
abl Chronic myelogenous leuke- 
Transloca- 
mia; lymphoma tion 
erbB-1 Squamous cell and lung car- 
Amplifica- 
cinoma; astrocytoma; glio- 
tion 
blastoma; leukemia 
erbB-2 Adenocarcinoma of breast, 
Amplifica- 
ovary and stomach tion 
fos osteoblastoma Overexpres- 
sion 
gip Carcinoma of ovary and ad- 
Point muta- 
renal gland tions 
gsp Adenoma of pituitary gland; 
Point muta- 
carcinoma of thyroid 
tions 
kit leukemia and lymphoma 
myc Burkitt's lymphoma; leuke- 
Transloca- 
mia; carcinoma of lung, 
tion 
breast and cervix; myeloma; 
Amplifica- 
neuropithelioma tion 
myb leukemia, lymphoma, mela- 
noma, colorectal carcinoma; 
neuroectodermal tumors 
L-myc Carcinoma of lung Amplifica- 
tion 
N-myc Neuroectodermal tumors 
Amplifica- 
(neuroblastoma and neuroe- 
tion 
pithelioma); small cell 
carcinoma of lung 
neu breast and ovarian carcino- 
Amplifica- 
ma tion 
H-ras Carcinoma of colon, lung, 
point muta- 
and/or prostate, bladder, breast, 
tions 
K-ras thyroid and pancreas; mela- 
noma; acute myelogenous and 
lymphoblastic leukemia; 
carcinoma of thyroid 
N-ras Carcinoma of genitourinary 
Point muta- 
tract and thyroid; melano- 
tions 
ma; leukemia 
ret Carcinoma of thyroid 
Rearrange- 
ment 
ros Astrocytoma ? 
K-sam Carcinoma of stomach 
Amplifica- 
tion 
sis Astrocytoma ? 
src Carcinoma of colon ? 
trk Carcinoma of thyroid 
Rearrange- 
ment 
______________________________________ 
As may be appreciated from the above table, a large number and variety of 
human tumors contain consistent point mutations in ras proto-oncogenes. 
Chromosomal translocations also contribute to tumorigenesis by activating 
proto-oncogenes to oncogenes, e.g., the translocation of c-abl to the BCR 
locus to form the hybrid oncogene bcr-abl which has been correlated with 
the occurrence of Philadelphia chromosome-positive leukemias. Other tumors 
carry abnormally amplified domains of DNA that can include proto-oncogenes 
and magnify their expression (Alitalo & Schwab, Adv. Cancer Res. 47, 
235-282, 1986). The potential of proto-oncogenes to participate in 
tumorigenesis arises from the fact that their protein products are relays 
in the biochemical circuitry that governs the phenotype of vertebrate 
cells (Bishop, Cell 64, 235-248, 1991). 
The three biochemical mechanisms by which proto-oncogenes act were recently 
reviewed by Bishop, id. The first mechanism is by phosphorylation of 
proteins at serine, threonine or tyrosine residues. The immediate role of 
the proto-oncogene product may be induction of the phosphorylation (as 
with some growth factors) or catalysis itself (as with the receptors for 
some growth factors). The second mechanism of proto-oncogene action is 
transmission of signals by GTPases (Bourne et al., Nature, 348, 125-131, 
1990. The ras family of oncogenes encode a variety of GTPase. Moreover, at 
least some heterotrimeric G proteins can also transform cells when 
suitably mutant in their .alpha. subunits. The corresponding 
proto-oncogenes are known as gsp (stimulatory G proteins) and gip 
(inhibitory G proteins). The third mechanism of proto-oncogene action 
consists of control of transcription from DNA. A variety of transcription 
factors, discussed below, are encoded by proto-oncogenes. 
Oncogenes/proto-oncogenes are broadly subdivided into two major groups: 
nuclear and cytoplasmic. This distinction is of course based upon on the 
cellular location of the encoded proteins and/or their place of action, 
but has also acquired a broader meaning in relationship to the model of 
tumorigenic conversion of primary embryo fibroblasts that is based on the 
cooperation between the cytoplasmic oncogene c-ras and the nuclear 
oncogene c-myc (Land et al., Nature 304, 602-606, 1983). 
The proto-oncogenes which encode proteins localized in the nucleus 
participate in the regulation of the proliferation of mammalian cells. 
They are believed to be directly involved in the regulation of gene 
expression that leads to cell proliferation, division, and 
differentiation. Many of these proteins are able to bind DNA. Studies have 
shown that transient expression of nuclear protein-encoding 
proto-oncogenes is required for cells to traverse specific points in the 
cell cycle. 
Nuclear proto-oncogenes which comprise transcription factors include, for 
example, erbA, evi-1, gli-1, maf, lyl-1, ets-1, ets-2, fos, jun, myb, myc, 
rel, vav, ski, and spi-1. The indicated genes may in some cases comprise a 
group of variants identified under a common name. For example, the jun 
family includes at least three distinct genes--c-jun, c-jun-B and c-jun-D. 
Antisense oligonucleotides hybridizable to the relevant mRNA may be 
prepared, based upon reported cDNA sequences. The following is a partial 
listing of references reporting DNAs for the indicated proto-oncogenes 
and/or reports of inhibition of cell proliferation with antisense 
oligonucleotides specific for the targeted genes: 
c-myc--Gazin et al., EMBO J. 3:383-387, 1984 (cDNA); Wickstrom et al., 
Proc. Natl. Acad. Sci. USA85, 1028-1032 (1988); Loke et al., Clin. Res. 
36(3), 443A (1988); Holt et al., Cell. Biol. 8, 963-973 (1988); Yokoyama 
et al., Proc. Natl. Acad. Sci. USA 84, 7363-7367 (1987); Harel-Bellan et 
al., J. Immunol. 140, 2431-2435 (1988) (inhibition of growth of leukemic 
cells by antisense oligonucleotides); 
L-myc--Kaye et al., Mol. Cel.Biol. 8:186-195, 1988 (cDNA); 
N-myc--Ibson & Rabbitts, Oncogene2:399-402, 1988 (cDNA); 
c-jun--Hattori et al., Proc. Natl. Acad. Sci. USA 85:9148-9152, 1988 
(cDNA); 
c-fos--van Straaten et al., Proc. Natl. Acad. Sci. USA 80:3183-3187, 1983 
(cDNA); Nercola et al., Biochem. Biophys. Res. Comm. 147, 288-294 (1987); 
Groger et al., Proc. Am. Assoc. Caner Res. 29, 439 (1988) (inhibition of 
growth of transformed cells by antisense oligonucleotide); 
c-myb--Majello et al., Proc. Natl. Acad. Sci. USA 83:9636-9640, 1986 
(cDNA); 
B-myb--Nomura et al., Nucl. Acid Res. 16:11075-11090, 1988 (cDNA); 
cyclin D1 (also known as bcl-1)--Xiong et al., Cell 65. 601-699, 1991 
(cDNA). 
The following is a partial listing of nuclear oncogenes, formed by 
translocation events. Each citation reports the relevant cDNA sequence. 
The oncogenes are established or purported transcriptional factors. 
PML/RAR.alpha.--Kakizura et al., Cell, 66:663-674, 1991; 
DEK/CAN--von Linden et al., Mol. Cell. Biol., 12: 1687-1697, 1992; 
AML1/MTG8--Miyoshi et al., EMBO J. 12:2715-2721, 1993; 
E2A/prl--Nouse et al., Cell, 60: 535-545, 1990; Kamps et al., Cell, 60: 
547-555 1990; 
ALL-1/AF-4--Gu et al., Cell 71: 701-708, 1992. 
Nucleotide sequences of various other oncogenes/-proto-oncogenes are 
disclosed in International Patent Application WO 94/00473, the entire 
disclosure of which is incorporated herein by reference. 
Certain of the nuclear oncogenes/proto-oncogenes code for proteins with 
DNA-binding activity. The nuclear proto-oncogenes comprising the jun 
family (c-jun, jun-B and jun-D), c-myb, the proto-oncogenes comprising the 
c-ets family (c-ets-1 and c-ets-2), and c-myc, recognize specific 
nucleotide core sequences. 
The proto-oncogene c-jun, which encodes the transcription activator protein 
AP-1, has been shown to bind to a specific heptameric consensus sequence 
TGACTCA (Bohmann et al., Science 238, 1386-1392, 1987; Angel et al., 
Nature 332, 166-1711, 1988). Jun-B has extensive amino acid sequence 
similarity to c-jun in the region that encodes the DNA-binding domain and, 
as expected, binds to the same DNA consensus sequence (Nakageppu et al., 
Cell 5, 907-915, 1988); jun-D, the third number of this family, behaves 
similarly (Nakageppu et al., 1988). The proteins encoded by c-ets-1 and 
c-ets-2 genes bind to a 14-base pair sequence from the oncogene-responsive 
domain of the polyoma enhancer, in which the ACTTCCT appears to be the 
essential portion of the domain (Wasylyk et al., Nature 346,191-193, 
1990). The DNA-binding activity also appears to be localized at the 
carboxy-terminal region of the c-ets-encoded protein (Wasylyk et al., 
1990). 
c-Myb encodes a protein that binds to a specific core sequence (pyAACG/TG) 
(Biedenkapp et al., Nature bv3351, 835-837, 1988). The DNA-binding 
activity of c-myb, unlike that of the c-jun and c-ets gene families, is 
localized in the amino-terminal portion of the protein (Klempnauer and 
Sippel, 1987). The c-fos product has been shown to bind nonspecifically to 
DNA (Renz et al., Nucleic Acid Res. 15, 277-292, 1987); however, when 
complexed to c-jun encoded proteins, the c-fos product has a marked 
stimulatory effect on their binding to AP-1 sites (Chiu et al., Cell 59, 
979-986, 1988; Halazonetis et al., Cell 55, 917-924, 1988). The human 
c-myc protein is a DNA-binding protein exhibiting a high nonspecific 
activity for double-stranded DNA (Persson et al., Science 225, 718-721, 
1984; Watt et al., Mol. Cell. Biol. 5, 448-456, 1985). Recently, it has 
been shown that a purified carboxyl terminal fragment of human c-myc binds 
in vitro in a sequence-specific manner to the sequence CACGTG (Blackwell 
et al., Science 250, 1149-1151, 1990). 
c-Myb up-regulates the expression of reporter genes linked to myb-binding 
sites (Weston and Bishop, Cell 58, 85-93, 1989; Sakura et al., Proc. Natl. 
Acad. Sci. U.S.A. 86, 5758-5762, 1989) and the cellular gene MIM-1, whose 
expression is promyelocytic-specific, appears to be directly regulated by 
c-myb and contains myb-binding sites in the 5' flanking region (Ness et 
al., Cell 59, 1115-1125, 1989). The MYB protein binds to DNA by virtue of 
an N-terminal region that contains a triple repeat. 
The CD34 antigen defines a subset of hematopoietic progenitor cells with 
self-renewal capacity and the ability to reconstitute hematopoiesis in 
irradiated primates and marrow-ablated humans. The c-myb gene plays a 
fundamental role in hematopoiesis, most likely through its transcriptional 
regulator function. The MYB protein transactivates the CD34 promotor via 
specific interaction with multiple MYB binding sites in the 5' flanking 
region of the CD34 antigen gene and induces expression of the endogenous 
CD34 mRNA in rodent fibroblasts, directly demonstrating that c-myb 
regulates the expression of the CD34 antigen (Melotti o et al., J. Exp. 
Med. 179, 1023-1028, 1994). 
It has been suggested that c-ets-1 and c-ets-2 transactivate the expression 
of reporter genes linked to c-ets binding sites; the c-ets binding domain 
is contiguous with the AP-1 binding site in the polyoma (Py) enhancer; 
this association generates a responsive element that is highly stimulated 
by the concomitant expression of c-jun and c-ets (Wasylyk et al., 1990). 
The c-rel gene is also a regulator of transcription. 
ErbA is another nuclear oncogene whose protein product binds nucleic acid. 
It codes for a thyroid hormone receptor, a member of the class of steroid 
hormone receptors. Upon binding its ligand, asteroid receptor activates 
expression of particular target genes by binding to its specific response 
element in a promotor or enhancer. These receptors, such as erbA, are 
therefore transcription factors that respond to binding particular 
ligands. 
Cytoplasmic oncogenes/proto-oncogenes include members of the ras and raf 
families of oncogenes, as well as various protein kinase types, most 
notably the protein tyrosine kinases. 
The ras gene family members are found expressed in human cancers more often 
than any other oncogene. Three ras genes have been characterized, 
designated c-H-ras, c-K-ras and c-N-ras. The three genes all encode 
proteins of 21,000 daltons molecular weight generally known as 
p21.sup.ras. These proteins are very homologous in amino acid sequence 
differing primarily at their C terminii. The cDNA sequences for each of 
the H-, K-and N-ras genes have been reported (Capon et al., Nature 302, 
33-37, 1983; Kahn et al., Anticancer Res. 7, 639-652, 1987; Hall & Brown, 
Nucl. Acid Res. 13, 5255-5268, 1985). 
The p21.sup.ras proteins belong to a family of signal-transducing monomeric 
proteins with GTP-binding activity and appear to play a central role in 
signal transduction pathways (Bourne et al., Nature 348:125 (1990-)). The 
IL-2, IL-3, CSF-1, GM-CSF, EGF, SCF and PDGF receptors (Satoh et al., 
Proc. Natl. Acad. Sci. USA88:3314 (1991); Duronio et al., Proc. Natl. 
Acad. Sci. USA 89:1587 (1992); Satoh et al., Proc. Natl. Acad. Sci. USA 
87:5993 (1990); Satoh et al., Proc. Natl. Acad. Sci. USA 87:7926 (1990; 
Gibbs et al., J. Biol. Chem. 265:20437 (1990)), and several oncogene 
products with constitutively enhanced tyrosine kinase activity (fms, src, 
abl, bcr-abl) (Gibbs et al., J. Biol. Chem. 265:20437 (1990); Smith et 
al., Nature 320:540 (1986); Mandanas et al., Blood 80 (Suppl.1):14a 
(1992)), activate p21.sup.ras proteins. 
The p21.sup.ras proteins bind guanine nucleotides with high affinity and 
hydrolyze GTP with low catalytic efficiency. p21.sup.ras is activated by 
the replacement of GDP by GTP, a process that is catalyzed by a guanine 
nucleotide-releasing factor. In the GTP form, p21.sup.ras proteins serve 
as signal transducers (Smith et al., Nature 320:540 (1986); Trahey and 
McCormick Science 238:542 (1987)) but are inactive in the GDP-bound form. 
In mammalian cells two proteins, p120 rasGTPase activating protein 
("rasGAP" or "p120-GAP") and NF-1, inactivate p21.sup.ras (Bollag and 
McCormick, Annu. Rev. Cell. Biol. 7:601 (1992)) by inducing a 100-fold 
increase of the intrinsically low GTPase activity of p21.sup.ras, which 
converts the active GTP-bound form to the inactive GDP-bound form by 
stimulation GTP-GDP exchange (Trahey and McCormick, Science 238:542 
(1987)). The active p21.sup.ras -GTP-bound form of p21.sup.ras is 
inactivated by an intrinsic GTPase activity that is catalyzed by the 
carboxylterminus domain of p120-GAP (Marshall et al., EMBO (Eur. Mol. 
Biol. Organ) J. 8:1105 (1989)). 
It has been shown that p21.sup.ras plays an important role in the formation 
of normal and leukemic hematopoietic colonies (Skorski et al., J. Exp. 
Med. 175:743, 1992), and that p120-GAP is an inhibitor of p21.sup.ras. A 
decrease in the GTPase activity observed in the activated ras oncogene 
product is believed to be responsible for its transforming activity 
(Seeburg et al., Nature 312:71, 1984). Thus, the binding of GTP with the 
diminished capacity to hydrolyze it would maintain the protein in a 
constitutively active state, thus sending a continuous signal to the cell 
along the mitogenic pathway. 
The raf proto-oncogene codes a protein-serine/threonine kinase. The 
activity of this enzyme is induced by direct or indirect action of diverse 
cell surface receptors, cytoplasmic protein tyrosine kinases, and ras 
(Morrison et al., Proc. Natl. Acad. Sci. USA 85, 8855-8859, 1988; Morrison 
et al., Cell 58, 649-657, 1988). The cDNA sequence for the c-raf gene has 
been reported (Bonner et al., Nucl. Acid Res. 14, 1009-1015, 1986). 
The protein tyrosine kinases encompass a large diverse group of oncogenes 
and proto-oncogenes which encode proteins which catalyze the transfer of a 
phosphate residue from a nucleoside triphosphate to the side chain of a 
tyrosine residue in a protein. The transforming potential of protein 
tyrosine kinases is activated by N-terminal or C-terminal rearrangements. 
These alterations may remove down-regulating domains of the protein and 
result in the constitutive activation of what is normally a conditionally 
regulated enzyme activity. Thus, when suitably mutated (or, in some 
instances, anomalously expressed), protein tyrosine kinases themselves 
become transforming proteins, acting through unwanted phosphorylation of 
their diverse substrates. Further, protein tyrosine kinases can be 
vehicles for transformation by disturbances elsewhere in signalling 
pathways., e.g., constitutive production of growth factors that act 
through protein tyrosine kinase receptors (Aaronson & Pierce, Cancer 
Cells2, 212-214, 1990) and the effects of phosphatases, which play crucial 
roles in governing the activity of protein tyrosine kinases (Hunter, Cell 
58, 1013-1016, 1989). 
One type of tyrosine protein kinase comprises the transmembrane protein 
kinases which span the plasma membrane. They contain large extracellular 
and cytoplasmic domains. One such category comprises the EGF family of 
growth factor receptors. The receptor has intrinsic tyrosine kinase 
activity that is activated by the binding of its ligand. EGF-1 is 
expressed in breast cancers and glioblastomas. EGF.sub.2 is found 
expressed in neuroblastomas. The cDNA sequence corresponding to the former 
is reported by Helin et al., Cell 70, 337-350 (1992). 
Further examples of the tyrosine kinase growth factor receptor family 
include erbB, fms, ros, kit, met, trk and neu oncogenes. Expression of met 
has been found in gastric carcinomas. The cDNA sequence of c-kit was 
reported by Vandenbark et al., Oncogene7, 1259-1266 (1992). 
Another type of tyrosine kinases includes a large number of nonintegral 
membrane-associated protein tyrosine kinases. The protein product of 
v-src, the prototype of this family, is associated with the plasma 
membrane but does not traverse the membrane. Oncogenic p60.sup.v-src 
encoded in Rous sarcoma virus and its cellular homolog p60.sup.c-src, are 
membrane-localized phosphoproteins that possess protein tyrosine kinase 
activity. The cDNA sequence of the normal cellular homologue, the 
proto-oncogene c-src, has been reported (Braeuninger et al., Proc. Natl. 
Acad. Sci. USA 88, 10411-10415, 1991). Normal p60.sup.c-src is tightly 
regulated in its kinase activity relative to p60.sup.v-src and generally 
is not oncogenic. Mutations in p60.sup.c-src that elevate its kinase 
activity also activate its oncogenic potential. It has been suggested that 
p60.sup.v-src and p60.sup.c-src associate with complexes containing 
p120-GAP and provide a biochemical link between these kinases and 
p120-GAP/ras traduction pathways (Brott et al., Proc. Natl. Acad. Sci. USA 
88, 755-759 , 1991). 
Other members of the tyrosine kinase family include fes, abl, fgr and yes. 
All of these proto-oncogene products are homologous in their tyrosine 
kinase domains. The tyrosine kinase domains as in the growth factor 
receptor tyrosine kinase family, is responsible for catalyzing the 
transfer of phosphate groups from ATP to tyrosine residues during 
auto-phosphorylation or transphosphorylation of target molecules. 
The aberrant expression of a nonintegral membrane associated tyrosine 
kinase is best illustrated by the abl proto-oncogene, the cDNA sequence of 
which is reported by Shtivelman et al., Cell 47, 277-284 (1986). Aberrant 
expression of abl results from the c-abl gene's translocation from the 
long arm of chromosome 9 to the breakpoint cluster region (bcr) on 
chromosome 22, resulting in the formation of bcr-abl hybrid genes. The 
break occurs near the end of the long arm of chromosome 9 (band 9q34) and 
in the upper half of chromosome 22 (band 22q11). The chimeric message is 
in turn translated into a larger chimeric abl protein (210 kDa) that has 
increased tyrosine kinase activity (Konopka et al., Cell 37, 1035 (1984); 
Kloetzer et al., Virology 140, 230 (1985); Konopka et al., Proc. Natl. 
Acad. Sci. U.S.A. 82, 1810 (1985)). The 210 kDa protein is considerably 
larger than the normal human abl protein of 145 kDa, and has a very high 
tyrosine kinase activity. The cDNA sequences of the various bcr-abl 
oncogenes have been reported: Shtivelman et al., Cell 47, 277 (1986); 
Mes-Masson et al., Proc. Natl. Acad. Sci. USA 83, 9768-9772 (1986); 
Fainstein et al., Nature 330, 386-388 (1987). 
Molecular strategies are being developed to downregulate unwanted gene 
expression, including oncogene expression. One such strategy involves 
inhibiting gene expression with oligonucleotides complementary in sequence 
to ther messenger RNA of a deleterious target gene. The so-called 
"antisense" oligonucleotides have been proposed as anti-cancer agents, by 
targeting various oncogenes or proto-oncogenes. See, for example, U.S. 
Pat. No. 5,098,890 (c-myb antisense for treating hematologic neoplasms, 
including use in bone marrow purging); international Patent Application WO 
91/93260 (c-abl antisense for treating myeloproliferative disorders); 
International Patent Application W092/19252 and Ratajczak et al., Proc. 
Natl. Acad. Sci. USA 89, 1710-1714 (1992) (c-kit for inhibiting malignant 
hematopoietic cell proliferation); International Patent Application 
W092/20348 and Melani et al., Cancer Res. 51; 2897-2901 (1991) (c-myb 
antisense for inhibiting proliferation of colon cancer cells); 
international Patent Application WO93/09789 (c-myb antisense for 
inhibiting malignant melanoma cell proliferation); International Patent 
Application WO92/22303 and Szcylick et al., Science 253, 562-565 (1991) 
(bcr-abl antisense for inhibiting leukemia cell proliferation); and U.S. 
Pat. No. 5,087,617 which describes bone marrow purging and in vivo therapy 
using antisense oligonucleotides to a variety of oncogenes of 
proto-oncogenes. The entire disclosure of each of the aforementioned 
references is incorporated by reference herein. 
Growing evidence suggests that cancer arises through a multistep process 
which involves activation of proto-oncogenes and loss of function of tumor 
suppressor genes (Fearon et al., Cell 61, 759 (1991). Oncogene cooperation 
was originally demonstrated in vitro (Murray et al., Cell 33, 749 (1983); 
Thompson et al., Cell 56, 917 (1989); Stasser et al., Nature 348 (1990)) 
and subsequently validated in vivo using transgenic mouse models (Adams et 
al., Science 254, 1161 (1991)). Chronic myelogenous leukemia (CML) 
illustrates well the concept of a multistep process in human malignancies, 
because the clinical course consists of two well-defined stages, i.e., a 
relatively indolent and long lasting chronic phase, and a terminal, more 
aggressive blast crisis (Kantarjan et al., Blood 82, 691 (1993)). At the 
genetic level, the predominant abnormality of the chronic phase is the 
Philadelphia chromosome (Ph.sup.1) translocation resulting in the 
formation of the bcr-abl oncogene. 
Some studies have indicated that specific combinations of oncogenes are 
able to cooperate to induce a transformed phenotype, and that oncogene 
products which act in the nucleus cooperate best with those that act in 
the cytoplasm. These studies have been recently reviewed by Hunter, Cell 
64, 249-270 (1991). 
Despite evidence of cooperation of nuclear and cytoplasmic oncogenes in 
transformation, there is no suggestion that simultaneous inhibition of 
both oncogene types can result in enhanced antitumor effect. Moreover, 
while antisense oligonucleotides have been indicated as being useful for 
the treatment of cancer, it has not been heretofore suggested to adopt 
multiple antisense oligonucleotides specific for diverse oncogenes to 
provide enhanced antineoplastic effect. 
SUMMARY OF THE INVENTION 
According to the present invention, a composition is provided comprising at 
least one first antisense oligonucleotide specific for a cytoplasmic 
oncogene or proto-oncogene and at least one second antisense 
oligonucleotide specific for a nuclear oncogene or proto-oncogene. 
According to one preferred embodiment of the invention, the first 
antisense oligonucleotide is specific for a ras or raf gene. According to 
another preferred embodiment, the first antisense oligonucleotide is 
specific for a gene which codes for a protein tyrosine kinase. 
The second antisense oligonucleotide is, according to one aspect of the 
invention, specific for a nuclear oncogene or proto-oncogene which encodes 
a transcriptional factor. 
According to one embodiment, each of the first and second oligonucleotides 
has a nucleotide sequence capable of forming a stable duplex with a 
portion of an mRNA transcript of a cytoplasmic oncogene/proto-oncogene, or 
with an mRNA transcript of a nuclear/oncogene or proto-oncogene, 
respectively. 
Each oligonucleotide is generally at least an 8-mer oligonucleotide, that 
is, the oligonucleotide is an oligomer containing at least 8 nucleotide 
residues, more preferably at least about 12 nucleotides. The preferred 
maximum size of the oligonucleotide is about 60 nucleotides, more 
preferably about 50 nucleotides, most preferably about 40 nucleotides. The 
oligomer is preferably an oligodeoxynucleotide. While oligonucleotides 
smaller than 12-mers may be utilized, they are statistically more likely 
to hybridize with non-targeted sequences, and for this reason may be less 
specific. In addition, a single mismatch may destabilize the hybrid. While 
oligonucleotides larger than 40-mers may be utilized, uptake may become 
somewhat more difficult without specialized vehicles or oligonucleotide 
carriers. Moreover, partial matching of long sequences may lead to 
non-specific hybridization, and non-specific effects. Most preferably, the 
oligonucleotide is a 15- to 40-mer oligodeoxynucleotide, more 
advantageously an 18- to 30-mer. 
While in principle oligonucleotides having a sequence complementary to any 
region of the target mRNA find utility in the present invention, preferred 
are oligonucleotides capable of forming a stable duplex with a portion of 
the transcript lying within about 50 nucleotides (preferably within about 
40 nucleotides) upstream (the 5' direction), or about 50 (preferably 40) 
nucleotides downstream (the 3' direction) from the translation initiation 
codon of the target mRNA. Also preferred are oligonucleotides which are 
capable of forming a stable duplex with a portion of the target mRNA 
transcript including the translation initiation codon. 
The invention is also a method for inhibiting the proliferation of 
neoplastic cells, comprising contacting such cells with a 
proliferation-inhibiting effective amount of at least one first antisense 
oligonucleotide specific for a cytoplasmic oncogene/proto-oncogene and at 
least one second antisense oligonucleotide specific for a nuclear 
oncogene/proto-oncogene. 
The invention also provides a method for treating neoplastic disease 
comprising administering to a patient in need of such treatment an 
effective amount of at least one first antisense oligonucleotide specific 
for a cytoplasmic oncogene/proto-oncogene and at least one second 
antisense oligonucleotide specific for a nuclear oncogene/proto-oncogene. 
In yet another embodiment, the invention is a method for purging bone 
marrow of neoplastic cells such as leukemic cells, or solid tumor cells 
which have metastasized to the bone marrow. Bone marrow cells aspirated 
from an individual afflicted with a neoplastic disease are treated with an 
effective amount of at least one first antisense oligonucleotide specific 
for a cytoplasmic oncogene/proto-oncogene and at least one second 
antisense oligonucleotide specific for a nuclear oncogene/proto-oncogene. 
The thus-treated cells are then returned to the body of the afflicted 
individual. 
According to another embodiment, the invention is an 
artificially-constructed gene comprising a first promotor segment and a 
segment containing DNA of a cytoplasmic oncogene or proto-oncogene DNA, 
and a second promotor segment and a segment containing DNA of a nuclear 
oncogene or proto-oncogene. The oncogene/-proto-oncogene DNA-containing 
segments are in inverted orientation such that transcription of the 
artificially-constructed gene produces RNA complementary to an mRNA 
transcript of the cytoplasmic oncogene or proto-oncogene and RNA 
complementary to an mRNA transcript of the nuclear oncogene or 
proto-oncogene. The gene may be introduced into target cells to inhibit 
the proliferation of those cells. The artificially-constructed gene may be 
introduced into the target cells by, for example, transfection, 
transduction with a viral vector, or microinjection. 
Definitions 
By "proto-oncogene" is meant a normal, cellular human gene, the alteration 
of which gives rise to a transforming allele or "oncogene". 
By "oncogene" is meant a human gene in a host cell which is responsible, in 
whole or in part, for the neoplastic transformation of the host cell. 
By "cytoplasmic oncogene" or "cytoplasmic proto-oncogene" is meant an 
oncogene/proto-oncogene the encoded protein of which is localized 
primarily in the cell cytoplasm. 
By "nuclear oncogene" or "nuclear proto-oncogene" is meant an oncogene or 
proto-oncogene the encoded protein of which is localized primarily in the 
cell nucleus. 
By "protein tyrosine kinase" is meant an enzyme which catalyzes the 
transfer of a phosphate residue form a nucleoside triphosphate to the side 
chain of a tyrosine amino acid residue in a protein. 
By "transcriptional factor" is meant the product of a nuclear oncogene or 
proto-oncogene which binds a target DNA segment to activate transcription 
of another gene. 
An "antisense oligonucleotide specific for" a targeted oncogene or 
proto-oncogene is meant an oligonucleotide having a sequence (i) capable 
of forming a stable triplex with a portion of the targeted oncogene, or 
(ii) capable of forming a stable duplex with a portion of an mRNA 
transcript of the targeted oncogene. 
The term "oligonucleotide" as used herein includes linear oligomers of 
natural or modified monomers or linkages, including deoxyribonucleosides, 
ribonucleosides, .alpha.-anomeric forms thereof, polyamide nucleic acids, 
and the like, capable of specifically binding to a target polynucleotide 
by way of a regular pattern of monomer-to-monomer interactions, such as 
Watson-Crick type of base pairing, Hoogsteen or reverse Hoogsteen types of 
base pairing, or the like. Usually, monomers are linked by phosphodiester 
bonds or analogs thereof to form oligonucleotides ranging in size from a 
few monomeric units, e.g., 3-4, to several hundreds of monomeric units. 
Analogs of phosphodiester linkages include: phosphorothioate, 
phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, 
phosphoroanilothioate, phosphoranilidate, phosphoramidate, and the like, 
as more fully described below. As used herein, "nucleoside" includes the 
natural nucleosides, including 2'-deoxy and 2'-hydroxyl forms, e.g., as 
described in Kornberg and Baker, DNA Replication, 2nd Ed. (Freeman, San 
Francisco, 1992). "Analogs" in reference to nucleosides includes synthetic 
nucleosides having modified base moieties and/or modified sugar moieties, 
e.g., described generally by Scheit, Nucleotide Analogs (John Wiley, New 
York, 1980). Such analogs include synthetic nucleosides designed to 
enhance binding properties, e.g., duplex or triplex stability, 
specificity, or the like. 
The term "phosphorothioate oligonucleotide" means an oligonucleotide 
wherein one or more of the internucleotide linkages is a phosphorothioate 
group, 
##STR1## 
as opposed to the phosphodiester group 
##STR2## 
which is characteristic of unmodified oligonucleotides. 
By "alkylphosphonate oligonucleoside" is meant an oligonucleotide wherein 
one or more of the internucleotide linkages is an alkylphosphonate group, 
##STR3## 
wherein R is an alkyl group, preferably methyl or ethyl. 
The term "modified oligonucleotide" is meant an oligonucleotide containing 
one or more modified monomers and/or linkages to enhance the stability or 
uptake of the oligonucleotide. 
"Stability" in reference to duplex or triplex formation roughly means how 
tightly an antisense oligonucleotide binds to its intended target 
sequence; more precisely, it means the free energy of formation of the 
duplex or triplex under physiological conditions. Melting temperature 
under a standard set of conditions, e.g., as described below, is a 
convenient measure of duplex and/or triplex stability. Preferably, 
antisense oligonucleotides of the invention are selected that have melting 
temperatures of at least 50.degree. C. under the standard conditions set 
forth below; thus, under physiological conditions and the preferred 
concentrations, duplex or triplex formation will be substantially favored 
over the state in which the antisense oligonucleotide and its target are 
dissociated. It is understood that a stable duplex or triplex may in some 
embodiments include mismatches between base pairs and/or among base 
triplets in the case of triplexes. Preferably, antisense oligonucleotides 
of the invention form perfectly matched duplexes and/or triplexes with 
their target polynucleotides. 
The term "downstream" when used in reference to a direction along a 
nucleotide sequence means the direction. Similarly, the term "upstream" 
means the 3'.fwdarw.5' direction. 
The term "targeted oncogene (or proto-oncogene) mRNA transcript" means the 
presently known mRNA transcript of the targeted oncogene (or 
proto-oncogene) and all variations thereof, or any further transcripts 
which may be elucidated. 
The term "S!ODN" means phosphorothioate oligodeoxynucleotide.

DETAILED DESCRIPTION OF THE INVENTION 
According to the present invention, at least one antisense oligonucleotide 
specific for at least one cytoplasmic oncogene or proto-oncogene, is 
administered to a patient with at least one antisense oligonucleotide 
specific for a nuclear oncogene or proto-oncogene, preferably an antisense 
oligonucleotide specific for a transcriptional factor. The two antisense 
oligonucleotides may be administered by any of the routes described 
hereinafter. While it is preferred that the two agents be administered 
simultaneously, such as in the form of a single pharmaceutical 
composition, the two agents may be administered separately, in sequence. 
While it is presently preferred that both oligonucleotides are 
administered through the same route, they may be administered through 
different routes. 
The antisense oligonuclerotide pair may comprise, for example, antisense 
oligonucleotides specific to any of the nuclear and cytoplasmic 
oncogenes/proto-oncogenes disclosed herein. Thus, for example, the 
targeted cytoplasmic gene may comprise c-erbB, c-fms, c-ras, c-kit, c-met, 
c-trk, c-neu, c-src, c-fes, c-abl, bcr-abl, c-fgr, or c-yes. Combinations 
of antisense oligonucleotides specific for the same or different 
cytoplasmic genes may be utilized. The targeted nuclear gene may comprise, 
for example, c-erbA, c-evi-1, c-gli-1, c-maf, c-lyl-1, c-ets, c-fos, 
c-jun, c-myb, c-myc, b-myb, N-myc, L-myc, c-rel, c-vav, c-ski, c-spi or 
cyclin D1. Combinations of antisense oligonucleotides specific for the 
same or different nuclear genes may be utilized. It should be appreciated 
that in the aforesaid listings, the indicated gene may comprise a group of 
variants identified under a common name, e.g., "c-jun" includes the 
specific genes c-jun, c-jun-B and c-jun-D. 
According to one preferred embodiment of the invention, the therapeutic 
combination comprises one or more antisense oligonucleotides specific for 
a ras gene in combination with one or more antisense oligonucleotides 
specific for a myc gene. By "ras" is meant any of the family of ras genes, 
such as N-ras, c-ras or H-ras. Similarly, by "myc" is meant any of the 
family of myc genes, such as c-myc, L-myc and N-myc, and by "jun" is meant 
any of the family of jun genes such as c-jun, c-junB and c-junD. The 
protein tyrosine kinases encoded by src, kit, bcr-abl, fms, and the 
receptor type kinases (insulin, IGF-1, EGF, etc.), all converge on RAS, 
which in turn binds RAF, which in turn activates MAP-kinase, which in turn 
phosphorylates nuclear effectors such as myc. The RAS protein also 
activates jun, which is in turn a regulator of all growth. A combination 
of antisense oligonucleotides specific for ras and myc genes is thus 
believed particularly useful against neoplastic disorders, e.g., CML, 
characterized by activated (i.e., oncogenic) protein tyrosine kinases. The 
combination may be used also, for example, for the treatment of epithelial 
tumors, such as tumors of the breast, prostate, colon, pancrease and 
gastric tract. 
According to another preferred embodiment of the invention, the therapeutic 
combination comprises one or more antisense oligonucleotides specific for 
a raf oncogene in combination with one or more antisense oligonucleotides 
specific for a jun gene. The combination is used for the treatment of the 
aforesaid tumors of epithelial origin. In yet another preferred 
embodiment; ras or raf antisense oligonucleotides are combined with myc 
antisense oligonucleotides, particularly c-myc, for the treatment of 
leukemia, particularly Ph.sup.1 -positive leukemias. Other combinations 
may be adopted for treatment of yet other neoplastic diseases. 
The following oncogene or proto-oncogene nucleotide sequences are set forth 
herein: 
______________________________________ 
c-jun SEQ ID NO:13 
c-H-ras SEQ ID NO:14 
c-K-ras SEQ ID NO:15 
c-N-ras SEQ ID NO:16 
c-raf SEQ ID NO:17 
EGF-1 SEQ ID NO:18 
c-fms SEQ ID NO:19 
c-ros SEQ ID NO:20 
c-kit SEQ ID NO:21 
c-met SEQ ID NO:22 
c-trk SEQ ID NO:23 
c-src1 SEQ ID NO:24 
c-src2 SEQ ID NO:25 
c-src3 SEQ ID NO:26 
c-src4 SEQ ID NO:27 
c-src5 SEQ ID NO:28 
c-src6 SEQ ID NO:29 
c-src7 SEQ ID NO:30 
c-src8 SEQ ID NO:31 
c-src9 SEQ ID NO:32 
c-src10 SEQ ID NO:33 
c-src11 SEQ ID NO:34 
c-abl SEQ ID NO:35 
bcr-abl SEQ ID NO:36 (b2a2 genotype) 
bcr-abl SEQ ID NO:37 (b3a2 genotype) 
bcr-abl SEQ ID NO:38 (b1a2 genotype) 
c-fgr SEQ ID NO:39 
c-yes SEQ ID NO:40 
c-myc SEQ ID NO:41 
L-myc SEQ ID NO:42 
c-ets SEQ ID NO:43 
c-fos SEQ ID NO:44 
c-myb SEQ ID NO:45 
B-myb SEQ ID NO:46 
c-rel SEQ ID NO:47 
c-vav SEQ ID NO:48 
c-ski SEQ ID NO:49 
c-spi SEQ ID NO:50 
cyclin D1 SEQ ID NO:51 
PML/RAR.alpha. 
SEQ ID NO:52 
AML1/MTG8 SEQ ID NO:53 
E2A/prl SEQ ID NO:54 
ALL-1/AF-4 SEQ ID NO:55. 
______________________________________ 
In the practice of the present invention, target oncogene/proto-oncogene 
polynucleotides may be single-stranded or double-stranded DNA or RNA; 
however, single-stranded DNA or RNA targets are preferred. It is 
understood that the target to which the oncogene/-proto-oncogene antisense 
oligonucleotides of the invention are directed include allelic forms of 
the targeted gene and mRNA. There is substantial guidance in the 
literature for selecting particular sequences for antisense 
oligonucleotides given a knowledge of the sequence of the target 
polynucleotide, e.g., Peyman and Ulmann, Chemical Reviews, 90:543-584, 
1990; Crooke, Ann. Rev. Pharmacal. Toxicol., 32:329-376 (1992); and 
Zamecnik and Stephenson, Proc. Natl. Acad. Sci., 75:280-284 (1974). 
Preferably, the sequences of antisense compounds are selected such that 
the G-C content is at least 60%. Preferred mRNA targets include the 5' cap 
site, tRNA primer binding site, the initiation codon site, the mRNA donor 
splice site, and the mRNA acceptor splice site, e.g., Goodchild et al., 
U.S. Pat. No. 4,806,463. 
Where the target polynucleotide comprises an mRNA transcript, 
oligonucleotides complementary to and hybridizable with any portion of the 
transcript are, in principle, effective for inhibiting translation, and 
capable of inducing the effects herein described. It is believed that 
translation is most effectively inhibited by blocking the mRNA at a site 
at or near the initiation codon. Thus, oligonucleotides complementary to 
the 5'-region of mRNA transcript are preferred. Oligonucleotides 
complementary to the oncogene/proto-oncogene mRNA, including the 
initiation codon (the first codon at the 5' end of the translated portion 
of the transcript), or codons adjacent the initiation codon, are 
preferred. 
While antisense oligomers complementary to the 5'-region of the 
oncogene/proto-oncogene mRNA transcripts are preferred, particularly the 
region including the initiation codon, it should be appreciated that 
useful antisense oligomers are not limited to those oligomers 
complementary to the sequences found in the translated portion of the mRNA 
transcript, but also includes oligomers complementary to nucleotide 
sequences contained in, or extending into, the 5'- and 3'-untranslated 
regions. 
Antisense oligonucleotides of the invention may comprise any polymeric 
compound capable of specifically binding to a target polynucleotide by way 
of a regular pattern of monomer-to-nucleoside interactions, such as 
Watson-Crick type of base pairing, Hoogsteen or reverse Hoogsteen types of 
base pairing, or the like. 
Antisense compounds of the invention may also contain pendent groups or 
moieties, either as part of or separate from the basic repeat unit of the 
polymer, to enhance specificity, nuclease resistance, delivery, or other 
property related to efficacy, e.g., cholesterol moieties, duplex 
intercalators such as acridine, poly-L-lysine, "end-capping" with one or 
more nuclease-resistant linkage groups such as phosphorothioate, and the 
like. 
For example, it is known that enhanced lipid solubility and/or resistance 
to nuclease digestion results by substituting an alkyl group or alkoxy 
group for a phosphate oxygen in the internucleotide phosphodiester linkage 
to form an alkylphosphonate oligonucleoside or alkylphosphotriester 
oligonucleotide. Non-ionic oligonucleotides such as these are 
characterized by increased resistance to nuclease hydrolysis and/or 
increased cellular uptake, while retaining the ability to form stable 
complexes with complementary nucleic acid sequences. The 
alkylphosphonates, in particular, are stable to nuclease cleavage and 
soluble in lipid. The preparation of alkylphosphonate oligonucleosides is 
disclosed in Tso et al., U.S. Pat. No. 4,469,863. 
Preferably, nuclease resistance is conferred on the antisense compounds of 
the invention by providing nuclease-resistant internucleosidic linkages. 
Many such linkages are known in the art, e.g., phosphorothioate: Zon and 
Geiser, Anti-Cancer Drug Design, 6:539-568 (1991); Stec et al., U.S. Pat. 
No. 5,151,510; Hirschbein, U.S. Pat. No. 5,166,387; Bergot, U.S. Pat. No. 
5,183,885; phosphorodithioates: Marshall et al., Science, 259:1564-1570 
(1993); Caruthers and Nielsen, International application PCT/US89/02293; 
phosphoramidates, e.g., --OP(.dbd.O)(NR.sup.1 R.sup.2)--O-- with R.sup.1 
and R.sup.2 hydrogen or C.sub.1 -C.sub.3 alkyl; Jager et al., 
Biochemistry, 27:7237-7246 (1988); Froehler et al., International 
application PCT/US90/03138; peptide nucleic acids: Nielsen et al., 
Anti-Cancer Drug Design, 8:53-63 (1993), International application 
PCT/EP92/01220; methylphosphonates: Miller et al., U.S. Pat. No. 
4,507,433, Ts' o et al., U.S. Pat. No. 4,469,863; Miller et al., U.S. Pat. 
4,757,055; and P-chiral linkages of various types, especially 
phosphorothioates, Stec et al., European patent application 506,242 (1992) 
and Lesnikowski, Bioorganic Chemistry, 21:127-155 (1993). Additional 
nuclease linkages include phosphoroselenoate, phosphorodiselenoate, 
phosphoroanilothioate, phosphoranilidate, alkylphosphotriester such as 
methyl- and ethylphosphotriester, carbonate such as carboxymethyl ester, 
carbamate, morpholino carbamate, 3'-thioformacetal, silyl such as dialkyl 
(C.sub.1 -C.sub.6)- or diphenylsilyl, sulfamate ester, and the like. Such 
linkages and methods for introducing them into oligonucleotides are 
described in many references, e.g., reviewed generally by Peyman and 
Ulmann, Chemical Reviews 90:543-584 (1990); Milligan et al., J. Med. 
Chem., 36:1923-1937 (1993); Matteucci et al., International application 
PCT/US91/06855. 
Resistance to nuclease digestion may also be achieved by modifying the 
internucleotide linkage at both the 5' and 3' termini with 
phosphoroamidites according to the procedure of Dagle et al., Nucl. Acids 
Res. 18, 4751-4757 (1990). 
Preferably, phosphorus analogs of the phosphodiester linkage are employed 
in the compounds of the invention, such as phosphorothioate, 
phosphorodithioate, phosphoramidate, or methylphosphonate. More 
preferably, phosphorothioate is employed as the nuclease resistant 
linkage. 
Phosphorothioate oligonucleotides contain a sulfur-for-oxygen substitution 
in the internucleotide phosphodiester bond. Phosphorothioate 
oligonucleotides combine the properties of effective hybridization for 
duplex formation with substantial nuclease resistance, while retaining the 
water solubility of a charged phosphate analogue. The charge is believed 
to confer the property of cellular uptake via a receptor (Loke et al., 
Proc. Natl. Acad. Sci., 86, 3474-3478 (1989)). 
It is understood that in addition to the preferred linkage groups, 
compounds of the invention may comprise additional modifications, e.g., 
boronated bases, Spielvogel et al., 5,130,302; cholesterol moieties, Shea 
et al., Nucleic Acids Research, 18:3777-3783 (1990) or Letsinger et al., 
Proc. Natl. Acad. Sci., 86:6553-6556 (1989); and 5-propynyl modification 
of pyrimidines, Froehler et al., Tetrahedron Lett., 33:5307-5310 (1992). 
Preferably, antisense compounds of the invention are synthesized by 
conventional means on commercially available automated DNA synthesizers, 
e.g., an Applied Biosystems (Foster City, Calif.) model 380B, 392 or 394 
DNA/RNA synthesizer. Preferably, phosphoramidite chemistry is employed, 
e.g., as disclosed in the following references: Beaucage and Iyer, 
Tetrahedron, 48:2223-2311 (1992); Molko et al., U.S. Pat. No. 4,980,460; 
Koster et al., U.S. Pat. No. 4,725,677; Caruthers et al., U.S. Pat. Nos. 
4,415,732; 4,458,066; and 4,973,679. 
In embodiments where triplex formation is desired, there are constraints on 
the selection of target sequences. Generally, third strand association via 
Hoogsteen type of binding is most stable along homopyrimidine-homopurine 
tracks in a double stranded target. Usually, base triplets form in T-A*T 
or C-G*C motifs (where "-" indicates Watson-Crick pairing and "*" 
indicates Hoogsteen type of binding); however, other motifs are also 
possible. For example, Hoogsteen base pairing permits parallel and 
antiparallel orientations between the third strand (the Hoogsteen strand) 
and the purine-rich strand of the duplex to which the third strand binds, 
depending on conditions and the composition of the strands. There is 
extensive guidance in the literature for selecting appropriate sequences, 
orientation, conditions, nucleoside type (e.g., whether ribose or 
deoxyribose nucleosides are employed), base modifications (e.g., 
methylated cytosine, and the like) in order to maximize, or otherwise 
regulate, triplex stability as desired in particular embodiments, e.g., 
Roberts et al., Proc. Natl. Acad. Sci., 88:9397-9401 (1991); Roberts et 
al., Science, 58:1463-1466 (1992); Distefano et al., Proc. Natl. Acad. 
Sci., 90:1179-1183 (1993); Mergny et al., Bio-chemistry, 30:9791-9798 
(1992); Cheng et al., J. Am. Chem. Soc., 114:4465-4474 (1992); Beal and 
Dervan, Nucleic Acids Research, 20:2773-2776 (1992); Beal and Dervan, J. 
Am. Chem. Soc., 114:4976-4982; Giovannangeli et al., Proc. Natl. Acad. 
Sci., 89:8631-8635 (1992); Moser and Dervan, Science, 238:645-650 (1987); 
McShan et al., J. Biol. Chem., 267:5712-5721 (1992); Yoon et al., Proc. 
Natl. Acad. Sci., 89:3840-3844 (1992); and Blume et al., Nucleic Acids 
Research, 20:1777-1784 (1992). 
The length of the oligonucleotide moieties is sufficiently large to ensure 
that specific binding will take place only at the desired target 
polynucleotide and not at other fortuitous sites, as explained in many 
references, e.g., Rosenberg et al., International application 
PCT/US92/05305; or Szostak et al., Meth. Enzymol, 68:419-429 (1979). The 
upper range of the length is determined by several factors, including the 
inconvenience and expense of synthesizing and purifying oligomers greater 
than about 30-40 nucleotides in length, the greater tolerance of longer 
oligonucleotides for mismatches than shorter oligonucleotides, whether 
modifications to enhance binding or specificity are present, whether 
duplex or triplex binding is desired, and the like. Usually, antisense 
compounds of the invention have lengths in the range of about 12 to 60 
nucleotides. More preferably, antisense compounds of the invention have 
lengths in the range of about 15 to 40 nucleotides; and most preferably, 
they have lengths in the range of about 18 to 30 nucleotides. 
In general, the antisense oligonucleotides used in the practice of the 
present invention will have a sequence which is completely complementary 
to a selected portion of the target polynucleotide. Absolute 
complementarity is not however required, particularly in larger oligomers. 
Thus, reference herein to a "nucleotide sequence complementary to" a 
target polynucleotide does not necessarily mean a sequence having 100% 
complementarity with the target segment. In general, any oligonucleotide 
having sufficient complementarity to form a stable duplex with the target 
(e.g. an oncogene mRNA) that is, an oligonucleotide which is 
"hybridizable", is suitable. Stable duplex formation depends on the 
sequence and length of the hybridizing oligonucleotide and the degree of 
complementarity with the target polynucleotide. Generally, the larger the 
hybridizing oligomer, the more mismatches may be tolerated. More than one 
mismatch probably will not be tolerated for antisense oligomers of less 
than about 21 nucleotides. One skilled in the art may readily determine 
the degree of mismatching which may be tolerated between any given 
antisense oligomer and the target sequence, based upon the melting point, 
and therefore the thermal stability, of the resulting duplex. 
Preferably, the thermal stability of hybrids formed by the antisense 
oligonucleotides of the invention are determined by way of melting, or 
strand dissociation, curves. The temperature of fifty percent strand 
dissociation is taken as the melting temperature, T.sub.m, which, in turn, 
provides a convenient measure of stability. T.sub.m measurements are 
typically carried out in a saline solution at neutral pH with target and 
antisense oligonucleotide concentrations at between about 1.0-2.0 .mu.M. 
Typical conditions are as follows: 150 mM NaCl and 10mM MgCl.sub.12 in a 
10 mM sodium phosphate buffer (pH 7.0) or in a 10mM Tris-HCl buffer (pH 
7.0). Data for melting curves are accumulated by heating a sample of the 
antisense oligonucleotide/target polynucleotide complex from room 
temperature to about 85.degree.-.degree. C. As the temperature of the 
sample increases, absorbance of 260 nm light is monitored at 1.degree. C. 
intervals, e.g., using a Cary (Australia) model 1E or a Hewlett-Packard 
(Palo Alto, Calif.) model HP 8459 UV/VIS spectrophotometer and model HP 
89100A temperature controller, or like instruments. Such techniques 
provide a convenient means for measuring and comparing the binding 
strengths of antisense oligonucleotides of different lengths and 
compositions. 
Pharmaceutical compositions of the invention include a pharmaceutical 
carrier that may contain a variety of components that provide a variety of 
functions, including regulation of drug concentration, regulation of 
solubility, chemical stabilization, regulation of viscosity, absorption 
enhancement, regulation of pH, and the like. The pharmaceutical carrier 
may comprise a suitable liquid vehicle or excipient and an optional 
auxiliary additive or additives. The liquid vehicles and excipients are 
conventional and commercially available. Illustrative thereof are 
distilled water, physiological saline, aqueous solutions of dextrose, and 
the like. For water soluble formulations, the pharmaceutical composition 
preferably includes a buffer such as a phosphate buffer, or other organic 
acid salt, preferably at a pH of between about 7 and 8. For formulations 
containing weakly soluble antisense compounds, micro-emulsions may be 
employed, for example by using a nonionic surfactant such as polysorbate 
80 in an amount of 0.04-0.05% (w/v), to increase solubility. Other 
components may include antioxidants, such as ascorbic acid, hydrophilic 
polymers, such as, monosaccharides, disaccharides, and other carbohydrates 
including cellulose or its derivatives, dextrins, chelating agents, such 
as EDTA, and like components well known to those in the pharmaceutical 
sciences, e.g., Remington's Pharmaceutical Science, latest edition (Mack 
Publishing Company, Easton, Pa.). 
Antisense compounds of the invention include the pharmaceutically 
acceptable salts thereof, including those of alkaline earths, e.g., sodium 
or magnesium, ammonium or NX.sub.4.sup.+, wherein X is C.sub.1 -C.sub.4 
alkyl. Other pharmaceutically acceptable salts include organic carboxylic 
acids such as acetic, lactic, tartaric, malic, isethionic, lactobionic, 
and succinic acids; organic sulfonic acids such as methanesulfonic, 
ethanesulfonic, and benzenesulfonic; and inorganic acids such as 
hydrochloric, sulfuric, phosphoric, and sulfamic acids. Pharmaceutically 
acceptable salts of a compound having a hydroxyl group include the anion 
of such compound in with a suitable cation such as Na.sup.+, 
NH.sub.4.sup.+, or the like. 
The antisense oligonucleotides are preferably administered parenterally, 
most preferably intravenously. The vehicle is designed accordingly. 
Alternatively, oligonucleotide may be administered subcutaneously via 
controlled release dosage forms. 
In addition to administration with conventional carriers, the antisense 
oligonucleotides may be administered by a variety of specialized 
oligonucleotide delivery techniques. Sustained release systems suitable 
for use with the pharmaceutical compositions of the invention include 
semi-permeable polymer matrices in the form of films, microcapsules, or 
the like, comprising polylactides; copolymers of L-glutamic acid and 
gamma-ethyl-L-glutamate, poly(2-hydroxyethyl methacrylate), and like 
materials, e.g., Rosenberg et al., International application 
PCT/US92/05305. 
The oligonucleotides may be encapsulated in liposomes for therapeutic 
delivery, as described for example in Liposome Technology, Vol. II, 
Incorporation of Drugs, Proteins, and Genetic Material, CRC Press. The 
oligonucleotide, depending upon its solubility, may be present both in the 
aqueous layer and in the lipidic layer, or in what is generally termed a 
liposomic suspension. The hydrophobic layer, generally but not 
exclusively, comprises phospholipids such as lecithin and sphingomyelin, 
steroids such as cholesterol, ionic surfactants such as diacetylphosphate, 
stearylamine, or phosphatidic acid, and/or other materials of a 
hydrophobic nature. 
The oligonucleotides may be conjugated to poly(L-lysine) to increase cell 
penetration. Such conjugates are described by Lemaitre et al., Proc. Natl. 
Acad. Sci. USA , 84, 648-652 (1987). The procedure requires that the 
3'-terminal nucleotide be a ribonucleotide. The resulting aldehyde groups 
are then randomly coupled to the epsilon-amino groups of lysine residues 
of poly(L-lysine) by Schiff base formation, and then reduced with sodium 
cyanoborohydride. This procedure converts the 3'-terminal ribose ring into 
a morpholine structure antisense oligomers. 
Antisense compounds of the invention also include conjugates of such 
oligonucleotides with appropriate ligand-binding molecules. The 
oligonucleotides may be conjugated for therapeutic administration to 
ligand-binding molecules which recognize cell-surface molecules, such as 
according to International Patent Application WO 91/04753. The 
ligand-binding molecule may comprise, for example, an antibody against a 
cell surface antigen, an antibody against a cell surface receptor, a 
growth factor having a corresponding cell surface receptor, an antibody to 
such a growth factor, or an antibody which recognizes a complex of a 
growth factor and its receptor. Methods for conjugating ligand-binding 
molecules to oligonucleotides are detailed in WO 91/04753. 
In particular, the growth factor to which the antisense oligonucleotide may 
be conjugated, may comprise transferrin or folate. 
Transferrin-polylysine-oligonucleotide complexes or 
folate-polylysine-oligonucleotide complexes may be prepared for uptake by 
cells expressing high levels of transferrin or folate receptor. The 
preparation of transferrin complexes as carriers of oligonucleotide uptake 
into cells is described by Wagner et al ., Proc. Natl. Acad. Sci. USA 87, 
3410-3414 (1990). Inhibition of leukemia cell proliferation by transferrin 
receptor-mediated uptake of c-myb antisense oligonucleotides conjugated to 
transferrin has been demonstrated by Citro et al., Proc. Natl. Acad. Sci. 
USA ., 89, 7031-7035 (1992). Cellular delivery of folate-macromolecule 
conjugates via folate receptor endocytosis, including delivery of an 
antisense oligonucleotide, is described by Low et al., U.S. Pat. No. 
5,108,921. Also see, Leamon et al., Proc. Natl. Acad. Sci. 88, 5572 
(1991). 
A preferred method of administration of oligonucleotides comprises either 
systemic or regional perfusion, as is appropriate. According to a method 
of regional perfusion, the afferent and efferent vessels supplying the 
extremity containing the lesion are isolated and connected to a low-flow 
perfusion pump in continuity with an oxygenator and a heat exchanger. The 
iliac vessels may be used for perfusion of the lower extremity. The 
axillary vessels are cannulated high in the axilla for upper extremity 
lesions. Oligonucleotide is added to the perfusion circuit, and the 
perfusion is continued for an appropriate time period, e.g., one hour. 
Perfusion rates of from 100 to 150 ml/minute may be employed for lower 
extremity lesions, while half that rate should be employed for upper 
extremity lesions. Systemic heparinization may be used throughout the 
perfusion, and reversed after the perfusion is complete. This isolation 
perfusion technique permits administration of higher doses of 
chemotherapeutic agent than would otherwise be tolerated upon infusion 
into the arterial or venous systemic circulation. 
For systemic infusion, the oligonucleotides are preferably delivered via a 
central venous catheter, which is connected to an appropriate continuous 
infusion device. Indwelling catheters provide long term access to the 
intravenous circulation for frequent administration of drugs over extended 
time periods. They are generally surgically inserted into the external 
cephalic or internal jugular vein under general or local anesthesia. The 
subclavian vein is another common site of catheterization. The infuser 
pump may be external, or may form part of an entirely implantable central 
venous system such as the INFUSAPORT system available from Infusaid Corp., 
Norwood, Mass. and the PORT-A-CATH system available from Pharmacia 
Laboratories, Piscataway, N.J. These devices are implanted into a 
subcutaneous pocket under local anesthesia. A catheter, connected to the 
pump injection port, is threaded through the subclavian vein to the 
superior vena cava. The implant contains a supply of oligonucleotide in a 
reservoir which may be replenished as needed by injection of additional 
drug from a hypodermic needle through a self-sealing diaphragm in the 
reservoir. Completely implantable infusers are preferred, as they are 
generally well accepted by patients because of the convenience, ease of 
maintenance and cosmetic advantage of such devices. 
As an alternative to treatment with exogenous oligonucleotides, antisense 
polynucleotide synthesis may be induced in situ by local treatment of the 
targeted neoplastic cells with a vector containing an 
artificially-constructed gene comprising transcriptional promotors and 
targeted oncogene/proto-oncogene DNA in inverted orientation. The DNA for 
insertion into the artificial gene in inverted orientation comprises cDNA 
which may be prepared, for example, by reverse transcriptase polymerase 
chain reaction from RNA using primers derived from the published target 
oncogene/proto-oncogene cDNA sequences. 
A first DNA segment for insertion contains cDNA of a cytoplasmic 
oncogene/proto-oncogene. A second DNA segment for insertion contains cDNA 
of a nuclear oncogene/proto-oncogene. The two segments are under control 
of corresponding first and second promotor segments. Upon transcription, 
the inverted oncogene/proto-oncogene segments, which are complementary to 
the corresponding targeted oncogene/proto-oncogenes, are produced in situ 
in the targeted cell. The endogenously produced RNAs hybridize to the 
relevant oncogene/proto-oncogene mRNAs, resulting in interference with 
oncogene function and inhibition of the proliferation of the targeted 
cell. 
The promotor segments of the artificially-constructed gene serve as signals 
conferring expression of the inverted oncogene/proto-oncogene sequences 
which lie downstream thereof. Each promotor will include all of the 
signals necessary for initiating transcription of the relevant downstream 
sequence. Each promotor may be of any origin as long as it specifies a 
rate of transcription which will produce sufficient antisense mRNA to 
inhibit the expression of the target oncogene/proto-oncogene, and 
therefore the proliferation of the targeted cells. Preferably, a highly 
efficient promotor such as a viral promotor is employed. Other sources of 
potent promotors include cellular genes that are expressed at high levels. 
The promotor segment may comprise a constitutive or a regulatable 
promotor. 
The artificial gene may be introduced by any of the methods described in 
U.S. Pat. No. 4,740,463, incorporated herein by reference. One technique 
is transfection; which can be done by several different methods. One 
method of transfection involves the addition of DEAE-dextran to increase 
the uptake of the naked DNA molecules by a recipient cell. See McCutchin, 
J. H. and Pagano, J. S., J. Natl. Cancer Inst. 41, 351-7 (1968). Another 
method of transfection is the calcium phosphate precipitation technique 
which depends upon the addition of Ca.sup.++ to a phosphate-containing DNA 
solution. The resulting precipitate apparently includes DNA in association 
with calcium phosphate crystals. These crystals settle onto a cell 
monolayer; the resulting apposition of crystals and cell surface appears 
to lead to uptake of the DNA. A small proportion of the DNA taken up 
becomes expressed in a transfectant, as well as in its clonal descendants. 
See Graham, F. L. and van der Eb, A. J., Virology 52, 456-467 (1973) and 
Virology 54, 536-539 (1973). 
Transfection may also be carried out by cationic phospholipid-mediated 
delivery. In particular, polycationic liposomes can be formed from 
N-1-(2,3-di-oleyloxy)propyl!-N,N,N-trimethylammonium chloride (DOT-MA). 
See Felgner et al., Proc. Natl. Acad. Sci., 84, 7413-7417 (1987) 
(DNA-transfection); Malone et al., Proc. Natl. Acad. Sci., 86, 6077-6081 
(1989) (RNA-transfection). 
Alternatively, the artificially-constructed gene can be introduced in to 
cells, in vitro or in vivo, via a transducing viral vector. See Tabin et 
al., Mol. Cel. Biol. 2,426-436 (1982). Use of a retrovirus, for example, 
will infect a variety of cells and cause the artificial gene to be 
inserted into the genome of infected cells. Such infection could either be 
accomplished with the aid of a helper retrovirus, which would allow the 
virus to spread through the organism, or the antisense retrovirus could be 
produced in a helper-free system, such as .PSI.2 like cells (See Mann et 
al., Cell 33, 153-160, 1983) that package amphotropic viruses. A 
helper-free virus might be employed to minimize spread throughout the 
organism. Viral vectors in addition to retroviruses can also be employed, 
such as papovaviruses, SV40-like viruses, or papilloma viruses. The use of 
retroviruses for gene transfer has been reviewed by Eglitis and Anderson, 
BioTechniques 6, 608-614 (1988). 
Vesicle fusion could also be employed to deliver the artificial gene. 
Vesicle fusion may be physically targeted to the malignant cells if the 
vesicle were approximately designed to be taken up by those cells. Such a 
delivery system would be expected to have a lower efficiency of 
integration and expression of the artificial gene delivered, but would 
have a higher specificity than a retroviral vector. A strategy of targeted 
vesicles containing papilloma virus or retrovirus DNA molecules might 
provide a method for increasing the efficiency of expression of targeted 
molecules. 
Particulate systems and polymers for in vitro and in vivo delivery of 
polynucleotides were extensively reviewed by Felgner in Advanced Drug 
Delivery Reviews 5, 163-187 (1990). Techniques for direct delivery of 
purified genes in vivo, without the use of retroviruses, has been reviewed 
by Felgner in Nature 349, 351-352 (1991). Such methods of direct delivery 
of polynucleotides may be utilized for local delivery of either exogenous 
oncogene antisense oligonucleotide or artificially-constructed genes 
producing oncogene antisense oligonucleotide in situ. 
Recently, Wolf et al. demonstrated that direct injection of non-replicating 
gene sequences in a non-viral vehicle is possible. See Science, 247, 
1465-1468 (1990). DNA injected directly into mouse muscle did not 
integrate into the host genome, and plasmid essentially identical to the 
starting material was recovered from the muscle months after injection. 
Interestingly, no special delivery system is required. Simple saline or 
sucrose solutions are sufficient to delivery DNA and RNA. 
The antisense oligonucleotides may be used as the primary therapeutic for 
the treatment of the disease state, or may be used in with 
non-oligonucleotide agents. In particular, the antisense oligonucleotides 
may find utility as bone marrow purging agents in the treatment of 
leukemias or cancers which have metastasized to the bone marrow. High dose 
chemotherapy coupled with autologous bone marrow rescue involves removing 
a portion of the patient's bone marrow, treating the patient with 
conventional chemotherapy or radiation to substantially destroy the 
remaining malignant bone marrow cells, treating the stored bone marrow 
with an agent to eradicate neoplastic cells, and returning the treated 
cells to the patient. The treated cells, when returned to the patient, may 
be stimulated by various known hematopoietic growth factors to repopulate 
the bone marrow with cells which do not carry the oncogenic transcript. 
According to a method for bone marrow purging, bone marrow is harvested 
from a donor by standard operating room procedures from the iliac bones of 
the donor. Methods of aspirating bone marrow from donors are well-known in 
the art. Examples of apparatus and processes for aspirating bone marrow 
from donors are disclosed in U.S. Pat. Nos. 4,481,946 and 4,486,188. 
Sufficient marrow is withdrawn so that the recipient, who is either the 
donor (autologous transplant) or another individual (allogeneic 
transplant), may receive from about 4.times.10.sup.8 to about 
8.times.10.sup.8 processed marrow cells per kg of bodyweight. This 
generally requires aspiration of about 750 to about 1000 ml of marrow. The 
aspirated marrow is filtered until a single cell suspension, known to 
those skilled in the art as a "buffy coat" preparation, is obtained. This 
suspension of leukocytes is treated with the relevant antisense 
oligonucleotides in a suitable carrier, advantageously in a concentration 
of about 50-200 .mu.g/ml. Alternatively, the leucocyte suspension may be 
stored in liquid nitrogen using standard procedures known to those skilled 
in the art until purging is carried out. The purged marrow can be stored 
frozen in liquid nitrogen until ready for use. Methods of freezing bone 
marrow and biological substances are disclosed, for example, in U.S. Pat. 
Nos. 4,107,937 and 4,117,881. 
Other methods of preparing bone marrow for treatment with antisense 
oligonucleotide may be utilized, which methods may result in even more 
purified preparations of hematopoietic cells than the aforesaid buffy coat 
preparation. 
While hematopoietic growth factors are typically added to the aspirated 
marrow or buffy coat preparation to stimulate growth of hematopoietic 
neoplasms, the amount of growth factor added in the practice of the 
present invention should be limited to only what is necessary to sustain 
the normal cell population. If too much growth factor is added, 
differential sensitivity to antisense inhibition as between normal and 
leukemic cells in the aspirated marrow may be lost. One skilled in the art 
may readily determine the appropriate amount of growth factor. Growth 
factors, if used, may include, for example, IL-3 and granulocyte 
macrophage colony stimulating factor (GM-CSF). The recombinant human 
versions of such growth factors are advantageously employed. 
After treatment with the antisense oligonucleotides, the cells to be 
transferred are washed with autologous plasma or buffer to remove 
unincorporated oligomer. The washed cells are then infused back into the 
patient. Other methods for bone marrow purging utilizing antisense 
oligonucleotide are disclosed in U.S. Pat. No. 5,087,617. 
According to a preferred treatment regimen for bone marrow purging, the 
aspirated bone marrow is contacted daily or twice daily for approximately 
one to four days with an amount of antisense oligonucleotides effective to 
overcome the malignant phenotype. 
For systemic or regional in vivo administration, the amount of antisense 
oligonucleotides may vary depending on the nature and extent of the 
neoplasm, the particular oligonucleotides utilized, and other factors. The 
actual dosage administered may take into account the size and weight of 
the patient, whether the nature of the treatment is prophylactic or 
therapeutic in nature, the age, health and sex of the patient, the route 
of administration, whether the treatment is regional or systemic, and 
other factors. Intercellular concentrations of from about 1 to about 200 
.mu.g/ml at the target polynucleotide may be employed, preferably from 
about 10 .mu.g/ml to about 100 .mu.g/ml. The patient should receive a 
sufficient daily dosage of antisense oligonucleotide to achieve these 
intercellular concentrations of combined oligonucleotides. The daily 
combined oligonucleotide dosage combination of nuclear and cytoplasmic 
oncogene/proto-oncogene-targetting oligonucleotides may range from about 
25 mg to about 2 grams per day, with at least about 250 mg being 
preferred. An effective human continuous intravenous infusion dosage, 
based upon animal studies employing antisense oligonucleotides targeting 
other genes in antileukemic therapy, is about 0.4 mg/kg/day. Greater or 
lesser amounts of oligonucleotide may be administered, as required. Those 
skilled in the art should be readily able to derive appropriate dosages 
and schedules of administration to suit the specific circumstance and 
needs of the patient. It is believed that a course of treatment may 
advantageously comprise infusion of the recommended daily dose as a 
continuous intravenous infusion over 7 days. The oligonucleotides may be 
given for a period of from about 3 to about 28 days, more preferably from 
about 7 to about 10 days. Those skilled in the art should readily be able 
to determine the optimal dosage in each case. For modified 
oligonucleotides, such as phosphorothioate oligonucleotides, which have a 
half life of from 24 to 48 hours, the treatment regimen may comprise 
dosing on alternate days. 
The ratio of the amounts of cytoplasmic gene-specific to nuclear 
gene-specific antisense oligonucleotide may vary over a broad range. 
Preferably, the ratio varies from about 10:1 to about 1:10, by weight, 
more preferably from about 4:1 to about 1:4, most preferably from about 
3:1 to about 1:3. According to one preferred embodiment of the invention, 
the two oligonucleotides are present in approximately equal amounts, by 
weight. Of course, it may be appreciated that where plural cytoplasmic 
oncogene-specific oligonucleotides and/or plural nuclear oncogene-specific 
oligonucleotides are utilized, the total weight of lo all such compounds 
is considered with respect to the aforementioned preferred 
cytoplasmic/nuclear antisense ratio. 
For ex vivo antineoplastic application, such as, for example, in bone 
marrow purging, the antisense oligonucleotides may be administered in 
amounts effective to kill neoplastic cells. Such amounts may vary 
depending on the extent to which malignant cells may arise in or have 
metastasized to the bone marrow, the particular oligonucleotide utilized, 
the relative sensitivity of the neoplastic cells to the oligonucleotide, 
and other factors. Total oligonucleotide concentrations from about 10 to 
200 .mu.g/ml per 10.sup.5 cells may be employed, preferably from about 40 
to 150 .mu.g/ml per 10.sup.5 cells. Supplemental dosing of the same or 
lesser amounts of oligonucleotide are advantageous to optimize the 
treatment. Thus, for purging bone marrow containing 2.times.10.sup.7 cell 
per ml of marrow volume, dosages of from about 2 to 40 mg antisense per ml 
of marrow may be effectively utilized, preferably from about 8 to 24 
mg/ml. Greater or lesser amounts of oligonucleotide may be employed. 
The effectiveness of the treatment may be assessed by routine methods which 
are used for determining whether or not remission has occurred. Such 
methods generally depend upon some of morphological, cytochemical, 
cytogenetic, immunologic and molecular analyses. In addition, remission 
can be assessed genetically by probing the level of expression of one or 
more relevant oncogenes. The reverse transcriptase polymerase chain 
reaction methodology can be used to detect even very low numbers of mRNA 
transcript. For example, RT-PCR has been used to detect and genotype the 
three known bcr-abl fusion sequences in Ph.sup.1 leukemias. See 
PCT/US9-2/05035 and Kawasaki et al., Proc. Natl. Acad. Sci. USA 85, 
5698-5702 (1988). 
Typically, therapeutic success is assessed by the decrease and the extent 
of the primary and any metastatic diseases lesions. For solid tumors, 
decreasing tumor size is the primary indicia of successful treatment. 
Neighboring tissues should be biopsied to determine the extent to which 
metastasis has occurred. Tissue biopsy methods are known to those skilled 
in the art. For non-solid tumors, i.e. the leukemias, treatment is 
monitored primarily by histological examination of the bone marrow for 
surviving leukemic cells. However, a significant number of leukemic cells 
may still exist when marrow examination provides normal results. For this 
reason, more recent methods for detecting leukemic cells have focused on 
detecting the presence of the gene for the relevant oncogene, or its 
corresponding mRNA, in cells of the bone marrow as a more sensitive test. 
See, for example, the following U.S. Pat. Nos. 4,681,840, 4,857,466 and 
4,874,853. The presence of even a few copies of the target oncogene can be 
effectively detected by amplification using reverse transcriptase 
polymerase chain reaction technology. For a detailed discussion of such 
methods, see for example, Cancer: Principles & Practice of Oncology, 
edited by V. T. DeVita, S. Hellman and S. A. Rosenberg, J. B. Lippincott 
Company, Philadelphia, Pa. (3rd ed., 1989). Methods for diagnosing and 
monitoring the progress of neoplastic disorders vary depending upon the 
nature of the particular disease. 
An antileukemic treatment plan is proposed as follows. Antisense 
oligonucleotides (phosphorothioate 24-mer) are administered as a 24-hour 
continuous intravenous infusion over 7 days. Each oligonucleotide is 
placed in 5% dextrose water and given at a daily dose ranging from about 
0.30 to about 2 mg/kg/day. The dosage may be escalated as needed. Bone 
marrow aspiration/biopsy is conducted 7, 14 and 21 days after the first 
cycle of therapy. The patient is evaluated for response on day 21. 
Additional cycles of therapy may be performed. For such additional cycles 
of therapy, a bone marrow biopsy will be performed 21 days after the 
initiation of therapy. Complete remission is determined by the presence of 
all of the following for a period of at least 4 weeks: (1) a white count 
below 10,000/mm.sup.3 with granulocytes &gt;1,000/mm.sup.3 ; (2) platelet 
count of .gtoreq.100,000/mm.sup.3 ; (3) absence of leukemic blasts from 
the peripheral blood; (4) a cellularity of bone marrow biopsy 
of.gtoreq.20%, with maturation of all cell lines; (5).gtoreq.5% blasts in 
the bone marrow; (6) the absence of detectable Auer rods; (7) the absence 
of organomegaly; (8) the absence of extramedullary leukemia, such as 
central nervous system or soft tissue involvement. 
According to one preferred embodiment, the invention comprises in vivo or 
ex vivo treatment of Ph.sup.1 -positive leukemias, that is, leukemias 
characterized by the chromosomal abnormality known as the Philadelphia or 
Ph.sup.1 chromosome. At the molecular level, the most notable feature is 
the translocation of the proto-oncogene c-abl from the long arm of 
chromosome 9 to the breakpoint cluster region (bcr) on chromosome 22, 
resulting in the formation of bcr-abl hybrid genes. The break occurs near 
the end of the long arm of chromosome 9 (band 9q34) and in the upper half 
of chromosome 22 (band 22q11). 
The c-abl proto-oncogene normally encodes a protein with tyrosine kinase 
activity. This activity is augmented in cells carrying bcr-abl hybrid 
genes. The gene located at the breakpoint on chromosome 22 is called bcr 
because the break in chromosome 22 in CML occurs in a very small 
5.8-kilobase (kb) segment (breakpoint cluster region) of the gene on 
chromosome 22. Two alternative first exons of the c-abl oncogene exist, 
namely exon 1a and exon 1b, which are spliced to the common splice 
acceptor site, exon 2. As a result of this configuration, at least two 
major c-abl messages are transcribed, differing in their 5' regions. 
(Shtivelman et al., Cell 47, 277 (1986); Bernards et al., Mol. Cell. Biol. 
7, 3231 (1987); Fainstein et al., Oncogene4, 1477-1481 (1989)). If exon 1b 
is used, the mRNA is 7.0 kb. If exon 1a is used, the mRNA is 6.0 kb. Each 
of exons 1a and 1b are preceded by a transcriptional promotor. The 9;22 
translocation in CML results in the abnormal juxtaposition of abl 
sequences adjacent to bcr sequences. The fusion leads to an 8.5 kb 
chimeric mRNA consisting of 5' BCR sequences and 3' abl sequences. The 
chimeric message is in turn translated into a larger chimeric abl protein 
(210 kDa) that has increased tyrosine kinase activity (Konopka et al., 
Cell 37, 1035 (1984); Kloetzer et al., Virology140, 230 (1985). 
Two major types of bcr-abl translocations are known, characterized by two 
different bcr-abl junctions. One translocation is between bcr exon 2 and 
abl exon 2, while another translocation is between bcr exon 3 and the same 
abl exon 2 (Shtivelman et al., Cell 47, 277-284 (1986)). The two types of 
junction have been referred to as the "L-6" (or "b2a2") and "K-28" (or 
"b3a2") junctions, respectively. The alternative splicing from two bcr-abl 
exons to the abl coding sequence results in two different bcr-abl fusion 
proteins, one including the 25 amino acids encoded by bcr exon 3 and one 
which lacks those amino acids. One or both of these junctions is detected 
in Ph.sup.1 -positive CML patients (Shtivelman et al., Blood 69, 971 
(1986)). 
A significant portion of acute lymphocytic leukemia (ALL) patients carry 
Ph.sup.1 chromosomes in their leukemic cells. Ph.sup.1 -positive ALL is 
generally regarded as being less responsive to chemotherapeutic treatment 
than Ph.sup.1 -negative forms of ALL. This is particularly true of 
children with Ph.sup.1 -positive ALL. 
Approximately one half of Ph.sup.1 -positive individuals afflicted with ALL 
express either of the two major bcr-abl junctions, L-6 or K-28. The 
remainder have bcr-abl genes characterized by a junction formed by the 
fusion of bcr exon 1 and c-abl exon 2 ("bla2" junction). See Fainstein et 
al., Nature 330, 386-388 (1987). 
Clinically, CML invariably progresses from the chronic phase into the blast 
crisis. In chronic phase CML, the increase in mature and immature myeloid 
elements in bone marrow and peripheral blood is the most characteristic 
feature (Koeffler et al., N. Engl. J. Med. 304, 201 (1981)). Kinetic 
studies indicate that these abnormal cells do not proliferate or mature 
faster than their normal counterparts. Instead, the basic defect 
underlying the exuberant granulopoiesis in CML appears to reside in the 
expansion of the myeloid progenitor cell pool in bone marrow and 
peripheral blood. Id. Nevertheless, the generation of terminally 
differentiated cells indicates that the process of hematopoiesis retains 
some normal features. In contrast, during blastic transformation, the 
leukemic cells exhibit a marked degree of differentiation arrest with a 
"blast" phenotype (Rosenthal et al., Am. J. Med. 63, 542 (1977)). The 
onset of the blastic transformation or "blast crisis" limits the 
therapeutic options available. The disease-free period, and consequently 
survival, is generally brief. Typically it is less than about four months. 
According to a preferred embodiment of the practice of the present 
invention, phi-positive leukemias are treated, either in vivo or ex vivo, 
with a combination of antisense oligonucleotides. Preferably, the 
oligonucleotides comprise at least one bcr-abl-specific antisense 
oligonucleotide, and at least one antisense oligonucleotide specific for a 
nuclear oncogene or proto-oncogene. 
Preferably, the bcr-abl antisense oligonucleotide is complementary to a 
position of the bcr-abl mRNA corresponding to the breakpoint junction 
between the bcr-derived and abl-derived portions of the mRNA. By 
"abl-derived portion" is meant that portion of the bcr-abl RNA transcript 
which results from the transcription of the abl coding sequence which is 
translocated to the bcr coding sequence in the chromosomal translocation 
event giving rise to formation of the Ph.sup.1 chromosome. Similarly, by 
"bcr-derived portion" of the bcr-abl transcript is meant that portion 
which results from the transcription of the bcr coding sequence which is 
juxtaposed to c-abl. This ensures specific hybridization to bcr-abl 
transcripts. Most preferably, the antisense molecule is complementary to a 
target mRNA sequence containing an about equal number of abl-derived 
nucleotides and bcr-derived nucleotides, that is, an about equal number of 
nucleotides on either side flanking the translocation breakpoint. 
Preferred antisense oligonucleotides complementary to the bcr-abl b1a2, 
b2a2 and b3a2 junctions are disclosed in International Patent Application 
W092/22303, the disclosure of which is incorporated herein by reference. 
The practice of the present invention is illustrated by the following 
non-limiting examples. Combinations of nuclear and cytoplasmic 
oligonucleotides were more effective than either oligonucleotide alone. 
EXAMPLE 1 
Effect of bcr-abl and c-myc Antisense Oligonucleotides on BV-173 Cells 
A. Phosphorothioate Oligodeoxynucleotides 
Phosphorothioate oligodeoxynucleotides (S!ODNs ) were synthesized on an 
Applied Biosystems model 390Z automated synthesizer. The sequence of the 
b2/a2 bcr-abl antisense S!ODN CGCTGAAGGG CTTCTTCCTT ATTGAT (SEQ ID NO:1) 
was complementary to a 26-nucleotide segment of the bcr-abl mRNA 
transcript spanning thirteen nucleotides upstream and downstream of the 
c-abl exon 2 and BCR exon 2 breakpoint junction. The sequence of the c-myc 
antisense S!ODN TTGGTGAAGC TAACGTTGAG GGGCAT (SEQ ID NO:3) was 
complementary to the first 26 nucleotides of the mRNA transcript beginning 
from the translation initiation codon. Corresponding sense 
oligonucleotides had the sequences ATCAATAAGG AAGAAGCCCT TCAGCG (bcr-abl, 
SEQ ID NO:2) and ATGCCCCTCA ACGTTAGCTT CACCAA (c-myc, SEQ ID NO:4). 
B. Cell Proliferation Assay 
Chronic myelogenous leukemia (BV173) cells (10.sup.4 /100 .mu.l/well) were 
placed in 96-well culture plates in RPMI medium supplemented with 10% 
fetal bovine serum, L-glutamine, and penicillin/streptomycin. For the 
protein studies and cell cycle analysis described below, 5.times.10.sup.6 
BV173 cells/20 ml of medium were placed in 175 cm.sup.2 LUX tissue culture 
flasks (Nunc, Inc., Naperville, Ill.). Sense or antisense S! ODNs were 
added at the beginning of culture and again (at 50% of the initial dose) 
24 and 48 hours later. The final concentrations of S! ODNs are indicated 
in FIG. 1A (10 .mu.g/ml), FIG. 1B (5 .mu.g/ml) and FIG. 1C (2.5 .mu.g/ml). 
Control cells were left untreated. Cells in 96-well plates were counted in 
Trypan blue on days +4,+6 and +8. Cells in flasks were centrifuged on 
HISTOPAQUE-1077, washed, counted and used for further studies. The results 
are shown in FIGS. 1A-1C: (.largecircle.) control; (.DELTA.) b2/a2 plus 
c-myc sense; (.quadrature.) b2/a2 antisense; (.box-solid.) c-myc 
antisense, (.circle-solid.) b2/a2 and c-myc antisense. 
C. Protein Analysis 
In this experiment, total cellular proteins were isolated from BV 173 cells 
after 72 hours of incubation without S! ODNs (control), or with 10 
.mu.g/ml of the above indicated S! ODNs and analyzed by SDS-PAGE and 
Western blotting for the expression of indicated proteins. Accordingly, 
10.sup.6 cells were solubilized in RIPA lysis buffer containing 10% 
deoxycholate, 2% NP-40, 02% SDS, and 10% glycerol, in Tris-buffered 
saline, pH 7.2. Proteins were separated on 7.5% SDS-PAGE and transferred 
to nitrocellulose (MCI, Westboro, Mass.). Filters were blocked in 0.5% 
gelatin in TBS and then incubated with murine monoclonal anti-ABL antibody 
(gift of Dr. R. Arlinghaus, M. D. Anderson Medical Center, Houston, Tex.), 
murine monoclonal anti-c-MYC antibody (Oncogene Science Inc., Uniondale, 
N.J.), and murine monoclonal anti-HSP 72/72 (Oncogene Science). Filters 
were washed 5 times with 0.2% TWEEN 0.25% NP-40 in TBS buffer and blotted 
with anti-murine polyclonal antibody linked to horseradish peroxidase 
(Amersham Corp., Arlington Heights, Ill.). Proteins were detected using 
the ECL Western blotting system (Amersham). The results are shown in FIG. 
2. 
D. Cell Cycle Analysis 
After incubation for 24, 48, and 72 hours in the presence of antisense S! 
ODNs (b2/a2, 10 .mu.g/ml; c-myc 10 .mu.g/ml; b2/a2, 2.5 .mu.g/ml; 
b2/a2+c-myc, 2.5 .mu.g/ml), DNA content of BV173 cells was determined by 
flow cytometry. Cells (10.sup.6) were fixed in 70% ethanol for 15 minutes 
at 4.degree. C., washed and incubated in 1 ml of PBS+0.1% NP-40+1 mg/ml of 
DNAse-free RNAse (Boehringer Mannheim Co., Indianapolis, Ind.) for 10 
minutes at room temperature. Propidium iodide (5 .mu.g/ml) was added and 
cells were analyzed by the EPICS PROFILE analyzer (Coulter). The results 
are shown in FIGS. 3A-3D for the following concentrations of the following 
antisense S! ODNs : 3A, b2/a2 10 .mu.g/ml; 3B, c-myc 1 .mu.g/ml, 3C, 
b2/a2 2.5 .mu.g/ml; 3D, b2/a2+c-myc 2.5 .mu.g/ml. 
E. Discussion 
In vitro proliferation of Philadelphia.sup.1 -positive BV173 cells which 
carry the bcr exon 2-abl exon 2 (b2/a2) junction was completely inhibited 
in the presence of b2/a2 or c-myc antisense oligodeoxynucleotides at a 
concentration of 10 .mu.g/ml each (FIG. 1A-1C), whereas the S! ODNs 
inhibited proliferation at a 2-and 4-fold lower final concentration, i.e., 
concentrations at which the individual S! ODNs were nearly or completely 
ineffective (FIG. 1A-1C). Sense S! ODNs were non-inhibitory at any 
concentration tested. 
Inhibition of BV173 cell proliferation by b2/a2 or c-myc antisense S! ODNs 
was accompanied by a down-regulation of bcr/abl and c-MYC protein levels, 
respectively (FIG. 2). Expression of MYC protein was also partially 
inhibited by b2/a2 antisense S! ODNs , which might rest in a functional 
linkage between bcr/abl and c-myc. The combined treatment with b2/a2+c-myc 
antisense S! ODNs downregulated both BCR/ABL and c-MYC protein 
expression. In this case downregulation of c-MYC proteins appears more 
pronounced than that obtained using the individual antisense S! ODNs . 
Analysis of cellular DNA content (cell cycle distribution) by flow 
cytometry revealed that treatment with b2/a2 or c-myc antisense S! ODNs , 
as well as with the of both antisense S! ODNs at concentrations affecting 
their proliferation, led after 48 and 72 hours to accumulation of cells in 
S phase of the cell cycle, concomitant with a decrease in the proportion 
of G1 and G2 cells, and with the appearance of cells with fractional DNA 
content (FIGS. 3A-3D). The changes in the cell cycle, when analyzed in 
light of the suppressed cell proliferation by antisense S! ODNs treatment 
(FIGS. 1A-1C), indicate a dramatically slowed cell progression through S 
phase. The cells with fractional DNA content are typical of cells dying by 
mode of apoptosis. The degraded, low molecular weight DNA from apoptotic 
cells is generally extracted prior to and during the staining procedure. 
Such cells, as well as apoptotic bodies, stain with much lower intensity 
with DNA fluorochromes, representing a "sub-G1" cell population on the DNA 
frequency histograms. This population is very heterogeneous with respect 
to DNA content, both after 48 and 72 hours (FIGS. 3A-3D), which indicates 
different degrees of DNA degradation in individual cells. This in turn is 
suggestive that cell death in these cultures was asynchronous. 
The apoptotic mode of cell death, and the asynchrony of apoptosis, were 
confirmed by observation of cell morphology following differential 
staining of DNA and protein (data not shown). The changes characteristic 
of apoptosis, involving cell shrinkage, chromatin condensation, 
fragmentation of nuclei, hyperchromicity of chromatin, and shedding of 
apoptotic bodies, were observed in all cultures treated with b2/a2, c-myc 
or of both antisense S! ODNs . After 48, and especially after 72 hours, 
there were numerous very late apoptotic cells in these cultures, 
containing very little, or almost no stainable DNA. 
Thus, the flow cytometric data indicate that exposure of cells to b2/a2 or 
c-myc antisense S! ODNs , or to both of these S! ODNs , while not 
precluding cell entrance into S phase, does prevent cell progression 
through the S phase. 
EXAMPLE 2 
Effect of bcr-abl and c-myc Antisense Oligonucleotides on Growth of CML 
Blast Crisis Patient Cells 
Bone marrow cells collected from CML patients in blast crisis were 
suspended (10.sup.5 cells/0.4 ml) in Iscove's modified Dulbecco medium 
supplemented with 2% of human AB serum, Hepes buffer, L-glutamine and 
peni/strepto. The cells were treated in liquid culture for 5 days with 
bcr-abl, or c-myc, or bcr-abl+c-myc sense (S) or antisense (AS) S! ODNs 
(80 .mu.g/ml added on day 0, 40 .mu.g/ml on day+1, and 40 .mu.g/ml on 
day+2). The S! ODNs doses were equally divided in the case of combination 
in liquid culture for 5 days. Then the cells were plated in 
methylcellulose and the colonies and clusters were counted after 7-12 days 
of incubation. The results shown in Table 1 represent mean.+-.standard 
deviation from two experiments, each performed in duplicate. 
TABLE 1 
______________________________________ 
Synergistic effect of bcr/abl + c-myc antisense 
S!ODNs on the growth of CML-BC cells 
S!ODNs COLONIES 
PATIENT bcr/abl c-myc mean .+-. SD 
______________________________________ 
A (b2/a2) -- -- 1365 .+-. 219 
S S 1259 .+-. 85 
AS -- 274 .+-. 31 
-- AS 245 .+-. 26 
AS AS 73 .+-. 21.sup.a 
B (b3/a2) -- -- 954 .+-. 85 
S S 974 .+-. 42 
AS -- 488 .+-. 18 
-- AS 451 .+-. 9 
AS AS 162 .+-. 38.sup.b 
C (b2/a2) -- -- 129 .+-. 16 
S S 140 .+-. 40 
AS -- 56 .+-. 5 
-- AS 51 .+-. 5 
AS AS 22 .+-. 6.sup.c 
______________________________________ 
.sup.a p = 0.017, and p = 0.019 in comparison to bcrabl AS, and cmyc AS 
group, respectively. 
.sup.b p = 0.008, and p = 0.009 in comparison to bcrabl AS, and cmyc AS 
group, respectively. 
.sup.c p &lt; 0.001 in comparison to bcrabl AS, and cmyc AS group. 
EXAMPLE 3 
In Vivo Effect of bcr-abl and c-myc Antisense Oligonucleotides 
The antileukemic effects of bcr-abl and c-myc ODNs, alone and in 
combination, were assessed in vivo as follows. 
A. Leukemic Cell Assay-4 Weeks Post-Transplantation of Leukemic Cells 
Immunodeficient SCID mice (males 8-10 weeks old, 20-22 g) were injected 
intravenously with 10.sup.6 BV173 cells, a regimen that produces a disease 
process reminiscent of that in humans. Seven days later, mice were 
systemically injected for 12 consecutive days with 1 mg/day/mouse of b2/a2 
sense+c-myc sense (6 days each, every other day), b2/a2 antisense, c-myc 
antisense or b2/a2+c-myc antisense (6 days each, every other day). Control 
mice were injected with diluent only. Four weeks after leukemia 
implantation, peripheral blood (PBL), spleen (SPL), and bone marrow (BMC) 
from one mouse per group were analyzed to assess the disease process. 
Leukemia growth in the mice was analyzed by assessing the tissues for 
CD1O+cells by immunocytometry and for clonogenic growth in methylcellulose 
as described by Skorski et al., Proc. Natl. Acad. Sci. USA 91:4504 (1994). 
Immunofluorescence assay (sensitivity 10.sup.-2) did not detect 
CD10+leukemic cells, whereas colony assay (sensitivity 10.sup.-3) revealed 
several clonogenic leukemia cells in BMC suspensions of control and sense 
S! ODNs -treated mice, but none from cell suspensions of mice treated 
with antisense S! ODNs either individually or in combination (not shown). 
RT-PCR amplification of bcr-abl transcripts present in the total RNA 
isolated from bone marrow and spleen, followed by Southern blot 
hybridization, revealed a relatively strong signal from amplification 
products of RNA isolated from control and sense S! ODNs -treated mice, 
but only a weak signal in RNA derived from tissue of mice treated with 
individual ODNs, and a nearly undetectable signal in RNA from the mouse 
treated with both b2/a2+c-myc antisense S! ODNs (not shown). Equal 
amounts of .beta.-actin transcript were detected in RNA samples from each 
tissue. 
B. Leukemic Cell Assay--8 Weeks Post-Transplantation of Leukemic Cells 
Mice were inoculated intravenously with 10.sup.6 BV173 cells and 7 days 
later, injected i.v. with sense (S) or antisense (AS) S! ODNs (1 
mg/mouse/day) for 12 consecutive days. In the group (b2/a2+c-myc) S! ODNs 
were injected every other day. Control mice were injected with diluent 
only. Leukemia growth in the mice was analyzed on day 56 by assessing 
peripheral blood leukocytes (PBL), spleen (SPL), and bone marrow cells 
(BMC) for CD10+cells by immunocytometry and for clonogenic growth in 
methylcellulose. The results are given in Table 2. Numbers show individual 
results obtained from 3 mice (A, B and C). NT=not tested. 
TABLE 2 
______________________________________ 
Presence of CD10+ and leukemia clonogenic cells 
in SCID mice injected with BV173 cells and treated 
with bcr-abl (b2/a2) and/or c-myc S!ODNs. 
Leukemic colonies/ 
% CD10-positive cells 
10.sup.5 cells 
Treatment 
Groups PBL SPL BMC PBL SPL BMC 
______________________________________ 
Control A 1.4 6.1 24.9 19 559 2519 
B 0 4.9 11.6 7 252 1579 
C 0 5.0 7.4 2 258 1166 
b2/a2 S + 
A NT 6.3 38.5 NT 588 3005 
c-myc S B 0 6.5 10.4 4 239 1389 
C 0 4.2 7.0 0 194 1214 
b2/a2 AS 
A 0 0 0 0 5 4 
B 0 0 0 0 5 9 
C 0 0 0 0 9 19 
c-myc AS 
A 0 0 0 0 13 20 
B 0 0 0 0 8 37 
C 0 0 0 0 4 22 
b2/a2 AS + 
A 0 0 0 0 0 0 
c-myc AS 
B 0 0 0 0 0 1 
C 0 0 0 0 0 0 
______________________________________ 
Immunofluorescence assay detected CD10+cells in peripheral blood (only one 
mouse positive), spleen and bone marrow of control and sense S! ODNs 
treated mice, but not in the corresponding tissues of the mice treated 
with antisense ODNs (Table 2). The more sensitive clonogenic assay 
revealed several leukemic colonies in peripheral blood, and abundant 
colonies in spleen and bone marrow of control and sense S! ODNs treated 
mice. In contrast, cell suspensions of c-myc or b2/a2 antisense-treated 
mice contained far fewer malignant clonogenic cells (Table 2). Only one of 
the mice treated with both b2/a2+c-myc antisense ODNs contained detectable 
clonogenic leukemic cells. 
C. Scoring of Superficial Liver Metastases 
Superficial liver metastases were scored in mice treated as described in 
part A., above. The result are described in Table 3, below. Numbers 
indicate visible liver metastases. Scoring of superficial liver metastases 
was consistent with immunofluorescence and clonogenic assays. Numerous 
metastatic nodules were visible on the surface of livers from control and 
sense-treated mice, several on the livers of mice treated with single 
antisense, and none on the organs from mice treated with both antisense 
S! ODNs . 
TABLE 3 
______________________________________ 
Superficial metastases in the liver of SCID mice 
injected with BV173 cells and treated with b2/a2, c-myc 
or b2/a2 + c-myc antisense (AS or sense (S) S!ODNs) 
Treatment Groups Number of Metastases 
______________________________________ 
Control 89, 54, 88 
b2/a2 + c-myc S 156, 107, 61 
b2/a2 AS 12, 10, 8 
c-myc AS 15, 15, 4 
b2/a2 AS + c-myc AS 
0, 0, 0 
______________________________________ 
D. Detection of bcr-abl Transcripts by Reverse Transcriptase-Polymerase 
Chain Reaction 
Cells were collected separately from various organs of S! ODNs treated 
SCID mice, 56 days after leukemia implantation. Total RNA was extracted 
from 10.sup.6 cells (Chromczynski et al., Anal. Biochem. 162, 156 (1987)), 
and divided into two portions. A 3' primer of ABL exon 2, 3' primer of 
.beta.-actin, 5' primer of BCR exon 2, 5' primer for .beta.-actin, and ABL 
and .beta.-actin probes recognizing amplified transcripts were all 
prepared according to published sequences (Szczylik et al., Science 253, 
562 (1991); Skorski et al., J. Clin. Invest. 92, 194 (1993); Caracciolo et 
al., ibid 85, 55 (1990)). One cell sample was reverse transcribed using 
400 U of Moloney murine leukemia virus reverse-transcriptase (Bethesda 
Research Laboratories, Gaithersburg, MD) and 0.1 .mu.g of 3'-end primer of 
abl exon 2 for 1 hour at 37.degree. C. The second sample was reverse 
transcribed using the .beta.-actin 3' primer. Resulting cDNA fragments 
were amplified with 5U Tag polymerase (Perkin Elmer Cetus, Norwalk, CT) in 
the presence of 5' primer of either BCR exon 2 or .beta.-actin, generating 
257-bp and 209-bp fragments of bcr-abl and .beta.-actin, respectively, 
during 50 cycles of PCR (Chromczynski et al., Anal. Biochem 162; 156 
(1987)). Reaction products were electrophoresed, transferred and 
hybridized, using the appropriate probes (c-abl or .beta.-actin). Blots 
were exposed 24 hours (bcr-abl) and 2 hours (.beta.-actin). 
The results are shown in FIG. 4, indicating detection of bcr-abl 
transcripts by RT-PCR in RNA from tissues of S!ODN treated (b2/a2+c-myc 
sense (S); b2/a2 antisense (AS); c-myc AS; or b2/a2+c-myc (AS) or 
untreated (control) leukemic SCID mice. The blot is representative of 
three different experiments using three mice/group (PBL=peripheral blood 
lymphocyte; SPL=spleen; BMC=bone marrow cell; LIV=liver; LNG =lung; and 
BRN=brain). 
RT-PCR amplification of bcr-abl transcripts in RNA isolated from various 
tissues of control and sense S! ODNs -treated animals (three mice/group) 
revealed bcr-abl transcripts in each of these tissues. Bcr-abl transcripts 
were also detected in all tissues except brain of mice treated with single 
antisense S! ODNs , but the signal was much weaker than observed with 
control and sense S! ODNs -treated mouse tissues. Even weaker signals 
were detected in the RNA isolated from all the organs except brain of mice 
injected with b2/a2 +c-myc antisense S! ODNs , suggesting that the 
leukemic cell load in mice treated with S! ODNs in was reduced as 
compared with that of mice treated with individual ODNs. Equal amounts of 
.beta.-actin detected in each group of organs indicated the integrity and 
equal loading of the amplified products. 
E. Quantitative RT-PCR Detection of bcr-abl Transcripts 
To confirm that the differences in the intensity of the bcr-abl bands 
corresponding to tissues of single versus combined antisense S! ODNs 
-treated mice reflected the difference in amounts of bcr-abl transcript in 
the tissues, quantitative RT-PCR (Qt/RT-PCR) was performed using the same 
amount of RNA isolated from bone marrow cells of b2/a2 and b2/a2+c-myc 
antisense S!ODN-treated mice, in the presence of increasing amounts of 
RNA from K562 cells (b3/a2) as a source of competitive bcr-abl RNA, and 
using optimal concentrations of primers. Integrity of the isolated RNA was 
confirmed by RT-PCR which detected similar amounts of .beta.-actin 
transcript. Accordingly, various amounts (zero, 0.1 ng, 1 ng, 10 ng, 100 
ng) of total RNA isolated from K562 (b3/a2 junction) cells were added as a 
source of competitive bcr-abl-containing RNA to the same amount of total 
RNA isolated from 10.sup.6 BMC obtained from b2/a2 AS or b2/a2 AS+c-myc 
AS-treated mice. Southern blot analysis of RT-PCR amplification products 
was performed. 
The results of the assay appear in FIG. 5 (lane 1, no K562 RNA; lane 2, 0.1 
ng; lane 3, 1 ng; lane 4, 10 ng; lane 5, 100 ng) The blot of FIG. 5 is 
representative of two different experiments. 
The analysis detected the b2/a2 fragment from BV173 RNA contaminating mouse 
BMC (FIG. 5, lower band) RNA, and the b3/a2 fragment from the K562 RNA 
(FIG. 5, upper band) added as competitor. 
The analysis revealed competitive blocking of the b2/a2 transcript (from 
BV173 cells present in the tissue) at lower K562 RNA concentrations when 
bone marrow cells were isolated from mice injected with both b2/a2 and 
c-myc antisense S! ODNs as compared to those receiving only one antisense 
S! ODNs (FIG. 5). This indicates the lower amounts of bcr-abl transcripts 
in bone marrow cell RNA from the combined versus single antisense 
ODN-treated mice. These results are consistent with those obtained by 
nonquantitative RT-PCR, immunofluorescence, and clonogenic assays, and by 
assessment of liver metastases. 
F. Leukemic Cell Assay--20 Weeks Post-Transplantation of Leukemic Cells 
Two other b2/a2+c-myc antisense S!ODN-treated mice (mice D and E) were 
subjected to leukemic cell assay 20 weeks after leukemia implantation. At 
this point, all mice treated with individual S! ODNs were dead. Leukemic 
colonies were counted after 9-day culture in methylcellulose. The 
intensity of the RT-PCR band was evaluated after blotting with a 
junction-specific .gamma..sup.32 P!-labelled probe and exposing the 
filters for different times. The assay results, set forth in Table 4, 
revealed different degrees of disease process as reflected by the tumor 
load of the two mice: (-) not detectable after 7-day exposure; (+) visible 
after 7-day exposure; (++) visible after 24 h exposure; (+++) visible 
after 1 hour exposure. The abbreviations in Table 4 are the same as in 
FIG. 4: 
TABLE 4 
__________________________________________________________________________ 
Leukemia growth in SCID mice 20 weeks after 
injection of 10.sup.6 BV 173 cells and treatment 
with b2/a2 + c-myc antisense S!ODNs 
Mice Leukemic Liver 
colonies/10.sup.5 cell 
bcr/abl mRNA levels metas 
PBL SPL BMC 
PBL SPL 
BMC LIV 
LNG BRN 
tases 
__________________________________________________________________________ 
D 0 2 236 
- + ++ + + - 0 
E 53 283 2387 
+ +++ 
+++ +++ 
+ + 23 
__________________________________________________________________________ 
G. Survival of Leukemic Cell-Transplanted Mice 
Differences in the survival of control, sense, single antisense and dual 
antisense S!ODN treated mice are summarized in FIG. 6: b2/a2 S+c-myc S 
(.box-solid.); b2/a2 AS (.tangle-solidup.), c-myc AS (.quadrature.); or 
b2/a2 AS c-myc AS (.circle-solid.). Control mice (.largecircle.) received 
diluent only. All nine control and nine sense S!ODN-treated mice died 
with diffuse leukemia, as confirmed by necropsy, 7-10 weeks after i.v. 
injection of 10.sup.6 BV173 leukemia cells (median survival time 
7.7.+-.0.8 and 8.3.+-.0.5 weeks, respectively). In contrast, the nine 
b2/a2 antisense S! ODNs - and nine c-myc antisense S! ODNs -treated mice 
died after 14-18 and 14-19 weeks, respectively, of leukemia growth (median 
survival time 14.7.+-.0.8 and 14.8.+-.0.9 weeks, respectively; p&lt;0.001 
compared with control groups). Seven of nine mice treated with both 
antisense S! ODNs survived significantly longer (median survival time 
26.0.+-.5.4 weeks; p&lt;0.001 compared to mice treated with either antisense 
ODNs). Two remaining mice were still alive 41 weeks after injection of 
leukemic cells, but one of them had minimal residual disease as revealed 
by RT-PCR detection of bcr-abl transcripts in peripheral blood (not 
shown). 
H. Detection of Intact S!ODN in Mouse Tissues and Leukemic Cells 
Infiltrating Bone Marrow and Spleen 
SCID mice were injected (1 mg/day/12 consecutive days) with b2/a2+c-myc AS 
S! ODNs . Twenty-four hours after the last injection, DNA obtained from 
10.sup.6 cells of various tissues was electrophoresed and intracellular 
S! ODNs were detected by specific hybridization with complementary 
oligoprobes. The S!ODN detection results are shown in FIG. 7A. For 
detection of intact S! ODNs in BV173 cells infiltrating mouse tissues, 
leukemic SCID mice were injected (1 mg/day/12 consecutive days) with 
bcr-abl, c-myc, or bcr-abl+c-myc AS S! ODNs . Twenty-four hours after the 
last injection, CD10+BV173 were isolated by immunosorting from bone marrow 
and spleen cell suspensions. After DNA isolation, intracellular S! ODNs 
were detected as described previously (Ratajczak et al., Proc. Natl. Acad. 
Sci. USA 89, 11823 (1993); Kitajima et al. Science 258, 1792 (1992); 
Higgins et al., PNAS90, 9901 (1993); Skorski et al., PNAS91, 4504 (1994); 
Huiya et al., ibid 31, 4499 (1994)). Standard 26-met antisense S! ODNs 
were run as controls. The results are shown in FIG. 7B. 
The leukemia suppressive effects of antisense S! ODNs correlated well with 
their detection in all organs examined except brain, although blot 
hybridization of tissue DNA isolated 1 day after the last injection showed 
highest ODNs concentrations in liver and spleen (FIG. 7A). S! ODNs were 
still detectable in these organs 7 days after the last injection (not 
shown). Intact b2/a2 and c-myc, antisense S! ODNs were simultaneously 
detected in vivo in leukemic cells infiltrating bone marrow and spleen of 
SCID mice one day after completion of the injection protocol, by 
immunosorting of CD10+cells and Southern blot hybridization of the 
isolated DNA with oligomer probes complementary to with c-myc or bcr-abl 
antisense S! ODNs (FIG. 7B). 
EXAMPLE 4 
Effect of c-raf and c-myc Antisense Oligonucleotides on BV173 Cells 
A. Phosphorothioate Oligodeoxynucleotides 
The following phosphorothioate oligodeoxynucleotides (S! ODNs ) were 
synthesized on an Applied Biosystems model 390Z automated synthesizer. The 
sequence of each antisense S!ODN was complementary to the first 26 
nucleotides of the mRNA transcript of the indicated oncogene, beginning 
from the translation initiation codon. 
c-myc (AS) TTGGTGAAGC TAACGTTGAG GGGCAT (SEQ ID NO:3) 
c-myc (S) ATGCCCCTCA ACGTTAGCTT CACCAA (SEQ ID NO:4) 
c-raf (AS) GGTGAGGGAG CGGGAGGCGG TCACAT (SEQ ID NO:5) 
c-raf (S) ATGTGACCGC CTCCCGCTCC CTCACC (SEQ ID NO:6) 
B. Cell Proliferation Assay 
BV173 cells (10.sup.4 /100 .mu.l/well) were placed in 96-well culture 
plates in RPMI medium supplemented with 10% fetal bovine serum, 
L-glutamine, and penicillin/streptomycin. Sense or antisense S! ODNs were 
added at the beginning of culture (20 .mu.g/ml) and again (at 50% of the 
initial dose) 24 and 48 hours later. Control wells received no oligomer. 
Sense oligonucleotide-treated cells received equal mixtures of c-raf and 
c-myc sense oligonucleotides. Cells in 96-well plates were counted in 
Trypan blue on days oncogenes. +4,+6 and +8. The oligonucleotide dosages 
and results appear in FIG. 8: (.largecircle.) control; (.quadrature.) 
c-raf plus c-myc sense; (.circle-solid.) c-raf antisense; (m) c-myc 
antisense, (.tangle-solidup.) c-tar and c-myc antisense. The results 
indicate that the c-raf and c-myc antisense oligonucleotides acted 
synergistically in inhibiting leukemic cell proliferation. 
EXAMPLE 5 
Effect of ras and c-myc Antisense Oligonucleotides on BV173 Cells 
The following phosphorothioate oligodeoxynucleotides (S! ODNs ) were 
synthesized: 
N-ras (AS) CACCACCAGT TTGTACTCAG TCAT (SEQ ID NO:7) 
N-ras (S) ATGACTGAGT ACAAACTGGT GGTG (SEQ ID NO:8) 
K-ras (AS) TACCACAAGT TTATATTCAG TCAT (SEQ ID NO:9) 
K-ras (S) ATGACTGAAT ATAAACTTGT GGTA (SEQ ID NO:10) 
H-ras (AS) CACCACCAGC TTATATTCCG TCAT (SEQ ID NO:11) 
H-ras (S) ATGACGGAAT ATAAGCTGGT GGTG (SEQ ID NO:12). The sequence of each 
antisense S!ODN was complementary to the first 24 nucleotides of the mRNA 
transcript of the indicated oncogene, beginning from the translation 
initiation codon. A cell proliferation assay according to the procedure of 
Example 4 was carried out, using ras and c-myc sense and antisense 
oligonucleotides. For ras oligonucleotide-treated cells, the cells 
received an equal mixture of a of the above N- , K-, and H-ras 
oligonucleotides. The oligonucleotide dosages and results appear in FIG. 
9: (.largecircle.) control; (.quadrature.) c-ras plus c-myc sense; 
(.circle-solid.) c-myc antisense; (.box-solid.) ras antisense, 
(.tangle-solidup.) ras and c-myc antisense. The results indicate that the 
c-ras and c-myc antisense oligonucleotides acted synergistically in 
inhibiting leukemic cell proliferation. 
Comparative Example 5 
Effect of ras and raf Antisense Oligonucleotides on BV173 Cells 
The procedure of Example 5 was repeated except that the c-raf 
oligonucleotides SEQ ID NO:5 (sense) and SEQ ID NO:6 (antisense) were 
substituted for the corresponding c-myc oligonucleotides. The results are 
shown in FIG. 10: (.largecircle.) control; (.quadrature.) c-raf plus ras 
sense; (.circle-solid.) c-tar antisense; (.box-solid.) ras antisense, 
(.tangle-solidup.) c-raf and ras antisense. The effect of antisense 
oligonucleotides to c-raf and ras, which are both cytoplasmic oncogenes, 
was not synergistic, suggesting that synergism requires antisense to at 
least one cytoplasmic oncogene and at least one nuclear oncogene. 
All references cited with respect to synthetic, preparative and analytical 
procedures are incorporated herein by reference. 
The present invention may be embodied in other specific forms without 
departing from the spirit or essential attributes thereof and, 
accordingly, reference should be made to the appended claims, rather than 
to the foregoing specification, as indication the scope of the invention. 
__________________________________________________________________________ 
SEQUENCE LISTING 
(1) GENERAL INFORMATION: 
(iii) NUMBER OF SEQUENCES: 55 
(2) INFORMATION FOR SEQ ID NO:1: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: 
CGCTGAAGGGCTTCTTCCTTATTGAT26 
(2) INFORMATION FOR SEQ ID NO:2: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: 
ATCAATAAGGAAGAAGCCCTTCAGCG26 
(2) INFORMATION FOR SEQ ID NO:3: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: 
TTGGTGAAGCTAACGTTGAGGGGCAT26 
(2) INFORMATION FOR SEQ ID NO:4: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: 
ATGCCCCTCAACGTTAGCTTCACCAA26 
(2) INFORMATION FOR SEQ ID NO:5: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: 
GGTGAGGGAGCGGGAGGCGGTCACAT26 
(2) INFORMATION FOR SEQ ID NO:6: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 26 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: 
ATGTGACCGCCTCCCGCTCCCTCACC26 
(2) INFORMATION FOR SEQ ID NO:7: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: 
CACCACCAGTTTGTACTCAGTCAT24 
(2) INFORMATION FOR SEQ ID NO:8: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: 
ATGACTGAGTACAAACTGGTGGTG24 
(2) INFORMATION FOR SEQ ID NO:9: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: 
TACCACAAGTTTATATTCAGTCAT24 
(2) INFORMATION FOR SEQ ID NO:10: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: 
ATGACTGAATATAAACTTGTGGTA24 
(2) INFORMATION FOR SEQ ID NO:11: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: 
CACCACCAGCTTATATTCCGTCAT24 
(2) INFORMATION FOR SEQ ID NO:12: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 24 Nucleotides 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single stranded 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: 
ATGACGGAATATAAGCTGGTGGTG24 
(2) INFORMATION FOR SEQ ID NO:13: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 3622 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: 
CCCGGGGAGGGGACCGGGGAACAGAGGGCCGAGAGGCGTGCGGCAGGGGGGAGGGTAGGA60 
GAAAGAAGGGCCCGACTGTAGGAGGGCAGCGGAGCATTACCTCATCCCGTGAGCCTCCGC120 
GGGCCCAGAGAAGAATCTTCTAGGGTGGAGTCTCCATGGTGACGGGCGGGCCCGCCCCCC180 
TGAGAGCGACGCGAGCCAATGGGAAGGCCTTGGGGTGACATCATGGGCTATTTTTAGGGG240 
TTGACTGGTAGCAGATAAGTGTTGAGCTCGGGCTGGATAAGGGCTCAGAGTTGCACTGAG300 
TGTGGCTGAAGCAGCGAGGCGGGAGTGGAGGTGCGCGGAGTCAGGCAGACAGACAGACAC360 
AGCCAGCCAGCCAGGTCGGCAGTATAGTCCGAACTGCAAATCTTATTTTCTTTTCACCTT420 
CTCTCTAACTGCCCAGAGCTAGCGCCTGTGGCTCCCGGGCTGGTGGTTCGGGAGTGTCCA480 
GAGAGCCTTGTCTCCAGCCGGCCCCGGGAGGAGAGCCCTGCTGCCCAGGCGCTGTTGACA540 
GCGGCGGAAAGCAGCGGTACCCCACGCGCCCGCCGGGGGACGTCGGCGAGCGGCTGCAGC600 
AGCAAAGAACTTTCCCGGCGGGGAGGACCGGAGACAAGTGGCAGAGTCCCGGAGCGAACT660 
TTTGCAAGCCTTTCCTGCGTCTTAGGCTTCTCCACGGCGGTAAAGACCAGAAGGCGGCGG720 
AGAGCCACGCAAGAGAAGAAGGACGTGCGCTCAGCTTCGCTCGCACCGGTTGTTGAACTT780 
GGGCGAGCGCGAGCCGCGGCTGCCGGGCGCCCCCTCCCCCTAGCAGCGGAGGAGGGGACA840 
AGTCGTCGGAGTCCGGGCGGCCAAGACCCGCCGCCGGCCGGCCACTGCAGGGTCCGCACT900 
GATCCGCTCCGCGGGGAGAGCCGCTGCTCTGGGAAGTGAGTTCGCCTGCGGACTCCGAGG960 
AACCGCTGCGCCCGAAGAGCGCTCAGTGAGTGACCGCGACTTTTCAAAGCCGGGTAGCGC1020 
GCGCGAGTCGACAAGTAAGAGTGCGGGAGGCATCTTAATTAACCCTGCGCTCCCTGGAGC1080 
GAGCTGGTGAGGAGGGCGCAGCGGGGACGACAGCCAGCGGGTGCGTGCGCTCTTAGAGAA1140 
ACTTTCCCTGTCAAAGGCTCCGGGGGGCGCGGGTGTCCCCCGCTTGCCAGAGCCCTGTTG1200 
CGGCCCCGAAACTTGTGCGCGCACGCCAAACTAACCTCACGTGAAGTGACGGACTGTTCT1260 
ATGACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAACGCCTCGTTCCTCCCG1320 
TCCGAGAGCGGACCTTATGGCTACAGTAACCCCAAGATCCTGAAACAGAGCATGACCCTG1380 
AACCTGGCCGACCCAGTGGGGAGCCTGAAGCCGCACCTCCGCGCCAAGAACTCGGACCTC1440 
CTCACCTCGCCCGACGTGGGGCTGCTCAAGCTGGCGTCGCCCGAGCTGGAGCGCCTGATA1500 
ATCCAGTCCAGCAACGGGCACATCACCACCACGCCGACCCCCACCCAGTTCCTGTGCCCC1560 
AAGAACGTGACAGATGAGCAGGAGGGGTTCGCCGAGGGCTTCGTGCGCGCCCTGGCCGAA1620 
CTGCACAGCCAGAACACGCTGCCCAGCGTCACGTCGGCGGCGCAGCCGGTCAACGGGGCA1680 
GGCATGGTGGCTCCCGCGGTAGCCTCGGTGGCAGGGGGCAGCGGCAGCGGCGGCTTCAGC1740 
GCCAGCCTGCACAGCGAGCCGCCGGTCTACGCAAACCTCAGCAACTTCAACCCAGGCGCG1800 
CTGAGCAGCGGCGGCGGGGCGCCCTCCTACGGCGCGGCCGGCCTGGCCTTTCCCGCGCAA1860 
CCCCAGCAGCAGCAGCAGCCGCCGCACCACCTGCCCCAGCAGATGCCCGTGCAGCACCCG1920 
CGGCTGCAGGCCCTGAAGGAGGAGCCTCAGACAGTGCCCGAGATGCCCGGCGAGACACCG1980 
CCCCTGTCCCCCATCGACATGGAGTCCCAGGAGCGGATCAAGGCGGAGAGGAAGCGCATG2040 
AGGAACCGCATCGCTGCCTCCAAGTGCCGAAAAAGGAAGCTGGAGAGAATCGCCCGGCTG2100 
GAGGAAAAAGTGAAAACCTTGAAAGCTCAGAACTCGGAGCTGGCGTCCACGGCCAACATG2160 
CTCAGGGAACAGGTGGCACAGCTTAAACAGAAAGTCATGAACCACGTTAACAGTGGGTGC2220 
CAACTCATGCTAACGCAGCAGTTGCAAACATTTTGAAGAGAGACCGTCGGGGGCTGAGGG2280 
GCAACGAAGAAAAAAAATAACACAGAGAGACAGACTTGAGAACTTGACAAGTTGCGACGG2340 
AGAGAAAAAAGAAGTGTCCGAGAACTAAAGCCAAGGGTATCCAAGTTGGACTGGGTTCGG2400 
TCTGACGGCGCCCCCAGTGTGCACGAGTGGGAAGGACTTGGTCGCGCCCTCCCTTGGCGT2460 
GGAGCCAGGGAGCGGCCGCCTGCGGGCTGCCCCGCTTTGCGGACGGGCTGTCCCCGCGCG2520 
AACGGAACGTTGGACTTTCGTTAACATTGACCAAGAACTGCATGGACCTAACATTCGATC2580 
TCATTCAGTATTAAAGGGGGGAGGGGGAGGGGGTTACAAACTGCAATAGAGACTGTAGAT2640 
TGCTTCTGTAGTACTCCTTAAGAACACAAAGCGGGGGGAGGGTTGGGGAGGGGCGGCAGG2700 
AGGGAGGTTTGTGAGAGCGAGGCTGAGCCTACAGATGAACTCTTTCTGGCCTGCTTTCGT2760 
TAACTGTGTATGTACATATATATATTTTTTAATTTGATTAAAGCTGATTACTGTCAATAA2820 
ACAGCTTCATGCCTTTGTAAGTTATTTCTTGTTTGTTTGTTTGGGTATCCTGCCCAGTGT2880 
TGTTTGTAAATAAGAGATTTGGAGCACTCTGAGTTTACCATTTGTAATAAAGTATATAAT2940 
TTTTTTATGTTTTGTTTCTGAAAATTCCAGAAAGGATATTTAAGAAAATACAATAAACTA3000 
TTGGAAAGTACTCCCCTAACCTCTTTTCTGCATCATCTGTAGATCCTAGTCTATCTAGGT3060 
GGAGTTGAAAGAGTTAAGAATGCTCGATAAAATCACTCTCAGTGCTTCTTACTATTAAGC3120 
AGTAAAAACTGTTCTCTATTAGACTTAGAAATAAATGTACCTGATGTACCTGATGCTATG3180 
TCAGGCTTCATACTCCACGCTCCCCCAGCGTATCTATATGGAATTGCTTACCAAAGGCTA3240 
GTGCGATGTTTCAGGAGGCTGGAGGAAGGGGGGTTGCAGTGGAGAGGGACAGCCCACTGA3300 
GAAGTCAAACATTTCAAAGTTTGGATTGCATCAAGTGGCATGTGCTGTGACCATTTATAA3360 
TGTTAGAAATTTTACAATAGGTGCTTATTCTCAAAGCAGGAATTGGTGGCAGATTTTACA3420 
AAAGATGTATCCTTCCAATTTGGAATCTTCTCTTTGACAATTCCTAGATAAAAAGATGGC3480 
CTTTGTCTTATGAATATTTATAACAGCATTCTGTCACAATAAATGTATTCAAATACCAAT3540 
AACAGATCTTGAATTGCTTCCCTTTACTACTTTTTTGTTCCCAAGTTATATACTGAAGTT3600 
TTTATTTTTAGTTGCTGAGGTT3622 
(2) INFORMATION FOR SEQ ID NO:14: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 6453 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: 
GGATCCCAGCCTTTCCCCAGCCCGTAGCCCCGGGACCTCCGCGGTGGGCGGCGCCGCGCT60 
GCCGGCGCAGGGAGGGCCTCTGGTGCACCGGCACCGCTGAGTCGGGTTCTCTCGCCGGCC120 
TGTTCCCGGGAGAGCCCGGGGCCCTGCTCGGAGATGCCGCCCCGGGCCCCCAGACACCGG180 
CTCCCTGGCCTTCCTCGAGCAACCCCGAGCTCGGCTCCGGTCTCCAGCCAAGCCCAACCC240 
CGAGAGGCCGCGGCCCTACTGGCTCCGCCTCCCGCGTTGCTCCCGGAAGCCCCGCCCGAC300 
CGCGGCTCCTGACAGACGGGCCGCTCAGCCAACCGGGGTGGGGCGGGGCCCGATGGCGCG360 
CAGCCAATGGTAGGCCGCGCCTGGCAGACGGACGGGCGCGGGGCGGGGCGTGCGCAGGCC420 
CGCCCGAGTCTCCGCCGCCCGTGCCCTGCGCCCGCAACCCGAGCCGCACCCGCCGCGGAC480 
GGAGCCCATGCGCGGGGCGAACCGCGCGCCCCCGCCCCCGCCCCGCCCCGGCCTCGGCCC540 
CGGCCCTGGCCCCGGGGGCAGTCGCGCCTGTGAACGGTGAGTGCGGGCAGGGATCGGCCG600 
GGCCGCGCGCCCTCCTCGCCCCCAGGCGGCAGCAATACGCGCGGCGCGGGCCGGGGGCGC660 
GGGGCCGGCGGGCGTAAGCGGCGGCGGCGGCGGCGGGTGGGTGGGGCCGGGCGGGGCCCG720 
CGGGCACAGGTGAGCGGGCGTCGGGGGCTGCGGCGGGCGGGGGCCCCTTCCTCCCTGGGG780 
CCTGCGGGAATCCGGGCCCCACCCGTGGCCTCGCGCTGGGCACGGTCCCCACGCCGGCGT840 
ACCCGGGAGCCTCGGGCCCGGCGCCCTCACACCCGGGGGCGTCTGGGAGGAGGCGGCCGC900 
GGCCACGGCACGCCCGGGCACCCCCGATTCAGCATCACAGGTCGCGGACCAGGCCGGGGG960 
CCTCAGCCCCAGTGCCTTTTCCCTCTCCGGGTCTCCCGCGCCGCTTCTCGGCCCCTTCCT1020 
GTCGCTCAGTCCCTGCTTCCCAGGAGCTCCTCTGTCTTCTCCAGCTTTCTGTGGCTGAAA1080 
GATGCCCCCGGTTCCCCGCCGGGGGTGCGGGGCGCTGCCCGGGTCTGCCCTCCCCTCGGC1140 
GGCGCCTAGTACGCAGTAGGCGCTCAGCAAATACTTGTCGGAGGCACCAGCGCCGCGGGG1200 
CCTGCAGGCTGGCACTAGCCTGCCCGGGCACGCCGTGGCGCGCTCCGCCGTGGCCAGACC1260 
TGTTCTGGAGGACGGTAACCTCAGCCCTCGGGCGCCTCCCTTTAGCCTTTCTGCCGACCC1320 
AGCAGCTTCTAATTTGGGTGCGTGGTTGAGAGCGCTCAGCTGTCAGCCCTGCCTTTGAGG1380 
GCTGGGTCCCTTTTCCCATCACTGGGTCATTAAGAGCAAGTGGGGGCGAGGCGACAGCCC1440 
TCCCGCACGCTGGGTTGCAGCTGCACAGGTAGGCACGCTGCAGTCCTTGCTGCCTGGCGT1500 
TGGGGCCCAGGGACCGCTGTGGGTTTGCCCTTCAGATGGCCCTGCCAGCAGCTGCCCTGT1560 
GGGGCCTGGGGCTGGGCCTGGGCCTGGCTGAGCAGGGCCCTCCTTGGCAGGTGGGGCAGG1620 
AGACCCTGTAGGAGGACCCCGGGCCGCAGGCCCCTGAGGAGCGATGACGGAATATAAGCT1680 
GGTGGTGGTGGGCGCCGGCGGTGTGGGCAAGAGTGCGCTGACCATCCAGCTGATCCAGAA1740 
CCATTTTGTGGACGAATACGACCCCACTATAGAGGTGAGCCTAGCGCCGCCGTCCAGGTG1800 
CCAGCAGCTGCTGCGGGCGAGCCCAGGACACAGCCAGGATAGGGCTGGCTGCAGCCCCTG1860 
GTCCCCTGCATGGTGCTGTGGCCCTGTCTCCTGCTTCCTCTAGAGGAGGGGAGTCCCTCG1920 
TCTCAGCACCCCAGGAGAGGAGGGGGCATGAGGGGCATGAGAGGTACCAGGGAGAGGCTG1980 
GCTGTGTGAACTCCCCCCACGGAAGGTCCTGAGGGGGTCCCTGAGCCCTGTCCTCCTGCA2040 
GGATTCCTACCGGAAGCAGGTGGTCATTGATGGGGAGACGTGCCTGTTGGACATCCTGGA2100 
TACCGCCGGCCAGGAGGAGTACAGCGCCATGCGGGACCAGTACATGCGCACCGGGGAGGG2160 
CTTCCTGTGTGTGTTTGCCATCAACAACACCAAGTCTTTTGAGGACATCCACCAGTACAG2220 
GTGAACCCCGTGAGGCTGGCCCGGGAGCCCACGCCGCACAGGTGGGGCCAGGCCGGCTGC2280 
GTCCAGGCAGGGGCCTCCTGTCCTCTCTGCGCATGTCCTGGATGCCGCTGCGCCTGCAGC2340 
CCCCGTAGCCAGCTCTCGCTTTCCACCTCTCAGGGAGCAGATCAAACGGGTGAAGGACTC2400 
GGATGACGTGCCCATGGTGCTGGTGGGGAACAAGTGTGACCTGGCTGCACGCACTGTGGA2460 
ATCTCGGCAGGCTCAGGACCTCGCCCGAAGCTACGGCATCCCCTACATCGAGACCTCGGC2520 
CAAGACCCGGCAGGTGAGGCAGCTCTCCACCCCACAGCTAGCCAGGGACCCGCCCCGCCC2580 
CGCCCCAGCCAGGGAGCAGCACTCACTGACCCTCTCCCTTGACACAGGGCAGCCGCTCTG2640 
GCTCTAGCTCCAGCTCCGGGACCCTCTGGGACCCCCCGGGACCCATGTGACCCAGCGGCC2700 
CCTCGCACTGTAGGTCTCCCGGGACGGCAGGGCAGTGAGGGAGGCGAGGGCCGGGGTCTG2760 
GGCTCACGCCCTGCAGTCCTGGGCCGACACAGCTCCGGGGAAGGCGGAGGTCCTTGGGGA2820 
GAGCTGCCCTGAGCCAGGCCGGAGCGGTGACCCTGGGGCCCGGCCCCTCTTGTCCCCAGA2880 
GTGTCCCACGGGCACCTGTTGGTTCTGAGTCTTAGTGGGGCTACTGGGGACACGGGCCGT2940 
AGCTGAGTCGAGAGCTGGGTGCAGGGTGGTCAAACCCTGGCCAGACCTGGAGTTCAGGAG3000 
GGCCCCGGGCCACCCTGACCTTTGAGGGGCTGCTGTAGCATGATGCGGGTGGCCCTGGGC3060 
ACTTCGAGATGGCCAGAGTCCAGCTTCCCGTGTGTGTGGTGGGCCTGGGGAAGTGGCTGG3120 
TGGAGTCGGGAGCTTCGGGCCAGGCAAGGCTTGATCCCACAGCAGGGAGCCCCTCACCCA3180 
GGCAGGCGGCCACAGGCCGGTCCCTCCTGATCCCATCCCTCCTTTCCCAGGGAGTGGAGG3240 
ATGCCTTCTACACGTTGGTGCGTGAGATCCGGCAGCACAAGCTGCGGAAGCTGAACCCTC3300 
CTGATGAGAGTGGCCCCGGCTGCATGAGCTGCAAGTGTGTGCTCTCCTGACGCAGGTGAG3360 
GGGGACTCCCAGGGCGGCCGCCACGCCCACCGGATGACCCCGGCTCCCCGCCCCTGCCGG3420 
TCTCCTGGCCTGCGGTCAGCAGCCTCCCTTGTGCCCCGCCCAGCACAAGCTCAGGACATG3480 
GAGGTGCCGGATGCAGGAAGGAGGTGCAGACGGAAGGAGGAGGAAGGAAGGACGGAAGCA3540 
AGGAAGGAAGGAAGGGCTGCTGGAGCCCAGTCACCCCGGGACCGTGGGCCGAGGTGACTG3600 
CAGACCCTCCCAGGGAGGCTGTGCACAGACTGTCTTGAACATCCCAAATGCCACCGGAAC3660 
CCCAGCCCTTAGCTCCCCTCCCAGGCCTCTGTGGGCCCTTGTCGGGCACAGATGGGATCA3720 
CAGTAAATTATTGGATGGTCTTGATCTTGGTTTTCGGCTGAGGGTGGGACACGGTGCGCG3780 
TGTGGCCTGGCATGAGGTATGTCGGAACCTCAGGCCTGTCCAGCCCTGGGCTCTCCATAG3840 
CCTTTGGGAGGGGGAGGTTGGGAGAGGCCGGTCAGGGGTCTGGGCTGTGGTGCTCTCTCC3900 
TCCCGCCTGCCCCAGTGTCCACGGCTTCTGGCAGAGAGCTCTGGACAAGCAGGCAGATCA3960 
TAAGGACAGAGAGCTTACTGTGCTTCTACCAACTAGGAGGGCGTCCTGGTCCTCCAGAGG4020 
GAGGTGGTTTCAGGGGTTGGGGATCTGTGCCGGTGGCTCTGGTCTCTGCTGGGAGCCTTC4080 
TTGGCGGTGAGAGGCATCACCTTTCCTGACTTGCTCCCAGCGTGAAATGCACCTGCCAAG4140 
AATGGCAGACATAGGGACCCCGCCTCCTGGGCCTTCACATGCCCAGTTTTCTTCGGCTCT4200 
GTGGCCTGAAGCGGTCTGTGGACCTTGGAAGTAGGGCTCCAGCACCGACTGGCCTCAGGC4260 
CTCTGCCTCATTGGTGGTCGGGTAGCGGCCAGTAGGGCGTGGGAGCCTGGCCATCCCTGC4320 
CTCCTGGAGTGGACGAGGTTGGCAGCTGGTCCGTCTGCTCCTGCCCCACTCTCCCCCGCC4380 
CCTGCCCTCACCCTACCCTTGCCCCACGCCTGCCTCATGGCTGGTTGCTCTTGGAGCCTG4440 
GTAGTGTCACTGGCTCAGCCTTGCTGGGTATACACAGGCTCTGCCACCCACTCTGCTCCA4500 
AGGGGCTTGCCCTGCCTTGGGCCAAGTTCTAGGTCTGGCCACAGCCACAGACAGCTCAGT4560 
CCCCTGTGTGGTCATCCTGGCTTCTGCTGGGGGCCCACAGCGCCCCTGGTGCCCCTCCCC4620 
TCCCAGGGCCCGGGTTGAGGCTGGGCCAGGCCCTCTGGGACGGGGACTTGTGCCCTGTCA4680 
GGGTTCCCTATCCCTGAGGTTGGGGGAGAGCTAGCAGGGCATGCCGCTGGCTGGCCAGGG4740 
CTGCAGGGACACTCCCCCTTTTGTCCAGGGAATACCACACTCGCCCTTCTCTCCAGCGAA4800 
CACCACACTCGCCCTTCTCTCCAGGGGACGCCACACTCCCCCTTCTGTCCAGGGGACGCC4860 
ACACTCCCCCTTCTCTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACAC4920 
TCGCCCTTCTCTCCAGGGGACGCCACACTCGCCCTTCTGTCCAGGGGACGCCACACTCGC4980 
CCTTCTCTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACACTCCCCCTT5040 
CTGTCCAGGGGACGCCACACTCCCCCTTCTCTCCAGGGGACGCCACACTCCCCCTTCTCT5100 
CCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACACTCCCCCTTCTGTCCAG5160 
GGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGA5220 
CGCCACACTCCCCCTTCTCTCCAGGGGACGCCACACTCCCCCTTCTCTCCAGGGGACGCC5280 
ACACTCCCCCTTCTGTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACAC5340 
TCCCCCTTCTCTCCAGGGGACGCCACACTCCCCCTTCTCTCCAGGGGACGCCACACTCCC5400 
CCTTCTGTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACACTCGCCCTT5460 
CTCTCCAGGGGACGCCACACTCGCCCTTCTCTCCAGGGGACGCCACACTTGCCCTTCTGT5520 
CCAGGGAATGCCACACTCCCCCTTCTCCCCAGCAGCCTCCGAGTGACCAGCTTCCCCATC5580 
GATAGACTTCCCGAGGCCAGGAGCCCTCTAGGGCTGCCGGGTGCCACCCTGGCTCCTTCC5640 
ACACCGTGCTGGTCACTGCCTGCTGGGGGCGTCAGATGCAGGTGACCCTGTGCAGGAGGT5700 
ATCTCTGGACCTGCCTCTTGGTCATTACGGGGCTGGGCAGGGCCTGGTATCAGGGCCCCG5760 
CTGGGGTTGCAGGGCTGGGCCTGTGCTGTGGTCCTGGGGTGTCCAGGACAGACGTGGAGG5820 
GGTCAGGGCCCAGCACCCCTGCTCCATGCTGAACTGTGGGAAGCATCCAGGTCCCTGGGT5880 
GGCTTCAACAGGAGTTCCAGCACGGGAACCACTGGACAACCTGGGGTGTGTCCTGATCTG5940 
GGGACAGGCCAGCCACACCCCGAGTCCTAGGGACTCCAGAGAGCAGCCCACTGCCCTGGG6000 
CTCCACGGAAGCCCCCTCATGCCGCTAGGCCTTGGCCTCGGGGACAGCCCAGCTAGGCCA6060 
GTGTGTGGCAGGACCAGGCCCCCATGTGGGAGCTGACCCCTTGGGATTCTGGAGCTGTGC6120 
TGATGGGCAGGGGAGAGCCAGCTCCTCCCCTTGAGGGAGGGTCTTGATGCCTGGGGTTAC6180 
CCGCAGAGGCCTGGGTGCCGGGACGCTCCCCGGTTTGGCTGAAAGGAAAGCAGATGTGGT6240 
CAGCTTCTCCACTGAGCCCATCTGGTCTTCCCGGGGCTGGGCCCCATAGATCTGGGTCCC6300 
TGTGTGGCCCCCCTGGTCTGATGCCGAGGATACCCCTGCAAACTGCCAATCCCAGAGGAC6360 
AAGACTGGGAAGTCCCTGCAGGGAGAGCCCATCCCCGCACCCTGACCCACAAGAGGGACT6420 
CCTGCTGCCCACCAGGCATCCCTCCAGGGATCC6453 
(2) INFORMATION FOR SEQ ID NO:15: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 5775 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: 
TCCTAGGCGGCGGCCGCGGCGGCGGAGGCAGCAGCGGCGGCGGCAGTGGCGGCGGCGAAG60 
GTGGCGGCGGCTCGGCCAGTACTCCCGGCCCCCGCCATTTCGGACTGGGAGCGAGCGCGG120 
CGCAGGCACTGAAGGCGGCGGCGGGGCCAGAGGCTCAGCGGCTCCCAGGTGCGGGAGAGA180 
GGCCTGCTGAAAATGACTGAATATAAACTTGTGGTAGTTGGAGCTTGTGGCGTAGGCAAG240 
AGTGCCTTGACGATACAGCTAATTCAGAATCATTTTGTGGACGAATATGATCCAACAATA300 
GAGGATTCCTACAGGAAGCAAGTAGTAATTGATGGAGAAACCTGTCTCTTGGATATTCTC360 
GACACAGCAGGTCAAGAGGAGTACAGTGCAATGAGGGACCAGTACATGAGGACTGGGGAG420 
GGCTTTCTTTGTGTATTTGCCATAAATAATACTAAATCATTTGAAGATATTCACCATTAT480 
AGAGAACAAATTAAAAGAGTTAAGGACTCTGAAGATGTACCTATGGTCCTAGTAGGAAAT540 
AAATGTGATTTGCCTTCTAGAACAGTAGACACAAAACAGGCTCAGGACTTAGCAAGAAGT600 
TATGGAATTCCTTTTATTGAAACATCAGCAAAGACAAGACAGGGTGTTGATGATGCCTTC660 
TATACATTAGTTCGAGAAATTCGAAAACATAAAGAAAAGATGAGCAAAGATGGTAAAAAG720 
AAGAAAAAGAAGTCAAAGACAAAGTGTGTAATTATGTAAATACAATTTGTACTTTTTTCT780 
TAAGGCATACTAGTACAAGTGGTAATTTTTGTACATTACACTAAATTATTAGCATTTGTT840 
TTAGCATTACCTAATTTTTTTCCTGCTCCATGCAGACTGTTAGCTTTTACCTTAAATGCT900 
TATTTTAAAATGACAGTGGAAGTTTTTTTTTCCTCGAAGTGCCAGTATTCCCAGAGTTTT960 
GGTTTTTGAACTAGCAATGCCTGTGAAAAAGAAACTGAATACCTAAGATTTCTGTCTTGG1020 
GGTTTTTGGTGCATGCAGTTGATTACTTCTTATTTTTCTTACCAAGTGTGAATGTTGGTG1080 
TGAAACAAATTAATGAAGCTTTTGAATCATCCCTATTCTGTGTTTTATCTAGTCACATAA1140 
ATGGATTAATTACTAATTTCAGTTGAGACCTTCTAATTGGTTTTTACTGAAACATTGAGG1200 
GACACAAATTTATGGGCTTCCTGATGATGATTCTTCTAGGCATCATGTCCTATAGTTTGT1260 
CATCCCTGATGAATGTAAAGTTACACTGTTCACAAAGGTTTTGTCTCCTTTCCACTGCTA1320 
TTAGTCATGGTCACTCTCCCCAAAATATTATATTTTTTCTATAAAAAGAAAAAAATGGAA1380 
AAAAATTACAAGGCAATGGAAACTATTATAAGGCCATTTCCTTTTCACATTAGATAAATT1440 
ACTATAAAGACTCCTAATAGCTTTTTCCTGTTAAGGCAGACCCAGTATGAATGGGATTAT1500 
TATAGCAACCATTTTGGGGCTATATTTACATGCTACTAAATTTTTATAATAATTGAAAAG1560 
ATTTTAACAAGTATAAAAAAATTCTCATAGGAATTAAATGTAGTCTCCCTGTGTCAGACT1620 
GCTCTTTCATAGTATAACTTTAAATCTTTTCTTCAACTTGAGTCTTTGAAGATAGTTTTA1680 
ATTCTGCTTGTGACATTAAAAGATTATTTGGGCCAGTTATAGCTTATTAGGTGTTGAAGA1740 
GACCAAGGTTGCAAGCCAGGCCCTGTGTGAACCTTGAGCTTTCATAGAGAGTTTCACAGC1800 
ATGGACTGTGTGCCCCACGGTCATCCGAGTGGTTGTACGATGCATTGGTTAGTCAAAAAT1860 
GGGGAGGGACTAGGGCAGTTTGGATAGCTCAACAAGATACAATCTCACTCTGTGGTGGTC1920 
CTGCTGACAAATCAAGAGCATTGCTTTTGTTTCTTAAGAAAACAAACTCTTTTTTAAAAA1980 
TTACTTTTAAATATTAACTCAAAAGTTGAGATTTTGGGGTGGTGGTGTGCCAAGACATTA2040 
ATTTTTTTTTTAAACAATGAAGTGAAAAAGTTTTACAATCTCTAGGTTTGGCTAGTTCTC2100 
TTAACACTGGTTAAATTAACATTGCATAAACACTTTTCAAGTCTGATCCATATTTAATAA2160 
TGCTTTAAAATAAAAATAAAAACAATCCTTTTGATAAATTTAAAATGTTACTTATTTTAA2220 
AATAAATGAAGTGAGATGGCATGGTGAGGTGAAAGTATCACTGGACTAGGTTGTTGGTGA2280 
CTTAGGTTCTAGATAGGTGTCTTTTAGGACTCTGATTTTGAGGACATCACTTACTATCCA2340 
TTTCTTCATGTTAAAAGAAGTCATCTCAAACTCTTAGTTTTTTTTTTTTACACTATGTGA2400 
TTTATATTCCATTTACATAAGGATACACTTATTTGTCAAGCTCAGCACAATCTGTAAATT2460 
TTTAACCTATGTTACACCATCTTCAGTGCCAGTCTTGGGCAAAATTGTGCAAGAGGTGAA2520 
GTTTATATTTGAATATCCATTCTCGTTTTAGGACTCTTCTTCCATATTAGTGTCATCTTG2580 
CCTCCCTACCTTCCACATGCCCCATGACTTGATGCAGTTTTAATACTTGTAATTCCCCTA2640 
ACCATAAGATTTACTGCTGCTGTGGATATCTCCATGAAGTTTTCCCACTGAGTCACATCA2700 
GAAATGCCCTACATCTTATTTTCCTCAGGGCTCAAGAGAATCTGACAGATACCATAAAGG2760 
GATTTGACCTAATCACTAATTTTCAGGTGGTGGCTGATGCTTTGAACATCTCTTTGCTGC2820 
CCAATCCATTAGCGACAGTAGGATTTTTCAACCCTGGTATGAATAGACAGAACCCTATCC2880 
AGTGGAAGGAGAATTTAATAAAGATAGTGCAGAAAGAATTCCTTAGGTAATCTATAACTA2940 
GGACTACTCCTGGTAACAGTAATACATTCCATTGTTTTAGTAACCAGAAATCTTCATGCA3000 
ATGAAAAATACTTTAATTCATGAAGCTTACTTTTTTTTTTTTGGTGTCAGAGTCTCGCTC3060 
TTGTCACCCAGGCTGGAATGCAGTGGCGCCATCTCAGCTCACTGCAACCTTCCATCTTCC3120 
CAGGTTCAAGCGATTCTCGTGCCTCGGCCTCCTGAGTAGCTGGGATTACAGGCGTGTGCA3180 
CTACACTCAACTAATTTTTGTATTTTTAGGAGAGACGGGGTTTCACCTGTTGGCCAGGCT3240 
GGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTTGGCCTCATAAACCTGTTTTGCA3300 
GAACTCATTTATTCAGCAAATATTTATTGAGTGCCTACCAGATGCCAGTCACCGCACAAG3360 
GCACTGGGTATATGGTATCCCCAAACAAGAGACATAATCCCGGTCCTTAGGTACTGCTAG3420 
TGTGGTCTGTAATATCTTACTAAGGCCTTTGGTATACGACCCAGAGATAACACGATGCGT3480 
ATTTTAGTTTTGCAAAGAAGGGGTTTGGTCTCTGTGCCAGCTCTATAATTGTTTTGCTAC3540 
GATTCCACTGAAACTCTTCGATCAAGCTACTTTATGTAAATCACTTCATTGTTTTAAAGG3600 
AATAAACTTGATTATATTGTTTTTTTATTTGGCATAACTGTGATTCTTTTAGGACAATTA3660 
CTGTACACATTAAGGTGTATGTCAGATATTCATATTGACCCAAATGTGTAATATTCCAGT3720 
TTTCTCTGCATAAGTAATTAAAATATACTTAAAAATTAATAGTTTTATCTGGGTACAAAT3780 
AAACAGTGCCTGAACTAGTTCACAGACAAGGGAAACTTCTATGTAAAAATCACTATGATT3840 
TCTGAATTGCTATGTGAAACTACAGATCTTTGGAACACTGTTTAGGTAGGGTGTTAAGAC3900 
TTGACACAGTACCTCGTTTCTACACAGAGAAAGAAATGGCCATACTTCAGGAACTGCAGT3960 
GCTTATGAGGGGATATTTAGGCCTCTTGAATTTTTGATGTAGATGGGCATTTTTTTAAGG4020 
TAGTGGTTAATTACCTTTATGTGAACTTTGAATGGTTTAACAAAAGATTTGTTTTTGTAG4080 
AGATTTTAAAGGGGGAGAATTCTAGAAATAAATGTTACCTAATTATTACAGCCTTAAAGA4140 
CAAAAATCCTTGTTGAAGTTTTTTTAAAAAAAGACTAAATTACATAGACTTAGGCATTAA4200 
CATGTTTGTGGAAGAATATAGCAGACGTATATTGTATCATTTGAGTGAATGTTCCCAAGT4260 
AGGCATTCTAGGCTCTATTTAACTGAGTCACACTGCATAGGAATTTAGAACCTAACTTTT4320 
ATAGGTTATCAAAACTGTTGTCACCATTGCACAATTTTGTCCTAATATATACATAGAAAC4380 
TTTGTGGGGCATGTTAAGTTACAGTTTGCACAAGTTCATCTCATTTGTATTCCATTGATT4440 
TTTTTTTTTCTTCTAAACATTTTTTCTTCAAAACAGTATATATAACTTTTTTTAGGGGAT4500 
TTTTTTTAGACAGCAAAAAACTATCTGAAGATTTCCATTTGTCAAAAAGTAATGATTTCT4560 
TGATAATTGTGTAGTGAATGTTTTTTAGAACCCAGCAGTTACCTTGAAAGCTGAATTTAT4620 
ATTTAGTAACTTCTGTGTTAATACTGGATAGCATGAATTCTGCATTGAGAAACTGAATAG4680 
CTGTCATAAAATGCTTTCTTTCCTAAAGAAAGATACTCACATGAGTTCTTGAAGAATAGT4740 
CATAACTAGATTAAGATCTGTGTTTTAGTTTAATAGTTTGAAGTGCCTGTTTGGGATAAT4800 
GATAGGTAATTTAGATGAATTTAGGGGAAAAAAAAGTTATCTGCAGTTATGTTGAGGGCC4860 
CATCTCTCCCCCCACACCCCCACAGAGCTAACTGGGTTACAGTGTTTTATCCGAAAGTTT4920 
CCAATTCCACTGTCTTGTGTTTTCATGTTGAAAATACTTTTGCATTTTTCCTTTGAGTGC4980 
CAATTTCTTACTAGTACTATTTCTTAATGTAACATGTTTACCTGGCCTGTCTTTTAACTA5040 
TTTTTGTATAGTGTAAACTGAAACATGCACATTTTGTACATTGTGCTTTCTTTTGTGGGT5100 
CATATGCAGTGTGATCCAGTTGTTTTCCATCATTTGGTTGCGCTGACCTAGGAATGTTGG5160 
TCATATCAAACATTAAAAATGACCACTCTTTTAATGAAATTAACTTTTAAATGTTTATAG5220 
GAGTATGTGCTGTGAAGTGATCTAAAATTTGTAATATTTTTGTCATGAACTGTACTACTC5280 
CTAATTATTGTAATGTAATAAAAATAGTTACAGTGACTATGAGTGTGTATTTATTCATGC5340 
AAATTTGAACTGTTTGCCCCGAAATGGATATGGATACTTTATAAGCCATAGACACTATAG5400 
TATACCAGTGAATCTTTTATGCAGCTTGTTAGAAGTATCCTTTTATTTTCTAAAAGGTGC5460 
TGTGGATATTATGTAAAGGCGTGTTTGCTTAAACAATTTTCCATATTTAGAAGTAGATGC5520 
AAAACAAATCTGCCTTTATGACAAAAAAATAGGATAACATTATTTATTTATTTCCTTTTA5580 
TCAATAAGGTAATTGATACACAACAGGTGACTTGGTTTTAGGCCCAAAGGTAGCAGCAGC5640 
AACATTAATAATGGAAATAATTGAATAGTTAGTTATGTATGTTAATGCCAGTCACCAGCA5700 
GGCTATTTCAAGGTCAGAAGTAATGACTCCATACATATTATTTATTTCTATAACTACATT5760 
TAAATCATTACCAGG5775 
(2) INFORMATION FOR SEQ ID NO:16: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2436 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: 
CTGCAGCTTCTAGGACCCGGTTTCTTTTACTGATTTAAAAACAAAACAAAAAAAAATAAA60 
AAAGTTGTGCCTGAAATGAATCTTGTTTTTTTTTTATAAGTAGCCGCCTGGTTACTGTGT120 
CCTGTAAAATACAGACATTGACCCTTGGTGTAGCTTCTGTTCAACTTTATATCACGGGAA180 
TGGATGGGTCTGATTTCTTGGCCCTCTTCTTGAATTGGCCATATACAGGGTCCCTGGCCA240 
GTGGACTGAAGGCTTTGTCTAAGATGACAAGGGTCAGCTCAGGGGATGTGGGGGAGGGCG300 
GTTTTATCTTCCCCCTTGTCGTTTGAGGTTTTGATCTCTGGGTAAAGAGGCCGTTTATCT360 
TTGTAAACACGAAACATTTTTGCTTTCTCCAGTTTTCTGTTAATGGCGAAAGAATGGAAG420 
CGAATAAAGTTTTACTGATTTTTGAGACACTAGCACCTAGCGCTTTCATTATTGAAACGT480 
CCCGTGTGGGAGGGGCGGGTCTGGGTGCGGCTGCCGCATGACTCGTGGTTCGGAGGCCCA540 
CGTGGCCGGGGCGGGGACTCAGGCGCCTGGCAGCCGACTGATTACGTAGCGGGCGGGGCC600 
GGAAGTGCCGCTCCTTGGTGGGGGCTGTTCATGGCGGTTCCGGGGTCTCCAACATTTTTC660 
CCGGTCTGTGGTCCTAAATCTGTCCAAAGCAGAGGCAGTGGAGCTTGAGGTTCTTGCTGG720 
TGTGAAATGACTGAGTACAAACTGGTGGTGGTTGGAGCAGGTGGTGTTGGGAAAAGCGCA780 
CTGACAATCCAGCTAATCCAGAACCACTTTGTAGATGAATATGATCCCACCATAGAGGAT840 
TCTTACAGAAAACAAGTGGTTATAGATGGTGAAACCTGTTTGTTGGACATACTGGATACA900 
GCTGGACAAGAAGAGTACAGTGCCATGAGAGACCAATACATGAGGACAGGCGAAGGCTTC960 
CTCTGTGTATTTGCCATCAATAATAGCAAGTCATTTGCGGATATTAACCTCTACAGGGAG1020 
CAGATTAAGCGAGTAAAAGACTCGGATGATGTACCTATGGTGCTAGTGGGAAACAAGTGT1080 
GATTTGCCAACAAGGACAGTTGATACAAAACAAGCCCACGAACTGGCCAAGAGTTACGGG1140 
ATTCCATTCATTGAAACCTCAGCCAAGACCAGACAGGGTGTTGAAGATGCTTTTTACACA1200 
CTGGTAAGAGAAATACGCCAGTACCGAATGAAAAAACTCAACAGCAGTGATGATGGGACT1260 
CAGGGTTGTATGGGATTGCCATGTGTGGTGATGTAACAAGATACTTTTAAAGTTTTGTCA1320 
GAAAAGAGCCACTTTCAAGCTGCACTGACACCCTGGTCCTGACTTCCTGGAGGAGAAGTA1380 
TTCCTGTTGCTGTCTTCAGTCTCACAGAGAAGCTCCTGCTACTTCCCCAGCTCTCAGTAG1440 
TTTAGTACAATAATCTCTATTTGAGAAGTTCTCAGAATAACTACCTCCTCACTTGGCTGT1500 
CTGACCAGAGAATGCACCTCTTGTTACTCCCTGTTATTTTTCTGCCCTGGGTTCTTCCAC1560 
AGCACAAACACACCTCAACACACCTCTGCCACCCCAGGTTTTTCATCTGAAAAGCAGTTC1620 
ATGTCTGAAACAGAGAACCAAACCGCAAACGTGAAATTCTATTGAAAACAGTGTCTTGAG1680 
CTCTAAAGTAGCAACTGCTGGTGATTTTTTTTTTCTTTTTACTGTTGAACTTAGAACTAT1740 
GCCTAATTTTTGGAGAAATGTCATAAATTACTGTTTTGCCAAGAATATAGTTATTATTGC1800 
TGTTTGGTTTGTTTATAATGTTATCGGCTCTATTCTCTAAACTGGCATCTGCTCTAGATT1860 
CATAAATACAAAAATGAATACTGAATTTTGAGTCTATCCTAGTCTTCACAACTTTGACGT1920 
AATTAAATCCAACTTTTCACAGTGAAGTGCCTTTTTCCTAGAAGTGGTTTGTAGACTCCT1980 
TTATAATATTTCAGTGGAATAGATGTCTCAAAAATCCTTATGCATGAAATGAATGTCTGA2040 
GATACGTCTGTGACTTATCTACCATTGAAGGAAAGCTATATCTATTTGAGAGCAGATGCC2100 
ATTTTGTACATGTATGAAATTGGTTTTCCAGAGGCCTGTTTTGGGGCTTTCCCAGGAGAA2160 
AGATGAAACTGAAAGCATATGAATAATTTCACTTAATAATTTTTACCTAATCTCCACTTT2220 
TTTCATAGGTTACTACCTATACAATGTATGTAATTTGTTTCCCCTAGCTTACTGATAAAC2280 
CTAATATTCAATGAACTTCCATTTGTATTCAAATTTGTGTCATACCAGAAAGCTCTACAT2340 
TTGCAGATGTTCAAATATTGTAAAACTTTGGTGCATTGTTATTTAATAGCTGTGATCAGT2400 
GATTTTCAAACCTCAAATATAGTATATTAACAAATT2436 
(2) INFORMATION FOR SEQ ID NO:17: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2977 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: 
CCGAATGTGACCGCCTCCCGCTCCCTCACCCGCCGCGGGGAGGAGGAGCGGGCGAGAAGC60 
TGCCGCCGAACGACAGGACGTTGGGGCGGCCTGGCTCCCTCAGGTTTAAGAATTGTTTAA120 
GCTGCATCAATGGAGCACATACAGGGAGCTTGGAAGACGATCAGCAATGGTTTTGGATTC180 
AAAGATGCCGTGTTTGATGGCTCCAGCTGCATCTCTCCTACAATAGTTCAGCAGTTTGGC240 
TATCAGCGCCGGGCATCAGATGATGGCAAACTCACAGATCCTTCTAAGACAAGCAACACT300 
ATCCGTGTTTTCTTGCCGAACAAGCAAAGAACAGTGGTCAATGTGCGAAATGGAATGAGC360 
TTGCATGACTGCCTTATGAAAGCACTCAAGGTGAGGGGCCTGCAACCAGAGTGCTGTGCA420 
GTGTTCAGACTTCTCCACGAACACAAAGGTAAAAAAGCACGCTTAGATTGGAATACTGAT480 
GCTGCGTCTTTGATTGGAGAAGAACTTCAAGTAGATTTCCTGGATCATGTTCCCCTCACA540 
ACACACAACTTTGCTCGGAAGACGTTCCTGAAGCTTGCCTTCTGTGACATCTGTCAGAAA600 
TTCCTGCTCAATGGATTTCGATGTCAGACTTGTGGCTACAAATTTCATGAGCACTGTAGC660 
ACCAAAGTACCTACTATGTGTGTGGACTGGAGTAACATCAGACAACTCTTATTGTTTCCA720 
AATTCCACTATTGGTGATAGTGGAGTCCCAGCACTACCTTCTTTGACTATGCGTCGTATG780 
CGAGAGTCTGTTTCCAGGATGCCTGTTAGTTCTCAGCACAGATATTCTACACCTCACGCC840 
TTCACCTTTAACACCTCCAGTCCCTCATCTGAAGGTTCCCTCTCCCAGAGGCAGAGGTCG900 
ACATCCACACCTAATGTCCACATGGTCAGCACCACGCTGCCTGTGGACAGCAGGATGATT960 
GAGGATGCAATTCGAAGTCACAGCGAATCAGCCTCACCTTCAGCCCTGTCCAGTAGCCCC1020 
AACAATCTGAGCCCAACAGGCTGGTCACAGCCGAAAACCCCCGTGCCAGCACAAAGAGAG1080 
CGGGCACCAGTATCTGGGACCCAGGAGAAAAACAAAATTAGGCCTCGTGGACAGAGAGAT1140 
TCAAGCTATTATTGGGAAATAGAAGCCAGTGAAGTGATGCTGTCCACTCGGATTGGGTCA1200 
GGCTCTTTTGGAACTGTTTATAAGGGTAAATGGCACGGAGATGTTGCAGTAAAGATCCTA1260 
AAGGTTGTCGACCCAACCCCAGAGCAATTCCAGGCCTTCAGGAATGAGGTGGCTGTTCTG1320 
CGCAAAACACGGCATGTGAACATTCTGCTTTTCATGGGGTACATGACAAAGGACAACCTG1380 
GCAATTGTGACCCAGTGGTGCGAGGGCAGCAGCCTCTACAAACACCTGCATGTCCAGGAG1440 
ACCAAGTTTCAGATGTTCCAGCTAATTGACATTGCCCGGCAGACGGCTCAGGGAATGGAC1500 
TATTTGCATGCAAAGAACATCATCCATAGAGACATGAAATCCAACAATATATTTCTCCAT1560 
GAAGGCTTAACAGTGAAAATTGGAGATTTTGGTTTGGCAACAGTAAAGTCACGCTGGAGT1620 
GGTTCTCAGCAGGTTGAACAACCTACTGGCTCTGTCCTCTGGATGGCCCCAGAGGTGATC1680 
CGAATGCAGGATAACAACCCATTCAGTTTCCAGTCGGATGTCTACTCCTATGGCATCGTA1740 
TTGTATGAACTGATGACGGGGGAGCTTCCTTATTCTCACATCAACAACCGAGATCAGATC1800 
ATCTTCATGGTGGGCCGAGGATATGCCTCCCCAGATCTTAGTAAGCTATATAAGAACTGC1860 
CCCAAAGCAATGAAGAGGCTGGTAGCTGACTGTGTGAAGAAAGTAAAGGAAGAGAGGCCT1920 
CTTTTTCCCCAGATCCTGTCTTCCATTGAGCTGCTCCAACACTCTCTACCGAAGATCAAC1980 
CGGAGCGCTTCCGAGCCATCCTTGCATCGGGCAGCCCACACTGAGGATATCAATGCTTGC2040 
ACGCTGACCACGTCCCCGAGGCTGCCTGTCTTCTAGTTGACTTTGCACCTGTCTTCAGGC2100 
TGCCAGGGGAGGAGGAGAAGCCAGCAGGCACCACTTTTCTGCTCCCTTTCTCCAGAGGCA2160 
GAACACATGTTTTCAGAGAAGCTCTGCTAAGGACCTTCTAGACTGCTCACAGGGCCTTAA2220 
CTTCATGTTGCCTTCTTTTCTATCCCTTTGGGCCCTGGGAGAAGGAAGCCATTTGCAGTG2280 
CTGGTGTGTCCTGCTCCCTCCCCACATTCCCCATGCTCAAGGCCCAGCCTTCTGTAGATG2340 
CGCAAGTGGATGTTGATGGTAGTACAAAAAGCAGGGGCCCAGCCCCAGCTGTTGGCTACA2400 
TGAGTATTTAGAGGAAGTAAGGTAGCAGGCAGTCCAGCCCTGATGTGGAGACACATGGGA2460 
TTTTGGAAATCAGCTTCTGGAGGAATGCATGTCACAGGCGGGACTTTCTTCAGAGAGTGG2520 
TGCAGCGCCAGACATTTTGCACATAAGGCACCAAACAGCCCAGGACTGCCGAGACTCTGG2580 
CCGCCCGAAGGAGCCTGCTTTGGTACTATGGAACTTTTCTTAGGGGACACGTCCTCCTTT2640 
CACAGCTTCTAAGGTGTCCAGTGCATTGGGATGGTTTTCCAGGCAAGGCACTCGGCCAAT2700 
CCGCATCTCAGCCCTCTCAGGAGCAGTCTTCCATCATGCTGAATTTTGTCTTCCAGGAGC2760 
TGCCCCTATGGGGCGGGCCGCAGGGCCAGCCTGTTTCTCTAACAAACAAACAAACAAACA2820 
GCCTTGTTTCTCTAGTCACATCATGTGTATACAAGGAAGCCAGGAATACAGGTTTTCTTG2880 
ATGATTTGGGTTTTAATTTTGTTTTTATTGCACCTGACAAAATACAGTTATCTGATGGTC2940 
CCTCAATTATGTTATTTTAATAAAATAAATTAAATTT2977 
(2) INFORMATION FOR SEQ ID NO:18: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2517 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: 
GGAATTCCGTGGCCGGGACTTTGCAGGCAGCGGCGGCCGGGGGCGGAGCGGGATCGAGCC60 
CTCGCCGAGGCCTGCCGCCATGGGCCCGCGCCGCCGCCGCCGCCTGTCACCCGGGCCGCG120 
CGGGCCGTGAGCGTCATGGCCTTGGCCGGGGCCCCTGCGGGCGGCCCATGCGCGCCGGCG180 
CTGGAGGCCCTGCTCGGGGCCGGCGCGCTGCGGCTGCTCGACTCCTCGCAGATCGTCATC240 
ATCTCCGCCGCGCAGGACGCCAGCGCCCCGCCGGCTCCCACCGGCCCCGCGGCGCCCGCC300 
GCCGGCCCCTGCGACCCTGACCTGCTGCTCTTCGCCACACCGCAGGCGCCCCGGCCCACA360 
CCCAGTGCGCCGCGGCCCGCGCTCGGCCGCCCGCCGGTGAAGCGGAGGCTGGACCTGGAA420 
ACTGACCATCAGTACCTGGCCGAGAGCAGTGGGCCAGCTCGGGGCAGAGGCCGCCATCCA480 
GGAAAAGGTGTGAAATCCCCGGGGGAGAAGTCACGCTATGAGACCTCACTGAATCTGACC540 
ACCAAGCGCTTCCTGGAGCTGCTGAGCCACTCGGCTGACGGTGTCGTCGACCTGAACTGG600 
GCTGCCGAGGTGCTGAAGGTGCAGAAGCGGCGCATCTATGACATCACCAACGTCCTTGAG660 
GGCATCCAGCTCATTGCCAAGAAGTCCAAGAACCACATCCAGTGGCTGGGCAGCCACACC720 
ACAGTGGGCGTCGGCGGACGGCTTGAGGGGTTGACCCAGGACCTCCGACAGCTGCAGGAG780 
AGCGAGCAGCAGCTGGACCACCTGATGAATATCTGTACTACGCAGCTGCGCCTGCTCTCC840 
GAGGACACTGACAGCCAGCGCCTGGCCTACGTGACGTGTCAGGACCTTCGTAGCATTGCA900 
GACCCTGCAGAGCAGATGGTTATGGTGATCAAAGCCCCTCCTGAGACCCAGCTCCAAGCC960 
GTGGACTCTTCGGAGAACTTTCAGATCTCCCTTAAGAGCAAACAAGGCCCGATCGATGTT1020 
TTCCTGTGCCCTGAGGAGACCGTAGGTGGGATCAGCCCTGGGAAGACCCCATCCCAGGAG1080 
GTCACTTCTGAGGAGGAGAACAGGGCCACTGACTCTGCCACCATAGTGTCACCACCACCA1140 
TCATCTCCCCCCTCATCCCTCACCACAGATCCCAGCCAGTCTCTACTCAGCCTGGAGCAA1200 
GAACCGCTGTTGTCCCGGATGGGCAGCCTGCGGGCTCCCGTGGACGAGGACCGCCTGTCC1260 
CCGCTGGTGGCGGCCGACTCGCTCCTGGAGCATGTGCGGGAGGACTTCTCCGGCCTCCTC1320 
CCTGAGGAGTTCATCAGCCTTTCCCCACCCCACGAGGCCCTCGACTACCACTTCGGCCTC1380 
GAGGAGGGCGAGGGCATCAGAGACCTCTTCGACTGTGACTTTGGGGACCTCACCCCCCTG1440 
GATTTCTGACAGGGCTTGGAGGGACCAGGGTTTCCAGAGTAGCTCACCTTGTCTCTGCAG1500 
CCCTGGAGCCCCCTGTCCCTGGCCGTCCTCCCAGCCTGTTTGGAAACATTTAATTTATAC1560 
CCCTCTCCTCTGTCTCCAGAAGCTTCTAGCTCTGGGGTCTGGCTACCGCTAGGAGGCTGA1620 
GCAAGCCAGGAAGGGAAGGAGTCTGTGTGGTGTGTATGTGCATGCAGCCTACACCCACAC1680 
GTGTGTACCGGGGGTGAATGTGTGTGAGCATGTGTGTGTGCATGTACCGGGGAATGAAGG1740 
TGAACATACACCTCTGTGTGTGCACTGCAGACACGCCCCAGTGTGTCCACATGTGTGTGC1800 
ATGAGTCCATCTCTGCGCGTGGGGGGGCTCTAACTGCACTTTCGGCCCTTTTGCTCGTGG1860 
GGTCCCACAAGGCCCAGGGCAGTGCCTGCTCCCAGAATCTGGTGCTCTGACCAGGCCAGG1920 
TGGGGAGGCTTTGGCTGGCTGGGCGTGTAGGACGGTGAGAGCACTTCTGTCTTAAAGGTT1980 
TTTTCTGATTGAAGCTTTAATGGAGCGTTATTTATTTATCGAGGCCTCTTTGGTGAGCCT2040 
GGGGAATCAGCAAAAGGGGAGGAGGGGTGTGGGGTTGATACCCCAACTCCCTCTACCCTT2100 
GAGCAAGGGCAGGGGTCCCTGAGCTGTTCTTCTGCCCCATACTGAAGGAACTGAGGCCTG2160 
GGTGATTTATTTATTGGGAAAGTGAGGGAGGGAGACAGACTGACTGACAGCCATGGGTGG2220 
TCAGATGGTGGGGTGGGCCCTCTCCAGGGGGCCAGTTCAGGGCCCAGCTGCCCCCCAGGA2280 
TGGATATGAGATGGGAGAGGTGAGTGGGGGACCTTCACTGATGTGGGCAGGAGGGGTGGT2340 
GAAGGCCTCCCCCAGCCCAGACCCTGTGGTCCCTCCTGCAGTGTCTGAAGCGCCTGCCTC2400 
CCCACTGCTCTGCCCCACCCTCCAATCTGCACTTTGATTTGCTTCCTAACAGCTCTGTTC2460 
CCTCCTGCTTTGGTTTTAATAAATATTTTGATGACGTTAAAAAAAGGAATTCGATAT2517 
(2) INFORMATION FOR SEQ ID NO:19: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 35100 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: 
AATTCACCAGTGAAGCCATCTGGTCCTGGGCTTTGCTTTGTCGGGAGGTTTTTGATTACT60 
GATTAAATTTCTTTTCTTGTTATAGGTTTATTTGGATTTTCTTTTTCTTCTTGAGTCAGC120 
TTTGATTGACATTCATGATTGCTAAAGGTTCAAAACACTTTTCTGAAAAAGAAAGTACAT180 
ATATACACTCATAAATATACATACAAACACACACATACACACCACACACACACCTGAGTA240 
CACGGGAATGATCATTTTCCTGGATCAATGTTATATCAGGATTTTTCAATTTCAAGAAGG300 
AACTTTAGGCTGGGTATAGTGGCTCATACCTATAATCCCAGTACTTTGGGAAGCCAAGGT360 
ATGCGAATCACTTGAGCTCAGGGGTTTGAGACCAGCCTGGACAACATGGTGAAACCCCAT420 
GTCTACCAAAAATACAGAAATTTGCTAGGAATGGTGGCACATGCCCCTGTAGTCCCAACT480 
ACTCAGGAGGATGAGGTAGGAGGATGGCTTGAGTCCGGGAGGTGGAGGTTGCAGTGAGCC540 
GAGATCACACTACTGCACTCCAGCCTGGGTGACAGAACCAAACCCTGTCTCAGAAAAAAA600 
AAAAGAAAAAAAGAAGAAGAAATGACCATGTTCTTTAGAGATAAGAAGTAAAATACTAAG660 
CGAATCAACTAAAAGAGGTAAAAGCAATTGCCTCCAGGAAAAGAGGGAGCAAAGGAATGC720 
TATATATTTTAAGAATTATGCAGAACAATTAGATTCTTTGTAAAAATAAATAAACAATGT780 
AAGTAACGCACAAAAGATAGTTTTATAACCAGACTGCTGGGATCCAAATCCTATCTCCAC840 
CATTTGGTAGCTGTTTGACTATGGACAAGCTTAAGGCACTTGATCTCTCTGAGCTTTAGT900 
TTTCCCATCTGTGAAATGAGAATGACAATAGTACTTACCTACATAAAGTTTTGCAGTACT960 
AAAGGAGACAGTGAATGTAAAAGGTTTGGCTAGTAAATGTCCTGTAAAAGGAAGCTTATT1020 
GCCAATATTATCAGGCTCTCCCAGACCAACCTGTATACAGGAAGAAAACAAACTCCGTTT1080 
CTCCTATAGTCTCACAACACAAAATACTTCTGACCCCAGATGTAGAGGATGGGGCATATT1140 
TCCCCATACACCAAGCAATCAACCAATTGTTCAGATTCTGCAGCAGACACGAATCTGGTG1200 
CCCTCCGATTCAATTTGAACACTATATTTACCTAGAGATAACGTCAGATCTCACAGCTTG1260 
AAGGCTTGAGCCAGGAGTTTGAGGCTGCAGTGAGCTATGATCGAGCCACAGAGCTCCAGC1320 
CTGGGCAACAGAGTGAAACTGCGTCTCTAAAATAATAATAATAAATTTTTAAAAGATATG1380 
CATTACTTTGGAGATTCCAAGGATTTTAGGAGTTGTAAGCCAGGACATCAGGGTAAAGAA1440 
AAAATATATATGTCACAATATCATGCAACCTAACTTCTCTTTGGGATCTGCCAGAGCCAC1500 
CTGATCACTCTGAAGACCCTCATTTGTGCTACTGACTAACGGTCTGGCTGCTCTTGGACA1560 
TGTCTCTTCTCCCAAGACCCCTTGAAGATGGCTTTAGAAGGGCCCCAAACTTAGCTAGCT1620 
CCCCCCAAGCTCAGGCTGGCCCTGCCCCAGACTGCGACCCCTCCCTCTTGGGTTCAAGGC1680 
TTTGTTTTCTTCTTAAAGACCCAAGATTTCCAAACTCTGTGGTTGCCTTGCCTAGCTAAA1740 
AGGGGAAGAAGAGGATCAGCCCAAGGAGGAGGAAGAGGAAAACAAGACAAACAGCCAGTG1800 
CAGAGGAGAGGAACGTGTGTCCAGTGTCCCGATCCCTGCGGAGCTAGTAGCTGAGAGCTC1860 
TGTGCCCTGGGCACCTTGCAGCCCTGCACCTGCCTGCCACTTCCCCACCGAGGCCATGGG1920 
CCCAGGAGTTCTGCTGCTCCTGCTGGTGGCCACAGCTTGGCATGGTAAGAGCAGAACGGG1980 
GGGTGGGGGACTTTGTTGGGGTGTGATGGAGAAGACCCCTGTGAAAGGATTCAGTCCTTG2040 
CCCCTCACTGGGTGTCCTCAGGCTGTTTTAGTCTCCCCAACACTGGACTGCAGGCTTGTG2100 
GGTATCTGCTTTGGAGAGGTAGTGGGGTGAAAAGAGATGGGTGTGGTGGAACTGGTCCAC2160 
CTGGTGCTGTGGATCTGTCCCAGCTCTGCCAGCGACTCACTGTGTGTCCTGAGCAAGCCT2220 
CTGATACTCTTGAGGCTTCAGTGTCCACTTCTATTCAATTGCAGGTGTTGGGGGCAGGGG2280 
GACAGTGATAGACTAGACCAGAGCAGTGCTTTTCATACTTTCCTGTGCATACAAGTTACC2340 
TGAGGATTTTGTTACAATGCAGATTCAGACTCAGTCGGTCTCAGGTGCGACCTGAGATTC2400 
TGTATATCCAACACACTCCTGGGAGATGTGAGATGCCGGCACTGCTGGTCCAGACCTACA2460 
CTGAGTTGGGAGGACCTGGAGAGCTCCTGATGGCTCTGGCAGCTCTGCCAGCCTGTGATT2520 
CGATGATTCTATGCAAGATCTGATTTGGAAGGGCCTGATAGGGGTGGTGGTTCTTCCTTG2580 
GGTGGCTTGTGTAAGGGGTCAGAGGGGAGAGACAAGAGGTTGGCCTCTCTGGCCCAGGGC2640 
TCAGGAGAGGGGAATTCGGGGTGAAATAGGTATAGGGCTAGAGGAGGGATTGGGAAGAGG2700 
CCAGTGAGGGTCTCCTGGACCAGAGCCCTCCCAGACACAGGCTGCCAAGTCTCAGGAGGT2760 
CCCCAGGCTGTAGCAGTTCTGCAGAATTTCCATCTGGGAGGGAACATGACTAGAGGTGAG2820 
GGGCTGCTGTGCTTGGCTTGTTGGCCCAACAAACACATTTCTATTGCCTGCTTATTCAAA2880 
GGGACCTTGGGGGAGGATGGGGATTGAAGGGGAGAAAGGACAGCCTCATACTGGCCTCTT2940 
CACAGAAGGACCCTAAGGCCGTGGCGCTTCTGGTCCCTGATGAGGAGGAGATGGCCCACT3000 
GACCATCCTTCTCTGGCCCAGGCAATCACACTGAGCTTGAGTATTTGGGTTTTTTTTTTT3060 
TTTTTCCTGAGACAGAGTCTCTCTCTGTCACCAGGCTGGAGTACAGTGGCACAATCTCGG3120 
CTCACTGCAACCTCCACCTCCCGGGTTCAAGTGTTTCTCCTGTCTCAGCCTCCCAAGCTG3180 
GGATTACAGGCATACACCATCATGACTGGCTAATTTTTGTATTTTTAGTAGAGATGGGAT3240 
TTCACCATGTTGGCCAAGCTGGTCTCGAACTCCTGACCTCAGGTGATCCACCTGCCTTGG3300 
CCTCCCAAAGTGTTGGGATTACTGGTGTGAGTCACGGCGCCCGGCCTGGACTTCTTATTT3360 
TGCAATGTAACTTACATGCAGTAGAAAGCACAGGTTCTTAAGTTCAATGAGGTCTGACAA3420 
ATGCACACACAGTGTACCCGCCACCCCCTTCATCTCAGAGAGTCCCACAGGTTTGATTTC3480 
ACTGCCTTGTCCTATCCTTACACCCACAACCTGCCTGTGGGGCAAAAACGGAAAAGTATC3540 
TGAGCCAGGTCTCAATTTAATTTTATTTTTTTTATTGAGATGGAGTCTTGTGGCCAGGCA3600 
TGGTGGCTCACACCTGTAATCCCAGCACTCTGGGAGGCCGAGGCGGGTGGATCACAAGAT3660 
CAGGAGTTTCAGACCAGCCTCGCCAATATGGTGAAGCCCCCTCTCTACTAAAAAATACAA3720 
AAATTAGCCGGGTGTGGTGGTGGGTTCCTGTAGTTCCAGCTACTCAGGAGGCTGAGGTGG3780 
GAGAATCACTTGAACCCGGGAGGCAGAGGTTGCAGTGAGCTGAGATCATGCCACTGCACT3840 
CCAGCCTAGGCGACAGAGCAAGACTCCATCTCCTTCCTTTCTTTCTTCCTTCCTTCCTTC3900 
CTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCTTTCTTTCTTTC3960 
TTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTTTTCTATCTTTTTGAGACCGAGTCT4020 
TGCTCTGTTGCCCAGGCTGGAGTGCAATGGCATGGATCTCGGCTCACTGCAACCTCCGCC4080 
TCCGGGGTTCAAGCAATTCTGCCACTCCTGAGTAGCTGTGATTACTGGTGCCTGCCACCA4140 
CACCCAGCTAATTTTTTTATTTTTGGTAGAGACAGGGTTTTATCATGCTGGCCATGCTGG4200 
TCTCGAACTCCTGAACTCAAGCGATCCCCCTGCCTTGGCGTCCCAAAGTGCTGGGATTAC4260 
AGGCATGAGCCACTGTGCCTGGCTTCAATCAATTTAGAAGTTTATTTTGCCAAGGTTAAG4320 
GACATGCTGGCGAGAAAAAAACATGGAGTCACAAAAACATTCTGTGGTCTGTGCCATTCT4380 
GGATGAATTCGAGGGCTTTAATATTTAAAGGGGAAAGTGGGCTGGAGGGGAAAAGGGGAG4440 
GTTGTGGTAATCCACATGTTGCAAAAGAAAAGCAGCAGGTAGGGGAACAGTCAATTATCT4500 
CGGTTCAGTAAATTGGCTCTTTACATAGGGAAAGTGAACATAGAGGAGCTGCCTGTGGGA4560 
TATTTTACCTTTTATCTGTCGCTATCTGCTTAGGAATAAAAGGCAAGGCAGCTTCTTGCA4620 
TGACTCAGTTTCCAGCTTGATTTTTCCTTTTGGCAGAGTGAATTAGGGTCCCAAGTTTTT4680 
ATTTTCCCTTCACAGGGGCATGGTGTGTGGGAGGGGGGCCAGATGGTTTTCCAGGGTCCA4740 
GTCCCAAGAGAAAGAAGAGATGGGGAGGCTGGAAACCTAAGTTTTCAGCCCAACAGACCA4800 
ATGATGAGTGGATGAGGGGCCACTGTGAGGAGACTGGGGATGGTATTGGAGGACCCTAGA4860 
GAGAGAGGGGGGCTCTCTCTTCATTACTGCGATGAGATCCTGGGCTGAAGAGGGGCTGTG4920 
TCCAGCCTTAGTGTGCAGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG4980 
TGTGTGTGTTGGGAGAGAAGAGTAGAGATTGGGGCACATTCTGGAAGTGATGAGGGAGGG5040 
GCTTCCAGGCAAGTGGGAGCTAGTGGAGAGGTGTGGGGCATGGGGAGAATTGGGGAGTGG5100 
AGATGAGAGGGGGGAAGAATGGACAGGCACAGAAGGGGACCTCAGTTAATGTTCATAAGC5160 
CCATGCCCCCACCCCGAGGAGGATGGGGGCCAAGCCGGCTTCCTTCCCTGCTAGCCAAGC5220 
CAGCAGGGGAAGTTGGCTGCGGAAGTTGCGGGTATCAGCCTTATCCTGCGTGAATACCTG5280 
GGACAATAGGATAGGACAAAATAGGGCAGACACCGCTCCCTGACCACATTTCCTGGAGGC5340 
CAAGGCAGGGTCTAGAGAGACAGGCTGGGGGAAGGGATGGGAGAAGCCCACTGTAAGGTG5400 
TGAGGCAGGTGTAAAAAAGGAACAAATGGAATCACAGAATCCAAGGTTAAAATCTTGAGC5460 
GATCAGAGTTGGCCCAGAAGGGACATTAGAAATGTAGCAATTAAAGCAGGTGCCCAGGGC5520 
AGGAGTAGTTCTATACATCATCTCACTCAACCTTCAGCTGAAGTTTTTGGGGTGGGAGCT5580 
GGGATTATTCCCATCAGACAGAAGAATAGCCTGAGGCTCAAAGAGGTTAAGAAACTAACC5640 
CAGCTGGTAAGGGAAGAACCAAGATCCAAACCCAAGTTGGTGTGAGCCCACACTCCAAGC5700 
TGTTTCCTGCTATAAAACCCCGGCCTGGGGGCCCTAGATTGCTGCAGCAGTGATAGGGCA5760 
GCCCCAGCTCTGTTGAGATTTGCTAAAAAGGCTGCTAGAAATGACACTTGTCCCTCTTCC5820 
TGGCAGTTGCACTGCATAGGAGGGCTACAACCCCAGGTGGCAGGCTTGGCAGTATTCACA5880 
ATTCACTCAATCCCGTTTGCTGATCAGAGTCTTGGGGAGAAGGGATGCACATTCTGATGA5940 
ATACAAAATCAAAACGTGAATTAAGCCATCCTGAAAGGACTTGAGAGAGGAAACCTTTCC6000 
AATTCTGGGCTCTATGGTGGGGCAGGGGGAATTTCCATTTCAAGGGGGTTTGCAGAGAAC6060 
AATGGAGATACCCTGAATTCACCGAAAGCCCTCGGGGTGGCCTGTCATTGTGCCCCCATC6120 
ACTGGGAAGAGGAAGGGCCAGAGCTGAGGAGTTGGATGGCCAGGGTCAGCCAGTGGGTCA6180 
GCGTCAGAGCCCAGCCTCACAGCTGCCCCGCAAGTGGCACTCCCTCTCCCTGCCTGGAGA6240 
GAGGAGAGTGGCTAGGAGGCTGGGGAAGCAGAAGTGAGAACATCCCTGTAGAAGGGCCAC6300 
AGGCTGAGCGGAAACCGGGGGCTGAGCCTGACGCCAACAATGTGTTTCCGCCCACACAGG6360 
CTGGGGGGCGCCTGGCAGCCCCTCGGAGGCTTGAATCAGCTCTCACTTCCCTCCTTTGCC6420 
CCTATTTTAGGCCCTGGAAAAATGCTGACGCTGCAGAGGCAACGGGCCTTCTTCCCGGAC6480 
AGCCTGATAGGGGTTTCAAGTTCTCTTTTCTCCTTCAAGAAAATTTTCCTTAAAAGAGAT6540 
TGGCTTCCCAGTAAACACAGATGTGTGGGGGTGCCGGGGTGAGCTGCTGGGTGTAGACTA6600 
GGTAATAAACATAGTGACTAACTCTTACTGAGCCATTTATTTGGTGACAGGTGATGTTCT6660 
AAAGTCTTCCCATGCATTTAAAATGCCTAACATACCAATGAGTGGGTACGATGATTGTCC6720 
CTGTTTTATAGGTGGGGAAACTGAGGCATGGCACCTCCCCATCCCACTGTGCTGCAGACC6780 
AGATGTCCATTGGTGGGAGCGGGCACACCAGGAGATTCTTGGGACCTCTCTAACTCTGCT6840 
GGGCTAAGATCCTACATCTCTTTTTTTTTCTTTCCCATATGAATTAAGCTGAGGACTTGG6900 
CCGTGAACATTCCATTCATTTGTTTCTTCATTCGGTGGTAGAAATACATCCACTTTGTAC6960 
ACAGGGTTAAAAGAGTCCATTCCTGGGGAGTAGAAAGATGGCATCACAGCAGGGAAGACT7020 
GAGGCAGGAGGCTGAGGACCCCAGGGGGACAGAGGCCTGGGTGAGAGGCTGAGCAAGCTG7080 
CAAGCCCCCTTTCTCAGAGGAGGGACCTCCTGGACATCAGAGACATCAGTCTGTCCCTGA7140 
GCAGGTTGAGGGTTAGGAGCTGAGCAAATGACCAGGGGGCAGGGGCTCGTTCAAGGTGGT7200 
CCCTTGATGGCACAGCACCATCCCTGCCAAGCTACCACCCATCTCAGAGTCAGGACGGCC7260 
CAAGGGGCGCATCCTAGACCTCACTTCTGTCTGCTGTCCCTCTCTCCCACCAGGTCAGGG7320 
AATCCCAGTGATAGAGCCCAGTGTCCCCGAGCTGGTCGTGAAGCCAGGAGCAACGGTGAC7380 
CTTGCGATGTGTGGGCAATGGCAGCGTGGAATGGGATGGCCCCCCATCACCTCACTGGAC7440 
CCTGTACTCTGATGGCTCCAGCAGCATCCTCAGCACCAACAACGCTACCTTCCAAAACAC7500 
GGGGACCTATCGCTGCACTGAGCCTGGAGACCCCCTGGGAGGCAGCGCCGCCATCCACCT7560 
CTATGTCAAAGGTGAGGAGTCTGAGCCTCCTCCCAAGAGGCCTGACCCGGCAGGCCCCAC7620 
TACAATGGGCCCTAAAATTAACAATCGTAACAATTCAGCTCTGCATTTACTGAGTGCTGG7680 
CTATGAGCAAGGACCTGGAAGAGCTGCTAATGTAATGCAGTCCTCACAACAACCCTGCAA7740 
GTCGGGTCTATGATGATGCATTTTCTAGAAGTGCAGGGAGGTTATCCAAGGTCACACAGC7800 
CTCACATAGTGGGACTAGACTGGAGCCCAGGTGCGCCTGACTCTGGAGCCACCACGCTGA7860 
AGCATCCGCTGAACTGTCCTGGCGTGGTGTGACCTCAGATGAATGATCAGCCTCTCTGAG7920 
CTTCCTTGTCACCTATGTCCAGGTACTCCTTGGCCCAGTGGAGGGAGGGCAGTTGTAACC7980 
CTGTGCCCTCCTCTACTCTAGACCCTGCCCGGCCCTGGAACGTGCTAGCACAGGAGGTGG8040 
TCGTGTTCGAGGACCAGGACGCACTACTGCCCTGTCTGCTCACAGACCCGGTGCTGGAAG8100 
CAGGCGTCTCGCTGGTGCGTGTGCGTGGCCGGCCCCTCATGCGCCACACCAACTACTCCT8160 
TCTCGCCCTGGCATGGCTTCACCATCCACAGGGCCAAGTTCATTCAGAGCCAGGACTATC8220 
AATGCAGTGCCCTGATGGGTGGCAGGAAGGTGATGTCCATCAGCATCCGGCTGAAAGTGC8280 
AGAAAGGTGCGTGGGGCATGGGGACCGGCAGCCAGGCCTGAAGAGTGGGGACAGAGAGCC8340 
GGCGGCCACATGGGTGGTGACTGGGGACTGGGTGTGATGGGGGGCAGTGGGATGTCCTCT8400 
TTCTTTCACTTCTTCCCCTCAATGGTTCCACGATCATCTATGGGGCAGGACTGACAAGGT8460 
GTCGGGGCAGGGAGACAAACCACATGTGAGCAAATAACTCAGTGGGCAAGGTCATCTCAG8520 
GTCATTGGACATGCTACAAAAATAAACATTCAACATGGTAGCTGAATAAGGAGTGTGTAG8580 
GGCGGGGAGCCTCACTGAGAAGGAAACACTTTATTAGAGCGGAAATCTGAATGACATGAA8640 
GAAGGTGGCTGTGCAAAGATCTGCTTCAGCAGGGGGACAGTGAGTACCAAGTGGTGAGGT8700 
GGGGACAGGCTCTGAATGTTCTAGGTATGGAAAGAGGACGGAAGCTCAGCCTCAGACATG8760 
GATTTCCCACTGGGGGCCTGCCTAAGGCCAAGTGCTGGGCATGTGTAGGAGGGATGCTGA8820 
GCCAAGAGGCAGGGAGGAGATGGTGGGTGCGTGTGATGGCTCTCGCGGTGGCCAGGTAAC8880 
AGTGGAGGTGGAGTCTCACCCTGCTGGGATGGCAGGCAGGATTCTGGTTTCTGGGAGGAC8940 
TGGTGAGAGCAAGCAGGACCCCAGCCTGAGGACCTGGGCTTGAGACAGCAATCAGTCCCT9000 
GTAACAAGGGCCAGGGTCAGAGTGAAGCAGCTAGCCCAATGCCACTGGGATCTGAAGCCA9060 
CTAAACCTGCCTAGGGGGTCAAAGGACCCCAGCTGTGTGGGCAGAGGAGGCCATTAGGGC9120 
TCTTTCCTGGCATTTCATCCTGCAGAGCCCTGGGCTGGCCAAGAGCCAAAGGTCCTGGGC9180 
CCTAGTTCTGCCTTGACCCCCCCTCAGGGACCTTGGGTGAGTCCTTTCATGTCCCTGGGC9240 
CTTAGGAATCTGGATTAGATTATCTTTCAACAGCAGCAATGGGCATAAATATGAATTCAA9300 
GGCCTACTGTGCATCAGGCATCTTGCTGGCTGCTGGAATATTCCTGTCACGGATTTGACA9360 
TTCGACTAGAGTCTAACTATTAAATAGAAAGTAAATACAAATGTGATGAGCAAGAAACCA9420 
AGCTGGGGAGTGGCGGGCATGGAGGTGCTGGGGAGGCTAATTCATATCAGCTGGTCACAG9480 
AAGCCTTGCTGAGGAATTTTTGAGCTAAAGATCTGAAGGATGAGAACAGCCTCCCATTTG9540 
AAGTGTGGGAGGAAAGGCATTCCAGGAGGGAAAGGTGGGTGCAAAGGCCCTGTGGTAGGA9600 
AAGAGGTCCAGCGGGCTGCAGTGCAGTGAACAAGGGGTGGGGTTATCAGGGCGGTCAGAA9660 
ACAGGTTGGGCTGTGGAAGGACTTTGACTTCTTTTCTGAGAGTAATGGGAAGCCCCAAAT9720 
GTTTACAGAGGAGAGAGGCATGGTCCCATTTATATTTGTAAGAGGTCACTTTGGTGAAGA9780 
ATCTAGGTGTGGGGGGCTTGGAGGGAGGCAGGGAGGTCTCTGAGGAGGCTGGTGCAGAAG9840 
TCCAGAGTGGAGAATGGTGACGGGACTGGGGAGGGGTAGAGGTGATGGAGAAAGTAGACT9900 
TTCCAAGGTCTCTTTAGGACAGGCCTTGCAGTGGGGGGACTGGGAGCATCAAGGCTGCCT9960 
CCCAGGATTTGGGATGGGGCAGTGATGGGGACCCTGGCCTGTGTGTCCTGGCCCATGGCA10020 
GGGAGGAGAGCAATATCTCTATCATATTCAGGGAGCCTGGGTGTTCAGGGGTCTCTCCCC10080 
CGGTCTCAGTCATCCCAGGGCCCCCAGCCTTGACACTGGTGCCTGCAGAGCTGGTGCGGA10140 
TTCGAGGGGAGGCTGCCCAGATCGTGTGCTCAGCCAGCAGCGTTGATGTTAACTTTGATG10200 
TCTTCCTCCAACACAACAACACCAAGGTCAGTCCCTGCAGATCACAAGGTGAAGTCTGGC10260 
CATCCTCCCAGCACACCAGGTTTCCCATGGTGGAGTCCTGGGCCCCCAACTCCAAACTGG10320 
CTGTCTTAGCTGAAGGCACAGCTCAGACTCCAGAGAGGGGTGCAGACTCACCCGAGATCT10380 
CACTCCCAGTCAGTAGCTGACACAGAATCAGGACTCATGCTTGTGCCGCTGAACTTTGTG10440 
GGGGTGGGTGGGGGGAGGTGGTTCTCTGTCACCTTGACACATGGCCTTTGCCCCAGCCTT10500 
TAGACAAAAGCCAGAGGTGAGCTCACTTCTGATTTAGCAAGGGTTTCCTAGGCCACCATT10560 
GAAGCCCAGGAATATAACAGCTATTTCAGAAAGACATTGGGAGAGAGGGAGGAGGAGGGA10620 
GGATTCCAGGAGGGACTCACGTTGGGCTGCCTCTAAGAGCCCCCTCCCTTCCCACTGCAC10680 
CTGCCGTGTTCCAGACACAGCCCTAAGCCACTTGCATGCATATCTCATTTACTCCTCACT10740 
ACAGTCTTGGGGCAGGGAGCCAGTATTAGCCCCATTTTACAAGTGAAGCAACAGGCTCAG10800 
AGGAAAGGCAGATAGTAATCCTTAAAGGCTGAGGATTGGAACCCAGATCTTTCTAATCCC10860 
TAAACTACCTTGGTATAACATCTCCATTCCTTCTGGCTGCAGCTCGCAATCCCTCAACAA10920 
TCTGACTTTCATAATAACCGTTACCAAAAAGTCCTGACCCTCAACCTCGATCAAGTAGAT10980 
TTCCAACATGCCGGCAACTACTCCTGCGTGGCCAGCAACGTGCAGGGCAAGCACTCCACC11040 
TCCATGTTCTTCCGGGTGGTAGGTAAGCATCAGGGTGGTGGTGGACAGTCGGTAGGGATC11100 
CTGCAGGAGTGTGAGCAGAAGGGTTTTGTTGAGGAAGCTGATGTCAGGGAAGGAGACCTG11160 
CTGAGGATATCTCTGCTGGAGTTTGTTTATCCAAGGCCTGGCTAAGGAGCCACTCTCCAG11220 
GAGCTTTCCCTTACCCTCTCCTGGGATCTCTCTCCCATCTTGGAGCTCTTACAGTGCATG11280 
GCTGCATTGGGTGCACCTTAGTGCCATTTTTTGTTTATTTGGGGATTGGGGTCCAGTAGC11340 
TCCCTACTGGACTTCATTTGTTCATTCTTTCATGCATTCCTTTATGGAAACATGAAAAGA11400 
CAATGATCACCCAGTGATTATGGGGGAAGCACAAGGTGTCCTGGGAACACTGAAGAGTCC11460 
CCCCAACCCAGGCTTCGAGAAGGTGGCCTCTAAACTGGGATGGGAAGAATGAAGGTGAGT11520 
TGGCCGGGCAGAAGGGTGGGAAAGGAAGGGGAACAGCGCTTCTGGCAGAGGGAGGAACAT11580 
ATGCAAGGCTCAAAGGCAAAGAGAACATAGATCATTTGGAACACTGAAAGAACTTGACAA11640 
CAGCTGGGATGTGGAGTGGTGTGAGGAGTGGCCACAGGGGAGCAGAGGAGGTGGCAGAAG11700 
CCGGAGGTAAAGGTGTCTTAAAGTGAGAAAGAATAACTGCATCTTAACCTATTGGGAGGT11760 
CATTGTAAAGAGGAGAGTGATGGGGTCAGATTGTACAGAGGAGGCACTTCGTGGTGGTCA11820 
GGAGCACACACTCCAGGGCAGTGTTCCAACCTGAGTCTGCCAAGGACTAGCAGGTTGCTA11880 
ACCACCCTGTGTCTCAGTTTTCCTACCTGTAAAATGAAGATATTAACAGTAACTGCCTTC11940 
ATAGATAGAAGATAGATAGATTAGATAGATAGATAGATAGATAGATAGATAGATAGATAG12000 
ATAGATAGATAGGAAGTACTTAGAACAGGGTCTGACACAGGAAATGCTGTCCAAGTGTGC12060 
ACCAGGAGATAGTATCTGAGAAGGCTCAGTCTGGCACCATGTGGGTTGGGTGGGAACCTG12120 
GAGGCTGGAGAATGGGCTGAAGATGGCCAGTGGTGTGTGGAAGAGTCTGAGATGCAGGGA12180 
TGAGGAAGAGAAAGGAGATAAGGATGACCTCCAGGTCTCTGGCTATGGTGATTGGGTGCA12240 
GGCAGTGGCAGTCACTGGACTCAGACCCTGAAGCAAGGCAGCAGCTCATCGGAGTGTGAG12300 
CAGGCTCTGAGACATTTAGGTCTGGCCGTGCCTCATGTGTTGAATGTTATGGGAGATGGA12360 
GGTGGCGAGGAGCATGAGAATCATGAGCATCACTGCCCCTAGAGTATGTGCAAGGCACTG12420 
GACTTGCAGCAGATTGTGAGCTCTGCTGTGGACCCCAATCTGCACTGGGAGCTTTGGCAG12480 
GGTAAAGGGGAAGAAGAGCAAAAGCACAAGAATTCAGTTACGGCTTCTAATCCTGTCTGC12540 
TTTCTAGTACAGGCATACAGTCATCACTCAAGAAATGTTTATGTTCATTCACACTTTGGG12600 
CCAGACACTGTTCTAGACATCGAGGATACAGCTGCAAGTGAAACAGATACAACAACCCCC12660 
GACTCATGAAGTGTGTGCTCTAGCTGGGAGTGGGCAAGCAATGAGCCAAGTAAATTATTA12720 
AAAAAACAAATTATATAGCATTTGCAGCTTCAGATAGGGTGTTCACCAAGGAAGATCTCA12780 
CTAGAAAGCTGATATTTGAGCAAAGGCTTAAATTGCTGAAGGAGCAAGCCATGCGGCCAT12840 
TTTGGAGAAGGGAGCTCCATCCTGCAGCGGGACTGTGCTTGCCATGTTCAGGGGACAAGT12900 
GGGCCAGTGTGGCTGCGGGGAGAGAGTGAGAAAAAAAGTGGTCTCAGATGAGGTCAGAGA12960 
GCTAAAGTGGGAAGGTGAGATGAAAGGAGGCTACCGCAGTGGTCCAGGCTGGAGCTGATG13020 
GTGGGTGGACTAGAGTGGTAATGGTGAAGGCAGCAGGAAGTTGTTGGTGTTTGGATGGAT13080 
GAATGGACTAATGGATGGATGAATAATAGATAGATGGATTGTTGAGAGAGACAGAGAAGA13140 
GAAAAGCCTTGCCCCCAAAAGCTCACAGACTACTTGGAGAGAGAAGAAAGCTACCTGGAG13200 
GGAGAACCAGATGCATGAAGCAGTGCAGATGTGGTGCCTAATGAGTGTGTAGTCTGGAAG13260 
GGCAGCAAAAGTCGAGTGGAGTGAGAGGTTCCTGTGTCCTGGAGCACTGAGTAGAGACTC13320 
CCTCATGGGGGTGAATCTTAAAGGATAAAGGGGCCTCTATAATGAAAAGGAGGAGGATGG13380 
GATTTCTGGTAGAGGAAATTGCTTGAGCAAAACCTCCAAGGTTGGAATGACTATGGTGTG13440 
TTCAGGGATGTTAGCAGACCCAGATGGGTGGAGCGTTGAGTGTGTGTGTGTAGGAAGGAA13500 
GAGGGGAGGTGGCTGGATGAGCACAGTGAGACCTGATTTGATTGAGAGCCTTGAACGCCA13560 
CGCTGAATAATGGAGGCAATGGGACGCCATAGAGGGCTTTTGAGTAGACATATATCAGTG13620 
TAGAAGGGTGAATTTCAGATTTTTAGACAGAATAGAGTAAGGAGAGGAGCTCTTAGAAAT13680 
CATCTAGTCCAGGGCTTGTGGCAGAGCCCTGAGGTTTTAAGAAGGCATGTCAGGGGCTAC13740 
CATGACAGGCACGGAGAGGCTGAGTGAATTGGGGTTCTTGCCACAATTCCCTTGCCTGAG13800 
ATTCAACAAGAGCAGCTGTATTACAATCTGTGCAAAATGTCATTAGGAGAAACTAGTTAG13860 
TAGCTGGGCGTGGTGGCATGCAACTGTTGTCCCAGCTACTCGGGAGGCTGAGGCCGGAGA13920 
ATCGCTTGAAGCTGGGAGGCGGAGGTTGCAGTGAGCAGAGACTGTGCCACTGCACTCCAG13980 
CCTGGATGACAGAGCAAGACTCTGTTTCAAAAAAAAAAAAAAAAAAAACTAGTCAGGACT14040 
CTTTCAGATACAAGTAATAGAAACCAACTCAAACTGGCCTAATTAAAAGGATTTTTTTCC14100 
TTATAGCTAAAAAGCTCATGGATATCAGCTTCAGGAACACTTGGATCCAGGTGTTCAGCT14160 
GATGCTGGAAAGAATCTATGACTCCCCAACTCTCAGCCCTGCCAGGAAGGCTTTCCCCTT14220 
GTAGGACTCCGACTATCCGCCTTGTAGTATCTGATCCAGCAACACCAGTAAAATGAGGGC14280 
TTCTCTTTTCCCAGAGTCTTAACAAAAATCATGGAATTGAGTGTTATGGACTCATGGATT14340 
CATGGTAACCCAAACCAATCACCGGGCCAGAGGGGACAGAGTACCCTCACTGGTTGGCCT14400 
GGGTTACACACCTACTCCAGAGCTATATTTGGAAGCCGCATTGACTGATTTATGACCAGA14460 
AGAAAGGGAAATGGATGAGGACACGTGAAATTGTGTGTGTATGTGTGTGTGTGTTTTCTT14520 
GCTGCCAAAAATTTTTCAAAAACTTGGAAAATCACAGATATATTCAATCTCTTCATTACA14580 
CAAATAAGGAGATGGAGGCACAAATGGGGATAGAGGGATTTGCCCAGGTTCTCCTAGGGC14640 
TTCAGTGAGAAAAGTTTTGATCCAGGGATTCTGAAGGGGGTGGTGAGAAGAGGGGTGTCA14700 
GAGGACCTGTCTTGGGTGGTGGGGACTATGTACCTGTGACATAGCTGCTCAGGGACTGGA14760 
TCAATGGGTGGATGACAAAATGGACAAATAAACAAGGACATCTTCCCACTAATGCCAGAT14820 
GCTTGTGTGTTCTGCTTTCCAGAGAGTGCCTACTTGAACTTGAGCTCTGAGCAGAACCTC14880 
ATCCAGGAGGTGACCGTGGGGGAGGGGCTCAACCTCAAAGTCATGGTGGAGGCCTACCCA14940 
GGCCTGCAAGGTTTTAACTGGACCTACCTGGGACCCTTTTCTGACCACCAGCCTGAGCCC15000 
AAGCTTGCTAATGCTACCACCAAGGACACATACAGGTACCACTTATCAGCTCCCGTCTAC15060 
ACAGCCCGACAACCAGATGGGGTATGCTTCAGCAAGCATCAGGACGCTTGGCTCATGTCC15120 
CAACCTTGGTGTATGACCTTGAGCAAGTCCCTGCCCCTTTCTGGGCTTCGCTTTCCCTGA15180 
CTTCATGGAATCCCAATATTGGTCATCTGTGTTTGAGATCTAGATGAAATTGACCTACCT15240 
CTCCATCCCACATCCTTGGGATAGTCAATGCCCCACCCAAGGATTCTACCATTTCTTGGG15300 
AGTGTGCATTCTCATTGGTCCCTCAAGAACCCTCAGCCTCATTCATTTTCCTCTCTTGGG15360 
GCCAATCCAAATGCAGAAAACAGCCCCACTCATAGACACACTCCTGATAATGACTGCACA15420 
AGTTATCTGCTACATACAAAAGCTTGGAGGGAGGGGAAGAGGGAATTAAGATCACACAAT15480 
CACAGATACATGAAATGTTCTTTAAAGGATTGTGATCACCCAGCCCCAAGAATTTCTCAC15540 
TGGCTGCTCTTCTCTGTAAGCTCAAAACTCTTCCCATGAAGTGCAATCTATAATAACTCC15600 
ACACCCCTCTTCTTCCGTCTCTCCACTCCCACAATCCTGTGTATTCCACACACATTTTAG15660 
AAATCTTTTTCCTGTCTGCTTGTGAACTGTGTTCTTGGGGTCTTGCTTTCTCATCCAAAG15720 
TGGCTTAAGCAGGTAGGTTCTAAATAAGAAAGCTTTGTGCCTAAGAGGAACACTCATACC15780 
AGGTATATCAGGTATTAACTCAGGTATTAAAATAGTTCCTTCTTTTCTTTCTTTTTATTA15840 
TTTTTTTTAGATGGAGTTTTGCTCTTGTTGCTGGAGTGCAATGGCACAATCTCGGCTCAC15900 
TGCAAACTCGGCCTCCCGGGTTCAAGTGATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGG15960 
ATTACAGATGCCCACCACCACACCCAGCTAATTTTTGTATTTTTAGTAGAGACAGAGTTT16020 
CACCATGTTGGCCAGGCTGGTCTCGAACTCCTGACCTCAGGTGATCTGCCTGCCTCGGCC16080 
TCCCAAGGTGCTAGGATTACAGGTGTGAGCCATCGTGCCTGGCCTGAAATAATCATTCAT16140 
ACCCTGCCCTTTCAGAGGGAGACAGTACAGCTTAAGGGCAGCGAATACGTGGTGTGCATG16200 
CCACACTCACTCTCATTCTTGTTTCTGCAACTCTGTTCTGCAGAGTGTAGATGCGGCCTC16260 
AGAGTCCTCCTCAACACAGGTCCCAGGCAGTATTTCCAGCATAGTTGGCTCATGAGAGAT16320 
CTGTTTGTCATCCCTGTGTGGATCCCTTAGACAACTTCAAAACTCTTTGGGATTCTCGTT16380 
CTAGCTCTGGAAGCCCAAACCTCATTGATTCCCACAATCTTGCTTGTCAATTGTCAGAAG16440 
CAACAAGGATGTTTTCTTGTCCTCATCTTCCTCCTCTCAGTTCCCTTCTGGTCCTTTCTG16500 
GCCAGGTCTCTGTCTTCCTCTCATTTAAAGCAGAAGTTCTGAATCTGGAATGTGTAGGCC16560 
CTTTGGAGGGGGCTGGTCCATGGATCGGTTTAATGGGTCCATAAGCCACAGAGACATTGA16620 
GGAAAGGAACACGAGATCCCCTAAAACACAGTAGTCTGGGCCCATTCAGCACAAGGCAGA16680 
CAAGCCTGGACACCAAACAGCCACAGAATTTTAGTTCATGTGATGGGTTGTTCATAATGG16740 
TGACTTTCAATTATCCAAAAAAGTCAAATTATTTTTAGTTAAAGGGGTTAGTTATCTCAA16800 
GAAGTGACCTGGGCAGAGGCCTTGTATATGCCCAGGGTCTGGCTGGATGAGACTGCTCTC16860 
TGAATACCATAGATTTTAGTCTAGTAGTAGCTGCAGACATTTCCCAAGCAAGAACTGGCC16920 
ATTTGCTATAATTTTTAAAATTTTATTTATTTTGACAGTGAACTGGGGGACTTTTTAAAA16980 
AATGTATTTATTACCTAAAACAACACATGTTCATTATGGACAAATTGTAAAATAGAGATT17040 
AAAGAAAGAATAAAACAAAAAATTTCCCAGAATCAGCCAAAGATGATTTTTATTGTTAGT17100 
TTTTGCTCCAGGGCCTTTTCTGTAATAAAGGGTACCATTGAATTGAGTGCCCACAAAGAT17160 
TCAACTTCTGTGTCAAGCACCCTAAAAAGGTCCTTTAATCCTCAAGCCAAGCCTGTGAAT17220 
TAATAACCATCGATATCACTCTCACAGCAAAGGAAGTGAGGGATCAGAGAGGTTAAGTAC17280 
TTGTCTAAGATCACACAGCCAAGAAACAGCAGCACCAGGACTTGAACCCCAGTCTCTGCA17340 
GCAACATGGCTCAGAACCCAGGGCCCTACATCCTGCCTCTTGTCTCTTTCTCAGTCCCTC17400 
TTGGCAAGGTTGGCACTTCAGGGATTTGTAGCAGGGATTGCAGCTTTCATGAAAGCTTAG17460 
TCCAGTGACAGTGGTCAACGTAGGCGACCTGTGATAGGCCTCCCAGCACCTTGAAGACAT17520 
CACCTCTATTAAACCTCGGGAAAAAAACACTTTCAGATAAGAAAACCAACTAAGGAAATG17580 
GGATTGGTGGTTTTTGCATGTCTCAATGGCACCCTGTCTGAGTATCTGGCTTACCCAAGG17640 
CCGTTGGGCCCTGAATATTTTACCAAAAATAAAATAAACCCCTTTAAGGCTGTTATCTGA17700 
CTGCAATCCTGGCAGGGGCCATACTAGGCTGGGGCTCACCAACACCACCTGATTCTCTCC17760 
TGCAGGCACACCTTCACCCTCTCTCTGCCCCGCCTGAAGCCCTCTGAGGCTGGCCGCTAC17820 
TCCTTCCTGGCCAGAAACCCAGGAGGCTGGAGAGCTCTGACGTTTGAGCTCACCCTTCGA17880 
TGTGAGTGCTGGGGCCGAGCGCCACCTGGGGCGGAGGCCCTGGGACTGCCTGGAGGGATG17940 
GGGTTGACTGGGGCAGGGCACAGGGAAGTAGGTACTGGGAGATTGGGAGGTGGCGGGGAA18000 
AGTGTGACTTGGGGCCTCCTCCTTTCTTCCTCAGACCCCCCAGAGGTAAGCGTCATATGG18060 
ACATTCATCAACGGCTCTGGCACCCTTTTGTGTGCTGCCTCTGGGTACCCCCAGCCCAAC18120 
GTGACATGGCTGCAGTGCAGTGGCCACACTGATAGGTAAGTGGGCTCCACTCACCTCCCT18180 
CACCTGGGCTCAGGGGCTGGGCACCCTGTGAGTGGGAGGGACATGCTGGCGCTGGGAACC18240 
CTGAAGCTCTGAGCCACATTCTGCTTTTGCCAGGTGTGATGAGGCCCAAGTGCTGCAGGT18300 
CTGGGATGACCCATACCCTGAGGTCCTGAGCCAGGAGCCCTTCCACAAGGTGACGGTGCA18360 
GAGCCTGCTGACTGTTGAGACCTTAGAGCACAACCAAACCTACGAGTGCAGGGCCCACAA18420 
CAGCGTGGGGAGTGGCTCCTGGGCCTTCATACCCATCTCTGCAGGTGAGAGGGAGCCTTC18480 
GCACCCGCACCGCCCCCCCGCCCGCCCCCCGCCCCTGCTCCTTTAGGCGGCTCCTCCCCC18540 
ACCCCCCACCGAGGGAGCTGGGGTTGGCTCCACCTTTGGAGCAGATCCTAGCAGTACCAA18600 
GGTCCACCTCTCTGGGCCAGTCCAAGCCCCTCCTGCCTGGCAGGTCCCCCGAAGCAGTAG18660 
GACGGGGTAGTCTCTGAGAAAGCAGAGAGAAAGCAGCCTGAAGAAACTGGCCCCCACTCT18720 
TGTCCCTGCACTCTAACTCATGCATCTATTCACAAGTATGTGCAGGCATTATGCACCGTG18780 
TGCCAGGGACGTGCCCTATGCAGGGAAGCAGTGCCTCCCCAGAGCTCAGAGGCTGATGAG18840 
GGAGGCAGGCAATGAGCAAGGAAACAGTCCATCTCCAGCTCGGGGCCAGCTAAGGACGGC18900 
CTTCTCCAACTCTCCCCTCTTGCTCCAGACACAGTCTATCCATTTGAGGTTGCTGTGCAA18960 
GAGGCTGCCCCGGGGGATGATGCCCGGCCCTGTGCACAACACAGGCTGCCTCTCTGCTTT19020 
ACACAAAGGCTCCTTACCAGCTAGTTCTGTGATTCTCAGAGGCCCACAGCATCCTCAGGC19080 
TTTTGACAACCAGGCTCTGGCACCCACTGTGTGCCAGACCCTGGCATCTGCCTGGCTCAG19140 
GGGTGGTCACTCACGTCCCCAGCTGCTGGCCTTGGAGCAACTGCTACCAGGGTCCAGCTG19200 
CAAGCAGGAGCCTGCGGCCGCGCTGGGCCTCACTGCTGGAGGTTGTATATTATAATAAAG19260 
CCAACATTTTGTTGAAGGCTTCTGCTGCGCCAGGCACTGTGTTAAGCTCTTTGTGGGGAT19320 
TATCTCGATTAACTCCTACAAACCTAGGAAATAAATAGAATTTTCCCTAGGCTCAATGTC19380 
ACACAGCTCCCAAGTGGCACAGGTGAAACTTGACTGCAGATCTAAGTTACTGATCTGAGC19440 
AAGGAAGTGGAAATTATGTTCTCCAAAACATCGCTAGAACTAGTAGTATAGATTCTGGGA19500 
AGAGGAGACTCAGGGGCCACAAGCCTGGCTTGCTAGACCCTCAGAAGGGCTGTATGATTC19560 
CAAAGGCATGTGGAGAAGCTGCAGGGGAAATGCAGGAGAGGAAGGTTGCAGTGTGACCTC19620 
CAGAAGGCCTTTCTGAACGAGCTTCCTGGAGGTGTAGTGCATGCAAGCCATGGCTGGGCA19680 
CCAGGCCAGGCCGCTGCAGAGAGGTTTCTTGCACTGGCAGAGGGTGAGACTGCATGACCC19740 
CAGAGGCTCCCTACCCCCAGCCACAGGAGGCTGTGACTCTGGACAGGGTTTGGGGCTGGG19800 
CATGAGCAGAGCTGAAGAGGCCGTCCTCTCTGCCTTTCTCGGGGAGGGTGTGCAGGAGAG19860 
GCTCCAGAGGCTTCCAGTGGAGGATGCTTCATTCAGTCAACAAGCATTTATTGAGCACCC19920 
ACTGTGTTCCAGGCAGTGTGCAGGCCTGACCTCAGGGGGCTCGGAGGCACCCCTGCCTGC19980 
TCACTGCTTTGCTTCATGCCTTCCAGGAGCCCACACGCATCCCCCGGATGAGTTCCTCTT20040 
CACACCAGTGGTGGTCGCCTGCATGTCCATCATGGCCTTGCTGCTGCTGCTGCTCCTGCT20100 
GCTATTGTACAAGTATAAGCAGGTGAGCCGGAGCGGAGTGGGGCTGCCAGGTGCCTGAGT20160 
GAGCCAGATTTGGATGGTACCCCCAGGCTGCATGGATTCACCCTTCCTCCTCCTCAGTCA20220 
GTCCATCAGCTAACAGCTCTTTAGTGGGTGCCTACTGTATGCCAACATGAGCCAGCTGCT20280 
GGGTGGCCTCTGAGGCTCTGCCCTAATAGCGTTTACTGTCTAGTGCGAGAGACAGGTGCT20340 
AATCAAATAGCCATTAAAGCAAGGGCACACCTGTAATCCCAGCTACTTGGGAGGTTGAGG20400 
CAGGGGGATTGCTTGAGGCCAGGAGTTAGGGACCAGCCTGGGTGATACAGCCAGATCCCA20460 
GCTCAAAAAACAAACAAAAAGCCGTGAAAGCAAGAGCATGGATTATAGAGTGAGAGGCTA20520 
TGAGGAGAGGAATGGCATTCTGAGGCAGCGCAGCCCTGGGATCCTGTCTCAGCCCAGGGG20580 
TGTCCTGGCACCCAGCACGGGGCAGAGGAAATGGATATACAAGCGTGGTGTCCCCTGGGC20640 
CAGGCCTGAGCCCTGCCCTAAGAAGCACATGGTCTAGTGAAGACGAGGGCCTGTGACCAT20700 
CATCCTCTTCATTATTTCATGTTACTGTCCTATTAGCCAAAGCCACAATTTAGTGCATGT20760 
TGCGTATAGTGTGCTTCCTGTGTCTGCTCAGTATATGACAGTGATTTGAGGGGCATTTTT20820 
CTATAGCATGTTACCTACATCATCTCATTTAATGCCCTCAGCAACCACTGTATGCAGCTA20880 
GCATTAGTCTATTTTACAGAGTTGTAAACTGAGGTTCTGAGAGGTTGGGACAGTTGCCCT20940 
TGTCTACAGCTGGTCAAAGGCAGAGTCTGGTTTTTAACCCTGAAGGAGGACTCACTCCAA21000 
AGCATGTCCCAATCATTATGTGAAACATTGACTCATCTTATTTTACCCTCACAAGAAGCT21060 
GGAGGCAGGAAGTATACTAGTCAGTATCTTACCCATCAGGAAGCTGAGGCTCAGCAAGGT21120 
TAAAAAAAAAACCCCAAGGGGCTGAGGGATAGGGTTGGCACTGGGCCCCAGGGGCTTCTG21180 
TCCCTAGAGCCCATGGCCTCCACTGCCTGCCTGCCCACACAAAGACCATGTGCAATGTGA21240 
TCAGAAGCTGAGAGGACCAGGCCAGAGGGCTGTGGGAGTTCAGAGGTGGACGGACTTTTC21300 
AGGCTGGTGGGTAAGGGAGACTGCCTGGAGGAGGTGGCTTGGCATTGGTGGGACGGGCTT21360 
TGGAGGATGAGGATGCAGCAGGGGAGATGACACTAAGGGAAAGGGTATCTCTGGGGGAGA21420 
GGGCAGAGTGTGCAGAGGTGCAGGTGAGGGAAGGACCAGGGTGGGGCTGGGGGTCTGAAG21480 
GGTTGGACCCCACCCTGTCGGTCCAAGGCCATCAGTGGGTTTGAACAAGGGAGTGGTGTG21540 
ATCAAGGACTGAATGACCCATCTTGTGTCCCCTTGGCTACCTTTTCTTCCCCACACCCCT21600 
TGGGGCTTTTGTGAGAAGAGGGCTTGAAGTGGGCAGGGTGGGAAGGATGTTGGGGGAGCC21660 
CCAGGGGCACATGGATCGGGATCTCTACTCCTGCCAGCACTCAGCATGAGAAGGCTGCTC21720 
TGAGGGCAGCCCCGGTCAATACCTCCGGATCTAGGTCCAGCTCTGACACTGTTTTGCCAT21780 
GTAACCTCAGCTGACTCGCTGTCCTCTCTGGGCCTTAGTTTCCCCTCTTATACCATGGGT21840 
CTGGGTGTTCTCTAACAGCCCCTCCTCCTCTGACATGCCAAGAGCCCACTGGTGGTCTAG21900 
TTTAAGCACCAGAAACTTGGACTTCAGTGAATCTGGGTCCAAATCCTGCCTCTGCCAAGC21960 
TCTGGCTATGGGGTGATGAGAAAGTTGGTGTGTCTGAGTCTCTTCTCCATTTGTAAAATG22020 
GGATCATTAACAGCCTGTTGTGAGGGATTCCGTACCACAACGCACATAGAGGACTGAGCG22080 
GGGTGCTGGACGAGACAGTCTCTGTGATGGGAGCTGCACACTCTTGTCCCAGGAGGAAGT22140 
TCGTTGGGGAACCAGAGTTAGCTCATGCCTCTTGGGATGGTGGAAGGAGGGGGAGGTCTG22200 
AGGTCGGGCATCATCTCCTTGACTACACACCCAAAGCGGTTGTTTGGCCCAGCCCACCCA22260 
CCTCCAGGGACAGGACCTTACTCACTCTCGGGGCCACCCGTTCCTTCTCTGAGCAGCTCC22320 
AATGTTTGCAAAGTTCTTCCTTACATGGAACTGAAAACTGCCTCGCAGTGCCCACAGAGC22380 
TGCCAGGACAGTCATGCAGAGATTCCAGAGAAGGGCCTAGGGCCCCCTGCGGCCCTTTCT22440 
GCCTTGGGCTGGCCAGCCCCCTTGGCTGTGGTTTAGGAACTCTGTATCCCCTCTCCACGG22500 
GACCATTTTTGGAACATGTCACCTCCACACTTCCTGTCCAGGAAATTCAGCTGCCCCTGG22560 
AGCCCATGCAAGGCTGCGAGAAGACTTGCAGCTACCCTCCTCCCCTACACCCATTCACAG22620 
ACCCTTTAGCTCCAGGCCGAGGTGTCCACCCATGGGAGCGGAGGGGGCAGGATGGTCATG22680 
CCCGTGCTAAGTGCCTGCCCTCCCATCCTCCTCTGCCTTGCCCCATGAGGTTCGGAGCCT22740 
TGCCCCTTCACTGGGGACTCAGCCCAGCCTCTCCTCATTGCCCAGGCCTGGGGAAAGAAG22800 
TGGCCTGTCTGTGGGGAGTGTTTGTTCTGCCTCAGGGCTGAATCATCACCTTTCTGTCCC22860 
CCAGAGTGACCACAAGGGGGGCCGTGGGGGAAGAGAAAAGGGCAGGAGTCAGCAGGCTCC22920 
CCTGGAGGAGGAGGCGCACAGGGAAATGGCTGAGGCAGCAGGGAAGGGAGGGTCCAGGGA22980 
GGCTGCTGGAAAGACTACGATTCTGGGGGCTGGAACTGAGCTCTGAGGAGCAACAGGAGG23040 
GTCCCCAAAGATTCCACTGGGAATTGTTCAGATCTCCACCTTCCTGTGAGAACATCCACT23100 
CACCCAGAACCAGCAGGCCTAGATGGGGAGGGGACCGGGACTTTGTCTCCATGCCCCCTT23160 
TGGTGGGGAGGATGGGAGGAAGGGAAGAAGTCAGGGGGTGGGCCTGGGGCTTAGGCCCAT23220 
TGCAAGGAATGAATGGGGTGATGTGCTTCAAGCATCTAGCCCAGCGCCCCACTCCCAGGA23280 
AGAGCTCAGGAAGAACCCGCTGCCATCATGACAATTACGTCCACCCTTCTCAGGGAGCCT23340 
CGCCCATCCCCACCTCTTGATCTCTCACTCATAGTTCTTTGGAAGAGAGGCTGCCTCTGG23400 
GTAGACGCCCATGAGCCCTTTCCAGGGATGGCACAGGTGCCCTGGGAGGTTTACATGCCC23460 
AGCAGGGGCAGGGGAGGGTTCCTGAGGCAGGCAGAAGGCAGCTTGGTCCGCTTCCAGAAA23520 
TTAGGAGCCTAGGATTCAGAAATCTGAGAATCCAGCCAAACCTCCATCCTCCTTGATCCC23580 
CTCCCTTTCAACAGTGCCCCCTGCCCAGCTGGGGGCAGGGAGGGGCTGACTCAGCCCAGC23640 
TGCAGAGGGACAGAGGAACAAGAAGTGGTAAGAAAAAACAGTCTTAGCCACAGAGGCTCC23700 
TAGAGATGGAAGTGGCCAGGAGAGGCTGAAGAATCCCCTCCTCGCCTTGTTGCTGTCTTT23760 
TGGGCTGGGAAGGCACCCACGGGCAGGATTTGGATCCTCAGAGGCTTGGGAAGCTCTTCT23820 
CCCTGGGTCCCGTTTCAGACTCTCTCCCAAGCTATAACGCAGAGGCTCTGAAGTTCACCT23880 
GCAGTCCGCCCTTCCAAATCAGAGCCTGGAAGTTAGTTCCTTCTCATTTCTAATTGCAGT23940 
CTTTTCTCTCTAACTACCAGCTAGAAGTTCTTCCTGATGGTTAGCTGGAAGCTTTCTCCC24000 
TGTCTCTCTCTTTAAAAATGTCCACATTTTATTTTTGATTCAGGGGATAGACGTACAGGT24060 
TTGTTGCATGCGTATGTTTCGTGATGCTGAGCTTTGGAATATGGATCCCATCACCTGCTA24120 
CTGAGCATAGCTCCCATAGTTTTTCAACCCTCGCCCGCTTCCACCCTCCCTGCTCTAGTA24180 
GCCCCCAGTGTCTGTTGGTGCCATCTTTATGCCCATGCACACTCAATATTTAGCTCCCAC24240 
TTATAAGTGAGAACATGCGGTATGTAGGTTTTCTGTTTCGGTGTTAATTTGCTTAGGATA24300 
ATGGCCTTCAGCTGCACCACGTTGCTGCAAAGGACATGACTGGAATCTTCTCTCTCAACC24360 
AGGACTTGCAGCTAAAGGCCAGCCTCCTCCCTAGCACCGGTCCACACTTCCTTTAAGTTT24420 
CTAGCTCGGGTGCCCAGGGAAGGAGCCCAGCTGCAGGCACAGCCAAGCTTGTCCCATCCC24480 
CAAGGCCTGGCCGGAAAGAGTTGCTCTGCTGACCCAGGGCCTCAGTGTCCTCCACCGCCC24540 
CAGCCCAGCTTCCACTTTCCCCCTCAACTTGGTCTTCCATCAGCATTTCTTATGGGCAAC24600 
CCTTAGCATGGTACTCCCCCTCAGCAGCTGACCCCTGGGCAAGAAACAGGGGCAGCCATT24660 
CCTCCTCCCCACATCCCAGGGCTTGCCTCCCCTGGCTGGGTGGTAACAGCATGGAGAGCC24720 
TAAGGAAGGAAATCAGGTCTTTCCAAAGGTGCTGGTCCTCCAGAATCTATCTAGTGGGCA24780 
GCGTCTCTCTTTCTCTCTCAAAAAGGTAAAGTCAAGGCTGGGTGCGATGGCTCACGCCTA24840 
TAATCCCAGCACTTTGAGAGGCCAAGGCAGAAGGATTGCTTGAGCCCAGGAGTTTGAGCC24900 
TAGTGAGCTATGATCGTGCCACTGCACTCCGGCATGAGTGAAGGAGCAAGACTCTGTCTC24960 
AAAAAAAAAAAGTCAGATGGCGACTCACCTGTGTCAAACTCTCAGGGTCTCTCACTGCCC25020 
GGCCAGGCATGGTAGCTCATGCCTGTAATCCCAGCACTTTGAGAGACCGAGGCAGGCAAA25080 
CTGCTTGAGCTCACGAGTTCAAGACCAGCCTAGGCTGCGACAAAGCCCCGTCTCTACAAA25140 
AATTAGCCAGGTGTGGTGCCACATGCTTGTAGTCCCGGCTGCTTGGGAGACTGAGGTGGG25200 
AGGATTGCTTGAACCTCGGGGGTCGAGGCTGTAGTGAGCCAAGACTGCCCCCACTGCATG25260 
CCAGTCTGGGGGACAGAGATCCTGTCTTGGAAAAAAAAAAATCCCAAAAGGGAACCCACT25320 
CACCTTATCATAGCCCTCAAGGCCTTCCTGTTTCTGGAATCTGCCCCCCACTTCCCTCAA25380 
GCCATGATGGCTGCCTTCCTATAGCTCAAACTTGCCAGGATCATTCCCATGTCAAGCATA25440 
CAGCATTTCCATGCACTGTTCCTGGAAAATTCTTCCTCTGATGGTCACATGGTGGGCTCT25500 
TTAGGGGCCTTCCCTGACTTATCTTACTTTATTTTCTTCATAGCACCACTTGAGAATCTC25560 
CTAGATACATGTTTATTTGCGTTTAATGCCTCTCTCAGCCACTAGAATGCAAACTCCATG25620 
GAGGGGCAGGGACTTTGTCCTGTTCAACTCTGAATCAGCGGTGCCTGACACAAATAGATG25680 
TTCAAGAAAGTATGTGGATGGGCTACTATTATTCAGCCTTAAAAAGGAAGGGAATTCTGA25740 
CCTGTGCTGCAGCATGAATGAACCTTGAAGACATTATGCTGGGTGAAATAAGGCAATCTC25800 
AATAGACACATGCTGTGTGAGTCCACTGAGGTGCAGTGCCTAGAGCAGTGCAATTCACAG25860 
AGACAGCAGAATCATGGTTGCCAGGGGCTGGAGGAGGGAAAGGGGAGTTGCTTTTTAACA25920 
GGAACAGAATTTCAGTTTTGCAAGATGAAAAGAGCTCTGGAAACTGGTTGCACAAGGTAG25980 
AATGTAATTTACTTAATACTACTGAACCATACACTTAAAAATGGTTGAAATGGTAAATTT26040 
CATGTATGTTTTATCACAATTAAAATATATATATATATTTGGATGGGAGGTTGGGTGGGT26100 
GGATGGATGGGTAGATGGATGGACAGATGAACGGATGGATAAGATCTCAAGTTCCACCCT26160 
CCCTCCTGGCTCAGGAATTACCAGATTATCAGAGATATCAGGGCCCTCAGAGGTTGTCTT26220 
GTCCAAGGTCTTCAATACACAAATAGTGAAACAGGCTTGGAGAAGGGAAGGTCACACAAC26280 
AAGGCAGAGTCAAGCAGGAACATGCTCTCAGTGCTATGTTCATGAGACGACCTCTCTCAG26340 
CCCAGAGCAGGCCTTGCCCTGCCTTCTCCCACTGGGCGCCTTGGGACTGCCCACACCCCT26400 
GCTCTTGGGGGTCAGAAACAAGGTCCAGGAACTGCCTGCCAGCCCCGACTGCCACGTGCT26460 
CCCTTCCTCTTCTGCAGAAGCCCAAGTACCAGGTCCGCTGGAAGATCATCGAGAGCTATG26520 
AGGGCAACAGTTATACTTTCATCGACCCCACGCAGCTGCCTTACAACGAGAAGTGGGAGT26580 
TCCCCCGGAACAACCTGCAGTTTGGTGAGATGGCAGCTCATCACTCCACAGCTTCCTATC26640 
ACAGGGCCTGTGGGGGTTGCAGGGAGCCCATGGGCCCTTGGACAGAGGCCCTTTGGTGCC26700 
CAGGGACTTAAGGGACCTGTGTGCGTGGCAGGTAAGACCCTCGGAGCTGGAGCCTTTGGG26760 
AAGGTGGTGGAGGCCACGGCCTTTGGTCTGGGCAAGGAGGATGCTGTCCTGAAGGTGGCT26820 
GTGAAGATGCTGAAGTGTGAGTGAGGGGAGGGGATGAGGGAAGGGATGGGGGTGGTAGAT26880 
GCTGGGGGTGGGCTGGCCCTGGTGTCACAAGAGGCATCACACACATTTCAACCTGTTGAA26940 
GCCTGGGGGACAGAGCTCAGGGGTGAGGACTTGGGTTTTCTTGTGAGCTCCAGGCACCCT27000 
CTGACTCCCGGCTCCAAGAAGGTCTAGGTCACCCTTTAGTTGTGAAGGGGCTCCTGACTG27060 
AGCTCCAAAAAGTCTGGGGGTGCAGAAAGGCCACCTATGGCCATGGCCTGGCCACAGTTT27120 
GGCTTCCTGTCACCTGAAGACCAGCTCAGTGACAGGCTCATCCCTTCTCTCTCTCTCTCT27180 
GCCATCTGTGTGTCTGCATTTTTCCTTCTCCTTCTTTTGGCTTCTGGTCACTCCGGGTCT27240 
TGGGATATGCCCTGCTTTCTCCCCTGGGTCTCTGCATTTGGTCCCCATGTATCTGTGTGG27300 
TGCTCTCTGTCCTGCCCTCTCCCTGTCTTTGGGACTGTGGTTCTTCCTCCCAGCCACGGC27360 
CCATGCTGATGAGAAGGAGGCCCTCATGTCCGAGCTGAAGATCATGAGCCACCTGGGCCA27420 
GCACGAGAACATCGTCAACCTTCTGGGAGCCTGTACCCATGGAGGTAAGGGCCTTGGGGT27480 
TCCTGGGGCCAAGGTCTTGGGGCCTCTGGGGAATCTCAGGGCCCCAGGGCTACCTTGTTC27540 
CGTCTTCTCCTTCTCAGGATCCTACTGCTCCAAGTGTCAGGGGGATCCCGGTCACAGCAT27600 
CCCTTAAACTCCTGGGCCCATCTCCTGGAATAGTCAGGAGCTGCACGGGCAGCTTGAGGT27660 
ATAAAGAGAGACTGATAGGGAGCATCGGAGCCCTTGGAGGAGGAGATGAATGTGCAAGCT27720 
CCTAGGCCCTGCTTCCAGGGAGCCGGATCCTCTGGGTCTGGAGTGAAGCCCCCCGCCTAC27780 
CTCTTATGAAGCTTCCATTCAAGGATGCTTGGACACTCTCCCCAGGGCCCCCAAAGGTGC27840 
CCCGGGCTTTGCTGGGACTCCAAGTGCCCCACATCCTCTTCACTGATAGCAGCTCTGACC27900 
TACAGTGAGCCGCCATAGCTTTCCTTTGAAGAAATAATTCTTGGGCTACATTTTTTTTAA27960 
GGTTGTCTTTTTTTTTTCATTTTTTGTTTTTTTTTTCTTGAGACGGAGCCTCACTCTGTC28020 
ACCCAGGCTGGAGTGCAGTGGTGCGATCTCGGCTCACTGCAACCTCTGCCTCCCAGGTTC28080 
AAGCAATTCTCCTGCCTCAACCTCCTGAGTAGTTGGAACTACAGGCACATGCCACCATGC28140 
CCGGCTGATTTTTTTGTATTTTTGTAGAGATGGGGTTTCACCATGTTAGCCAGGATGGTC28200 
TCGATCTCCTGACCTCGTGATCCACCCACCTTGGCCTCCCAAAGTGCTGAGATTACAGGC28260 
ATGAGCCACCGTGCCCCGCCAAAGCCATCTGTTTTAAACAAATGGAACTACTGAGGCACA28320 
AGGAAACTTGCTCACAGAGCCGAGGTTAGAACTCAGCTATGCTGAGTCCAAGTCCAGTGG28380 
CCTCACTGCCCCCAGTCTCATGCTCCTGTTCATGGAGGGGAGCACTCAGCACCTCCCTCA28440 
CCCCACACCCTTGGCTGCTCTAGGCCCTGTACTGGTCATCACGGAGTACTGTTGCTATGG28500 
CGACCTGCTCAACTTTCTGCGAAGGAAGGCTGAGGCCATGCTGGGACCCAGCCTGAGCCC28560 
CGGCCAGGACCCCGAGGGAGGCGTCGACTATAAGAACATCCACCTCGAGAAGAAATATGT28620 
CCGCAGGTAGCCCCTGGCAAAGGACAAGAAAAAGGCCAGGTCTGGGAGGCAGGATCCGAG28680 
TCTGTCTTCAAAGCCAGCTCAGGGTTGGATGGCTCATGAATGGGTGGCTATGCAGCCCTC28740 
ACCTGCCACCTGTGTCATGGGAAGTAGCCACCACAGGTTTTATGGCCATCTCTTGTTTCT28800 
CTACTCCTTTTCCCCTTCATTCAACAAATATTTGAACACCTACCGTGTTCTGGGAGTGTG28860 
GAGGGCAAAGATGGGCAGCTCATAATCTGGTGGAGATATGCATCAATGAAATCACCACCC28920 
AGTGTGTGTAAAAGATCAACCAAGATCTGTGCCTGGAGCCCTAGTAAGAGATGGGCAGAT28980 
GTGGCCGGGTGCAGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGCGGGCA29040 
GATCACCTGAGGATGGGAGTTCGAGACCAGCCTTACCAACAAGGTGAAACCCCGTCTCTA29100 
TTAAATATACAAAATTAGCCGGGCGTGGTGGCGCATGCCTATAATCCCAGCTACTCGGGA29160 
GGCTGAGGCGGGAGAATTGCTTGAACCCAGGAGGCAGAGGTTGCTGTGAGCTGAGATCAC29220 
ACCATTGCACTCCAGCCTGGGCAACAAGAATGAAACTCCGTCTCAAAAAAAAAGAGAGAT29280 
GGCTCTGTTGTCCTGTTGCTGTGATTCCTGGAAGCCATCCAGAACAGAGCCATCCAACAG29340 
ACAGAGCCACATGGGGAACCAAAGAGAGGAAGTGGGGAGATTCATGTCACACATGAGTCA29400 
GGGTTAGAGGTGGAGCCTGGACTAGAATCCTGCTCTCTTGACTTCCAGTCCAGGAGTCAC29460 
CCAAGCCACACTGCTGTCCTGGAGGTCTCTGTCTCAGGGGCTTGTGGGGTCAGGACAGGA29520 
TCAGAACAAGAAGGGTGTACACTGCGCCCTCATCCTAGATACTGTCAGCTGCCACGCCTG29580 
GGGAGGCAAAAGAGAAGGAGGCCATCTCTTCACCCAGGGCCTTAAAAATGGGGGCCTGGC29640 
AGCATCACTTCCTCTTCTGATTCCCTGACACTTCTATGAGGGTGGCACACACTAGGCCTC29700 
TGAAGATCAGATCAAAATGAGCACCAAAGGAAAGTATTAGCTTCCATCTTCAAATACGCA29760 
GATGGGGAAAGTATTCCCAGAGTGGGTAATTTCGAGGGCAAATGGCCTGTAAACCAACTC29820 
TGTCAAAGGATTCCAGGCTGTTAACGGAAGCATAGTTTCTACAAGGGAGCGGAAGGTTTT29880 
TTCGGTTTCTCCTTCTGGGAACACTAGAATATGGACATTGTCAAGGTACACATCTCTAGC29940 
GCAGAGGGGACAGGAGGGAGAGAGAAATCCTATCTGGCTGGAACGTTAGGAGCAGTAGTG30000 
CTTCAGTCTACAGTAGTGCTTCTCAAATTCTCTACCCCAAGTGTGCTCTCATAGGCATCT30060 
CTTGAGGACTGTTGGAAGTGCACCACCTCAGGCCCATCCACCCAGGCCTGCTGATTCAAA30120 
ATCTGCATTGCAGAGATTCCCGGGGTGATTTATCTGCACATGAGTTGCAGCGTAAGCAGC30180 
ACTGCTCTAGACCAGTGGGCCTCAGCTTAGGCTGTACTTTGTGATCACCTGGGGAGATTT30240 
AAATCTGTGAATGACTGTTTTGTCCCTAGAGTTTCTGAAGTATTAGTAATTAGCCTGATC30300 
CTAAAAGCTCCCGAAGTGATTTTAATGTGAAGCCAGGGGTGTGAGGCACTGTCCAGAGAA30360 
GAGAGGGCACAAGGGGCCCTAGAATATGCCCCAATTCTAGTAGGGCTGTTATGGGGAAGA30420 
GGACTCCAACTTCTCTGTGGCCCTTGAGGGTAGAGCAGGGGCTAGGAGGAAAATCTCAGG30480 
GGTAGATTGGCATTAGGAACAGTGAAGAACTTTCTCACAGGCAGAGCTGCCCAAAACCAG30540 
AATGGGTTGTAAGCTCCCTCACCGGGGACAGCCGAGCAGAGACCAATGCTCACTCAGATG30600 
GAGTGTGGCAGGAGGGTTTCTTATCAGAAAGGGAGGTTCCAGTTGACCATGGGGTGGTGG30660 
GTGGTCAAGGCCTGAGCTGAGCAGTGCAGTGATGATGACTGACCTCTGCCCCCCAACCCT30720 
CTCTCCTATGTAGGGACAGTGGCTTCTCCAGCCAGGGTGTGGACACCTATGTGGAGATGA30780 
GGCCTGTCTCCACTTCTTCAAATGACTCCTTCTCTGAGCAAGGTGAGGAGGTCCCAGGGC30840 
CAGGCCCCATTTGCTTGATAACAAGGGAAAAGGAGAAGGGGCTGCTGGGGTGAGGGGTGG30900 
GGAGTGTGGCAGGGCTGCCCTGACGCCTCTTCCCACCCTAGACCTGGACAAGGAGGATGG30960 
ACGGCCCCTGGAGCTCCGGGACCTGCTTCACTTCTCCAGCCAAGTAGCCCAGGGCATGGC31020 
CTTCCTCGCTTCCAAGAATGTGAGTAGGAACCTGGCCCTGGCTCATAGCCACCCAGGTCT31080 
GTGCTCCGGGGAGGCTGGATGAGTGACGATGGGGAGGAGGAAACGGGAGCCTGTGAGGGG31140 
GTAGGGGAGGAGACAGAGTATGAGAGAGTCATTTGGGCAGCAGCTGCAAGGATGAGTGGG31200 
AGAAAGCTGTGCCCAGGGCTGGAGCTCTGGGGCTGGGCACCTGTGTCCCCAGCGTGAAGA31260 
TGAGGAAGGGTACCAGGCTTTCTTCATTCGTTTTTACTAAATAGTGTATGAGAGACAACA31320 
GTTGTCTCTGCTCATAAAGCACGTGGTCTGGTGGGGATGATAACGGAAGCTTCCTCAGAA31380 
TTTTGGGGATATTAGATAACGTATAAAGTGCGCTCGGCCTAGGAAGAAGTGCCAGGGAAT31440 
GGGAGCTCTTGCCATCTTCCTTAGAACAGATTCGGGAGTCAGTGGTTTGATTGTTGGCTC31500 
TGCCACCTGCTCCGTGACTTTAAGCAACTATTTAAATTCTGTGCCTCAGTTTCTACACCT31560 
ATAAAAATGGGCATAACGATTGTTGAAAAGAAAAAGGGTTCAATGTGTGCAGAGTTTAGG31620 
GAAGGGCCTGGCAGATAGCAGCTGCTATGATCAGAAGTAACGGTAGGGTTTGGAGACTGC31680 
TCTCTGCACGGAAGCCCTTCGCTTCTGGGGCCTGAGCAGACCAGTCAGAGGACAAAGGGT31740 
GAGAAGGGCCATGGCTGCTCAGGGTAATGGGGGTTTCTAAGCATTAAATGATCAGATCAC31800 
GATACACATTCTCAGATCCTGGGCCCTGGTAGAAGGTATAGACAAGGGTTTGTGGTAAAG31860 
GACCAAAACTGTTGTTCACTCCAGCAGGGACTCCAAAGCCATGTGGGGCCCTCCCTGCCA31920 
TCCTCCTCACCTCAGGCTCAGGTAGGAGAAGGCCCAAGACTAACCCTGCAGTGCTTTCCC31980 
TCAGTGCATCCACCGGGACGTGGCAGCGCGTAACGTGCTGTTGACCAATGGTCATGTGGC32040 
CAAGATTGGGGACTTCGGGCTGGCTAGGGACATCATGAATGACTCCAACTACATTGTCAA32100 
GGGCAATGTAAGTGCTGGGAGGGCTTGGGTCAGGCTGGGGAGGGGGTGAAGAGTCGGGGC32160 
CCAAAATAACTGGGGACTGTCATCCCAGGCCCGCCTGCCTGTGAAGTGGATGGCCCCAGA32220 
GAGCATCTTTGACTGTGTCTACACGGTTCAGAGCGACGTCTGGTCCTATGGCATCCTCCT32280 
CTGGGAGATCTTCTCACTTGGTGAGCCACTGGGCCCACTCCAGGCAGAGCCTGGGGCTGG32340 
CTCCTCTGGTTGCCCCACTGGTGGACAAAGCTGTTTGGTGCCCAGGACACAGCGAGGGTT32400 
GGTGAGAGTGCAGGAATGGGCAAGGGCTCTCGAAACCCAGCATCGTGGCTCCTGCGGGAC32460 
TCGGCAGACCCTCTGCCCCTGACAGGCGCTCCTTTCTGGCTCTTCCCTCGTTTGTCTCTG32520 
CTCAGTTGCTGTTACCTGTTACCCTCCTTTGTCACTGTTTCCCTCCTTTGTCTGAAATCT32580 
ACAGACCCTTGAAGATGCAGCTCTCTACTACTAGGCTCTAGTAGAAAGAACTGCTATTTC32640 
CCGAGGACTAGGCACAAGGACTTGTACTCAGTTCTTAAATACGCTGCTCCTATACCCTCA32700 
TAACCACCTGACTGTCCACACTTTAACGATACACAGCTGAAGCTTTGGTCTGATTCCAAA32760 
GCCTGTGCAAGAATGTTTGGTGTGATAAGGCCTGGATAGAGGCTCACACCTTCCTAAAGC32820 
CTAAGCCTGCCACACACTGGCTGGCACACAGGAAGCACCGGGTAAGAGTAGCTGCTGTTG32880 
CAGATGTTGTCAAGTGGGACCCTTTAAACCCAGTCTAAGATGTGTGTGGGTGTGCGGGAA32940 
TGGGGAGAAGACAATGGGCATGGCCTCTTACCTGATCTTGGCCTTTGCAGGGCTGAATCC33000 
CTACCCTGGCATCCTGGTGAACAGCAAGTTCTATAAACTGGTGAAGGATGGATACCAAAT33060 
GGCCCAGCCTGCATTTGCCCCAAAGAATATGTAAGCGAAGGGATCCCAGGGAGGGAAAAG33120 
GACACCCCAGGCTTTCGCTGGAAAGGGATGGAAGGCCGTGTGGCCCTGATCTTTCCCTGT33180 
CCAAAATGTTCCAGGGTCAGACTTTATCTCTCCCATAGTGGACACAACAAGCCCCTTTTG33240 
AGTTCAAGCTATGGGGGATGTTCTCAGAGAAGCAGCTGTTCACTAGGGCTGGTCCTAACC33300 
GACCACTTTTCCTTTTTTTTTTTTTTTTTTTTTGAGACAGCATCTTGCTCTGTAGCCCGG33360 
GCTGGAGCGCAGTGATGTGTGCAATCATAGCTCACTGCAGCCTCAATCTTCAGGGCTCAA33420 
GCAATCCTTTGGCCTCAGCCTCCCAAACAGCTGGGACTACAGGTGTGCACCACCAAGCCC33480 
AGCTATTTTTAAAAAATTTTTTAGTAGAGATGGGATCTCACTATGTTGTCCAGGCTGGTC33540 
TGGAACTCCTGGCCTTATGCAATCCTCCTGCATCAACCTCCCAAAGTGTTGGGATTACAG33600 
GAATGAGCCACTGCACCTGTCCCTAAACAGACTTTTAAGAGATCGTTATTACAGTTACCC33660 
TGAGGATACCAAAATGGCCTCATCTGTCAGAATGAGGGTGATGAGAGTACCCTTCTGCAA33720 
GGGTTACTGTGAGGATTAAATGGTAAAGCATGCCAAGGACTTGGCATAGGTTTTATACTA33780 
AACTTACTTTGACTGGGTTTGGGGACCTCTGCTGGGTAGGTCTCTCTAGGGGTGTGTGTT33840 
AATGGCCCCTGGACCCTAGGGAGCTGCCCATGGGCATCCTCTGTCCTATCTCCCAGATAC33900 
AGCATCATGCAGGCCTGCTGGGCCTTGGAGCCCACCCACAGACCCACCTTCCAGCAGATC33960 
TGCTCCTTCCTTCAGGAGCAGGCCCAAGAGGACAGGAGAGAGCGGGTGAGTGGGGTGAGG34020 
CTTGGGGTGGGTGGCCGGTAAAGCACGTTGGGCTGGGCCTGATGGATCTGGACTGACAGT34080 
TTCTGGTCCCTCCCACCCTCAGGACTATACCAATCTGCCGAGCAGCAGCAGAAGCGGTGG34140 
CAGCGGCAGCAGCAGCAGTGAGCTGGAGGAGGAGAGCTCTAGTGAGCACCTGACCTGCTG34200 
CGAGCAAGGGGATATCGCCCAGCCCTTGCTGCAGCCCAACAACTATCAGTTCTGCTGAGG34260 
AGTTGACGACAGGGAGTACCACTCTCCCCTCCTCCAAACTTCAACTCCTCCATGGATGGG34320 
GCGACACGGGGAGAACATACAAACTCTGCCTTCGGTCATTTCACTCAACAGCTCGGCCCA34380 
GCTCTGAAACTTGGGAAGGTGAGGGATTCAGGGGAGGTCAGAGGATCCCACTTCCTGAGC34440 
ATGGGCCATCACTGCCAGTCAGGGGCTGGGGGCTGAGCCCTCACCCCCCGCCTCCCCTAC34500 
TGTTCTCATGGTGTTGGCCTCGTGTTTGCTATGCCAACTAGTAGAACCTTCTTTCCTAAT34560 
CCCCTTATCTTCATGGAAATGGACTGACTTTATGCCTATGAAGTCCCCAGGAGCTACACT34620 
GATACTGAGAAAACCAGGCTCTTTGGGGCTAGACAGACTGGCAGAGAGTGAGATCTCCCT34680 
CTCTGAGAGGAGCAGCAGATGCTCACAGACCACACTCAGCTCAGGCCCCTTGGAGCAGGA34740 
TGGCTCCTCTAAGAATCTCACAGGACCTCTTAGTCTCTGCCCTATACGCCGCCTTCACTC34800 
CACAGCCTCACCCCTCCCACCCCCATACTGGTACTGCTGTAATGAGCCAAGTGGCAGCTA34860 
AAAGTTGGGGGTGTTCTGCCCAGTCCCGTCATTCTGGGCTAGAAGGCAGGGGACCTTGGC34920 
ATGTGGCTGGCCACACCAAGCAGGAAGCACAAACTCCCCCAAGCTGACTCATCCTAACTA34980 
ACAGTCACGCCGTGGGATGTCTCTGTCCACATTAAACTAACAGCATTAATGCAGTCAGCC35040 
TCTGGTTCTTTGTGCCACATGAGTACCTGCAAATTCCCTGGAACGTCTTTCTTTCCTTCC35100 
(2) INFORMATION FOR SEQ ID NO:20: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 218 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: 
ATTTATTATTTTTTGCAGAAAGAGCACTTCAAATAATTTACAGAACCAGAATTTAAGGTG60 
GAAGATGACATTTAATGGATCCTGCAGTAGTGTTTGCACATGGAAGTCCAAAAACCTGAA120 
AGGAATATTTCAGTTCAGAGTAGTAGCTGCAAATAATCTAGGGTTTGGTGAATATAGTGG180 
AATCAGTGAGAATATTATATTAGTTGGAGGTATGTTAC218 
(2) INFORMATION FOR SEQ ID NO:21: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 5084 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: 
GATCCCATCGCAGCTACCGCGATGAGAGGCGCTCGCGGCGCCTGGGATTTTCTCTGCGTT60 
CTGCTCCTACTGCTTCGCGTCCAGACAGGCTCTTCTCAACCATCTGTGAGTCCAGGGGAA120 
CCGTCTCCACCATCCATCCATCCAGGAAAATCAGACTTAATAGTCCGCGTGGGCGACGAG180 
ATTAGGCTGTTATGCACTGATCCGGGCTTTGTCAAATGGACTTTTGAGATCCTGGATGAA240 
ACGAATGAGAATAAGCAGAATGAATGGATCACGGAAAAGGCAGAAGCCACCAACACCGGC300 
AAATACACGTGCACCAACAAACACGGCTTAAGCAATTCCATTTATGTGTTTGTTAGAGAT360 
CCTGCCAAGCTTTTCCTTGTTGACCGCTCCTTGTATGGGAAAGAAGACAACGACACGCTG420 
GTCCGCTGTCCTCTCACAGACCCAGAAGTGACCAATTATTCCCTCAAGGGGTGCCAGGGG480 
AAGCCTCTTCCCAAGGACTTGAGGTTTATTCCTGACCCCAAGGCGGGCATCATGATCAAA540 
AGTGTGAAACGCGCCTACCATCGGCTCTGTCTGCATTGTTCTGTGGACCAGGAGGGCAAG600 
TCAGTGCTGTCGGAAAAATTCATCCTGAAAGTGAGGCCAGCCTTCAAAGCTGTGCCTGTT660 
GTGTCTGTGTCCAAAGCAAGCTATCTTCTTAGGGAAGGGGAAGAATTCACAGTGACGTGC720 
ACAATAAAAGATGTGTCTAGTTCTGTGTACTCAACGTGGAAAAGAGAAAACAGTCAGACT780 
AAACTACAGGAGAAATATAATAGCTGGCATCACGGTGACTTCAATTATGAACGTCAGGCA840 
ACGTTGACTATCAGTTCAGCGAGAGTTAATGATTCTGGAGTGTTCATGTGTTATGCCAAT900 
AATACTTTTGGATCAGCAAATGTCACAACAACCTTGGAAGTAGTAGATAAAGGATTCATT960 
AATATCTTCCCCATGATAAACACTACAGTATTTGTAAACGATGGAGAAAATGTAGATTTG1020 
ATTGTTGAATATGAAGCATTCCCCAAACCTGAACACCAGCAGTGGATCTATATGAACAGA1080 
ACCTTCACTGATAAATGGGAAGATTATCCCAAGTCTGAGAATGAAAGTAATATCAGATAC1140 
GTAAGTGAACTTCATCTAACGAGATTAAAAGGCACCGAAGGAGGCACTTACACATTCCTA1200 
GTGTCCAATTCTGACGTCAATGCTGCCATAGCATTTAATGTTTATGTGAATACAAAACCA1260 
GAAATCCTGACTTACGACAGGCTCGTGAATGGCATGCTCCAATGTGTGGCAGCAGGATTC1320 
CCAGAGCCCACAATAGATTGGTATTTTTGTCCAGGAACTGAGCAGAGATGCTCTGCTTCT1380 
GTACTGCCAGTGGATGTGCAGACACTAAACTCATCTGGGCCACCGTTTGGAAAGCTAGTG1440 
GTTCAGAGTTCTATAGATTCTAGTGCATTCAAGCACAATGGCACGGTTGAATGTAAGGCT1500 
TACAACGATGTGGGCAAGACTTCTGCCTATTTTAACTTTGCATTTAAAGGTAACAACAAA1560 
GAGCAAATCCATCCCCACACCCTGTTCACTCCTTTGCTGATTGGTTTCGTAATCGTAGCT1620 
GGCATGATGTGCATTATTGTGATGATTCTGACCTACAAATATTTACAGAAACCCATGTAT1680 
GAAGTACAGTGGAAGGTTGTTGAGGAGATAAATGGAAACAATTATGTTTACATAGACCCA1740 
ACACAACTTCCTTATGATCACAAATGGGAGTTTCCCAGAAACAGGCTGAGTTTTGGGAAA1800 
ACCCTGGGTGCTGGAGCTTTCGGGAAGGTTGTTGAGGCAACTGCTTATGGCTTAATTAAG1860 
TCAGATGCGGCCATGACTGTCGCTGTAAAGATGCTCAAGCCGAGTGCCCATTTGACAGAA1920 
CGGGAAGCCCTCATGTCTGAACTCAAAGTCCTGAGTTACCTTGGTAATCACATGAATATT1980 
GTGAATCTACTTGGAGCCTGCACCATTGGAGGGCCCACCCTGGTCATTACAGAATATTGT2040 
TGCTATGGTGATCTTTTGAATTTTTTGAGAAGAAAACGTGATTCATTTATTTGTTCAAAG2100 
CAGGAAGATCATGCAGAAGCTGCACTTTATAAGAATCTTCTGCATTCAAAGGAGTCTTCC2160 
TGCAGCGATAGTACTAATGAGTACATGGACATGAAACCTGGAGTTTCTTATGTTGTCCCA2220 
ACCAAGGCCGACAAAAGGAGATCTGTGAGAATAGGCTCATACATAGAAAGAGATGTGACT2280 
CCCGCCATCATGGAGGATGACGAGTTGGCCCTAGACTTAGAAGACTTGCTGAGCTTTTCT2340 
TACCAGGTGGCAAAGGGCATGGCTTTCCTCGCCTCCAAGAATTGTATTCACAGAGACTTG2400 
GCAGCCAGAAATATCCTCCTTACTCATGGTCGGATCACAAAGATTTGTGATTTTGGTCTA2460 
GCCAGAGACATCAAGAATGATTCTAATTATGTGGTTAAAGGAAACGCTCGACTACCTGTG2520 
AAGTGGATGGCACCTGAAAGCATTTTCAACTGTGTATACACGTTTGAAAGTGACGTCTGG2580 
TCCTATGGGATTTTTCTTTGGGAGCTGTTCTCTTTAGGAAGCAGCCCCTATCCTGGAATG2640 
CCGGTCGATTCTAAGTTCTACAAGATGATCAAGGAAGGCTTCCGGATGCTCAGCCCTGAA2700 
CACGCACCTGCTGAAATGTATGACATAATGAAGACTTGCTGGGATGCAGATCCCCTAAAA2760 
AGACCAACATTCAAGCAAATTGTTCAGCTAATTGAGAAGCAGATTTCAGAGAGCACCAAT2820 
CATATTTACTCCAACTTAGCAAACTGCAGCCCCAACCGACAGAAGCCCGTGGTAGACCAT2880 
TCTGTGCGGATCAATTCTGTCGGCAGCACCGCTTCCTCCTCCCAGCCTCTGCTTGTGCAC2940 
GACGATGTCTGAGCAGAATCAGTGTTTGGGTCACCCCTCCAGGAATGATCTCTTCTTTTG3000 
GCTTCCATGATGGTTATTTTCTTTTCTTTCAACTTGCATCCAACTCCAGGATAGTGGGCA3060 
CCCCACTGCAATCCTGTCTTTCTGAGCACACTTTAGTGGCCGATGATTTTTGTCATCAGC3120 
CACCATCCTATTGCAAAGGTTCCAACTGTATATATTCCCAATAGCAACGTAGCTTCTACC3180 
ATGAACAGAAAACATTCTGATTTGGAAAAAGAGAGGGAGGTATGGACTGGGGGCCAGAGT3240 
CCTTTCCAAGGCTTCTCCAATTCTGCCCAAAAATATGGTTGATAGTTTACCTGAATAAAT3300 
GGTAGTAATCACAGTTGGCCTTCAGAACCATCCATAGTAGTATGATGATACAAGATTAGA3360 
AGCTGAAAACCTAAGTCCTTTATGTGGAAAACAGAACATCATTAGAACAAAGGACAGAGT3420 
ATGAACACCTGGGCTTAAGAAATCTAGTATTTCATGCTGGGAATGAGACATAGGCCATGA3480 
AAAAAATGATCCCCAAGTGTGAACAAAAGATGCTCTTCTGTGGACCACTGCATGAGCTTT3540 
TATACTACCGACCTGGTTTTTAAATAGAGTTTGCTATTAGAGCATTGAATTGGAGAGAAG3600 
GCCTCCCTAGCCAGCACTTGTATATACGCATCTATAAATTGTCCGTGTTCATACATTTGA3660 
GGGGAAAACACCATAAGGTTTCGTTTCTGTATACAACCCTGGCATTATGTCCACTGTGTA3720 
TAGAAGTAGATTAAGAGCCATATAAGTTTGAAGGAAACAGTTAATACCATTTTTTAAGGA3780 
AACAATATAACCACAAAGCACAGTTTGAACAAAATCTCCTCTTTTAGCTGATGAACTTAT3840 
TCTGTAGATTCTGTGGAACAAGCCTATCAGCTTCAGAATGGCATTGTACTCAATGGATTT3900 
GATGCTGTTTGACAAAGTTACTGATTCACTGCATGGCTCCCACAGGAGTGGGAAAACACT3960 
GCCATCTTAGTTTGGATTCTTATGTAGCAGGAAATAAAGTATAGGTTTAGCCTCCTTCGC4020 
AGGCATGTCCTGGACACCGGGCCAGTATCTATATATGTGTATGTACGTTTGTATGTGTGT4080 
AGACAAATATTTGGAGGGGTATTTTTGCCCTGAGTCCAAGAGGGTCCTTTAGTACCTGAA4140 
AAGTAACTTGGCTTTCATTATTAGTACTGCTCTTGTTTCTTTTCACATAGCTGTCTAGAG4200 
TAGCTTACCAGAAGCTTCCATAGTGGTGCAGAGGAAGTGGAAGGCATCAGTCCCTATGTA4260 
TTTGCAGTTCACCTGCACTTAAGGCACTCTGTTATTTAGACTCATCTTACTGTACCTGTT4320 
CCTTAGACCTTCCATAATGCTACTGTCTCACTGAAACATTTAAATTTTACCCTTTAGACT4380 
GTAGCCTGGATATTATTCTTGTAGTTTACCTCTTTAAAAACAAAACAAAACAAAACAAAA4440 
AACTCCCCTTCCTCACTGCCCAATATAAAAGGCAAATGTGTACATGGCAGAGTTTGTGTG4500 
TTGTCTTGAAAGATTCAGGTATGTTGCCTTTATGGTTTCCCCCTTCTACATTTCTTAGAC4560 
TACATTTAGAGAACTGTGGCCGTTATCTGGAAGTAACCATTTGCACTGGAGTTCTATGCT4620 
CTCGCACCTTTCCAAAGTTAACAGATTTTGGGGTTGTGTTGTCACCCAAGAGATTGTTGT4680 
TTGCCATACTTTGTCTGAAAAATTCCTTTGTGTTTCTATTGACTTCAATGATAGTAAGAA4740 
AAGTGGTTGTTAGTTATAGATGTCTAGGTACTTCAGGGGCACTTCATTGAGAGTTTTGTC4800 
TTGCCATACTTTGTCTGAAAAATTCCTTTGTGTTTCTATTGACTTCAATGATAGTAAGAA4860 
AAGTGGTTGTTAGTTATAGATGTCTAGGTACTTCAGGGGCACTTCATTGAGAGTTTTGTC4920 
AATGTCTTTTGAATATTCCCAAGCCCATGAGTCCTTGAAAATATTTTTTATATATACAGT4980 
AACTTTATGTGTAAATACATAAGCGGCGTAAGTTTAAAGGATGTTGGTGTTCCACGTGTT5040 
TTATTCCTGTATGTTGTCCAATTGTTGACAGTTCTGAAGAATTC5084 
(2) INFORMATION FOR SEQ ID NO:22: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 4626 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: 
GAATTCCGCCCTCGCCGCCCGCGGCGCCCCGAGCGCTTTGTGAGCAGATGCGGAGCCGAG60 
TGGAGGGCGCGAGCCAGATGCGGGGCGACAGCTGACTTGCTGAGAGGAGGCGGGGAGGCG120 
CGGAGCGCGCGTGTGGTCCTTGCGCCGCTGACTTCTCCACTGGTTCCTGGGCACCGAAAG180 
ATAAACCTCTCATAATGAAGGCCCCCGCTGTGCTTGCACCTGGCATCCTCGTGCTCCTGT240 
TTACCTTGGTGCAGAGGAGCAATGGGGAGTGTAAAGAGGCACTAGCAAAGTCCGAGATGA300 
ATGTGAATATGAAGTATCAGCTTCCCAACTTCACCGCGGAAACACCCATCCAGAATGTCA360 
TTCTACATGAGCATCACATTTTCCTTGGTGCCACTAACTACATTTATGTTTTAAATGAGG420 
AAGACCTTCAGAAGGTTGCTGAGTACAAGACTGGGCCTGTGCTGGAACACCCAGATTGTT480 
TCCCATGTCAGGACTGCAGCAGCAAAGCCAATTTATCAGGAGGTGTTTGGAAAGATAACA540 
TCAACATGGCTCTAGTTGTCGACACCTACTATGATGATCAACTCATTAGCTGTGGCAGCG600 
TCAACAGAGGGACCTGCCAGCGACATGTCTTTCCCCACAATCATACTGCTGACATACAGT660 
CGGAGGTTCACTGCATATTCTCCCCACAGATAGAAGAGCCCAGCCAGTGTCCTGACTGTG720 
TGGTGAGCGCCCTGGGAGCCAAAGTCCTTTCATCTGTAAAGGACCGGTTCATCAACTTCT780 
TTGTAGGCAATACCATAAATTCTTCTTATTTCCCAGATCATCCATTGCATTCGATATCAG840 
TGAGAAGGCTAAAGGAAACGAAAGATGGTTTTATGTTTTTGACGGACCAGTCCTACATTG900 
ATGTTTTACCTGAGTTCAGAGATTCTTACCCCATTAAGTATGTCCATGCCTTTGAAAGCA960 
ACAATTTTATTTACTTCTTGACGGTCCAAAGGGAAACTCTAGATGCTCAGACTTTTCACA1020 
CAAGAATAATCAGGTTCTGTTCCATAAACTCTGGATTGCATTCCTACATGGAAATGCCTC1080 
TGGAGTGTATTCTCACAGAAAAGAGAAAAAAGAGATCCACAAAGAAGGAAGTGTTTAATA1140 
TACTTCAGGCTGCGTATGTCAGCAAGCCTGGGGCCCAGCTTGCTAGACAAATAGGAGCCA1200 
GCCTGAATGATGACATTCTTTTCGGGGTGTTCGCACAAAGCAAGCCAGATTCTGCCGAAC1260 
CAATGGATCGATCTGCCATGTGTGCATTCCCTATCAAATATGTCAACGACTTCTTCAACA1320 
AGATCGTCAACAAAAACAATGTGAGATGTCTCCAGCATTTTTACGGACCCAATCATGAGC1380 
ACTGCTTTAATAGGACACTTCTGAGAAATTCATCAGGCTGTGAAGCGCGCCGTGATGAAT1440 
ATCGAACAGAGTTTACCACAGCTTTGCAGCGCGTTGACTTATTCATGGGTCAATTCAGCG1500 
AAGTCCTCTTAACATCTATATCCACCTTCATTAAAGGAGACCTCACCATAGCTAATCTTG1560 
GGACATCAGAGGGTCGCTTCATGCAGGTTGTGGTTTCTCGATCAGGACCATCAACCCCTC1620 
ATGTGAATTTTCTCCTGGACTCCCATCCAGTGTCTCCAGAAGTGATTGTGGAGCATACAT1680 
TAAACCAAAATGGCTACACACTGGTTATCACTGGGAAGAAGATCACGAAGATCCCATTGA1740 
ATGGCTTGGGCTGCAGACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTTTG1800 
TTCAGTGTGGCTGGTGCCACGACAAATGTGTGCGATCGGAGGAATGCCTGAGCGGGACAT1860 
GGACTCAACAGATCTGTCTGCCTGCAATCTACAAGGTTTTCCCAAATAGTGCACCCCTTG1920 
AAGGAGGGACAAGGCTGACCATATGTGGCTGGGACTTTGGATTTCGGAGGAATAATAAAT1980 
TTGATTTAAAGAAAACTAGAGTTCTCCTTGGAAATGAGAGCTGCACCTTGACTTTAAGTG2040 
AGAGCACGATGAATACATTGAAATGCACAGTTGGTCCTGCCATGAATAAGCATTTCAATA2100 
TGTCCATAATTATTTCAAATGGCCACGGGACAACACAATACAGTACATTCTCCTATGTGG2160 
ATCCTGTAATAACAAGTATTTCGCCGAAATACGGTCCTATGGCTGGTGGCACTTTACTTA2220 
CTTTAACTGGAAATTACCTAAACAGTGGGAATTCTAGACACATTTCAATTGGTGGAAAAA2280 
CATGTACTTTAAAAAGTGTGTCAAACAGTATTCTTGAATGTTATACCCCAGCCCAAACCA2340 
TTTCAACTGAGTTTGCTGTTAAATTGAAAATTGACTTAGCCAACCGAGAGACAAGCATCT2400 
TCAGTTACCGTGAAGATCCCATTGTCTATGAAATTCATCCAACCAAATCTTTTATTAGTA2460 
CTTGGTGGAAAGAACCTCTCAACATTGTCAGTTTTCTATTTTGCTTTGCCAGTGGTGGGA2520 
GCACAATAACAGGTGTTGGGAAAAACCTGAATTCAGTTAGTGTCCCGAGAATGGTCATAA2580 
ATGTGCATGAAGCAGGAAGGAACTTTACAGTGGCATGTCAACATCGCTCTAATTCAGAGA2640 
TAATCTGTTGTACCACTCCTTCCCTGCAACAGCTGAATCTGCAACTCCCCCTGAAAACCA2700 
AAGCCTTTTTCATGTTAGATGGGATCCTTTCCAAATACTTTGATCTCATTTATGTACATA2760 
ATCCTGTGTTTAAGCCTTTTGAAAAGCCAGTGATGATCTCAATGGGCAATGAAAATGTAC2820 
TGGAAATTAAGGGAAATGATATTGACCCTGAAGCAGTTAAAGGTGAAGTGTTAAAAGTTG2880 
GAAATAAGAGCTGTGAGAATATACACTTACATTCTGAAGCCGTTTTATGCACGGTCCCCA2940 
ATGACCTGCTGAAATTGAACAGCGAGCTAAATATAGAGTGGAAGCAAGCAATTTCTTCAA3000 
CCGTCCTTGGAAAAGTAATAGTTCAACCAGATCAGAATTTCACAGGATTGATTGCTGGTG3060 
TTGTCTCAATATCAACAGCACTGTTATTACTACTTGGGTTTTTCCTGTGGCTGAAAAAGA3120 
GAAAGCAAATTAAAGATCTGGGCAGTGAATTAGTTCGCTACGATGCAAGAGTACACACTC3180 
CTCATTTGGATAGGCTTGTAAGTGCCCGAAGTGTAAGCCCAACTACAGAAATGGTTTCAA3240 
ATGAATCTGTAGACTACCGAGCTACTTTTCCAGAAGATCAGTTTCCTAATTCATCTCAGA3300 
ACGGTTCATGCCGACAAGTGCAGTATCCTCTGACAGACATGTCCCCCATCCTAACTAGTG3360 
GGGACTCTGATATATCCAGTCCATTACTGCAAAATACTGTCCACATTGACCTCAGTGCTC3420 
TAAATCCAGAGCTGGTCCAGGCAGTGCAGCATGTAGTGATTGGGCCCAGTAGCCTGATTG3480 
TGCATTTCAATGAAGTCATAGGAAGAGGGCATTTTGGTTGTGTATATCATGGGACTTTGT3540 
TGGACAATGATGGCAAGAAAATTCACTGTGCTGTGAAATCCTTGAACAGAATCACTGACA3600 
TAGGAGAAGTTTCCCAATTTCTGACCGAGGGAATCATCATGAAAGATTTTAGTCATCCCA3660 
ATGTCCTCTCGCTCCTGGGAATCTGCCTGCGAAGTGAAGGGTCTCCGCTGGTGGTCCTAC3720 
CATACATGAAACATGGAGATCTTCGAAATTTCATTCGAAATGAGACTCATAATCCAACTG3780 
TAAAAGATCTTATTGGCTTTGGTCTTCAAGTAGCCAAAGCGATGAAATATCTTGCAAGCA3840 
AAAAGTTTGTCCACAGAGACTTGGCTGCAAGAAACTGTATGCTGGATGAAAAATTCACAG3900 
TCAAGGTTGCTGATTTTGGTCTTGCCAGAGACATGTATGATAAAGAATACTATAGTGTAC3960 
ACAACAAAACAGGTGCAAAGCTGCCAGTGAAGTGGATGGCTTTGGAAAGTCTGCAAACTC4020 
AAAAGTTTACCACCAAGTCAGATGTGTGGTCCTTTGGCGTCGTCCTCTGGGAGCTGATGA4080 
CAAGAGGAGCCCCACCTTATCCTGACGTAAACACCTTTGATATAACTGTTTACTTGTTGC4140 
AAGGGAGAAGACTCCTACAACCCGAATACTGCCCAGACCCCTTATATGAAGTAATGCTAA4200 
AATGCTGGCACCCTAAAGCCGAAATGCGCCCATCCTTTTCTGAACTGGTGTCCCGGATAT4260 
CAGCGATCTTCTCTACTTTCATTGGGGAGCACTATGTCCATGTGAACGCTACTTATGTGA4320 
ACGTAAAATGTGTCGCTCCGTATCCTTCTCTGTTGTCATCAGAAGATAACGCTGATGATG4380 
AGGTGGACACACGACCAGCCTCCTTCTGGGAGACATCATAGTGCTAGTACTATGTCAAAG4440 
CAACAGTCCACACTTTGTCCAATGGTTTTTTCACTGCCTGACCTTTAAAAGGCCATCGAT4500 
ATTCTTTGCTCCTTGCCATAGGACTTGTATTGTTATTTAAATTACTGGATTCTAAGGAAT4560 
TTCTTATCTGACAGAGCATCAGAACCAGAGGCTTGGTCCCACAGGCCAGGGACCAATGCG4620 
CTGCAG4626 
(2) INFORMATION FOR SEQ ID NO:23: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2301 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: 
GTCGACCGGAGGGCAGGAGGAGCAGGAGGAGCAGGAGCAGGAGGAGCAGGAGGAGCAGGA60 
GGAGCAGGAGGAGCAGGAGGAGCAGGAACAGGAGGAGGAGGAGGAGGAGAAGGAGGAGCA120 
GGAAGAGCAGGAGGAGGAGGAGCAGGAGCAGGAGGAGCAGGAGGGAGAGGAGGCTGCAAC180 
GCCGAGCGGAGGAGGCAGGAACCGGAGCGCGAGCAGTAGCTGGGTGGGCACCATGGCTGG240 
GATCACCACCATCGAGGCGGTGAAGCGCAAGATCCAGGTTCTGCAGCAGCAGGCAGATGA300 
TGCAGAGGAGCGAGCTGAGCGCCTCCAGCGAGAAGTTGAGGGAGAAAGGCGGGCCCGGGA360 
ACAGGCTGAGGCTGAGGTGGCCTCCTTGAACCGTAGGATCCAGCTGGTTGAAGAAGAGCT420 
GGACCGTGCTCAGGAGCGCCTGGCCACTGCCCTGCAAAAGCTGGAAGAAGCTGAAAAAGC480 
TGCTGATGAGAGTGAGAGAGGTATGAAGGTTATTGAAAACCGGGCCTTAAAAGATGAAGA540 
AAAGATGGAACTCCAGGAAATCCAACTCGAAGAAGCTAAGCACATTGCAGAAGAGGCAGA600 
TAGGAAGTATGAAGAGGTGGCTCGTAAGTTGGTGATCATTGAAGGAGACTTGGAACGCAC660 
AGAGGAACGAGCTGAGCTGGCAGAGTCGCGTTGCCGAGAGATGGATGAGCAGATTAGACT720 
GATGGACCAGAACCTGAAGTGTCTGAGTGCTGCCGAAGAAAAGTACTCTCAAAAAGAAGA780 
TAAATATGAGGAAGAAATCAAGATTCTTACTGATAAACTCAAGGAGGCAGAGACCCGTGC840 
TGAGTTTGCTGAGAGATCGGTAGCCAAGCTGGAAAAGACAATTGATGACCTGGAAGACAC900 
TAACAGCACATCTGGAGACCCGGTGGAGAAGAAGGACGAAACACCTTTTGGGGTCTCGGT960 
GGCTGTGGGCCTGGCCGTCTTTGCCTGCCTCTTCCTTTCTACGCTGCTCCTTGTGCTCAA1020 
CAAATGTGGACGGAGAAACAAGTTTGGGATCAACCGCCCGGCTGTGCTGGCTCCAGAGGA1080 
TGGGCTGGCCATGTCCCTGCATTTCATGACATTGGGTGGCAGCTCCCTGTCCCCCACCGA1140 
GGGCAAAGGCTCTGGGCTCCAAGGCCACATCATCGAGAACCCACAATACTTCAGTGATGC1200 
CTGTGTTCACCACATCAAGCGCCGGGACATCGTGCTCAAGTGGGAGCTGGGGGAGGGCGC1260 
CTTTGGGAAGGTCTTCCTTGCTGAGTGCCACAACCTCCTGCCTGAGCAGGACAAGATGCT1320 
GGTGGCTGTCAAGGCACTGAAGGAGGCGTCCGAGAGTGCTCGGCAGGACTTCCAACGTGA1380 
GGCTGAGCTGCTCACCATGCTGCAGCACCAGCACATCGTGCGCTTCTTCGGCGTCTGCAC1440 
CGAGGGCCGCCCCCTGCTCATGGTCTTCGAGTATATGCGGCACGGGGACCTCAACCGCTT1500 
CCTCCGATCCCATGGACCCGATGCCAAGCTGCTGGCTGGTGGGGAGGATGTGGCTCCAGG1560 
CCCCCTGGGTCTGGGGCAGCTGCTGGCCGTGGCTAGCCAGGTCGCTGCGGGGATGGTGTA1620 
CCTGGCGGGTCTGCATTTTGTGCACCGGGACCTGGCCACACGCAACTGTCTAGTGGGCCA1680 
GGGACTGGTGGTCAAGATTGGTGATTTTGGCATGAGCAGGGATATCTACAGCACCGACTA1740 
TTACCGTGTGGGAGGCCGCACCATGCTGCCCATTCGCTGGATGCCGCCCGAGAGCATCCT1800 
GTACCGTAAGTTCACCACCGAGAGCGACGTGTGGAGCTTCGGCGTGGTGCTCTGGGAGAT1860 
CTTCACCTACGGCAAGCAGCCCTGGTACCAGCTCTCCAACACGGAGGCAATCGACTGCAT1920 
CACGCAGGGACGTGAGTTGGAGCGGCCACGTGCCTGCCCACCAGAGGTCTACGCCATCAT1980 
GCGGGGCTGCTGGCAGCGGGAGCCCAGCAACGCCACAGCATCAAGGATGTGCACGCCCGG2040 
CTGCAAGCCCTGGCCTAGGCACCTCCTGTCTACCTGGATGTCCTGGGCTAGGGGGCCGGC2100 
CCAGGGGCTGGGAGTGGTTAGCCGGAATACTGGGGCCTGCCCTCAGCATCCCCCATAGCT2160 
CCCAGCAGCCCCAGGGTGATCTCGAAGTATCTAATTCGCCCTCAGCATGTGGGAAGGGAC2220 
AGGTGGGGGCTGGGAGTAGAGGATGTTCCTGCTTCTCTAGGCAAGGTCCCGTCGTAGCAA2280 
TTATATTTATTATGGGAATTC2301 
(2) INFORMATION FOR SEQ ID NO:24: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 271 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: 
CTGCCAGGACCATGGGTAGCAACAAGAGCAAGCCCAAGGATGCCAGCCAGCGGCGCCGCA60 
GCCTGGAGCCCGCCGAGAACGTGCACGGCGCTGGCGGGGGCGCTTTCCCCGCCTCGCAGA120 
CCCCCAGCAAGCCAGCCTCGGCCGACGGCCACCGCGGCCCCAGCGCGGCCTTCGCCCCCG180 
CGGCCGCCGAGCCCAAGCTGTTCGGAGGCTTCAACTCCTCGGACACCGTCACCTCCCCGC240 
AGAGGGCGGGCCCGCTGGCCGGTCAGTGCGC271 
(2) INFORMATION FOR SEQ ID NO:25: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 118 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: 
CTCTCTGCAGGTGGAGTGACCACCTTTGTGGCCCTCTATGACTATGAGTCTAGGACGGAG60 
ACAGACCTGTCCTTCAAGAAAGGCGAGCGGCTCCAGATTGTCAACAACACGTGAGTGC118 
(2) INFORMATION FOR SEQ ID NO:26: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 113 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: 
CCTGCTCAGAGAGGGAGACTGGTGGCTGGCCCACTCGCTCAGCACAGGACAGACAGGCTA60 
CATCCCCAGCAACTACGTGGCGCCCTCCGACTCCATCCAGGCTGAGGAGTTAG113 
(2) INFORMATION FOR SEQ ID NO:27: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 115 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: 
CCCCCAGGTGGTATTTTGGCAAGATCACCAGACGGGAGTCAGAGCGGTTACTGCTCAATG60 
CAGAGAACCCGAGAGGGACCTTCCTCGTGCGAGAAAGTGAGACCACGAAAGGTAC115 
(2) INFORMATION FOR SEQ ID NO:28: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 164 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: 
GCCCCGCAGGTGCCTACTGCCTCTCAGTGTCTGACTTCGACAACGCCAAGGGCCTCAACG60 
TGAAGCACTACAAGATCCGCAAGCTGGACAGCGGCGGCTTCTACATCACCTCCCGCACCC120 
AGTTCAACAGCCTGCAGCAGCTGGTGGCCTACTACTCCAGTGAG164 
(2) INFORMATION FOR SEQ ID NO:29: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 170 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: 
CCTCCTCAGAACACGCCGATGGCCTGTGCCACCGCCTCACCACCGTGTGCCCCACGTCCA60 
AGCCGCAGACTCAGGGCCTGGCCAAGGATGCCTGGGAGATCCCTCGGGAGTCGCTGCGGC120 
TGGAGGTCAAGCTGGGCCAGGGCTGCTTTGGCGAGGTGTGGATGGGTAAG170 
(2) INFORMATION FOR SEQ ID NO:30: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 194 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: 
CCTCAACAGGGACCTGGAACGGTACCACCAGGGTGGCCATCAAAACCCTGAAGCCTGGCA60 
CGATGTCTCCAGAGGCCTTCCTGCAGGAGGCCCAGGTCATGAAGAAGCTGAGGCATGAGA120 
AGCTGGTGCAGTTGTATGCTGTGGTTTCAGAGGAGCCCATTTACATCGTCACGGAGTACA180 
TGAGCAAGGGTGAG194 
(2) INFORMATION FOR SEQ ID NO:31: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 91 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: 
TCTGCCCAGGGAGTTTGCTGGACTTTCTCAAGGGGGAGACAGGCAAGTACCTGCGGCTGC60 
CTCAGCTGGTGGACATGGCTGCTCAGGTGAG91 
(2) INFORMATION FOR SEQ ID NO:32: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 165 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: 
CTGCAGATCGCCTCAGGCATGGCGTACGTGGAGCGGATGAACTACGTCCACCGGGACCTT60 
CGTGCAGCCAACATCCTGGTGGGAGAGAACCTGGTGTGCAAAGTGGCCGACTTTGGGCTG120 
GCTCGGCTCATTGAAGACAATGAGTACACGGCGCGGCAAGGTGGG165 
(2) INFORMATION FOR SEQ ID NO:33: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 146 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: 
TTCCTGCAGGTGCCAAATTCCCCATCAAGTGGACGGCTCCAGAAGCTGCCCTCTATGGCC60 
GCTTCACCATCAAGTCGGACGTGTGGTCCTTCGGGATCCTGCTGACTGAGCTCACCACAA120 
AGGGACGGGTGCCCTACCCTGGTAAG146 
(2) INFORMATION FOR SEQ ID NO:34: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 255 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: 
CTGCCACAGGGATGGTGAACCGCGAGGTGCTGGACCAGGTGGAGCGGGGCTACCGGATGC60 
CCTGCCCGCCGGAGTGTCCCGAGTCCCTGCACGACCTCATGTGCCAGTGCTGGCGGAAGG120 
AGCCTGAGGAGCGGCCCACCTTCGAGTACCTGCAGGCCTTCCTGGAGGACTACTTCACGT180 
CCACCGAGCCCCAGTACCAGCCCGGGGAGAACCTCTAGGCACAGGCGGGCCCAGACCGGC240 
TTCTCGGCTTGGATC255 
(2) INFORMATION FOR SEQ ID NO:35: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 3623 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: 
CGCGGCCGCCCTGGGCGGGCGCGGGCGGCGGGCGGCGGTGAGGGCGGCCTGCGGGGCGGC60 
GCCCGGGGGCCGGGCCGAGCCGGGCCTGAGCCGGGCCCGGACCGAGCTGGGAGAGGGGCT120 
CCGGCCCGATCGTTCGCTTGGCGCAAAATGTTGGAGATCTGCCTGAAGCTGGTGGGCTGC180 
AAATCCAAGAAGGGGCTGTCCTCGTCCTCCAGCTGTTATCTGGAAGAAGCCCTTCAGCGG240 
CCAGTAGCATCTGACTTTGAGCCTCAGGGTCTGAGTGAAGCCGCTCGTTGGAACTCCAAG300 
GAAAACCTTCTCGCTGGACCCAGTGAAAATGACCCCAACCTTTTCGTTGCACTGTATGAT360 
TTTGTGGCCAGTGGAGATAACACTCTAAGCATAACTAAAGGTGAAAAGCTCCGGGTCTTA420 
GGCTATAATCACAATGGGGAATGGTGTGAAGCCCAAACCAAAAATGGCCAAGGCTGGGTC480 
CCAAGCAACTACATCACGCCAGTCAACAGTCTGGAGAAACACTCCTGGTACCATGGGCCT540 
GTGTCCCGCAATGCCGCTGAGTATCCGCTGAGCAGCGGGATCAATGGCAGCTTCTTGGTG600 
CGTGAGAGTGAGAGCAGTCCTAGCCAGAGGTCCATCTCGCTGAGATACGAAGGGAGGGTG660 
TACCATTACAGGATCAACACTGCTTCTGATGGCAAGCTCTACGTCTCCTCCGAGAGCCGC720 
TTCAACACCCTGGCCGAGTTGGTTCATCATCATTCAACGGTGGCCGACGGGCTCATCACC780 
ACGCTCCATTATCCAGCCCCAAAGCGCAACAAGCCCACTGTCTATGGTGTGTCCCCCAAC840 
TACGACAAGTGGGAGATGGAACGCACGGACATCACCATGAAGCACAAGCTGGGCGGGGGC900 
CAGTACGGGGAGGTGTACGAGGGCGTGTGGAAGAAATACAGCCTGACGGTGGCCGTGAAG960 
ACCTTGAAGGAGGACACCATGGAGGTGGAAGAGTTCTTGAAAGAAGCTGCAGTCATGAAA1020 
GAGATCAAACACCCTAACCTAGTGCAGCTCCTTGGGGTCTGCACCCGGGAGCCCCCGTTC1080 
TATATCATCACTGAGTTCATGACCTACGGGAACCTCCTGGACTACCTGAGGGAGTGCAAC1140 
CGGCAGGAGGTGAACGCCGTGGTGCTGCTGTACATGGCCACTCAGATCTCGTCAGCCATG1200 
GAGTACCTAGAGAAGAAAAACTTCATCCACAGAGATCTTGCTGCCCGAAACTGCCTGGTA1260 
GGGGAGAACCACTTGGTGAAGGTAGCTGATTTTGGCCTGAGCAGGTTGATGACAGGGGAC1320 
ACCTACACAGCCCATGCTGGAGCCAAGTTCCCCATCAAATGGACTGCACCCGAGAGCCTG1380 
GCCTACAACAAGTTCTCCATCAAGTCCGACGTCTGGGCATTTGGAGTATTGCTTTGGGAA1440 
ATTGCTACCTATGGCATGTCCCCTTACCCGGGAATTGACCGTTCCCAGGTGTATGAGCTG1500 
CTAGAGAAGGACTACCGCATGAAGCGCCCAGAAGGCTGCCCAGAGAAGGTCTATGAACTC1560 
ATGCGAGCATGTTGGCAGTGGAATCCCTCTGACCGGCCCTCCTTTGCTGAAATCCACCAA1620 
GCCTTTGAAACAATGTTCCAGGAATCCAGTATCTCAGACGAAGTGGAAAAGGAGCTGGGG1680 
AAACAAGGCGTCCGTGGGGCTGTGACTACCTTGCTGCAGGCCCCAGAGCTGCCCACCAAG1740 
ACGAGGACCTCCAGGAGAGCTGCAGAGCACAGAGACACCACTGACGTGCCTGAGATGCCT1800 
CACTCCAAGGGCCAGGGAGAGAGCGATCCTCTGGACCATGAGCCTGCCGTGTCTCCATTG1860 
CTCCCTCGAAAAGAGCGAGGTCCCCCGGAGGGCGGCCTGAATGAAGATGAGCGCCTTCTC1920 
CCCAAAGACAAAAAGACCAACTTGTTCAGCGCCTTGATCAAGAAGAAGAAGAAGACAGCC1980 
CCAACCCCTCCCAAACGCAGCAGCTCCTTCCGGGAGATGGACGGCCAGCCGGAGCGCAGA2040 
GGGGCCGGCGAGGAAGAGGGCCGAGACATCAGCAACGGGGCACTGGCTTTCACCCCCTTG2100 
GACACAGCTGACCCAGCCAAGTCCCCAAAGCCCAGCAATGGGGCTGGGGTCCCCAATGGA2160 
GCCCTCCGGGAGTCCGGGGGCTCAGGCTTCCGGTCTCCCCACCTGTGGAAGAAGTCCAGC2220 
ACGCTGACCAGCAGCCGCCTAGCCACCGGCGAGGAGGAGGGCGGTGGCAGCTCCAGCAAG2280 
CGCTTCCTGCGCTCTTGCTCCGTCTCCTGCGTTCCCCATGGGGCCAAGGACACGGAGTGG2340 
AGGTCAGTCACGCTGCCTCGGGACTTGCAGTCCACGGGAAGACAGTTTGACTCGTCCACA2400 
TTTGGAGGGCACAAAAGTGAGAAGCCGGCTCTGCCTCGGAAGAGGGCAGGGGAGAACAGG2460 
TCTGACCAGGTGACCCGAGGCACAGTAACGCCTCCCCCCAGGCTGGTGAAAAAGAATGAG2520 
GAAGCTGCTGATGAGGTCTTCAAAGACATCATGGAGTCCAGCCCGGGCTCCAGCCCGCCC2580 
AACCTGACTCCAAAACCCCTCCGGCGGCAGGTCACCGTGGCCCCTGCCTCGGGCCTCCCC2640 
CACAAGGAAGAAGCCTGGAAAGGCAGTGCCTTAGGGACCCCTGCTGCAGCTGAGCCAGTG2700 
ACCCCCACCAGCAAAGCAGGCTCAGGTGCACCAAGGGGCACCAGCAAGGGCCCCGCCGAG2760 
GAGTCCAGAGTGAGGAGGCACAAGCACTCCTCTGAGTCGCCAGGGAGGGACAAGGGGAAA2820 
TTGTCCAAGCTCAAACCTGCCCCGCCGCCCCCACCAGCAGCCTCTGCAGGGAAGGCTGGA2880 
GGAAAGCCCTCGCAGAGGCCCGGCCAGGAGGCTGCCGGGGAGGCAGTCTTGGGCGCAAAG2940 
ACAAAAGCCACGAGTCTGGTTGATGCTGTGAACAGTGACGCTGCCAAGCCCAGCCAGCCG3000 
GCAGAGGGCCTCAAAAAGCCCGTGCTCCCGGCCACTCCAAAGCCACACCCCGCCAAGCCG3060 
TCGGGGACCCCCATCAGCCCAGCCCCCGTTCCCCTTTCCACGTTGCCATCAGCATCCTCG3120 
GCCTTGGCAGGGGACCAGCCGTCTTCCACTGCCTTCATCCCTCTCATATCAACCCGAGTG3180 
TCTCTTCGGAAAACCCGCCAGCCTCCAGAGCGGGCCAGCGGCGCCATCACCAAGGGCGTG3240 
GTCTTGGACAGCACCGAGGCGCTGTGCCTCGCCATCTCTGGGAACTCCGAGCAGATGGCC3300 
AGCCACAGCGCAGTGCTGGAGGCCGGCAAAAACCTCTACACGTTCTGCGTGAGCTATGTG3360 
GATTCCATCCAGCAAATGAGGAACAAGTTTGCCTTCCGAGAGGCCATCAACAAACTGGAG3420 
AATAATCTCCGGGAGCTTCAGATCTGCCCGGCGTCAGCAGGCAGTGGTCCGGCGGCCACT3480 
CAGGACTTCAGCAAGCTCCTCAGTTCGGTGAAGGAAATCAGTGACATAGTGCAGAGGTAG3540 
CAGCAGTCAGGGGTCAGGTGTCAGGCCCGTCGGAGCTGCCTGCAGCACATGCGGGCTCGC3600 
CCATACCCATGACAGTGGCTGAG3623 
(2) INFORMATION FOR SEQ ID NO:36: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 257 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: 
CACAGCATTCCGCTGACCATCAATAAGGAAGAAGCCCTTCAGCGGCCAGTAGCATCTGAC60 
TTTGAGCCTCAGGGTCTGAGTGAAGCCGCTCGTTGGAACTCCAAGGAAAACCTTCTCGCT120 
GGACCCAGTGAAAATGACCCCAACCTTTTCGTTGCACTGTATGATTTTGTGGCCAGTGGA180 
GATAACACTCTAAGCATAACTAAAGGTGAAAAGCTCCGGGTCTTAGGCTATAATCACAAT240 
GGGGAATGGTGTGAAGC257 
(2) INFORMATION FOR SEQ ID NO:37: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 266 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: 
GTCATCGTCCACTCAGCCACTGGATTTAAGCAGAGTTCAAAAGCCCTTCAGCGGCCAGTA60 
GCATCTGACTTTGAGCCTCAGGGTCTGAGTGAAGCCGCTCGTTGGAACTCCAAGGAAAAC120 
CTTCTCGCTGGACCCAGTGAAAATGACCCCAACCTTTTCGTTGCACTGTATGATTTTGTG180 
GCCAGTGGAGATAACACTCTAAGCATAACTAAAGGTGAAAAGCTCCGGGTCTTAGGCTAT240 
AATCACAATGGGGAATGGTGTGAAGC266 
(2) INFORMATION FOR SEQ ID NO:38: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 80 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: 
GATGGCGAGGGCGCCTTCCATGGAGACGCAGAAGCCCTTCAGCGGCCAGTAGCATCTGAC60 
TTTGAGCCTCAGGGTCTGAG80 
(2) INFORMATION FOR SEQ ID NO:39: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 139 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: 
GTTCTGTTCTGTGCCTACAGTGAAGGTGACTGGTGGGAGGCTCGGTCTCTCAGCTCCGGA60 
AAAACTGGCTGCATTCCCAGCAACTACGTGGCCCCTGTTGACTCAATCCAAGCTGAAGAG120 
TAAGTAGGGATTGGGGCAA139 
(2) INFORMATION FOR SEQ ID NO:40: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 1804 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: 
GGATCCTCAGGGGTAACACCTTTTGGAGGTGGGCATCTTCCTCATTCTCAGTGGTGCCAA60 
GTTCATATCCTGCTGGCTTAACACGTGGTGTTACTATATTTGTGGCCTTATATGATTATG120 
AAGCTAGAACTACAGAAGACCTTTCATTTAAGAAGGGTGAAAAATTTCAAATAATTAACA180 
ATACAGAAGGAGACTGGTGGGAAGCAAGATCAATCACTACAGGAAAGAATGGTTATATCC240 
TGAGCAGTTATGTAGCGCCTGCAGATTCCATTCAGGCAGAAGAATGGTATTTTGGCAAAA300 
TGGGGAGAAAAGATGCTGAAAGATTACTTCTGAATCCTGGAAATTAATGAGGTATTTTCT360 
TAGGAAGAGAGAGTGAAATGGCTGGGTGCAGTGGCTCATGCCTGTAATCCCAGCACTTTG420 
GGAGGCCGAGTTGGGCGGATCACCTGAGGTCAGGAGTTCGAGACTAGCCTGGCCAACATG480 
GTGAAACCCCATCTCTACTAAAAAAAAAAGTACAAAATTAGCTGGACGTGGTGGTGAGTG540 
CCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGCAGAATCACTTGAACCTGGGAGGCGG600 
AGGTTGCAGTGAGCTGAGATCGCGCCACTGCACTCCAGCCTCGGCGACAAGAGCAAAAAC660 
TCCGTCTAAAAAACAAATAAGCAAACAGAACAAAACAAAACAAAAACGAGAGAGCGAAAC720 
TACTAAAGGTGCTTATTCCCTCTCTATTCGTGATTGGGATGAGGTAAGGGGTGACAATGT780 
GAAACACCACAAAATTAGGAAACTTGACAATGGTAGATACTATATCACAACCAGAGAACA840 
ACTTGATACTCTGCAGAAATTGGCAAAACACTACACAGAACATGCTGATGGTTTATGCCA900 
CAAGTTAACAACTGTGTGTCCAACTGTGAAACCTCAGATTCAAGGTCTAGCAAAAGATGC960 
TTGGGAAATCCCTTGATAATCTTTGCGACTAGAGGTTAAACTAGGACAAGGATGTTTTGG1020 
CAAAGTGTGGATGGGAATATGGAATGGAACCACAAAAGTAGCAATCAAAACACTAAAACC1080 
AGGTACAATGATGCCAGAAGCTTTTCTTCAAGAAGCTCAGGTAATGAAAAAAATAAGACA1140 
TGGTAAACTTGTTCCACTATATGCTGTTGTTTCTGAAGAGCCAATTTACATTGTCACTGA1200 
ATTGATGTCAAAAGGAAGCTTATTCAATTTCCTTAAGGAAGGAGATGGAAAGTATTTGAA1260 
GCTTCCACAAATGGTTGATATGCCTGCTCAGATTGCTGATGGTATGGCATATATTAAAAG1320 
AATGAACTATATTCACCGAGATCTCTGGGCTGCTAATATTCTTGTAGGAGAAAATCTTCT1380 
GTGCAAAATAGCAGATTTTGGTTTAGCAAGGTTAATTGAAGACAATGAATACACATCAAG1440 
ACAAGGTGCAGAATTTCCAATCAAATGGACAGCTCCTGAAGTTGCACTGTATGGTGGGTT1500 
TACAATAAAGTCTGGTGTCTGCTCATTTGGAATTCTACAGACAGAACTGGTAACAAAGGG1560 
CAGAGTGCCATATCCAGGTATGGTGAACCATGAAATACTGGAACAGGTGGAGCGAGGATA1620 
CAGGATGCCTTGCCCTCAGGGCTGTCCAGAATCCCTCCATGAATTGATGAATCTGTGTTG1680 
GAAGAAGGACCCTGATGAAAGACCAACATTTGAATATGTTCAGTCCTTCTTGGGAGACTA1740 
CTTCACTGCTACAGAGCCATAGTACCAGCCAGGAGAAAACTTCTAATTCAAGTAGCCTAT1800 
TTTA1804 
(2) INFORMATION FOR SEQ ID NO:41: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 8082 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: 
AGCTTGTTTGGCCGTTTTAGGGTTTGTTGGAATTTTTTTTTCGTCTATGTACTTGTGAAT60 
TATTTCACGTTTGCCATTACCGGTTCTCCATAGGGTGATGTTCATTAGCAGTGGTGATAG120 
GTTAATTTTCACCATCTCTTATGCGGTTGAATAGTCACCTCTGAACCACTTTTTCCTCCA180 
GTAACTCCTCTTTCTTCGGACCTTCTGCAGCCAACCTGAAAGAATAACAAGGAGGTGGCT240 
GGAAACTTGTTTTAAGGAACCGCCTGTCCTTCCCCCGCTGGAAACCTTGCACCTCGGACG300 
CTCCTGCTCCTGCCCCCACCTGACCCCCGCCCTCGTTGACATCCAGGCGCGATGATCTCT360 
GCTGCCAGTAGAGGGCACACTTACTTTACTTTCGCAAACCTGAACGCGGGTGCTGCCCAG420 
AGAGGGGGCGGAGGGAAAGACGCTTTGCAGCAAAATCCAGCATAGCGATTGGTTGCTCCC480 
CGCGTTTGCGGCAAAGGCCTGGAGGCAGGAGTAATTTGCAATCCTTAAAGCTGAATTGTG540 
CAGTGCATCGGATTTGGAAGCTACTATATTCACTTAACACTTGAACGCTGAGCTGCAAAC600 
TCAACGGGTAATAACCCATCTTGAACAGCGTACATGCTATACACACACCCCTTTCCCCCG660 
AATTGTTTTCTCTTTTGGAGGTGGTGGAGGGAGAGAAAAGTTTACTTAAAATGCCTTTGG720 
GTGAGGGACCAAGGATGAGAAGAATGTTTTTTGTTTTTCATGCCGTGGAATAACACAAAA780 
TAAAAAATCCCGAGGGAATATACATTATATATTAAATATAGATCATTTCAGGGAGCAAAC840 
AAATCATGTGTGGGGCTGGGCAACTAGCTGAGTCGAAGCGTAAATAAAATGTGAATACAC900 
GTTTGCGGGTTACATACAGTGCACTTTCACTAGTATTCAGAAAAAATTGTGAGTCAGTGA960 
ACTAGGAAATTAATGCCTGGAAGGCAGCCAAATTTTAATTAGCTCAAGACTCCCCCCCCC1020 
CCCCAAAAAAAGGCACGGAAGTAATACTCCTCTCCTCTTCTTTGATCAGAATCGATGCAT1080 
TTTTTGTGCATGACCGCATTTCCAATAATAAAAGGGGAAAGAGGACCTGGAAAGGAATTA1140 
AACGTCCGGTTTGTCCGGGGAGGAAAGAGTTAACGGTTTTTTTCACAAGGGTCTCTGCTG1200 
ACTCCCCCGGCTCGGTCCACAAGCTCTCCACTTGCCCCTTTTAGGAAGTCCGGTCCCGCG1260 
GTTCGGGTACCCCCTGCCCCTCCCATATTCTCCCGTCTAGCACCTTTGATTTCTCCCAAA1320 
CCCGGCAGCCCGAGACTGTTGCAAACCGGCGCCACAGGGCGCAAAGGGGATTTGTCTCTT1380 
CTGAAACCTGGCTGAGAAATTGGGAACTCCGTGTGGGAGGCGTGGGGGTGGGACGGTGGG1440 
GTACAGACTGGCAGAGAGCAGGCAACCTCCCTCTCGCCCTAGCCCAGCTCTGGAACAGGC1500 
AGACACATCTCAGGGCTAAACAGACGCCTCCCGCACGGGGCCCCACGGAAGCCTGAGCAG1560 
GCGGGGCAGGAGGGGCGGTATCTGCTGCTTTGGCAGCAAATTGGGGGACTCAGTCTGGGT1620 
GGAAGGTATCCAATCCAGATAGCTGTGCATACATAATGCATAATACATGACTCCCCCCAA1680 
CAAATGCAATGGGAGTTTATTCATAACGCGCTCTCCAAGTATACGTGGCAATGCGTTGCT1740 
GGGTTATTTTAATCATTCTAGGCATCGTTTTCCTCCTTATGCCTCTATCATTCCTCCCTA1800 
TCTACACTAACATCCCACGCTCTGAACGCGCGCCCATTAATACCCTTCTTTCCTCCACTC1860 
TCCCTGGGACTCTTGATCAAAGCGCGGCCCTTTCCCCAGCCTTAGCGAGGCGCCCTGCAG1920 
CCTGGTACGCGCGTGGCGTGGCGGTGGGCGCGCAGTGCGTTCTCTGTGTGGAGGGCAGCT1980 
GTTCCGCCTGCGATGATTTATACTCACAGGACAAGGATGCGGTTTGTCAAACAGTACTGC2040 
TACGGAGGAGCAGCAGAGAAAGGGAGAGGGTTTGAGAGGGAGCAAAAGAAAATGGTAGGC2100 
GCGCGTAGTTAATTCATGCGGCTCTCTTACTCTGTTTACATCCTAGAGCTAGAGTGCTCG2160 
GCTGCCCGGCTGAGTCTCCTCCCCACCTTCCCCACCCTCCCCACCCTCCCCATAAGCGCC2220 
CCTCCCGGGTTCCCAAAGCAGAGGGCGTGGGGGAAAAGAAAAAAGATCCTCTCTCGCTAA2280 
TCTCCGCCCACCGGCCCTTTATAATGCGAGGGTCTGGACGGCTGAGGACCCCCGAGCTGT2340 
GCTGCTCGCGGCCGCCACCGCCGGGCCCCGGCCGTCCCTGGCTCCCCTCCTGCCTCGAGA2400 
AGGGCAGGGCTTCTCAGAGGCTTGGCGGGAAAAAGAACGGAGGGAGGGATCGCGCTGAGT2460 
ATAAAAGCCGGTTTTCGGGGCTTTATCTAACTCGCTGTAGTAATTCCAGCGAGAGGCAGA2520 
GGGAGCGAGCGGGCGGCCGGCTAGGGTGGAAGAGCCGGGCGAGCAGAGCTGCGCTGCGGG2580 
CGTCCTGGGAAGGGAGATCCGGAGCGAATAGGGGGCTTCGCCTCTGGCCCAGCCCTCCCG2640 
CTGATCCCCCAGCCAGCGGTCCGCAACCCTTGCCGCATCCACGAAACTTTGCCCATAGCA2700 
GCGGGCGGGCACTTTGCACTGGAACTTACAACACCCGAGCAAGGACGCGACTCTCCCGAC2760 
GCGGGGAGGCTATTCTGCCCATTTGGGGACACTTCCCCGCCGCTGCCAGGACCCGCTTCT2820 
CTGAAAGGCTCTCCTTGCAGCTGCTTAGACGCTGGATTTTTTTCGGGTAGTGGAAAACCA2880 
GGTAAGCACCGAAGTCCACTTGCCTTTTAATTTATTTTTTTATCACTTTAATGCTGAGAT2940 
GAGTCGAATGCCTAAATAGGGTGTCTTTTCTCCCATTCCTGCGCTATTGACACTTTTCTC3000 
AGAGTAGTTATGGTAACTGGGGCTGGGGTGGGGGGTAATCCAGAACTGGATCGGGGTAAA3060 
GTGACTTGTCAAGATGGGAGAGGAGAAGGCAGAGGGAAAACGGGAATGGTTTTTAAGACT3120 
ACCCTTTCGAGATTTCTGCCTTATGAATATATTCACGCTGACTCCCGGCCGGTCGGACAT3180 
TCCTGCTTTATTGTGTTAATTGCTCTCTGGGTTTTGGGGGGCTGGGGGTTGCTTTGCGGT3240 
GGGCAGAAAGCCCCTTGCATCCTGAGCTCCTTGGAGTAGGGACCGCATATCGCCTGTGTG3300 
AGCCAGATCGCTCCGCAGCCGCTGACTTGTCCCCGTCTCCGGGAGGGCATTTAAATTTCG3360 
GCTCACCGCATTTCTGACAGCCGGAGACGGACACTGCGGCGCGTCCCGCCCGCCTGTCCC3420 
CGCGGCGATTCCAACCCGCCCTGATCCTTTTAAGAAGTTGGCATTTGGCTTTTTAAAAAG3480 
CAATAATACAATTTAAAACCTGGGTCTCTAGAGGTGTTAGGACGTGGTGTTGGGTAGGCG3540 
CAGGCAGGGGAAAAGGGAGGCGAGGATGTGTCCGATTCTCCTGGAATCGTTGACTTGGAA3600 
AAACCAGGGCGAATCTCCGCACCCAGCCCTGACTCCCCTGCCGCGGCCGCCCTCGGGTGT3660 
CCTCGCGCCCGAGATGCGGAGGAACTGCGAGGAGCGGGGCTCTGGGCGGTTCCAGAACAG3720 
CTGCTACCCTTGGTGGGGTGGCTCCGGGGGAGGTATCGCAGCGGGGTCTCTGGCGCAGTT3780 
GCATCTCCGTATTGAGTGCGAAGGGAGGTGCCCCTATTATTATTTGACACCCCCCTTGTA3840 
TTTATGGAGGGGTGTTAAAGCCCGCGGCTGAGCTCGCCACTCCAGCCGGCGAGAGAAAGA3900 
AGAAAAGCTGGCAAAAGGAGTGTTGGACGGGGGCGGTACTGGGGGTGGGGACGGGGGCGG3960 
TGGAGAGGGAAGGTTGGGAGGGGCTGCGGTGCCGGCGGGGGTAGGAGAGCGGCTAGGGCG4020 
CGAGTGGGAACAGCCGCAGCGGAGGGGCCCCGGCGCGGAGCGGGGTTCACGCAGCCGCTA4080 
GCGCCCAGGCGCCTCTCGCCTTCTCCTTCAGGTGGCGCAAAACTTTGTGCCTTGGATTTT4140 
GGCAAATTGTTTTCCTCACCGCCACCTCCCGCGGCTTCTTAAGGGCGCCAGGGCCGATTT4200 
CGATTCCTCTGCCGCTGCGGGGCCGACTCCCGGGCTTTGCGCTCCGGGCTCCCGGGGGAG4260 
CGGGGGCTCGGCGGGCACCAAGCCGCTGGTTCACTAAGTGCGTCTCCGAGATAGCAGGGG4320 
ACTGTCCAAAGGGGGTGAAAGGGTGCTCCCTTTATTCCCCCACCAAGACCACCCAGCCGC4380 
TTTAGGGGATAGCTCTGCAAGGGGAGAGGTTCGGGACTGTGGCGCGCACTGCGCGCTGCG4440 
CCAGGTTTCCGCACCAAGACCCCTTTAACTCAAGACTGCCTCCCGCTTTGTGTGCCCCGC4500 
TCCAGCAGCCTCCCGCGACGATGCCCCTCAACGTTAGCTTCACCAACAGGAACTATGACC4560 
TCGACTACGACTCGGTGCAGCCGTATTTCTACTGCGACGAGGAGGAGAACTTCTACCAGC4620 
AGCAGCAGCAGAGCGAGCTGCAGCCCCCGGCGCCCAGCGAGGATATCTGGAAGAAATTCG4680 
AGCTGCTGCCCACCCCGCCCCTGTCCCCTAGCCGCCGCTCCGGGCTCTGCTCGCCCTCCT4740 
ACGTTGCGGTCACACCCTTCTCCCTTCGGGGAGACAACGACGGCGGTGGCGGGAGCTTCT4800 
CCACGGCCGACCAGCTGGAGATGGTGACCGAGCTGCTGGGAGGAGACATGGTGAACCAGA4860 
GTTTCATCTGCGACCCGGACGACGAGACCTTCATCAAAAACATCATCATCCAGGACTGTA4920 
TGTGGAGCGGCTTCTCGGCCGCCGCCAAGCTCGTCTCAGAGAAGCTGGCCTCCTACCAGG4980 
CTGCGCGCAAAGACAGCGGCAGCCCGAACCCCGCCCGCGGCCACAGCGTCTGCTCCACCT5040 
CCAGCTTGTACCTGCAGGATCTGAGCGCCGCCGCCTCAGAGTGCATCGACCCCTCGGTGG5100 
TCTTCCCCTACCCTCTCAACGACAGCAGCTCGCCCAAGTCCTGCGCCTCGCAAGACTCCA5160 
GCGCCTTCTCTCCGTCCTCGGATTCTCTGCTCTCCTCGACGGAGTCCTCCCCGCAGGGCA5220 
GCCCCGAGCCCCTGGTGCTCCATGAGGAGACACCGCCCACCACCAGCAGCGACTCTGGTA5280 
AGCGAAGCCCGCCCAGGCCTGTCAAAAGTGGGCGGCTGGATACCTTTCCCATTTTCATTG5340 
GCAGCTTATTTAACGGGCCACTCTTATTAGGAAGGAGAGATAGCAGATCTGGAGAGATTT5400 
GGGAGCTCATCACCTCTGAAACCTTGGGCTTTAGCGTTTCCTCCCATCCCTTCCCCTTAG5460 
ACTGCCCATGTTTGCAGCCCCCCTCCCCGTTTGTCTCCCACCCCTCAGGAATTTCATTTA5520 
GGTTTTTAAACCTTCTGGCTTATCTTACAACTCAATCCACTTCTTCTTACCTCCCGTTAA5580 
CATTTTAATTGCCCTGGGGCGGGGTGGCAGGGAGTGTATGAATGAGGATAAGAGAGGATT5640 
GATCTCTGAGAGTGAATGAATTGCTTCCCTCTTAACTTCCGAGAAGTGGTGGGATTTAAT5700 
GAACTATCTACAAAAATGAGGGGCTGTGTTTAGAGGCTAGGCAGGGCCTGCCTGAGTGCG5760 
GGAGCCAGTGAACTGCCTCAAGAGTGGGTGGGCTGAGGAGCTGGGATCTTCTCAGCCTAT5820 
TTTGAACACTGAAAAGCAAATCCTTGCCAAAGTTGGACTTTTTTTTTTCTTTTATTCCTT5880 
CCCCCGCCCTCTTGGACTTTTGGCAAAACTGCAATTTTTTTTTTTTTATTTTTCATTTCC5940 
AGTAAAATAGGGAGTTGCTAAAGTCATACCAAGCAATTTGCAGCTATCATTTGCAACACC6000 
TGAAGTGTTCTTGGTAAAGTCCCTCAAAAATAGGAGGTGCTTGGGAATGTGCTTTGCTTT6060 
GGGTGTGTCCAAAGCCTCATTAAGTCTTAGGTAAGAATTGGCATCAATGTCCTATCCTGG6120 
GAAGTTGCACTTTTCTTGTCCATGCCATAACCCAGCTGTCTTTCCCTTTATGAGACTCTT6180 
ACCTTCATGGTGAGAGGAGTAAGGGTGGCTGGCTAGATTGGTTCTTTTTTTTTTTTTTTC6240 
CTTTTTTAAGACGGAGTCTCACTCTGTCACTAGGCTGGAGTGCAGTGGCGCAATCAACCT6300 
CCAACCCCCTGGTTCAAGAGATTCTCCTGCCTCAGCCTCCCAAGTAGCTGGGACTACAGG6360 
TGCACACCACCATGCCAGGCTAATTTTTGTAATTTTAGTAGAGATGGGGTTTCATCGTGT6420 
TGGCCAGGATGGTCTCTCCTGACCTCACGATCCGCCCACCTCGGCCTCCCAAAGTGCTGG6480 
GATTACAGGTGTGAGCCAGGGCACCAGGCTTAGATGTGGCTCTTTGGGGAGATAATTTTG6540 
TCCAGAGACCTTTCTAACGTATTCATGCCTTGTATTTGTACAGCATTAATCTGGTAATTG6600 
ATTATTTTAATGTAACCTTGCTAAAGGAGTGATTTCTATTTCCTTTCTTAAAGAGGAGGA6660 
ACAAGAAGATGAGGAAGAAATCGATGTTGTTTCTGTGGAAAAGAGGCAGGCTCCTGGCAA6720 
AAGGTCAGAGTCTGGATCACCTTCTGCTGGAGGCCACAGCAAACCTCCTCACAGCCCACT6780 
GGTCCTCAAGAGGTGCCACGTCTCCACACATCAGCACAACTACGCAGCGCCTCCCTCCAC6840 
TCGGAAGGACTATCCTGCTGCCAAGAGGGTCAAGTTGGACAGTGTCAGAGTCCTGAGACA6900 
GATCAGCAACAACCGAAAATGCACCAGCCCCAGGTCCTCGGACACCGAGGAGAATGTCAA6960 
GAGGCGAACACACAACGTCTTGGAGCGCCAGAGGAGGAACGAGCTAAAACGGAGCTTTTT7020 
TGCCCTGCGTGACCAGATCCCGGAGTTGGAAAACAATGAAAAGGCCCCCAAGGTAGTTAT7080 
CCTTAAAAAAGCCACAGCATACATCCTGTCCGTCCAAGCAGAGGAGCAAAAGCTCATTTC7140 
TGAAGAGGACTTGTTGCGGAAACGACGAGAACAGTTGAAACACAAACTTGAACAGCTACG7200 
GAACTCTTGTGCGTAAGGAAAAGTAAGGAAAACGATTCCTTCTAACAGAAATGTCCTGAG7260 
CAATCACCTATGAACTTGTTTCAAATGCATGATCAAATGCAACCTCACAACCTTGGCTGA7320 
GTCTTGAGACTGAAAGATTTAGCCATAATGTAAACTGCCTCAAATTGGACTTTGGGCATA7380 
AAAGAACTTTTTTATGCTTACCATCTTTTTTTTTTCTTTAACAGATTTGTATTTAAGAAT7440 
TGTTTTTAAAAAATTTTAAGATTTACACAATGTTTCTCTGTAAATATTGCCATTAAATGT7500 
AAATAACTTTAATAAAACGTTTATAGCAGTTACACAGAATTTCAATCCTAGTATATAGTA7560 
CCTAGTATTATAGGTACTATAAACCCTAATTTTTTTTATTTAAGTACATTTTGCTTTTTA7620 
AAGTTGATTTTTTTCTATTGTTTTTAGAAAAAATAAAATAACTGGCAAATATATCATTGA7680 
GCCAAATCTTAAGTTGTGAATGTTTTGTTTCGTTTCTTCCCCCTCCCAACCACCACCATC7740 
CCTGTTTGTTTTCATCAATTGCCCCTTCAGAGGGCGGTCTTAAGAAAGGCAAGAGTTTTC7800 
CTCTGTTGAAATGGGTCTGGGGGCCTTAAGGTCTTTAAGTTCTTGGAGGTTCTAAGATGC7860 
TTCCTGGAGACTATGATAACAGCCAGAGTTGACAGTTAGAAGGAATGGCAGAAGGCAGGT7920 
GAGAAGGTGAGAGGTAGGCAAAGGAGATACAAGAGGTCAAAGGTAGCAGTTAAGTACACA7980 
AAGAGGCATAAGGACTGGGGAGTTGGGAGGAAGGTGAGGAAGAAACTCCTGTTACTTTAG8040 
TTAACCAGTGCCAGTCCCCTGCTCACTCCAAACCCAGGAATT8082 
(2) INFORMATION FOR SEQ ID NO:42: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 7011 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: 
CGGGCCGCATCAGCCCTCCTCCTGTTTGCGCTCCCCAGCGTGCAATTTATTTGGGGGGCT60 
ACCGGGGATTGAACGGAGCGGGCGAGCGCTGCCAGGAGGTGGGGCCGGCCCCACCTGTCG120 
ACTGCCCGTAGTAGGCAGGGAGAGGGCGGGGTTTGTCCCATAGGGCCCGCCCCCCAGTCC180 
CTGGGTCCCGGGCGCGCGACGAGATATAAGGCAGTCAGGAAACAATGCGCCTGCAGCTCG240 
CGCTCCCGCGCCGATCCCGAGAGCGTCCGGGCCGCCGTGCGCGAGCGAGGGAGGGCGCGC300 
GCGCGGGGGGGGCGCGCTCGTGAGTGCGGGCCGCGCTCTCGGCGGCGCGCATGTGCGTGT360 
GTGCTGGCTGCCGGGCTGCCCCGAGCCGGCGGGGAGCCGGTCCGCTCCAGGTGGCGGGCG420 
GCTGGAGCGAGGTGAGGCTGCGGGTGGCCAGGGCACGGGCGCGGGTCCCGCGGTGCGGGC480 
TGGCTGCAGGCTGCCTTCTGGGCACGGCGCGCCCCCGCCCGGCCCCGCCGGGCCCTGGGA540 
GCTGCGCTCCGGGCGGCGCTGGCAAAGTTTGCTTTGAACTCGCTGCCCACAGTCGGGTCC600 
GCGCGCTGCGATTGGCTTCCCCTACCACTCTGACCCGGGGCCCGGCTTCCCGGGACGCGA660 
GGACTGGGCGCAGGCTGCAAGCTGGTGGGGTTGGGGAGGAACGAGAGCCCGGCAGCCGAC720 
TGTGCCGAGGGACCCGGGGACACCTCCTTCGCCCGGCCGGCACCCGGTCAGCACGTCCCC780 
CCTTCCCTCCCGCAGGGAGCGGACATGGACTACGACTCGTACCAGCACTATTTCTACGAC840 
TATGACTGCGGGGAGGATTTCTACCGCTCCACGGCGCCCAGCGAGGACATCTGGAAGAAA900 
TTCGAGCTGGTGCCATCGCCCCCCACGTCGCCGCCCTGGGGCTTGGGTCCCGGCGCAGGG960 
GACCCGGCCCCCGGGATTGGTCCCCCGGAGCCGTGGCCCGGAGGGTGCACCGGAGACGAA1020 
GCGGAATCCCGGGGCCACTCGAAAGGCTGGGGCAGGAACTACGCCTCCATCATACGCCGT1080 
GACTGCATGTGGAGCGGCTTCTCGGCCCGGGAACGGCTGGAGAGAGCTGTGAGCGACCGG1140 
CTCGCTCCTGGCGCGCCCCGGGGGAACCCGCCCAAGGCGTCCGCCGCCCCGGACTGCACT1200 
CCCAGCCTCGAAGCCGGCAACCCGGCGCCCGCCGCCCCCTGTCCGCTGGGCGAACCCAAG1260 
ACCCAGGCCTGCTCCGGGTCCGAGAGCCCAAGCGACTCGGGTAAGGACCTCCCCGAGCCA1320 
TCCAAGAGGGGGCCACCCCATGGGTGGCCAAAGCTCTGCCCCTGCCTGAGGTCAGGCATT1380 
GGCTCTTCTCAAGCTCTTGGGCCATCTCCGCCTCTCTTTGGCTGAAGCTGCCCGTGTAGT1440 
CCCCAACCGTGTCTGTCTGGCACGTGGGTGTGTTGGTAAACAGTTTGGAAAAGTGGCGTG1500 
GGAGCCAGCCTCCCTTTGATGATTATTGGAGCCCCAGGGGACAAGGGATTTGAGGTGAGG1560 
GTTGGCGCTTAGAGAGGACAATACTGGGGTTGGACTGTAAGGGATTGAAGGGGGTACCTT1620 
AAGAGACACTCCAAACCTGAAGTTTTTTTGCTGCTGCCTCTTTCCCTAGGAAACTCACAC1680 
TCCCCTAGGGGGAGAAGAAGCCGAGAGCCTTTTGTGCAAAGCCAAAACCTTCGTCCTTTT1740 
AAAAACCTAGGTCTCCAGTTGGCTTTACTTTAAAATGCCAATAATAAATGCCCTCTTCTC1800 
GTGCCTCCCCACCACCACTTACCACTCGTGCATCCCTGAGACAGGGAGGGAAGAATGAAC1860 
ACTCCCCATTAACAGATGGAAAAACTGAGGCTTAGAGATAGACAATCACTACAAGTCAGC1920 
TCCAGCTTTCTGCCATCTAGCCAGCCCCTCTTCCCCAATGCTCCATCCCAACCAGGCACC1980 
TCTTCCTTGATGTTTGGGGTCTTTGTGGTAGCTTATCTTAGAAGCACTACACCTTGCCTT2040 
GCTGTTTGTCCTGAGATGGAAAAGTGTCCTTCTTGCTCCCCCTCAATAGATCTCCAGCGT2100 
CAGCTGCTCCCTGGCATTCAACAAATATTCACTGGCCCCTACTTTGTGGCAATCTGTGGG2160 
CTACATGCTGGGGTCAAGGCAGTAGAACTCCAGGCCCTCCTCTCCCATCCTTGATGCAAG2220 
TGCAACCTCGCTGAGGGCAGACTGGGGCATCCTGTGCCACTAAACTACATTGTTCTTATT2280 
CTGGCATCTTAGACCTCCACACCCGTGAGAAATCCTGGAGAGGGTATTTTTGTAGAGTGT2340 
AGACTGTGGCTAGTGACAAATAAATTAGGACCAAGAAAGCTCACTGTAGCTTTTAGGAAT2400 
AACTTTTACACGACCATTTGATAGGGAACTGGGGAATGGGGTATGGAAGTTTTCCTACAC2460 
TTGAGAGAAAAAATAGGATAACAAAAATTAAAAGTCTTTTTTTCCTGGTCCACTGTGTTA2520 
AGGTCATTTTTAACCAGCTTGCTTTCTACACCAAGAGTTTATGTTTGTTTAATGGCTGGA2580 
AAGAGAATCTTGAGATCAAAAAACCAATAAAGATGTATCTCTACAACGGCTGGTGGAGTG2640 
GTAGAGTGGAAAGAGCATTGCTTTGGAAGTTGGAACATTTTAGTTTGAGATCCAGAACGT2700 
TACAAAGGTGATATGTGGACTTCGCTGATCTGGGCCTCAGTTTCCCCATTTGCACACGAT2760 
GGGGTTGGACTTGATTGTCCTGCTGATGACATTTCCTTGTCTGGATAGAGTAAGACACTA2820 
CTCTCTGAAAGGGAGAATGGTGTGCTTAAATTATTTCTTTCTTAGATAGAATCTTCCTGA2880 
GCCACGAGGCTTAACACTGAAAATTAAAGGTTTGGGATGTAGGAAAGCCTGCTGAATCAT2940 
TTTCTAACCTACCCTTTAACCTGAACCTGTTTGTGAGCTTCTAGTTCACTCACAGGCCAC3000 
ATGGCCTGGAACAAAATGCAACAGATTGCAAACAATGAGGCGGGGGGTGGGGAAAGTGAT3060 
TGGCAGCAGAGCTCACCCAATAGGGGCTAGGGGCTGGGTAAGACAGAATTCCAAACACAG3120 
CGTAATCAGCCAATCATGGGCTTTGGGGCCAGGAGGGCTGAATGGTCAGGTTTATTAATG3180 
GAGAAATAATGCGATTGTCCACACAATGGAAGCCTTCCTGACAAAGGGGCTCAAGCTTCC3240 
TGATATGCAAAGAAGCTGAGAACGGAGCTCTTCCTTTGCCGAGGCCGAGATCCATTAAGG3300 
TCGGACTTCTGTGTGGAGGCTGCAAAATGTGTGGAGCAGGAGGAGACTTTTCTCCCAATT3360 
GCCCCTCTCCTGGTTAGGTTAACCTAAGAGACCTTCAAGCCAGTGAATGAGAAGGGCGTG3420 
TCCAGGTGTCTCCAGGTCTCTGGTGTTATGAGCCCCATATCTGGGACATTCTGCTGCCCA3480 
GTCTCTGCCTCTGGTGCAGGTAGTTTGGAAATGGTCGCTTGTACCTTTGTGAAGTTCCTG3540 
CAGCTTCGCCGACCTATGATTACAAATCTAACCTTCTAGTCCAGGGAAGGAGGTGGGGCA3600 
GGCGACCTATAAATGATGGATGACTTTAGAAACCCATTGAACCCAGGAGCAAAATGCTCC3660 
TAAGGGAAACCCTTTCCCTCCCCTCTGTGGGTGAAGAGGGATGGGTTGTAGCCCTCCCTT3720 
CTCTGAATCTTCAGCTGAAAGGGATGGCAGAATAGAGAGGTGGGGGAATAATAGGATTTA3780 
TAACTTGTGAAAAGTAACAATTCCCCAAGTGCAGGCTGTGCTGGGCAGGAACAAAGGGCA3840 
GCTCTGCCCACAGACCCCTCATTTACAATTCTGATGGGGCATGAAAGAGCCCGACTGGGG3900 
AAGATCTTTATAGCTAAACTTTGTCCCAGGCCGGTAGCTCTTTCTCTCCAACCCCTCCGT3960 
GGGGGAGGGGAGAGCCTTTGCAGACTGGGGGCTGTTGGCTTGGGTCTGCCTTTTGTTCTT4020 
ATCTAAGCCTTGCTGTGCAAAAGGAAATTGGAGAATATTTTCCTTCTTGCTAATGTCCCC4080 
TCCTTTCCTTCACTGTGCCCTTACCACATTACAAATGAATCAGCTTTCTGCTCACCTCGA4140 
TTTGTATATATCTAAATTGGAAAAATGTCTCCTACCTTCCCAAGCACCAGCGTAGACAGC4200 
TAAAGCTGTAGGGTCTATGTTTGTGTTTCTCATGGGATGTGTTTCTTCTCTTGATCTCTT4260 
TTCTCGGACAGAGAATGAAGAAATTGATGTTGTGACAGTAGAGAAGAGGCAGTCTCTGGG4320 
TATTCGGAAGCCGGTCACCATCACGGTGCGAGCAGACCCCCTGGATCCCTGCATGAAGCA4380 
TTTCCACATCTCCATCCATCAGCAACAGCACAACTATGCTGCCCGTTTTCCTCCAGAAAG4440 
CTGCTCCCAAGAAGAGGCTTCAGAGAGGGGTCCCCAAGAAGAGGTTCTGGAGAGAGATGC4500 
TGCAGGGGAAAAGGAAGATGAGGAGGATGAAGAGATTGTGAGTCCCCCACCTGTAGAAAG4560 
TGAGGCTGCCCAGTCCTGCCACCCCAAACCTGTCAGTTCTGATACTGAGGATGTGACCAA4620 
GAGGAAGAATCACAACTTCCTGGAGCGCAAGAGGCGGAATGACCTGCGTTCGCGATTCTT4680 
GGCGCTGAGGGACCAGGTGCCCACCCTGGCCAGCTGCTCCAAGGCCCCCAAAGTAGTGAT4740 
CCTAAGCAAGGCCTTGGAATACTTGCAAGCCCTGGTGGGGGCTGAGAAGAGGATGGCTAC4800 
AGAGAAAAGACAGCTCCGATGCCGGCAGCAGCAGTTGCAGAAAAGAATTGCATACCTCAG4860 
TGGCTACTAACTGACCAAAAAGCCTGACAGTTCTGTCTTACGAAGACACAAGTTTATTTT4920 
TTAACCTCCCTCTCCCCTTTAGTAATTTGCACATTTTGGTTATGGTGGGACAGTCTGGAC4980 
AGTAGATCCCAGAATGCATTGCAGCCGGTGCACACACAATAAAGGCTTGCATTCTTGGAA5040 
ACCTTGAAACCCAGCTCTCCCTCTTCCCTGACTCATGGGAGTGCTGTATGTTCTCTGGCG5100 
CCTTTGGCTTCCCAGCAGGCAGCTGACTGAGGAGCCTTGGGGTCTGCCTAGCTCACTAGC5160 
TCTGAAGAAAAGGCTGACAGATGCTATGCAACAGGTGGTGGATGTTGTCAGGGGCTCCAG5220 
CCTGCATGAAATCTCACACTCTGCATGAGCTTTAGGCTAGGAAAGGATGCTCCCAACTGG5280 
TGTCTCTGGGGTGATGCAAGGACAGCTGGGCCTGGATGCTCTCCCTGAGGCTCCTTTTTC5340 
CAGAAGACACACGAGCTGTCTTGGGTGAAGACAAGCTTGCAGACTTGATCAACATTGACC5400 
ATTACCTCACTGTCAGACACTTTACAGTAGCCAAGGAGTTGGAAACCTTTATGTATTATG5460 
ATGTTAGCTGACCCCCTTCCTCCCACTCCCAATGCTGCGACCCTGGGAACACTTAAAAAG5520 
CTTGGCCTCTAGATTCTTTGTCTCAGAGCCCTCTGGGCTCTCTCCTCTGAGGGAGGGACC5580 
TTTCTTTCCTCACAAGGGACTTTTTTGTTCCATTATGCCTTGTTATGCAATGGGCTCTAC5640 
AGCACCCTTTCCCACAGGTCAGAAATATTTCCCCAAGACACAGGGAAATCGGTCCTAGCC5700 
TGGGGCCTGGGGATAGCTTGGAGTCCTGGCCCATGAACTTGATCCCTGCCCAGGTGTTTT5760 
CCGAGGGGCACTTGAGGCCCAGTCTTTTCTCAAGGCAGGTGTAAGACACTCAGAGGGAGA5820 
ACTGTACTGCTGCCTCTTTCCCACCTTCCTCATCTCAATCCTTGAGCGGCAAGTTTGAAG5880 
TTCTTCTGGAACCATGCAAATCTGTCCTCCTCATGCAATTCCAAGGAGCTTGCTGGCTCT5940 
GCAGCCACCTCTGGGCCCCTTCCAGCCTGCCATGAATCAGATATCTTTCCCAGAATCTGG6000 
GCGTTTCTGAAGTTTTGGGGAGAGCTGTTGGGACTCATCCAGTGCTCCAGAAGGTGGACT6060 
TGCTTCTGGGGGGTTTTAAAGGAGCCTCCAGGAGATATGCTTAGCCAACCATGATGGATT6120 
TTACCCCAGCTGGACTCGGCAGCTCCAAGTGGAATCCACGTGCAGCTTCTAGTCTGGGAA6180 
AGTCACCCAACCTAGCAGTTGTCATGTGGGTAACCTCAGGCACCTCTAAGCCTGTCCTGG6240 
AAGAAGGACCAGCAGCCCCTCCAGAACTCTGCCCAGGACAGCAGGTGCCTGCTGGCTCTG6300 
GGTTTGGAAGTTTGGGGTGGGTAGGGGGTGGTAAGTACTATATATGGCTCTGGAAAACCA6360 
GCTGCTACTTCCAAATCTATTGTCCATAATGGTTTCTTTCTGAGGTTGCTTCTTGGCCTC6420 
AGAGGACCCCAGGGGATGTTTGGAAATAGCCTCTCTACCCTTCTGGAGCATGGTTTACAA6480 
AAGCCAGCTGACTTCTGGAATTGTCTATGGAGGACAGTTTGGGTGTAGGTTACTGATGTC6540 
TCAACTGAATAGCTTGTGTTTTATAAGCTGCTGTTGGCTATTATGCTGGGGGAGTCTTTT6600 
TTTTTTATATTGTATTTTTGTATGCCTTTTGCAAAGTGGTGTTAACTGTTTTTGTACAAG6660 
GAAAAAAACTCTTGGGGCAATTTCCTGTTGCAAGGGTCTGATTTATTTTGAAAGGCAAGT6720 
TCACCTGAAATTTTGTATTTAGTTGTGATTACTGATTGCCTGATTTTAAAATGTTGCCTT6780 
CTGGGACATCTTCTAATAAAAGATTTCTCAAACATGTCAGAGTGGGGGCAGCTTATGCCA6840 
CCTGAGTCCTCCTCAACCACGGAAAACTATTTCAGGGTAGCCACAAGTGATCCAGAGGGC6900 
TGCACTTCTCTAACCATGTTGCTAACCTGGTCATTCCACTCTGGGTTCCTGAAATGCCAT6960 
TTCAGACATGTTGAAACAATGTAGGCTCAGTACTCAGTGAACACGGAATTC7011 
(2) INFORMATION FOR SEQ ID NO:43: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 1604 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: 
GAATTCCGGGCGAGGGCCGGGCAGGAGGAGCGGGCGCGCGGCGGGCGAGGCTGGGACCCG60 
AGCGCGCTCACTTCGCCGCAAAGTGCCAACTTCCCCTGGAGTGCCGGGCGCGCACCGTCC120 
GGGCGCGGGGGAAAGAAAGGCAGCGGGAATTTGAGATTTTTGGGAAGAAAGTCGGATTTC180 
CCCCGTCCCCTTCCCCCTGTTACTAATCCTCATTAAAAAGAAAAACAACAATAACTGCAA240 
ACTTGCTACCATCCCGTACGTCCCCCACTCCTGGCACCATGAAGGCGGCCGTCGATCTCA300 
AGCCGACTCTCACCATCATCAAGACGGAAAAAGTCGATCTGGAGCTTTTCCCCTCCCCGG360 
ATATGGAATGTGCAGATGTCCCACTATTAACTCCAAGCAGCAAAGAAATGATGTCTCAAG420 
CATTAAAAGCTACTTTCAGTGGTTTCACTAAAGAACAGCAACGACTGGGGATCCCAAAAG480 
ACCCCCGGCAGTGGACAGAAACCCATGTTCGGGACTGGGTGATGTGGGCTGTGAATGAAT540 
TCAGCCTGAAAGGTGTAGACTTCCAGAAGTTCTGTATGAATGGAGCAGCCCTCTGCGCCC600 
TGGGTAAAGACTGCTTTCTCGAGCTGGCCCCAGACTTTGTTGGGGACATCTTATGGGAAC660 
ATCTAGAGATCCTGCAGAAAGAGGATGTGAAACCATATCAAGTTAATGGAGTCAACCCAG720 
CCTATCCAGAATCCCGCTATACCTCGGATTACTTCATTAGCTATGGTATTGAGCATGCCC780 
AGTGTGTTCCACCATCGGAGTTCTCAGAGCCCAGCTTCATCACAGAGTCCTATCAGACGC840 
TCCATCCCATCAGCTCGGAAGAGCTCCTCTCCCTCAAGTATGAGAATGACTACCCCTCGG900 
TCATTCTCCGAGACCCTCTCCAGACAGACACCTTGCAGAATGACTACTTTGCTATCAAAC960 
AAGAAGTCGTCACCCCAGACAACATGTGCATGGGGAGGACCAGTCGTGGTAAACTCGGGG1020 
GCCAGGACTCTTTTGAAAGCATAGAGAGCTACGATAGTTGTGATCGCCTCACCCAGTCCT1080 
GGAGCAGCCAGTCATCTTTCAACAGCCTGCAGCGTGTTCCCTCCTATGACAGCTTCGACT1140 
CAGAGGACTATCCGGCTGCCCTGCCCAACCACAAGCCCAAGGGCACCTTCAAGGACTATG1200 
TGCGGGACCGTGCTGACCTCAATAAGGACAAGCCTGTCATTCCTGCTGCTGCCCTAGCTG1260 
GCTACACAGGCAGTGGACCAATCCAGCTATGGCAGTTTCTTCTGGAATTACTCACTGATA1320 
AATCCTGTCAGTCTTTTATCAGCTGGACAGGAGATGGCTGGGAATTCAAACTTTCTGACC1380 
CAGATGAGGTGGCCAGGAGATGGGGAAAGAGGAAAAACAAACCTAAGATGAATTATGAGA1440 
AACTGAGCCGTGGCCTACGCTACTATTACGACAAAAACATCATCCACAAGACAGCGGGGA1500 
AACGCTACGTGTACCGCTTTGTGTGTGACCTGCAGAGCCTGCTGGGGTACACCCCTGAGG1560 
AGCTGCACGCCATGCTGGACGTCAAGCCAGATGCCGACGAGTGA1604 
(2) INFORMATION FOR SEQ ID NO:44: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 3565 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: 
GCAGCCGGGCGGCCGCAGAAGCGCCCAGGCCCGCGCGCCACCCCTCTGGCGCCACCGTGG60 
TTGAGCCCGTGACGTTTACACTCATTCATAAAACGCTTGTTATAAAAGCAGTGGCTGCGG120 
CGCCTCGTACTCCAACCGCATCTGCAGCGAGCAACTGAGAAGCCAAGACTGAGCCGGCGG180 
CCGCGGCGCAGCGAACGAGCAGTGACCGTGCTCCTACCCAGCTCTGCTTCACAGCGCCCA240 
CCTGTCTCCGCCCCTCGGCCCCTCGCCCGGCTTTGCCTAACCGCCACGATGATGTTCTCG300 
GGCTTCAACGCAGACTACGAGGCGTCATCCTCCCGCTGCAGCAGCGCGTCCCCGGCCGGG360 
GATAGCCTCTCTTACTACCACTCACCCGCAGACTCCTTCTCCAGCATGGGCTCGCCTGTC420 
AACGCGCAGGTAAGGCTGGCTTCCCGTCGCCGCGGGGCCGGGGGCTTGGGGTCGCGGAGG480 
AGGAGACACCGGGCGGGACGCTCCAGTAGATGAGTAGGGGGCTCCCTTGTGCCTGGAGGG540 
AGGCTGCCGTGGCCGGAGCGGTGCCGGCTCGGGGGCTCGGGACTTGCTCTGAGCGCACGC600 
ACGCTTGCCATAGTAAGAATTGGTTCCCCCTTCGGGAGGCAGGTTCGTTCTGAGCAACCT660 
CTGGTCTGCACTCCAGGACGGATCTCTGACATTAGCTGGAGCAGACGTGTCCCAAGCACA720 
AACTCGCTAACTAGAGCCTGGCTTCTTCGGGGAGGTGGCAGAAAGCGGCAATCCCCCCTC780 
CCCCGGCAGCCTGGAGCACGGAGGAGGGATGAGGGAGGAGGGTGCAGCGGGCGGGTGTGT840 
AAGGCAGTTTCATTGATAAAAAGCGAGTTCATTCTGGAGACTCCGGAGCGGCGCCTGCGT900 
CAGCGCAGACGTCAGGGATATTTATAACAAACCCCCTTTCAAGCAAGTGATGCTGAAGGG960 
ATAACGGGAACGCAGCGGCAGGATGGAAGAGACAGGCACTGCGCTGCGGAATGCCTGGGA1020 
GGAAAAGGGGGAGACCTTTCATCCAGGATGAGGGACATTTAAGATGAAATGTCCGTGGCA1080 
GGATCGTTTCTCTTCACTGCTGCATGCGGCACTGGGAACTCGCCCCACCTGTGTCCGGAA1140 
CCTGCTCGCTCACGTCGGCTTTCCCCTTCTGTTTTGTTCTAGGACTTCTGCACGGACCTG1200 
GCCGTCTCCAGTGCCAACTTCATTCCCACGGTCACTGCCATCTCGACCAGTCCGGACCTG1260 
CAGTGGCTGGTGCAGCCCGCCCTCGTCTCCTCTGTGGCCCCATCGCAGACCAGAGCCCCT1320 
CACCCTTTCGGAGTCCCCGCCCCCTCCGCTGGGGCTTACTCCAGGGCTGGCGTTGTGAAG1380 
ACCATGACAGGAGGCCGAGCGCAGAGCATTGGCAGGAGGGGCAAGGTGGAACAGGTGAGG1440 
AACTCTAGCGTACTCTTCCTGGGAATGTGGGGGCTGGGTGGGAAGCAGCCCCGGAGATGC1500 
AGGAGCCCAGTACAGAGGATGAAGCCACTGATGGGGCTGGCTGCACATCCGTAACTGGGA1560 
GCCCTGGCTCCAAGCCCATTCCATCCCAACTCAGACTCTGAGTCTCACCCTAAGAAGTAC1620 
TCTCATAGTTTCTTCCCTAAGTTTCTTACCGCATGCTTTCAGACTGGGCTCTTCTTTGTT1680 
CTCTTGCTGAGGATCTTATTTTAAATGCAAGTCACACCTATTCTGCAACTGCAGGTCAGA1740 
AATGGTTTCACAGTGGGGTGCCAGGAAGCAGGGAAGCTGCAGGAGCCAGTTCTACTGGGG1800 
TGGGTGAATGGAGGTGATGGCAGACACTTTTACTGAATGTCGGTCTTTTTTTGTGATTAT1860 
TCTAGTTATCTCCAGAAGAAGAAGAGAAAAGGAGAATCCGAAGGGAAAGGAATAAGATGG1920 
CTGCAGCCAAATGCCGCAACCGGAGGAGGGAGCTGACTGATACACTCCAAGCGGTAGGTA1980 
CTCTGTGGGTTGCTCCTTTTTAAAACTTAAGGGAAAGTTGGAGATTGAGCATAAGGGCCC2040 
TTGAGTAAGACTGTGTCTTATGCTTTCCTTTATCCCTCTGTATACAGGAGACAGACCAAC2100 
TAGAAGATGAGAAGTCTGCTTTGCAGACCGAGATTGCCAACCTGCTGAAGGAGAAGGAAA2160 
AACTAGAGTTCATCCTGGCAGCTCACCGACCTGCCTGCAAGATCCCTGATGACCTGGGCT2220 
TCCCAGAAGAGATGTCTGTGGCTTCCCTTGATCTGACTGGGGGCCTGCCAGAGGTTGCCA2280 
CCCCGGAGTCTGAGGAGGCCTTCACCCTGCCTCTCCTCAATGACCCTGAGCCCAAGCCCT2340 
CAGTGGAACCTGTCAAGAGCATCAGCAGCATGGAGCTGAAGACCGAGCCCTTTGATGACT2400 
TCCTGTTCCCAGCATCATCCAGGCCCAGTGGCTCTGAGACAGCCCGCTCCGTGCCAGACA2460 
TGGACCTATCTGGGTCCTTCTATGCAGCAGACTGGGAGCCTCTGCACAGTGGCTCCCTGG2520 
GGATGGGGCCCATGGCCACAGAGCTGGAGCCCCTGTGCACTCCGGTGGTCACCTGTACTC2580 
CCAGCTGCACTGCTTACACGTCTTCCTTCGTCTTCACCTACCCCGAGGCTGACTCCTTCC2640 
CCAGCTGTGCAGCTGCCCACCGCAAGGGCAGCAGCAGCAATGAGCCTTCCTCTGACTCGC2700 
TCAGCTCACCCACGCTGCTGGCCCTGTGAGGGGGCAGGGAAGGGGAGGCAGCCGGCACCC2760 
ACAAGTGCCACTGCCCGAGCTGGTGCATTACAGAGAGGAGAAACACATCTTCCCTAGAGG2820 
GTTCCTGTAGACCTAGGGAGGACCTTATCTGTGCGTGAAACACACCAGGCTGTGGGCCTC2880 
AAGGACTTGAAAGCATCCATGTGTGGACTCAAGTCCTTACCTCTTCCGGAGATGTAGCAA2940 
AACGCATGGAGTGTGTATTGTTCCCAGTGACACTTCAGAGAGCTGGTAGTTAGTAGCATG3000 
TTGAGCCAGGCCTGGGTCTGTGTCTCTTTTCTCTTTCTCCTTAGTCTTCTCATAGCATTA3060 
ACTAATCTATTGGGTTCATTATTGGAATTAACCTGGTGCTGGATATTTTCAAATTGTATC3120 
TAGTGCAGCTGATTTTAACAATAACTACTGTGTTCCTGGCAATAGTGTGTTCTGATTAGA3180 
AATGACCAATATTATACTAAGAAAAGATACGACTTTATTTTCTGGTAGATAGAAATAAAT3240 
AGCTATATCCATGTACTGTAGTTTTTCTTCAACATCAATGTTCATTGTAATGTTACTGAT3300 
CATGCATTGTTGAGGTGGTCTGAATGTTCTGACATTAACAGTTTTCCATGAAAACGTTTT3360 
ATTGTGTTTTTAATTTATTTATTAAGATGGATTCTCAGATATTTATATTTTTATTTTATT3420 
TTTTTCTACCTTGAGGTCTTTTGACATGTGGAAAGTGAATTTGAATGAAAAATTTAAGCA3480 
TTGTTTGCTTATTGTTCCAAGACATTGTCAATAAAAGCATTTAAGTTGAATGCGACCAAC3540 
CTTGTGCTCTTTTCATTCTGGAAGT3565 
(2) INFORMATION FOR SEQ ID NO:45: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 3225 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: 
GGCGGCAGCGCCCTGCCGACGCCGGGGAGGGACGCAGGCAGGCGGCGGGCAGCGGGAGGC60 
GGCACCCCGGTGCTCCCCGCGGCTCTCGGCGGAGCCCCGCCGCCCGCCGCGCCATGGCCC120 
GAAGACCCCGGCACAGCATATATAGCAGTGACGAGGATGATGAGGACTTTGAGATGTGTG180 
ACCATGACTATGATGGGCTGCTTCCCAAGTCTGGAAAGCGTCACTTGGGGAAAACAAGGT240 
GGACCCGGGAAGAGGATGAAAAACTGAAGAAGCTGGTGGAACAGAATGGAACAGATGACT300 
GGAAAGTTATTGCCAATTATCTCCCGAATCGAACAGATGTGCAGTGCCAGCACCGATGGC360 
AGAAAGTACTAAACCCTGAGCTCATCAAGGGTCCTTGGACCAAAGAAGAAGATCAGAGAG420 
TGATAGAGCTTGTACAGAAATACGGTCCGAAACGTTGGTCTGTTATTGCCAAGCACTTAA480 
AGGGGAGAATTGGAAAACAATGTAGGGAGAGGTGGCATAACCACTTGAATCCAGAAGTTA540 
AGAAAACCTCCTGGACAGAAGAGGAAGACAGAATTATTTACCAGGCACACAAGAGACTGG600 
GGAACAGATGGGCAGAAATCGCAAAGCTACTGCCTGGACGAACTGATAATGCTATCAAGA660 
ACCACTGGAATTCTACAATGCGTCGGAAGGTCGAACAGGAAGGTTATCTGCAGGAGTCTT720 
CAAAAGCCAGCCAGCCAGCAGTGGCCACAAGCTTCCAGAAGAACAGTCATTTGATGGGTT780 
TTGCTCAGGCTCCGCCTACAGCTCAACTCCCTGCCACTGGCCAGCCCACTGTTAACAACG840 
ACTATTCCTATTACCACATTTCTGAAGCACAAAATGTCTCCAGTCATGTTCCATACCCTG900 
TAGCGTTACATGTAAATATAGTCAATGTCCCTCAGCCAGCTGCCGCAGCCATTCAGAGAC960 
ACTATAATGATGAAGACCCTGAGAAGGAAAAGCGAATAAAGGAATTAGAATTGCTCCTAA1020 
TGTCAACCGAGAATGAGCTAAAAGGACAGCAGGTGCTACCAACACAGAACCACACATGCA1080 
GCTACCCCGGGTGGCACAGCACCACCATTGCCGACCACACCAGACCTCATGGAGACAGTG1140 
CACCTGTTTCCTGTTTGGGAGAACACCACTCCACTCCATCTCTGCCAGCGGATCCTGGCT1200 
CCCTACCTGAAGAAAGCGCCTCGCCAGCAAGGTGCATGATCGTCCACCAGGGCACCATTC1260 
TGGATAATGTTAAGAACCTCTTAGAATTTGCAGAAACACTCCAATTTATAGATTCTTTCT1320 
TAAACACTTCCAGTAACCATGAAAACTCAGACTTGGAAATGCCTTCTTTAACTTCCACCC1380 
CCCTCATTGGTCACAAATTGACTGTTACAACACCATTTCATAGAGACCAGACTGTGAAAA1440 
CTCAAAAGGAAAATACTGTTTTTAGAACCCCAGCTATCAAAAGGTCAATCTTAGAAAGCT1500 
CTCCAAGAACTCCTACACCATTCAAACATGCACTTGCAGCTCAAGAAATTAAATACGGTC1560 
CCCTGAAGATGCTACCTCAGACACCCTCTCATCTAGTAGAAGATCTGCAGGATGTGATCA1620 
AACAGGAATCTGATGAATCTGGATTTGTTGCTGAGTTTCAAGAAAATGGACCACCCTTAC1680 
TGAAGAAAATCAAACAAGAGGTGGAATCTCCAACTGATAAATCAGGAAACTTCTTCTGCT1740 
CACACCACTGGGAAGGGGACAGTCTGAATACCCAACTGTTCACGCAGACCTCGCCTGTGC1800 
GAGATGCACCGAATATTCTTACAAGCTCCGTTTTAATGGCACCAGCATCAGAAGATGAAG1860 
ACAATGTTCTCAAAGCATTTACAGTACCTAAAAACAGGTCCCTGGCGAGCCCCTTGCAGC1920 
CTTGTAGCAGTACCTGGGAACCTGCATCCTGTGGAAAGATGGAGGAGCAGATGACATCTT1980 
CCAGTCAAGCTCGTAAATACGTGAATGCATTCTCAGCCCGGACGCTGGTCATGTGAGACA2040 
TTTCCAGAAAAGCATTATGGTTTTCAGAACAGTTCAAGTTGACTTGGGATATATCATTCC2100 
TCAACATGAAACTTTTCATGAATGGGAGAAGAACCTATTTTTGTTGTGGTACAACAGTTG2160 
AGAGCACGACCAAGTGCATTTAGTTGAATGAAGTCTTCTTGGATTTCACCCAACTAAAAG2220 
GATTTTTAAAAATAAATAACAGTCTTACCTAAATTATTAGGTAATGAATTGTAGCCAGTT2280 
GTTAATATCTTAATGCAGATTTTTTTAAAAAAAAACATAAAATGATTTATCTGGTATTTT2340 
AAAGGATCCAACAGATCAGTATTTTTTCCTGTGATGGGTTTTTTGAAATTTGACACATTA2400 
AAAGGTACTCCAGTATTTCACTTTTCTCGATCACTAAACATATGCATATATTTTTAAAAA2460 
TCAGTAAAAGCATTACTCTAAGTGTAGACTTAATACCATGTGACATTTAATCCAGATTGT2520 
AAATGCTCATTTATGGTTAATGACATTGAAGGTACATTTATTGTACCAAACCATTTTATG2580 
AGTTTTCTGTTAGCTTGCTTTAAAAATTATTACTGTAAGAAATAGTTTTATAAAAAATTA2640 
TATTTTTATTCAGTAATTTAATTTTGTAAATGCCAAATGAAAAACGTTTTTTGCTGCTAT2700 
GGTCTTAGCCTGTAGACATGCTGCTAGTATCAGAGGGGCAGTAGAGCTTGGACAGAAAGA2760 
AAAGAAACTTGGTGTTAGGTAATTGACTATGCACTAGTATTTCAGACTTTTTAATTTTAT2820 
ATATATATACATTTTTTTTCCTTCTGCAATACATTTGAAAACTTGTTTGGGAGACTCTGC2880 
ATTTTTTATTGTGGTTTTTTTGTTATTGTTGGTTTATACAAGCATGCGTTGCACTTCTTT2940 
TTTGGGAGATGTGTGTTGTTCATGTTCTATGTTTTGTTTTGTGTGTAGCCTGACTGTTTT3000 
ATAATTTGGGAGTTCTCGATTTGATCCGCATCCCCTGTGGTTTCTAAGTGTATGGTCTCA3060 
GAACTGTTGCATGGATCCTGTGTTTGCAACTGGGGAGACAGAAACTGTGGTTGATAGCCA3120 
GTCACTGCCTTAAGAACATTTGATGCAAGATGGCCAGCACTGAACTTTTGAGATATGACG3180 
GTGTACTTACTGCCTTGTAGCAAAATAAAGATGTGCCCTTATTTT3225 
(2) INFORMATION FOR SEQ ID NO:46: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2638 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: 
GCTGACGCCTTCGAGCGCGGCCCGGGGCCCGGAGCGGCCGGAGCAGCCCGGGTCCTGACC60 
CCGGCCCGGCTCCCGCTCCGGGCTCTGCCGGCGGGCGGGCGAGCGCGGCGCGGTCCGGGC120 
CGGGGGGATGTCTCGGCGGACGCGCTGCGAGGATCTGGATGAGCTGCACTACCAGGACAC180 
AGATTCAGATGTGCCGGAGCAGAGGGATAGCAAGTGCAAGGTCAAATGGACCCATGAGGA240 
GGACGAGCAGCTGAGGGCCCTGGTGAGGCAGTTTGGACAGCAGGACTGGAAGTTCCTGGC300 
CAGCCACTTCCCTAACCGCACTGACCAGCAATGCCAGTACAGGTGGCTGAGAGTTTTGAA360 
TCCAGACCTTGTCAAGGGGCCATGGACCAAAGAGGAAGACCAAAAAGTCATCGAGCTGGT420 
TAAGAAGTATGGCACAAAGCAGTGGACACTGATTGCCAAGCACCTGAAGGGCCGGCTGGG480 
GAAGCAGTGCCGTGAACGCTGGCACAACCACCTCAACCCTGAGGTGAAGAAGTCTTGCTG540 
GACCGAGGAGGAGGACCGCATCATCTGCGAGGCCCACAAGGTGCTGGGCAACCGCTGGGC600 
CGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAATGCTGTGAAGAATCACTGGAACTC660 
TACCATCAAAAGGAAGGTGGACACAGGAGGCTTCTTGAGCGAGTCCAAAGACTGCAAGCC720 
CCCAGTGTACTTGCTGCTGGAGCTCGAGGACAAGGACGGCCTCCAGAGTGCCCAGCCCAC780 
GGAAGGCCAGGGAAGTCTTCTGACCAACTGGCCCTCCGTCCCTCCTACCATAAAGGAGGA840 
GGAAAACAGTGAGGAGGAACTTGCAGCAGCCACCACATCGAAGGAACAGGAGCCCATCGG900 
TACAGATCTGGACGCAGTGCGAACACCAGAGCCCTTGGAGGAATTCCCGAAGCGTGAGGA960 
CCAGGAAGGCTCCCCACCAGAAACGAGCCTGCCTTACAAGTGGGTGGTGGAGGCAGCTAA1020 
CCTCCTCATCCCCGCTGTGGGTTCTAGCCTCTCTGAAGCCCTGGACTTGATCGAGTCGGA1080 
CCCTGATGCTTGGTGTGACCTGAGTAAATTTGACCTCCCTGAGGAACCATCTGCAGAGGA1140 
CAGTATCAACAACAGCCTAGTGCAGCTGCAAGCGTCACATCAGCAGCAAGTCCTGCCACC1200 
CCGCCAGCCTTCCGCCCTGGTGCCCAGTGTGACCGAGTACCGCCTGGATGGCCACACCAT1260 
CTCAGACCTGAGCCGGAGCAGCCGGGGCGAGCTGATCCCCATCTCCCCCAGCACTGAAGT1320 
CGGGGGCTCTGGCATTGGCACACCGCCCTCTGTGCTCAAGCGGCAGAGGAAGAGGCGTGT1380 
GGCTCTGTCCCCTGTCACTGAGAATAGCACCAGTCTGTCCTTCCTGGATTCCTGTAACAG1440 
CCTCACGCCCAAGAGCACACCTGTTAAGACCCTGCCCTTCTCGCCCTCCCAGTTTCTGAA1500 
CTTCTGGAACAAACAGGACACATTGGAGCTGGAGAGCCCCTCGCTGACATCCACCCCAGT1560 
GTGCAGCCAGAAGGTGGTGGTCACCACACCACTGCACCGGGACAAGACACCCCTGCACCA1620 
GAAACATGCTGCGTTTGTAACCCCAGATCAGAAGTACTCCATGGACAACACTCCCCACAC1680 
GCCAACCCCGTTCAAGAACGCCCTGGAGAAGTACGGACCCCTGAAGCCCCTGCCACAGAC1740 
CCCGCACCTGGAGGAGGACTTGAAGGAGGTGCTGCGTTCTGAGGCTGGCATCGAACTCAT1800 
CATCGAGGACGACATCAGGCCCGAGAAGCAGAAGAGGAAGCCTGGGCTGCGGCGGAGCCC1860 
CATCAAGAAAGTCCGGAAGTCTCTGGCTCTTGACATTGTGGATGAGGATGTGAAGCTGAT1920 
GATGTCCACACTGCCCAAGTCTCTATCCTTGCCGACAACTGCCCCTTCAAACTCTTCCAG1980 
CCTCACCCTGTCAGGTATCAAAGAAGACAACAGCTTGCTCAACCAGGGCTTCTTGCAGGC2040 
CAAGCCCGAGAAGGCAGCAGTGGCCCAGAAGCCCCGAAGCCACTTCACGACACCTGCCCC2100 
TATGTCCAGTGCCTGGAAGACGGTGGCCTGCGGGGGGACCAGGGACCAGCTTTTCATGCA2160 
GGAGAAAGCCCGGCAGCTCCTGGGCCGCCTGAAGCCCAGCCACACATCTCGGACCCTCAT2220 
CTTGTCCTGAGGTGTTGAGGGTGTCACGAGCCCATTCTCATGTTTACAGGGGTTGTGGGG2280 
GCAGAGGGGGTCTGTGAATCTGAGAGTCATTCAGGTGACCTCCTGCAGGGAGCCTTCTGC2340 
CACCAGCCCCTCCCCAGACTCTCAGGTGGAGGCAACAGGGCCATGTGCTGCCCTGTTGCC2400 
GAGCCCAGCTGTGGGCGGCTCCTGGTGCTAACAACAAAGTTCCACTTCCAGGTCTGCCTG2460 
GTTCCCTCCCCAAGGCCACAGGGAGCTCCGTCAGCTTCTCCCAAGCCCACGTCAGGCCTG2520 
GCCTCATCTCAGACCCTGCTTAGGATGGGGGATGTGGCCAGGGGTGCTCCTGTGCTCACC2580 
CTCTCTTGGTGCATTTTTTTGGAAGAATAAAATTGCCTCTCTCTTTGAAAAAAAAAAA2638 
(2) INFORMATION FOR SEQ ID NO:47: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 790 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: 
AGAATTTAGAAGCAGGGAGATGTAATTAGAGAATATGTCATTACCTAGAAATGAAGCCAC60 
AAAGTCTAAAGTAAAGCAGTTAGAAAGGAAGTGGACAGATAAATAGATGATTAATGTATT120 
TAGTGTCATTTATCTATACACTAAAACTTTTATTCTGTGAATGCTTTTCCTCAAATTCTT180 
CCCTGCAAAAAGAAATAAAATATTACTAAGGTAGCAACTCATTTTTTTGAAAATCCTTTA240 
TATTTAGGTGCTCCAAATACTGCAGAATTAAGGATTTGTCGTGTAAACAAGAATTGTGGA300 
AGTGTCAGAGGAGGAGATGAAATATTTCTACTTTGTGACAAAGTTCAGAAAGGTATTTAT360 
TTATTTCATTGAATTTAGAATAAATTTTAGATTAATAGATGCAGTTACTTTGTTTTCCCA420 
TTTTTTTTTTTTTGGTTTCTTATTGACTAGATGACATAGAAGTTCGTTTTGTGTTGAACG480 
ATTGGGAAGCAAAAGGCATCTTTTCACAAGCTGATGTACACCGTCAAGTAGCCATTGTTT540 
TCAAAACTCCACCATATTGCAAAGCTATCACAGAACCCGTAACAGTAAAAATGCAGTTGC600 
GGAGACCTTCTGACCAGGAAGTTAGTGAATCTATGGATTTTAGATATCTGCCAGATGAAA660 
AAGGTATGACATTTTGCTGGTAATAATTTATATATTTCTTGAAGTGGTCCTGCTAATAAC720 
ATCTTCTTGTAATATTCATTTGAGTACAGTTATGTATATTCATAATTTATGTTTCTTTTC780 
CTGGAAGCTT790 
(2) INFORMATION FOR SEQ ID NO:48: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2757 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: 
CTAGGCTTTTGCAAAAAGCTTCACGCTGCCGCAAGCACTCAGGGCGCAAGGGCTGCTAAA60 
GGAAGCGGAACACGTAGAAAGCCAGTCCGCAGAAACGGTGCTGACCCCGGATGAATGTCA120 
GCTACTGGGCTATCTGGACAAGGGAAAACGCAAGCGCAAAGAGAAAGCAGTTCCTGTGCC180 
TTAAGAACATTAGAACCTTCCTGTCCACCTGCTGTGAGAAGTTCGGCCTCAAGCGGAGCG240 
AGCTCTTCGAAGCCTTTGACCTCTTCGATGTGCAGGATTTTGGCAAGGTCATCTACACCC300 
TGTCTGCTCTGTCCTGGACCCCGATCGCCCAGAACAGGGGGATCATGCCCTTCCCCACCG360 
AGGAGGAGAGTGTAGGTGATGAAGACATCTACAGTGGCCTGTCCGACCAGATCGACGACA420 
CGGTGGAGGAGGATGAGGACCTGTATGACTGCGTGGAGAATGAGGAGGCGGAAGGCGACG480 
AGATCTATGAGGACCTCATGCGCTCGGAGCCCGTGTCCATGCCGCCCAAGATGACAGAGT540 
ATGACAAGCGCTGCTGCTGCCTGCGGGAGATCCAGCAGACGGAGGAGAAGTACACTGACA600 
CGCTGGGCTCCATCCAGCAGCATTTCTTGAAGCCCCTGCAACGGTTCCTGAAACCTCAAG660 
ACATTGAGATCATCTTTATCAACATTGAGGACCTGCTTCGTGTTCATACTCACTTCCTAA720 
AGGAGATGAAGGAAGCCCTGGGCACCCCTGGCGCACCGAATCTCTACCAGGTCTTCATCA780 
AATACAAGGAGAGGTTCCTCGTCTATGGCCGCTACTGCAGCCAGGTGGAGTCAGCCAGCA840 
AACACCTGGACCGTGTGGCCGCAGCCCGGGAGGACGTGCAGATGAAGCTGGAGGAATGTT900 
CTCAGAGAGCCAACAACGGGAGGTTCACTGCGCGACCTGCTGATGGTGCCTATGCAGCGA960 
GTTCTCAAATATCACCTCCTTCTCCAGGAGCTGGTGAAACACACGCAGGAGGCGATGGAG1020 
CAAGGAAACTGCGGCTGGCCCTGGATGCCATGAGGGACCTGGCTCAGTGCGTGAACGAGG1080 
TCAAGCGAGACAACGAGACACTGCGACAGATCACCAATTTCCAGCTGTCCATTGAGAACC1140 
TGGACCAGTCTCTGGCTCACTATGGCCGGCCCAAGATCGACGGGGAACTCAAGATCACCT1200 
CGGTGGAACGGCGCTCCAAGATGGACAGGTATGCCTTCCTGCTCGACAAAGCTCTACTCA1260 
TCTGTAAGCGCAGGGGAGACTCCTATGACCTCAAGGACTTTGTAAACCTGCACAGCTTCC1320 
AGGTTCGGGATGACTCTTCAGGAGACCGAGACAACAAGAAGTGGAGCCACATGTTCCTCC1380 
TGATCGAGGACCAAGGTGCCCAGGGCTATGAGCTGTTCTTCAAGACAAGAGAATTGAAGA1440 
AGAAGTGGATGGAGCAGTTTGAGATGGCCATCTCCAACATCTATCCGGAGAATGCCACCG1500 
CCAACGGGCATGACTTCCAGATGTTCTCCTTTGAGGAGACCACATCCTGCAAGGCCTGTC1560 
AGATGCTGCTTAGAGGTACCTTCTATCAGGGCTACCGCTGCCATCGGTGCCGGGCATCTG1620 
CACACAAGGAGTGTCTGGGGAGGGTCCCTCCATGTGGCCGACATGGGCAAGATTTCCCAG1680 
GAACTATGAAGAAGGACAAACTACATCGCAGGGCTCAGGACAAAAAGAGGAATGAGCTGG1740 
GTCTGCCCAAGATGGAGGTGTTTCAGGAATACTACGGGCTTCCTCCACCCCCTGGAGCCA1800 
TTGGACCCTTTCTACGGCTCAACCCTGGAGACATTGTGGAGCTCACGAAGGCTGAGGCTG1860 
AACAGAACTGGTGGGAGGGCAGAAATACATCTACTAATGAAATTGGCTGGTTTCCTTGTA1920 
ACAGGGTGAAGCCCTATGTCCATGGCCCTCCTCAGGACCTGTCTGTTCATCTCTGGTACG1980 
CAGGCCCCATGGAGCGGGCAGGGGCAGAGAGCATCCTGGCCAACCGCTCGGACGGGACTT2040 
TCTTGGTGCGGCAGAGGGTGAAGGATGCAGCAGAATTTGCCATCAGCATTAAATATAACG2100 
TCGAGGTCAAGCACACGGTTAAAATCATGACAGCAGAAGGACTGTACCGGATCACAGAGA2160 
AAAAGGCTTTCCGGGGGCTTACGGAGCTGGTGGAGTTTTACCAGCAGAACTCTCTAAAGG2220 
ATTGCTTCAAGTCTCTGGACACCACCTTGCAGTTCCCCTTCAAGGAGCCTGAAAAGAGAA2280 
CCATCAGCAGGCCAGCAGTGGGAAGCACAAAGTATTTTGGCACAGCCAAAGCCCGCTATG2340 
ACTTCTGCGCCCGTGACCGTTCAGAGCTGTCGCTCAAGGAGGGTGACATCATCAAGATCC2400 
TTAACAAGAAGGGACAGCAAGGCTGGTGGCGAGGGGAGATCTATGGCCGGGTTGGCTGGT2460 
TCCCTGCCAACTACGTGGAGGAAGATTATTCTGAATACTGCTGAGCCCTGGTGCCTTGGC2520 
AGAGAGACGAGAAACTCCAGGCTCTGAGCCCGGCGTGGCGAGGCAGCGGACCAGGGGCTG2580 
TGACAGCTCCGGCGGGTGGAGACTTTGGGATGGACTGGAGGAGGCCAGCGTCCAGCTGGC2640 
GGTGCTCCCGGGATGTGCCCTGACATGGTTAATTTATAACACCCCGATTTTCCTCTTGGG2700 
TCCCCTCAAGCAGACGGGGGCTCAAGGGGGTTACATTTAATAAAAGGATGAAGATGG2757 
(2) INFORMATION FOR SEQ ID NO:49: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 4175 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: 
TCCTCGTCGTCTGTGGATTGCTAAACCTGAGTGGGAAGGGGGGGGAAAAAAAAAAGGGTG60 
GGTTGTTGTTTTGTTTAAAAAAAGAAAAAATCCCTTAAGTGGATTTGTACCAGCGTGGAA120 
GATAACTGGGGATTTTTGTTGTTTGTTTTGGGAATAGAAACTAAAAAATGGAGACTGTAA180 
GTAGAAGCAGCTTCCAGCCTCATCCAGGACTGCAGAAGACCTTGGAACAGTTTCATCTGA240 
GCTCTATGAGCTCCCTGGGTGGCCCTGCTGCTTTCTCAGCGCGATGGGCACAGGAGATGT300 
ACAAGAAAGACAATGGCAAAGACCCAGCGGAACCTGTACTGCATCTGCCCCCTATCCAGC360 
CCCCCCCGGTGATGCCTGGTCCCTTCTTCATGCCCTCGGACAGATCCACTGAGAGGTGCG420 
AGACCATCCTGGAAGGGGAAACCATCTCCTGCTTCGTGGTGGGTGGGGAAAAGCGCCTTT480 
GCTTGCCCCAGATCCTGAACTCGGTGCTCAGGGACTTCTCCCTGCAGCAGATCAATTCGG540 
TGTGCGATGAGCTACACATTTACTGCTCCAGATGCACCGCTGACCAGCTGGAGATCCTCA600 
AAGTCATGGGCATCTTGCCCTTCTCTGCCCCCTCCTGCGGGCTGATCACTAAAACTGATG660 
CTGAGAGGCTTTGCAATGCCTTGCTTTATGGTGGCACCTATCCTCCCCACTGCAAGAAGG720 
AATTCTCTAGCACGATTGAGCTGGAGCTTACAGAGAAGAGCTTCAAGGTGTACCACGAGT780 
GCTTTGGGAAGTGTAAGGGACTCCTGGTACCAGAGCTTTACAGTAACCCCAGCGCAGCCT840 
GCATCCAGTGCTTGGACTGCAGGCTCATGTACCCGCCTCACAAATTTGTGGTCCACTCTC900 
ACAAATCCCTGGAAAACAGGACTTGCCACTGGGGCTTTGACTCTGCAAACTGGAGGTCCT960 
ACATCCTCCTTAGCCAGGATTACACTGGGAAAGAGGAGAAAGCTAGGCTGGGCCAGCTCT1020 
TAGATGAAATGAAAGAAAAATTTGACTATAACAACAAATACAAGAGGAAAGCCCCCAGGA1080 
ACCGTGAGTCTCCTAGAGTTCAGCTCCGCCGGACCAAAATGTTCAAGACAATGCTGTGGG1140 
ATCCAGCTGGAGGTTCAGCGGTACTGCAGCGTCAGCCAGATGGAAATGAGGTCCCTTCAG1200 
ATCCTCCTGCTTCCAAGAAAACCAAAATAGACGACTCCGCTTCCCAATCTCCAGCTTCTA1260 
CTGAGAAGGAAAAGCAGTCCAGTTGGTTACGGTCCTTATCCAGTTCATCTAATAAGAGCA1320 
TTGGCTGTGTCCATCCCCGTCAGCGTCTCTCAGCTTTCCGGCCCTGGTCCCCTGCTGTAT1380 
CAGCAAATGAGAAAGAGCTCTCAACCCATCTTCCTGCATTGATCCGAGACAGCAGTTTTT1440 
ACTCCTACAAAAGCTTTGAGAATGCTGTGGCCCCCAACGTGGCACTCGCACCTCCTGCCC1500 
AACAGAAAGTTGTGAGCAACCCACCCTGTGCCACAGTGGTGTCCCGGAGCAGCGAACCGC1560 
CGAGCAGCGCTGCGCAGCCACGGAAAAGAAAACATGCTGCAGAAACCCCGGCTGTCCCAG1620 
AGCCAGTGGCCACGGTTACTGCCCCTGAAGAGGATAAGGAATCAGAAGCAGAAATTGAAG1680 
TAGAGACCAGGGAGGAATTCACCTCCTCCTTATCCTCGCTCTCCTCCCCATCCTTTACTT1740 
CATCCAGCTCTGCAAAGGACATGAGCTCACCTGGGATGCAAGCCCCAGTCCCAGTCAACA1800 
GTTCATATGAGGTTGCAGCACATTCTGACTCTCACAGCAGTGGGTTGGAAGCTGAGCTGG1860 
AGCACCTAAGGCAGGCCCTGGACAGTGGCCTAGATACAAAAGAAGCCAAAGAAAAATTCC1920 
TCCATGAAGTTGTTAAAATGAGAGTGAAGCAGGAAGAGAAGCTAAATGCTGCCTTGCAAG1980 
CCAAACGCAGCCTACATCAGGAGCTGGAGTTCCTCAGAGTGGCAAAGAAGGAGAAACTGA2040 
GAGAAGCAACGGAGGCAAAACGCAACTTAAGGAAAGAGATTGAGCGTCTGAGAGCTGAGA2100 
ATGAGAAGAAAATGAAGGAAGCAAACGAGTCTCGGATACGGCTAAAGAGGGAACTGGAAC2160 
AAGCCAGGCAGATCCGGGTTTGCGACAAGGGTTGTGAAGCTGGCAGGCTTCGGGCCAAGT2220 
ACTCTGCCCAGATTGAGGACCTACAGGTTAAGCTTCAGCATGCAGAGGCTGACAGGGAGC2280 
AGCTCCGAGCTGACCTGATGCATGAGAGGGAGGCTCGAGAACACTTGGAAAAAGTAGTCA2340 
AGGAACTTCAGGAACAGCTGTGGCCTAAATCAAGCAGTCAATCCAGCAGTGAAAACACAA2400 
CGAGCAACATGGAGAATTAAACCACGTCGTCTAATACAACAGAATGACATATATGCACAG2460 
TAAGGGAGGATGGGTGGGGTACGTGTGTAAGTGCATGTGTGAGTAGTTGTGTCTTAACAC2520 
ACAGATCTAGGAATATGGATTCTTATTAGTTGGAAGGCAAATGTTACTCTTTATAACAGA2580 
AGCACTGAATTACGCCTCTTTTTTTTTCCAATCCATATAGCACAACATCTTACTGTGCCT2640 
ATAAAACACAAATGTGTTTATAAACAAAATACTTTTAAGTCCACAGCAAATTTTCTACTG2700 
GCAAACTCCAAGCAAGCAGCATCCTCCAACTAGAATCAGAGTAAAAGGCAAGCATGGCAG2760 
TGTTTTCATGTTGCCCTTCTGCCTGTCGGAACATTTTGGAATTTAAAAACAAACTTTTCT2820 
TATAAGCTATTTAAAGTAATTCATTACACAGACTTGGTATTAAAAAAAATTAACAAGATT2880 
TTTTATAACGAACCTTTAAAAGCAAAACAAAAACCTTCGATGCACAATTTTTACGACTTG2940 
TTAAAGGCTTTGGGATTCTTACTGCAGAAGCCCTTTGGTGATGATGCCATTTCATTAGCA3000 
GTTTTTTTTAATCCTGTCCTGTGGTTGTATGAGAATTTCAGAGTGCTTTTCAAAGTTGAT3060 
TTTTTTCCTTAGAAACAATCACCTTCATTTCCTGTCCTGAACACAAGAAGAAAGGAAGAT3120 
GCAGGACTGTAAGGGCGTGGGGGAGGGCAGGAAGAGAAGATGGACGCTTTGGAATTATAA3180 
ACCCAGCCTTACAGACTTCAGTGTTTCAAATCACGCCATGTTTTCTAAAGACGTCTTCAT3240 
TAATCGATGTGTTCAAAAGACTCACTTCATCCAAGAGCACTTCAGCTTTAGGAAAAGAAA3300 
GAAGGAAGTAAAGGAAGGAAATGGATGACCTGTTAAGTTGGTTGAGAAATAAAGCAGAAG3360 
ATGTGTTTTGAAGTCATTCTGAAATCTTCGCGTCAGCTTTCAGTTCTCTGGAAAACTCAT3420 
CTTTGTTGCACCATCTTACCATAGAATTCAGTATTTACCTACTTCTATTCTGAACTGTTT3480 
GTCAGGATTTCTGTGCCCAAGGAGAGTGCAACACCGCATTATTGGATACTACAGAAAAGA3540 
AAAACCACGTTTTTGCTGCTGTGAATAAGCCTACATCTTTTTTAAAAGAAAAACTTCTGT3600 
TTTTAAGAATAGAAATTACTTTAATTTTGGGATCCGAGCCGCAGCCCTGGAATAGAAATG3660 
CAGCCTACCATCACTCTGTCTTACTACCATTGTTAGCGTCGTCGTTCATTTTTTTTTAAA3720 
CTGCACTTTGTCAGAACCTCACTCTGCATTTTATTCCATATTTTGGAAGTTTACAAGTTC3780 
AGCATTCTCGATTCTGCTCTGCAGATGTTAAAATCATCACCACCATTTTCCACCACGCGA3840 
CACCTCGGCCGTCATTTCCATGTATGCAAAAGAAGAACTCAGTGGGTACAGAATGCTACC3900 
AAATACAAAGGCAGCAGAGCAGCGTGCTGCTGGTTGGGTTTCACAGCTGCGCTGCACGGC3960 
TGTGGCTGTCGAGGCTGGGAAGTGCTCAAATACAGTTGGTGCTTTACTGAATGAGAGAGG4020 
AGTTATTTTCACCCACACACACTCACCTCTGATACACTCAAGCTCAGTGAAAAGTTGATC4080 
TGGGGCTGCAGTTGTGCCTTCCAGCTCATTTTTCCTCTCAGCATCTTCTATAGGCAATGC4140 
TGACACTTTTTTTTTAAACCTTAAAGAATAAAAAG4175 
(2) INFORMATION FOR SEQ ID NO:50: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 1364 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: 
AAAATCAGGAACTTGTGCTGGCCCTGCAATGTCAAGGGAGGGGGCTCACCCAGGGCTCCT60 
GTAGCTCAGGGGGCAGGCCTGAGCCCTGCACCCGCCCCACGACCGTCCAGCCCCTGACGG120 
GCACCCCATCCTGAGGGGCTCTGCATTGGCCCCCACCGAGGCAGGGGATCTGACCGACTC180 
GGAGCCCGGCTGGATGTTACAGGCGTGCAAAATGGAAGGGTTTCCCCTCGTCCCCCCTCC240 
ATCAGAAGACCTGGTGCCCTATGACACGGATCTATACCAACGCCAAACGCACGAGTATTA300 
CCCCTATCTCAGCAGTGATGGGGAGAGCCATAGCGACCATTACTGGGACTTCCACCCCCA360 
CCACGTGCACAGCGAGTTCGAGAGCTTCGCCGAGAACAACTTCACGGAGCTCCAGAGCGT420 
GCAGCCCCCGCAGCTGCAGCAGCTCTACCGCCACATGGAGCTGGAGCAGATGCACGTCCT480 
CGATACCCCCATGGTGCCACCCCATCCCAGTCTTGGCCACCAGGTCTCCTACCTGCCCCG540 
GATGTGCCTCCAGTACCCATCCCTGTCCCCAGCCCAGCCCAGCTCAGATGAGGAGGAGGG600 
CGAGCGGCAGAGCCCCCCACTGGAGGTGTCTGACGGCGAGGCGGATGGCCTGGAGCCCGG660 
GCCTGGGCTCCTGCCTGGGGAGACAGGCAGCAAGAAGAAGATCCGCCTGTACCAGTTCCT720 
GTTGGACCTGCTCCGCAGCGGCGACATGAAGGACAGCATCTGGTGGGTGGACAAGGACAA780 
GGGCACCTTCCAGTTCTCGTCCAAGCACAAGGAGGCGCTGGCGCACCGCTGGGGCATCCA840 
GAAGGGCAACCGCAAGAAGATGACCTACCAGAAGATGGCGCGCGCGCTGCGCAACTACGG900 
CAAGACGGGCGAGGTCAAGAAGGTGAAGAAGAAGCTCACCTACCAGTTCAGCGGCGAAGT960 
GCTGGGCCGCGGGGGCCTGGCCGAGCGGCGCCACCCGCCCCACTGAGCCCGCAGCCCCCG1020 
CCGGCCCCGCCAGGCCTCCCCGCTGGCCATAGCATTAAGCCCTCGCCCGGCCCGGACACA1080 
GGGAGGACGCTCCCGGGGCCCAGAGGCAGGACTGTGGCGGGCCGGGCTCCGTCACCCGCC1140 
CCTCCCCCCACTCCAGGCCCCCTCCACATCCCGCTTCGCCTCCCTCCAGGACTCCACCCC1200 
GGCTCCCGACGCCAGCTGGGCGTCAGACCCACCGGCAACCTTGCAGAGGACGACCCGGGG1260 
TACTGCCTTGGGAGTCTCAAGTCCGTATGTAAATCAGATCTCCCCTCTCACCCCTCCCAC1320 
CCATTAACCTCCTCCCAAAAAACAAGTAAAGTTATTCTCAATCC1364 
(2) INFORMATION FOR SEQ ID NO:51: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 1325 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: 
GCAGTAGCAGCGAGCAGCAGAGTCCGCACGCTCCGGCGAGGGGCAGAAGAGCGCGAGGGA60 
GCGCGGGGCAGCAGAAGCGAGAGCCGAGCGCGGACCCAGCCAGGACCCACAGCCCTCCCC120 
AGCTGCCCAGGAAGAGCCCCAGCCATGGAACACCAGCTCCTGTGCTGCGAAGTGGAAACC180 
ATCCGCCGCGCGTACCCCGATGCCAACCTCCTCAACGACCGGGTGCTGCGGGCCATGCTG240 
AAGGCGGAGGAGACCTGCGCGCCCTCGGTGTCCTACTTCAAATGTGTGCAGAAGGAGGTC300 
CTGCCGTCCATGCGGAAGATCGTCGCCACCTGGATGCTGGAGGTCTGCGAGGAACAGAAG360 
TGCGAGGAGGAGGTCTTCCCGCTGGCCATGAACTACCTGGACCGCTTCCTGTCGCTGGAG420 
CCCGTGAAAAAGAGCCGCCTGCAGCTGCTGGGGGCCACTTGCATGTTCGTGGCCTCTAAG480 
ATGAAGGAGACCATCCCCCTGACGGCCGAGAAGCTGTGCATCTACACCGACGGCTCCATC540 
CGGCCCGAGGAGCTGCTGCAAATGGAGCTGCTCCTGGTGAACAAGCTCAAGTGGAACCTG600 
GCCGCAATGACCCCGCACGATTTCATTGAACACTTCCTCTCCAAAATGCCAGAGGCGGAG660 
GAGAACAAACAGATCATCCGCAAACACGCGCAGACCTTCGTTGCCTCTTGTGCCACAGAT720 
GTGAAGTTCATTTCCAATCCGCCCTCCATGGTGGCAGCGGGGAGCGTGGTGGCCGCAGTG780 
CAAGGCCTGAACCTGAGGAGCCCCAACAACTTCCTGTCCTACTACCGCCTCACACGCTTC840 
CTCTCCAGAGTGATCAAGTGTGACCCAGACTGCCTCCGGGCCTGCCAGGAGCAGATCGAA900 
GCCCTGCTGGAGTCAAGCCTGCGCCAGGCCCAGCAGAACATGGACCCCAAGGCCGCCGAG960 
GAGGAGGAAGAGGAGGAGGAGGAGGTGGACCTGGCTTGCACACCCACCGACGTGCGGGAC1020 
GTGGACATCTGAGGGGCCCAGGCAGGCGGGCGCCACCGCCACCCGCAGCGAGGGCGGAGC1080 
CGGCCCCAGGTGCTCCACATGACAGTCCCTCCTCTCCGGAGCATTTTGATACCAGAAGGG1140 
AAAGCTTCATTCTCCTTGTTGTTGGTTGTTTTTTCCTTTGCTCTTTCCCCCTTCCATCTC1200 
TGACTTAAGCAAAAGAAAAAGATTACCCAAAAACTGTCTTTAAAAGAGAGAGAGAGAAAA1260 
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA1320 
AAAAA1325 
(2) INFORMATION FOR SEQ ID NO:52: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 3036 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: 
CTCCCCTTCAGCTTCTCTTCACGCACTCCAAGATCTAAACCGAGAATCGAAACTAAGCTG60 
GGGTCCATGGAGCCTGCACCCGCCCGATCTCCGAGGCCCCAGCAGGACCCCGCCCGGCCC120 
CAGGAGCCCACCATGCCTCCCCCCGAGACCCCCTCTGAAGGCCGCCAGCCCAGCCCCAGC180 
CCCAGCCCTACAGAGCGAGCCCCCGCTTCGGAGGAGGAGTTCCAGTTTCTGCGCTGCCAG240 
CAATGCCAGGCGGAAGCCAAGTGCCCGAAGCTGCTGCCTTGTCTGCACACGCTGTGCTCA300 
GGATGCCTGGAGGCGTCGGGCATGCAGTGCCCCATCTGCCAGGCGCCCTGGCCCCTAGGT360 
GCAGACACACCCGCCCTGGATAACGTCTTTTTCGAGAGTCTGCAGCGGCGCCTGTCGGTG420 
TACCGGCAGATTGTGGATGCGCAGGCTGTGTGCACCCGCTGCAAAGAGTCGGCCGACTTC480 
TGGTGCTTTGAGTGCGAGCAGCTCCTCTGCGCCAAGTGCTTCGAGGCACACCAGTGGTTC540 
CTCAAGCACGAGGCCCGGCCCCTAGCAGAGCTGCGCAACCAGTCGGTGCGTGAGTTCCTG600 
GACGGCACCCGCAAGACCAACAACATCTTCTGCTCCAACCCCAACCACCGCACCCCTACG660 
CTGACCAGCATCTACTGCCGAGGATGTTCCAAGCCGCTGTGCTGCTCGTGCGCGCTCCTT720 
GACAGCAGCCACAGTGAGCTCAAGTGCGACATCAGCGCAGAGATCCAGCAGCGACAGGAG780 
GAGCTGGACGCCATGACGCAGGCGCTGCAGGAGCAGGATAGTGCCTTTGGCGCGGTTCAC840 
GCGCAGATGCACGCGGCCGTCGGCCAGCTGGGCCGCGCGCGTGCCGAGACCGAGGAGCTG900 
ATCCGCGAGCGCGTGCGCCAGGTGGTAGCTCACGTGCGGGCTCAGGAGCGCGAGCTGCTG960 
GAGGCTGTGGACGCGCGGTACCAGCGCGACTACGAGGAGATGGCCAGTCGGCTGGGCCGC1020 
CTGGATGCTGTGCTGCAGCGCATCCGCACGGGCAGCGCGCTGGTGCAGAGGATGAAGTGC1080 
TACGCCTCGGACCAGGAGGTGCTGGACATGCACGGTTTCCTGCGCCAGGCGCTCTGCCGC1140 
CTGCGCCAGGAGGAGCCCCAGAGCCTGCAAGCTGCCGTGCGCACCGATGGCTTCGACGAG1200 
TTCAAGGTGCGCCTGCAGGACCTCAGCTCTTGCATCACCCAGGGGAAAGCCATTGAGACC1260 
CAGAGCAGCAGTTCTGAAGAGATAGTGCCCAGCCCTCCCTCGCCACCCCCTCTACCCCGC1320 
ATCTACAAGCCTTGCTTTGTCTGTCAGGACAAGTCCTCAGGCTACCACTATGGGGTCAGC1380 
GCCTGTGAGGGCTGCAAGGGCTTCTTCCGCCGCAGCATCCAGAAGAACATGGTGTACACG1440 
TGTCACCGGGACAAGAACTGCATCATCAACAAGGTGACCCGGAACCGCTGCCAGTACTGC1500 
CGACTGCAGAAGTGCTTTGAAGTGGGCATGTCCAAGGAGTCTGTGAGAAACGACCGAAAC1560 
AAGAAGAAGAAGGAGGTGCCCAAGCCCGAGTGCTCTGAGAGCTACACGCTGACGCCGGAG1620 
GTGGGGGAGCTCATTGAGAAGGTGCGCAAAGCGCACCAGGAAACCTTCCCTGCCCTCTGC1680 
CAGCTGGGCAAATACACTACGAACAACAGCTCAGAACAACGTGTCTCTCTGGACATTGAC1740 
CTCTGGGACAAGTTCAGTGAACTCTCCACCAAGTGCATCATTAAGACTGTGGAGTTCGCC1800 
AAGCAGCTGCCCGGCTTCACCACCCTCACCATCGCCGACCAGATCACCCTCCTCAAGGCT1860 
GCCTGCCTGGACATCCTGATCCTGCGGATCTGCACGCGGTACACGCCCGAGCAGGACACC1920 
ATGACCTTCTCGGACGGGCTGACCCTGAACCGGACCCAGATGCACAACGCTGGCTTCGGC1980 
CCCCTCACCGACCTGGTCTTTGCCTTCGCCAACCAGCTGCTGCCCCTGGAGATGGATGAT2040 
GCGGAGACGGGGCTGCTCAGCGCCATCTGCCTCATCTGCGGAGACCGCCAGGACCTGGAG2100 
CAGCCGGACCGGGTGGACATGCTGCAGGAGCCGCTGCTGGAGGCGCTAAAGGTCTACGTG2160 
CGGAAGCGGAGGCCCAGCCGCCCCCACATGTTCCCCAAGATGCTAATGAAGATTACTGAC2220 
CTGCGAAGCATCAGCGCCAAGGGGGCTGAGCGGGTGATCACGCTGAAGATGGAGATCCCG2280 
GGCTCCATGCCGCCTCTCATCCAGGAAATGTTGGAGAACTCAGAGGGCCTGGACACTCTG2340 
AGCGGACAGCCGGGGGGTGGGGGGCGGGACGGGGGTGGCCTGGCCCCCCCGCCAGGCAGC2400 
TGTAGCCCCAGCCTCAGCCCCAGCTCCAACAGAAGCAGCCCGGCCACCCACTCCCCGTGA2460 
CCGCCCACGCCACATGGACACAGCCCTCGCCCTCCGCCCCGGCTTTTCTCTGCCTTTCTA2520 
CCGACCATGTGACCCCGCACCAGCCCTGCCCCCACCTGCCCTCCCGGGCAGTACTGGGGA2580 
CCTTCCCTGGGGGACGGGGAGGGAGGAGGCAGCGACTCCTTGGACAGAGGCCTGGGCCCT2640 
CAGTGGACTGCCTGCTCCCACAGCCTGGGCTGACGTCAGAGGCCGAGGCCAGGAACTGAG2700 
TGAGGCCCCTGGTCCTGGGTCTCAGGATGGGTCCTGGGGGCCTCGTGTTCATCAAGACAC2760 
CCCTCTGCCCAGCTCACCACATCTTCATCACCAGCAAACGCCAGGACTTGGCTCCCCCAT2820 
CCTCAGAACTCACAAGCCATTGCTCCCCAGCTGGGGAACCTCAACCTCCCCCCTGCCTCG2880 
GTTGGTGACAGAGGGGGTGGGACAGGGGCGGGGGGTTCCCCCTGTACATACCCTGCCATA2940 
CCAACCCCAGGTATTAATTCTCGCTGGTTTTGTTTTTATTTTAATTTTTTTGTTTTGATT3000 
TTTTTAATAAGAATTTTCATTTTAAGCAAAAAAAAA3036 
(2) INFORMATION FOR SEQ ID NO:53: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 4287 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: 
CATAGAGCCAGCGGGCGCGGGCGGGACGGGCGCCCCGCGGCCGGACCCAGCCAGGGCACC60 
ACGCTGCCCGGCCCTGCGCCGCCAGGCACTTCTTTCCGGGGCTCCTAGGGACGCCAGAAG120 
GAAGTCAACCTCTGCTGCTTCTCCTTGGCCTGCGTTGGACCTTCCTTTTTTTGTTGTTTT180 
TTTTTGTTTTTCCCCTTTCTTCCTTTTGAATTAACTGGCTTCTTGGCTGGATGTTTTCAA240 
CTTCTTTCCTGGCTGCGAACTTTTCCCCAATTGTTTTCCTTTTACAACAGGGGGAGAAAG300 
TGCTCTGTGGTCCGAGGCGAGCCGTGAAGTTGCGTGTGCGTGGCAGTGTGCGTGGCAGGA360 
TGTGCGTGCGTGTGTAACCCGAGCCGCCCGATCTGTTTCGATCTGCGCCGCGGAGCCCTC420 
CCTCAAGGCCCGCTCCACCTGCTGCGGTTACGCGGCGCTCGTGGGTGTTCGTGCCTCGGA480 
GCAGCTAACCGGCGGGTGCTGGGCGACGGTGGAGGAGTATCGTCTCGCTGCTGCCCGAGT540 
CAGGGCTGAGTCACCCAGCTGATGTAGACAGTGGCTGCCTTCCGAAGAGTGCGTGTTTGC600 
ATGTGTGTGACTCTGCGGCTGCTCAACTCCCAACAAACCAGAGGACCAGCCACAAACTTA660 
ACCAACATCCCCAAACCCGAGTTCACAGATGTGGGAGAGCTGTAGAACCCTGAGTGTCAT720 
CGACTGGGCCTTCTTATGATTGTTGTTTTAAGATTAGCTGAAGATCTCTGAAACGCTGAA780 
TTTTCTGCACTGAGCGTTTTGACAGAATTCATTGAGAGAACAGAGAACATGACAAGTACT840 
TCTAGCTCAGCACTGCTCCAACTACTGAAGCTGATTTTCAAGGCTACTTAAAAAAATCTG900 
CAGCGTACATTAATGGATTTCTGTTGTGTTTAAATTCTCCACAGATTGTATTGTAAATAT960 
TTTATGAAGTAGAGCATATGTATATATTTATATATACGTGCACATACATTAGTAGCACTA1020 
CCTTTGGAAGTCTCAGCTCTTGCTTTTCGGGACTGAAGCCAGTTTTGCATGATAAAAGTG1080 
GCCTTGTTACGGGAGATAATTGTGTTCTGTTGGGACTTTAGACAAAACTCACCTGCAAAA1140 
AACTGACAGGCATTAACTACTGGAACTTCCAAATAATGTGTTTGCTGATCGTTTTACTCT1200 
TCGCATAAATATTTTAGGAAGTGTATGAGAATTTTGCCTTCAGGAACTTTTCTAACAGCC1260 
AAAGACAGAACTTAACCTCTGCAAGCAAGATTCGTGGAAGATAGTCTCCACTTTTTAATG1320 
CACTAAGCAATCGGTTGCTAGGAGCCCATCCTGGGTCAGAGGCCGATCCGCAGAACCAGA1380 
ACGTTTTCCCCTCCTGGACTGTTAGTAACTTAGTCTCCCTCCTCCCCTAACCACCCCCGC1440 
CCCCCCCCACCCCCCGCAGTAATAAAGGCCCCTGAACGTGTATGTTGGTCTCCCGGGAGC1500 
TGCTTGCTGAAGATCCGCGCCCCTGTCGCCGTCTGGTAGGAGCTGTTTGCAGGGTCCTAA1560 
CTCAATCGGCTTGTTGTGATGCGTATCCCCGTAGATGCCAGCACGAGCCGCCGCTTCACG1620 
CCGCCTTCCACCGCGCTGAGCCCAGGCAAGATGAGCGAGGCGTTGCCGCTGGGCGCCCCG1680 
GACGCCGGCGCTGCCCTGGCCGGCAAGCTGAGGAGCGGCGACCGCAGCATGGTGGAGGTG1740 
CTGGCCGACCACCCGGGCGAGCTGGTGCGCACCGACAGCCCCAACTTCCTCTGCTCCGTG1800 
CTGCCTACGCACTGGCGCTGCAACAAGACCCTGCCCATCGCTTTCAAGGTGGTGGCCCTA1860 
GGGGATGTTCCAGATGGCACTCTGGTCACTGTGATGGCTGGCAATGATGAAAACTACTCG1920 
GCTGAGCTGAGAAATGCTACCGCAGCCATGAAGAACCAGGTTGCAAGATTTAATGACCTC1980 
AGGTTTGTCGGTCGAAGTGGAAGAGGGAAAAGCTTCACTCTGACCATCACTGTCTTCACA2040 
AACCCACCGCAAGTCGCCACCTACCACAGAGCCATCAAAATCACAGTGGATGGGCCCCGA2100 
GAACCTCGAAATCGTACTGAGAAGCACTCCACAATGCCAGACTCACCTGTGGATGTGAAG2160 
ACGCAATCTAGGCTGACTCCTCCAACAATGCCACCTCCCCCAACTACTCAAGGAGCTCCA2220 
AGAACCAGTTCATTTACACCGACAACGTTAACTAATGGCACGAGCCATTCTCCTACAGCC2280 
TTGAATGGCGCCCCCTCACCACCCAATGGCTTCAGCAATGGGCCTTCCTCTTCTTCCTCC2340 
TCCTCTCTGGCTAATCAACAGCTGCCCCCAGCCTGTGGTGCCAGGCAACTCAGCAAGCTG2400 
AAAAGGTTCCTTACTACCCTGCAGCAGTTTGGCAATGACATTTCACCCGAGATAGGAGAA2460 
AGAGTTCGCACCCTCGTTCTGGGACTAGTGAACTCCACTTTGACAATTGAAGAATTTCAT2520 
TCCAAACTGCAAGAAGCTACTAACTTCCCACTGAGACCTTTTGTCATCCCATTTTTGAAG2580 
GCCAACTTGCCCCTGCTGCAGCGTGAGCTCCTCCACTGCGCAAGACTGGCCAAACAGAAC2640 
CCTGCCCAGTACCTCGCCCAGCATGAACAGCTGCTTCTGGATGCCAGCACCACCTCACCT2700 
GTTGACTCCTCAGAGCTGCTTCTCGATGTGAACGAAAACGGGAAGAGGCGAACTCCAGAC2760 
AGAACCAAAGAAAATGGCTTTGACAGAGAGCCTTTGCACTCAGAACATCCAAGCAAGCGA2820 
CCATGCACTATTAGCCCAGGCCAGCGGTACAGTCCAAATAACGGCTTATCCTACCAGCCC2880 
AATGGCCTGCCTCACCCTACCCCACCTCCACCTCAGCATTACCGTTTGGATGATATGGCC2940 
ATTGCCCACCACTACAGGGACTCCTATCGACACCCCAGCCACAGGGACCTCAGGGACAGA3000 
AACAGACCTATGGGGTTGCATGGCACACGTCAAGAAGAAATGATTGATCACAGACTAACA3060 
GACAGAGAATGGGCAGAAGAGTGGAAACATCTTGACCATCTGTTAAACTGCATAATGGAC3120 
ATGGTAGAAAAAACAAGGCGATCTCTCACCGTACTAAGGCGGTGTCAAGAAGCAGACCGG3180 
GAAGAATTGAATTACTGGATCCGGCGGTACAGTGACGCCGAGGACTTAAAAAAAGGTGGC3240 
GGCAGTAGCAGCAGCCACTCTAGGCAGCAGAGTCCCGTCAACCCAGACCCAGTTGCACTA3300 
GACGCGCATCGGGAATTCCTTCACAGGCCTGCGTCTGGATACGTGCCAGAGGAGATCTGG3360 
AAGAAAGCTGAGGAGGCCGTCAATGAGGTGAAGCGCCAGGCGATGACGGAGCTGCAGAAG3420 
GCCGTGTCTGAGGCGGAGCGGAAAGCCCACGACATGATCACAACAGAGAGGGCCAAGATG3480 
GAGCGCACGGTCGCCGAGGCCAAACGGCAGGCGGCGGAGGACGCACTGGCAGTTATCAAT3540 
CAGCAGGAGGATTCAAGCGAGAGTTGCTGGAATTGTGGCCGTAAAGCGAGTGAAACCTGC3600 
AGTGGCTGTAACACAGCCCGATACTGTGGCTCATTTTGCCAGCACAAAGACTGGGAGAAG3660 
CACCATCACATCTGTGGACAGACCCTGCAGGCCCAGCAGCAGGGAGACACACCTGCAGTC3720 
AGCTCCTCTGTCACGCCCAACAGCGGGGCTGGGAGCCCGATGGACACACCACCAGCAGCC3780 
ACTCCGAGGTCAACCACCCCGGGAACCCCTTCCACCATAGAGACAACCCCTCGCTAGACG3840 
TGAACTCAGAACTGTCGGAGGAAAGACAACACAACCAACGCGAAACCAATTCCTCATCCT3900 
CAGATGCTCAAAGTTGTTTTTTTTGTTTGTTTGTTTATTAGATGAATTATCCTATTTCAG3960 
TACTTCAGCAAGAGAGAACCTAACTGTATCTTGAGGTGGTAGTAAAACACAGAGGGCCAG4020 
TAACGGGTCGTAATGACTTATTGTGGATAACAAAGATATCTTTTCTTTAGAGAACTGAAA4080 
AGAGAGCAGAGAATATAACATGAAATGATAGATTTGACCTCCTCCCTGTTATTTTCAAGT4140 
AGCTGGGATTTTAAACTAGATGACCTCATTAACCGATGCTTTACCAAACAGCAAACCAAG4200 
AGATTGCTAATTGCTGTTGAAAGCAAAAATGCTAATATTAAAAGTCACAATGTTCTTTAT4260 
ATACAATAATGGAAAAAAAAAAAAAAA4287 
(2) INFORMATION FOR SEQ ID NO:54: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 2952 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: 
ACGCGCCGCGTGCCCGGCCGCGCCCAGCAGGGTTTCCAGGCCTGAGGTGCCCGCCCTGGC60 
CCCAGGAGAATGAACCAGCCGCAGAGGATGGCGCCTGTGGGCACAGACAAGGAGCTCAGT120 
GACCTCCTGGACTTCAGCATGATGTTCCCGCTGCCTGTCACCAACGGGAAGGGCCGGCCC180 
GCCTCCCTGGCCGGGGCGCAGTTCGGAGGTTCAGGTCTTGAGGACCGGCCCAGCTCAGGC240 
TCCTGGGGCAGCGGCGACCAGAGCAGCTCCTCCTTTGACCCCAGCCGGACCTTCAGCGAG300 
GGCACCCACTTCACTGAGTCGCACAGCAGCCTCTCTTCATCCACATTCCTGGGACCGGGA360 
CTCGGAGGCAAGAGCGGTGAGCGGGGCGCCTATGCCTCCTTCGGGAGAGACGCAGGCGTG420 
GGCGGCCTGACTCAGGCTGGCTTCCTGTCAGGCGAGCTGGCCCTCAACAGCCCCGGGCCC480 
CTGTCCCCTTCGGGCATGAAGGGGACCTCCCAGTACTACCCCTCCTACTCCGGCAGCTCC540 
CGGCGGAGAGCGGCAGACGGCAGCCTAGACACGCAGCCCAAGAAGGTCCGGAAGGTCCCG600 
CCGGGTCTTCCATCCTCGGTGTACCCACCCAGCTCAGGTGAGGACTACGGCAGGGATGCC660 
ACCGCCTACCCGTCCGCCAAGACCCCCAGCAGCACCTATCCCGCCCCCTTCTACGTGGCA720 
GATGGCAGCCTGCACCCCTCAGCCGAGCTCTGGAGTCCCCCGGGCCAGGCGGGCTTCGGG780 
CCCATGCTGGGTGGGGGCTCATCCCCGCTGCCCCTCCCGCCCGGTAGCGGCCCGGTGGGC840 
AGCAGTGGAAGCAGCAGCACGTTTGGTGGCCTGCACCAGCACGAGCGTATGGGCTACCAG900 
CTGCATGGAGCAGAGGTGAACGGTGGGCTCCCATCTGCATCCTCCTTCTCCTCAGCCCCC960 
GGAGCCACGTACGGCGGCGTCTCCAGCCACACGCCGCCTGTCAGCGGGGCCGACAGCCTC1020 
CTGGGCTCCCGAGGGACCACAGCTGGCAGCTCCGGGGATGCCCTCGGCAAAGCACTGGCC1080 
TCGATCTACTCCCCGGATCACTCAAGCAATAACTTCTCGTCCAGCCCTTCTACCCCCGTG1140 
GGCTCCCCCCAGGGCCTGGCAGGAACGTCACAGTGGCCTCGAGCAGGAGCCCCCGGTGCC1200 
TTATCGCCCAGCTACGACGGGGGTCTCCACGGCCTGCAGAGTAAGATAGAAGACCACCTG1260 
GACGAGGCCATCCACGTGCTCCGCAGCCACGCCGTGGGCACAGCCGGCGACATGCACACG1320 
CTGCTGCCTGGCCACGGGGCGCTGGCCTCAGGTTTCACCGGCCCCATGTCACTGGGCGGG1380 
CGGCACGCAGGCCTGGTTGGAGGCAGCCACCCCGAGGACGGCCTCGCAGGCAGCACCAGC1440 
CTCATGCACAACCACGCGGCCCTCCCCAGCCAGCCAGGCACCCTCCCTGACCTGTCTCGG1500 
CCTCCCGACTCCTACAGTGGTTTTGAGTATCCGAGGAGCCCAGGAGGAGGAACCCACAGA1560 
CCCCCAGCTGATGCGGCTGGACAACATGCTGTTAGCGGAAGGCGTGGCGGGGCCTGAGAA1620 
GGGCGGAGGGTCGGCGGCAGCGGCGGCAGCGGCGGCGGCTTCTGGAGGGGCAGGTTCAGA1680 
CAACTCAGTGGAGCATTCAGATTACAGAGCCAAACTCTCACAGATCAGACAAATCTACCA1740 
TACGGAGCTGGAGAAATACGAGCAGGCCTGCAACGAGTTCACCACCCACGTGATGAATCT1800 
CCTGCGAGACGAAAGCCGGACCAGGCCCATCTCCCCAAAGGAGATTGAGCGGATGGTCAG1860 
CATCATCCACCGCAAGTTCAGCTCCATCCAGATGCAGCTCAAGCAGAGCACGTGCGAGGC1920 
GGTGATGATCCTGCGTTCCCGATTTCTGGATGCGCGGCGGAAGAGACGGAATTTCAACAA1980 
GCAAGCGACAGAAATCCTGAATGAATATTTCTATTCCCATCTCAGCAACCCTTACCCCAG2040 
TGAGGAAGCCAAAGAGGAGTTAGCCAAGAAGTGTGGCATCACAGTCTCCCAGGTATCAAA2100 
CTGGTTTGGAAATAAGCGAATCCGGTACAAGAAGAACATAGGTAAATTTCAAGAGGAAGC2160 
CAATATTTATGCTGCCAAAACAGCTGTCACTGCTACCAATGTGTCAGCCCATGGAAGCCA2220 
AGCTAACTCGCCCTCAACTCCCAACTCGGCTGGTTCTTCCAGTTCTTTTAACATGTCAAA2280 
CTCTGGAGATTTGTTCATGAGCGTGCAGTCACTCAATGGGGATTCTTACCAAGGGGCCCA2340 
GGTTGGAGCCAACGTGCAATCACAGGTGGATACCCTTCGCCATGTTATCAGCCAGACAGG2400 
AGGATACAGTGATGGACTCGCAGCCAGTCAGATGTACAGTCCGCAGGGCATCAGTGCTAA2460 
TGGAGGTTGGCAGGATGCTACTACCCCTTCATCAGTGACCTCCCCTACAGAAGGCCCTGG2520 
CAGTGTTCACTCTGATACCTCCAACTGATCTCCCAGCAATCGCATCCCGGCTGACCCTCT2580 
GCCCCAGTTGGGGCAGGGGCAGGAGGGAGGGTTTCTCTCCCAAAGCTGAAGCGGTCAGAC2640 
TGGAGGTCGAAGCAATCAGCAAACACAATAAGAGTCTCCTTCTCTTCTCTTCTTTGGGAT2700 
GCTATTTCAGCCAATCTGGACACTTCTTTATACTCTCTTCCCTTTTTTTTCTGGGTAGAA2760 
GCCACCCTTCCCTGCCTCCAGCTGTCAGCCTGGTTTTCGTCATCTTCCCTGCCCCTGTGC2820 
CTCTGTCCTAGACTTCCCGGGGTCCCCGCCCTCTCTCATATCACTGAAGGATATTTTCAA2880 
CAATTAGAGGAATTTAAAGAGGAAAAAAATTACAAAGAAAATAATAAAAGTGTTTGTACG2940 
TTTTCAAAAAAA2952 
(2) INFORMATION FOR SEQ ID NO:55: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 14255 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: 
GCGGCGGCGGCGGCGGGAAGCAGCGGGGCTGGGGTTCCAGGGGGAGCGGCCGCCGCCTCA60 
GCAGCCTCCTCGTCGTCCGCCTCGTCTTCGTCTTCGTCATCGTCCTCAGCCTCTTCAGGG120 
CCGGCCCTGCTCCGGGTGGGCCCGGGCTTCGACGCGGCGCTGCAGGTCTCGGCCGCCATC180 
GGCACCAACCTGCGCCGGTTCCGGGCCGTGTTTGGGGAGAGCGGCGGGGGAGGCGGCAGC240 
GGAGAGGATGAGCAATTCTTAGGTTTTGGCTCAGATGAAGAAGTCAGAGTGCGAAGTCCC300 
ACAAGGTCTCCTTCAGTTAAAACTAGTCCTCGAAAACCTCGTGGGAGACCTAGAAGTGGC360 
TCTGACCGAAATTCAGCTATCCTCTCAGATCCATCTGTGTTTTCCCCTCTAAATAAATCA420 
GAGACCAAATCTGGAGATAAGATCAAGAAGAAAGATTCTAAAAGTATAGAAAAGAAGAGA480 
GGAAGACCTCCCACCTTCCCTGGAGTAAAAATCAAAATAACACATGGAAAGGACATTTCA540 
GAGTTACCAAAGGGAAACAAAGAAGATAGCCTGAAAAAAATTAAAAGGACACCTTCTGCT600 
ACGTTTCAGCAAGCCACAAAGATTAAAAAATTAAGAGCAGGTAAACTCTCTCCTCTCAAG660 
TCTAAGTTTAAGACAGGGAAGCTTCAAATAGGAAGGAAGGGGGTACAAATTGTACGACGG720 
AGAGGAAGGCCTCCATCAACAGAAAGGATAAAGACCCCTTCGGGTCTCCTCATTAATTCT780 
GAACTGGAAAAGCCCCAGAAAGTCCGGAAAGACAAGGAAGGAACACCTCCACTTACAAAA840 
GAAGATAAGACAGTTGTCAGACAAAGCCCTCGAAGGATTAAGCCAGTTAGGATTATTCCT900 
TCTTCAAAAAGGACAGATGCAACCATTGCTAAGCAACTCTTACAGAGGGCAAAAAAGGGG960 
GCTCAAAAGAAAATTGAAAAAGAAGCAGCTCAGCTGCAGGGAAGAAAGGTGAAGACACAG1020 
GTCAAAAATATTCGACAGTTCATCATGCCTGTTGTCAGTGCTATCTCCTCGCGGATCATT1080 
AAGACCCCTCGGCGGTTTATAGAGGATGAGGATTATGACCCTCCAATTAAAATTGCCCGA1140 
TTAGAGTCTACACCGAATAGTAGATTCAGTGCCCCGTCCTGTGGATCTTCTGAAAAATCA1200 
AGTGCAGCTTCTCAGCACTCCTCTCAAATGTCTTCAGACTCCTCTCGATCTAGTAGCCCC1260 
AGTGTTGATACCTCCACAGACTCTCAGGCTTCTGAGGAGATTCAGGTACTTCCTGAGGAG1320 
CGGAGCGATACCCCTGAAGTTCATCCTCCACTGCCCATTTCCCAGTCCCCAGAAAATGAG1380 
AGTAATGATAGGAGAAGCAGAAGGTATTCAGTGTCGGAGAGAAGTTTTGGATCTAGAACG1440 
ACGAAAAAATTATCAACTCTACAAAGTGCCCCCCAGCAGGAGACCTCCTCGTCTCCACCT1500 
CCACCTCTGCTGACTCCACCGCCACCACTGCAGCCAGCCTCCAGTATCTCTGACCACACA1560 
CCTTGGCTTATGCCTCCAACAATCCCCTTAGCATCACCATTTTTGCCTGCTTCCACTGCT1620 
CCTATGCAAGGGAAGCGAAAATCTATTTTGCGAGAACCGACATTTAGGTGGACTTCTTTA1680 
AAGCATTCTAGGTCAGAGCCACAATACTTTTCCTCAGCAAAGTATGCCAAAGAAGGTCTT1740 
ATTCGCAAACCAATATTTGATAATTTCCGACCCCCTCCACTAACTCCCGAGGACGTTGGC1800 
TTTGCATCTGGTTTTTCTGCATCTGGTACCGCTGCTTCAGCCCGATTGTTTTCGCCACTC1860 
CATTCTGGAACAAGGTTTGATATGCACAAAAGGAGCCCTCTTCTGAGAGCTCCAAGATTT1920 
ACTCCAAGTGAGGCTCACTCTAGAATATTTGAGTCTGTAACCTTGCCTAGTAATCGAACT1980 
TCTGCTGGAACATCTTCTTCAGGAGTATCCAATAGAAAAAGGAAAAGAAAAGTGTTTAGT2040 
CCTATTCGATCTGAACCAAGATCTCCTTCTCACTCCATGAGGACAAGAAGTGGAAGGCTT2100 
AGTAGTTCTGAGCTCTCACCTCTCACCCCCCCGTCTTCTGTCTCTTCCTCGTTAAGCATT2160 
TCTGTTAGTCCTCTTGCCACTAGTGCCTTAAACCCAACTTTTACTTTTCCTTCTCATTCC2220 
CTGACTCAGTCTGGGGAATCTGCAGAGAAAAATCAGAGACCAAGGAAGCAGACTAGTGCT2280 
CCGGCAGAGCCATTTTCATCAAGTAGTCCTACTCCTCTCTTCCCTTGGTTTACCCCAGGC2340 
TCTCAGACTGAAAGAGGGAGAAATAAAGACAAGGCCCCCGAGGAGCTGTCCAAAGATCGA2400 
GATGCTGACAAGAGCGTGGAGAAGGACAAGAGTAGAGAGAGAGACCGGGAGAGAGAAAAG2460 
GAGAATAAGCGGGAGTCAAGGAAAGAGAAAAGGAAAAAGGGATCAGAAATTCAGAGTAGT2520 
TCTGCTTTGTATCCTGTGGGTAGGGTTTCCAAAGAGAAGGTTGTTGGTGAAGATGTTGCC2580 
ACTTCATCTTCTGCCAAAAAAGCAACAGGGCGGAAGAAGTCTTCATCACATGATTCTGGG2640 
ACTGATATTACTTCTGTGACTCTTGGGGATACAACAGCTGTCAAAACCAAAATACTTATA2700 
AAGAAAGGGAGAGGAAATCTGGAAAAAACCAACTTGGACCTCGGCCCAACTGCCCCATCC2760 
CTGGAGAAGGAGAAAACCCTCTGCCTTTCCACTCCTTCATCTAGCACTGTTAAACATTCC2820 
ACTTCCTCCATAGGCTCCATGTTGGCTCAGGCAGACAAGCTTCCAATGACTGACAAGAGG2880 
GTTGCCAGCCTCCTAAAAAAGGCCAAAGCTCAGCTCTGCAAGATTGAGAAGAGTAAGAGT2940 
CTTAAACAAACCGACCAGCCCAAAGCACAGGGTCAAGAAAGTGACTCATCAGAGACCTCT3000 
GTGCGAGGACCCCGGATTAAACATGTCTGCAGAAGAGCAGCTGTTGCCCTTGGCCGAAAA3060 
CGAGCTGTGTTTCCTGATGACATGCCCACCCTGAGTGCCTTACCATGGGAAGAACGAGAA3120 
AAGATTTTGTCTTCCATGGGGAATGATGACAAGTCATCAATTGCTGGCTCAGAAGATGCT3180 
GAACCTCTTGCTCCACCCATCAAACCAATTAAACCTGTCACTAGAAACAAGGCACCCCAG3240 
GAACCTCCAGTAAAGAAAGGACGTCGATCGAGGCGGTGTGGGCAGTGTCCCGGCTGCCAG3300 
GTGCCTGAGGACTGTGGTGTTTGTACTAATTGCTTAGATAAGCCCAAGTTTGGTGGTCGC3360 
AATATAAAGAAGCAGTGCTGCAAGATGAGAAAATGTCAGAATCTACAATGGATGCCTTCC3420 
AAAGCCTACCTGCAGAAGCAAGCTAAAGCTGTGAAAAAGAAAGAGAAAAAGTCTAAGACC3480 
AGTGAAAAGAAAGACAGCAAAGAGAGCAGTGTTGTGAAGAACGTGGTGGACTCTAGTCAG3540 
AAACCTACCCCATCAGCAAGAGAGGATCCTGCCCCAAAGAAAAGCAGTAGTGAGCCTCCT3600 
CCACGAAAGCCCGTCGAGGAAAAGAGTGAAGAAGGGAATGTCTCGGCCCCTGGGCCTGAA3660 
TCCAAACAGGCCACCACTCCAGCTTCCAGGAAGTCAAGCAAGCAGGTCTCCCAGCCAGCA3720 
CTGGTCATCCCGCCTCAGCCACCTACTACAGGACCGCCAAGAAAAGAAGTTCCCAAAACC3780 
ACTCCTAGTGAGCCCAAGAAAAAGCAGCCTCCACCACCAGAATCAGGTCCAGAGCAGAGC3840 
AAACAGAAAAAAGTGGCTCCCCGCCCAAGTATCCCTGTAAAACAAAAACCAAAAGAAAAG3900 
GAAAAACCACCTCCGGTCAATAAGCAGGAGAATGCAGGCACTTTGAACATCCTCAGCACT3960 
CTCTCCAATGGCAATAGTTCTAAGCAAAAAATTCCAGCAGATGGAGTCCACAGGATCAGA4020 
GTGGACTTTAAGGAGGATTGTGAAGCAGAAAATGTGTGGGAGATGGGAGGCTTAGGAATC4080 
TTGACTTCTGTTCCTATAACACCCAGGGTGGTTTGCTTTCTCTGTGCCAGTAGTGGGCAT4140 
GTAGAGTTTGTGTATTGCCAAGTCTGTTGTGAGCCCTTCCACAAGTTTTGTTTAGAGGAG4200 
AACGAGCGCCCTCTGGAGGACCAGCTGGAAAATTGGTGTTGTCGTCGTTGCAAATTCTGT4260 
CACGTTTGTGGAAGGCAACATCAGGCTACAAAGCAGCTGCTGGAGTGTAATAAGTGCCGA4320 
AACAGCTATCACCCTGAGTGCCTGGGACCAAACTACCCCACCAAACCCACAAAGAAGAAG4380 
AAAGTCTGGATCTGTACCAAGTGTGTTCGCTGTAAGAGCTGTGGATCCACAACTCCAGGC4440 
AAAGGGTGGGATGCACAGTGGTCTCATGATTTCTCACTGTGTCATGATTGCGCCAAGCTC4500 
TTTGCTAAAGGAAACTTCTGCCCTCTCTGTGACAAATGTTATGATGATGATGACTATGAG4560 
AGTAAGATGATGCAATGTGGAAAGTGTGATCGCTGGGTCCATTCCAAATGTGAGAATCTT4620 
TCAGGTACAGAAGATGAGATGTATGAGATTCTATCTAATCTGCCAGAAAGTGTGGCCTAC4680 
ACTTGTGTGAACTGTACTGAGCGGCACCCTGCAGAGTGGCGACTGGCCCTTGAAAAAGAG4740 
CTGCAGATTTCTCTGAAGCAAGTTCTGACAGCTTTGTTGAATTCTCGGACTACCAGCCAT4800 
TTGCTACGCTACCGGCAGGCTGCCAAGCCTCCAGACTTAAATCCCGAGACAGAGGAGAGT4860 
ATACCTTCCCGCAGCTCCCCCGAAGGACCTGATCCACCAGTTCTTACTGAGGTCAGCAAA4920 
CAGGATGATCAGCAGCCTTTAGATCTAGAAGGAGTCAAGAGGAAGATGGACCAAGGGAAT4980 
TACACATCTGTGTTGGAGTTCAGTGATGATATTGTGAAGATCATTCAAGCAGCCATTAAT5040 
TCAGATGGAGGACAGCCAGAAATTAAAAAAGCCAACAGCATGGTCAAGTCCTTCTTCATT5100 
CGGCAAATGGAACGTGTTTTTCCATGGTTCAGTGTCAAAAAGTCCAGGTTTTGGGAGCCA5160 
AATAAAGTATCAAGCAACAGTGGGATGTTACCAAACGCAGTGCTTCCACCTTCACTTGAC5220 
CATAATTATGCTCAGTGGCAGGAGCGAGAGGAAAACAGCCACACTGAGCAGCCTCCTTTA5280 
ATGAAGAAAATCATTCCAGCTCCCAAACCCAAAGGTCCTGGAGAACCAGACTCACCAACT5340 
CCTCTGCATCCTCCTACACCACCAATTTTGAGTACTGATAGGAGTCGAGAAGACAGTCCA5400 
GAGCTGAACCCACCCCCAGGCATAGAAGACAATAGACAGTGTGCGTTATGTTTGACTTAT5460 
GGTGATGACAGTGCTAATGATGCTGGTCGTTTACTATATATTGGCCAAAATGAGTGGACA5520 
CATGTAAATTGTGCTTTGTGGTCAGCGGAAGTGTTTGAAGATGATGACGGATCACTAAAG5580 
AATGTGCATATGGCTGTGATCAGGGGCAAGCAGCTGAGATGTGAATTCTGCCAAAAGCCA5640 
GGAGCCACCGTGGGTTGCTGTCTCACATCCTGCACCAGCAACTATCACTTCATGTGTTCC5700 
CGAGCCAAGAACTGTGTCTTTCTGGATGATAAAAAAGTATATTGCCAACGACATCGGGAT5760 
TTGATCAAAGGCGAAGTGGTTCCTGAGAATGGATTTGAAGTTTTCAGAAGAGTGTTTGTG5820 
GACTTTGAAGGAATCAGCTTGAGAAGGAAGTTTCTCAATGGCTTGGAACCAGAAAATATC5880 
CACATGATGATTGGGTCTATGACAATCGACTGCTTAGGAATTCTAAATGATCTCTCCGAC5940 
TGTGAAGATAAGCTCTTTCCTATTGGATATCAGTGTTCCAGGGTATACTGGAGCACCACA6000 
GATGCTCGCAAGCGCTGTGTATATACATGCAAGATAGTGGAGTGCCGTCCTCCAGTCGTA6060 
GAGCCGGATATCAACAGCACTGTTGAACATGATGAAAACAGGACCATTGCCCATAGTCCA6120 
ACATCTTTTACAGAAAGTTCATCAAAAGAGAGTCAAAACACAGCTGAAATTATAAGTCCT6180 
CCATCACCAGACCGACCTCCTCATTCACAAACCTCTGGCTCCTGTTATTATCATGTCATC6240 
TCAAAGGTCCCCAGGATTCGAACACCCAGTTATTCTCCAACACAGAGATCCCCTGGCTGT6300 
CGACCGTTGCCTTCTGCAGGAAGTCCTACCCCAACCACTCATGAAATAGTCACAGTAGGT6360 
GATCCTTTACTCTCCTCTGGACTTCGAAGCATTGGCTCCAGGCGTCACAGTACCTCTTCC6420 
TTATCACCCCAGCGGTCCAAACTCCGGATAATGTCTCCAATGAGAACTGGGAATACTTAC6480 
TCTAGGAATAATGTTTCCTCAGTCTCCACCACCGGGACCGCTACTGATCTTGAATCAAGT6540 
GCCAAAGTAGTTGATCATGTCTTAGGGCCACTGAATTCAAGTACTAGTTTAGGGCAAAAC6600 
ACTTCCACCTCTTCAAATTTGCAAAGGACAGTGGTTACTGTAGGCAATAAAAACAGTCAC6660 
TTGGATGGATCTTCATCTTCAGAAATGAAGCAGTCCAGTGCTTCAGACTTGGTGTCCAAG6720 
AGCTCCTCTTTAAAGGGAGAGAAGACCAAAGTGCTGAGTTCCAAGAGCTCAGAGGGATCT6780 
GCACATAATGTGGCTTACCCTGGAATTCCTAAACTGGCCCCACAGGTTCATAACACAACA6840 
TCTAGAGAACTGAATGTTAGTAAAATCGGCTCCTTTGCTGAACCCTCTTCAGTGTCGTTT6900 
TCTTCTAAAGAGGCCCTCTCCTTCCCACACCTCCATTTGAGAGGGCAAAGGAATGATCGA6960 
GACCAACACACAGATTCTACCCAATCAGCAAACTCCTCTCCAGATGAAGATACTGAAGTC7020 
AAAACCTTGAAGCTATCTGGAATGAGCAACAGATCATCCATTATCAACGAACATATGGGA7080 
TCTAGTTCCAGAGATAGGAGACAGAAAGGGAAAAAATCCTGTAAAGAAACTTTCAAAGAA7140 
AAGCATTCCAGTAAATCTTTTTTGGAACCTGGTCAGGTGACAACTGGTGAGGAAGGAAAC7200 
TTGAAGCCAGAGTTTATGGATGAGGTTTTGACTCCTGAGTATATGGGCCAACGACCATGT7260 
AACAATGTTTCTTCTGATAAGATTGGTGATAAAGGCCTTTCTATGCCAGGAGTCCCCAAA7320 
GCTCCACCCATGCAAGTAGAAGGATCTGCCAAGGAATTACAGGCACCACGGAAACGCACA7380 
GTCAAAGTGACACTGACACCTCTAAAAATGGAAAATGAGAGTCAATCCAAAAATGCCCTG7440 
AAAGAAAGTAGTCCTGCTTCCCCTTTGCAAATAGAGTCAACATCTCCCACAGAACCAATT7500 
TCAGCCTCTGAAAATCCAGGAGATGGTCCAGTGGCCCAACCAAGCCCCAATAATACCTCA7560 
TGCCAGGATTCTCAAAGTAACAACTATCAGAATCTTCCAGTACAGGACAGAAACCTAATG7620 
CTTCCAGATGGCCCCAAACCTCAGGAGGATGGCTCTTTTAAAAGGAGGTATCCCCGTCGC7680 
AGTGCCCGTGCACGTTCTAACATGTTTTTTGGGCTTACCCCACTCTATGGAGTAAGATCC7740 
TATGGTGAAGAAGACATTCCATTCTACAGCAGCTCAACTGGGAAGAAGCGAGGCAAGAGA7800 
TCAGCTGAAGGACAGGTGGATGGGGCCGATGACTTAAGCACTTCAGATGAAGACGACTTA7860 
TACTATTACAACTTCACTAGAACAGTGATTTCTTCAGGTGGAGAGGAACGACTGGCATCC7920 
CATAATTTATTTCGGGAGGAGGAACAGTGTGATCTTCCAAAAATCTCACAGTTGGATGGT7980 
GTTGATGATGGGACAGAGAGTGATACTAGTGTCACAGCCACAACAAGGAAAAGCAGCCAG8040 
ATTCCAAAAAGAAATGGTAAAGAAAATGGAACAGAGAACTTAAAGATTGATAGACCTGAA8100 
GATGCTGGGGAGAAAGAACATGTCACTAAGAGTTCTGTTGGCCACAAAAATGAGCCAAAG8160 
ATGGATAACTGCCATTCTGTAAGCAGAGTTAAAACACAGGGACAAGATTCCTTGGAAGCT8220 
CAGCTCAGCTCATTGGAGTCAAGCCGCAGAGTCCACACAAGTACCCCCTCCGACAAAAAT8280 
TTACTGGACACCTATAATACTGAGCTCCTGAAATCAGATTCAGACAATAACAACAGTGAT8340 
GACTGTGGGAATATCCTGCCTTCAGACATTATGGACTTTGTACTAAAGAATACTCCATCC8400 
ATGCAGGCTTTGGGTGAGAGCCCAGAGTCATCTTCATCAGAACTCCTGAATCTTGGTGAA8460 
GGATTGGGTCTTGACAGTAATCGTGAAAAAGACATGGGTCTTTTTGAAGTATTTTCTCAG8520 
CAGCTGCCTACAACAGAACCTGTGGATAGTAGTGTCTCTTCCTCTATCTCAGCAGAGGAA8580 
CAGTTTGAGTTGCCTCTAGAGCTACCATCTGATCTGTCTGTCTTGACCACCCGGAGTCCC8640 
ACTGTCCCCAGCCAGAATCCCAGTAGACTAGCTGTTATCTCAGACTCAGGGGAGAAGAGA8700 
GTAACCATCACAGAAAAATCTGTAGCCTCCTCTGAAAGTGACCCAGCACTGCTGAGCCCA8760 
GGAGTAGATCCAACTCCTGAAGGCCACATGACTCCTGATCATTTTATCCAAGGACACATG8820 
GATGCAGACCACATCTCTAGCCCTCCTTGTGGTTCAGTAGAGCAAGGTCATGGCAACAAT8880 
CAGGATTTAACTAGGAACAGTAGCACCCCTGGCCTTCAGGTACCTGTTTCCCCAACTGTT8940 
CCCATCCAGAACCAGAAGTATGTGCCCAATTCTACTGATAGTCCTGGCCCGTCTCAGATT9000 
TCCAATGCAGCTGTCCAGACCACTCCACCCCACCTGAAGCCAGCCACTGAGAAACTCATA9060 
GTTGTTAACCAGAACATGCAGCCACTTTATGTTCTCCAAACTCTTCCAAATGGAGTGACC9120 
CAAAAAATCCAATTGACCTCTTCTGTTAGTTCTACACCCAGTGTGATGGAGACAAATACT9180 
TCAGTATTGGGACCCATGGGAGGTGGTCTCACCCTTACCACAGGACTAAATCCAAGCTTG9240 
CCAACTTCTCAATCTTTGTTCCCTTCTGCTAGCAAAGGATTGCTACCCATGTCTCATCAC9300 
CAGCACTTACATTCCTTCCCTGCAGCTACTCAAAGTAGTTTCCCACCAAACATCAGCAAT9360 
CCTCCTTCAGGCCTGCTTATTGGGGTTCAGCCTCCTCCGGATCCCCAACTTTTGGTTTCA9420 
GAATCCAGCCAGAGGACAGACCTCAGTACCACAGTAGCCACTCCATCCTCTGGACTCAAG9480 
AAAAGACCCATATCTCGTCTACAGACCCGAAAGAATAAAAAACTTGCTCCCTCTAGTACC9540 
CCTTCAAACATTGCCCCTTCTGATGTGGTTTCTAATATGACATTGATTAACTTCACACCC9600 
TCCCAGCTTCCTAATCATCCAAGTCTGTTAGATTTGGGGTCACTTAATACTTCATCTCAC9660 
CGAACTGTCCCCAACATCATAAAAAGATCTAAATCTAGCATCATGTATTTTGAACCGGCA9720 
CCCCTGTTACCACAGAGTGTGGGAGGAACTGCTGCCACAGCGGCAGGCACATCAACAATA9780 
AGCCAGGATACTAGCCACCTCACATCAGGGTCTGTGTCTGGCTTGGCATCCAGTTCCTCT9840 
GTCTTGAATGTTGTATCCATGCAAACTACCACAACCCCTACAAGTAGTGCGTCAGTTCCA9900 
GGACACGTCACCTTAACCAACCCAAGGTTGCTTGGTACCCCAGATATTGGCTCAATAAGC9960 
AATCTTTTAATCAAAGCTAGCCAGCAGAGCCTGGGGATTCAGGACCAGCCTGTGGCTTTA10020 
CCGCCAAGTTCAGGAATGTTTCCACAACTGGGGACATCACAGACCCCCTCTACTGCTGCA10080 
ATAACAGCGGCATCTAGCATCTGTGTGCTCCCCTCCACTCAGACTACGGGCATAACAGCC10140 
GCTTCACCTTCTGGGGAAGCAGACGAACACTATCAGCTTCAGCATGTGAACCAGCTCCTT10200 
GCCAGCAAAACTGGGATTCATTCTTCCCAGCGTGATCTTGATTCTGCTTCAGGGCCCCAG10260 
GTATCCAACTTTACCCAGACGGTAGACGCTCCTAATAGCATGGGACTGGAGCAGAACAAG10320 
GCTTTATCCTCAGCTGTGCAAGCCAGCCCCACCTCTCCTGGGGGTTCTCCATCCTCTCCA10380 
TCTTCTGGACAGCGGTCAGCAAGCCCTTCAGTGCCGGGTCCCACTAAACCCAAACCAAAA10440 
ACCAAACGGTTTCAGCTGCCTCTAGACAAAGGGAATGGCAAGAAGCACAATGTTTCCCAT10500 
TTGCGGACCAGTTCTTCTGAAGCACACATTCCAGACCAAGAAACGACATCCCTGACCTCA10560 
GGCACAGGGACTCCAGGAGCAGAGGCTGAGCAGCAGGATACAGCTAGCGTGGAGCAGTCC10620 
TCCCAGAAGGAGTGTGGGCAACCTGCAGGGCAAGTCGCTGTTCTTCCGGAAGTTCAGGTG10680 
ACCCAAAATCCAGCAAATGAACAAGAAAGTGCAGAACCTAAAACAGTGGAAGAAGAGGAA10740 
AGTAATTTCAGCTCCCCACTGATGCTTTGGCTTCAGCAAGAACAAAAGCGGAAGGAAAGC10800 
ATTACTGAGAAAAAACCCAAGAAAGGACTTGTTTTTGAAATTTCCAGTGATGATGGCTTT10860 
CAGATCTGTGCAGAAAGTATTGAAGATGCCTGGAAGTCATTGACAGATAAAGTCCAGGAA10920 
GCTCGATCAAATGCCCGCCTAAAGCAGCTCTCATTTGCAGGTGTTAACGGTTTGAGGATG10980 
CTGGGGATTCTCCATGATGCAGTTGTGTTCCTCATTGAGCAGCTGTCTGGTGCCAAGCAC11040 
TGTCGAAATTACAAATTCCGTTTCCACAAGCCAGAGGAGGCCAATGAACCCCCCTTGAAC11100 
CCTCACGGCTCAGCCAGGGCTGAAGTCCACCTCAGGAAGTCAGCATTTGACATGTTTAAC11160 
TTCCTGGCTTCTAAACATCGTCAGCCTCCTGAATACAACCCCAATGATGAAGAAGAGGAG11220 
GAGGTACAGCTGAAGTCAGCTCGGAGGGCAACTAGCATGGATCTGCCAATGCCCATGCGC11280 
TTCCGGCACTTAAAAAAGACTTCTAAGGAGGCAGTTGGTGTCTACAGGTCTCCCATCCAT11340 
GGCCGGGGTCTTTTCTGTAAGAGAAACATTGATGCAGGTGAGATGGTGATTGAGTATGCC11400 
GGCAACGTCATCCGCTCCATCCAGACTGACAAGCGGGAAAAGTATTACGACAGCAAGGGC11460 
ATTGGTTGCTATATGTTCCGAATTGATGACTCAGAGGTAGTGGATGCCACCATGCATGGA11520 
AATGCTGCACGCTTCATCAATCACTCGTGTGAGCCTAACTGCTATTCTCGGGTCATCAAT11580 
ATTGATGGGCAGAAGCACATTGTCATCTTTGCCATGCGTAAGATCTACCGAGGAGAGGAA11640 
CTCACTTACGACTATAAGTTCCCCATTGAGGATGCCAGCAACAAGCTGCCCTGCAACTGT11700 
GGCGCCAAGAAATGCCGGAAGTTCCTAAACTAAAGCTGCTCTTCTCCCCCAGTGTTGGAG11760 
TGCAAGGAGGCGGGGCCATCCAAAGCAACGCTGAAGGCCTTTTCCAGCAGCTGGGAGCTC11820 
CCGGATTGCGTGGCACAGCTGAGGGGCCTCTGTGATGGCTGAGCTCTCTTATGTCCTATA11880 
CTCACATCAGACATGTGATCATAGTCCCAGAGACAGAGTTGAGGTCTCGAAGAAAAGATC11940 
CATGATCGGCTTTCTCCTGGGGCCCCTCCAATTGTTTACTGTTAGAAAGTGGGAATGGGG12000 
TCCCTAGCAGACTTGCCTGGAAGGAGCCTATTATAGAGGGTTGGTTATGTTGGGAGATTG12060 
GGCCTGAATTTCTCCACAGAAATAAGTTGCCATCCTCAGGTTGGCCCTTTCCCAAGCACT12120 
GTAAGTGAGTGGGTCAGCCAAAGCCCCAAATGGAGGGTTGGTTAGATTCCTGACAGTTTG12180 
CCAGCCAGCCGCCACCTACAGCGTCTGTCGAACAAACAGAGGTCTGGTGGTTTTCCCTAC12240 
TGTCCTCCCACTCGAGAGTTCACTTCTGGTTGGGAGACAGGATTCCTAGCACCTCCGGTG12300 
TCAAAAGGCTGTCATGGGGTTGTGCCAATTAATTACCAAACATTGAGCCTGCAGGCTTTG12360 
AGTGGGAGTGTTGCCCCCAGGAGCCTTATCTCAGCCAATTACCTTTCTTGACAGTAGGAG12420 
CGGCTTCCCTCTCCCATTCCCTCTTCACTCCCTTTTCTTCCTTTCCCCTGTCTTCATGCC12480 
ACTGCTTTCCCATGCTTCTTTCGGTTGTAGGGGAGACTGACTGCCTGCTCAAGGACACTC12540 
CCTGCTGGGCATAGGATGTGCCTGCAAAAAGTTCCCTGAGCCTGTAAGCACTCCAGGTGG12600 
GGAAGTGGACAGGAGCCATTGGTCATAACCAGACAGAATTTGGAAACATTTTCATAAAGC12660 
TCCATGGAGAGTTTTAAAGAAACATATGTAGCATGATTTTGTAGGAGAGGAAAAAGATTA12720 
TTTAAATAGGATTTAAATCATGCAACAACGAGAGTATCACAGCCAGGATGACCCTTGGGT12780 
CCCATTCCTAAGACATGGTTACTTTATTTTCCCCTTGTTAAGACATAGGAAGACTTAATT12840 
TTTAAACGGTCAGTGTCCAGTTGAAGGCAGAACACTAATCAGATTTCAAGGCCCACAACT12900 
TGGGGACTAGACCACCTTATGTTGAGGGAACTCTGCCACCTGCGTGCAACCCACAGCTAA12960 
AGTAAATTCAATGACACTACTGCCCTGATTACTCCTTAGGATGTGGTCAAAACAGCATCA13020 
AATGTTTCTTCTCTTCCTTTCCCCAAGACAGAGTCCTGAACCTGTTAAATTAAGTCATTG13080 
GATTTTACTCTGTTCTGTTTACAGTTTACTATTTAAGGTTTTATAAATGTAAATATATTT13140 
TGTATATTTTTCTATGAGAAGCACTTCATAGGGAGAAGCACTTATGACAAGGCTATTTTT13200 
TAAACCGCGGTATTATCCTAATTTAAAAGAAGATCGGTTTTTAATAATTTTTTATTTTCA13260 
TAGGATGAAGTTAGAGAAAATATTCAGCTGTACACACAAAGTCTGGTTTTTCCTGCCCAA13320 
CTTCCCCCTGGAAGGTGTACTTTTTGTTGTTTAATGTGTAGCTTGTTTGTGCCCTGTTGA13380 
CATAAATGTTTCCTGGGTTTGCTCTTTGACAATAAATGGAGAAGGAAGGTCACCCAACTC13440 
CATTGGGCCACTCCCCTCCTTCCCCTATTGAAGCTCCTCAAAAGGCTACAGTAATATCTT13500 
GATACAACAGATTCTCTTCTTTCCCGCCTCTCTCCTTTCCGGCGCAACTTCCAGAGTGGT13560 
GGGAGACGGCAATCTTTACATTTCCCTCATCTTTCTTACTTCAGAGTTAGCAAACAACAA13620 
GTTGAATGGCAACTTGACATTTTTGCATCACCATCTGCCTCATAGGCCACTCTTTCCTTT13680 
CCCTCTGCCCACCAAGTCCTCATATCTGCAGAGAACCCATTGATCACCTTGTGCCCTCTT13740 
TTGGGGCAGCCTGTTGAAACTGAAGCACAGTCTGACCACTCACGATAAAGCAGATTTTCT13800 
CTGCCTCTGCCACAAGGTTTCAGAGTAGTGTAGTCCAAGTAGAGGGTGGGGCACCCTTTT13860 
CTCGCCGCAAGAAGCCCATTCCTATGGAAGTCTAGCAAAGCAATACGACTCAGCCCAGCA13920 
CTCTCTGCCCCAGGACTCATGGCTCTGCTGTGCCTTCCATCCTGGGCTCCCTTCTCTCCT13980 
GTGACCTTAAGAACTTTGTCTGGTGGCTTTGCTGGAACATTGTCACTGTTTTCACTGTCA14040 
TGCAGGGAGCCCAGCACTGTGGCCAGGATGGCAGAGACTTCCTTGTCATCATGGAGAAGT14100 
GCCAGCAGGGGACTGGGAAAAGCACTCTACCCAGACCTCACCTCCCTTCCTCCTTTTGCC14160 
CATGAACAAGATGCAGTGGCCCTAGGGGTTCCACTAGTGTCTGCTTTCCTTTATTATTGC14220 
ACTGTGTGAGGTTTTTTTGTAAATCCTTGTATTCC14255 
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